BACKGROUND Primary biliary cholangitis(PBC)is a chronic autoimmune-mediated cholestatic liver disease.Nanoparticles encapsulating rapamycin(ImmTOR)suppress adaptive immune responses and induce the hepatic tolerogenic ...BACKGROUND Primary biliary cholangitis(PBC)is a chronic autoimmune-mediated cholestatic liver disease.Nanoparticles encapsulating rapamycin(ImmTOR)suppress adaptive immune responses and induce the hepatic tolerogenic immune response.AIM To investigate the effects of ImmTOR in PBC mouse models.METHODS PBC models were induced in C57BL/6 mice by two immunizations of 2-octynoic acid-coupled bovine serum albumin at two-week intervals,and polycytidylic acid every three days.The PBC mouse models were separated into the treatment group and the control group.The levels of alkaline phosphatase(ALP)and alanine aminotransferase in the mice were detected using an automatic biochemical analyzer.Liver and spleen mononuclear cells were analyzed by flow cytometry,and serum anti-mitochondrial antibodies(AMA)and the related cytokines were analyzed by enzyme-linked immunosorbent assay.Liver histopathology was examined by hematoxylin and eosin staining and scored.RESULTS After treatment with ImmTOR,the ALP level was significantly decreased(189.60 U/L±27.25 U/L vs 156.00 U/L±17.21 U/L,P<0.05),the level of AMA was reduced(1.28 ng/mL±0.27 ng/mL vs 0.56 ng/mL±0.07 ng/mL,P<0.001)and the expression levels of interferon gamma and tumor necrosis factorαwere significantly decreased(48.29 pg/mL±10.84 pg/mL vs 25.01 pg/mL±1.49 pg/mL,P<0.0001)and(84.24 pg/mL±23.47 pg/mL vs 40.66 pg/mL±14.65 pg/mL,P<0.001).The CD4+T lymphocytes,CD8+T lymphocytes and B lymphocytes in the liver were significantly reduced,with statistically significant differences(24.21%±6.55%vs 15.98%±3.03%,P<0.05;9.09%±1.91%vs 5.49%±1.00%,P<0.001;80.51%±2.96%vs 75.31%±4.34%,P<0.05).The expression of CD8+T lymphocytes and B lymphocytes in the ImmTOR treatment group also decreased(9.09%±1.91%vs 5.49%±1.00%,P<0.001;80.51%±2.96%vs 75.31%±4.34%,P<0.05).The liver pathology of PBC mice in the treatment group showed reduced inflammation and a decreased total pathology score,and the difference in the scores was statistically significant(4.50±2.88 vs 1.75±1.28,P<0.05).CONCLUSION ImmTOR can improve biochemistry and pathology of liver obvious by inhibiting the expression of CD8+T cells and B cells,and reducing the titer of AMA.展开更多
Surgical intervention is currently the primary treatment for hepatolithiasis;how-ever,some patients still experience residual stones and high recurrence rates after surgery.Cholesterol metabolism seems to play an impo...Surgical intervention is currently the primary treatment for hepatolithiasis;how-ever,some patients still experience residual stones and high recurrence rates after surgery.Cholesterol metabolism seems to play an important role in hepatoli-thiasis pathogenesis.A high cholesterol diet is one of the significant reasons for the increasing incidence of hepatolithiasis.Therefore,regular diet and appropriate medical intervention are crucial measures to prevent hepatolithiasis and reduce recurrence rate after surgery.Reducing dietary cholesterol and drugs that increase cholesterol stone solubility are key therapeutic approaches in treating hepato-lithiasis.This article discusses the cholesterol metabolic pathways related to the pathogenesis of hepatolithiasis,as well as food intake and targeted therapeutic drugs.展开更多
BACKGROUND Fungal esophagitis(FE)is caused by fungal invasion of the esophageal mucosa.Under endoscopy,the esophageal mucosa shows edema,congestion,erosion,and ulceration,and bleeds easily when touched,and the surface...BACKGROUND Fungal esophagitis(FE)is caused by fungal invasion of the esophageal mucosa.Under endoscopy,the esophageal mucosa shows edema,congestion,erosion,and ulceration,and bleeds easily when touched,and the surface of the mucosa is covered with small white spots like"bean curd residue".Clinical cases showing typical FE under endoscopic imaging but negative esophageal mucosal brush(referred to as suspected FE)have increased the difficulty and challenge of clinical diagnosis and treatment.At present,the esophageal fungal flora of suspected case has not been thoroughly studied.AIM To characterize the fungal flora in FE,suspected FE,and the esophageal normal controls(NCs),and to identify marker species to improve detection of FE.METHODS This was a case-control study.A total of 19 patients with FE,16 with suspected FE,and 10 NCs were selected by endoscopy.The esophageal cell brush samples of each group were sequenced by internal transcribed spacer(ITS)1 and analyzed by bioinformatics.RESULTS In FE and suspected FE patients,species richness,species diversity and species evenness,as measured by the Chao1 index,Shannon index and Pielou index,were lower than in the NCs,and the comparison between the FE and NCs was the most significant(P<0.05).Compared with the NCs,the relative abundance of Candida in FE and suspected FE patients was significantly increased(P<0.001),while the relative abundance of Yarrowia was significantly decreased(P<0.05).Moreover,Yarrowia abundance in the FE group was significantly lower than in the NCs and suspected FE groups(P<0.001).The area under the curve for Candida in FE and suspected FE patients was 99.5%(P<0.05)and 81.3%(P<0.05),respectively.Finally,compared with FE patients,the relative abundance of Ascomycota and Candida in the esophageal flora of suspected FE patients was decreased,while the relative abundance of Yarrowia,Thermomyces and Pichia was increased.CONCLUSION ITS showed that composition of the fungal community was similar in the FE and suspected FE groups.ITS can be used as an auxiliary diagnostic method for FE and provide a theoretical basis for follow-up diagnosis and treatment.展开更多
基金Supported by Cultivation Project of Hebei Natural Science Foundation-Precision Medicine Joint Fund,No.H2021206239.
文摘BACKGROUND Primary biliary cholangitis(PBC)is a chronic autoimmune-mediated cholestatic liver disease.Nanoparticles encapsulating rapamycin(ImmTOR)suppress adaptive immune responses and induce the hepatic tolerogenic immune response.AIM To investigate the effects of ImmTOR in PBC mouse models.METHODS PBC models were induced in C57BL/6 mice by two immunizations of 2-octynoic acid-coupled bovine serum albumin at two-week intervals,and polycytidylic acid every three days.The PBC mouse models were separated into the treatment group and the control group.The levels of alkaline phosphatase(ALP)and alanine aminotransferase in the mice were detected using an automatic biochemical analyzer.Liver and spleen mononuclear cells were analyzed by flow cytometry,and serum anti-mitochondrial antibodies(AMA)and the related cytokines were analyzed by enzyme-linked immunosorbent assay.Liver histopathology was examined by hematoxylin and eosin staining and scored.RESULTS After treatment with ImmTOR,the ALP level was significantly decreased(189.60 U/L±27.25 U/L vs 156.00 U/L±17.21 U/L,P<0.05),the level of AMA was reduced(1.28 ng/mL±0.27 ng/mL vs 0.56 ng/mL±0.07 ng/mL,P<0.001)and the expression levels of interferon gamma and tumor necrosis factorαwere significantly decreased(48.29 pg/mL±10.84 pg/mL vs 25.01 pg/mL±1.49 pg/mL,P<0.0001)and(84.24 pg/mL±23.47 pg/mL vs 40.66 pg/mL±14.65 pg/mL,P<0.001).The CD4+T lymphocytes,CD8+T lymphocytes and B lymphocytes in the liver were significantly reduced,with statistically significant differences(24.21%±6.55%vs 15.98%±3.03%,P<0.05;9.09%±1.91%vs 5.49%±1.00%,P<0.001;80.51%±2.96%vs 75.31%±4.34%,P<0.05).The expression of CD8+T lymphocytes and B lymphocytes in the ImmTOR treatment group also decreased(9.09%±1.91%vs 5.49%±1.00%,P<0.001;80.51%±2.96%vs 75.31%±4.34%,P<0.05).The liver pathology of PBC mice in the treatment group showed reduced inflammation and a decreased total pathology score,and the difference in the scores was statistically significant(4.50±2.88 vs 1.75±1.28,P<0.05).CONCLUSION ImmTOR can improve biochemistry and pathology of liver obvious by inhibiting the expression of CD8+T cells and B cells,and reducing the titer of AMA.
基金Supported by Hebei Natural Science Foundation,No.H2022206539Hebei Provincial Government Funded Clinical Talents Training Project,No.ZF2023143.
文摘Surgical intervention is currently the primary treatment for hepatolithiasis;how-ever,some patients still experience residual stones and high recurrence rates after surgery.Cholesterol metabolism seems to play an important role in hepatoli-thiasis pathogenesis.A high cholesterol diet is one of the significant reasons for the increasing incidence of hepatolithiasis.Therefore,regular diet and appropriate medical intervention are crucial measures to prevent hepatolithiasis and reduce recurrence rate after surgery.Reducing dietary cholesterol and drugs that increase cholesterol stone solubility are key therapeutic approaches in treating hepato-lithiasis.This article discusses the cholesterol metabolic pathways related to the pathogenesis of hepatolithiasis,as well as food intake and targeted therapeutic drugs.
基金Supported by Hebei Province 2023 Annual Medical Science Research Project,No.20230597Hebei Province 2024 Annual Medical Applicable Technology Tracking Project,No.GZ2024017.
文摘BACKGROUND Fungal esophagitis(FE)is caused by fungal invasion of the esophageal mucosa.Under endoscopy,the esophageal mucosa shows edema,congestion,erosion,and ulceration,and bleeds easily when touched,and the surface of the mucosa is covered with small white spots like"bean curd residue".Clinical cases showing typical FE under endoscopic imaging but negative esophageal mucosal brush(referred to as suspected FE)have increased the difficulty and challenge of clinical diagnosis and treatment.At present,the esophageal fungal flora of suspected case has not been thoroughly studied.AIM To characterize the fungal flora in FE,suspected FE,and the esophageal normal controls(NCs),and to identify marker species to improve detection of FE.METHODS This was a case-control study.A total of 19 patients with FE,16 with suspected FE,and 10 NCs were selected by endoscopy.The esophageal cell brush samples of each group were sequenced by internal transcribed spacer(ITS)1 and analyzed by bioinformatics.RESULTS In FE and suspected FE patients,species richness,species diversity and species evenness,as measured by the Chao1 index,Shannon index and Pielou index,were lower than in the NCs,and the comparison between the FE and NCs was the most significant(P<0.05).Compared with the NCs,the relative abundance of Candida in FE and suspected FE patients was significantly increased(P<0.001),while the relative abundance of Yarrowia was significantly decreased(P<0.05).Moreover,Yarrowia abundance in the FE group was significantly lower than in the NCs and suspected FE groups(P<0.001).The area under the curve for Candida in FE and suspected FE patients was 99.5%(P<0.05)and 81.3%(P<0.05),respectively.Finally,compared with FE patients,the relative abundance of Ascomycota and Candida in the esophageal flora of suspected FE patients was decreased,while the relative abundance of Yarrowia,Thermomyces and Pichia was increased.CONCLUSION ITS showed that composition of the fungal community was similar in the FE and suspected FE groups.ITS can be used as an auxiliary diagnostic method for FE and provide a theoretical basis for follow-up diagnosis and treatment.
