Objective: To investigate the status of condom use and its influencing factors among men who have sex with men (MSM), so as to provide a basis for improving condom utilization rates and AIDS prevention and control in this population. Methods: From May to October 2024, a snowball sampling method was employed to recruit MSM in Songjiang District, Shanghai Municipality. Self-administered questionnaires were used to collect data on demographic characteristics, AIDS-related knowledge, sexual behaviors, pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP), and condom use in the past six months. Multivariable logistic regression model was used to analyze the influencing factors for consistent condom use. Results: A total of 921 MSM were surveyed, with a median age of 29.00 (interquartile range, 9.00) years. Among them, 697 (75.68%) were aware of AIDS-related knowledge, 826 (89.69%) expressed willingness to use PrEP, and 835 (90.66%) were willing to use PEP. Additionally, 787 (85.45%) MSM reported their age at first homosexual intercourse as ≥18 years, while 519 (56.35%) reported consistent condom use in the past six months. Multivariable logistic regression analysis revealed that MSM who were aware of AIDS-related knowledge (OR=0.582, 95% CI: 0.423-0.801), willing to use PrEP (OR =0.611, 95% CI: 0.385-0.969), and whose age at first homosexual intercourse was <18 years (OR=0.480, 95% CI: 0.330-0.700) were less likely to consistent use condoms. Conclusion The proportion of consistent condom use among the MSM remains relatively low, which is primarily associated with AIDS-related knowledge, willingness to use PrEP, and the age at first homosexual intercourse.

Background/Aims: Regorafenib is recommended by guidelines and trials as a sequential second-line therapy following progression on first-line sorafenib or lenvatinib in hepatocellular carcinoma (HCC). However, efficacy is limited, highlighting the urgent need to screen suitable patients and develop sensitization strategies. Methods: Acquired sorafenib- or lenvatinib-resistant (SR or LR) HCC cell lines and organoids were established. Genome-wide CRISPR library screen was performed in SR or LR cell strains to identify synthetic lethal targets of regorafenib. RNA-seq and FITC-regorafenib efflux assay were used to elucidate ERBB3-driven downstream signaling. Preclinical mouse models of cell line- and patient-derived xenografts and clinical cohorts of HCC patients were employed to validate the efficacy of ERBB3-guided patient stratification. Results: Screening with CRISPR library, we showed that inhibition of ERBB3 was synthetic lethal with regorafenib in SR or LR cell strains and organoids. Mechanistically, SR or LR triggered feedback activation of ERBB3 signaling and mediated regorafenib efflux via ERBB3-HIF1A-ABCB1 cascade pathway, limiting sensitivity to regorafenib. Moreover, ERBB3-low tumors following SR or LR exhibited significant sensitivity to regorafenib, suggesting its potential as a predictive biomarker to screen optimal candidates for sequential therapy. Seribantumab, an ERBB3-targeting monoclonal antibody, inhibited ERBB3-HIF1A-ABCB1 cascade, and its combination with regorafenib exerted marked synergistic anti-tumor effects on ERBB3-high tumors resistant to sorafenib or lenvatinib both in vitro and in vivo. Conclusions This study revealed that ERBB3 was a key resistance factor driving limited efficacy to sequential regorafenib, but also an effective therapeutic target whose inhibition enhanced regorafenib sensitivity after SR or LR.

Background/Aims: Natural killer (NK) cell function is generally considered dampened in chronic hepatitis B virus (HBV) infection; however, the NK cell pool exhibits phenotypic and functional heterogeneity, and the antibody--mediated effect of NK cells remains less characterized. This study evaluated the dynamic changes in antibody-mediated NK cell responses and the involvement of distinct NK subsets across disease stages and during antiviral treatment. Methods: A T-cell receptor-like antibody specific for the HBV core 18–27 peptide (cTCRL-Ab) was used to determine the antibody-mediated effect of NK cells, and an array of NK cell surface markers were analyzed in cross-sectional and longitudinal cohorts of patients with chronic HBV infection. Single-cell RNA sequencing (scRNA-seq) was performed to identify the heterogeneity of NK subsets. Results: The cTCRL-Ab enabled the detection of NK cell cytolytic activity and IFNγ production. Notably, cTCRL-Ab-mediated NK cell responses were compromised in chronically HBV-infected patients, particularly in those receiving pegylated interferon-α (Peg-IFNα), which was associated with the downregulation of CD16 expression. Correspondingly, Peg-IFNα inhibited cTCRL-Ab-mediated NK cell function by reducing CD16 expression in vitro. scRNA-seq revealed that CD16 downregulation occurred mainly within a dysfunctional CD16hi NK subset exhibiting exhaustion properties. In contrast, an activated CD16hiNK subpopulation (CX3CR1⁺KLRC2–CD16hi) with high cytotoxicity was enriched in patients who experienced favorable treatment responses. Furthermore, the intrahepatic CX3CR1+KLRC2–CD16hi subset tended to exhibit functional restoration in HBsAg-loss individuals. Conclusions Our data contribute to the understanding of antibody-mediated responses of NK cells in chronic HBV infection, and highlight a previously unappreciated functional CX3CR1+KLRC2–CD16hiNK subset as a potential therapeutic target.

Objective: To examine the prevalence of e-cigarette use and associated factors among primary and secondary school students in Pudong New Area, Shanghai, and to explore the pathways linking harm perception of e-cigarettes, interpersonal social influence, and attitudes toward e-cigarette use with experimentation behavior, in order to provide scientific basis for further optimizing the prevention and control strategies of e-cigarette among adolescents. Methods: From September to October 2025, a multi stage cluster random sampling method was used to select 5 144 primary and secondary school students aged 8-19 years from 47 primary and secondary schools in Pudong New Area, Shanghai, to conduct an anonymous questionnaire survey. The questionnaire collected information on e-cigarette use, harm perception of e-cigarette, interpersonal social influence, and attitudes toward e-cigarette use. The Chi-square test was applied to analyze the differences in cigarette and e-cigarette use behavior among primary and secondary school students with different demographic characteristics. Structural equation modeling (SEM) was constructed using Mplus 8.3 software, and the bootstrap method was utilized to test the mediating effects. Results: The reported rates of cigarette experimentation, e-cigarette experimentation, and current e-cigarette use among primary and secondary school students were 1.85%, 2.10%, and 0.70%, respectively. Higher reporting rates of e-cigarette experimentation were observed among boys (2.82%), secondary school students aged 16-19 (3.39%), senior high school students (3.05%), and those with weekly pocket money >100 yuan ( 6.11% ) ( χ 2=11.67, 8.61, 8.00, 54.18, all P <0.05). Structural pathway analysis results demonstrated that e-cigarette harm perception positively predicted interpersonal social influence ( β =0.61) and e-cigarette use attitude ( β = 0.53 ), and interpersonal social influence ( β =0.65) and e-cigarette use attitude ( β =0.25) further promoted e-cigarette experimentation behavior among primary and secondary school students (all P <0.01), with interpersonal social influence playing a major mediating role (indirect effect=0.40). Conclusions E-cigarette experimentation behavior among primary and secondary school students in Pudong New Area is jointly influenced by multiple psychosocial factors. Intervention strategies should strengthen interpersonal social factors such as family and peers on the basis of health education, thereby constructing a comprehensive prevention and control strategy for e-cigarette use among primary and secondary school students.

Objective To explore the role of neogambogic acid in the characteristics of colorectal cancer stem cells (CRC-CSCs) through the Wnt/β-catenin signaling pathway. Methods The colorectal cells SW480 and HCT166 were divided into control group and neogambogic acid groups (1.5, 3, 6, and 12 μmol/L). The viability of CRC-CSCs was determined by MTT method, and spheroid and clone formation assays were used to assess the capacity of spheroid formation and self-renewal ability of the cells. The effects of neogambogic acid on the apoptosis and cell cycle of CRC-CSCs were evaluated by flow cytometry assays. Real-time quantitative PCR was used to detect the mRNA expression levels of relative markers (CD133, CD44, ALDH1, Oct4, and Nanog) of CRC-CSCs, and the protein expression levels of the self-renewal marker (PCNA), apoptosis markers (cleaved caspase-3 and cleaved caspase-9), and Wnt/β-catenin signaling pathway markers (p-GSK3β, GSK3β, β-catenin, and Wnt) were analyzed using Western blot. Results Compared with the control group, after neogambogic acid treatment, the viability of SW480 and HCT116 cells decreased (P<0.05), the spheroid forming ability and the clone numbers of CRC-CSCs decreased (P<0.001, P<0.01) but the cell apoptosis rate increased (P<0.01), and cell cycle was arrested in G₀/G₁ phase. Moreover, neogambogic acid downregulated the mRNA and protein expression of relative markers of CRC-CSCs (CD133, CD44, ALDH1, Oct4, and Nanog), PCNA, p-GSK3β, β-catenin, and Wnt (P<0.05) and upregulated the expression of cleaved caspase-3, cleaved caspase-9, and GSK3β (P<0.01). Conclusion Neogambogic can inhibit the stem cell properties of colorectal cells via inhibition of Wnt/β-catenin signaling pathway. As a result, neogambogic acid may be an attractive agent against colorectal cancer.

BACKGROUND:Total flavonoids from Sophora flavescens have a variety of pharmacological effects,including anti-inflammatory,immunomodulatory,antioxidant,and anti-hepatic injury,but the therapeutic effects and mechanisms in non-alcoholic fatty liver disease are not clear.OBJECTIVE:To reveal the mechanism of total flavonoids from Sophora flavescens in the treatment of non-alcoholic fatty liver disease using bioinformatics,network pharmacology and zebrafish experimental validation.METHODS:A zebrafish model of non-alcoholic fatty liver disease was constructed to observe lipid accumulation,pathomorphologic changes,and expression of inflammatory genes in the liver of zebrafish after treatment with total flavonoids from Sophora flavescens.The active ingredients of total flavonoids from Sophora flavescens and non-alcoholic fatty liver disease-related targets were obtained from TCMSP,Swiss Target Prediction,and Bat-man databases.STRING was used to perform protein-protein interaction network analysis,GO functional enrichment and KEGG pathway enrichment analysis.Based on the GSE33814 dataset,the differentially expressed genes of total flavonoids from Sophora flavescens and non-alcoholic fatty liver disease intersection targets were screened out.Correlation analysis and receiver operating characteristic curve were performed using R4.3.2 software.Core genes were verified by the validation set GSE89632.RT-qPCR and western blot assays were performed to verify the expression of core pathway-related genes and proteins.RESULTS AND CONCLUSION:(1)Total flavonoids from Sophora flavescens could improve lipid accumulation in the liver of zebrafish with non-alcoholic fatty liver disease,significantly inhibited the elevation of lipid and aminotransferase levels in zebrafish(P<0.05),and regulated the expression of genes related to inflammation and lipid metabolism.(2)A total of 168 common targets were obtained using the network pharmacology,and top 10 core genes,identified by Cytoscape topology analysis,were HSP90AA1,STAT3,PIK3R1,MAPK1,AKT1,RXRA,PIK3CA,EGFR,JAK2,and ESR1.GO and KEGG analysis pathways mainly included insulin resistance,lipids,and atherosclerosis.There were a total of 59 differentially expressed genes after intersection of total flavonoids from Sophora flavescens and non-alcoholic fatty liver disease targets.The receiver operating characteristic curve and validation set analyses yielded six core targets that were significantly different between healthy individuals and patients with non-alcoholic fatty liver disease(P<0.01).(3)RT-PCR and western blot results verified that total flavonoids from Sophora flavescens inhibited the activation of the JAK2/STAT3 signaling pathway in zebrafish.To conclude,total flavonoids from Sophora flavescens may alleviate the inflammatory response through the JAK2/STAT3 signaling pathway,thus inhibiting lipid accumulation and improving non-alcoholic fatty liver disease.

Objective To investigate the correlation between early clinical outcomes following endoscopic surgery for unilateral lumbar disc herniation and variations in the cross-sectional area of the sciatic nerve.Methods Fifty-two patients(n=52)with unilateral lumbar disc herniation were recruited from June 2023 to June 2024 at the Pain Department of the First Affiliated Hospital of Nanchang University.The cross-sectional area(CSA)values of bilateral sciatic nerves were measured at the gluteal sciatic tuberosity-great femoral rotor level using ultrasound before and on the 4th day after surgery.The change in nerve cross-sectional area ΔCSA and sciatic nerve swelling rate(SR-SN)were calculated.Patient BMI(Body Mass Index),visual analog scale(VAS),Japanese Orthopaedic Association score(JOA),Oswestry Disability Index(ODI),and Treatment Improvement Rate(TIR)were collected preoperatively and on postoperative day 4.Changes in sciatic nerve cross-sectional area in unilateral lumbar disc herniation and its relationship to clinical outcomes were analyzed using the scoring scales as controls.Results Compared to the preoperative period,there was a significant decrease in VAS and ODI scores,as well as an increase in JOA score on the 4th postoperative day(P<0.01).Furthermore,surgical intervention led to substantial improve-ment in clinical outcomes for the patients.Prior to surgery,the CSA value of the affected side of the sciatic nerve was greater than that of the healthy side(P<0.01).Although CSA value decreased on the affected side after surgery,it remained higher than that of the healthy side(P<0.01).Additionally,there was a significant difference between SR-SN values on both sides with higher values observed on the affected side(P<0.01).Notably,△CSA on the affected side exhibited a negative correlation with postoperative VAS score,JOA score,and treatment improvement rate(P<0.05);The SR-SN on the affected side exhibited a positive correlation with BMI and negative correlations with postoperative VAS score,JOA score,and treatment improvement rate(P<0.05).However,no significant correlations were observed between △CSA,SR-SN,and ODI score on the affected side.(P>0.05).Conclusions In patients undergoing endoscopic surgery for lumbar disc herniation,a greater change in the cross-sectional area of the affected sciatic nerve before and after the operation is associated with more pronounced improvement in early symptoms.However,further investigation is required to explore the relationship between this change and recovery of both lumbar spine and lower limb function.

A 53-year-old female patient with type 2 diabetes mellitus,hypertension,and hyperlipidemia,on long-term therapy with metformin,gliclazide,dapagliflozin,sacubitril/valsartan,lercanidipine,and atorvastatin,was initiated on semaglutide due to obesity and suboptimal glycemic control.Patient using semaglutide 0.25 mg and 0.5 mg without adverse effects,and developed gastric discomfort after adjusting dose to 0.75 mg.She remained on this dose for 7 weeks.Upon further dose escalation to 1 mg,she experienced persistent nausea,vomiting,and diarrhea.Fifteen days later,she was admitted to the hospital with impaired consciousness.Laboratory findings revealed blood urea nitrogen of 35.4 mmol·L-1 and serum creatinine of 825 μmol·L-1.The patient was diagnosed with acute kidney injury(AKI),which was considered related to semaglutide,metformin,dapagliflozin,and sacubitril/valsartan.All medications were discontinued.Following symptomatic treatment including fluid resuscitation,volume expansion,and hemodialysis,the patient's renal function gradually recovered.The association between AKI and semaglutide,metformin,dapagliflozin,and sacubitril/valsartan was evaluated using the Naranjo's Assesment Scale,the results were all"probable".This case highlighted that clinical use of semaglutide requires careful consideration of concomitant medications and vigilance for renal impairment.In the event of AKI,prompt assessment,discontinuation of medications with potential renal impairment and symptomatic management were necessary to ensure safe medication administration.

Background and purpose:The colorectal cancer screening program for community residents in Shanghai has been implemented for 12 years since 2013.This study aimed to analyze the impact of screening on the colorectal cancer incidence,stage and survival outcomes based on their screening participation status.Methods:This study used registry-based cohort study method.The registered residents in Shanghai from 2013 to 2017 who met the screening age range were divided into screening group and non-screening group.The data of colorectal cancer cases after being included in groups were obtained from the Population Based Cancer Registry.We calculated age-standardized cumulative incidence and age-group cumulative incidence,diagnosis stage and survival rate of colorectal cancer by gender,age and year of diagnosis.We used the Joinpoint regression method to calculate the annual change percentage for cumulative incidence trend analysis.The life table method and EdererⅡ method were used to calculate the 5-year observed survival rates and expected survival rates of colorectal cancer cases.Finally the 5-year relative survival rates were obtained.Results:The study included 1 687 689 participants aged 50-74 in screening group and 4 713 307 participants in non-screening group.During a 5-year follow-up period,there were 10 333 and 20 904 new cases of colorectal cancer diagnosed in the two groups,respectively.The age-standardized 5-year cumulative incidence in the screening group was 555.33/105,with an average annual increase of 33.32%(P＜0.05).The age-standardized 5-year cumulative incidence in the non-screening group was 529.85/105,with an average annual increase of 48.13%(P＜0.05).There was no statistically significant difference between the screening group and the non-screening group in the age-standardized 5-year cumulative incidence(X=0.25,P=0.804).The lower the age group,the greater the difference between the screening group and the non-screening group in the annual average change percentage of the age-standardized cumulative incidence.The stages 0-Ⅰ of newly diagnosed colorectal cancer cases in the screening group and non-screening group accounted for 14.70%and 7.46%,respectively,with a statistically significant difference in composition between the two groups(P＜0.05).The 5-year relative survival rate of the screening group was 73.94%,while the non-screening group was 59.66%.The survival rate indicators of the former were significantly higher than those of the latter,and the difference was statistically significant.The survival rate of the former was significantly higher than that of the latter(73.94%vs 59.66%),and the difference was statistically significant(P＜0.05).The survival rate of females in both groups of cases was higher than that of males,and the survival rate decreased with increasing age-groups at diagnosis.Conclusion:With the implementation of the colorectal cancer screening program,the growth trend of the incidence rate of colorectal cancer among the screening participants has been curbed,and the early stages of colorectal cancer cases diagnosed and the 5-year survival rate were significantly improved.In order to reduce the incidence rate of colorectal cancer in the whole population,it is necessary to vigorously promote the screening coverage of the appropriate population,especially to increase the proportion of lower age groups participating in screening.We should also pay attention to the screening quality of the elderly groups and improve the compliance of colonoscopy in high-risk participants.At the same time,we should further optimize the refined management of screening for different genders,ages,and risk groups.

AIM To establish the quantitative models for gallic acid,mononucleoside,loganin,resveratrol,and rhein in Yishen Xiezhuo Mixture.METHODS HPLC was adopted in the content determination of various effective components,after which the near-infrared spectroscopy(NIRS)data were collected in 128 batches of samples and pretreatment was conducted,competitive adaptive reweighting sampling(CARS)algorithm was used for screening wavelength,partial least square method(PLS)regression analysis was performed.RESULTS There were no significant differences between the predicted values obtained by PLS models and measured values obtained by HPLC for various effective components(P＞0.05).CONCLUSION The quantitative models established by NIRS combined with chemometrics display good predictive performance,which can be used for the rapid determination of effective components in Yishen Xiezhuo Mixture,and provide a reference for the rapid monitoring of other traditional Chinese medicine preparations in production processes.