Objective To investigate the potential core target and its mechanism of Simiao San(SMS)in the treatment of rheumatoid arthritis(RA)using network pharmacology and animal experiments.Methods Active components and corresponding SMS targets were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and cross-referenced with the Universal Protein(UniProt)database.RA-related targets were screened from The Human Gene Database(GeneCards),Online Mendelian Inheritance in Man(OMIM),Therapeutic Target Database(TTD),DrugBank,and Disease Gene Network(DisGeNet).Protein-protein interaction(PPI)networks were constructed for shared targets between SMS and RA using Search Tool for the Retrieval of Interacting Genes/Proteins(STRING),followed by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses via The Database for Annotation,Visualization and Integrated Discovery(DAVID).A"herb active component-disease target-signaling pathway"network was established to predict the mechanism of SMS in RA treatment.Molecular docking was performed between aryl hydrocarbon receptor(AHR)and the core active components of SMS to identify AHR-targeting constituents.For animal experiments,30 female SPF-grade C57/BL mice were randomly divided into normal,model,methotrexate(1.52 mg/kg,every 3 days),and SMS(12.48 g/kg,daily)groups with a 30-day intervention.Ankle diameter and arthritis index scores were measured.HE staining was used to assess joint inflammation,whereas immunohistochemistry(IHC)was used to measure cytochrome P450 1A1(CYP1A1),nuclear factor kappa B subunit p65(p65),and phosphorylated p65(p-p65)protein expression levels.Multiplex immunofluorescence(mIHC)was used to evaluate forkhead box protein P3(FOXP3)and interleukin-17A(IL-17A)protein expression.Results Forty-one active components and 228 targets of SMS were identified from TCMSP,whereas 1,207 RA-related targets were extracted from GeneCards,OMIM,TTD,DrugBank,and DisGeNet.Ninety-four overlapping targets were analyzed,yielding 612 GO terms and 143 KEGG pathways.Molecular docking of the ligand-binding domain of AHR with the top 10 Degree values of compounds of SMS(quercetin,stigmasterol,wogonin,beta-sitosterol,kaempferol,baicalein,et al.)revealed that stigmasterol,beta-sitosterol,(S)-canadine,and isocorypalmine was able to bind to AHR stably.In vivo,compared to the model group,the mice of the SMS and methotrexate groups joint swelling and arthritis index scores reduced(P<0.01).IHC indicated elevated CYP1A1 protein and decreased p65 and p-p65 protein levels in the SMS and methotrexate groups(P<0.05,P<0.01).mIHC demonstrated reduced IL-17A and increased FOXP3 protein expression in the SMS and methotrexate groups(P<0.05,P<0.01).Conclusion SMS alleviates joint inflammation in RA mice,potentially by targeting AHR,one of the core targets.SMS may suppress excessive inflammatory responses by activating AHR and inhibiting p65 phosphorylation.Additionally,SMS modulates the helper T cells 17/regulatory T cells balance by downregulating IL-17A and upregulating FOXP3.These results suggest that AHR is a key mediator in T-cell immune regulation.

Objective:To establish an evaluation index system for patient safety education targeted at undergraduate nursing interns.Methods:Based on the CIPP (Context, Input, Process, Product) evaluation model, a preliminary draft of the index system was developed using a literature review and semi-structured interviews. The Delphi method and the Analytic Hierarchy Process were applied to finalize the index system.Results:Two rounds of Delphi expert consultation were conducted. In the first round, 23 questionnaires were distributed, and 20 valid responses were received (effective response rate: 86.96%) . Among them, 15 experts (75.00%) provided revision suggestions. In the second round, 20 questionnaires were distributed, and 19 valid responses were received (effective response rate: 95.00%) , with two experts (10.53%) offering suggestions. The expert authority coefficients for the two rounds were 0.900 and 0.921, respectively. Kendall's coordination coefficients were 0.272 and 0.273 ( P<0.01) . The final evaluation system consisted of four first-level indicators, eight second-level indicators, and 18 third-level indicators. Conclusions:The evaluation index system constructed in this study is scientifically grounded and reliable. However, its practical utility and applicability require further validation.

ObjectiveTo explore the impact of exogenous chitosan on the growth and metabolism of Glycyrrhiza uralensis Fisch. (G. uralensis) and to improve the quality of cultivated G. uralensis for both medicine and food and aid in the increase in the content of effective components in G. uralensis.MethodsIn this study, whole G. uralensis plants were treated with exogenous chitosan, and comprehensive analyses of secondary metabolites and proteins were conducted using liquid chromatography with tandem mass spectrometry and isobaric tag for relative and absolute quantitation, respectively. Effects of chitosan induction on endogenous hormones of G. uralensis were analyzed using an enzyme-linked immunosorbent assay. Gene ontology function annotation and Kyoto Encyclopedia of Genes and Genomes pathway annotation were conducted to study the effect of chitosan induction on the proteome.ResultsChitosan induction significantly increased the levels of flavonoids in G. uralensis; however, the variation in triterpenoids was not substantial. Biological processes, including photosynthesis, secondary metabolism, and abiotic stress responses, were significantly enriched. Additionally, the photosynthetic pathway, photosynthesis-antenna protein pathway, and plant hormone signal transduction pathway were significantly enriched. In the flavonoid biosynthesis pathway, the upstream-related enzyme phenylalanine ammonia-lyase (PAL) and the downstream-related enzymes chalcone synthase (CHS), polyketide reductase (PKR), chalcone isomerase (CHI), and vestitone reductase (VR) were significantly upregulated.ConclusionsOur findings suggest that chitosan induction may promote the tricarboxylic acid (TCA) cycle, and the TCA cycle enhancement significantly upregulated PAL, CHS, PKR, CHI, and VR, the five key enzymes involved in flavonoid synthesis of G. uralensis, indicating that chitosan induction activated the entire metabolic pathway associated with flavonoids in G. uralensis. Our findings provide a reference for improving the quality of cultivated G. uralensis from the perspective of pharmacodynamic components.

Receptor-interacting protein kinase 1 (RIPK1) plays an essential role in regulating the necroptosis and apoptosis in cerebral ischemia-reperfusion (I/R) injury. However, the regulation of RIPK1 kinase activity after cerebral I/R injury remains largely unknown. In this study, we found the downregulation of protein arginine methyltransferase 1 (PRMT1) was induced by cerebral I/R injury, which negatively correlated with the activation of RIPK1. Mechanistically, we proved that PRMT1 directly interacted with RIPK1 and catalyzed its asymmetric dimethylarginine, which then blocked RIPK1 homodimerization and suppressed its kinase activity. Moreover, pharmacological inhibition or genetic ablation of PRMT1 aggravated I/R injury by promoting RIPK1-mediated necroptosis and apoptosis, while PRMT1 overexpression protected against I/R injury by suppressing RIPK1 activation. Our findings revealed the molecular regulation of RIPK1 activation and demonstrated PRMT1 would be a potential therapeutic target for the treatment of ischemic stroke.

Objective To investigate the potential core target and its mechanism of Simiao San(SMS)in the treatment of rheumatoid arthritis(RA)using network pharmacology and animal experiments.Methods Active components and corresponding SMS targets were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and cross-referenced with the Universal Protein(UniProt)database.RA-related targets were screened from The Human Gene Database(GeneCards),Online Mendelian Inheritance in Man(OMIM),Therapeutic Target Database(TTD),DrugBank,and Disease Gene Network(DisGeNet).Protein-protein interaction(PPI)networks were constructed for shared targets between SMS and RA using Search Tool for the Retrieval of Interacting Genes/Proteins(STRING),followed by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses via The Database for Annotation,Visualization and Integrated Discovery(DAVID).A"herb active component-disease target-signaling pathway"network was established to predict the mechanism of SMS in RA treatment.Molecular docking was performed between aryl hydrocarbon receptor(AHR)and the core active components of SMS to identify AHR-targeting constituents.For animal experiments,30 female SPF-grade C57/BL mice were randomly divided into normal,model,methotrexate(1.52 mg/kg,every 3 days),and SMS(12.48 g/kg,daily)groups with a 30-day intervention.Ankle diameter and arthritis index scores were measured.HE staining was used to assess joint inflammation,whereas immunohistochemistry(IHC)was used to measure cytochrome P450 1A1(CYP1A1),nuclear factor kappa B subunit p65(p65),and phosphorylated p65(p-p65)protein expression levels.Multiplex immunofluorescence(mIHC)was used to evaluate forkhead box protein P3(FOXP3)and interleukin-17A(IL-17A)protein expression.Results Forty-one active components and 228 targets of SMS were identified from TCMSP,whereas 1,207 RA-related targets were extracted from GeneCards,OMIM,TTD,DrugBank,and DisGeNet.Ninety-four overlapping targets were analyzed,yielding 612 GO terms and 143 KEGG pathways.Molecular docking of the ligand-binding domain of AHR with the top 10 Degree values of compounds of SMS(quercetin,stigmasterol,wogonin,beta-sitosterol,kaempferol,baicalein,et al.)revealed that stigmasterol,beta-sitosterol,(S)-canadine,and isocorypalmine was able to bind to AHR stably.In vivo,compared to the model group,the mice of the SMS and methotrexate groups joint swelling and arthritis index scores reduced(P<0.01).IHC indicated elevated CYP1A1 protein and decreased p65 and p-p65 protein levels in the SMS and methotrexate groups(P<0.05,P<0.01).mIHC demonstrated reduced IL-17A and increased FOXP3 protein expression in the SMS and methotrexate groups(P<0.05,P<0.01).Conclusion SMS alleviates joint inflammation in RA mice,potentially by targeting AHR,one of the core targets.SMS may suppress excessive inflammatory responses by activating AHR and inhibiting p65 phosphorylation.Additionally,SMS modulates the helper T cells 17/regulatory T cells balance by downregulating IL-17A and upregulating FOXP3.These results suggest that AHR is a key mediator in T-cell immune regulation.

Objective:To establish an evaluation index system for patient safety education targeted at undergraduate nursing interns.Methods:Based on the CIPP (Context, Input, Process, Product) evaluation model, a preliminary draft of the index system was developed using a literature review and semi-structured interviews. The Delphi method and the Analytic Hierarchy Process were applied to finalize the index system.Results:Two rounds of Delphi expert consultation were conducted. In the first round, 23 questionnaires were distributed, and 20 valid responses were received (effective response rate: 86.96%) . Among them, 15 experts (75.00%) provided revision suggestions. In the second round, 20 questionnaires were distributed, and 19 valid responses were received (effective response rate: 95.00%) , with two experts (10.53%) offering suggestions. The expert authority coefficients for the two rounds were 0.900 and 0.921, respectively. Kendall's coordination coefficients were 0.272 and 0.273 ( P<0.01) . The final evaluation system consisted of four first-level indicators, eight second-level indicators, and 18 third-level indicators. Conclusions:The evaluation index system constructed in this study is scientifically grounded and reliable. However, its practical utility and applicability require further validation.

Rheumatoid arthritis （RA） is a systemic autoimmune disease with local joint pain as the main clinical manifestation. It is one of the diseases specifically responding to traditional Chinese medicine （TCM）. The occurrence of RA is not only related to innate factors like genetic disorder but also associated with environmental factors， such as diets and microbial infection. The intestine， a vital human organ with digestive and immune functions， is a place where microorganisms colonize and exert intestinal metabolism-improving， barrier-protecting， and immunomodulatory effects. As the research on the onset and treatment of RA is deepening， the potential relationship of intestinal structural and functional abnormalities with the pathogenesis and progression of RA has been revealed. As clinical and experimental studies indicated， joint inflammation coexists with the impaired barrier function， imbalanced immune cells， and disordered gut microbiota. The theory of the gut-joint axis in the pathogenesis， progression， and treatment of RA is highly consistent with the holistic view in TCM. The recent pharmacological studies have shown that Chinese medicine prescriptions and active components can inhibit inflammation， protect joints， and maintain the intestinal function. This article summarizes the basic connotation of the gut-joint axis in RA and the mechanism by which TCM protect the intestinal barrier and modulate the immunity by regulating the gut microbiota structure and improving microbial metabolism in the treatment of RA. This review gives insights into the future research on the gut-joint axis in RA.

Objective:To explore the ovarian function and its influencing factors in women of child-bearing age with systemic lupus erythematosus(SLE).Methods:A total of 107 female patients diag-nosed with SLE at Peking University People's Hospital from January 2017 to May 2024,aged between 20 and 40 years,were included in the study.At the same time,40 matched healthy women aged between 20 and 40 years were selected as controls.Serum levels of anti-Müllerian hormone(AMH)were measured using the chemiluminescence method in both the control group and the SLE patients.The general clinical characteristics and medication history(including hormones,immunosuppressants,and biological agents)of the SLE patients were obtained through case retrieval.Changes in serum AMH levels before and after treatment with biological agents in the SLE patients were analyzed.Results:(1)The AMH levels in the SLE patients were significantly lower than those in the healthy control group[1.475(0.344,3.030)μg/L vs.2.934(1.893,4.761)μg/L,P＜0.001].(2)The level of AMH in the SLE patients with normal menstruation was significantly higher than that in the patients with irregular menstruation[1.931(0.638,3.414)μg/L vs.0.335(0.159,1.527)μg/L,P=0.004].No statistical differences were found in clinical characteristics and laboratory indicators between the groups with decreased AMH group and normal AMH group.(3)The multivariate logistic regression analysis revealed that age(OR=1.124,95％CI:1.033-1.224,P=0.007)and disease duration(OR=1.100,95％CI:1.017-1.190,P=0.018)were identified as significant risk factors for the decline in AMH levels.(4)After 6 months of treatment with telitacicept,the AMH level was significantly higher than that before treatment[2.050(0.763,4.259)μg/L vs.1.988(0.473,2.822)μg/L,P=0.043].There was no signifi-cant difference in AMH level between patients receiving rituximab treatment for 6 months[2.026(0.376,2.267)μg/L vs.1.545(0.503,3.414)μg/L,P=0.127].Conclusion:Ovarian function is decreased in SLE patients of childbearing age,and age and disease duration are the risk factors.The utilization of biological agents demonstrates favorable safety profiles regarding ovarian function in child-bearing-age patients with SLE.

Objective To investigate the prevalence of nonalcoholic fatty liver disease and the risk factors in Jingyuan county of Ningxia Autonomous Region.Methods The population proportionate sampling method was applied to enroll a representative sample of 10 639 adults in Jingyuan county and the study was conducted using questionnaires and physical examinations.A total of 10 553 people were included in the analysis after excluding those with missing data.High-resolution ultrasound was used to examine the liver and fasting blood was collected in the morning for measurement of blood glucose,blood lipid,and uric acid.The participants were divided into two groups of those with and without nonalcoholic fatty liver disease;the difference in blood biochemical indexes between fatty liver and non-fatty liver groups was compared,and the logistic regression model was used to explore the risk factors affecting the prevalence of fatty liver.Results The prevalence of nonalcoholic fatty liver disease was 7.60％.The prevalence of thyroid nodules was higher in men than in women (8.60％ vs.6.82％,x2=1 1.772,P=0.001).The prevalence rate of fatty liver increased with age (x2=57.336,P＜0.001),the prevalence rates among ≥18 years-＜29 years,≥30 years-＜39 years,≥40years-＜49 years,≥50 years-＜59 years,≥60 years-＜69 years,and above 70 years were 2.92％,6.50％,8.81％,9.59％,8.08％,and 4.77％ respectively.The detection rate of overweight,obesity,abdominal obesity,impaired fasting glucose,impaired glucose tolerance,diabetes,hypertension,hyperuricemia,and dyslipidemia were higher in nonalcoholic fatty liver disease group than in the normal group (P＜0.05).Logistic regression analysis showed that nonalcoholic fatty liver disease group had a higher risk for overweight,obesity,abdominal obesity,impaired fasting glucose,impaired glucose tolerance,diabetes,hypertension,hyperurcemia,and dyslipidemia (OR=5.41,12.45,2.99,1.85,2.05,3.30,1.41,2.23,and 1.98).Conclusion The incidence of nonalcoholic fatty liver in Jingyuan county of Ningxia Autonomous Region was higher.The groups of overweight,obesity,abdominal obesity,impaired fasting glucose,impaired glucose tolerance,diabetes,hypertension,hyperuricemia,and dyslipidemia were high risk factors for nonalcoholic fatty liver disease.

Objective: To investigate relationship between the clinicopathological features and prognosis of T1 esophageal carcinoma. Methods: Data from 212 T1 primary esophageal cancer patients, who underwent radical surgery in The Fourth Hospital of Hebei Medical University from Jan 2001 to Dec 2009 were enrolled. There were 148 males and 64 females. There were 91 patients with stage pT1a and 121 patients with stage pT1b. Results: The survival of the 212 patients was 27~108 months, and the median survival was 80.8 months. The 1, 3, and 5 year survival rates of patients with stage T1a were 100%, 97.8% and 94.5%, respectively, and the median survival was 86.8 months. The 1, 3, and 5 year survival rates of patients with stage T1b were 100%, 95.9% and 74.4%, respectively, and the median survival was 76.2 months. The rate of lymph node metastasis in 121 patients with stage T1b was 26.4% (32/121). The lymph node metastasis rates in patients with stage sm1, sm2 and sm3 were 11.6% (3/26), 15.0% (6/40) and 41.8% (23/55), respectively. There was no significant difference in lymph node metastasis between stage sm1 patients and stage sm2 patients (P=0.973). Lymph node metastasis rates in patients with stage sm3 were higher than those in stage sm1 and sm2 (P<0.05). Conclusion Radical resection of esophageal carcinoma with peripheral lymph node dissection is recommended for patients with T1b esophageal carcinoma.