Sestrin 2 attenuates sepsis‐associated encephalopathy through the promotion of autophagy in hippocampal neurons

Sepsis‐associated encephalopathy (SAE) has typically been associated with a poor prognosis. Although sestrin 2 (SESN2) plays a crucial role in metabolic regulation and the stress response, its expression and functional roles in SAE are still unclear. In the present study, SAE was established in mice through caecal ligation and puncture (CLP). The adeno‐associated virus 2 (AAV2)‐mediated SESN2 expression (ie overexpression and knockdown) system was injected into the hippocampi of mice with SAE, and subsequently followed by electron microscopic analysis, the Morris water maze task and pathological examination. Our results demonstrated an increase of SESN2 in the hippocampal neurons of mice with SAE, 2‐16 hours following CLP. AAV2‐mediated ectopic expression of SESN2 attenuated brain damage and loss of learning and memory functions in mice with SAE, and these effects were associated with lower pro‐inflammatory cytokines in the hippocampus. Mechanistically, SESN2 promoted unc‐51‐like kinase 1 (ULK1)‐dependent autophagy in hippocampal neurons through the activation of the AMPK/mTOR signalling pathway. Finally, AMPK inhibition by SBI‐0206965 blocked SESN2‐mediated attenuation of SAE in mice. In conclusion, our findings demonstrated that SESN2 might be a novel pharmacological intervention strategy for SAE treatment through promotion of ULK1‐dependent autophagy in hippocampal neurons.     

乳果糖联合双歧杆菌三联活菌胶囊在轻微性肝性脑病患者中的应用效果

目的探讨乳果糖联合双歧杆菌三联活菌胶囊在轻微性肝性脑病(MHE)患者中的应用效果。方法选择2015年1月至2019年4月在我院消化科住院就诊的94例MHE患者为研究对象,随机分为观察组和对照组各47例。两组患者均予基础治疗。观察组患者在基础治疗上加用双歧杆菌三联活菌胶囊(630 mg/次,2次/d,温开水送服)联合乳果糖口服液(20 mL/次,3次/d,口服)治疗,连用8周。对照组患者单用乳果糖口服液治疗,剂量、用法及疗程同观察组。观察两组患者治疗前后血氨、血清内毒素(ET)、数字连接试验(NCT)时间和数字符号实验(DST)评分及肠道菌群数量的变化,并比较肝性脑病(HE)的转变率。结果治疗8周后,两组患者血氨、ET和NCT时间均较治疗前明显下降,DST评分较治疗前明显上升,且观察组变化幅度大于对照组(均P0.05)。治疗8周后,两组患者肠道双歧杆菌和乳杆菌数量较治疗前显著增加,大肠埃希菌数量较治疗前显著减少,且观察组变化幅度大于对照组(均P0.05)。治疗后观察组患者HE的转变率为8.51%(4/47),明显低于对照组的23.40%(11/47),差异有统计学意义(χ~2=3.89,P=0.049)。结论乳果糖联合双歧杆菌三联活菌胶囊能显著改善MHE患者智力测验结果,降低HE转化率,其作用机制可能与其能纠正患者肠道菌群紊乱,降低血氨水平,控制内毒素血症相关。     

Molecular characterization of rotaviruses obtained from patients with rotavirus-associated encephalitis/encephalopathy

Group A rotavirus (RVA) rarely causes severe complications such as encephalitis/encephalopathy. However, the pathophysiology of this specific complication remains unclear. Next-generation sequence analysis was used to compare the entire genome sequences of RVAs detected in patients with encephalitis/encephalopathy and gastroenteritis. This study enrolled eight patients with RVA encephalitis/encephalopathy and 10 with RVA gastroenteritis who were treated between February 2013 and July 2014. Viral RNAs were extracted from patients' stool, and whole-genome sequencing analysis was carried out to identify the specific gene mutations in RVA obtained from patients with severe neurological complications. Among the eight encephalitis/encephalopathy cases, six strains were DS-1-like G1P[8] and the remaining two were Wa-like G1P[8] (G1-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1). Meanwhile, eight of the 10 viruses detected in rotavirus gastroenteritis patients were DS-1-like G1P[8], and the remaining two were Wa-like G1P[8]. These strains were further characterized by conducting phylogenetic analysis. No specific clustering was demonstrated in RVAs detected from encephalitis/encephalopathy patients. Although the DS-1-like G1P[8] strain was predominant in both groups, no specific molecular characteristics were detected in RVAs from patients with severe central nervous system complications.     

Apelin-36, a potent peptide,protects against ischemic brain injury by activating the PI3K/Akt pathway

Apelin is an endogenous ligand of G protein-coupled receptor-apelin and angiotensin-1-like receptor (APJ). The biological effects of apelin–APJ system are reported in multiple systems including cardiovascular, endocrinal, and gastrointestinal system. Previous studies had shown that apelin-13 is a potential protective agent on cardiac ischemia; however, the role of apelin in the central nervous system remained unknown. In this study, we investigated therapeutic effects of apelin-36, a long form of apelin, in ischemic brain injury models. We found that apelin-36 reduced cerebral infarct volume in the middle cerebral artery occlusion (MCAO) model and the neonatal hypoxic/ischemic (H/I) injury model. Apelin-36 improved neurological deficits in the MCAO model and promoted long-term functional recovery after H/I brain injury. We further explored the protective mechanisms of apelin-36 on H/I brain injury. We clearly demonstrated that apelin-36 significantly reduced the levels of cleaved caspase-3 and Bax, two well-established apoptotic markers after H/I injury, indicating the anti-apoptotic activity of apelin-36 in ischemic injury. Since apelin-36 increased the level of phosphorylated Akt after H/I injury, we treated neonates with a specific PI3K inhibitor LY294002. We found that LY294002 decreased the phosphorylated Akt level and attenuated protective effects of apelin-36 on apoptosis. These suggested that the PI3K/Akt pathway was at least in part involved in the anti-apoptotic mechanisms of apelin-36. Our findings demonstrated that apelin-36 was a promising therapeutic agent on the treatment of ischemic brain injury.     

Review: A review on classical and atypical scrapie in caprine: Prion protein gene polymorphisms and their role in the disease

Scrapie is a naturally occurring transmissible spongiform encephalopathy in sheep and goat. It has been known for ~250 years and is characterised by the accumulation of an abnormal isoform of a host-encoded prion protein that leads to progressive neurodegeneration and death. Scrapie is recognised in two forms, classical and atypical scrapie. The susceptibility to both types of scrapie is influenced by polymorphisms of the prion protein gene (PRNP). Sheep susceptibility or resistance to classical scrapie is strongly regulated by the polymorphisms at codons 136, 154 and 171 of the PRNP. The genetic role in atypical scrapie in sheep has been defined by polymorphisms at codons 141, 154 and 171, which are associated with different degrees of risk in the occurrence of the ovine disease. Progress has been achieved in the prevention of scrapie in sheep due to efficient genetic breeding programmes based on eradication and control of the disease. In Europe, the success of these programmes has been verified by applying eradication and genetic selection plans. In general terms, the ovine selection plans aim to eliminate and reduce the susceptible allele and to enrich the resistant allele ARR. During outbreaks all susceptible animals are slaughtered, only ARR/ARR resistant rams and sheep and semi-resistant females are preserved. In the occurrence of scrapie positive goats a complete cull of the flock (stamping out) is performed with great economic loss and severe risk of extinction for the endangered breeds. The ability to select scrapie-resistant animals allows to define new breeding strategies aimed to boost genetic progress while reducing costs during scrapie outbreaks. Allelic variants of PRNP can be protective for caprine scrapie, and the knowledge of their distribution in goats has become very important. Over the past few years, the integration of genetic information on goat populations could be used to make selection decisions, commonly referred to as genetic selection. The objective of this review was to summarise the main findings of polymorphisms of the caprine prion protein (PrP) gene and to discuss the possible application of goat breeding schemes integrating genetic selection, with their relative advantages and limitations.     

乳果糖和枯草杆菌屎球菌二联活菌治疗轻微性肝性脑病疗效观察

目的:探讨乳果糖和枯草杆菌屎球菌二联活菌治疗肝硬化所致轻微性肝性脑病(MHE)的疗效。方法:将患有MHE的患者84例随机分为四组,对照组(A组,仅接受肝硬化综合治疗),乳果糖组(B组,在A组基础上加用乳果糖口服液),枯草杆菌屎球菌二联活菌组(C组,在A组基础上加用枯草杆菌屎球菌二联活菌胶囊),联合组(D组,在A组基础上联合应用乳果糖和枯草杆菌屎球菌二联活菌胶囊),每组均治疗4周。分别于治疗后第一周,第二周,第四周观察患者的数字连接实验(NCT)、数字符号实验(DST)结果,血氨变化及不良反应的发生情况。结果:B、C、D组NCT时间,DST分数及血氨均较A组改善明显,其中以D组最显著(P0.05),且随着治疗时间延长,B、C、D组以上各指标逐渐改善,其中D组以治疗后2周效果最明显(P0.05)。四组均无明显不良反应,其中D组不良反应率最低。结论:单用乳果糖与单用枯草杆菌二联活菌均可改善MHE患者的病情,但联合用药效果明显优于单药治疗,且随用药时间延长,疗效明显,安全性高,值得在临床推广。     

脑电图检查对新生儿缺氧缺血性脑病的早期诊断及预后判断价值

目的:探讨脑电图检查对新生儿缺氧缺血性脑病早期诊断及预后判断的临床意价值。方法:本研究所选研究对象为我院2011年3月至2014年3月住院的91例出生后一天内的窒息新生儿,对其行脑电图检查,根据脑电图的检查结果将其分为四组,分别为正常组、轻度异常组、中度异常组、重度异常组。对上述四组患儿进行随访,时间点为出生后3个月、6个月,采用婴幼儿发育量表对患儿的智能发育进行测评,对各组智能发育的差异进行比较。结果:(1)91例患儿中,脑电图异常的有83例,异常率为91.21%,脑电图的异常程度与临床分度基本一致;(2)对患儿随访至3个月时,轻度、中度、重度异常组患儿的智力发育指数与运动发育指数的平均值与正常组患儿相比,具有显著差异(P0.05);(3)对患儿随访至6个月时,轻度异常组患儿的智力发育指数与运动发育指数的平均值与正常组患儿相比,无显著差异(P0.05)。中度、重度异常组患儿的智力发育指数与运动发育指数的平均值与正常组患儿相比,具有显著差异(P0.05)。结论:早期脑电图检查结果对新生儿缺氧缺血性脑病的早期诊断有利,为临床上早期干预提供了重要的参考依据。     

重症急性胰腺炎并发胰性脑病的临床特点及相关影响因素分析

目的:探究重症急性胰腺炎并发胰性脑病(PE)的临床特点及相关影响因素分析。方法:本研究于2008年3月~2015年3月期间,选择我院收治的重症急性胰腺炎患者93例为研究对象,根据患者是否并发PE临床症状将其分为PE组和非PE组。收集所有患者基本资料、实验室检查指标及病原学培养检查资料,采用logistics回归对PE发病的影响因素进行分析。结果:93例重症急性胰腺炎中23例被诊断为PE,发病率为24.73%,临床主要表现为兴奋性、烦躁不安、谵妄等症状;PE组患者APACHEⅡ评分、MODS发生率、肌酐、甘油三脂水平及真菌感染率均高于非PE组,差异有统计学意义(P0.05);多因素logistics回归显示,高APACHEⅡ评分和高甘油三脂是PE发生的危险因素(OR=3.221,2.973;均P0.05)。结论:重症急性胰腺炎并发PE的发病率较高,临床有较高的APACHEⅡ评分、MODS发生率、肌酐、甘油三脂水平及真菌感染率,其中高APACHEⅡ评分和高甘油三脂是PE发生的危险因素。