Type 2 alveolar epithelial cell(AT2)senescence plays a crucial role in the onset andprogression of pulmonary fibrosis.Recent studies have revealed a close relationship betweenAT2 senescence and pulmonary fibrosis,sugg...Type 2 alveolar epithelial cell(AT2)senescence plays a crucial role in the onset andprogression of pulmonary fibrosis.Recent studies have revealed a close relationship betweenAT2 senescence and pulmonary fibrosis,suggesting that senescent cells have a dual role inthe injury repair process of lung tissue.On the one hand,senescent AT2 loses its repairfunction,and on the other hand,senescent cells exacerbate the inflammatory and fibroticprocesses by secreting senescence-associated secretory phenotype.In this paper,we willreview the biological mechanisms and pathological features of AT2 senescence and itsrelationship with the development of pulmonary fibrosis,and discuss current therapeuticintervention strategies,including the potential of small molecule drugs,cellular therapies,gene editing techniques,and traditional Chinese medicine.Finally,the paper summarizesthe challenges of current research and suggests future research directions.展开更多
目的探讨瞬时弹性成像技术(Fibro Scan)、天冬氨酸氨基转移酶和血小板比率指数(aspartate aminotransferase-to-platelet ratio index,APRI)及其二者联合检测肝硬化患者合并食管胃底静脉曲张破裂出血风险的相关性和诊断预测价值.方法将...目的探讨瞬时弹性成像技术(Fibro Scan)、天冬氨酸氨基转移酶和血小板比率指数(aspartate aminotransferase-to-platelet ratio index,APRI)及其二者联合检测肝硬化患者合并食管胃底静脉曲张破裂出血风险的相关性和诊断预测价值.方法将210例病毒性肝炎肝炎后肝硬化患者根据2015年《肝硬化门静脉高压食管胃静脉曲张出血的防治指南》分为无、有出血组,分别为153、57例;搜集患者在1 wk内的Fibro Scan值[肝脏硬度值(liver stiffness measurement,L S M)]和A P R I值.组间比较采用t检验,利用受试者工作特征曲线(receiver operating characteristic curve,ROC)分析LSM、APRI、LSM+APRI对肝硬化患者出血风险的预测价值,并比较LSM、APRI及LSM+APRI的ROC曲线下面积(area under curve,AUC).结果有、无出血组的LSM值分别是28.49 k Pa±9.46 k Pa,22.87 k Pa±6.95 k Pa,APRI值分别是2.99±1.11,2.13±1.01,有明显的统计学意义.有无出血风险的LSM、APRI、LSM+APRI的AUC分别是0.669、0.727、0.722,表明APRI、LSM+APRI对食管胃底静脉曲张破裂出血具有良好的诊断效果.结论APRI及Fibro Scan联合APRI对肝硬化患者合并食管胃底静脉曲张破裂出血风险存在有效的预测价值.展开更多
Fibrosing cholestatic hepatitis(FCH) is a variant of viral hepatitis reported in hepatitis B virus or hepatitis C virus infected liver,renal or bone transplantation recipients and in leukemia and lymphoma patients aft...Fibrosing cholestatic hepatitis(FCH) is a variant of viral hepatitis reported in hepatitis B virus or hepatitis C virus infected liver,renal or bone transplantation recipients and in leukemia and lymphoma patients after conventional cytotoxic chemotherapy.FCH constitutes a well-described form of fulminant hepatitis having extensive fibrosis and severe cholestasis as its most characteristic pathological findings.Here,we report a case of a 49-year-old patient diagnosed with small-cell lung cancer who developed this condition following conventional chemotherapy-induced immunosuppression.This is the first reported case in the literature of FCH after conventional chemotherapy for a solid tumor.In addition to a detailed report of the case,a physiopathological examination of this potentially life-threatening condition and its treatment options are discussed.展开更多
To explore the pathological features and thedifferential diagnosis of recurrent HBV after livertransplantation.Methods: One case of liver transplantation for HBVcirrhosis was subjected to liver biopsises on time post-...To explore the pathological features and thedifferential diagnosis of recurrent HBV after livertransplantation.Methods: One case of liver transplantation for HBVcirrhosis was subjected to liver biopsises on time post-operatively.Results: 25 days after liver transplantation, serologicHBsAg, HBeAg and HBV-DNA of the patient becamenegative, but HBsAg was positive again on day 58 af-ter liver transplantation. Histopathological examina-tion showed balloon-like changes of hepatocytes withfragmental necrosis, fibrosis in the portal areas andaround the portal veins, cholestasis in some hepato-cytes and canaliculi, and positive HBsAg and HBcAgwith immunohistochemical staining. Clinically hepaticenzyme levels progressively increased, maintained forsome time, and decreased rapidly at last. Stubborn hy-poproteinemia was associated with the aggregation ofgeneral condition of the patient.Conclusions: Fibrosing cholestatic hepatitis (FCH) is aspecial type in recurrent infection of HBV after livertransplantation. It has a serious clinical process andspecific pathological changes different from those ofthe usual HBV.展开更多
This is a very unusual case with unexpected findings. In spite of sophisticated investigation tests such as MRI and pul?monary angiogram, it may be very difficult to identify the nature of pulmonary artery stenosis or...This is a very unusual case with unexpected findings. In spite of sophisticated investigation tests such as MRI and pul?monary angiogram, it may be very difficult to identify the nature of pulmonary artery stenosis or occlusion.展开更多
Frontal fibrosing alopecia(FFA) is a recently described form of primary cicatricial alopecia, characterized by progressive recession of the frontotemporal hairline and eyebrow loss, occurring predominantly in postmeno...Frontal fibrosing alopecia(FFA) is a recently described form of primary cicatricial alopecia, characterized by progressive recession of the frontotemporal hairline and eyebrow loss, occurring predominantly in postmenopausal women. The incidence of FFA has increased significantly during the last decade and we may be facing an epidemic of the disease. Because this condition causes permanent hair loss, prompt diagnosis and treatment are essential for obtaining optimal outcome. This article reviews existing knowledge on epidemiology, etiopathogenesis, clinico-histological features, diagnosis,and treatment modalities of FFA.展开更多
目的早期诊断对提高原发性肝癌患者生存率尤为关键,本研究旨在探讨肝脏瞬时弹性硬度检查(Fibroscan)诊断早期乙型肝炎(简称乙肝)相关肝癌的临床价值。方法选取156例慢性乙肝患者,分为肝癌组(51例)和非肝癌组(105例),收集所有研究对象的...目的早期诊断对提高原发性肝癌患者生存率尤为关键,本研究旨在探讨肝脏瞬时弹性硬度检查(Fibroscan)诊断早期乙型肝炎(简称乙肝)相关肝癌的临床价值。方法选取156例慢性乙肝患者,分为肝癌组(51例)和非肝癌组(105例),收集所有研究对象的临床资料及相关实验室检查结果,并采用Fibroscan测定肝硬度值(LS),分析肝癌的高危因素、LS评价肝纤维化的临床价值。结果肝癌家族史、HBV-DNA水平(log10>5 IU/ml)、AFP水平(>400 mg/L)、高LS值(>13 k Pa)是肝癌发生的危险因素(均P<0.05)。当LS诊断界值为13 k Pa时,Fibroscan诊断肝癌的灵敏度和特异度分别为82.35%、78.09%;当LS诊断界值为18 k Pa,Fibroscan诊断肝癌的灵敏度下降(62.75%),特异度升高(88.57%)。结论 LS和慢性乙肝患者发生肝癌的风险密切相关,Fibroscan作为一种无创预测肝癌的方式,在肝癌早期诊断中有积极意义。展开更多
Hepatic stellate cells(HSCs)are the primary fibrogenic cells in the liver,and their activation plays a crucial role in the development and progression of hepatic fibrosis.Here,we report that retinoid X receptor-alpha(...Hepatic stellate cells(HSCs)are the primary fibrogenic cells in the liver,and their activation plays a crucial role in the development and progression of hepatic fibrosis.Here,we report that retinoid X receptor-alpha(RXRα),a unique member of the nuclear receptor superfamily,is a key modulator of HSC activation and liver fibrosis.RXRαexerts its effects by modulating calcium/calmodulin-dependent protein kinase kinaseβ(CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha(AMPKα).In addition,we demonstrate that K-80003,which binds RXRαby a unique mechanism,effectively suppresses HSC activation,proliferation,and migration,thereby inhibiting liver fibrosis in the CCl4 and amylin liver NASH(AMLN)diet animal models.The effect is mediated by AMPKαactivation,promoting mitophagy in HSCs.Mechanistically,K-80003 activates AMPKαby inducing RXRαto form condensates with CaMKKβand AMPKαvia a two-phase process.The formation of RXRαcondensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ.Our results reveal a crucial role of RXRαin liver fibrosis regulation through modulating mitochondrial activities in HSCs.Furthermore,they suggest that K-80003 and related RXRαmodulators hold promise as therapeutic agents for fibrosis-related diseases.展开更多
基金supported by the Tianjin Wuqing District Health and Health Research Project(WQWJ202403).
文摘Type 2 alveolar epithelial cell(AT2)senescence plays a crucial role in the onset andprogression of pulmonary fibrosis.Recent studies have revealed a close relationship betweenAT2 senescence and pulmonary fibrosis,suggesting that senescent cells have a dual role inthe injury repair process of lung tissue.On the one hand,senescent AT2 loses its repairfunction,and on the other hand,senescent cells exacerbate the inflammatory and fibroticprocesses by secreting senescence-associated secretory phenotype.In this paper,we willreview the biological mechanisms and pathological features of AT2 senescence and itsrelationship with the development of pulmonary fibrosis,and discuss current therapeuticintervention strategies,including the potential of small molecule drugs,cellular therapies,gene editing techniques,and traditional Chinese medicine.Finally,the paper summarizesthe challenges of current research and suggests future research directions.
文摘目的探讨瞬时弹性成像技术(Fibro Scan)、天冬氨酸氨基转移酶和血小板比率指数(aspartate aminotransferase-to-platelet ratio index,APRI)及其二者联合检测肝硬化患者合并食管胃底静脉曲张破裂出血风险的相关性和诊断预测价值.方法将210例病毒性肝炎肝炎后肝硬化患者根据2015年《肝硬化门静脉高压食管胃静脉曲张出血的防治指南》分为无、有出血组,分别为153、57例;搜集患者在1 wk内的Fibro Scan值[肝脏硬度值(liver stiffness measurement,L S M)]和A P R I值.组间比较采用t检验,利用受试者工作特征曲线(receiver operating characteristic curve,ROC)分析LSM、APRI、LSM+APRI对肝硬化患者出血风险的预测价值,并比较LSM、APRI及LSM+APRI的ROC曲线下面积(area under curve,AUC).结果有、无出血组的LSM值分别是28.49 k Pa±9.46 k Pa,22.87 k Pa±6.95 k Pa,APRI值分别是2.99±1.11,2.13±1.01,有明显的统计学意义.有无出血风险的LSM、APRI、LSM+APRI的AUC分别是0.669、0.727、0.722,表明APRI、LSM+APRI对食管胃底静脉曲张破裂出血具有良好的诊断效果.结论APRI及Fibro Scan联合APRI对肝硬化患者合并食管胃底静脉曲张破裂出血风险存在有效的预测价值.
文摘Fibrosing cholestatic hepatitis(FCH) is a variant of viral hepatitis reported in hepatitis B virus or hepatitis C virus infected liver,renal or bone transplantation recipients and in leukemia and lymphoma patients after conventional cytotoxic chemotherapy.FCH constitutes a well-described form of fulminant hepatitis having extensive fibrosis and severe cholestasis as its most characteristic pathological findings.Here,we report a case of a 49-year-old patient diagnosed with small-cell lung cancer who developed this condition following conventional chemotherapy-induced immunosuppression.This is the first reported case in the literature of FCH after conventional chemotherapy for a solid tumor.In addition to a detailed report of the case,a physiopathological examination of this potentially life-threatening condition and its treatment options are discussed.
文摘To explore the pathological features and thedifferential diagnosis of recurrent HBV after livertransplantation.Methods: One case of liver transplantation for HBVcirrhosis was subjected to liver biopsises on time post-operatively.Results: 25 days after liver transplantation, serologicHBsAg, HBeAg and HBV-DNA of the patient becamenegative, but HBsAg was positive again on day 58 af-ter liver transplantation. Histopathological examina-tion showed balloon-like changes of hepatocytes withfragmental necrosis, fibrosis in the portal areas andaround the portal veins, cholestasis in some hepato-cytes and canaliculi, and positive HBsAg and HBcAgwith immunohistochemical staining. Clinically hepaticenzyme levels progressively increased, maintained forsome time, and decreased rapidly at last. Stubborn hy-poproteinemia was associated with the aggregation ofgeneral condition of the patient.Conclusions: Fibrosing cholestatic hepatitis (FCH) is aspecial type in recurrent infection of HBV after livertransplantation. It has a serious clinical process andspecific pathological changes different from those ofthe usual HBV.
文摘This is a very unusual case with unexpected findings. In spite of sophisticated investigation tests such as MRI and pul?monary angiogram, it may be very difficult to identify the nature of pulmonary artery stenosis or occlusion.
文摘Frontal fibrosing alopecia(FFA) is a recently described form of primary cicatricial alopecia, characterized by progressive recession of the frontotemporal hairline and eyebrow loss, occurring predominantly in postmenopausal women. The incidence of FFA has increased significantly during the last decade and we may be facing an epidemic of the disease. Because this condition causes permanent hair loss, prompt diagnosis and treatment are essential for obtaining optimal outcome. This article reviews existing knowledge on epidemiology, etiopathogenesis, clinico-histological features, diagnosis,and treatment modalities of FFA.
文摘目的早期诊断对提高原发性肝癌患者生存率尤为关键,本研究旨在探讨肝脏瞬时弹性硬度检查(Fibroscan)诊断早期乙型肝炎(简称乙肝)相关肝癌的临床价值。方法选取156例慢性乙肝患者,分为肝癌组(51例)和非肝癌组(105例),收集所有研究对象的临床资料及相关实验室检查结果,并采用Fibroscan测定肝硬度值(LS),分析肝癌的高危因素、LS评价肝纤维化的临床价值。结果肝癌家族史、HBV-DNA水平(log10>5 IU/ml)、AFP水平(>400 mg/L)、高LS值(>13 k Pa)是肝癌发生的危险因素(均P<0.05)。当LS诊断界值为13 k Pa时,Fibroscan诊断肝癌的灵敏度和特异度分别为82.35%、78.09%;当LS诊断界值为18 k Pa,Fibroscan诊断肝癌的灵敏度下降(62.75%),特异度升高(88.57%)。结论 LS和慢性乙肝患者发生肝癌的风险密切相关,Fibroscan作为一种无创预测肝癌的方式,在肝癌早期诊断中有积极意义。
基金supported by grants from the National Natural Science Foundation of China,China(81672749,81772993,81971551,82302954,and K2918001)Natural Science Foundation of Fujian Province,China(2024J08346)+4 种基金Xiamen Municipal Bureau of Ocean Development,China(16PYY007SF17 and 23YYZP022QCB33)Xiamen Science&Technology Department,China(3502Z20231022,3502Z20193004,3502Z20150007,and 2023CXY0107)National Key R&D Program of China,China(2020YFA0112900)the Postdoctoral Science Foundation of China(2023M732956)fund from NucMito Pharmaceuticals Co.,Ltd.,China.
文摘Hepatic stellate cells(HSCs)are the primary fibrogenic cells in the liver,and their activation plays a crucial role in the development and progression of hepatic fibrosis.Here,we report that retinoid X receptor-alpha(RXRα),a unique member of the nuclear receptor superfamily,is a key modulator of HSC activation and liver fibrosis.RXRαexerts its effects by modulating calcium/calmodulin-dependent protein kinase kinaseβ(CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha(AMPKα).In addition,we demonstrate that K-80003,which binds RXRαby a unique mechanism,effectively suppresses HSC activation,proliferation,and migration,thereby inhibiting liver fibrosis in the CCl4 and amylin liver NASH(AMLN)diet animal models.The effect is mediated by AMPKαactivation,promoting mitophagy in HSCs.Mechanistically,K-80003 activates AMPKαby inducing RXRαto form condensates with CaMKKβand AMPKαvia a two-phase process.The formation of RXRαcondensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ.Our results reveal a crucial role of RXRαin liver fibrosis regulation through modulating mitochondrial activities in HSCs.Furthermore,they suggest that K-80003 and related RXRαmodulators hold promise as therapeutic agents for fibrosis-related diseases.
