替格瑞洛在冠心病合并慢性阻塞性肺病中应用的有效性和安全性meta分析

目的 分析在冠心病合并慢性阻塞性肺病（COPD）中应用替格瑞洛的安全性以及有效性。方法 计算机检索中国知网、维普、PubMed、OVID、web of science等国内外数据库,收集在冠心病合并COPD患者中应用替格瑞洛对比氯吡格雷的临床试验。本次试验的主要终点为冠心病合并COPD患者呼吸困难发生率、出血发生率以及心血管源性不良事件的发生率。结果 本次研究共纳入7篇文献,meta分析结果显示,对比氯吡格雷组,替格瑞洛组呼吸困难发生率显著升高（24.5% vs 13.8%,OR：2.04,95%CI：1.56 2.66,P<0.05）;但替格瑞洛组在心肌梗死率（6.8% vs 10.6%,OR：0.61,95%CI：0.43 0.87,P<0.05）、卒中发生率（1.1% vs 2.9%,OR：0.41,95%CI：0.20 0.84,P<0.05）、心源性死亡率（4.9% vs 8.8%,OR：0.53,95%CI：0.35 0.79,P<0.05）上均比氯吡格雷组具有显著优势。结论 替格瑞洛在冠心病合并COPD患者中呼吸困难的发生率较高,但心血管源性不良事件的发生率显著低于氯吡格雷组。     

肺部相关疾病外周血T淋巴细胞表面标志物表达分析

目的观察肺部相关疾病外周血T淋巴细胞表面标志物的表达,从细胞免疫水平探究肺部相关疾病发病机制。方法选择2016年1-12月于浙江省绍兴市立医院呼吸科就诊的肺部疾病患者84例,根据诊断结果分为肺结核组(n=34)、肺癌组(n=25)及非结核性肺炎组(n=25),同时设立健康对照组(n=35)。检测各组外周血T细胞表面表达CD3^+CD4^+、CD3^+CD8^+、CD3^+CD45RA+/CD45RO^+、CD3^+HLA-DR^+、CD8^+HLA-DR^+、CD4^+CD25^+的百分比,采用t检验对结果进行统计分析。结果肺结核组、肺癌组、非结核性肺炎组外周血T淋巴细胞表面标志物CD4^+/CD8^+比值(1.01±0.48、1.17±0.39、1.35±0.55)低于健康对照组(1.48±0.52,t=2.562,t=2.341,t=2.112,P<0.05);肺结核组、肺癌组、非结核性肺炎组表达CD3^+CD45RO^+的T细胞占总淋巴细胞百分比(65.20%±12.63%、56.70%±9.98%、55.90%±9.29%)高于健康对照组(49.60%±11.52%,t=3.422,t=2.647,t=2.084,P<0.05),且肺结核组高于肺癌和非结核性肺炎组(t=2.153,t=3.112,P<0.05);肺结核组、肺癌组表达CD3^+HLA-DR^+的T细胞占总淋巴细胞百分比(19.59%±7.01%、21.7%±7.34%)高于健康对照组(11.40%±5.33%,t=2.383,t=2.533,P<0.05);肺结核组表达CD8^+HLA-DR^+T细胞占总淋巴细胞百分比(11.26%±4.88%)高于健康对照组(7.10%±3.07%,t=2.244,P<0.05);肺结核组和肺癌组表达CD4^+CD25^+的T细胞占总淋巴细胞百分比(10.70%±3.06%、10.40%±2.33%)高于健康对照组(8.20%±2.79%,t=2.647,t=2.662,P<0.05)。结论肺结核、肺癌和肺炎患者外周血T淋巴细胞表面标志表达改变,尤以肺结核患者改变最显著,可能与肺结核独特的发病机制有关。     

酪氨酸激酶抑制剂对CD19 CAR-T细胞在难治/复发Ph阳性急性淋巴细胞白血病中扩增的影响

目的 观察酪氨酸激酶抑制剂(tyrosine kinase inhibitors, TKIs)对CD19嵌合抗原受体修饰（CAR）T细胞在难治/复发Ph+急性淋巴细胞白血病（ALL）中的扩增、疗效及不良反应的影响。方法 收集10例难治/复发Ph+ ALL患者（TKIs组）和16例难治/复发Ph阴性B ALL患者（非TKIs组）,TKIs组给予TKIs口服。在输注CD19 CAR T细胞后第0、4、7、14、21和28天分别检测外周血中CD19 CAR T细胞,分析两组输注后的疗效及不良反应。结果 TKIs组外周血中CD19 CAR T细胞的峰值高于非TKIs组,两组差异有统计学意义（P=0.0037）;两组细胞因子峰值、细胞因子释放综合征（CRS）分级、第14天完全缓解（CR）率、总生存率（OS）和无病生存率（DFS）差异均无统计学意义（P>0.05）。结论 TKIs促进CD19 CAR T细胞在难治/复发Ph+ ALL中的扩增,不抑制CD19 CAR T细胞的疗效,不加重其不良反应,近期及远期疗效肯定。     

SWE评估非酒精性脂肪肝病大鼠肝纤维化程度

目的 探讨剪切波弹性成像(SWE)技术评估非酒精性脂肪肝病(NAFLD)大鼠肝纤维化程度的应用价值。 方法 SD大鼠88只,随机分为对照组(40只)和实验组(44只),对照组给予普通饲喂,实验组通过不同饮食建立不同纤维化分期的NAFLD大鼠模型,分别于第 1、2、3、8、12周末行大鼠肝脏SWE检查及病理分析。 结果 所有大鼠肝脏Emean与肝纤维化程度呈显著正相关(r=0.82,P＜0.001)。不同纤维化分期的Emean组间差异有统计学意义(F=25.5,P＜0.05);除了F1和F2组之间Emean没有显着差异(P＞0.05),其余任意两组之间的肝 Emean 比较差异均有统计学意义(均P＜0.05)。SWE诊断肝纤维化≥F1、≥F2、≥F3、＝F4的截值分别为6.3、7.4、8.6、9.7kPa,曲线下面积(AUC)分别为0.87、0.89、0.93、0.98,敏感性和特异性分别为83.3%、93.3%、100%、100%和85.5％、83.1%、91.3%、92.7%。 结论 SWE技术可有效评估NAFLD的肝纤维化程度。     

MicroRNA regulation and therapeutic targeting of survivin in cancer

Survivin, the smallest member of IAP (inhibitor of apoptosis) family, is a dual functional protein acting as a critical apoptosis inhibitor and key cell cycle regulator. Survivin is usually expressed in embryonic tissues during development and undetectable in most terminally differentiated tissues. Numerous studies demonstrate that survivin is selectively upregulated in almost all types of human malignancies and its overexpression positively correlates with poor prognosis, tumor recurrence, and therapeutic resistance. This differential expression of survivin in tumors and normal tissues draws a great interest to develop survivin-targeted therapy for cancer treatment. Nonetheless, the molecular mechanisms controlling survivin expression in malignant tumor cells have not been fully understood. While aberrant activation of receptor tyrosine kinases (RTKs) and the downstream signaling, such as PI-3K/Akt, MEK/MAPK, mTOR, and STAT pathways, have frequently been shown to upregulate survivin, recent data suggest that a class of noncoding RNAs, microRNAs (miRNAs) also play an important role in survivin dysregulation in human cancers. Here, we focus on survivin expression-regulated by specific miRNAs binding to the 3’-UTR of survivin mRNA, and summarize the latest advances on survivin-targeted therapy in clinical trials and the therapeutic potential of survivin-targeting miRNAs in cancer.     

Gold nano-particles (AuNPs) carrying anti-EBV-miR-BART7-3p inhibit growth of EBV-positive nasopharyngeal carcinoma

Epstein-Barr virus (EBV) infection is a major etiological factor for nasopharyngeal carcinoma (NPC). Several EBV-encoded BART miRNAs have been associated with viral latency, immune escape, cell survival, cell proliferation and apoptosis. Here, we report that EBV-miR-BART7-3p, an EBV-encoded BART miRNA highly expressed in NPC, was correlated with cell-cycle progression in vitro and increased tumor formation in vivo. This viral miRNA stimulated the PTEN/PI3K/Akt pathway and induced c-Myc and c-Jun. Knockdown of PTEN mimicked EBV-miR-BART7-3p-induced tumorigenic phenotype. Based on these results, we conducted a therapeutic experiment by using gold nano-particles (AuNPs) carrying anti-EBV-miR-BART7-3p. Silencing of EBV-miR-BART7-3p reduced tumor growth in animal model. We conclude that EBV-miR-BART7-3p favors carcinogenesis, representing a potential target for miRNA-based therapy.     

The binding of key fishy off-flavor compounds to silver carp proteins: a thermodynamic analysis

The binding of key fishy off-flavor compounds (KFOCs), heptanal, octanal, nonanal, and 1-octen-3-ol, to silver carp proteins (total myofibrillar protein, myosin, and actin) was studied. Myosin was the primary binding receptor for all four KFOCs, and it showed the strongest binding at neutral pH and at higher ionic strengths. Thermodynamic models were applied to evaluate the number of binding sites, the binding constant, and the Gibbs free energy for the binding of the KFOCs to myosin. Myosin had approximately 1.0 sites for binding with the three linear-chain aldehydes and about 1.6 sites for binding with 1-octen-3-ol. Moreover, myosin showed the highest affinity for 1-octen-3-ol, and both its binding constant and its number of binding sites with the three linear-chain aldehydes were negatively correlated with the chain length. For all four KFOCs, the trends of the Gibbs free energies were the opposite of those observed for the binding constant and the number of binding sites. These results may provide a theoretical basis for improving the deodorization efficiency of traditional surimi rinsing methods by adjusting the properties of the solutions used.

Myosin was shown to be the primary binding receptor of the four KFOCs and showed the strongest binding under neutral pH and high ionic strength. Its affinity for 1-octen-3-ol was the highest.     

Surgical malpractice claims in the United States

Despite ongoing reform, there is still significant physician concern regarding the impact of medical claims on their practices. It is important that physicians and healthcare risk management professionals have a good understanding of the outcomes of medical malpractice to participate in its restructuring as needed and to prevent potentially harmful practices. In our study, we reviewed National Practitioner Data Bank (NPDB) paid malpractice claim reports from September 1, 1990, through July 30, 2011, and identified the 10 most common surgery‐related allegations against physicians, excluding those listed as unspecified. Data were collected on the number of claims, the cost of the claims, and physician and patient characteristics.