醛糖还原酶和晚期糖基化终末产物受体对糖尿病视网膜病变神经元凋亡的影响

目的　探究醛糖还原酶和晚期糖基化终末产物受体对糖尿病视网膜病变神经元凋亡的影响。方法　Wistar大鼠36只，随机分为对照组、模型组、转染组，后两组建立糖尿病大鼠模型。模型建立成功后，构建含有晚期糖基化终末产物受体siRNA的质粒并利用慢病毒转染入转染组大鼠体内。造模后4周、8周、12周，记录各组大鼠体质量及空腹血糖。造模后9周，禁食6 h，测定口服葡萄糖耐量。造模后12周，处死全部大鼠后，TUNEL法检测各组大鼠视网膜神经元凋亡情况，荧光分光光度计测定醛糖还原酶活性，Western blotting法测定晚期糖基化终末产物受体的表达，RT-PCR检测视网膜中Bcl-2和Bax mRNA相对表达量。结果　造模后4周、8周、12周，转染组和模型组的大鼠体质量均低于对照组（均为P<0.05）；造模后12周，转染组大鼠体质量高于模型组（P<0.05）。造模后4周、8周、12周，各组内大鼠空腹血糖水平均无明显变化（均为P>0.05），转染组和模型组大鼠的空腹血糖水平均高于对照组（均为P<0.05）。模型组和转染组大鼠在口服葡萄糖后30 min时，血糖水平均高于对照组（均为P<0.05）；在120 min时分别下降至最低，但仍高于对照组（均为P<0.05）。模型组和转染组的视网膜神经元凋亡指数、醛糖还原酶活性、晚期糖基化终末产物受体和Bax mRNA相对表达量均高于对照组（均为P<0.05），且转染组均高于模型组（均为P<0.05）。模型组和转染组的Bcl-2 mRNA相对表达量均低于对照组（均为P<0.05），转染组低于模型组（P<0.05）。结论　晚期糖基化终末产物结合受体后产生大量的氧自由基损伤，可能是导致糖尿病视网膜神经元凋亡，进而导致糖尿病视网膜病变发生的机制之一。     

镇江市护士分层培训及分层进阶现况分析

目的调查镇江市各医院护士分层培训及分层进阶的方法及现状。方法2018年4—5月间采用自行设计的调查问卷,对全市医院的护理人员进行随机抽样调查。结果调查显示镇江市96.45%的护士受医院分层培训及分层进阶这一模式的管理。其中N1占16.77%,N2占29.5%,N3占41.9%,N4占8.7%,其他占3.11%。有24.53%的护士对医院目前的分层培训方式感到满意并认为无需改进,40.99%的护士表示满意,但需要改进,29.19%的护士表示基本满意,需要改进,5.28%的护士表示不满意需要较大改进。95.82%的医院科室对不用层级的护士有不同的核心能力要求并根据不同核心能力要求进行培训。结论护士分层培训几分层进阶这一管理模式在镇江各医院都有体现,但各医院实行的方式有较大差异,配套的管理方式也有待完善。     

Why We Need Continuous Pharmaceutical Manufacturing and How to Make It Happen

We make the case for why continuous pharmaceutical manufacturing is essential, what the barriers are, and how to overcome them. To overcome them, government action is needed in terms of tax incentives or regulatory incentives that affect time.     

The impact of circumferential tumour location on the clinical outcome of rectal cancer patients managed with neoadjuvant chemoradiotherapy followed by total mesorectal excision

AimTo investigate the impact of circumferential tumour location on neoadjuvant chemoradiotherapy (CRT) response and its prognostic value for locally advanced rectal cancer (LARC) patients after CRT and surgery.MethodsA retrospective study was performed on 486 patients with LARC who received neoadjuvant CRT and surgical treatment. The rate of pathological complete response (pCR) and survival among patients with anteriorly, laterally, and posteriorly located tumours were compared. Logistic regression was performed to identify pCR predictors.ResultsThe anterior tumours exhibited the highest pCR rate of 26.7%, which was slightly higher than the 20.0% and 12.3% for lateral and posterior tumours, respectively (P = 0.006). The 5-year Overall survival (OS) rates after CRT were similar among the anterior, lateral, and posterior groups (anterior vs lateral vs posterior: 81.1% vs 89.9% vs 84.1%, P = 0.6368). Multivariate analysis revealed that the circumferential tumour location, post-CRT serum CEA and post-CRT tumour thickness measured by MRI were independently correlated with achieving pCR.ConclusionThis study is the first, to the best of our knowledge, to show that anterior LARC exhibited the highest pCR rate after neoadjuvant CRT. Patients with anterior rectal cancers do not have different prognoses from those with non-anterior cancers if they undergo neoadjuvant CRT.     

Use of a Checklist During Observation of a Simulated Cardiac Arrest Scenario Does Not Improve Time to CPR and Defibrillation Over Observation Alone for Subsequent Scenarios

Theory: Immersive simulation is a common mode of education for medical students. Observation of clinical simulations prior to participation is believed to be beneficial, though this is often a passive process. Active observation may be more beneficial. Hypotheses: The hypothesis tested in this study was that the active use of a simple checklist during observation of an immersive simulation would result in better participant performance in a subsequent scenario compared with passive observation alone. Methods: Medical students were randomized to either passive or active (with checklist) observation of an immersive simulation involving cardiac arrest prior to participating in their own simulation. Performance measures included time to cardiopulmonary resuscitation (CPR) and time to defibrillation and were compared between first and second scenarios as well as between passive and active observers. Results: Seventy-nine simulations involving 232 students were conducted. Mean time to CPR was 18 seconds (SD = 11.6) for those using the checklist and 24 seconds (SD = 15.8) for those who observed passively (M difference = 6 seconds), t(35) = 1.46, p =.153. Time to defibrillation was 94 seconds (SD = 26.4) for those using the checklist and 92 seconds (SD = 23.8) for those who observed passively (M difference = –2 seconds), t(38) =.21, p =.837. Time to CPR was 24 seconds (SD = 15.8) for passive observers and 31 seconds (SD = 21.0; M difference = 7 seconds), t(35) = 1.13, p =.265, for their first scenario counterparts. Time to CPR was 18 seconds (SD = 11.6) for active observers and 36 seconds (SD = 26.2; M difference = 18 seconds), t(24) = 2.81, p =.010, for their first scenario counterparts. Time to defibrillation was 92 seconds (SD = 23.8) for passive observers and 125 seconds (SD = 32.2; M difference = 33 seconds), t(33) = 3.63, p =.001, for their first scenario counterparts. Time to defibrillation was 94 seconds (SD = 26.4) for the active observers and 132 seconds (SD = 52.9; M difference = 38 seconds), t(28) =.46, p =.008, for their first scenario counterparts. Conclusions: Observation alone leads to improved performance in the management of a simulated cardiac arrest. The active use of a simple skills-based checklist during observation did not appear to improve performance over passive observation alone.     

高龄妊娠的产前咨询

高龄妊娠是指孕妇妊娠年龄≥35岁，近年来其发生率不断增高，已经逐步成为目前我国围产医学关注的热点问题。针对高龄妊娠中的生殖遗传问题，需特别关注女性的生育力下降的情况，其自然流产发生率升高，胎儿染色体异常和胎儿结构畸形的发生率增加，这就更加强调了产前筛查和诊断的重要性，以及需要关注常常与高龄妊娠相伴随的男性高龄生育的问题。做好上述问题的咨询和管理是完成高质量高龄妊娠围产保健的关键。     

肝内胆管癌新辅助治疗共识与争议

肝内胆管癌（ICC）恶性程度高，症状隐匿，早期症状不明显，由于缺乏有效的筛查，确诊时多处于进展期，大多失去手术切除机会。目前，根治性手术仍是惟一可以使病人获得长期生存的治疗方式，但存在切除率低、术后易复发等难题。新辅助治疗能缩小原有病灶及转移的淋巴结，提高R0切除率，对于无法切除的局部晚期ICC，新辅助治疗可使局部进展的ICC降期为可切除，也可改善肝移植病人的预后。但目前对ICC行新辅助治疗的潜在效用仍存在争议。