The REporting of studies Conducted using Observational Routinely-collected health Data (RECORD) Statement

Routinely collected health data, obtained for administrative and clinical purposes without specific a priori research goals, are increasingly used for research. The rapid evolution and availability of these data have revealed issues not addressed by existing reporting guidelines, such as Strengthening the Reporting of Observational Studies in Epidemiology (STROBE). The REporting of studies Conducted using Observational Routinely collected health Data (RECORD) statement was created to fill these gaps. RECORD was created as an extension to the STROBE statement to address reporting items specific to observational studies using routinely collected health data. RECORD consists of a checklist of 13 items related to the title, abstract, introduction, methods, results, and discussion section of articles, and other information required for inclusion in such research reports. This document contains the checklist and explanatory and elaboration information to enhance the use of the checklist. Examples of good reporting for each RECORD checklist item are also included herein. This document, as well as the accompanying website and message board (http://www.record-statement.org), will enhance the implementation and understanding of RECORD. Through implementation of RECORD, authors, journals editors, and peer reviewers can encourage transparency of research reporting.     

果蝇程序化死亡基因5(PDCD5)同源cDNA的克隆和序列分析

 为了解人类白血病细胞凋亡相关新基因 TFAR1 9(PDCD5,programmed cell death5)在不同种属间的序列同源性 ,利用 EST(expression sequence tag)拼接、RT- PCR、DNA序列测定技术及计算机分析技术 ,首次成功地进行了果蝇 PDCD5同源 c DNA编码区基因克隆和序列分析 .发现果蝇与小鼠及果蝇与人 PDCD5在核苷酸水平上分别有 57.5%和 57.1 %的同源性 ,在氨基酸水平上分别有 46.8%和 46.4%的同源性 .功能区分析发现 ,果蝇 PDCD5c DNA编码 1 33个氨基酸 ,计算机预测可能是一种核蛋白 ,含 5个可能的酪蛋白激酶 (casein kinase )磷酸化位点 ,2个可能的 PKC磷酸化位点 ,与人 PDCD5的功能区类似 .因而果蝇 PDCD5是与人 PDCD5同源的新基因 ,可能都与细胞程序化死亡相关 .     

乙肝患者肝纤维化血清标志物表达水平及其临床意义

目的探讨乙肝患者肝纤维化血清标志物表达水平及其与病情、病程的关系。方法用R IA方法对135例乙肝患者进行血清透明质酸酶(HA)、层粘连蛋白(LN)、Ⅲ型胶原前体(PⅢC)、Ⅳ型胶原(ⅣC)检测。结果乙肝患者血清中HA、LN、PⅢC和ⅣC水平分别为(338.7±122.6)、(226.2±43.3)、(152.8±33.7)和(132.6±41.1)μg/L。其中,急性黄疸肝炎、慢性肝炎轻度、慢性肝炎中度、慢性肝炎重度、肝硬变代偿期、肝硬变失代偿期、肝癌和肝硬变+肝癌患者HA、LN、PⅢC和ⅣC水平分别为(134.2±101.4)、(185.1±104.5)、(373.5±147.1)、(445.5±123.6)、(477.3±186.0)、(653.7±98.5)、(597.5±91.3)和(723.6±110.4)μg/L;(106.7±31.3)、(179.5±28.5)、(234.6±66.1)、(287.3±57.0)、(294.8±66.4)、(345.6±61.2)、(322.1±71.0)和(357.8±88.3)μg/L;(103.5±19.2)、(108.6±21.4)、(145.3±37.3)、(194.5±41.7)、(188.8±39.5)、(247.6±48.0)、(251.3±37.3)和(286.7±35.8)μg/L;(49.6±14.7)、(83.4±15.3)、(134.5±50.5)、(178.7±61.4)、(183.2±61.3)、(256.8±72.4)、(217.7±64.5)和(281.1±57.0)μg/L。结论肝癌、肝硬化、肝硬变+肝癌和慢性肝炎重度患者存在明显的肝纤维化征象,急性黄疸肝炎、慢性肝炎轻度患者肝纤维化程度较轻,在一定范围内肝纤维化程度与肝病的病情、病程关系密切。     

Genome analysis of a hyper acetone‐butanol‐ethanol (ABE) producing Clostridium acetobutylicum BKM19

Previously the development of a hyper acetone‐butanol‐ethanol (ABE) producing Clostridium acetobutylicum BKM19 strain capable of producing 30.5% more total solvent by random mutagenesis of its parental strain PJC4BK, which is a buk mutant C. acetobutylicum ATCC 824 strain is reported. Here, BKM19 and PJC4BK strains are re‐sequenced by a high‐throughput sequencing technique to understand the mutations responsible for enhanced solvent production. In comparison with the C. acetobutylicum PJC4BK, 13 single nucleotide variants (SNVs), one deletion and one back mutation SNV are identified in the C. acetobutylicum BKM19 genome. Except for one SNV found in the megaplasmid, all mutations are found in the chromosome of BKM19. Among them, a mutation in the thlA gene encoding thiolase is further studied with respect to enzyme activity and butanol production. The mutant thiolase (thlA^V5A) is showed a 32% higher activity than that of the wild‐type thiolase (thlA^WT). In batch fermentation, butanol production is increased by 26% and 23% when the thlA^V5A gene is overexpressed in the wild‐type C. acetobutylicum ATCC 824 and in its derivative, the thlA‐knockdown TKW‐A strain, respectively. Based on structural analysis, the mutation in thiolase does not have a direct effect on the regulatory determinant region (RDR). However, the mutation at the 5^th residue seems to influence the stability of the RDR, and thus, increases the enzymatic activity and enhances solvent production in the BKM19 strain.     

Antitumor therapeutic effects of e7 subunit and DNA vaccines in an animal cervical cancer model: antitumor efficacy of e7 therapeutic vaccines is dependent on tumor sizes, vaccine doses, and vaccine delivery routes

We previously reported that E7 subunit and DNA vaccines are both capable of inducing antitumor protection through induction of antigen-specific CTL. In this study, we investigated their ability to control established tumors according to tumor size, vaccine doses, and vaccine delivery routes. Antitumor therapeutic efficacy of both vaccine types was dependent on tumor burden. However, E7 subunit vaccines induced a higher level of antitumor therapeutic activities at the tested dose compared to DNA vaccines. This was concomitant with induction of antibody, CTL, and IFN-gamma responses, as well as histologic changes (heavy infiltration of lymphocytes and presence of apoptotic bodies). In vaccine dose titration assays, 50 and 100 microg of DNA vaccines exhibited an equivalent antitumor efficacy to 0.5 and 1 microg of E7 subunit vaccines, respectively, i.e., a 100-fold difference in E7 dosage, suggesting the importance of vaccine doses for achieving antitumor immunity. Furthermore, tumors of a larger size were controlled by intratumoral injection with E7 subunit vaccines, underscoring the importance of vaccine delivery routes for antitumor therapeutic efficacy. Thus, these data suggest that antitumor therapeutic efficacy of E7 therapeutic vaccines is determined by vaccine doses, vaccine delivery routes, and tumor sizes, and that these vaccines could be another addition to conventional therapy modalities against cervical cancer.     

IGF1在脑缺血大鼠脑组织中的表达与通络救脑注射液的脑保护作用

目的:观察脑缺血模型大鼠血清及脑组织中IGF1蛋白表达水平,以及通络救脑注射液对该因子表达水平的影响,分析通络救脑注射液的脑保护作用途径。方法:以线栓法制作大鼠大脑中动脉缺血模型(MCAO),将SD大鼠随机分为空白对照组、模型组及通络救脑注射药组,分别在造模后12小时、24小时、3天、7天4个时间点采取动物血清和脑组织,以免疫组化、酶联免疫(ELISA)以及RTPCR的方法,分别检测IGF1的表达部位及定量检测该因子的蛋白及mRNA表达水平,并测定血清NSE含量。结果:IGF1在正常脑组织有表达,在脑缺血后24小时表达增多,此后随脑缺血时间的延长不断减少;通络救脑组IGF1各时间点表达均高于模型组。模型组血清NSE水平显著升高,各时间点与正常组均有显著差异,通络救脑注射液组血清NSE水平在12小时、1天和7天时显著低于模型组。结论:大鼠脑缺血损伤后IGF1表达减少与神经元的坏死有相关性,通络救脑注射液能够提高其表达水平,对缺血损伤的脑组织发挥保护作用。     

宫颈电环切除术与冷刀锥切术治疗宫颈上皮内瘤变的临床比较

目的:比较宫颈电环切除术(LEEP)与冷刀宫颈锥切术治疗宫颈上皮内瘤变(CIN)的临床疗效。方法:回顾性分析分别行LEEP(96例)与冷刀锥切术(78例)治疗的CINⅡ-Ⅲ级患者的临床资料,比较两组患者手术时间、术中出血量、脱痂期出血量及切口愈合时间。结果:LEEP组患者术中出血量(13.5±2.6 mL)、手术时间(12.8±1.9 min)分别少于或短于冷刀宫颈锥切组(26.4±3.7 mL;24.9±2.5 min)(P0.01),两组患者脱痂期出血量、术后切口愈合时间无统计学差异。结论:LEEP治疗CINⅡ-Ⅲ级患者较冷刀锥切术治疗术中出血少,手术时间短,值得临床推广。     

Human neutrophil clearance of bacterial pathogens triggers anti-microbial γδ T cell responses in early infection

Human blood Vγ9/Vδ2 T cells, monocytes and neutrophils share a responsiveness toward inflammatory chemokines and are rapidly recruited to sites of infection. Studying their interaction in vitro and relating these findings to in vivo observations in patients may therefore provide crucial insight into inflammatory events. Our present data demonstrate that Vγ9/Vδ2 T cells provide potent survival signals resulting in neutrophil activation and the release of the neutrophil chemoattractant CXCL8 (IL-8). In turn, Vγ9/Vδ2 T cells readily respond to neutrophils harboring phagocytosed bacteria, as evidenced by expression of CD69, interferon (IFN)-γ and tumor necrosis factor (TNF)-α. This response is dependent on the ability of these bacteria to produce the microbial metabolite (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP), requires cell-cell contact of Vγ9/Vδ2 T cells with accessory monocytes through lymphocyte function-associated antigen-1 (LFA-1), and results in a TNF-α dependent proliferation of Vγ9/Vδ2 T cells. The antibiotic fosmidomycin, which targets the HMB-PP biosynthesis pathway, not only has a direct antibacterial effect on most HMB-PP producing bacteria but also possesses rapid anti-inflammatory properties by inhibiting γδ T cell responses in vitro. Patients with acute peritoneal-dialysis (PD)-associated bacterial peritonitis--characterized by an excessive influx of neutrophils and monocytes into the peritoneal cavity--show a selective activation of local Vγ9/Vδ2 T cells by HMB-PP producing but not by HMB-PP deficient bacterial pathogens. The γδ T cell-driven perpetuation of inflammatory responses during acute peritonitis is associated with elevated peritoneal levels of γδ T cells and TNF-α and detrimental clinical outcomes in infections caused by HMB-PP positive microorganisms. Taken together, our findings indicate a direct link between invading pathogens, neutrophils, monocytes and microbe-responsive γδ T cells in early infection and suggest novel diagnostic and therapeutic approaches.     

Future Impact of Various Interventions on the Burden of COPD in Canada: A Dynamic Population Model

Background

Chronic obstructive pulmonary disease (COPD) is a growing economic burden worldwide. Smoking cessation is thought to be the single most effective way of reducing the economic burden of COPD. The impact of other strategies such as interventions that predict risk of disease, reduce progression of disease, or reduce exacerbations has not been systematically studied.

Objectives

We estimated the economic and clinical burden of COPD over the next 25 years in Canada and the impact of three potential interventions (screening test for predisposition to COPD, new drugs to avoid progression into more severe disease stages, and predictive test for exacerbations) on COPD burden.

Methods

Using a dynamic simulation model, we projected the total burden of COPD (cost, morbidity, and mortality) from 2011 to 2035 using the population of Canada as a case study. The model stratified population based on sex, age, smoking status, respiratory symptoms, and their COPD stage. The cost and quality adjusted life years (QALYs) associated with each intervention were estimated.

Results

The model indicates that annual societal cost of COPD is $4.52 billion (B) Canadian dollars in 2011 and will reach $3.61B ($7.33B undiscounted) per year in 2035. Over the next 25 years, COPD will be responsible for approximately $101.4B in societal costs ($147.5B undiscounted) and 12.9 million QALYs lost (19.0 million undiscounted). Our results suggested that the best strategy to reduce the financial burden of COPD is by reducing exacerbations. Smoking cessation, while it is the cornerstone of COPD prevention, has only a modest effect in attenuating the financial burden of COPD over the next 25 years in Western countries such as Canada.

Conclusion

Our data suggest that any intervention that can reduce the number of exacerbations has a substantial impact on morbidity and costs of COPD and should be considered in conjunction with the ongoing efforts to reduce smoking rates.