This study aimed to explore the mechanism of a novel mutation （p.Lys38Glu） in apolipoprotein H （APOH） gene causing hereditary beta2-glycoprotein I （β2GPI） deficiency and thrombosis in a proband with thrombophil...This study aimed to explore the mechanism of a novel mutation （p.Lys38Glu） in apolipoprotein H （APOH） gene causing hereditary beta2-glycoprotein I （β2GPI） deficiency and thrombosis in a proband with thrombophilia. The plasma level of β2GPI was measured by ELISA and Western blotting, and anti-β2GPI antibody by ELISA. Lupus anticoagulant （LA） was assayed using the dilute Russell viper venom time. Deficiency of the major natural anticoagulants including protein C （PC）, protein S （PS）, antithrombin （AT） and thrombomodulin （TM） was excluded from the proband. A mutation analysis was performed by amplification and sequencing of the APOH gene. Wild type and mutant （c.112A〉G） APOH expression plasmids were constructed and transfected into HEK293T cells. The results showed that the thrornbin generation capacity of the proband was higher than that of the other family members. Missense mutation p.Lys38Glu in APOH gene and LA coexisted in the proband. The mutation led to β2GPI deficiency and thrombosis by impairing the protein production and inhibiting the platelet aggregation. It was concluded that the recurrent thrombosis of the proband is associated with the coexistence ofp.Lys38Glu mutation in APOH gene and LA in plasma.展开更多
目的探索肺结核患者血清甲壳质酶蛋白40(chitinase protein 40,YKL-40)、β-防御素-2(human beta defensin 2,HBD-2)水平及其对肺结核的诊断价值。方法选取2021年6月—2023年6月山东省立医院收治的86例肺结核患者为肺结核组,根据痰涂片...目的探索肺结核患者血清甲壳质酶蛋白40(chitinase protein 40,YKL-40)、β-防御素-2(human beta defensin 2,HBD-2)水平及其对肺结核的诊断价值。方法选取2021年6月—2023年6月山东省立医院收治的86例肺结核患者为肺结核组,根据痰涂片结果分为活动性肺结核组(n=50)和非活动性肺结核组(n=36),另选取86例来自我院体检中心的健康受试者作为对照组。检测所有受试者血清中YKL-40、HBD-2水平并分析肺结核患者血清中YKL-40与HBD-2的相关性;采用受试者工作特征(receiver operating characteristic,ROC)曲线分析血清中YKL-40、HBD-2水平对肺结核及活动性肺结核的诊断价值。结果肺结核组血清YKL-40、HBD-2水平高于对照组(P均<0.05);活动性肺结核组血清YKL-40、HBD-2水平高于非活动性肺结核组(P均<0.05)。肺结核患者血清中YKL-40与HBD-2的水平呈正相关(r=0.601)。YKL-40、HBD-2及2者联合诊断肺结核的曲线下面积(area under the curve,AUC)分别为0.895、0.922、0.962,2者联合诊断优于单独诊断;YKL-40、HBD-2及2者联合诊断活动性肺结核的AUC分别为0.891、0.881、0.959,2者联合诊断优于单独诊断。结论肺结核患者血清YKL-40、HBD-2水平显著升高,且随病情加重而升高,2者对肺结核及活动性肺结核的具有一定的诊断价值。展开更多
Aim: We aimed to elucidate whether beta2-glycoprotein I (β2GPI) cooperation with hepatitis B surface antigen (HBsAg) promoted hepatocellular carcinogenesis enhanced by the lipopolysaccharide (LPS) via activation of n...Aim: We aimed to elucidate whether beta2-glycoprotein I (β2GPI) cooperation with hepatitis B surface antigen (HBsAg) promoted hepatocellular carcinogenesis enhanced by the lipopolysaccharide (LPS) via activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and expression of tumor necrosis factor-α(TNF-α), interleukin-1β (IL-1β), and alpha fetal protein (AFP) in liver cancer cells. Methods: Liver cancer cells (SMMC-7721) were transiently transfected with β2GPI and/or HBsAg and were subjected to LPS treatment. TNF-α, IL-1β, and AFP expression were measured in all groups by ELISA. NF-κB activation was assessed by non-radioactive electrophoretic mobility shift assay (EMSA) and was quantified in all groups. Results: Cells transfected with β2GPI and/or HBsAg induced activation of NF-κB, with the highest activation seen in the doubly β2GPI- and HBsAg-transfected cells treated with LPS. Non-transfected cells treated with LPS exhibited lower activation compared to either β2GPI- or HBsAg-transfected cells with LPS treatment. In addition, cells transfected with β2GPI and/or HBsAg induced significantly increased expression of TNF-α, IL-1β and AFP, with the highest levels again seen in the doubly β2GPI- and HBsAg-transfected cells treated with LPS. Conclusion: These observations suggest that the activity of NF-κB induced by β2GPI and HBsAg was enhanced by LPS. Expression of TNF-α, IL-1β and AFP increased in β2GPI and HBsAg cotransfected liver cancer cells.展开更多
Objective:To investigate the expression of matrix metalloproteinase-2(MMP-2),matrix metalloproteinase-9(MMP-9),and transforming growth factor beta 1(TGF beta 1)in the kidney tissue of rats with pyelonephritis and thei...Objective:To investigate the expression of matrix metalloproteinase-2(MMP-2),matrix metalloproteinase-9(MMP-9),and transforming growth factor beta 1(TGF beta 1)in the kidney tissue of rats with pyelonephritis and their relationship with pyelonephritis by establishing a rat model of acute pyelonephritis.Methods:80 male Wistar rats were randomly divided into a control group and an experimental group,with 40 rats each.The rats of the control group were injected with and saline and those of the experimental group were injected with 10μg/mL Escherichia coli(E.coli)and saline(1:100);the solutions for both groups were administered every 3 days for 7 days.The expressions of MMP-2,MMP-9 and TGF beta 1 in the kidney tissues of rats in each group were observed.Results:The expression of MMP-9 and TGF beta 1in the kidney tissue of rat acute pyelonephritis model rats was significantly higher than those of the control group(P<0.01);the MMP-9 mRNA content in the kidney tissue of the experimental group was significantly higher than that of the control group(P<0.05);the TGF beta 1 mRNA content in the renal tissue of the experimental group increased significantly compared to the(P<0.05);MMP-2,MMP-9 and TGF beta 1 began to express in the early stage of pyelonephritis until the complete formation of renal pelvic edema.The difference between groups was statistically significant(P<0.01).Conclusion:MMP-9 and TGF beta 1 are important factors regulating renal tubular epithelial cell injury and inflammatory response.展开更多
The incidence and prevalence of youth-onset type 2 diabetes mellitus(T2DM)are increasing.The rise in frequency and severity of childhood obesity,inclination to sedentary lifestyle,and epigenetic risks related to prena...The incidence and prevalence of youth-onset type 2 diabetes mellitus(T2DM)are increasing.The rise in frequency and severity of childhood obesity,inclination to sedentary lifestyle,and epigenetic risks related to prenatal hyperglycemia exposure are important drivers of the youth-onset T2DM epidemic and might as well be responsible for the early onset of diabetes complications.Indeed,youth-onset T2DM has a more extreme metabolic phenotype than adult-onset T2DM,with greater insulin resistance and more rapid deterioration of beta cell function.Therefore,intermediate complications such as microalbuminuria develop in late childhood or early adulthood,while end-stage complications develop in mid-life.Due to the lack of efficacy and safety data,several drugs available for the treatment of adults with T2DM have not been approved in youth,reducing the pharmacological treatment options.In this mini review,we will try to address the present challenges and pitfalls related to youth-onset T2DM and summarize the available interventions to mitigate the risk of microvascular and macrovascular complications.展开更多
目的通过比较聚乙二醇洛塞那肽与利拉鲁肽治疗肥胖2型糖尿病的疗效,为临床治疗该类疾病选择更高效的用药方案。方法选取东南大学医学院附属南京同仁医院2022年1月至2023年10月予以相应治疗的肥胖2型糖尿病患者共136例作为此次试验对象,...目的通过比较聚乙二醇洛塞那肽与利拉鲁肽治疗肥胖2型糖尿病的疗效,为临床治疗该类疾病选择更高效的用药方案。方法选取东南大学医学院附属南京同仁医院2022年1月至2023年10月予以相应治疗的肥胖2型糖尿病患者共136例作为此次试验对象,按照随机数字表法分成68例A组(聚乙二醇洛塞那肽治疗)与68例B组(利拉鲁肽治疗)。比较治疗前后两组肥胖相关指标、治疗前后两组血脂相关指标、治疗前后两组血糖指标以及治疗后不良反应发生率。结果治疗后两组体质量、腰臀比、体质量指数(BMI)和腰围均下降,B组体质量和BMI[分别为(80.31±7.62)kg和(24.13±1.82)kg·m^(-2)]低于A组体质量[分别为(83.65±7.93)kg和BMI(25.34±1.84)kg·m^(-2)](体质量:t=2.504,P=0.014;BMI:t=3.855,P<0.05);治疗后两组甘油三酯(TG)、血清总胆固醇(TC)和低密度脂蛋白(LDL)均下降,高密度脂蛋白胆固醇(HDL-C)上升(均P<0.05);治疗后两组餐后2 h血糖(2 h FBG)、空腹血糖(FBG)、糖化血红蛋白(HbAlc)、胰岛素抵抗指数(HOMA-IR)水平均下降,空腹血糖胰岛素(FINS)、β细胞功能指数(HOMA-β)水平均上升,A组2 h FBG、FBG[分别为(7.86±1.12)mmol·L^(-1)、(6.18±0.71)mmol·L^(-1)]低于B组[分别为2 h FBG(8.72±1.34)mmol·L^(-1)和FBG(7.02±0.62)mmol·L^(-1)](2 h FBG:t=4.061,P<0.05;FBG:t=7.349,P<0.05),A组HOMA-β[(74.62±3.78)%]高于B组[(62.79±3.56)%](t=18.937,P<0.05);两组不良反应发生率比较差异无统计学意义(20.59%vs 25.00%,χ^(2)=0.376,P=0.540)。结论对于肥胖2型糖尿病患者,聚乙二醇洛塞那肽与利拉鲁肽均能有效减轻体质量、调节血脂、降低血糖水平以及增强胰岛β细胞的功能,且安全性相似。然而,在降低体质量方面,利拉鲁肽的效果更为显著,而聚乙二醇洛塞那肽在改善胰岛β细胞功能和降低血糖方面则表现更为出色。展开更多
文摘This study aimed to explore the mechanism of a novel mutation （p.Lys38Glu） in apolipoprotein H （APOH） gene causing hereditary beta2-glycoprotein I （β2GPI） deficiency and thrombosis in a proband with thrombophilia. The plasma level of β2GPI was measured by ELISA and Western blotting, and anti-β2GPI antibody by ELISA. Lupus anticoagulant （LA） was assayed using the dilute Russell viper venom time. Deficiency of the major natural anticoagulants including protein C （PC）, protein S （PS）, antithrombin （AT） and thrombomodulin （TM） was excluded from the proband. A mutation analysis was performed by amplification and sequencing of the APOH gene. Wild type and mutant （c.112A〉G） APOH expression plasmids were constructed and transfected into HEK293T cells. The results showed that the thrornbin generation capacity of the proband was higher than that of the other family members. Missense mutation p.Lys38Glu in APOH gene and LA coexisted in the proband. The mutation led to β2GPI deficiency and thrombosis by impairing the protein production and inhibiting the platelet aggregation. It was concluded that the recurrent thrombosis of the proband is associated with the coexistence ofp.Lys38Glu mutation in APOH gene and LA in plasma.
文摘目的探索肺结核患者血清甲壳质酶蛋白40(chitinase protein 40,YKL-40)、β-防御素-2(human beta defensin 2,HBD-2)水平及其对肺结核的诊断价值。方法选取2021年6月—2023年6月山东省立医院收治的86例肺结核患者为肺结核组,根据痰涂片结果分为活动性肺结核组(n=50)和非活动性肺结核组(n=36),另选取86例来自我院体检中心的健康受试者作为对照组。检测所有受试者血清中YKL-40、HBD-2水平并分析肺结核患者血清中YKL-40与HBD-2的相关性;采用受试者工作特征(receiver operating characteristic,ROC)曲线分析血清中YKL-40、HBD-2水平对肺结核及活动性肺结核的诊断价值。结果肺结核组血清YKL-40、HBD-2水平高于对照组(P均<0.05);活动性肺结核组血清YKL-40、HBD-2水平高于非活动性肺结核组(P均<0.05)。肺结核患者血清中YKL-40与HBD-2的水平呈正相关(r=0.601)。YKL-40、HBD-2及2者联合诊断肺结核的曲线下面积(area under the curve,AUC)分别为0.895、0.922、0.962,2者联合诊断优于单独诊断;YKL-40、HBD-2及2者联合诊断活动性肺结核的AUC分别为0.891、0.881、0.959,2者联合诊断优于单独诊断。结论肺结核患者血清YKL-40、HBD-2水平显著升高,且随病情加重而升高,2者对肺结核及活动性肺结核的具有一定的诊断价值。
文摘Aim: We aimed to elucidate whether beta2-glycoprotein I (β2GPI) cooperation with hepatitis B surface antigen (HBsAg) promoted hepatocellular carcinogenesis enhanced by the lipopolysaccharide (LPS) via activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and expression of tumor necrosis factor-α(TNF-α), interleukin-1β (IL-1β), and alpha fetal protein (AFP) in liver cancer cells. Methods: Liver cancer cells (SMMC-7721) were transiently transfected with β2GPI and/or HBsAg and were subjected to LPS treatment. TNF-α, IL-1β, and AFP expression were measured in all groups by ELISA. NF-κB activation was assessed by non-radioactive electrophoretic mobility shift assay (EMSA) and was quantified in all groups. Results: Cells transfected with β2GPI and/or HBsAg induced activation of NF-κB, with the highest activation seen in the doubly β2GPI- and HBsAg-transfected cells treated with LPS. Non-transfected cells treated with LPS exhibited lower activation compared to either β2GPI- or HBsAg-transfected cells with LPS treatment. In addition, cells transfected with β2GPI and/or HBsAg induced significantly increased expression of TNF-α, IL-1β and AFP, with the highest levels again seen in the doubly β2GPI- and HBsAg-transfected cells treated with LPS. Conclusion: These observations suggest that the activity of NF-κB induced by β2GPI and HBsAg was enhanced by LPS. Expression of TNF-α, IL-1β and AFP increased in β2GPI and HBsAg cotransfected liver cancer cells.
基金Health Commission of Hebei Province:Chuanxiong Extract Improves Inflammatory Response in Rats with Pyelonephritis through IL-6/STAT3 Signaling Pathway(Project number:20231486)。
文摘Objective:To investigate the expression of matrix metalloproteinase-2(MMP-2),matrix metalloproteinase-9(MMP-9),and transforming growth factor beta 1(TGF beta 1)in the kidney tissue of rats with pyelonephritis and their relationship with pyelonephritis by establishing a rat model of acute pyelonephritis.Methods:80 male Wistar rats were randomly divided into a control group and an experimental group,with 40 rats each.The rats of the control group were injected with and saline and those of the experimental group were injected with 10μg/mL Escherichia coli(E.coli)and saline(1:100);the solutions for both groups were administered every 3 days for 7 days.The expressions of MMP-2,MMP-9 and TGF beta 1 in the kidney tissues of rats in each group were observed.Results:The expression of MMP-9 and TGF beta 1in the kidney tissue of rat acute pyelonephritis model rats was significantly higher than those of the control group(P<0.01);the MMP-9 mRNA content in the kidney tissue of the experimental group was significantly higher than that of the control group(P<0.05);the TGF beta 1 mRNA content in the renal tissue of the experimental group increased significantly compared to the(P<0.05);MMP-2,MMP-9 and TGF beta 1 began to express in the early stage of pyelonephritis until the complete formation of renal pelvic edema.The difference between groups was statistically significant(P<0.01).Conclusion:MMP-9 and TGF beta 1 are important factors regulating renal tubular epithelial cell injury and inflammatory response.
文摘The incidence and prevalence of youth-onset type 2 diabetes mellitus(T2DM)are increasing.The rise in frequency and severity of childhood obesity,inclination to sedentary lifestyle,and epigenetic risks related to prenatal hyperglycemia exposure are important drivers of the youth-onset T2DM epidemic and might as well be responsible for the early onset of diabetes complications.Indeed,youth-onset T2DM has a more extreme metabolic phenotype than adult-onset T2DM,with greater insulin resistance and more rapid deterioration of beta cell function.Therefore,intermediate complications such as microalbuminuria develop in late childhood or early adulthood,while end-stage complications develop in mid-life.Due to the lack of efficacy and safety data,several drugs available for the treatment of adults with T2DM have not been approved in youth,reducing the pharmacological treatment options.In this mini review,we will try to address the present challenges and pitfalls related to youth-onset T2DM and summarize the available interventions to mitigate the risk of microvascular and macrovascular complications.
文摘目的通过比较聚乙二醇洛塞那肽与利拉鲁肽治疗肥胖2型糖尿病的疗效,为临床治疗该类疾病选择更高效的用药方案。方法选取东南大学医学院附属南京同仁医院2022年1月至2023年10月予以相应治疗的肥胖2型糖尿病患者共136例作为此次试验对象,按照随机数字表法分成68例A组(聚乙二醇洛塞那肽治疗)与68例B组(利拉鲁肽治疗)。比较治疗前后两组肥胖相关指标、治疗前后两组血脂相关指标、治疗前后两组血糖指标以及治疗后不良反应发生率。结果治疗后两组体质量、腰臀比、体质量指数(BMI)和腰围均下降,B组体质量和BMI[分别为(80.31±7.62)kg和(24.13±1.82)kg·m^(-2)]低于A组体质量[分别为(83.65±7.93)kg和BMI(25.34±1.84)kg·m^(-2)](体质量:t=2.504,P=0.014;BMI:t=3.855,P<0.05);治疗后两组甘油三酯(TG)、血清总胆固醇(TC)和低密度脂蛋白(LDL)均下降,高密度脂蛋白胆固醇(HDL-C)上升(均P<0.05);治疗后两组餐后2 h血糖(2 h FBG)、空腹血糖(FBG)、糖化血红蛋白(HbAlc)、胰岛素抵抗指数(HOMA-IR)水平均下降,空腹血糖胰岛素(FINS)、β细胞功能指数(HOMA-β)水平均上升,A组2 h FBG、FBG[分别为(7.86±1.12)mmol·L^(-1)、(6.18±0.71)mmol·L^(-1)]低于B组[分别为2 h FBG(8.72±1.34)mmol·L^(-1)和FBG(7.02±0.62)mmol·L^(-1)](2 h FBG:t=4.061,P<0.05;FBG:t=7.349,P<0.05),A组HOMA-β[(74.62±3.78)%]高于B组[(62.79±3.56)%](t=18.937,P<0.05);两组不良反应发生率比较差异无统计学意义(20.59%vs 25.00%,χ^(2)=0.376,P=0.540)。结论对于肥胖2型糖尿病患者,聚乙二醇洛塞那肽与利拉鲁肽均能有效减轻体质量、调节血脂、降低血糖水平以及增强胰岛β细胞的功能,且安全性相似。然而,在降低体质量方面,利拉鲁肽的效果更为显著,而聚乙二醇洛塞那肽在改善胰岛β细胞功能和降低血糖方面则表现更为出色。
