AIM: To investigate the effect and potential mechanism of liraglutide(LIR)combined with neural stem cells(NSCs)in alleviating diabetic retinopathy(DR)in rats.METHODS:A DR rat model was established using a high-fat diet combined with a single intraperitoneal injection of streptozotocin(STZ). Rats in the control group were fed a normal diet and received an intraperitoneal injection of citric acid-sodium citrate buffer. After modeling, the rats were divided into the control group, DR group, DR+LIR group, DR+BMSCs group, DR+NSCs group, DR+BMSCs+LIR group, and DR+NSCs+LIR group. According to the grouping instructions, rats were given intraperitoneal injection of LIR at 200 μg/(kg·d)and intravitreal injection of bone marrow mesenchymal stem cells(BMSCs), or NSCs, or the combined therapy accordingly for 8 wk. Fasting blood glucose(FBG)and serum insulin levels, as well as retinal oxidative stress indexes and serum inflammatory indexes, were detected in each group. Retinopathy was evaluated by hematoxylin-eosin(HE)staining, retinal cell apoptosis was detected by TUNEL staining, SIRT1 expression in retinal tissues was detected by immunohistochemistry, and BDNF expression in retinal tissues was detected by immunofluorescence. The transcriptional levels of cZNF532, miR-29a-3p, SIRT1, TGF-β1, NRF2, Keap1, and BDNF in retinal tissues were detected by qRT-PCR, and the protein expression levels of SIRT1, TGF-β1, SMAD2/3, p-SMAD2/3, NRF2, Keap1, p65, and p-p65 in retinal tissues were detected by Western blot. RESULTS:Compared with the other groups of rats, the retinal morphology of rats in the DR+NSCs+LIR group was significantly improved, the levels of FBG, TNF-α, IL-1β, IL-6 and MDA were decreased(all P<0.05), the serum insulin level and the levels of SOD, CAT, and GSH-Px were increased(all P<0.05), the TUNEL-positive rate of retinal cells was reduced(all P<0.05). The expression levels of cZNF532, SIRT1, NRF2, and BDNF in retinal tissue were up-regulated(all P<0.05), whereas the expression levels of miR-29a-3p, TGF-β1, p-SMAD2/3, Keap1, and p-p65 were down-regulated(all P<0.05). CONCLUSION:LIR combined with NSCs alleviates DR by regulating the cZNF532-miR-29a-3p-SIRT1 network and its downstream TGF-β/SMAD, NF-κB, and Keap1/NRF2 signaling pathways.

ObjectiveThis study aims to observe the effect of sinomenine （SIN） on fatty acid binding protein 4 （FABP4） in synovial tissue of rats with osteoarthritis （OA） and investigate the therapeutic mechanism of SIN on OA， further providing new ideas for the management of osteoarthritis by traditional Chinese medicine （TCM）. MethodsAn OA rat model was constructed and randomly divided into a control group， an OA group， an OA + SIN-L group （50 mg·kg^-1）， an OA + SIN-M （100 mg·kg^-1）， an OA + SIN-H （200 mg·kg^-1）， and an OA + prednisone （PDN） group （5 mg·kg^-1）. Following surgical modeling for three weeks， an appropriate medication was administered for four weeks. During modeling and administration， a hot plate test was performed to detect the pain and swelling of the knee joints of the rats. The periarticular tissue was collected for arthropathological observation at the end of drug administration. The expression of cleaved Caspase-3， B-cell lymphoma-2 （Bcl-2）， Bcl-2 associated X protein （Bax）， and FABP4 in the synovial tissue of rats was detected by Western blot and real-time quantitative polymerase chain reaction （Real-time PCR）， and the expression and distribution of FABP4 protein in the synovial membrane were detected by immunofluorescence. ResultsCompared with those in the control group， the levels of inflammatory factors and FABP4 in the serum of rats in the OA group were significantly increased （P<0.05， P<0.01）， and joint swelling was significantly elevated （P<0.01）. The thermal pain threshold was significantly reduced （P<0.01）， and the expression of FABP4 protein and the fluorescence intensity were significantly increased （P<0.01）. The synovial tissue exhibited significantly increased inflammatory infiltration， proliferated fibroblasts， and an elevated apoptotic index （P<0.05， P<0.01）. Compared with those in the OA group， the serum lipid metabolism indexes of rats in the SIN administration group gradually returned to normal （P<0.05， P<0.01）， while the levels of inflammatory factors and FABP4 in the serum of rats in the SIN-administered group were significantly reduced （P<0.05， P<0.01）， and joint swelling was significantly decreased （P<0.05， P<0.01）. The thermal pain threshold was significantly elevated （P<0.05， P<0.01）， and the expression of FABP4 protein and fluorescence intensity in the synovial tissue were significantly decreased （P<0.05， P<0.01）. The synovial tissue displayed significantly reduced inflammatory infiltration and a decreased apoptotic index （P<0.05， P<0.01）. ConclusionThe therapeutic effect of SIN on OA may be related to the down-regulation of FABP4 expression， reduction of apoptosis， and inhibition of inflammatory factor expression.

Objective To explore the clinical,pathological,imaging characteristics,treatment,and prognosis of primary pericardial mesothelioma(PPM).Methods The clinical,pathological and imaging data of 11 PPM patients diagnosed in Peking Union Medical College Hospital from 2014 to 2024 were retrospectively collected,the Kaplan-Meier curve was calculated by Log-Rank test to determine the prognostic factors of the patients.Results The median age of the 11 patients was 48 years,including one well-differentiated papillary mesothelioma,and ten malignant mesothelioma.CA125 was elevated in all patients.PET/CT all indicated increased pericardial metabolism.Male patients and patients with ECOG score>2 points had worse prognosis(P=0.018,P=0.01,re?spectively).Compared with the untreated group(4 cases),both immunotherapy(3 cases)and chemotherapy(3 ca?ses)can prolong patient survival(P=0.025,P=0.025,respectively),and the benefit of immunotherapy was greater than chemotherapy(P=0.049 9).Conclusions This study is the largest single center pericardial mesothe?lioma cohort in China.CA125 and PET/CT contributes to the diagnosis of PPM,and immunotherapy might be the future direction of PPM treatment.

Objective To explore the diagnosis and treatment experience of malignant peritoneal mesothelioma by analyzing the clinical characteristics of patients with single center peritoneal mesothelioma.Methods Retrospec-tively analyze the clinical data,including age and treatment regimens,of 99 patients with malignant peritoneal mes-othelioma admitted to Peking Union Medical College Hospital from June 2012 to July 2023.Kaplan-Meier for surviv-al analysis and Logistic and Cox regression were applied to assess the impact of factors like age and treatment regi-mens on survival time.Results The median age of diagnosis for 99 patients with peritoneal mesothelioma was 56 years,of which 82 were pathologically diagnosed.Among them,38 cases(51.4%)underwent tumor cell reduction surgery,and 57 cases(77.0%)underwent systemic or local treatment.The median survival time for all patients was 43 years.The age of diagnosis may affect the prognosis of patients with malignant mesothelioma,and those aged≥65 at the time of diagnosis have a worse prognosis.Conclusions Malignant peritoneal mesothelioma is a rare but invasive malignant tumor with a poor prognosis.There is still a need to develop novo drugs and comprehensive treat-ment strategies.

Objective To investigate the serum interleukin-17A(IL-17A)and chemokine CXC motif ligand 13(CXCL13)levels in children with cough variant asthma and their clinical significance.Methods A total of 108 children with cough variant asthma admitted to Meihe Maternity Hospital from November 2021 to Febru-ary 2023 were selected as the study group,and 86 healthy children who underwent physical examinations dur-ing the same period were selected as the control group.The levels of serum IL-17A and CXCL13 in the two groups were detected by enzyme-linked immunosorbent assay.Multivariate Logistic regression was used to an-alyze the factors influencing the occurrence of cough variant asthma.Receiver operating characteristic(ROC)curve was plotted to analyze the diagnostic value of serum IL-17A and CXCL13 expressions for cough variant asthma.Results The levels of serum IL-17A and CXCL13 in the study group were both higher than those in the control group(P＜0.05).The levels of serum IL-17A and CXCL13 in children with cough variant asthma were negatively correlated with forced vital capacity(FVC),forced expiratory volume in one second(FEV1),maximal expiratory flow rate(PEF),and FEV1/FVC and basal respiratory conductivity(Grs cont),while positively correlated with initial resistance value(Rrs cont).Multivariate Logistic regression analysis indicated that FVC,FEV1,PEF,FEV1/FVC,and Grs cont were protective factors influencing the occurrence of cough variant asthma(P＜0.05).However,Rrs cont,IL-17A and CXCL13 were risk factors affecting the occurrence of cough variant asthma(P＜0.05).The area under the curve(AUC)of serum IL-17A and CXCL13 levels for diagnosing cough variant asthma were 0.920 and 0.867,respectively.The AUC of the combined diagnosis of the two was 0.937,which was significantly greater than that of the diagnosis of CXCL1 alone(Z=2.194,P=0.028).Conclusion The levels of serum IL-17A and CXCL13 in children with cough variant asthma are upreg-ulated,and both are related to the lung function and airway responsiveness of children with cough variant asthma.The combined detection of serum IL-17A and CXCL13 levels has a high diagnostic value for cough variant asthma.

Background Work-related musculoskeletal disorders (WMSDs), as one of the major occupational health issues worldwide, have shown an increasing positive rate year by year. Due to the unique demands of work, operating room nurses exhibit a higher positive rate of WMSDs compared to other occupational groups, necessitating active attention and intervention. Objective To estimate the prevalence of WMSDs among operating room nurses in tertiary hospitals, explore the characteristics and latent categories of WMSDs, and analyze the influencing factors associated with the occurrence of WMSDs. Method Using a randomized cluster sampling method, operating room nurses from nine tertiary hospitals in Urumqi were selected as study participants between December 2023 and January 2024. Data were collected through a general information questionnaire, an ergonomic questionnaire for operating room nurses, and the Chinese Musculoskeletal Disorders Questionnaire. Latent class analysis was employed to examine the patterns of WMSDs among the nurses, while chi-square test and multinomial logistic regression were utilized to analyze the influencing factors of WMSDs. Result A total of 411 valid questionnaires were collected in this survey. The positive rate of WMSDs among operating room nurses in the tertiary hospitals of Urumqi over the past year was 91.9%. The positive rates, ordered from highest to lowest by body region, were neck (79.1%), shoulders (70.3%), and lower back (68.1%). The operating room nurses were categorized into three distinct groups by latent class analysis: multi-site pain group, neck-shoulder-back pain group, and neck and lower back pain group. The results of the multinomial logistic regression models revealed that gender, job strain level, ergonomic load level in the operating room, and exposure to cold or drafty working conditions or not were significant influencing factors for reporting WMSDs among operating room nurses. Specifically, having less than 5 years of work experience, low ergonomic load level, low job strain, and moderate job strain were identified as protective factors against WMSDs. Conversely, exposure to cold or drafty working environments and being female were identified as risk factors for WMSDs. The logistic regression models also indicated that compared to the neck-lower back pain group, the neck-shoulder-back pain group had a higher probability of reporting low job strain (OR=0.168, 95%CI: 0.029, 0.968) and being female (OR=4.847, 95%CI: 2.506, 9.378). In contrast, when comparing to the neck-lower back pain group, the multi-site pain group had a higher probability of reporting, low-level ergonomic workload (OR=0.079, 95%CI: 0.015, 0.412), low job strain (OR=0.019, 95%CI: 0.002, 0.145), moderate job strain (OR=0.080, 95%CI: 0.016, 0.401), high job strain (OR=0.132, 95%CI: 0.027, 0.647), less than 5 years of work experience (OR=0.173, 95%CI: 0.044, 0.683), being female (OR=2.424, 95%CI: 1.130, 5.200), and exposure to cold or drafty working environments (OR=3.277, 95%CI: 1.657, 6.481). Conclusion The positive rate WMSDs among operating room nurses in tertiary hospitals is notably high in Urumqi, with distinct co-occurrence characteristics observed within the population. To mitigate the risk of WMSDs, it is essential to implement targeted health education and prevention training programs tailored to different patterns of WMSDs. Additionally, improving working conditions, optimizing human resource allocation , and other proactive measures should be undertaken. These efforts will effectively reduce the incidence of WMSDs among operating room nurses and safeguard their occupational health.

Objective:To explore the clinical efficacy of three different surgical timings of modified cervical cerclage in twin pregnant women with cervical insufficiency.Methods:The clinical data of 73 twin pregnant women who underwent modified cervical cerclage and had pregnancy outcomes in Qilu Hospital of Shandong University (Qingdao) from April 2014 to July 2023 were retrospectively analyzed. According to the different timings of surgery, they were divided into prophylactic cerclage group, ultrasound-indicated cerclage group (further divided into cervical length (CL)≤15 mm and 15 mm10 mg/L was a risk factor for preterm birth before 34 weeks of gestation ( OR=5.230, 95% CI: 1.616-16.929; P=0.006). Conclusions:In twin pregnant women with cervical insufficiency, prophylactic cerclage has the same surgical effect as ultrasound-indicated cerclage, while both prophylactic cerclage and ultrasound-indicated cerclage could significantly improve maternal and fetal outcomes compared with emergency cerclage. Twin pregnancies with CL≤15 mm might benefit from cervical cerclage. Postoperative CRP>10 mg/L is an independent risk factor for preterm birth before 34 weeks of gestation.

Objective:To investigate the efficacy of radiotherapy in patients with advanced esophageal cancer receiving first-line chemoimmunotherapy.Methods:A retrospective analysis was conducted on the data of 137 patients with Stage Ⅳ esophageal squamous cell carcinoma (ESCC) treated at our hospital from January 2018 to May 2023. These patients were divided into two groups: a group treated with first-line chemoimmunotherapy combined with radiotherapy (chemoimmunotherapy + radiotherapy group, n = 43) and a group treated with only chemoimmunotherapy ( n = 94). Inverse probability of treatment weighting (IPTW) was applied to balance baseline characteristics between the groups. With overall survival (OS) and progression-free survival (PFS) as study endpoints, the survival data were analyzed using the Kaplan-Meier method, the log-rank test, and the Cox regression method. Results:Before calibration, the chemoimmunotherapy + radiotherapy group significantly outperformed the sole chemoimmunotherapy group in median PFS (13.6 months vs. 7.0 months; HR: 0.501, 95% CI: 0.309-0.811, P = 0.005). After calibration using the COX proportional-hazards model for age, gender, Eastern Cooperative Oncology Group (ECOG) performance status, smoking history, T/N/M stage, and tumor location, the chemoimmunotherapy + radiotherapy group still had significant advantages in PFS (14.7 months vs. 7.0 months; HR: 0.441, 95% CI: 0.261-0.745, P = 0.002). IPTW analysis further confirmed this trend (13.9 months vs. 7.0 months; HR: 0.492, 95% CI: 0.304-0.795, P < 0.001). Specifically, the median OS of the chemoimmunotherapy + radiotherapy group demonstrated significant improvement in all analyses: pre-calibration (29.5 months vs. 18.0 months; HR: 0.507, 95% CI: 0.297-0.867, P = 0.013), after calibration using the Cox model (27.5 months vs. 16.7 months; HR: 0.470, 95% CI: 0.266-0.830, P = 0.009), and after calibration using IPTW (29.5 months vs. 16.9 months; HR: 0.448, 95% CI: 0.262-0.764, P < 0.001). Conclusions:The combination of radiotherapy and first-line chemoimmunotherapy can significantly improve survival outcomes of patients with advanced ESCC, suggesting its potential as a standard treatment strategy.

Objective:To evaluate strategies for screening and diagnosing Lynch syndrome associated endom-etrial carcinoma(LS-EC)in clinical practice and analyze clinicopathological characteristics of LS-EC.Methods:A total of 258 patients with endometrial carcinoma who underwent surgery in The Fourth Hospital of Hebei Medical University from January 2019 to January 2022 were included.All enrolled patients underwent postoperative immu-nohistochemical testing for mismatch repair(MMR)proteins.Based on the expression status of the four MMR proteins,the patients were divided into deficient mismatch repair(d-MMR)group(57 cases)and proficient mis-match repair(p-MMR)group(201 cases).Among them,23 patients in the d-MMR group underwent germline gene testing for Lynch syndrome(LS).According to germline gene testing results,these patients were further classified into LS-EC(n=8)and non-LS-EC(n=15)groups.Clinicopathological features of LS-EC patients were analyzed.Results:Among the 258 endometrial carcinoma patients,57cases(22.1%)exhibited d-MMR,with MLH1 and PMS2 co-deletion being the most common(61.4%,35/57).Among the23 d-MMR patients who under-went genetic testing,8 cases(34.8%)were identified as having LS-EC,including 5 cases(62.5%)of MLH1 gene mutation,1 case(12.5%)of MSH2 gene mutation,1 case(12.5%)of PMS2 gene mutation and 1 case(12.5%)of MSH6 gene mutation.Compared with the non-LS-EC group,the LS-EC patients showed significant familial aggregation and higher pathological grade(P<0.05).Conclusions:Immunohistochemical analysis of MMR proteins combined with family history represents an effective screening strategy for LS-EC,however defini-tive diagnosis requires germline genetic testing.Among LS-EC cases,MLH1 is the most frequently mutated gene.LS-EC patients are characterized by familial clustering and high pathological grade.Discrepancies between immu-nohistochistochemistry and genetic testing results present challenges in the definitive diagnosis of LS-EC.

Protein arginine methyltransferase 5 (PRMT5) acts as an oncogene in liver cancer, yet its roles and in-depth molecular mechanisms within the liver cancer immune microenvironment remain mostly undefined. Here, we demonstrated that disruption of tumor-intrinsic PRMT5 enhances CD8⁺ T-cell-mediated antitumor immunity both in vivo and in vitro. Further experiments verified that this effect is achieved through downregulation of the inhibitory immune checkpoint molecule, fibrinogen-like protein 1 (FGL1). Mechanistically, PRMT5 catalyzed symmetric dimethylation of transcription factor 12 (TCF12) at arginine 554 (R554), prompting the binding of TCF12 to FGL1 promoter region, which transcriptionally activated FGL1 in tumor cells. Methylation deficiency at TCF12-R554 residue downregulated FGL1 expression, which promoted CD8⁺ T-cell-mediated antitumor immunity. Notably, combining the PRMT5 methyltransferase inhibitor GSK591 with PD-L1 blockade efficiently inhibited liver cancer growth and improved overall survival in mice. Collectively, our findings reveal the immunosuppressive role and mechanism of PRMT5 in liver cancer and highlight that targeting PRMT5 could boost checkpoint immunotherapy efficacy.