Neuroendocrine,epigenetic, and intergenerational effects of general anesthetics

The progress of modern medicine would be impossible without the use of general anesthetics (GAs). Despite advancements in refining anesthesia approaches, the effects of GAs are not fully reversible upon GA withdrawal. Neurocognitive deficiencies attributed to GA exposure may persist in neonates or endure for weeks to years in the elderly. Human studies on the mechanisms of the long-term adverse effects of GAs are needed to improve the safety of general anesthesia but they are hampered not only by ethical limitations specific to human research, but also by a lack of specific biological markers that can be used in human studies to safely and objectively study such effects. The latter can primarily be attributed to an insufficient understanding of the full range of the biological effects induced by GAs and the molecular mechanisms mediating such effects even in rodents, which are far more extensively studied than any other species. Our most recent experimental findings in rodents suggest that GAs may adversely affect many more people than is currently anticipated. Specifically, we have shown that anesthesia with the commonly used GA sevoflurane induces in exposed animals not only neuroendocrine abnormalities (somatic effects), but also epigenetic reprogramming of germ cells (germ cell effects). The latter may pass the neurobehavioral effects of parental sevoflurane exposure to the offspring, who may be affected even at levels of anesthesia that are not harmful to the exposed parents. The large number of patients who require general anesthesia, the even larger number of their future unexposed offspring whose health may be affected, and a growing number of neurodevelopmental disorders of unknown etiology underscore the translational importance of investigating the intergenerational effects of GAs. In this mini review, we discuss emerging experimental findings on neuroendocrine, epigenetic, and intergenerational effects of GAs.     

精索静脉曲张手术后患者的管理策略

手术治疗精索静脉曲张在改善精液质量、提高配偶自然怀孕率和缓解局部疼痛症状中的作用已为多数医生所认同。随着手术方式的改进,越来越多的精索静脉曲张患者接受手术治疗,然而,临床对手术后患者的管理还重视不够。本文系统介绍了对精索静脉曲张手术后患者的疗效判断和后续治疗选择,包括观察随诊、非手术治疗方法和再手术。     

Exact confidence intervals for the average causal effect on a binary outcome

Based on the physical randomization of completely randomized experiments, in a recent article in Statistics in Medicine, Rigdon and Hudgens propose two approaches to obtaining exact confidence intervals for the average causal effect on a binary outcome. They construct the first confidence interval by combining, with the Bonferroni adjustment, the prediction sets for treatment effects among treatment and control groups, and the second one by inverting a series of randomization tests. With sample size n, their second approach requires performing O(n⁴)randomization tests. We demonstrate that the physical randomization also justifies other ways to constructing exact confidence intervals that are more computationally efficient. By exploiting recent advances in hypergeometric confidence intervals and the stochastic order information of randomization tests, we propose approaches that either do not need to invoke Monte Carlo or require performing at most O(n²)randomization tests. We provide technical details and R code in the Supporting Information . Copyright © 2016 John Wiley & Sons, Ltd.     

Clinical Diagnostic Implications of Body Fluid MiRNA in Oral Squamous Cell Carcinoma: A Meta-Analysis

Oral cancer, predominantly oral squamous cell carcinoma (OSCC), is one of the most leading causes of cancers worldwide. Due to a low 5-year survival rate, highly effective methods for the early detection of OSCC are totally needed. MicroRNAs (miRNAs), as promising biomarkers, can bring insights into tumorigenesis of oral cancers. However, studies on the accuracy of miRNAs detection in OSCC have inconsistent conclusions, leading us to conduct this meta-analysis. The aim of this study was to systematically review the articles investigating the diagnostic value of miRNAs in OSCC.The PubMed, Embase, Chinese National Knowledge Infrastructure (CNKI), Web of Science were searched (updated to June 11th, 2015) to identify all articles evaluating the diagnostic yield of miRNAs for OSCC. The pooled sensitivity, specificity, and other diagnostic parameters were used to assess the performance of miRNAs assays on OSCC detection. Statistical analysis was conducted by employing the R software.The present meta-analysis comprised 23 studies from 10 articles, including 598 OSCC patients and 320 healthy individuals, available for analysis. The summary receiver operator characteristic (SROC) curve was plotted. Meanwhile, the pooled diagnostic parameters and the area under curve (AUC) were calculated based on all included studies. The pooled diagnostic parameters calculated from all 23 studies were as follows: pooled sensitivity of 0.759 (95% CI: 0.701–0.809), pooled specificity of 0.773 (95% CI: 0.713–0.823) and AUC of 0.832, which indicates a relatively high diagnostic accuracy of miRNAs in differentiating OSCC patients from healthy controls. Meanwhile, In addition, subgroup analyses were conducted to access the heterogeneity between studies, which is based on specimen (serum/plasma/blood/saliva/ tissue) and ethnicity (Asian/Caucasian).In summary, our meta-analysis suggests that miRNAs might be used in noninvasive screening tests for OSCC, which needs further large-scale studies to be validated.     

早期十全大补汤联合肠内营养乳剂治疗胃癌术后(气血两虚证)喂养不耐受临床评价

目的探讨早期使用十全大补汤联合肠内营养乳剂(TP)治疗胃癌术后(气血两虚证)发生喂养不耐受(FI)的影响因素及对营养指标、中医证候积分的影响。方法回顾性分析术后早期行十全大补汤联合TP治疗的80例胃癌术后(气血两虚)患者的病历资料,根据是否出现FI分为耐受组(34例)和不耐受组(46例)。FI的相关影响因素进行单因素及多因素分析,并观察FI对患者营养指标、中医证候积分的影响。结果单因素分析显示,患者术后第1天下床活动时间、开始肠内营养(EN)的时间、使用营养泵、早期灌肠与FI的发生密切相关(P <0. 05);多因素Logistic回归分析显示,患者第1天下床活动时间≥2 h[OR=0. 022,P=0. 001,95%CI(0. 002,0. 223)]、使用营养泵[OR=0. 021,P=0. 000,95%CI(0. 003,0. 162)]是FI发生的独立危险因素;术后10 d,耐受组患者白蛋白(ALB)、血红蛋白(Hb)升高水平优于不耐受组(P <0. 05),中医证候积分显著低于不耐受组(P <0. 05)。结论胃癌术后(气血两虚证)患者早期给予十全大补汤联合TP治疗开始后,患者第1天下床活动时间不短于2 h、使用营养泵能有效减少FI的发生,并改善了患者的营养状态,减轻了中医临床症状。     

Baicalin-loaded PEGylated lipid nanoparticles: characterization,pharmacokinetics, and protective effects on acute myocardial ischemia in rats

Context: Baicalin has many pharmacological activities, including protective function against myocardial ischemia by antioxidant effects and free radical scavenging activity. However, its rapid elimination half-life in plasma and poor water solubility limits its clinical efficacy.

Objective: Novel baicalin-loaded PEGylated nanostructured lipid carriers (BN-PEG-NLC) were developed to improve bioavailability of BN, to prolong retention time in vivo and to enhance its protective effect.

Methods: In this study, BN-PEG-NLC were prepared by the emulsion-evaporation and low temperature-solidification method using a mixture of glycerol monostearate and polyethylene glycol monostearate as solid lipids, and oleic acid as the liquid lipid. The physicochemical properties of NLC were characterized. The pharmacokinetic and pharmacodynamic behaviors of BN-PEG-NLC or BN-NLC were evaluated in acute MI rats.

Results and discussion: The particle size, zeta potential, and entrapment efficiency for BN-PEG-NLC were observed as 83.9?nm, ?32.1?mV, and 83.5%, respectively. The release profiles of BN from both BN-PEG-NLC and BN-NLC were fitted to the Ritger–Peppas modal, which presented burst release initially and prolonged release afterwards. Pharmacokinetics results indicated that BN-PEG-NLC exhibited a 7.2-fold increase in AUC in comparison to BN solution, while a 3-fold increase in comparison to BN-NLC. Biodistribution results revealed that BN-PEG-NLC exhibited higher heart drug concentration compared with BN-NLC as well as BN solution. In the present study, BN-PEG-NLC significantly ameliorated infarct size.

Conclusion: The results of the present study imply that PEG-NLC could be the biocompatible carriers for heart-targeted drug delivery to improve myocardial ischemia.