Testing for familial aggregation of functional traits

In a genetic epidemiology study of a trait, prior to collecting genotype data the foremost task is to test for familial aggregation and examine heritability. Recently, functional traits have drawn attentions from investigators. Here, to test for familial aggregation of a functional trait in the family studies, a test constructed based on the leading functional principal component of heritability, which is a summary measure of temporal genetic variation in a functional trait, is proposed. The p‐value of the test can be approximated by a permutation procedure given the family structure. The asymptotic distribution of the test statistic is derived. Simulations are carried out to examine the size and the power of the test. The proposed methods are applied to the total cholesterol data in the Framingham Heart Study. Copyright © 2009 John Wiley & Sons, Ltd.     

抑癌基因PTEN在胃癌中的表达及临床意义

目的探讨胃癌组织中PTEN基因表达与胃癌临床病理的关系及其对预后的判断价值。方法应用免疫组化SP技术和图像分析技术,研究PTEN在胃癌和正常胃黏膜组织中的表达情况及阳性表达面积、强阳性表达面积,分析与病理参数的关系,并采用Kaplan-Meier生存曲线分析不同表达水平对术后生存率的影响。结果发现胃癌组织PTEN表达阳性率、阳性面积、强阳性面积均明显低于正常胃黏膜组织（P〈0.01）。胃癌组织PTEN表达与胃癌组织分化程度、浸润深度、淋巴转移、肿瘤分期明显相关,术后3、5 a生存率低表达者明显低于高表达者（P均〈0.05）。结论PTEN基因表达低下或丢失与胃癌发生、浸润、转移有关,可作为预测术后生存率的指标。     

Peritoneal dialysis patient survival: a comparison between a Swedish and a Korean centre.

BACKGROUND: Dialysis patient mortality remains high, and this high mortality may be due to many factors. In peritoneal dialysis (PD) patients, old age, co-morbid diseases, malnutrition, low residual renal function (RRF) and a high peritoneal transport rate have been shown to influence survival, but the relative importance of these factors may differ between different patient populations. Besides, centre practice patterns may differ between centres and may influence patient survival. In addition, the literature suggests that dialysis patient survival may be better in Asian than in Caucasian patients. METHODS: The influence of centre and patient characteristics on patient survival was investigated in 132 Korean and 106 Swedish incident PD patients, who underwent initial biochemical measurements and assessment of adequacy of dialysis, nutritional status, RRF and peritoneal transport characteristics. RESULTS: At the start of PD, Korean patients had a higher prevalence of diabetes, peritoneal Kt/V(urea), peritoneal creatinine clearance and peritoneal fluid removal, and lower body mass index, RRF and dialysate to plasma creatinine concentration ratio (D/P Cr) compared with Swedish patients. Significantly more patients from Korea were placed on temporary haemodialysis before PD (100 out of 132) when compared with Swedish patients (21 out of 106). During the follow-up, there was a significantly higher rate of transfer to other units in Korea and a significantly higher rate of kidney transplantation in Sweden. On Kaplan-Meier analysis, overall patient survival did not differ and relative risk for death was also not different between the two centres even after adjustment for age, diabetes, cardiovascular disease, RRF and D/P Cr. On Cox proportional hazards multivariate analysis, age, diabetes, RRF and D/P Cr were found to be independent predictors of mortality in the combined cohort of patients. While age, diabetes and D/P Cr were independent predictors of mortality in Korean patients, age and RRF independently predicted mortality in Swedish patients. CONCLUSION: Although there were significant differences in centre and patient characteristics, we were unable to confirm a survival advantage for Korean over Swedish PD patients. The results of this study suggest that the reported difference in survival between Asian and Caucasian dialysis patients may have been due, in part, to differences in centre and patient characteristics rather than to race as such. The genetic influence on patient characteristics remains, however, to be elucidated.     

不同采血针对新生儿足跟采血成功率的影响

目的：探讨不同采血针在新生儿疾病筛查采血中的采血效果。方法：采用三种采血针分别对2126例（A组）、1786例（B组）、1471例（C组）新生儿进行足跟采血，比较其采血成功率。结果：A、B、C三组之间差异有统计学意义（P〈0．01）。结论：采用7号一次性注射针头采血（C组）可明显提高采血成功率。     

不同疗法对肌筋膜疼痛病人的自主神经功能的影响

目的：本研究的目的是观察注射疗法及复合小针刀疗法治疗肌筋膜疼痛综合征对自主神经系统功能的影响。方法：选择40例诊断明确的肌筋膜疼痛病人，随机分为两组，每组20例。Ⅰ组：采用注射疗法治疗；IS组：采用注射疗法加小针刀治疗。观察两组病人治疗前后心率变异（HRV）的频域变化，低频LF、超低频LLF、高频HF、低高频比LF／HF及心率变异指数HR-Ⅵ；用视觉模拟评分法（VAS）评定治疗前后疗效并随访观察其远期疗效。结果：①HRV频域指标组内比较：LF、LLF、HF以及HRVI治疗前舆治疗后1min比较有显着性差异（P〈0．05），与5min、10min比较有非常显着性差异（P〈0．01）。LF／HF治疗前与治疗后5min、10min比较有显着性差异（P〈0．05）。组间治疗后1、5、10min，两两比较无显着性差异。②组间比较：病人治疗后临床症状、VAS评分均较治疗前降低．治疗前后IS组有非常显着性差异（P〈0．01）。两组VAS降低率有非常显着性差异（P〈0．01）。③回访病例中，两组治疗有效率比较有显着性差异（P〈0．05）。结论：注射疗法以及复合小针刀疗法均可有效改善肌筋膜疼痛病人的自主神经功能，其机制可能是通过调节、稳定自主神经系统功能达到缓解疼痛。注射疗法复合小针刀疗法的远期疗效优于单纯注射疗法。     

Atrial premature complexes and heart rate have prognostic significance in 1-month atrial fibrillation recurrence after electrical cardioversion.

AIMS: The aim of this study was to investigate the significance of simple 24-h Holter (24H) data after electrical cardioversion (CV) for atrial fibrillation (AF) recurrence. METHODS: We prospectively studied 47 consecutive patients subjected to CV, who successfully converted to sinus rhythm. All underwent echocardiography and 24H after CV. AF recurrence was studied at 14 days and 1 month by second 24H or by interim report of AF. RESULTS: About 53.2% remained in sinus rhythm (group I) and the rest recurred to AF (group II). Group I had fewer atrial premature complexes per hour (APC/h) (P = 0.002) and lower maximum (max HR), average, and minimum heart rates compared with group II (all Ps < 0.05). The optimal value of APC/h and max HR with best sensitivity and specificity was 32 APC/h and 90 bpm, respectively. These findings were the predictors of AF recurrence [hazard ratio (HR) = 4.5 with 95% CI = 1.7-11.7 and HR = 4.3 with 95% CI = 1.7-10.9, respectively]. Patients with the combination of both predictors had greater HR of AF recurrence compared with those with < 32 APC/h and max HR < 90 bpm (HR = 8.8 with 95% CI = 2.5-31.4). CONCLUSION: Patients with frequent APC/h and high max HR are at high risk for 1-month AF recurrence after electrical CV.     

岳阳市1993～2002年性病流行病学分析

目的 了解岳阳市10年来性病的发病趋势和流行特点，为政府部门制定性病防治策略提供科学依据。方法 用性病疫情软件汇总分析全市性病疫情报告的年度报表。结果 岳阳市10年共报告8种性病6492例，其中：淋病2851例，非淋菌性病尿道炎888例，尖锐湿疣2425例，梅毒192例，生殖器疱疹117例，软下疳7例，性病性淋巴肉芽肿3例，HIV感染9例。年平均发病率为12．71／10万，年平均增长率为1，34％。同时，数据显示传染来源中非婚性接触4909例，占总例数的75，62％，性乱人群是性病传播的主要方式。结论 岳阳市性病仍属于低发地区，目前正处于逐步扩散期。尖锐湿疣、梅毒上升幅度较大，应加强防治力度，控制疾病的流行。     

下肢动脉硬化闭塞症的外科治疗

目的:探讨外科治疗下肢动脉硬化闭塞症的临床经验。方法:从1995年7月～2002年7月共对292例(313条肢体)动脉硬化闭塞症病人进行外科治疗,其中20条患肢施行解剖外血管重建术,38条患肢施行了腔内外科治疗或合并开放性血管重建手术,255条患肢施行了开放性手术重建下肢血供。结果:手术成功者患肢的踝肱指数与术前比较显著增加(P<0.01),症状得到明显改善。平均随访时间3.1年(0.5～7年),解剖外重建组移植血管一期通畅率为56%,腔内外科组通畅率为78%,开放性手术组通畅率为72%。结论:病人的全身情况、动脉病变的范围和程度是选择下肢动脉硬化闭塞症外科治疗方法的主要依据,为取得较好的长期通畅率和临床效果需要重视围手术期处理和术后随访。     

17β-雌二醇对子宫内膜异位症患者在位子宫内膜间质细胞β-catenin mRNA和蛋白表达的影响

目的研究17β-雌二醇(17β-E2)对子宫内膜异位症(内异症)患者在位子宫内膜间质细胞β-catenin mRNA和蛋白表达的影响,探讨Wnt/β-catenin信号通路在介导雌激素促进内异症发生发展的作用。方法体外分离培养内异症患者在位子宫内膜间质细胞。用不同浓度17β-E2处理子宫内膜间质细胞48 h;此后选用10-10mol/L 17β-E2处理子宫内膜间质细胞12、24和48 h,逆转录聚合酶链反应(RT-PCR)和免疫印迹法(Western blotting)检测17β-E2处理前后子宫内膜间质细胞β-catenin mRNA和蛋白的表达水平。同法分析雌激素受体拮抗剂ICI182,780(10-6mol/L)对17β-E2促进β-catenin mRNA和蛋白表达的影响。免疫组织化学染色观察17β-E2作用后β-catenin在子宫内膜间质细胞中的定位。结果17β-E2能明显促进内异症患者在位子宫内膜间质细胞β-catenin mRNA和蛋白的表达,并呈剂量和时间依赖性,于10-10mol/L作用48 h最明显。雌激素受体拮抗剂ICI182,780能明显抑制17β-E2对子宫内膜间质细胞β-catenin mRNA和蛋白的表达。免疫组织化学染色发现17β-E2能促进β-catenin在子宫内膜间质细胞核内的表达。结论雌激素可能通过激活Wnt/β-catenin信号通路促进内异症在位子宫内膜的异位种植。     

Mutant ryanodine receptors in catecholaminergic polymorphic ventricular tachycardia generate delayed afterdepolarizations due to increased propensity to Ca2+ waves.

AIMS: Mutations in cardiac ryanodine receptors (RyR2s) are linked to catecholaminergic polymorphic ventricular tachycardia (CPVT), characterized by risk of polymorphic ventricular tachyarrhythmias and sudden death during exercise. Arrhythmias are caused by gain-of-function defects in RyR2, but cellular arrhythmogenesis remains elusive. METHODS AND RESULTS: We recorded endocardial monophasic action potentials (MAPs) at right ventricular septum in 15 CPVT patients with a RyR2 mutation (P2,328S, Q4,201R, and V4,653F) and in 12 control subjects both at baseline and during epinephrine infusion (0.05 microg/kg/min). At baseline 3 and during epinephrine infusion, four CPVT patients, but none of the control subjects, showed delayed afterdepolarizations (DADs) occasionally coinciding with ventricular premature complexes. In order to study the underlying mechanisms, we expressed two types of mutant RyR2 (P2,328S and V4,653F) causing CPVT as well as wild-type RyR2 in HEK 293 cells. Confocal microscopy of Fluo-3 loaded cells transfected with any of the three RyR2s showed no spontaneous subcellular Ca(2+) release events at baseline. Membrane permeable cAMP analogue (Dioctanoyl-cAMP) triggered subcellular Ca(2+) release events as Ca(2+) sparks and waves. Cells expressing mutant RyR2s showed spontaneous Ca(2+) release events at lower concentrations of cAMP than cells transfected with wild-type RyR2. CONCLUSION: CPVT patients show DADs coinciding with premature action potentials in MAP recordings. Expression studies suggest that DADs are caused by increased propensity of abnormal RyR2s to generate spontaneous Ca(2+) waves in response to cAMP stimulation. Increased sensitivity of mutant RyR2s to cAMP may explain the occurrence of arrhythmias during exercise or emotional stress in CPVT.