脑小血管病(cerebral small vessel disease,CSVD)是老年人最常见的脑血管疾病,也是引起认知功能障碍的最常见原因之一。目前对CSVD的治疗有很大的局限性。CSVD的病理机制、临床表现和影像学表现的异质性,以及对本病缺乏共识,均可影响...脑小血管病(cerebral small vessel disease,CSVD)是老年人最常见的脑血管疾病,也是引起认知功能障碍的最常见原因之一。目前对CSVD的治疗有很大的局限性。CSVD的病理机制、临床表现和影像学表现的异质性,以及对本病缺乏共识,均可影响相关药物临床试验的进展。为了给CSVD的治疗提供可靠的依据,并为今后的临床实践增加特异性药物的选择,国家神经系统疾病临床医学研究中心和中国卒中学会脑小血管病分会联合起草本共识。期望规范CSVD相关临床试验来评价药物的疗效和安全性,为CSVD的治疗提供可靠的证据支持。展开更多
中国卒中防治正面临巨大挑战。2018年,中国脑血管病的死亡率为149.49/10万,造成了157万人死亡。脑血管病是我国居民的第三位死亡原因,位列恶性肿瘤和心脏病之后。2013年,卒中年龄标化患病率和发病率分别为1114.8/10万和246.8/10万人年...中国卒中防治正面临巨大挑战。2018年,中国脑血管病的死亡率为149.49/10万,造成了157万人死亡。脑血管病是我国居民的第三位死亡原因,位列恶性肿瘤和心脏病之后。2013年,卒中年龄标化患病率和发病率分别为1114.8/10万和246.8/10万人年。根据2017年全球疾病负担研究,1990-2017年卒中造成的过早死亡损失寿命年(year of life lost,YLL)增加了14.6%,卒中由造成YLL的第三位原因跃升为第一位;卒中造成的全年龄组伤残调整生命年(disability-adjusted life year,DALY)的绝对数和百分率也呈持续增长趋势,2017年卒中是造成全年龄组DALY的首位原因。脑血管病的主要危险因素包括行为危险因素(如吸烟和酗酒)和既往疾病(如高血压、糖尿病、血脂异常和心房颤动)。卒中存活者中最普遍的危险因素是高血压(63.0%~84.2%)和吸烟(31.7%~47.6%),心房颤动的比例相对最低(2.7%~7.4%)。这些主要的危险因素在人群中流行水平也较高,并呈持续增长的趋势。根据最新的国家流行病学调查数据,我国15岁及以上人群的现在吸烟率为26.6%(现在吸烟人数为3.08亿)。18岁及以上人群的高血压年龄标化患病率为25.2%;高胆固醇血症的标化患病率为5.8%;糖尿病标化患病率为10.9%。40岁及以上人群心房颤动的标化患病率为2.31%。医院质量监测系统(Hospital Quality Monitoring System,HQMS)数据显示,2018年我国1853家三级医院共计收治3010204例卒中住院患者,其中2466785例(81.9%)为缺血性卒中(ischemic stroke,IS),447609例(14.9%)为脑出血(intracerebral hemorrhage,ICH),95810例(3.2%)为蛛网膜下腔出血(subarachnoid hemorrhage,SAH)。入院患者的平均年龄为66岁,近60%为男性。在IS、ICH和SAH中,分别有1555例(0.1%)、2774例(0.6%)和1347例(1.4%)为儿童卒中(年龄<18岁)。超过三分之一(1063892例,35.3%)患者的医保类型为城镇居民基本医疗保险,其次是城镇职工基本医疗保险(699513例,23.2%)和新型农村合作医疗保险(489361例,16.3%)。卒中患者的主要危险因素为高血压(IS:67.4%,ICH:77.2%,SAH:49.1%),主要并发症是肺炎或肺部感染(IS:10.1%,ICH:31.4%,SAH:25.2%)。卒中住院患者的死亡/非医嘱离院率为8.3%,从IS患者的5.8%到ICH患者的19.5%。住院时间的中位数(四分位数间距)为10.0(7.0~14.0)d,从IS患者的10.0(7.0~13.0)d到SAH患者的14.0(8.0~22.0)d。中国卒中中心联盟的数据显示,指南推荐的IS、ICH和SAH患者关键绩效指标执行的综合评分分别为0.77±0.21、0.72±0.28和0.59±0.32。展开更多
我国正面临着全球最大的卒中挑战。全球疾病负担(global burden of disease,GBD)研究结果显示,2019年我国新发卒中394万例,卒中患者达到2876万例,卒中死亡人数为219万例。此外,卒中也是我国伤残调整生命年(disability-adjusted life yea...我国正面临着全球最大的卒中挑战。全球疾病负担(global burden of disease,GBD)研究结果显示,2019年我国新发卒中394万例,卒中患者达到2876万例,卒中死亡人数为219万例。此外,卒中也是我国伤残调整生命年(disability-adjusted life years,DALYs)的首位原因,2019年卒中所致DALYs达到4590万。近期的几项大型流行病学调查对与卒中有关的既往疾病数据进行了更新。2018年我国18~69岁成人的超重和肥胖率分别为34.4%和16.8%;18岁及以上无高血压病史的成人中50.9%处于高血压前期,成人高血压的加权患病率为27.5%。根据美国糖尿病学会诊断标准,2017年我国18岁及以上成人中,总糖尿病和糖尿病前期的加权患病率分别为12.8%和35.2%;45岁以上成人的心房颤动加权患病率为1.8%,患者人数相当于790万人。医院质量监测系统(hospital quality monitoring system,HQMS)中1672家三级公立医院的数据显示,2019年收治卒中病例3411168例,其中缺血性卒中(ischemic stroke,IS)2818875例(82.6%),脑出血(intracebral hemorrhage,ICH)485474例(14.2%),蛛网膜下腔出血(subarachnoid hemorrhage,SAH)106819例(3.1%)。中位年龄为66岁,59.6%为男性。在IS、ICH和SAH中儿童卒中(年龄<18岁)分别有1379例(<0.1%)、2604例(0.5%)和1250例(1.2%)。超过三分之一[1231519例(36.1%)]的卒中病例参加了城镇居民基本医疗保险,其次是城镇职工基本医疗保险[891103例(26.1%)]和新型农村合作医疗保险[543108例(15.9%)]。主要危险因素是高血压(IS 57.3%、ICH 69.9%、SAH 44.1%),主要并发症是肺炎或肺部感染(IS 10.4%、ICH 34.6%、SAH29.7%)。总体的院内死亡/非医嘱离院率为8.5%,从IS的6.0%到SAH的20.6%不等。住院时间为9.0(6.0~13.0)d,范围从IS的10.0(7.0~13.0)d到ICH的14.0(8.0~22.0)d。HQMS中2847家二级公立或民营医院的数据也有类似的结果。HQMS的数据显示,内蒙古自治区、安徽省、西藏自治区和北京市去外省就医比例较高。北京市、天津市、上海市和宁夏回族自治区等省外来诊患者比例较高。2019年中国卒中中心联盟(Chinese Stroke Center Alliance,CSCA)联合1337家医院进行了调查,汇总323601例卒中数据显示,指南推荐的IS、ICH和SAH患者关键绩效指标综合评分分别为0.78±0.20分、0.69±0.27分和0.60±0.31分。展开更多
北京天坛医院王拥军教授团队进行的氯吡格雷在急性非致残性脑血管病高危患者中的应用（Clopidogrel in High-risk Patients with Acute Nondisabling Cerebrovascular Events,CHANCE）研究首次证实,氯吡格雷联合阿司匹林双重抗血小板治...北京天坛医院王拥军教授团队进行的氯吡格雷在急性非致残性脑血管病高危患者中的应用（Clopidogrel in High-risk Patients with Acute Nondisabling Cerebrovascular Events,CHANCE）研究首次证实,氯吡格雷联合阿司匹林双重抗血小板治疗小卒中或短暂性脑缺血发作（transient ischemic attacks,TIA）优于单纯阿司匹林治疗。展开更多
Human enteroviruses are less well-known causes of acute bronchiolitis. In recent years, Enterovirus D68 [EV D68] has emerged as significant cause of epidemic viral bronchiolitis and pneumonia in the United States and ...Human enteroviruses are less well-known causes of acute bronchiolitis. In recent years, Enterovirus D68 [EV D68] has emerged as significant cause of epidemic viral bronchiolitis and pneumonia in the United States and other countries. Chronic bronchiolitis has not been previously attributed to EV D68. We documented EV D68 in open lung biopsies of a young adult patient who was frequently admitted to the hospital for severe exacerbation of respiratory infections and subsequently developed progressive respiratory insufficiency. The difficulty of diagnosis and potential economic impact of this illness is discussed.展开更多
Jetting of epoxies and other materials is going to change the way people do dispensing. For thelast twenty years, dispensing has evolved from merely pushing fluid through a needle to a highly automatedproduction proce...Jetting of epoxies and other materials is going to change the way people do dispensing. For thelast twenty years, dispensing has evolved from merely pushing fluid through a needle to a highly automatedproduction process. Controlling fluid deposition, needle positioning and dispensed volume accuracy hasdramatically improved in recent years. Additionally, speed has increased while software has simplified operationalcontrol. Now jet dispensing fluids has become practical and it is going to have as large an impact on theelectronics assembly industry that Ink Jet printing has had in the office / home environment.展开更多
DNA hypermethylation of tumor suppressor genes has been frequently observed in cancer patients, and therefore, may provide a valuable biomarker for cancer prevention and treatment. DNA hypermethylation may also provid...DNA hypermethylation of tumor suppressor genes has been frequently observed in cancer patients, and therefore, may provide a valuable biomarker for cancer prevention and treatment. DNA hypermethylation may also provide an important mechanism in cancer progression. Lung cancer is strongly associated with exposure to environmental carcinogens, especially tobacco smoke. DNA damage generated by tobacco smoke is believed to play an important role in lung cancer development. XPC is a DNA damage recognition protein required for DNA repair and other DNA damage responses and attenuated XPC protein levels have been detected in many lung cancer patients. We studied the role of XPC protein deficiency in tobacco smoke-caused DNA hypermethylation of important tumor suppressor genes. Using both normal human fibroblasts (NF) and XPC-deficient hu man fibroblasts (XPC), our DNA methylation studies demonstrated that the XPC deficiency caused elevated levels of DNA hypermethylation in both Brca1 and Mlh1 tumor suppressor genes following exposure to tobacco smoke condensate (TSC). The results of our ChIP studies revealed that the XPC deficiency led to an increased binding of DNA methyltransferase 3A (DNMT3A) at the promoter region CpG island-containing sequences of these genes under the TSC treatment;however, this increase was partially diminished with prior treatment with caffeine. The results of our immuno-precipitation (IP) studies demonstrated a protein-protein interaction of the ATR with DNMT3A. Our western blots revealed that the XPC deficiency caused an increase in TSC-induced ATR phosphorylation at serine 428, an indicator of ATR activation. All these results suggest that XPC deficiency causes an accelerated DNA hypermethylation in important tumor suppressor genes under tobacco smoke exposure and activation of the ATR signaling pathway is involved in this DNA hypermethylation process.展开更多
After decades of research, functional dyspepsia (FD) remains one of the most elusive gastrointestinal disorders. Endoscopic appearance of mild inflammation of the gastric mucosa without ulceration and microscopic evid...After decades of research, functional dyspepsia (FD) remains one of the most elusive gastrointestinal disorders. Endoscopic appearance of mild inflammation of the gastric mucosa without ulceration and microscopic evidence of mild chronic inflammation are often considered as normal findings since no etiology could be found other than H. Pylori. Enteroviruses infect the gastrointestinal tract and have been shown to persist in the stomach of symptomatic patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). In this study, we evaluated FD patients with and without the diagnosis of ME/CFS, and were able to support the viral protein staining with finding of double-stranded RNA in 63% of the same stomach biopsies by immunoperoxidase staining. Furthermore, we clarified the possible cross-reaction with creatine kinase brain subtype (CKB), present in parietal cells, using antibody competition experiments and western blot analysis of stomach proteins. Viral protein+ and dsRNA+ biopsies were infectious in SCID mice. More research is needed to elucidate the mechanism of enterovirus infection of the stomach associated with FD and chronic gastritis.展开更多
Background: Enterovirus (EV) can cause gastroenteritis and are known to replicate in Peyer’s patches of terminal ileum. EV has been found in the intestinal specimens from immunocompromised patients with regional ente...Background: Enterovirus (EV) can cause gastroenteritis and are known to replicate in Peyer’s patches of terminal ileum. EV has been found in the intestinal specimens from immunocompromised patients with regional enteritis, and another study demonstrates the presence of enterovirus in the resected terminal ileum of immunocompetent pediatric patients with Crohn’s disease (CD). Cluster outbreaks of CD have also been reported in the literature but the cause of the disease remains elusive. Materials and Methods: A small cluster of pathologically proven CD occurred in our geographic area in 2004-2005, concurrently with an epidemic of Echovirus 18 (E18) meningitis. Serum samples of these and other CD patients and control subjects were tested for neutralizing antibodies of 11 common typeable enteroviruses and Echovirus 18;and tissue samples of CD patients, and terminal ileum and colon biopsies of normal controls were tested for the presence of viral capsid protein 1 (VP1) by immunoperoxidase staining. Results: Immunoperoxidase staining demonstrated VP1 in a rare epithelial granuloma, in diseased muscle of terminal ileum and also in colon biopsies of CD patients. Significantly elevated E18 neutralizing antibody was found in patients with pathologically-proven Crohn’s disease, as compared to control subjects. Conclusion: In this small observational study, EV VP1 is consistently demonstrated in tissue samples of CD patients as compared to control subjects;and neutralizing antibody for E18 was found in all of the patients with available serum samples. Larger cross-sectional studies will be needed to define the role of E18 in this chronic disease.展开更多
文摘脑小血管病(cerebral small vessel disease,CSVD)是老年人最常见的脑血管疾病,也是引起认知功能障碍的最常见原因之一。目前对CSVD的治疗有很大的局限性。CSVD的病理机制、临床表现和影像学表现的异质性,以及对本病缺乏共识,均可影响相关药物临床试验的进展。为了给CSVD的治疗提供可靠的依据,并为今后的临床实践增加特异性药物的选择,国家神经系统疾病临床医学研究中心和中国卒中学会脑小血管病分会联合起草本共识。期望规范CSVD相关临床试验来评价药物的疗效和安全性,为CSVD的治疗提供可靠的证据支持。
文摘中国卒中防治正面临巨大挑战。2018年,中国脑血管病的死亡率为149.49/10万,造成了157万人死亡。脑血管病是我国居民的第三位死亡原因,位列恶性肿瘤和心脏病之后。2013年,卒中年龄标化患病率和发病率分别为1114.8/10万和246.8/10万人年。根据2017年全球疾病负担研究,1990-2017年卒中造成的过早死亡损失寿命年(year of life lost,YLL)增加了14.6%,卒中由造成YLL的第三位原因跃升为第一位;卒中造成的全年龄组伤残调整生命年(disability-adjusted life year,DALY)的绝对数和百分率也呈持续增长趋势,2017年卒中是造成全年龄组DALY的首位原因。脑血管病的主要危险因素包括行为危险因素(如吸烟和酗酒)和既往疾病(如高血压、糖尿病、血脂异常和心房颤动)。卒中存活者中最普遍的危险因素是高血压(63.0%~84.2%)和吸烟(31.7%~47.6%),心房颤动的比例相对最低(2.7%~7.4%)。这些主要的危险因素在人群中流行水平也较高,并呈持续增长的趋势。根据最新的国家流行病学调查数据,我国15岁及以上人群的现在吸烟率为26.6%(现在吸烟人数为3.08亿)。18岁及以上人群的高血压年龄标化患病率为25.2%;高胆固醇血症的标化患病率为5.8%;糖尿病标化患病率为10.9%。40岁及以上人群心房颤动的标化患病率为2.31%。医院质量监测系统(Hospital Quality Monitoring System,HQMS)数据显示,2018年我国1853家三级医院共计收治3010204例卒中住院患者,其中2466785例(81.9%)为缺血性卒中(ischemic stroke,IS),447609例(14.9%)为脑出血(intracerebral hemorrhage,ICH),95810例(3.2%)为蛛网膜下腔出血(subarachnoid hemorrhage,SAH)。入院患者的平均年龄为66岁,近60%为男性。在IS、ICH和SAH中,分别有1555例(0.1%)、2774例(0.6%)和1347例(1.4%)为儿童卒中(年龄<18岁)。超过三分之一(1063892例,35.3%)患者的医保类型为城镇居民基本医疗保险,其次是城镇职工基本医疗保险(699513例,23.2%)和新型农村合作医疗保险(489361例,16.3%)。卒中患者的主要危险因素为高血压(IS:67.4%,ICH:77.2%,SAH:49.1%),主要并发症是肺炎或肺部感染(IS:10.1%,ICH:31.4%,SAH:25.2%)。卒中住院患者的死亡/非医嘱离院率为8.3%,从IS患者的5.8%到ICH患者的19.5%。住院时间的中位数(四分位数间距)为10.0(7.0~14.0)d,从IS患者的10.0(7.0~13.0)d到SAH患者的14.0(8.0~22.0)d。中国卒中中心联盟的数据显示,指南推荐的IS、ICH和SAH患者关键绩效指标执行的综合评分分别为0.77±0.21、0.72±0.28和0.59±0.32。
文摘Human enteroviruses are less well-known causes of acute bronchiolitis. In recent years, Enterovirus D68 [EV D68] has emerged as significant cause of epidemic viral bronchiolitis and pneumonia in the United States and other countries. Chronic bronchiolitis has not been previously attributed to EV D68. We documented EV D68 in open lung biopsies of a young adult patient who was frequently admitted to the hospital for severe exacerbation of respiratory infections and subsequently developed progressive respiratory insufficiency. The difficulty of diagnosis and potential economic impact of this illness is discussed.
文摘Jetting of epoxies and other materials is going to change the way people do dispensing. For thelast twenty years, dispensing has evolved from merely pushing fluid through a needle to a highly automatedproduction process. Controlling fluid deposition, needle positioning and dispensed volume accuracy hasdramatically improved in recent years. Additionally, speed has increased while software has simplified operationalcontrol. Now jet dispensing fluids has become practical and it is going to have as large an impact on theelectronics assembly industry that Ink Jet printing has had in the office / home environment.
文摘DNA hypermethylation of tumor suppressor genes has been frequently observed in cancer patients, and therefore, may provide a valuable biomarker for cancer prevention and treatment. DNA hypermethylation may also provide an important mechanism in cancer progression. Lung cancer is strongly associated with exposure to environmental carcinogens, especially tobacco smoke. DNA damage generated by tobacco smoke is believed to play an important role in lung cancer development. XPC is a DNA damage recognition protein required for DNA repair and other DNA damage responses and attenuated XPC protein levels have been detected in many lung cancer patients. We studied the role of XPC protein deficiency in tobacco smoke-caused DNA hypermethylation of important tumor suppressor genes. Using both normal human fibroblasts (NF) and XPC-deficient hu man fibroblasts (XPC), our DNA methylation studies demonstrated that the XPC deficiency caused elevated levels of DNA hypermethylation in both Brca1 and Mlh1 tumor suppressor genes following exposure to tobacco smoke condensate (TSC). The results of our ChIP studies revealed that the XPC deficiency led to an increased binding of DNA methyltransferase 3A (DNMT3A) at the promoter region CpG island-containing sequences of these genes under the TSC treatment;however, this increase was partially diminished with prior treatment with caffeine. The results of our immuno-precipitation (IP) studies demonstrated a protein-protein interaction of the ATR with DNMT3A. Our western blots revealed that the XPC deficiency caused an increase in TSC-induced ATR phosphorylation at serine 428, an indicator of ATR activation. All these results suggest that XPC deficiency causes an accelerated DNA hypermethylation in important tumor suppressor genes under tobacco smoke exposure and activation of the ATR signaling pathway is involved in this DNA hypermethylation process.
文摘After decades of research, functional dyspepsia (FD) remains one of the most elusive gastrointestinal disorders. Endoscopic appearance of mild inflammation of the gastric mucosa without ulceration and microscopic evidence of mild chronic inflammation are often considered as normal findings since no etiology could be found other than H. Pylori. Enteroviruses infect the gastrointestinal tract and have been shown to persist in the stomach of symptomatic patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). In this study, we evaluated FD patients with and without the diagnosis of ME/CFS, and were able to support the viral protein staining with finding of double-stranded RNA in 63% of the same stomach biopsies by immunoperoxidase staining. Furthermore, we clarified the possible cross-reaction with creatine kinase brain subtype (CKB), present in parietal cells, using antibody competition experiments and western blot analysis of stomach proteins. Viral protein+ and dsRNA+ biopsies were infectious in SCID mice. More research is needed to elucidate the mechanism of enterovirus infection of the stomach associated with FD and chronic gastritis.
文摘Background: Enterovirus (EV) can cause gastroenteritis and are known to replicate in Peyer’s patches of terminal ileum. EV has been found in the intestinal specimens from immunocompromised patients with regional enteritis, and another study demonstrates the presence of enterovirus in the resected terminal ileum of immunocompetent pediatric patients with Crohn’s disease (CD). Cluster outbreaks of CD have also been reported in the literature but the cause of the disease remains elusive. Materials and Methods: A small cluster of pathologically proven CD occurred in our geographic area in 2004-2005, concurrently with an epidemic of Echovirus 18 (E18) meningitis. Serum samples of these and other CD patients and control subjects were tested for neutralizing antibodies of 11 common typeable enteroviruses and Echovirus 18;and tissue samples of CD patients, and terminal ileum and colon biopsies of normal controls were tested for the presence of viral capsid protein 1 (VP1) by immunoperoxidase staining. Results: Immunoperoxidase staining demonstrated VP1 in a rare epithelial granuloma, in diseased muscle of terminal ileum and also in colon biopsies of CD patients. Significantly elevated E18 neutralizing antibody was found in patients with pathologically-proven Crohn’s disease, as compared to control subjects. Conclusion: In this small observational study, EV VP1 is consistently demonstrated in tissue samples of CD patients as compared to control subjects;and neutralizing antibody for E18 was found in all of the patients with available serum samples. Larger cross-sectional studies will be needed to define the role of E18 in this chronic disease.
