Camrelizumab is a humanized monoclonal antibody(m Ab)against human PD-1.It demonstrated a single digit nanomolar binding affinity to human and cynomolgus monkey PD-1,but no cross-reactivity to murine PD-1.It exhibited...Camrelizumab is a humanized monoclonal antibody(m Ab)against human PD-1.It demonstrated a single digit nanomolar binding affinity to human and cynomolgus monkey PD-1,but no cross-reactivity to murine PD-1.It exhibited potent PD-1/PD-L1 blocking activity as well as the T cell activation in vitro.The distinct binding sites of cameralizumab were perfectly overlapped with the PD-L1 binding sites,which supported its excellent ability in blocking PD-1/PD-L1 interaction.It also significantly inhibited the growth of murine MC-38 and B16 F10 cell in humanized PD-1 transgenic mice with a superior inhibitory effect compared with the other marketed anti-PD-1 antibodies.Furthermore,camrelizumab also displayed a favorable pharmacokinetic(PK)and safety profile in cynomolgus monkeys.Besides,we showed that camrelizumab only bound to VEGFR2 with a very low affinity and did not activate VEGF pathways even at very high doses.Collectively,we provided evidence that cameralizumab was an ideal therapeutic candidate for cancer treatment,encouraging further evaluation of its efficacy/safety in the clinical setting.展开更多
[Objectives]To analyze the relationship between serum 8-hydroxydeoxyguanosine(8-OHdG),heart fatty acid-binding protein(H-FABP),C-reactive protein(CRP)levels and clinical efficacy and short-term prognosis in patients w...[Objectives]To analyze the relationship between serum 8-hydroxydeoxyguanosine(8-OHdG),heart fatty acid-binding protein(H-FABP),C-reactive protein(CRP)levels and clinical efficacy and short-term prognosis in patients with ischemic cardiomyopathy.[Methods]The clinical data of 100 patients with ischemic cardiomyopathy from October 2021 to November 2022 were retrospectively analyzed,and the serum levels of 8-OHdG,H-FABP and CRP were compared before and one week after treatment.The patients were followed up for 12 months after discharge,and the incidence of major adverse cardiovascular events(MACE)was counted during the follow-up period.Univariate and multivariate Logistic regression analysis were used to analyze the prognostic factors of patients with ischemic cardiomyopathy in the near future,and the predictive value of serum 8-OHdG,H-FABP and CRP levels for the prognosis of patients was evaluated by ROC curve.[Results]After 1 week of treatment,the serum levels of 8-OHdG,H-FABP and CRP in patients with ischemic cardiomyopathy were significantly lower than those before treatment(P<0.05).During the follow-up period,34 patients developed MACE;the serum levels of 8-OHdG,H-FABP and CRP in the MACE group were higher than those in the non-MACE group,and the differences were statistically significant(P<0.05).Multivariate Logistic regression analysis showed that 8-OHdG,H-FABP and CRP were the risk factors of MACE in patients with ischemic cardiomyopathy(P<0.05).ROC curve analysis showed that the combined prediction of 8-OHdG,H-FABP and CRP for MACE in patients with ischemic cardiomyopathy was higher than that of CRP,H-FABP and 8-OHdG alone(P<0.05).[Conclusions]8-OHdG,H-FABP and CRP are closely related to the clinical efficacy and short-term prognosis of patients with ischemic cardiomyopathy,and the detection of serum 8-OHdG,H-FABP and CRP levels can help to evaluate the clinical efficacy and short-term prognosis of patients with ischemic cardiomyopathy.展开更多
Theα7 nicotinic acetylcholine receptors(nAChRs)are widely expressed in the central and peripheral nervous systems and are important drug targets for the treatment of neurological diseases.However,differentiation of t...Theα7 nicotinic acetylcholine receptors(nAChRs)are widely expressed in the central and peripheral nervous systems and are important drug targets for the treatment of neurological diseases.However,differentiation of the agonists and antagonists of the nAChR is difficult.In this study we aimed to develop a reliable and efficient computational approach for differentiation of the agonists from the antagonists of the nAChR based on a systematical analysis of 123 ligands(87 agonists,12 partial agonists,and 24 antagonists)binding with the extracellular domain of theα7 n AChR chimera.Our results suggest that the ligand size and ligand binding affinity cannot differentiate the agonists from the antagonists of the nAChR.The ligand efficiency that considers both ligand binding affinity and size for the agonists is overall more left shifted in comparison to the antagonists,but the values of the ligand efficiency still cannot differentiate the agonists from the antagonists unless the values are either relatively high(more than-0.3 kcal mol^-1)or relatively low(less than-0.45 kcal mol^-1).Our results suggest that accurate prediction of the agonist or antagonist of the nAChR is challenging and the ligand innate configuration has to be considered as an extra for differentiation of the agonists from the antagonists of the nAChR.展开更多
目的探究参芪地黄汤联合常规西医治疗对早期糖尿病肾病患者胱抑素C(Cys-C)和视黄醇结合蛋白(RBP)水平的影响。方法回顾性选取2017年6月至2019年12月华北理工大学附属开滦总医院收治的早期糖尿病肾病患者90例作为研究对象,按照治疗方式...目的探究参芪地黄汤联合常规西医治疗对早期糖尿病肾病患者胱抑素C(Cys-C)和视黄醇结合蛋白(RBP)水平的影响。方法回顾性选取2017年6月至2019年12月华北理工大学附属开滦总医院收治的早期糖尿病肾病患者90例作为研究对象,按照治疗方式不同分为观察组和对照组,每组各45例。所有患者均接受常规西医治疗(胰岛素控糖,缬沙坦分散片控制血压),观察组患者在此基础上使用参芪地黄汤治疗。观察2组患者治疗前、治疗3个月后的血糖[空腹血糖(FBG)、餐后2 h血糖(2 h PBG)]、肾功能(肌酐、24 h尿蛋白、24 h尿清蛋白)、血清Cys-C和尿RBP表达情况、中医证候评分、临床疗效及不良反应发生情况。结果治疗前,2组患者的FBG、2 h PBG、肌酐、24 h尿蛋白、24 h尿清蛋白、血清Cys-C、尿RBP水平、中医证候评分比较,差异均无统计学意义(P>0.05);治疗3个月后,观察组患者FBG、2 h PBG、肌酐、24 h尿总蛋白、24 h尿清蛋白、血清Cys-C、尿RBP水平、中医证候评分较对照组降低更明显,差异均有统计学意义(P<0.05)。观察组患者治疗有效率86.67%,显著高于对照组的64.44%,差异有统计学意义(P<0.05)。观察组患者不良反应总发生率8.89%,与对照组的11.11%比较,差异无统计学意义(P>0.05)。结论与常规西医治疗相比,参芪地黄汤联合常规西医治疗早期糖尿病肾病患者具有良好疗效,可更好地改善早期糖尿病肾病患者血糖、肾功能,显著降低血清Cys-C和尿RBP水平。展开更多
BACKGROUND Colorectal cancer(CRC) is one of the main causes of cancer-related deaths in China and around the world. Advanced CRC(ACRC) patients suffer from a low cure rate though treated with targeted therapies. The r...BACKGROUND Colorectal cancer(CRC) is one of the main causes of cancer-related deaths in China and around the world. Advanced CRC(ACRC) patients suffer from a low cure rate though treated with targeted therapies. The response rate is about 50% to chemotherapy and cetuximab, a monoclonal antibody targeting epidermal growth factor receptor(EGFR) and used for ACRC with wild-type KRAS. It is important to identify more predictors of cetuximab efficacy to further improve precise treatment. Autophagy, showing a key role in the cancer progression, is influenced by the EGFR pathway. Whether autophagy can predict cetuximab efficacy in ACRC is an interesting topic.AIM To investigate the effect of autophagy on the efficacy of cetuximab in colon cancer cells and ACRC patients with wild-type KRAS.METHODS ACRC patients treated with cetuximab plus chemotherapy, with detailed data and tumor tissue, at Sun Yat-sen University Cancer Center from January 1, 2005,to October 1, 2015, were studied. Expression of autophagy-related proteins[Beclin1, microtubule-associated protein 1 A/B-light chain 3(LC3), and 4 Ebinding protein 1(4 E-BP1)] was examined by Western blot in CRC cells and by immunohistochemistry in cancerous and normal tissues. The effect of autophagy on cetuximab-treated cancer cells was confirmed by MTT assay. The associations between Beclin1, LC3, and 4 E-BP1 expression in tumor tissue and the efficacy of cetuximab-based therapy were analyzed.RESULTS In CACO-2 cells exposed to cetuximab, LC3 and 4 E-BP1 were upregulated, and P62 was downregulated. Autophagosome formation was observed, and autophagy increased the efficacy of cetuximab. In 68 ACRC patients,immunohistochemistry showed that Beclin1 levels were significantly correlated with those of LC3(0.657, P < 0.001) and 4 E-BP1(0.211, P = 0.042) in ACRC tissues.LC3 was significantly overexpressed in tumor tissues compared to normal tissues(P < 0.001). In 45 patients with wild-type KRAS, the expression levels of these three proteins were not related to progression-free survi展开更多
文摘Camrelizumab is a humanized monoclonal antibody(m Ab)against human PD-1.It demonstrated a single digit nanomolar binding affinity to human and cynomolgus monkey PD-1,but no cross-reactivity to murine PD-1.It exhibited potent PD-1/PD-L1 blocking activity as well as the T cell activation in vitro.The distinct binding sites of cameralizumab were perfectly overlapped with the PD-L1 binding sites,which supported its excellent ability in blocking PD-1/PD-L1 interaction.It also significantly inhibited the growth of murine MC-38 and B16 F10 cell in humanized PD-1 transgenic mice with a superior inhibitory effect compared with the other marketed anti-PD-1 antibodies.Furthermore,camrelizumab also displayed a favorable pharmacokinetic(PK)and safety profile in cynomolgus monkeys.Besides,we showed that camrelizumab only bound to VEGFR2 with a very low affinity and did not activate VEGF pathways even at very high doses.Collectively,we provided evidence that cameralizumab was an ideal therapeutic candidate for cancer treatment,encouraging further evaluation of its efficacy/safety in the clinical setting.
基金Scientific Research Project of Health Industry in Hainan Province(21A200439).
文摘[Objectives]To analyze the relationship between serum 8-hydroxydeoxyguanosine(8-OHdG),heart fatty acid-binding protein(H-FABP),C-reactive protein(CRP)levels and clinical efficacy and short-term prognosis in patients with ischemic cardiomyopathy.[Methods]The clinical data of 100 patients with ischemic cardiomyopathy from October 2021 to November 2022 were retrospectively analyzed,and the serum levels of 8-OHdG,H-FABP and CRP were compared before and one week after treatment.The patients were followed up for 12 months after discharge,and the incidence of major adverse cardiovascular events(MACE)was counted during the follow-up period.Univariate and multivariate Logistic regression analysis were used to analyze the prognostic factors of patients with ischemic cardiomyopathy in the near future,and the predictive value of serum 8-OHdG,H-FABP and CRP levels for the prognosis of patients was evaluated by ROC curve.[Results]After 1 week of treatment,the serum levels of 8-OHdG,H-FABP and CRP in patients with ischemic cardiomyopathy were significantly lower than those before treatment(P<0.05).During the follow-up period,34 patients developed MACE;the serum levels of 8-OHdG,H-FABP and CRP in the MACE group were higher than those in the non-MACE group,and the differences were statistically significant(P<0.05).Multivariate Logistic regression analysis showed that 8-OHdG,H-FABP and CRP were the risk factors of MACE in patients with ischemic cardiomyopathy(P<0.05).ROC curve analysis showed that the combined prediction of 8-OHdG,H-FABP and CRP for MACE in patients with ischemic cardiomyopathy was higher than that of CRP,H-FABP and 8-OHdG alone(P<0.05).[Conclusions]8-OHdG,H-FABP and CRP are closely related to the clinical efficacy and short-term prognosis of patients with ischemic cardiomyopathy,and the detection of serum 8-OHdG,H-FABP and CRP levels can help to evaluate the clinical efficacy and short-term prognosis of patients with ischemic cardiomyopathy.
基金supported by the Fundamental Research Funds for the Central Universities (No. 201762011 for R. Y.)National Laboratory Director Fund from the Qingdao National Laboratory of Marine Science and Technology (No. QNLM201709)the NSFC-Shandong Joint Fund (No. U1406402)
文摘Theα7 nicotinic acetylcholine receptors(nAChRs)are widely expressed in the central and peripheral nervous systems and are important drug targets for the treatment of neurological diseases.However,differentiation of the agonists and antagonists of the nAChR is difficult.In this study we aimed to develop a reliable and efficient computational approach for differentiation of the agonists from the antagonists of the nAChR based on a systematical analysis of 123 ligands(87 agonists,12 partial agonists,and 24 antagonists)binding with the extracellular domain of theα7 n AChR chimera.Our results suggest that the ligand size and ligand binding affinity cannot differentiate the agonists from the antagonists of the nAChR.The ligand efficiency that considers both ligand binding affinity and size for the agonists is overall more left shifted in comparison to the antagonists,but the values of the ligand efficiency still cannot differentiate the agonists from the antagonists unless the values are either relatively high(more than-0.3 kcal mol^-1)or relatively low(less than-0.45 kcal mol^-1).Our results suggest that accurate prediction of the agonist or antagonist of the nAChR is challenging and the ligand innate configuration has to be considered as an extra for differentiation of the agonists from the antagonists of the nAChR.
文摘目的探究参芪地黄汤联合常规西医治疗对早期糖尿病肾病患者胱抑素C(Cys-C)和视黄醇结合蛋白(RBP)水平的影响。方法回顾性选取2017年6月至2019年12月华北理工大学附属开滦总医院收治的早期糖尿病肾病患者90例作为研究对象,按照治疗方式不同分为观察组和对照组,每组各45例。所有患者均接受常规西医治疗(胰岛素控糖,缬沙坦分散片控制血压),观察组患者在此基础上使用参芪地黄汤治疗。观察2组患者治疗前、治疗3个月后的血糖[空腹血糖(FBG)、餐后2 h血糖(2 h PBG)]、肾功能(肌酐、24 h尿蛋白、24 h尿清蛋白)、血清Cys-C和尿RBP表达情况、中医证候评分、临床疗效及不良反应发生情况。结果治疗前,2组患者的FBG、2 h PBG、肌酐、24 h尿蛋白、24 h尿清蛋白、血清Cys-C、尿RBP水平、中医证候评分比较,差异均无统计学意义(P>0.05);治疗3个月后,观察组患者FBG、2 h PBG、肌酐、24 h尿总蛋白、24 h尿清蛋白、血清Cys-C、尿RBP水平、中医证候评分较对照组降低更明显,差异均有统计学意义(P<0.05)。观察组患者治疗有效率86.67%,显著高于对照组的64.44%,差异有统计学意义(P<0.05)。观察组患者不良反应总发生率8.89%,与对照组的11.11%比较,差异无统计学意义(P>0.05)。结论与常规西医治疗相比,参芪地黄汤联合常规西医治疗早期糖尿病肾病患者具有良好疗效,可更好地改善早期糖尿病肾病患者血糖、肾功能,显著降低血清Cys-C和尿RBP水平。
文摘BACKGROUND Colorectal cancer(CRC) is one of the main causes of cancer-related deaths in China and around the world. Advanced CRC(ACRC) patients suffer from a low cure rate though treated with targeted therapies. The response rate is about 50% to chemotherapy and cetuximab, a monoclonal antibody targeting epidermal growth factor receptor(EGFR) and used for ACRC with wild-type KRAS. It is important to identify more predictors of cetuximab efficacy to further improve precise treatment. Autophagy, showing a key role in the cancer progression, is influenced by the EGFR pathway. Whether autophagy can predict cetuximab efficacy in ACRC is an interesting topic.AIM To investigate the effect of autophagy on the efficacy of cetuximab in colon cancer cells and ACRC patients with wild-type KRAS.METHODS ACRC patients treated with cetuximab plus chemotherapy, with detailed data and tumor tissue, at Sun Yat-sen University Cancer Center from January 1, 2005,to October 1, 2015, were studied. Expression of autophagy-related proteins[Beclin1, microtubule-associated protein 1 A/B-light chain 3(LC3), and 4 Ebinding protein 1(4 E-BP1)] was examined by Western blot in CRC cells and by immunohistochemistry in cancerous and normal tissues. The effect of autophagy on cetuximab-treated cancer cells was confirmed by MTT assay. The associations between Beclin1, LC3, and 4 E-BP1 expression in tumor tissue and the efficacy of cetuximab-based therapy were analyzed.RESULTS In CACO-2 cells exposed to cetuximab, LC3 and 4 E-BP1 were upregulated, and P62 was downregulated. Autophagosome formation was observed, and autophagy increased the efficacy of cetuximab. In 68 ACRC patients,immunohistochemistry showed that Beclin1 levels were significantly correlated with those of LC3(0.657, P < 0.001) and 4 E-BP1(0.211, P = 0.042) in ACRC tissues.LC3 was significantly overexpressed in tumor tissues compared to normal tissues(P < 0.001). In 45 patients with wild-type KRAS, the expression levels of these three proteins were not related to progression-free survi
