Objective:To investigate the association of skeletal muscle fat index(SMFI) with insulin resistance and type 2 diabetes mellitus.Methods:This retrospective study included 1 100 patients from Department of Geriatric, Renji Hospital, Shanghai Jiao Tong University School of Medicine from October 2020 to October 2023. The SMFI measured by chest computed tomography(CT) is used as an indicator to evaluate the quality of skeletal muscle. Spearman and linear regression analysis were used to evaluate the association between SMFI and homoeostasis model assessment for insulin resistance(HOMA-IR). Multivariate logistic regression analysis and restricted cubic spline(RCS) were used to analyze the association of HOMA-IR with the prevalence of type 2 diabetes mellitus. Finally, interaction and stratified analyses were conducted according to age, sex, body mass index, estimated glomerular filtration rate, uric acid, skeletal muscle index(SMI), smoking, alcohol drinking, hypertension, and dyslipidemia.Results:SMFI showed a significant positive correlation with HOMA-IR( r=0.385, P<0.001). Each 1-unit increase in SMFI led to 0.009, 0.011, 0.004, 0.004, and 0.004 rise in HOMA-IR across adjusted models(all P<0.05). Then subjects were stratified into tertiles( T1, T2, and T3) according to SMFI. Logistic regression analysis revealed that the prevalence of type 2 diabetes mellitus significantly increased in T2( OR=2.37, 95% CI 1.30-4.31, P=0.005) and T3( OR=2.85, 95% CI 1.39-5.86, P=0.004) compared to T1. RCS analysis showed that the prevalence of type 2 diabetes mellitus increased with the increase of SMFI when SMFI<157.195. The results of subgroup analysis showed that female, under 60 years old, body mass index<24 kg/m 2, uric acid<420 μmol/L, low SMI, non-smoking, non-alcoholic drinking, and non-hypertensive individuals with higher SMFI were more likely to develop type 2 diabetes mellitus. Conclusions:Elevated SMFI is positively associated with insulin resistance and type 2 diabetes mellitus risk. Reducing SMFI below 157.195 may significantly lower the risk of type 2 diabetes mellitus.

Objective:To construct the risk prediction nomogram model of acute kidney injury (AKI) with R language and traditional statistical methods based on the large sample clinical database, and verify the accuracy of the model.Methods:It was a a retrospective case control study. The patients who met the diagnostic criteria of AKI in Tongji Hospital of Tongji University from January 1 to December 31, 2021 were screened in the clinical database, and the patients with monitored serum creatinine within 48 hours but without AKI were included as the control group. The demographic data, disease history, surgical history, medication history and laboratory test data were collected to screen the risk factors of AKI in clinic.Firstly, based on multivariate logistic regression analysis and forward stepwise logistic regression analysis, the selected risk factors were included to construct the nomogram model. At the same time, cross validation, bootstrap validation and randomly split sample validation were used for internal verification, and clinical data of patients in the sane hospital after one year (January to December, 2022) were collected for external verification. The receiver-operating characteristic curve was used to determine the discrimination of the model, and calibration curve and decision curve analysis were carried out to evaluate the accuracy and clinical net benefit, respectively.Results:A total of 5 671 patients were enrolled in the study, with 1 884 AKI patients (33.2%) and 3 787 non-AKI patients (66.7%). Compared with non-AKI group, age, and proportions of surgical history, renal replacement therapy, hypertension, diabetes, cerebrovascular accident,chronic kidney disease, drug use histories and mortality in AKI group were all higher (all P<0.05). Multivariate logistic regression analysis showed that the independent influencing factors of AKI were surgical history, hypertension, cerebrovascular accident, diabetes, chronic kidney disease, diuretics, nitroglycerin, antidiuretic hormones, body temperature, serum creatinine, C-reactive protein, red blood cells, white blood cells, D-dimer, myoglobin, hemoglobin, blood urea nitrogen, brain natriuretic peptide, aspartate aminotransferase, alanine aminotransferase, triacylglycerol, lactate dehydrogenase, total bilirubin, activated partial thromboplastin time, blood uric acid and potassium ion (all P<0.05). Finally, the predictive factors in the nomogram were determined by forward stepwise logistic regression analysis, including chronic kidney disease, hypertension, myoglobin, serum creatinine and blood urea nitrogen, and the area under the curve of the prediction nomogram model was 0.926 [95% CI 0.918-0.933, P<0.001]. The calibration curve showed that the calibration effect of nomogram was good ( P>0.05). The decision curve showed that when the risk threshold of nomogram model was more than 0.04, the model construction was useful in clinic. In addition, the area under the curve of receiver-operating characteristic curve predicted by nomograph model in external validation set was 0.876 (95% CI 0.865-0.886), which indicated that nomograph model had a high discrimination degree. Conclusion:A nomogram model for predicting the occurrence of AKI is established successfully, which is helpful for clinicians to find high-risk AKI patients early, intervene in time and improve the prognosis.

Objective By investigating the effects of miR-379-5p on the proliferation,invasion and metastasis of mouse breast cancer 4T1 cells,we aimed to provide new therapeutic targets for the clinical inhibition of breast cancer proliferation,invasion,and metastasis.Methods After plasmid transfection,4T1 cells were utilized to detect the expression of miR-379-5p using fluorescence quantitative PCR.While 5-ethynyl-2'doxyuridine(EdU)cell proliferation and Transwell assays were employed to detect changes in the proliferation and invasion ability of 4T1 cells in each group.The migration ability of 4T1 cells after overexpression and knockdown of miR-379-5p was examined by scratch healing assay.A transplanted tumor model of breast cancer was established in BABL/c mice,and the effects of overexpressing miR-379-5p on tumor growth and the number and size of lung metastases were observed.Results EdU result showed that knocking down miR-379-5p enhanced the proliferation ability of the cells compared with the control group cells,and miR-379-5p overexpression reduced the capacity of breast cancer cells to proliferate(P＜0.05).Transwell and wound healing assays showed that miR-379-5p knockdown enhanced,while miR-379-5p overexpression significantly inhibited,the invasion and migratory ability of breast cancer cells(P＜0.01).An in vivo tumorigenesis experiment with BABL/c mice showed that miR-379-5p overexpression significantly slowed the tumor growth rate(P＜0.05)and inhibited lung metastasis(P＜0.01).Conclusions MiR-379-5p plays a role in tumor gene suppression in breast cancer and inhibits the proliferation,invasion,and migration of mouse breast cancer 4T1 cells.

Objective:Exploring the role and mechanism of gremlin-1 in lipotoxicity-mediated pancreatic β-cell dysfunction.Methods:The model of lipid toxicity-mediated pancreatic β-cell dysfunction was constructed using palmitic acid(PA) to treat mouse pancreatic β-cells(MIN6). Initially, to clarify the effects of lipotoxicity on islet β-cells, the cellular lipid deposition and changes in the levels of insulin caused by PA were detected. The effects of PA on gremlin-1 expression and its downstream signaling pathway BMPs/Smads were further investigated using qPCR and Western Blot assay. Subsequently, recombinant mouse gremlin-1 protein and BMP signaling pathway inhibitor LDN193189 were used to intervene the cells to explore the effects of gremlin-1 and its downstream signaling pathway BMPs/Smads on pancreatic islet β-cells.Results:PA could reduce pancreatic β-cell viability and insulin secretion capacity( P<0.05). Meanwhile, PA inhibited the expression and secretion of cell gremlin-1 and upregulated BMP-4 and its downstream Smad-1 and Smad-5( P<0.05). Intervention of cells with recombinant mouse gremlin-1 protein resulted in a significant elevation of insulin secretion and a concomitant decrease in the expression of key molecules in the BMP4/Smads signaling pathway( P<0.05). And inhibition of the BMP4/Smads signaling pathway ameliorated PA-induced pancreatic β-cell dysfunction. Conclusion:Gremlin-1 is involved in the regulation of lipotoxicity-mediated pancreatic islet β-cell dysfunction, and this effect may be associated with activation of BMP4/Smads signaling pathway.

Objective:To investigate the association of skeletal muscle fat index(SMFI) with insulin resistance and type 2 diabetes mellitus.Methods:This retrospective study included 1 100 patients from Department of Geriatric, Renji Hospital, Shanghai Jiao Tong University School of Medicine from October 2020 to October 2023. The SMFI measured by chest computed tomography(CT) is used as an indicator to evaluate the quality of skeletal muscle. Spearman and linear regression analysis were used to evaluate the association between SMFI and homoeostasis model assessment for insulin resistance(HOMA-IR). Multivariate logistic regression analysis and restricted cubic spline(RCS) were used to analyze the association of HOMA-IR with the prevalence of type 2 diabetes mellitus. Finally, interaction and stratified analyses were conducted according to age, sex, body mass index, estimated glomerular filtration rate, uric acid, skeletal muscle index(SMI), smoking, alcohol drinking, hypertension, and dyslipidemia.Results:SMFI showed a significant positive correlation with HOMA-IR( r=0.385, P<0.001). Each 1-unit increase in SMFI led to 0.009, 0.011, 0.004, 0.004, and 0.004 rise in HOMA-IR across adjusted models(all P<0.05). Then subjects were stratified into tertiles( T1, T2, and T3) according to SMFI. Logistic regression analysis revealed that the prevalence of type 2 diabetes mellitus significantly increased in T2( OR=2.37, 95% CI 1.30-4.31, P=0.005) and T3( OR=2.85, 95% CI 1.39-5.86, P=0.004) compared to T1. RCS analysis showed that the prevalence of type 2 diabetes mellitus increased with the increase of SMFI when SMFI<157.195. The results of subgroup analysis showed that female, under 60 years old, body mass index<24 kg/m 2, uric acid<420 μmol/L, low SMI, non-smoking, non-alcoholic drinking, and non-hypertensive individuals with higher SMFI were more likely to develop type 2 diabetes mellitus. Conclusions:Elevated SMFI is positively associated with insulin resistance and type 2 diabetes mellitus risk. Reducing SMFI below 157.195 may significantly lower the risk of type 2 diabetes mellitus.

Objective To investigate the effect of fenofibrate on glucolipid metabolism and insulin sensitivity in lipoprotein lipase heterozygous knockout ( LPL+/-) mice, and to explore its mechanism. Methods LPL+/- mice and wild type ( WT) C57 mice were selected and divided into 3 groups ( n=6 each group):LPL+/-( FB) group, LPL+/-(W)group,andWTgroup.MiceinLPL+/-(FB)groupweregavagedwithfenofibrate(50mg·kg-1·d-1)for8 weeks. Mice in LPL+/-( W) and WT groups were orally fed with the same volume water as that in LPL+/-( FB) group for 8 weeks. Body weight was observed. Plasma triglyceride ( TG ) and free fatty acid ( FFA ) were measured. Intraperitoneal glucose tolerance test in 3 groups of mice were performed. The glucose area under the curve ( AUCG) and homeostasis model assessment for insulin resistance index ( HOMA-IR) were calculated. Insulin-stimulated Ser473 Akt phosphorylation in liver and skeletal muscle was measured by Western blot. Reactive oxygen species ( ROS) levels in liver and skeletal muscle were determined by dihydroethidium staining method and superoxide dismutase ( SOD) and catalase ( CAT) mRNA expression levels were detected by real-time PCR. Results Compared with LPL+/-( W) mice, body weight of LPL+/-( FB) mice was lowered, plasma TG and FFA levels were decreased by about 46.0％and 76.5％respectively, and fasting insulin level and HOMA-IR were decreased while there were no significant differences in fasting glucose level and AUCG between two groups. Insulin-stimulated Ser473 Akt phosphorylation levels in liver and skeletal muscle of LPL+/-mice were enhanced by fenofibrate. ROS level in skeletal muscle of LPL+/-( FB) mice was lower than that in LPL+/-( W) mice while there was no significant difference in ROS of liver between two groups. Fenofibrate significantly increased SOD and CAT mRNA expressions in skeletal muscle of LPL+/-mice, but not in liver. Conclusion Fenofibrate reduces body weight, ameliorates lipid metabolism, and improves insulin sensitivity in LPL+/- mice, with reduced oxidative stress.

Objective To analyze the differential expression of microRNA-146a (miR-146a) in monocyte-macrophage cell line (THP-1 cells) after induction by Cryptococcus neoformans (C.neoformans,reference strain WM148) or Cryptococcus gattii (C.gattii,reference strain R265),and investigate the mechanism of miR-146a in regulating the inflammatory response of cryptococcal meningitis.Methods The cultured THP-1 cells were divided into two groups to be induced by C.neoformans or C.gattii,respectively.THP-1 cells were induced with inactivated WN148 (or R265) strains at multiplicity of infection (MOI) of 5 in all experiments.The supematant and the cell pellet were collected separately after incubation.The expression of miR-146a was measured by real-time quantitative PCR (qRT-PCR) technique.The levels of TNF-u and IL-6 release were assayed by ELISA.Results The expression of miR-146a increased significantly in the C.neoformans induction group compared to 0 h.It reached peak at 3 h (P＜0.01),and then declined gradually.The level of TNF-α increased in supematant and reached peak at 12 h.The expression of IL-6 did not change significantly at each time point.The expression of miR-146a and TNF-α increased gradually and reached peak at 12 h in the C.gattii induction group (P ＜0.01),but the change did not reach statistical significance at 3 h,6 h time points.The expression of IL-6 gradually increased,and reached peak at 12 h time point.Conclusions Following stimulation with C.neoformans or C.gattii,the expression ofmiR-146a in THP-1 cells showed different patterns over time.The expression levels of TNF-α and IL-6 showed different patterns.These findings suggest that there may be different regulatory mechanisms in the THP-1 cells-associated inflammatory response after stimulation by inactivated C.neoformans and C.gattii strains.

FXYD6, FXYD domain containing ion transport regulator 6, has been reported to affect the activity of Na(+)/K(+)-ATPase and be associated with mental diseases. Here, we demonstrate that FXYD6 is up-regulated in hepatocellular carcinoma (HCC) and enhances the migration and proliferation of HCC cells. Up-regulation of FXYD6 not only positively correlates with the increase of Na(+)/K(+)-ATPase but also coordinates with the activation of its downstream Src-ERK signaling pathway. More importantly, blocking FXYD6 by its functional antibody significantly inhibits the growth potential of the xenografted HCC tumors in mice, indicating that FXYD6 represents a potential therapeutic target toward HCC. Altogether, our results establish a critical role of FXYD6 in HCC progression and suggest that the therapy targeting FXYD6 can benefit the clinical treatment toward HCC patients.
Animals ; Antibodies, Monoclonal ; pharmacology ; Antineoplastic Agents ; pharmacology ; Carcinoma, Hepatocellular ; drug therapy ; metabolism ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Female ; HEK293 Cells ; Humans ; Ion Channels ; antagonists & inhibitors ; metabolism ; Liver Neoplasms ; drug therapy ; metabolism ; Mice, Inbred BALB C ; Mice, Nude ; Sodium-Potassium-Exchanging ATPase ; metabolism ; Tumor Burden ; drug effects ; Xenograft Model Antitumor Assays

Objective To explore the clinical safety and validity of Da Vinci surgical system in distal pancreatic tumor resection.Methods The clinical data of 14 patients with distal pancreatic tumor underwent robotic surgeries by using Da Vinci surgical system from January 2009 to June 2012 were retrospectively analyzed.Results The average operation time was 343.93 (170-575) min,average blood loss was 192.5 (10-700) ml,without blood trahsfusion.Pathologic examination showed:pancreatic ductal adenocarcinoma in 7 patients,pancreatic cystadenoma in 1 patient,mucous cystadenoma in 1 patient,cystadenocarcinoma in 1 patient,high levels of pancreatic ductal intraepithelial neoplasia in 1 patient,insulinoma in 1 patient,solid pseudo-papillary tumor in 2 patients.Two patients with pancreatic leaks after operation and then relieved after conservative medical therapy.Others were discharged from hospital without complications.The average hospital stay was 10.64 d.Conclusions Da Vinci surgical system is safe and effective in treatment for patients with distal pancreatic rumor with minimally invasive advantage.Because lack of surgical experience and small sample,a large sample with long term follow-up of high-quality clinical research is required and then update the system to evaluate the efficacy and safety.

ObjectiveTo explore the value of expanded radical resection for gallbladder cancer located respectively at body and bottom of the gallbladder and at the neck.MethodsIn this study,91 cases of gallbladder cancer were macropathologically divided into two groups, one with the lesion at the body and bottom of the gallbladder and the other at the neck, survival analysis was made accordingly. Three different kinds of resection were performed: the expanded radical resection, the standard radical resection and palliative operation.ResultsThe overall median survival rate of patients undergoing expanded radical operation was significantly longer than that of the cases doing other two procedures, that was 27. 1 ± 2. 4,10. 7 ±2. 2,4. 7 ±2.2 (months) respectively for body and bottom cancer, and 8.5 ±2. 1,6. 7 ± 1.9,3.1 ± 1.1 (months) respectively for neck cancer. For cancer at the body and bottom RO was achieved by expanded radical resection in 16/18(88％ ) cases and by standard radical resection in 7/12(58％ ) cases, while for cancer at the neck it was in 6/16(38％ ) cases, and in 3/13 (23％)cases only.ConclusionsThe median survival time is longer and RO resection rate is higher in patients with the cancer at the body and bottom than these at the neck of the gallbladder.