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.     

A randomized study on the effect of modified behavioral activation treatment for depressive symptoms in rural left-behind elderly

Objective: To evaluate the effectiveness of a modified behavioral activation treatment (MBAT) intervention on reducing depressive symptoms in rural left-behind elderly.

Method: This is a randomized study registered in Chinese Clinical Trial Registry (ChiCTR-IOR-17011289). Eighty rural left-behind elderly people who had a Geriatric Depression Scale (GDS) score between 11 and 25 were randomly assigned to the intervention (n?=?40) and control group (n?=?40). The intervention group received both MBAT and regular treatment for 8 weeks while the control group received regular treatment. Both groups were assessed with the GDS, Beck Anxiety Inventory (BAI), and Oxford Happiness Questionnaire (OHQ) at baseline, immediately post-intervention, and at 3 months post-intervention.

Results: There were a total of 73 participants that completed the intervention. The scores of GDS and BAI decreased significantly, but the scores of OHQ increased significantly in the intervention group after 8 sessions of MBAT (P?<?.01). The reduction in depression symptoms after the intervention was maintained at the 3-month follow-up. Significant differences in GDS, BAI, and OHQ scores were observed between the intervention group and the control group (P?<?.01).

Conclusion: MBAT produced a significantly greater reduction in depressive symptoms than regular care in rural left-behind elderly.

Clinical or methodological significance of this article: A modified behavioral activation (BA) psychotherapy can significantly reduce the recurrence and seriousness of depression symptoms in the left-behind elderly with mild to moderate depression. This study also suggests that further study of the MBAT as an intervention will provide a direction for the management of mental health in rural left-behind elders.     

肠道菌群与恶性肿瘤的研究进展

人类微生物群是由寄生在人体上皮屏障的细菌和其他微生物组成的，其中大部分位于肠道内，与宿主之间形成共生的关系。机体肠道微生物的组成虽然受到年龄、饮食、生活方式等因素的影响，但在正常生理情况下是相对稳定的。近年来，肠道菌群与恶性肿瘤的关系越来越受到重视。肠道菌群不但能够维持局部稳态，还能调节机体代谢、炎症和免疫等生理过程。有研究表明，微生物群，特别是肠道菌群能够显著调节机体对癌症治疗的反应性以及机体对毒副反应的敏感性。检查肠道菌群中各菌种之间的比例可作为筛查恶性肿瘤的新方法。本文将综述微生物群具有影响肿瘤的发生发展、抗肿瘤治疗疗效以及药物不良反应的证据，以及其中所涉及的微生物种类，从而为恶性肿瘤精准治疗提供证据。     

山东济宁某医院门诊患者幽门螺杆菌感染检测分析

目的探讨分析山东济宁地区自然人群幽门螺杆菌的流行病学特征,为防治提供参考。方法于2012-05/2013-05采集山东济宁市第一人民医院胃镜室就诊患者580例,采用14C-UBT检测法与血清幽门螺杆菌Ig G抗体ELISA法对所有研究对象的幽门螺杆菌感染情况进行检测,并结合相关问卷调查,分析其流行病学特征。结果该医院门诊患者幽门螺杆菌总感染率45.2%,其中男性感染率59.5%,女性感染率40.5%,不同性别感染幽门螺杆菌感染阳性率差异比较无统计学意义(P0.05);各年龄段幽门螺杆菌的感染率从31.4%~53.1%不等,农民、商人及工人幽门螺杆菌感染率分别为78.6%、70.7%、68.8%,高于其他职业,差异有统计学意义(P0.05),但各年龄段间幽门螺杆菌感染率的差异比较无统计学意义(P0.05)。幽门螺杆菌感染与吸烟、饮酒、家庭收入无关,差异无统计学意义(均P0.05),与个人饮食卫生习惯、家庭教育程度及职业有关,差异有统计学意义(P0.05)。结论山东济宁市某医院门诊患者幽门螺杆菌总感染率较高,其感染率与职业、个人及家庭生活习惯等有关。     

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.     

In Vivo Kinematics of Functional Ankle Instability Patients and Lateral Ankle Sprain Copers During Stair Descent

Patients with mechanic ankle instability experience increased tibiotalar and subtalar joint laxity. However, in vivo joint kinematics in functional ankle instability (FAI) patients and lateral ankle sprain (LAS) copers, especially during dynamic activities, are poorly understood. Ten FAI patients, 10 LAS copers, and 10 healthy controls were included in this study. A dual fluoroscopic imaging system was used to analyze the tibiotalar and subtalar joint kinematics during stair descent. Five key poses of stair descent were analyzed. Kinematic data from six degrees of freedom were calculated utilizing a solid modeling software. The range of motion and joint positions in each degree of freedom were compared among the three groups. The tibiotalar joints of FAI patients and LAS copers were significantly more inverted than those of healthy controls during the foot strike (p = 0.016, = 0.264). The subtalar joints of FAI patients were significantly more anteriorly translated (pose 2, p = 0.003, = 0.352; pose 3, p < 0.001, = 0.454; pose 4, p = 0.004, = 0.334), inverted (pose 4, p = 0.027, = 0.234; pose 5,p = 0.034, = 0.221), and externally rotated (pose 4, p = 0.037, = 0.217; pose 5; p = 0.004, = 0.331) than those of healthy controls during the mid‐stance and the heel off. The FAI patients showed excessive tibiotalar inversion and subtalar joint hypermobility during stair descent. Meanwhile, the LAS copers maintained subtalar joint stability, and only showed excessive tibiotalar inversion in foot strike. These data provide insight into the mechanisms behind the development of FAI after initial LAS. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1860–1867, 2019