ObjectiveTo investigate the changes in the expression levels of Yes-associated protein 1 （YAP1） and human collagen type Ⅵ alpha 1 （COL6A1） in pancreatic cancer under hyperglycemic conditions and their association with prognosis. MethodsGEPIA database and R software were used to analyze the expression levels of YAP1 and COL6A1 and their correlation in pancreatic cancer， as well as their impact on the prognosis of patients with pancreatic cancer. The cBioPortal database was used to identify the co-expressed genes of YAP1 and COL6A1 in pancreatic cancer， and the gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analyses were performed. Quantitative real-time PCR and Western blot were used to measure the mRNA and protein expression levels of YAP1 and COL6A1 in human pancreatic cancer PANC-1 cells cultured under hyperglycemic or normoglycemic conditions. A nude mouse model of pancreatic cancer with type 2 diabetes was established， and immunohistochemistry was used to measure the expression of YAP1 and COL6A1 in subcutaneous tumor tissue. Clinical specimens and data of 96 patients with pancreatic cancer were collected from January 2016 to January 2020 in the First Affiliated Hospital of Guangxi Medical University， Guangxi Medical University Cancer Hospital and Wuming Hospital Affiliated to Guangxi Medical University. Among them， 48 patients with pancreatic cancer and diabetes were enrolled as study group， and 48 patients with pancreatic cancer alone were enrolled as control group； immunohistochemistry was used to measure the expression levels of YAP1 and COL6A1 in tissue samples from both groups， and their association with clinical indicators and survival outcomes was analyzed. The t-test was used for comparison of continuous data between groups， and the chi-square test or the Mann-Whitney U test was used for comparison of categorical data between groups； the Pearson correlation analysis was used for normally distributed continuous variables， while the Spearman correlation analysis was used for discontinuous variables or non-normally distributed variables. The Kaplan-Meier method was used to plot survival curves， and the Log-rank test was used for comparison of survival rates. The Cox proportional hazards model was used to perform univariate and multivariate analyses. ResultsBoth YAP1 and COL6A1 were highly expressed in pancreatic cancer， with a strong correlation between them （r=0.85， P<0.001）， and they were associated with the poor prognosis of patients （hazard ratio ［HR］=1.8 and 1.5， both P<0.05）. YAP1 and COL6A1 were significantly correlated with 219 and 122 genes， respectively （r=0.83 and 0.86， both P<0.05）， and the GO and KEGG enrichment analyses showed that these genes affected the development and progression of pancreatic cancer through extracellular matrix-receptor interaction， the Hippo signaling pathway， and the phosphatidylinositol 3-kinase/protein kinase B signaling pathway. Quantitative real-time PCR and Western blot showed that there were significant increases in the mRNA and protein expression levels of YAP1 and COL6A1 in human pancreatic cancer PANC-1 cells under hyperglycemic conditions （mRNA expression： t=4.726 and 6.197， both P<0.05； protein expression： t=6.826 and 5.254， both P<0.05）. Immunohistochemistry showed that there were significant increases in the expression levels of YAP1 and COL6A1 in subcutaneous tumor tissue of nude mice， with a positive correlation between them （r=0.985， P<0.001）. For the clinical specimens of pancreatic cancer tissue， immunohistochemistry showed that there were significant increases in the positive expression levels of YAP1 and COL6A1 proteins in the study group， with a positive correlation between them （r=0.882， P<0.001）. The multivariate analysis of clinical data showed that lymph node metastasis （HR=0.083， 95% confidence interval ［CI］： 0.030 — 0.231， P<0.05）， distant organ metastasis （HR=0.166， 95%CI： 0.065 — 0.420， P<0.05）， YAP1 expression level （HR=2.027， 95%CI： 1.065 — 3.857， P<0.05）， and COL6A1 expression level （HR=2.044， 95%CI： 1.019 — 4.099， P<0.05） were independent influencing factors for the prognosis of patients with pancreatic cancer. The survival analysis showed that the high YAP1 expression group had a significantly lower 2-year survival rate than the low YAP1 expression group （6.82% vs 25.00%， χ²=16.382， P<0.001）， and the high COL6A1 expression group had a significantly lower 2-year survival rate than the low COL6A1 expression group （14.58% vs 18.75%， χ²=4.579， P=0.032）. ConclusionThe hyperglycemic environment promotes the high expression of YAP1 and COL6A1 in pancreatic cancer， which is associated with poor prognosis in patients.

ObjectiveTo evaluate the effect of neuromuscular electrical stimulation (NMES) on pain, quadriceps strength and motor function of patients after total knee arthroplasty (TKA). MethodsThe databases of CNKI, Wanfang data, VIP, PubMed, Embase, Cochrane, Web of Science and Scopus were retrieved from inception to April, 2025. Randomized controlled trials (RCT) related to the intervention of NMES after TKA were collected. The quality of the included literature was evaluated using the Cochrane Risk of Bias Assessment Tool and the Physical Therapy Evidence Database (PEDro) scale. Meta-analysis was performed with RevMan 5.4. ResultsA total of twelve RCT were included, involving 772 subjects. The PEDro scale score ranged from four to seven. NMES improved postoperative quadriceps muscle strength (SMD = 0.61, 95%CI 0.34 to 0.88, P < 0.001) and knee flexion range of motion (SMD = 1.35, 95%CI 0.30 to 2.41, P = 0.010), and reduced the Timed Up and Go Test (TUGT) time (SMD = -0.86, 95%CI -1.45 to -0.26, P = 0.005). Compared with the control group, the intervention group achieved better outcomes in the 2-Minute Walk Test (2MWT) (SMD = 19.44, 95%CI 10.44 to 30.43, P < 0.001), 3-Minute Walk Test (SMD = 23.57, 95%CI 14.77 to 32.36, P < 0.001), 6-Minute Walk Test (SMD = 42.29, 95%CI 9.71 to 74.86, P = 0.010), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) (SMD = -0.52, 95%CI -1.00 to -0.04, P = 0.040), as well as the Physical Component Summary (PCS) (SMD = 2.90, 95%CI 0.73 to 5.06, P = 0.009) and Mental Component Summary (MCS) (SMD = 2.84, 95%CI 1.40 to 4.28, P = 0.040) of the 36-Item Short Form Health Survey (SF-36). Subgroup analysis demonstrated that two to four weeks after surgery, NMES enhanced patients' quadriceps muscle strength (SMD = 0.90, 95%CI 0.58 to 1.21, P < 0.001), shortened TUGT time (SMD = -1.28, 95%CI -2.57 to -0.02, P < 0.05) and increased walking distance in 2MWT (SMD = 20.43, 95%CI 10.44 to 30.43, P < 0.001). For patients followed up for two to three months, NMES yielded improvements in WOMAC scores (SMD = -0.44, 95%CI -0.79 to -0.09, P = 0.010) and SF-36 MCS scores (SMD = 4.17, 95%CI 2.43 to 5.91, P < 0.001). ConclusionNMES can significantly improve the quadriceps strength and walking ability of the TKA patients two to four weeks after surgery, and enhance the quality of life of patients two to three months after surgery.

Irritable bowel syndrome （IBS） is a functional bowel disorder characterized primarily by abdominal pain and altered defecation habits. In recent years， traditional Chinese medicine （TCM） has made progress in multiple aspects of IBS research and treatment， including syndrome distribution， development of TCM formulas， clinical efficacy evaluation， external therapies， and psychosocial regulation. However， it still faces challenges such as over-reliance on symptomatic manifestations rather than biomarkers for diagnostic criteria， and the lack of high-quality evidence-based data supporting the efficacy of TCM formulas in treating IBS. This paper proposed that TCM diagnosis and treatment of IBS should adhere to the strategy of integrating the holistic concept with syndrome differentiation and treatment， combining TCM external therapies such as acupuncture， moxibustion and acupoint application）， and emphasizing individualized diagnosis and treatment for psychosomatic abnormalities. Future research should integrate multi-omics technologies， artificial intelligence and other methods to deepen the understanding of the pathogenesis of IBS and the mechanisms of TCM formulas， so as to promote the standardization and internationalization of TCM in the diagnosis and treatment of IBS.

ObjectiveThis paper aims to investigate and evaluate the staged efficacy and safety of the representative empirical prescription of the “Zhu Ke Jiao” theory， Qijia Rougan prescription， combined with entecavir in the treatment of hepatic fibrosis in chronic hepatitis B. MethodsA multicenter randomized controlled clinical study was conducted， and 101 patients diagnosed with chronic hepatitis B-related hepatic fibrosis （CHB-HF） who met the diagnosis and inclusion criteria were randomly assigned to an observation group （Qijia Rougan prescription + entecavir） and a control group （entecavir）. The treatment duration was 24 weeks. Liver stiffness measurement （LSM）， fibrosis-4 index （FIB-4）， portal vein diameter， hepatitis B serology， biochemical indicators， hepatic fibrosis markers in serum ［hyaluronic acid （HA）， laminin （LN）， procollagen Ⅲ peptide （PⅢP）， and type Ⅳ collagen （Ⅳ-C）］， and traditional Chinese medicine syndrome scores were used as efficacy evaluation indicators. Efficacy assessments and explorations of different staged subgroups of Qijia Rougan prescription were conducted according to LSM values based on the Metavir pathological staging standard. ResultsA total of 98 cases were included for statistical analysis， with 49 cases in the observation group and 49 in the control group. The general data of the patients in both groups were comparable. Compared with the same group before treatment， the observation group showed a significant reduction in LSM and FIB-4 （P<0.01）， as well as notable improvements in LN， Ⅳ-C， and various TCM syndrome scores （P<0.05， P<0.01）. When compared to the control group after treatment， the observation group demonstrated significant improvements in LSM， FIB-4， and various TCM syndrome score indicators （P<0.05， P<0.01）， indicating that the observation group performed better than the control group. Subgroup analysis of the regression of hepatic fibrosis stages showed that compared to the same group before treatment， the observation group had better improvement in regression of stages F2 and F3 （P<0.05）. When compared to the control group after treatment， the observation group exhibited superior improvement in regression of stage F3 （P<0.05）. No adverse events occurred in either group during the treatment period. ConclusionCompared with entecavir alone， the combination of Qijia Rougan prescription and entecavir significantly improves the degree of hepatic fibrosis and clinical TCM symptoms in patients. The optimal intervention period is primarily during stage F3， which is a potential “interception” point of the “Zhu Ke Jiao” theory.

Pulmonary fibrosis（PF） is a progressive and life-threatening disease with limited therapeutic options， highlighting the urgent need for innovative drug discovery strategies. To address this challenge， the authors propose the formula-originated rational intelligent screening&translation（FIRST）， a systematic framework for developing anti-fibrotic monomers derived from classical traditional Chinese medicine（TCM）. The strategy integrates three key dimensions， including tissue-oriented intelligent screening of active compounds， structural optimization based on drug-target spatial interactions and plant biosynthetic pathways， and cross-scale validation of drug. We further highlight its applications in discovering tissue-oriented novel drugs from clinically validated TCM， the development and mechanistic elucidation of anti-fibrotic therapeutics， as well as the clinical translation and secondary development of candidate drugs. This strategy paves the way for first-in-class， formula-derived monomeric drugs with defined structures， clarified mechanisms， and proven safety， offering a transformative avenue to meet the urgent therapeutic needs of PF and setting a new paradigm for TCM-based drug innovation.

Pulmonary fibrosis（PF） is a progressive and life-threatening disease with limited therapeutic options， highlighting the urgent need for innovative drug discovery strategies. To address this challenge， the authors propose the formula-originated rational intelligent screening&translation（FIRST）， a systematic framework for developing anti-fibrotic monomers derived from classical traditional Chinese medicine（TCM）. The strategy integrates three key dimensions， including tissue-oriented intelligent screening of active compounds， structural optimization based on drug-target spatial interactions and plant biosynthetic pathways， and cross-scale validation of drug. We further highlight its applications in discovering tissue-oriented novel drugs from clinically validated TCM， the development and mechanistic elucidation of anti-fibrotic therapeutics， as well as the clinical translation and secondary development of candidate drugs. This strategy paves the way for first-in-class， formula-derived monomeric drugs with defined structures， clarified mechanisms， and proven safety， offering a transformative avenue to meet the urgent therapeutic needs of PF and setting a new paradigm for TCM-based drug innovation.

The study focuses on the concept of multifunctional traditional Chinese medicine (TCM) formulas and aims to evaluate the efficacy of the classical formula Xiaoyao San (逍遥散). Study employs the integrated evidence chain (Eff-iEC) method to organize, integrate, and evaluate its therapeutic efficacy in treating different diseases with the same therapy, and to investigate the feasibility of using Eff-iEC to evaluate the multifunctionality of TCM formulas. The evaluation covered Xiaoyao San's therapeutic effects on depression, premenstrual syndrome, chronic hepatitis, irritable bowel syndrome, dyspepsia, and menopausal syndrome. Concurrently, the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system was used for evaluation, and authoritative medical documents were incorporated to corroborate the recognition of Xiaoyao San within the medical community. Depression and menopausal syndrome received higher ratings than other conditions in the Eff-iEC, GRADE, and Medical Community Recognition assessments. The Eff-iEC evidence grade for Xiaoyao San was rated as "High" or above for chronic hepatitis, irritable bowel syndrome, dyspepsia, and menopausal syndrome. Premenstrual syndrome received a "Moderate ⁺" rating. The GRADE evidence level was "Low-〇〇⨁⨁" for depression, premenstrual syndrome, and chronic hepatitis; "Moderate-〇⨁⨁⨁" for dyspepsia and menopausal syndrome; and "Very Low-〇〇〇⨁" for irritable bowel syndrome. Depression and menopausal syndrome had the highest inclusion frequency, appearing in all 4 categories. Premenstrual syndrome, chronic hepatitis, and dyspepsia are not recommended in Western medical guidelines, but they are included in TCM guidelines, the China National Basic Medical Insurance Drug List, and the China National Essential Drug List. Irritable bowel syndrome appears only in the China National Basic Medical Insurance Drug List and China National Essential Drug List. The evaluation results obtained using the Eff-iEC method align with Medical Community Recognition, providing an objective and comprehensive assessment of Xiaoyao San's efficacy. The findings suggest that Xiaoyao San has strong evidence for treating depression and menopausal syndrome. However, further experimental and clinical trials are needed to assess its efficacy in treating premenstrual syndrome, chronic hepatitis, irritable bowel syndrome, and dyspepsia. These results support the clinical efficacy and rational use of Xiaoyao San, expand the application scope of the Eff-iEC method, and offer valuable insights and methodological references for the comparative evaluation of multifunctional TCM formulas.

ObjectiveTo evaluate the efficacy and safety of Janus kinase （JAK） inhibitors combined with Chinese herbal medicine （CHM） in treating rheumatoid arthritis （RA）. MethodsClinical data from 169 RA patients were retrospectively collected. Among them， 71 cases received JAK inhibitors as the control group， while 98 cases received JAK inhibitors plus CHM as the observation group， both treated for 24 weeks. The rheumatoid factor （RF）， cyclic citic peptide antibody （anti-CCP）， erythrocyte sedimentation rate （ESR）， C-reactive protein （CRP）， and white blood cell count （WBC） were recorded before and after treatment. Databases including CNKI， Wanfang， VIP， PubMed and Web of Science were searched from inception till August 31st， 2025 for randomized controlled trials （RCTs） on the combined use of JAK inhibitors and CHM for RA. The methodological quality of the included studies was evaluated using the risk of bias assessment tool. Meta-analyses were performed for RF， anti-CCP， ESR， CRP， 28-joint disease activity score （DAS28）， overall clinical effective rate， and incidence of adverse events. Sensitivity analysis were also performed. ResultsThe retrospective study demonstrated that after treatment， ESR， CRP， and anti-CCP levels decreased in the observation group， while ESR and CRP levels decreased in the control group （P＜0.05）. Moreover， ESR and RF levels in the observation group were lower than those in the control group （P＜0.05）. A total of 9 RCTs involving 770 patients were included in the meta-analysis. The results indicated that the JAK inhibitors plus CHM group was superior to the JAK inhibitors group in reducing RF （MD=-8.97， 95%CI -15.01 to -2.94， P=0.004）， CRP （MD=-3.34， 95%CI -3.82 to -2.86， P＜0.001）， ESR （MD=-5.33， 95%CI -7.98 to -2.69， P＜0.001）， and DAS28 score （MD=-0.54， 95%CI -0.74 to -0.34， P＜0.001）， as well as in improving the overall clinical effective rate （OR=4.53， 95%CI 2.55 to 8.03， P＜0.001）. No statistically significant differences were observed between groups in anti-CCP levels （SMD=-2.08， 95%CI -4.41 to 0.24， P=0.080） or incidence of adverse events （OR=0.93， 95%CI 0.55 to 1.57， P=0.790）. ConclusionThe combination of JAK inhibitors and CHM demonstrates remarkable efficacy in treating RA， contributing to improved disease activity and reduced inflammatory markers with a favorable safety profile.

Objective:To explore the safety and short-term efficacy of single-port robotic transanal total mesorectal excision (SPr-taTME).Methods:The retrospective and descriptive study was conducted. The clinicopathological data of six patients who underwent SPr-taTME at Daping Hospital of Army Medical University from October to November 2024 were collected. There were 3 males and 3 females, aged (65±5)years. Observation indicators: (1) intraoperative situations; (2) postoperative situations; (3) follow-up. Measurement data with normal distribution were represen-ted as Mean± SD, measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers. Results:(1) Intraoperative situations. All patients successfully underwent SPr-taTME without conversion to laparotomy or blood transfusion. There was no intraoperative complication such as accidental hemorrhage or adjacent organ injury. No intra-operative adverse events or mortality occurred. The operation time of the 6 patients was 286(range, 240?400)minutes. The time of transanal platform setup and robotic docking was (21±10)minutes, transanal dissection time was (97±45)minutes, and transabdominal dissection time was (90±35)minutes. The volume of intraoperative blood loss was (47±14)mL. Among the six patients, 1 case underwent synchronous transanal and transabdominal surgery, while 5 cases underwent non-synchronous procedures. Specimens were extracted transanally in 5 cases and via an auxiliary abdominal incision in 1 case. The single-port robotic platform was utilized for the abdominal surgery in 3 cases, while laparoscopy was used in 3 cases. Splenic flexure mobilization was performed in 3 cases and omitted in the other 3 cases. Three patients underwent hand-sewn sigmoid colon-anal anastomosis, 1 case underwent modified Bacon pull-through anastomosis, 1 case received stapled sigmoidorectal anastomosis, 1 case underwent sigmoid colostomy without anastomosis due to significant bowel edema. Two cases didn′t undergo intestinal stoma, 2 cases underwent virtual ileostomy, 1 case underwent ileostomy, and 1 case underwent sigmoid colostomy. (2) Postoperative situations. All patients started water drinking and out‐of‐bed activities on postoperative day 1 and liquid diet intake on postoperative day 2. The time to postoperative first flatus was 1(range, 1?3)days, and duration of postoperative hospital stay was (8±2)days.The total number of lymph nodes dissected was 13±2, with the number of positive lymph nodes as 0(range, 0?3) and the distance of distal resection margin as (23±8)mm. Pathological examination of 6 patients showed 1 case in stage T1N0, 2 cases in stage ypT0N0, 1 case in ypT1N0, 1 case in ypT3N1, and 1 case in ypT0N1. The degree of mesorectal integrity was complete in 5 patients and nearly complete in 1 patient. The surgical specimens of 6 patients showed negative in distal, proximal and circumferential margin. (3) Follow-up. All 6 patients completed the 30-day postoperative follow-up. None of the patients experienced postoperative complication such as bleeding, intestinal obstruction or anastomotic leakage. There was no readmission within 30 days after surgery. Digital rectal examination or colonoscopy on postoperative 30 day confirmed no anastomosis-related complications, including stenosis, dehiscence or anastomotic leakage. All 6 patients survived.Conclusion:The SPr-taTME is safe and feasible, with satisfactory short-term efficacy.

Objective To obtain tree shrew Vasorin(VASN)recombinant protein through prokaryotic expression and purification,prepare monoclonal antibody against tree shrew VASN by immunizing mice with this protein,and preliminarily evaluate its application value.Methods Reverse transcription-polymerase chain reaction(RT-PCR)was used to amplify the full-length sequence of tree shrew VASN gene in vitro.The tree shrew VASN gene fragment was inserted into pET-30a vector to construct pET-30a-VASN recombinant plasmid.The recombinant plasmid was subjected to double digestion with BamH Ⅰ and Sal Ⅰfor identification,and its correctness was further verified by sequencing.The recombinant plasmid with correct sequencing was transformed into BL21(DE3)competent cells,and isopropyl β-D-thiogalactoside(IPTG)was used to induce expression of VASN recombinant protein.Proteins were separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis(SDS-PAGE),and the VASN recombinant protein was purified by KCI.Purified recombinant protein was used to immunize BALB/c mice for four times,and serum antibody titer was detected by enzyme-linked immunosorbent assay(ELISA).Splenocytes from mice with serum antibody titer above 1:10 000 were used for cell fusion with myeloma cells.Hypoxanthine-aminopterin-thymidine(HAT)culture medium was first used to screen hybridoma cells.ELISA was used to screen positive hybridoma cell lines that could secrete specific antibodies,and monoclonal hybridoma cell lines were obtained by limiting dilution method.VASN monoclonal antibodies were prepared in large quantities by ascites induction method,purified using rProtein G,and the affinity and in vitro reaction specificity of the monoclonal antibodies were detected by ELISA and Western blotting.Results The full-length sequence of the tree shrew VASN gene was successfully amplified and the recombinant plasmid vector of tree shrew pET-30a-VASN was constructed.The sequence obtained by sequencing of the recombinant plasmid vector was identical to the tree shrew VASN target gene sequence.Recombinant protein VASN mainly existed in the form of inclusion bodies,and the purity after purification reached 90％,meeting the requirements of subsequent immunization experiments.After four immunizations with recombinant protein VASN,mouse serum antibody titer reached 1:729 000.Monoclonal positive hybridoma cell lines were obtained through ascites induction and purification,and the constant affinity value of monoclonal antibodies measured by ELISA reached 2.59x107 L/mol.Western blotting results showed that the tree shrew VASN monoclonal antibody could bind to tree shrew VASN recombinant protein,but it showed no binding reaction with porcine retinol-binding protein 4 recombinant protein,human VASN-leucine rich repeat recombinant protein,or bovine serum albumin.Anti-tree shrew VASN monoclonal antibody could specifically recognize VASN protein in tree shrew heart,liver,spleen,lung,kidney and muscle,with clear bands and clean background.Immunohistochemical detection results showed that this monoclonal antibody could recognize VASN protein in tree shrew spleen,lung,and tree shrew immortalized fibroblasts with high VASN mRNA expression levels,and the detection results were positive.Conclusion Monoclonal antibody against tree shrew VASN is successfully prepared.This antibody can be used for immunohistochemical detection of tree shrew immortalized fibroblasts,spleen tissue,and lung tissue,providing an important tool for further research on the function of VASN in tree shrew models.