采用DSA设备评价吞咽功能的初步探讨

目的:探讨运用DSA设备作吞咽功能检查的价值。材料和方法:用DSA设备对正常组24例,咽异感症患者32例,做上至颅底、下达第七颈椎平面的正侧位动态采集,了解吞咽状况,并行咽传输时间测定,进行对照研究。结果:正常对照组咽传输时间为1.441±0.302s,咽异感症患者咽传输时间为1.367±0.409s,两组结果相比统计学上无显著差异,但后者较易发生咽部钡剂滞留等改变。结论:DSA机由于采集速度快,不但在心血管检查及介入治疗方面有重要意义,而且在非血管性脏器的动力学检查中也起着一定的作用。由于能完整记录钡剂通过咽部的全过程,故此方法是吞咽功能检查的良好方法之一。     

Transporting carriers for intracellular targeting delivery via non-endocytic uptake pathways

Abstract

To develop novel therapies for clinical treatments, it increasingly depends on sophisticated delivery systems that facilitate the drugs entry into targeting cells. Profound understanding of cellular uptake routes for transporting carriers promotes the optimization of performance in drug delivery systems. Although endocytic pathway is the most important part of cellular uptake routes for many delivery systems, it suffers the trouble of enzymatic degradation of transporting carriers trapped in endosomes/lysosomes. Therefore, it is desirable to develop alternative transporting methods for delivery systems via non-endocytic pathways to achieve more effective intracellular delivery. In this review, we summarize the literature exploring transporting carriers that mediate intracellular delivery via non-endocytic pathways to present the current research status in this field. Cell-penetrating peptides, pH (low) insertion peptides, and nanoparticles are categorized to exhibit their ability to directly transport various cargos into cytoplasm via non-endocytic uptake in different cell lines. It is hoped that this review can spur the interesting on development of drug delivery systems via non-endocytic uptake pathway.     

Of men and mice: Human X-linked retinoschisis and fidelity in mouse modeling

X-linked Retinoschisis (XLRS) is an early-onset transretinal dystrophy, often with a prominent macular component, that affects males and generally spares heterozygous females because of X-linked recessive inheritance. It results from loss-of-function RS1 gene mutations on the X-chromosome. XLRS causes bilateral reduced acuities from young age, and on clinical exam and by ocular coherence tomography (OCT) the neurosensory retina shows foveo-macular cystic schisis cavities in the outer plexiform (OPL) and inner nuclear layers (INL). XLRS manifests between infancy and school-age with variable phenotypic presentation and without reliable genotype-phenotype correlations. INL disorganization disrupts synaptic signal transmission from photoreceptors to ON-bipolar cells, and this reduces the electroretinogram (ERG) bipolar b-wave disproportionately to photoreceptor a-wave changes. RS1 gene expression is localized mainly to photoreceptors and INL bipolar neurons, and RS1 protein is thought to play a critical cell adhesion role during normal retinal development and later for maintenance of retinal structure. Several independent XLRS mouse models with mutant RS1 were created that recapitulate features of human XLRS disease, with OPL-INL schisis cavities, early onset and variable phenotype across mutant models, and reduced ERG b-wave to a-wave amplitude ratio. The faithful phenotype of the XLRS mouse has assisted in delineating the disease pathophysiology. Delivery to XLRS mouse retina of an AAV8-RS1 construct under control of the RS1 promoter restores the retinal structure and synaptic function (with increase of b-wave amplitude). It also ameliorates the schisis-induced inflammatory microglia phenotype toward a state of immune quiescence. The results imply that XLRS gene therapy could yield therapeutic benefit to preserve morphological and functional retina particularly when intervention is conducted at earlier ages before retinal degeneration becomes irreversible. A phase I/IIa single-center, open-label, three-dose-escalation clinical trial reported a suitable safety and tolerability profile of intravitreally administered AAV8-RS1 gene replacement therapy for XLRS participants. Dose-related ocular inflammation occurred after dosing, but this resolved with topical and oral corticosteroids. Systemic antibodies against AAV8 increased in dose-dependent fashion, but no antibodies were observed against the RS1 protein. Retinal cavities closed transiently in one participant. Technological innovations in methods of gene delivery and strategies to further reduce immune responses are expected to enhance the therapeutic efficacy of the vector and ultimate success of a gene therapy approach.     

血脑屏障上P-糖蛋白及其调节因素研究新进展

许多中枢神经系统疾病药物治疗的疗效都受到血脑屏障的影响,而P-糖蛋白作为ABC超家族的成员之一,是血脑屏障上最为重要的一环,也是限制药物进入脑中的最重要的屏障。因此对于P-糖蛋白的调节将改变进入脑中药的浓度,也就对许多脑科疾病例如神经系统肿瘤、癫痫、艾滋病脑病的治疗产生很大的影响。本文主要论述了BBB上P-糖蛋白的特性、研究方法、调节因素,以及临床应用方面的研究进展情况,旨在为增加药物的BBB通透性、提高脑内靶点药物浓度提供新的研究思路。     

血脑屏障上的P-糖蛋白及其转运功能研究进展

P-糖蛋白(P-glycoprotein,P-gp)是一个由分子量170-180KD组成的糖蛋白,其主动的药物外排作用是造成肿瘤细胞产生多药耐药性(Multidrug resistance,MDR)的重要原因。近年来研究发现,P-糖蛋白在机体正常组织如血脑屏障(blood-brain barrier,BBB)也呈高度表达。本文归纳了P-糖蛋白的逆转剂及其底物的特征,系统介绍了血脑屏障上P-糖蛋白的转运功能及其研究方法,期望为P-糖蛋白逆转剂的应用以及中枢神经系统疾病的治疗提供帮助。     

缺氧对心肌细胞内游离钙离子浓度和SERCA2表达的影响及薯蓣皂甙的干预作用

目的　研究缺氧对心肌细胞内游离钙离子浓度和肌浆网上的钙离子ATP酶(SERCA2 )的表达的影响及薯蓣皂甙的干预作用。方法　在离体心肌细胞培养基础上制备心肌细胞缺氧模型 ,随机分为 4组 :正常对照组 ,缺氧损伤组 ,薯蓣皂甙组 ,钙拮抗剂组。分别测定各组心肌细胞内游离钙离子的浓度 (FURA2 /AM荧光探针法 )和SERCA2的含量 (Westernblot法 )。结果　缺氧损伤组心肌细胞内游离钙离子的浓度较正常对照组明显增加 ,SERCA2的表达明显减弱 (P均 <0 0 1 ) ;薯蓣皂甙组和钙拮抗剂组心肌细胞内游离钙离子的浓度较缺氧损伤组明显降低 (P <0 0 1 ) ,SERCA2的表达明显增强 (P <0 0 5 )。结论　薯蓣皂甙通过增强肌浆网上钙泵SERCA2的表达减轻缺氧心肌细胞的钙超负荷 ,它对缺氧心肌细胞具有保护作用 ,其作用与钙拮抗剂类似。     

基于智慧化轨道物流标本转运标准化管理应用效果研究

目的：探讨智慧化轨道物流标准化转运模式在临床检验标本转运中的应用效果。方法：选取我院2021年9月份临床10844件标本作为对照组。选取我院2021年11月份8681份样本为观察组。对照组采用传统人工模式转运,观察组采用智慧化轨道物流小车转运,比较两组间的平均标本转运时间。结果：有效节省人力时间（节省2.9个人力）,观察组标本转运时间明显短于对照组（P<0.01）,观察组标本差错率与泼洒率明显低于对照组（P<0.05）。结论：智慧化轨道物流转运标本标准化管理提升临床检验标本转运效率效果显著。     

骨搬运治疗胫骨骨缺损中滑移段外固定取出后发生回缩现象的相关因素分析

目的 探讨骨搬运治疗胫骨骨缺损过程中在对合端愈合前滑移段外固定去除后发生回缩现象的相关因素。方法 回顾性研究。纳入2009年1月—2019年12月无锡市人民医院和无锡市骨科医院胫骨骨缺损应用骨搬运治疗,在对合端愈合前滑移段外固定去除或失效发生不同程度回缩的41例患者,男25例、女16例,年龄18～71(40±15)岁。用Pearson相关分析滑移段回缩距离与患者年龄、性别、受伤至手术时间、骨缺损长度、手术次数、滑移段长度、骨搬运长度、滑移段固定时间和外固定去除或松动失效前、后两次影像学检查的间隔时间等9个因素的相关性,筛选出有统计学意义的影响因素再行多元线性回归分析。结果 41例患者中,受伤至骨搬运时间7～95(40.54±25.65)d,骨缺损长度5.0～11.0(6.90±1.20)cm,手术次数1～5(1.64±0.82)次,滑移段长度4.8～12.0(9.68±2.24)cm,骨搬运长度4.5～11.0(6.76±1.64)cm,滑移段固定时间3.5～11.5 (7.47±1.94)个月,间隔时间5～21(10.16±4.07)d,滑移段回缩距离1.5～30.0(8.73±7.99)mm。Pearson相关分析显示,滑移段回缩距离与滑移段固定时间呈负相关,与骨搬运长度和滑移段长度呈正相关,差异均有统计学意义(r=-0.897、0.501、0.419, P值均＜0.05);滑移段回缩距离与年龄、性别、受伤至手术时间、骨缺损长度、手术次数和间隔时间均无相关性,差异均无统计学意义(P值均＞0.05)。多元线性回归分析显示,骨搬运长度和滑移段固定时间与滑移段发生回缩存在线性关系(t=-10.385、3.027, P值均＜0.05)。回归方程:＾Y_{回缩距离(mm)}=27.081-2.805X_{滑移段固定时间(月)}+0.447X_{骨搬运长度(cm)}(R²=0.805, F=13.256, P＜0.01)。结论 骨搬运过程回缩程度与滑移段长度、骨搬运长度、固定时间相关,其中骨搬运长度和固定时间与滑移段回缩程度存在线性关系。     

刘启泉教授基于“随变而调气”论治慢性萎缩性胃炎

“随变而调气”出自《灵枢·卫气失常》,此治则虽针对针刺治疗而设,但其适用范围绝不限于此,在中医辨证施治过程中亦有重要指导意义。慢性萎缩性胃炎(CAG)是消化系统多发病、难治病,临床起病隐匿、病程较长。刘启泉教授临证之时,认为CAG病机复杂,虚实相兼,以气机不调为基本病机,且CAG患者同病不同症,是因多种病因交织引起气机变化,气机不畅发为呕恶,气滞生湿而生月真胀,气不行血而成痛症,气机不降发为嗳气,气行不畅以致食积。刘启泉教授承古法创新义,临证中将“随变而调气”治则,延伸至治疗CAG中,因变而随治,以调气治之,以行气、理气、降气、运气四法调治CAG,常得佳效。     

子宫内缺血缺氧及再灌注中胎鼠脑组织内质网与线粒体ATP酶的动态变化

目的　观察胎鼠宫内缺血缺氧后 ,线粒体与内质网钙离子 腺苷三磷酸酶 (Ca2 + ATPase)与钠离子 钾离子腺苷三磷酸酶 (Na+ K+ ATPase)的变化 ,及细胞内Ca2 + 超载与紊乱的机理。方法　制备胎鼠宫内不同程度缺血缺氧及再灌注模型 (缺血缺氧组 :缺血缺氧时间分别为 15、30、4 5、6 0min ;再灌注组 :缺血缺氧 15min后 ,分别再灌注 1、4、8、15、2 4h) ,各时间点分别有胎鼠 7～ 11只 ,假手术组胎鼠 12只。分离出胎鼠脑组织中线粒体与内质网 (匀浆后称微粒体 )行酶活性测定。结果　缺血缺氧组 :缺血缺氧 15、30、4 5、6 0min时 ,线粒体Ca2 + ATPase活性明显减弱 ,分别为 (6 1± 0 5 )、(5 7±0 8)、(5 7± 0 5 )、(5 4 1± 0 7) μmolPi/mg(蛋白·小时 ) ,差异有极显著性 (P <0 0 1) ;Na+ K+ ATPase活性也进行性降低 (P <0 0 1)。内质网Ca2 + ATPase活性变化不明显 (P >0 0 5 ) ,而Na+ K+ ATPase活性仍进行性降低 (P <0 0 1)。再灌注组 :1、4、8、15、2 4h时 ,线粒体Ca2 + ATPase活性明显减弱 ,分别为(7 0± 1 0 )、(6 8± 1 2 )、(7 5± 0 8)、(7 2± 0 9)、(6 7± 0 9) μmolPi/mg(蛋白·小时 ) ,差异有极显著性(P <0 0 1) ;内质网Ca2 + ATPase活性变化不明显 (P >0 0 5 ) ;Na+