Background Major depressive disorder (MDD) is a common but severe psychiatric illness characterized by depressive mood and diminished interest. Both nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing 1 (NLRP1) inflammasome and autophagy have been reported to implicate in the pathological processes of depression. However, the mechanistic interplay between NLRP1 inflammasome, autophagy, and depression is still poorly known. Methods Animal model of depression was established by chronic social defeat stress (CSDS). Depressive-like behaviors were determined by social interaction test (SIT), sucrose preference test (SPT), open field test (OFT), forced swim test (FST), and tail-suspension test (TST). The protein expression levels of NLRP1 inflammasome complexes, pro-inflammatory cytokines, phosphorylated-phosphatidylinositol 3-kinase (p-PI3K)/PI3K, phosphorylated-AKT (p-AKT)/AKT, phosphorylated-mechanistic target of rapamycin (p-mTOR)/mTOR, brain-derived neurotrophic factor (BDNF), phosphorylated-tyrosine kinase receptor B (p-TrkB)/TrkB, Bcl-2-associated X protein (Bax)/B-cell lymphoma-2 (Bcl2) and cleaved cysteinyl aspartate-specific proteinase-3 (caspase-3) were examined by western blotting. The mRNA expression levels of pro-inflammatory cytokines were tested by quantitative real-time PCR. The interaction between proteins was detected by immunofluorescence and coimmunoprecipitation. Neuronal injury was assessed by Nissl staining. The autophagosomes were visualized by transmission electron microscopy. Nlrp1a knockdown was performed using an adeno-associated virus (AAV) vector containing Nlrp1a –shRNA–eGFP infusion. Results CSDS exposure caused a bidirectional change in hippocampal autophagy function, which was activated in the initial period but impaired at the later stage. In addition, CSDS exposure increased the expression levels of hippocampal NLRP1 inflammasome complexes, pro-inflammatory cytokines, p-PI3K, p-AKT and p-mTOR in a time-dependent manner. Interestingly, NLRP1 is immunoprecipitated with mTOR but not PI3K/AKT and CSDS exposure facilitated the immunoprecipitation between them. Hippocampal Nlrp1a knockdown inhibited the activity of PI3K/AKT/mTOR signaling, rescued the impaired autophagy and ameliorated depressive-like behavior induced by CSDS. In addition, rapamycin, an autophagy inducer, abolished NLRP1 inflammasome-driven inflammatory reactions, alleviated depressive-like behavior and exerted a neuroprotective effect. Conclusions Autophagy dysfunction contributes to NLRP1 inflammasome-linked depressive-like behavior in mice and the regulation of autophagy could be a valuable therapeutic strategy for the management of depression.

目的 探究DAPT对慢性应激诱导的小鼠抑郁样行为的作用及机制.方法 C57BL/6J小鼠给予慢性社会挫败应激(chronic social defeat stress,CSDS)处理 10 d 以建立抑郁模型,药物处理组小鼠每天腹腔注射DAPT 5 mg·kg1.通过社会接触、糖水偏爱、旷场、强迫游泳和悬尾实验来评价小鼠的抑郁样行为;采用Western blot检测小鼠海马NLRP3、ASC、caspase-1、TNF-α、p62、Atg7、Atg5 和 Beclin1 蛋白的表达,运用ELISA检测小鼠海马IL-1 β和IL-18的表达水平.结果 CSDS诱导小鼠出现明显的抑郁样行为,同时增加了小鼠海马NLRP3、ASC、caspase-1的表达和炎症因子TNF-α、IL-1 β和IL-18的水平,另外,CSDS处理小鼠海马自噬相关蛋白Atg7、Atg5和Beclin1表达明显减少,而p62的表达则明显增加.DAPT处理能明显改善CSDS诱导的小鼠抑郁样行为,并能抑制 NLRP3、ASC、caspase-1、TNF-α、IL-1 β、IL-18以及p62蛋白表达的增加和Atg7、Atg5和Beclin1蛋白表达的减少.结论 DAPT能够改善慢性应激诱导的小鼠抑郁样行为,其机制可能与其抑制NLRP3炎症小体激活和上调自噬功能有关.

Objective:To evaluate the safety and efficacy of autologous whole blood external application in treating diabetes foot chronic wounds, and to explore the mechanism of the therapy.Methods:The patients with chronic wounds of diabetes foot admitted to Hunan People′s Hospital from January to December in 2020 were enrolled. According to the random number table method, the patients were divided into control group and experimental group (autologous whole blood group). In the case of active control of underlying diseases, two groups of patients were advanced to nibble debridement, and the control group was treated with active oxygen and hypochlorite disinfectant (DAVIC) combined with foam dressing. The experimental group was treated with DAVIC, autologous whole blood external application combined with foam dressing. On the day of treatment and the 3rd, 6th, 9th and 15th days of treatment, the local wound conditions were observed, adverse reactions, wound healing rate, capillary count and growth factor expression were recorded. The growth factors included platelet derived growth factor (PDGF), vascular endothelial growth factor (VEGF), epidermal growth factor (EGF) and transforming growth factor-β1 (TGF-β1) and insulin-like growth factor-1 (IGF-1). The general condition, capillary count, growth factor expression and wound healing rate of the two groups were compared by independent sample t-test and χ2 test. Results:Forty patients with chronic wounds of diabetes foot were included in the study.There were 20 cases in the experimental group and 20 cases in the control group. There was no significant difference in gender distribution, age, wound area, Wagner grade, glycosylated hemoglobin, leukocyte count, hypertension and hyperlipidemia, ankle brachial index between the two groups ( P>0.05). There were no adverse reactions in both groups after treatment. There was no significant difference in wound healing rate and capillary count between the two groups on the day and the third day of treatment; on the 6th, 9th and 15th day, there was significant difference between the two groups ( P<0.05), and the experimental group was higher than the control group. The growth factors (PDGF, VEGF, EGF, TGF-β1, IGF-1) in the granulation tissue of the experimental group and the control group were expressed in a small amount on the 3rd day, and the expression increased gradually on the 9th and 15th day. There was no significant difference in the expression between the two groups on the 3rd day of treatment, but there was significant difference on the 9th and 15th day of treatment ( P<0.05). The expression in the experimental group was higher than that in the control group. Conclusions:Autologous whole blood can increase the healing rate of diabetes foot chronic wounds. Autologous whole blood may promote wound healing by increasing the number of capillary and growth factor in chronic wound of diabetes foot.

慢性难愈合创面的治疗具有耗时长、费用高、难治愈等特点.近年来,随着慢性难愈合创面发病原因及防控关键技术的进一步研究,其诊疗技术逐渐呈现多样化,且最近研究发现,自体全血中含有的血浆及具有生物活性、生物相容性以及代谢活性等的活细胞能够通过促进修复细胞的增殖、分化,缩短炎症反应期,加快肉芽组织生长等多种途径加速创面的愈合,且具有经济成本低、技术环境要求低、操作简单、安全有效等优点.本研究主要针对自体全血在慢性难愈合创面中的应用研究进展进行综述,以期为自体全血在慢性难愈合创面中的治疗提供理论依据.

目的 研究一种银离子过氧化氢手消毒液的消毒性能及安全性.方法 采用悬液定量杀菌试验和动物试验方法,对该消毒液杀灭微生物的效果和安全性进行观察.结果 该消毒液中银离子含量为100 mg/L,过氧化氢含量为质量分数0.752％.以该消毒液原液作用0.5 min,对悬液内金黄色葡萄球菌和大肠杆菌的杀灭对数值均>5.00,对悬液内白色念珠菌的杀灭对数值>4.00,对流感病毒、副流感病毒及新城疫病毒有明显的灭活作用.以该消毒液原液作擦拭消毒作用1 min,对手上自然菌的杀灭对数值>1.00.该消毒液小鼠急性经口毒性试验LD50>5000 mg/(kg·bw);其原液对家兔完整皮肤刺激指数为0,对小鼠骨髓嗜多染红细胞无致微核作用.结论 该手消毒液能快速杀灭细菌繁殖体、真菌和病毒,属于无毒级物质.

目的 评价一种以乙醇和银离子为主要成分的免洗手消毒液(安可信)的效果及其安全性.方法 采用悬液定量杀菌试验、消毒剂对手消毒现场试验、急性经口毒性试验和小鼠骨髓嗜多染红细胞微核试验等方法,研究该免洗手消毒液杀菌效果以及安全性.结果 银离子浓度为41.6 mg/kg、乙醇含量为54.4％(w/w)的该免洗手消毒液作用1 min,对大肠埃希菌、金黄色葡萄球菌和铜绿假单胞菌平均杀灭对数值＞3.00;对白假丝酵母菌的平均杀灭对数值＞4.00.该免洗手消毒液原液经37℃恒温培养箱保存3个月后,样品乙醇含量下降率为0.37％,银离子含量无下降.该免洗手消毒液对小鼠急性经口毒性LD50＞5 000 mg/kg,对新西兰家兔皮肤无刺激性,小鼠骨髓嗜多染红细胞微核试验结果为阴性.结论 安可信银离子免洗手消毒液对细菌和真菌具有较好消毒作用;对人体无皮肤刺激;各项指标均符合国家要求.

目的 观察一种以银离子和过氧化氢为主要成分的消毒液的消毒效果及其安全性.方法 采用悬液定量杀菌方法和动物试验法,对某过氧化氢银离子复方消毒液杀灭微生物效果及其安全性进行评价.结果 该复方消毒液含银离子100μg/g与过氧化氢35 g/kg.用该复方消毒液原液作用0.5 min,对悬液内白色念珠菌的杀灭对数值>4.00,对大肠杆菌和铜绿假单胞杆菌的杀灭对数值均>5.00;作用1.0 min对金黄色葡萄球菌的杀灭对数值>5.00.该复方消毒液原液作用1.0 h,对流感病毒、副流感病毒和新城疫病毒均可有效灭活.该复方消毒液对小鼠急性口服LD50值>5000 mg/(kg·bw),对新西兰兔最高皮肤刺激指数为0,小鼠骨髓嗜多染红细胞微核实验结果为阴性.结论 该过氧化氢银离子复方消毒液对细菌和病毒均具有良好的消毒效果,属无毒级物质,对动物完整皮肤无刺激性.

[Purpose] To analyze the composition of patients with malignant tumors in a general hospital of Tibet.[Methods] The medical records of patients with malignant tumors admitted in the People's Hospital of Tibet Autonomous Region during September 2013 to August 2017 were collected.According to ICD-10,all cases were categorized and the proportion of cancers was analyzed by time,gender and age.[Results] Total 1929 cases with malignant tumor were admitted,the average age of patients was 53.78±13.01 years and the male to females ratio was 1.38∶1.The top five cancers were gastric cancer,liver cancer,breast cancer,esophageal cancer and colorectal cancer;gastric cancer,liver cancer,esophageal cancer,lung cancer and colorectal cancer for males and breast cancer,stomach cancer,liver cancer,esophageal cancer and colorectal cancer for females.The incidence peak was in the age group of 40～69,accounting for 75.80％.[Conclusion] The constitution of malignant diseases in Tibet region is different from other regions in China,so it is important to take cancer surveillance and prevention measures accordingly.