Diagnostic challenges for a novel SH2D1A mutation associated with X‐linked lymphoproliferative disease

Mutations in SH2D1A, encoding the intracellular adaptor signaling lymphocyte activation molecule associated protein (SAP), are associated with X‐linked lymphoproliferative disease type 1 (XLP1). We identified a novel hemizygous SH2D1A c.49G > A (p.E17K) variant in a 21‐year‐old patient with fatal Epstein‐Barr virus infection–associated hemophagocytic lymphohistiocytosis. Cellular and biochemical assays revealed normal expression of the SAP variant protein, yet binding to phosphorylated CD244 receptor was reduced by >95%. Three healthy brothers carried the SH2D1A c.49G > A variant. Thus, data suggest that this variant represents a pathogenic mutation, but with variable expressivity. Importantly, our results highlight challenges in the clinical interpretation of SH2D1A variants and caution in using functional flow cytometry assays for the diagnosis of XLP1.     

经内镜鼻胰管引流在重症急性胰腺炎治疗中的应用

目的 :初步总结经内镜鼻胰管引流在重症急性胰腺炎治疗中应用的疗效。　方法 :自 1998年 3月以来 ,在重症急性胰腺炎患者入院后常规非手术监测治疗的同时 ,随机床旁行经内镜置放鼻胰管引流 14例。其中明确合并胆结石 8例。观察每天胰管引流量和入院后第 5天在体温、心率、白细胞计数、血糖、血钙、动脉氧分压和血、尿淀粉酶的变化 ,并与第 1天比较 ,记录治疗结果和住院时间。　结果 :经鼻胰管引流时间为 (7.3± 4 .0 )天 ,前 5天的胰液引流量分别为每天 (2 36 .4± 176 .6 )、(2 87.1± 16 4 .7)、(2 84 .6± 2 16 .4 )、(435 .0± 35 7.8)ml和 (377.8± 2 2 3.8)ml。入院后第 1天和第 5天的体温为 (38.2± 0 .6 )和 (37.2± 0 .8)℃ (P <0 .0 1)、心率为 (10 2 .3± 17.0 )和 (82 .9± 14 .5 )次 /min(P <0 .0 1) ,白细胞计数为 (14 .6± 4 .2 )和 (10 .1± 5 .4 )× 10 9/L(P <0 .0 5 ) ,血糖为 (10 .0± 4 .9)和 (8.6± 3.3)mmol/L(P >0 .0 5 ) ,血钙为 (2 .1± 0 .2 )和 (2 .2± 0 .2 )mmol/L(P >0 .0 5 )　动脉氧分压为 (78.0± 16 .3)和 (113.0± 4 1.6 )mmHg(P <0 .0 1) ,血淀粉酶为 (6 95 .7± 4 4 5 .2 )和 (82 .6± 4 7.1)U/L(P <0 .0 1) ,尿淀粉酶为 (3174 .1± 2 5 4 2 .5 )和(2 86 .8± 2     

血清淀粉样P成分的DNA结合特性

目的 检测血清淀粉样P成分(SAP)与不同DNA的结合活性并研究SAP与DNA的结合是否有利于此类抗原的清除，探讨它在SLE发生发展中的作用及意义。方法 用亲和层析和凝胶过滤方法自小鼠和人血清中纯化SAP，分别提取来自细菌、质粒、酵母、小鼠淋巴细胞等不同DNA，用DOT-EIA方法检测SAP与它们的结合活性，用巨噬细胞吞噬实验观察SAP与DNA结合后对DNA清除的影响。结果 人和小鼠SAP均与细菌DNA结合最强，其次为质粒、酵母DNA，与淋巴细胞DNA和小牛胸腺DNA的结合较弱，与单链λDNA结合最弱；与来源于活化状态小鼠淋巴细胞DNA的结合力高于非活化状态；SAP与活化淋巴细胞DNA结合后可促进巨噬细胞对DNA的吞噬。结论 SAP与不同DNA结合活性各异。     

Drosophila dSAP18 is a nuclear protein that associates with chromosomes and the nuclear matrix, and interacts with pinin, a protein factor involved in RNA splicing

SAP18 is a highly conserved protein that was proposed to be involved in multiple cellular processes from autophagy to gene regulation and mRNA processing. In this paper we show that, in Drosophila, dSAP18 is a predominantly nuclear protein that associates to both chromosomes and the nuclear matrix. dSAP18 becomes nuclear early during development, at the onset of cellularization, and remains so all through embryo development. dSAP18 is also nuclear in salivary glands, ovaries and cultured S2 cells. Here we also show that dSAP18 forms a complex with the Drosophila homolog of pinin (dPnn), a protein factor involved in mRNA splicing. dSAP18-dPnn interaction was confirmed in vivo, through co-immunoprecipitation experiments, as well as in vitro, through GST pull-down assays. These results are discussed in the context of the possible functions played by SAP18.     

基于KAP模式护理对重症急性胰腺炎患者康复的影响

目的探讨基于KAP模式护理对重症急性胰腺炎(SAP)患者康复的影响。方法选择我院2018年8月至2019年8月收治的SAP患者88例,随机分为两组各44例。对照组采用常规护理模式,观察组在对照组基础上采用基于KAP模式护理。比较两组的护理效果。结果护理后,观察组的腹痛、腹胀持续时间以及住院时间均短于对照组,RASS评分低于对照组,GCS评分高于对照组,差异有统计学意义(P<0.05)。结论基于KAP模式护理可缩短重症急性胰腺炎患者的临床症状持续时间及住院时间,改善患者的疼痛状况及生存质量。     

急性重症胰腺炎合并真菌感染分析及对策

目的探讨急性重症性胰腺炎(SAP)合并真菌感染特点及影响感染的高危因素。方法对1995年以来我院共收治SAP病人82例,根据病因分为两组:胆原性为(A组)46例,其他原因(饮酒、不明原因等)为(B组)36例。对患者入院时APCHEⅡ积分、肠麻痹、留置尿管、静脉营养、高血糖、肝功能障碍、应用抗生素情况等相关因素进行统计学分析。结果82例合并真菌感染22例,发生率为26.8%,A组合并真菌感染发生率21.7%,B组合并真菌感染发生率33.3%。有APCHEⅡ积分、肠麻痹、肠外营养、抗生素应用4个变量进入回归方程。四项指标危险因素与真菌感染发生率有明显相关(p<0.05)。结论对于APCHEⅡ积分(15.45±4.56)以上尤其是非胆原性SAP,肠麻痹和肠外营养≥7d、连续联合应用抗生素≥15d者应高度重视有真菌感染危险。     

重亚硫酸盐修饰直接测序技术检测p16基因甲基化的研究

目的建立稳定的重亚硫酸盐直接测序技术，检测p16基因甲基化状况。方法提取正常人全血基因组DNA．建立起稳定的重亚硫酸盐直接测序平台，利用该技术检测结直肠癌细胞株pl6基因甲基化状况。结果应用列联表的Fisher，Exact Test比较3种纯化方法的测序结果，乙醇／醋酸钠和过柱纯化与SAP—ExonI纯化法比较，测序结果差异有统计学意义（P〈0．05）；应用重亚硫酸盐直接测序技术，可检测出p16基因目的片段中CpG岛所有CpG位点的甲基化状况。结论应用SAP—ExonI纯化法，建立了稳定的重亚硫酸盐直接测序技术，并可检测出目的片段中CpG岛所有CpG位点的甲基化状况。     

131Ⅰ-SAP的制备及应用安全性研究

目的探讨一种新型淀粉样变性诊断标记物131I-SAP的制备方法及其应用安全性。方法应用Iodogen法对SAP标准品进行131I标记;纸层析法测定131I-SAP的标记率与放射化学纯度。将131I-SAP分别于4℃和37℃新鲜人血清中0h,24h,48h,72h和96h,测定放射化学纯度,评价其体外稳定性。对131I-SAP进行热原、异常毒性等安全性实验。结果131I-SAP的标记率为70.6%,96h后的放射化学纯度仍大于90%。热原、异常毒性实验均为阴性。结论131I-SAP具有较好的体外稳定性,并且无热原及明显毒性反应,适合进一步临床实验及应用的安全性。     

High-resolution manometry and impedance-pH/manometry: valuable tools in clinical and investigational esophagology

Both high-resolution manometry (HRM) and impedance-pH/manometry monitoring have established themselves as research tools and both are now emerging in the clinical arena. Solid-state HRM capable of simultaneously monitoring the entire pressure profile from the pharynx to the stomach along with pressure topography plotting represents an evolution in esophageal manometry. Two strengths of HRM with pressure topography plots compared with conventional manometric recordings are (1) accurately delineating and tracking the movement of functionally defined contractile elements of the esophagus and its sphincters, and (2) easily distinguishing between luminal pressurization attributable to spastic contractions and that resultant from a trapped bolus in a dysfunctional esophagus. Making these distinctions objectifies the identification of achalasia, distal esophageal spasm, functional obstruction, and subtypes thereof. Ambulatory intraluminal impedance pH monitoring has opened our eyes to the trafficking of much more than acid reflux through the esophageal lumen. It is clear that acid reflux as identified by a conventional pH electrode represents only a subset of reflux events with many more reflux episodes being composed of less acidic and gaseous mixtures. This has prompted many investigations into the genesis of refractory reflux symptoms. However, with both technologies, the challenge has been to make sense of the vastly expanded datasets. At the very least, HRM is a major technological tweak on conventional manometry, and impedance pH monitoring yields information above and beyond that gained from conventional pH monitoring studies. Ultimately, however, both technologies will be strengthened as outcome studies evaluating their utilization become available.     

红细胞分布宽度对急性重症胰腺炎患者院内死亡的预测价值

目的：探讨红细胞分布宽度（ red blood cell distribution width, RDW）对急性重症胰腺炎（ severe acute pancreatitis, SAP）患者院内死亡的预测价值。方法95例SAP患者,按住院期间是否死亡分为死亡组和非死亡组。分析两组患者的基本临床资料,通过二分类Logistic回归分析得出院内死亡的危险因素,绘制ROC曲线,分析RDW对SAP患者院内死亡的预测价值。结果死亡组的血糖、血钙、血肌酐、氧合指数、白蛋白、乳酸脱氢酶、血红蛋白、红细胞压积、RDW、APACHEⅡ评分与Ranson 评分等指标与非死亡组比较差异有统计学意义（ P＜0．05）;二分类Logistic回归分析显示,RDW、APACHEⅡ评分、Ranson 评分、白蛋白、氧合指数、血肌酐等指标为院内死亡的独立危险因素（P ＜0．05）;ROC 曲线分析显示,RDW 曲线下面积为0．907（95％CI 0．928～0．968,P＝0．000）,APACHEⅡ评分为0．864（95％CI 0．812～0．915,P＝0．000）,氧合指数为0．848（95％CI 0．785～0．833,P＝0．001）。结论 RDW是SAP患者预后的独立预测因子,对SAP患者院内死亡的预测价值较高。