One-third of patients with autoimmune hepatitis(AIH)have cirrhosis at the time of diagnosis.The relevance of these variables,although unknown,is believed to be critical in AIH because of suspected interactions between...One-third of patients with autoimmune hepatitis(AIH)have cirrhosis at the time of diagnosis.The relevance of these variables,although unknown,is believed to be critical in AIH because of suspected interactions between the gut microbiome and genetic factors.Dysbiosis of the gut flora and elevated polymeric immunoglobulin receptor(pIgR)levels have been observed in both patients and mouse models.Moreover,there is a direct relationship between pIgR expression and transaminase levels in patients with AIH.In this study,we aimed to explore how pIgR influences the secretion of regenerating islet-derived 3 beta(Reg3b)and the flora composition in AIH using in vivo experiments involving patients with AIH and a concanavalin A-induced mouse model of AIH.Reg3b expression was reduced in pIgR gene(Pigr)-knockout mice compared to that in wild-type mice,leading to increased microbiota disruption.Conversely,exogenous pIgR supplementation increased Reg3b expression and maintained microbiota homeostasis.RNA sequencing revealed the participation of the interleukin(IL)-17 signaling pathway in the regulation of Reg3b through pIgR.Furthermore,the introduction of external pIgR could not restore the imbalance in gut microbiota in AIH,and the decrease in Reg3b expression was not apparent following the inhibition of signal transducer and activator of transcription 3(STAT3).In this study,pIgR facilitated the upregulation of Reg3b via the STAT3 pathway,which plays a crucial role in preserving the balance of the intestinal microbiota in AIH.Through this research,we discovered new molecular targets that can be used for the diagnosis and treatment of AIH.展开更多
In this editorial,we review the work of Razali et al published in World J Gas-troenterology,with a particular focus on the effect of rs10889677 variation in the phosphatidylinositol 3-kinase(PI3K)pathway and buparlisi...In this editorial,we review the work of Razali et al published in World J Gas-troenterology,with a particular focus on the effect of rs10889677 variation in the phosphatidylinositol 3-kinase(PI3K)pathway and buparlisib on colitis-associated cancer.The role of PI3K in promoting cancer progression has been widely recognized,as it is involved in regulating the survival,differentiation,and prolif-eration of cancer cells.The complement Clq/TNF-related protein 6(CTRP6)is a newer tumor-associated factor.Recent studies have revealed the pro-tumor effect of CTRP6 in gastric cancer,hepatocellular carcinoma,colorectal cancer,and other gastrointestinal tumors through the PI3K pathway.This article attempts to reveal the mechanism through which the CTRP6 affects the development of digestive system tumors through the PI3K pathway by summarizing recent research.展开更多
单克隆免疫球蛋白相关C3肾小球肾炎(C3 glomerulopathy with monoclonal gammopathy,C3G-MIg)是一种罕见的单克隆免疫球蛋白病,是50岁以上患者肾损伤的重要病因。C3GMIg关键的发病机制是单克隆免疫球蛋白作为自身抗体或通过直接裂解C3...单克隆免疫球蛋白相关C3肾小球肾炎(C3 glomerulopathy with monoclonal gammopathy,C3G-MIg)是一种罕见的单克隆免疫球蛋白病,是50岁以上患者肾损伤的重要病因。C3GMIg关键的发病机制是单克隆免疫球蛋白作为自身抗体或通过直接裂解C3的方式,过度激活补体旁路途径,导致补体沉积进而损伤肾脏。针对产生单克隆免疫球蛋白的B细胞或浆细胞及过度激活的补体旁路途径,C3G-MIg的治疗可采取支持治疗、化疗、克隆抗体联合治疗的方法。本文回顾了有关C3G-MIg的研究,综述其发病机制、临床表现及治疗进展,为临床诊治C3G-MIg提供新思路。展开更多
Serum C3, C4, IgG and IgM levels were evaluated in healthy post-menopausal women receiving short-term hormone replacement therapy （HRT） regimens and in untreated women. Serum C3, C4, IgM and IgG levels were assessed...Serum C3, C4, IgG and IgM levels were evaluated in healthy post-menopausal women receiving short-term hormone replacement therapy （HRT） regimens and in untreated women. Serum C3, C4, IgM and IgG levels were assessed in 54 women receiving HRT therapy （CEE 0.625 mg＋MPA 2.5 mg/day）, and in 54 control women not receiving HRT. The results showed that the mean serum C3 and C4 levels were significantly higher in women receiving HRT than those untreated women （P〈0.01）. There was significant difference in IgG and IgM levels between two groups. It was concluded that HRT might be involved in the development of cardiovascular diseases through inflammatory mechanisms, as suggested by increased serum levels of C3 and C4.展开更多
BACKGROUND Alport syndrome(AS)is an inherited disease of the glomerular basement membrane caused by mutations in genes encodingα3,α4,orα5 chains of type IV collagen.It manifests with hematuria or proteinuria,which ...BACKGROUND Alport syndrome(AS)is an inherited disease of the glomerular basement membrane caused by mutations in genes encodingα3,α4,orα5 chains of type IV collagen.It manifests with hematuria or proteinuria,which is often accompanied by hearing impairments and ocular abnormalities.Histopathologically,AS shows mesangial proliferation and sometimes incidental immunoglobulin A(IgA)deposition.Hematuria or proteinuria is also a common presentation in patients with IgA nephropathy that makes it difficult to differentially diagnose AS and IgA nephropathy solely based on these clinical and pathological features.CASE SUMMARY Herein,we present the case of a 59-year-old female patient who was admitted to our hospital with persistent microscopic hematuria and occasional proteinuria that had lasted for>2 years.This patient had a familial history of renal disease and was diagnosed with autosomal dominant AS(ADAS)and IgA nephropathy based on the findings of renal biopsy as well as genetic testing performed using whole-exome sequencing,which suggested that the patient carried a novel heterozygous variation(c.888G>A:p.Gln296Gln)in the COL4A3 gene that enriches the mutation spectrum of ADAS.The proband received an angiotensin receptor blocker therapy after a definitive diagnosis was established.After one year of therapy,a significant reduction in proteinuria was observed.The number of microscopic red blood cells per high-power field decreased to one-quarter of the baseline levels.Renal function also maintained well during the follow-up.CONCLUSION Our case highlights the significance of performing kidney biopsy and genetic testing in the diagnosis of AS and familial IgA nephropathy.展开更多
基金supported by the National Natural Science Foundation of China(82070593)the Zhejiang Provincial Natural Science Foundation(LD21H030002)+1 种基金the Department of Science and Technology of Zhejiang Province(ZY2019008)the Youth Program of the National Natural Science Foundation of China(82200632).
文摘One-third of patients with autoimmune hepatitis(AIH)have cirrhosis at the time of diagnosis.The relevance of these variables,although unknown,is believed to be critical in AIH because of suspected interactions between the gut microbiome and genetic factors.Dysbiosis of the gut flora and elevated polymeric immunoglobulin receptor(pIgR)levels have been observed in both patients and mouse models.Moreover,there is a direct relationship between pIgR expression and transaminase levels in patients with AIH.In this study,we aimed to explore how pIgR influences the secretion of regenerating islet-derived 3 beta(Reg3b)and the flora composition in AIH using in vivo experiments involving patients with AIH and a concanavalin A-induced mouse model of AIH.Reg3b expression was reduced in pIgR gene(Pigr)-knockout mice compared to that in wild-type mice,leading to increased microbiota disruption.Conversely,exogenous pIgR supplementation increased Reg3b expression and maintained microbiota homeostasis.RNA sequencing revealed the participation of the interleukin(IL)-17 signaling pathway in the regulation of Reg3b through pIgR.Furthermore,the introduction of external pIgR could not restore the imbalance in gut microbiota in AIH,and the decrease in Reg3b expression was not apparent following the inhibition of signal transducer and activator of transcription 3(STAT3).In this study,pIgR facilitated the upregulation of Reg3b via the STAT3 pathway,which plays a crucial role in preserving the balance of the intestinal microbiota in AIH.Through this research,we discovered new molecular targets that can be used for the diagnosis and treatment of AIH.
文摘In this editorial,we review the work of Razali et al published in World J Gas-troenterology,with a particular focus on the effect of rs10889677 variation in the phosphatidylinositol 3-kinase(PI3K)pathway and buparlisib on colitis-associated cancer.The role of PI3K in promoting cancer progression has been widely recognized,as it is involved in regulating the survival,differentiation,and prolif-eration of cancer cells.The complement Clq/TNF-related protein 6(CTRP6)is a newer tumor-associated factor.Recent studies have revealed the pro-tumor effect of CTRP6 in gastric cancer,hepatocellular carcinoma,colorectal cancer,and other gastrointestinal tumors through the PI3K pathway.This article attempts to reveal the mechanism through which the CTRP6 affects the development of digestive system tumors through the PI3K pathway by summarizing recent research.
文摘单克隆免疫球蛋白相关C3肾小球肾炎(C3 glomerulopathy with monoclonal gammopathy,C3G-MIg)是一种罕见的单克隆免疫球蛋白病,是50岁以上患者肾损伤的重要病因。C3GMIg关键的发病机制是单克隆免疫球蛋白作为自身抗体或通过直接裂解C3的方式,过度激活补体旁路途径,导致补体沉积进而损伤肾脏。针对产生单克隆免疫球蛋白的B细胞或浆细胞及过度激活的补体旁路途径,C3G-MIg的治疗可采取支持治疗、化疗、克隆抗体联合治疗的方法。本文回顾了有关C3G-MIg的研究,综述其发病机制、临床表现及治疗进展,为临床诊治C3G-MIg提供新思路。
文摘Serum C3, C4, IgG and IgM levels were evaluated in healthy post-menopausal women receiving short-term hormone replacement therapy （HRT） regimens and in untreated women. Serum C3, C4, IgM and IgG levels were assessed in 54 women receiving HRT therapy （CEE 0.625 mg＋MPA 2.5 mg/day）, and in 54 control women not receiving HRT. The results showed that the mean serum C3 and C4 levels were significantly higher in women receiving HRT than those untreated women （P〈0.01）. There was significant difference in IgG and IgM levels between two groups. It was concluded that HRT might be involved in the development of cardiovascular diseases through inflammatory mechanisms, as suggested by increased serum levels of C3 and C4.
基金Supported by The Major Project of Zhejiang Administration of Traditional Chinese Medicine,No.2020ZZ008.
文摘BACKGROUND Alport syndrome(AS)is an inherited disease of the glomerular basement membrane caused by mutations in genes encodingα3,α4,orα5 chains of type IV collagen.It manifests with hematuria or proteinuria,which is often accompanied by hearing impairments and ocular abnormalities.Histopathologically,AS shows mesangial proliferation and sometimes incidental immunoglobulin A(IgA)deposition.Hematuria or proteinuria is also a common presentation in patients with IgA nephropathy that makes it difficult to differentially diagnose AS and IgA nephropathy solely based on these clinical and pathological features.CASE SUMMARY Herein,we present the case of a 59-year-old female patient who was admitted to our hospital with persistent microscopic hematuria and occasional proteinuria that had lasted for>2 years.This patient had a familial history of renal disease and was diagnosed with autosomal dominant AS(ADAS)and IgA nephropathy based on the findings of renal biopsy as well as genetic testing performed using whole-exome sequencing,which suggested that the patient carried a novel heterozygous variation(c.888G>A:p.Gln296Gln)in the COL4A3 gene that enriches the mutation spectrum of ADAS.The proband received an angiotensin receptor blocker therapy after a definitive diagnosis was established.After one year of therapy,a significant reduction in proteinuria was observed.The number of microscopic red blood cells per high-power field decreased to one-quarter of the baseline levels.Renal function also maintained well during the follow-up.CONCLUSION Our case highlights the significance of performing kidney biopsy and genetic testing in the diagnosis of AS and familial IgA nephropathy.
