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/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 evaluate the incidence, treatment, and survival outcomes of Swyer syndrome with gonadal non-dysgerminoma malignant germ cell tumor (MGCT-NDG). Methods: A retrospective study was performed on Swyer syndrome patients with MGCT-NDG between January 2011 and December 2022 in Peking Union Medical College Hospital to investigate their characteristics and outcomes. Results: A total of 15 patients (4.9%, 15/307) with Swyer syndrome were identified in 307 MGCT-NDG patients. The average age at diagnosis of MGCT-NDG and Swyer syndrome were (16.8±6.7) and (16.7±6.6) years, respectively. Six cases were preoperatively diagnosed as Swyer syndrome, of which 4 cases received bilateral gonadectomy with or without hysterectomy, while the other 2 cases underwent removal of gonadal tumor and unilateral gonadectomy with hysterectomy, respectively. Of the 9 patients postoperatively diagnosed as Swyer syndrome, unilateral gonadectomy, removal of gonadal tumor, and unilateral gonadectomy with hysterectomy were performed in 6 patients, 2 patients, and 1 patient, respectively. Mixed malignant germ cell tumor (MGCT;10 cases), yolk sac tumor (4 cases), and immature teratoma (1 case) were the pathological subtypes, in the descending order. There were International Federation of Gynecology and Obstetrics (FIGO) stage Ⅰ in 6 cases, stage Ⅱ in 3 cases, stage Ⅲ in 5 cases, and stage Ⅳ in 1 case, respectively. Eleven patients received reoperation for residual gonadectomy after a average delay of (7.9±6.2) months, including 8 MGCT-NDG patients and 1 gonadoblastoma patient, no tumor involved was seen in the remaining gonads in the other 2 cases. Ten patients experienced at least one recurrence, with a median event free survival of 9 months (5, 30 months), of which 2 patients received surgery only at the time of initial treatment. All patients with recurrence received surgery and combined with postoperative chemotherapy. After a median follow-up of 25 months (15, 42 months), 10 patients were disease-free, 3 patients died of the tumor, 1 died of side effects of leukemia chemotherapy, and 1 survived with disease. Conclusion: The incidence rate of Swyer syndrome in patients with MGCT-NDG is about 4.9%; timely diagnosis and bilateral gonadectomy should be emphasized to reduce the risk of reoperation and second carcinogenesis in this population.
Female ; Humans ; Retrospective Studies ; Gonadal Dysgenesis, 46,XY/surgery* ; Gonadoblastoma/surgery* ; Neoplasms, Germ Cell and Embryonal/surgery* ; Ovarian Neoplasms/pathology*

Objective To evaluate the efficacy and safety of brexpiprazole in treating acute schizophrenia.Methods Patients with schizophrenia were randomly divided into treatment group and control group.The treatment group was given brexpiprozole 2-4 mg·d-1 orally and the control group was given aripiprazole 10-20 mg·d-1orally,both were treated for 6 weeks.Clinical efficacy of the two groups,the response rate at endpoint,the changes from baseline to endpoint of Positive and Negative Syndrome Scale(PANSS),Clinical Global Impression-Improvement(CGI-S),Personal and Social Performance scale(PSP),PANSS Positive syndrome subscale,PANSS negative syndrome subscale were compared.The incidence of treatment-related adverse events in two groups were compared.Results There were 184 patients in treatment group and 186 patients in control group.After treatment,the response rates of treatment group and control group were 79.50％(140 cases/184 cases)and 82.40％(150 cases/186 cases),the scores of CGI-I of treatment group and control group were(2.00±1.20)and(1.90±1.01),with no significant difference(all P＞0.05).From baseline to Week 6,the mean change of PANSS total score wese(-30.70±16.96)points in treatment group and(-32.20±17.00)points in control group,with no significant difference(P＞0.05).The changes of CGI-S scores in treatment group and control group were(-2.00±1.27)and(-1.90±1.22)points,PSP scores were(18.80±14.77)and(19.20±14.55)points,PANSS positive syndrome scores were(-10.30±5.93)and(-10.80±5.81)points,PANSS negative syndrome scores were(-6.80±5.98)and(-7.30±5.15)points,with no significant difference(P＞0.05).There was no significant difference in the incidence of treatment-related adverse events between the two group(69.00％vs.64.50％,P＞0.05).Conclusion The non-inferiority of Brexpiprazole to aripiprazole was established,with comparable efficacy and acceptability.

Objective:To investigate the prospective association of sleep duration with the development of chronic obstructive pulmonary disease (COPD) in adults in Suzhou.Methods:The study used the data of 53 269 participants aged 30-79 years recruited in the baseline survey from 2004 to 2008 and the follow-up until December 31, 2017 of China Kadoorie Biobank (CKB) conducted in Wuzhong District, Suzhou. After excluding participants with airflow limitation, self-reported chronic bronchitis/emphysema/coronary heart disease history at the baseline survey and abnormal or incomplete data, a total of 45 336 participants were included in the final analysis. The association between daily sleep duration and the risk for developing COPD was analyzed by using a Cox proportional hazard regression model, and the hazard ratio ( HR) values and their 95% CI were calculated. The analysis was stratified by age, gender and lifestyle factors, and cross-analysis was conducted according to smoking status and daily sleep duration. Results:The median follow-up time was 11.12 years, with a total of 515 COPD diagnoses in the follow-up. After adjusting for potential confounders, multifactorial Cox proportional hazard regression analysis showed that daily sleep duration ≥10 hours was associated with higher risk for developing COPD ( HR=1.42, 95% CI: 1.03-1.97). The cross analysis showed that excessive daily sleep duration increased the risk for COPD in smokers ( HR=2.49, 95% CI: 1.35-4.59, interaction P<0.001). Conclusion:Longer daily sleep duration (≥10 hours) might increase the risk for COPD in adults in Suzhou, especially in smokers.

Objective:To investigate the association between quantified CT (QCT)-measured body composition and metabolic syndrome (MS) components in obese populations before bariatric surgery.Methods:A cross-sectional study. A retrospective analysis was conducted on a cohort of 97 obese patients scheduled for weight-loss surgery at the First Affiliated Hospital of Wannan Medical College from January 2021 to March 2023. The patients′ body mass index (BMI), biochemical parameters and body composition measurements obtained by QCT were recorded. The patients were stratified into groups based on gender, obesity severity and the number of MS components. Differences in body composition among the groups were compared. Additionally, the correlations between each body composition parameter and metabolic indicators were analyzed. The diagnostic efficacy of each body composition parameter for identifying obese individuals with different MS components was assessed using receiver operating characteristic (ROC) curve analysis.Results:There were 75 females (77.3%). Male obese patients had higher total abdominal fat area [(693.23±148.90) vs (574.99±114.89) cm 2, t=-3.958, P<0.001], visceral fat area [(289.65±57.67) vs (195.60±57.37) cm 2, t=-6.753, P<0.001], fat content of pancreatic head [27.45%(21.65%, 45.48%) vs 21.60%(17.6%, 26.9%), Z=-2.675, P=0.007], and skeletal muscle index [73.36(68.74, 81.26) vs 61.52(55.74, 66.41) cm 2/m 2, Z=-5.246, P<0.001]. With the increase of obesity, abdominal fat mainly increases in subcutaneous fat. With the increase of MS components (MS2 group, MS3 group, MS4 group, MS5 group), the abdominal fat area, abdominal fat/subcutaneous fat, liver fat content, pancreatic head fat content, and skeletal muscle index of patients all increased accordingly. In diagnosing the presence of two components of MS, area under the curve of visceral fat area was the largest (AUC=0.706, 95% CI=0.577-0.834). For diagnosing the presence of three, four and five components of MS, area under curve of liver fat content were all the largest (MS3=0.712, 95% CI=0.605-0.818; MS4=0.652, 95% CI=0.537-0.766; MS5=0.706, 95% CI=0.576-0.836). Conclusion:There are differences in QCT body composition among obese patients with different MS components, and there is a correlation between each body composition and MS component. Among them, intra-abdominal fat area and liver fat content are of great value in evaluating obese patients with different MS components.

ObjectiveTo construct a quantitative prediction model of three indicators（moisture absorption rate， film thickness and coating weight gain） during the coating process of Vitamin C Yinqiao tablets（VCYT） by near-infrared spectroscopy（NIRS）， and to realize the endpoint judgment. MethodReal-time NIRS data of 4 batches of VCYT during the coating process were collected by diffuse reflection method. The coating method employed was the rolling coating method， and the samples were obtained at the spray stage from the coater's sampling port every 10 minutes， and 57 batches of samples（about 1 800 tablets） were collected at various coating times， the tablets were embedded in molten paraffin， cut longitudinally， and observed by stereomicroscope. The film thickness， with a target value of 38 μm， was then measured using Motic Images Advanced 3.2 software. Furthermore， the mositure absorption rate of samples， aiming for a target value of 3%， was determined in accordance with guiding principles for drug hygroscopicity testing in the 2020 edition of Chinese Pharmacopoeia， and 3 samples were randomly selected from each batch（10 tablets per batch）， and the coating weight gain was calculated（target value of 4%）. Partial least squares regression（PLSR） was used to construct a quantitative model of the 3 coating indicators， and the predicted values of the coating indicators were smoothed using the moving average method and used to determine the coating endpoints. ResultThe prediction determination coefficients（R_p²） for moisture absorption rate， film thickness and coating weight gain were 0.933 4， 0.932 6 and 0.965 9， the root mean square errors of prediction（RMSEP） were 0.163 5%， 1.870 9 μm and 0.240 3%， the relative percent deviations（RPD） were 3.711 0， 2.760 7 and 5.415 8， respectively. The results of the external validation set demonstrated that the real-time predicted values obtained by the models exhibited the same trend as the measured values， and the coating endpoint could be accurately predicted（with a prediction error of less than 7.32 min and a relative error of less than 5.63%）. ConclusionThe established NIRS model exhibits excellent predictive performance and can be used for quality control of VCYT during the coating process.

Objective To explore the mechanism of mesenchymal epithelial transformation(EMT)mediated by Wnt/β-catenin signaling pathway in the inhibition of endometrial fibrosis by endometrial mesenchymal stem cells(eMSCs).Methods Eighteen female SD rats were randomly divided into Sham group,Model group and eMSCs group,with 6 rats in each group.Rats in Sham group merely had laparotomy without any treatment.A rat model of intrauterine adhesion(IUA)was established in the Model group and eMSCs group.In eMSCs group,the total a-mount of eMSCs cell suspension transplanted immediately after model injury was 0.05 ml(2×107 cells/ml)per u-terus for treatment.Three weeks later,the uterus with unilateral injury was collected for hematoxylin-eosin(HE)staining and Masson staining.Endometrial fibrosis,EMT,Wnt/β-catenin pathway protein expression were analyzed by protein blot.Results In the Model group,the structure of the uterine cavity was destroyed and the number of glands were significantly reduced with a large number of blue collagen fibers were accumulated.However,after eM-SCs treatment,the number of endometrial glands increased,and the fibrotic area decreased significantly.Compared with Sham group,the expression levels of type I collagen and α-SMA protein in Model group increased significantly(P<0.05),but decreased significantly in eMSCs group(P<0.05).In the Model group,the expressions of N-cadherin,vimentin and ZEB1 increased significantly,while the expression of E-cadherin decreased.However,in eMSCs group,the changes of protein of the above molecules were completely opposite.Compared with Sham group,the expression of β-catenin and C-myc increased in Model group(P<0.05).Compared with the Model group,the expressions of CyclinE,β-catenin and C-myc increased in eMSCs group(P<0.05).Conclusion eMSCs can promote endometrial repair in IUA rats by inhibiting EMT and endometrial fibrosis,which is partly achieved by ac-tivating Wnt/β-catenin signaling pathway.

Objective Tissue uptake and distribution of nano-/microplastics was studied at a single high dose by gavage in vivo.Methods Fluorescent microspheres (100 nm, 3 μm, and 10 μm) were given once at a dose of 200 mg/(kg·body weight). The fluorescence intensity (FI) in observed organs was measured using the IVIS Spectrum at 0.5, 1, 2, and 4 h after administration. Histopathology was performed to corroborate these findings.Results In the 100 nm group, the FI of the stomach and small intestine were highest at 0.5 h, and the FI of the large intestine, excrement, lung, kidney, liver, and skeletal muscles were highest at 4 h compared with the control group (P < 0.05). In the 3 μm group, the FI only increased in the lung at 2 h (P < 0.05). In the 10 μm group, the FI increased in the large intestine and excrement at 2 h, and in the kidney at 4 h (P < 0.05). The presence of nano-/microplastics in tissues was further verified by histopathology. The peak time of nanoplastic absorption in blood was confirmed.Conclusion Nanoplastics translocated rapidly to observed organs/tissues through blood circulation;however, only small amounts of MPs could penetrate the organs.