糖尿病周围神经病变综合康复治疗60例疗效观察

目的 探讨综合康复治疗对于糖尿病周围神经病变的临床疗效.方法 研究纳入120例糖尿病周围神经病变的患者,按照完全随机分组法分为常规治疗组和综合康复治疗组,其中常规治疗组(60例)患者采用常规方法治疗,综合康复治疗组(60例)患者在常规方法之外接受红外线照射和/或高压氧治疗.对比常规治疗组和综合康复治疗组的治疗效果.结果 治疗1个月后,综合康复治疗组患者的显著有效率(78.56% vs 50.00%)和总有效率(96.67% vs 86.67%)均高于常规治疗组,差异有统计学意义(显著有效率:χ2=11.868,P=0.001;总有效率:χ2=3.927,P=0.048).治疗后综合康复组患者腓总神经[(43.5 ±3.1)vs(37.3 ±2.9)m· s-1]和胫神经传导速度[(44.5 ±3.2)vs(38.6 ±2.5)m· s-1]均显著高于常规治疗组患者(腓总神经:t=12.815,P<0.001;胫神经:t=11.102,P<0.001).结论 综合康复治疗能够明显改善糖尿病周围神经病变患者症状,提高患者周围神经功能.     

A univariate perspective of multivariate genome‐wide association analysis

Multiple correlated phenotypes are frequently collected in genome‐wide association studies (GWASs), and a systematic, simultaneous analysis of multiple phenotypes can integrate the signals from single phenotypes, therefore increasing the power of detecting genetic signals. However, fundamental questions remain open, including the conditions and reasons under which the multivariate analysis is beneficial, how a highly significant signal arises in the multivariate analysis. To understand these issues, we propose to decompose the multivariate model into a series of simple univariate models. This transformation offers a clearer quantitative analysis of the circumstances under which a multivariate approach can be beneficial for the bivariate phenotypes case. A real data analysis is employed to illustrate how to interpret how the signals arising from multivariate GWASs.     

186例消化系统恶性肿瘤患者UGT1A1*6、UGT1A1*28基因多态性的检测和分析

目的：检测和分析消化系统恶性肿瘤患者UGT1A1^*6、UGT1A1^*28基因多态性。方法：收集186例消化系统恶性肿瘤患者血液标本,采用焦磷酸测序方法对UGT1A1^*6、UGT1A1^*28基因多态性进行检测,并对基因多态性频率进行统计分析。结果：186例消化系统恶性肿瘤患者样本具有群体代表性。UGT1A1^*6基因多态性为野生型G/G占比63.4%、杂合型G/A占比32.8%、突变纯合型AA占比3.8%;UGT1A1^*28基因多态性为野生型TA6/TA6占比75.8%、杂合型TA6/TA7占比21.5%、突变纯合型TA7/TA7占比2.7%;UGT1A1^*6和^*28基因多态性为野生型G/G且TA6/TA6占比48.9%,单点变异型G/G且TA6/TA7占比12.4%、G/A且TA6/TA6占比23.1%,双点变异型G/G且TA7/TA7占比2.2%、G/A且TA6/TA7占比9.1%、A/A且TA6/TA6占比3.8%,三点变异型G/A且TA7/TA7占比0.5%。患者UGT1A1^*6与UGT1A1^*28基因多态性频率分布之间具有显著性差异（P<0.05）。3个不同年龄段患者之间,胃癌、结直肠癌、其他消化系统恶性肿瘤患者之间的UGT1A1^*28、UGT1A1^*6和^*28基因型分布具有显著性差异（P<0.05）。结论：消化系统恶性肿瘤患者应用伊立替康时,应联合检测UGT1A1^*6和UGT1A1^*28基因多态性,同时密切关注患者的肿瘤类型以及年龄差异。     

RN181 is a tumour suppressor in gastric cancer by regulation of the ERK/MAPK–cyclin D1/CDK4 pathway

RN181, a RING finger domain-containing protein, is an E3 ubiquitin ligase. However, its biological function and clinical significance in cancer biology are obscure. Here, we report that RN181 expression is significantly down-regulated in 165 tumour tissues of gastric carcinoma (GC) versus adjacent non-tumour tissues, and inversely associated with tumour differentiation, tumour size, clinical stage, and patient's overall survival. Alterations of RN181 expression in GC cells by retrovirus-transduced up-regulation and down-regulation demonstrated that RN181 functions as a tumour suppressor to inhibit growth of GC in both in vitro culture and in vivo animal models by decreasing tumour cell proliferation and increasing tumour cell apoptosis. Cell cycle analysis revealed that RN181 controls the cell cycle transition from G1 to S phase. Mechanistic studies demonstrated that RN181 inhibits ERK/MAPK signalling, thereby regulating the activity of cyclin D1–CDK4, and consequently controlling progression in the cell cycle from G1 to S phase. Restoring CDK4 in GC cells rescued the inhibitory phenotype produced by RN181 in vitro and in vivo, suggesting a dominant role of CDK4 in control of the tumour growth by RN181. Importantly, RN181 expression is inversely correlated with the expression of cyclin D1 and CDK4 in GC clinical samples, substantiating the role of the RN181–cyclin D1/CDK4 pathway in control of the tumour growth of GC. Our results provide new insights into the pathogenesis and development of GC and rationale for developing novel intervention strategies against GC by disruption of ERK/MAPK–cyclin D1/CDK4 signalling. In addition, RN181 may serve as a novel biomarker for predicting clinical outcome of GC. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.     

Impact of the variations in potential glycosylation sites of the hemagglutinin of H9N2 influenza virus

Variations in the potential glycosylation sites were observed in hemagglutinin (HA) sequences of H9N2 avian influenza virus isolated in China, deposited in the Influenza Virus Resource of NCBI before 2017, which showed a deleted glycosylation site at amino acid residue 218, and an introduced glycosylation site at amino acid residue 313. Based on the variations in the glycosylation sites at these amino acids, H9N2 avian influenza viruses could be divided into three categories. Firstly, most of the H9N2 influenza viruses were 218G⁺ viruses; less 313G⁺ viruses were isolated between 1997 and 2004. Secondly, the occurrence of the 218G⁺/313G⁺ viruses increased, while the 218G⁺/313G^? viruses decreased from 2005 to 2012. Thirdly, from 2013 to 2016, the 218G^?/313G⁺ viruses were predominant compared to the 218G⁺/313G⁺ viruses. Here, based on an F/98 virus backbone, a 218G⁺/313G^? virus, two reassortment viruses were generated, and named rF/HA218G⁺/313G⁺ and rF/HA 218G⁺/313G^?, respectively. HA protein migration demonstrated that the glycosylation sites at amino acid residues 313 and 218 were both functional. The absence of the glycosylation site at amino acid residue 218 and the presence of the glycosylation site at amino acid residue 313 increased antibody binding and moderately prevented the virus from escaping neutralization with homologous antisera. Additionally, compared to the F/98 virus (218G⁺/313G^?), the viruses rF/HA218G⁺/313G⁺ or rF/HA218G^?/313G⁺ showed significantly increased infectivity of MDCK cells, chicken embryo eggs, and trachea and lung tissue of SPF chickens, but did not display differences in airborne spread in chickens or infectivity of mice compared with its parental virus F/98.

     

循环肿瘤细胞的微流控芯片分离及其物理性质测量分析

目的建立一种使用微吸管测量具有良好生理活性的循环肿瘤细胞(circulating tumor cells, CTCs)弹性模量的方法。方法使用商品化的微流控芯片富集血液中具有良好生理活性的CTCs,使用EpCAM抗体确定CTCs,并使用微吸管测量其弹性模量,同时与癌细胞系弹性模量相对比。结果对于癌细胞系的弹性模量,不仅在不同细胞系间存在较大的差异,在同一细胞系间也存在较大的异质性。血液中CTCs相比于同种癌细胞系属于弹性模量较小的癌细胞。结论该方法能够获得生理活性较好的CTCs并测量其弹性模量,为进一步研究CTCs力学特性与癌症诊断和治疗预后之间的相关关系,推进癌细胞物理标志物的发展提供细胞力学数据支持。     

镁基植入体植入兔股骨后周围骨微结构变化趋势

目的研究镁基植入体植入兔股骨不同时间点周围骨微结构参数的变化规律。方法将直径2 mm、长7 mm有螺纹及无螺纹的高纯镁(99.99 wt.%)钉植入兔股骨髁,对照组为钻孔组及健康组。在术后8、12、16周进行Micro-CT扫描和分析,得到各组微结构参数,包括:骨质密度(BMD)、骨体积分数(BV/TV)、骨小梁厚度(Tb.Th)、骨小梁数量(Tb.N)、骨小梁分离度(Tb.Sp)。结果 8周时无螺纹镁钉组BMD、BV/TV显著高于健康组,Tb.N显著高于钻孔组与健康组,Tb.Sp显著低于健康组;12周时有螺纹镁钉组BMD、BV/TV、Tb.N显著高于钻孔组与健康组,Tb.Th显著高于健康者,Tb.Sp显著低于钻孔组与健康组;16周时无螺纹镁钉组的BMD、BV/TV、Tb.N显著高于钻孔组与健康组,Tb.Sp显著低于钻孔组与健康组。结论镁基植入体促使周围骨组织的BMD、BV/TV、Tb.Th、Tb.N更高,Tb.Sp更低,说明其骨整合与骨生长状况良好,镁基植入体能有效促进骨再生。研究结果为镁基植入体的骨科临床应用提供理论依据。     

沿海地区孕妇尿碘检测水平分析

目的调查本地区孕妇人群尿碘水平,指导孕妇合理适度补碘,提高新生儿出生质量。方法采用砷铈催化分光光度法进行尿碘水平的检测。结果在2189例孕妇标本中,调查对象尿碘水平中位数为143.1μg/L;尿碘水平低于适宜水平者1187例,占54.2%,高于适宜水平者313例,占14. 3%。孕早、中、晚期3组的孕妇尿碘中位数分别为141.8、144. 6、131.3μg/L,各孕期孕妇的尿碘水平差异无统计学意义(χ~2=0.941,P>0.05)。结论该地区虽属沿海地区,但近半数及以上的孕妇尿碘水平处于不足状态,孕妇尿碘水平总体偏低。     

尼拉帕尼：聚腺苷二磷酸-核糖聚合酶抑制剂

尼拉帕尼（Niraparib,商品名Zejula^TM）是聚腺苷二磷酸-核糖聚合酶（PARP）的口服小分子抑制剂,PARP抑制是治疗由DNA修复基因（如BRCA1和BRCA2）特异性畸变引起的DNA修复机制缺陷的癌症的有效策略。尼拉帕尼于2017年3月在美国获批,维持治疗复发性上皮性卵巢癌、输卵管癌、原发性腹膜癌的成年患者,这些患者对铂类化疗有完全或部分反应,推荐剂量为口服300 mg/d,直到疾病发生恶化或产生无法接受的不良反应。临床研究结果表明该药可以延长患者的无恶化生存期,为治疗卵巢癌提供了有效和可靠的治疗手段。     

羟考酮联合加巴喷丁治疗中重度癌性疼痛的Meta-分析

目的 系统评价羟考酮联合加巴喷丁应用中重度癌性疼痛的有效性和安全性。方法 检索PubMed、Medline、中国期刊全文数据库（CNKI）、维普中文科技期刊全文数据库（VIP）、中国生物医学全文数据库（CBM）和万方数据库中关于羟考酮联合加巴喷丁治疗癌性疼痛的随机对照研究,检索时限为2000年1月至2017年8月。由2名研究者独立提取数据、评价质量,并交叉核对。采用RevMan 5.2软件进行Meta-分析。结果 共纳入10项研究,687例患者。Meta-分析结果显示：羟考酮联合加巴喷丁较羟考酮单用能显著提高疼痛缓解率[OR=3.85,95%CI（2.25~6.60）,P<0.000 01]和降低疼痛评分[MD=-0.83,95%CI（-0.95~-0.70）,P<0.000 01];能显著减少羟考酮的剂量[MD=-17.10,95%CI（-20.16~-14.04）,P<0.000 01];能显著减少便秘[OR=0.58,95%CI（0.42,0.82）,P=0.002]和恶心呕吐[OR=0.55,95%CI（0.37,0.82）,P=0.003]的发生率;能显著提高细胞免疫（CD4、CD8、CD4/CD8）和体液免疫（IgA、IgG、IgM）水平,差异均有统计学意义（P<0.01）。结论 羟考酮联合加巴喷丁能显著提高疼痛缓解率、降低疼痛评分,减少羟考酮平均日剂量,增强免疫功能,减少便秘和恶心呕吐等不良反应发生率,但两组头痛头晕、嗜睡和尿潴留的发生率无统计学差异。