30 results about "Latent tuberculosis" patented technology

The invention belongs to the field of biological medicine, and relates to a tuberculosis molecular marker combination and application thereof. Specifically, the invention relates to a molecular marker combination, which comprises (A) nucleic acid for coding GLRX protein, and one or more of nucleic acid for coding FCGR1A protein, nucleic acid for coding IFITM1 protein and nucleic acid for coding UBE2L6 protein; or (B) a GLRX protein, and one or more selected from the group consisting of an FCGR1A protein, an IFITM1 protein, and a UBE2L6 protein. The molecular marker combination can effectively diagnose the active tuberculosis or effectively distinguish the active tuberculosis from latent tuberculosis infection and normal control, and has high sensitivity and specificity.

The present application relates to the technical field of diagnostic markers, in particular to a marker combination and its application in diagnosing active tuberculosis and distinguishing between latent tuberculosis infection and active tuberculosis. The lectin combination provided by the present application can be used as a marker for ATB diagnosis and distinguishing between LTBI and ATB, and has high specificity and sensitivity. The lectin combination provided by the present application in combination with detection of specific antibodies of mycobacterium tuberculosis antigens can further improve the diagnostic effect. The marker and its detection products provided by the present application have good application potential in ATB diagnosis and distinguishing between LTBI and ATB, and are expected to overcome the limitations of existing diagnostic techniques, improve the diagnostic accuracy and sensitivity of tuberculosis, and provide new ideas and technical means for early detection, precise treatment and effective prevention and control of tuberculosis.

The invention discloses a gene marker for diagnosing latent tuberculosis infection and application of the gene marker, and belongs to the technical field of biological medicine. According to the present invention, the latent tuberculosis infection early diagnosis marker is screened based on the peripheral blood whole genome DNA methylation map, the new target is provided for the diagnosis of latent tuberculosis infection, the diagnosis efficiency of the marker is evaluated through pyrosequencing, the corresponding detection kit and the use method are developed, and the rapid and accurate diagnosis of latent tuberculosis infection is achieved.

The invention discloses a plasma exosome marker of tuberculosis (TB) and application of the plasma exosome marker, and belongs to the field of biomedical diagnosis, the plasma exosome marker comprises hsa-miR-451a, hsa-miR-1908-5p and hsa-miR-1268b, the expression of hsa-miR-451a in the plasma exosome of an active TB patient is up-regulated, and the expression of the hsa-miR-451a and the expression of the hsa-miR-451a and the expression of the hsa-miR-1908-5p are down-regulated. The expression levels of the markers are detected by using a droplet digital PCR technology, and a multinomial logistic regression diagnosis model is constructed based on a detection result. Experiments prove that when the three miRNA combinations are used for distinguishing active tuberculosis from healthy control (HC), the area (AUC) under a working characteristic curve of a subject reaches 0.970; when latent tuberculosis infection (LTBI) is distinguished from a healthy control, AUC is 0.971; and when the secondary miRNA combination of the hsa-miR-451a and the hsa-miR-1268b is used for distinguishing the asymptomatic tuberculosis (aTB) from the healthy control, the AUC is 0.880. The TB early diagnosis accuracy is remarkably improved, the non-invasive advantage is achieved, wide application prospects are achieved in the aspects of preparation of diagnostic reagents and kits, clinical diagnosis, disease monitoring and the like, and global tuberculosis prevention and control work is powerfully promoted.

The invention discloses a deep learning auxiliary prevention and treatment management platform for latent tuberculosis infection, and relates to the technical field of latent tuberculosis infection auxiliary prevention. Comprising a data acquisition and dynamic monitoring module, a data preprocessing and organization module, a conflict feature extraction and analysis module, a deep learning conflict evaluation module and a dynamic weight adjustment and optimization module, and it is ensured that each input can be dynamically monitored in the data fusion process, so that basic data is provided for subsequent conflict detection, feature extraction and intelligent evaluation. According to the method, multi-modal data fusion parameters are monitored in real time, conflict features are extracted, data source conflicts are intelligently evaluated by means of a deep learning model, the weight is dynamically adjusted, and the data fusion process is optimized. According to the scheme, the risk assessment accuracy of latent tuberculosis infection is improved, misdiagnosis and missed diagnosis are avoided, and precise medical treatment and personalized treatment implementation are promoted.

The invention relates to the technical field of diagnostic markers, in particular to a marker combination for diagnosing active tuberculosis and distinguishing latent tuberculosis infection and active tuberculosis and application of the marker combination. The lectin combination which can be used for ATB diagnosis and can distinguish LTBI and ATB is obtained by detecting the IgG glycosylation condition in the onset process of tuberculosis, and the lectin combination can be used as a marker for ATB diagnosis and distinguishing LTBI and ATB, and has high specificity and sensitivity; a new thought and method are provided for distinguishing different stages of tuberculosis and early accurate diagnosis of ATB, and the lectin combination is combined with the tuberculosis antigen to detect the specific antibody, so that the diagnosis effect can be further improved. The marker combination and the detection product thereof provided by the invention have relatively good application potential in ATB diagnosis and LTBI and ATB distinguishing.

This invention discloses miRNA biomarkers for the auxiliary diagnosis of tuberculosis and their applications. This invention claims protection for the use of substances for detecting miRNAs in serum exosomes in the preparation of products; the purpose of said products is for the diagnosis or auxiliary diagnosis of tuberculosis patients or for the diagnosis or auxiliary diagnosis of active pulmonary tuberculosis patients. The miRNAs are any one or any combination of the following five miRNAs: miR-28-3p, miR-193b-5p, miR-370-3p, miR-1246, and miR-2110. This invention also claims protection for the use of substances for detecting serum exosome miRNAs in the preparation of products; the purpose of said products is for the diagnosis or auxiliary diagnosis of latent tuberculosis infection. The miRNAs are any one or any combination of the following three miRNAs: let-7e-5p, let-7d-5p, and miR-140-5p. This invention lays the foundation for further development of rapid early diagnosis techniques and methods for tuberculosis.

The invention belongs to the technical field of tuberculosis detection, and provides a microRNA combination for bimodal differentiation of tuberculosis infection, a kit and a detection system. Nine specific microRNAs and one specific internal reference microRNA are taken as markers, the microRNAs in plasma are rapidly released by adopting a direct splitting method, the relative expression quantity of the markers is synchronously detected in combination with a tailing method reverse transcription technology, a four-group primer grouping amplification technology and a fluorescent PCR technology, a comprehensive risk value is calculated through a built-in algorithm, and latent tuberculosis infection, active infection and a negative state are synchronously distinguished. According to the invention, sputum samples are not needed, the detection is rapid and efficient, the detection sensitivity and specificity of active tuberculosis infection reach 92%, the detection sensitivity and specificity of latent tuberculosis infection reach 93%, the detection specificity reaches 90%, the operation is convenient, and the application range is wide.

The application discloses a gene marker for diagnosing latent tuberculosis infection and application thereof, and belongs to the technical field of biological medicine. The application screens a latent tuberculosis infection early diagnosis marker based on peripheral blood whole genome DNA methylation map, provides a new target for diagnosing latent tuberculosis infection, evaluates the diagnosis efficiency of the marker through pyrosequencing, develops a corresponding detection kit and a use method, and realizes rapid and accurate diagnosis of latent tuberculosis infection.

The disclosure concerns a method of obtaining information about the disease status of an individual by processing input data using a trained machine learning algorithm model to generate an output representing the information. The disclosure also concerns a related computer program, data processing apparatus, and system, as well as a method for training a machine learning algorithm model to generate information about the disease status of an individual. The information may, for example, relate to the presence, absence or type of M. tuberculosis complex infection in the individual.

The invention discloses a three-gene combination, a primer probe set and a system for qPCR (quantitative polymerase chain reaction) rapid screening of tuberculosis progression risk and application of the three-gene combination, the primer probe set and the system. The method comprises the following steps: firstly, screening out candidate genes APOL1, C1QC and SOCS1 which are stable across time windows and have high prediction performance; then a three-gene combination scoring you model (PRI3) composed of APOL1, C1QC and SOCS1 is constructed and used for predicting the risk that a latent tuberculosis infected individual progresses into active tuberculosis within a set time window; the method comprises the following steps of: firstly, selecting a reference model (RISK6, Sweeney3, Gliddon4 and BATF2), then performing performance verification in an independent verification queue, and comparing with the existing reference model (RISK6, Sweeney3, Gliddon4 and BATF2), and the result shows that the scoring model disclosed by the invention can keep stable performance in adult population and multiple time windows (such as 0-6 months, 0-12 months and 0-24 months). The scheme of the invention is suitable for crowd screening, disease early warning and individualized intervention decision.

There are provided methods of method of determining the latent tuberculosis (TB) infection status in an individual comprising: (i) providing a sample comprising T-cells; (ii) exposing the sample of (i) to one or more TB antigens; (iii) identifying T-cells in the sample that are CD4 positive and secrete IFN-γ in response to TB antigens; (iv) identifying those cells of (iii) which are also HLA-DR positive; and optionally (v) calculating the cells identified in (iv) as a percentage of those identified in (iii); wherein the identification of cells in (iv) and / or the percentage of cells calculated in (v) correlates to latent TB infection status of the individual, and wherein steps (iii) and (iv) can be carried out either sequentially or simultaneously. There are also provided compositions and kits for use in such methods.

The invention relates to a tuberculosis antigen specific host biomarker for detecting tuberculosis infection and a kit, and belongs to the field of biological medicines. The biomarker comprises IFN gamma, CXCL10, IL-2, IL-3, GBP6, ULBP2, CXCL11, ATP13A3, RHOV, ATP2B1, IL-22 and MMP1 (Metallocin Protein Protein 1). According to the present invention, the specific RD1 region antigen or peptide pool from mycobacterium tuberculosis and the specific RD2 region antigen or peptide pool from mycobacterium tuberculosis are jointly used as the antigen irritants to stimulate peripheral whole blood or peripheral blood mononuclear cells (PBMCs) of an individual to be detected, and then the expression quantity change of the host biomarker before and after the stimulation is detected; the kit can effectively distinguish tuberculosis infected patients from non-tuberculosis infected individuals, can identify and diagnose active tuberculosis and latent tuberculosis infected patients, solves the defects of insufficient sensitivity and limited specificity of the existing diagnostic technology, and has high diagnostic efficiency.

The invention discloses a biomarker for early risk early warning of latent tuberculosis infection, an early risk early warning model and application thereof. Specifically, the invention discloses a biomarker (an SCO2 gene, an MT1G gene, a CREB5 gene, a PARP9 gene, an ATF3 gene, an MUC1 gene and / or an MGST1 gene) and / or an application of a substance for detecting the biomarker in preparation of a product for early risk warning of latent tuberculosis infection or an application in construction of an early risk warning model of latent tuberculosis infection. The biomarker and the model constructed by using the biomarker are accurate and reliable through ROC curve verification, and are suitable for wide popularization. By performing early risk early warning on latent tuberculosis infection on the to-be-detected subject, decision support can be provided for clinicians, personalized or further prevention or treatment suggestions can be provided for patients, or early dry treatment and the like can be performed on high-risk patients, so that optimal disease management is realized.

The invention relates to a mycobacterium tuberculosis antigen combination, mRNA (messenger Ribonucleic Acid) for coding the same and a vaccine. The antigen combination comprises antigens in a group I and a group II or antigen fragments thereof: I: Rv3619, Rv3620 and Rv1468; and, II: at least one of Rv1886, Rv2029, Rv1813, Rv2234, Rv3310, Rv0125, and Rv1196, as well as a method for preparing the same. The mycobacterium tuberculosis mRNA vaccine is prepared by using the mycobacterium tuberculosis mRNA vaccine to help a mycobacterium tuberculosis infected person to remove and reduce pathogens in pulmonary infection focuses and macrophages, so that latent tuberculosis is inhibited from being converted into active tuberculosis, and / or an uninfected person is protected from mycobacterium tuberculosis infection or severe infection.

The application discloses an activity / inactivity tuberculosis recognition system based on an improved 3D network, which comprises an image feature acquisition module, a data preprocessing module, an image segmentation module and an image classification recognition module. The image feature acquisition module is used for acquiring lung tuberculosis CT chest image features. The data preprocessing module is used for performing data preprocessing on the acquired lung tuberculosis CT chest image features. The image segmentation module is used for segmenting the preprocessed lung tuberculosis CT chest image features to acquire lung parenchyma image features, and a segmentation model adopted is a 3D ResUNet segmentation model. The image classification recognition module is used for performing prediction classification on the lung parenchyma image features after image segmentation. An image classification model adopted is a 3D ResUNet50 classification model, and the 3D ResUNet50 classification model is combined with a multi-scale attention module to obtain image output features. Then, grouping convolution and channel shuffling are used to process the image output features, the categories of active and inactive tuberculosis are predicted, and the confidence score of the model is generated. The application can improve the CT image classification accuracy of the model.

The present disclosure provides a use of a fusion protein EH containing a tuberculous allergen or a pharmaceutical composition containing the fusion protein EH in the preparation of a reagent or kit for immunological diagnosis of tuberculosis, auxiliary diagnosis of tuberculosis or screening of latent tuberculosis infection of Mycobacterium tuberculosis, the fusion protein EH containing ESAT6 and HspX. The recombinant allergen EH provided by the present disclosure has good specificity and high sensitivity, can be suitable for large-scale screening, and is a new generation of LTBI screening and diagnosis product technology with application and development potential. The recombinant allergen EH provided by the present disclosure has lower toxicity compared with EC, and is safer.

The application discloses a library of superior peptide segments and a kit for differential diagnosis of active tuberculosis and latent tuberculosis infection. Whole peptide segments of tuberculosis virulence antigens ESAT-6 and CFP-10 are screened, the interfering peptide segments are removed, and new libraries of superior peptide segments containing the two virulence antigens are obtained. Whole peptide segments of tuberculosis latency-related antigens Rv1733c long peptide and Rv2028c long peptide are screened, the interfering peptide segments are removed, and new libraries of superior peptide segments containing the two latency-related antigens are obtained. The libraries can improve the accuracy of differential diagnosis of ATB and LTBI and reduce the cost. On this basis, the corresponding kit is developed.

The application discloses a fusion protein PP13138R and application thereof in tuberculosis prevention. Specifically disclosed is a fusion protein comprising HTL, CTL and B cell epitopes in series, PorB, PADRE and RS-09. The application screens 34 epitopes for Mycobacterium tuberculosis, which have good immunogenicity and antigenicity and no toxicity and no sensitization, and have the characteristics of high population coverage and the like. The auxiliary peptide PADRE is further added to improve the immunogenicity of the vaccine, and the PorB and RS-09 are added to endow the vaccine with a targeted delivery function. In-vitro experiments prove that the PP13138R can stimulate human peripheral blood mononuclear cells to produce an immune response, and is an advantage protective antigen. The PP13138R has the advantages of simple preparation method, low cost, high yield and higher safety as a vaccine. The application has great value for the prevention and treatment of active tuberculosis and latent tuberculosis infection.

The invention relates to a novel coding gene Rv3864c (-4341113-4341511) of mycobacterium tuberculosis H37Rv and a coding protein of the novel coding gene Rv3864c (-4341113-4341511). The Rv3864c gene has high specificity, secretory property and antigenicity, and can be independently or jointly used for clinical rapid screening of latent tuberculosis infected persons and active tuberculosis patients and protecting human bodies from being infected by mycobacterium tuberculosis.

The application can diagnose the infection of a tuberculosis patient by detecting the expression amount of the LLGL2 gene, and the detection method is simple, fast, and has high detection quality and accuracy, and the sensitivity and specificity are all greater than 80%. When the expression amount of the biomarker LLGL2 gene is greater than 1.476, the subject is judged as a latent tuberculosis infection patient; when the expression amount of the biomarker LLGL2 gene is less than or equal to 1.476, the subject is judged as not suspected to be a latent tuberculosis infection patient, and needs further diagnosis. When the expression amount of the biomarker LLGL2 gene is less than 0.8653, the subject is judged as an active tuberculosis patient; when the expression amount of the biomarker LLGL2 gene is greater than or equal to 0.8653, the subject is judged as not suspected to be an active tuberculosis patient, and needs further diagnosis.

The invention discloses a method for detecting latent infection of tubercle bacillus, and belongs to the field of tuberculosis detection. According to the method, detection of latent infection of tubercle bacillus is completed through the steps of sample collection, sample treatment, marker detection, data analysis, result judgment and the like. According to the invention, mycobacterium tuberculosis specific extracellular RNA (exoRNA) is selected as a novel biomarker. Compared with the traditional protein or DNA marker, the exoRNA has higher sensitivity and specificity, and can reflect the existence and activity state of the pathogen earlier and more accurately. The application of the marker effectively reduces the risk of cross reaction caused by bacillus calmette guerin vaccine inoculation or nontuberculous mycobacterium infection, thereby improving the reliability of the detection result. According to the invention, a high-throughput sequencing technology and an artificial intelligence algorithm are combined, and an intelligent diagnosis model is constructed. The method not only can realize qualitative judgment of LTBI, but also can finely distinguish infection states by analyzing the combination and expression profile of the exoRNA markers.

The invention relates to the technical field of diagnostic markers, in particular to a marker combination and application thereof in diagnosing active tuberculosis and distinguishing latent tuberculosis infection and active tuberculosis. The lectin combination provided by the invention can be used as a marker for ATB diagnosis and distinguishing of LTBI and ATB, and has relatively high specificity and sensitivity. The lectin combination provided by the invention is combined with the mycobacterium tuberculosis antigen to detect the specific antibody, so that the diagnosis effect can be further improved. The marker and the detection product thereof provided by the invention have relatively good application potential in ATB diagnosis and LTBI and ATB distinguishing, and are expected to overcome the limitation of the existing diagnosis technology, improve the diagnosis accuracy and sensitivity of tuberculosis, and provide a new thought and technical means for early discovery, precise treatment and effective prevention and control of tuberculosis.

The invention provides a mycobacterium tuberculosis fusion antigen which can be used as a subunit vaccine for preventing acute tuberculosis infection and treating latent tuberculosis infection. On the basis, the invention also constructs a nucleic acid vaccine to provide effective anti-tuberculosis protection capability. The mycobacterium tuberculosis fusion antigen and the nucleic acid vaccine thereof are expected to become a novel anti-tuberculosis vaccine.

The application discloses a fusion protein HP13138PB and application thereof in tuberculosis prevention. Specifically disclosed is a fusion protein comprising HTL, CTL and B cell epitopes in series, HBD-3, PSM alpha 4 and PADRE. The application screens 34 epitopes for mycobacterium tuberculosis, which have good immunogenicity and antigenicity and no toxicity and sensitization, and have the characteristics of high population coverage and the like. The immunogenicity of the vaccine is improved by further adding antibacterial peptide HBD-3 and auxiliary peptide PADRE, and PSM alpha 4 is added to endow the vaccine with targeted delivery function. In-vitro experiments prove that HP13138PB can stimulate human peripheral blood mononuclear cells to produce an immune response, and is an advantage protective antigen. The HP13138PB as a vaccine has the advantages of simple preparation method, low cost, high yield and higher safety and the like. The application has great value for the prevention and treatment of active tuberculosis and latent tuberculosis infection.

The invention belongs to the field of biological medicine, and relates to a tuberculosis molecular marker combination and application thereof. Specifically, the invention relates to a molecular marker combination, which comprises (A) nucleic acid for coding TAP1 protein, and one or more of nucleic acid for coding GBP5 protein, nucleic acid for coding UBE2L6 protein and nucleic acid for coding SERPING1 protein; or (B) a TAP1 protein, and one or more selected from the group consisting of a GBP5 protein, a UBE2L6 protein and an SERPING1 protein. The molecular marker combination can effectively diagnose the active tuberculosis, effectively distinguish the active tuberculosis from bacterial pneumonia, or distinguish the active tuberculosis from latent tuberculosis infection and normal control, and has high sensitivity and specificity.

This invention discloses the polypeptide fusion protein CP13138P and its application in tuberculosis prevention. Specifically, it discloses a fusion protein comprising tandem HTL, CTL, and B-cell epitopes, CTB, Pam2Cys, and PADRE. This invention screened 34 epitopes targeting Mycobacterium tuberculosis, which exhibit excellent immunogenicity and antigenicity, are non-toxic and non-sensitizing, and have high population coverage. In vitro experiments demonstrate that CP13138P can stimulate an immune response in human peripheral blood mononuclear cells (PBMCs), increasing IFN-γ in PBMCs. + The number of T lymphocytes is significantly increased, and they secrete significantly high levels of more than a dozen cytokines, including G-CSF, making them a dominant protective antigen. CP13138P, as a vaccine, has advantages such as simple preparation method, low cost, high yield, and enhanced safety. This invention has significant value for the prevention and treatment of active tuberculosis and latent tuberculosis infection.

This invention discloses the fusion protein PP19128R and its application in the prevention or treatment of Mycobacterium tuberculosis infection. Specifically, it discloses a fusion protein comprising tandem HTL, CTL, and B-cell epitopes, PorB, RS-09, and PADRE. This invention screened 39 epitopes targeting Mycobacterium tuberculosis, which exhibit excellent immunogenicity and antigenicity, are non-toxic and non-sensitizing, and have high population coverage. The helper peptide PADRE is further added to enhance the immunogenicity of the vaccine, and PorB and RS-09 are added to endow the vaccine with targeted delivery function. In vitro experiments demonstrate that PP19128R can stimulate an immune response in human peripheral blood mononuclear cells, making it a superior protective antigen. PP19128R as a vaccine has advantages such as simple preparation method, low cost, high yield, and enhanced safety. This invention has significant value for the prevention and treatment of active tuberculosis and latent tuberculosis infection.

The invention discloses a detection device for distinguishing active tuberculosis and latent tuberculosis infection, and belongs to the technical field of tuberculosis detection. Comprising a shell and a suction cylinder, a transmission mechanism is arranged in the shell, the transmission mechanism is connected with a suction mechanism used for sucking cerebrospinal fluid, first limiting mechanisms matched with each other are arranged at the top of the suction mechanism, and the suction mechanism is located in the suction cylinder; a second limiting mechanism used in cooperation with the first limiting mechanism is arranged on the side of the first limiting mechanism. According to the detection device, through the design of the transmission mechanism, efficient transmission of mechanical energy is achieved; a plurality of grooves in the fixed block are rotationally matched with the shifting wheel, so that multiple collection operations are supported; the suction mechanism is matched with the sampling port to collect cerebrospinal fluid into the suction tube, so that the cerebrospinal fluid is prevented from being in contact with epidermal tissues, and the risk of secondary infection after puncture operation is remarkably reduced; in the device design, the first limiting mechanism and the second limiting mechanism are matched with each other to limit the suction pipe and the push rod, and the suction pipe is prevented from rebounding.

The present invention relates to a composition and imaging technology for evaluating the immune response of T cells, and in particular, to the technological field of T cell activation analysis and infectious disease diagnosis using lens-free shadow imaging. According to the present invention, activation of T cells can be effectively induced through a T cell activation composition composed of a specific component combination (PHA, PMA, ionomycin, etc.), and T cell activation-specific image parameters (MMD_SD etc.) can be acquired from the activated T cells through lens-free shadow imaging technology. Moreover, since a T cell activity analysis device and method using these parameters exhibit significant performance in diagnosing the presence or absence of latent tuberculosis infection, the present invention has the effect of providing a biological composition that can be used for T cell functional analysis, creating a non-labeling immunodiagnostic platform, and presenting a novel analytical index for LTBI diagnosis.