A retrospective study on oral anticoagulant prophylaxis in 103 Italian patients with hereditary thrombophilia and thrombosis

Summary The clinical records of 103 Italian patients with inherited thrombophilia and thrombosis were reviewed to estimate the incidence of thrombotic recurrences and major bleeding complications according to the different duration of oral anticoagulant prophylaxis (OAP). The incidence of the first thrombotic recurrence was 2.9, 7.4 and 10.8×100 patients/year, respectively, in subjects receiving lifelong OAP, stopping OAP after a mean of 9 months (range 1–30 months) or not receiving OAP. The probability to remain free from thrombotic recurrences in patients undergoing lifelong OAP, as estimated by the Kaplan-Meier method, was significantly higher in comparison with untreated patients (p<0.001), but did not reach the statistical significance in comparison with patients who stopped prophylaxis. The incidence of further thrombotic recurrences was 1.2, 21.1 and 22.3×100 patients/year, respectively, in the three groups defined above. The difference between patients who prolonged indefinitely OAPvs those who stopped or did not receive OAP was statistically significant (p=0.003). Two intracranial bleedings, one of which fatal, were observed in patients undergoing lifelong OAP, whereas no major bleeding complications occurred in the other two groups. Our study supports the recommendations to continue indefinitely OAP in patients with inherited thrombophilia and recurrent thrombosis, but suggests caution in starting lifelong prophylaxis soon after the first thrombotic event in all patients. Members of the Study Group: F. Baudo (Milano); M. Berrettini (Perugia); G. Castaman (Vicenza); N. Ciavarella (Bari); S. Coccheri (Bologna); V. De Stefano (Roma); A. G. Dettori (Parma); N. Erba (Merate); G. Leone (Roma); P. M. Mannucci (Milano); C. Manotti (Parma); M. G. Mazzucconi (Roma); G. Palareti (Bologna); F. Panicucci (Pisa); E. Pogliani (Monza); F. Rodeghiero (Vicenza); A. Tripodi (Milano).     

五常法在病区管理中的应用对比

目的:探讨病区管理的新方法。方法:选取我院骨科两个手术病区分别作为五常法实验组与对照组,实验组病区施行五常法管理,对照组按现有管理模式管理,观察期半年,根据季度护士长查房结果、患者满意度、护士满意度等进行评价,比较两组管理方法的差别。结果:实验组实行五常法管理以后,护士满意度、患者满意度明显提高,病区护士站的物品摆放、无菌物品的合格率、护士取放物品的效率也比对照组高。结论:五常法的应用提高了护理管理质量,值得临床推广。     

20(S)⁃原人参二醇止血作用及其机制

目的通过体内和体外实验研究20(S)?原人参二醇对小鼠凝血系统的作用和对人/鼠血小板的活化作用,探讨原人参二醇的止血作用及相关的作用机制。方法小鼠断尾和肝划痕法观察小鼠出血时间;自动血液分析仪检测大鼠血常规;自动凝血分析仪检测大鼠凝血四项指标;酶联免疫吸附法检测血小板中环磷酸腺苷(cAMP)和环磷酸鸟苷(cGMP)水平;Cytation 5多功能酶标仪检测洗涤人血小板内钙离子的浓度([Ca²⁺]i);比色法观察血小板的聚集率;流式细胞术检测洗涤人血小板中CD62P和PAC?1相关表达。结果原人参二醇能缩短小鼠的出血时间;增加红细胞参数中的红细胞数量(RBC)和红细胞压积(HCT),提高血小板参数中血小板数量(PLT)和血小板压积(PCT);缩短大鼠活化部分凝血活酶时间(APTT),中剂量和高剂量组可增加纤维蛋白原的表达。同时,原人参二醇能提高大鼠洗涤血小板cAMP水平、血小板内[Ca²⁺]i和血小板聚集度;增加洗涤人血小板CD62P释放和PAC?1表达。结论原人参二醇具有一定的止血作用,一方面通过激活大鼠的内源性凝血系统,影响体内血小板和红细胞参数,促进血浆中纤维蛋白原生成;另一方面通过影响钙离子和cAMP信号通路,增加血小板Ca²⁺内流、CD62P释放和促进PAC?1的表达,最终诱导血小板聚集,形成血栓,发挥止血作用。     

刃针搜法治疗脑梗死后感觉障碍的临床研究

目的:探究刃针搜法治疗脑梗死后感觉障碍的临床作用机制。方法:将90例脑梗死后感觉障碍患者随机分为刃针治疗组、针刺对照组、药物对照组,每组30例。3组患者分别治疗14 d,评价治疗效果,并进行治疗前后的血液流变学、神经元功能、血流动力学、体感诱发电位等相关指标检测。结果:治疗后刃针治疗组疗效明显高于其他两组,差异有统计学意义(P<0.05)。与治疗前比较,3组患者治疗后Fugl-Meyer评分显著提高(P<0.05);患侧体感诱发电位(SEP)N20潜伏期明显缩短(P<0.05)、波幅明显增高(P<0.05);血浆粘度、血小板聚集率、纤维蛋白原等血液流变学指标明显改善(P<0.05);血清S100B、基质金属蛋白酶-9(MMP-9)显著下降(P<0.05),金属蛋白酶组织抑制剂-1(TIMP-1)显著升高(P<0.05);病侧大脑中动脉舒张末期血流速度(Vd)、收缩期最大血流速度(Vs)、平均血流速度(Vm)显著升高;刃针治疗组上述指标变化较药物对照组和针刺对照组显著(P<0.05)。结论:刃针搜法通过改善脑梗死后感觉障碍患者脑部组织血液循环和供血情况、改善神经元功能、促进感觉神经传导通路修复等作用机制达到治疗效果。     

头孢丙烯及其他4种抗生素对社区获得性呼吸道感染病原菌体外抗菌活性比较

目的 :调查头孢丙烯及其他 4种抗生素对社区获得性呼吸道感染细菌的体外抗菌活性。方法 :肺炎链球菌、流感嗜血杆菌和卡他莫拉菌用全自动细菌分析系统的革兰阳性菌鉴定卡GPI、奈瑟及嗜血杆菌鉴定卡NHI做最终鉴定。药物敏感性试验采用Etest方法测定MIC。结果 :共计测定了 15 5株肺炎链球菌、97株流感嗜血杆菌、2 0株卡他莫拉菌、12株苯唑西林敏感的金黄色葡萄球菌 ,19株 β 溶血链球菌的药物敏感性试验。结果表明肺炎链球菌对 5种常用抗生素的敏感率分别为 :头孢丙烯 90 .3%、头孢克罗 85 .2 % ,阿奇霉素 2 5 .8%、青霉素 80 .6 %、阿莫西林 克拉维酸为 94 .2 %。流感嗜血杆菌对头孢丙烯和头孢克罗敏感率均为 97.9%。结论 :头孢丙烯对社区获得性呼吸道感染的 5种主要病原菌均显示了很高的体外抗菌活性。     

金骨莲胶囊对人乳腺癌MDA-MB-231细胞的抑制作用及机制

目的 研究金骨莲胶囊对人三阴性乳腺癌（TNBC）细胞MDA-MB-231增殖的影响,探讨金骨莲胶囊对TNBC的治疗作用机制。方法 利用超高效液相色谱-质谱联用（UPLC-MS/MS）技术,对金骨莲胶囊的成分进行分析鉴定。通过用噻唑蓝（MTT）比色法观察金骨莲胶囊（0.125,0.25,0.5,1,2 g·L^-1）对人乳腺癌细胞MDA-MB-231的增殖抑制作用。采用Hoechst 33258染色检测金骨莲胶囊处理MDA-MB-231细胞24 h后的细胞核凋亡形态学的变化。采用流式细胞仪检测金骨莲胶囊不同质量浓度和作用时间对MDA-MB-231细胞凋亡及周期分布情况。通过蛋白免疫印迹法（Western blot）检测各组细胞多聚二磷酸腺苷核糖聚合酶（PARP）,原癌基因蛋白（c-Myc）,细胞周期蛋白B₁（cyclin B₁）和磷酸化胞外信号调节激酶（p-ERK）的蛋白表达水平。结果 该研究利用UPLC-MS/MS技术鉴定了金骨莲胶囊提取物中113个化合物成分。MTT比色法显示,与空白组比较,金骨莲胶囊组（0.125,0.25,0.5,1,2 g·L^-1）细胞抑制率显著增加（P<0.01）,半数抑制浓度（IC₅₀）为（0.13±0.02）g·L^-1;流式细胞术结果显示,与空白组比较,金骨莲胶囊组（1 g·L^-1）细胞凋亡率显著升高（P<0.01）,金骨莲胶囊组（0.5,1 g·L^-1）细胞处于S期的数量明显增加（P<0.05,P<0.01）;Western blot结果显示,与空白组比较,金骨莲胶囊组（0.5,1 g·L^-1）细胞中的PARP,c-Myc,cyclin B₁蛋白表达水平显著降低（P<0.01）,金骨莲胶囊组（1 g·L^-1）p-ERK蛋白表达水平显著降低（P<0.01）。结论 金骨莲胶囊可抑制MDA-MB-231细胞增殖,使细胞周期阻滞于S期,并诱导其凋亡,其机制可能与其抑制MDA-MB-231细胞MAPK信号通路有关。     

肿瘤相关成纤维细胞在甲状腺乳头状癌组织中的表达及其意义

目的检测甲状腺乳头状癌(papillary thyroid carcinoma,PTC)相关成纤维细胞(tumor-associated fibroblasts,TAFs)中成纤维细胞特异性蛋白-1(fibroblast-specific protein 1,FSP1/S100A4)、平滑肌肌动蛋白-ɑ(ɑ-smooth-muscle actin,ɑ-SMA)和成纤维细胞活化蛋白(fibroblast-activated protein,FAP-ɑ)的表达,探究其与PTC发生、发展的关系。方法通过免疫组化SP法检测FSP1/S100A4、ɑ-SMA、FAP-ɑ在正常甲状腺组织和PTC中的表达情况,并分析这些指标与重要临床病理参数的关系。结果FSP1/S100A4、ɑ-SMA和FAP-ɑ在PTC间质细胞中可见阳性表达,而在正常甲状腺组织的滤泡上皮或间质细胞内均不表达。患者肿瘤的大小、是否有淋巴结转移及TNM的不同分期与FAP-ɑ的阳性病例数有统计学差异(χ^2=6.833,P<0.05;χ^2=10.296,P<0.05;χ^2=4.910,P<0.05);ɑ-SMA阳性病例数在是否被膜侵犯、淋巴结转移有显著差异(χ^2=6.008,P<0.05;χ^2=11.766,P<0.05),而S100A4的阳性病例数在患者的性别、年龄、瘤体的大小、有无被膜侵犯、有无淋巴结转移及患者的TNM分期差异均没有统计学意义(P>0.05)。结论PTC中TAFs的存在可能提示肿瘤具有较强的侵袭转移能力,TAFs有望成为PTC诊疗的一个新靶点。     

Characterization and evolution of the coronavirus porcine epidemic diarrhoea virus HLJBY isolated in China

A strain of porcine epidemic diarrhoea virus (PEDV), namely HLJBY, was isolated in Heilongjiang province, China. To provide insight into the understanding of the phylogenetic and the current epidemiological status of PEDV, PEDV HLJBY was compared with CV777 and other PEDV strains deposited in the GenBank. The homology between the entire genomic nucleotide sequences of PEDV HLJBY and CV777 was 97.7%. The homology of M gene was the highest (99.0%). However, the homology of ORF3 gene was 97.7%, and protein of ORF3 was 90.1%. In addition, HLJBY showed the highest nucleotide identity (99.9%) with PEDV‐SX/China/2017 strain and lowest similarity (91.2%) to PEDV/Belgorod/dom/2008 strain. We analysed the changes in S gene and its protein of PEDV HLJBY with 65 historic PEDV strains. The highest nucleotide identity was 99.9% compared with PEDV‐SX/China/2017 strain, and the lowest nucleotide identity was 60.0% compared with PEDV/Belgorod/dom/2008 strain. The length of deduced amino acid sequences of S proteins varied from 1,372 to 1,390 amino acids (aa). Compared with most aa sequences of S proteins, HLJBY exhibited 5 aa deletions (position 55, 59–61, 144). Analysis and comparison of open reading frame 3 (ORF3) proteins between HLJBY strain and other PEDV strains were also focused in this study. We revealed that the length of deduced amino acid sequences of ORF3 proteins was 80–224 aa among tested strains and the identity of HLJBY ORF3 amino acids with other PEDV strains was 71.4%–98.9%. ORF3 protein of both HLJBY strain and PEDV‐SX/China/2017 strain consists of 91 aa, with 133 aa deletions at their C' end in relation to the other tested PEDV strains. The phylogenetic tree based on different proteins or genes resulted in different phylogenetic groups. For pathogenicity evaluation of PEDV HLJBY strain, colostrum deprivation piglets were challenged with PEDV HLJBY, and PEDV reference strain CV777 as a control, the results showed that animals challenged with either of these PEDV strains developed diarrhoea, and histopathological examination of small intestines of challenged animals showed acute viral enteritis with villous atrophy in either PEDV HLJBY‐P10 or PEDV CV777‐P8 inoculated piglets.     

Prevalence of human papillomavirus in oral epithelial dysplasia: Systematic review and meta‐analysis

The purpose of this systematic review and meta‐analysis was to estimate the overall and type‐specific prevalence of human papillomavirus (HPV) DNA in oral epithelial dysplasia and assess p16^INK4a overexpression in relation to HPV‐status. A systematic literature search identified 31 eligible studies (832 cases) evaluating the presence of HPV DNA in oral epithelial dysplasia cases by PCR. Of these, six studies evaluated p16^INK4a overexpression in relation to HPV‐status. The overall pooled prevalence of HPV DNA in oral epithelial dysplasia was 27.2% (95% CI: 17.6‐38.1). We observed substantial interstudy heterogeneity, which could not be explained by differences in continent, tissue type, or severity of epithelial dysplasia. HPV16 was the predominant genotype detected. Moreover, 62.2% of HPV positive and 17.8% of HPV negative oral epithelial dysplasia samples stained intensively positive for p16^INK4a. This meta‐analysis found that 27% of oral epithelial dysplasia harbor HPV DNA. Whether this represents a transient infection or has a carcinogenic role is unknown.     

长链非编码 RNA 在骨关节炎软骨损伤中的调控作用

目的总结长链非编码 RNA（long non-coding RNA，lncRNA）在骨关节炎（osteoarthritis，OA）软骨损伤中的调控作用。方法广泛查阅近年国内外相关文献，介绍 lncRNA 的分子功能和作用机制，并详细阐述其对 OA 病理过程的调控作用。结果OA 病理特征是关节软骨退变和滑膜组织炎症，但其病因和病理机制尚未明确。lncRNA 是一类异质性非编码 RNA，在许多炎症相关疾病中起调控作用并且发挥广泛的生物学功能。lncRNA 是参与 OA 发病机制的调节器，在 OA 软骨中异常表达，从而导致软骨细胞外基质变性。结论目前对于 lncRNA 调控 OA 的病理作用及软骨细胞生物学功能已有初步研究，但 lncRNA 及其调控网络在 OA 的发病机制、调节炎症途径的方式尚不明确，有待进一步探索。