Objective:To investigate the protective effect of Akebia saponin D(ASD)on non-alcoholic fatty liver disease(NAFLD)in rats by regulating IL-6/STAT3 axis.Methods:Fifty SD rats were separated into control group,model group,low dose ASD group(ASD 20 mg/kg),high dose ASD group(ASD 40 mg/kg)and inhibitor group(ASD 40 mg/kg+IL-6/STAT3 signal pathway inhibitor LMT-28 3 mg/kg),with 10 rats in each group.Rats in control group were fed with standard diet,while the other four groups were fed with high fat and high sugar diet.All rats were fed for 6 consecutive weeks,and the corresponding dose of drugs was injected intraperitoneally from the 7th week,which were given drugs for 8 consecutive weeks.All rats were weighed to calculate liver index;levels of serum total cholesterol(TC),alanine aminotransferase(ALT),aspartate aminotransferase(AST)and triglyceride(TG)were mea-sured by automatic biochemical analyzer;HE staining was used to observe pathological changes of rats liver;oil red staining was used to observe lipid accumulation in rats liver;expressions of IL-6,JAK1,STAT3 in rats liver were detected by qRT-PCR;Western blot was used to detect expressions of IL-6,JAK1,p-JAK1,STAT3 and p-STAT3 proteins.Results:Compared with control group,hepatocytes in liver tissue of model group were swollen,accompanied by many ballooning changes,severe cytoplasmic vacuolization,the structure of hepatic lobule was unclear,and accompanied by inflammatory cell infiltration,and obvious red granular lipid droplets occupied most of the cytoplasm,body mass,liver index,levels of serum TC,ALT,AST,TG,expressions of IL-6,JAK1,STAT3 mRNAs,and IL-6,p-JAK1/JAK1,p-STAT3/STAT3 proteins in liver tissue of rats were obviously increased(P<0.05);compared with model group,damage of hepatic lobule structure in low and high doses ASD groups were reduced,swelling and vacuolization of liver cells were reduced,and accumulation of lipid droplets in liver tissue was obviously reduced.Body mass,liver index,levels of serum TC,ALT,AST and TG in rats were obviously decreased(P<0.05),while expressions of IL-6,JAK1,STAT3 mRNAs and IL-6,p-JAK1/JAK1,p-STAT3/STAT3 proteins in liver tissue were further increased(P<0.05);LMT-28,an inhibitor of IL-6/STAT3 signaling pathway,attenuated the liver protective effect of ASD on NAFLD rats.Conclusion:ASD can protect liver of NAFLD rats by activating IL-6/STAT3 signaling pathway.

Objective:To investigate the association of skeletal muscle function(including muscle strength and physical performance) and insulin resistance as well as type 2 diabetes mellitus(T2DM).Methods:The retrospective study included 942 patients who visited the Department of Geriatrics at Renji Hospital, Shanghai Jiao Tong University School of Medicine, between October 2020 and July 2024. Low skeletal muscle function was defined as either reduced muscle strength or impaired physical performance. Muscle strength was assessed by grip strength, while physical performance was evaluated using the 5-time chair stand test. The associations between muscle function, insulin resistance, and T2DM were analyzed.Results:A significant association was observed between decreased skeletal muscle function and a higher prevalence of T2DM( P=0.001). Further analysis revealed that decreased physical performance was significantly associated with increased T2DM prevalence( P<0.001), whereas reduced muscle strength showed no significant association with T2DM prevalence( P=0.331). Linear regression analysis indicated that both the homeostasis model assessment of insulin resistance(HOMA2-IR) and fasting blood glucose levels increased significantly with longer chair stand times( P<0.05). Restrictive cubic spline(RCS) analysis demonstrated a nonlinear relationship between chair-rising time and HOMA2-IR. Notably, when the cumulative chair-rising time exceed 8.1 s, HOMA2-IR increased significantly with prolonged chair stand time. Logistic regression analysis showed that compared with patients with normal physical performance, those with decreased physical performance had significantly higher odds of T2DM( OR=2.64, P<0.001) and insulin resistance( OR=2.34, P=0.002). Conclusion:Decline in physical performance is significantly positively associated with insulin resistance and the risk of T2DM. Morever, when the cumulative chair stand time exceed 8.1 s, HOMA2-IR increases progressively with further prolongation of chair stand time.

Objective:To investigate the association of skeletal muscle function(including muscle strength and physical performance) and insulin resistance as well as type 2 diabetes mellitus(T2DM).Methods:The retrospective study included 942 patients who visited the Department of Geriatrics at Renji Hospital, Shanghai Jiao Tong University School of Medicine, between October 2020 and July 2024. Low skeletal muscle function was defined as either reduced muscle strength or impaired physical performance. Muscle strength was assessed by grip strength, while physical performance was evaluated using the 5-time chair stand test. The associations between muscle function, insulin resistance, and T2DM were analyzed.Results:A significant association was observed between decreased skeletal muscle function and a higher prevalence of T2DM( P=0.001). Further analysis revealed that decreased physical performance was significantly associated with increased T2DM prevalence( P<0.001), whereas reduced muscle strength showed no significant association with T2DM prevalence( P=0.331). Linear regression analysis indicated that both the homeostasis model assessment of insulin resistance(HOMA2-IR) and fasting blood glucose levels increased significantly with longer chair stand times( P<0.05). Restrictive cubic spline(RCS) analysis demonstrated a nonlinear relationship between chair-rising time and HOMA2-IR. Notably, when the cumulative chair-rising time exceed 8.1 s, HOMA2-IR increased significantly with prolonged chair stand time. Logistic regression analysis showed that compared with patients with normal physical performance, those with decreased physical performance had significantly higher odds of T2DM( OR=2.64, P<0.001) and insulin resistance( OR=2.34, P=0.002). Conclusion:Decline in physical performance is significantly positively associated with insulin resistance and the risk of T2DM. Morever, when the cumulative chair stand time exceed 8.1 s, HOMA2-IR increases progressively with further prolongation of chair stand time.

Objective:To investigate the protective effect of Akebia saponin D(ASD)on non-alcoholic fatty liver disease(NAFLD)in rats by regulating IL-6/STAT3 axis.Methods:Fifty SD rats were separated into control group,model group,low dose ASD group(ASD 20 mg/kg),high dose ASD group(ASD 40 mg/kg)and inhibitor group(ASD 40 mg/kg+IL-6/STAT3 signal pathway inhibitor LMT-28 3 mg/kg),with 10 rats in each group.Rats in control group were fed with standard diet,while the other four groups were fed with high fat and high sugar diet.All rats were fed for 6 consecutive weeks,and the corresponding dose of drugs was injected intraperitoneally from the 7th week,which were given drugs for 8 consecutive weeks.All rats were weighed to calculate liver index;levels of serum total cholesterol(TC),alanine aminotransferase(ALT),aspartate aminotransferase(AST)and triglyceride(TG)were mea-sured by automatic biochemical analyzer;HE staining was used to observe pathological changes of rats liver;oil red staining was used to observe lipid accumulation in rats liver;expressions of IL-6,JAK1,STAT3 in rats liver were detected by qRT-PCR;Western blot was used to detect expressions of IL-6,JAK1,p-JAK1,STAT3 and p-STAT3 proteins.Results:Compared with control group,hepatocytes in liver tissue of model group were swollen,accompanied by many ballooning changes,severe cytoplasmic vacuolization,the structure of hepatic lobule was unclear,and accompanied by inflammatory cell infiltration,and obvious red granular lipid droplets occupied most of the cytoplasm,body mass,liver index,levels of serum TC,ALT,AST,TG,expressions of IL-6,JAK1,STAT3 mRNAs,and IL-6,p-JAK1/JAK1,p-STAT3/STAT3 proteins in liver tissue of rats were obviously increased(P<0.05);compared with model group,damage of hepatic lobule structure in low and high doses ASD groups were reduced,swelling and vacuolization of liver cells were reduced,and accumulation of lipid droplets in liver tissue was obviously reduced.Body mass,liver index,levels of serum TC,ALT,AST and TG in rats were obviously decreased(P<0.05),while expressions of IL-6,JAK1,STAT3 mRNAs and IL-6,p-JAK1/JAK1,p-STAT3/STAT3 proteins in liver tissue were further increased(P<0.05);LMT-28,an inhibitor of IL-6/STAT3 signaling pathway,attenuated the liver protective effect of ASD on NAFLD rats.Conclusion:ASD can protect liver of NAFLD rats by activating IL-6/STAT3 signaling pathway.

Objective:To analyze the efficacy and safety of daratumumab plus dexamethasone in the treatment of renal injury patients with light chain amyloidosis, and to provide clinical reference.Methods:It was a single center retrospective observational study. The clinical data before and after daratumumab treatment of renal injury patients with light chain amyloidosis treated with daratumumab plus dexamethasone from December 2021 to August 2022 were retrospectively collected. The hematologic response, kidney response, prognosis, and adverse events were analyzed. The treatment regimen was 16 mg/kg intravenous infusion of daratumumab on day 1 + 20 mg intravenous push of dexamethasone on day 1-2, once every 2 weeks. The follow-up was up to February 28, 2023.Results:The study included 18 patients, with age of (58.4±7.7) years old, and a male to female ratio of 11∶7. Eleven patients were newly diagnosed and 7 patients were retreated. There were 7, 5, 5 and 1 patients, respectively at the stage Ⅰ, Ⅱ, Ⅲ and Ⅳ of light chain amyloidosis according to 2012 Mayo stage criteria. The median course of disease before onset was 2.5 (1.0, 8.0) months and the follow-up time was (8.7±2.8) months. The patients received (10±3) times of treatment. The overall hematologic response rates were 9/13, 11/13 and 13/13 at 1 month, 3 months, and 6 months respectively after treatment, meanwhile 8/13, 10/13 and 12/13 achieved at least very good partial response at 1 month, 3 months, and 6 months respectively (the other 5 patients did not undergo detailed evaluation due to baseline difference of serum free κ and λ light chain <20 mg/L). The median duration of hematologic response was 16 (13, 40) days. At 3 months, 6 months and the end of follow-up, 10, 13 and 13 of 18 patients respectively achieved renal response, and the median duration of response was 66 (26, 182) days. During follow-up, the median difference of serum free κ and λ light chain decreased by 93% (72%, 97%). Until the last follow-up, one patient died of organ hemorrhage. Other infusion reactions, leukopenia, neutropenia and infection all improved after symptomatic treatments.Conclusion:Daratumumab plus dexamethasone treatment is effective for light chain amyloidosis nephropathy in inducing hematologic remission and kidney remission, with good safety.

Temporomandibular joint (TMJ) diseases are common clinical conditions. The number of patients with TMJ diseases is large, and the etiology, epidemiology, disease spectrum, and treatment of the disease remain controversial and unknown. To understand and master the current situation of the occurrence, development and prevention of TMJ diseases, as well as to identify the patterns in etiology, incidence, drug sensitivity, and prognosis is crucial for alleviating patients′suffering.This will facilitate in-depth medical research, effective disease prevention measures, and the formulation of corresponding health policies. Cohort construction and research has an irreplaceable role in precise disease prevention and significant improvement in diagnosis and treatment levels. Large-scale cohort studies are needed to explore the relationship between potential risk factors and outcomes of TMJ diseases, and to observe disease prognoses through long-term follw-ups. The consensus aims to establish a standard conceptual frame work for a cohort study on patients with TMJ disease while providing ideas for cohort data standards to this condition. TMJ disease cohort data consists of both common data standards applicable to all specific disease cohorts as well as disease-specific data standards. Common data were available for each specific disease cohort. By integrating different cohort research resources, standard problems or study variables can be unified. Long-term follow-up can be performed using consistent definitions and criteria across different projects for better core data collection. It is hoped that this consensus will be facilitate the development cohort studies of TMJ diseases.

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 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.

Spinal cord injury (SCI) causes motor, sensory, and autonomic dysfunctions. The gut microbiome has an important role in SCI, while short-chain fatty acids (SCFAs) are one of the main bioactive mediators of microbiota. In the present study, we explored the effects of oral administration of exogenous SCFAs on the recovery of locomotor function and tissue repair in SCI. Allen's method was utilized to establish an SCI model in Sprague-Dawley (SD) rats. The animals received water containing a mixture of 150 mmol/L SCFAs after SCI. After 21 d of treatment, the Basso, Beattie, and Bresnahan (BBB) score increased, the regularity index improved, and the base of support (BOS) value declined. Spinal cord tissue inflammatory infiltration was alleviated, the spinal cord necrosis cavity was reduced, and the numbers of motor neurons and Nissl bodies were elevated. Enzyme-linked immunosorbent assay (ELISA), real-time quantitative polymerase chain reaction (qPCR), and immunohistochemistry assay revealed that the expression of interleukin (IL)‍-10 increased and that of IL-17 decreased in the spinal cord. SCFAs promoted gut homeostasis, induced intestinal T cells to shift toward an anti-inflammatory phenotype, and promoted regulatory T (Treg) cells to secrete IL-10, affecting Treg cells and IL-17⁺ γδ T cells in the spinal cord. Furthermore, we observed that Treg cells migrated from the gut to the spinal cord region after SCI. The above findings confirm that SCFAs can regulate Treg cells in the gut and affect the balance of Treg and IL-17⁺ γδ T cells in the spinal cord, which inhibits the inflammatory response and promotes the motor function in SCI rats. Our findings suggest that there is a relationship among gut, spinal cord, and immune cells, and the "gut-spinal cord-immune" axis may be one of the mechanisms regulating neural repair after SCI.
Animals ; Rats ; Interleukin-17 ; Rats, Sprague-Dawley ; Recovery of Function ; Spinal Cord Injuries/drug therapy* ; T-Lymphocytes, Regulatory ; Receptors, Antigen, T-Cell, gamma-delta/immunology*