沙参麦冬汤加减对阴虚肺热证肺炎支原体肺炎恢复期患者免疫炎症反应的影响

目的:观察沙参麦冬汤加减对肺炎支原体肺炎恢复期患者阴虚肺热证的疗效及对免疫炎症反应的调节作用。方法:将148例患者按随机数字表法分为对照组和观察组各74例。研究期间对照组脱落、失访2例,剔除3例完成70例;观察组脱落、失访4例,完成71例。两组患者均口服阿奇霉素片,10 mg·kg~(-1)·d~(-1),连服3 d;和匹多莫德颗粒剂,0.4～0.8 g/次,2次/d;和氨溴特罗口服溶液,2.5～15 mL/次,2次/d。对照组口服养阴清肺口服液,5～10 mL/次,2～3次/d;观察组内服沙参麦冬汤加减,1剂/d。两组疗程均为7 d。进行治疗前后咳嗽症状评分和咳嗽视觉模拟评分(VAS);记录咳嗽、肺部湿啰音,咯痰消失时间和胸片复常时间;进行治疗前后阴虚肺热证评分和莱塞斯特咳嗽问卷(LCQ)评分;检测治疗前后T淋巴细胞亚群(CD3+,CD4+,CD8+和CD4+/CD8+)和白细胞介素-6(IL-6),IL~(-1)0,肿瘤坏死因子-α(TNF-α),P物质(SP),降钙素原基因相关肽(CGRP)水平;进行治疗后安全性评价。结果:观察组疾病疗效总有效为95.77%(68/71),优于对照组的82.86%(58/70)(χ2=6.186,P0.05);观察组患者咳嗽症状积分和VAS评分均明显低于对照组(P0.01);观察组患者LCQ量表各维度评分和LCQ总分均高于对照组(P0.01);观察组患者咳嗽、肺部湿啰音、咯痰消失时间及胸片复常时间均短于对照组(P0.01);观察组CD3+,CD4+,CD4+/CD8+均高于对照组(P0.01),CD8+低于对照组(P0.01);观察组血清IL-6,IL~(-1)0,TNF-α水平和痰液中SP和CGRP水均低于对照组(P0.01)。结论:在西医常规治疗的基础上,采用沙参麦冬汤加减内服治疗MPP恢复期阴虚肺热证患者,可减轻咳嗽程度,缩短病程,改善了生活质量,提高了细胞免疫功能,减轻了炎性损伤,降低了咳嗽敏感性,有较好的临床疗效,且使用安全。     

基于动态优化算法的复杂生物网络的状态调控

近年研究表明,某些药物能改变基因调控网络(GRNs)中的调控反应参数,促使细胞从病变状态转移到正常状态。在此基础上,有学者构建了基于吸引子和分岔理论的状态调控框架。现有的控制策略中,控制信号规律都是自行拟定的,并且所使用的参数扰动法仅能求出单控制变量情况下状态转移所需的时间。因此,针对以非线性常微分方程组(ODEs)形式描述的复杂生物网络,本文提出了一种基于动态优化算法改变网络状态的最优调控方法,在掌握生物网络基本特性的基础上建立了动态优化问题,并以简单低维的三节点GRN和复杂高维的癌症GRN为例,利用MATLAB计算得到单控制变量及多控制变量条件下的最优控制策略。本文所提方法旨在实现精确且快速的状态调控,为试验研究和实际治疗提供参考依据。     

MKS1 基因变异所致Joubert 综合征1 例临床及基因分析

目的对Joubert 综合征进行临床特点和遗传学分析。方法回顾分析1例确诊的Joubert 综合征患儿的临床资料。结果患儿男性,3个月,双眼不追视、发育落后,四肢肌张力偏低。头颅磁共振示"磨牙征"。全外显子测序显示患儿MKS1基因c.1411_c.1412insG及c.44AG复合杂合突变。Sanger测序验证c.1411_c.1412insG移码突变来自于父亲,已有报道;c.44AG错义突变来自于母亲,未见报道,根据ACMG指南为可能致病变异。患儿确诊为Joubert综合征。结论确诊患儿为Joubert综合征,新发现c.44AG错义突变。     

Association of methylenetetrahydrofolate reductase C677T polymorphism with the pre-eclampsia risk in Hakka pregnant women in Southern China

Abstract

The aim of this study is to clarify the possible association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and pre-eclampsia in Hakka pregnant women in southern China. Pre-eclampsia and normal pregnant women were consecutively collected and MTHFR C677T genotypes were determined by the DNA sequencing method. One hundred and thirteen pre-eclampsia patients were CC homozygote (113 of 191, 59.2%), 68 of 191 (35.6%) were CT heterozygote, and 10 of 191 (5.2%) were TT homozygote, with the frequency of the T allele equal to 0.77. This is in comparison with the normal control group where 106 of 202 (52.5%) were CC homozygote, 83 of 202 (41.1%) were CT heterozygote, and 13 of 202 (6.4%) were TT homozygote, with the frequency of the T allele equal to 0.27. No statistically significant differences were observed in genotype or allele frequencies between the pre-eclampsia and normal control for the C677T polymorphism of MTHFR gene (p?>?.05). The findings of this study suggest that polymorphisms of MTHFR C677T genes were not associated with pre-eclampsia in Hakka pregnant women from southern China, but additional studies are necessary to explore the mechanisms involving it.     

基于线粒体COⅠ基因的广西不同地区福寿螺遗传多态性分析

目的 通过对广西不同地区福寿螺的COⅠ基因进行分析,以了解广西福寿螺种群的遗传多态性。方法 从南宁市横县、桂林市全州县和荔浦县、贺州市富川县、百色市田林县和崇左市凭祥县共计6个县区采集福寿螺样本,提取DNA并进行COⅠ基因的PCR扩增及测序。运用MAGE 7.0将本研究获得的单倍型与GenBank中的福寿螺单倍型使用邻接法构建系统进化树,并计算个体间的遗传距离,分析其遗传多样性。结果 COⅠ基因长度为493 bp,从11个样本鉴定出2种单倍型：单倍型1（Haplotype 1）和单倍型2（Haplotype 2）。其中9个样本为Haplotype 1,分别来源于南宁市横县（2个）、贺州市富川县（1个）、桂林市荔浦县（1个）、百色市田林县（2个）、崇左市凭祥县（3个）,该单倍型与小管福寿螺遗传距离最近,为0.047;2个样本为Haplotype 2,分别源自为南宁市横县和桂林市全州,与孤岛福寿螺遗传距离最近,为0.062。根据上述条件所构建的进化树形成了7个分支,分别为P. canaliculata、P. camena、P. insularum、P. paludosa、P. diffusa、P. haustrum、和外群Pilaconica。Haplotype 1与来自美国夏威夷 （GenBank登录号 EU 523129）的P. canaliculata组成一个分支,Haplotype 2与来自巴西（GenBank登录号EF514942）的P. insularum组成一个分支,且置信值均在98%以上。结论 初步判断广西地区存在小管福寿螺与孤岛福寿螺两种类型的福寿螺,其种群内没有发现遗传分化。     

Oncogenic properties and signaling basis of the PAX8-GLIS3 fusion gene

Hyalinizing trabecular tumors of the thyroid are rare and mostly benign epithelial neoplasms of follicular cell origin, which have recently been shown to be underpinned by the PAX8-GLIS3 fusion gene. In our study, we sought to investigate the potential oncogenic mechanisms of the PAX8-GLIS3 fusion gene. Forced expression of PAX8-GLIS3 was found to increase proliferation, clonogenic potential and migration of human nonmalignant thyroid (Nthy-ori 3-1) and embryonic kidney (HEK-293) cells. Moreover, in xenografts, Nthy-ori 3-1 PAX8-GLIS3 expressing cells generated significantly larger and more proliferative tumors compared to controls. These oncogenic effects were found to be mediated through activation of the Sonic Hedgehog (SHH) pathway. Targeting of smoothened (SMO), a key protein in the SHH pathway, using the small molecule inhibitor Cyclopamine partially reversed the increased proliferation, colony formation and migration in PAX8-GLIS3 expressing cells. Our data demonstrate that the oncogenic effects of the PAX8-GLIS3 fusion gene are, at least in part, due to an increased activation of the SHH pathway.     

Cytokine-related genes play critical roles in extrafollicular growth of follicular lymphoma cells

Follicular lymphoma (FL) is a germinal center-derived B-cell lymphoma that is known to proliferate in the intrafollicular region. However, lymphoma cells can be identified in the extrafollicular regions, which are related to disease dissemination. We purified the intrafollicular and extrafollicular regions of FL cells by laser microdissection and conducted microarray analysis in order to characterize the gene expression profiles of FL cells from both regions. BCL2 and genes of germinal B-cell markers clearly separated intrafollicular and extrafollicular regions of reactive follicular hyperplasia, suggesting the adequacy of the current analysis. In FL cases, cytokine-related genes were significantly enriched in extrafollicular regions compared with those in the intrafollicular regions. In intrafollicular regions of FL, cell-cycle–related genes were enriched. We found that the FL cells in the extrafollicular region more strongly expressed IL3RA and CXCL12 than those of intrafollicular regions. The cytokines might be also derived from stroma cells in the extrafollicular regions, which may initiate activation and migration of the tumor cells to this region. Our results suggest that FL cell interaction with surrounding stroma cells plays an important role in the pathophysiology of FL and that such interactions should be a good target for therapy.