A second individual with rhizomelic spondyloepimetaphyseal dysplasia and homozygous variant in GNPNAT1

Spondyloepimetaphyseal dysplasias (SEMDs) belong to a clinically and genetically heterogeneous group of inherited skeletal disorders defined by a defect in the growth and shape of vertebrae, epiphyses and metaphyses. Rhizomelic SEMD is characterized by a disproportionate small stature caused by severe shortening and deformation of the limbs’ proximal bones, with the cranio-facial sphere unaffected. We report a second individual, an 8-year-old girl, with autosomal recessive rhizomelic SEMD associated with a homozygous exonic missense variant, c.226G > A p.(Glu76Lys), in GNPNAT1 identified by trio genome sequencing. Our data corroborate the recent findings of Ain et al. and further delineate the clinical and radiographic features of this form of SEMD associated with rhizomelic dysplasia while outlining a potential hotspot in this newly described genetic disorder.     

高渗盐水和甘露醇在动脉瘤性蛛网膜下腔出血患者降低颅内压中的应用

目的比较3%高渗盐水和20%甘露醇治疗重症动脉瘤性蛛网膜下腔出血所致颅内压增高的疗效.方法25例动脉瘤性蛛网膜下腔出血患者出现颅内压增高事件时, 随机交替接受等渗透剂量的160 mL 3%高渗盐水与150 mL 20%甘露醇进行降低颅内压治疗, 连续监测患者颅内压、平均动脉压、脑灌注压及中心静脉压.记录有效降低颅内压持续时间、颅内压最大降幅及其时间, 用药前及用药后1 h、3 h血钠水平及血浆渗透压.结果3%高渗盐水和20%甘露醇均可降低颅内压(均 P < 0.01), 两者的降低颅内压作用持续时间及颅内压降幅差异均无统计学意义(均 P >0.05).患者脑灌注压较用药前均上升(均 P < 0.01), 平均动脉压先上升后下降, 但差异无统计学意义( P >0.05).患者中心静脉压稍有波动, 但差异均无统计学意义(均 P >0.05).20%甘露醇治疗后患者血钠下降, 3%高渗盐水治疗后患者血钠值上升, 变化均有统计学意义(均 P < 0.05).20%甘露醇及3%高渗盐水治疗后患者血浆渗透压均先上升后下降, 变化均有统计学意义(均 P < 0.01). 结论3%高渗盐水可作为治疗动脉瘤性蛛网膜下腔出血所致颅内压增高患者的一线治疗药物.     

Vaccination inhibits the human adenoviral transduction in a mouse keratoconjunctivitis model

Adenovirus infections are a major cause of epidemic keratoconjunctivitis (EKC), which can lead to corneal subepithelial infiltrates and multifocal corneal opacity. In the current study, we investigated the use of an E1/E3-deleted adenovirus serotype 5 (Ad5) vector as a vaccine administered intramuscularly (IM) or intranasally (IN) against subsequent challenges with a luciferase-expressing Ad5 (Ad5-Luci) vector via eyedrop. We evaluated the adaptive immune response to Ad5 vector vaccination and confirmed a robust polyfunctional CD8 T cell response in splenic cells. Neutralizing Ad5 antibodies were also measured in the sera of vaccinated mice as well as Ad5 antibody in the eye wash solutions. Upon challenge with Ad5-Luci vector 8 weeks post the primary immunization, transduction was significantly reduced by > 70% in the vaccinated mice, which was slightly better in IM- vs. that in IN-vaccinated animals. Resistance to subsequent challenge was observed 10 months post primary IM vaccination, with sustained reduction up to 60% in the Ad5-Luci vector transduction. Passive immunization of naive mice with antisera from IM to vaccinated mice subsequently challenged with the Ad5-Luci vector resulted in approximately 40% loss in transduction efficiency. Furthermore, the mice that received IM immunization with or without CD8 T cell depletion showed > 40% and 70% reductions, respectively, in Ad8 genomic copies after Ad8 topical challenge. We conclude that Ad-vector vaccination successfully induced an adaptive immune response that prevented subsequent Ad transduction in the cornea and conjunctiva-associated tissues in a mouse model of adenovirus keratoconjunctivitis, and that both cellular and humoral immunity play an important role in preventing Ad transduction.     

聚焦解决护理模式结合健康教育对银屑病患者心理状态、应对方式的影响

目的 探讨聚焦解决护理模式结合健康教育对银屑病患者心理状态、应对方式的影响。方法 选取2020年2月至2021年2月我院收治的100例银屑病患者,随机分为观察组(聚焦解决护理模式结合健康教育)与对照组(常规健康教育)。比较两组的心理状态及应对方式。结果 干预后,观察组的焦虑自评量表(SAS)、抑郁自评量表(SDS)评分低于对照组(P<0.05)。干预后,观察组的面对评分高于对照组,屈服、回避评分低于对照组(P<0.05)。干预后,观察组的病耻感评分低于对照组(P<0.05)。结论 聚焦解决护理模式结合健康教育可有效改善银屑病患者的不良情绪,减轻病耻感,转变疾病应对方式。     

Evodiamine-inspired dual inhibitors of histone deacetylase 1 (HDAC1) and topoisomerase 2 (TOP2) with potent antitumor activity

A great challenge in multi-targeting drug discovery is to identify drug-like lead compounds with therapeutic advantages over single target inhibitors and drug combinations. Inspired by our previous efforts in designing antitumor evodiamine derivatives, herein selective histone deacetylase 1 (HDAC1) and topoisomerase 2 (TOP2) dual inhibitors were successfully identified, which showed potent in vitro and in vivo antitumor potency. Particularly, compound 30a was orally active and possessed excellent in vivo antitumor activity in the HCT116 xenograft model (TGI = 75.2%, 150 mg/kg, p.o.) without significant toxicity, which was more potent than HDAC inhibitor vorinostat, TOP inhibitor evodiamine and their combination. Taken together, this study highlights the therapeutic advantages of evodiamine-based HDAC1/TOP2 dual inhibitors and provides valuable leads for the development of novel multi-targeting antitumor agents.     

硫酸镁、硝苯地平和酚妥拉明治疗妊高症

目的探讨对妊娠高血压综合征患者给予硫酸镁联合硝苯地平以及酚妥拉明治疗的临床效果。方法抽取医院在2018年2月-2019年2月所接收的156例妊娠高血压综合征患者,将其按照数字随机表的方法分为单纯组和联合组,每组分别为78例。单纯组给予单纯的硫酸镁进行治疗,联合组在单纯组给予硝苯地平以及酚妥拉明进行联合治疗,比较患者的治疗效果。结果联合组的治疗有效率显著高于单纯组,治疗前血压水平差异无统计学意义(P>0.05),治疗后联合组的收缩压和舒张压水平均低于单纯组,P<0.05,两组差异有统计学意义。结论对妊娠高血压综合征患者给予硫酸镁联合硝苯地平和酚妥拉明进行联合治疗,有效改善患者的血压水平。     

"钾维普"停搏液对幼鼠心脏缺血期舒张力的影响

目的 研究“钾维普“停搏液对SD幼鼠心脏缺血期舒张力的影响.方法 健康SD幼鼠32只随机分为正常灌注组、缺血再灌注组、传统高钾组和“钾维普“组,采用Langendorff离体心脏灌流模型,比较“钾维普“停搏液、传统高钾停搏液对缺血期心脏舒张力的影响.结果 缺血期间,传统高钾停搏液停搏的心脏舒张力上升217.8%,“钾维普“停搏液停搏的心脏舒张力降低11%.结论 “钾维普“停搏液停搏的心脏缺血期间基础张力降低,有利于缺血心肌的保护.     

Low Molecular Weight Dextran Sulfate: A Strong Candidate Drug to Block IBMIR in Clinical Islet Transplantation

The instant blood-mediated inflammatory reaction (IBMIR) is triggered in clinical islet transplantation when human pancreatic islets come in contact with blood and may explain the initial tissue loss associated with this procedure. Low molecular weight dextran sulfate (LMW-DS; MM 5000), today available for clinical use, inhibits both complement and coagulation activation. In a tubing loop model, LMW-DS at concentrations ranging from 0.01 to 1 g/L showed a dose-dependent inhibition of IBMIR with an inhibition of coagulation and complement activation and less consumption of platelets and other blood cells. In blood or plasma APTT was demonstrated to be an excellent method for monitoring the LMW-DS concentration both in vitro and in vivo in a nonhuman primate model. The toxicity was assessed using a glucose challenge test and the pharmacokinetics was tested in the nonhuman primate model. Here, we present a tentative protocol for using LMW-DS in clinical islet transplantation.     

Lugol液染色对食管早期癌和癌前病变的诊断价值

目的 探讨Lugol液染色对食管早期癌和癌前病变的诊断价值。方法 对45例食管黏膜可疑病变经内镜以2％Lugol液喷洒染色，观察黏膜染色情况，并取活检送病理组织学检查。结果 45例食管病变染色后，39例呈浅染色或不染色，其中食管癌8例（食管早期癌5例，进展期癌3例），Barrett食管5例，轻至中度不典型增生1l例。本组Lugol液染色对食管早期癌和癌前病变的检出率达46．7％。结论 内镜下应用Lugol液染色结合活检有助于食管早期癌和癌前病变的诊断，且操作简便，具有重要的临床价值。