This study investigated the mechanism underlying electroacupuncture therapy for vascular dementia through electroacupuncture at the acupoints of Baihui （DU20）, Dazhui （DU14）, and bilateral Shenshu （BL23） in a ra...This study investigated the mechanism underlying electroacupuncture therapy for vascular dementia through electroacupuncture at the acupoints of Baihui （DU20）, Dazhui （DU14）, and bilateral Shenshu （BL23） in a rat model of vascular dementia produced by bilateral middle cerebral artery occlusion. Morris water maze test showed that electroacupuncture improved the learning ability of vascular dementia rats. Western blot assay revealed that the expression of p70 ribosomal protein S6 kinase and ribosomal protein S6 in vascular dementia rats was significantly increased after electroacupuncture, compared with the model group that was not treated with acupuncture. The average escape latency was also shortened after electroacupuncture, and escape strategies in the spatial probe test improved from edge and random searches, to linear and trending swim pathways. The experimental findings indicate that electroacupuncture improves learning and memory ability by up-regulating expression of p70 ribosomal protein S6 kinase and ribosomal protein S6 in the hippocampus of vascular dementia rats.展开更多
BACKGROUND Systemic lupus erythematosus(SLE)is an autoimmune disease characterized by systemic involvement and multiple autoantibodies in the serum.Patients with protein C(PC)and protein S(PS)deficiency are prone to t...BACKGROUND Systemic lupus erythematosus(SLE)is an autoimmune disease characterized by systemic involvement and multiple autoantibodies in the serum.Patients with protein C(PC)and protein S(PS)deficiency are prone to thrombosis.In contrast,patients with primary hyperfibrino-lysis tend to bleed.CASE SUMMARY A 52-year-old female patient with bilateral pleural effusion was diagnosed with"tuberculous pleurisy"and treated with anti-tuberculosis drugs and prednisone.The coagulation-related laboratory results showed decreased fibrinogen,PC activity,PS activity,and antithrombinШactivity.The immune-related laboratory results showed positive antinuclear antibody,anti-Smith antibody,anticardiolipin antibody(ACL),anti-β2-glycoprotein I antibody(aβ2GPI)and direct Coomb’s test and decreased complement 3 and complement 4.Thoracoscopy was performed and bloody pleural fluid was drained.Pathology of the pleural biopsy showed lymphocytes,plasma cells,and a few eosinophils in adipose and fibrous connective tissue.Results of whole exome sequencing of blood showed no genetic mutations suggesting the presence of hereditary hematological diseases.The patient was finally diagnosed with SLE and primary hyperfibrinolysis,and was treated with prednisolone,hydroxychloroquine,and compound cyclophosphamide.CONCLUSION PC and PS deficiency in SLE might be related to ACL and aβ2GPI.SLE and primary hyperfibrinolysis can coexist in one patient,with both a risk of thrombosis and a risk of bleeding.展开更多
A 76-year-old woman was diagnosed as having left lilac deep vein thrombosis due to a hereditary deficiency of protein S, seventeen members of her family were studied with the measurements of total protein S (TPS), fre...A 76-year-old woman was diagnosed as having left lilac deep vein thrombosis due to a hereditary deficiency of protein S, seventeen members of her family were studied with the measurements of total protein S (TPS), free protein S (FPS), protein C (PC) and anti-thrombin-Ⅲ(AT-Ⅲ). The results showed that the level of FPS of thepatient was only 7%, while that of TPS 137.1%. Her secondson had a low FPS level (13.4%) too, and his TPS level was 48.1%. PC and AT-Ⅲwere all normal It was thus the first case of hereditary PS dificiency reported in China.展开更多
Objective: To assess the cerebral injury in on-pump beating-heart procedures under mild hypothermia in comparison with traditional on-pump arrested-heart procedures under moderate hypothermia. Methods: Forty patients,...Objective: To assess the cerebral injury in on-pump beating-heart procedures under mild hypothermia in comparison with traditional on-pump arrested-heart procedures under moderate hypothermia. Methods: Forty patients, 20 with congenital heart disease (CHD) and 20 of rheumatic heart disease (RHD), were divided into 2 groups: Control group (group A, n=20) including 10 patients suffering from CHD as group A1 and the left 10 from RHD as group A2; and experiment group (group B, n=20) which consisting of group B1 (10 with CHD) and group B2 (10 of RHD). The patients in group A underwent traditional arrested-heart procedures, and those in group B were operated on with beating-heart procedures. Arterial blood samples were collected at preoperation (time A), 20 min after cardiopulmonary bypass (CPB) starting (time B), 1 h after CPB (time C) and 24 h postoperation (time D) respectively. Plasma contents of neuron-specific enolase (NSE) and protein S-100b were measured with sensitive ELISA. All the patients received echoencephalography (EEG) before and 1 week after operation. Results: The plasma contents of protein S-100b were increased very significantly at time B, C and D in comparison with those at time A (P<0.01), and that of patients in group A1 was significantly higher than that in group B at time B (P<0.05). There was no significant difference at other time points. At time B, the plasma contents of NSE were significantly higher in group A than in group B, and in group A1 and B1 than in group A2 and B2. What's more, at time B, the former fell back to their preoperative levels, but the latter remained still higher levels than the preoperative ones (P<0.01). No significant difference was found in the abnormality rates of postoperative EEG between 2 groups. Conclusion: The perioperative plasma contents of NSE and protein S-100b are not significantly higher in group B than in group A. On-pump beating-heart procedures do not make more serious cerebral dysfunction than the traditional arrested-heart procedures.展开更多
The Tyro3, Axl and Mer (TAM) receptor tyrosine kinases are activated by endogenous ligands, protein S1 (PROS1) and growth arrest-specific gene 6 (Gas6), and those have important effects on cell biology. These receptor...The Tyro3, Axl and Mer (TAM) receptor tyrosine kinases are activated by endogenous ligands, protein S1 (PROS1) and growth arrest-specific gene 6 (Gas6), and those have important effects on cell biology. These receptors (Rs) can be shad from the cell membrane and their soluble(s) forms can be found in plasma. We investigated the fluctuation and interactive role of sTAMRs and its ligands in patients with hepatocellular carcinoma (HCC), hepatitis groups, and healthy normal adult controls (NC). The measurement cases were 45 patients with HCC group (stage 1 in 4, stage 2 in 8, stage 3 in 16, and stage 4 in 17), 4 patients with fulminant hepatitis (FH), 14 patients with acute hepatitis (AH), 10 patients with chronic hepatitis (CH), 16 patients with liver cirrhosis (LC), and 20 NCs matched by age. Plasma levels of three sTAMRs and their ligands were measured by ELISA. In comparison with NCs, Gas6, des-γ-carboxy Gas6, and sTAMRs levels were significantly higher in HCC patients, but free PROS1 levels were significantly lower. The sTyro3 and sAxl levels peaked HCC stages 2 and 3 respectively, and gradually decreased afterwards while maintaining high levels. sMer levels increased with the progression of HCC. Gas6 and des-γ-carboxy Gas6 levels gradually increased, and PROS1 levels decreased with the progression of HCC. Gas6 levels were positively correlated with sAxl levels, whereas sMer levels were negatively correlated with free PROS1 levels. sTAMRs and Gas6 levels increased in parallel to the progression of HCC fibrosis. Through the progression of HCC, Axl played the major role in TAMRs activation. However, sTYro3 continued increasing rapidly from the early stage, and that of Mer increased throughout the progression. Roles of Axl may be changed in Mer, because des-γ-carboxy Gas6 levels increasing with Gas6 in the advanced stage of HCC cannot send a signal to Axl.展开更多
PC and PS antigens were measured in 370 cases of 12 different diseases and 14 women at third trimester of pregnancy. The PC level was found significantly raised in coronary heart disease, diabetes, nephrotic syndrome,...PC and PS antigens were measured in 370 cases of 12 different diseases and 14 women at third trimester of pregnancy. The PC level was found significantly raised in coronary heart disease, diabetes, nephrotic syndrome, stroke, aplastic anemia and the third trimester of pregnancy, decreased in chronic hepatitis, acute fulminant hepatitis, cirrhosis and deep vein thrombosis (DVT) and no change in acute hepatitis, primary liver carcinoma, Buerger’s disease and leukemia. Total PS was increased in type Ⅱdiabetes, acute lymphocytic leukemia and DVT, and decreased in Berger’s disease, liver diseases, aplastic anemia and the third trimester of pregnancy. In majority of the cases, the total PS and free PS changed parallelly except in Buerger’s disease, DVT and preeclampsia. No correlation was found between PC and PS, PC and AT-Ⅲ.展开更多
The spike protein(S)of SARS-CoV-2 is responsible for viral attachment and entry,thus a major factor for host suscep-tibility,tissue tropism,virulence and pathogenicity.The S is divided with S1 and S2 region,and the S1...The spike protein(S)of SARS-CoV-2 is responsible for viral attachment and entry,thus a major factor for host suscep-tibility,tissue tropism,virulence and pathogenicity.The S is divided with S1 and S2 region,and the S1 contains the receptor-binding domain(RBD),while the S2 contains the hydrophobic fusion domain for the entry into the host cell.Numerous host proteases have been implicated in the activation of SARS-CoV-2 S through various c leavage sites.In this article,we review host proteases including furin,trypsin,transmembrane protease serine 2(TMPRSS2)and cathepsins in the activation of SARS-CoV-2 S.Many betacoronaviruses including SARS-CoV-2 have polybasic residues at the S1/S2 site which is subjected to the cleavage by furin.The S1/S2 cleavage facilitates more assessable RBD to the receptor ACE2,and the binding triggers further conformational changes and exposure of the S2'site to proteases such as type Il transmembrane serine proteases(TTPRs)including TMPRSS2.In the presence of TMPRSS2 on the target cells,SARS-CoV-2 can utilize a direct entry route by fusion of the viral envelope to the cellular membrane.In the absence of TMPRSS2,SARS-CoV-2 enter target cells via endosomes where multiple cathepsins cleave the S for the successful entry.Additional host proteases involved in the cleavage of the S were discussed.This article also includes roles of 3C-like protease inhibitors which have inhibitory activity against cathepsin L in the entry of SARS-CoV-2,and discussed the dual roles of such inhibitors in virus replication.展开更多
目的研究G_(2)/S期应答相关蛋白1(G_(2) and S phase-expressed protein 1,GTSE1)在肝细胞癌(hepatocellular carcinoma,HCC)中的表达、免疫学作用和预后分析,及其潜在作用机制。方法使用公共数据库癌症基因组图谱(The Cancer Genome At...目的研究G_(2)/S期应答相关蛋白1(G_(2) and S phase-expressed protein 1,GTSE1)在肝细胞癌(hepatocellular carcinoma,HCC)中的表达、免疫学作用和预后分析,及其潜在作用机制。方法使用公共数据库癌症基因组图谱(The Cancer Genome Atlas,TCGA)提供的数据,用Kaplan-Meier、肿瘤免疫评估资源(Tumor Immune Estimation Resource,TIMER)数据库和基因表达谱交互分析(Gene Expression Profiling Interactive Analysis,GEPIA)数据库进行GTSE1基因表达、免疫学作用及预后分析,通过免疫组化实验验证GTSE1在临床样本中的表达,应用R软件对GTSE1相关差异基因进行基因本体(gene ontology,GO)和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)富集分析。结果GTSE1在人类癌组织中显著高表达,且与肝细胞癌预后不良显著相关(P<0.05);GTSE1基因表达与HCC中浸润性免疫细胞的丰度显著相关(P<0.001)。GTSE1相关的差异表达基因主要富集于核分裂、细胞器裂变、离子通道活性等基因模块;其参与的信号通路主要包括神经活性配体-受体的相互作用、细胞周期等。结论GTSE1在HCC中的表达显著上调并与患者预后不良显著相关,且在免疫细胞浸润中发挥重要作用,可作为HCC的预后标志物和免疫治疗靶点。展开更多
基金supported by the National Natural Science Foundation of China, No. 81001541
文摘This study investigated the mechanism underlying electroacupuncture therapy for vascular dementia through electroacupuncture at the acupoints of Baihui （DU20）, Dazhui （DU14）, and bilateral Shenshu （BL23） in a rat model of vascular dementia produced by bilateral middle cerebral artery occlusion. Morris water maze test showed that electroacupuncture improved the learning ability of vascular dementia rats. Western blot assay revealed that the expression of p70 ribosomal protein S6 kinase and ribosomal protein S6 in vascular dementia rats was significantly increased after electroacupuncture, compared with the model group that was not treated with acupuncture. The average escape latency was also shortened after electroacupuncture, and escape strategies in the spatial probe test improved from edge and random searches, to linear and trending swim pathways. The experimental findings indicate that electroacupuncture improves learning and memory ability by up-regulating expression of p70 ribosomal protein S6 kinase and ribosomal protein S6 in the hippocampus of vascular dementia rats.
文摘BACKGROUND Systemic lupus erythematosus(SLE)is an autoimmune disease characterized by systemic involvement and multiple autoantibodies in the serum.Patients with protein C(PC)and protein S(PS)deficiency are prone to thrombosis.In contrast,patients with primary hyperfibrino-lysis tend to bleed.CASE SUMMARY A 52-year-old female patient with bilateral pleural effusion was diagnosed with"tuberculous pleurisy"and treated with anti-tuberculosis drugs and prednisone.The coagulation-related laboratory results showed decreased fibrinogen,PC activity,PS activity,and antithrombinШactivity.The immune-related laboratory results showed positive antinuclear antibody,anti-Smith antibody,anticardiolipin antibody(ACL),anti-β2-glycoprotein I antibody(aβ2GPI)and direct Coomb’s test and decreased complement 3 and complement 4.Thoracoscopy was performed and bloody pleural fluid was drained.Pathology of the pleural biopsy showed lymphocytes,plasma cells,and a few eosinophils in adipose and fibrous connective tissue.Results of whole exome sequencing of blood showed no genetic mutations suggesting the presence of hereditary hematological diseases.The patient was finally diagnosed with SLE and primary hyperfibrinolysis,and was treated with prednisolone,hydroxychloroquine,and compound cyclophosphamide.CONCLUSION PC and PS deficiency in SLE might be related to ACL and aβ2GPI.SLE and primary hyperfibrinolysis can coexist in one patient,with both a risk of thrombosis and a risk of bleeding.
文摘A 76-year-old woman was diagnosed as having left lilac deep vein thrombosis due to a hereditary deficiency of protein S, seventeen members of her family were studied with the measurements of total protein S (TPS), free protein S (FPS), protein C (PC) and anti-thrombin-Ⅲ(AT-Ⅲ). The results showed that the level of FPS of thepatient was only 7%, while that of TPS 137.1%. Her secondson had a low FPS level (13.4%) too, and his TPS level was 48.1%. PC and AT-Ⅲwere all normal It was thus the first case of hereditary PS dificiency reported in China.
文摘Objective: To assess the cerebral injury in on-pump beating-heart procedures under mild hypothermia in comparison with traditional on-pump arrested-heart procedures under moderate hypothermia. Methods: Forty patients, 20 with congenital heart disease (CHD) and 20 of rheumatic heart disease (RHD), were divided into 2 groups: Control group (group A, n=20) including 10 patients suffering from CHD as group A1 and the left 10 from RHD as group A2; and experiment group (group B, n=20) which consisting of group B1 (10 with CHD) and group B2 (10 of RHD). The patients in group A underwent traditional arrested-heart procedures, and those in group B were operated on with beating-heart procedures. Arterial blood samples were collected at preoperation (time A), 20 min after cardiopulmonary bypass (CPB) starting (time B), 1 h after CPB (time C) and 24 h postoperation (time D) respectively. Plasma contents of neuron-specific enolase (NSE) and protein S-100b were measured with sensitive ELISA. All the patients received echoencephalography (EEG) before and 1 week after operation. Results: The plasma contents of protein S-100b were increased very significantly at time B, C and D in comparison with those at time A (P<0.01), and that of patients in group A1 was significantly higher than that in group B at time B (P<0.05). There was no significant difference at other time points. At time B, the plasma contents of NSE were significantly higher in group A than in group B, and in group A1 and B1 than in group A2 and B2. What's more, at time B, the former fell back to their preoperative levels, but the latter remained still higher levels than the preoperative ones (P<0.01). No significant difference was found in the abnormality rates of postoperative EEG between 2 groups. Conclusion: The perioperative plasma contents of NSE and protein S-100b are not significantly higher in group B than in group A. On-pump beating-heart procedures do not make more serious cerebral dysfunction than the traditional arrested-heart procedures.
文摘The Tyro3, Axl and Mer (TAM) receptor tyrosine kinases are activated by endogenous ligands, protein S1 (PROS1) and growth arrest-specific gene 6 (Gas6), and those have important effects on cell biology. These receptors (Rs) can be shad from the cell membrane and their soluble(s) forms can be found in plasma. We investigated the fluctuation and interactive role of sTAMRs and its ligands in patients with hepatocellular carcinoma (HCC), hepatitis groups, and healthy normal adult controls (NC). The measurement cases were 45 patients with HCC group (stage 1 in 4, stage 2 in 8, stage 3 in 16, and stage 4 in 17), 4 patients with fulminant hepatitis (FH), 14 patients with acute hepatitis (AH), 10 patients with chronic hepatitis (CH), 16 patients with liver cirrhosis (LC), and 20 NCs matched by age. Plasma levels of three sTAMRs and their ligands were measured by ELISA. In comparison with NCs, Gas6, des-γ-carboxy Gas6, and sTAMRs levels were significantly higher in HCC patients, but free PROS1 levels were significantly lower. The sTyro3 and sAxl levels peaked HCC stages 2 and 3 respectively, and gradually decreased afterwards while maintaining high levels. sMer levels increased with the progression of HCC. Gas6 and des-γ-carboxy Gas6 levels gradually increased, and PROS1 levels decreased with the progression of HCC. Gas6 levels were positively correlated with sAxl levels, whereas sMer levels were negatively correlated with free PROS1 levels. sTAMRs and Gas6 levels increased in parallel to the progression of HCC fibrosis. Through the progression of HCC, Axl played the major role in TAMRs activation. However, sTYro3 continued increasing rapidly from the early stage, and that of Mer increased throughout the progression. Roles of Axl may be changed in Mer, because des-γ-carboxy Gas6 levels increasing with Gas6 in the advanced stage of HCC cannot send a signal to Axl.
文摘PC and PS antigens were measured in 370 cases of 12 different diseases and 14 women at third trimester of pregnancy. The PC level was found significantly raised in coronary heart disease, diabetes, nephrotic syndrome, stroke, aplastic anemia and the third trimester of pregnancy, decreased in chronic hepatitis, acute fulminant hepatitis, cirrhosis and deep vein thrombosis (DVT) and no change in acute hepatitis, primary liver carcinoma, Buerger’s disease and leukemia. Total PS was increased in type Ⅱdiabetes, acute lymphocytic leukemia and DVT, and decreased in Berger’s disease, liver diseases, aplastic anemia and the third trimester of pregnancy. In majority of the cases, the total PS and free PS changed parallelly except in Buerger’s disease, DVT and preeclampsia. No correlation was found between PC and PS, PC and AT-Ⅲ.
基金National Institutes of Health(NIH)(grants R01 A/130092 and Al161085).
文摘The spike protein(S)of SARS-CoV-2 is responsible for viral attachment and entry,thus a major factor for host suscep-tibility,tissue tropism,virulence and pathogenicity.The S is divided with S1 and S2 region,and the S1 contains the receptor-binding domain(RBD),while the S2 contains the hydrophobic fusion domain for the entry into the host cell.Numerous host proteases have been implicated in the activation of SARS-CoV-2 S through various c leavage sites.In this article,we review host proteases including furin,trypsin,transmembrane protease serine 2(TMPRSS2)and cathepsins in the activation of SARS-CoV-2 S.Many betacoronaviruses including SARS-CoV-2 have polybasic residues at the S1/S2 site which is subjected to the cleavage by furin.The S1/S2 cleavage facilitates more assessable RBD to the receptor ACE2,and the binding triggers further conformational changes and exposure of the S2'site to proteases such as type Il transmembrane serine proteases(TTPRs)including TMPRSS2.In the presence of TMPRSS2 on the target cells,SARS-CoV-2 can utilize a direct entry route by fusion of the viral envelope to the cellular membrane.In the absence of TMPRSS2,SARS-CoV-2 enter target cells via endosomes where multiple cathepsins cleave the S for the successful entry.Additional host proteases involved in the cleavage of the S were discussed.This article also includes roles of 3C-like protease inhibitors which have inhibitory activity against cathepsin L in the entry of SARS-CoV-2,and discussed the dual roles of such inhibitors in virus replication.
文摘目的研究G_(2)/S期应答相关蛋白1(G_(2) and S phase-expressed protein 1,GTSE1)在肝细胞癌(hepatocellular carcinoma,HCC)中的表达、免疫学作用和预后分析,及其潜在作用机制。方法使用公共数据库癌症基因组图谱(The Cancer Genome Atlas,TCGA)提供的数据,用Kaplan-Meier、肿瘤免疫评估资源(Tumor Immune Estimation Resource,TIMER)数据库和基因表达谱交互分析(Gene Expression Profiling Interactive Analysis,GEPIA)数据库进行GTSE1基因表达、免疫学作用及预后分析,通过免疫组化实验验证GTSE1在临床样本中的表达,应用R软件对GTSE1相关差异基因进行基因本体(gene ontology,GO)和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)富集分析。结果GTSE1在人类癌组织中显著高表达,且与肝细胞癌预后不良显著相关(P<0.05);GTSE1基因表达与HCC中浸润性免疫细胞的丰度显著相关(P<0.001)。GTSE1相关的差异表达基因主要富集于核分裂、细胞器裂变、离子通道活性等基因模块;其参与的信号通路主要包括神经活性配体-受体的相互作用、细胞周期等。结论GTSE1在HCC中的表达显著上调并与患者预后不良显著相关,且在免疫细胞浸润中发挥重要作用,可作为HCC的预后标志物和免疫治疗靶点。
