BACKGROUND:Ankylosing spondylitis is closely related to the occurrence and development of psoriasis,but the key genes and regulatory mechanisms are still unclear.OBJECTIVE:To establish an artificial neural network model of genes shared by ankylosing spondylitis and psoriasis based on the GEO database and evaluate its effect,and also to determine whether there is a causal relationship between the expression of key genes and the two diseases using Mendelian randomization.METHODS:Datasets GSE25101(816 ankylosing spondylitis samples and 816 healthy control samples),GSE30999(85 psoriasis samples and 85 healthy control samples),GSE73754(52 ankylosing spondylitis samples and 20 healthy control samples),and GSE14905(33 psoriasis samples and 49 healthy control samples)were downloaded from the GEO database.GSE25101 and GSE30999 were used as the training datasets of ankylosing spondylitis and psoriasis,respectively,and their respective differentially expressed genes were identified through difference analysis to obtain the common driver genes of the two diseases,and the key core genes were further screened out based on Mendelian randomization.The key core genes were further screened out,and artificial neural network models were constructed based on the key core genes and validated in external datasets GSE73754 and GSE14905,followed by the construction of the corresponding nomogram to predict the incidence rates of the diseases.Also,the results of immune infiltration in ankylosing spondylitis and psoriasis were analyzed.Finally,Mendelian randomization was used to assess causal relationships between key genes and diseases,and drug-gene interactions were analyzed using the Dgidb database to predict drug targets.RESULTS AND CONCLUSION:(1)A total of 61 differential genes were obtained in ankylosing spondylitis and 4 309 differential genes were obtained in psoriasis.Eight shared differential genes were obtained after intersection,and five key genes(DNMT1,GNG11,CDC25B,S100A8,and S100A12)were further screened by machine learning.The key genes were utilized to build artificial neural network models of ankylosing spondylitis and psoriasis,with the area under curve values of 0.979 and 0.989 in the training sets GSE25101 and GSE30999,respectively,and 0.818 and 0.874 in the external validation datasets GSE73754 and GSE14905,respectively.(2)Nomogram was constructed based on the five core genes,and the calibration curves showed that the predicted probabilities of the nomogram models were almost the same as that of the ideal model.Immune cell infiltration showed that the key genes were associated with activated B cells,natural killer cells,γδ T cells,follicular helper T cells,monocytes,plasma cell-like dendritic cells,and neutrophils.Mendelian randomization showed that S100A8 was a risk factor for the occurrence of ankylosing spondylitis and psoriasis.Finally,DGldb screening was utilized to obtain 81 targeted drugs,only 16 of which,including methotrexate,atogepant,ubrogepant,rimegepant,eptinezumab,azacitidine,selenium,hydroxyurea,ifosfamide,floxuridine,curcumin,mitoxantrone,cisplatin,arsenic trioxide,diethylstilbestrol,and decitabine,were approved by the U.S.Food and Drug Administration.(3)A large number of successful cases have been accumulated in international databases,research results and data analysis of European groups,especially in genomics and disease phenotyping studies.These experiences provide valuable references for the epidemiological characterization of diseases in China,genetic diversity and their response to the environment and lifestyle.(4)An artificial neural network model of the common driver genes of ankylosing spondylitis and psoriasis was constructed and validated,the causal relationship between the key genes and the pathogenesis of the two diseases was discovered,and the targeted drugs for potential treatments were predicted,which hopefully provides a new perspective for exploring their pathogenesis and therapeutic directions.

BACKGROUND:Ankylosing spondylitis is closely related to the occurrence and development of psoriasis,but the key genes and regulatory mechanisms are still unclear.OBJECTIVE:To establish an artificial neural network model of genes shared by ankylosing spondylitis and psoriasis based on the GEO database and evaluate its effect,and also to determine whether there is a causal relationship between the expression of key genes and the two diseases using Mendelian randomization.METHODS:Datasets GSE25101(816 ankylosing spondylitis samples and 816 healthy control samples),GSE30999(85 psoriasis samples and 85 healthy control samples),GSE73754(52 ankylosing spondylitis samples and 20 healthy control samples),and GSE14905(33 psoriasis samples and 49 healthy control samples)were downloaded from the GEO database.GSE25101 and GSE30999 were used as the training datasets of ankylosing spondylitis and psoriasis,respectively,and their respective differentially expressed genes were identified through difference analysis to obtain the common driver genes of the two diseases,and the key core genes were further screened out based on Mendelian randomization.The key core genes were further screened out,and artificial neural network models were constructed based on the key core genes and validated in external datasets GSE73754 and GSE14905,followed by the construction of the corresponding nomogram to predict the incidence rates of the diseases.Also,the results of immune infiltration in ankylosing spondylitis and psoriasis were analyzed.Finally,Mendelian randomization was used to assess causal relationships between key genes and diseases,and drug-gene interactions were analyzed using the Dgidb database to predict drug targets.RESULTS AND CONCLUSION:(1)A total of 61 differential genes were obtained in ankylosing spondylitis and 4 309 differential genes were obtained in psoriasis.Eight shared differential genes were obtained after intersection,and five key genes(DNMT1,GNG11,CDC25B,S100A8,and S100A12)were further screened by machine learning.The key genes were utilized to build artificial neural network models of ankylosing spondylitis and psoriasis,with the area under curve values of 0.979 and 0.989 in the training sets GSE25101 and GSE30999,respectively,and 0.818 and 0.874 in the external validation datasets GSE73754 and GSE14905,respectively.(2)Nomogram was constructed based on the five core genes,and the calibration curves showed that the predicted probabilities of the nomogram models were almost the same as that of the ideal model.Immune cell infiltration showed that the key genes were associated with activated B cells,natural killer cells,γδ T cells,follicular helper T cells,monocytes,plasma cell-like dendritic cells,and neutrophils.Mendelian randomization showed that S100A8 was a risk factor for the occurrence of ankylosing spondylitis and psoriasis.Finally,DGldb screening was utilized to obtain 81 targeted drugs,only 16 of which,including methotrexate,atogepant,ubrogepant,rimegepant,eptinezumab,azacitidine,selenium,hydroxyurea,ifosfamide,floxuridine,curcumin,mitoxantrone,cisplatin,arsenic trioxide,diethylstilbestrol,and decitabine,were approved by the U.S.Food and Drug Administration.(3)A large number of successful cases have been accumulated in international databases,research results and data analysis of European groups,especially in genomics and disease phenotyping studies.These experiences provide valuable references for the epidemiological characterization of diseases in China,genetic diversity and their response to the environment and lifestyle.(4)An artificial neural network model of the common driver genes of ankylosing spondylitis and psoriasis was constructed and validated,the causal relationship between the key genes and the pathogenesis of the two diseases was discovered,and the targeted drugs for potential treatments were predicted,which hopefully provides a new perspective for exploring their pathogenesis and therapeutic directions.

Objective:To investigate the correlation between triglyceride-glucose-body mass index (TyG-BMI index) and the outcome of young patients with acute ischemic stroke (AIS).Methods:Consecutive young patients with first-ever AIS (aged 18-45 years) admitted to Pingyi County People's Hospital and Qingdao Municipal Hospital from January 2020 to December 2023 were included retrospectively. The demographic data, vascular risk factors, baseline blood pressure, baseline laboratory tests, classification of stroke etiology, baseline National Institutes of Health Stroke Scale (NIHSS) scores, and main treatment methods were collected. At 3 months after the onset of stroke, the modified Rankin Scale was used for outcome evaluation. A score of 0-2 was defined as good outcome and >2 were defined as poor outcome. Multivariate logistic regression analysis was used to identify independent factors associated with poor outcome in young patients with AIS. Results:A total of 253 young patients with AIS were enrolled, including 196 males (77.5%), aged 38.65±5.34 years; baseline NIHSS score 3.03±2.88. At 90 days after onset, 206 patients (81.4%) had good outcome, while 47 (18.6%) had poor outcome. The poor outcome group had significantly higher systolic blood pressure, triglycerides, fasting blood glucose, triglyceride glucose (TyG) index, body mass index (BMI), TyG-BMI index, and baseline NIHSS score than those of the good outcome group (all P<0.05). Multivariate logistic regression analysis showed that after adjusting for gender, systolic blood pressure, baseline NIHSS score, and antiplatelet drug use, the TyG-BMI index was significantly independently associated with the poor outcome in young patients with AIS (odds ratio 1.039, 95% confidence interval 1.021-1.057; P<0.001). Conclusion:A higher baseline TyG-BMI index is independently associated with the poor outcome in young patients with AIS.

OBJECTIVE: To observe the clinical efficacy of acupuncture based on "status-target coherence" theory combined with Kegel exercises for vaginal laxity syndrome (VLS). METHODS: Sixty-six patients with VLS were randomized into an observation group (33 cases, 2 cases dropped out, 1 case was discontinued) and a control group (33 cases, 5 cases dropped out). The observation group was treated with acupuncture combined with Kegel exercises, acupuncture was applied to bilateral Ciliao (BL32), Zhongliao (BL33), Sanyinjiao (SP6), etc. The control group was treated with Kegel exercises. Both acupuncture and Kegel exercises were performed once every other day, three times a week for 12 weeks. Before and after treatment, the vaginal laxity questionnaire (VLQ) score, pelvic floor muscle strength (vaginal resting pressure, vaginal systolic pressure, vaginal contraction duration), degree of vaginal laxity and sexual satisfaction questionnaire (SSQ) grade were observed in both groups. RESULTS: After treatment, the VLQ score, vaginal resting pressure, vaginal systolic pressure, vaginal contraction duration in the observation group were elevated compared with those before treatment (P<0.05), and SSQ grade was improved (P<0.05); and the above indexes in the observation group were better than those in the control group (P<0.05). There were no significant difference before and after treatment in the degree of vaginal laxity in the two groups (P>0.05). CONCLUSION Acupuncture based on "status-target coherence" theory combined with Kegel exercises can effectively enhance the strength of pelvic floor muscles, improve the symptoms of vaginal laxity, and improve the satisfaction of sexual life, and its therapeutic effect is better than Kegel exercises alone.
Humans ; Female ; Adult ; Vagina/physiopathology* ; Acupuncture Therapy ; Exercise Therapy ; Young Adult ; Middle Aged ; Treatment Outcome ; Acupuncture Points ; Combined Modality Therapy ; Vaginal Diseases/therapy*

Purpose: This study examined the diagnostic value of high-frequency ultrasound (HFUS) features in differentiating between benign and malignant skin lesions. Methods: A total of 1,392 patients with 1,422 skin lesions who underwent HFUS examinations were included in an initial dataset (cohort 1) to identify features indicative of malignancy. Qualitative clinical and HFUS characteristics were recorded for all lesions. To determine which HFUS and clinical features were suggestive of malignancy, univariable and multivariable logistic regression analyses were employed. The diagnostic performance of HFUS features combined with clinical information was evaluated. This assessment was validated using internal data (cohort 2) and multicenter external data (cohort 3). Results: Features significantly associated with malignancy included age above 60 years; lesion location in the head, face, and neck or genital regions; changes in macroscopic appearance; crawling or irregular growth pattern; convex or irregular base; punctate hyperechogenicity; blood flow signals; and feeding arteries. The area under the receiver operating characteristic curve, sensitivity, and specificity of HFUS features combined with clinical information were 0.946, 92.5%, and 86.9% in cohort 1; 0.870, 93.1%, and 80.8% in cohort 2 (610 lesions); and 0.864, 86.2%, and 86.6% in cohort 3 (170 lesions), respectively. However, HFUS is not suitable for evaluating lesions less than 0.1 mm in thickness or lesions exhibiting surface hyperkeratosis. Conclusion In a clinical setting, the integration of HFUS with clinical information exhibited good diagnostic performance in differentiating malignant and benign skin lesions. However, its utility was limited in evaluating extremely thin lesions and those exhibiting hyperkeratosis.

The irrational use of Chinese patent medicines （CPM） is becoming more and more prominent， which makes the demand for clinical practice guidelines of CPM gradually increase. In order to make domestic scholars understand the latest developments and existing problems of the CPM guidelines， and promote its development， this paper introduced the concept of CPM guidelines， summarized the characteristics of the two development modes， namely “taking CPM as the key” and “taking disease/syndrome as the key”， and analyzed the current methodological status of developing and reporting CPM guidelines. Based on the existed problems， three suggestions have been put forward to optimize the quality of CPM guidelines， which were clarifying the target users and scope of CPM guidelines， establishing an open and transparent mechanism of the personnel involvement and process steps， and formulating implementable and operable recommendations for the use of CPM.

The identification of clinical questions for clinical practice guidelines of Chinese patent medicine （CPM） is important for subsequent evidence retrieval， evaluation of evidence quality， formation of recommendations. This paper described a methodological proposal for the identification of clinical questions for CPM guidelines to highlight the characteristics of Chinese patent medicine and reflect its effect in specific stage of the disease. Considering four aspects， namely， the drug of Chinese patent medicine （D）， the specific disease stage （S）， comparison （C）， and specific outcome （O）， DSCO framework has been proposed to formulate the clinical questions. Multi-source information through scientific research， policy or standard documents， and clinical data are suggested for collecting clinical questions， and clear selection criteria should be set to finalize the clinical questions to be addressed by the guideline. In addition， the above process needs to be transparently and publicly reported in order to ensure the clarity and completeness of the guidelines.

The retrieval and evaluation of evidence is the basis for the development of clinical practice guidelines for Chinese patent medicine. As traditional Chinese medicine has a different development trajectory and utilization characteristics from modern medicine， there is certain differences in terms of evidence composition， retrieval and integration.This paper discussed multi-source body of evidence on Chinese patent medicine based on modern evidence-based medicine and ancient medical literature， and summarized the retrieval strategy as well as the possible problems and solving methods. For different types of evidence on Chinese patent medicine， the corresponding evaluation tools have been recommended， and the order to integrate the evidence based on the quality of the evidence from high to low is suggested. Finally， a multi-source based evidence retrieval-evaluation-integration scheme for Chinese patent medicine has been formed， which will provide a methodological reference for practitioners in the development of clinical practice guidelines for Chinese patent medicine.

Recommendation formation is a key component of clinical practice guidelines for Chinese patent medicine （CPM）， and should encompass the determination of the strength and direction of the recommendation， the rationale for the recommendation， and the methodology for implementing the recommendation. Recommendations can be formed through formal consensus and informal consensus. The strength and direction of recommendations for CPM guidelines should be determined by considering the quality of evidence for CPMs， the priority of the clinical questions， the pros and cons of efficacy and adverse effects， patient acceptance， the feasibility of the recommendation and the availability of resources， social fairness， economic benefits， and other influencing factors. In order to better guide guideline developers to consider these factors more rationally， this article provideed a detailed explanation of each factor in the context of the characteristics of TCM.

ObjectiveThe differential expression of microRNAs （miRNAs） between the active stage and the remission stage of ulcerative colitis （UC） was analyzed by bioinformatics method， and the regulatory relationship was constructed by screening the differentially expressed genes （DEGs）. The mechanism of Xizhuo Jiedu recipe in the treatment of UC was speculated and verified by animal experiments. MethodThe miRNAs data set of colonic mucosa tissue of UC patients was obtained from the gene expression database （GEO）， and the most differentially expressed miRNAs were screened by GEO2R， Excel， and other tools as research objects. TargetScan， miRTarbase， miRDB， STRING， TRRUST， and Matescape databases were used to screen key DEGs， predict downstream transcription factors （TFs）， gene ontology （GO）， and conduct Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis. The key signaling pathways were selected for animal experiments. In animal experiments， the UC mouse model was prepared by making the mouse freely drink 2.5% dextran sodium sulfate （DSS）. Xiezhu Jiedu recipe and mesalazine were given by gavage for seven days， and the inflammatory infiltration of colonic mucosa was observed by hematoxylin-eosin （HE） staining. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of miR-155-5p in colon tissue. Immunohistochemistry and Western blot were used to detect the protein expression levels of cytokine signal transduction inhibitor （SOCS1）， phosphorylated transcriptional signal transductor and activator 3 （p-STAT3）， phosphorylated Janus kinase 2 （p-JAK2）， and retinoic acid-associated orphan receptor-γt （ROR-γt）. The expression levels of transforming growth factor-β （TGF-β）， interleukin-17 （IL-17）， interleukin-6 （IL-6）， and interleukin-10 （IL-10） in serum were detected by enzyme linked immunosorbent assay （ELISA）. ResultThe GSE48957 dataset was screened from the GEO database， and miR-155-5p was selected as the research object from the samples in the active and remission stages. 131 DEGs were screened. The GO/KEGG enrichment analysis was closely related to biological processes such as positive regulation of miRNA transcription and protein phosphorylation， as well as signaling pathways such as stem cell signaling pathway， IL-17 signaling pathway， and helper T cell 17 （Th17） cell differentiation. The Matescape database was used to screen out 10 key DEGs， among which SOCS1 was one of the key DEGs of miR-155-5p. Further screening of the TFS of key DEGs revealed that STAT3 was one of the main TFs of SOCS1. The results of animal experiments showed that Xiezhu Jiedu Recipe could effectively down-regulate the mRNA expression of miR-155-5p and protein expression of p-STAT3， p-JAK2， and ROR-γt in colon tissue of UC mice and the expression of IL-17 and IL-6 in serum of UC mice， up-regulate the protein expression of SOCS1 and the expression of TGF-β and IL-10， increase the level of anti-inflammatory factors， and reduce inflammatory cell infiltration. ConclusionIt is speculated that Xizhuo Jiedu recipe may interfere with SOCS1 by regulating the expression of miR-155-5p in UC mice， inhibit the phosphorylation of STAT3， inhibit the differentiation of CD4⁺ T cells into Th17 cells， reduce the levels of pro-inflammatory factors （IL-17 and IL-6）， and increase the levels of anti-inflammatory factors （TGF-β and IL-10）. As a result， the inflammation of colon mucosa in UC mice was alleviated.