Objective:To explore the efficacy of subcutaneous injection of granulocyte-macrophage colony-stimulating factor (GM-CSF) in preventing invasive fungal disease (IFD) in patients with multiple myeloma (MM).Methods:The clinical data of 222 patients who were admitted to the Second Hospital of Harbin Medical University from January 2015 to June 2021 were retrospectively analyzed. The patients was given GM-CSF (3-5 μg·kg -1·d -1, GM-CSF group) or granulocyte colony-stimulating factor (G-CSF, 2-5 μg·kg -1·d -1, G-CSF group) when neutrophils (ANC) ≤1.5×10 9/L after induction chemotherapy. Patients were discontinued when white blood cell count (WBC) ≥10.0×10 9/L. The incidence of IFD (including confirmed, clinical and proposed diagnosis) and breakthrough invasive fungal infections was compared between the two groups. Results:The incidence of IFD was 8.1% (18/222) in all patients. The incidence of IFD was 3.5% (3/85) and 10.9% (15/137) in the GM-CSF and G-CSF groups, respectively, and the difference between the two groups was statistically significant ( χ2 = 3.88, P = 0.049). In 9 patients of GM-CSF group receiving fungal infection prophylaxis and in 15 patients of G-CSF group receiving fungal infection prophylaxis, the incidence of breakthrough invasive fungal infections was 0 and 7 cases, respectively, and the difference between the two groups was statistically significant ( P = 0.022). Conclusions:GM-CSF application in MM patients can reduce the incidence of IFD and breakthrough invasive fungal infections.

Myelodysplastic syndrome (MDS) represents a group of neoplasms with extensive heterogeneity. Recurrent mutations in dozens of driver genes have been identified in over 90% of MDS cases, although fusion genes are rarely seen. We first report the competitive evolved sub‐clonal breakpoint cluster region (BCR)::ABL1 and novel MSI2::PC fusion gene in MDS with del(5q) in initial diagnosis that underwent dismal progression. However, the BCR::ABL1 clone vanished while the MSI2::PC clone rose to the major one with disease progression. A novel MSI2::PC fusion transcript was identified in initial diagnosis and disease progression of the patient through transcriptome sequencing (RNA‐seq) and Quantitative reverse transcription polymerase Chain Reaction (PCR) showed MSI2::PC/ABL1 expression at initial diagnosis and disease progression. In addition, mutation screening of 300 leukemia driver genes identified ARID2 c.5046del/p.F1682Lfs*19 and ZNF292 c.4565A > G/p.Q1522R mutation in bone marrow sample at initial diagnosis and disease progression. In conclusion, the dynamic process of the two fusion and phenotype manifestations may help to understand further the molecular significance of the anomalies of BCR::ABL1, MSI2, and PC in oncogenesis.

目的:探讨结直肠癌(colorectal cancer,CRC)肿瘤引流淋巴结(tumor-draining lymph node,TDLN)中T细胞的免疫学特性及其抗肿瘤作用.方法:收集2018年12月至2021年1月贵州医科大学附属医院收治的33例CRC患者的临床资料和淋巴结标本.采用染料法示踪,配对采集CRC患者TDLN和非肿瘤引流淋巴结(non-TDLN,NTDLN).用流式细胞术检测已制备成单细胞悬液的TDLN和NTDLN中免疫细胞亚群和功能表型差异,酶联免疫斑点法比较TDLN和NTDLN中肿瘤反应性T细胞比例,多色免疫荧光组织化学技术分析两种淋巴结中免疫细胞空间分布情况.体外扩增TDLN-T细胞,检测其T细胞亚群和表型变化以及肿瘤免疫反应能力.结果:与NTDLN相比,TDLN中含有更高比例肿瘤反应性T细胞(P＜0.05),调节性T(Treg)细胞比例较高(P＜0.01),但单核样髓源性抑制细胞比例较低(P＜0.05),T细胞活化标志物ICOS、CD28和抑制标志物PD-1、TIGIT比例均显著升高(P＜0.05或P＜0.01).Treg细胞和滤泡性T细胞主要分布在淋巴结皮质区和生发中心.TDLN-T细胞扩增后,以CD8+T细胞为主(P＜0.01),ICOS、CD28表达升高(P＜0.05或P＜0.01),肿瘤反应性T细胞比例升高(P＜0.01).结论:CRC的TDLN中T细胞处于免疫激活状态,同时高表达免疫抑制标志物;体外培养可以增加TDLN-T细胞活化水平,并提高抗肿瘤T细胞比例.

Leukemia is the second common blood cancer after lymphoma, and its incidence rate has an increasing trend in recent years. Acute myeloid leukemia (AML) is one of the prevalent forms of leukemia. Although previous studies have investigated the methylation profile for AML patients, the AML methylation subtypes based on the genome-wide methylome are still unclear. In the present study, we identified three methylation subtypes for AML samples based on the methylation profiles at CGI, CGI shore, CGI shelf, and opensea genomic contexts. Analyzing the molecular characteristics and clinical factors of the three subtypes revealed different methylation patterns and clinical outcomes between them. Further analysis revealed subtype dependent marker genes and their promoter CpG sites with regulatory function. Finally, we found that combining the AML patient age and methylation pattern brought better clinical outcome classification. In conclusion, we identified AML methylation subtypes and their marker genes, these results may help to excavate potential targets for clinical therapy and the development of precision medicine for AML patients.

Thymoma is an uncommon neoplasia derived from the epithelial cells of the thymus, which leads to immune dysregulation and is associated with a series of autoimmune diseases. However, the concurrence of these disease entities is rare, and the exact mechanisms of these diseases are still unclear. We have admitted several cases who were diagnosed with thymoma, autoimmune haemolytic anaemia, and pure red cell aplasia. These cases were the first to report the concurrence of these three disorders. After thymectomy, anaemia improved, haemolytic cells decreased, and haemoglobin was normalized.

目的 探讨miRNA-720在多发性骨髓瘤(multiple myeloma,MM)患者血清中的表达水平及其临床意义.方法 20例体检健康者为对照组,60例初诊MM患者为MM组,提取各组血清RNA样本;实时定量PCR检测各组血清miRNA-720的表达水平,并分析miRNA表达水平与其他临床特征及预后的关系.结果 多发性骨髓瘤患者外周血miRNA-720的表达水平明显高于对照组(P<0.01),且不随年龄、性别、疾病分期、血红蛋白、骨髓浆细胞百分比、β2微球蛋白、血清白蛋白、血清肌酐、M蛋白(P>0.05)而变化.结论 血清miRNA-720可作为MM发展的促进因子,且可能是MM的诊断因素、疗效评价指标和预后指标,可作为MM个体化的预后评价及疗效评价方法之一.

Multiple myeloma (MM) is a plasma cell neoplasm which constitutes about 10% of all hematologic malignancies. Despite bortezomib is a promising new generation of drugs for MM, its clinical use is limited by peripheral neurotoxicity in the vast majority of patients, which can be severe and require a reduction of dose or even treatment withdrawal. Tumor necrosis factor-α (TNF-α), as the most important inflammatory factor, could induce the inflammatory response and expression of heparanase (HPSE), which may play a crucial role in peripheral neuropathy after chemotherapy. However, the role of TNF-α in bortezomib-induced peripheral neuropathy (BIPN) has not been reported. In this study, treatment-emergent neuropathy was assessed by total neuropathy score and electrophysiological examination. The expression level of TNF-α and HPSE were evaluated by enzyme-linked immunosorbent assay. The effects of anti-TNF-α on the evolution of neuropathy were tested in rat models of neurotoxicity. The results indicated that with the augment of cumulative dose of bortezomib, the incidence of neuropathy was increased. Moreover, bortezomib administration induced the expression of TNF-α. With the increased expression of TNF-α, neuropathy was exacerbated. TNF-α-induced expression of HSPE was secondary to the development of neuropathy. Co-administration of anti-TNF-α in bortezomib therapy has a potential neuroprotective effect on BIPN in rats. TNF-α participates in the pathogenesis of BIPN, which represents an attractive target for future therapeutic intervention.

目的 探讨WT1基因在真性红细胞增多症中的表达及临床意义.方法 采用逆转录-聚合酶链反应方法检测30例真性红细胞增多症患者,10例正常人外周血的WT1基因表达,并同时记录这30例真性红细胞增多症患者的JAK2基因情况.结果 10例正常人未检测到WT1基因的表达,30例真性红细胞增多症患者中有11例阳性(36.67％).根据血红蛋白值分期,Ⅰ期未测到WT1 mRNA的表达,Ⅱ期阳性率36.36％,Ⅲ期阳性率63.64％,对WT1基因的相对量分析发现:从Ⅰ～Ⅲ期WT1 mRNA的表达水平逐渐增加,经统计学分析各期间均有差异,JAK2基因阳性率在3个分期中逐渐增加,经t检验每两组间比较均有统计学意义.结论 WT1基因相对表达量与JAK2基因阳性率与分期进展有关.RT-PCR检测WT1基因的表达可作为真性红细胞增多症的一个风险评估指标.

Objectives This study aimed to investigate the risk miRNAs (microRNAs) for AML (acute myeloid leukemia) prognosis and related regulatory mechanisms. Methods MiRNA and gene expression data, as well as clinical data of 176 patients were first downloaded from TCGA. Then miRNAs and genes significantly affecting the survival time based on KM survival curve were identified using Log Rank test. Next, COX proportional-hazard regression analysis was performed to screen the risk miRNAs (P-value < 0.05). Common genes from survival analysis and predicted by miRWalk were used to construct the miRNA regulatory network with the risk miRNAs. Finally, a protein-protein interaction (PPI) network was constructed, as well as functional annotation and pathway enrichment analysis. Results The survival analysis revealed 33 miRNAs and 1,377 genes significantly affecting the survival time. HR values of nine miRNAs (up-regulated hsa-mir-606, 520a, 137, 362, 599, 600, 202, 639and down-regulated 502) were either >1 or <1. The miRNA regulatory network contained 477 nodes and 944 edges. The top ten genes of the constructed PPI network were EGFR, EIF4G1, REL, TOP1, COL14A1, HDAC3, MRPL49, PSMA2, TOP2A and VCAM1 successively. According to pathway enrichment analysis, 6 KEGG pathways and 6 REACTOME pathways were obtained respectively. Conclusion Up-regulated hsa-mir-520a, 599, 606, 137 and 362 may increase the prognostic risk for AML patients via regulating the expression of corresponding target genes, especially COL14A1, HDAC3, REL, EGFR, PSMA2, EIF4G1, MRPL49 and TOP1.

Objective To investigate the effect of neuropeptide Y(NPY)Y1 receptor subtype on cardiac hypertrophy,and to determine the role of Ca2+/CaM-CaMKⅡ-MEF2 signaling pathway in this process. Methods The primary cultured SD rat cardiomyocytes were stimulated with different concentrations of NPY or Y1 receptor agonists,Leu31 and Pro34 NPY. The 3Tritium-leucine(3H-Leu)incorporation assay was used to assess the rate of protein synthesis in cardiomyocytes. The mRNA expressions of the hypertrophy-related genes ANF andβ-MHC were measured by fluorescence quantitative PCR. The immunofluorescence staining was used to determine the surface area of cardiomyocytes and expression of cardiomyocyte MEF2. Results The effects of Leu31, Pro34 NPY and NPY were similar. Both of them significantly increased the incorporation of cardiomyocytes 3H-Leu(P<0.05). The mRNA expressions of cardiomyocytes ANF and β-MHC were significantly up-regulated(P<0.05). The surface area of cardiomyocytes significantly increased [(2270.93±80.09)μm2 vs(3340.64±101.06)μm2;(2256.57±57.0)μm2 vs(2915.48±43.39)μm2;all P<0.05]. The CaMKⅡinhibitor KN-93 could effectively block the stimulatory effects of Leu31 and Pro34 NPY on protein synthesis rate and hypertrophy gene expression in cardiomyocytes. The expression of MEF2 in cardiomyocytes remarkably increased after stimulation of Leu31 and Pro34 NPY for 24 h (P<0.05). Conclusion The neuropeptide Y1 receptor subtype induces cardiac hypertrophy via Ca2+/CaM-CaMKⅡ-MEF2 signalingpathway.

MM is a heterogeneous disorder and several serum microRNAs were found to have potential as diagnostic biomarkers in myeloma. We measured the expression of PB miRNA-720 and miRNA-1246 in 60 newly diagnosed MM patients by qPCR. The expression levels of PB miRNAs are significantly higher in myeloma patients, and can be used as a diagnosis test for myeloma, moreover increased expression of these PB miRNAs were associated with shorter PFS. Our study demonstrate that PB miRNA-720 and miRNA-1246 might act as a promoting factor in the development of MM and could be a diagnostic factor, therapeutic effect evaluator and prognostic indicator in the prognosis of MM.Objective: Multiple myeloma (MM) is a heterogeneous disorder, encompassing several related entities that share the common characteristic of being composed of monoclonal plasma cells (PCs). MicroRNAs (miRNAs) are small noncoding RNAs that control the expression of many target messenger RNAs involved in normal cell functions. Two serum microRNAs, miRNA-720 and miRNA-1246, were found to have potential as diagnostic biomarkers in myeloma. Therefore, we investigated a possible correlation of peripheral blood (PB) miRNA expression with diagnosis and prognosis. Methods: We measured the expression of PB miRNA-720 and miRNA-1246 in 60 newly diagnosed MM patients by quantitative real-time PCR analyses. And analysed the relationship about the expression levels of miRNAs with other clinical features. Results: The expression levels of PB miRNAs are significantly higher in myeloma patients compared to controls and do not change with age, gender, disease stage, hemoglobin, bone marrow PC percentage, beta(2) microglobulin, serum albumin, calcium serum, serum creatinine, and myeloma protein, and independent of the deletion of chromosome 13, suggesting that the expression levels of PB miRNA-720 and miRNA-1246 can be used as a diagnostic test for myeloma. We first discovered that increased expression of PB miRNA-720 and miRNA-1246 were associated with shorter progression-free survival, indicating poor prognosis. Conclusion: Our study demonstrated that PB miRNA-720 and miRNA-1246 might act as a promoting factor in the development of MM and could be a diagnostic factor, therapeutic effect evaluator, and prognostic indicator in the prognosis of MM. The miRNAs have a significant value of appreciation of individual patients' behavior during the chemotherapy and evaluation the therapeutic strategies.

Immune thrombocytopenia purpura (ITP) is characterized by destruction of circulating platelets and the presence of antiplatelet IgG antibodies, which opsonize platelets for splenic clearance resulting in low levels of circulating platelets, and the disease severity can be predicted neither by antibody isotype nor by titer, indicating that other factors also play a role. Although the main cause of ITP remains unclear, but its relationship with some infection was demonstrated, including viral or bacterial infections. C-reactive protein (CRP), a member of the pentraxin family, is a major acute-phase protein in humans and is a clinical marker of infection. We aimed to investigate the correlation between the levels of CRP and the presence of antiplatelet IgG antibodies in adults with newly diagnosed ITP. CRP levels and platelet counts were measured in the blood samples from a 60 ITP patient (with confirmed anti-GPIIb/IIIa antibodies), 60 infection patients (all without anti-GPIIb/IIIa antibodies) and 60 normal individuals. The bleeding score, recover time of intravenous immune globulin (IVIg) therapy and the number of megakaryocytes in bone marrow were recorded in ITP patients. The platelet count, bleeding score, recover time of intravenous immune globulin (IVIG) therapy and the number of megakaryocytes in bone marrow and CRP concentrations were compared in ITP group using Spearman's correlation coefficient. We examined the influence of intraperioneal CRP administration on antibody-mediated platelet destruction in mice. There were no statistical differences in gender, age and body mass index among the three groups (P>0.05). Though CRP levels are significantly elevated in ITP patients and infection patients (P<0.05), the platelet count was markedly lower only in ITP patients. We found that CRP was inert toward platelets without antiplatelet antibodies in this study. There are a significant correlation between CRP levels and platelet counts, bleeding severity and the number of megakaryocytes in bone marrow aspiration (r=-0.5079, r=0.5498, r=0.4172, P<0.001, respectively). Moreover, a significant correlation was observed between the recovery time of platelet count and CRP levels (r=-0.5569, P<0.001). In mice, platelet count was lower in Anti-CD41 (0.75 μg)+, CRP (200 μg) group as compared with Anti-CD41 (0.75 μg)+, CRP(-) group and Anti-CD41 (0.75 μg)-, CRP (200 μg) group (P<0.05). In summary, this study indicated that CRP levels are significantly elevated in ITP patients all with confirmed anti-GPIIb/IIIa antibodies, which is able to predict the clinical bleeding severity of ITP patients. The slower CRP levels reduction after IVIg treatment predicted slower platelet count recovery in ITP.

目的:研究利伐沙班对行急诊PCI治疗后的ST段抬高型心肌梗死(STEMI)患者高凝状态的效果.方法:选取60例STEMI患者为研究对象,采取回顾性分析法,分为研究组和对照组,各30例,研究组给予利伐沙班治疗,对照组给予氯呲格雷治疗.检测两组患者的D-D、PT、APTT以及FIB血浆凝血指标含量并进行比较;记录两组患者治疗后主要心血管事件和出血并发症并比较.结果:研究组患者治疗后D-D含量高于对照组,差异有统计学意义(P＜0.05),两组患者治疗后主要心血管事件和出血并发症差异无统计学意义(P＞0.05).结论:利伐沙班口服治疗STEMI患者,可一定程度上缓解高凝状态,简单、方便,可以作为治疗STEMI患者新型抗凝治疗策略,但由于本次研究存在样本量较小以及长期随访时间不充分等问题,需后期进一步采取大样本以及长期随访,再做进一步评价.

Silent information regulator type-1 (SIRT1) is the best-studied member of the Sirtuin (Sir2) family of nicotinamide dinucleotide (NAD)-dependent class III histone deacetylases (HDACs). Rrecently, it is suggested that SIRT1 may be involved in the development of malignant tumors including mouse lymphoma, but has not yet been explored in Angioimmunoblastic T-cell lymphoma (AITL). Therefore, we investigated the prevalence and the prognostic impact of SIRT1 expression in AITL. Immunohistochemical expression of SIRT1, p53 were evaluated by using a 2mm core from 45 AITL patients. Positive expression of SIRT1 was seen in 71.11% (32 of 45) of patients and p53 expression were seen in 53.33% (24 of 45). SIRT1 and p53 expression were significantly associated with shorter PFS by univariate analysis (P=0.009 and P < 0.001, respectively), multivariate analysis also shows that SIRT1 expression relate to worse prognosis. We also suggest inferior survival in AITL with the combined expression of SIRT1 and clinical characteristics of high IPI scores, high clinical stage, increased serum LDH, decreased HGB and increased -Globulin. In conclusion, our results indicate that SIRT1 is strongly expressed in AITL and it act as a clinically significant prognostic indicator for AITL patients, may also serve as a therapeutic target in AITL.

目的:比较标准剂量美罗华与小剂量美罗华治疗原发免疫性血小板减少症(ITP)中的临床疗效及安全性.方法:选取哈尔滨医科大学附属第一、第二医院自2010年-2015年常规治疗无效的原发免疫性血小板减少症(ITP)患者,共18例,分为两个实验组,分别给予应用标准剂量美罗华(375 mg/m2,每周1次,共4次),患者8例,小剂量美罗华(每次100mg,每周1次,共4次),患者10例,观察两组患者临床效果、治疗前后血小板水平及不良反应的发生情况.结果:小剂量美罗华治疗4周后有效率较标准剂量无明显差别(P＞0.05);小剂量美罗华治疗ITP不良反应率相对标准剂量要显著降低低(P＜0.05).结论:小剂量美罗华治疗原发免疫性血小板减少症(ITP)的临床疗效与标准剂量美罗华相当,但安全性更高.

OBJECTIVETo investegate the role of calcineurin (CaN) and its downstream nuclear factor of activated T-cells (NFATc3) in abdominal aorta restenosis following balloon dilatation in rats.METHODSSD rats were randomly divided into sham-operated group, balloon group and cyclosporine A (CsA) group. The rats in the latter two groups were subjected to abdominal aorta injury with balloon dilatation, and those in CsA group were treated with CsA at the daily dose of 12.5 mg/kg from 3 days before the surgery to the end of the experiment. Thirty days afer the injury, histological analysis of the arterial wall was carried out with HE staining and immunohistochemistry. The expressions of CaN and NFATc3 in the abdominal aortas were detected with rea1-time PCR, and serum concentration of MCP-1 was determined using enzyme-linked immunosorbent assay.RESULTSIntimal hyperplasia with irregular thickness of the neointima was observed in the aorta of rats with ballon injury. In rats with CsA treatment, the area of the intimal layers and the ratio of the intimal to the medial layers were obviously lower than those in the balloon injury group (P<0.05). Compared to those in the sham-operated group, the expressions of calcineurin protein and mRNA and NFATc3 mRNA in the arterial wall and serum level of MCP-1 increased significantly in the ballon injury group (P<0.05). CsA treatment significantly suppressed aorta restenosis and the alterations of CaN, NFATc3 and serum MCP-1 induced by ballon dilatation (P<0.05).CONCLUSIONSCaN-NFATc3 signal transduction pathway mediates restenosis of rat abdominal aorta following ballon dilatation, and CsA can attenuate the restenosis by suppressing this pathway.

目的:探讨预防性应用抗生素对糖皮质激素治疗老年特发性血小板减少性紫癜并发感染的影响.方法:将哈尔滨医科大学附属第二医院血液科2012年3月～2015年3月的收治的72例老年特发性血小板减少性紫癜患者随机分为两组,自应用糖皮质激素第一天开始观察15天,观察组自应用糖皮质激素开始即使用抗生素,对照组不常规应用抗生素,以出现感染症状即开始应用抗生素,同时定为观察终止.比较两组患者感染发生率的差异.结果:观察组感染发生率为38.89％,对照组为69.44％,较观察组显著升高,差异有统计学意义(P＜0.05).两组患者感染发生部分的分布情况比较无统计学差异口＞0.05),以呼吸系统感染发生率最高,其次是尿路感染.结论:预防性的使用抗生素可以降低糖皮质激素治疗老年特发性血小板减少性紫癜患者过程中感染的发生率.

目的：评价替格瑞洛对ST段抬高型急性冠脉综合征合并糖尿病患者的心肌保护作用。方法选择ST段抬高型急性冠脉综合征合并糖尿病患者157例，随机分为对照组（78例）和观察组（79例）。在经皮冠脉介入治疗（ PCI）和常规治疗基础上，对照组给予氯吡格雷，观察组给予替格瑞洛，维持治疗6个月。比较两组患者血清肌酸激酶同工酶（ CK－MB）和心肌肌钙蛋白（ cTnI）水平，左心室舒张末内径（ LVDD）、左心室射血分数（ LVEF）等功能指标，以及主要不良心血管事件（ MACE）的发生率和治疗期间出血等不良反应。结果治疗前两组患者的基线资料差异无统计学意义。 PCI术后24 h，两组患者的CK－MB、cTnI水平差异无统计学意义但维持在较高水平；术后72 h，两项指标逐渐降低，且观察组显著低于对照组。 PCI术后1周和6个月，两组患者的血小板聚集率（ADP）、心脏功能指标LVEF和LVDD较治疗前有显著改善（P＜0.05），且观察组显著低于对照组。 PCI术后6个月，观察组不良心血管事件显著低于对照组（ P＜0.05）。治疗期间，除观察组呼吸困难患者高于对照组外，其他不良反应的发生率差异无统计学意义。结论对于糖尿病合并ST段抬高型急性冠脉综合征患者，替格瑞洛能有效地改善心肌损伤，降低不良心血管事件发生率，且不增加出血风险。

目的 探讨疏血通注射液联合氯吡格雷治疗急性非ST段抬高心肌梗死的临床疗效和安全性.方法 将80例急性非ST段抬高心肌梗死患者随机为分两组,每组40例.对照组予常规治疗及氯吡格雷300 mg负荷量治疗,观察组予常规治疗及疏血通注射液联合氯吡格雷600 mg负荷量治疗,比较两组治疗效果、心电图ST段的变化、近期主要不良心血管事件(MACE)发生率及出血并发症.结果 治疗后总有效率观察组为97.5%,对照组为87.5%,两组比较差异具有统计学意义(P＜0.05);观察组心电图ST段下降幅度和缺血导联个数显著低于对照组(P＜0.05);观察组30 d MACE总发生率明显低于对照组(27.5% vs 10.0%,P＜0.05),两组患者出血并发症发生率无统计学意义(7.5% vs 5.0%,P＞0.05).结论疏血通注射液联合氯吡格雷600 mg负荷量可明显改善心肌供血和降低心血管事件的发生率,并且用药安全性好.

Cardiac hypertrophy is a compensatory stage of the heart in response to stress such as pressure overload (PO), which can develop into heart failure (HF) if left untreated. Resveratrol has been reported to prevent the development of hypertrophy and contractile dysfunction induced by PO. However, other studies found that resveratrol treatment for a longer period of time failed to regress cardiac hypertrophy. The aim of this study is to determine the timing of resveratrol treatment to achieve antihypertrophic effect and investigate whether resveratrol prevents the development of HF through preservation of myocardium structure and modulation of Ca2+ handling proteins.