A Chinese medicine composition for treating gastric precancerous lesions and its application

Abstract

The invention relates to the technical field of traditional Chinese medicine compositions, and in particular to a traditional Chinese medicine composition for treating gastric precancerous lesions and an application thereof. The traditional Chinese medicine composition comprises the following raw materials in parts by weight: 15-25 parts of lily, 5-15 parts of cassia twig, 10-20 parts of white peony root, 1-10 parts of jujube, 5-15 parts of atractylodes, 5-15 parts of magnolia bark, 5-15 parts of tangerine peel, 1-10 parts of liquorice, 1-10 parts of coptis root, 10-20 parts of smilax glabra, 10-20 parts of dandelion and 10-20 parts of oldenlandia diffusa. The lily in this prescription is mainly used to dispel rheumatism in the spleen and stomach / internal organs; cinnamon twig and white peony root are used together to harmonize the Ying and Wei, yin and yang, and jujube is used to replenish qi and nourish the middle, and combined with lily to make Lily and Cinnamon Twig Decoction; Atractylodes macrocephala dispels wind, dries dampness and strengthens the spleen, Smilax glabra dispels wind, removes dampness and relieves numbness, Magnolia officinalis aromatizes bitterness and dryness, Tangerine peel regulates qi, dries dampness and wakes up the spleen, Licorice harmonizes all the medicines, replenishes qi, strengthens the spleen and harmonizes the middle, dandelion and Hedyotis diffusa clear away heat and detoxify, Coptis chinensis clears heat and dries dampness; the whole prescription realizes the integration of treating the middle jiao with treating rheumatism in the spleen and stomach, and includes internal organ rheumatism, damp-heat, and spleen dampness / internal dampness into the treatment scope at the same time, achieving the simultaneous treatment of the three dampnesses. It is a clinically effective prescription for treating precancerous lesions of the stomach.

Description

Technical Field

[0001] The present invention relates to the technical field of Chinese medicine compositions, and in particular to a Chinese medicine composition for treating gastric precancerous lesions and application thereof. Background Art

[0002] Chronic atrophic gastritis (CAG) refers to a precancerous disease or precancerous state of gastric cancer, and the accompanying intestinal metaplasia (IM) and dysplasia (Dys) are called precancerous lesions of gastric cancer (hereinafter referred to as PLGC).

[0003] At present, TCM has a diverse understanding of the pathogenesis of PLGC. It is mainly believed that it is based on spleen and stomach deficiency (Qi deficiency, Yin deficiency), and that it is manifested by inflammatory toxins, blood stasis, phlegm coagulation, Qi stagnation, dampness obstruction and other pathogenic factors. It is a mixture of deficiency and excess, cold and heat. On this basis, the following theories have been derived: (1) Treating PLGC from the perspective of spleen deficiency: Lu Zhizheng, a master of traditional Chinese medicine, advocates treating PLGC from the perspective of Yin deficiency, advocating both attack and supplementation, protecting stomach Yin, harmonizing the spleen and stomach, invigorating Qi and nourishing Yin, and the effect is as good as a drum; (2) Treating PLGC from the perspective of inflammatory toxins: In modern medicine, PLGC goes through the process of "chronic non-atrophic gastritis → chronic atrophic gastritis → chronic gastritis". The “inflammation-to-cancer transformation from chronic atrophic gastritis with intestinal metaplasia to chronic atrophic gastritis with dysplasia / atypical hyperplasia / intraepithelial neoplasia to gastric cancer” has become a consensus in the industry. (3) Treating PLGC from the perspective of blood stasis: Xu Jingfan, a master of traditional Chinese medicine, believes that the evolution of pathological syndromes from gastritis to gastric cancer is accompanied by “blood stasis”. Based on the rules of blood stasis-removing drug compatibility and the pathology of gastric mucosa, blood stasis-removing drugs should be selected. That is, TCM lacks a unified consensus on PLGC. Doctors often make syndrome differentiation and treatment based on their own understanding and experience, and often treat from the perspectives of spleen deficiency, inflammatory toxins, and blood stasis.

[0004] From the perspective of traditional Chinese medicine and Western medicine, digestive tract tumors are closely related to dampness, which may be the basis and key to the pathogenesis of PLGC. So far, no research has been published on the treatment of PLGC from the perspective of rheumatism, especially visceral / organ rheumatism, whether from the perspective of modern medicine, comorbidities, or traditional Chinese medicine. Summary of the invention

[0005] In order to solve the above problems, based on the existing theories of treating gastric precancerous lesions, the present invention provides a Chinese medicine composition for treating gastric precancerous lesions and its application, which treats gastric precancerous lesions from the perspective of dampness (mainly visceral / organ rheumatism).

[0006] In a first aspect, the present invention provides a traditional Chinese medicine composition for treating gastric precancerous lesions, comprising the following raw materials in parts by weight: 15-25 parts of lily, 5-15 parts of cinnamon twig, 10-20 parts of white peony root, 1-10 parts of jujube, 5-15 parts of atractylodes, 5-15 parts of magnolia bark, 5-15 parts of tangerine peel, 1-10 parts of licorice, 1-10 parts of coptis root, 10-20 parts of smilax glabra, 10-20 parts of dandelion, and 10-20 parts of oldenlandia diffusa.

[0007] Preferably, the following raw materials are included in weight proportions: 15-25 parts of lily, 5-15 parts of cinnamon twig, 10-20 parts of white peony root, 1-10 parts of jujube, 5-15 parts of atractylodes, 5-15 parts of magnolia bark, 5-15 parts of tangerine peel, 1-10 parts of licorice, 1-10 parts of coptis root, 10-20 parts of smilax glabra, 10-20 parts of dandelion, 10-20 parts of oldenlandia diffusa, and 10-30 parts of pseudoginseng, as a prescription for patients with obvious spleen deficiency.

[0008] Preferably, the following raw materials are included in parts by weight: 15-25 parts of lily, 5-15 parts of cinnamon twig, 10-20 parts of white peony root, 1-10 parts of jujube, 5-15 parts of atractylodes, 5-15 parts of magnolia bark, 5-15 parts of tangerine peel, 1-10 parts of licorice, 1-10 parts of coptis root, 10-20 parts of smilax glabra, 10-20 parts of dandelion, 10-20 parts of oldenlandia diffusa, and 15-30 parts of coix seed, as a prescription for when dampness and turbidity are obvious.

[0009] Preferably, the following raw materials are included in weight proportions: 15-25 parts of lily, 5-15 parts of cinnamon twig, 10-20 parts of white peony root, 1-10 parts of jujube, 5-15 parts of atractylodes, 5-15 parts of magnolia bark, 5-15 parts of tangerine peel, 1-10 parts of licorice, 1-10 parts of coptis root, 10-20 parts of smilax glabra, 10-20 parts of dandelion, 10-20 parts of oldenlandia diffusa, and 5-10 parts of fritillaria thunbergii, as a prescription for when the condition is accompanied by obvious phlegm-dampness.

[0010] Preferably, the following raw materials are included in weight proportions: 15-25 parts of lily, 5-15 parts of cinnamon twig, 10-20 parts of white peony root, 1-10 parts of jujube, 5-15 parts of atractylodes, 5-15 parts of magnolia bark, 5-15 parts of tangerine peel, 1-10 parts of licorice, 1-10 parts of coptis root, 10-20 parts of smilax glabra, 10-20 parts of dandelion, 10-20 parts of oldenlandia diffusa, 15-30 parts of oyster, and 15-30 parts of corrugated paper, as a prescription for symptoms accompanied by excessive gastric acid.

[0011] Preferably, the following raw materials are included in parts by weight: 15-25 parts of lily, 5-15 parts of cinnamon twig, 10-20 parts of white peony root, 1-10 parts of jujube, 5-15 parts of atractylodes, 5-15 parts of magnolia bark, 5-15 parts of tangerine peel, 1-10 parts of licorice, 1-10 parts of coptis root, 10-20 parts of smilax glabra, 10-20 parts of dandelion, 10-20 parts of oldenlandia diffusa, 10-20 parts of ebony, 15-30 parts of oyster, and 5-15 parts of clematis, as a prescription for symptoms accompanied by polyps.

[0012] Preferably, the following raw materials are included in parts by weight: 15-25 parts of lily, 5-15 parts of cinnamon twig, 10-20 parts of white peony root, 1-10 parts of jujube, 5-15 parts of atractylodes, 5-15 parts of magnolia bark, 5-15 parts of tangerine peel, 1-10 parts of licorice, 1-10 parts of coptis root, 10-20 parts of smilax glabra, 10-20 parts of dandelion, 10-20 parts of oldenlandia diffusa, and 10-20 parts of aconite, as a prescription for symptoms accompanied by qi stagnation and depression.

[0013] Preferably, the following raw materials are included in parts by weight: 15-25 parts of lily, 5-15 parts of cinnamon twig, 10-20 parts of white peony root, 1-10 parts of jujube, 5-15 parts of atractylodes, 5-15 parts of magnolia bark, 5-15 parts of tangerine peel, 1-10 parts of licorice, 1-10 parts of coptis root, 10-20 parts of smilax glabra, 10-20 parts of dandelion, 10-20 parts of oldenlandia diffusa, 15-30 parts of angelica dahurica, and 10-20 parts of bupleurum, as a prescription for pain symptoms.

[0014] Preferably, the raw materials are included in the following weight proportions: 15-25 parts of lily, 5-15 parts of cinnamon twig, 10-20 parts of white peony root, 1-10 parts of jujube, 5-15 parts of atractylodes, 5-15 parts of magnolia bark, 5-15 parts of tangerine peel, 1-10 parts of licorice, 1-10 parts of coptis root, 10-20 parts of smilax glabra, and 15-30 parts of barbata.

[0015] Preferably, the raw materials are included in the following weight proportions: 15-25 parts of lily, 5-15 parts of cinnamon twig, 10-20 parts of white peony root, 1-10 parts of jujube, 5-15 parts of atractylodes, 5-15 parts of magnolia bark, 5-15 parts of tangerine peel, 1-10 parts of licorice, 1-10 parts of coptis root, 10-20 parts of smilax glabra, and 15-30 parts of lobelia.

[0016] Preferably, the following raw materials are included in parts by weight: 15-25 parts of lily, 5-15 parts of cinnamon twig, 10-20 parts of white peony root, 1-10 parts of jujube, 5-15 parts of atractylodes, 5-15 parts of magnolia bark, 5-15 parts of tangerine peel, 1-10 parts of licorice, 10-20 parts of smilax glabra, 10-20 parts of dandelion, 10-20 parts of oldenlandia diffusa, 10-15 parts of gardenia, and 10-15 parts of bamboo leaves, as a prescription for when accompanied by excessive heart fire.

[0017] The Chinese medicine composition of the present invention is derived from a prescription based on clinical experience. Lily is the main medicine in the prescription, which is mainly used to eliminate rheumatism in the spleen and stomach / internal organs; cinnamon twig and white peony root harmonize the Ying and Wei, yin and yang, and jujube is added to invigorate qi and tonify the middle. The three medicines are combined into cinnamon twig soup, which is combined with lily to form lily and cinnamon twig soup, which serves as the base of the prescription, harmonizes the Ying and Wei externally and regulates the internal organs internally, so as to "build up the middle / harmony the middle", and together play the role of eliminating rheumatism in the spleen and stomach / internal organs.

[0018] Atractylodes lancea dispels wind, dries dampness and strengthens the spleen, while Smilax glabra dispels wind, removes dampness and relieves numbness. Both herbs in the prescription are mainly used to assist Lily and Cinnamon Twig Decoction in dispelling rheumatism in the spleen, stomach / internal organs, while also strengthening the effect of drying dampness.

[0019] Atractylodes lancea can dry out dampness and strengthen the spleen, and can remove dampness and turbidity in the middle burner, so that the dampness is removed and the spleen can function properly; Magnolia officinalis can be aromatic and bitter and dry, which can help Atractylodes lancea to promote qi and remove dampness; Tangerine peel can regulate qi and harmonize the stomach, dry out dampness and invigorate the spleen, and help Atractylodes lancea and Magnolia officinalis in their drying dampness; Licorice can harmonize all the medicines, and can also invigorate qi, strengthen the spleen and harmonize the middle. The four medicines are combined into Pingwei Powder, which is mainly used to "pacify the stomach" and mainly remove spleen dampness / internal dampness, and can also help remove rheumatism in the spleen, stomach / viscera.

[0020] Dandelion and Hedyotis diffusa clear heat and detoxify, Coptis chinensis clears heat and dries dampness, and Smilax glabra detoxifies and removes dampness. The four herbs work together to clear heat / inflammatory toxicity (including damp heat), and are mainly used for "detoxification". They can also help to remove rheumatism in the spleen, stomach, and internal organs. Lobelia and Scutellaria barbata also have the effect of clearing heat and detoxifying. After using the prescription for a period of time, the patient may develop resistance to dandelion and Hedyotis diffusa, and when the treatment is ineffective, Scutellaria barbata or Lobelia barbata can be used in rotation with dandelion and Hedyotis diffusa.

[0021] When the heart fire is strong, remove the coptis root, add gardenia and bamboo leaves to clear heat and dampness, purge fire and relieve restlessness; when the spleen is weak, add Pseudostellaria baicalensis to invigorate qi and strengthen the spleen; when dampness and turbidity are obvious, add coix seed to invigorate the spleen, promote water and eliminate dampness; when phlegm and dampness are obvious, add Fritillaria thunbergii to resolve phlegm and disperse nodules; when there is excessive gastric acid, add oyster and corrugated seeds to reduce acid and relieve pain; when there is polyp problem, add black plum, oyster and clematis to dispel rheumatism and disperse nodules; when there is qi stagnation and qi stagnation, add August twig to soothe the liver, regulate qi and harmonize the stomach; when there is pain, add Angelica dahurica and Corydalis to dispel wind and dampness, promote qi and relieve pain. The whole formula realizes the integration of strengthening the middle jiao and treating spleen and stomach rheumatism, and includes rheumatism (visceral / visceral rheumatism), damp heat, spleen dampness / internal dampness into the treatment scope at the same time, realizing the simultaneous treatment of three dampnesses, and creating a clinical effective formula for treating gastric precancerous lesions.

[0022] In a second aspect, the present invention provides use of the above-mentioned traditional Chinese medicine composition for treating gastric precancerous lesions in the preparation of a drug for treating gastric precancerous lesions.

[0023] In a third aspect, the present invention provides a medicine for treating gastric precancerous lesions, comprising the above-mentioned Chinese medicine composition for treating gastric precancerous lesions and pharmaceutically acceptable excipients.

[0024] Compared with the prior art, the present invention has the following beneficial effects:

[0025] The present invention provides a traditional Chinese medicine composition for treating precancerous lesions of the stomach. In the prescription, lily mainly dispels rheumatism of the spleen and stomach / viscera; cinnamon twig and white peony root are used together to harmonize the Ying and Wei, yin and yang, and jujube is used to invigorate qi and nourish the middle, and is combined with lily to form lily and cinnamon twig soup; atractylodes macrocephala dispels wind, dries dampness and strengthens the spleen, smilax glabra dispels wind, removes dampness and relieves numbness, magnolia officinalis aromatizes bitterness and dryness, tangerine peel regulates qi, dries dampness and wakes up the spleen, liquorice harmonizes various medicines, invigorates qi, strengthens the spleen and harmonizes the middle, dandelion and oldenlandia diffusa clear away heat and detoxify, and coptis root clears heat and dries dampness; the whole prescription realizes the integration of strengthening the middle jiao and treating rheumatism of the spleen and stomach, and simultaneously includes rheumatism of the viscera, damp-heat and spleen dampness / internal dampness into the treatment scope, realizes the simultaneous treatment of the three dampnesses, and establishes a clinically effective prescription for treating precancerous lesions of the stomach. By regulating proteins and metabolites related to multiple pathways such as central carbon metabolism, glycolysis / gluconeogenesis, pyruvate metabolism, arachidonic acid metabolism, biosynthesis of unsaturated fatty acids and tyrosine metabolism, it inhibits inflammation and cancer, regulates sugar metabolism and immune function, and exerts multi-target and multi-pathway therapeutic effects. Clinical retrospective cohort studies have shown that the effective rate of intensive treatment of dampness in PLGC is as high as 82.6%; the results of prospective cohort studies have shown that the effective rate of intensive treatment of dampness in PLGC is 84.80%, and no adverse reactions have been observed, with high safety. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. The drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0027] Figure 1 The overall technical roadmap for the clinical trial study 1 of the present invention;

[0028] Figure 2 The overall technical roadmap for the clinical trial study 2 of the present invention;

[0029] Figure 3 The analytical flow chart of the proteomics study in the clinical trial study 2 of the present invention;

[0030] Figure 4 This is a volcano map of the differential proteins before and after the enhanced dampness treatment and regulation of PLGC in the proteomics study of the clinical trial study 2 of the present invention, in which the blue marks are significantly down-regulated proteins, the red marks are significantly up-regulated proteins, and the proteins with no significant difference are marked in gray;

[0031] Figure 5 This is a KEGG enrichment pathway diagram of differential proteins in the proteomics study of clinical trial study 2 of the present invention, with the vertical axis representing each KEGG metabolic pathway and the horizontal axis representing the number of differentially expressed metabolites contained in the KEGG metabolic pathway;

[0032] Figure 6 This is the statistical distribution diagram of the GO secondary classification of the enhanced dampness-regulating protein in the proteomics study in the clinical trial study 2 of the present invention;

[0033] Figure 7 This is an analytical flow chart of the non-targeted metabolomics study in the clinical trial study 2 of the present invention;

[0034] Figure 8-a This is a volcano plot of differential metabolites between the PLGC group and the healthy group in the non-targeted metabolomics study in the clinical trial study 2 of the present invention, where proteins marked in blue are significantly down-regulated, proteins marked in red are significantly up-regulated, and proteins with no significant difference are marked in gray; Figure 8-b This is a volcano diagram of the differential metabolites before and after the intensive dampness treatment of PLGC in the non-targeted metabolomics study in the clinical trial study 2 of the present invention, in which the blue marks are significantly down-regulated proteins, the red marks are significantly up-regulated proteins, and the proteins with no significant difference are marked in gray;

[0035] FIG9 is a heat map of correlation coefficients of significantly differentially expressed proteins and significantly differentially expressed metabolites in the combined analysis of proteomics and metabolomics in the clinical trial study 2 of the present invention; wherein, Figure 9-a This is the correlation coefficient matrix heat map of the significantly different proteins and metabolites in A vs C. Figure 9-b This is a heat map of the correlation coefficient matrix between proteins and metabolites with significant differences between A and B. The correlation coefficient r between proteins and metabolites is represented by color; r>0 indicates positive correlation, which is represented by red; r<0 indicates negative correlation, which is represented by blue. The darker the color, the stronger the correlation.

[0036] FIG10 is a hierarchical cluster diagram showing the correlation between significantly differentially expressed proteins and significantly differentially expressed metabolites in the combined analysis of proteomics and metabolomics in the clinical trial study 2 of the present invention; wherein, Figure 10-a This is the hierarchical clustering diagram of the correlation between proteins and metabolites with significant differences between A and C. Figure 10-b This is a hierarchical clustering diagram of the correlation between proteins and metabolites with significant differences between A and B; the correlation coefficient r between proteins and metabolites is represented by color; r>0 indicates positive correlation, which is represented by red; r<0 indicates negative correlation, which is represented by blue, and the darker the color, the stronger the correlation; p value reflects the significance level of the correlation, p value <0.05 is represented by *, and p value <0.001 is represented by ***;

[0037] Fig.11This is the central carbon metabolism pathway diagram of cancer analyzed by proteomics and metabolomics in clinical trial study 2 of the present invention. The square boxes in the figure represent proteins, and the circles represent metabolites. The proteins or metabolites in the red / green background boxes belong to the differential proteins or metabolites detected this time, among which red represents up-regulated proteins or metabolites, and green represents down-regulated proteins / metabolites. DETAILED DESCRIPTION

[0038] The technical solution of the present invention will be clearly and completely described below in conjunction with specific embodiments. Obviously, the described embodiments are only part of the embodiments of the present invention, rather than all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative work belong to the protection scope of the present invention.

[0039] Example 1

[0040] The embodiment of the present invention provides a traditional Chinese medicine composition for treating gastric precancerous lesions, comprising the following raw materials in parts by weight: 20 parts of lily, 10 parts of cinnamon twig, 15 parts of white peony root, 5 parts of jujube, 10 parts of atractylodes, 10 parts of magnolia bark, 10 parts of tangerine peel, 5 parts of licorice, 5 parts of coptis root, 15 parts of smilax glabra, 15 parts of dandelion, and 15 parts of oldenlandia diffusa.

[0041] Example 2

[0042] The embodiment of the present invention provides a traditional Chinese medicine composition for treating gastric precancerous lesions, which is different from the embodiment 1 in that the raw materials further include 25 portions of Pseudostellariae Radix.

[0043] Example 3

[0044] The embodiment of the present invention provides a traditional Chinese medicine composition for treating gastric precancerous lesions, which is different from the embodiment 1 in that the raw materials further include 25 portions of coix seeds.

[0045] Example 4

[0046] The embodiment of the present invention provides a traditional Chinese medicine composition for treating gastric precancerous lesions, which is different from the embodiment 1 in that the raw materials further include 10 portions of Fritillaria thunbergii.

[0047] Example 5

[0048] The embodiment of the present invention provides a traditional Chinese medicine composition for treating gastric precancerous lesions, which is different from the embodiment 1 in that the raw materials further include 25 parts of oysters and 25 parts of corrugated shells.

[0049] Example 6

[0050] The embodiment of the present invention provides a traditional Chinese medicine composition for treating gastric precancerous lesions. The difference from the embodiment 1 is that the raw materials further include 15 parts of black plums, 25 parts of oysters and 10 parts of clematis.

[0051] Example 7

[0052] The embodiment of the present invention provides a traditional Chinese medicine composition for treating gastric precancerous lesions, which is different from the embodiment 1 in that the raw materials further include 15 portions of August 24th.

[0053] Example 8

[0054] The embodiment of the present invention provides a traditional Chinese medicine composition for treating gastric precancerous lesions, which is different from the embodiment 1 in that the raw materials further include 25 parts of Angelica dahurica and 15 parts of Rhizoma Corydalis.

[0055] Example 9

[0056] The embodiment of the present invention provides a traditional Chinese medicine composition for treating gastric precancerous lesions, which is different from the embodiment 1 in that 20 parts of Scutellaria barbata are added to replace 15 parts of Taraxacum mongolicum and 15 parts of Hedyotis diffusa in the prescription.

[0057] Example 10

[0058] The embodiment of the present invention provides a traditional Chinese medicine composition for treating gastric precancerous lesions, which is different from the embodiment 1 in that 20 parts of Lobelia chinensis are added to replace 15 parts of Taraxacum mongolicum and 15 parts of Hedyotis diffusa in the prescription.

[0059] Embodiment 11

[0060] The embodiment of the present invention provides a traditional Chinese medicine composition for treating gastric precancerous lesions, which is different from the embodiment 1 in that 12 parts of gardenia and 12 parts of bamboo leaves are added to replace 5 parts of coptis chinensis in the prescription.

[0061] Example 12

[0062] The embodiment of the present invention provides a traditional Chinese medicine composition for treating gastric precancerous lesions, comprising the following raw materials in parts by weight: 15 parts of lily, 5 parts of cinnamon twig, 10 parts of white peony root, 1 part of jujube, 5 parts of atractylodes, 5 parts of magnolia bark, 5 parts of tangerine peel, 1 part of licorice, 1 part of coptis root, 10 parts of smilax glabra, 10 parts of dandelion, and 10 parts of oldenlandia diffusa.

[0063] Embodiment 13

[0064] This embodiment of the present invention provides a traditional Chinese medicine composition for treating gastric precancerous lesions, which is different from Example 12 in that the raw materials also include 10 portions of Pseudostellariae Radix.

[0065] Embodiment 14

[0066] This embodiment of the present invention provides a traditional Chinese medicine composition for treating gastric precancerous lesions, which is different from Example 12 in that the raw materials also include 15 portions of coix seeds.

[0067] Embodiment 15

[0068] This embodiment of the present invention provides a traditional Chinese medicine composition for treating gastric precancerous lesions, which is different from Example 12 in that the raw materials also include 5 portions of Fritillaria thunbergii.

[0069] Example 16

[0070] This embodiment of the present invention provides a traditional Chinese medicine composition for treating gastric precancerous lesions, which is different from Example 12 in that the raw materials also include 15 parts of oysters and 15 parts of corrugated shells.

[0071] Embodiment 17

[0072] The embodiment of the present invention provides a traditional Chinese medicine composition for treating gastric precancerous lesions, which is different from Example 12 in that the raw materials also include 10 parts of black plums, 15 parts of oysters and 5 parts of clematis.

[0073] Embodiment 18

[0074] The embodiment of the present invention provides a traditional Chinese medicine composition for treating gastric precancerous lesions, which is different from the embodiment 12 in that the raw materials further include 10 portions of August 24th.

[0075] Embodiment 19

[0076] The embodiment of the present invention provides a traditional Chinese medicine composition for treating gastric precancerous lesions, which is different from Example 12 in that the raw materials also include 15 parts of Angelica dahurica and 10 parts of Rhizoma Corydalis.

[0077] Embodiment 20

[0078] The embodiment of the present invention provides a traditional Chinese medicine composition for treating gastric precancerous lesions, which is different from Example 12 in that 15 parts of Scutellaria barbata are added to replace 10 parts of Taraxacum mongolicum and 10 parts of Hedyotis diffusa in the prescription.

[0079] Embodiment 21

[0080] The embodiment of the present invention provides a traditional Chinese medicine composition for treating gastric precancerous lesions, which is different from Example 12 in that 15 parts of Lobelia chinensis are added to replace 10 parts of Taraxacum mongolicum and 10 parts of Hedyotis diffusa in the prescription.

[0081] Embodiment 22

[0082] The embodiment of the present invention provides a traditional Chinese medicine composition for treating gastric precancerous lesions, which differs from Example 12 in that 10 parts of Gardenia jasminoides and 10 parts of bamboo leaves are added to replace 1 part of Coptis chinensis in the prescription.

[0083] Embodiment 23

[0084] The embodiment of the present invention provides a traditional Chinese medicine composition for treating gastric precancerous lesions, comprising the following raw materials in parts by weight: 25 parts of lily, 15 parts of cinnamon twig, 20 parts of white peony root, 10 parts of jujube, 15 parts of atractylodes, 15 parts of magnolia bark, 15 parts of tangerine peel, 10 parts of licorice, 10 parts of coptis root, 20 parts of smilax glabra, 20 parts of dandelion, and 20 parts of oldenlandia diffusa.

[0085] Embodiment 24

[0086] This embodiment of the present invention provides a traditional Chinese medicine composition for treating gastric precancerous lesions, which differs from Example 23 in that the raw materials also include 30 portions of Pseudostellariae Radix.

[0087] Embodiment 25

[0088] This embodiment of the present invention provides a traditional Chinese medicine composition for treating gastric precancerous lesions, which is different from Example 23 in that the raw materials also include 30 portions of coix seeds.

[0089] Embodiment 26

[0090] This embodiment of the present invention provides a traditional Chinese medicine composition for treating gastric precancerous lesions, which differs from Example 23 in that the raw materials also include 10 portions of Fritillaria thunbergii.

[0091] Embodiment 27

[0092] This embodiment of the present invention provides a traditional Chinese medicine composition for treating gastric precancerous lesions, which is different from Example 23 in that the raw materials also include 30 parts of oysters and 30 parts of corrugated shells.

[0093] Embodiment 28

[0094] This embodiment of the present invention provides a traditional Chinese medicine composition for treating gastric precancerous lesions, which is different from Example 23 in that the raw materials also include 20 parts of black plums, 30 parts of oysters and 15 parts of Clematis chinensis.

[0095] Embodiment 29

[0096] This embodiment of the present invention provides a traditional Chinese medicine composition for treating gastric precancerous lesions, which is different from Example 23 in that the raw materials also include 20 portions of August 24th.

[0097] Embodiment 30

[0098] This embodiment of the present invention provides a traditional Chinese medicine composition for treating gastric precancerous lesions, which is different from Example 23 in that the raw materials also include 30 parts of Angelica dahurica and 20 parts of Corydalis yanhusuo.

[0099] Embodiment 31

[0100] The embodiment of the present invention provides a traditional Chinese medicine composition for treating gastric precancerous lesions, which differs from Example 23 in that 30 parts of Scutellaria barbata are added to replace 20 parts of Taraxacum mongolicum and 20 parts of Hedyotis diffusa in the prescription.

[0101] Embodiment 32

[0102] The embodiment of the present invention provides a traditional Chinese medicine composition for treating gastric precancerous lesions, which is different from Example 23 in that 30 parts of Lobelia chinensis are added to replace 20 parts of Taraxacum mongolicum and 20 parts of Hedyotis diffusa in the prescription.

[0103] Embodiment 33

[0104] The embodiment of the present invention provides a traditional Chinese medicine composition for treating gastric precancerous lesions, which differs from Example 23 in that 10 parts of Gardenia jasminoides and 10 parts of bamboo leaves are added to replace 1 part of Coptis chinensis in the prescription.

[0105] Typical case examples

[0106] 1. Cai, male, 62 years old, chronic atrophic gastritis with intestinal metaplasia history of more than 3 years, complained of occasional pain in the upper abdomen, a little belching, no bloating, no pantothenic acid, sleep OK, two bowel movements OK, pale red tongue, thin white and slightly greasy fur, moist pulse. Gastroscopy suggests chronic atrophic gastritis, and pathological prompts: moderate inflammation, moderate atrophy and intestinal metaplasia. The prescription of the embodiment of the present invention 1 is boiled and then taken as a decoction, one dose per day, divided into two doses in the morning and evening, and after taking the medicine for 3 months continuously, the upper abdominal pain is alleviated, and the belching symptoms disappear, and the medicine is continued for 3 months, and the gastroscopy prompts for review: chronic atrophic gastritis, and pathological prompts: mild inflammation, mild atrophy.

[0107] 2. Zhang, male, 44 years old, had symptoms of dull pain and discomfort in the epigastric region when hungry 5 years ago. Gastroscopy showed chronic atrophic gastritis, and pathological indications: moderate inflammation, moderate to severe atrophy and intestinal metaplasia. Symptoms include poor spirit, easy fatigue, dull pain and discomfort in the epigastric region when fasting, no bloating, acid reflux, nausea and vomiting, and cannot eat more. Sleep is normal, diarrhea occurs, urine is adjusted, tongue is white, white and greasy, and pulse is thin and smooth. The Chinese medicine in Example 2 of the present invention is boiled and taken as a decoction, one dose per day, taken twice in the morning and evening, and taken for 6 months. The patient complained that the spirit was good, the symptoms of dull pain and discomfort in the epigastric region were relieved, sleep was good, and the two stools were adjusted. Rechecking the gastroscopy showed: chronic atrophic gastritis, and pathological indications: mild inflammation, mild atrophy, and mild intestinal metaplasia.

[0108] 3. Chen, female, 64 years old, upper abdominal distension, discomfort, dull pain, easy diarrhea, less food, early satiety, poor sleep, frequent urination. Pale tongue, with tooth marks, white and slippery fur, fine and smooth pulse. Gastroscopy in 2017: chronic atrophic gastritis (gastric body, gastric antrum), pathological prompts: severe inflammation, severe atrophy, moderate intestinal metaplasia. The prescription of Example 3 of the present invention is boiled and taken as a decoction, one dose per day, twice a day, morning and evening, and taken for 6 consecutive months. The patient reported that the symptoms such as upper abdominal distension, dull pain, etc. were relieved, the appetite was good, the sleep was good, the two bowel movements were adjusted, the tongue was pale, with tooth marks, thin white fur, and slow pulse. Re-examination of gastroscopy prompts: chronic atrophic gastritis (gastric body, gastric antrum), pathological prompts: mild inflammation, mild atrophy, mild intestinal metaplasia.

[0109] 4. Li, 55 years old, female, upper abdominal pain for 2 years, dizziness, nausea, belching, no acid reflux, normal appetite, poor sleep, rotten stool, urination. Pale and dark tongue, thick and greasy white fur, stringy and slippery pulse. Gastroscopy: chronic atrophic gastritis, pathological prompts: moderate inflammation, moderate atrophy, moderate intestinal metaplasia, mild dysplasia. The prescription of the embodiment of the present invention 4 is boiled and taken as a decoction, one dose per day, taken twice in the morning and evening, and the gastroscopy prompts after taking the medicine for 6 months: chronic atrophic gastritis, pathological prompts: mild inflammation, mild atrophy, mild intestinal metaplasia. The patient's upper abdominal pain, dizziness, nausea, belching, rotten stool and other symptoms are alleviated to varying degrees.

[0110] 5. Wang, 24 years old, male, postprandial blockage for more than 1 year, belching and acid reflux, occasional burning sensation, normal appetite, good sleep, unformed stool, regular urine, pale red tongue, slightly yellow and greasy fur, and stringy and slippery pulse. Our hospital gastroscopy: chronic atrophic antral gastritis with erosion, reflux esophagitis. Pathology: severe inflammation, mild atrophy, moderate intestinal metaplasia. The prescription of the embodiment of the present invention 5 is boiled and taken as a decoction, one dose per day, divided into two doses in the morning and evening. After taking the medicine for 3 months, the patient complained that the postprandial blockage was significantly reduced, and the belching and acid reflux symptoms were improved. Thereafter, the medication was intermittently taken for 3 months within half a year, and the gastroscopy was reviewed to prompt: chronic atrophic antral gastritis, and the pathological prompt was: mild inflammation, mild atrophy. The postprandial blockage was not obvious, there was no belching and acid reflux, no burning sensation, appetite and sleep were good, and the two bowel movements were good, the tongue was pale red, the fur was slightly white, and the pulse was slightly stringy.

[0111] 6. Li, male, 67 years old, epigastric dull pain, belching, no acid reflux and heartburn, good appetite, good sleep at night, loose stools, 2-3 times a day, frequent urination. Pale red tongue, thin yellow greasy fur, stringy and fine pulse. Gastroscopy in 2017: chronic atrophic gastritis with erosion; multiple gastric polyps (removed). Pathology: (gastric angle) moderate inflammation, mild atrophy, moderate intestinal metaplasia. The prescription of Example 6 of the present invention is boiled in water to obtain a decoction for taking, one dose per day, twice a day, morning and evening, and re-examined after taking the medicine for 6 months: epigastric dull pain and discomfort are significantly improved, no belching, no acid reflux and heartburn, good appetite, good sleep at night, 1-2 times a day, good quality, and regular urination. Pale red tongue, thin and slightly greasy fur, stringy and fine pulse. Re-examination of gastroscopy suggests: chronic atrophic antral gastritis, pathological prompts: mild inflammation, mild atrophy.

[0112] 7. Luo, female, 56 years old, upper abdominal pain and discomfort with belching, dull pain when hungry, slightly relieved after eating, depressed, good sighing, good appetite, normal sleep, 2-3 bowel movements per day, good urination, pale tongue, tooth marks, white and greasy fur, and a stringy and slippery pulse. Gastroscopy in our hospital: chronic atrophic gastritis, gastric polyp forceps removal. Pathology: moderate inflammation, moderate atrophy, moderate to severe intestinal metaplasia. The prescription of Example 7 of the present invention is boiled in water to obtain a decoction for taking, one dose per day, twice a day, morning and evening. After taking the medicine for 6 months, the patient's above symptoms have improved. Reexamination of the gastroscopy prompts: chronic atrophic gastritis, pathological prompts: mild inflammation, mild atrophy, mild intestinal metaplasia.

[0113] 8. Wang, male, 62 years old, repeated upper abdominal pain, belching, no acid reflux, good appetite, poor sleep, rotten stool, slightly more urine, dark tongue, white and slippery tongue coating, stringy pulse. Gastroscopy prompts: chronic atrophic gastritis (gastric antrum), pathology: severe inflammation, moderate atrophy, moderate intestinal metaplasia, mild dysplasia. The prescription of Example 8 of the present invention is boiled and taken as a decoction, one dose per day, twice a day, morning and evening. After taking the medicine for half a year, the patient's self-reported stomach pain symptoms were significantly improved, and other symptoms disappeared. Re-examination of gastroscopy prompts: chronic atrophic gastritis, pathology prompts: mild inflammation, mild atrophy, mild intestinal metaplasia.

[0114] 9. Wang, male, 43 years old, had symptoms of epigastric pain and discomfort 2 years ago, and gastroscopy showed chronic atrophic gastritis, and pathological indications: moderate inflammation, moderate atrophy, and mild intestinal metaplasia. The first visit complained of epigastric pain, no bloating, no belching, no pantothenic acid, general sleep, two bowel movements, pale red tongue, thin yellow fur, slightly greasy, and stringy pulse. The prescription of the embodiment of the present invention 1 was boiled and taken with a decoction, one dose per day, taken twice a day in the morning and evening, and after taking the medicine for 2 months, the number of epigastric pain attacks was reduced; continued to take the medicine for 1 month, and the symptoms of the follow-up visit were the same as before, then the dandelion and white flower oldenlandia diffusa in the side were removed, and Scutellaria barbata was added as an alternative medicine, that is, the prescription of the embodiment of the present invention 9 was changed to continue treatment, and the symptoms of epigastric pain were relieved after taking the medicine for 1 month, and then continued to take the medicine for 2 months, and the gastroscopy was reviewed to prompt: chronic atrophic gastritis, and pathological indications: mild inflammation, mild atrophy.

[0115] 10. Zhou, female, 37 years old, chronic atrophic gastritis with intestinal metaplasia for more than 4 years, complained of occasional pain in the upper abdomen, a little bloating, no belching, no heartburn, good sleep, normal bowel movements, pale red tongue, thin yellowish greasy coating, and soft pulse. Gastroscopy showed chronic atrophic gastritis, and pathology showed: moderate inflammation, severe atrophy, and moderate intestinal metaplasia. The prescription of Example 1 of the present invention was boiled in water to obtain a decoction for taking, one dose per day, twice a day, morning and evening. After taking the medicine for 2 weeks, the patient reported that the upper abdominal pain was relieved and the bloating was relieved. After continuing to take the medicine for 1 month, the symptoms did not improve significantly, so the dandelion and oldenlandia diffusa in the prescription were removed, and Lobelia was added as an alternative medicine, that is, the prescription of Example 10 of the present invention was changed to continue treatment. After taking the medicine for 2 weeks, the patient reported that the number of abdominal pain attacks decreased. After continuing to take the medicine for 1 month, the patient reported that the condition was stable in the near future, and the symptoms were not significantly improved compared with the last visit. Then the patient was changed to take the prescription of Example 1 of the present invention for continued treatment. After taking the medicine for 3 months, the patient reported that the abdominal pain and bloating symptoms were significantly improved. The follow-up gastroscopy showed: chronic atrophic gastritis, and the pathological results showed: mild inflammation, moderate atrophy, and mild intestinal metaplasia.

[0116] 11. Chen, male, 55 years old, epigastric distension, dull pain, no belching, occasional pantothenic acid, irritability, mouth sores, difficulty falling asleep, loose stools, yellow urine. Red tip of tongue, yellow greasy fur, stringy pulse. Gastroscopy prompts: chronic atrophic gastritis, pathological prompts: moderate inflammation, moderate atrophy, mild intestinal metaplasia. The prescription of the embodiment of the present invention 11 is boiled to obtain a decoction for taking, one dose per day, twice a day, morning and evening, and continuous medication for 3 months. The patient reported that the symptoms of epigastric distension, dull pain, and pantothenic acid improved, and then intermittent medication for 3 months. The re-examination complained that the discomfort symptoms basically disappeared, the appetite was good, the sleep was improved, the two bowel movements were good, the tongue was light red, the fur was thin and yellow and slightly greasy, and the pulse was stringy. Re-examination of the gastroscopy prompts: chronic atrophic gastritis, pathological prompts: mild inflammation, mild atrophy.

[0117] Clinical trial study 1 Retrospective cohort study of intensive treatment of dampness in PLGC

[0118] 1.1 Research subjects

[0119] 1.1.1 Subject Source and Diagnostic Criteria

[0120] The research subjects were selected from patients with gastric precancerous lesions who visited the outpatient and emergency departments of Guangdong Provincial Hospital of Traditional Chinese Medicine (Dade Road General Hospital, Ersha Island Branch, University Town Branch, and Fangcun Branch) from January 1, 2017 to December 31, 2019. The diagnostic criteria were based on the "Trial Opinions on Endoscopic Classification and Treatment of Chronic Gastritis" formulated by the Digestive Endoscopy Branch of the Chinese Medical Association in 2003. Pathological diagnosis was used as the diagnostic gold standard, and clinical manifestations and gastroscopy were combined for judgment.

[0121] 1.1.2 Estimation of sample size

[0122]

[0123] Taking α=0.05, β=0.1, k=4, and using a two-sided test, Zα=1.96, Zβ=1.28, according to the literature review, the sample effectiveness is P1: 86.67%, P2: 56.25%. Substituting into the formula, it is found that 34 samples are needed for the exposed group and 136 samples are needed for the non-exposed group.

[0124] 1.2 Research Methods

[0125] 1.2.1 Inclusion criteria

[0126] (1) The cases were from the outpatient and emergency departments of Guangdong Provincial Hospital of Traditional Chinese Medicine from January 1, 2017 to December 31, 2019; (2) Patients with chronic atrophic gastritis, intestinal metaplasia, or dysplasia confirmed by pathology. Western medicine diagnosis was "chronic atrophic gastritis", "intestinal metaplasia of gastric mucosa", "dysplasia of gastric mucosa" and other gastric precancerous lesions; (3) The cases had at least two pathological examination results recorded or followed up before and after treatment.

[0127] 1.2.2 Exclusion criteria

[0128] (1) Patients who need to be hospitalized after being diagnosed by a doctor; (2) Patients who do not have or cannot follow up the results of two pathological examinations before and after treatment; (3) Patients with gastric or esophageal malignant tumors or patients with suspected malignant changes in pathological diagnosis; (4) Patients with serious primary diseases of the heart, brain, liver, kidney, and hematopoietic system, as well as mental illness.

[0129] 1.2.3 Definition of exposure factors and groups

[0130] Definition of exposure factors: Whether or not the patient received intensive anti-rheumatic intervention for 1 month or more was considered an exposure factor. In the present study, the Chinese medicine composition in Example 1 is used as a prescription for strengthening the treatment of dampness. Due to individual differences, the prescription drugs may be slightly increased or decreased, that is, when the patient is accompanied by obvious symptoms of spleen deficiency, the Chinese medicine composition in Example 2 is used as a prescription; when the patient is accompanied by obvious symptoms of dampness and turbidity, the Chinese medicine composition in Example 3 is used as a prescription; when the patient is accompanied by obvious symptoms of phlegm and dampness, the Chinese medicine composition in Example 4 is used as a prescription; when the patient is accompanied by symptoms of excessive gastric acid, the Chinese medicine composition in Example 5 is used as a prescription; when the patient is accompanied by symptoms of polyps, the Chinese medicine composition in Example 6 is used as a prescription; when the patient is accompanied by symptoms of qi stagnation, the Chinese medicine composition in Example 7 is used as a prescription; when the patient is accompanied by pain symptoms, the Chinese medicine composition in Example 8 is used as a prescription; when the patient is treated with the Chinese medicine composition in Example 1 for a period of time and the symptoms are not significantly relieved, the Chinese medicine composition in Example 9 or Example 10 is used as a prescription to replace Example 1; when the patient is accompanied by symptoms of excessive heart fire, the Chinese medicine composition in Example 11 is used as a prescription. The definition of the exposed group: receiving intensive anti-wetting intervention for ≥ 1 month, with prescription medication added or subtracted based on individual differences. The definition of the non-exposed group: receiving intensive anti-wetting intervention for less than 1 month or all other treatments except intensive anti-wetting intervention.

[0131] 1.2.4 Research content The electronic medical record information of the cases that meet the above description was collected using the information collection form and Excel 2007. The information collection form was developed and modified according to the clinical situation, and then determined in combination with expert opinions. The collected information includes:

[0132] 1.2.4.1 Basic information: demographic and sociological information (name, gender, age, contact number, medical card number, registration number, etc.).

[0133] 1.2.4.2 Clinical symptoms: Clinical symptoms and signs related to stomach pain, bloating, epigastric fullness, upper abdominal tenderness, etc.; abnormal emotions and manifestations such as anxiety and depression.

[0134] 1.2.4.3 Examination: Gastroscopy and pathological examination results before and after treatment.

[0135] 1.2.4.4 Western medicine: Western medicine diagnosis of gastric mucosal lesions, comorbidities, HP infection, etc.

[0136] 1.2.4.5 Traditional Chinese Medicine: TCM diagnosis, use of TCM treatments, specific prescriptions and prescription changes.

[0137] 1.2.4.6 Outcome indicators: pathological changes before and after treatment.

[0138] 1.2.4.7 Safety evaluation: adverse events occurring during treatment, corresponding treatment methods and outcomes.

[0139] 1.2.5 Criteria for determining efficacy

[0140] Gastric precancerous lesions are a pathological concept, and the development process is: chronic atrophic gastritis → intestinal metaplasia → dysplasia. Pathological changes are used as the gold standard for judging the efficacy. The observation content of the pathological report includes three variables: atrophy, intestinal metaplasia, and dysplasia. Each variable is divided into four levels: none, mild, moderate, and severe. The development process of PLGC is used as the criterion for judging the efficacy, that is, the reduction or disappearance of intrinsic gland atrophy, intestinal metaplasia, or dysplasia is effective, deterioration is ineffective, and no improvement or deterioration is no change.

[0141] 1.2.6 Implementation Methods

[0142] The design and implementation of the study refer to the relevant technical specifications of the Center for Evidence-Based Medicine. The overall technical route is shown in Figure 1 .

[0143] 1.2.7 Statistical analysis methods

[0144] SPSS26.0 was used for statistical analysis, and the count data were expressed as frequency and percentage (%); chi-square test or Fisher's exact test was used to compare the count data, and Fisher's exact test was used when more than 20% of the expected counts were <5; rank-sum test was used to compare the rank data, and a two-sided test was uniformly used, with P < 0.05 indicating statistical significance, and P < 0.01 indicating statistically significant differences.

[0145] 1.3 Efficacy statistics of patients in the exposed and non-exposed groups

[0146] 1.3.1 Basic Information

[0147] A total of 274 patients with pathologically diagnosed gastric precancerous lesions who visited the outpatient and emergency departments of Guangdong Provincial Hospital of Traditional Chinese Medicine from 2017 to 2019 were included in this study. According to different exposure factors, they were divided into an exposed group of 46 cases and a non-exposed group of 228 cases. According to statistics, general clinical data showed that there was no statistical difference between the two groups of patients in terms of gender, age, degree of inflammation, degree of atrophy, degree of intestinal metaplasia, and degree of dysplasia (P>0.05), and they were comparable, as shown in Table 1.

[0148] 1.3.1.1 Gender and age distribution statistics

[0149] Statistics showed that there were 46 cases in the exposed group (24 males and 22 females, aged 29 to 72 years, including 2 cases ≤35 years old, 32 cases 36-60 years old, and 12 cases ≥61 years old), and 228 cases in the non-exposed group (113 males and 115 females, aged 24 to 80 years, including 6 cases ≤35 years old, 142 cases 36-60 years old, and 80 cases ≥61 years old).

[0150] 1.3.1.2 Statistics of disease severity

[0151] Table 1 Distribution of inflammation, atrophy, intestinal metaplasia and dysplasia in the two groups of patients

[0152]

[0153]

[0154] Note: According to the rank sum test, the results in Table 1 showed that there was no statistically significant difference in the distribution of inflammation, atrophy, intestinal metaplasia and dysplasia between the two groups of patients (P>0.05), indicating that the two groups of patients were comparable in terms of the degree of inflammation, atrophy, intestinal metaplasia and dysplasia.

[0155] 1.3.2 Overall and stratified efficacy statistics of the exposed and non-exposed groups

[0156] 1.3.2.1 Statistics of overall efficacy differences between the exposed group and the non-exposed group

[0157] Table 2 Distribution of efficacy of patients in the two groups

[0158]

[0159] Note: According to the rank sum test, the results in Table 2 showed that the effective rate of the exposed group was 82.6%, and the effective rate of the non-exposed group was 65.4%. The comparison of the therapeutic effect distribution of the two groups of patients was P=0.029, which was statistically significant (P<0.05, P>0.01). It can be seen that both the exposed group and the non-exposed group have certain therapeutic effects on PLGC, and the therapeutic effect of the exposed group is better than that of the non-exposed group.

[0160] 1.3.2.2 Statistical differences in efficacy between the exposed and non-exposed groups

[0161] Table 3 Distribution of therapeutic effects on atrophy, intestinal metaplasia and dysplasia in two groups of patients

[0162]

[0163]

[0164] Note: According to the rank sum test, the results in Table 5 show that there is no statistical significance in the comparison of the efficacy distribution of atrophy and dysplasia between the two groups of patients (P>0.05), indicating that the exposed group and the non-exposed group have similar efficacy in improving atrophy and dysplasia. However, the comparison of the efficacy distribution of intestinal metaplasia between the two groups of patients is statistically significant (P=0.001) (P<0.01). The effective rate of improving intestinal metaplasia in the exposed group is 69.5%, and the effective rate of improving intestinal metaplasia in the non-exposed group is 41.7%, indicating that the exposed group is significantly better than the non-exposed group in improving intestinal epithelial metaplasia.

[0165] 1.3.3 Safety evaluation

[0166] During the entire treatment process, 2 patients in the non-exposed group experienced adverse reactions, one of whom had worsening constipation, which was relieved after using lactulose and enema; another patient developed diarrhea symptoms, which improved after the prescription was adjusted, and the remaining patients showed no abnormalities; no adverse events were observed in the exposed group, and both treatment regimens had high safety.

[0167] From the above, it can be seen that strengthening dampness treatment can improve the condition of PLGC patients to a certain extent. In order to maximize its clinical efficacy, it is of great significance to further explore its superior treatment population. The 46 patients in the exposure group were divided into two groups according to the efficacy for exploratory analysis. 38 effective patients entered the effective group, and the remaining 8 ineffective or unchanged patients entered the non-effective group. Statistical analysis factors include: gender, age, HP infection, gastroesophageal reflux, gastric ulcer and other comorbidities, anxiety, and abnormal emotional manifestations of depression.

[0168] The results showed that among the 8 patients in the ineffective group, 7 were male and 1 was female; while among the 38 patients in the effective group, 17 were male and 21 were female. The gender distribution between the two groups was statistically significant (P < 0.05). It can be seen that gender differences have an impact on the efficacy of intensive treatment of dampness in PLGC. Compared with male patients, female patients have better efficacy. The age of the two groups of patients was explored and it was found that there were 1, 6, and 1 patients ≤35 years old, 36-60 years old, and ≥61 years old in the ineffective group, respectively; while there were 1, 26, and 11 patients in the effective group, respectively. The age distribution of the two groups of patients was not statistically significant (P > 0.05), indicating that the efficacy of intensive treatment of dampness in PLGC in patients of all ages is equivalent. The two groups of patients were explored for HP infection. There were 0 patients with HP infection and 8 patients without HP infection in the non-effective group, while there were 7 patients with HP infection and 31 patients without HP infection in the effective group. There was no statistical significance in the distribution of HP infection between the two groups (P>0.05), indicating that the presence or absence of HP infection had no effect on the outcome of PLGC using enhanced dampness treatment. The two groups of patients were explored for gastroesophageal reflux, gastric ulcer and other comorbidities. There were 2 patients with gastroesophageal reflux and gastric ulcer in the non-effective group, and 6 patients without gastroesophageal reflux and gastric ulcer, while there were 4 and 34 patients in the effective group, respectively. There was no statistical significance in the distribution of comorbidities (P>0.05), indicating that the presence or absence of reflux, gastric ulcer and other comorbidities did not affect the efficacy of PLGC using enhanced dampness treatment. An exploration of whether the two groups of patients had abnormal emotional expressions such as anxiety and depression revealed that there were 6 patients with abnormal emotional expressions in the non-effective group, 2 patients without abnormal emotional expressions, and 15 and 23 patients in the effective group, respectively. There was no statistically significant comparison of the distribution of abnormal emotional expressions between the two groups of patients (P>0.05), indicating that the efficacy of intensive dampness treatment intervention for PLGC is equivalent between patients with abnormal emotional expressions and those without abnormal emotional expressions.

[0169] Clinical trial study 2: Prospective cohort study of intensive dampness treatment intervention for PLGC

[0170] 2.1 Research subjects

[0171] 2.1.1 Subject Source and Diagnostic Criteria

[0172] The subjects were selected from patients with gastric precancerous lesions who were recruited from the outpatient clinic and gastroscopy room of Guangdong Provincial Hospital of Traditional Chinese Medicine from October 1, 2019 to September 1, 2021. The diagnostic criteria for gastric precancerous lesions refer to the pathological diagnostic criteria of the 2017 "Chinese Consensus on Chronic Gastritis" (Shanghai), "Consensus on the Diagnosis and Treatment of Chronic Atrophic Gastritis with Integrated Traditional Chinese and Western Medicine (2017)" and "Diagnosis and Treatment of Chronic Gastritis with Integrated Traditional Chinese and Western Medicine", and patients with chronic atrophic gastritis and / or intestinal metaplasia and / or dysplasia were included. Clinical manifestations and gastroscopy diagnosis were used as auxiliary diagnosis basis.

[0173] 2.1.2 Inclusion and Exclusion Criteria

[0174] 2.1.2.1 Inclusion criteria: (1) age range 18-75 years old; (2) meet the above diagnostic criteria; (3) informed and consent to receive treatment.

[0175] 2.1.2.2 Exclusion criteria: (1) Patients with gastric mucosal cancer; (2) Patients with other serious digestive system diseases, such as peptic ulcer, gastric bleeding, and organic lesions of the bile duct, pancreas, etc.; (3) Patients with other malignant tumors; (4) Patients with serious heart, lung, liver, kidney and other systemic diseases; (5) Pregnant or lactating women; (6) Patients with severe cognitive impairment; (7) Other conditions that the researchers believe are not suitable for participation in this study.

[0176] 2.1.2.3 Dropout and exclusion criteria: (1) subjects whose disease was misdiagnosed; (2) subjects who could not persist in the study or voluntarily withdrew, resulting in missing clinical data; (3) subjects who were lost to follow-up.

[0177] 2.1.2.4 Termination criteria: (1) Severe adverse reactions occur during medication; (2) Malignant tumors or other serious systemic diseases develop.

[0178] 2.2 Research Methods

[0179] 2.2.1 Queue Implementation

[0180] According to whether the patients chose intensive anti-rheumatic intervention as the exposure factor, they were divided into an exposed group and a non-exposed group. The exposed group was those who received intensive anti-rheumatic treatment (at least 3 months). The non-exposed group was those who received other treatments.

[0181] 2.2.2 Estimation of sample size

[0182] NCSS-PASS V11.0 software was used for statistical analysis, and the sample size estimation formula for prospective cohort studies was used:

[0183]

[0184] According to the bilateral α=0.05,β=0.10, the corresponding u α 、u β Available table: u α =1.6449,u β =1.2816.

[0185] According to the results of the previous retrospective cohort study, the effective rate of taking intensive anti-dampness intervention for 3 months is about 89%, and the effective rate of the non-exposed group is about 65%. Under the condition of 80% test power and test level α = 0.05, the sample size is calculated to be 45 cases per group. Considering the dropout rate of 10%, 49 cases are needed in each group, and the sample size of the prospective cohort study is initially determined to be about 98 cases.

[0186] 2.2.3 Registration indicators

[0187] According to the prospective cohort study registration model, the patients' demographic and sociological data, lifestyle and disease-related conditions, TCM syndrome elements, and gastric mucosal pathology evaluation were collected, and a 6-month observation and follow-up was conducted.

[0188] 2.2.3.1 Population sociological data: gender, age, occupation, marital history, educational level, etc.

[0189] 2.2.3.2 Lifestyle habits and disease-related conditions: emotional state, eating rhythm, eating habits, smoking and drinking history, family history, etc.

[0190] 2.2.3.3 Elements of TCM disease and syndrome: symptoms, syndrome elements, tongue, pulse and other information of the four examinations.

[0191] The syndrome factor standard refers to Zhu Wenfeng's "Syndrome Factor Differentiation" and "Syndrome Part of TCM Clinical Diagnosis and Treatment Terminology":

[0192] 2.2.3.4 Evaluation of gastric mucosal pathology: All patients underwent gastroscopy before and after treatment, and gastric mucosal tissue was obtained for pathological examination to observe the pathological conditions of the gastric mucosa, including inflammation, activity, glandular atrophy, intestinal metaplasia, and dysplasia grade.

[0193] 2.2.4 Efficacy evaluation

[0194] The guidelines do not recommend the use of composite indicators as a criterion for determining clinical efficacy. When evaluating clinical efficacy, the use of composite indicators is prone to problems such as data being unable to be traced back and being rough in actual implementation. Therefore, each clinical efficacy evaluation indicator is evaluated and explained separately.

[0195] 2.2.4.1 Pathological efficacy evaluation

[0196] Pathological diagnosis is the main criterion for judging whether patients with gastric precancerous lesions have progressed. The pathological conditions of gastric mucosal tissues before and after treatment were observed, including chronic inflammation, inflammatory activity, glandular atrophy, intestinal metaplasia, and dysplasia, which were divided into 4 levels (-, +, ++, +++) according to none, mild, moderate, and severe. According to the changes in the degree of pathology before and after treatment, the disease was divided into improvement, stability, and progression.

[0197] Improvement is defined as a reduction of at least one degree in chronic inflammation of the mucosa, inflammatory activity, glandular atrophy, intestinal metaplasia, and dysplasia; stability is defined as no change in the levels of chronic inflammation of the mucosa, inflammatory activity, glandular atrophy, intestinal metaplasia, and dysplasia; progression is defined as disease progression if the levels of chronic inflammation of the mucosa, inflammatory activity, glandular atrophy, intestinal metaplasia, and dysplasia progress or worsen by at least one degree.

[0198] 2.2.4.2 TCM symptom score

[0199] The quantified standard for grading symptoms of chronic atrophic gastritis in the Consensus on Diagnosis and Treatment of Chronic Gastritis with Integrated Traditional Chinese and Western Medicine in China and the Guiding Principles for Clinical Research of New Chinese Medicines was used to formulate the standard. Each single symptom was scored according to its severity (none, mild, moderate, severe). The main symptoms were assigned 0, 2, 4, and 6 points, respectively, and the secondary symptoms were assigned 0, 1, 2, and 3 points. The sum of the scores of each single item was the total symptom score, and the differences in the scores of each single symptom and the total symptom score were compared.

[0200] 2.2.5 Safety evaluation

[0201] Any adverse events that occurred during the observation process must be carefully questioned and traced. All adverse events must be determined in terms of their nature, severity, and relevance to the drug, and strictly recorded in the case report form. The next treatment measure will be determined based on the patient's condition, and whether to terminate the study will be determined.

[0202] 2.2.6 Analysis of differential characteristics of the population with advantages in intensive dampness treatment intervention

[0203] The exposed group was regrouped according to the therapeutic effect, and the two groups were compared in terms of gender, age, marital status, educational level, emotional state, eating rhythm and hobbies, smoking history, drinking history, Hp infection, family history, disease course and distribution of TCM disease syndrome elements.

[0204] 2.2.7 Statistical analysis methods

[0205] SPSS 26.0 software was used to perform statistical analysis on the relevant data. Count data were expressed as frequency and percentage (%), and compared using chi-square test or Fisher's exact test; measurement data that conformed to normal distribution were expressed as mean plus or minus standard deviation. Indicates that the data do not conform to the normal distribution using the median (M) and quartiles (P 25 , P 75 ) description; independent sample t test was used to compare the means between the two groups if they met the normal distribution and variance homogeneity; if they did not meet the normal distribution, rank sum test was used; rank sum test was used for rank data.

[0206] 2.2.8 Ethical Review

[0207] This trial was conducted in accordance with the Declaration of Helsinki and relevant Chinese clinical trial research standards and regulations. This study was approved by the Ethics Committee of the Second Affiliated Hospital of Guangzhou University of Chinese Medicine (BF2020-026-01). The ethics committee of the applicant unit passed the WHO-SIDCER certification and the World Federation of Chinese Medicine Societies "Traditional Chinese Medicine Clinical Research Ethics Review Platform" certification. The technical roadmap of this study is shown in Figure 2

[0208] 2.3 Research Results

[0209] 2.3.1 Comparison of efficacy between the exposed and non-exposed groups

[0210] According to the inclusion, exclusion and removal criteria, a total of 106 registered cases were collected, of which 4 were lost due to loss to follow-up and 8 were lost due to missing gastroscopy data. Finally, 94 patients were included in the analysis, including 46 in the exposed group and 48 in the non-exposed group.

[0211] 2.3.1.1 General Information

[0212] (1) Gender: There were 14 males (30.4%) and 32 females (69.6%) in the exposed group; there were 17 males (35.4%) and 31 females (64.6%) in the non-exposed group. The c2 test showed no significant difference in gender distribution between the two groups (P>0.05), indicating that the gender distribution of the two groups was balanced and comparable.

[0213] (2) Age: The maximum age of patients in the exposed group and the non-exposed group was 73 years old, and the minimum age was 25 years old. In the exposed group, 1 patient was under 30 years old (2.2%), 7 patients were between 30 and 39 years old (15.2%), 8 patients were between 40 and 49 years old (17.4%), 13 patients were between 50 and 59 years old (28.3%), and 17 patients were over 60 years old (37.0%). In the non-exposed group, 1 patient was under 30 years old (2.1%), 2 patients were between 30 and 39 years old (4.2%), 4 patients were between 40 and 49 years old (8.3%), 22 patients were between 50 and 59 years old (45.8%), and 19 patients were over 60 years old (39.6%). Fisher's exact test showed that there was no significant difference in age distribution between the two groups (P>0.05), and they were comparable.

[0214] (3) Educational level: In the exposed group, 13 patients (28.3%) had a bachelor's degree or above, 21 patients (45.7%) had a high school education, 9 patients (19.6%) had a junior high school education, and 3 patients (6.5%) had an elementary school education or below. In the non-exposed group, 17 patients (35.4%) had a bachelor's degree or above, 19 patients (39.6%) had a high school education, 5 patients (10.4%) had a junior high school education, and 7 patients (14.6%) had an elementary school education or below. The corrected c2 test showed no significant difference in the distribution of educational levels between the two groups (P>0.05), indicating that the two groups were comparable.

[0215] (4) Family history: Seven patients (15.2%) in the exposed group had a family history of gastric cancer; four patients (8.3%) in the non-exposed group had a family history of gastric cancer. The c2 test showed no significant difference between the two groups (P>0.05), indicating that the two groups were comparable.

[0216] (5) Others: ① Marriage: 87 people were married, 5 people were unmarried, and 2 people were divorced or widowed. ② Eating habits: In terms of eating rhythm, 80 people ate moderately, 1 person often overate, 6 people often ate less or did not eat, and 7 people had irregular eating times; in terms of eating habits, 84 people had no obvious preference, 5 people liked hot food, 4 people preferred roasted and pickled food, and 2 people liked to eat greasy food. ③ Living habits: 4 people had a history of smoking, and 6 people had a history of drinking.

[0217] 2.3.1.2 Medical condition information

[0218] (1) Disease course: In the exposed group, 23 cases (50.0%) had a disease course of ≤1 year, 20 cases (43.5%) had a disease course of 1-5 years, and 3 cases (6.5%) had a disease course of more than 5 years; in the non-exposed group, 27 cases (56.3%) had a disease course of ≤1 year, 20 cases (41.7%) had a disease course of 1-5 years, and 1 case (2.1%) had a disease course of more than 5 years. Fisher's exact test showed that there was no significant difference in the distribution of disease course between the two groups (P>0.05), and the distribution was balanced and comparable.

[0219] (2) Hp infection: There were 10 patients (21.7%) with positive Hp infection in the exposed group and 10 patients (20.8%) with positive Hp infection in the non-exposed group. The C2 test showed no significant difference in Hp infection between the two groups (P>0.05), indicating that the two groups were comparable.

[0220] (3) Distribution of pathological conditions:

[0221] ①Inflammation degree: In the exposure group, 14 cases (30.4%) had mild inflammation, 22 cases (47.8%) had moderate inflammation, and 10 cases (21.7%) had severe inflammation; in the non-exposed group, 10 cases (20.8%) had mild inflammation, 24 cases (50.0%) had moderate inflammation, and 14 cases (29.2%) had severe inflammation. There was no significant difference in the degree of inflammation between the two groups by c2 test (P>0.05).

[0222] ② Activity: In the exposed group, 11 cases (23.9%) had no activity, 27 cases (58.7%) had mild activity, 6 cases (13.0%) had moderate activity, and 2 cases (4.3%) had severe activity; in the non-exposed group, 10 cases (22.3%) had no activity, 26 cases (56.4%) had mild activity, 9 cases (16.0%) had moderate activity, and 3 cases (5.3%) had severe activity. Fisher's exact test showed no significant difference in inflammatory activity between the two groups (P>0.05).

[0223] ③ Degree of atrophy: In the exposed group, 38 patients had mild atrophy (82.6%), 8 patients had moderate atrophy (17.4%); in the non-exposed group, 40 patients had mild atrophy (83.3%), 7 patients had moderate atrophy (14.6%), and 1 patient had severe atrophy (2.1%). Fisher's exact test showed no significant difference in the degree of atrophy between the two groups (P>0.05).

[0224] ④ Intestinal metaplasia: In the exposed group, there were 4 cases (8.7%) without intestinal metaplasia, 18 cases (39.1%) with mild intestinal metaplasia, 21 cases (45.7%) with moderate intestinal metaplasia, and 3 cases (6.5%) with severe intestinal metaplasia; in the non-exposed group, there were 5 cases (10.4%) without intestinal metaplasia, 16 cases (33.3%) with mild intestinal metaplasia, 25 cases (52.1%) with moderate intestinal metaplasia, and 2 cases (4.2%) with severe intestinal metaplasia. Fisher's exact test showed no significant difference in the degree of intestinal metaplasia between the two groups (P>0.05).

[0225] ⑤ Dysplasia: 7 patients (15.2%) in the exposed group had mild dysplasia; 4 patients (8.3%) in the non-exposed group had mild dysplasia, and 1 patient (2.1%) had moderate dysplasia. Fisher's exact test showed no significant difference in the degree of dysplasia between the two groups before treatment (P>0.05), which was comparable.

[0226] 2.3.1.3 Information on TCM disease syndrome elements

[0227] In terms of the distribution of TCM syndrome factors, there were 22 patients (47.8%) with qi deficiency in the exposed group and 28 patients (58.3%) with qi deficiency in the non-exposed group; 22 patients (47.8%) with qi stagnation in the exposed group and 20 patients (41.7%) with qi stagnation in the non-exposed group; 9 patients (19.6%) with blood stasis in the exposed group and 7 patients (14.6%) with blood stasis in the non-exposed group; 25 patients (54.3%) with dampness resistance in the exposed group and 25 patients (52.1%) with dampness resistance in the non-exposed group; 9 patients (19.6%) with yin deficiency in the exposed group and 13 patients (27.1%) with yin deficiency in the non-exposed group; 10 patients (22.2%) with heat toxicity in the exposed group and 14 patients (29.2%) with heat toxicity in the non-exposed group. There was no significant difference in TCM syndrome factors between the two groups by c2 test (P>0.05).

[0228] 2.3.1.4 Clinical efficacy

[0229] (1) Comparison of inflammation, activity, atrophy, intestinal metaplasia, and dysplasia between the two groups

[0230] In terms of inflammation, the difference between the exposed group before and after treatment was statistically significant (P < 0.05), and the degree of inflammation was alleviated after treatment compared with that before treatment. The difference between the non-exposed group before and after treatment was statistically significant (P < 0.05), and the degree of inflammation was alleviated after treatment. There was no statistically significant difference between the two groups after treatment (P > 0.05); in terms of inflammatory activity, the difference between the exposed group before and after treatment was statistically significant (P < 0.05), and the inflammatory activity was alleviated after treatment compared with that before treatment. There was no significant difference between the non-exposed group before and after treatment (P > 0.05), and the difference between the two groups after treatment was statistically significant (P < 0.05), and the inflammatory activity of the exposed group after treatment was lighter than that of the non-exposed group. In terms of atrophy, the difference between the exposed group before and after treatment was statistically significant ( There was no significant difference between the two groups before and after treatment (P>0.05). In terms of intestinal metaplasia, there was a significant difference between the exposed group before and after treatment (P<0.05). The degree of intestinal metaplasia was reduced after treatment compared with that before treatment. There was no significant difference between the non-exposed group before and after treatment (P>0.05). There was a significant difference between the two groups after treatment (P<0.05). The degree of atrophy in the exposed group was lighter than that in the non-exposed group after treatment. In terms of dysplasia, there was no significant difference between the two groups before and after treatment (P>0.05). There was no significant difference between the two groups after treatment (P>0.05). See Table 4 for details.

[0231] Table 4 Comparison of inflammation, activity, atrophy, intestinal metaplasia and dysplasia between the two groups

[0232]

[0233] Note: Comparison before and after treatment within the same group, *P<0.05, **P<0.01; comparison between the two groups, △P<0.05, △△P<0.01.

[0234] (2) Comparison of overall efficacy

[0235] After treatment, a total of 67 patients in the two groups improved, 4 had no significant changes, and 23 deteriorated. Among them, 39 patients (84.8%) in the exposure group improved, 2 patients (4.3%) were stable, and 5 patients (10.9%) progressed. In the non-exposed group, 28 patients (58.3%) improved, 2 patients (4.2%) were stable, and 18 patients (37.5%) progressed. According to the rank sum test, the overall efficacy of the two groups was significantly different (P < 0.05), and the overall efficacy of the exposure group was better than that of the non-exposed group, as shown in Table 5.

[0236] Table 5 Comparison of overall efficacy between the two groups of patients

[0237]

[0238] (3) Comparison of TCM symptom scores

[0239] The TCM symptom scores of the two groups before and after treatment are shown in Table 6. Before treatment, there was no significant difference in the symptom scores of epigastric pain, bloating, belching, poor appetite, acid reflux and heartburn and the total score between the two groups (P>0.05). After treatment, the epigastric pain, bloating, belching, poor appetite, acid reflux and heartburn and the total score of the exposed group were lower than those before treatment, and the difference was statistically significant (P<0.05); after treatment, there was no significant difference in epigastric pain, bloating, belching, poor appetite and the total score of the non-exposed group compared with those before treatment (P>0.05), and the difference in acid reflux and heartburn was statistically significant compared with those before treatment (P<0.05). After treatment, there was a significant difference in epigastric pain and the total score between the two groups (P<0.05), and the epigastric pain and the overall symptom score of the exposed group were significantly improved compared with the non-exposed group.

[0240] Table 6 Comparison of TCM symptom scores between the two groups before and after treatment

[0241]

[0242]

[0243] Note: Comparison of symptom scores before and after treatment within the same group, *P<0.05, **P<0.01; comparison of symptom scores between the two groups, △P<0.05, △△P<0.01.

[0244] (4) Safety evaluation

[0245] The adverse reactions of the two groups were statistically analyzed. During the observation period, one patient in the non-exposed group developed diarrhea, and the symptoms were relieved after oral administration of berberine hydrochloride. The other patients showed no obvious abnormalities. No adverse reactions occurred in the exposed group.

[0246] 2.4 Strengthen the exploration of populations with advantages in treating dampness

[0247] Intensive treatment of dampness has a good therapeutic effect on PLGC. However, there are certain individual differences. In order to explore the characteristics of its superior population, 46 patients in the intensive treatment of dampness cohort who had adopted the treatment regimen in Example 1 were divided according to the efficacy. 39 patients were effective and 7 patients were ineffective. They were included in the effective group and the ineffective group respectively, and the difference factors were compared.

[0248] The differences in age, gender, marital status, educational level, emotional state, dietary rhythm and hobbies, smoking history, drinking history, Hp infection, family history and course of disease between the effective group and the ineffective group of the intensive treatment of dampness cohort were compared. The results showed that there were no significant differences in age, gender, marital status, educational level, dietary rhythm and hobbies, smoking history, drinking history, family history and course of disease between the two groups (P>0.05), and there were significant differences in emotional state and Hp infection between the two groups (P<0.05), as shown in Table 7. The distribution of TCM disease syndrome elements between the two groups was compared, and there was no significant difference in the distribution of qi deficiency, qi stagnation, blood stasis, dampness obstruction, yin deficiency and heat toxicity (P>0.05), indicating that there was no significant difference in the efficacy of intensive treatment of dampness intervention among patients with different syndrome elements of PLGC.

[0249] Table 7 Emotional status and Hp infection status of the effective and ineffective groups in the intensive treatment of dampness cohort

[0250]

[0251] Note: *P<0.05.

[0252] 2.5 Multi-omics studies

[0253] On the basis of the above clinical research, a multi-omics study on the regulation of PLGC "inflammation-cancer" process by intensive dampness treatment was carried out to reveal its mechanism of action. 12 patients in the exposure group were selected, and 10 healthy people who underwent physical examination in our hospital were selected as the control group. The blood samples of the exposure group before treatment were marked as group A, the blood samples after intensive dampness treatment were marked as group B, and the blood samples of healthy people were marked as group C.

[0254] 2.5.1 Proteomic studies

[0255] The main process of plasma proteomics research is as follows: Figure 3The analysis results showed that there were 365 differentially expressed proteins in group A compared with group C, 84 of which were up-regulated and 281 were significantly down-regulated. The differentially expressed proteins with gene names and annotation information were further screened as potential biomarkers for PLGC by searching the database. The results showed that there were 49 significantly differentially expressed proteins, including 35 up-regulated proteins and 14 down-regulated proteins.

[0256] The potential biomarkers screened were annotated with GO functions. The potential biomarkers mainly participated in biological processes involving cellular processes, biological regulation, response to stimuli, metabolic processes, localization, immune system processes, positive regulation of biological processes, etc.; cell localization included extracellular regions, cell parts, organelles, cell membranes, etc.; the main molecular functions involved included binding, catalytic activity, molecular function regulation, antioxidant activity, structural molecular activities, etc.

[0257] KEGG pathway enrichment analysis was performed on the PLGC potential biomarker protein set to reveal the life activities that the potential markers were involved in. After Fisher's exact test, the top 20 enriched signaling pathways (P value < 0.1) were displayed, mainly involving phagosomes, viral myocarditis, pathogenic Escherichia coli infection, glycolysis / gluconeogenesis, thyroid hormone synthesis, dilated cardiomyopathy, hematopoietic cell lineage, Staphylococcus aureus infection, natural killer cell-mediated cytotoxicity, asthma and other signaling pathways.

[0258] KEGG pathways are divided into 7 branches: metabolism, genetic information processing, environmental information processing, cellular processes, organic systems, human diseases, and drug development. The relationship between many pathways is displayed through a bar chart.

[0259] The significantly different proteins between group B (after intensive anti-wetting treatment) and group A (before intensive anti-wetting treatment) were screened with FC>1.2 or <0.83 and P<0.05 as the standard. A total of 48 differentially expressed proteins were found between group A and group B, of which 15 proteins were upregulated and 33 proteins were downregulated in group B compared with group A. The volcano plot is shown in Figure 4 .

[0260] GO functional annotation was performed on the significantly different proteins in group B vs A, and the differential protein bioengineering before and after the enhanced dampness treatment and regulation of PLGC mainly involved cellular processes, metabolic processes, stimulus responses, biological regulation, immune system processes, etc.; cell localization in cells, cell parts, extracellular regions, etc.; molecular functions involved binding, catalytic activity, etc.

[0261] The KEGG pathway enrichment analysis was performed on the significantly different proteins in group B vs A to reveal the life activities they participated in. After Fisher's exact test, the top 20 enriched signal pathways (P value < 0.1) were displayed, mainly involving African trypanosomiasis, phagosomes, hematopoietic cell lineage, complement and coagulation cascade, asthma, allogeneic transplant rejection, primary immunodeficiency, intestinal immune network producing IgA, autoimmune thyroid disease and other pathways, see Figure 5 .

[0262] The obtained differential proteins were intersected with the differential proteins between group A and group C to explore the differential proteins that were significantly adjusted after the intensive treatment of dampness in PLGC. The results showed that 9 differential proteins showed significant adjustment after intensive treatment of dampness, close to the level of healthy people, namely: tumor necrosis factor receptor-associated protein 1, L-lactate dehydrogenase, phosphatidylinositol-specific phospholipase D1, manno-oligosaccharide 1,2-α-mannosidase IA, immunoglobulin J chain, immunoglobulin λ variable, Ig heavy chain variable region, immunoglobulin heavy constant, CD5 antigen-like, IGHV3-7 protein.

[0263] GO functional enrichment analysis was performed on the PLGC marker proteins that were significantly adjusted after intensive dampness treatment, such as Figure 6 As shown in the figure, the proteins related to PLGC in the intensive dampness treatment intervention mainly involve the response to stimulation, cellular process, metabolic process, biological regulation, immune system process, etc.; the cell localization is in cells, cell parts, extracellular regions, etc.; the molecular functions involve binding, catalytic activity, etc.

[0264] KEGG pathway analysis was performed on the PLGC marker protein set that was significantly corrected by intensive dampness treatment. The results showed that intensive dampness treatment may be involved in signaling pathways including glycosylphosphatidylinositol (GPI)-anchor biosynthesis, propionate metabolism, different types of N-glycan biosynthesis, pyruvate metabolism, cysteine ​​and methionine metabolism, N-glycan biosynthesis, central carbon metabolism of cancer, glycolysis / gluconeogenesis, glucagon signaling pathway, HIF-1 signaling pathway, etc.

[0265] 2.5.2 Non-targeted metabolomics studies

[0266] The main process of non-targeted metabolomics research is as follows: Figure 7 shown.

[0267] Results: The t-test was used to screen for differential metabolites with FC>1.2 or <0.83 and P<0.05. After preliminary screening, a total of 39 differential metabolites were obtained, which were displayed in a volcano plot. Figure 8-a. The differential metabolites with OPLS-DA VIP>1 were further selected as potential biomarkers. The screening results showed that there were 9 differential metabolites in positive ion mode and 19 differential metabolites in negative ion mode between group A and group C, of ​​which 14 were up-regulated and 14 were down-regulated in group A compared with group C. The metabolites with significant changes mainly belonged to lipid and lipid molecules, organic acids and their derivatives, organic heterocyclic compounds, benzene ring compounds, phenylpropane and polyketone, and organic oxygen compounds.

[0268] In order to more comprehensively reflect the relationship between samples and the differences in the expression patterns of metabolites in different samples, the expression levels of all samples and differential metabolites were subtracted from the average value of the group to which they belonged and then divided by the root mean square of the group number for standardization. Then, the distance matrix was calculated and hierarchical cluster analysis was performed on each group of samples. The results showed that the expression of samples in groups A and C was similar in positive and negative ion modes.

[0269] KEGG pathway enrichment analysis was performed on the 28 potential markers identified, and pathways with P>0.1 were taken as potential metabolic pathways. Finally, 7 pathway metabolisms were identified, including sphingolipid metabolism, biosynthesis of unsaturated fatty acids, tyrosine metabolism, PPAR signaling pathway, glycine, serine and threonine metabolism, arachidonic acid metabolism, and sphingolipid signaling pathway.

[0270] Using FC>1.2 or <0.83, P<0.05 as the standard, we screened the differential metabolites before and after the intensive treatment of PLGC, and obtained a total of 144 differential metabolites. Figure 8-b The differential metabolites with VIP>1 were further selected. The screening results showed that there were 30 differential metabolites between group A and group B in the positive ion mode, and 60 differential metabolites between group A and group B in the negative ion mode, among which 43 metabolites in group B were up-regulated compared with group A, and 47 metabolites were down-regulated.

[0271] In order to more comprehensively reflect the relationship between samples and the differences in the expression patterns of metabolites in different samples, the expression of all samples and differential metabolites was subtracted from the average value of the group to which they belonged and then divided by the root mean square of the group number for standardization. Then the distance matrix was calculated and hierarchical clustering analysis was performed on each group of samples to form a clustering tree that showed the similarity between samples. The results showed that the expression of samples in groups A and B was similar in positive and negative ion modes.

[0272] KEGG pathway enrichment analysis was performed on the 90 differential metabolites identified, and pathways with P>0.1 were used as potential metabolic pathways. Finally, 37 metabolic pathways were enriched, including central carbon metabolism of cancer, protein digestion and absorption aminoacyl tRNA biosynthesis, ABC transport, mineral absorption, glycine, serine and threonine metabolism, amino acid biosynthesis, pentose and glucuronic acid interconversion, valine, leucine and isoleucine biosynthesis and other metabolic pathways.

[0273] Among the 28 biomarkers of PLGC, intensive dampness treatment had a callback effect on 25 of them, making their metabolism tend to the level of healthy people. Among them, 9 were statistically significant (P < 0.05), including: arachidonic acid, N-lauroyl sarcosine, p-hydroxyphenylethanol, fructose, linoleic acid, L-serine, 4-hydroxycinnamic acid, thymine, and xylitol.

[0274] KEGG pathway enrichment analysis was performed on 25 regulated potential markers using the MetaboAnalyst 5.0 platform, and pathways with P>0.1 were taken as potential metabolic pathways. Finally, three metabolic pathways were obtained, including arachidonic acid metabolism, biosynthesis of unsaturated fatty acids, and tyrosine metabolism.

[0275] 2.5.3 Combined proteomics and metabolomics analysis

[0276] The quantitative information of all significantly differentially expressed proteins and metabolites was log2 standardized. Based on the Pearson correlation analysis method, the correlation coefficients between significantly differentially expressed proteins and significantly differentially expressed metabolites in groups A and C and A and B were calculated. The R package corrplot (R Version 3.5.1) was used to construct matrix heat maps and hierarchical clustering heat maps based on the Pearson correlation coefficient. Based on the KEGG database information, KEGG pathway annotations were performed for significantly differentially expressed proteins and differentially expressed metabolites, and the KEGG annotation information of the two omics was integrated.

[0277] As a result, a matrix heat map was drawn based on the content information of differentially expressed proteins and differentially expressed metabolites. The blue dotted line in the figure is used as the dividing line, and the correlation coefficient matrix heat map is divided into four quadrants. The upper left corner shows the correlation between significantly differential proteins, the lower right corner shows the correlation between significantly differential metabolites, and the upper right corner and the lower left corner both show the correlation between significantly differential proteins and significantly differential metabolites, which are mirror-symmetrical. As shown in Figure 9, there is a certain degree of correlation between metabolomics data and proteomics data.

[0278] The significantly different proteins and metabolites were subjected to correlation hierarchical clustering analysis to more intuitively reflect the differences in expression patterns of the significantly different proteins and metabolites, as shown in Figure 10. Proteins and metabolites clustered in the same cluster have similar expression patterns and may be in relatively close reaction steps in the biological process.

[0279] The KEGG pathways in which the potential biomarker proteins and metabolites of PLGC participate were compared, mainly involving the metabolic pathways of cysteine ​​and methionine, the regulatory pathways of inflammatory mediators on TRP channels, and the central carbon metabolism pathway in cancer. KEGG pathway analysis was performed on the differential metabolites and differential proteins before and after intensive dampness treatment, and there were 13 main pathways involved, including protein digestion and absorption, central carbon metabolism of cancer, tryptophan metabolism, cysteine ​​and methionine metabolism, glyoxylate and dicarboxylic acid metabolism, African trypanosomiasis, pyruvate metabolism and other signaling pathways. The central carbon metabolism pathway in cancer is an important pathway in which the two groups of differential proteins and metabolites participate, which is visualized as shown in the figure. Fig.11 .

[0280] 2.6 Study on the interaction and effector mechanism of mRNAs based on immune balance

[0281] For samples with biological replicates: Differential expression analysis of two conditions / groups was performed using the DESeq R package (1.8.3). P values ​​were adjusted using the Benjamini & Hochberg method. By default, a corrected P value of 0.05 was set as the threshold for significant differential expression. For samples without biological replicates: Differential expression analysis of two samples was performed using the DEGseq (2010) R package. P values ​​were adjusted using qvalue (Storey et al, 2003). qvalue < 0.01 and |log2(foldchange)| > 1 were set as the threshold for significant differential expression by default.

[0282] Gene ontology (GO) enrichment analysis was used for target gene candidates of differentially expressed miRNAs (hereinafter referred to as “target gene candidates”). Based on the Wallenius non-central hypergeometric distribution of GOseq (Young et al., 2010), which can adjust for gene length bias, GO enrichment analysis was performed.

[0283] KEGG (Kanehisa et al., 2008) is a database resource for understanding the high-level functions and utility of biological systems (such as cells, organisms, and ecosystems) from molecular-level information, especially large-scale molecular datasets generated by genome sequencing and other high-throughput experimental technologies (http: / / www.genome.jp / kegg / ). We used KOBAS (Mao et al., 2005) software to test the statistical enrichment of target gene candidates in KEGG pathways.

[0284] The results showed that there were 610 differentially expressed genes between PLGC patients and healthy volunteers. There were 1,040 differentially expressed genes in PLGC patients before and after intensive dampness treatment intervention, of which 448 were upregulated and 592 were downregulated. The differentially expressed genes were enriched in 306 pathways, of which 41 were significantly enriched (padj<0.05), mainly including Phagosome, Tuberculosis, Lysosome and other signaling pathways.

[0285] The present invention is further described above with the aid of specific embodiments. However, it should be understood that the specific description here should not be construed as limiting the essence and scope of the present invention. Various modifications made to the above embodiments by ordinary technicians in the field after reading this specification are all within the scope of protection of the present invention.

Claims

1. A Chinese medicine composition for treating gastric precancerous lesions, characterized in that: The invention comprises the following raw materials in parts by weight: 15-25 parts of lily, 5-15 parts of cassia twig, 10-20 parts of white peony root, 1-10 parts of jujube, 5-15 parts of atractylodes, 5-15 parts of magnolia bark, 5-15 parts of tangerine peel, 1-10 parts of licorice, 1-10 parts of coptis root, 10-20 parts of smilax glabra, 10-20 parts of dandelion and 10-20 parts of oldenlandia diffusa.

2. The Chinese medicine composition for treating gastric precancerous lesions according to claim 1, characterized in that: The invention comprises the following raw materials in parts by weight: 15-25 parts of lily, 5-15 parts of cassia twig, 10-20 parts of white peony root, 1-10 parts of jujube, 5-15 parts of atractylodes, 5-15 parts of magnolia bark, 5-15 parts of tangerine peel, 1-10 parts of licorice, 1-10 parts of coptis root, 10-20 parts of smilax glabra, 10-20 parts of dandelion, 10-20 parts of oldenlandia diffusa, and 10-30 parts of pseudoginseng.

3. The Chinese medicine composition for treating gastric precancerous lesions according to claim 1, characterized in that: The invention comprises the following raw materials in parts by weight: 15-25 parts of lily, 5-15 parts of cassia twig, 10-20 parts of white peony root, 1-10 parts of jujube, 5-15 parts of atractylodes, 5-15 parts of magnolia bark, 5-15 parts of tangerine peel, 1-10 parts of licorice, 1-10 parts of coptis root, 10-20 parts of smilax glabra, 10-20 parts of dandelion, 10-20 parts of oldenlandia diffusa and 15-30 parts of coix seed.

4. The Chinese medicine composition for treating gastric precancerous lesions according to claim 1, characterized in that: The invention comprises the following raw materials in parts by weight: 15-25 parts of lily, 5-15 parts of cassia twig, 10-20 parts of white peony root, 1-10 parts of jujube, 5-15 parts of atractylodes, 5-15 parts of magnolia bark, 5-15 parts of tangerine peel, 1-10 parts of licorice, 1-10 parts of coptis root, 10-20 parts of smilax glabra, 10-20 parts of dandelion, 10-20 parts of oldenlandia diffusa and 5-10 parts of fritillaria.

5. The Chinese medicine composition for treating gastric precancerous lesions according to claim 1, characterized in that: The invention comprises the following raw materials in parts by weight: 15-25 parts of lily, 5-15 parts of cassia twig, 10-20 parts of white peony root, 1-10 parts of jujube, 5-15 parts of atractylodes, 5-15 parts of magnolia bark, 5-15 parts of tangerine peel, 1-10 parts of licorice, 1-10 parts of coptis root, 10-20 parts of smilax glabra, 10-20 parts of dandelion, 10-20 parts of oldenlandia diffusa, 15-30 parts of oyster, and 15-30 parts of corrugated paper.

6. The Chinese medicine composition for treating gastric precancerous lesions according to claim 1, characterized in that: The invention comprises the following raw materials in parts by weight: 15-25 parts of lily, 5-15 parts of cassia twig, 10-20 parts of white peony root, 1-10 parts of jujube, 5-15 parts of atractylodes, 5-15 parts of magnolia bark, 5-15 parts of tangerine peel, 1-10 parts of licorice, 1-10 parts of coptis root, 10-20 parts of smilax glabra, 10-20 parts of dandelion, 10-20 parts of oldenlandia diffusa, 10-20 parts of ebony, 15-30 parts of oyster and 5-15 parts of clematis.

7. The Chinese medicine composition for treating gastric precancerous lesions according to claim 1, characterized in that: The invention comprises the following raw materials in parts by weight: 15-25 parts of lily, 5-15 parts of cassia twig, 10-20 parts of white peony root, 1-10 parts of jujube, 5-15 parts of atractylodes, 5-15 parts of magnolia bark, 5-15 parts of tangerine peel, 1-10 parts of licorice, 1-10 parts of coptis root, 10-20 parts of smilax glabra, 10-20 parts of dandelion, 10-20 parts of oldenlandia diffusa and 10-20 parts of atractylodes.

8. The Chinese medicine composition for treating gastric precancerous lesions according to claim 1, characterized in that: The invention comprises the following raw materials in parts by weight: 15-25 parts of lily, 5-15 parts of cassia twig, 10-20 parts of white peony root, 1-10 parts of jujube, 5-15 parts of atractylodes, 5-15 parts of magnolia bark, 5-15 parts of tangerine peel, 1-10 parts of licorice, 1-10 parts of coptis root, 10-20 parts of smilax glabra, 10-20 parts of dandelion, 10-20 parts of oldenlandia diffusa, 15-30 parts of angelica dahurica, and 10-20 parts of bupleurum.

9. A Chinese medicine composition for treating gastric precancerous lesions, characterized in that: The invention comprises the following raw materials in parts by weight: 15-25 parts of lily, 5-15 parts of cassia twig, 10-20 parts of white peony root, 1-10 parts of jujube, 5-15 parts of atractylodes, 5-15 parts of magnolia bark, 5-15 parts of tangerine peel, 1-10 parts of licorice, 1-10 parts of coptis root, 10-20 parts of smilax glabra and 15-30 parts of barbata scutellaria.

10. A Chinese medicine composition for treating gastric precancerous lesions, characterized in that: The invention comprises the following raw materials in parts by weight: 15-25 parts of lily, 5-15 parts of cassia twig, 10-20 parts of white peony root, 1-10 parts of jujube, 5-15 parts of atractylodes, 5-15 parts of magnolia bark, 5-15 parts of tangerine peel, 1-10 parts of licorice, 1-10 parts of coptis root, 10-20 parts of smilax glabra and 15-30 parts of lobelia.

11. A Chinese medicine composition for treating gastric precancerous lesions, characterized in that: The invention comprises the following raw materials in parts by weight: 15-25 parts of lily, 5-15 parts of cassia twig, 10-20 parts of white peony root, 1-10 parts of jujube, 5-15 parts of atractylodes, 5-15 parts of magnolia bark, 5-15 parts of tangerine peel, 1-10 parts of licorice, 10-20 parts of smilax glabra, 10-20 parts of dandelion, 10-20 parts of oldenlandia diffusa, 10-15 parts of gardenia, and 10-15 parts of bamboo leaf.

12. Use of the Chinese medicinal composition for treating gastric precancerous lesions according to any one of claims 1 to 11 in preparing a drug for treating gastric precancerous lesions.

13. A drug for treating gastric precancerous lesions, characterized in that: The invention comprises the traditional Chinese medicine composition for treating gastric precancerous lesions according to any one of claims 1 to 11 and pharmaceutically acceptable excipients.

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