74 results about "Kawasaki disease" patented technology

The present invention relates to 5-thia-omega-substituted phenylprostaglandin E derivatives of the formula (I)(wherein, all the symbols are as defined in the specification), process for producing them and pharmaceutical compositions comprising them as active ingredient.The compounds of the formula (I) can bind to PGE2 receptors (especially, subtype EP4) strongly, so they are expected to be useful for prevention and / or treatment of immunological diseases (autoimmune diseases such as amyotrophic lateral sclerosis (ALS), multiple sclerosis, Sjoegren's syndrome, chronic rheumarthrosis and systemic lupus erythematosus etc., and rejection after organ transplantation etc.), asthma, abnormal bone formation, neuronal cell death, lung failure, liver damage, acute hepatitis, nephritis, renal insufficiency, hypertension, myocardiac ischemia, systemic inflammatory response syndrome, ambustion pain, sepsis, hemophagous syndrome, macrophage activation syndrome, Still's disease, Kawasaki disease, burn, systemic granulomatosis, ulcerative colitis, Crohn's disease, hypercytokinemia at dialysis, multiple organ failure, and shock etc. Further, it is thought that EP4 subtype receptor relates to sleeping disorder and blood platelet aggregation, so the compounds of the present invention are expected to be useful for the prevention and / or treatment of such diseases.

A method, kit and device for diagnosing Kawasaki Disease are provided. The invention provides detecting an expression level of at least two Kawasaki Disease diagnostic biomarkers in a biological sample from a patient with a capture agent and diagnosing the patient as having Kawasaki Disease when the expression levels of the at least two diagnostic biomarkers in the patient biological sample are higher than the normal expression levels of the same biomarkers in a biological sample from a control subject. The first Kawasaki Disease diagnostic biomarker disclosed in the present invention is a cardiomyocyte biomarker, and the second Kawasaki Disease diagnostic biomarker is an inflammatory biomarker. The invention further provides detecting an expression level of a third biomarker, interferon type-I biomarker, in the patient biological sample with a capture agent and diagnosing the patient as having Kawasaki Disease when the expression level of interferon type-I biomarker is lower than the expression level in a control subject.

The invention provides a Kawasaki disease classification and prediction method based on medical data modeling. The method comprises the following steps: S1, data sample selection: extracting a valid sample which can be modeled from a sample data set; S2, feature sieving: sieving 19 features conforming to field medical auxiliary diagnosis application from a feature set for constructing sample data for modeling; S3, Kawasaki disease classifying model construction and evaluation: fitting an Xtrain data set on a training set by using a random forest classifying method, recording optimal modeling parameters and weights of all selected features, and classifying and predicting a test set sample according to the classifying model. In the Kawasaki disease classification and prediction method, Kawasaki disease relevant data are analyzed and modelled systemically, and an evaluation method for model prediction is provided, so that the model can be used for performing effective auxiliary diagnosis on a Kawasaki disease of a patient based on Kawasaki disease data, effective prevention and intervention and treatment are performed at the early stage of attacking, and a basis is laid for a best treatment effect.

Methods for diagnosis of Kawasaki disease (KD) are disclosed. In particular, the invention relates to the use of biomarkers for aiding diagnosis, prognosis, and treatment of KD, and more specifically to biomarkers that can be used to distinguish KD from other inflammatory diseases, including infectious illness and acute febrile illness.

A molecule for use in a method of treatment or diagnosis of Kawasaki Disease in an individual, the molecule comprising: (a) CACNA2D3; (b) CAMK2D; (c) KCNIP4; (d) ANGPT1; (e) NAALADL2; (f) ZFHX3; (g) MPHOSPH10; (h) a sequence having at least 90% sequence identity to any of (a) to (g); or (i) a modulator of any of (a) to (e). We also describe the use of Pregabalin ((3S)-3-(aminomethyl)-5-methyl-hexanoic acid) in the treatment or prevention of Kawasaki Disease in an individual.

The pharmaceutical composition comprising the compound of the invention having 8-azaprostaglandin skeleton represented by formula (I)(wherein, all the symbols have the same meanings as that of the specification) a salt thereof, a solvate thereof or a cyclodextrin clathrate thereof, or a prodrug thereof and them as active ingredient have EP4 agonistic action and thus are considered useful for the prevention and / or treatment of immunological diseases, asthma, neuronal cell death, arthritis, lung failure, pulmonary fibrosis, pulmonary emphysema, bronchitis, chronic obstructive pulmonary disease, liver damage, acute hepatitis, nephritis, renal insufficiency, hypertension, myocardial ischemia, systemic inflammatory response syndrome, sepsis, hemophagous syndrome, macrophage activation syndrome, Still's disease, Kawasaki disease, burn, systemic granulomatosis, ulcerative colitis, Crohn's disease, hypercytokinemia at dialysis, multiple organ failure, shock and glaucoma, etc. Furthermore, the compounds also have an action of accelerating bone formation, so it is expected to be useful for the prevention and / or treatment of diseases associated with loss in bone mass, for example, primary osteoporosis, secondary osteoporosis, bone metastasis of cancer, hypercalcemia, Paget's disease, bone loss, osteonecrosis, bone formation after bone operation, alternative treatment for bone grafting.

The invention provides a Kawasaki disease risk assessment model building method and system based on ensemble learning; the method comprises the following steps: extracting valid samples from a sampledata set for building a model and model assessment; selecting at least 10 feature items that comply with field medical auxiliary diagnosis applications from a feature set that forms the sample data; respectively using a random forest, Boosting, a linear model and a nerve network algorithm to build a Kawasaki disease prevalence risk prediction basic model and a classification valve domain t; usinga Naive Bayes algorithm for integration, and evaluating the Kawasaki disease risks according to a comparison result between two types of posterior probabilities. The method can effectively solve the problems that most classifiers are over-fitting, can adopt advantages and avoid weaknesses, thus providing the more accurate assessment model.

The invention discloses a boosting algorithm-based construction method and construction system of a Kawasaki disease risk assessment model. The construction method includes the following steps that: valid samples that can be used for modeling assessment are extracted from a sample data set; 10 features that meet on-site medical auxiliary diagnosis application are selected from the feature set of the valid sample; the incomplete data set of the valid samples is randomly divided into a training set and a verification set; a boosting method is adopted to fit the training set, so as to perform model construction, and a ten-fold cross-validation method is adopted to record optimal model parameters; and the verification set is adopted to calculate a model classification threshold t according toan ROC curve, and therefore, the Kawasaki disease risk assessment model is constructed. The invention also provides a corresponding Kawasaki disease risk assessment system for assessing data to be assessed so as to obtain a KDx score. With the system and method of the invention adopted, the rate of misdiagnosis and the rate of missed diagnosis of the Kawasaki disease can be decreased, and patientscan obtain effective prevention, intervention and treatment in the early stage of the disease.

The invention discloses a construction method and a construction system for a Kawasaki disease risk assessment model based on a neural network algorithm. The construction method comprises the steps: extracting valid samples which can be used for modeling and assessment from a sample data set; selecting ten features meeting field medical auxiliary diagnostic application from the feature set of thevalid samples; randomly dividing the incomplete data set of the valid samples into a training set and a validation set; fitting the training set by using the neural network method to construct the model and recording the optimal model parameters by using the ten-fold cross-validation method; and calculating the model classification threshold t by using the validation set according to the ROC curveso as to construct the Kawasaki disease risk assessment model. The corresponding Kawasaki disease risk assessment system is also constructed to be applied to assessment of the data to be assessed soas to obtain the KDx score. The misdiagnosis rate and the missed diagnosis rate of the Kawasaki disease can be reduced so that the patients can obtain effective prevention, intervention and treatmentin the early stage of the disease.

The present invention relates to the determination of levels or expression of particular biomarkers in biological samples which can be utilized to diagnose, prognose, and treat Kawasaki disease in subjects, and further to select subjects who would benefit from a Kawasaki disease therapy other than, or in addition to, IVIG treatment. Accordingly, the present invention encompasses methods and compositions that utilize these biomarkers for the diagnosis, prognosis, and treatment of Kawasaki disease.

The invention discloses a logistic algorithm-based construction method of a Kawasaki disease risk assessment model and a construction system. The construction method includes the following steps that:valid samples that can be used for modeling evaluation are extracted from a sample data set; 10 features that meet on-site medical assistance diagnosis are screened out from the feature set of the valid samples; the incomplete data set of the valid samples is randomly divided into a training set and a verification set; a logistic method is adopted to fit the training set, so that model construction can be performed, a cross-validation method is adopted to adjust a fitting function, optimal model parameters are recorded; and the verification set is adopted to calculate a model classification threshold t according to an ROC curve, and therefore, the Kawasaki disease risk assessment model can be constructed. According to the invention, a corresponding Kawasaki disease risk assessment systemfor evaluating data to be evaluated is constructed, so that a KDx score is obtained. With the method and system of the invention adopted, the reduction of the misdiagnosis and missed diagnosis of Kawasaki disease can be benefitted, and patients can obtain effective prevention, intervention and treatment in the early stage of the disease.

The invention discloses a construction method and construction system of a Kawasaki disease risk assessment model. The construction method includes the following steps that: valid samples that can beused for modeling evaluation are extracted from a sample data set; 10 features that meet on-site medical auxiliary diagnosis application are extracted from the feature set of the valid samples; the incomplete data set of the valid samples is randomly divided into a training set and a verification set; a random forest method is used to fit the training set so as to perform model construction, and optimal model parameters are recorded according to out-of-bag error; and a model classification threshold t is calculated with the verification set according to an ROC curve, so that the Kawasaki disease risk assessment model can be constructed. The assessment model constructed by using the construction method and construction system of the invention can quickly and effectively perform auxiliary assessment on patients with suspected Kawasaki disease, and can help reduce the misdiagnosis rate and missed diagnosis rate of the patients, and therefore, the patients can obtain effective prevention,intervention and treatment in the early stage of the disease, and basis can be provided for the achievement of optimal treatment effects.

The invention discloses a primer group, probe and kit for kawasaki disease detection. The primer group comprises a reverse transcription primer, an amplification primer and a probe sequence. A nucleic acid sequence combination can effectively qualitatively / quantitatively detect hsa-miR-197, hsa- miR-671, hsa-miR1246 and hsa-miR4436. Through the nucleic acid sequence and the kit and the like, reverse transcription can be performed on target miRNA effectively, positive samples and negative samples are distinguished better, detection results are judged more easily, and obtained results are more accurate.

The invention discloses a DNA probe pool for detecting kawasaki disease related gene and SNP locus, as well as preparation method and application thereof. The DNA probe pool comprises 558 oligonucleotide probe sequences which are shown by SEQ ID NO:3-SEQ ID NO:560. Each oligonucleotide probe sequence comprises a 21bp universal sequence at the 5' end, a 120bp sequence which can be specifically bonded with gene, and a 21bp universal sequence at the 3' end; the 21bp universal sequence at the 5' end and the 21bp universal sequence at the 3' end of the oligonucleotide probe sequence are shown by SEQ ID NO:1-SEQ ID NO:2 respectively. According to the detection method disclosed by the invention, the detection cost can be reduced, the detection precision can be improved, and an in-vitro qualitative detection means can be provided for the kawasaki disease pathogenesis, prognosis and medicinal cure effect, as well as an effective auxiliary diagnosis way can be provided for reducing coronary artery lesion and other heart diseases triggered in the late phase of kawasaki disease.

The invention relates to the technical field of biology and particularly provides application of a Kawasaki disease-associated substance to preparation of a kit for Kawasaki disease coronary artery disease risk assessment as a biomarker. The Kawasaki disease-associated substance is selected from one or more of a Kawasaki disease-associated gene or fragments thereof, mRNA transcribed from the Kawasaki disease-associated gene or the fragments thereof and proteins encoded by the Kawasaki disease-associated gene or the fragments thereof. The Kawasaki disease-associated gene comprises one or eightof a CD247 gene, a TNFRSF1A gene, an SMAD2 gene, an MMP9 gene, a BMP2 gene, an ACVR2B gene, a CXCL14 gene and a CD14 gene. The Kawasaki disease coronary artery disease risk diagnosis and detection kitprovided by the invention can assess the Kawasaki disease coronary artery disease risk in Kawasaki disease patients and suspicious children, so that medical personnel can take appropriate treatment or preventive measures as soon as possible.

The invention discloses a biomarker for diagnosing kawasaki diseases and a kit and application. The biomarker for diagnosing kawasaki diseases comprises 11 miRNAs such as miR-223-3p, miR-182-5p, miR-183-5p, miR-378-3p, miR-30c-5p, miR-148a-3p, miR-27a-3p, miR-145 miR-140-3p, miR-125a-5p and miR-30e-3p. The kit comprises primers for performing PCR (Polymerase Chain Reaction) detection on the 11 miRNAs. The content of the 11 miRNAs can be acquired by using the kit with corresponding PCR kits, and the risk of kawasaki diseases can be calculated through CT (Computed Tomography) values. The biomarker has the advantages of high sensitivity, good stability and the like, and the detection rate of kawasaki diseases in early diagnosis is increased.

The invention provides application of HBP protein as a diagnostic marker of Kawasaki disease, and discloses application of HBP protein as a diagnostic marker of Kawasaki disease in preparing diagnostic products of Kawasaki disease and a kit for diagnosing the Kawasaki disease. The experimental results show that the plasma HBP level in acute Kawasaki patients is significantly higher than that in healthy children and general patients infected with fever, the higher HBP concentration is significantly correlated with coronary artery injury in Kawasaki disease, and the HBP level is higher in insensitive patients treated with IVIG than in sensitive patients treated with IVIG. The invention finds that plasma HBP can be used to differentiate Kawasaki disease from infected fever patients, wherein the area under ROC curve (area under the curve, AUC) is 0.88, the optimal diagnostic threshold is 52.5pg / mL, the sensitivity is 88.3%, and the specificity is 74.0%. Therefore, plasma HBP protein of patients can be used as a potential marker for distinguishing diagnosis of Kawasaki disease from infected fever.

The invention provides a prediction method and prediction system for the coronary artery damage complication of the kawasaki disease. The method comprises the following steps that: collecting 21 items of original parameters for establishing an SVM (Support Vector Machine) model, wherein the original modeling parameters comprise genders, ages, fever time during doctor seeing, clinical classification, CRP (C Reactive Protein) detection values, WBC (White Blood Cell) values, PLT (Platelet) values, Hb (Hemoglobin) values, ALT (alanine aminotransferase) values, AST (aspartate aminotransferas) values, ALB (albumin) values, gamma-globulin service time and clinic diagnosis symptom indexes, and the clinic diagnosis symptom indexes comprise conjunctival injection, rash, cracked lips, raspberry tongues, lymphadenectasis of neck, hand and foot scleredema, digit peeling, crissum peeling and vaccinated scar inflammation; carrying out discretization processing on the original parameter to obtain an SVM feature value corresponding to the original parameter; taking the SVM feature value as basic data to construct an SVM model, and predicting the coronary artery damage complication of the kawasaki disease through the SVM model. By use of the method, patients can be subjected to early-stage intervention treatment, the recovery of the coronary artery damage is accelerated, and the method has an important meaning and value for the diagnosis and treatment of the kawasaki disease.

The invention discloses a traditional Chinese medicine preparation for preventing and treating coronary artery injury of a kawasaki disease. The traditional Chinese medicine preparation is prepared from the following raw materials in parts by weight: 9 parts of root of kudzu vine, 6 parts of salviae miltiorrhizae and 6 parts of ligusticum wallichii. According to the pharmacological action of the primary chemical components of root of kudzu vine, salviae miltiorrhizae and ligusticum wallichii, the traditional Chinese medicine preparation is proved to have the functions of increasing coronary blood-flow volume, improving blood oxygen supply of myocardium, reducing the oxygen consumption of myocardium, improving microcirculation, reducing the surface activity of blood platelets, inhibiting platelet aggregation and preventing thrombogenesis. In traditional Chinese medicine, the root of kudzu vine is a medicine for relieving exterior disorder, and salviae miltiorrhizae and ligusticum wallichii are medicines for invigorating blood circulation and eliminating stasis. The root of kudzu vine, the salviae miltiorrhizae and the ligusticum wallichii are compatible. The preparation meets compatibility principles of various drugs. However, kawasaki disease is systematic vascular inflammation which primarily induces infantile coronary artery injury. The preparation facilitates the preventionand treatment of coronary artery disease of kawasaki disease. The traditional Chinese medicine preparation is reasonable in formula compatibility, remarkable in effect, low in cost, small in side effect, obvious in curative effect after clinical application and worth being popularized.

The present invention relates to methods and compositions for diagnosis of inflammatory disorders, and in non-limiting embodiments, of inflammatory disorders associated with elevated interleukin-1β (“IL-1β”), based on increased levels of follistatin-like protein 1 (“FSTL-1”). In particular non-limiting embodiments, the invention further provides for methods of identifying subjects with systemic onset juvenile idiopathic arthritis (“SOJIA”) who are at increased risk for developing macrophage activation syndrome (“MAS”) comprising detecting, in said subjects, hyper-increased levels of FSTL-1. In additional non-limiting embodiments, the invention provides for methods of identifying subjects with Kawasaki disease who are at increased risk of developing aortic aneurysms comprising detecting, in said subjects, hyper-increased levels of FSTL-1.

The invention provides a prediction method and system for a gamma globulin non-reactive Kawasaki disease. The method comprises the following steps of collecting 21 original parameters of an SVM model, wherein the original parameters for modeling include gender, age, fever time during doctor seeing, clinical classification, a CRP detection value, a WBC value, a PLT value, an Hb value, an ALT value, an AST value, an ALB value, gamma globulin usage time and clinical diagnosis symptom indexes, and the clinical diagnosis symptom indexes include conjunctival congestion, rash, cracked lips, strawberry-like tongue, neck lymphadenectasis, hand and foot scleredema, digit desquamation, perianal desquamation and vaccinated scar redness and swelling; performing discretization processing on the original parameters to obtain SVM eigenvalues corresponding to the original parameters; and building the SVM model by taking the SVM eigenvalues as basic data, and predicting gamma globulin non-reactive complications of the Kawasaki disease through the SVM model. According to the prediction method and system, patients can be subjected to early intervention treatment, thereby facilitating coronary artery injury recovery; and the prediction method and system has important significance and value for diagnosis and treatment of the Kawasaki disease.

The invention provides an early diagnosis reagent for the children Kawasaki disease and application thereof. The reagent is a thrombospondin detection reagent and can be used for early diagnosis of Kawasaki disease. The invention also provides application of the reagent in preparation of a kit for early diagnosis of Kawasaki disease. The kawasaki disease is diagnosed in an assisted mode by detecting the content of thrombospondin in blood plasma of a suspected child patient and thus the suspected child patient can be diagnosed and treated in the early stage, so that cardiovascular diseases andother pathological changes are prevented.

The present invention relates to the discovery that etanercept reduces the rate of resistance to intravenous gamma globulin (IVIG) in subjects with acute Kawasaki disease (KD). In certain embodiments, the co-administration of etanercept and IVIG more effectively treats acute KD in subjects older than 12 months than IVIG alone. In other embodiments, the co-administration of etanercept and IVIG ameliorates coronary artery dilation in high risk subjects.

The present invention provides nucleic acid markers for rapid diagnosis of KD and a kit for detection of the nucleic acid markers. The nucleic acid markers are 4 miRNAs, and the kit comprises primers for quantitative detection of the 4 miRNAs by fluorescent quantitative PCR. The diagnosis of KD can be performed only by quantificationally detecting the contents of the 4 miRNAs in serum exosomes and then analyzing the Ct values of the 4 miRNAs. The present invention possesses the advantages of easily-obtained sample, simple operation, high specificity, time saving, accurate and reliable detection result, etc., so children with KD can be timely and accurately diagnosed. Particularly, KD can be easily distinguished from common virus infection with similar symptoms only by one test. The present invention may play an important role in rapid diagnosis of KD of children and further provide a direction for developing rapid diagnostic kit of KD.

The invention provides a reagent for predicting treatment reactivity of children with Kawasaki disease and an application of the reagent, and mainly provides the reagent for detecting an intravenous human immunoglobulin (IVIG) non-responsive Kawasaki disease susceptibility gene and a kit containing the reagent. The reagent can evaluate the reactivity of the children with the Kawasaki disease to IVIG treatment by detecting 5 SNP loci of 3 genes (rs10056474 or rs746994 of an SMAD5 gene, rs76863441 of a PLA2G7 gene, and / or rs16944 or rs1143627 of an IL-1B gene) of a patient. The kit has the characteristics of simple operation and low costs; and the reagent and kit provided by the invention can provide a basis for screening IVIG non-responsive high-risk children as early as possible and guiding clinical doctors to take reasonable intervention and treatment measures, and is in line with the development trend of precision medicine.

The invention discloses a traditional Chinese medicine composition for treating kawasaki disease. The traditional Chinese medicine composition is prepared from the following components in parts by weight: 6 parts of gypsum, 3 parts of cornu bubali, 4 parts of herba lophatheri, 3 parts of fructus forsythia and 2 parts of radix salviae miltiorrhizae. According to the traditional Chinese medicine composition, the gypsum clears heat and reduces fire, resolves the flesh and relieves exterior syndromes, promotes eruption and dissolves purpura, realizes detoxification and expels epidemic diseases, and engenders liquid and allays thirst; the cornu bubali clears heat, cools blood, realizes detoxification, and treats warm disease hyperpyrexia, macule generation, hematemesisand spontaneous external bleeding, and ulcer pyogenic infections; the herba lophatheri is cool and antipyretic, cools nutrients and protects yin, and contributes to prognostic recovery of pediatric patients; the fructus forsythia clears heat, realizes detoxification, removes stasis, realizes detumescence, can lower the inflammatory factor level, nourishes yin and generates body fluid, and clears away heart-fire and benefits the spleen; and the radix salviae miltiorrhizae promotes blood circulation to remove blood stasis, improves microcirculation, inhibits blood coagulation, activates fibrinolysis and inhibits thrombosis. The traditional Chinese medicine composition disclosed by the invention accords with the compatibility principles of various medicines, and the preparation of the traditional Chinese medicine composition can be used for treating kawasaki disease; and a formula is reasonable in compatibility and remarkable in effect, the cost is low, side effects are small, and clinical efficacy is remarkable.

The invention discloses an antibody, a reagent and a kit for Kawasaki disease treatment effect evaluation and application of the antibody, the reagent and the kit. The antibody can be used as a markerfor Kawasaki disease treatment effect evaluation and can also be used for preparing a biomarker for high-risk judgment, a new thought is provided for clinical Kawasaki disease treatment effect evaluation, and the misdiagnosis rate of Kawasaki diseases can be reduced.