Heat shock protein is a key therapeutic target for nerve repair in autoimmune peripheral neuropathy and severe peripheral nerve injury

Guillain-Barré syndrome (GBS) is an autoimmune peripheral neuropathy and a common cause of neuromuscular paralysis. Preceding infection induces the production of anti-ganglioside (GD) antibodies attacking its own peripheral nerves. In severe proximal peripheral nerve injuries that require long-distance axon regeneration, motor functional recovery is virtually nonexistent. Damaged axons fail to regrow and reinnervate target muscles. In mice, regenerating axons must reach the target muscle within 35 days (critical period) to reform functional neuromuscular junctions and regain motor function. Successful functional recovery depends on the rate of axon regeneration and debris removal (Wallerian degeneration) after nerve injury. The innate-immune response of the peripheral nervous system to nerve injury such as timing and magnitude of cytokine production is crucial for Wallerian degeneration. In the current study, forced expression of human heat shock protein (hHsp) 27 completely reversed anti-GD-induced inhibitory effects on nerve repair assessed by animal behavioral assays, electrophysiology and histology studies, and the beneficial effect was validated in a second mouse line of hHsp27. The protective effect of hHsp27 on prolonged muscle denervation was examined by performing repeated sciatic nerve crushes to delay regenerating axons from reaching distal muscle from 37 days up to 55 days. Strikingly, hHsp27 was able to extend the critical period of motor functional recovery for up to 55 days and preserve the integrity of axons and mitochondria in distal nerves. Cytokine array analysis demonstrated that a number of key cytokines which are heavily involved in the early phase of innate-immune response of Wallerian degeneration, were found to be upregulated in the sciatic nerve lysates of hHsp27 Tg mice at 1 day postinjury. However, persistent hyperinflammatory mediator changes were found after chronic denervation in sciatic nerves of littermate mice, but remained unchanged in hHsp27 Tg mice. Taken together, the current study provides insight into the development of therapeutic strategies to enhance muscle receptiveness (reinnervation) by accelerating axon regeneration and Wallerian degeneration.     

不同类型瓷贴面与树脂水门汀对贴面密合度与微渗漏的影响

目的:观察瓷贴面类型及树脂水门汀对瓷贴面边缘密合度及微渗漏的影响。方法:36颗上颌中切牙随机均分为四组进行贴面修复,A组:IPS e.max Press瓷贴面+RelyXTM Veneer树脂水门汀;B组:IPS e.max Press瓷贴面+Vitique树脂水门汀;C组:CAD/CAM长石质瓷贴面+RelyXTM Veneer树脂水门汀;D组:CAD/CAM长石质瓷贴面+Vitique树脂水门汀。贴面粘接后经冷热循环老化、亚甲基蓝染色,在显微镜下观测贴面唇面中央及近远中轴角区纵截面边缘密合度及微渗漏情况。结果:A、B、C、D组平均密合度分别为(0.037±0.007)mm、(0.044±0.012)mm、(0.046±0.014)mm、(0.038±0.004)mm,龈边缘染料渗入平均深度分别为(0.143±0.085)mm、(0.148±0.087)mm、(0.236±0.074)mm、(0.158±0.036)mm,组间均无显著差异。B、C、D组近远中轴角区微渗漏情况重于唇面正中区。结论:单颗贴面内部不同区域密合度较一致,但近远中轴角区微渗漏情况更严重,贴面类型及树脂水门汀对瓷贴面平均边缘密合度及微渗漏无显著影响。     

碳青霉烯耐药高毒力肺炎克雷伯菌的实验室研究及与临床转归相关危险因素分析

目的　研究碳青霉烯耐药高毒力肺炎克雷伯菌（ hypervirulent and carbapenem-resistant Klebsiella pneumonia, CR-HvKP）实验室检测及临床转归相关危险因素。方法　回顾性研究 2016年 12月～ 2017年 12月河北医科大学第二医院 CR-HvKP感染患者 20例,对患者临床资料进行分析,采用 PCR检测毒力基因 (rmpA和 rmpA2)、血清型（ K1和 K2）以及碳青霉烯酶基因（ KPC-2,NDM-1,OXA,VIM和 IMP）。结果　20例 CR-HvKP感染患者中,毒力基因 rmpA2均为阳性,拉丝试验阳性 17例（85%）,K2血清型 16例（80%）和碳青霉烯酶基因 KPC-2型 18例（90%）。标本来源主要为痰 /肺泡灌洗液 16例（80%）,治疗好转 9例 (45%)和治疗无效 11例 (55%)。患者使用气管插管辅助呼吸以及感染并发症危及生命的感染性休克治疗无效和好转比较 ,差异均具有统计学意义 (χ2=5.690～ 7.593,均 P<0.05)。结论　CR-HvKP感染临床治愈率低,传播性强,应引起高度重视。     

超声心动图在卵圆孔通道血流受限合并心功能异常产前诊断中的应用价值

目的探讨超声心动图在单纯卵圆孔通道血流受限（FOCR）合并心功能异常胎儿产前诊断及预后评估中的应用价值。 方法回顾性选取2018年10月至2020年5月在河北生殖妇产医院检查,产前超声心动图诊断为单纯FOCR且心血管整体评分（CVPS）提示心功能异常的胎儿16例,分析其初诊、分娩前及出生后的超声心动图特征、CVPS及心功能变化,并随访其妊娠结局和预后。 结果14例表现为卵圆孔内径或卵圆孔通道有效分流口内径＜3 mm,2例表现为卵圆孔内径/房间隔总长度＜0.33。16例胎儿分娩前均表现为右心房与左心房横径比（RA/LA）、右心室与左心室横径比（RV/LV）、主肺动脉与升主动脉内径比（MPA/AAO）比值增大,且随孕龄增大而增大,卵圆孔通道分流流速（V-FO）＞40 cm/s。16例胎儿中,14例初诊FOCR时CVPS为8~9分,2例初诊未发现心功能异常,CVPS为10分。16例胎儿分娩前,11例表现为轻度心力衰竭,CVPS为8~9分;5例表现为中度心力衰竭,CVPS为6~7分。9例分娩前CVPS较初诊FOCR时减低。16例胎儿出生后,1例于新生儿期死亡;余15例均存活。存活患儿中13例复查超声心动图,心脏结构正常;1例分娩前CVPS为6分,出生后复查可疑心肌病;1例分娩前CVPS为8分,出生后复查不除外原发性肺动脉高压。 结论超声心动图在FOCR诊断及评估中具有重要价值;应用超声心动图进行CVPS评分可动态观测并评估胎儿心功能变化,对评估胎儿宫内情况及指导分娩时机具有重要意义。     

慢性肾脏病患者血清胎盘生长因子水平及其与左心室结构和功能的关系

目的 探讨慢性肾脏病(CKD)患者血清胎盘生长因子(placental growth factor,PLGF)水平及其与左心室结构和功能的关系.方法 选取CKD非透析患者72例,年龄、性别相匹配的健康体检者16例作为对照组.采用酶联免疫吸附法测定血清PLGF浓度,心脏超声评定心脏形态和结构.结果 (1)CKD患者血清PLGF显著高于对照组[3.32(2.97,19.77) ng/L比2.33 (2.27,2.49) ng/L,P＜0.01];且随着肾功能的减退,PLGF水平进行性升高(P＜ 0.05/6).(2)CKD各期患者的室间隔厚度(IVST)和左室后壁厚度(LVPWT)升高,射血分数(EF)下降.(3)CKD患者左心室肥厚组血清PLGF显著高于非左心室肥厚组[19.05 (3.31,21.05) ng/L比2.99 (2.60,3.32) ng/L,P＜0.05].PLGF高浓度组左室肥厚发生率显著高于PLGF低浓度组(70％比18％,P＜ 0.01).(4)相关分析显示PLGF与左心室质量指数、收缩压、舒张压、24 h尿蛋白、血肌酐(Scr)、血尿酸(UA)、血尿素氮(BUN)、甲状旁腺激素(iPTH)、高血压病史呈正相关(P＜0.05),与左心室射血分数、血红蛋白(Hb)、血白蛋白(Alb)、肾小球滤过率(eGFR)呈负相关(P＜0.01).多元线性逐步回归分析显示,血肌酐、血红蛋白、射血分数、血尿酸是PLGF的独立相关因素(P＜0.05).结论 CKD患者血清PLGF显著升高,PLGF与CKD患者心脏结构和功能改变密切相关,其可能参与CKD患者心血管事件的发生.     

关注系统性红斑狼疮继发性骨质疏松

系统性红斑狼疮（systemic lupus erythematosus,SLE)是多系统损害的自身免疫性疾病,糖皮质激素和免疫抑制剂是治疗的主要药物。SLE的骨损害包括骨量减少、骨质疏松(osteoporosis. OP)、无菌性骨坏死和骨折,随着SLE生存期的延长,心血管并发症和OP成为影响患者生活质量和生存的主要因素,同时OP对于心血管的发病也有促进作用,是目前备受关注的并发症。OP是一种以骨量减少和骨组织的细微结构破坏为特征的全身性疾病。关于SLE的骨质疏松也存在不少争议,主要集中在OP的发病率和骨质疏松与激素治疗关系两个方面。就OP发病率来讲,不同的研究得出的结论不同。SLE的骨质疏松涉及多种机制包括炎性因素、免疫介导的因素、固有因素、代谢因素、药物因素和疾病本身的因素。SLE相关的骨质疏松的治疗首先是治疗原发病,此外健康的生活方式包括钙剂和维生素D的补充也非常重要,对诊断骨质疏松的SLE患者应及时给予双膦酸盐治疗。     

Effect of Intravenous Administration of Liposomal Prostaglandin E1 on Microcirculation in Patients with ST Elevation Myocardial Infarction Undergoing Primary Percutaneous Intervention

Background:

Several studies have demonstrated that primary percutaneous coronary intervention (PCI) can result in reperfusion injury. This study aims to investigate the effectiveness of liposomal prostaglandin E1 (Lipo-PGE1, Alprostadil, Beijing Tide Pharmaceutical Co., Ltd.) for enhancing microcirculation in reperfusion injury. In addition, this study determined the optimal administration method for acute ST elevation myocardial infarction (STEMI) patients undergoing primary PCI.

Methods:

Totally, 68 patients with STEMI were randomly assigned to two groups: intravenous administration of Lipo-PGE1 (Group A), and no Lipo-PGE1 administration (Group B). The corrected thrombolysis in myocardial infarction (TIMI) frame count (cTFC) and myocardial blush grade (MBG) were calculated. Patients were followed up for 6 months. Major adverse cardiac events (MACE) were also measured.

Results:

There was no significant difference in the baseline characteristics between the two groups. The cTFC parameter in Group A was significantly lower than Group B (18.06 ± 2.06 vs. 25.31 ± 2.59, P < 0.01). The ratio of final MBG grade-3 was significantly higher (P < 0.05) in Group A (87.9%) relative to Group B (65.7%). There was no significant difference between the two groups in final TIMI-3 flow and no-reflow. Patients were followed up for 6 months, and the occurrence of MACE in Group A was significantly lower than that in Group B (6.1% vs. 25.9% respectively, P < 0.05).

Conclusions:

Myocardial microcirculation of reperfusion injury in patients with STEMI, after primary PCI, can be improved by administering Lipo-PGE1.     

Knockdown of long noncoding RNA SPRY4-IT1 suppresses glioma cell proliferation,metastasis and epithelial-mesenchymal transition

Long noncoding RNAs (lncRNAs), a class of ribonucleic molecules, participate in various cellular processes. They are highly expressed in several types of cancer and their expression was related to pathophysiological characteristics of tumor growth, therefore, they can be considered as a promising diagnostic tool and a convenient prognostic biomarker. SPRY4-IT1, belonging to a group of intron-retained lncRNAs, was reported to affect tumor development of many types of cancer. However, the expression and the role of SPRY4-IT1 in glioma are still unclear. Therefore, in this study, we examined for the first time the expression and role of SPRY4-IT1 in glioma cells. The results of our study showed that SPRY4-IT1 was up-regulated in human glioma tissues and cell lines. Knockdown of SPRY4-IT1 could inhibit glioma cell growth and migration. Moreover, knockdown of SPRY4-IT1 could inhibit epithelial-mesenchymal transition (EMT) phenotype in glioma cells. Based on these findings, SPRY4-IT1 may be used as a new target for diagnosis and treatment of glioma.     

顺铂联合雷帕霉素或3-甲基腺嘌呤对肺腺癌A549细胞抑制作用的研究

目的观察非小细胞肺癌(non small cell lung cancer,NSCLC)中肺腺癌A549细胞在顺铂(cisplatin,CP)联合雷帕霉素(rapamycin,RAPA)或3-甲基腺嘌呤(3-methyladenine,3-MA)作用下的结果,为提高顺铂的化疗效果提供理论依据。方法 2013年3月至2014年6月期间,通过对人肺腺癌细胞株A549(由河北医科大学第四医院科研中心提供)经四甲基偶氮唑盐3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT)实验检测顺铂、雷帕霉素和3-MA对A549细胞的增殖抑制率,计算出各药物的50%细胞抑制浓度(50%inhibitory concentration,IC50),并以此作为实验浓度。实验分为4组:对照组(无药物干预)、顺铂组(加15μmol/L的顺铂)、顺铂+雷帕霉素组(加10nmol/L的雷帕霉素1h后再加15μmol/L的顺铂)、顺铂+3-MA组(加3μmol/L的3-MA 1h后再加15μmol/L的顺铂),将对数生长期的肺癌A549细胞以每孔1.0×10^6/ml密度接种于6孔培养板中,待细胞长至孔底面积约70%~80%后分别加入稀释好的药物,分别培养24、48、72h。肺癌A549细胞的生长迁移情况用细胞划痕实验检测,mTOR、LC3-Ⅱ及Bax mRNA和蛋白的表达情况用RT-PCR(逆转录-聚合酶链反应)、Western blot(蛋白质印迹)法检测。数据处理采用SPSS 17.0统计软件进行分析。结果顺铂IC50:15μmol/L;雷帕霉素IC50:10nmol/L;3-MA IC50:3μmol/L。划痕实验显示24h顺铂+雷帕霉素组细胞迁移能力最弱,48h和72h顺铂+3-MA组细胞迁移能力最弱。RT-PCR显示顺铂+雷帕霉素组LC3-ⅡmRNA的2-△△Ct值(24h:1.686±0.069;48h:1.803±0.083;72h:1.836±0.056)与顺铂组(24h:1.489±0.031;48h:1.325±0.007;72h:1.428±0.080)相比表达量均明显上升(24hF=149.780,P<0.01;48hF=111.599,P<0.01;72hF=167.855,P<0.01);而顺铂+3-MA组的Bax mRNA的2-△△Ct值(48h:1.864±0.104;72h:1.935±0.068),与顺铂组(48h:1.346±0.080,72h:1.462±0.029)相比,表达量均明显上升(48hF=52.853,72hF=202.118;P值均<0.01)。Western blot显示顺铂+雷帕霉素组LC3-Ⅱ蛋白(48h:0.556±0.010;72h:0.571±0.009)与顺铂组(48h:0.426±0.0107;72h:0.492±0.009)相比表达量均显著上升(48hF=372.056,72hF=930.500;P值均<0.01);而顺铂+3-MA组的Bax蛋白(48h:0.897±0.022;72h:0.916±0.005),与顺铂组(48h:0.463±0.011;72h:0.581±0.007)相比,表达量均显著上升(48hF=1100.412,72hF=5715.778;P值均<0.01)。结论顺铂联合雷帕霉素或3-MA较单独使用顺铂能更好的抑制A549细胞的生长,长时间用药时顺铂联合3-MA作用最强。