Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation. Methods: The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation. Results: MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs. Conclusions In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.

Objective To examine the changing prevalence and antimicrobial resistance profiles of Burkholderia cepacia in 52 hospitals across China from 2015 to 2021.Methods A total of 9 261 strains of B.cepacia were collected from 52 hospitals between January 1,2015 and December 31,2021.Antimicrobial susceptibility of the strains was tested using Kirby-Bauer method or automated antimicrobial susceptibility testing systems according to a unified protocol.The results were interpreted according to the breakpoints released in the Clinical & Laboratory Standards Institute(CLSI)guidelines(2023 edition).Results A total of 9 261 strains of B.cepacia were isolated from all age groups,especially elderly patients.The proportion was 11.1％(1 032 strains)in children,significantly lower than the proportion in adults.About half(46.5％,4 310/9 261)of the strains were isolated from patients at least 60 years old and 42.3％(3 919/9 261)of the strains were isolated from young adults.Most isolates(71.1％)were isolated from sputum and respiratory secretions,followed by urine(10.7％)and blood samples(8.1％).B.cepacia isolates were highly susceptible to the five antimicrobial agents recommended in the CLSI M100 document(33rd edition,2023).B.cepacia isolates showed relatively higher resistance rates to meropenem and levofloxacin.However,the resistance rates to ceftazidime,trimethoprim-sulfamethoxazole,and minocycline remained below 8.1％.The percentage of B.cepacia strains resistant to levofloxacin was the highest compared to other antibiotics in any of the three age groups(from 12.4％in the patients＜18 years old to 20.6％in the patients aged 60 years or older).Conclusions B.cepacia is one of the clinically important non-fermenting gram-negative bacteria.Accurate and timely reporting of antimicrobial susceptibility test results and ongoing antimicrobial resistance surveillance are helpful for rational prescription of antimicrobial agents and proper prevention and control of nosocomial infections.

Numerous studies have shown that depression is main-ly associated with the abnormal expression of connexin 43(Cx43)in astrocytes(Astro)and its mediated dysfunction of gap junction(GJ).However,the molecular mechanism of post-translational modifications targeting Cx43 to regulate neuroin-flammation-associated depression is still unclear.Post-transla-tional modifications of Cx43 mainly include phosphorylation of specific amino acid sites by PKC,PKA,PKG,MAPK and PTK,and protein degradation of Cx43 through the K48/K63 polyubiq-uitylation and deubiquitination pathways,which ultimately lead to protein degradation through K48/K63 polyubiquitination and deubiquitination.These modifications are ultimately involved in the regulation of neuroinflammatory responses through the associ-ation of GJ function.In this paper,we systematically review the role of Cx43 post-translational modifications in neuroinflamma-tion,with the aim of further exploring the potential application of targeting these modifications to modulate the inflammatory re-sponse mechanism in improving depressive symptoms.

Aim To explore the mechanism by which dioscin regulates IL-17+γδT cells in the treatment of arthritis.Methods A collagen-induced arthritis(CIA)model was established in DBA/1 mice using bovine type Ⅱ collagen.The mice were randomly divid-ed into the CIA model group,methotrexate(MTX)positive control group,and dioscin low-dose(Dioscin-L),medium-dose(Dioscin-M),and high-dose(Dios-cin-H)groups.After intervention,the therapeutic effects were evaluated using scoring methods.Joint pathological damage was analyzed by hematoxylin and eosin(HE)staining.The levels of anti-collagen-spe-cific antibodies and the pro-inflammatory cytokine IL-17 were measured by ELISA.The expressions of γδT cells and their subtypes,as well as the secretion level of IL-17,were detected by flow cytometry.Results Dioscin significantly reduced the arthritis severity score in collagen-induced arthritis(CIA)mice,alleviated joint pathological damage,inhibited the production of IL-17 by splenic lymphocytes and the levels of anti-col-lagen-specific antibodies total IgG and IgG3,and de-creased the proportion of γδT cells in the lymph nodes,splenic γδT cells,and the Vδ4+T-cell subset.The level of IL-17 produced by the Vδ4 subtype in the lymph nodes of the intervention groups was lower than that in the model group,but the difference was not sta-tistically significant.Conclusion Dioscin has signifi-cant therapeutic effect on CIA,and its mechanism may be through the inhibition of γδT cells,but it is unlikely to be related to IL-17 derived from γδT cells.

Objective:To explore the potential profiles of health literacy in patients with chronic atrophic gastritis (CAG) and analyze their influencing factors.Methods:A cross-sectional study was conducted to select CAG patients admitted to Nanjing Hospital of Traditional Chinese Medicine or attending outpatient clinics from January 2023 to June 2024 by convenience sampling method, and all patients participated in this study two months after treatment. The General Information Questionnaire, the General Self-Efficacy Scale, and the All-around Health Literacy Measurement Scale (AAHLS) were used to conduct the questionnaire survey. The three dimensions of AAHLS were used as exogenous indicators for potential profile analysis, to compare the differences in general information and self-efficacy of patients with different potential profiles, and to analyze the influencing factors of different potential profiles of health literacy in CAG patients by multi classification Logistic regression.Results:The recovery rate of valid questionnaires was 97.71%(256/262). Among the 256 patients, there were 164 males and 92 females, with 86 patients aged 18-44 years old, 110 patients aged 45-59 years old, and 60 patients aged ≥ 60 years old. The health literacy of CAG patients was categorized into 3 potential profiles, including the high health literacy-appraisal and application competence group (14.84%, 38/256), the medium health literacy-appraisal and application competence group (32.81%, 84/256), and the low health literacy-appraisal and application competence group (52.34%, 134/256). The results of multi classification Logistic regression analysis showed that when the low health literacy-appraisal and application competence group was used as a reference, aged 18-44 years old ( OR=8.954, 95% CI 2.049-39.127), poor self-efficacy ( OR=0.089, 95% CI 0.027-0.293), duration of disease <5 years ( OR=0.049, 95% CI 0.014-0.169), per capita monthly household income<3 000 yuan ( OR=0.072, 95% CI 0.018-0.299), and primary school education or below ( OR=0.016, 95% CI 0.003-0.088) were independent influences in the the high health literacy-appraisal and application competence group (all P<0.05); poorer self-efficacy ( OR=0.458, 95% CI 0.251-0.834) and per capita monthly household income<3 000 yuan ( OR=0.212, 95% CI 0.100-0.453) were independent influences in the medium health literacy-appraisal and application competence group (both P<0.05). Conclusions:The health literacy of CAG patients is obviously heterogeneous, and healthcare professionals in clinical work should adopt targeted assessment and intervention according to the different characteristics of each category in order to improve the health literacy of CAG patients.

AIM To investigate the impact of varying dosages of Supplemented Wendan Decoction on the PI3K/Akt/FOXO1 glycolipid metabolic pathway in 3T3-L1 adipocytes.METHODS The CCK-8 assay was used to determine the concentration of Supplemented Wendan Decoction-medicated serum.The mature adipocytes differentiated from 3T3-L1 preadipocytes after induction were further divided into the blank control group,the model group,the rosiglitazone group(10 mg/L),and the Supplemented Wendan Decoction groups(5％,10％,and 20％),followed by the sample collections after 48 hours of treatment.Oil red O staining quantified lipid accumulation in 3T3-L1 adipocytes;extracellular glucose levels were measured using glucose oxidase(GOD)assay;RT-qPCR analyzed mRNA expressions of IRS-1,PI3K,Akt,GLUT4,IL-6,TNF-α and IL-1β;Western blot assessed protein expressions of INSR,IRS-1,PI3K-p85,Akt,FOXO1 and GLUT4.RESULTS No significant changes in cell viability(P＞0.05)were observed in 3T3-L1 preadipocytes exposed to serum containing supplemented Wendan Decoction at different concentrations for 24,48,or 72 hours.The 3T3-L1 preadipocytes held the capacity to differentiate into mature adipocytes within a 14-day induction period.Compared to the model group,all supplemented Wendan Decoction groups exhibited reduced lipid accumulation in adipocytes and downregulated mRNA expression of IRS-1,IL-6,TNF-α and IL-1β(P＜0.01);the low-dose group demonstrated increased mRNA expressions of PI3K and GLUT4(P＜0.05,P＜0.01),alongside elevated protein expressions of INSR,IRS-1,PI3K-p85,Akt and GLUT4(P＜0.05,P＜0.01);the medium-dose group showed enhanced GLUT4 mRNA expression,and upregulated protein expressions of INSR and FOXO1(P＜0.01).After 24 hours intervention,the high-dose Supplemented Wendan Decoction group exhibited increased glucose consumption in adipocytes(P＜0.01),and elevated protein expression of INSR,Akt and FOXO1(P＜0.05,P＜0.01).CONCLUSION Supplemented Wendan Decoction reduces lipid accumulation in adipocytes,regulates glucose and lipid metabolism,and promotes metabolic homeostasis through PI3K/Akt/FOXO1 signaling pathway.

Purpose To investigate the immunohistochemical HER2 expression in a large group of patients with urothelial carcinoma and to compare the results with the pathologic features and survival rate.Methods A total of 519 urothelial carcinoma specimens were collected from two centers.HER2 expression was measured by EnVision immuno-histochemistry.HER2 expression was compared with clinicopathological parameters,and further analyzed in relation to patient prognosis.Results The median age of the 519 patients was 66 years with a male to female ratio of 1.93∶1.Among them,160 cases were radical specimens,and 359 were transurethral resection specimens.The overall HER2 positivity rate was 61.7％(320/519),of which 148 cases(28.5％)were HER2 1+,238(45.9％)were HER2 2+,and 82(15.8％)were HER2 3+.In addition,51 cases(9.8％)were HER2-negative.HER2-positive ex-pression was associated with age,tumor location,histological grade,histological type,surgical approach,lymphovas-cular invasion,and neural invasion(all P＜0.05),but there was no significant correlation with gender,pT stage,muscular invasion,or lymph node metastasis.Univariate and multivariate logistic regression analysis showed that age≥ 66 years,higher tumor grade,and lymphovascular invasion were risk factors for positive HER2 expression,and high histological grade and lymphovascular invasion were independent risk factors affecting HER2 expression after controlling for confounders.Survival analysis showed no significant difference in recurrence-free survival between patients with HER2-positive and HER2-negative non-muscle-invasive urothelial carcinoma(P=0.274).Conclusion High histologic grade,tumor lymphovascular invasion,and neural invasion were associated with positive HER2 expression in patients with urothelial carcinoma,and higher histologic grade and lymphovascular invasion are important factors affect-ing HER2 expression.However,HER2-positive expression may not affect the prognosis of patients with non-muscle-invasive bladder urothelial carcinoma.

Objective To optimize the design of the existing water conductivity control system for pharmaceutical water equipment of full membrane process so as to solve its problems in precision and long cycle time due to water source,ambient temperature and intermittent working mode.Methods The optimized water conductivity control system was composed of an alkali metering pump,a conductivity sensor and a programmable logic controller(PLC),which used a fuzzy proportional-integral-derivative(PID)controller to regulate the water conductivity of pharmaceutical water equipment of full membrane process,and the particle swarm optimization(PSO)algorithm to optimize the parameters of the fuzzy PID controller.A simulation model was established with MATLAB software to verify the performance of the optimized control system.Results Simulation results showed the optimized control system had reductions in overshoot(by 19％)and adjustment time(by 29％)when compared with the fuzzy PID control system,and enhanced control efficiency effectively.Conclusion The optimized control system optimized by the PSO algorithm improves the quality of produced water,and can meet the demands for rapid and safe production of pharmaceutical water by pharmaceutical water equipment of full membrane process in different conditions.[Chinese Medical Equipment Journal,2025,46(6):14-19]

OBJECTIVE To assess the current status of hospital-acquired infections and their economic burden in or-thopedic patients based on diagnosis-related groups(DRG).METHOD Based on the National Health Insurance dis-ease diagnosis-related groups,32 413 orthopedic patients from a tertiary care hospital in Beijing in 2021 were grouped,hospital-acquired infections were retrospectively analyzed,and the direct and indirect economic burdens of different DRG groups were assess using indictors such as hospitalization time and cost,bed turnover loss,and labor time loss.RESULTS A total of 32 413 patients were included,the incidence of hospital-acquired infection was 0.47％(153/32 413),the site of infection was predominantly the surgical site(57.99％),and hospital-acquired infections in the hematologic system had a greater impact on cost-consumption indices and time-consumption indi-ces.The infection cases were concentrated in 19.58％of the DRGs groups.The IF23 group(lower limb bone sur-gery with complications and comorbidities)had the highest direct economic burden(24 010 yuan/case)due to hos-pital-acquired infections,and the increase in the cost of consumables and medication was the main factor causing the direct economic burden.At both the hospital level and family-society level,the top three DRG groups in terms of indirect economic burden due to hospital-acquired infections were IB15,IB13 and IF23.CONCLUSION Hospital-acquired infections in orthopedic patients have a tendency to be concentrated,quantitatively assessment of their e-conomic burden based on DRGs not only illustrates the importance of hospital-acquired infection prevention and control,but also accurately identifies the disease groups that require focused management,providing an evidence-based basis for precise prevention and control of hospital-acquired infections.

Objective To investigate the distribution and antimicrobial resistance profiles of common pathogens isolated from cerebrospinal fluid(CSF)in CHINET program from 2015 to 2021.Methods The bacterial strains isolated from CSF were identified in accordance with clinical microbiology practice standards.Antimicrobial susceptibility test was conducted using Kirby-Bauer method and automated systems per the unified CHINET protocol.Results A total of 14 014 bacterial strains were isolated from CSF samples from 2015 to 2021,including the strains isolated from inpatients(95.3％)and from outpatient and emergency care patients(4.7％).Overall,19.6％of the isolates were from children and 80.4％were from adults.Gram-positive and Gram-negative bacteria accounted for 68.0％and 32.0％,respectively.Coagulase negative Staphylococcus accounted for 73.0％of the total Gram-positive bacterial isolates.The prevalence of MRSA was 38.2％in children and 45.6％in adults.The prevalence of MRCNS was 67.6％in adults and 69.5％in children.A small number of vancomycin-resistant Enterococcus faecium(2.2％)and linezolid-resistant Enterococcus faecalis(3.1％)were isolated from adult patients.The resistance rates of Escherichia coli and Klebsiella pneumoniae to ceftriaxone were 52.2％and 76.4％in children,70.5％and 63.5％in adults.The prevalence of carbapenem-resistant E.coli and K.pneumoniae(CRKP)was 1.3％and 47.7％in children,6.4％and 47.9％in adults.The prevalence of carbapenem-resistant Acinetobacter baumannii(CRAB)and Pseudomonas aeruginosa(CRPA)was 74.0％and 37.1％in children,81.7％and 39.9％in adults.Conclusions The data derived from antimicrobial resistance surveillance are crucial for clinicians to make evidence-based decisions regarding antibiotic therapy.Attention should be paid to the Gram-negative bacteria,especially CRKP and CRAB in central nervous system(CNS)infections.Ongoing antimicrobial resistance surveillance is helpful for optimizing antibiotic use in CNS infections.