TGFβ1抗体复合生物蛋白胶预防术后肌腱粘连

目的:研究TGFβ1抗体复合生物蛋白胶(FG)预防鞘管区屈肌腱粘连的作用和对肌腱愈合的影响.方法:将72只来亨鸡(leghorn)按随机化原则分为单纯TGFβ1抗体(TGFβ1 Ab)组、单纯生物蛋白胶(FG)组、TGFβ1抗体复合FG(TGFβ1 Ab FG)组及生理盐水(NS)组,每组各18只.分别将鸡左足第3,4趾趾深屈肌腱横断,作The 4-strand Cruciate repair缝合,在损伤周围注入药物.术后5 d行早期功能锻炼,在第1,3,8 wk处死取材,分别进行大体观察、组织学检查、生物力学测试.结果:TGFβ1 Ab复合FG组术后3,8 wk,缝合处粘连程度评分、肌腱滑动距离及模拟主动屈曲度均优于其余三组,且差异有统计学意义(P＜0.05).四个处理组的最大抗断裂载荷差异无统计学意义(P＞0.05).结论:TGFβ1抗体复合生物蛋白胶可以有效预防术后肌腱粘连,不影响肌腱的正常愈合进程.     

Functional Fiber Reduces Mice Obesity by Regulating Intestinal Microbiota

Obesity may cause metabolic syndrome and has become a global public health problem, and dietary fibers (DF) could alleviate obesity and metabolic syndrome by regulating intestinal microbiota. We developed a functional fiber (FF) with a synthetic mixture of polysaccharides, high viscosity, water-binding capacity, swelling capacity, and fermentability. This study aimed to investigate the effect of FF on obesity and to determine its prevention of obesity by modulating the gut microbiota. Physiological, histological, and biochemical parameters, and gut microbiota composition were investigated in the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB). The results demonstrated that 12% FF could promote a reduction in body weight and epididymal adipocyte area, augment insulin sensitivity, and stimulate heat production from brown adipose tissue (BAT) (p < 0.05). Compared with the HFD, 12% FF could also significantly improve the intestinal morphological integrity, attenuate systemic inflammation, promote intestinal microbiota homeostasis, and stabilize the production of short-chain fatty acids (SCFAs) (p < 0.05). Consistent with the results of 12% FF, the LFD could significantly reduce the body weight and epididymal adipocyte area relative to the HFD (p < 0.05), but the LFD and HFD showed no significant difference (p > 0.05) in the level of inflammation and SCFAs. Meanwhile, 12% FF supplementation showed an increase (p < 0.05) in the abundance of the Bifidobacterium, Lactococcus, and Coprococcus genus in the intestine, which had a negative correlation with obesity and insulin resistance. Additionally, the treatment with antibiotics (12% FF + AB) could inhibit the effect of FF in the HFD. The Kyoto Encyclopedia of Genes and Genomes (KEGG) function prediction revealed that 12% FF could significantly inhibit the cyanogenic amino acid metabolic pathway and decrease the serum succinate concentration relative to the HFD group. The overall results indicate that 12% FF has the potential to reduce obesity through the beneficial regulation of the gut microbiota and metabolites.     

GOS Ameliorates Nonalcoholic Fatty Liver Disease Induced by High Fat and High Sugar Diet through Lipid Metabolism and Intestinal Microbes

The treatment of nonalcoholic fatty liver disease (NAFLD) remains very challenging. This study investigated the therapeutic effect of galactose oligosaccharide (GOS), an important prebiotic, on NAFLD through in vivo and in vitro experiments and preliminarily explored the mechanism by which GOS improves liver lipid metabolism and inflammation through liver and intestinal microbiological analysis. The results of mouse liver lipidomics showed that GOS could promote body thermogenesis in mice with high-fat and high-sugar diet (HFHSD)-induced NAFLD, regulate lipolysis in liver fat cells, and accelerate glycine and cholesterol metabolism. GOS dose-dependently reduced the contents of total cholesterol (TC) and triglyceride (TG) in cells and reduced the accumulation of lipid droplets in cells. GOS also reduced the Firmicutes/Bacteroidetes ratio and altered the composition of the intestinal microbiota in mice fed a HFHSD. GOS can improve liver lipid metabolism and intestinal structure of NAFLD. These results provide a theoretical and experimental basis supporting the use of GOS as a health food with anti-NAFLD functions.     

壮肝逐瘀煎对肝纤维化大鼠TβRⅠ/Ⅱ、Smad3、Smad4、Smad7表达的影响

目的研究壮肝逐瘀煎对肝纤维化(HF)大鼠TβRⅠ/Ⅱ、Smad3、Smad4、Smad7表达的影响,探讨其抗HF的作用机制.方法 44只wistar大鼠随机取8只作为正常对照组,正常饲养.剩余大鼠采用CCl4复合因素法进行HF造模,第4 w随机处死4只,证实HF形成后,随机分为病理模型组、壮肝逐瘀煎组、秋水仙碱组、大黄虫丸组.病理模型组予生理盐水灌胃,其余3组分别给予相应药物灌胃.12 w后获取肝组织,苏木精-伊红染色,观察HF的程度.免疫组织化学染色、图像分析方法对TβRⅠ/Ⅱ、Smad3、Smad4、Smad7的组织分布进行半定量分析.结果 壮肝逐瘀煎组、秋水仙碱组、大黄虫丸组与病理模型组比较,肝小叶结构趋于正常,纤维间隔明显变薄,肝组织TβRⅠ/Ⅱ、Smad3、Smad4表达显著减少(P＜0.01),Smad7表达显著增加(P＜0.01),壮肝逐瘀煎组优于秋水仙碱组、大黄虫丸组.结论 壮肝逐瘀煎能够显著改善HF大鼠肝组织的病理变化,具有明显的抗HF作用,其作用机制可能与壮肝逐瘀煎调控TβRⅠ/Ⅱ、Smad3、Smad4、Smad7的表达有关.     

Topology Optimization of Piezoelectric Energy Harvesters for Enhanced Open-Circuit Voltage Subjected to Harmonic Excitations

Energy harvesting devices made of piezoelectric material are highly anticipated energy sources for power wireless sensors. Tremendous efforts have been made to improve the performance of piezoelectric energy harvesters (PEHs). Noticeably, topology optimization has shown an attractive potential to design PEHs with enhanced energy conversion efficiency. In this work, an alternative yet more practical design objective was considered, where the open-circuit voltage of PEHs is enhanced by topologically optimizing the through-thickness piezoelectric material distribution of plate-type PEHs subjected to harmonic excitations. Compared to the conventional efficiency-enhanced designs, the open-circuit voltage of PEHs can be evidently enhanced by the proposed method while with negligible sacrifice on the energy conversion efficiency. Numerical investigations show that the voltage cancellation effect due to inconsistent voltage phases can be effectively ameliorated by optimally distributed piezoelectric materials.     

非酒精性脂肪肝病患者粪便中短链脂肪酸改变的临床研究

目的探索非酒精性脂肪肝病（NAFLD）不同状态下粪便短链脂肪酸（SCFAs）的差异,为寻找NAFLD疾病发生发展机制和可能的治疗靶点提供支持。方法通过气相色谱-质谱分析,检测非酒精性脂肪肝（NAFL）、非酒精性脂肪肝炎（NASH）、NAFLD相关肝硬化粪便中乙酸、丙酸、丁酸三种主要SCFAs水平和构成差异。结果纳入分析80例,其中健康志愿者9例,NAFL患者27例,NASH患者20例,NAFLD相关肝硬化24例。NAFLD相关肝硬化组患者SCFAs总含量（P=0.004,P=0.0001,P=0.001）、粪便丁酸（P=0.045,P=0.0001,P=0.0001）、乙酸水平（P=0.010,P=0.0001,P=0.012）分别显著低于健康志愿者、NAFL组和NASH组,丙酸水平（P=0.024）显著低于NAFL组。NAFLD相关肝硬化组患者SCFAs中丁酸所占比例显著低于NASH组（P=0.016）。结论 NAFLD肝硬化患者粪便存在主要SCFAs水平的降低,其中丁酸构成比例降低更为明显,这可能是NAFLD进入肝硬化特征改变之一,提示SCFAs水平变化对NAFLD疾病进展可能有一定预测作用,补充肠道SCFAs可能作为NAFLD相关肝硬化新的治疗靶点。     

TRPV4 Regulates Soman-Induced Status Epilepticus and Secondary Brain Injury via NMDA Receptor and NLRP3 Inflammasome

Nerve agents are used in civil wars and terrorist attacks, posing a threat to public safety. Acute exposure to nerve agents such as soman (GD) causes serious brain damage, leading to death due to intense seizures induced by acetylcholinesterase inhibition and neuronal injury resulting from increased excitatory amino-acid levels and neuroinflammation. However, data on the anticonvulsant and neuroprotective efficacies of currently-used countermeasures are limited. Here, we evaluated the potential effects of transient receptor vanilloid 4 (TRPV4) in the treatment of soman-induced status epilepticus (SE) and secondary brain injury. We demonstrated that TRPV4 expression was markedly up-regulated in rat hippocampus after soman-induced seizures. Administration of the TRPV4 antagonist GSK2193874 prior to soman exposure significantly decreased the mortality rate in rats and reduced SE intensity. TRPV4-knockout mice also showed lower incidence of seizures and higher survival rates than wild-type mice following soman exposure. Further in vivo and in vitro experiments demonstrated that blocking TRPV4 prevented NMDA receptor-mediated glutamate excitotoxicity. The protein levels of the NLRP3 inflammasome complex and its downstream cytokines IL-1β and IL-18 increased in soman-exposed rat hippocampus. However, TRPV4 inhibition or deletion markedly reversed the activation of the NLRP3 inflammasome pathway. In conclusion, our study suggests that the blockade of TRPV4 protects against soman exposure and reduces brain injury following SE by decreasing NMDA receptor-mediated excitotoxicity and NLRP3-mediated neuroinflammation. To our knowledge, this is the first study regarding the “dual-switch” function of TRPV4 in the treatment of soman intoxication.Electronic supplementary materialThe online version of this article (10.1007/s12264-021-00662-3) contains supplementary material, which is available to authorized users.     

Energy metabolism disorders and potential therapeutic drugs in heart failure

Heart failure (HF) is a global public health problem with high morbidity and mortality. A large number of studies have shown that HF is caused by severe energy metabolism disorders, which result in an insufficient heart energy supply. This deficiency causes cardiac pump dysfunction and systemic energy metabolism failure, which determine the development of HF and recovery of heart. Current HF therapy acts by reducing heart rate and cardiac preload and afterload, treating the HF symptomatically or delaying development of the disease. Drugs aimed at cardiac energy metabolism have not yet been developed. In this review, we outline the main characteristics of cardiac energy metabolism in healthy hearts, changes in metabolism during HF, and related pathways and targets of energy metabolism. Finally, we discuss drugs that improve cardiac function via energy metabolism to provide new research ideas for the development and application of drugs for treating HF.KEY WORDS: Heart failure, Energy deficit, Cardiac dysfunction, Energy metabolism, Substrate metabolism, Hormones, Natural products, Synthetic drugs     

ICU呼吸机相关肺炎的病原菌分析

目的分析呼吸机相关肺炎病原学构成情况,为临床治疗提供依据。方法对本院2003年3月至2006年9月期间收住的53例VAP病人病原菌进行培养,并对致病菌进行药敏试验。结果共检出128株细菌,其中革兰阴性菌98株（76．56％）,革兰阳性菌14株（10．94％）,真菌16株（12．50％）;前5位致病菌分别为：铜绿假单胞菌（34株）、克雷伯菌属（20株）、金黄色葡菌球菌（13株）、白假丝酵母菌（13株）、大肠埃希菌（10株）。结论革兰阴性菌为主,对多种抗生素耐药是VAP的临床病原菌学特点,革兰阴性菌中以铜绿假胞菌居首位。临床上合理使用抗生素至关重要。