代谢解毒酶活性变化和击倒抗性基因突变在白纹伊蚊菊酯类杀虫剂抗性产生中的作用

目的 探讨代谢解毒酶活性变化和击倒抗性（kdr）基因突变在白纹伊蚊菊酯类抗性机制中的作用。方法 2017年8月至9月分别在山东省济南市千佛山公园（JN）、浙江省杭州市上茅家埠（HZ）、上海市宝山区宝山六村（BS）、上海市杨浦区共青森林公园（YP）和海南省海口市美兰区居民区（HK）采集现场白纹伊蚊（生物测定均为抗性种群）,检测其代谢解毒酶谷胱甘肽S-转移酶（GST）和多功能氧化酶（MFO）的活性并与敏感品系的白纹伊蚊比较,采用分类回归树方法（CART）分析GST和MFO活性变化及kdr突变（I1532和F1534）在抗性产生中的贡献率。结果 白纹伊蚊敏感品系的GST和MFO的活性基线水平均高于现场抗性种群BS和HK（P均<0.01）。BS种群接触溴氰菊酯后与未接触杀虫剂的基线相比,GST和MFO变化不明显（P>0.05）,接触氯菊酯后GST活性升高（P<0.05）,MFO活性也升高（P<0.01）;HK种群接触溴氰菊酯后GST活性差异不明显（P>0.05）、MFO活性升高（P<0.01）,接触氯菊酯后GST和MFO活性变化均不明显（P均>0.05）。5个现场抗性种群接触溴氰菊酯和氯菊酯后的GST和MFO活性与敏感品系的基线相比,变化无规律。CART分析结果显示,白纹伊蚊对溴氰菊酯的抗性产生中GST活性和kdr F1534突变的贡献率较大,其次是MFO活性,kdr I1532突变贡献率最小;对氯菊酯的抗性产生中,kdr F1534突变的贡献率最大,其次是GST和MFO活性,kdr I1532突变无贡献。结论 代谢解毒酶GST和MFO活性水平不适合作为判断白纹伊蚊种群对菊酯类杀虫剂抗性的单因素指标;代谢解毒酶活性变化和kdr突变可能是白纹伊蚊对菊酯类杀虫剂抗性产生中相互协同的2种机制。     

巨噬细胞功能M1/M2极性化在心血管疾病中的研究进展

巨噬细胞是先天免疫系统的主要细胞,具有可塑性和异质性,在机体的免疫应答、组织稳态、重塑等多方面发挥重要功能。根据功能极性可分为M1(促炎)和M2(抗炎)2个亚型。M1/M2巨噬细胞在响应局部微环境的刺激反应过程中,通过改变其功能极化,获得特定的功能表型并分泌不同的细胞因子。巨噬细胞通过改变代谢重编程以适应其功能变化。M2巨噬细胞以氧化磷酸化和脂肪酸为能量代谢的主要方式,而M1巨噬细胞为无氧糖酵解。目前研究发现在心血管疾病中,巨噬细胞可能通过其功能极性变化引起巨噬细胞激活、组织浸润、释放促炎性细胞因子而参与心血管疾病的发生。本文对巨噬细胞功能极化、代谢重编程在心血管疾病中的作用进行综述。     

10140例肾结石患者临床合并症及相关因素分析

目的 评估肾结石患者的人口学分布和临床合并症特点并探索其相关因素,为临床防治提供依据。方法 回顾性分析2017年1月至2020年12月海军军医大学附属长海医院门诊及住院患者中影像学报告为肾结石的10140例患者。根据受累肾脏情况,分为单侧肾结石组(单侧组)及双侧肾结石组(双侧组),分析两组人群在年龄、性别、实验室检查、常见临床合并症上的差异,采用logistic回归探寻可能影响双侧肾结石形成的相关因素。结果 10140例肾结石患者的平均年龄为57.75±13.30岁,男女比例为2.25:1。其中单侧组8171例（80.6%）,双侧组1969例（19.6%）。所有肾结石患者最常见的临床合并症依次为高血压病(HT)、肿瘤、高尿酸血症、糖尿病(DM)、冠心病(CHD)、脑血管疾病。两组在年龄、性别的分布,以及HT、肿瘤、高尿酸血症、CHD的合并率方面差异有统计学意义(P<0.05);而在体重指数(BMI)、DM、脑血管疾病的合并率方面差异无统计学意义(P>0.05)。实验室检查方面,单侧组血清肌酐(Cr)、尿酸(UA)、尿pH值水平低于双侧组(P<0.05);而高密度脂蛋白胆固醇(HDL-C)水平高于双侧组(P<0.05);空腹血糖(FPG)、甘油三酯(TG)、胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)水平方面两组之间差异无统计学意义(P>0.05)。此外,性别(男性)、高尿酸血症可能是双侧肾结石形成的重要相关因素(P<0.05),而合并肿瘤则更倾向于表现为单侧肾结石患者(P<0.05)。结论 肾结石更多见于中年男性,代谢综合征相关疾病在肾结石的发展过程扮演了重要角色,有必要加强这些疾患的早期防治。肾结石患者肿瘤合并率高,提示两者存在关联。此外,较单侧肾结石而言,男性、合并高尿酸血症与双侧肾结石形成关系更密切,应当引起重视。     

Combined Liver Transplantation and Gastric Sleeve Resection for Patients With Medically Complicated Obesity and End‐Stage Liver Disease

Obesity is increasingly common before and after liver transplantation (LT), yet optimal management remains unclear. Our aim was to analyze the effectiveness of a multidisciplinary protocol for obese patients requiring LT, including a noninvasive pretransplant weight loss program, and a combined LT plus sleeve gastrectomy (SG) for obese patients who failed to lose weight prior to LT. Since 2006, all patients referred LT with a BMI > 35 were enrolled. There were 37 patients who achieved weight loss and underwent LT alone, and 7 who underwent LT combined with SG. In those who received LT alone, weight gain to BMI > 35 was seen in 21/34, post‐LT diabetes (DM) in 12/34, steatosis in 7/34, with 3 deaths plus 3 grafts losses. In patients undergoing the combined procedure, there were no deaths or graft losses. One patient developed a leak from the gastric staple line, and one had excess weight loss. No patients developed post‐LT DM or steatosis, and all had substantial weight loss (mean BMI = 29). Noninvasive pretransplant weight loss was achieved by a majority, though weight gain post‐LT was common. Combined LT plus SG resulted in effective weight loss and was associated with fewer post‐LT metabolic complications. Long‐term follow‐up is needed.     

Effects of cigarette smoking on iodine 123 N-isopropyl-p-iodoamphetamine clearance from the lung

Iodine 123 N-isopropyl p-iodoamphetamine (¹²³I-IMP), originally developed as a brain scanning agent, is also taken up by the lung. To evaluate the effects of cigarette smoking on the kinetics of IMP in the lung, we studied ¹²³I-IMP clearance from the lung in 18 volunteers (8 non-smokers and 10 smokers). After the injection of 111 MBq of ¹²³I-IMP into the medial cubital vein, the time-activity curve for 60 min and the regional activity using 1 frame per minute and a 64 × 64 matrix were obtained. The ¹²³I-IMP clearance curve was described as follows: C (t) = A ₁e^–k ₁ t+ A ₂e^–k ₂ t (A1, A ₂: intercepts, and k ₁, k ₂: slopes of the exponential components). ¹²³I-IMP clearance was delayed in smokers, and k ₂ was smaller in smokers. Also, a correlation between k ₁, k ₂, and the number of cigarettes smoked per day was found (r = –0.65, r = –0.74, respectively, P<0.01). In conclusion, this study suggests that the delayed clearance and retention of ¹²³I-IMP in the lung indicate lung metabolic disorders due to cigarette smoking.Offprint requests to: K. Kato     

老年高血压患者血小板活化检测及临床意义

为探讨老年高血压患者血小板活化及其临床意义，采用流式细胞术（FCM）以单克隆抗体分子作为分子探针检测健康老年人及老年高血压无并发症患者血小板膜上糖蛋白GPⅡa/Ⅲa(PAC-1)及P－选择素（CD62P）的表达量。结果表明，老年高血压患者血小板膜上PAC－1的表达量较健康老年人高（P＜0．01），与当日平均血压无相关关系，而CD62P的表达量与健康对照组比较差异无显著性意义。提示通过FCM检测血小板膜上PAC－1的表达量，可了解高血压患者体内血小板活化度，对临床用抗血小板药有指导意义。     

Impaired macrophage leishmanicidal activity at cutaneous temperature

Summary Temperature is one of the primary influences upon the pathogenesis of cutaneous leishmaniasis. In this study, we measured the temperature of murine leishmanial lesions and determined the ability of lymphokine (LK) activated macrophages to kill Leishmania major at these temperatures. The temperature of leishmanial lesions in BALB/c and C3H/HeN mice ranged from 27°C to 32°C. We found that LK activated resident or inflammatory macrophages exhibited significantly less leishmanicidal activity in vitro at temperatures closer to those measured in vivo . The decrease in microbicidal activity was not due to the enhanced growth of the parasites at lower temperatures, since impaired killing was also observed against non-replicating radiation attenuated amastigotes. Finally, the tumoricidal activity of macrophages was found to be significantly depressed at temperatures below 37°C, indicating a generalized impairment of macrophage function at these temperatures. These findings suggest that impaired macrophage microbicidal activity at cutaneous temperatures may contribute to parasite survival, and imply that healing of leishmanial lesions, as well as other cutaneous infections, may require an exceptionally potent local LK response.     

Plasma Total Prekallikrein/Kallikrein Activity in Rheumatoid Arthritis with and without Amyloidosis

ABSTRACT Following exposure to kaolin, plasma samples were assayed for total prekallikrein/kallikrein activity in 19 patients with rheumatoid arthritis (RA), 39 patients with RA complicated by amyloidosis, 13 patients with nonamyloid nephropathy and 54 healthy subjects. Increased total kallikrein activity was found in RA patients with amyloidosis and in patients with nonamyloid nephropathy. The concentrations of the plasma kallikrein inhibitors Cl-inactivator and α2-macroglobulin were normal in RA patients without amyloidosis, whereas they were increased in patients with amyloidosis as well as in patients with nonamyloid nephropathy. The results suggest that the increased activity of plasma kaolinstimulated kallikrein in RA patients with amyloidosis is due to the nephropathy per se and probably reflects increased levels of prekallikrein.     

Coordinate‐based (ALE) meta‐analysis of brain activation in patients with fibromyalgia

There are an increasing number of neuroimaging studies that allow a better understanding of symptoms, neural correlates and associated conditions of fibromyalgia. However, the results of these studies are difficult to compare, as they include a heterogeneous group of patients, use different stimulation paradigms, tasks, and the statistical evaluation of neuroimaging data shows high variability. Therefore, this meta‐analytic approach aimed at evaluating potential alterations in neuronal brain activity or structure related to pain processing in fibromyalgia syndrome (FMS) patients, using quantitative coordinate‐based “activation likelihood estimation” (ALE) meta‐analysis. 37 FMS papers met the inclusion criteria for an ALE analysis (1,264 subjects, 274 activation foci). A pooled ALE analysis of different modalities of neuroimaging and additional analyses according functional and structural changes indicated differences between FMS patients and controls in the insula, amygdala, anterior/mid cingulate cortex, superior temporal gyrus, the primary and secondary somatosensory cortex, and lingual gyrus. Our analysis showed consistent results across FMS studies with potential abnormalities especially in pain‐related brain areas. Given that similar alterations have already been demonstrated in patients with other chronic pain conditions and the lack of adequate control groups of chronic pain subjects in most FMS studies, it is not clear however, whether these findings are associated with chronic pain in general or are unique features of patients with FMS. Hum Brain Mapp 37:1749–1758, 2016. © 2016 Wiley Periodicals, Inc .     

Spatial memory extinction differentially affects dorsal and ventral hippocampal metabolic activity and associated functional brain networks

Previous studies showed the involvement of brain regions associated with both spatial learning and associative learning in spatial memory extinction, although the specific role of the dorsal and ventral hippocampus and the extended hippocampal system including the mammillary body in the process is still controversial. The present study aimed to identify the involvement of the dorsal and ventral hippocampus, together with cortical regions, the amygdaloid nuclei, and the mammillary bodies in the extinction of a spatial memory task. To address these issues, quantitative cytochrome c oxidase histochemistry was applied as a metabolic brain mapping method. Rats were trained in a reference memory task using the Morris water maze, followed by an extinction procedure of the previously acquired memory task. Results show that rats learned successfully the spatial memory task as shown by the progressive decrease in measured latencies to reach the escape platform and the results obtained in the probe test. Spatial memory was subsequently extinguished as shown by the descending preference for the previously reinforced location. A control naïve group was added to ensure that brain metabolic changes were specifically related with performance in the spatial memory extinction task. Extinction of the original spatial learning task significantly modified the metabolic activity in the dorsal and ventral hippocampus, the amygdala and the mammillary bodies. Moreover, the ventral hippocampus, the lateral mammillary body and the retrosplenial cortex were differentially recruited in the spatial memory extinction task, as shown by group differences in brain metabolic networks. These findings provide new insights on the brain regions and functional brain networks underlying spatial memory, and specifically spatial memory extinction. © 2016 Wiley Periodicals, Inc.