Myocardial infarction (MI) is a cardiovascular disease with high morbidity and mortality. Clinically, rehabilitation after massive MI often has a poor prognosis. Therefore, it is necessary to explore the therapeutic methods of myocardial protection after MI. As a first-line treatment for type 2 diabetes, metformin has been found to have a certain protective effect on myocardial tissue. However, its pharmacological mechanism remains unclear. In this study, we investigated key factors that reduced MI with metformin. Through in vivo, in vitro, and in silico analyses, we identified HSF1 as a key target for metformin. HSF1 could up-regulate the transcriptional level of AMPKα2 through transcriptional activation and stimulate the activity of the downstream AMPK/mTOR signaling pathway. Metformin stimulated cardiomyocytes to form stress granules (SGs), and knockdown of HSF1 reversed this process. Furthermore, HSF1 exhibited better in vitro affinity for metformin than AMPK, suggesting that HSF1 may be a more sensitive target for metformin.

Zinc finger protein 667 (ZNF667, also referred as Mipu1), a widely expressed KRAB/C2H2-type zinc finger transcription factor, can protect against hypoxic-ischemic myocardial injury. Pro-angiogenesis is regarded as a promising strategy for the treatment of acute myocardial infarction (AMI). However, whether ZNF667 is involved in the angiogenesis following AMI remains to be elucidated. The present study reported that the expression of ZNF667 in CD31-positive endothelial cells (ECs) was upregulated in the heart of AMI mice. Hypoxic challenge (1% oxygen) promoted the mRNA and protein expression of ZNF667 in the human umbilical vein endothelial cells (HUVECs) in a time-dependent manner. Moreover, ZNF667 promoted hypoxia-induced invasion and tube formation of HUVECs. Mechanically, ZNF667 could directly bind to the promoter of anti-angiogenic gene VASH1 and inhibit its expression. Consequently, VASH1 overexpression abolished hypoxic challenge or ZNF667 overexpression-induced invasion and tube formation of HUVECs. Further bioinformatic analyses suggested that overexpression of ZNF667 or knockdown of VASH1-induced differentially expressed genes in HUVECs were greatly enriched in the Wnt signaling pathway (DAAM1, LEF1, RAC2, FRAT1, NFATc2 and WNT5A). Together, these data suggested that ZNF667 facilitates myocardial ischemia-driven angiogenesis through transcriptional repression of VASH1 and regulation of Wnt signaling pathway.

Objective: The present study aimed to investigate whether the drug nicorandil can improve cardiac remodeling after myocardial infarction (MI) and the underlying mechanisms. Methods: Mouse MI was established by the ligation of the left anterior descending coronary artery and H9C2 cells were cultured to investigate the underlying molecular mechanisms. The degree of myocardial collagen (Col) deposition was evaluated by Masson's staining. The expressions of nucleolin, autophagy and myocardial remodeling-associated genes were measured by Western blotting, qPCR, and immunofluorescence. The apoptosis of myocardial tissue cells and H9C2 cells were detected by TUNEL staining and flow cytometry, respectively. Autophagosomes were observed by transmission electron microscopy. Results: Treatment with nicorandil mitigated left ventricular enlargement, improved the capacity of myocardial diastolic-contractility, decreased cardiomyocyte apoptosis, and inhibited myocardial fibrosis development post-MI. Nicorandil up-regulated the expression of nucleolin, promoted autophagic flux, and decreased the expres-sions of TGF-beta 1 and phosphorylated Smad2/3, while enhanced the expression of BMP-7 and phosphorylated Smad1 in myocardium. Nicorandil decreased apoptosis and promoted autophagic flux in H2O2-treated H9C2 cells. Autophagy inhibitors 3-methyladenine (3MA) and chloroquine diphosphate salt (CDS) alleviated the effects of nicorandil on apoptosis. Knockdown of nucleolin decreased the effects of nicorandil on apoptosis and nicorandil-promoted autophagic flux of cardiomyocytes treated with H2O2. Conclusions: Treatment with nicorandil alleviated myocardial remodeling post-MI through up-regulating the expression of nucleolin, and subsequently promoting autophagy, followed by regulating TGF-beta/Smad signaling pathway.

Purpose: To explore the molecular mechanism of promoting cervical cancer by HSF1 in vivo and in vitro. Methods: The expression of HSF1 in 110 paraffin-embedded cervical cancer sections of different grades was examined via immunohistochemistry analyses. Expression of HSF1 downstream targets Metadherin (MTDH), VEGF-C and CD31 were studied using immunohistochemistry analyses. HSF1 transcriptional activity in the MTDH promoter region was detected by EMSA, CHIP and luciferase. Cell proliferation and clonality were detected by MTT and clonal formation assay. Cell migration and invasion ability were investigated by scratch analysis and transwell assay. HSF1-mediated tumorigenesis in vivo was examined in xenograft models. Results: HSF1 expression of cervical cancer cell line was increased compared to normal human cervical tissues. HSF1 enhanced the expression of MTDH, VEGF-C and CD31. HSF1 can combine with MTDH promoter to promote the expression of MTDH. HSF1 enhanced HeLa cell proliferation and clone formation. Furthermore, HSF1 increased HeLa cells migration and invasion in vitro. In the transplanted tumor model, HSF1 inhibited tumor growth in vivo after interference, and reduced the expression of MTDH, VEGF-C and CD31. Discussion: HSF1 can promote the proliferation, metastasis and invasion of cervical cancer.

Palmitic acid (PA)-induced myocardial injury is considered a critical contributor to the development of obesity and type 2 diabetes mellitus (T2DM)-related cardiomyopathy. However, the underlying mechanism has not been fully understood. Here, we demonstrated that PA induced the cell death of H9c2 cardiomyoblasts in a dose- and time-dependent manner, while different ferroptosis inhibitors significantly abrogated the cell death of H9c2 cardiomyoblasts and primary neonatal rat cardiomyocytes exposed to PA. Mechanistically, PA decreased the protein expression levels of both heat shock factor 1 (HSF1) and glutathione peroxidase 4 (GPX4) in a dose- and time-dependent manner, which were restored by different ferroptosis inhibitors. Overexpression of HSF1 not only alleviated PA-induced cell death and lipid peroxidation but also improved disturbed iron homeostasis by regulating the transcription of iron metabolism-related genes (e.g., Fth1, Tfrc, Slc40a1). Additionally, PA-blocked GPX4 protein expression was evidently restored by HSF1 overexpression. Inhibition of endoplasmic reticulum (ER) stress rather than autophagy contributed to HSF1-mediated GPX4 expression. Moreover, GPX4 overexpression protected against PA-induced ferroptosis, whereas knockdown of GPX4 reversed the anti-ferroptotic effect of HSF1. Consistent with the in vitro findings, PA-challenged Hsf1−/− mice exhibited more serious ferroptosis, increased Slc40a1 and Fth1 mRNA expression, decreased GPX4 and TFRC expression and enhanced ER stress in the heart compared with Hsf1+/+ mice. Altogether, HSF1 may function as a key defender against PA-induced ferroptosis in cardiomyocytes by maintaining cellular iron homeostasis and GPX4 expression.

Excessive inflammatory responses after myocardial infarction leads to poor heart remodeling and heart dysfunction. Our research aims to investigate the effect of metformin on cardiac inflammatory response after myocardial infarction and clarify its potential mechanism.

Ovarian cancer (OC) is the most lethal gynaecological malignancy, characterized by high recurrence and mortality. However, the mechanisms of its pathogenesis remain largely unknown, hindering the investigation of the functional roles. This study sought to identify key hub genes that may serve as biomarkers correlated with prognosis. Here, we conduct an integrated analysis using the weighted gene co-expression network analysis (WGCNA) to explore the clinically significant gene sets and identify candidate hub genes associated with OC clinical phenotypes. The gene expression profiles were obtained from the MERAV database. Validations of candidate hub genes were performed with RNASeqV2 data and the corresponding clinical information available from The Cancer Genome Atlas (TCGA) database. In addition, we examined the candidate genes in ovarian cancer cells. Totally, 19 modules were identified and 26 hub genes were extracted from the most significant module (R-2 = .53) in clinical stages. Through the validation of TCGA data, we found that five hub genes (COL1A1, DCN, LUM, POSTN and THBS2) predicted poor prognosis. Receiver operating characteristic (ROC) curves demonstrated that these five genes exhibited diagnostic efficiency for early-stage and advanced-stage cancer. The protein expression of these five genes in tumour tissues was significantly higher than that in normal tissues. Besides, the expression of COL1A1 was associated with the TAX resistance of tumours and could be affected by the autophagy level in OC cell line. In conclusion, our findings identified five genes could serve as biomarkers related to the prognosis of OC and may be helpful for revealing pathogenic mechanism and developing further research.

HSPB1 is a major member of the small molecule heat shock protein family that protects against oxidative stress. HSPB1 forms homo-oxidized HSPB1 through its only cysteine residue, and then affected the function of HSPB1. However, the role of homo-oxidized HSPB1 in oxidative stress remains largely unknown. In the present study, we observed that H2O2 treatment obviously induced the formation of homo-oxidized HSPB1 through its own cysteine in a dose-dependent manner in H9c2 cells, which was regulated by N-acetylcysteine. HSPB1C137S mutant accelerated H9c2 cells apoptosis and decreased the phosphorylation of HSPB1 during oxidative stress. Meanwhile, HSPB1 and Keap1 formed the the complex in H9c2 cells exposed to H2O2, whereas HSPB1C137S mutant did not bind to Keap1. Furthermore, HSPB1C137S mutant attenuated the recruitment of HSPB1-Keap1 complex to the cellular insoluble fractions, and inhibited the oxidation of Keap1 induced by H2O2. Immunocytofluorescence and western-blot revealed that HSPB1C137S mutant reduced the translocation of Nrf-2 to the nuclear, leading to the decrease in mRNA levels of Nrf-2-dependent genes such as Gclm, HMOX1 and Txnrd following H2O2 stimulation. Importantly, Dual-luciferase reporter assay further indicated that HSPB1C137S mutant reduced the activity of Decr1, HMOX1 and Gclm promoter in H9c2 cells exposed to H2O2. Additionally, HSPB1C137S mutant partially attenuated the activity of NADPH, HO-1 and r-GCL. Taken together, our findings suggested that homo-oxidized HSPB1 attenuates the cardiomyocytes oxidative stress damage via upholding the oxidized Keap1 and activating the Keap1/Nrf-2 signaling pathway.

Acute myocardial infarction (AMI) induced myocardial fibrosis is one of the foremost pathological features and major causes of heart dysfunction. Nicorandil has been shown to exert a beneficial effect on the cardiac fibrosis after myocardial infarction, but the potential mechanisms remain to be clarified.

Myocardial ischaemia is usually accompanied by inflammatory response which plays a critical role in the myocardial healing and scar formation, while persistent inflammatory response contributes greatly to the myocardial remodeling and consequent heart failure. Metformin (Met), a widely used hypoglycemic drug, has increasingly been shown to exert remarkable cardioprotective effect on ischaemic myocardial injury such as acute myocardial infarction (AMI). However, the underlying mechanisms are still far from being fully understood. In this study, a mouse model of AMI was established through ligating the left anterior descending coronary artery (LAD), 100 mg/kg Met was given immediately after operation once daily for 3 days. It was demonstrated that Met effectively improved the cardiac haemodynamics (LVSP, LVEDP, + dp/dt, - dp/dt), diminished the infarct size, alleviated the disarrangement of myocardial cells and reduced the infiltration of inflammatory cells (macrophages, neutrophils and lymphocytes) in the heart of AMI mice. Mechanistically, Met decreased the expression of NLRP3 and enhanced the accumulation of LC3 puncta in F4/80-positive macrophages in the heart of AMI mice. Single cell suspension of cardiac macrophages was prepared from AMI mice and exhibited increased NLRP3 mRNA and protein expression. In contrast, Met decreased the expression of NLRP3 and p62, whereas increased the ratio of LC3II/LC3I. Additionally, both conditioned medium from H9c2 cardiomyocytes exposed to hydrogen peroxide (H9c2-H2O2-CM) and combination of mtDNA and ATP (mtDNA-ATP) increased the expression of NLRP3 and cleaved caspase-1 (p10) as well as intracellular ROS production in RAW264.7 macrophages, which were abrogated by Met treatment. Strikingly, chloroquine (CQ), 3-methyladenine (3-MA) and knockdown of autophagy-related gene (Atg5) abrogated the inhibitory effects of Met on H9c2-H2O2-CM and mtDNA-ATP-induced NLRP3 expression, release of IL-1 beta and IL-18 as well as ROS production in RAW264.7 macrophages. Collectively, these findings suggest that Met protects against ischaemic myocardial injury through alleviating autophagy-ROS-NLRP3 axis-mediated inflammatory response in macrophages.

Proangiogenesis is generally regarded as an effective approach for treating ischemic heart disease. Vascular endothelial growth factor (VEGF)-A is a strong and essential proangiogenic factor. Reactive oxygen species (ROS), endoplasmic reticulum (ER) stress, and autophagy are implicated in the process of angiogenesis. This study is designed to clarify the regulatory mechanisms underlying VEGF-A, ROS, ER stress, autophagy, and angiogenesis in acute myocardial infarction (AMI). A mouse model of AMI was successfully established by occluding the left anterior descending coronary artery. Compared with the sham-operated mice, the microvessel density, VEGF-A content, ROS production, expression of vascular endothelial cadherin, positive expression of 78 kDa glucose-regulated protein/binding immunoglobulin protein (GRP78/Bip), and LC3 puncta in CD31-positive endothelial cells of the ischemic myocardium were overtly elevated. Moreover, VEGF-A exposure predominantly increased the expression of beclin-1, autophagy-related gene (ATG) 4, ATG5, inositol-requiring enzyme-1 (IRE-1), GRP78/Bip, and LC3-II/LC3-I as well as ROS production in the human umbilical vein endothelial cells (HUVECs) in a dose and time-dependent manner. Both beclin-1 small interfering RNA and 3-methyladenine treatment predominantly mitigated VEGF-A-induced tube formation and migration of HUVECs, but they failed to elicit any notable effect on VEGF-A-increased expression of GRP78/Bip. Tauroursodeoxycholic acid not only obviously abolished VEGF-A-induced increase of IRE-1, GRP78/Bip, beclin-1 expression, and LC3-II/LC3-I, but also negated VEGF-A-induced tube formation and migration of HUVECs. Furthermore, N-acetyl- l-cysteine markedly abrogated VEGF-A-increased ROS production, IRE-1, GRP78/Bip, beclin-1 expression, and LC3-II/LC3-I in the HUVECs. Taken together, our data demonstrated that increased spontaneous production of VEGF-A may induce angiogenesis after AMI through initiating ROS-ER stress-autophagy axis in the vascular endothelial cells.

MIP2, one of WDR26 isoforms, encodes a 498 amino acid protein with an amino-terminal CTLH domain and five carboxyl-terminal WD40 motifs. MIP2 is localized to the mitochondria and protects cardiomyocytes against oxidative stress; however, nothing is known about how MIP2 confers its cytoprotection. Using co-immunoprecipitation (co-IP) method to isolate MIP2-protein complex from Sprague -Dawley rat heart, followed by mass spectrometry analysis, we have identified VDAC1, a protein located at mitochondria, as a novel MIP2-interacting protein in the myocardium of rat hearts as well as H9c2 cells. This interaction was further confirmed by co-IP assays in the myocardial tissues and H9c2 cardiomyocytes, and by protein overlay assay (POA) in vitro. It was shown that MIP2 overexpression alleviated the H2O2-induced increase of VDAC1 and cell damage, and MIP2 deficiency aggravated the increase of VDAC1 and cell damage in H2O2 -treated H9c2 cells. Our research suggests that the protective effect of MIP2 on the cardiomyocytes against oxidative stress is partly associated with its interaction with VDAC1 and thus inhibiting its expression.

Heat-shock protein B1 (HSPB1) is a multifunctional protein that protects against oxidative stress; however, its function in antioxidant pathways remains largely unknown. Here, we sought to determine the roles of HSPB1 in H9c2 cells subjected to oxidative stress. Using nonreducing sodium dodecyl sulfate polyacrylamide gel electrophoresis, we found that increased HSPB1 expression promoted the reduced states of glutathione reductase (GR), peroxiredoxin 1 (Prx1), and thioredoxin 1, whereas knockdown of HSPB1 attenuated these responses following oxidative stress. Increased HSPB1 expression promoted the activation of GR and thioredoxin reductase. Conversely, knockdown of HSPB1 attenuated these responses following oxidative stress. Importantly, overexpression of HSPB1 promoted the complex formation between HSPB1 and oxidized Prx1, leading to dephosphorylation of STE-mammalian STE20-like kinase 1 (MST1) in H9c2 cells exposed to H2O (2), whereas downregulation of HSPB1 induced the opposite results. Mechanistically, HSPB1 regulated the Hippo pathway by enhancing the dephosphorylation of MST1, resulting in reduced phosphorylation of LATS1 and Yes-associated protein (YAP). Moreover, HSPB1 regulated YAP-dependent gene expression. Thus, HSPB1 promoted the reduced state of endogenous antioxidant pathways following oxidative stress in H9c2 cells and improved the redox state of the cytoplasm via modulation of the Hippo signaling pathway.

Hydroxysafflor Yellow A (HSYA), a most representative ingredient of Carthamus tinctorius L., had long been used in treating ischaemic cardiovascular diseases in China and exhibited prominently anticoagulant and pro-angiogenic activities, but the underlying mechanisms remained largely unknown. This study aimed to further elucidate the pro-angiogenic effect and mechanism of HSYA on ischaemic cardiac dysfunction. A C57 mouse model of acute myocardial infarction (AMI) was firstly established, and 25 mg/kg HSYA was intraperitoneally injected immediately after operation and given once, respectively, each morning and evening for 2 weeks. It was found that HSYA significantly improved ischaemia-induced cardiac haemodynamics, enhanced the survival rate, alleviated the myocardial injury and increased the expressions of CD31, vascular endothelial growth factor-A (VEGF-A) and nucleolin in the ischaemic myocardium. In addition, HSYA promoted the migration and tube formation of human umbilical vein endothelial cells (HUVECs), enhanced the expressions of nucleolin, VEGF-A and matrix metalloproteinase-9 (MMP-9) in a dose- and time-dependent manner. However, down-regulation of nucleolin expression sharply abrogated the effect mentioned above of HSYA. Further protein-RNA coimmunoprecipitation and immunoprecipitation-RT-PCR assay showed that nucleolin binded to VEGF-A and MMP-9 mRNA and overexpression of nucleolin up-regulated the mRNA expressions of VEGF-A and MMP-9 in the HUVECs through enhancing the stability of VEGF-A and MMP-9 mRNA. Furthermore, HSYA increased the mRNA expressions of VEGF-A and MMP-9 in the extract of antinucleolin antibody-precipitated protein from the heart of AMI mice. Our data revealed that nucleolin mediated the pro-angiogenic effect of HSYA through post-transcriptional regulation of VEGF-A and MMP-9 expression, which contributed to the protective effect of HSYA on ischaemic cardiac dysfunction.

Resveratrol, a polyphenol compound derived from various edible plants, protects against sepsis-induced acute kidney injury (AKI) via its anti-inflammatory activity, but the underlying mechanisms remain largely unknown. In this study, a rat model of sepsis was established by cecal ligation and puncture (CLP), 30 mg/kg resveratrol was intraperitoneally administrated immediately after the CLP operation. HK-2 cells treated by 1 μg/ml lipopolysaccharide, 0.2 μM tunicamycin, 2.5 mM irestatin 9389 and 20 μM resveratrol were used for in vitro study. The results demonstrated that resveratrol significantly improved the renal function and tubular epithelial cell injury and enhanced the survival rate of CLP-induced rat model of sepsis, which was accompanied by a substantial decrease of the serum content and renal mRNA expressions of TNF-α, IL-1β and IL-6. In addition, resveratrol obviously relieved the endoplasmic reticulum stress, inhibited the phosphorylation of inositol-requiring enzyme 1(IRE1) and nuclear factor-κB (NF-κB) in the kidney. In vitro studies showed that resveratrol enhanced the cell viability, reduced the phosphorylation of NF-κB and production of inflammatory factors in lipopolysaccharide and tunicamycin-induced HK-2 cells through inhibiting IRE1 activation. Taken together, administration of resveratrol as soon as possible after the onset of sepsis could protect against septic AKI mainly through inhibiting IRE1-NF-κB pathway-triggered inflammatory response in the kidney. Resveratrol might be a readily translatable option to improve the prognosis of sepsis.

Acute necrotizing pancreatitis (ANP) is a common severe critical illness with a high mortality rate. Resveratrol, a polyphenol compound derived from various plants such as grape skin, peanut, berry and veratrum, exhibits multiple biological activities, especially potent anti-inflammatory activity, but its effect on ANP has not yet been fully elucidated. The present study aimed to investigate the effects of resveratrol on L-arginine-induced ANP and the possible mechanisms. A mouse model of ANP was established by 2 hourly intraperitoneal injections of 8% L-arginine (4 g/kg). Then the mice were treated by intragastric administration of resveratrol (80 mg/kg) every 12 h immediately after the second injection of L-arginine. Mice with ANP showed increased apoptosis of pancreatic acinar cells, pancreatic myeloperoxidase activity, serum lactate dehydrogenase activity, amylase, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) levels as well as decreased serum IL-10 level, pancreatic expression of heat shock factor 1 (HSF1), sirtuin 1 (SIRT1) and p53, but the ratio of acetylated HSF1 and p53 was markedly increased. Resveratrol enhanced the survival rate of mice with ANP from 47.8 to 71.4% and obviously restored the changes in mice with ANP as mentioned above. Additionally, interactions between SIRT1 and p53 and between SIRT1 and HSF1 in the pancreas of the mice were confirmed by co-immunoprecipitation. These data suggest that resveratrol protects against L-arginine-induced ANP, which may be related to the enhancement of SIRT1-mediated deacetylation of p53 and HSF1.

临床医学八年制教育的目标是通过八年的系统性临床和基础医学教育培养具有扎实的临床医学知识、活跃的科学创新思维、出色的科研素质以及优秀的临床与科研转化能力的医学专业博士,早期科研训练是临床医学八年制教育的重要环节,对启蒙医学生的科研思维、培养其科研创新能力及发现和解决临床问题的能力均具有十分重要的意义.本文主要阐述了我国八年制医学生早期科研训练的现状、目标及实践方法,分析了早期科研训练中的难点,如课程学习与科研训练时间分配的不平衡、早期科研训练积极性的欠缺以及早期科研训练机会多样性的不足,针对以上问题提出了相应的解决方法,并对八年制早期科研训练未来的发展方向进行了展望.

目的：建立大鼠心肌缺血再灌注损伤模型和氧化应激损伤细胞模型，研究抗肌萎缩蛋白Dp71在损伤心肌及细胞中的表达，探讨其拮抗心肌细胞凋亡的作用及其分子机制。方法：阻断SD大鼠冠状动脉左前降支血流30 min后恢复血流复制心肌缺血再灌注损伤模型，观察心肌形态学、LDH变化及心肌细胞凋亡；检测再灌注不同时间心脏Dp71蛋白和mRNA表达。建立H9c2细胞氧化应激损伤模型，检测H2 O2刺激后细胞中Dp71蛋白和mRNA的表达。 H9c2细胞转染Dp71过表达质粒，流式细胞术检测Dp71高表达对H2 O2诱导H9c2细胞凋亡率的影响。 Western blot检测过表达Dp71对细胞中lamin B1和Bcl－2蛋白表达的影响；对H2 O2刺激下lamin B1和Bcl2蛋白表达改变的影响。结果：与假手术组相比，再灌注损伤组HE染色心肌出现明显形态改变，LDH明显增加， IR组心肌细胞凋亡数显著增加。 IR后各时点Dp71 mRNA和蛋白表达水平均增加（ P＜0．05）。0．2 mmol／L H2 O2刺激细胞16 h Dp71蛋白及mRNA表达明显升高（ P＜0．05）。 H9c2细胞中转染Dp71过表达质粒可抑制H2 O2所诱导的细胞凋亡；H9c2细胞中过表达Dp71引起lamin B1和Bcl2表达增高，高表达的Dp71可以抑制过氧化氢刺激引起的lamin B1和Bcl2表达下降。结论：Dp71 mRNA和蛋白表达在大鼠心肌缺血再灌注损伤模型和H2 O2诱导H9c2氧化应激损伤模型中明显升高。 H9c2细胞过表达Dp71通过提高Bcl2和lamin B1表达而抑制H2 O2诱导的细胞凋亡。

目的：VEGF－VASH1（vasohibin－1）通路在血管新生过程的精细调节中发挥重要作用，转录因子锌指蛋白667（zinc finger protein 667， ZNF667）具有促进血管新生作用。本研究主要探讨ZNF667对上述通路中VEGF和VASH1表达的调控，以期阐明ZNF667促进血管新生的分子机制。方法：采用LAD建立慢性心肌缺血小鼠模型，采用HE染色和CD31免疫组化分析缺血心肌组织形态学变化及微血管形成。采用Matrigel、划痕和Transwell分析HUVEC管型形成和迁移；采用Western blot、ELISA和定量PCR分别检测ZNF667和VASH1蛋白质和mRNA表达；mRNA测序分析ZNF667过表达HUVEC的mRNA差异表达；染色质免疫沉淀（ chromatin immunoprecipitation ， ChIP）检测ZNF667与VEGF和VASH1启动子区结合情况。结果：免疫组化和HE染色显示与假手术组相比，缺血心肌中组织损伤加重伴随有CD31＋微血管数目增加，同时心肌组织中VEGF和ZNF667蛋白和mRNA表达呈时间依赖性增加，而VASH1表达降低。 mRNA测序、ELISA和定量PCR显示ZNF667过表达可促进HUVEC中VEGF表达而抑制VASH1表达。 VASH1过表达可抑制VEGF和ZNF667的促HUVEC管型形成和迁移作用。 ChIP显示ZNF667与VEGF（－346～－350 bp；－265～－269 bp）和VASH1（－170～－175 bp）基因启动子区结合。结论：HUVEC中ZNF667靶向调节VEGF－VASH1通路促进管型形成和迁移作用，这一调节机制可能参与缺血心肌中微血管新生过程。

急性胰腺炎是临床常见的急腹症之一,其病因及发病机制复杂,死亡率居高不下.目前,急性胰腺炎被定义为一种以急性炎症和胰腺实质坏死为特征的炎症性疾病,按照其严重程度分为轻度急性胰腺炎、中度重症急性胰腺炎、重症急性胰腺炎.急性胰腺炎的发生机制尚未完全阐明,目前主要存在几种学说,包括胰酶的自身消化、腺泡细胞凋亡、过度炎症反应、微循环改变、钙超载及肠道细菌易位学说等.本文主要对急性胰腺炎的定义、病因、分型、发生机制和治疗策略的研究进展进行了综述.