Background: Nonalcoholic fatty liver disease, a progressive condition caused by the accumulation of fat in the liver, begins with simple steatosis and can potentially progress to metabolic dysfunction-associated steatohepatitis (MASH) in the presence of inflammation and fibrosis, ultimately leading to cirrhosis or hepatocellular carcinoma. Increasing evidence indicates that sodiumglucose cotransporter 2 (SGLT2) inhibitors effectively alleviate MASH in mouse models. However, there is a lack of research on the effects of enavogliflozin on liver disease. In the present study, we investigated the effects of SGLT2 inhibitors on MASH induced by a high-fat, high-cholesterol (HFHC) diet in mice. Methods: Male C57BL/6 mice were fed a normal chow diet, HFHC diet, or HFHC diet with enavogliflozin for 12 weeks. LX-2 and HepG2 cells were treated with enavogliflozin in the presence of various pathological stimuli. Results: The HFHC diet induced excessive hepatic lipid accumulation, inflammation, and severe fibrosis. Administration of enavogliflozin not only ameliorated hepatic steatosis and fibrotic conditions but also suppressed the production of inflammatory cytokines. Positive outcomes were also observed in in vitro experiments, where enavogliflozin demonstrated the ability to impede the activation of hepatic stellate cells and alleviate lipid accumulation in hepatocytes. The potential pathway through which enavogliflozin attenuated liver fibrosis development may be associated with the transforming growth factor β1/Smad signaling pathway. Conclusion Our results suggest that enavogliflozin is effective in a mouse model of MASH by attenuating hepatic steatosis, suppressing inflammation, and improving liver fibrosis.

In 2023, nonalcoholic fatty liver disease was renamed metabolic dysfunction-associated steatotic liver disease by the American and European liver associations. This new nomenclature recognizes metabolic dysfunction as the central driver of the disease, and the diagnostic criteria now require the presence of hepatic steatosis plus at least one of five cardiometabolic risk factors. B-mode ultrasonography remains the most common and practical method for detecting hepatic steatosis, although newer ultrasound techniques based on attenuation, backscatter, and speed of sound have gained traction as tools to diagnose and quantify hepatic steatosis. Additionally, ultrasound elastography is increasingly used in routine clinical practice to assess liver fibrosis, diagnose cirrhosis, and identify clinically significant portal hypertension.

In 2023, nonalcoholic fatty liver disease was renamed metabolic dysfunction-associated steatotic liver disease by the American and European liver associations. This new nomenclature recognizes metabolic dysfunction as the central driver of the disease, and the diagnostic criteria now require the presence of hepatic steatosis plus at least one of five cardiometabolic risk factors. B-mode ultrasonography remains the most common and practical method for detecting hepatic steatosis, although newer ultrasound techniques based on attenuation, backscatter, and speed of sound have gained traction as tools to diagnose and quantify hepatic steatosis. Additionally, ultrasound elastography is increasingly used in routine clinical practice to assess liver fibrosis, diagnose cirrhosis, and identify clinically significant portal hypertension.

Background: The genetic basis for hyperglycaemia in pregnancy remain unclear. This study aimed to uncover the genetic determinants of gestational diabetes mellitus (GDM) and investigate their applications. Methods: We performed a meta-analysis of genome-wide association studies (GWAS) for GDM in Chinese women (464 cases and 1,217 controls), followed by de novo replications in an independent Chinese cohort (564 cases and 572 controls) and in silico replication in European (12,332 cases and 131,109 controls) and multi-ethnic populations (5,485 cases and 347,856 controls). A polygenic risk score (PRS) was derived based on the identified variants. Results: Using the genome-wide scan and candidate gene approaches, we identified four susceptibility loci for GDM. These included three previously reported loci for GDM and type 2 diabetes mellitus (T2DM) at MTNR1B (rs7945617, odds ratio [OR], 1.64; 95% confidence interval [CI],1.38 to 1.96]), CDKAL1 (rs7754840, OR, 1.33; 95% CI, 1.13 to 1.58), and INS-IGF2-KCNQ1 (rs2237897, OR, 1.48; 95% CI, 1.23 to 1.79), as well as a novel genome-wide significant locus near TBR1-SLC4A10 (rs117781972, OR, 2.05; 95% CI, 1.61 to 2.62; Pmeta=7.6×10-9), which has not been previously reported in GWAS for T2DM or glycaemic traits. Moreover, we found that women with a high PRS (top quintile) had over threefold (95% CI, 2.30 to 4.09; Pmeta=3.1×10-14) and 71% (95% CI, 1.08 to 2.71; P=0.0220) higher risk for GDM and abnormal glucose tolerance post-pregnancy, respectively, compared to other individuals. Conclusion Our results indicate that the genetic architecture of glucose metabolism exhibits both similarities and differences between the pregnant and non-pregnant states. Integrating genetic information can facilitate identification of pregnant women at a higher risk of developing GDM or later diabetes.

In 2023, nonalcoholic fatty liver disease was renamed metabolic dysfunction-associated steatotic liver disease by the American and European liver associations. This new nomenclature recognizes metabolic dysfunction as the central driver of the disease, and the diagnostic criteria now require the presence of hepatic steatosis plus at least one of five cardiometabolic risk factors. B-mode ultrasonography remains the most common and practical method for detecting hepatic steatosis, although newer ultrasound techniques based on attenuation, backscatter, and speed of sound have gained traction as tools to diagnose and quantify hepatic steatosis. Additionally, ultrasound elastography is increasingly used in routine clinical practice to assess liver fibrosis, diagnose cirrhosis, and identify clinically significant portal hypertension.

Objective To explore the association between aspartate aminotransferase(AST)/alanine aminotransferase(ALT)ratio and metabolic syndrome(MS)in elderly hypertensive patients,and to provide reference for early detection and prevention of MS in elderly hypertensive patients.Methods A questionnaire survey and physical examination were conducted among 616 elderly hypertensive patients at community health service centers.Participants were divided into two groups based on MS status:MS group(n=334)and non-MS group(n=282).According to AST/ALT levels,participants were divided into four groups:q1 group(AST/ALT ≤0.88,n=156),q2 group(0.88＜AST/ALT ≤ 1.10,n=155),q3 group(1.10＜AST/ALT ≤ 1.37,n=154),and q4 group(AST/ALT＞1.37,n=151).Blood biochemical parameters including triglycerides(TG),high-density lipoprotein cholesterol(HDL-C),AST,ALT,and blood glucose were measured.The impact of AST/ALT levels on MS was analyzed using a Logistic regression model,while the risk prediction for MS occurrence was evaluated through receiver operating characteristic(ROC)curves.Results MS group showed higher body mass index(BMI),TG,ALT levels,abnormal glucose levels,female proportion,and abdominal obesity rate compared to non-MS group.HDL-C and AST/ALT values of MS group were lower than those in non-MS patients(P＜0.05).Logistic regression analysis revealed that after adjusting for BMI,smoking,alcohol consumption,physical activity,education level,marital status,TG,HDL-C,and glucose levels,both q3 and q4 groups demonstrated reduced MS risk compared to group q1 group(P＜0.05).ROC curve analysis indicated that the area under the curve for AST/ALT in MS was 0.638(P＜0.05).Conclusion The level of AST/ALT was negatively correlated with MS in elderly hypertensive patients,and AST/ALT has certain predictive value for the risk of MS in elderly hypertensive patients.

Objective:To observe any effect of supplementing treatment according to the Early Start Denver model (ESDM) with repeated transcranial magnetic stimulation (rTMS) in the treatment of children with autism spectrum disorder (ASD).Methods:Sixty-seven children on the autism spectrum aged 2 or 3 years were randomly divided into a control group of 33 and an observation group of 34. Both groups were treated as specified by the ESDM for 24 weeks, but the observation group additionally received rTMS. At 12 and 24 weeks, both groups were evaluated using the Autism Behavior Checklist, the Childhood Autism Rating Scale (CARS), the revised version of the Repetitive Behavior Scale (RBS-R), Gesell Development Schedules, and the Autism Treatment Evaluation Checklist (ATEC).Results:The CARS, Gesell, RBS-R and ATEC results of both groups had improved significantly after 12 weeks, with further improvements observed another 12 weeks later, when the average Autism Behavior Checklist scores had also improved significantly. At that point the results of the observation group were significantly better than those of the control group, on average.Conclusions:Combining ESDM and rTMS can significantly relieve the main symptoms of autism and improve the comprehensive development of children on the autism spectrum 2 or 3 years old. Therefore, such combination is worthy of application in clinical practice.

Objective:To compare the efficacy and safety of crisaborole ointment 2% versus pimecrolimus cream 1% in the treatment of mild to moderate atopic dermatitis in children aged 2 years or older.Methods:A multicenter, randomized, open-label, controlled clinical trial was conducted. A total of 120 pediatric patients aged 2 - 17 years with mild to moderate atopic dermatitis were enrolled from departments of dermatology of 8 hospitals in China between March 2022 and February 2023. The participants were randomly assigned in a 1∶1 ratio to the crisaborole group and the pimecrolimus group, and received the treatment with crisaborole ointment 2% and pimecrolimus cream 1% respectively, twice a day for 4 weeks. Visits were scheduled at baseline/on day 1, as well as on days 8, 15, and 29. The primary efficacy outcome was the percentage of patients achieving the Investigator's Static Global Assessment (ISGA) success (defined as clear [0] or almost clear [1] on the ISGA scale, combined with ≥ 2‐grade improvement from baseline) on day 29. The secondary efficacy outcomes included changes in the Eczema Area and Severity Index (EASI) total scores from baseline to day 29, percentages of patients achieving ISGA improvement (defined as clear [0] or almost clear [1] on the ISGA scale), as well as changes in the Peak Pruritus Numerical Rating Scale (NRS) scores, Dermatology Life Quality Index (DLQI) /Infants' Dermatology Life Quality Index (IDLQI) /Children's Dermatology Life Quality Index (CDLQI) scores, and in the Dermatitis Family Impact (DFI) scores. Drug safety was evaluated according to the incidence of adverse events. Categorical data were compared using the chi-square test. Since measurement data did not follow a normal distribution, the rank sum test was used for comparisons of measurement data between groups.Results:A total of 106 children with mild to moderate atopic dermatitis were included in the per-protocol analysis set, with 52 in the crisaborole group (26 males and 26 females) and 54 in the pimecrolimus group (27 males and 27 females). There were no significant differences in age, disease duration, ISGA and EASI scores at baseline between the two groups (all P > 0.05). On day 29, 22 patients (42.31%) in the crisaborole group and 25 (46.30%) in the pimecrolimus group achieved ISGA success, with no significant difference between the two groups ( χ2 = 0.17, P = 0.68) ; 35 patients (67.31%) in the crisaborole group and 45 (83.33%) in the pimecrolimus group achieved ISGA improvement, also with no significant difference between the two groups ( χ2 = 3.68, P = 0.06) ; additionally, there were no significant differences in the EASI, pruritus NRS, DLQI/IDLQI/CDLQI, or DFI scores between the two groups (all P > 0.05). Adverse reactions to the two topical agents were mainly local reactions such as mild to moderate pain, itching, or worsening of itching, and no obvious systemic adverse reactions occurred. The incidence of drug-related adverse reactions was 46.15% (24 cases) in the crisaborole group and 37.04% (20 cases) in the pimecrolimus group, with no significant difference between the two groups ( χ2 = 0.91, P = 0.34) . Conclusion:The efficacy of crisaborole ointment 2% was comparable to that of pimecrolimus cream 1% in the treatment of mild to moderate atopic dermatitis in children aged ≥ 2 years, and it yielded early and rapid improvement in the quality of life of patients and their families, with good safety and tolerability profiles.

Aim To study the effect of p-benzoyl sali-droside(pOBz)on angiogenesis after ischemic stroke and to explore the underlying mechanism.Methods The MCAO model was prepared by suture method.Rats were divided into four groups:sham,MCAO,pOBz administration,and edaravone positive control,treated for seven days.The mNSS was used to assess the neurological impairment.Western blotting was em-ployed to detect CD31,NICD,and Hes-1 protein ex-pression,while immunofluorescence staining was ap-plies to quantify CD31-positive cells in ischemic brain tissue.In vitro an OGD/R model was established in HUVECs.Following treatment with varying pOBz con-centrations(0.01,0.1,1 μmol·L-1),the CCK-8 as-say was uses to measure cell viability,and in vitro tube formation assay was utilized to evaluate angiogenesis.Western blotting was employed again to assess CD31,NICD and Hes-1 protein levels.To further elucidate the mechanism,HUVEC were treated with the Notch inhibitor DAPT prior to grouping and pOBz administra-tion,and the same parameters were evaluated.Results pOBz significantly reduced the mNSS score of MCAO rats,increased CD31-positive cell counts,and upregu-lated CD31,NICD,and Hes-1 protein expression(P＜0.01).In vitro results further showed that pOBz could dose-dependently increase the survival rate and angio-genesis ability of HUVEC induced by OGD/R,and promote CD31,NICD and Hes-1 proteins(P＜0.01),and Notch inhibitor DAPT could reverse the above effects of pOBz.Conclusion pOBz promotes angio-genesis in HUVEC,and its mechanism involves activa-tion of the Notch signaling pathway.