Remarkable progress has been made in developing intramuscular vaccines against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2);however,they are limited with respect to eliciting local immunity in the respi...Remarkable progress has been made in developing intramuscular vaccines against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2);however,they are limited with respect to eliciting local immunity in the respiratory tract,which is the primary infection site for SARS-CoV-2.To overcome the limitations of intramuscular vaccines,we constructed a nasal vaccine candidate based on an influenza vector by inserting a gene encoding the receptor-binding domain(RBD)of the spike protein of SARSCoV-2,named CA4-d NS1-n CoV-RBD(d NS1-RBD).A preclinical study showed that in hamsters challenged 1d after single-dose vaccination or 9 months after booster vaccination,d NS1-RBD largely mitigated lung pathology,with no loss of body weight.Moreover,such cellular immunity is relatively unimpaired for the most concerning SARS-Co V-2 variants,especially for the latest Omicron variant.In addition,this vaccine also provides cross-protection against H1N1 and H5N1 influenza viruses.The protective immune mechanism of d NS1-RBD could be attributed to the innate immune response in the nasal epithelium,local RBD-specific T cell response in the lung,and RBD-specific Ig A and Ig G response.Thus,this study demonstrates that the intranasally delivered d NS1-RBD vaccine candidate may offer an important addition to the fight against the ongoing coronavirus disease 2019 pandemic and influenza infection,compensating limitations of current intramuscular vaccines.展开更多
目的探讨钠-葡萄糖协同转运蛋白2(SGLT-2)抑制剂联合血管紧张素转换抑制剂(ACEI)治疗糖尿病肾病的疗效及对患者血清胱抑素C(CysC)、β_(2)微球蛋白(β_(2)-MG)、高敏C反应蛋白(hs-CRP)的影响。方法选取2019年3月至2020年6月珠海市中西...目的探讨钠-葡萄糖协同转运蛋白2(SGLT-2)抑制剂联合血管紧张素转换抑制剂(ACEI)治疗糖尿病肾病的疗效及对患者血清胱抑素C(CysC)、β_(2)微球蛋白(β_(2)-MG)、高敏C反应蛋白(hs-CRP)的影响。方法选取2019年3月至2020年6月珠海市中西医结合医院内分泌科收治的80例糖尿病肾病患者作为研究对象,按随机数表法分为观察组和对照组各40例。对照组患者采用培哚普利片治疗,观察组患者在对照组治疗的基础上联合达格列净片治疗,均持续治疗3个月。比较两组患者治疗3个月后的临床疗效,治疗前及治疗3个月后的空腹血糖(FPG)、餐后2 h血糖(2 hPG)、糖化血红蛋白(HbA1c)、尿素氮(BUN)、血肌酐(SCr)、24 h尿蛋白定量(24 h UAER)、血清CysC、β_(2)-MG、hs-CRP水平和治疗期间的不良反应发生情况。结果治疗后,观察组患者的临床疗效总有效率为87.50%,明显高于对照组的65.00%,差异有统计学意义(P<0.05);治疗3个月后,观察组患者的FPG、2 hPG、HbA1c、BUN、SCr、24 h UAER分别为(6.16±1.30)mmol/L、(8.04±1.36)mmol/L、(6.90±0.63)%、(8.76±1.56)mmol/L、(105.57±8.31)μmol/L、(1.46±0.22)g,均明显低于对照组的(7.08±1.17)mmol/L、(9.22±1.41)mmol/L、(7.34±0.55)%、(10.08±1.74)mmol/L、(122.84±9.23)μmol/L、(1.95±0.30)g,差异均有统计学意义(P<0.05);治疗3个月后,观察组患者的血清CysC、β_(2)-MG、hs-CRP水平分别为(1.20±0.25)mg/L、(1.69±0.21)mg/L、(6.14±1.28)mg/L,明显低于对照组的(1.76±0.34)mg/L、(2.05±0.26)mg/L、(7.60±1.33)mg/L,差异均有统计学意义(P<0.05);观察组和对照组患者的不良反应总发生率分别为10.00%和7.50%,差异无统计学意义(P>0.05)。结论SGLT-2抑制剂达格列净联合ACEI培哚普利治疗糖尿病肾病患者的疗效显著,且可有效降低血清CysC、β_(2)-MG、hs-CRP水平,值得临床推广。展开更多
基金supported by the National Program on Key Research Project of China(2020YFC0842600)the National Natural Science Foundation of China(82041038,81871651,and 81991491)+1 种基金the Major Science and Technology Program of Fujian Province(2020YZ014001)the Natural Science Foundation of Fujian Province(2021J02006)。
文摘Remarkable progress has been made in developing intramuscular vaccines against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2);however,they are limited with respect to eliciting local immunity in the respiratory tract,which is the primary infection site for SARS-CoV-2.To overcome the limitations of intramuscular vaccines,we constructed a nasal vaccine candidate based on an influenza vector by inserting a gene encoding the receptor-binding domain(RBD)of the spike protein of SARSCoV-2,named CA4-d NS1-n CoV-RBD(d NS1-RBD).A preclinical study showed that in hamsters challenged 1d after single-dose vaccination or 9 months after booster vaccination,d NS1-RBD largely mitigated lung pathology,with no loss of body weight.Moreover,such cellular immunity is relatively unimpaired for the most concerning SARS-Co V-2 variants,especially for the latest Omicron variant.In addition,this vaccine also provides cross-protection against H1N1 and H5N1 influenza viruses.The protective immune mechanism of d NS1-RBD could be attributed to the innate immune response in the nasal epithelium,local RBD-specific T cell response in the lung,and RBD-specific Ig A and Ig G response.Thus,this study demonstrates that the intranasally delivered d NS1-RBD vaccine candidate may offer an important addition to the fight against the ongoing coronavirus disease 2019 pandemic and influenza infection,compensating limitations of current intramuscular vaccines.
文摘目的探讨钠-葡萄糖协同转运蛋白2(SGLT-2)抑制剂联合血管紧张素转换抑制剂(ACEI)治疗糖尿病肾病的疗效及对患者血清胱抑素C(CysC)、β_(2)微球蛋白(β_(2)-MG)、高敏C反应蛋白(hs-CRP)的影响。方法选取2019年3月至2020年6月珠海市中西医结合医院内分泌科收治的80例糖尿病肾病患者作为研究对象,按随机数表法分为观察组和对照组各40例。对照组患者采用培哚普利片治疗,观察组患者在对照组治疗的基础上联合达格列净片治疗,均持续治疗3个月。比较两组患者治疗3个月后的临床疗效,治疗前及治疗3个月后的空腹血糖(FPG)、餐后2 h血糖(2 hPG)、糖化血红蛋白(HbA1c)、尿素氮(BUN)、血肌酐(SCr)、24 h尿蛋白定量(24 h UAER)、血清CysC、β_(2)-MG、hs-CRP水平和治疗期间的不良反应发生情况。结果治疗后,观察组患者的临床疗效总有效率为87.50%,明显高于对照组的65.00%,差异有统计学意义(P<0.05);治疗3个月后,观察组患者的FPG、2 hPG、HbA1c、BUN、SCr、24 h UAER分别为(6.16±1.30)mmol/L、(8.04±1.36)mmol/L、(6.90±0.63)%、(8.76±1.56)mmol/L、(105.57±8.31)μmol/L、(1.46±0.22)g,均明显低于对照组的(7.08±1.17)mmol/L、(9.22±1.41)mmol/L、(7.34±0.55)%、(10.08±1.74)mmol/L、(122.84±9.23)μmol/L、(1.95±0.30)g,差异均有统计学意义(P<0.05);治疗3个月后,观察组患者的血清CysC、β_(2)-MG、hs-CRP水平分别为(1.20±0.25)mg/L、(1.69±0.21)mg/L、(6.14±1.28)mg/L,明显低于对照组的(1.76±0.34)mg/L、(2.05±0.26)mg/L、(7.60±1.33)mg/L,差异均有统计学意义(P<0.05);观察组和对照组患者的不良反应总发生率分别为10.00%和7.50%,差异无统计学意义(P>0.05)。结论SGLT-2抑制剂达格列净联合ACEI培哚普利治疗糖尿病肾病患者的疗效显著,且可有效降低血清CysC、β_(2)-MG、hs-CRP水平,值得临床推广。
