Novel missense mutation in VPS33B is associated with isolated low gamma‐glutamyltransferase cholestasis: Attenuated,incomplete phenotype of arthrogryposis,renal dysfunction,and cholestasis syndrome

The typical phenotype of arthrogryposis, renal dysfunction, and cholestasis (ARC) syndrome involves three cardinal symptoms as the name describes, harboring biallelic mutations on VPS33B or VIPAS39. Except for ARC syndrome, low gamma‐glutamyltransferase (GGT) cholestasis often implies hereditary hepatopathy of different severity; however, some remain undiagnosed. Several monogenic defects typically with multiorgan manifestations may only present liver dysfunction at times, such as DGUOK defect and AGL defect. Previously, four VPS33B mutated cases were reported without arthrogryposis, or with less severe symptoms and longer lifespan, indicating the possibility of incomplete ARC phenotype of isolated hepatopathy. So we retrospectively reviewed all patients with confirmed VPS33B/VIPARS39 defect in our center and identified three presenting isolated low‐GGT cholestasis with intractable pruritus. Distinguished from others with typical ARC phenotype, these patients did not suffer the other two typical characteristics, survived much longer, and shared a novel missense VPS33B variation c.1726T>C, p.Cys576Arg, causing declined protein expression and abolished interaction with VIPAS39 in‐vitro. Serum bile acid profiles of our VPS33B/VIPAS39 mutated patients revealed similar changes to primary defect of bile salt export pump, among which those with isolated cholestasis phenotype had a higher level of total secondary bile acids than that with typical ARC phenotype, indicating the partial residual function of VPS33B.     

Hierarchical Archimedean copula models for the analysis of binary familial data

Archimedean copulas are commonly used in a wide range of statistical models due to their simplicity, manageable analytical expressions, rich choices of generator functions, and other workable properties. However, the exchangeable dependence structure inherent to Archimedean copulas limits its application to familial data, where the dependence among family members is often different. When response variables are binary, modeling the familial associations becomes more challenging due to the stringent constraints imposed on the dependence parameters. This paper proposes hierarchical Archimedean copulas to account for the natural hierarchical dependence structure in familial data and addresses the details in the modeling of binary familial data and the inference based on maximum likelihood estimate. An example showing the flexibility of this powerful tool is also presented with possible extension to other similar studies.     

高山红景天多糖的硫酸化修饰及DPPH自由基清除活性研究

目的优选高山红景天多糖(RSP)的最佳硫酸化修饰条件,提高RSP的抗氧化活性。方法利用氯磺酸-吡啶法对RSP进行了硫酸化修饰,并通过单因素实验确定了硫酸化反应的最佳工艺条件;应用红外光谱(IR)和扫描电子显微镜(SEM)对RSP和硫酸化高山红景天多糖(S-RSP)的理化性质进行了分析;通过测定RSP和S-RSP对1,1-二苯基-2-三硝基苯肼(DPPH)自由基的清除能力,考察了S-RSP的取代度(DS)与多糖抗氧化活性之间的关系。结果当氯磺酸与吡啶的体积比为1∶4、反应时间为2 h、反应温度为60℃时,制得的S-RSP的含硫量最大值为18.83%,取代度最大值为2.38。RSP经硫酸化修饰后,增强了其抗氧化活性,S-RSP的DS与DPPH自由基清除能力存在一定的正比例关系。结论氯磺酸与吡啶的体积比影响S-RSP的DS大小;RSP经硫酸化修饰后通过改变多糖的极性而增加了其抗氧化能力。     

LC-MS/MS分析银杏二萜内酯葡胺注射液在人尿液中的代谢产物

目的:研究银杏二萜内酯葡胺注射液在人尿液中的主要代谢产物及其代谢途径。方法:3名受试者静脉滴注银杏二萜内酯葡胺注射液后收集0~6 h的尿样,分别按酸化和不酸化样品处理后,以液相色谱-串联质谱法(LC-MS/MS)对样品进行分析。采用ACE C_(18)-AR色谱柱(4.6 mm×150 mm,3μm),酸性HPLC条件流动相Ⅰ为乙腈-0.4%甲酸铵水溶液(p H3.2)梯度洗脱,中性HPLC条件流动相Ⅱ为乙腈-水梯度洗脱,流速0.7 m L·min~(-1)。通过比较空白尿样和给药后尿样的总离子流和提取离子流色谱图以及各个色谱峰的保留时间、准分子离子和二级碎片离子,分析银杏内酯A(GA),银杏内酯B(GB)和银杏内酯K(GK)在人体内可能的代谢产物。结果:除原型药外,共鉴定了12个代谢产物,其中GA相关的代谢产物有6个,包括5个Ⅰ相和1个Ⅱ相代谢产物;GB相关的有4个,包括1个Ⅰ相和3个Ⅱ相代谢产物;GK相关的有2个,包括1个Ⅰ相和1个Ⅱ相代谢产物。结论:GA在人体内主要的代谢途径为羟基化和内酯环水解,并可进一步共价结合成硫酸酯;GB主要的代谢途径为羟基化和内酯环水解,并可进一步共价结合成硫酸酯、葡萄糖醛酸苷或谷胱甘肽结合物;GK在人体内主要的代谢途径为甲基化葡萄糖醛酸结合反应。     

建构主义理念下的《医古文》趣味互动教学设计

《医古文》课程的传统教学模式存在较大问题,难以达到良好的教学效果。为了改进教学方法,提升教学质量,现以建构主义和形成性教学评价为理论基础,举例采用两种趣味互动教学方式,培养学生对传统文化的兴趣,夯实学生的基础知识,提高学生的古文应用能力。证明趣味互动教学法符合当今学生的认知规律,具有独到的优势,并值得推广。     

Glomus tumor of the index finger

A 41-year-old female patient presented with localized worsening subungual pain of her right index finger. Subsequent diagnostic evaluation revealed the presence of a glomus tumor. A glomus tumor is a rare tumor with a predilection for the hand. Classic symptoms include pain, pain with pressure, and pain with cold temperature. We present a completely updated literature review that addresses the epidemiology, pathology, presentation, diagnostic evaluation, classification, histology, genetics, and treatment options for glomus tumors.     

Self Tapping Screws v/s Erich Arch Bar for Inter Maxillary Fixation: A Comparative Clinical Study in the Treatment of Mandibular Fractures

Introduction and Objective  

Numerous methods have been described for achievement of Intermaxillary fixation in the treatment of fractures of facial skeleton. Conventional methods like Erich arch bars and eyelet wires are currently most common methods for achieving intermaxillary fixation (IMF), but they have their own disadvantages. Since 1989, IMF using intraoral self tapping IMF screws has been introduced for treatment of mandibular fractures. The aim of this work was to compare the efficacy, advantages, disadvantages indications and potential complications associated with Erich archbar v/s self tapping IMF screws in the management of mandibular fractures.