Background:On May 8,2018,the China National Medical Products Administration(NMPA)approved anlotinib,an orally administered anti-angiogenesis inhibitor,for the treatment of patients with advanced non-small cell lung ca...Background:On May 8,2018,the China National Medical Products Administration(NMPA)approved anlotinib,an orally administered anti-angiogenesis inhibitor,for the treatment of patients with advanced non-small cell lung can-cer(NSCLC)who have progressed after treatment with two or more lines of prior systemic chemotherapy.Main body of the abstract:China NMPA reviewed and inspected a regional double-blinded,placebo-controlled,Phase III trial comparing the overall survival(OS)of NSCLC patients between the anlotinib and placebo arms.A total of 437 patients were randomized(2:1)to receive either anlotinib(n=294)or placebo(n=143)once daily on a 2-week on and 1-week off schedule.Patients with epidermal growth factor receptor(EGFR)or activating anaplastic lymphoma kinase(ALK)genomic tumor aberrations should have disease progression on NMPA-approved therapy.Anlotinib is the first NMPA-approved drug for patients with advanced NSCLC who have progressed on at least two lines of prior systemic chemotherapies in China.The approval was based on a statistically and clinically significant improvement in median OS with anlotinib(9.46 months)compared with placebo[6.37 months;hazard ratio(HR])=0.70,95%confidence interval(CI)=0.55-0.89;two-sided log-rank P=0.002].The confirmed objective response rate(ORR)was 9.2%in the anlotinib arm and 0.7%in the placebo arm.The median duration of response(DoR)was 4.83 months,with a 95%CI of 3.31-6.97 months.The toxicity profile of anlotinib was consistent with that of known anti-angiogenesis inhibitors.Common adverse drug reactions(ADRs)in anlotinib-treated patients included hypertension(67.4%),hand-foot syndrome(43.9%),hemoptysis(14.0%),thyroid stimulating hormone(TSH)elevation(46.6%),and corrected QT interval(QTc)prolongation(26.2%).Short conclusion:Anlotinib demonstrated a clinically significant OS prolongation as a novel therapeutic option for advanced or metastatic NSCLC following at least two lines of chemotherapy.展开更多
No effective drug treatments are available for coronavirus disease 2019(COVID-19).Host-directed therapies targeting the underlying aberrant immune responses leading to pulmonary tissue damage,death,or long-term functi...No effective drug treatments are available for coronavirus disease 2019(COVID-19).Host-directed therapies targeting the underlying aberrant immune responses leading to pulmonary tissue damage,death,or long-term functional disability in survivors require clinical evaluation.We performed a parallel assigned controlled,non-randomized,phase 1 clinical trial to evaluate the safety of human umbilical cord-derived mesenchymal stem cells(UC-MSCs)infusions in the treatment of patients with moderate and severe COVID-19 pulmonary disease.The study enrolled 18 hospitalized patients with COVID-19(n=9 for each group).The treatment group received three cycles of intravenous infusion of UC-MSCs(3×107 cells per infusion)on days 0,3,and 6.Both groups received standard COVID-treatment regimens.Adverse events,duration of clinical symptoms,laboratory parameters,length of hospitalization,serial chest computed tomography(CT)images,the PaO2/FiO2 ratio,dynamics of cytokines,and IgG and IgM anti-SARS-CoV-2 antibodies were analyzed.No serious UC-MSCs infusion-associated adverse events were observed.Two patients receiving UC-MSCs developed transient facial flushing and fever,and one patient developed transient hypoxia at 12 h post UC-MSCs transfusion.Mechanical ventilation was required in one patient in the treatment group compared with four in the control group.All patients recovered and were discharged.Our data show that intravenous UC-MSCs infusion in patients with moderate and severe COVID-19 is safe and well tolerated.Phase 2/3 randomized,controlled,double-blinded trials with long-term follow-up are needed to evaluate the therapeutic use of UC-MSCs to reduce deaths and improve long-term treatment outcomes in patients with serious COVID-19.展开更多
The pathogenesis of the second major neurodegenerative disorder, Parkinson’s disease(PD), is closely associated with the dysfunction of potassium(K~+ ) channels. Therefore, PD is also considered to be an ion channel ...The pathogenesis of the second major neurodegenerative disorder, Parkinson’s disease(PD), is closely associated with the dysfunction of potassium(K~+ ) channels. Therefore, PD is also considered to be an ion channel disease or neuronal channelopathy. Mounting evidence has shown that K~+ channels play crucial roles in the regulations of neurotransmitter release, neuronal excitability, and cell volume. Inhibition of K~+ channels enhances the spontaneous firing frequency of nigral dopamine(DA)neurons, induces a transition from tonic firing to burst discharge, and promotes the release of DA in the striatum.Recently, three K~+ channels have been identified to protect DA neurons and to improve the motor and non-motor symptoms in PD animal models: small conductance(SK)channels, A-type K~+ channels, and KV7/KCNQ channels.In this review, we summarize the physiological and pharmacological effects of the three K~+ channels. We also describe in detail the laboratory investigations regarding K~+ channels as a potential therapeutic target for PD.展开更多
目的通过数据挖掘软件及方法从多个维度系统整理徐振晔教授针对大肠癌的临证思维方法及用药规律,为中医药诊治大肠癌提供借鉴。方法采用回顾性临床研究的方法,选取2016年1月至2021年3月期间徐振晔教授门诊治疗的经病理或影像学诊断、至...目的通过数据挖掘软件及方法从多个维度系统整理徐振晔教授针对大肠癌的临证思维方法及用药规律,为中医药诊治大肠癌提供借鉴。方法采用回顾性临床研究的方法,选取2016年1月至2021年3月期间徐振晔教授门诊治疗的经病理或影像学诊断、至少有2次以上复诊且持续服药2个月及以上有临床症状减轻的大肠癌患者病案。在纳入病例前,将患者的基本信息、临床症状、辨证分型、涉及脏腑、病理因素、临床用药等进行数据预处理及统一、标准化和规范化。在EXCEL中输入所有处理好的病案数据,采用统计产品与服务解决方案25(Statistical Product and Service Solutions,SPSS25)作临床数据有关的频次及聚类分析;在此基础上,采取IBM数据挖掘平台SPSS Modeler 18对临床症状及处方作关联规则分析。结果本研究最终纳入87例患者,279张中药处方。从主要症状频次分析,就诊大肠癌患者中出现纳呆、乏力、大便溏、消瘦、夜寐不安、腹胀、腰酸以及口干占到前八位。出现频次较高的辨证分型为脾虚精亏。病理因素中湿和瘀最多,占50.179%和39.068%。相关脏腑中脾胃、肾、肠、肝最多,占96.774%和41.219%、24.373%、17.921%。纳入分析的279张处方中按照频次排序为黄芪、白术、鸡内金、白茯苓、白花蛇舌草、菝葜、预知子、黄精、野葡萄藤及绞股蓝。四味药排名前五的高置信度组合有黄精、菝葜、鸡内金、黄芪,黄精、白花蛇舌草、鸡内金、黄芪,黄精、鸡内金、白术、黄芪,黄精、鸡内金、白茯苓、黄芪,太子参、黄精、白茯苓以及白术。药物和症状经过聚类后分为六大类。结论徐振晔教授在大肠癌诊治中提倡健脾养精,佐以健脾化湿、化痰散结、疏肝理气、清热解毒、活血通络等法则综合运用的学术思想,为启发中医药对大肠癌的辨证论治拓展了新思路。展开更多
Silica-supported CuCo catalysts were prepared by impregnation method with different impregnation sequence for higher alcohols synthesis. These catalysts were characterized by H2-TPR, XRD, N2 adsorption, XPS techniques...Silica-supported CuCo catalysts were prepared by impregnation method with different impregnation sequence for higher alcohols synthesis. These catalysts were characterized by H2-TPR, XRD, N2 adsorption, XPS techniques and CO selective hydrogenation reaction measurement. The effects of impregnation sequence on the structure and performance of catalysts were investigated, and there were important influences on the selectivity to higher alcohols. There was a strong synergistic effect between copper and cobalt for the co-impregnated sample. The CuCo/SiO2 catalyst prepared by co- impregnation showed a better yield of total alcohols, and a higher selectivity to total alcohols which reached 51.5%.展开更多
目的探讨近三十年来我国循环系统疾病死亡率变化趋势及其影响因素,应用早死所致的寿命损失年(Years of life lost, YLLs)对1990—2017年中国城市和农村循环系统疾病负担进行综合评价。方法以中国年鉴的数据为基础,采用Joinpoint回归分...目的探讨近三十年来我国循环系统疾病死亡率变化趋势及其影响因素,应用早死所致的寿命损失年(Years of life lost, YLLs)对1990—2017年中国城市和农村循环系统疾病负担进行综合评价。方法以中国年鉴的数据为基础,采用Joinpoint回归分析计算死亡率年度变化百分比,采用标准方法计算循环系统疾病YLL,根据我国2010年人口普查结果的年龄别构成比对粗死亡率以及YLL率进行标化。结果1990—2017年中国城市和农村居民的循环系统疾病粗死亡率均呈上升趋势,城市标化死亡率有明显下降趋势。1990—2017年,随着年龄的增长,城市和农村居民循环系统疾病的死亡率增加;1990年城市循环系统疾病年龄别死亡率总体上高于农村,而2017年农村循环系统疾病年龄别死亡率已经超过了城市。1990—2017年城市和农村的YLLs分别增长了211.6%和26.1%,城市和农村标化YLL率分别下降了37.9%和12.8%。结论1990—2017年中国城市居民循环系统疾病标化死亡率呈明显下降趋势,而城市和农村居民的循环系统疾病YLLs均增加。展开更多
基金This work was supported by the Grant from Chinese National Major Project for New Drug Innovation(Grant No.2017ZX09304015)
文摘Background:On May 8,2018,the China National Medical Products Administration(NMPA)approved anlotinib,an orally administered anti-angiogenesis inhibitor,for the treatment of patients with advanced non-small cell lung can-cer(NSCLC)who have progressed after treatment with two or more lines of prior systemic chemotherapy.Main body of the abstract:China NMPA reviewed and inspected a regional double-blinded,placebo-controlled,Phase III trial comparing the overall survival(OS)of NSCLC patients between the anlotinib and placebo arms.A total of 437 patients were randomized(2:1)to receive either anlotinib(n=294)or placebo(n=143)once daily on a 2-week on and 1-week off schedule.Patients with epidermal growth factor receptor(EGFR)or activating anaplastic lymphoma kinase(ALK)genomic tumor aberrations should have disease progression on NMPA-approved therapy.Anlotinib is the first NMPA-approved drug for patients with advanced NSCLC who have progressed on at least two lines of prior systemic chemotherapies in China.The approval was based on a statistically and clinically significant improvement in median OS with anlotinib(9.46 months)compared with placebo[6.37 months;hazard ratio(HR])=0.70,95%confidence interval(CI)=0.55-0.89;two-sided log-rank P=0.002].The confirmed objective response rate(ORR)was 9.2%in the anlotinib arm and 0.7%in the placebo arm.The median duration of response(DoR)was 4.83 months,with a 95%CI of 3.31-6.97 months.The toxicity profile of anlotinib was consistent with that of known anti-angiogenesis inhibitors.Common adverse drug reactions(ADRs)in anlotinib-treated patients included hypertension(67.4%),hand-foot syndrome(43.9%),hemoptysis(14.0%),thyroid stimulating hormone(TSH)elevation(46.6%),and corrected QT interval(QTc)prolongation(26.2%).Short conclusion:Anlotinib demonstrated a clinically significant OS prolongation as a novel therapeutic option for advanced or metastatic NSCLC following at least two lines of chemotherapy.
基金supported by The National Key R&D Program of China(2020YFC0841900,2020YFC0844000)The Innovation Groups of the National Natural Science Foundation of China(81721002)+2 种基金The National Science and Technology Major Project(2017YFA0105703)The Military Emergency Research Project for COVID-19(BWS20J006)The Project for Innovation of Military Medicine of China(16CXZ045).
文摘No effective drug treatments are available for coronavirus disease 2019(COVID-19).Host-directed therapies targeting the underlying aberrant immune responses leading to pulmonary tissue damage,death,or long-term functional disability in survivors require clinical evaluation.We performed a parallel assigned controlled,non-randomized,phase 1 clinical trial to evaluate the safety of human umbilical cord-derived mesenchymal stem cells(UC-MSCs)infusions in the treatment of patients with moderate and severe COVID-19 pulmonary disease.The study enrolled 18 hospitalized patients with COVID-19(n=9 for each group).The treatment group received three cycles of intravenous infusion of UC-MSCs(3×107 cells per infusion)on days 0,3,and 6.Both groups received standard COVID-treatment regimens.Adverse events,duration of clinical symptoms,laboratory parameters,length of hospitalization,serial chest computed tomography(CT)images,the PaO2/FiO2 ratio,dynamics of cytokines,and IgG and IgM anti-SARS-CoV-2 antibodies were analyzed.No serious UC-MSCs infusion-associated adverse events were observed.Two patients receiving UC-MSCs developed transient facial flushing and fever,and one patient developed transient hypoxia at 12 h post UC-MSCs transfusion.Mechanical ventilation was required in one patient in the treatment group compared with four in the control group.All patients recovered and were discharged.Our data show that intravenous UC-MSCs infusion in patients with moderate and severe COVID-19 is safe and well tolerated.Phase 2/3 randomized,controlled,double-blinded trials with long-term follow-up are needed to evaluate the therapeutic use of UC-MSCs to reduce deaths and improve long-term treatment outcomes in patients with serious COVID-19.
基金supported by the National Natural Science Foundation of China(31671054 and 81430024)the Postdoctoral Science Foundation of China(2017M610412)the Bureau of Science and Technology of Qingdao Municipality,China(17-1-1-44-jch)
文摘The pathogenesis of the second major neurodegenerative disorder, Parkinson’s disease(PD), is closely associated with the dysfunction of potassium(K~+ ) channels. Therefore, PD is also considered to be an ion channel disease or neuronal channelopathy. Mounting evidence has shown that K~+ channels play crucial roles in the regulations of neurotransmitter release, neuronal excitability, and cell volume. Inhibition of K~+ channels enhances the spontaneous firing frequency of nigral dopamine(DA)neurons, induces a transition from tonic firing to burst discharge, and promotes the release of DA in the striatum.Recently, three K~+ channels have been identified to protect DA neurons and to improve the motor and non-motor symptoms in PD animal models: small conductance(SK)channels, A-type K~+ channels, and KV7/KCNQ channels.In this review, we summarize the physiological and pharmacological effects of the three K~+ channels. We also describe in detail the laboratory investigations regarding K~+ channels as a potential therapeutic target for PD.
文摘目的通过数据挖掘软件及方法从多个维度系统整理徐振晔教授针对大肠癌的临证思维方法及用药规律,为中医药诊治大肠癌提供借鉴。方法采用回顾性临床研究的方法,选取2016年1月至2021年3月期间徐振晔教授门诊治疗的经病理或影像学诊断、至少有2次以上复诊且持续服药2个月及以上有临床症状减轻的大肠癌患者病案。在纳入病例前,将患者的基本信息、临床症状、辨证分型、涉及脏腑、病理因素、临床用药等进行数据预处理及统一、标准化和规范化。在EXCEL中输入所有处理好的病案数据,采用统计产品与服务解决方案25(Statistical Product and Service Solutions,SPSS25)作临床数据有关的频次及聚类分析;在此基础上,采取IBM数据挖掘平台SPSS Modeler 18对临床症状及处方作关联规则分析。结果本研究最终纳入87例患者,279张中药处方。从主要症状频次分析,就诊大肠癌患者中出现纳呆、乏力、大便溏、消瘦、夜寐不安、腹胀、腰酸以及口干占到前八位。出现频次较高的辨证分型为脾虚精亏。病理因素中湿和瘀最多,占50.179%和39.068%。相关脏腑中脾胃、肾、肠、肝最多,占96.774%和41.219%、24.373%、17.921%。纳入分析的279张处方中按照频次排序为黄芪、白术、鸡内金、白茯苓、白花蛇舌草、菝葜、预知子、黄精、野葡萄藤及绞股蓝。四味药排名前五的高置信度组合有黄精、菝葜、鸡内金、黄芪,黄精、白花蛇舌草、鸡内金、黄芪,黄精、鸡内金、白术、黄芪,黄精、鸡内金、白茯苓、黄芪,太子参、黄精、白茯苓以及白术。药物和症状经过聚类后分为六大类。结论徐振晔教授在大肠癌诊治中提倡健脾养精,佐以健脾化湿、化痰散结、疏肝理气、清热解毒、活血通络等法则综合运用的学术思想,为启发中医药对大肠癌的辨证论治拓展了新思路。
基金National Natural Science Foundation of China(20590360)New Century Excellent Talent Project of China(NCET-05-0783)
文摘Silica-supported CuCo catalysts were prepared by impregnation method with different impregnation sequence for higher alcohols synthesis. These catalysts were characterized by H2-TPR, XRD, N2 adsorption, XPS techniques and CO selective hydrogenation reaction measurement. The effects of impregnation sequence on the structure and performance of catalysts were investigated, and there were important influences on the selectivity to higher alcohols. There was a strong synergistic effect between copper and cobalt for the co-impregnated sample. The CuCo/SiO2 catalyst prepared by co- impregnation showed a better yield of total alcohols, and a higher selectivity to total alcohols which reached 51.5%.
文摘目的探讨近三十年来我国循环系统疾病死亡率变化趋势及其影响因素,应用早死所致的寿命损失年(Years of life lost, YLLs)对1990—2017年中国城市和农村循环系统疾病负担进行综合评价。方法以中国年鉴的数据为基础,采用Joinpoint回归分析计算死亡率年度变化百分比,采用标准方法计算循环系统疾病YLL,根据我国2010年人口普查结果的年龄别构成比对粗死亡率以及YLL率进行标化。结果1990—2017年中国城市和农村居民的循环系统疾病粗死亡率均呈上升趋势,城市标化死亡率有明显下降趋势。1990—2017年,随着年龄的增长,城市和农村居民循环系统疾病的死亡率增加;1990年城市循环系统疾病年龄别死亡率总体上高于农村,而2017年农村循环系统疾病年龄别死亡率已经超过了城市。1990—2017年城市和农村的YLLs分别增长了211.6%和26.1%,城市和农村标化YLL率分别下降了37.9%和12.8%。结论1990—2017年中国城市居民循环系统疾病标化死亡率呈明显下降趋势,而城市和农村居民的循环系统疾病YLLs均增加。
