Different Roles of N-Terminal and C-Terminal Domains in Calmodulin for Activation of Bacillus anthracis Edema Factor

Bacillus anthracis adenylyl cyclase toxin edema factor (EF) is one component of the anthrax toxin and is essential for establishing anthrax disease. EF activation by the eukaryotic Ca²⁺-sensor calmodulin (CaM) leads to massive cAMP production resulting in edema. cAMP also inhibits the nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase, thus reducing production of reactive oxygen species (ROS) used for host defense in activated neutrophils and thereby facilitating bacterial growth. Methionine (Met) residues in CaM, important for interactions between CaM and its binding partners, can be oxidized by ROS. We investigated the impact of site-specific oxidation of Met in CaM on EF activation using thirteen CaM-mutants (CaM-mut) with Met to leucine (Leu) substitutions. EF activation shows high resistance to oxidative modifications in CaM. An intact structure in the C-terminal region of oxidized CaM is sufficient for major EF activation despite altered secondary structure in the N-terminal region associated with Met oxidation. The secondary structures of CaM-mut were determined and described in previous studies from our group. Thus, excess cAMP production and the associated impairment of host defence may be afforded even under oxidative conditions in activated neutrophils.     

腹腔镜辅助阴式广泛子宫切除加盆腔淋巴清扫术在早期宫颈癌的临床应用分析

目的:探讨腹腔镜辅助阴式广泛子宫切除加盆腔淋巴清扫术(LAVRH)在早期宫颈癌的临床效果。方法:采用系统回顾性分析,对2010年2月到2012年3月在我科手术治疗的53例宫颈癌患者进行分析。其中LAVRH组38例为研究组,开腹组15例为对照组。比较两组患者手术时间、术中出血量、手术并发症、术后肠道功能恢复时间、切口愈合情况。结果:两组均未发生严重并发症。手术时间:LAVRH组(268.95 29.69)分钟,开腹组(252 29.57)分钟;出血量:LAVRH组术(229.74 90.75)ml,开腹组(522.66 140.48)ml;术后肠道功能恢复时间:LAVRH组(44.58 9.28)小时,开腹组(57.47 8.98)小时;两组术后尿潴留发生率以腹腔镜组较高,但无显著性差异(P>0.05);两组均达到淋巴清除彻底。结论:腹腔镜辅助阴式广泛子宫切除加盆腔淋巴清扫术具有微创、恢复快、术中出血量少等优点,近期疗效满意,远期效果仍需要大量样本的论证研究。     

基于知识图谱构建和定性访谈法探析张忠德教授辨治间质性肺病临床特征与方药规律＊

目的 构建个性化知识图谱技术和定性访谈法结合，进一步挖掘张忠德教授辨治间质性肺疾病临证特征与用药规律。方法 采用回顾性分析，系统收集张忠德教授广东省中医院门诊2010年8月至2020年8月治疗间质性肺疾病病历，按照诊断标准、纳入标准、排除标准，严格筛选后，通过广东省中医院大数据挖掘团队中医药大数据智能处理与知识服务系统进行数据挖掘分析，并通过多元化视觉定性访谈法，将定量与定性分析有效结合。结果 共筛选出347首方，共141味药物，常用药物频次 ≥ 84次的药物有10味，其中党参、麦芽、黄芪、紫菀、白术等为核心用药，通过症状与药物推理知识地图显示，党参、炒麦芽、黄芪、大枣、太子参、山萸肉、巴戟天等为主要治疗用药；临证遣方用药知识关联分析，得知咳嗽、耳鸣、心悸、水肿、头痛、胸闷、恶寒等为多见，针对咳嗽，首选紫苏子、橘红、桂枝等温肺降气通阳之品等；频繁聚集显示，常用药对炒麦芽-炒白术、黄芪-党参、黄精-菟丝子、前胡-紫菀、炙枇杷叶-浙贝母等；聚类分析结果得到4组关系密切的聚类新药物组合；以脾为中轴，肺肾共扶为主的“平调五脏论”，分期阶梯辨治间质性肺疾病。结论 张忠德教授认为间质性肺疾病，虚实夹杂为多见，应从肺、脾、肾着手，采用平调五脏论分期阶梯辨治，用药配伍精简，以和为贵，以平为期。     

Application of metabolomics in establishing primary nephrotic syndrome diagnosis model

Objective To establish diagnosis model and explore related metabolic pathways by analyzing the serum metabolic profile of patients with primary nephrotic syndrome (PNS) through metabolomics. Methods Thirty PNS patients hospitalized in Huai'an First People's Hospital between December 2010 and April 2012 were enrolled. High performance liquid chromatography-mass spectrometry (LC-MS) was employed to detect metabolites in the serum of 30 PNS patients and 30 healthy controls. Metabolic fingerprint profiling and multivariate pattern recognition analysis were combined to establish disease-specific metabolic diagnosis model, and metabolic pathway analysis was performed. Results PNS group and control group could be well separated by principal component analysis (PCA) model as well as partial least-squares discriminant analysis (PLS-DA) model with Q2 of 0.300. There was well interpretation in PLA-DA model (R2X=0.581，R2Y=0.452). Compared with healthy controls，PNS patients had decreased cholestane 3, 7, 12, 15 alcohol, acyl glycerine, phytosphingosine and tryptophan, and increased sphingomyelin, arginine and glutamic acid (all VIP＞1, P＜0.05). The metabolic disorders pathways of PNS patients included sphingolipid metabolism, arginine and proline metabolism, linoleic acid metabolism and pyrimidine metabolism (all impact＞0.10 and P＜0.05). Conclusions Metabolomics combined with multivariate pattern recognition analysis may be a new tool for diagnosis and monitoring of PNS.     

Prostate volume as an independent predictor of prostate cancer in men with PSA of 10–50?ng ml?1

Prostate volume (PV) has been shown to be associated with prostate cancer (PCa) detection rates in men with a prostate-specific antigen (PSA) in the ‘grey zone'' (2.0–10.0 ng ml⁻¹). However, the PSA ‘grey zone'' in Asian men should be higher because the incidence of PCa in Asian men is relatively low. Therefore, we evaluated the association between PV and PCa detection rates in men with PSAs measuring 10–50 ng ml⁻¹. Men who underwent a 13-core prostatic biopsy with PV documentation participated in the study. A multivariate stepwise regression was used to evaluate whether the PV at time of prostate biopsy could predict the risk of PCa. The rates of PCa among men in different PSA ranges, stratified by PV medians (<60 and ≥60 ml), were calculated. There were 261 men included in the final analysis. PV was the strongest predictor of PCa risk (odds ratio, 0.02; P<0.001) compared to other variables. The PCa rates in men with PVs measuring <60 and ≥60 ml in the 10–19.9 ng ml⁻¹ PSA group were 40.6% and 15.1%, respectively, while the rates for men with PSAs measuring 20–50 ng ml⁻¹ were 65.1% and 26.8%. PV is an independent predictor of PCa in men with PSA measuring 10–50 ng ml⁻¹. In clinical practice, particularly for those countries with lower incidences of PCa, PV should be considered when counselling patients with PSAs measuring 10–50 ng ml⁻¹ regarding their PCa risks.     

Psychological health and HIV transmission among female sex workers: a systematic review and meta-analysis

Current HIV prevention interventions for female sex workers (FSWs) have tended to target the cognitive factors in changing their behaviors, yet little attention has been paid to the psychological factors that influence the behavior of women in sex work. This review aimed to explore the associations between the psychological health of FSWs and HIV risk. A total of eight studies published in English before July 2013 were identified and reviewed. FSWs had reported psychological issues, including depression, suicidal thoughts as well as lower quality of life, and the pooled prevalence of probable depression was as high as 62.4%. The majority of studies showed that higher scores in psychological health problems were associated with increased HIV risk behavior, in particular inconsistent condom use, or sexually transmitted infections. Among the five studies which measured symptoms of depression, four documented that higher depression scores were significantly associated with inconsistent condom use among FSWs with their clients and/or partners. Meta-analysis using a fixed-effects model was performed to examine the association between depression and inconsistent condom use and found that higher scores in depression were significantly associated with inconsistent condom use (odds ratio?=?2.57, p?相似文献   

Vitamin D,folate, and potential early lifecycle environmental origin of significant adult phenotypes

Background and objectives: Vitamin D and folate are highly UV sensitive, and critical for maintaining health throughout the lifecycle. This study examines whether solar irradiance during the first trimester of pregnancy influences vitamin D receptor (VDR) and nuclear folate gene variant occurrence, and whether affected genes influence late-life biochemical/clinical phenotypes.Methodology: 228 subjects were examined for periconceptional exposure to solar irradiance, variation in vitamin D/folate genes (polymerase chain reaction (PCR)), dietary intake (food frequency questionnaire (FFQ)) and important adult biochemical/clinical phenotypes.Results: Periconceptional solar irradiance was associated with VDR-BsmI (P = 0.0008^wk7), TaqI (P = 0.0014^wk7) and EcoRV (P = 0.0030^wk6) variant occurrence between post-conceptional weeks 6–8, a period when ossification begins. Similar effects were detected for other VDR gene polymorphisms. Periconceptional solar irradiance was also associated with 19 bp del-DHFR (P = 0.0025^wk6), and to a lesser extent C1420T-SHMT (P = 0.0249^wk6), a folate-critical time during embryogenesis. These same genes were associated with several late-life phenotypes: VDR-BsmI, TaqI and ApaI determined the relationship between dietary vitamin D and both insulin (P < 0.0001/BB, 0.0007/tt and 0.0173/AA, respectively) and systolic blood pressure (P = 0.0290/Bb, 0.0299/Tt and 0.0412/AA, respectively), making them important early and late in the lifecycle. While these and other phenotype associations were found for the VDR variants, folate polymorphism associations in later-life were limited to C1420T-SHMT (P = 0.0037 and 0.0297 for fasting blood glucose and HbA1c levels, respectively). We additionally report nutrient–gene relationships with body mass index, thiol/folate metabolome, cognition, depression and hypertension. Furthermore, photoperiod at conception influenced occurrence of VDR-Tru9I and 2R3R-TS genotypes (P = 0.0120 and 0.0360, respectively).Conclusions and implications: Findings identify environmental and nutritional agents that may interact to modify gene–phenotype relationships across the lifecycle, offering new insight into human ecology. This includes factors related to both disease aetiology and the evolution of skin pigmentation.