The prevalence of LRRK2 Gly2385Arg variant in Chinese Han population with Parkinson's disease.

We conducted a case-control study to determine the prevalence of the LRRK2 Gly2385Arg variant in patients with Parkinson's disease in Han population in mainland China. Heterozygous LRRK2 Gly2385Arg variant was identified in 14 of 235 patients with Parkinson's disease (5.69%), but not in 214 unrelated healthy controls. Multivariate analysis indicated the frequency of Gly2385Arg variant in the female patients with early age at onset is higher than their male counterparts. The founder haplotype analysis showed the variant carriers shared the same founder. Clinically, the LRRK2 Gly2385Arg carriers presented with classical Parkinson's disease symptoms. Our study indicates that the LRRK2 Gly2385Arg variant is a potential ethnic-specific genetic risk factor of Parkinson's disease within Chinese Han ethnicity.     

早发2型糖尿病骨密度、骨代谢变化及影响因素分析

  目的  研究早发2型糖尿病(T2DM)骨密度、骨代谢水平改变并探讨其影响因素。  方法  选取2018年1月—2021年12月在上海交通大学医学院附属新华医院内分泌科住院的初诊年龄≤40岁的2型糖尿病患者201例为早发组,另以本院与早发组年龄、性别相匹配的非糖尿病患者107例为对照组。比较2组一般临床资料及腰椎L_1~4平均骨密度(BMD)、骨代谢水平差异。  结果  (1)校正BMI后,早发组与对照组BMD比较差异无统计学意义(F=1.004,P>0.05),早发组1型原胶原氨基端前肽(P1NP)、骨钙素、25(OH)D₃、甲状旁腺激素均低于对照组(t=3.941、6.556、7.123、4.620,均P＜0.05),2组1型胶原羧基端肽β特殊序列(β-CTX)比较差异无统计学意义(t=1.684,P>0.05)。(2)影响因素分析结果显示,BMD与年龄呈独立负相关关系(95% CI:-0.007~-0.001,P=0.012),与BMI(95% CI:0.004~0.014,P=0.001)、糖化血红蛋白(95% CI:0.002~0.021,P=0.014)呈独立正相关关系;β-CTX与年龄(95% CI:-0.013~-0.003,P=0.001)、TC(95% CI:-0.079~-0.015,P=0.004)呈独立负相关关系,女性(95% CI:-0.177~-0.020,P=0.014)是β-CTX降低的独立危险因素;P1NP与年龄(95% CI:-0.831~-0.137,P=0.007)、空腹血糖(95% CI:-1.815~-0.333,P=0.005)、TG(95% CI:-0.635~-0.508,P=0.004)呈独立负相关关系。  结论  早发2型糖尿病患者的骨密度与非糖尿病人群相比未见明显差异,但骨形成标志物降低,年龄、性别、BMI、血糖、血脂水平是其骨密度、骨代谢水平改变的独立影响因素。      

全反式维甲酸对人乳腺癌MCF-7细胞凋亡的影响

目的:探讨全反式维甲酸(ATRA)对人乳腺癌MCF-7细胞凋亡的影响及作用途径.方法:在人乳腺癌细胞株MCF-7培养基中加入一定浓度ATRA和PKC-δ的专一抑制剂rottlerin(RO)并分组,通过SubG1assay by FACS、琼脂糖凝胶电泳检测基因组DNA ladder来观察ATRA对MCF-7的影响.结果:在浓度为5μM的ATRA作用下,MCF-7的凋亡率显著高于其它各组(P＜0.01),并可观察到明显梯状DNA.结论:ATRA能够诱导乳腺癌MCF-7细胞凋亡,但受PKC-δ的专一抑制剂RO的抑制.     

A homozygous MITF mutation leads to familial Waardenburg syndrome type 4

Waardenburg syndrome (WS) is a genetic disorder characterized by hearing loss and pigmentary abnormalities with variable penetrance. Though heterozygous mutations in MITF are a major cause for Waardenburg syndrome type 2 (WS2), homozygous mutations in this gene and the associated phenotype have been rarely characterized. In this study, we identified a novel p.R223H mutation in MITF in a Chinese Han family with variable WS features. Both parents carried a heterozygous p.R223H mutation. They had normal hearing, and premature greying of the hair is their only pigmentary abnormality. In contrast, their two children both carried a homozygous p.R223H mutation and had classic WS features including profound hearing loss, heterochromia irides and marked pigmentary abnormalities in hair and skin. Interestingly, the two affected children also have persistent chronic constipation since the neonatal period, symptoms suggestive of Waardenburg syndrome type 4 (WS4). Our study revealed a likely association between homozygous mutations in MITF and WS4, which implies a dosage effect for the underlying pathogenesis mechanism.     

儿童原发性夜间遗尿症生理心理治疗的疗效及随访评估

目的应用生理心理治疗观察儿童原发性夜间遗尿症(PNE)的临床远期疗效,并探讨其治疗机制。方法对2004年9月至2006年1月在上海交通大学医学院附属上海儿童医学中心发育行为儿科应用生理心理治疗PNE患儿的资料进行回顾性分析,治疗中2周随访1次(随访观察6个月),治疗结束后1个月随访1次,家长每日记录患儿遗尿频率和夜间自行起床排尿次数。B超测定治疗前和治疗结束时最大憋尿状态下的膀胱容量。统计分析生理心理治疗的远期疗效,遗尿频率、膀胱容量以及夜间自行起床排尿次数的变化情况,采用Logistic回归分析影响生理心理治疗远期疗效的危险因素。结果研究期间应用生理心理治疗的68例PNE患儿远期疗效为:治愈43例(63.2%),显效18例(26.5%),部分有效5例(7.4%),无效2例(2.9%)。治疗前平均遗尿频率为每周(6.12±1.32)次,停止治疗6个月后遗尿频率为每周(1.23±0.18)次(t=2.65,P=0.011)。治疗前平均夜间自行起床排尿次数为每周(0.72±0.15)次,停止治疗6个月后平均夜间自行起床排尿次数为每周(6.83±1.16)次(t=2.25,P=0.026)。治疗前患儿平均膀胱容量/...     

Animal models of asthma: Innovative methods of lung research and new pharmacological targets

Allergic diseases like bronchial asthma are increasing in societies with western lifestyle. In the last years substantial progress was made in the understanding of the underlying mechanisms and explanations like the hygiene hypothesis were developed. However the exact mechanisms of the physiological and immunological events in the lung leading to bronchial asthma are still not fully understood. Therefore, animal models of asthma have been established and improved to study the complex cellular interactions in vivo. Since mice became the most frequently used animal species the methods for detecting lung physiology, e.g. lung function measurements were adapted to the small size of the murine lung. Laser-dissection and precision cut lung slices have become common techniques to get a view into distinct lung compartments and cells. In addition genomic and proteomic approaches are now used widely. On the other hand a major conclusion of the workshop stated that more than one species is necessary in research and for pharmacological screening in asthma and COPD. The resulting new understanding in the mechanisms of asthma pathogenesis has lead to a rapid identification of novel pharmaceutical targets for treatment of the disease.     

正常踝关节内、外侧韧带的解剖及其影像学表现

目的:探讨正常踝关节内、外侧韧带的解剖形态及其MRI和CT表现。方法:6例正常人踝关节新鲜标本MRI扫描,解剖显示内、外侧韧带后,CT断层扫描与MRI对照观察踝关节内、外侧韧带的影像学表现;在30例正常志愿者踝关节的MRI上测量内、外韧带的宽度及厚度。结果:MRI横断面及冠状面可充分显示踝关节内、外侧韧带及其周围组织的解剖结构;踝关节内、外侧韧带在冠状面及横断面上所测的宽、厚度,男女间存在一定的差异。结论:MRI能清晰地显示踝关节的解剖结构,所测量的正常踝关节内、外侧韧带的宽、厚度数据,为临床诊断踝关节内、外侧韧带的病变提供了形态学依据。     

Large duplication in LMBR1 gene in a large Chinese pedigree with triphalangeal thumb polysyndactyly syndrome

Polydactyly and syndactyly are digital abnormalities in limb‐associated birth defects usually caused by genetic disorders. In this study, a five‐generation Chinese pedigree was found with triphalangeal thumb polysyndactyly syndrome (TPTPS), showing an autosomal dominant pattern of inheritance. We utilized linkage analysis and whole genome sequencing (WGS) for the genetic diagnosis of this pedigree. Linkage analysis was performed using a genome‐wide single nucleotide polymorphism (SNP) chip and three genomic regions were identified in chromosomes 2, 6, and 7 with significant linkage signals. WGS discovered a copy number variation (CNV) mutation caused by a large duplication region at the tail of chromosome 7 located in exons 1–5 of the LMBR1 gene, including the zone of polarizing activity regulatory sequence (ZRS), with a length of approximately 180 kb. A real‐time polymerase chain reaction (PCR) assay confirmed the duplication. The findings of our study supported the notion that large duplications including the ZRS caused TPTPS. Our study showed that linkage analysis in combination with WGS could successfully identify the disease locus and causative mutation in TPTPS, which could help elucidate the molecular mechanisms and genotype–phenotype correlations in polydactyly.     

Logistic回归和ROC曲线分析多种肿瘤标志物在结直肠癌中的诊断价值

目的:应用Logistic回归和ROC曲线探讨CEA、CA199及CA50在结直肠癌诊断中的应用价值.方法:结直肠癌患者75例,良性结直肠病患者35例,正常人49例,分别应用化学发光免疫分析测定CEA,电化学发光免疫分析测定CA199,免疫放射分析测定CA50,通过ROC曲线分析CEA、CA199、CA50及各种Logistic回归结果的ROC曲线下面积(AUC).结果:结直肠癌-良性结直肠病中,CA50的AUC要高于CA199的AUC,而CEA、CA50两项联合诊断结直肠癌的AUC(0.875)要高于CEA、CA199、CA50三项联合诊断的AUC(0.604),且CEA、CA50两项联检诊断的AUC高于CEA、CA199或CA50任意单一检查的AUC.在结直肠癌-正常对照组中,三项肿瘤标志物联检的AUC(0.866)均高于三项肿瘤标志物单一检查的AUC,无论在结直肠癌-正常对照组中还是结直肠癌-良性结直肠病中CEA的AUC都高要于CA199或CA50.结论:CEA在诊断结直肠癌有一定的临床应用价值,CA50联合CEA检测可为临床鉴别良恶性结直肠病提供有效的参考,而CEA、CA199及CA50三者联检对鉴别良恶性结直肠病的意义不大.作为一种统计手段,Logistic回归可改善诊断的灵敏度和特异性.