Current therapies for obesity and related complications have been shown to have limited benefits,including unsatisfactory weight loss and poor metabolic improvement.With recent developments in bariatric surgery,promis...Current therapies for obesity and related complications have been shown to have limited benefits,including unsatisfactory weight loss and poor metabolic improvement.With recent developments in bariatric surgery,promising advancements have been made in clinical and scientific research,particularly in the management of obesity and diabetes.Vertical sleeve gastrectomy(VSG)has become increasingly popular due to its safety,simplicity,展开更多
Type 2 diabetes(T2D)is characterized by the malfunction of pancreaticβcells.Susceptibility and pathogenesis of T2D can be affected by multiple factors,including sex differences.However,the mechanisms underlying sex d...Type 2 diabetes(T2D)is characterized by the malfunction of pancreaticβcells.Susceptibility and pathogenesis of T2D can be affected by multiple factors,including sex differences.However,the mechanisms underlying sex differences in T2D susceptibility and pathogenesis remain unclear.Using single-cell RNA sequencing(scRNA-seq),we demonstrate the presence of sexually dimorphic transcriptomes in mouseβcells.Using a high-fat diet-induced T2D mouse model,we identified sex-dependent T2D altered genes,suggesting sex-based differences in the pathological mechanisms of T2D.Furthermore,based on islet transplantation experiments,we found that compared to mice with sexmatched islet transplants,sex-mismatched islet transplants in healthy mice showed down-regulation of genes involved in the longevity regulating pathway ofβcells.Moreover,the diabetic mice with sex-mismatched islet transplants showed impaired glucose tolerance.These data suggest sexual dimorphism in T2D pathogenicity,indicating that sex should be considered when treating T2D.We hope that our findings could provide new insights for the development of precision medicine in T2D.展开更多
Background:Renal cell carcinoma (RCC) is frequently associated with paraneoplastic inflammatory syndrome (PIS).This study aimed at exploring the connections between the survival rate and specific gene alterations...Background:Renal cell carcinoma (RCC) is frequently associated with paraneoplastic inflammatory syndrome (PIS).This study aimed at exploring the connections between the survival rate and specific gene alterations and the potential mechanism.Methods:We retrospectively studied 69 surgical RCC cases from August 2014 to February 2016,including 18 cases of clear cell RCC (ccRCC) demonstrating elevated pretreatment serum C-reactive protein (CRP,Group A).Twelve of the 18 cases were symptomized with febrile episode.We also selected 49 cases ofccRCC with normal pretreatment CRP (Group B).Using 22 microsatellite markers,we compared the incidence of loss of heterozygosity (LOH) between Group A and Group B.All statistical tests are two-sided.Results:The 3p LOH was common in both Group A (89%) and Group B (92%).The frequency of 14q LOH in Group A (16 of 18) was higher than Group B (4 of 49,χ^2 =40.97 P 〈 0.0001).The 3p and 14q LOH were the characteristics of ccRCC with elevated acute phase reactants,including PIS,regardless of the presence of metastasis.On the contrary,14q LOH was a rare genomic alternation in advanced-staged ccRCC without PIS.The overall survival of patients with elevated CRP (33.3%) was lower than its counterparts (6.1%,hazard ratio=1.852,P 〈 0.0001) in Kaplan-Meier curve.Conclusions:The results imply that the disruption ofa 14q gene(s) might result in not only the inflammatory manifestations in the tumor host but also the poor survival rate as well.The isolation of the gene(s) on 14q might be a vital goal in the treatment of PIS-associated RCC.展开更多
基金supported by the National Natural Science Foundation of China(81370938)Shanghai Municipal Commission of Health and Family Planning(XYQ2011002)+2 种基金Shanghai Science and Technology Committee(11PJ1402000)Shenkang Hospital Development Center(SHDC12012220)the ‘‘Strategic Priority Research Program” of the Chinese Academy of Science(XDB13030500)
文摘Current therapies for obesity and related complications have been shown to have limited benefits,including unsatisfactory weight loss and poor metabolic improvement.With recent developments in bariatric surgery,promising advancements have been made in clinical and scientific research,particularly in the management of obesity and diabetes.Vertical sleeve gastrectomy(VSG)has become increasingly popular due to its safety,simplicity,
基金This work was supported by the National Key R&D Program of China(Grant Nos.2016YFA0102200,2017YFA0106500,2018YFA0107102,and 2020YFA0112500 awarded to WL,Grant No.2018YFA0107602 awarded to ZS)Key Project of the Science and Technology Commission of Shanghai Municipality,China(Grant No.19JC1415300 awarded to WL)+2 种基金the National Key R&D Program of China(Grant No.2018YFD0900604 awarded to WS)the National Natural Science Foundation of China(Grant Nos.41676119 and 41476120 awarded to WS)the start-up fund from Ocean University of China(awarded to WS).
文摘Type 2 diabetes(T2D)is characterized by the malfunction of pancreaticβcells.Susceptibility and pathogenesis of T2D can be affected by multiple factors,including sex differences.However,the mechanisms underlying sex differences in T2D susceptibility and pathogenesis remain unclear.Using single-cell RNA sequencing(scRNA-seq),we demonstrate the presence of sexually dimorphic transcriptomes in mouseβcells.Using a high-fat diet-induced T2D mouse model,we identified sex-dependent T2D altered genes,suggesting sex-based differences in the pathological mechanisms of T2D.Furthermore,based on islet transplantation experiments,we found that compared to mice with sexmatched islet transplants,sex-mismatched islet transplants in healthy mice showed down-regulation of genes involved in the longevity regulating pathway ofβcells.Moreover,the diabetic mice with sex-mismatched islet transplants showed impaired glucose tolerance.These data suggest sexual dimorphism in T2D pathogenicity,indicating that sex should be considered when treating T2D.We hope that our findings could provide new insights for the development of precision medicine in T2D.
基金This work was supported by grants from the National Natural Science Foundations of China (No. 81171996, and No. 81272289).
文摘Background:Renal cell carcinoma (RCC) is frequently associated with paraneoplastic inflammatory syndrome (PIS).This study aimed at exploring the connections between the survival rate and specific gene alterations and the potential mechanism.Methods:We retrospectively studied 69 surgical RCC cases from August 2014 to February 2016,including 18 cases of clear cell RCC (ccRCC) demonstrating elevated pretreatment serum C-reactive protein (CRP,Group A).Twelve of the 18 cases were symptomized with febrile episode.We also selected 49 cases ofccRCC with normal pretreatment CRP (Group B).Using 22 microsatellite markers,we compared the incidence of loss of heterozygosity (LOH) between Group A and Group B.All statistical tests are two-sided.Results:The 3p LOH was common in both Group A (89%) and Group B (92%).The frequency of 14q LOH in Group A (16 of 18) was higher than Group B (4 of 49,χ^2 =40.97 P 〈 0.0001).The 3p and 14q LOH were the characteristics of ccRCC with elevated acute phase reactants,including PIS,regardless of the presence of metastasis.On the contrary,14q LOH was a rare genomic alternation in advanced-staged ccRCC without PIS.The overall survival of patients with elevated CRP (33.3%) was lower than its counterparts (6.1%,hazard ratio=1.852,P 〈 0.0001) in Kaplan-Meier curve.Conclusions:The results imply that the disruption ofa 14q gene(s) might result in not only the inflammatory manifestations in the tumor host but also the poor survival rate as well.The isolation of the gene(s) on 14q might be a vital goal in the treatment of PIS-associated RCC.