亚低温抑制重型颅脑创伤诱导Tau蛋白过度磷酸化的实验研究

目的 观察亚低温对重型颅脑创伤诱导的Tau蛋白磷酸化的影响.方法 体外研究通过细胞液压冲击仪建立SK-N-SH细胞损伤模型,观察冲击1h、6h和12h后Tau蛋白的磷酸化水平.体内研究通过小动物液压冲击仪建立大鼠重型颅脑损伤模型(2.4 atm),接受或不接受亚低温治疗(33℃,4h).观察液压冲击6h、24 h和72 h后Tau蛋白的磷酸化水平,以及亚低温对此变化的影响.结果 SK-N-SH细胞在液压冲击后,Tau蛋白在Thr231和Ser396位点的磷酸化水平从1h开始升高,到6h左右达到高峰.SD大鼠在液压冲击后,Tau蛋白在Thr231和Ser396位点的磷酸化水平从6h开始升高,到24h左右达到高峰,到72 h仍处于高水平;免疫组化的结果也显示,大鼠脑部海马CA1区和皮质区的Tau蛋白磷酸化水平在Thr231位点也明显增高.亚低温可显著逆转液压冲击诱导的SD大鼠Tau蛋白过度磷酸化(P＜0.01).结论 亚低温可抑制重型颅脑创伤诱导的Tau蛋白过度磷酸化.     

颅内压监测对重型颅脑创伤患者预后与疾病负担影响的队列研究

目的 了解颅内压(ICP)监测在重型颅脑创伤(TBI)患者中的应用情况及其对预后和经济负担的影响.方法 抽取上海市5家二级以上综合性医院在2009年1月至2011年1月间收治的重型TBI住院患者535例,按是否行ICP监测分为两组(ICP组和非ICP组),对比两组患者的病死率,急性期总住院费用,住院天数,寿命年费用及质量调整寿命年费用.结果 重型TBI患者行ICP监测的比例为28.0％.ICP组患者的住院病死率为16.7％,显著低于非ICP组患者的住院病死率32.2％(P＜0.001).多元Logistic回归分析显示行ICP监测的患者死亡风险仅为非ICP监测患者的0.32倍(95％ CI,0.19,0.54).重型颅脑创伤患者行ICP监测可使病死率下降15.5％,但平均多耗费住院费用69 620元(P＜0.001);行ICP监测的寿命年费用中位数为5 995元,显著高于未行ICP监测的寿命年费用中位数2 236元(P＜0.001);行ICP监测的质量调整寿命年费用中位数为11 558元,显著高于未行ICP监测的寿命年费用中位数3 938元(P＜0.001).结论 我国重型TBI行ICP监测的比例仍较低,重型TBI患者行ICP监测可能会增加经济负担,但却大大降低患者病死率.     

缺血修饰白蛋白对重型颅脑损伤患者早期心肌损伤的评估价值

目的探讨缺血修饰白蛋白（IMA）对重型颅脑损伤继发心肌损伤的早期诊断价值及其与患者预后的关系。方法检测52例重型颅脑损伤患者（实验组）血清IMA、心肌肌钙蛋白（cTnI）、肌酸激酶同工酶（CK～MB）、肌红蛋白（MYO）,并检测同期46例健康体检者血清IMA。结果实验组血清IMA水平显著高于对照组（P〈0．01）。实验组血清IMA、cTnI、MYO、CK-MB阳性率分别为78．84％、53．85％、32．69％、30．77％,IMA的阳性率显著高于cTnI、MYO、CK—MB的阳性率（P〈0．01）。GCS6-8分组、4-5分组、3分组的ACB值分别为（67.21±5．96）U／ml、（52．85±5．13）U／ml、（40．78±4．85）U／ml,三组间ACB值有统计学差异（P〈0．05）。预后差（GOS评分4～5分）患者血清IMA水平显著低于预后好患者（GOS评分1～3分,P〈0．01）。结论IMA对重型颅脑损伤继发心肌损伤的早期诊断有重要价值,并且检测IMA有助于评估重型颅脑损伤患者的病情严重程度及预后。     

新型冠状病毒肺炎患者继发感染的危险因素分析

摘要：目的　探讨新型冠状病毒肺炎（COVID-19）患者继发细菌感染的危险因素。方法　回顾性分析天津市海河医院收治的136例COVID-19患者的临床资料,根据临床诊断结果分为继发细菌性肺炎（继发感染组,44例）和非继发感染组（92例）。比较2组患者临床特征、治疗、疾病转归等差异,Logistic回归分析患者继发感染的危险因素。结果　继发感染组患者年龄、合并基础疾病比例高于非继发感染组（P＜0.01）,入院的氧合指数（OI）＜400 mmHg、高热（体温>39 ℃）、重症、合并急性呼吸窘迫综合征（ARDS）、低蛋白血症、心功能不全比例也均高于非继发感染组,接受机械通气治疗、有创操作、激素治疗比例及住院时间均高于非继发感染组（P＜0.05）。Logistics 回归分析显示,合并基础疾病（OR=4.613,95%CI：1.756~12.118）、激素治疗（OR=2.403,95%CI：1.012~6.422）、入院OI＜400 mmHg（OR=6.534,95%CI：2.064~20.691）、低蛋白血症（OR=12.949,95%CI：3.284~51.067）是继发细菌感染的独立危险因素。结论　COVID-19继发感染与患者入院氧合指数低于400 mmHg、低蛋白血症、激素治疗、基础疾病关系密切,临床尽早干预可预防患者继发感染,有利于改善预后。     

The Cardiovascular Effects of Treatment with Hydroxychloroquine and Azithromycin

Hydroxychloroquine combined with azithromycin has been investigated for activity against coronavirus disease 2019 (COVID-19), but concerns about adverse cardiovascular (CV) effects have been raised. This study evaluated claims data to determine if risks for CV events were increased with hydroxychloroquine alone or combined with azithromycin. We identified data from 43,752 enrollees that qualified for analysis. The number of CV events increased by 25 (95% confidence interval [CI]: 8, 42, p=0.005) per 1000 people per year of treatment with hydroxychloroquine alone compared with pretreatment levels and by 201 (95% CI: 145, 256, p<0.001) events per 1000 people per year when individuals took hydroxychloroquine and azithromycin. These rates translate to an additional 0.34 (95% CI: 0.11, 0.58) CV events per 1000 patients placed on a 5-day treatment with hydroxychloroquine monotherapy and 2.75 (95% CI: 1.99, 3.51) per 1000 patients on a 5-day treatment with both hydroxychloroquine and azithromycin. The rate of adverse events increased with age following exposure to hydroxychloroquine alone and combined with azithromycin. For females aged 60 to 79 years prescribed hydroxychloroquine, the rate of adverse CV events was 0.92 per 1000 patients on 5 days of therapy, but it increased to 4.78 per 1000 patients when azithromycin was added. The rate of adverse CV events did not differ significantly from zero for patients 60 years of age or younger. These data suggest that hydroxychloroquine with or without azithromycin is likely safe in individuals under 60 years of age if they do not have additional CV risks. However, the combination of hydroxychloroquine and azithromycin should be used with extreme caution in older patients.     

Progress and prospects in the management of bacterial infections and developments in Phytotherapeutic modalities

The advent of antibiotics revolutionized medical care resulting in significantly reduced mortality and morbidity caused by infectious diseases. However, excessive use of antibiotics has led to the development of antibiotic resistance and indeed, the incidence of multidrug-resistant pathogens is considered as a major disadvantage in medication strategy, which has led the scholar's attention towards innovative antibiotic sources in recent years. Medicinal plants contain a variety of secondary metabolites with a wide range of therapeutic potential against the resistant microbes. Therefore, the aim of this review is to explore the antibacterial potential of traditional herbal medicine against bacterial infections. More than 200 published research articles reporting the therapeutic potential of medicinal plants against drug-resistant microbial infections were searched using different databases such as Google Scholar, Science Direct, PubMed and the Directory of Open Access Journals (DOAJ), etc., with various keywords like medicinal plants having antibacterial activities, antimicrobial potentials, phytotherapy of bacterial infection, etc. Articles were selected related to the efficacious herbs easily available to local populations addressing common pathogens. Various plants such as Artocarpus communis, Rheum emodi, Gentiana lutea L., Cassia fistula L., Rosemarinus officinalis, Argemone maxicana L, Hydrastis canadensis, Citrus aurantifolia, Cymbopogon citrates, Carica papaya, Euphorbia hirta, etc, were found to have significant antibacterial activities. Although herbal preparations have promising potential in the treatment of multidrug-resistant bacterial infection, still more research is required to isolate phytoconstituents, their mechanism of action as well as to find their impacts on the human body.     

儿童感染后闭塞性细支气管炎临床分析

目的探讨儿童感染后闭塞性细支气管炎(PIBO)的临床特点。方法选择2013年2月至2017年3月,于武汉儿童医院诊治的26例PIBO患儿为研究对象。回顾性分析其临床特点、病原学检查结果、影像学及肺功能检查结果、治疗和转归。本研究遵循的程序符合2013年修订的《世界医学协会赫尔辛基宣言》。结果对纳入的26例PIBO患儿的研究结果如下。①主要临床表现:26例(100.0%)患儿表现为反复咳嗽及喘息,21例(80.8%)肺部闻及细湿啰音,14例(53.8%)合并活动后气促。②病原学检查结果:主要为腺病毒9例(34.6%),肺炎支原体8例(30.8%),麻疹病毒3例(11.5%)。③辅助检查结果:对26例患儿进行胸部高分辨率CT(HRCT)的检查结果显示,26例(100.0%)均为马赛克灌注征呈阳性,合并支气管扩张为2例(7.7%),合并肺实变为13例(50.0%),合并肺不张为7例(26.9%);肺功能检查结果异常患者中,20例(76.9%)为阻塞性通气功能障碍,3例(11.5%)为混合性通气功能障;对11例患儿进行纤维支气管镜检查结果均显示支气管内膜炎症。④治疗与转归:对26例患儿均使用糖皮质激素及口服阿奇霉素治疗后,15例(57.7%)病情好转,11例(42.3%)临床症状反复或持续存在,本组无一例患儿死亡。结论本组PIBO患儿表现为反复咳嗽、喘息,多为阻塞性通气功能障碍,胸部HRCT可见肺部特异性马赛克灌注征。腺病毒感染是该病患儿最常见病因。糖皮质激素和阿奇霉素治疗PIBO可能有效,本组PIBO患儿的总体预后欠佳。     

COVID-19 adenovirus vector vaccine induces higher interferon and pro-inflammatory responses than mRNA vaccines in human PBMCs,macrophages and moDCs

BackgroundDuring the COVID-19 pandemic multiple vaccines were rapidly developed and widely used throughout the world. At present there is very little information on COVID-19 vaccine interactions with primary human immune cells such as peripheral blood mononuclear cells (PBMCs), monocyte-derived macrophages and dendritic cells (moDCs).MethodsHuman PBMCs, macrophages and moDCs were stimulated with different COVID-19 vaccines, and the expression of interferon (IFN-λ1, IFN-α1), pro-inflammatory (IL-1β, IL-6, IL-8, IL-18, CXCL-4, CXCL-10, TNF-α) and Th1-type cytokine mRNAs (IL-2, IFN-γ) were analyzed by qPCR. In addition, the expression of vaccine induced spike (S) protein and antiviral molecules were studied in primary immune cells and in A549 lung epithelial cells.ResultsAdenovirus vector (Ad-vector) vaccine AZD1222 induced high levels of IFN-λ1, IFN-α1, CXCL-10, IL-6, and TNF-α mRNAs in PBMCs at early time points of stimulation while the expression of IFN-γ and IL-2 mRNA took place at later times. AZD1222 also induced IFN-λ1, CXCL-10 and IL-6 mRNA expression in monocyte-derived macrophages and DCs in a dose-dependent fashion. AZD1222 also activated the phosphorylation of IRF3 and induced MxA expression. BNT162b2 and mRNA-1273 mRNA vaccines failed to induce or induced very weak cytokine gene expression in all cell models. None of the vaccines enhanced the expression of CXCL-4. AZD1222 and mRNA-1273 vaccines induced high expression of S protein in all studied cells.ConclusionsAd-vector vaccine induces higher IFN and pro-inflammatory responses than the mRNA vaccines in human immune cells. This data shows that AZD1222 readily activates IFN and pro-inflammatory cytokine gene expression in PBMCs, macrophages and DCs, but fails to further enhance CXCL-4 mRNA expression.     

Adherence to vaccination guidelines of patients with complete splenectomy in Norway, 2008–2020

The spleen is responsible for blood filtration and mounting an immune response against pathogens. In some people the spleen must be surgically removed because of traumatic events or oncological and hematological conditions. These patients are at higher risk of developing diseases caused by encapsulated bacteria throughout their lives. Thus, immunisations are advised for splenectomised persons to prevent infection caused by Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae type b (Hib). This study assessed vaccination coverage (VC) among Norwegian patients with surgical asplenia. Using the Nomesco Classification of Surgical Procedures codes, patient information (age, sex, date of initial diagnosis and date of surgery) was acquired from the Norwegian Patient Registry. The National Immunization Register provided information on vaccination status and data of any subsequent invasive bacterial infections were obtained from the Norwegian Surveillance System for Communicable Diseases. From the total population of Norway, 3155 patients who had undergone complete splenectomy were identified. Of these, 914 (29.0%) had received at least one dose of pneumococcal conjugate vaccine (PCV), 1324 (42.0%) at least one dose of pneumococcal polysaccharide vaccine and 589 (18.7%) had received both. Only 4.2% of the patients had received two doses of a meningococcal ACWY conjugate vaccine, while 8.0% of 1467 patients splenectomised after 2014 had received at least two doses of a serogroup B meningococcal vaccine. The VC for Hib was 18.7%. Nearly all splenectomised children under the age of 10 were vaccinated with Hib and PCV as these vaccines are included in the childhood immunisation program. For all vaccines, VC decreased with age. Twenty-nine invasive bacterial infections were registered post-splenectomy in 25 patients. Vaccination according to national recommendations could have prevented at least 8 (28%) of these infections. Our study showed that efforts are required to increase VC of splenectomised individuals in Norway.