脊髓小脑共济失调2型家系ATXN2基因中间重复病例表型与分子遗传学特征

目的探讨脊髓小脑共济失调2型(SCA2)致病基因ATXN2异常等位基因中间重复个体的表型和分子遗传学特点。方法针对2005—2018年中日友好医院神经科运动障碍与神经遗传病研究中心收集的1383个常染色体显性遗传共济失调家系的先证者和部分家系成员,采用荧光标记毛细管电泳片段分析方法进行动态突变检测,对携带ATXN2基因中间重复的个体进行临床表型和遗传特征分析。结果共检出163个家系(包含先证者和家系成员共203人)携带异常扩展的ATXN2基因CAG重复序列,其中93个家系中有107例的异常扩展等位基因重复次数在29~34次之间。在其中的20个亲子对中,父系遗传16个,异常等位基因的代间扩展增加0~28次,母系遗传4个,异常等位基因的代间扩展增加0~4次。结论对于临床拟诊SCA2家系患者,需对其亲代或成年子代个体进行ATXN2基因检测,以免漏诊。动态突变基因检测有助于识别中间重复的个体,对明确家系致病基因和遗传咨询至关重要。     

Hepatotoxicity of cantharidin is associated with the altered bile acid metabolism

Cantharidin (CTD) is an effective antitumor agent. However, it exhibits significant hepatotoxicity, the mechanism of which remains unclear. In this study, biochemical and histopathological analyses complemented with ultra-high-performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS)-based targeted metabolomic analysis of bile acids (BAs) were employed to investigate CTD-induced hepatotoxicity in rats. Sixteen male and female Sprague–Dawley rats were randomly divided into two groups: control and CTD (1.0 mg/kg) groups. Serum and liver samples were collected after 28 days of intervention. Biochemical, histopathological, and BA metabolomic analyses were performed for all samples. Further, the key biomarkers of CTD-induced hepatotoxicity were identified via multivariate and metabolic pathway analyses. In addition, metabolite–gene–enzyme network and Kyoto Encyclopedia of Genes and Genomes pathway analyses were used to identify the signaling pathways related to CTD-induced hepatotoxicity. The results revealed significantly increased levels of biochemical indices (alanine aminotransferase, aspartate aminotransferase, and total bile acid). Histopathological analysis revealed that the hepatocytes were damaged. Further, 20 endogenous BAs were quantitated via UHPLC-MS/MS, and multivariate and metabolic pathway analyses of BAs revealed that hyocholic acid, cholic acid, and chenodeoxycholic acid were the key biomarkers of CTD-induced hepatotoxicity. Meanwhile, primary and secondary BA biosynthesis and taurine and hypotaurine metabolism were found to be associated with the mechanism by which CTD induced hepatotoxicity in rats. This study provides useful insights for research on the mechanism of CTD-induced hepatotoxicity.     

学龄期近视进展儿童调节功能的客观检查和分析

目的　对学龄期近视进展儿童进行调节功能的客观检查与分析，观察调节功能与近视进展之间的相关性。方法　选取2017年至2018年在首都医科大学附属北京同仁医院视光学门诊定期就诊的71名学龄期儿童为研究对象，根据受试者近年的屈光度进展速度，按≤0.50 D·a^-1、>0.50~1.00 D·a^-1、>1.00~1.50 D·a^-1、>1.50 D·a^-1分为4组，使用人眼调节分析仪对受试者进行调节功能的客观测量与分析，记录不同调节刺激视标下4组的客观调节反应值和客观调节微波动值，并作对比。结果　在所有调节视标上，各组随着调节刺激幅度增加，客观调节反应值也逐渐增加，4组在不同调节刺激视标下的客观调节反应值及平均的客观调节反应值差异均无统计学意义（均为P＞0.05）。≤0.50 D·a^-1、>0.50~1.00 D·a^-1、>1.00~1.50 D·a^-1、>1.50 D·a^-1近视进展速度组调节微波动值分别为（62.2±5.6）D、（62.5±5.3）D、（66.5±6.0）D和（58.0±6.5）D，4组间差异有统计学意义（F=6.424，P=0.001），在+0.50~-0.50 D、-2.00 D调节刺激视标下，4组的客观调节微波动值比较差异均有统计学意义（均为P＜0.05），在其余调节刺激视标下差异均无统计学意义（均为P＞0.05）。结论　对于学龄期儿童的近视进展速度，客观调节微波动值相对于客观调节反应值可能是一个更为敏感的相关指标。     

Severe lumbar spinal stenosis combined with Guillain-Barré syndrome: A case report

BACKGROUNDGuillain-Barré syndrome (GBS) is a rare disorder that typically presents with ascending weakness, pain, paraesthesias, and numbness, which mimic the findings in lumbar spinal stenosis. Here, we report a case of severe lumbar spinal stenosis combined with GBS.CASE SUMMARYA 70-year-old man with a history of lumbar spinal stenosis presented to our emergency department with severe lower back pain and lower extremity numbness. Magnetic resonance imaging confirmed the diagnosis of severe lumbar spinal stenosis. However, his symptoms did not improve postoperatively and he developed dysphagia and upper extremity numbness. An electromyogram was performed. Based on his symptoms, physical examination, and electromyogram, he was diagnosed with GBS. After 5 d of intravenous immunoglobulin (0.4 g/kg/d for 5 d) therapy, he gained 4/5 of strength in his upper and lower extremities and denied paraesthesias. He had regained 5/5 of strength in his extremities when he was discharged and had no symptoms during follow-up.CONCLUSIONGBS should be considered in the differential diagnosis of spinal disorder, even though magnetic resonance imaging shows severe lumbar spinal stenosis. This case highlights the importance of a careful diagnosis when a patient has a history of a disease and comes to the hospital with the same or similar symptoms.     

广泛性焦虑障碍心理治疗研究进展

总结广泛性焦虑症(generalized anxiety disorder,GAD)心理治疗方法,分析不同心理治疗的疗效及研究进展,为今后多角度、整合式运用各种心理疗法治疗GAD提供新思路.     

对比四维子宫输卵管超声造影与子宫输卵管造影评估输卵管通畅性效能:Meta分析

目的 采用Meta分析对比四维子宫输卵管超声造影（4D-HyCoSy）与子宫输卵管造影（HSG）评估输卵管通畅性的效能。方法 系统搜索PubMed、Cochrane Library、Embase、Web of Science、中国生物医学文献数据库、中国知网、万方医学网及维普数据库中建库至今有关4D-HyCoSy和/或HSG评估输卵管通畅性的文献。由2名研究人员依据纳入标准和排除标准筛选文献并提取信息；分别计算4D-HyCoSy和HSG评估输卵管通畅性的合并敏感度（SEN）、特异度（SPE）及诊断比值比（DOR），绘制综合受试者工作特征（SROC）曲线，获得曲线下面积（AUC），并以Medcalc 19.1.1统计软件比较AUC。结果 最终纳入19篇文献、1 358例疑似输卵管因素导致不孕患者，其中4篇同时采用4D-HyCoSy及HSG评估输卵管通畅性，10篇仅以4D-HyCoSy评估，5篇仅以HSG评估。Meta分析结果显示，4D-HyCoSy评估输卵管通畅性的合并SEN、SPE及DOR分别为0.92[95%CI（0.91，0.94）]、0.91[95%CI（0.89，0.93）]及115.06[95%CI（54.23，224.10）]；HSG评估输卵管通畅性的合并SEN、SPE及DOR分别为0.84[95%CI（0.81，0.87）]、0.80[95%CI（0.76，0.83）]及28.64[95%CI（10.08，81.35）]。4D-HyCoSy评估输卵管通畅性的AUC为0.98[95%CI（0.96，0.99）]，HSG为0.93[95%CI（0.90，0.95）]，差异有统计学意义（Z=6.97，P<0.01）。结论 4D-HyCoSy评估输卵管通畅性的效能高于HSG。     

刺果甘草全基因组Survey及叶绿体基因组特征分析＊

目的 基于基因组Survey分析对刺果甘草Glycyrrhiza pallidiflora Maxim.基因组大小和杂合率进行估计，并通过叶绿体基因组序列特征对其在甘草属Glycyrrhiza L.中的系统发育位置进行研究。方法 使用二代测序技术对刺果甘草进行测序，采用K-mer方法对测序reads进行分析，估算刺果甘草基因组大小和杂合率，使用生物信息学方法进行叶绿体基因组组装、注释和系统发育分析。结果 Survey分析结果显示其基因组大小约为577.82 Mb，杂合度约为0.31%，重复序列比例约为53.72%。叶绿体基因组长度为127，267 bp，不具有典型的四分体结构，总GC含量为34.32%，包含110个基因，其中76个蛋白质编码基因，30个tRNA基因和4个rRNA基因。系统发育分析表明，刺果甘草与圆果甘草G. squamulosa Franch.亲缘较接近。结论 刺果甘草存在低杂合和重复序列较多的特点，为了更好地对全基因组进行序列拼接和组装，可尝试采用三代测序结合二代测序的分析策略进行基因组组装；刺果甘草叶绿体全基因组比对和系统发育分析，为后续开展甘草属遗传多样性研究和分子鉴定标记筛选提供了重要依据。