The genetic load for hereditary hearing impairment in Chinese population and its clinical implication

Objective To understand the genetic load in the Chinese population for improvement in diagnosis, prevention and rehabilitation of deafness. Methods DNA samples, immortalized cell lines as well as detailed clinical and audiometric data were collected through a national genetic resources collecting network. Two conventional genetic approaches were used in the studies. Linkage analysis in X chromosome and autosomes with microsatellite markers were performed in large families for gene mapping and positional cloning of novel genes. Candidate gene approach was used for screening the mtDNA 12SrRNA, GJB2 and SLC26A4 mutations in population-based samples. Results A total of 2,572 Chinese hearing loss families or sporadic cases were characterized in the reported studies, including seven X-linked, one Y-linked, 28 large and multiplex autosomal dominant heating loss families, 607 simplex autosomal recessive hereditary hearing loss families, 100 mitochondrial inheritance families, 147 GJB2 induced heating loss cases, 230 cases with enlarged vestibular aqueduct(EVA) syndrome, 169 sporadic cases with auditory neuropathy, and 1,283 sporadic sensorineural hearing loss cases. Through linkage analysis or sequence analysis, two X-linked families were found transmitting two novel mutations in the POU3F4 gene, while another X-linked family was mapped onto a novel locus, nominated as A UNX1 (auditory neuropathy, X-linked locus 1). The only Y-linked family was mapped onto the DFNY1 locus(Y-linked locus 1, DFNY1). Eight of the 28 autosomal dominant families were linked to various autosomal loci. In population genetics studies, 2,567 familial cases and sporadic patients were subjected to mutation screening for three common hearing loss genes: mtDNA 12S rRNA 1555G, GJB2 and SLC26A4. The auditory neuropathy cases in our samples were screened for OTOF gene mutations. Conclusions These data show that the Chinese population has a genetic load on hereditary heating loss. Establishing personalized surveillance and prevention models for hearing loss based on genetic research will provide the opportunity to decrease the prevalence of deafness in the Chinese population.     

黄芩苷和牛血清白蛋白双缓释制剂的制备及释药性能检测

目的:将黄芩苷和牛血清白蛋白(bovine serum albumin,BSA)载入壳聚糖温敏凝胶,构建双缓释体系,检测凝胶对药物的体外释放情况。方法:采用乳化缩聚法制备黄芩苷-明胶微球(gelatin microspheres,GMS);用不同配比的壳聚糖溶液和β-甘油磷酸钠(β-glycerophosphate,β-GP)溶液制备壳聚糖温敏凝胶,观察在37℃的成胶情况,选择最佳配比;在此基础上,将不同浓度的黄芩苷-GMS与BSA共混于壳聚糖凝胶溶液,测定载药后的成胶情况及黄芩苷和BSA的体外释放情况。结果:成功制备了黄芩苷-GMS,载药率5.62%,包封率72.05%;1.8%壳聚糖溶液与9%的β-GP混合10min后可获得状态良好的凝胶;加载两种药物后的凝胶溶液相转变时间未发生改变;30d时低浓度组累积释放了63.79%,两个较高浓度组分别释放了74.86%、77.63%。结论:壳聚糖温敏凝胶可以同时负载黄芩苷-GMS和BSA两种药物,在室温下呈溶液状态,37℃下经过10min可转变成半固体凝胶,在体外释药可达30d。黄芩苷和牛血清白蛋白双缓释制剂的制备和释药性能检测为牙周组织修复再生药物的研制提供了基础。     

血清游离睾酮浓度与男性年龄的相关性研究

目的：检测不同年龄组男性血清游离睾酮水平,研究血清游离睾酮与男性年龄的相关性。方法：按不同年龄段受试者分为5个组,采用ELISA法对血清游离睾酮水平进行检测。用方差分析和相关性检验对结果进行统计学分析。结果：不同年龄组（〉60岁、50-岁、40-岁、30-岁及〈30岁组）受试者血清游离睾酮水平分别为：16．23＋10．45ng／L、18．82＋10．54ng／L、23．55＋13．25ng／L、22．27＋11．07ng／L及24．39＋13．43ng／L。统计学分析结果表明,〈30岁、30-岁及40-岁组与〉60岁、50-岁组相比有明显差异（P〈0．05）。血清游离睾酮的浓度与男性年龄成显著负相关（P〈0．05）。结论：本研究证实在50岁后,随年龄增长男性体内血清游离睾酮表达水平呈下降趋势,这在病理和生理上对临床工作都具有指导意义。     

川崎病与支原体感染的相关性研究

目的研究川崎病(Kawasaki disease,KD)与支原体感染(Mycoplasma pneumomiae,MP)的相关性。方法回顾性分析2012年3月~2014年2月于我院被确诊为KD的84例患儿的病历资料,其中按照患者是否有支原体感染分为观察组和对照组。观察组KD患者为有支原体感染(43例),对照组KD患者无MP感染(41例)。对两组患者分别进行血白细胞计数(WBC)、超敏C反应蛋白(CRP)、红细胞沉降率(ESR)、血红蛋白(HB)以及血小板计数(PLT)的检测和分析。对两组患者是否存在冠脉损伤进行分析比较。结果观察组无冠脉损伤者占34.9%(15/43),明显低于对照组的58.5%(24/41),观察组冠脉损伤者占比65.1%(28/43),显著高于对照组的41.5%(17/41),差异均有统计学意义(P<0.05);观察组的CRP指标水平为(68.9±14.7)mg/L,明显高于对照组的(52.8±8.2)mg/L,观察组的ESR指标水平为(42.6±15.9)mm/h,显著高于对照组的(21.6±6.1)mm/h,差异均有统计学意义(P<0.05)。结论MP感染为KD的病因之一,MP感染与患者冠脉损伤呈正相关,MP感染引起的免疫介导损伤和炎症反应是发生KD的重要途径。     

Guidelines for tuberculosis prophylaxis during anti‐tumour necrosis factor‐α treatment: Indian Rheumatology Association

India is home to a large patient population of both rheumatoid arthritis (RA) and tuberculosis (TB). As the usage of biologic agents in RA increases in India, the issue of TB reactivation and prophylaxis becomes very pertinent. The consensus view of an expert group from the Indian Rheumatology Association is presented. Tuberculin testing has limited utility in India and isoniazid prophylaxis seems to be a reasonable option. It is hoped that this report shall pave the way for formal guidelines.     

高静水压对内皮细胞一氧化氮合酶抑制物的影响及卡托普利的干预作用

目的 :观察高静水压培养的人脐静脉内皮细胞 (HUVECs)内源性一氧化氮 (NO)合酶抑制物———不对称二甲精氨酸 (ADMA)的影响及卡托普利的保护作用。方法 :采用改良的Jaffe法培养原代HUVECs,取生长良好的3～ 6代HUVECs用于实验 ,分为①大气压组 :加等量DMEM培养液 ;②高静水压组 ;③高压加卡托普利组。测定上清液中ADMA、左旋精氨酸 (L arg)、NO和内皮素 (ET)的浓度 ,并测定血管紧张素转化酶 (ACE)的活性。结果 :高静水压组ADMA、ET的量、细胞内钙 [Ca2 + ]i及ACE活性增加 ,而NO的量减少。卡托普利干预后 ,上清液中ADMA、ET的浓度减少 ,ACE活性降低 ,NO的量增加 ,而L arg水平无明显变化。结论 :高静水压通过增加ADMA导致内皮功能紊乱 ,卡托普利则能通过减少ADMA减轻高压导致的内皮细胞代谢功能障碍     

多层螺旋CT血管造影显示颞浅动脉

目的 探讨头颅MSCT血管造影(MSCTA)对颞浅动脉(STA)的显示能力及临床应用价值。方法 对88例头颅MSCTA原始图像数据分别进行遮盖容积重建(SVR)、MIP及CPR,观察STA是否有明显分支,记录血管杈的位置,测量STA主干、额支及顶支的管径,并评价3种重建图像的质量。结果 88例中,80例左侧STA(LSTA)及77例右侧STA(RSTA)可见明显额支及顶支,血管杈均位于颧弓上或颧弓水平;8例LSTA及11例RSTA未见明显额支或顶支。LSTA主干、额支及顶支直径分别为(2.26±0.39)mm、(1.71±0.25)mm及(1.74±0.26)mm;RSTA主干、额支及顶支直径分别为(2.32±0.46)mm、(1.81±0.25)mm及(1.81±0.19)mm。SVR与MIP图像质量评分差异无统计学意义(Z=-2.11,P>0.05),且均高于CPR(Z=-7.94、-7.48,P均<0.01)。2名诊断医师对SVR及MIP图像质量评分的一致性均较好(Kappa=0.92、0.85),对CPR图像质量评分的一致性一般(Kappa=0.51)。结论 头颅MSCTA可清晰、准确地显示STA的解剖结构。     

人野生型P53与反义mdm2基因融合体真核表达载体的构建及其在Mc3细胞中的表达

目的构建P^53与反义mdm2 cDNA序列真核表达载体，并探讨其在人黏液表皮样癌高转移细胞株Mc3细胞中的表达。方法应用分子克隆技术，将mdm2 cDNA序列反向插入到含有P^53基因序列pDOR—Neo中的P^53。基因序列下游，构成含有P^53基因与反义mdm2基因融合基因的逆转录病毒表达载体。经酶切分析鉴定后命名为pDOR—Neo—P^53-F mdm2并将重组载体通过脂质体转染Mc3细胞，通过G418筛选转染阳性细胞，并采用Westernblot方法检测P^53蛋白表达。结果酶切鉴定证实重组载体含有P^53与反义mdm2 cDNA片段，实验结果表明：转染后P^53蛋白（1．35&#177;0．14）较对照组P^53蛋白（6．26&#177;0．11）含量显著减低（P〈0．01），转染空载体P^53蛋白（6．24土0．12）与对照组比较无统计学差异（P〉0．05）。结论P^53与反义mdm2基因融合体真核表达载体构建成功，并表达野生型P^53蛋白和封闭mdm2基因，为今后进一步研究打下了基础。