BACKGROUND Islets of Langerhans beta cells diminish in autoimmune type 1 diabetes mellitus(T1DM).Teplizumab,a humanized anti-CD3 monoclonal antibody,may help T1DM.Its long-term implications on clinical T1DM developmen...BACKGROUND Islets of Langerhans beta cells diminish in autoimmune type 1 diabetes mellitus(T1DM).Teplizumab,a humanized anti-CD3 monoclonal antibody,may help T1DM.Its long-term implications on clinical T1DM development,safety,and efficacy are unknown.AIM To assess the effectiveness and safety of teplizumab as a therapeutic intervention for individuals with T1DM.METHODS A systematic search was conducted using four electronic databases(PubMed,Embase,Scopus,and Cochrane Library)to select publications published in peerreviewed journals written in English.The odds ratio(OR)and risk ratio(RR)were calculated,along with their 95%CI.We assessed heterogeneity using Cochrane Q and I2 statistics and the appropriate P value.RESULTS There were 8 randomized controlled trials(RCTs)in the current meta-analysis with a total of 1908 T1DM patients from diverse age cohorts,with 1361 patients receiving Teplizumab and 547 patients receiving a placebo.Teplizumab was found to have a substantial link with a decrease in insulin consumption,with an OR of 4.13(95%CI:1.72 to 9.90).Teplizumab is associated with an improved Cpeptide response(OR 2.49;95%CI:1.62 to 3.81)and a significant change in Glycated haemoglobin A1c(HbA1c)levels in people with type 1 diabetes[OR 1.75(95%CI:1.03 to 2.98)],and it has a RR of 0.71(95%CI:0.53 to 0.95).CONCLUSION In type 1 diabetics,teplizumab decreased insulin consumption,improved C-peptide response,and significantly changed HbA1c levels with negligible side effects.Teplizumab appears to improve glycaemic control and diabetes management with good safety and efficacy.展开更多
Objective: IMpower210(NCT02813785) explored the efficacy and safety of single-agent atezolizumab vs.docetaxel as second-line treatment for advanced non-small cell lung cancer(NSCLC) in East Asian patients.Methods: Key...Objective: IMpower210(NCT02813785) explored the efficacy and safety of single-agent atezolizumab vs.docetaxel as second-line treatment for advanced non-small cell lung cancer(NSCLC) in East Asian patients.Methods: Key eligibility criteria for this phase Ⅲ, open-label, randomized study included age ≥18 years;histologically documented advanced NSCLC per the Union for International Cancer Control/American Joint Committee on Cancer staging system(7th edition);Eastern Cooperative Oncology Group performance status of 0 or 1;and disease progression following platinum-based chemotherapy for advanced or metastatic NSCLC. Patients were randomized 2:1 to receive either atezolizumab(1,200 mg) or docetaxel(75 mg/m^(2)). The primary study endpoint was overall survival(OS) in the intention-to-treat(ITT) population with wild-type epidermal growth factor receptor expression(ITT EGFR-WT) and in the overall ITT population.Results: Median OS in the ITT EGFR-WT population(n=467) was 12.3 [95% confidence interval(95% CI),10.3-13.8] months in the atezolizumab arm(n=312) and 9.9(95% CI, 7.8-13.9) months in the docetaxel arm[n=155;stratified hazard ratio(HR), 0.82;95% CI, 0.66-1.03]. Median OS in the overall ITT population was 12.5(95% CI, 10.8-13.8) months with atezolizumab treatment and 11.1(95% CI, 8.4-14.2) months(n=377) with docetaxel treatment(n=188;stratified HR, 0.87;95% CI, 0.71-1.08). Grade 3/4 treatment-related adverse events(TRAEs) occurred in 18.4% of patients in the atezolizumab arm and 50.0% of patients in the docetaxel arm.Conclusions: IMpower210 did not meet its primary efficacy endpoint of OS in the ITT EGFR-WT or overall ITT populations. Atezolizumab was comparatively more tolerable than docetaxel, with a lower incidence of grade3/4 TRAEs.展开更多
冠状动脉粥样硬化性心脏病(coronary atherosclerotic heart disease,CHD)的发病率及病死率居全球首位,而低密度脂蛋白胆固醇(low density lipoprotein-cholesterol,LDL-C)的升高是CHD的主要危险因素,因此降低LDL-C水平可有效减少CHD的...冠状动脉粥样硬化性心脏病(coronary atherosclerotic heart disease,CHD)的发病率及病死率居全球首位,而低密度脂蛋白胆固醇(low density lipoprotein-cholesterol,LDL-C)的升高是CHD的主要危险因素,因此降低LDL-C水平可有效减少CHD的发病风险。临床上降脂药物如他汀类虽能够有效降低LDL-C水平,但仍有部分患者无法达到降脂目标或者无法耐受。前蛋白转化酶枯草溶菌素9(proprotein convertase subtilisin/kexin type 9,PCSK9)抑制剂作为新一代的降脂药物,越来越受到重视。其通过对PCSK9的抑制作用,增加低密度脂蛋白受体的循环利用,能够显著降低血清中LDL-C水平。目前PCSK9抑制剂已进入Ⅲ期临床试验,试验结果显示其具有良好的降脂效果和耐受性。该文就PCSK9抑制剂最新进展和面临的问题作一综述。展开更多
AIM: To set up a new method to detect tissue inhibitors of metalloproteinase-1 and -2(TIMP-1 and TIMP-2) in sera of patients with hepatic cirrhosis, and to investigate the expression and location of TIMP-1 and TIMP-2 ...AIM: To set up a new method to detect tissue inhibitors of metalloproteinase-1 and -2(TIMP-1 and TIMP-2) in sera of patients with hepatic cirrhosis, and to investigate the expression and location of TIMP-1 and TIMP-2 in liver tissue of patients with hepatic cirrhosis, and the correlation between TIMPs in liver and those in sera so as to discuss whether TIMPs can be used as a diagnosis index of hepatic fibrosis. METHODS: The monoclonal antibodies (McAbs) of TIMP-1 and TIMP-2 were used to sensitize erythrocytes, and solid-phase absorption to sensitized erythrocytes (SPASE) was used to detect TIMP-1 and TIMP-2 in the sera of patients with hepatic cirrhosis. Meanwhile, with the method of in situ hybridization and immunohistochemistry, we studied the mRNA expression and antigen location of TIMP-1 and TIMP-2 in the livers of 40 hepatic cirrhosis patients with pathologic diagnosis. RESULTS: With SPASE, they were 16.4% higher in the acute hepatitis group, 33.3% higher in the chronic hepatitis group, and the positive rates were 73.6% and 61.2% respectively in sera of hepatic cirrhosis patients, which were remarkably higher than those in chronic hepatitis and acute hepatitis group (P【0.001). In 40 samples of hepatic cirrhosis tissues, all of them showed positive expression of TIMP-1 and TIMP-2 mRNA detected with immunohistochemistry or in situ hybridization (positive rate was 100%). Expression of TIMPs in different degrees could be found in liver tissue with cirrhosis. TIMPs were located in cytoplasm of liver cells of patients with hepatic cirrhosis. There was a significant correlation between serum TIMPs level and liver TIMPs level. CONCLUSION: SPASE is a useful method to detect the TIMP-1 and TIMP-2 in sera of patients with hepatic cirrhosis, and TIMP-1 and TIMP-2 can be considered as a useful diagnostic index of hepatic fibrosis, especially TIMP-1.展开更多
Magnetic Resonance imaging (MR imaging) as a powerful non-invasive modality is of high global interest for early cancer detection. The aim of this study was the synthesis of nanodendrimer and its conjugate with monocl...Magnetic Resonance imaging (MR imaging) as a powerful non-invasive modality is of high global interest for early cancer detection. The aim of this study was the synthesis of nanodendrimer and its conjugate with monoclonal antibody C595 against breast cancer cell, followed by its chelating with gadolinium for its magnetic property. First, anti-MUC-1 monoclonal antibody C595 was coupled to a biodegradable biocompatible Anionic Linear Globular Dendrimer G2 (having polyethylene glycol core and citric acid shell). Then prepared nanocomplex loaded by gadolinium to make novel agent of functional MR imaging. Anticancer effects and MR imaging parameters of the prepared nanoconjugate was investigated under in vitro conditions doing performing several studies such as evaluation of monoclonal antibody C595 binding to mucine-1 (MUC-1) cell, its purification, size of nanoconjugate and relaxivity measurements. The obtained data showed a powerful relaxations as well as selective MUC-1 antigen binding to the cell. Based on the findings from the present research Gd3+-ALGDG2-C595 nano-probe may be a potential breast molecular imaging and therapeutic agent. However, further investigations by in vivo studies and clinical trials are in the pipeline.展开更多
肿瘤免疫治疗可通过抑制多种免疫检查点信号通路发挥作用,其中PD-1(Programmed cell death 1)/PD-L1(Programmed cell death ligand 1)通路抗体抑制剂获得极大成功。但随着PD-1/PD-L1单克隆抗体的临床应用,诸如生产成本高、实体肿瘤组...肿瘤免疫治疗可通过抑制多种免疫检查点信号通路发挥作用,其中PD-1(Programmed cell death 1)/PD-L1(Programmed cell death ligand 1)通路抗体抑制剂获得极大成功。但随着PD-1/PD-L1单克隆抗体的临床应用,诸如生产成本高、实体肿瘤组织穿透力弱、免疫原性,免疫相关副反应严重等越来越多的限制与不足被逐渐发现。而小分子免疫检查点抑制剂的研究逐渐受到重视,其中肽类免疫检查点抑制剂具有高度的特异性和亲和力,被认为是一类具有潜力的抗体药物的补充和替代产品。文章对近年来PD-1/PD-L1肽类抑制剂的研究进行了综述。展开更多
文摘BACKGROUND Islets of Langerhans beta cells diminish in autoimmune type 1 diabetes mellitus(T1DM).Teplizumab,a humanized anti-CD3 monoclonal antibody,may help T1DM.Its long-term implications on clinical T1DM development,safety,and efficacy are unknown.AIM To assess the effectiveness and safety of teplizumab as a therapeutic intervention for individuals with T1DM.METHODS A systematic search was conducted using four electronic databases(PubMed,Embase,Scopus,and Cochrane Library)to select publications published in peerreviewed journals written in English.The odds ratio(OR)and risk ratio(RR)were calculated,along with their 95%CI.We assessed heterogeneity using Cochrane Q and I2 statistics and the appropriate P value.RESULTS There were 8 randomized controlled trials(RCTs)in the current meta-analysis with a total of 1908 T1DM patients from diverse age cohorts,with 1361 patients receiving Teplizumab and 547 patients receiving a placebo.Teplizumab was found to have a substantial link with a decrease in insulin consumption,with an OR of 4.13(95%CI:1.72 to 9.90).Teplizumab is associated with an improved Cpeptide response(OR 2.49;95%CI:1.62 to 3.81)and a significant change in Glycated haemoglobin A1c(HbA1c)levels in people with type 1 diabetes[OR 1.75(95%CI:1.03 to 2.98)],and it has a RR of 0.71(95%CI:0.53 to 0.95).CONCLUSION In type 1 diabetics,teplizumab decreased insulin consumption,improved C-peptide response,and significantly changed HbA1c levels with negligible side effects.Teplizumab appears to improve glycaemic control and diabetes management with good safety and efficacy.
基金funded by F. Hoffmann-La Roche Ltd. F. Hoffmann-La Roche Ltd sponsored the IMpower210 study。
文摘Objective: IMpower210(NCT02813785) explored the efficacy and safety of single-agent atezolizumab vs.docetaxel as second-line treatment for advanced non-small cell lung cancer(NSCLC) in East Asian patients.Methods: Key eligibility criteria for this phase Ⅲ, open-label, randomized study included age ≥18 years;histologically documented advanced NSCLC per the Union for International Cancer Control/American Joint Committee on Cancer staging system(7th edition);Eastern Cooperative Oncology Group performance status of 0 or 1;and disease progression following platinum-based chemotherapy for advanced or metastatic NSCLC. Patients were randomized 2:1 to receive either atezolizumab(1,200 mg) or docetaxel(75 mg/m^(2)). The primary study endpoint was overall survival(OS) in the intention-to-treat(ITT) population with wild-type epidermal growth factor receptor expression(ITT EGFR-WT) and in the overall ITT population.Results: Median OS in the ITT EGFR-WT population(n=467) was 12.3 [95% confidence interval(95% CI),10.3-13.8] months in the atezolizumab arm(n=312) and 9.9(95% CI, 7.8-13.9) months in the docetaxel arm[n=155;stratified hazard ratio(HR), 0.82;95% CI, 0.66-1.03]. Median OS in the overall ITT population was 12.5(95% CI, 10.8-13.8) months with atezolizumab treatment and 11.1(95% CI, 8.4-14.2) months(n=377) with docetaxel treatment(n=188;stratified HR, 0.87;95% CI, 0.71-1.08). Grade 3/4 treatment-related adverse events(TRAEs) occurred in 18.4% of patients in the atezolizumab arm and 50.0% of patients in the docetaxel arm.Conclusions: IMpower210 did not meet its primary efficacy endpoint of OS in the ITT EGFR-WT or overall ITT populations. Atezolizumab was comparatively more tolerable than docetaxel, with a lower incidence of grade3/4 TRAEs.
文摘冠状动脉粥样硬化性心脏病(coronary atherosclerotic heart disease,CHD)的发病率及病死率居全球首位,而低密度脂蛋白胆固醇(low density lipoprotein-cholesterol,LDL-C)的升高是CHD的主要危险因素,因此降低LDL-C水平可有效减少CHD的发病风险。临床上降脂药物如他汀类虽能够有效降低LDL-C水平,但仍有部分患者无法达到降脂目标或者无法耐受。前蛋白转化酶枯草溶菌素9(proprotein convertase subtilisin/kexin type 9,PCSK9)抑制剂作为新一代的降脂药物,越来越受到重视。其通过对PCSK9的抑制作用,增加低密度脂蛋白受体的循环利用,能够显著降低血清中LDL-C水平。目前PCSK9抑制剂已进入Ⅲ期临床试验,试验结果显示其具有良好的降脂效果和耐受性。该文就PCSK9抑制剂最新进展和面临的问题作一综述。
基金the Postdoctoral Science Foundation of China,No.1999-10 State Postdoctoral Foundation Commission
文摘AIM: To set up a new method to detect tissue inhibitors of metalloproteinase-1 and -2(TIMP-1 and TIMP-2) in sera of patients with hepatic cirrhosis, and to investigate the expression and location of TIMP-1 and TIMP-2 in liver tissue of patients with hepatic cirrhosis, and the correlation between TIMPs in liver and those in sera so as to discuss whether TIMPs can be used as a diagnosis index of hepatic fibrosis. METHODS: The monoclonal antibodies (McAbs) of TIMP-1 and TIMP-2 were used to sensitize erythrocytes, and solid-phase absorption to sensitized erythrocytes (SPASE) was used to detect TIMP-1 and TIMP-2 in the sera of patients with hepatic cirrhosis. Meanwhile, with the method of in situ hybridization and immunohistochemistry, we studied the mRNA expression and antigen location of TIMP-1 and TIMP-2 in the livers of 40 hepatic cirrhosis patients with pathologic diagnosis. RESULTS: With SPASE, they were 16.4% higher in the acute hepatitis group, 33.3% higher in the chronic hepatitis group, and the positive rates were 73.6% and 61.2% respectively in sera of hepatic cirrhosis patients, which were remarkably higher than those in chronic hepatitis and acute hepatitis group (P【0.001). In 40 samples of hepatic cirrhosis tissues, all of them showed positive expression of TIMP-1 and TIMP-2 mRNA detected with immunohistochemistry or in situ hybridization (positive rate was 100%). Expression of TIMPs in different degrees could be found in liver tissue with cirrhosis. TIMPs were located in cytoplasm of liver cells of patients with hepatic cirrhosis. There was a significant correlation between serum TIMPs level and liver TIMPs level. CONCLUSION: SPASE is a useful method to detect the TIMP-1 and TIMP-2 in sera of patients with hepatic cirrhosis, and TIMP-1 and TIMP-2 can be considered as a useful diagnostic index of hepatic fibrosis, especially TIMP-1.
文摘Magnetic Resonance imaging (MR imaging) as a powerful non-invasive modality is of high global interest for early cancer detection. The aim of this study was the synthesis of nanodendrimer and its conjugate with monoclonal antibody C595 against breast cancer cell, followed by its chelating with gadolinium for its magnetic property. First, anti-MUC-1 monoclonal antibody C595 was coupled to a biodegradable biocompatible Anionic Linear Globular Dendrimer G2 (having polyethylene glycol core and citric acid shell). Then prepared nanocomplex loaded by gadolinium to make novel agent of functional MR imaging. Anticancer effects and MR imaging parameters of the prepared nanoconjugate was investigated under in vitro conditions doing performing several studies such as evaluation of monoclonal antibody C595 binding to mucine-1 (MUC-1) cell, its purification, size of nanoconjugate and relaxivity measurements. The obtained data showed a powerful relaxations as well as selective MUC-1 antigen binding to the cell. Based on the findings from the present research Gd3+-ALGDG2-C595 nano-probe may be a potential breast molecular imaging and therapeutic agent. However, further investigations by in vivo studies and clinical trials are in the pipeline.
文摘肿瘤免疫治疗可通过抑制多种免疫检查点信号通路发挥作用,其中PD-1(Programmed cell death 1)/PD-L1(Programmed cell death ligand 1)通路抗体抑制剂获得极大成功。但随着PD-1/PD-L1单克隆抗体的临床应用,诸如生产成本高、实体肿瘤组织穿透力弱、免疫原性,免疫相关副反应严重等越来越多的限制与不足被逐渐发现。而小分子免疫检查点抑制剂的研究逐渐受到重视,其中肽类免疫检查点抑制剂具有高度的特异性和亲和力,被认为是一类具有潜力的抗体药物的补充和替代产品。文章对近年来PD-1/PD-L1肽类抑制剂的研究进行了综述。
