多囊卵巢综合征患者Ⅰ级亲属异常家族史与其临床表型的相关性

目的探讨多囊卵巢综合征（PCOS）患者Ⅰ级亲属异常家族史与PCOS患者临床表型的相关性。方法选择2004年8月至2006年4月在北京大学第三医院生殖医学中心诊断为PCOS的不孕症患者139例,计算体重指数（BMI）、腰围臀围比值（WHR）并进行多毛评分,测定卵泡刺激素（FSH）、黄体生成素（LH）、泌乳素、睾酮、雄烯二酮（A）、雌二醇水平,进行口服糖耐量试验（OGTT）及胰岛素释放试验等。收集PCOS患者Ⅰ级亲属的异常家族史,并分析其与PCOS患者临床表型的相关性。结果（1）有糖尿病家族史PCOS患者与无糖尿病家族史者相比,WHR（分别为0．99±0．10、0．79±0．08）、多毛评分[分别为（1．9±1．2）、（1．8±1．2）分]、月经稀发周期[分别为（108±10）、（92±19）d]均明显增加,稳态模型胰岛素抵抗指数（HOMA-IR,分别为3．5±2．0、2．7±1．6）、葡萄糖曲线下面积[GLUAUC,分别为（836±245）、（748±139）nmol·L^-1·min^-1]、胰岛素曲线下面积[INSAUC,分别为（9670±458z）、（7330±4311）mIU·L^-1·min^-1]、空腹血糖（FG）水平[分别为（5．0±1．1）、（4．8±0．5）mmol/L]、空腹胰岛素（FINS）水平[分别为（15±8）、（11±8）mIU／L]和A水平[分别为（11±6）、（8±5）nmol／L]均明显升高,胰岛初期分泌功能指数（△I60／△G60,分别为32±22、52±30）、胰岛素敏感指数（ISI,分别为0．019±0．011、0．033±0．014）和葡萄糖处置指数（DI,分别为18±10、30±22）明显降低,以上各指标两者间比较,差异均有统计学意义（P〈0．05）。（2）有月经紊乱家族史PCOS患者与无月经紊乱家族史者相比,WHR（分别为0．99±0．09、0．80±0．10）明显增加,多毛评分[分别为（1．9±1．0）、（1．6±1．1）分]也明显增加,月经稀发周期[分别为（105±28）、（84±31）d]明显延长,HOMA-IR和FINS水平[分别为（3．6±2．4）、（2．5±1．7）和（15±14）、（12±11）mIU／L]明显升高,而胰岛B细胞功能指数（HOMA-β）、ISI和DI（分别为178±134和207±175,0．017±0．019和0．034±0．012,23±18和28±19）明显降低,以上各指标两者间比较,差异均有统计学意义（P〈0．05）。（3）有早秃家族史PCOS患者与无早秃家族史者相比,BMI[分别为（26±4）、（23±5）kg／m^2]和多毛评分[分别为（2．1±1．1）、（1．7±1．3）分]也明显增加,DI（分别为20±11、30±23）明显降低,差异均有统计学意义（P〈0．05）。（4）有高血压家族史PCOS患者与无高血压家族史者相比,△I60／△G60（分别为34±27、50±30）明显降低,FINS水平[分别为（13±10）、（10±9）mIU／L]明显升高,上述指标两者间比较,差异均有统计学意义（P〈0．05）。（5）冠心病家族史则对上述各指标无明显影响（P〉0．05）。结论糖尿病家族史对PCOS患者临床表型影响最大,其次为月经紊乱家族史、早秃家族史、高血压家族史等,冠心病家族史则对PCOS患者临床表型无明显影响。     

小胶质细胞在脑缺血中的作用

小胶质细胞在脑缺血后炎症中起着重要作用.大量研究表明,小胶质细胞是高度可塑的细胞,可应对不同微环境信呈现不同的表型和功能.小胶质细胞可极化为经典激活的促炎性M1型或替代激活的抗炎性M2型,在缺血性损伤中起着不同的作用.抑制M1而刺激M2有可能成为缺血性卒中治疗的一个新途径.     

心脏型肌球蛋白结合蛋白C基因缺失突变导致肥厚型心肌病特点分析

目的观察肥厚型心肌病（HCM）患者心脏型肌球蛋白结合蛋白C基因（MYBPC3）缺失突变及其表型的特点。方法在100例HCM患者中对MYBPC3的所有外显子及其侧翼内含子序列进行基因扫描,聚合酶链反应（PCR）扩增目的片段,双脱氧末段终止法测序。对突变患者进行家系调查,分析其表型特点。结果在两例先证者中分别发现两个缺失突变14262_14264delAAG和14364delG,均位于外显子25。表型分析发现两例先证者均有劳力性胸闷、胸痛和晕厥史,超声心动图表现为不对称性肥厚（室间隔/左室后壁分别为2.5、3.2）,但SAM征阴性,发病年龄分别为38岁和29岁。结论缺失突变是MYBPC3基因突变的常见形式,14262_14264delAAG或14364delG突变导致的HCM表现为不对称性心肌肥厚,患者容易出现晕厥等症状,应该警惕心源性猝死的发生。     

Clinical Characteristics of Atopic Dermatitis in Korean School-Aged Children and Adolescents According to Onset Age and Severity

BackgroundAtopic dermatitis (AD) is a heterogeneous disease with different age of onset, disease course, clinical symptoms, severity, and risk of comorbidity. The characteristics of children with AD also vary by age or country. However, little is known about the clinical characteristics of AD in Korean school-aged children and adolescents. Furthermore, there are few studies on phenotypic differences according to onset age. This study aimed to explore the clinical characteristics and phenotypes according to onset age and severity of AD in children and adolescents in Korea.MethodsAD patients aged 6–18 years who presented to 18 hospitals nationwide were surveyed. The patients were examined for disease severity by pediatric allergy specialists, and data on history of other allergic diseases, familial allergy history, onset age, trigger factors, lesion sites, treatment history and quality of life were collected. The results of the patient’s allergy test were also analyzed. The patients were classified into infancy-onset (< 2 years of age), preschool-onset (2–5 years of age), and childhood-onset (≥ 6 years of age) groups. Study population was analyzed for clinical features according to onset-age groups and severity groups.ResultsA total of 258 patients with a mean age of 10.62 ± 3.18 years were included in the study. Infancy-onset group accounted for about 60% of all patients and presented significantly more other allergic diseases, such as allergic rhinitis and asthma (P = 0.002 and P = 0.001, respectively). Food allergy symptoms and diagnoses were highly relevant to both earlier onset and more severe group. Inhalant allergen sensitization was significantly associated with both infancy-onset group and severe group (P = 0.012 and P = 0.024, respectively). A family history of food allergies was significantly associated with infancy-onset group (P = 0.036). Severe group was significantly associated with a family history of AD, especially a paternal history of AD (P = 0.048 and P = 0.004, respectively). Facial (periorbital, ear, and cheek) lesions, periauricular fissures, hand/foot eczema, and xerosis were associated with infancy-onset group. The earlier the onset of AD, the poorer the quality of life (P = 0.038). Systemic immunosuppressants were used in only 9.6% of the patients in the severe group.ConclusionThis study analyzed the clinical features of AD in Korean children and adolescents through a multicenter nationwide study and demonstrated the phenotypic differences according to onset age and severity. Considering the findings that the early-onset group is more severe and accompanied by more systemic allergic diseases, early management should be emphasized in young children and infants.     

Redefying the therapeutic strategies against cardiorenal morbidity and mortality: Patient phenotypes

Chronic kidney disease(CKD) patients face an unacceptably high morbidity and mortality, mainly from cardiovascular diseases. Diabetes mellitus, arterial hypertension and dyslipidemia are highly prevalent in CKD patients. Established therapeutic protocols for the treatment of diabetes mellitus, arterial hypertension,and dyslipidemia are not as effective in CKD patients as in the general population. The role of non-traditional risk factors(RF) has gained interest in the last decades. These entail ...     

新疆地区维吾尔族成骨不全九例患儿基因型与表型分析

目的探讨新疆地区维吾尔族儿童成骨不全基因变异谱系及临床表型特点.方法回顾性分析2013年1月至2017年12月新疆医科大学第一附属医院儿科就诊的9例(男4例、女5例)维吾尔族成骨不全患儿的临床资料,按照经典Sillence分型进行临床分型.检测成骨不全相关基因,利用美国医学遗传学和基因组学协会指南、InterVar、Alamut功能软件评估变异致病性,分析基因变异谱系特点.结果9例患儿年龄3岁6月龄~15岁,临床表现为反复骨折、骨骼畸形、矮小、蓝巩膜、听力异常、牙本质发育不全、关节韧带松弛.其中成骨不全Ⅲ型6例、Ⅳ型3例.9例患儿中共发现3种基因(COL1A1、COL1A2和SERPINF1)的9个候选变异,其中5个变异位点为国际首次报道,经评估均为可能致病性变异.结论新疆维吾尔族成骨不全临床表型复杂多样,但均有骨折及骨骼畸形.基因型与国内外报道有差异,SERPINF1基因可能在维吾尔族人群中更为高发,维吾尔族成骨不全的遗传异质性及独特的基因变异谱系,进一步为成骨不全的基因型与表型相关性提供了依据.     

纯合型家族性高胆固醇血症家系基因型与表型分析

目的对1个纯合型家族性高胆固醇血症(HoFH)家系进行遗传学分析.方法前瞻性研究.选择西安市儿童医院心内科2018年10月确诊的1个HoFH家系先证者及家系成员共20人为研究对象,收集临床资料,提取基因组DNA,对先证者进行全外显子靶向捕获二代测序,并在家系内进行Sanger测序验证.对家系成员杂合突变携带者和未携带者的基因型与表型进行分析.结果先证者为7岁10月龄男性患儿,生后尾骨处皮肤可见圆形绿豆大小黄色皮肤突起,3~4岁起双侧肘关节、膝关节及跟腱处皮肤逐渐出现直径0.5~1.5 cm的黄色瘤样结节,患儿身高、体重、智力发育与同龄儿相同.家族其他成员无类似皮肤黄瘤.患儿总胆固醇(TC)18.16~21.24 mmol/L,低密度脂蛋白胆固醇(LDL-C)14.08~15.51 mmol/L,颈部超声提示双侧颈动脉及椎动脉弥漫性硬化斑块,心脏彩超提示主动脉瓣增厚、钙化.基因检测确定了先证者LDLR基因携带c.418G>A(p.E140K)纯合突变,分别遗传自患儿父母,二人为近亲结婚,均携带LDLR-E140K基因杂合突变.家系中携带LDLR-E140K基因杂合突变成员TC、LDL-C和载脂蛋白B分别为(8.40±0.13)、(6.79±0.01)、(1.95±0.05)mmol/L,明显高于未携带者[(4.59±0.28)、(3.35±0.39)、(0.86±0.10)mmol/L,t=7.269、4.595、6.311,P均<0.05].结论LDLR-E140K基因纯合突变致儿童HoFH,携带纯合突变的先证者临床表型最严重,携带杂合突变的家系成员均有高胆固醇血症表型,LDLR-E 140K是家族性高胆固醇血症的致病性变异.     

Characteristics of Pruritus according to Morphological Phenotype of Psoriasis and Association with Neuropeptides and Interleukin-31

BackgroundPruritus is a common symptom in psoriasis. However, few studies have assessed the characteristics of pruritus according to morphological phenotypes of psoriasis.ObjectiveTo investigate the characteristics of pruritus according to morphological phenotypes of psoriasis and to assess the association with inflammatory mediators related to pruritus.MethodsPsoriasis patients were divided into 2 groups according to clinical phenotype: eruptive inflammatory (EI) and chronic stable (CS). Clinical data of pruritus were assessed by an itch questionnaire. Serum neuropeptides and cytokines including substance P, histamine, vasoactive intestinal peptide, neuropeptide Y, calcitonin gene-related peptide and interleukin-31 (IL-31) were quantitatively measured.ResultsIn total, 50 patients with psoriasis (30 male, 20 female; mean age, 45.7 years) were studied (EI, n=15 and CS, n=35). Pruritus was reported by 80% of EI and CS patients. There were no significant differences in prevalence of pruritus, pruritus intensity, severity of psoriasis, serum neuropeptides, or IL-31 between the 2 groups.ConclusionThe morphological phenotype does not seem to be an important factor affecting the prevalence and characteristics of pruritus in psoriasis.     

感染表型慢性阻塞性肺疾病

COPD是一种慢性炎症性病变,可累及大小气道、肺实质以及肺血管.引起COPD的危险因素众多,其中下呼吸道感染,尤其是细菌感染是导致COPD发生及急性加重的一个重要原因,以至有学者提出一个全新概念——感染表型COPD.本文拟对感染表型COPD概念提出背景及感染表型COPD的特征作一综述.     

中国人Wilson病ATP7B基因Thr935Met突变与临床表型的关系研究

目的　探讨Wilson病 (Wilsondisease,WD)ATP7B基因突变的高频位点之一Thr 935Met与临床表现的关系。方法　应用PCR技术扩增 90例WD患者和 30例正常人ATP7B基因第 12外显子 ,其PCR产物行限制性内切酶TaiI酶切分析。结果　正常人组酶切未见异常。 90例WD组第 12外显子有 10例Thr 935Met杂合突变 ,未见纯合突变 ,检出率为 11 1%。突变组的平均发病年龄为 19 10岁± 8 5 2岁 ,无突变组的平均发病年龄为 14 0 0岁± 7 4 2岁 ,差异有显著意义 (P =0 0 4 7)。结论　Thr 935Met突变组患者的发病年龄迟于未见该点突变组的患者 ,而性别、首发症状及铜生化水平与该点突变无明显相关性。