Acidosis, a common feature of cerebral ischemia and hypoxia, results in neuronal damage and death. This study aimed to investigate the protective effects and mechanisms of action of melatonin against acidosis-induced neuronal damage. SH-SY5Y cells were exposed to an acidic environment to simulate acidosis, and a photothrombotic (PT) infarction model was used to establish an animal model of cerebral ischemia of male C57/BL6J mice. Both in vivo and in vitro studies demonstrated that acidosis increased cytoplasmic transcription factor EB (TFEB) levels, reduced nuclear TFEB levels, and suppressed autophagy, as evidenced by elevated p62 levels, a higher LC3-II/LC3-I ratio, decreased synapse-associated proteins (PSD-95 and synaptophysin), and increased neuronal apoptosis. In contrast, melatonin promoted the nuclear translocation of TFEB, enhanced autophagy, and reversed neuronal apoptosis. Moreover, the role of TFEB in melatonin’s neuroprotective effects was validated by modulating TFEB nuclear translocation. In conclusion, melatonin mitigates acidosis-induced neuronal damage by promoting the nuclear translocation of TFEB, thereby enhancing autophagy. These findings offer new insights into potential treatments for acidosis.

Addressing the treatment of depression is crucial; nevertheless, the etiology and pathogenesis remain unelucidated. Therefore, this study investigated the effects of teriflunomide (TF) on corticosterone (CORT)-induced depression-like behaviors in mice. Notably, TF administration resulted in a substantial amelioration of anxiety and depression-like behaviors observed in CORT-treated mice. This was evidenced by behavioral assessments conducted via the sucrose preference test (SPT), open-field test (OFT), novelty-suppressed feeding test (NSFT), forced swimming test (FST), and tail suspension test (TST). The administration of CORT inflicts damage upon oligodendrocytes and neurons within the hippocampus. Our findings indicate that TF offers significant protective effects on oligodendrocytes, mitigating apoptosis both in vivo and in vitro. Additionally, TF was found to counteract the CORT-induced neuronal loss and synaptic damage, as demonstrated by an increase in Nissl-positive cells across hippocampal regions CA1, CA3, and the dentate gyrus (DG) alongside elevated levels of synapse-related proteins including PSD-95 and synaptophysin. Additionally, TF treatment facilitated a reduction in the levels of apoptosis-related proteins while simultaneously augmenting the levels of Bcl2. Our findings indicate that TF administration effectively mitigates CORT-induced depression-like behaviors and reverses damage to oligodendrocytes and neurons in the hippocampus, suggesting TF as a promising candidate for depression.

Post-stroke cognitive impairment (PSCI) remains the most common consequence of ischemic stroke. In this study, we aimed to investigate the role and mechanisms of melatonin (MT) in improving cognitive dysfunction in stroke mice. We used CoCl2-induced hypoxia-injured SH-SY5Y cells as a cellular model of stroke and photothrombotic-induced ischemic stroke mice as an animal model. We found that the stroke-induced upregulation of mitophagy, apoptosis, and neuronal synaptic plasticity was impaired both in vivo and in vitro. The results of the novel object recognition test and Y-maze showed significant cognitive deficits in the stroke mice, and Nissl staining showed a loss of neurons in the stroke mice. In contrast, MT inhibited excessive mitophagy both in vivo and in vitro and decreased the levels of mitophagy proteins PINK1 and Parkin, and immunofluorescence staining showed reduced co-localization of Tom20 and LC3. A significant inhibition of mitophagy levels could be directly observed under transmission electron microscopy. Furthermore, behavioral experiments and Nissl staining showed that MT ameliorated cognitive deficits and reduced neuronal loss in mice following a stroke. Our results demonstrated that MT inhibits excessive mitophagy and improves PSCI. These findings highlight the potential of MT as a preventive drug for PSCI, offering promising therapeutic implications.

A label-free and activatable strategy was developed for in situ detection of exosomal miRNA in ovarian cancer by combining hairpin-shaped nucleic acid probes with DNA-AgNCs.

文章在阐述相关背景的基础上,首先从优化教学内容、创新教学模式、改革考核方式三个方面提出了医学研究生分子生物学课程模块化教学改革路径,然后对医学研究生分子生物学课程模块化教学改革进行了反思.

Lung adenocarcinoma (LUAD) is a common malignancy throughout the world with high levels of mortality and morbidity. In the present study, potential biomarkers and treatment targets for LUAD were investigated using data from The Cancer Genome Atlas. Overall, 4,485 differentially expressed genes (DEGs) were identified (1,857 upregulated and 2,628 downregulated) between tumor and adjacent control tissues. Functional analysis with Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, Gene Set Variation Analysis and Gene Set Enrichment Analysis revealed significant enrichment of the DEGs in pathways related to system development, cell cycle and cell adhesion. Weighted gene co-expression network analysis distinguished ten co-expression modules on inclusion of the clinical profiles of patients with LUAD. Of these, the blue/turquoise modules showed peak association with tumor onset. Analysis of hub modules identified five hub genes, namely ANGPTL7, SLC6A4, PTPRQ, KCNA4 and TEDC2 (also known as C16orf59). Survival analysis revealed associations between hub-gene expression profiles and patient prognosis. Downregulation of SLC6A4 in LUAD tumor tissues was confirmed using immunohistochemistry. Additional assays (Cell Counting Kit-8, colony formation, scratch assay, cell cycle, Transwell invasion assay and cell adhesion assay) revealed that SLC6A4 overexpression inhibited A549 cell growth, invasion and migration. The findings demonstrated that the hub genes could act as treatment targets or new biomarkers for LUAD.

【目的】探讨纤维蛋白原/白蛋白值（FAR）、D-二聚体（DD）与急性心肌梗死（AMI）患者冠脉病变程度的相关性。【方法】选择2020年6月至2022年7月湖南师范大学附属第一医院收治的201例AMI患者（观察组），选择同期于湖南师范大学附属第一医院行冠脉造影检查的80例结果正常者（对照组）。采用多因素Logistic回归分析FAR、DD与AMI的相关性，根据累及病变支的数目及冠脉狭窄程度对AMI患者亚组FAR、DD进行分析，采用受试者工作曲线（ROC曲线）评估FAR、DD预测AMI及冠脉重度狭窄的效能。【结果】观察组患者FAR、DD均高于对照组，差异均有统计学意义（P<0.001）。多因素Logistic回归分析显示，FAR、DD是AMI发生的危险因素（P<0.05）。不同亚组结果显示：多支病变组FAR、DD均高于单支病变组，双支病变组DD高于单支病变组，差异均有统计学意义（P<0.05）；重度狭窄组FAR、DD均高于轻度狭窄组，重度狭窄组DD高于中度狭窄组，差异均有统计学意义（P<0.05）。ROC曲线结果显示：FAR、DD预测AMI的ROC曲线下面积分别为0.721、0.71，敏感度分别为80.3%、87.3%；预测冠脉重度狭窄ROC曲线下面积分别为0.609、0.658，特异度分别为91.2%和91.2%。【结论】高水平FAR、DD与AMI发生存在相关性，且对AMI患者冠脉病变严重程度具有一定的诊断价值。

Oxidative stress-induced neuronal cell death contributes significantly to the physiological processes of a number of neurological disorders. Polydatin (PD) has been reported to protect against Alzheimer's disease (AD), ischemic stroke and traumatic brain injury. However, the underlying neuroprotective mechanisms remain to be elucidated. The current study suggested that PD activates AKT/cAMP response element-binding protein (CREB) signaling and induces neuroglobin (Ngb) to protect neuronal cells from hydrogen peroxide (H2O2) in vitro. PD inhibited the H2O2-induced neuronal cell death of primary mouse cortical neurons and N2a cells. Functional studies showed that PD attenuated H2O2-induced mitochondrial dysfunction and mitochondrial reactive oxygen species production. Mechanistically, PD was verified to induce the phosphorylation of AKT and CREB and increase the protein level of Ngb. The luciferase assay results showed that Ngb transcriptional activity was activated by CREB, especially after PD treatment. It was further indicated that PD increased the transcription of Ngb by enhancing the binding of CREB to the promoter region of Ngb. Finally, Ngb knockdown largely attenuated the neuroprotective role of PD against H2O2. The results indicated that PD protected neuronal cells from H2O2 by activating CREB/Ngb signaling in neuronal cells, indicating that PD has a neuroprotective effect against neurodegenerative diseases.

目的:建立基于重组弓形虫致密颗粒蛋白7(GRA7)的纳米金免疫传感器检测血清GRA7抗体,评价其检测性能.方法:体外合成gra7基因,构建重组表达质粒pQE-60-gra7,表达并纯化GRA7,Western blot鉴定其免疫活性;种子生长法制备金纳米棒,构建GRA7的纳米金免疫传感器检测人血清GRA7抗体,评价其灵敏度和特异度,并计算阳性、阴性预测值以及诊断效率.结果:成功构建重组表达质粒pQE-60-gra7,纯化GRA7显示良好的反应原性;GRA7的纳米金免疫传感器检测人血清弓形虫GRA7抗体的灵敏度、特异度、阳性预测值、阴性预测值和诊断效率分别为73.21％、100％、100％、77.94％、86.24％.结论:重组弓形虫GRA7的纳米金免疫传感器可用于弓形虫GRA7抗体的检测.

Increased focus has been placed on the role of histone deacetylase inhibitors as crucial players in subarachnoid hemorrhage (SAH) progression. Therefore, this study was designed to expand the understanding of SAH by exploring the downstream mechanism of the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) in SAH. The expression of TDP-43 in patients with SAH and rat models of SAH was measured. Then, western blot analysis, immunofluorescence staining, and transmission electron microscope were used to investigate the in vitro effect of TDP-43 on a neuronal cell model of SAH established by oxyhemoglobin treatment. Immunofluorescence staining and coimmunoprecipitation assays were conducted to explore the relationship among histone deacetylase 1 (HDAC1), heat shock protein 70 (HSP70), and TDP-43. Furthermore, the in vivo effect of HDAC1 on SAH was investigated in rat models of SAH established by endovascular perforation. High expression of TDP-43 in the cerebrospinal fluid of patients with SAH and brain tissues of rat models of SAH was observed, and TDP-43 accumulation in the cytoplasm and the formation of inclusion bodies were responsible for axonal damage, abnormal nuclear membrane morphology, and apoptosis in neurons. TDP-43 degradation was promoted by the HDAC1 inhibitor SAHA via the acetylation of HSP70, alleviating SAH, and this effect was verified in vivo in rat models. In conclusion, SAHA relieved axonal damage and neurological dysfunction after SAH via the HSP70 acetylation-induced degradation of TDP-43, highlighting a novel therapeutic target for SAH.

目的 了解长沙市无偿献血者HIV感染情况,评估长沙市采供血机构的检测策略和处理措施的有效性.方法 收集了2016-2020年长沙市无偿献血者HIV检测数据,分析了初筛、确证检测数据.并将结果录入SPSS 19.0软件进行统计分析.结果 长沙市献血者HIV初筛阳性率为0.14％(1070/777937),HIV确证阳性率为2.02/万(157/777937).每年HIV初筛阳性率变化无显著性差异(dy=0.029,P=0.392),每年1,3,7,8和10月初筛阳性率相对较高.HIV确证阳性人群均为ELISA双试剂检测阳性.不确定人群S/CO值主要分布在0.5-5范围内,占60.7％.HIV不确定人群确证结果以单p24条带出现为主,出现率为64.3％.结论 长沙市无偿献血者HIV初筛阳性率不高且近5年来没有显著的变化趋势.长沙市采供血机构目前筛查HIV检测策略和处理措施合理高效,能够有效降低因HIV初筛阳性造成的血液报废,也能够有效降低HIV输血传播的风险.

克隆和表达结核分枝杆菌热休克蛋白16.3（Hsp16.3）,建立纳米金免疫传感器检测结核病患者血清Hsp16.3抗体。PCR扩增hsp16.3基因,构建重组表达质粒pQE30-hsp16.3,表达和纯化Hsp16.3,Western blot分析其反应原性;晶种生长法制备金纳米棒并连接Hsp16.3,建立纳米金免疫传感器检测血清Hsp16.3抗体,接受者操作特性（ROC）曲线评价其灵敏度和特异性。成功构建重组表达质粒pQE30-hsp16.3,纯化Hsp16.3具有良好的反应原性;Hsp16.3的纳米金免疫传感器分别检测50例结核病患者、42例非结核肺病患者和50例体检健康者血清,红移值大于3.5的例数分别为42、7、1例;ROC曲线显示,曲线下面积0.888（P＜0.01）,界值3.5,灵敏度82%,特异性98%。结果表明,Hsp16.3的纳米金免疫传感器可用于检测结核病血清Hsp16.3抗体。

目的 对医学检验技术专业发展和就业形势进行调查,为医学检验技术专业教育改革提供参考.方法 采用问卷星对湖南师范大学医学院和南华大学衡阳医学院2015级至2019级医学检验技术专业学生共623人进行匿名调查,用描述法分析调查结果.结果 大部分学生对医学检验技术专业发展持有信心,但仍有部分学生对自己所学专业缺乏自信;在严峻的就业形势和高质量社会要求下,大部分学生认为需要提升自己的综合能力,希望学校优化实践教学环节;本科毕业后,学生主要就业途径是自主择业和校园招聘,也有很多学生选择考研深造,以适应愈加激烈的就业竞争环境.结论 医学检验技术教育改革应以医院检验科岗位能力需求及医学发展和社会需求为导向,从课程体系、人才培养方案等方面进行改革,培养符合社会发展需求的复合型医学检验技术人才.

目的:分析2019年衡阳市某三甲医院常见致病菌的分布及其对常用抗菌药物的耐药情况,为临床合理用药提供依据.方法:使用VITEK2全自动仪器法进行菌株鉴定和药敏试验,根据CLSI 2019年版标准判读结果,使用软件WHONET 5.6进行数据分析.结果:2019年共收集临床非重复分离株8953株,其中革兰阳性菌占29％,革兰阴性菌占71％.位列前5的分离株分别为大肠埃希菌(19.8％)、鲍曼不动杆菌(17.7％)、肺炎克雷伯菌(14.5％)、铜绿假单胞菌(10.0％)、肺炎链球菌(6.7％).肺炎克雷伯菌耐药情况比大肠埃希菌严重,对于哌拉西林/他唑巴坦、头孢替坦、阿米卡星、亚胺培南和厄他培南,大肠埃希菌保持高度敏感性(>90％),而肺炎克雷伯菌仅对厄他培南高度敏感(100％).鲍曼不动杆菌对大多数抗菌药物耐药性都较强(>75％),对亚胺培南的耐药率更是高达84.4％.耐甲氧西林金黄色葡萄球菌(MRSA)和耐甲氧西林表皮葡萄球菌(MRSE)的检出率分别为37.9％和78.9％,耐万古霉素、利奈唑胺的葡萄球菌未检出.结论:该院临床分离菌对常用抗菌药物耐药率较高,耐药菌以革兰阴性细菌为主,鲍曼不动杆菌耐药最为严重.

目的:探讨程序性细胞死亡蛋白4(programmed cell death protein 4,PDCD4)对人类慢性粒细胞白血病细胞系K562细胞活力、凋亡以及基因表达变化的影响.方法:通过慢病毒感染的方法在K562细胞系中过表达PDCD4基因并筛选获得稳定表达的细胞系;采用RT-qPCR和Western blot分别检测PDCD4 mRNA和蛋白的表达水平;CCK-8法检测细胞活力;流式细胞术检测细胞周期和细胞凋亡情况;应用转录组测序(RNA sequencing,RNA-seq)分析PDCD4过表达组和对照组的基因表达差异及其相关的功能与信号通路,RT-qPCR验证测序结果的准确性.结果:成功建立了稳定过表达PDCD4的K562细胞系;PDCD4过表达可显著抑制K562细胞的活力,引起细胞周期阻滞并促进阿糖胞苷诱导的细胞凋亡(P<0.05);RNA-seq结果显示,在K562细胞中过表达PDCD4可引起大量的基因表达发生变化,表达明显差异的基因共有394个,其中上调16个,下调378个,主要涉及细胞周期、凋亡、细胞自噬和代谢等方面,选取的6个基因的RT-qPCR检测结果和RNA-seq的结果一致.结论:PDCD4可抑制K562细胞活力、阻滞细胞周期进展、促进细胞凋亡;RNA-seq确定了PDCD4对K562细胞基因表达谱的变化.

目的:构建带有HA标签的人MDM2截短体N端和C端重组真核表达载体,并检测截短体与NLK的相互作用.方法:用聚合酶链式反应(PCR)扩增人MDM2基因N端和C端编码序列,通过双酶切方法构建重组真核表达载体,转染至293T细胞,免疫印迹检测蛋白表达,免疫共沉淀检测MDM2截短体与NLK的相互作用.结果:菌落PCR与测序鉴定表明HA-MDM2-N和HA-MDM2-C截短体重组真核表达质粒构建成功,HA-MDM2-N,HA-MDM2-C有特异性表达,HA-MDM2-C与NLK结合较强,HA-MDM2-N与NLK结合较弱.结论:人MDM2截短体N端(MDM2-N)和C端(MDM2-C)均与NLK存在相互作用.

以独立学院五年制临床医学专业实践教学改革为突破,通过整合构建专业基础实验课程,创新和完善以能力培养为核心的跨学科、多层次、多环节实践教学途径,构建有利于学生创新意识和实践能力培养的实践教学模式,初步实现提高临床专业学生综合实践能力的教学目标,对高等医学院校的教学研究和课程改革具有积极的推动作用.

Alzheimer’s disease (AD) poses a significant threat to human life and health. The intraneuronal accumulation of β-amyloid (Aβ) plaques in the brains of AD patients results in neuronal cell death, which is a key factor that triggers multiple changes in the pathogenesis of AD. The inhibition of Aβ-induced neuronal cell death may potentially help in the intervention and treatment of AD. Our previous study reported that tumor necrosis factor α-induced protein 1 (TNFAIP1) is induced by and promotes Aβ 25–35 -induced neurotoxicity in mouse neuronal cells, but the roles and regulatory mechanisms of TNFAIP1 are still largely unknown. In this study, our experimental results show that TNFAIP1 and p-TNFAIP1 (phosphorylation of TNFAIP1 at Ser280) are overexpressed in the neurons of the cortex and hippocampus in the brains of APP/PS1 mice, and the transcription factor NF-κB is involved in the Aβ-induced upregulation of TNFAIP1. Moreover, our results suggest that TNFAIP1 contributes to the Aβ-induced reactive oxygen species (ROS) production, decreased mitochondrial membrane potential (∆Ψm), and neuronal cell death in human SH-SY5Y cells. We further revealed that Aβ increases the binding of TNFAIP1 to RhoB, and knockdown of RhoB attenuates the TNFAIP1-induced apoptosis of human SH-SY5Y cells. These data suggest that TNFAIP1 is closely associated with AD pathogenesis, and overexpression of TNFAIP1 in the neurons of the brains of AD patients plays a role in apoptosis, at least in part, via RhoB signaling.

目的 克隆表达弓形虫主要表面抗原1截短型片段(tSAG1),建立tSAG1纳米金免疫传感器,用于检测弓形虫抗体. 方法 PCR扩增tSAG1基因片段并克隆降至pMD18-T载体,测序鉴定后亚克隆至表达载体pET-28a(+),异丙基-β-D-硫代半乳糖苷(IPTG)诱导表达tSAG1,金属螯合层析法进行纯化,Western blot分析其免疫活性;采用种子生长法制备金纳米棒,偶联tSAG1,构建纳米金免疫传感器,用于检测人血清弓形虫抗体,计算其敏感度、特异度、阳性及阴性预测值和诊断效率. 结果 构建了重组表达质粒pET-28a(+)-tSAG1,表达纯化获得具有反应原性的tSAG1,其相对分子质量约为30×103.用制备的tSAG1纳米金免疫传感器检测人血清弓形虫抗体的敏感度、特异度、阳性预测值、阴性预测值及诊断效率分别为80.9％、90.0％、90.2％、80.6％和85.2％. 结论 基于重组tSAGl的纳米金免疫传感器可用于弓形虫抗体的检测.