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.

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.

BACKGROUND:Degenerative scoliosis is defined as a condition that occurs in adulthood with a coronal cobb angle of the spine>10° accompanied by sagittal deformity and rotational subluxation,which often produces symptoms of spinal cord and nerve compression,such as lumbar pain,lower limb pain,numbness,weakness,and neurogenic claudication.The finite element method is a mechanical analysis technique for computer modelling,which can be used for spinal mechanics research by building digital models that can realistically restore the human spine model and design modifications. OBJECTIVE:To review the application of finite element method in the etiology and treatment of degenerative scoliosis. METHODS:The literature databases CNKI,PubMed,and Web of Science were searched for articles on the application of finite element method in degenerative scoliosis published before October 2023.Search terms were"finite element analysis,biomechanics,stress analysis,degenerative scoliosis,adult spinal deformity"in Chinese and English.Fifty-four papers were finally included. RESULTS AND CONCLUSION:(1)The biomechanical findings from the degenerative scoliosis model constructed using the finite element method were identical to those from the in vivo experimental studies,which proves that the finite element method has a high practical value in degenerative scoliosis.(2)The study of the etiology and treatment of degenerative scoliosis by the finite element method is conducive to the prevention of the occurrence of the scoliosis,slowing down the progress of the scoliosis,the development of a more appropriate treatment plan,the reduction of complications,and the promotion of the patients'surgical operation.(3)The finite element method has gradually evolved from a single bony structure to the inclusion of soft tissues such as muscle ligaments,and the small sample content is increasingly unable to meet the research needs.(4)The finite element method has much room for exploration in degenerative scoliosis.

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 investigate the occupational health literacy (OHL) level and its influencing factors of key populations in Jinhua City, Zhejiang Province, so as to provide a basis for promoting occupational health. Methods: The front-line workers of 7 secondary industry enterprises (institutions) and 15 tertiary industry enterprises (institutions) in Jinhua City were selected from April to October 2023 using a stratified random cluster sampling method. Date of gender, age, length of service, and OHL were collected using the National Occupational Health Literacy Monitoring Survey for Key Population Personal Questionnaire. Factors affecting OHL level among key populations were identified using multivariable logistic regression model. Results: A total of 3 305 people were investigated, including 1 750 males (52.95%) and 1 555 females (47.05%). The median age and the length of service were 37 (interquartile range, 17) and (interquartile range, 9) years, respectively. The level of OHL was 45.63%. Multivariable logistic regression analysis identified gender (female, OR=1.675, 95%CI: 1.428-1.964), educational level (junior high school, OR=1.499, 95%CI: 1.089-2.063; high school, OR=1.905, 95%CI: 1.361-2.667; junior college, OR=4.065, 95%CI: 2.858-5.782; bachelor degree and above, OR=5.087, 95%CI: 3.597-7.194), personal monthly income (3 000-< 5 000 yuan, OR=1.373, 95%CI: 1.035-1.821; 5 000-<7 000 yuan, OR=1.653, 95%CI: 1.230-2.220; ≥7 000 yuan, OR=1.798, 95%CI: 1.322-2.447) and length of service (2-<6 years, OR=1.265, 95%CI: 1.032-1.551; 6-<11 years, OR=1.517, 95%CI: 1.184-1.943; ≥11 years, OR=1.337, 95%CI: 1.040-1.719) as factors affecting OHL level among key populations. Conclusions The OHL level of the key populations in Jinhua City is related to gender, age, education level, personal monthly income, and length of service. It is necessary to strengthen the occupational health education and health promotion of the key populations.

Background::Clinical opportunistic screening is a cost-effective cancer screening modality. This study aimed to establish an easy-to-use diagnostic model serving as a risk stratification tool for identification of individuals with malignant gastric lesions for opportunistic screening.Methods::We developed a questionnaire-based diagnostic model using a joint dataset including two clinical cohorts from northern and southern China. The cohorts consisted of 17,360 outpatients who had undergone upper gastrointestinal endoscopic examination in endoscopic clinics. The final model was derived based on unconditional logistic regression, and predictors were selected according to the Akaike information criterion. External validation was carried out with 32,614 participants from a community-based randomized controlled trial.Results::This questionnaire-based diagnostic model for malignant gastric lesions had eight predictors, including advanced age, male gender, family history of gastric cancer, low body mass index, unexplained weight loss, consumption of leftover food, consumption of preserved food, and epigastric pain. This model showed high discriminative power in the development set with an area under the receiver operating characteristic curve (AUC) of 0.791 (95% confidence interval [CI]: 0.750–0.831). External validation of the model in the general population generated an AUC of 0.696 (95% CI: 0.570–0.822). This model showed an ideal ability for enriching prevalent malignant gastric lesions when applied to various scenarios.Conclusion::This easy-to-use questionnaire-based model for diagnosis of prevalent malignant gastric lesions may serve as an effective prescreening tool in clinical opportunistic screening for gastric cancer.

Objective This study aimed to explore the diagnostic concordance of fractional flow reserve(FFR)and quantitative flow ratio(QFR)and the characteristics affecting this concordance.Methods Patients with non-acute myocardial infarction admitted to the Department of Cardiology,Peking University Third Hospital between January 2019 and December 2021 were enrolled.The patients were divided into four groups:FFR+/QFR+and FFR-/QFR-,FFR+/QFR-and FFR-/QFR+with FFR or QFR≤0.80 as positive and＞0.80 as negative.Using FFR as the gold standard,the diagnostic value of QFR was analyzed,and differences in clinical features and pathological characteristics among the groups were compared.Results A total of 236 patients were included.The mean age was(64.48±9.63)years,and 67.8％were male.All patients had 30％-70％coronary stenosis.The consistency rate of QFR and FFR was 78.0％(n=184),and the Person correlation coefficient was 0.557(P＜0.001).Among FFR+patients,the minimum lumen diameter was larger[(1.56±0.34)mm vs.(1.39±0.31)mm,P=0.019],lesion length was shorter[(21.37±11.73)mm vs.(36.86±18.09)mm,P＜0.001],and coronary angiography-based index of microcirculartory resistance(AMR)was higher[(277.50±28.87)mmHg·s/m vs.(178.02±49.13)mmHg·s/m,P＜0.001]in the disconcordance group.Multivariate regression analysis suggested that AMR[OR 0.93,95％CI 0.88-0.99,P=0.030]and lesion length[OR 1.27,95％CI 1.01-1.60,P=0.045]were independent predictors of disconcordance.In the FFR-group,the lesion length was longer[(33.08±16.05)mm vs.(21.40±13.36)mm,P=0.020],and AMR[(169.66±24.01)mmHg·s/m vs.(265.95±44.78)mmHg·s/m,P＜0.001]and low-density lipoprotein-C[1.57(1.10,1.97)mmol/L vs.2.15(1.79,2.74)mmol/L,P=0.031]were lower in the disconcordance group.No statistically significant variables were identified by multivariate regression.Conclusions QFR had high diagnostic value compared with FFR.In the FFR+group,AMR and lesion length may have affected the diagnostic consistency of QFR and FFR.The study provided more evidence for the clinical application of QFR.

Objective:To study lncRNA MEG3 expression and its relationship with Th17/CD4+T cells in patients with non-small cell lung cancer(NSCLC)with different pleural effusion severity and prognosis.Methods:A total of 104 NSCLC malignant pleural effusion patients admitted to Quanzhou First Hospital Affiliated to Fujian Medical University from January 2020 to December 2022 were selected as research subjects,and divided into three groups based on amount of pleural effusion,including small amount of pleural effusion group(35 cases),moderate amount of pleural effusion group(42 cases)and large amount of pleural effusion group(27 cases).According to actual development and prognosis of patient's disease,they were divided into good prognosis group(29 cases without recurrence and metastasis)and poor prognosis group(75 cases with recurrence and metastasis).Another 60 patients with benign pleural effusion due to pneumonia who were treated in Quanzhou First Hospital Affiliated to Fujian Medical University at same time were selected as control group.MEG3 expression in pleural effusion of two groups was detected by real-time fluorescent quantita-tive PCR,and peripheral venous blood of subjects was collected.Th17 cell and CD4+T cell ratios of peripheral blood were detected by flow cytometry,and Th17/CD4+T was calculated.lncRNA MEG3 and peripheral blood Th17 and CD4+T levels in each group of patients compared.Logistic regression analysis was used to analyze pleural effusion and prognostic factors in NSCLC.Results:lncRNA MEG3 expression and CD4+T percentage in pleural effusion in NSCLC group were lower than control group,while Th17 percentage and Th17/CD4+T were higher than control group(P<0.05).lncRNA MEG3 expression and CD4+T percentage in large pleural effusion group were lower than small and moderate pleural effusion groups.lncRNA MEG3 expression and CD4+T percentage in modarate pleural effusion group were lower than small pleural effusion group,while Th17 percentage and Th17/CD4+T in large pleural effusion group were higher than small and moderate pleural effusion groups.Th17/CD4+T was higher in small amount pleural effusion group(P<0.05).lncRNA MEG3 expression and CD4+T percentage in poor prognosis group were lower than those in good prognosis group,while Th17 percentage and Th17/CD4+T were higher than good prognosis group(P<0.05).Logistic regression analysis showed that lncRNA MEG3 was a protective factor for NSCLC pleural effusion,and Th17/CD4+T was a risk factor(P<0.05),lncRNA MEG3 was a protective factor of NSCLC prognosis,and Th17/CD4+T was a risk factor(P<0.05).Conclusion:lncRNA MEG3 expression and Th17/CD4+T in NSCLC patients with different pleural effusion severity and prognosis is not same.lncRNA MEG3 is a risk factor for NSCLC pleural effusion and prognosis,while Th17/CD4+T is a risk factor,which can be used as an effective biomarker for pleural effusion severity and progno-sis diagnosis.

Investigating the species/biovars,distribution patterns,and genetic correlations of Brucella from sheep in north-west China is critical to reveal the population and epidemiological characteristics of the Brucella melitensis.In this study,con-ventional identification and AMOS-PCR were used to determine the species/biovars of Brucella isolated from 13 regions in northwest China.MLST and MLVA-16 genotyping methods were used to analyze the genetic characteristics of the strains.Con-ventional identification and AMOS-PCR detection revealed that 59 Brucella melitensis were isolated in this study,in-cluding 22 strains from Inner Mongolia,17 strains from Xin-jiang,13 strains from Gansu,and 7 strains from Qinghai,of which 58 strains were B.melitensis biovar 3,and one strain was B.melitensis biovar 1.MLST analysis indicated that 90％(53/59)of B.melitensis were of ST8 sequence type,the dominant epidemic population.The MLVA-11 survey demonstrated that 59 B.melitensis strains clustered into six MLVA-11 genotypes,and 87％of the strains were of MLVA-11 genotype 116.Therefore,the predominant strains in the northwest region were from the Eastern Mediterranean lineage.MLVA-16 divided 59 strains of B.melitensis into 40 gen-otypes,eight of which were shared genotypes.Each genotype was composed of two to seven strains from the same region,thereby indicating that the cases of each shared genotype were outbreaks from a common source of infection.All shared MLVA-16 genotypes comprised strains from the same province,thus indicating apparent regional clustering characteristics of strains in each province.In a genetic comparison between populations and isolated strains from the spleens of sheep,multiple identical MLVA-16 genotypes were found to be composed of strains from different hosts.These findings indicated a transmission path-way from sheep/goats to humans.B.melitensis biovar 3 was the main pathogen causing animal brucellosis in the northwest re-gion,and infected sheep were the main brucellosis infection source in the regional population.The ST8 strains were the domi-nant epidemic population,and the MLVA genotype of strains in each region showed clear regional clustering characteristics.

Objective:This study aims to evaluate the performance of digital PCR (dPCR) detecting multiple and single copies genes of the Epstein-Barr virus (EBV) for nucleic acid quantification and explore their applicability in clinical settings.Methods:Compared the sensitivity, specificity, precision, lower limit of detection (LoD), and linearity for multicopy BamHI-W dPCR and single-copy EBNA1 dPCR systems. Linear regression analysis using the least squares method was employed to evaluate the linearity. Additionally, we analyzed plasma samples from 182 patients with suspected EBV-related diseases between January and July 2022 at the Southern Medical University Southern Hospital, using both dPCR and quantitative PCR (qPCR) for EBV DNA quantification. Linear regression analysis using the least squares method was conducted to assess their quantitative correlation.Results:The dPCR systems for both multicopy and single-copy genes showed excellent linearity ( R 2 values of 0.992 and 0.997, respectively, both P<0.001). The LoD were 188 IU/ml for BamHI-W gene and 358 IU/ml for EBNA1 gene dPCR systems. The logarithmic coefficient of variation ( CV) values for high-concentration samples (1 000 000 IU/ml) were 0.34% and 0.21% for the BamHI-W gene and EBNA1 gene dPCR assays, respectively, while for low-concentration samples (5 000 IU/ml) were 0.98% and 0.64%, respectively. In the detection of seven common clinical infectious pathogens and EBV positive samples, only EBV-positive samples yielded positive signals in the dPCR detection system, with no cross-reaction with other pathogens. In 182 samples, the positive detection rates were 47.80% (87/182) for BamHI-W gene and 35.16% (64/182) for EBNA1 gene dPCR, compared to 43.41% (79/182) for qPCR. Linear correlation analysis with qPCR showed R2 values of 0.837 for BamHI-W gene and 0.763 for EBNA1 gene dPCR (both P<0.001). The BamHI-W gene copy number ranged from 3 to 18 copies per clinical sample, with patient-specific variations. There was a high consistency in viral load trends between the multicopy BamHI-W gene and single-copy EBNA1 gene dPCR systems within individual patients. Conclusions:The dPCR methods detecting EBV multiple and single copies genes showed high sensitivity, specificity, precision, and quantitative accuracy, suitable for clinical sample analysis. The multicopy BamHI-W gene dPCR method notably enhances detection sensitivity and can be used as a supplement to current EBV DNA load detection methods, especially in low-concentration samples. For within-patient EBV DNA monitoring, the multicopy gene method proves more effective, while inter-patient comparisons might necessitate single-copy gene methods or normalize them using the same standard.