Electrochemical,spectroscopic, and molecular docking studies of the interaction between the anti-retroviral drug indinavir and dsDNA

In this study, an electrochemical DNA biosensor was developed using a straightforward methodology to investigate the interaction of indinavir with calf thymus double-stranded deoxyribonucleic acid (ct-dsDNA) for the first time. The decrease in the oxidation signals of deoxyguanosine (dGuo) and deoxyadenosine (dAdo), measured by differential pulse voltammetry, upon incubation with different concentrations of indinavir can be attributed to the binding mode of indinavir to ct-dsDNA. The currents of the dGuo and dAdo peaks decreased linearly with the concentration of indinavir in the range of 1.0–10.0 μg/mL. The limit of detection and limit of quantification for indinavir were 0.29 and 0.98 μg/mL, respectively, based on the dGuo signal, and 0.23 and 0.78 μg/mL, respectively, based on the dAdo signal. To gain further insights into the interaction mechanism between indinavir and ct-dsDNA, spectroscopic measurements and molecular docking simulations were performed. The binding constant (K_b) between indinavir and ct-dsDNA was calculated to be 1.64 × 10⁸ M⁻¹, based on spectrofluorometric measurements. The obtained results can offer insights into the inhibitory activity of indinavir, which could help to broaden its applications. That is, indinavir can be used to inhibit other mechanisms and/or hallmarks of viral diseases.     

2006年至2008年上海市住院腹泻患儿A组轮状病毒的分子流行病学调查

目的 分析上海地区住院腹泻患儿A组轮状病毒(RV)基因型别、流行季节及年龄分布,以了解本地区A组RV的分子流行病学动态变化特征,为婴幼儿腹泻的预防和控制提供理论依据.方法 2006年1月至2008年12月共收集来自复旦大学附属儿科医院5岁以下腹泻患儿的5176份粪便标本.抽取其中RV抗原阳性标本380份,采用套式多重RT-PCR法进行RV的基因分型.结果 2006-2008年RV腹泻主要的流行季节是10-12月份,＜3岁的患儿占全部患儿的96.8％.380份粪标本中,222份为G3型,占58.4％,41份为G9型,占10.8％.3年间G1型、G2型均少见,G混合型以G3和G9型的混合为主.2006年和2008年均以P[8]型的流行为主,分别占64.6％(53/82)和46.8％(58/124).2007年以P[4]型为主,占38.5％(67/174).P[6]和P[9]型所占比例较低,P混合型以P[8]和P[4]型的混合为主.G未分型和P未分型在3年间均呈上升趋势.P[8]G3型(20.5％)是上海地区2006-2008年间最主要的A组RV流行株,其次包括P[4]G3型及P[m]G3型.结论 2006-2008年上海地区A组RV显示了新的分子流行病学变化特征,包括主要流行型别的改变,流行型别更趋于多样化.     

A home‐based progressive resistance exercise programme for patients with venous leg ulcers: a feasibility study

This study aimed to assess the feasibility of a home‐based exercise programme and examine the effects on the healing rates of venous leg ulcers. A 12‐week randomised controlled trial was conducted investigating the effects of an exercise intervention compared to a usual care group. Participants in both groups (n = 13) had active venous ulceration and were treated in a metropolitan hospital outpatients clinic in Australia. Data were collected on recruitment from medical records, clinical assessment and questionnaires. Follow‐up data on progress in healing and treatments were collected fortnightly for 12 weeks. Calf muscle pump function data were collected at baseline and 12 weeks from recruitment. Range of ankle motion data were collected at baseline, 6 and 12 weeks from recruitment. This pilot study indicated that the intervention was feasible. Clinical significance was observed in the intervention group with a 32% greater decrease in ulcer size (P = 0·34) than the usual care group, and a 10% (P = 0·74) improvement in the number of participants healed in the intervention group compared to the usual care group. Significant differences between groups over time were observed in calf muscle pump function parameters [ejection fraction (P = 0·05), residual volume fraction (P = 0·04)] and range of ankle motion (P = 0·01). This pilot study is one of the first to examine and measure clinical healing rates for participants involved in a home‐based progressive resistance exercise programme. Further research is warranted with a larger multi‐site study.     

北京市2019年腹泻病例中札如病毒基因特征分析

目的 了解北京市肠道门诊散发腹泻病例中札如病毒的基因型别及特征。方法 收集2019年北京市肠道门诊散发腹泻病例的粪便样本,应用实时荧光RT-PCR对样本进行札如病毒核酸检测,对阳性样本应用不同种RT-PCR方法进行札如病毒衣壳蛋白VP1区和聚合酶RdRp区部分基因片段扩增,对扩增阳性产物进行测序,应用BioEdit 7.0.9.0软件对序列进行比对,应用Mega 6.06软件构建进化树进行分析。结果 札如病毒总检出率为2.89%（44/1 522）,<5岁病例的检出率为3.34%（18/539）,≥5岁病例的检出率为2.64%（26/983）。衣壳蛋白VP1区基因测序成功23株,包括8个基因型（GⅠ.2型6株、GⅠ.1型和GⅡ.3型各5株,GⅠ.3型和GⅡ.5型各2株,GⅠ.5型、GⅡ.1型和GⅣ.1型各1株）;≥5岁病例占16株,GⅠ.2型构成比最高（37.50%,6/16）,<5岁病例占7株,GⅠ.1型和GⅡ.3型构成比最高（均为42.86%,3/7）;每个基因型内部相似性为95.5%~100.0%,与不同年份、不同国家的人源或污水源的51株参考株相似性为92.2%~100.0%。聚合酶RdRp区测序成功25株8个基因型（9株GⅡ.P3型,4株GⅠ.P3型,GⅠ.P1型、GⅠ.P2型和GⅡ.P1型各为3株,GⅠ.P5型、GⅡ.P5型和GⅣ.P1型各为1株）;≥5岁病例占15株,GⅡ.P3型构成比最高（40.00%,6/15）,<5岁病例占10株,GⅠ.P1型、GⅡ.P1型和GⅡ.P3型构成比最高（均为30.00%,3/10）;每个基因型内部相似性为94.0%~100.0%,与不同年份、不同国家的人源或污水源的39株参考株相似性为90.2%~99.1%。结论 札如病毒是北京市散发腹泻病例的病原之一,主要基因组为GⅠ和GⅡ,基因型多样且分散;≥5岁和<5岁人群腹泻病例主要基因型不同。     

痛泻要方联合匹维溴铵治疗腹泻型肠易激综合征临床研究

目的 观察痛泻要方联合匹维溴铵治疗腹泻型肠易激综合征的临床疗效。方法 收集280例腹泻型肠易激综合症患者,每组70人,分为4组：初治试验组、初治对照组、复治试验组、复治对照组。初治试验组和复治试验组给予痛泻要方和匹维溴铵,初治对照组和复治对照组给予匹维溴铵。4组疗程都为4周,观察治疗前后症状总积分和疗效。结果 治疗后4组症状总积分较治疗前均有显著降低（P<0.05）。复治对照组治疗前后症状总积分差值显著小于初治对照组和复治试验组（P<0.05）。初治组和复治组之间的临床疗效差异无统计学意义（P>0.05）,对照组和试验组之间的临床疗效差异有统计学意义（P<0.05）,复治试验组和复治对照组之间的临床疗效差异也有统计学意义（P<0.05）。结论 痛泻要方联合匹维溴铵可提高腹泻型肠易激综合征的疗效,在有过相关药物治疗史的复治患者中疗效尤为明显。     

Pathogens transmitted in animal feces in low- and middle-income countries

Animals found in close proximity to humans in low-and middle-income countries (LMICs) harbor many pathogens capable of infecting humans, transmissible via their feces. Contact with animal feces poses a currently unquantified—though likely substantial—risk to human health. In LMIC settings, human exposure to animal feces may explain some of the limited success of recent water, sanitation, and hygiene interventions that have focused on limiting exposure to human excreta, with less attention to containing animal feces.We conducted a review to identify pathogens that may substantially contribute to the global burden of disease in humans through their spread in animal feces in the domestic environment in LMICs. Of the 65 potentially pathogenic organisms considered, 15 were deemed relevant, based on burden of disease and potential for zoonotic transmission. Of these, five were considered of highest concern based on a substantial burden of disease for which transmission in animal feces is potentially important: Campylobacter, non-typhoidal Salmonella (NTS), Lassa virus, Cryptosporidium, and Toxoplasma gondii. Most of these have a wide range of animal hosts, except Lassa virus, which is spread through the feces of rats indigenous to sub-Saharan Africa. Combined, these five pathogens cause close to one million deaths annually. More than half of these deaths are attributed to invasive NTS. We do not estimate an overall burden of disease from improperly managed animal feces in LMICs, because it is unknown what proportion of illnesses caused by these pathogens can be attributed to contact with animal feces.Typical water quantity, water quality, and handwashing interventions promoted in public health and development address transmission routes for both human and animal feces; however, sanitation interventions typically focus on containing human waste, often neglecting the residual burden of disease from pathogens transmitted via animal feces. This review compiles evidence on which pathogens may contribute to the burden of disease through transmission in animal feces; these data will help prioritize intervention types and regions that could most benefit from interventions aimed at reducing human contact with animal feces.     

免疫抑制剂血药浓度与肾移植术后腹泻的关联性分析

目的 探讨免疫抑制剂霉酚酸酯（MMF）、他克莫司（FK506）血药浓度与肾移植术后腹泻之间的关系。方法 选取2015年8月至2017年8月在安徽医科大学第一附属医院行肾移植手术的146例受者,根据术后是否发生腹泻分为两组,未发生腹泻的患者为非腹泻组（83例）、发生腹泻且大于1次者为腹泻组（63例）,测定受者的霉酚酸谷浓度（MPA-C₀）和FK506谷浓度（FK506-C₀）,记录术后出现的腹泻情况,运用统计软件分析MPA-C₀和FK506-C₀与腹泻间的关系。结果 腹泻组与非腹泻组之间MPA-C₀差异无统计学意义（P>0.05）,FK506-C₀差异有统计学意（P<0.001）;ROC曲线分析显示,FK506-C₀仅在术后1个月差异有统计学意义（曲线下面积0.607,P<0.05）,FK506 C₀<11.15 ng/mL是术后1个月发生腹泻的截断值,敏感度51.90%,特异性63.60%;MPA-C₀与FK506-C₀对腹泻发生不存在交互作用（P>0.05）。结论 MPA-C₀与腹泻的发生没有关联性,而较高的FK506-C₀易导致肾移植术后腹泻,其中术后1个月FK506-C₀ <11.15 ng/mL是发生腹泻的的最佳截断值。     

布拉氏酵母菌对不同年龄阶段肺炎患儿抗生素相关性腹泻的预防效果

目的 探讨布拉氏酵母菌对不同年龄阶段急性支气管肺炎住院患儿发生抗生素相关性腹泻（AAD）的预防效果。方法 按入院时间将2014年3月-2017年3月326例急性支气管肺炎住院患儿分为对照组（n=155）与研究组（n=171）,两组均静脉应用抗生素治疗,同时仅研究组加服布拉氏酵母菌散,疗程5 d。比较两组腹泻发生情况及腹泻治疗效果。结果 研究组AAD的发生率为22.22%,明显低于对照组的34.19%,差异有统计学意义（P<0.05）;研究组≤ 2岁患儿的AAD发生率显著低于对照组,差异有统计学意义（P<0.05）,但两组>2岁患儿的AAD发生率比较差异无统计学意义。≤ 2岁患儿AAD发生率为38.17%,显著高于>2岁患儿（14.28%）,差异有统计学意义（P<0.05）。研究组2岁以下及2岁以上AAD患儿腹泻持续时间明显短于对照组,差异有统计学意义（P<0.05）,且研究组中2岁以上AAD患儿腹泻持续时间明显短于2岁以下。研究组2岁以下及2岁以上AAD患儿72 h好转率均明显高于对照组,差异有统计学意义（P<0.05）。与治疗前相比,两组2岁以下及2岁以上AAD患儿血清IgG水平明显升高,同组治疗前后比较差异有统计学意义（P<0.05）;治疗后,研究组2岁以下及2岁以上AAD患儿血清IgG水平明显高于对照组,差异有统计学意义（P<0.05）;且研究组2岁以上患儿IgG水平显著高于2岁以下患儿,差异有统计学意义（P<0.05）。结论 对于急性支气管肺炎患儿,在合理使用抗生素的同时补充布拉氏酵母菌对AAD有良好的预防效果,尤其是婴幼儿AAD表现出更好的预防效果,可提高患儿免疫能力,改善免疫系统功能,且无不良反应。     

纳洛酮联合小牛血清去蛋白治疗急性颅脑损伤的临床研究

目的探讨纳洛酮联合小牛血清去蛋白治疗急性颅脑损伤的临床效果。方法选取2015年8月—2017年8月重庆市开州区人民医院收治的急性颅脑损伤患者122例,随机分为对照组(61例)和治疗组(61例)。对照组静脉滴注小牛血清去蛋白注射液,30 m L加入5%葡萄糖注射液250 m L,1次/d。治疗组在对照组基础上静脉滴注盐酸纳洛酮注射液,0.3mg/(kg·d)。两组患者均连续治疗7 d。观察两组临床疗效,比较治疗前后两组格拉斯哥昏迷量(GCS)评分、血液流变学指标、及肿瘤坏死因子(TNF)-α、IL-6和神经元特异性烯醇化酶(NSE)水平。结果治疗后,对照组和治疗组临床总有效率分别为78.7%、93.4%,两组比较差异具有统计学意义(P0.05)。治疗后,两组GCS评分中运动、语言、睁眼及GCS总评分均显著升高(P0.05);且治疗组GCS评分明显高于对照组(P0.05)。治疗后,两组全血黏度(WBV)、血浆黏度(PV)和红细胞聚集指数(EAI)值均显著下降(P0.05);且治疗组比对照组降低的更显著(P0.05)。治疗后,两组血清TNF-α、IL-6、NSE水平均明显降低(P0.05);且治疗组比对照组降低的更明显,(P0.05)。结论纳洛酮联合小牛血清去蛋白治疗急性颅脑损伤可迅速缓解患者症状体征,减轻炎性损伤,改善神经功能,具有一定的临床推广应用价值。     

TTS联合药物治疗小儿腹泻的疗效观察和护理

目的比较经皮给药(trandermal therapeutic system,TTS)与药物联合治疗小儿腹泻的疗效。方法将160例患儿按性别、年龄随机分为对照组和观察组,两组患儿给予常规心理护理、抗生素、对症治疗。观察组在原有护理模式的基础上增加经皮给药疗法。结果观察组有效率、护理满意度高于对照组。结论经皮给药与药物联合治疗小儿腹泻病的疗效优于单纯药物治疗,护士为患儿提供个性化全程护理,是提高疗效、促进痊愈的基础。