目的 分析乳腺癌细胞中Snail与MTDH基因的作用,明确Snail是否通过结合于MTDH的启动子区域促进乳腺癌转移。方法 克隆、转染Snail基因至乳腺癌细胞,观察过表达Snail的乳腺癌细胞中MTDHmRNA及蛋白表达的变化;再使用免疫共沉淀法检测Snail与MTDH基因的共作用。结果 转染Snail基因进入乳腺癌MDA-MB-435细胞后,转染组、空白组和对照组中MTDHmRNA的表达水平分别为1.61±0.22、1.02±0.18、0.99±0.20,转染组高于空白组和对照组,差异有统计学意义(P<0.05),而后两组表达无差异(P>0.05);Westren blot检测结果显示,Snail可促进MTDH蛋白的表达;免疫共沉淀显示,Snail与MTDH在细胞内存在相互结合作用。结论 Snail在乳腺癌细胞中可通过结合于MTDH基因的启动子区域,促进MTDHmRNA转录及相关蛋白的表达,从而导致乳腺癌转移。

Objective To investigate the function of Snail to MTDH gene in breast cancer cells. Methods We observed the changement of MTDHmRNA and protein expression in breast cancer cell line MDA-MB-435 after transfected with Snail gene. Then, we used co-immunoprecipitation to determine the domain of Snail and MTDH binding in vitro. Results After transfected with Snail gene into MDA-MB-435 cell, the expression levels of MTDHmRNA in transfection group, blank group and control group were 1.61±0.22,1.02±0.18,0.99±0.20. The level of transfection group was significantly higher than the other groups(P< 0.05). Western blot showed that the expression of MTDH protein can be promoted by Snail. Co-immunoprecipitation showed that Snail and MTDH are binding interactions in breast cancer cell line MDA-MB-43. Conclusion Snail can promote transcription and expression of MTDH in breast cancer cells by binding to the promoter region of the MTDH gene resulting in metastasis of breast cancer.

目的 探讨抗增殖蛋白2（PHB2）脓毒症心肌损伤线粒体功能的调控机制。方法 体外培养大鼠心肌细胞株（H9C2）,分为对照组、脂多糖（LPS）组、LPS+PHB2 siRNA（si-PHB2）组。检测氧化应激指标细胞内丙二醛（MDA）水平、荧光探针检测细胞内活性氧（ROS）水平;线粒体指标：三磷酸腺苷（ATP）水平、线粒体膜电位、线粒体电镜、线粒体半定量评分;免疫印迹法检测PHB2、PTEN诱导激酶1（PTNKI）、帕金蛋白（Parkin）、线粒体转录因子（TFAM）的表达。结果 LPS刺激后MDA水平和ROS水平升高、ATP水平低,LPS+si-PHB2组MDA（6.21±0.39 vs 3.59±0.33, P<0.05）、细胞内的ROS（15 131.37±88.72 vs 8 628.67±71.95, P<0.05）的水平较LPS组升高,ATP（3.46±0.34 vs 4.52±0.25, P<0.05）和线粒体膜电位水平（0.33±0.04 vs 0.55±0.09, P<0.05）进一步降低;电镜观察显示与正常组相比,LPS组、LPS+si-PHB2组出现不同程度线粒体损伤,线粒体损伤半定量评分显示LPS+si-PHB2组的损伤较LPS组更为明显（1.42±0.10 vs 0.81±0.04, P<0.05）; 免疫印迹法结果显示LPS处理后PHB2、PINK1、Parkin 表达上调,TFAM表达下调,LPS+si-PHB2组的线粒体自噬相关蛋白PINK1（1.33±0.06 vs 1.79±0.21, P<0.05）、Parkin（1.43±0.08 vs 1.86±0.09, P<0.05）和线粒体生物发生关键蛋白TFAM（0.29±0.01 vs 0.74±0.06, P<0.05）表达均较LPS组降低。结论 LPS可促进大鼠心肌细胞PHB2表达,si-PHB2干扰后线粒体自噬蛋白和生物发生蛋白表达抑制,心肌细胞氧化应激损害和线粒体功能障碍加重,提示PHB2表达上调可能恢复线粒体稳态改善脓毒症心肌损伤的线粒体功能。

Objective To explore the regulatory mechanism of septic myocardial injury by prohibitin 2（PHB2）. Methods Rat myocardial cell lines（H9C2）were cultured in vitro and divided into control group,LPS group,LPS + PHB2 siRNA（si-PHB2） group. The indicators for detecting oxidative stress include the levels of intracellular malondialdehyde（MDA）and reactive oxygen species（ROS）. The indicators for mitochondrial detection include adenosine triphosphate（ATP）levels,mitochondrial membrane potential,mitochondrial electron microscopy,and semi-quantitative mitochondrial scoring. Western blotting was used to detect the expression of PHB2,PTEN induced putative kinase（PINK1）,Parkin,mitochondrial transcription factor A（TFAM）. Results After LPS stimulation,MDA level and intracellular ROS level increased,ATP level decreased. Compared with LPS group,MDA（6. 21±0. 39 vs 3. 59±0. 33, P<0. 05）level and intracellular ROS level（15 131. 37±88. 72 vs 8 628. 67±71. 95, P<0. 05）in LPS + si-PHB2 group increased significantly,while ATP（3. 46±0. 34 vs 4. 52±0. 25, P<0. 05）and MMP（0. 33±0. 04 vs 0. 55±0. 09, P<0. 05）level further decreased. Compared with the normal group,the structure of mitochondria in LPS group and LPS + si-PHB2 group was damaged in different degree. The semi-quantitative score of mitochondrial damage showed that the damage in LPS + si-PHB2 group was more obvious than that in LPS group（1. 42±0. 10 vs 0. 81±0. 04, P<0. 05）. Western blotting showed that the expression of PHB2,PINK1 and Parkin were up-regulated and the expression of TFAM was down-regulated after LPS treatment,mitohagy-related proteins PINK1（1. 33±0. 06 vs 1. 79±0. 21, P<0. 05）,Parkin（1. 43±0. 08 vs 1. 86±0. 09, P<0. 05）and mitochondrial biogenetic protein TFAM（0. 29±0. 01 vs 0. 74±0. 06, P<0. 05）in LPS+si-PHB2 group were lower than those in LPS group. Conclusions LPS can promote the expression of PHB2 in rat cardiomyocytes. After interfering with PHB2 expression,we found that mitochondrial autophagy and biogenesis are inhibited,and mitochondrial dysfunction,oxidative stress exacerbated,suggesting that the up-regulation of PHB2 expression may restore mitochondrial homeostasis and improve mitochondrial function in septic myocardial injury.

       目的   探讨NXT629改善肝胆结石形成的相关机制。方法   对C57BL/6J小鼠分别采用常规饮食或成石饮食（LD）喂养，并在LD组小鼠注射PPAR-α拮抗剂NXT629。通过苏木精-伊红染色法染色分析肝脂肪病变，油红O染色检测肝脏脂质的积累，分光光度法检测胆汁或血清中总胆固醇、甘油三酯、磷脂、总胆汁酸、胆固醇饱和指数、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇指标；qPCR法检测小鼠肝组织中ABCG5/8、CYP7A1、CYP7B1、PPAR-α和ABCB11 mRNA的表达情况。结果  NXT629通过靶向PPAR-α降低LD组小鼠肝脏中的ABCG5、ABCG8、ABCB11 mRNA水平以及增加CYP7A1、CYP7B1 mRNA水平，进而减少LD诱导的肝胆结石形成并改善脂质代谢紊乱。结论  NXT629可能通过影响脂代谢相关基因表达改善肝胆结石。

       Objective  To explore the mechanism on NXT629 improves hepatolithiasis formation．Methods  C57BL/6J mice were fed either a regular diet or a lithogenic diet（LD），with the LD group receiving injections of PPAR-α inhibitor NXT629．Liver steatosis was analyzed via HE staining，hepatic lipid accumulation was detected by Oil Red O staining，and total cholesterol，triglycerides，phospholipids，total bile acids，cholesterol saturation index，low density lipoprotein cholesterol，and high density lipoprotein cholesterol levels in bile or serum were measured using assay kits．RT-qPCR was employed to determine the mRNA expression of ABCG5/8，CYP7A1，CYP7B1，PPAR-α，and ABCB11 in mouse liver tissues．Results  The results showed that NXT629 target PPAR-α to down-regulate the mRNA levels of ABCG5，ABCG8，and ABCB11 in the livers of LD-fed mice，while increasing the mRNA levels of CYP7A1 and CYP7B1，thereby  reducing LD-induced hepatolithiasis formation and improving lipid metabolism disorders．Conclusions  NXT629 can improve cholesterol gallstones by affecting the expression of genes related to lipid metabolism．

       目的   探讨复方黄芪颗粒（CHG）的抗疲劳作用及其机制。方法  48只雄性BALB/C小鼠随机分为空白对照组、低剂量（9.1 g/kg）、中剂量（18.2 g/kg）、高剂量（27.3 g/kg）CHG 3个试验组，每组12只。试验组给予不同剂量的复方黄芪颗粒溶液灌胃，空白对照组小鼠给予等体积生理盐水。给药30 d后，检测小鼠体内相关指标变化，观察其抗疲劳作用并分析相关机制。结果   与空白对照组相比，试验组小鼠体质量差异无统计学意义（P＞0.05），小鼠力竭游泳时间及转棒耐力时间均明显延长（P＜0.01），血尿素氮（BUN）、乳酸脱氢酶（LDH）、丙二醛（MDA）水平明显降低（P＜0.01），肝糖原和肌糖原水平升高（P＜0.05），超氧化物歧化酶（SOD）活性升高（P＜0.01）。体外抗氧化试验表明CHG以剂量依赖性方式清除2，2-联氮-二（3-乙基-苯并噻唑-6-磺酸）二铵盐（ABTS）和1，1-二苯基-2-三硝基苯肼（DPPH）自由基。当CHG质量浓度为100.000 0 mg/mL时，CHG对DPPH自由基清除能力可达85.030 3%。当CHG质量浓度为25.000 0 mg/mL时，CHG对ABTS自由基清除能力可达96.357 2%。结论  CHG具有抗疲劳的作用，其作用机制可能与抗氧化作用相关。

      Objective  To investigate the anti-fatigue effects of compound Huangqi granules（CHG）and its mechanism．Methods  Forty-eight male BALB/C mice were randomly divided into blank control group，9.1，18.2，27.3 g/kg CHG group（test groups）．The test groups received different concentrations of CHG solution by gavage，and the blank control group mice were given equal volume saline．After 30 days of administration，the mice were tested，meanwhile the anti-fatigue effect and mechanism were investigated．Results  Compared with blank control group，there was no significant difference in body weight（P＞0.05）．The exhaustive swimming time and rod turning endurance time of mice were significantly prolonged（P＜0.01）．The serum levels of blood urea nitrogen，lactate dehydrogenase and malondialdehyde were significantly decreased（P＜0.01），while the liver and muscle glycogen levels（P＜0.05）and superoxide dismutase activity were increased（P＜0.01）．In vitro antioxidant tests showed that CHG can remove （1，1-Diphenyl-2-picrylhydrazyl，ABTS） and （2，2’-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid，DPPH） free radicals in a dose-dependent manner．When the CHG concentration is 100 mg/mL，the DPPH free  radical scavenging ability of CHG can reach 85.030 3%．When the CHG concentration was 25 mg/mL，the scavenging ability of CHG to ABTS free radicals reached 96.357 2%．Conclusions  CHG has anti-fatigue effect，and its mechanism may be related to anti-oxidation effect．

       炎症性肠病（IBD）是一种以反复腹痛、腹泻、血便和体重降低为主要表现的慢性特发性性疾病，主要分为溃疡性结肠炎与克罗恩病两种类型。近年来，IBD的患病率随着城市化和工业化进展迅速升高，给中国和全球的公共健康带来沉重的负担。随着人类基因组技术的发展，越来越多的证据表明，遗传学因素在IBD发病过程中起着不可或缺的作用。在亚欧人群中，通过大规模全基因组关联研究现已明确了320个IBD易感基因位点。IBD易感基因在影响机体的细胞代谢、免疫功能调节、肠道上皮屏障和微生物清除等多个方面发挥着重要作用。本文就IBD相关易感基因及其多态性的研究进展进行综述，从基因层面揭示IBD发病的分子机制，并对探索IBD因人而异的个性化治疗方案提供帮助。

    Inflammatory bowel disease（IBD）is a chronic idiopathic disease characterized by recurrent abdominal pain，diarrhea，bloody stools，and weight loss．Ulcerative colitis and Crohn’s disease represent the two main types of IBD．In recent years，the prevalence of IBD has increased rapidly with the advancement of industrialization，imposing a heavy burden on public health in China and globally．Currently，with the development of genomics，a growing body of evidence suggests that genetic factors play an indispensable role in the pathogenesis of IBD．In the Eurasian population，320 IBD susceptibility gene loci have been identified through large-scale genome-wide association studies．IBD susceptibility genes play a crucial role in various aspects affecting cellular metabolism，immune function regulation，intestinal epithelial barrier，and microbial clearance．This article reviews the susceptibility genes and their polymorphisms associated with IBD，revealing the molecule mechanisms of IBD from gene perspectives and contributing to the development of personalized treatment strategies tailored to individual IBD patients．

       结直肠癌（CRC）是全球第三大最常见的癌症，也是癌症相关死亡的第二大常见原因。结直肠癌肝转移（CRLM）是导致CRC患者死亡的主要原因，根治性肝切除术是目前有望治愈CRLM的唯一途径，但大部分患者不能进行根治性肝切除术。通过早期发现并进行针对性干预，能够改善患者的治疗效果及预后。文章通过综述CRLM的发病机制、诊疗现状及最新纳米诊疗方法，为深入探索高效诊疗方法提供思路。

      Colorectal cancer（CRC）is the third most common cancer and the second most common cause of cancer-related death worldwide．Colorectal cancer liver metastases（CRLM）are the leading cause of death in patients with CRC．Radical hepatectomy is the only way to cure CRLM so far，while most patients cannot undergo radical hepatectomy．CRLM treatment efficacy and prognosis can be improved by early diagnosis and specialized intervention．This paper reviews the pathogenesis，diagnosis，and treatment status of CRLM and the latest nano-diagnosis and treatment methods so as to provide ideas for in-depth exploration of efficient diagnosis and treatment methods．

       目的  采用网络药理学方法与分子对接技术分析白头翁汤治疗细菌性痢疾（BD）的潜在活性成分与作用机制。方法  借助中药系统药理学数据库与分析平台（TCMSP）及PubChem数据库检索筛选白头翁汤方的化学成分和作用靶点，通过Uniprot数据库校正基因名，同时通过比较毒物基因组学数据库（CTD）、药物靶标数据库（TTD）、GeneCards数据库和药物和药物靶标数据库（DRUGBANK）获得BD相关疾病靶点。经在线绘图平台微生信分析“活性成分-疾病”交集靶点，使用Cyoscape 3.7.2软件构建可视化的中药-活性成分-靶点网络、蛋白质互作网络，筛选潜在的关键活性成分与核心靶点；通过Metascape数据库对进行靶点的基因本体（GO）功能分析和京都百科全书基因和基因组通路数据库（KEGG）通路富集分析，同时使用Cyoscape 3.7.2软件构建基因-通路网络，筛选潜在的通路及其作用机制。同时采用分子对接技术对白头翁汤中关键活性成分和BD核心靶点进行分析。结果  白头翁汤共筛选出266个潜在活性成分，其中，槲皮素、β-谷甾醇、异鼠李素、异延胡索单酚碱、小檗红碱、豆甾醇等66个关键活性成分可通过肿瘤坏死因子（TNF）、白细胞介素-6（IL-6）、前列腺素内过氧化物合酶2（PTGS2）、丝氨酸/苏氨酸蛋白激酶1（AKT1）、血管内皮生长因子A（VEGFA）、V-rel网状内皮细胞病毒癌基因同源物A（RELA）、半胱氨酸天冬氨酸蛋白酶3（CASP3）、白细胞介素-8（CXCL8）、白细胞介素-1B（IL-1B）、丝裂原活化蛋白激酶1（MAPK1）、白细胞介素-10（IL-10）等33个潜在交集靶点作用于BD。GO基因功能分析共得到生物过程（BP）条目20个、细胞组成（CC）条目6个、分子功能（MF）条目9个（P＜0.01），主要涉及外部凋亡过程、细胞迁移正向调控、细胞因子受体结合、蛋白同源二聚活性、TNF受体超家族结合等生物进程。KEGG通路富集分析确定13条信号通路（P＜0.01），主要涉及癌症信号通路、白细胞介素-17（IL-17）信号通路等关键通路。分子对接结果显示槲皮素、β-谷甾醇、异鼠李素、异延胡索单酚碱等核心活性成分与TNF、IL-6、PTGS2核心靶点具有良好的结合效应（结合能＜-5 kJ/mol）。结论  白头翁汤主要通过槲皮素、β-谷甾醇等潜在的多种活性成分作用于TNF、IL-6、IL-1B、PTGS2、AKT1、VEGFA等潜在的关键靶点调控IL-17等信号通路，从而发挥治疗细菌性痢疾的作用，符合中药复方多成分、多靶标、多途径起效的显著特征。

      Objective To analyze the potential active ingredients and mechanism of Baitouweng Decoction in the treatment of bacillary dysentery（BD）by means of network pharmacology and molecular docking technology．Methods With the help of the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（Traditional Chinese Medicine Systems Pharmacology Database，TCMSP）and PubChem database to search and screen the chemical composition and target of Baitouweng Decoction，the gene name was corrected through the Uniprot database，and the CTD database，TTD database，GeneCards database and DRUGBANK database obtain BD-related disease targets．The intersection target was obtained through the online  drawing platform，and Cytoscape 3.7.2 was used to construct a network of Pulsatilla active ingredient-component disease intersection target．The protein-protein interaction analysis of the intersection target was performed through the String database，and the Cytoscape 3.7.2 software was used for visualization．The Metascape database platform performed GO function analysis and KEGG pathway enrichment analysis on the target to predict its mechanism of action．The  key active ingredient compounds in Baitouweng Decoction were molecularly docked with the core protein in the intersection target．Results A total of 266 potential active ingredients in Baitouweng Decoction were screened，of which 66 key active ingredients such as quercetin，β-sitosterol，isorhamnetin，Isocorypalmine，berberine，stigmasterol，etc．It acts on BD through 33 potential intersection targets such as TNF，IL-6，PTGS2，AKT1，VEGFA，RELA，CASP3，CXCL8，IL-1B，MAPK1，IL-10．GO gene function analysis yielded a total of 20 biological process（BP）entries，6 cell composition（CC）entries，and 9 molecular function（MF）entries（P＜0.01），which mainly involve external apoptosis process and positive regulation of cell migration，Cytokine receptor binding，protein homodimerization activity，tumor necrosis factor receptor superfamily binding and other biological processes．KEGG pathway enrichment analysis identified 13 signal pathways（P＜0.01），mainly related to key pathways such as cancer signal pathway and IL-17 signal pathway．The results of molecular docking showed that the core active ingredients such as quercetin，β-sitosterol，isorhamnetin，Isocorypalmine and TNF，IL-6，PTGS2 core targets have good binding effects（binding energy ＜-5 KJ /mol）．Conclusions Baitouweng Decoction modulated signaling pathways involving IL-17 through its active constituents like quercetin and β-sitosterol，targeting key molecules such as TNF，IL-6，IL-1β，PTGS2，AKT1，and VEGFA，reflecting the multi-target therapeutic approach of traditional Chinese medicine．

       近几十年来，全球近视患病率不断上升，已成为全世界主要的公共卫生问题之一。众多研究表明户外活动能有效控制近视的发生和发展。本文综述了户外活动对近视防控作用的研究进展及其作用机制，以期为近视防控提供新的思路。

     In recent decades, the prevalence of myopia has been increasing globally, becoming one of the major public health issues worldwide. Numerous studies indicate that outdoor activities can effectively control the onset and progression of myopia. This article reviews the research progress on prevention and control effect and mechanism of outdoor activities on myopia, hoping to provide new insights for myopia prevention and control.