The underlying mechanisms in atherosclerotic vascular diseases are not entirely clear, posing a challenging hurdle to treatment. Inflammation is a root cause of atherosclerosis (AS); therefore, anti-inflammatory agents have potential for its management. Sweroside, possessing anti-inflammatory properties, emerges as a potential agent to impede AS progression. In this study, we investigated the effects of sweroside on AS mice and elucidated its molecular mechanisms. We conducted in vivo experiments using an apolipoprotein E mice model of AS to explore the effects of sweroside on vascular inflammation adhesion responses, endothelial injury and AS. In vitro experiments, mouse aorta endothelial cells were treated with palmitic acid (PA) and sweroside, and the protective effects of sweroside on endothelial injury were analysed. AS is a chronic inflammatory disease and activation of nuclear factor κB (NF-κB) signalling contributes to inflammatory reactions and AS. Mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) has been identified as an upstream target of NF-κB signalling. We detected MAP4K4/NF-κB signalling pathways using gene siRNA silencing and knockdown assays and investigated the protective effects of sweroside in PA-mediated endothelial injury and western-diet-induced AS. The findings demonstrated that sweroside attenuated vascular inflammation, adhesion responses, and leukocyte homing and alleviated endothelial injury and atherosclerosis in vivo. Sweroside attenuated endothelial inflammation, apoptosis, permeability and adhesion responses induced by PA in vitro. Sweroside alleviated endothelial injury and atherosclerosis through MAP4K4/NF-κB signalling. Hence, sweroside is a promising candidate for treating AS, acting by targeting the MAP4K4/NF-κB pathway.

In recent years, inflammatory disorders have emerged as a significant concern for human health. Through ongoing research on anti-inflammatory agents, alpinetin has shown promising anti-inflammatory properties, including involvement in epigenetic modification pathways. As a crucial regulator of epigenetic modifications, Mecp2 may play a role in modulating the epigenetic effects of alpinetin, potentially impacting its anti-inflammatory properties. To test this hypothesis, two key components, p65 (a member of NF-KB family) and p300 (a type of co-activator), were screened by the expression profiling microarray, which exhibited a strong correlation with the intensity of LPS stimulation in mouse macrophages. Meanwhile, alpinetin demonstrates the anti-inflammatory properties through its ability to disrupt the synthesis of p65 and its interaction with promoters of inflammatory genes, yet it did not exhibit similar effects on p300. Additionally, Mecp2 can inhibit the binding of p300 by attaching to the methylated inflammatory gene promoter induced by alpinetin, leading to obstacles in promoter acetylation and subsequently impacting the binding of p65, ultimately enhancing the anti-inflammatory capabilities of alpinetin. Similarly, in a sepsis mouse model, it was observed that homozygotes overexpressing Mecp2 showed a greater reduction in organ damage and improved survival rates compared to heterozygotes when administered by alpinetin. However, blocking the expression of DNA methyltransferase 3A (DNMT3A) resulted in the loss of Mecp2's anti-inflammatory assistance. In conclusion, Mecp2 may augment the anti-inflammatory effects of alpinetin through epigenetic 'crosstalk', highlighting the potential efficacy of a combined therapeutic strategy involving Mecp2 and alpinetin for anti-inflammatory intervention.

Objective To explore the application effect of BOPPPS model + network course platform in internal science teaching. Methods A total of 116 clinical medical undergraduates in grade 2023 of College of Adult Continuing Education of Hunan University of Medicine were randomly divided into experimental class and control class with 58 students in each class by numerical table method. From April to May 2024, BOPPPS+ network course platform teaching will be implemented in the experimental class, while traditional teaching will be carried out in the control class. At the end of the experiment, the teaching design satisfaction survey, independent learning ability test and internal medicine learning level test were carried out. SPSS 20.0 software was used for statistical analysis, Chi-square test was used for counting data comparison between two classes, and T-test was used for measurement data comparison. Results The satisfaction of teaching design in the experimental class was 50 (86.2%), which was significantly higher than that in the control class 43 (74.1%), the difference was statistically significant. The total score of independent learning in the experimental class (254.3±6.7) was significantly higher than that of the control class (236.0±7.4), and the differences were statistically significant. The scores of internal medicine test, theory test and total score of experimental class were (35.8±2.2)(46.7+5.1)(81.6±2.6) points respectively, which were significantly higher than that of control class (34.8±2.2)(43.4±4.3)(78.6+4.7) points, with statistical differences. Conclusion BOPPPS model+ network course platform teaching can greatly improve students' satisfaction, autonomous learning ability and internal medicine learning level.

BackgroundNon-small cell lung cancer (NSCLC) accounts for more than 80% of lung cancer (LC) cases, making it the primary cause of cancer-related mortality worldwide. T-box transcription factor 5 (TBX5) is an important regulator of embryonic and organ development and plays a key role in cancer development. Here, our objective was to investigate the involvement of TBX5 in ferroptosis within LC cells and the underlying mechanisms.MethodsFirst, TBX5 expression was examined in human LC cells. Next, overexpression of TBX5 and Yes1-associated transcriptional regulator (YAP1) and knockdown of TEA domain 1 (TEAD1) were performed in A549 and NCI-H1703 cells. The proliferation ability of A549 and NCI-H1703 cells, GSH, MDA, ROS, and Fe2+ levels were measured. Co-immunoprecipitation (Co-IP) was performed to verify whether TBX5 protein could bind YAP1. Then TBX5, YAP1, TEAD1, GPX4, p53, FTH1, SLC7A11 and PTGS2 protein levels were assessed. Finally, we verified the effect of TBX5 on ferroptosis in LC cells in vivo.ResultsTBX5 expression was down-regulated in LC cells, especially in A549 and NCI-H1703 cells. Overexpression of TBX5 significantly decreased proliferation ability of A549 and NCI-H1703 cells, downregulated GPX4 and GSH levels, and upregulated MDA, ROS, and Fe2+ levels. Co-IP verified that TBX5 protein could bind YAP1. Moreover, oe-YAP1 promoted proliferation ability of A549 and NCI-H1703 cells transfected with Lv-TBX5, upregulated GPX4 and GSH levels and downregulated MDA, ROS, and Fe2+ levels. Additionally, oe-YAP1 promoted FTH1 and SLC7A11 levels and inhibited p53 and PTGS2 levels in A549 and NCI-H1703 cells transfected with Lv-TBX5. However, transfection with si-TEAD1 further reversed these effects. In vivo experiments further validated that TBX5 promoted ferroptosis in LC cells.ConclusionsTBX5 inhibited the activation of YAP1-TEAD1 pathway to promote ferroptosis in LC cells.

Tetrahydroxy stilbene glucoside (TSG) from Polygonum multiflorum exerts neuroprotective effects after ischemic stroke. We explored whether TSG improved ischemic stroke injury via PTEN-induced kinase 1 (PINK1)/Parkin-mediated mitophagy. Oxygen glucose deprivation/reoxygenation (OGD/R) in vitro model and middle cerebral artery occlusion (MCAO) rat model were established. Cerebral injury was assessed by neurological score, hematoxylin and eosin staining, 2,3,5-triphenyltetrazolium chloride staining, and brain water content. Apoptosis, cell viability, and mitochondrial membrane potential were assessed by flow cytometry, cell counting kit-8, and JC-1 staining, respectively. Colocalization of LC3-labeled autophagosomes with lysosome-associated membrane glycoprotein 2-labeled lysosomes or translocase of outer mitochondrial membrane 20-labeled mitochondria was observed with fluorescence microscopy. The ubiquitination level was determined using ubiquitination assay. The interaction between molecules was validated by coimmunoprecipitation and glutathione S-transferase pull-down. We found that TSG promoted mitophagy and improved cerebral ischemia/reperfusion damage in MCAO rats. In OGD/R-subjected neurons, TSG promoted mitophagy, repressed neuronal apoptosis, upregulated Y-box binding protein-1 (YBX1), and activated PINK1/Parkin signaling. TSG upregulated ubiquitin-specific peptidase 10 (USP10) to elevate YBX1 protein. Furthermore, USP10 inhibited ubiquitination-dependent YBX1 degradation. USP10 overexpression activated PINK1/Parkin signaling and promoted mitophagy, which were reversed by YBX1 knockdown. Moreover, TSG upregulated USP10 to promote mitophagy and inhibited neuronal apoptosis. Collectively, TSG facilitated PINK1/Parkin pathway-mediated mitophagy by upregulating USP10/YBX1 axis to ameliorate ischemic stroke.

Background:Colorectal cancer (CRC) is a common malignancy, with high incidence and high mortality rates. Cuproptosis, a novel form of copper-induced programmed cell death, contributes to tumor progression. However, whether cuproptosis-related genes (CRGs) play a role in CRC remains unclear. This study aims to elucidate the role of CRGs in CRC development, patient prognosis, and immune response. Methods:We performed bioinformatics analysis of the differential expression of CRGs between CRC and normal tissues. Least absolute shrinkage and selection operator (LASSO), and univariate and multivariate Cox analyses were employed to identify risk factors, which were used to construct a risk score model. Patients with CRC were categorized into high- and low-risk groups based on their median risk scores. Receiver operating characteristic curve analysis was used to verify the predictive accuracy of the risk model. A nomogram was developed for CRC through univariate and multivariate Cox regression analyses. The chemotherapeutic drug sensitivity was compared between patients with high and low CDKN2A/DLAT expression using the Wilcoxon rank-sum test. Spearman's correlation and TISIDB database analyses were conducted to determine relationships between CDKN2A or DLAT and immune cell infiltration. Results:Eight of ten identified CRGs exhibited significant differential expression between CRC and normal tissues. Among the eight significant differential expression CRGs, CDKN2A and DLAT were identified as independent risk factors for predicting overall survival (OS) in CRC. Patients with CRC in the low-risk group had longer OS than those in the high-risk group. The risk score model had good predictive accuracy for OS. Based on CDKN2A, DLAT and some clinical characteristics, a prognostic nomogram was developed to predict OS for CRC patients and showed good predictive ability. CDKN2A and DLAT expressions were significantly associated with chemotherapeutic drug sensitivity and immune cell infiltration in CRC, and the molecular subtypes and immune subtypes differed between CDKN2A and DLAT. Conclusions:Our research revealed the prognostic value of CRGs, particularly CDKN2A and DLAT, in CRC and demonstrated the relationship between CDKN2A/DLAT and immune infiltration in CRC, thereby contributing to the outcome evaluation of patients with CRC and identifying novel targets for CRC immunotherapy.

Long noncoding RNAs (LncRNAs) are essential to regulate the pathogenesis of coronary artery disease (CAD). This study was conducted to analyze the functionality of long noncoding RNA cancer susceptibility candidate 11 (lncRNA CASC11) in oxidized low-density lipoprotein (ox-LDL)-induced injury of cardiac microvascular endothelial cells (CMECs). CMECs were treated with ox-LDL to induce the CAD cell model. The cellular expression levels of CASC11 and histone deacetylase 4 (HDAC4) were determined by real-time quantitative polymerase chain reaction or Western blot assay. Cell absorbance, apoptosis, angiogenesis, and inflammation were evaluated by cell counting kit-8, flow cytometry, tube formation, and enzyme-linked immunosorbent assays. The subcellular localization of CASC11 was examined by the nuclear/cytoplasmic fractionation assay. The binding of human antigen R (HuR) to CASC11 and HDAC4 was analyzed by RNA immunoprecipitation. HDAC4 stability was determined after actinomycin D treatment. CASC11 was found to be decreased in the CAD cell model. CASC11 upregulation increased cell viability and angiogenesis and reduced apoptosis and inflammation. CASC11 bound to HuR and improved HDAC4 expression. HDAC4 downregulation counteracted the protective role of CASC11 overexpression in CMECs. In summary, CASC11 alleviated ox-LDL-induced injury of CMECs by binding to HuR and stabilizing HDAC4.

In this study, we investigated the effect of sweroside (SOS) on hepatic steatosis in mice and elucidated its molecular mechanisms. We conducted in vivo experiments using a C57BL/6 mice model of nonalcohol fatty liver disease (NAFLD) to explore the effect of SOS on hepatic steatosis in NAFLD mice. In in vitro experiments, primary mouse hepatocytes were treated with palmitic acid and SOS, and the protective effects of SOS on inflammation, lipogenesis, and fat deposition were analyzed. Autophagy-related protein levels and their related signaling pathways were evaluated in both in vivo and in vitro experiments. The results demonstrated that SOS decreased the high-fat-induced intrahepatic lipid content both in vivo and in vitro. The autophagy level in the liver was decreased in NAFLD mice but was reactivated following SOS intervention. SOS intervention was found to partially activate autophagy via the adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling pathway. Consequently, when the AMPK/mTOR pathway was suppressed or autophagy was inhibited, the beneficial effects of SOS intervention on hepatic steatosis were diminished. These results indicate that SOS intervention attenuates hepatic steatosis by promoting autophagy in the liver of NAFLD mice, in part by activating the AMPK/mTOR signaling pathway.

In this study, we investigated the effects of sweroside on podocyte injury in diabetic nephropathy (DN) mice and elucidated its molecular mechanisms. We conducted in vivo experiments using a C57BL/6 mice model of DN to explore the effects of sweroside on proteinuria and podocyte injury in DN mice. In in vitro experiments, conditionally immortalized mouse podocytes were treated with high glucose and sweroside, and the protective effects of sweroside on podocyte injury were analyzed. In vitro, Akt/BAD pathways were detected using gene siRNA silencing assays and found to be involved in the protective roles of sweroside in high glucose-mediated podocyte injury. In vivo, sweroside significantly decreased albuminuria in DN mice (p < 0.01). periodic acid-Schiff staining showed that sweroside alleviated the glomerular volume and mesangium expansion in DN mice. Consistently, western blot and reverse transcription-polymerase chain reaction analyses showed that the profibrotic molecule expression in the glomeruli declined in sweroside-treated DN mice. Immunofluorescent results showed that sweroside preserved nephrin and podocin expression, and transmission electron microscopy showed that sweroside attenuated podocyte injury. In DN mice, sweroside decreased podocyte apoptosis, and increased nephrin, podocin expression and decreased desmin and HIF1α expression. These results confirmed that sweroside ameliorated albuminuria, glomerulomegaly, and glomerulosclerosis in these mice. Experiments in vitro revealed that sweroside improved HG-induced podocyte injury and apoptosis. Sweroside stimulated activation of the Akt/BAD pathway and upregulated Bcl-2-associated death promoter (BAD) and p-Akt. Overall, sweroside protected podocytes from injury and prevented the progression of DN, providing a novel strategy for the treatment of DN.

Replication protein A 3 (RPA3) is a significant component of replication protein A and has been documented to function as an oncogene in several types of cancers. However, the role and underlying mechanism of RPA3 in lung adenocarcinoma (LUAD) remains unknown. In this study, messenger expression of RPA3 and survival probability in LUAD were predicted by the UALCAN database. The combination of RPA3 with cyclin-dependent kinases regulatory subunit 2 (CKS2) were characterized by the humanbase and STRING databases and verified by co-immunoprecipitation. Cell viability was assessed by Cell Counting Kit-8 assay and colony formation assay. Flow cytometric analysis and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay were used to determine cell cycle and cell apoptosis, respectively. The expressions of protein kinase B/mammalian target of rapamycin (AKT/mTOR) pathway and autophagy-related proteins were examined by western blot assay. Significantly, we revealed that RPA3 expression was upregulated in LUAD and is associated with poor prognosis in LUAD patients. RPA3 and CKS2 expression was highly expressed in LUAD cell lines and the interaction between RPA3 and CKS2 was confirmed. RPA3 silencing inhibited A549 cell viability, blocked cell cycle and promoted cell apoptosis, as well as induction of autophagy and inhibition of AKT/mTOR signaling. CKS2 overexpression reversed the effects of RPA3 silencing on A549 cells. In addition, RPA3 knockdown enhanced cisplatin sensitivity of A549 cells through blocking the AKT/mTOR signaling. These results suggested that RPA3 might control LUAD cell autophagy and enhance cisplatin sensitivity by regulation of AKT/mTOR signaling via targeting CKS2.

目的 探讨基于学习通平台的7E教学模式在诊断学问诊教学中的应用效果.方法 选取2018级临床医学专业本科三年级学生126名(对照组)和2019级临床医学专业本科三年级学生133名(观察组)作为研究对象.对照组采用传统教学法进行教学,观察组采用基于学习通平台的7E教学方法进行教学.教学结束后对两组学生进行问诊技能考核,比较两组学生的问诊技能考核评分及对问诊教学模式的评价情况.结果 观察组学生的问诊技能考核成绩及对问诊教学模式的满意程度均高于对照组(均P<0.05);观察组学生对激发学习兴趣、提高学习效率、增强与患者沟通的信心与能力、加深对常见症状的理解、明确常见症状的问诊内容和思路、提升人文关怀能力等方面的评价均优于对照组(均P<0.05).结论 基于学习通平台的7E教学模式能更好提升临床医学生诊断学问诊的教学效果,提高学生临床问诊的实践技能水平.

Objective To explore the cultivation and application effect of critical thinking ability in the class teaching of clinical-thinking training for diagnostics. Method To select as teaching objects 2 groups of junior students who major in clinical medicine in a 5-year program at Hunan University of Medicine — Group 1 with 182 students and Group 2 with 178 students. Group 1 functions as a control group and Group 2 an experimental group. The control group uses both the traditional teaching and classroom discussion methods for teaching, while the experimental group uses the method of “real cases+ critical thinking” for teaching. Before the class, the students in the experimental group are provided with two cases for their preview work; during the class, they are introduced into case scenes through videos; after the class, the teaching effects of the 2 groups are evaluated through the chapter tests, CTDI-CV scores, and questionnaires. The survey data are statistically analyzed with SPSS20.0 software, and the t test is used for comparison between the two groups. Results The chapter test and the critical thinking ability test for the students in the experimental group score in total respectively (87.17±6.56) and (301.05±29.58), both of which are higher than those of the control group (the two kinds of scores for the control group are (79.27±7.36) and (254.23±24.74) respectively), with the differences statistically significant (P<0.05). The questionnaire-response rate of the experimental group students stands at 100%; most students believe that “real cases + critical thinking” in the class teaching could improve students' clinical-thinking ability in diagnosing diseases, cultivate students’ good character of selfless dedication, and familiarize students with the clinical characteristics of related diseases. Conclusion In the teaching process of clinical-thinking training for diagnostics, applying both the real cases and critical thinking is conducive to improving the teaching effect, and therefore it is worth promoting in clinical teaching and practice.

Background:Recently, inflammation has become a major threat to human health. Studies have confirmed that some Chinese traditional medicine ingredients may effectively interfere with the expression of inflammatory mediators through epigenetic modification, showing a great potential of the application.Objective:To investigate the role of the PPAR/DNMT3A pathway in the reversal of galangin-mediated inflammatory lung injury, promote the development of new anti-inflammatory drugs, reduce the side effects of chemical synthetic drugs on the body, and prove the effectiveness and safety of galangin in inhibiting inflammatory response and injury.Methods:120 rats were randomly divided into 6 groups: (Group 1) LPS group; (Group 2) LPS + galangin group; (Group 3) LPS + galangin +  GW9662 group; (Group 4) LPS + galangin + DNMT3A siRNA group; (Group 5) LPS + galangin + siRNA negative group; (Group 6) control group. The model of inflammatory lung injury was established by intrathecal instillation of LPS in the first five groups and NS in the control group. SD survival rate was recorded every 24 hours after modeling, lasting for 168 hours. The lung tissues were taken 168 hours after the establishment of the model. The pathological morphology of lung tissue was observed after the staining under the light microscope, and the lung dry/wet weight ratio was calculated after drying. After NS was perfused into lung tissue, the lavage fluid was collected and the levels of IL-6 and TNF-a were measured by ELISA. The contents of PPAR, DNMT3A, phosphorylated p65, and ERK in monocytes were detected by the WB method, and the binding contents of p65 and AP-1 in the promoter regions of IL-6 and TNF-a genes were detected by the Chip-qPCR method.Results:Intraperitoneal injection of galangin could inhibit the synthesis of alveolar inflammatory factors (TFs) in the SD model of lung injury induced by LPS, reduce the degree of pathological injury of lung tissue, and improve the survival rate of the SD model. GW9662 can completely reverse the protective effect, while DNMT3A interference can only partially block its protective effect. In addition, galangin could significantly inhibit the LPS-induced expression of p65 and AP-1 in alveolar monocytes and their binding content in the promoter region of inflammatory genes by activating PPAR/DNMT3A pathway. GW9662 could completely reverse the inhibitory effect of galangin. DNMT3A interference could restore the binding content of transcription factors at the promoter of the inflammatory gene but had no significant effect on its synthesis.Conclusion:Galangin can interfere with the binding of transcription factors to inflammatory gene promoters through the methylation modification induced by PPAR/DNMT3A pathway, so as to inhibit the synthesis of inflammatory molecules and reverse inflammatory lung injury.

"临床医学概要"是医学影像技术专业的核心课程及专业基础必修考试课程,在教学过程中存在临床思维能力弱、运用知识的能力不足、授课形式及考核方式单一、学时少内容多、教学资源共享性差等问题.为有效解决上述问题,根据医学影像技术专业特点,结合湖南医药学院办学定位及特色,合理设置教学目标,对"临床医学概要"课程进行教学改革及探索,取得了较好的成效,旨在提高教学质量,提升教学效果,提高学生的综合素质,培养合格的医学应用型人才.

Nonsmall‐cell lung carcinoma (NSCLC) is one of the deadliest malignancies in the world. LncRNAs are confirmed to be involved in the progression of NSCLC. Meanwhile, lncRNA CRNDE is known to be upregulated in NSCLC; however, the mechanism by which CRNDE regulates the tumourigenesis of NSCLC remains unclear. To test the function of CRNDE in NSCLC, cell proliferation, invasion, and migration were investigated by colony formation and Transwell assays, respectively. qPCR and Western blotting were applied to test gene and protein levels. In addition, the relationship among CRNDE, miR‐455‐3p, and HDAC2 was explored by dual‐luciferase and RIP assays. The data revealed that the expression of CRNDE was upregulated in NSCLC tissues, while miR‐455‐3p was downregulated. CRNDE knockdown inhibited the viability, migration and invasion of NSCLC cells or epidermal growth factor receptor gene (EGFR)‐mutant NSCLC cells. Moreover, inhibition of miR‐455‐3p exhibited the opposite effect. CRNDE bound with miR‐455‐3p, and HDAC2 was found to be targeted by miR‐455‐3p. Meanwhile, miR‐455‐3p downregulation reversed the effect of CRNDE knockdown on NSCLC cell function. Furthermore, miR‐455‐3p notably inhibited the growth and invasion of NSCLC cells via downregulation of HDAC2. Knockdown of CRNDE attenuated NSCLC progression via modulation of the miR‐455‐3p/HDAC2 axis. Thus, those findings might provide a novel strategy against NSCLC.

Objective:To evaluate the effect of teaching method based on online resource-sharing mechanism in diagnostic teaching.Methods:From September, 2019 to July, 2020, totally 720 students of 5-year curriculum of clinical medicine enrolled in 2017 in Hunan University of Medicine were selected and divided into experimental group and control group with 360 students in each. In the teaching of diagnostics, off-line teaching combined with online resource-sharing approach was adopted in the experimental group, while off-line traditional teaching approach was adopted in the control group. At the end of the teaching, theoretical examination method was used to compare the results of the two groups , and the questionnaire survey was used to investigate the experimental group students' evaluation on the effect of online resource-sharing method.Results:Both midterm and final test scores of the experimental group [(83.25±5.72) and (85.14±7.65)] were significantly higher than those of the control group [(78.02±5.39) and (77.36±7.45)](all P<0.01). The results of the questionnaire survey showed that 85.0%(306/360) of the students in the experimental group believed that the network resource-sharing method in teaching of diagnostics greatly improved their autonomic learning capacity. Conclusions:The teaching approaches of online resource sharing diagnostic course improves the learning outcomes and autonomic learning attitude of students.

目的 通过分析武陵山片区人群候选基因MTHFR、CBS、ALDH2易感位点多态性、饮食习惯偏好以及两者的交互作用与H型高血压的发病关联,从而揭示H型高血压的流行病学危险因素.方法 2020年10-12月,将875例研究对象分为对照组、单纯高血压组以及单纯高同型半胱氨酸血症(hyperho-mocysteine,HHcy)组以及H型高血压组.通过问卷调查获得一般资料,抽取血样本进行生化指标检测,同时对MTHFR、CBS、ALDH2基因对应的易感位点rs1413355、rs6586283以及rs190914158进行测序,分析上述位点多态性与H型高血压的相关性,并采用二分类logistic回归以及线性优势比模型计算饮食习惯与基因分型对H型高血压形成的交互作用.结果 武陵山片区人群中rs1413355、rs190914158位点变异均与HHcy有关,但与血压异常无相关性,rs190914158位点变异与胰岛素抵抗以及血脂水平异常有相关性.多因素logistic回归分析显示,在作为独立变量时,易感位点以及饮食习惯均不能导致H型高血压,rs190914158位点突变和腌制饮食偏好之间的交互作用仍然为发病的危险因素,且与线性优势比模型计算结果吻合.结论 武陵山片区人群候选基因ALDH2 rs190914158位点变异可能导致包括同型半胱氨酸在内的多种代谢障碍,并且与腌制饮食偏好在促成H型高血压发病过程中存在交互作用.

Background Ischemic stroke, also known as cerebrovascular accident or cerebral stroke, occupies the first place in the world's top 10 causes of death, with high incidence, mortality and disability rates. Objectives To investigate the effect of stilbene glycoside upregulated SIRT3/AMPK expression on neuronal mitochondrial autophagy and neuronal apoptosis in ischemic stroke. Material and methods The PC12 cells were cultured without serum to construct an ischemic neuron model. The cells were divided into 6 groups: normal group (untreated cells), model group (ischemic treated cells), TSG group (stilbene glycoside treatment), NC group (SIRT3 and AMPK negative control treatment), si-SIRT3 group (SIRT3 silencing treatment), TSG+si-SIRT3 group (joint treatment), and TSG+si-SIRT3+oe-AMPK group (joint treatment). Cell survival and the expression of related molecules were detected. Results Compared with normal group, the model group had significantly decreased cell survival rate, mitochondrial membrane potential, as well as the expression of Bcl-2, LC3II/I, P62, PINK1, Parkin, SIRT3, AMPK, and p-AMPK, while showing significantly increased proportion of apoptosis and the expression of caspase 3 and Bax. Compared with the model group, TSG treatment promoted cell survival rate and mitochondrial autophagy, and inhibited apoptosis, while SIRT3 silencing treatment reduced cell survival rate and mitochondrial autophagy, and increased apoptosis. The SIRT3 silencing could block the inhibitory effect of TSG on the apoptosis of ischemic PC12 cells and promote mitochondrial autophagy, and AMPK overexpression could save the apoptosis of ischemic PC12 cells caused by SIRT3 silencing, and promote mitochondrial autophagy. Conclusions By promoting the expression of SIRT3/AMPK, TSG promotes mitochondrial autophagy in ischemic neurons and inhibits their apoptosis.

Non-small cell lung cancer (NSCLC) has been a severe clinical disease and its treatments remain unsatisfactory. We aimed to investigate the influence of miR-520e on PI3K/Akt pathway in NSCLC via targeting caspase activation and recruitment domain containing 5 (NLRC5) and demonstrated the potential therapeutic effect of miR-520e. The expressions of miR-520e and NLRC5 were assessed in NSCLC cell lines using RT-qPCR. miR-520e mimic, mimic negative control (NC), NLRC5 overexpression (OV), OV-NC were transfected into A549 cells, respectively. Cell counting kit-8, colony formation and Transwell assays were respectively performed to assess the capacities of cell proliferation, colony formation and invasion. Cell apoptosis was analyzed using flow cytometry. Expressions of NLRC5, p/t-AKT, p/t-PI3K were identified using western blotting. miR-520e was downregulated while NLRC5 was overexpressed in A549 cells. miR-520e mimic significantly weakened the proliferation, colony formation, invasion and migration of A549 cells and promoted cell apoptosis. miR-520e overexpression had an obvious inhibitory effect on the PI3K-Akt pathway. Interestingly, overexpression of NLRC5 could attenuate these effects of miR-520e on A549 cells. Besides, miR-520e can directly target NLRC5. Our findings suggested that miR-520 may serve as a key regulator in NSCLC via targeting NLRC5 and might indicate a novel solution to this intractable cancer.

<span id="ChDivSummary" name="ChDivSummary" class="abstract-text">目的探讨生长阻滞特异性转录本5（growth arrest-specific transcript 5,GAS5）对肺纤维化的影响及分子机制。方法采用生物信息学、荧光素酶报告基因分析GAS5、miR-21、ADAMTS-1间的竞争性内源RNA（ceRNA）关系。SD大鼠分为对照组、LV-GAS5组和LV-GAS5+miR-21 agomir组,经气管内注入博莱霉素A5建立肺纤维化模型后,分别给予尾静脉注射0.2 mL的PBS、LV-GAS5、LV-GAS5+miR-21 agomir。d 28,处死大鼠,收集血液,采用ELISA分析血清PICP和PⅢNP水平,提取肺组织,HE染色和Masson染色观察病理改变,并用qRT-PCR检测GAS5、miR-21、ADAMTS-1表达,Western blot检测ADAMTS-1、ColⅠ、ColⅢ表达。结果GAS5、miR-21、ADAMTS-1之间存在ceRNA调控模式。与对照组比较,GAS5过表达减轻肺组织病理改变,降低血清PICP、PⅢNP水平,上调肺组织GAS5、ADAMTS-1表达,降低肺组织miR-21、ColⅠ、ColⅢ水平（P &lt;0.01）。此外,miR-21agomir处理逆转了GAS5过表达对肺纤维化大鼠肺组织病理改变、胶原沉积和ADAMTS-1表达的影响（P &lt;0.01）。结论GAS5通过内源性吸附miR-21,上调ADAMTS-1表达,促进ColⅠ、ColⅢ降解,减轻肺纤维化病变。</span>