基孔肯雅病毒的分子变异及其流行趋势

由基孔肯雅病毒（Chikungunya virus,CHIKV）引起的基孔肯雅热已从仅在非洲南部、东南亚和印度部分热带地区流行的蚊媒传染病传播至亚热带地区的多个国家。既往CHIKV的传播主要以埃及伊蚊作为传播媒介,2004年基孔肯雅热疫情在南亚地区的暴发流行中,出现了能够以地区分布更为广泛的白纹伊蚊为媒介传播病毒进化株,这也成为是基孔肯雅热流行区域不断扩大的重要原因。研究表明CHIKV主要是通过其基因组中编码的包膜糖蛋白（envelope glycoproteins）的多次突变以不断增强其对白纹伊蚊的适应性。对CHIKV进化规律和基因突变特征的研究不仅可以为研究病毒对蚊媒适应性的分子机制提供线索,还可以对可能的基孔肯雅热暴发流行提供预警。     

基孔肯雅病毒,不容小觑——肆虐美洲的“登革病毒”

2014年,一种类似于登革热的传染病——基孔肯雅热席卷了中南美洲,其病原体为基孔肯雅病毒,隶属于披膜病毒科甲病毒属的单股正链RNA病毒,传播媒介主要是伊蚊属,尤其是白纹伊蚊和埃及伊蚊。基孔肯雅热的临床症状与登革热十分相似,临床上需要鉴别诊断。2010年该疾病在我国广东曾小规模流行,其对人民健康造成的危害以及所带来的经济负担不亚于登革热,应高度重视,遏制其蔓延。     

云南基孔肯雅热研究概况

基孔肯雅热（Chikungunyafever,CHIK）是由基孔肯雅病毒（Chikungunyavirus,CHIKV）引起的一种急性自然疫源性传染病,经伊蚊叮咬而传播。由于CHIK的分布与其传播媒介伊蚊的分布密切相关,因此云南具有引起本病流行的条件,是CHIK主要流行省份之一。本文拟对云南CHIK研究的历史和现状做一综述。     

云南白纹伊蚊经卵传递基孔肯雅病毒的研究

用基孔肯雅病毒经口感染雌性白纹伊蚊，对其子１代，分６５批（３３５８只）用组织培养和小白鼠方法分离基孔肯雅病毒，幼虫、雌性和雄性成虫的批阳性率依次为２７．５％（８／２９）、２５．００％（６／２４）和１６．１９％（２／１２）。同时从子２、３代幼虫和成虫中亦查出病毒。此结果表明该蚊具有将基孔肯雅病毒经卵传递给后代的能力，云南白纹伊蚊在基扎肯雅病毒保存和传播中起重要作用。     

淄博市首例输入性基孔肯雅热流行病学调查及防控策略研究

目的了解基孔肯雅热的流行病学特征,探索行之有效的防控策略,为今后防控工作提供依据。方法通过对病例进行流行病学个案调查和实验室检测的方法,结合基孔肯雅热非洲疫情流行情况,提出防控策略。结果个案调查得知该病例的主要临床表现和流行病学史符合基孔肯雅热发病特点,实验室检测结果为基孔肯雅热病毒核酸阳性。结论基孔肯雅热在我国仍存在局部暴发流行的可能性,根据该病流行病学特征,加强入境旅客的检验检疫工作,做好口岸蚊虫媒介的监测和控制,普及防蚊灭蚊健康教育,提高医疗机构临床诊断能力,大力开展爱国卫生运动,是切断传播途径的有效防控策略。     

云南省腾冲市首例输入性基孔肯雅热病例的调查处置

目的 分析腾冲市1例基孔肯雅热病例的发现、诊断、个案调查和处置情况,为基孔肯雅病热的防控提供依据。方法 对腾冲市人民医院报告的1例疑似基孔肯雅热病例采集患者血液,用Real-time PCR法进行基孔肯雅病毒核酸检测;开展流行病学、临床表现及诊疗过程、媒介伊蚊调查;采取环境整治、灭蚊、防蚊隔离治疗,追踪同行人员、密切接触者及家庭周围人群控制疫情。结果 患者2019年7月31日出现发热、头疼、关节疼痛,8月1日出现皮疹,基孔肯雅热病毒核酸检测阳性,发病前有缅甸探亲史,确认为缅甸输入性病例,经对症支持治疗痊愈;同行人员、密切接触者及家庭周围人群未发现疑似症状者;滇滩岳家寨、猴桥及滇滩口岸均捕获白纹伊蚊,未发现埃及伊蚊,布雷图指数（BI）分别为4.00、9.80、3.85;灭蚊喷洒90余户,面积2.3万m²,处置后,布雷图指数（BI）控制在5以下。结论 病例为腾冲市首例输入性基孔肯雅热,调查处置及时有效,未发生继发病例。     

基孔肯雅热的流行现况及其防治对策

基孔肯雅热(Chikungunya fever,CHIK)是由基孔肯雅病毒(Chikungunya virus,CHIKV)引起的一种急性传染病。本文针对基孔肯雅热的病原学、流行现况、诊断方法、防治对策等方面做一综述。     

阳江市一起基孔肯雅热暴发疫情流行病学调查

目的了解基孔肯雅热的流行特征,探索有效的防控策略,为今后防控工作提供依据。方法根据病例定义进行病例搜索,对符合病例定义的病例进行流行病学调查;采用酶联免疫吸附试验方法检测登革热病毒IgM和IgG抗体;采用实时荧光定量逆转录聚合酶链反应方法检测登革热病毒核酸和基孔肯雅热病毒核酸。结果 2010年9月12日至10月21日,阳江市某建筑工地发生基孔肯雅热病27例,总罹患率为11.07%(27/244);其中男性17例,占62.96%,女性10例,占37.04%;检测15份恢复期病例血样登革热病毒IgM和IgG抗体,其中2份病例血样IgM抗体阳性,其余13份为阴性,15份病例血样IgG抗体均为阴性;检测5份现症病例血样,登革热病毒核酸均为阴性,2份基孔肯雅热病毒核酸阳性。结论这是一起基孔肯雅热暴发疫情,加强出入境检疫、开展医疗机构症状监测和控制传播疾病的媒介密度是预防控制孔肯雅热的重要措施。     

基孔肯雅热传播媒介监测与分析

目的监测与分析基孔肯雅热的传播媒介伊蚊的孳生情况,为我万江区制定基孔肯雅热的防控措施提供科学依据。方法使用布雷图指数和诱蚊诱卵指数。结果消除蚊虫孳生地,才能有效地降低伊蚊的密度,减少伊蚊传播基孔肯雅热的可能性。     

广州市一起输入性基孔肯雅热病例的调查分析

目的对广州市一起疑似输入性基孔肯雅热疫情进行调查和分析,为证实该病例为输入性基孔肯雅热提供科学依据。方法结合流行病学调查分析、临床症状和实验室检测结果进行分析。结果该病例由疫源地搭飞机来广州,在疫源地曾经被蚊虫叮咬,入境时有发热、关节痛等症状,采集静脉血经实验室检测为基孔肯雅病毒阳性。结论此次疫情为一起输入性基孔肯雅热疫情。当地政府加强对疫点的消杀、风险评估,同时充分发挥与海关的联防联控机制,加强入境筛查、信息通报、病例转运,以及对前往疫区的人员进行健康教育。     

不同年龄组基孔肯雅热患者的临床表现比较

目的 分析不同年龄组基孔肯雅热患者的临床表现.方法 130例基孔肯雅热患者,按年龄分为三组:＜30岁、30～岁、≥60岁组,分析其临床症状的差异.结果 三组患者均出现发热,皮疹的发生率分别为86.8%、91.4%、90.9%,关节痛的比例分别为86.8%、91.4%、95.5%,关节痛持续时间超过14d的比例分别为2.6%、30.0%、36.4%;与＜30岁组比较,30～岁和≥60岁组患者出现关节痛持续时间超过14 d以及累及3个或以上关节的比例高,差异均有统计学意义(x2= 13.026,P=0.001;x2＝6.792,P=0.034).结论 基孔肯雅热主要表现为发热、皮疹、关节痛,中、老年组患者出现关节疼痛持续时间较长,累及的关节多.     

基孔肯雅病毒云南株的动物敏感性研究

目的：了解ＣＨＩＫ病毒云南株对不同动物的致病性。方法：选择８种动物经三种途径接种病毒悬液，观察发病情况，检测病毒血症，脏器带毒情况及病理变化。结果：ＣＨＩＫ病毒云南株可使乳小白鼠、乳豚鼠、雏鸡、树鼠句等发病或死亡，除大白鼠外都查到病毒血症，多数动物的主要脏器检测到病毒，并有不同程度的病理改变。结论：树鼠句可作为研究ＣＨＩＫ病毒致病机理、免疫反应等的动物模型；本病在自然界中以隐性感染为主     

深圳市首例基孔肯雅病毒的形态学及分子遗传特征分析

目的 对深圳市首发基孔肯雅病毒(CHIKV)进行分离、增殖培养、浓缩、形态学观察及构建系统发生树分析,为后续基因组信息解析、蛋白组分析、单克隆抗体制备及疫苗研发等应用性研究提供实验基础.方法 利用C6/36细胞从病人血清中分离CHIKV,采用BHK-21细胞对CHIKV进行大量的增殖培养,经7％PEG8000浓缩,超薄切片和负染观察CHIKV显微结构;对分离得到的CHIKV株进行全基因组测序和构建系统发生树,结合流行病学资料对其分子遗传特征进行分析.结果 CHIKV被成功分离并浓缩;在透射电镜下观察CHIKV的直径约为70 nm,圆形有包膜,表面有纤突;CHIKV(SZ-20101028)基因组长为12 377bp,属于E1-A226突变株;该病毒是最近10年来在印度洋岛屿爆发流行的新亚型,与流行病学调查资料相吻合.结论 以现有的条件建立了一种稳定、快速培养浓缩CHIKV的方法,并初步对CHIKV进行了形态观察和溯源性分析.     

Structural Basis for Complementary and Alternative Medicine: Phytochemical Interaction with Non-Structural Protein 2 Protease—A Reverse Engineering Strategy

Objective: To understand the druggability of the bioactive compounds from traditional herbal formulations "Nilavembu Kudineer" and "Swasthya Raksha Amruta Peya" to heal chikungunya virus (CHIKV) infection. Methods: The efficiency of twenty novel chemical entities from "Nilavembu Kudineer" and "Swasthya Raksha Amruta Peya" to inhibit CHIKV infection in silico were evaluated. Ligands were prepared using Ligprep module of Schr?dinger. Active site was identified using SiteMap program. Grid box was generated using receptor grid generation wizard. Molecular docking was carried out using Grid Based Ligand Docking with Energetics (GLIDE) program. Results: Molecular docking studies showed that among twenty compounds, andrographoside, deoxyandrographoside, neoandrographolide, 14-deoxy-11-oxoandrographolide, butoxone and oleanolic acid showed GLIDE extra precision (XP) score of –9.10, –8.72, –8.25, –7.38, –7.28 and –7.01, respectively which were greater than or comparable with chloroquine (reference compound) XP score (–7.08) and were found to interact with the key residues GLU 1043, LYS 1045, GLY 1176, LEU 1203, HIS 1222 and LYS 1239 which were characteristic functional unit crucial for replication of CHIKV. Conclusion: The binding affinity and the binding mode of chemical entities taken from herbal formulations with non-structural protein 2 protease were understood and our study provided a novel strategy in the development and design of drugs for CHIKV infection.     

Value of D-Dimers in patients with acute aortic dissection

Objective: To evaluatel the value of D-dimers in patients with acute aortic dissection (AAD). Methods: This study consisted of 16 patients with AAD and 27 non-AAD patients. Serum D-dimets were measured by Sta-Liatest D-DI immunoturbidimetric assay. Results: D-dimer level was higher (P ＜ 0.001) in patients with AAD(7.91 ± 5.52 μg/ml) than that in non- AAD group(1.57±1.24 μg/ml). D-dimer was positive (＞0.4 μg/ml) in all patients with AAD and in 10 control group patients (37%). Among patients with acute AAD, D-dimers tended to be higher in Stanford A than in Stanford B (8.67 ± 4.31 μg/ml vs. 3.24±1.27 μg/ml, P ＜0.01). D-dimer values tended to be higher in more extended disease(3.84 ± 1.65 μg/ml, 8.57 ± 3.58 μg/ml and 11.87 ± 5.69 μg/ml in thoracic aorta, thoracic and abdominal aorta, thoracic and abdominal aorta and iliacal arteries, respectively, P ＜ 0.05 for both 8.57 ± 3.58 and 11.87 ± 5.69 vs. 3.84 ± 1.65 ). Including the control group into the analysis, we found a sensitivity of 100%, a negative predictive value of 100%, and a specificity of 66% and a positive predictive value of 64% for D-dimer in diagnosis of AAD in our patients with suspected AAD. Conclusion: D-dimer was elevated in patients with AAD. A negative D-dimer test result could be useful in excluding AAD.     

Research of combined liver-kidney transplantation model in rats

Objective： To set up a simple and reliable rat model of combined liver-kidney transplantation. Methods： SD rats served as both donors and recipients. 4℃ sodium lactate Ringer＇s was infused from portal veins to donated livers,and from abdominal aorta to donated kidneys, respectively. Anastomosis of the portal vein and the inferior vena cava （IVC） inferior to the right kidney between the graft and the recipient was performed by a double cuff method, then the superior hepatic vena cava with suture. A patch of donated renal artery was anastomosed to the recipient abdominal aorta. The urethra and bile duct were reconstructed with a simple inside bracket. Results： Among 65 cases of combined liver-kidney transplantation, the success rate in the late 40 cases was 77.5%. The function of the grafted liver and kidney remained normal. Conclusion： This rat model of combined liver-kidney transplantation can be established in common laboratory conditions with high success rate and meet the needs of renal transplantation experiment.     

BLOOD PRESSURE CHANGE WITH AGE IN SALT-SENSITIVE TEENAGERS

Objective To observe blood pressure change with age in salt-sensitive teenagers whose salt sensitivity were determined by repeated testing.Methods Salt sensitivity was determined through intravenous infusion of normal saline combined with volume-depletion by oral diuretic furosemide in 55 teenagers. After five years, salt sensitivity was re-examined and subject blood pressure was followed up. Blood pressure changes in salt-sensitive teenagers were compared to that of non-salt sensitive teenagers over five years.Results After 5 years, the repetition rate of salt sensitivity determined by intravenous saline loading is 92.7%. In teenagers with salt sensitivity on the baseline, both the systolic blood pressure increments and increment rates were much higher than non-salt sensitive teenagers (12.7±12.1 mmHg vs. 2.8±5.2 mmHg, P＜ 0.01; 12.2%± 12.0% vs. 2.5% ±4.4%, P＜ 0.001,respectively). There was a similar trend for diastolic blood pressure (8.4 ± 6.4 mmHg vs. 3.7 ± 6.4 mmHg, P = 0.052; 13.2% ±10.6 % vs. 6.8%± 10.1%, P = 0.053, respectively).Conclusions Salt sensitivity determined by intravenous saline loading showed good reproducibility. Blood pressure increments with age were much higher in salt-sensitive teenagers than non-salt sensitive teenagers, especially in terms of systolic blood pressure.     

安心颗粒对急诊经皮冠状动脉介入术后生活质量影响的研究

目的：评价使用安心颗粒对急诊经皮冠状动脉介入术（PPCI）术后生活质量的影响.方法：将160例接受PPCI的急性ST段抬高型心肌梗死患者随机分为安心颗粒组（术前顿服安心颗粒8.8g,术后安心颗粒4.4 g/次,每日2次）和对照组（仅接受基础药物治疗）.所有患者均服用阿司匹林、氯吡格雷和阿托伐他汀.分别在入院时、出院前1d、出院后180 d时,应用心肌梗死多维度量表（MIDAS）、中文版SF-36评价量表对患者生活质量评分.并观察术后30 d以内的出血并发症、血小板减少症发生情况.结果：入院时和出院前1d,两组患者的心肌梗死MIDAS、SF-36量表评分比较无差异（P＞0.05）;出院后180 d时,与对照组比较,安心颗粒组MIDAS、SF-36评分明显减低（P＜0.05）;组内与入院时比较,两组出院前1d、出院后180 d时,MIDAS、SF-36评分均降低（P＜0.05）.两组患者在随访期间均无大量出血、少量出血、重度和极重度血小板减少症发生,安心颗粒组有4例、对照组有7例发生不明显出血（P＞0.05）.两组发生轻度血小板减少症的患者数比较无差异（P＞0.05）.结论：PPCI使用安心颗粒,能改善急性ST段抬高型心肌梗死患者的生活质量,且不增加出血风险.     

The comparative studies of the influences of Urapidil and Nicardipine on sino-atrial node function, atrio-ventricular node function and hemodynamics

Objective:To investigate the influences of urapidil and nicardipine on rabbit sinus function,atrio-ventricular node function and hemodynamics.Methods:Thirty-two Angora's rabbits were selected and randomly divided into four groups.U1 group:urapidil 0.25 mg/kg;U2 group:urapidil 0.5 mg/kg;N1 group:nicardipine 10 μg/kg;N2 group:nicardipine 20 μg/kg.All these medicine were administrated within 30 seconds.Measurements were taken before and after the administration of urapidil or nicardipine for the following data:mean blood pressure(MAP),heart rate(HR),sino-atrial conduction time(SACT),maximal sinoatrial recovery time(SNRTmax)corrected sinus node recovery time(CSNRT),index of sinus node recovery time(SNRTI),Wenckebach A-V conduction frequency (WB),and P-R interval.Results:Significant MAP and HR changes were identified in all of the four groups before and after administration of both urapidil and nicardipine.No significant changes could be found in the rest of the parameters.Intergroup analysis showed that SACT and CSNRT of N1 and N2 groups were shorter than those of the U2 group(P＜0.01);the MAP decreased(P＜0.01)and the HR increased drastically(P＜0.01).Conclusions:Neither urapidil(0.25 mg/kg,0.5 mg/kg)nor nicardipine(10μg/kg,20μg/kg)has any significant influence on rabbit sinus function or rabbit atrio-ventricular node function.Nicardipine could be a better choice than urapidil for parafunctional sinus node patients.