NLRP3炎症小体与糖尿病心肌病的关系及中医药调控研究进展

糖尿病心肌病（DCM）是糖尿病的并发症之一,是指发生在糖尿病中,其发病机制区别于其他心血管疾病如冠心病、心脏瓣膜病、亦或先天性心脏病的一种特发类心肌病,亦是多年以来糖尿病患者的主要致死病因之一。研究表明,DCM的发病机制与胰岛素抵抗、多种炎症反应激活、氧化应激增加、冠状动脉微循环受阻、晚期糖基化终产物（AGEs）积累等过程有密切联系。而在多种炎症反应中,NOD样受体蛋白3（NLRP3）炎症小体激活可通过炎症的级联反应诱导分泌出大量促炎细胞因子,继而介导细胞焦亡过程,促进心肌损伤。目前基于NLRP3炎症小体在DCM损伤防治重要作用功能,国内外开展了大量中医药实验研究,证明了黄芪多糖、人参皂苷Rb₁等中药提取物或单味中药如云芝、冬虫夏草亦或抵挡汤、加味桃核承气汤等组方制剂及针刺、中医运动疗法等可通过调控NLRP3炎症小体的相关通路从而抑制其组装或激活,降低炎症反应,进而抑制DCM中心肌的重构,改善DCM的心脏功能。该文就NLRP3炎症小体与DCM的关系及中医药在此领域中发挥抗炎效应的研究进展进行综述,旨在为DCM开发治疗手段提供新的思路。     

脾阴虚证大鼠模型中水通道蛋白及肠道菌群的变化分析

目的：以脾阴虚证模型大鼠为研究对象,探析脾阴虚对胃肠吸收、水液代谢及肠道菌群的影响。方法：采用荤素饮食不节、负重疲劳游泳和温热伤阴药灌胃复合因素建立脾阴虚证大鼠模型,观察空白组和模型组大鼠的体质量、进食量、饮水量、游泳持续时间的变化;苏木素-伊红（HE）染色观察胃和结肠组织病理损伤情况;间苯三酚法检测尿D-木糖排泄率;酶联免疫吸附测定法（ELISA）检测血清中胃泌素（GAS）含量;蛋白免疫印迹法（Western blot）检测胃组织中血管活性肠肽（VIP）、水通道蛋白3(AQP3)、AQP4的相对表达水平;实时荧光定量聚合酶链式反应（Real-time PCR）检测胃组织中VIP、AQP3、AQP4的mRNA相对表达水平;16S rDNA测序分析其肠道菌群的变化。结果：与空白组比较,一般体征结果显示,模型组大鼠体质量和进食量均明显降低,饮水量明显增多（P<0.05,P<0.01）,游泳持续时间显著减少（P<0.01）;病理检测结果显示,模型组大鼠胃组织黏膜出现排列不齐,结肠组织黏膜可见明显变薄或有残缺,上皮细胞出现坏死甚至脱落现象;与空白组比较,模型组大鼠尿D-木糖排...     

鹰嘴豆芽素A通过调节TLR4/NF-κB/NLRP3信号通路减轻卵清蛋白诱导哮喘大鼠的气道炎症

[目的] 探讨鹰嘴豆芽素A（BCA）通过调节Toll样受体4（TLR4）/核因子-κB（NF-κB）/NOD样受体蛋白3（NLRP3）信号通路对卵清蛋白（OVA）诱导哮喘大鼠气道炎症的影响。[方法] 将SD大鼠分为对照（CK）组、模型（Model）组、低剂量BCA组（BCA-L组,25 mg/kg）、高剂量BCA组（BCA-H组,100 mg/kg）、地塞米松阳性对照组（Dex组,1 mg/kg）、BCA-H+LPS（TLR4激活剂）组（100 mg/kg+0.1 mg/kg）,每组12只。除CK组,其他组均通过OVA诱导构建哮喘大鼠模型。建模成功24 h后,进行给药处理,给药每日1次,持续10 d。利用动物肺功能测定仪检测大鼠吸气阻力、呼气阻力、肺通气顺应性的变化;吉姆萨（Giemsa）染色检测支气管肺泡灌洗液（BALF）中细胞总数、淋巴细胞数、嗜酸性粒细胞数、中性粒细胞数;酶联免疫吸附剂测定（ELISA）检测BALF中肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）、干扰素-γ（IFN-γ）水平;苏木精-伊红染色法（HE）染色检测大鼠肺组织病理变化;免疫组化检测大鼠肺组织中嗜酸性粒细胞趋化因子（Eotaxin）表达;蛋白质印迹法（Western Blot）检测大鼠肺组织中TLR4、p-NF-κB p65、NLRP3蛋白表达。[结果] 与CK组比较,Model组大鼠吸气阻力、呼气阻力、BALF中细胞总数、淋巴细胞数、嗜酸性粒细胞数、中性粒细胞数、TNF-α、IL-1β、IFN-γ水平升高,肺组织中的支气管及血管周围炎性细胞浸润明显,肺组织中Eotaxin阳性染色面积百分数、TLR4、p-NF-κB p65、NLRP3蛋白表达升高,肺通气顺应性降低（P<0.05）;与Model组比较,BCA-L组、BCA-H组、Dex组对应指标变化趋势与上述相反（P<0.05）;LPS减弱了高剂量BCA对哮喘大鼠气道炎症的改善作用。[结论] BCA可能通过抑制TLR4/NF-κB/NLRP3信号通路减轻OVA诱导哮喘大鼠的气道炎症。     

胎儿脑灰质异位合并FLNA基因突变病例报告

报告1例产前超声联合胎儿颅脑磁共振成像（magnetic resonance imaging,MRI）诊断胎儿脑灰质异位合并细丝蛋白A（filamin A,FLNA）基因突变的病例。患者超声检测结果显示侧脑室外壁凹凸不平,颅后窝池宽,透明隔间腔略窄,小脑延髓池轻度增宽。MRI诊断结果为胎儿脑灰质异位合并大枕大池。羊水穿刺获得脱落细胞,采用全外显子测序和基因拷贝数变异（copy number variations,CNV）分析,显示与脑灰质异位疾病相关的FLNA基因外显子出现缺失,其为可能导致脑灰质异位的致病基因。因此,超声结合胎儿颅脑MRI能有效提高脑灰质异位的诊断率,其中染色体检查可筛查出部分致病原因,并对下次妊娠提供帮助。该病例可丰富临床医生对胎儿大脑灰质异位的产前超声检查、合并畸形、临床表现等的认识。     

Associations Between Thyroid Hormone Levels and Urinary Concentrations of Bisphenol A,F, and S in 6-Year-old Children in Korea

ObjectivesBisphenol A (BPA) is used in the electrical, mechanical, medical, and food industries. Previous studies have suggested that BPA is an endocrine disruptor. Regulation of BPA has led to increased use of bisphenol F (BPF) and bisphenol S (BPS). However, few studies have investigated the associations of BPF and BPS with thyroid dysfunction in children. Our study investigated the associations of prenatal BPA and early childhood BPA, BPF, and BPS exposure with thyroid function in 6-year-old children.MethodsPrenatal BPA concentrations were measured during the second trimester of pregnancy in an established prospective birth cohort. We measured urinary BPA, BPF, and BPS concentrations and thyroid hormone levels (thyroid-stimulating hormone, total T₃, and free T₄) in 6-year-old children (n=574). We examined the associations between urinary bisphenol concentrations and percentage change of thyroid hormone concentrations using multivariate linear regression. We also compared thyroid hormone levels by dividing the cohort according to BPA, BPF, and BPS concentrations.ResultsThe associations between prenatal BPA and total T₃ levels were statistically significant in all models, except for girls when using a crude model. The associations between urinary BPA and BPS concentrations and levels of all thyroid hormones were not statistically significant. However, we observed that lower free T₄ levels (−1.94%; 95% confidence interval, −3.82 to −0.03) were associated with higher urinary BPF concentrations in girls only.ConclusionsOur findings identified significant associations between prenatal BPA exposure and total T₃ levels in all children and between BPF exposure and free T₄ levels in girls only.     

Effect of Heat-Killed Lactobacillus casei DKGF7 on a Rat Model of Irritable Bowel Syndrome

Non-viable bacteria, referred to as “paraprobiotics,” have attracted attention as potentially safer alternatives to probiotics. The aim of this study was to investigate the efficacy of heat-killed Lactobacillus casei DKGF7 on the symptomatic improvement of irritable bowel syndrome (IBS) in a rat disease model and to elucidate the underlying mechanisms that contribute to the beneficial effects of heat-killed probiotics. Seven male Wistar rats were induced with IBS by restraint stress and administered heat-killed L. casei DKGF7 for four weeks and then compared with seven rats in the control group. Stool consistency measured four weeks after initial treatment was the primary outcome measure. To investigate the mechanism of action of the heat-killed bacteria on IBS, we measured serum corticosterone levels, inflammatory cytokines in colon tissue, and expression of tight junction proteins (TJPs) in the epithelium. The treatment group showed significantly better stool consistency scores than the control group at week 4, as well as at every measured time point (all p values < 0.05). The treatment group showed lower serum corticosterone levels, lower colonic inflammatory cytokine levels, and higher expression of TJPs compared with the control group. Paraprobiotics such as heat-killed L. casei DKGF7 can improve stool consistency in a rat IBS model, which may indicate a potential therapeutic strategy for IBS treatment.     

Sex-Dependent Effects of 7,8-Dihydroxyflavone on Metabolic Health Are Associated with Alterations in the Host Gut Microbiome

7,8-Dihydroxyflavone (DHF) is a naturally occurring flavonoid that has been reported to protect against a variety of pathologies. Chronic administration of DHF prevents high-fat diet (HFD)-induced obesity in female, but not male, mice. However, the mechanisms underlying this sexual dimorphism have not been elucidated. We have discovered that oral DHF supplementation significantly attenuates fat mass, hepatic lipid accumulation, and adipose tissue inflammation in female mice. In contrast, male mice were not protected from adiposity, and had a paradoxical worsening of hepatic lipid accumulation and adipose tissue inflammation upon DHF supplementation. Consistent with these sexually dimorphic effects on body weight and metabolic health, 7,8-DHF induced early and stable remodeling of the female intestinal microbiome. DHF supplementation significantly increased gut microbial diversity, and suppressed potentially detrimental bacteria, particularly Desulfovibrionaceae, which are pro-inflammatory and positively associated with obesity and inflammation. Changes in the female gut microbiome preceded alterations in body weights, and in silico analyses indicated that these early microbial changes were highly predictive of subsequent weight gain in female mice. While some alterations in the intestinal microbiome were also observed in male DHF-supplemented mice, these changes were distinct from those in females and, importantly, were not predictive of subsequent body weight changes in male animals. The temporality of microbial changes preceding alterations in body weight in female mice suggests a role for the gut microbiome in mediating the sexually dimorphic effects of DHF on body weight. Given the significant clinical interest in this flavonoid across a wide range of pathologies, further elucidation of these sexually dimorphic effects will aid the development of effective clinical therapies.     

Effects of a Short-Term “Fat Adaptation with Carbohydrate Restoration” Diet on Metabolic Responses and Exercise Performance in Well-Trained Runners

Periodized carbohydrate availability can enhance exercise capacity, but the effects of short-term fat adaptation carbohydrate restoration (FACR) diets on metabolic responses and exercise performance in endurance athletes have not been conclusively determined. This study aimed to investigate the effect of a FACR diet on measures of resting metabolism, exercise metabolism, and exercise performance. Well-trained male runners (n = 8) completed a FACR dietary intervention (five days’ carbohydrate < 20% and fat > 60% energy, plus one-day carbohydrate ≥ 70% energy), and a control high-carbohydrate (HCHO) diet for six days (carbohydrate > 60% energy; fat < 20% energy) in a randomized crossover design. Pre- and post-intervention metabolic measures included resting metabolic rate (RMR), respiratory quotient (RQ), maximum fat oxidation rate during exercise (MFO), and maximum fat oxidation intensity (FATmax). Measures of exercise performance included maximal oxygen uptake (VO₂max), running economy (RE), and 5 km running time trial (5 km-TT). In FACR compared with HCHO, there were significant improvements in FATmax (p = 0.006) and RE (p = 0.048). There were no significant differences (p > 0.05) between FACR and HCHO in RMR, RQ, VO₂max, or 5 km-TT. Findings suggest that a short-term (six days) FACR diet may facilitate increased fat oxidation and submaximal exercise economy but does not improve 5 km-TT performance.     

Seminar-CBT教学法在中职护理《内科护理学》教学中的应用与实施

目的:探讨在中职《内科护理学》教学中联合应用专题研讨课(Seminar)和案例教学法(Case-based teaching,CBT)的实施效果。方法:在中职《内科护理学》课程中实施Seminar-CBT教学法,采用自设问卷调查的形式,在课程结束后收集学生对《内科护理学》结合Seminar-CBT教学法的态度和学习效果的自我评价。结果:观察组成绩考核优于对照组(P<0.05),Seminar-CBT教学法的教学反馈各条目积极评价率均在85%以上。结论:Seminar-CBT教学法应用于中职护理《内科护理学》教学,操作性和可行性强,有利于提高学生灵活应用内科护理学知识的能力。     

Correction to: Factor Structure and Equivalence of Maternal Resources for Care in Bangladesh,Vietnam, and Ethiopia

Maternal and Child Health Journal - The article “Factor Structure and Equivalence of Maternal Resources for Care in Bangladesh, Vietnam, and Ethiopia”, written by Sulochana Basnet,...