Search

Supplementary Tables 1-7 from Serum microRNA Profiles Serve as Novel Biomarkers for HBV Infection and Diagnosis of HBV-Positive Hepatocarcinoma

Diagnosis of hepatitis B virus (HBV)-positive hepatocellular carcinoma (HCC), particularly HCC independent of cirrhosis etiology, presents a great challenge because of a lack of biomarkers. Here we test the hypothesis that expression profiles of microRNAs (miRNAs) in serum can serve as biomarkers for diagnosis of HBV infection and HBV-positive HCC. We recruited 513 subjects (210 controls and 135 HBV-, 48 hepatitis C virus (HCV)-, and 120 HCC-affected individuals) and employed a strategy of initial screening by Solexa sequencing followed by validation with TaqMan probe-based quantitative reverse transcription-PCR assay. First, because of a close link between chronic hepatitis B and HCC, we compared miRNA expression profiles in HBV serum with that in control serum and successfully obtained 13 miRNAs that were differentially expressed in HBV serum. This 13-miRNA–based biomarker accurately discriminated not only HBV cases from controls and HCV cases, but also HBV-positive HCC cases from control and HBV cases. Second, we directly compared miRNA expressions in HCC serum with those in controls and identified 6 miRNAs that were significantly upregulated in HCC samples. Interestingly, 2 of these miRNAs, miR-375 and miR-92a, were also identified by our first approach as HBV specific. When we employed 3 of these miRNAs (miR-25, miR-375, and let-7f) as biomarkers, we could clearly separate HCC cases from controls, and miR-375 alone had an ROC of 0.96 (specificity: 96%; sensitivity: 100%) in HCC prediction. In conclusion, our study demonstrates for the first time that serum miRNA profiles can serve as novel and noninvasive biomarkers for HBV infection and HBV-positive HCC diagnosis. Cancer Res; 70(23); 9798–807. ©2010 AACR.

Objective In this prospective cohort study, we aimed to evaluate the association between dietary habits and the risk of developing hepatocellular carcinoma (HCC) in hepatitis B surface antigen (HBsAg)-positive carriers in Qidong, an hepatitis B virus (HBV)-epidemic area in China. Methods A total of 3199 HBsAg carriers aged 30-70 years in a prospective cohort in Qidong, China from 2007 to 2011 were included in the study. At baseline, all participants self-reported their dietary habits in a questionnaire interview. A follow-up check-up was performed every 6 months to identify HCC cases until November 2017. Cox's regression analysis and an interaction analysis were performed to estimate the relative risks of HCC in terms of baseline diet. Results Among 3199 HBsAg-positive participants, 270 developed HCC (143.86/100 000 person-years [PYs]). Compared with participants who rarely consume garlic, the risk of HCC in those who consumed it ≥ once per week decreased along with the increase in frequency (HR = 1.00, 0.90 and 0.62 in those who consumed it rarely vs those who consumed it 1-6 times per week and ≥ 7 times per week, respectively). This study found a synergistic effect between garlic and tea consumption on the risk of HCC (P = 0.039 for a multiplicative interaction). Conclusions HBsAg carriers should improve their diet. Regular consumption of garlic and tea drinking may reduce the HCC incidence in HBsAg carriers.

SummaryEmbryo implantation requires temporospatial maternal-embryo dialog to regulate the interactions between an activated blastocyst and a receptive endometrium; however, the details of the related cell-specific coordination is largely unknown because of the cellular complexity and dynamic developmental processes of both the embryo and endometrium during peri-implantation. By comparing single-cell RNA (scRNA) data obtained from entire uteri of pregnant and pseudo-pregnant mice with embryos that were in the oviduct (dpc2.5 days post-coitum [dpc]) or had entered the uterus (after 3.5 dpc), we found a maternal estrogen and progesterone signaling-dependent functional differentiation process in which progesterone induced estrogen-responsive luminal epithelial cells to differentiate into two new types of epithelial cells: adhesion epithelial cells (AECs) and supporting epithelial cells (SECs) on 2.5 dpc. In addition to maternal signaling data, the uterine scRNA and corresponding embryo bulk sequencing data were obtained, and analyses revealed that embryonic Pdgfa and Efna3/4 signaling activated AECs and SECs, enhancing the attachment of embryos to the endometrium after implantation. Specifically, embryonic signaling induced additional transformation of AECs by preventing adjacent AECs, but not AECs away from the embryo in the implantation chamber, from undergoing apoptosis. Furthermore, we demonstrated that epithelial cell differentiation and related regulatory signaling were largely conserved in humans and mice. In the human endometrium, developmental defects of SOX9-positive epithelial cells similar to luminal epithelial cells were related to thin endometrium. Our work provides comprehensive and systematic information on endometrial luminal epithelial cell development directed by maternal and embryonic signaling, which is important for endometrial receptivity and embryo implantation.

PTEN is known as a tumor suppressor and plays essential roles in brain development. Here, we report that PTEN in primary sensory neurons is involved in processing itch and thermal information in adult mice. Deletion of PTEN in the dorsal root ganglia (DRG) is achieved in adult Drg11-Cre

About 15% couples suffer from infertility, half of which are caused by male factors. Male infertility usually manifests as teratozoospermia, oligospermia and/or asthenospermia, of which the most severe form is azoospermia. In this review, we summarize the recent progress in the study of genetic factors involved in nonobstructive azoospermia and teratozoospermia, Recently, with the rapid development of high-throughput chips and sequencing technologies, many genetic factors of spermatogenesis have been discovered and analyzed. For the nonobstructive azoospermia, genome-wide association studies (GWAS) and high-throughput sequencing revealed many risk loci of nonobstructive azoospermia. For the teratozoospermia, the application of whole-exome sequencing (WES) revealed a series of disease-causing genes, greatly enriching our knowledge of teratozoospermia including multiple morphological abnormalities of the flagella (MMAF). The discovery of lots of disease genes helped the characterization of the pathological mechanisms of male infertility. Therefore, a comprehensive and in-depth understanding of genetic factors in spermatogenesis abnormalities will play important roles in the clinical diagnosis, treatment and genetic counseling of male infertility.育龄人群中约15%的夫妻被不孕不育困扰,其中男方因素导致的不孕不育约占50%。男性不育通常由精子发生障碍导致,呈现为少、弱、畸形精子症,最严重的是无精子症。本文以精子发生障碍为主线,重点综述了非梗阻性无精子症和畸形精子症的遗传学病因研究。近年来,随着高通量芯片和测序技术的快速发展,无精子症和畸形精子症的遗传学因素得以深入的揭示与解析。围绕无精子症,全基因组关联研究与高通量测序研究揭示了一批非梗阻性无精子症的风险位点和致病基因;围绕畸形精子症,全外显子测序等研究鉴定了一系列致病基因,极大地丰富了精子鞭毛多发性形态异常等精子畸形的遗传学病因。大量致病基因的发现,促进了男性不育病理机制的阐明。全面而深入地了解精子发生障碍中的遗传因素,对男性不育的诊断、临床治疗和遗传咨询具有重要的意义。.

Hui Wang,1,* Cui-Ying Li,1,* Hai-Ling Zha,1 Di Xu,1 Zhi-Bin Hu2 1Department of Ultrasound, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, People’s Republic of China; 2Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, 211166, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhi-Bin HuDepartment of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, No. 101 Longmian Avenue, Jiangning District, Nanjing, 211166, Jiangsu, People’s Republic of ChinaTel +86-25-86868437Email Zhibin_hu@njmu.edu.cnDi XuDepartment of Ultrasound, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu, People’s Republic of ChinaTel +86-25-83714511Email xudi_doctor@163.comPurpose: To investigate the diagnostic and predictive value of strain ratios in the regions of interests (ROIs) in reference tissue for breast tumor.Patients and Methods: A total of 707 lesions in 665 consecutive patients were examined with B-mode Breast Imaging-Reporting and Data System (BI-RADS) and Ultrasonic elastography (UE). Elasticity score (ES) and strain ratio (SR) in each lesion were calculated. Receiver operating characteristic (ROC) curves were used to assess the diagnostic value of BI-RADS, ES, SR1, SR2, BI-RADS combined with ES (BI-RADS+ES), BI-RADS combined with SR1 (BI-RADS+SR1), and BI-RADS combined with SR2 (BI-RADS+SR2). The sensitivity, specificity, and areas under the ROC curves (Az) were obtained. Scatter plots were generated to demonstrate the correlation between SR1 and SR2. Kruskal-Walls H-test, Mann–Whitney U-test and one-way ANOVA were performed to evaluate SRs and tumor-related variables. Multiple linear regression analysis was carried out to determine variables independently associated with SRs.Results: BI-RADS had high sensitivity and low specificity in the diagnosis of breast tumor. The specificity of BI-BADS combined with ES or SR was even higher. The Az value of BI-RADS+ES or BI-RADS+SRs was higher than that of BI-RADS (P < 0.001). The Az value of ES was higher than those of SR1 and SR2 (P < 0.001), and those of SR1 and SR2 were similar. SR1 and SR2 were highly positively correlated. There was no statistical difference between Az values of BI-RADS+ES, BI-RADS+SR1, and BI-RADS+SR2. Indistinct margin, high histologic grade, histological type, and negative human epidermal growth factor receptor (Her-2) were associated with SR1 and SR2. Progesterone receptor (PR) status and molecular subtype were associated with SR2. Histologic grade and tumor margin were significantly associated with SR1, and tumor margin was associated with SR2.Conclusion: SRs in different ROIs in the reference tissue at the same depth showed no different diagnostic value for breast tumor. Both SR1 and SR2 could be useful in assessing the biological characteristics of invasive breast carcinoma.Keywords: conventional ultrasonography, Breast Imaging-Reporting and Data System, ultrasonic elastography, elasticity score, strain ratio

BACKGROUND: To reveal detailed histopathological changes, virus distributions, immunologic properties and multi-omic features caused by SARS-CoV-2 in the explanted lungs from the world's first successful lung transplantation of a COVID-19 patient. MATERIALS AND METHODS: A total of 36 samples were collected from the lungs. Histopathological features and virus distribution were observed by optical microscope and transmission electron microscope (TEM). Immune cells were detected by flow cytometry and immunohistochemistry. Transcriptome and proteome approaches were used to investigate main biological processes involved in COVID-19-associated pulmonary fibrosis. RESULTS: The histopathological changes of the lung tissues were characterized by extensive pulmonary interstitial fibrosis and haemorrhage. Viral particles were observed in the cytoplasm of macrophages. CD3+ CD4- T cells, neutrophils, NK cells, I³/I´ T cells and monocytes, but not B cells, were abundant in the lungs. Higher levels of proinflammatory cytokines iNOS, IL-1s and IL-6 were in the area of mild fibrosis. Multi-omics analyses revealed a total of 126 out of 20,356 significant different transcription and 114 out of 8,493 protein expression in lung samples with mild and severe fibrosis, most of which were related to fibrosis and inflammation. CONCLUSIONS: Our results provide novel insight that the significant neutrophil/ CD3+ CD4- T cell/ macrophage activation leads to cytokine storm and severe fibrosis in the lungs of COVID-19 patient and may contribute to a better understanding of COVID-19 pathogenesis.

In order to filter out image noise better and make it have better clarity, continuity and anti-noise performance in image edge extraction. Firstly, this paper constructs a new threshold function, compared with the traditional soft and hard threshold function and some existing improved methods, the threshold function has better adjustability and it is also continuous and almost smooth everywhere. When dealing with the wavelet coefficients, the real information on them can be retained more, and the noise can be effectively filtered at the same time. The simulation experiment shows that the image processed by the new threshold function has a high PSNR and a small MSE, which can be closer to the original image. Finally, the improved threshold function de-noising algorithm and the dyadic wavelet transform modulus maximum edge detection algorithm are combined to apply to image edge detection. By combining the advantages of the two algorithms, so that we can get clearer and more continuous image edges, and the contour is more complete.

Background and Purpose— Although the relationship between depression and stroke risk has been investigated, findings in previous reports were conflicting. The aim of this study was to prospectively examine the effect of major depressive episodes (MDE) on stroke incidence and further assess the potential dose–response relationship between number of depression symptoms and subsequent stroke risk in Chinese population. Methods— A total of 199 294 men and 288 083 women aged 30 to 79 years without a history of stroke, heart disease, and cancer in the China Kadoorie Biobank cohort were followed from 2004 to 2013. A World Health Organization Composite International Diagnostic Interview-Short Form was used to access MDE according to Diagnostic and Statistical Manual of Mental Disorders-IV criteria. Stroke events were ascertained through death certificates, medical records, and health insurance data. Results— Past year MDE was marginally associated with a 15% increased risk of stroke (adjusted hazard ratio, 1.15; 95% confidence interval, 0.99–1.33) in the fully adjusted model, and the association was steeper and statistically significant in individuals aged 2 , and no history of diabetes mellitus. Moreover, there was a positive dose–response relationship between the number of depression symptoms and increased stroke risk ( P trend =0.011). In addition, smoking status significantly interacted with MDE on stroke onset ( P for multiplicative interaction=0.025). Conclusions— Findings from this large prospective study suggest that the presence of MDE is a risk factor for stroke, especially in smokers.

An in situ observation system was developed to monitor the magnetic domain structure in the process of rubbing. By means of this system, the magnetic domain motion beneath the sliding area was observed while a carbon steel 1045/316 L stainless steel pin specimen rubbed on a pure iron block specimen under certain loads. Experiments showed that plastic deformation stimulated changes in magnetic domain beneath the rubbing surface as a result of sliding friction, which means plastic deformation was a crucial activation factor for tribo-magnetization. Then the variations of the magnetic domain structure beneath the rubbing surface with the increasing of rubbing cycles were characterized. From experimental results the relation between plastic deformation in tribological process and the original process in mechanism of the tribo-magnetization phenomenon was discussed.

// Yao Liu 1, 2, * , Qun Zhou 1, * , Xiao-Shun He 1 , Li-Ming Song 3 , Lin Chen 3 , Wei-Juan Jiao 1 , Tong Shen 1 , Su Yao 3 , Hua Wu 1 , Zhi-Bin Hu 2 , Tian-Ming Gao 4 , Jian-Ming Li 1, 3 1 Department of Pathology, Medical College of Soochow University, Suzhou 215123, People’s Republic of China 2 Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing 211166, People’s Republic of China 3 Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, People’s Republic of China 4 Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, People’s Republic of China * These authors have contributed equally to this work Correspondence to: Jian-Ming Li, e-mail: jianmingli@suda.edu.cn Tian-Ming Gao, e-mail: tgao@fimmu.com Zhi-Bin Hu, e-mail: zhibin_hu@njmu.edu.cn Keywords: ERBB4, hepatitis B virus, polymorphism, inflammation Received: August 13, 2015 Accepted: December 05, 2015 Published: December 18, 2015 ABSTRACT Background: The role of ERBB4 in liver disease has seldom been reported. This study aims to find genetic markers at ERBB4 for chronic hepatitis B virus (HBV) infection and determine the role of ERBB4 in liver injury. Methods: We selected and genotyped three single nucleotide polymorphisms and one insertion/deletion (Ins/Del) at the 5' and 3’ untranslated region (UTR) of ERBB4 in a case-control study including 1344 pairs of HBV carriers and HBV natural clearance subjects. The luciferase reporter system was applied to study the regulative role of Ins/Del on ERBB4. Further, ERBB4 knockout mice were used to study the role of ERBB4 in liver injury. Proteomic quantification was performed by HPLC-MS/MS analysis to identify liver protein profile change between liver-specific ERBB4 knockout and control mice. Results: rs6147150 Ins/Del and rs1836724 T>C at the 3’ UTR of ERBB4 were associated with reduced risk of chronic HBV infection ( P = 0.002 and 0.004, respectively). Besides, the 12bp deletion at the 3’ UTR increased ERBB4 expression due to lacking let-7c binding site. In addition, loss of ERBB4 led to more severe acute or chronic inflammation in mouse liver injury models. Further, quantitative proteomic analysis and data from the cancer genome atlas revealed that ACLY, an enzyme key for de novo lipogenesis, was negatively correlated with ERBB4. Conclusions: ERBB4 plays protective role from liver injury and its 3'UTR genetic variants could be genetic markers for chronic HBV infection.

The etiology of persistent hepatitis B virus (HBV) infection is complex and multifactorial, polygenic event with viral, environmental and genetic components being considered as the risk factors. Genome-wide association study (GWAS) has been applied into the exploration of genetic etiology of persistent hepatitis B virus infection among Chinese. However, the mechanisms beyond the genetic variants identified by GWAS located in noncoding regions are largely unknown. To further explore the causal gene of persistent hepatitis B virus (HBV) infection, we used a new approach developed by Gusev and Ko, leveraging expression imputation from large-scale GWAS data by using a small set of individuals with both genotype and gene expression data as a reference panel, to perform a transcriptome-wide association study (TWAS).Based on Genotype-Tissue Expression (GTEx) database, we included 97 individuals with both gene expression data in liver and SNP array data in blood as a reference panel. We first estimated the cis SNP heritability (cis-hg2) for each gene in 97 liver tissues using genome-wide complex trait analysis (GCTA) software, and kept cis-heritable genes for subsequent analysis. Then, we estimated the effect sizes of cis-SNPs on gene expression using genome-wide efficient mixed-model association (GEMMA) algorithm. Using the effect sizes trained from the reference panel, we imputed the gene expression levels for our existing NJMU HEP GWAS cohort (951 persistent hepatitis B virus (HBV) infection patients and 937 controls) and correlated the imputed gene expression values with persistent hepatitis B virus (HBV) infection trait. The cis-hg2 estimate was significantly nonzero for 2588 genes (P Citation Format: Jing Han, Jing Ni, Meng Zhu, Jin Guang Fu, Zhi Bin Hu. Transcriptome-wide association study revealed a novel gene associated with persistent hepatitis B virus infection among Chinese [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-176.

Objective: The PI3K/PTEN/AKT/mTOR signaling pathway has been implicated in resistance to cisplatin. In the current study, we determined whether common genetic variations in this pathway are associated with platinum-based chemotherapy response and clinical outcome in advanced non-small cell lung cancer (NSCLC) patients. Methods: Seven common single nucleotide polymorphisms (SNPs) in core genes of this pathway were genotyped in 199 patients and analyzed for associations with chemotherapy response, progression-free survival (PFS) and overall survival (OS). Results: Logistic regression analysis revealed an association between AKT1 rs2494752 and response to treatment. Patients carrying heterozygous AG had an increased risk of disease progression after two cycles of platinum-based chemotherapy compared to those with AA genotype (Adjusted odds ratio (OR)=2.18, 95% confidence interval (CI): 1.00-4.77, which remained significant in the stratified analyses). However, log-rank test and cox regression detected no association between these polymorphisms in the PI3K pathway genes and survival in advanced NSCLC patients. Conclusions: Our findings suggest that genetic variants in the PI3K/PTEN/AKT/mTOR pathway may predict platinum-based chemotherapy response in advanced NSCLC patients in a Chinese population.

Objective: NBS1 plays a key role in the repair of DNA double-strand break (DSB). We conducted this study to investigate the effect of two critical polymorphisms (rs1805794 and rs13312840) in NBS1 on treatment response and prognosis of advanced non-small cell lung cancer (NSCLC) patients with platinum-based chemotherapy. Methods: Using TaqMan methods, we genotyped the two polymorphisms in 147 NSCLC patients. Odds ratios (ORs) and their 95% confidential intervals (CIs) were calculated as a measure of difference in the response rate of platinum-based chemotherapy using logistic regression analysis. The Kaplan-Meier and log-rank tests were used to assess the differences in progression-free survival (PFS) and overall survival (OS). Cox proportional hazards model was applied to assess the hazard ratios (HRs) for PFS and OS. Results: Neither of the two polymorphisms was significantly associated with treatment response of platinum-based chemotherapy. However, patients carrying the rs1805794 CC variant genotype had a significantly improved PFS compared to those with GG genotype (16.0 vs. 8.0 months, P = 0.040). Multivariable cox regression analysis further showed that rs1805974 was a significantly favorable prognostic factor for PFS [CC/CG vs. GG: Adjusted HR = 0.62, 95% CI: 0.39-0.99; CC vs. CG/GG: Adjusted HR = 0.56, 95% CI: 0.32-0.97). Similarly, rs13312840 with a small sample size also showed a significant association with PFS (CC vs. CT/TT: Adjusted HR = 25.62, 95% CI: 1.53-428.39). Conclusions: Our findings suggest that NBS1 polymorphisms may be genetic biomarkers for NSCLC prognosis especially PFS with platinum-based chemotherapy in the Chinese population.

Insulin-like growth factors (IGFs) and their receptors play a crucial role in regulating cell proliferation, differentiation, and apoptosis. Insulin-like growth factor-binding protein-3 is the most abundant insulin-like growth factor receptor in the serum and binds the majority of insulin-like growth factors. Studies reported that circulating level of insulin-like growth factor-binding protein-3 was modulated by functional genetic variants of insulin-like growth factor-binding protein-3 and, therefore, maybe associated with the risk of gastric cancer. In this case-control study of 576 gastric cancer cases and 647 cancer-free control participants in a high-risk Chinese population, we tested the hypothesis that functional polymorphisms A-202C and Gly32Ala of insulinlike growth factor-binding protein-3 are associated with risk of gastric cancer. We found that the variant 32Ala allele was associated with a significantly increased risk of gastric cancer (adjusted odds ratio=1.84, 95% confidence interval=1.45-2.33 for 32Gly/Ala and odds ratio=2.39, 95% confidence interval=1.47-3.90 for 32Ala/Ala, respectively), compared with the wild-type homozygote 32Gly/Gly. Although the A-202C variant was not significantly associated with gastric cancer risk in the single locus analysis, we found a significant locus-locus interaction between insulin-like growth factor-binding protein-3 A-202C and Gly32Ala loci on gastric cancer risk (Pint

Photocatalytic degradation kinetics of acetamiprid was studied by both of single-variable-at-a-time (SVAT) and central composite design (CCD) experiments based on four factors, such as catalyst dosages, substrate concentration, temperature and pH values. The results indicated that degradation of acetamiprid followed pseudo first-order kinetics by Langmuir-Hinshelwood model, increased with the increasing of temperature and the decreasing of substrate concentration. The photocatalytic degradation kinetic rate of acetamiprid was low in acid solutions, while high in weak acidic and alkaline solutions. After studying the synergistic effects of these four classic parameters, the optimal experiment conditions for photocatalytic degradation of acetamiprid were obtained as follows: TiO2 at 2.30 g x L(-1), initial acetamiprid concentration of 90.0 μmol x L(-1), temperature of 37.5 degrees C and pH value at 5.0. Lastly, 7 degradation intermediates of acetamiprid were detected during photocatalytic process by HPLC, and 6 of them exhibited more polar than the parent molecule.

To study the association of polymorphisms in the potassium voltage-gated channel, KQT-like subfamily,member 1(KCNQ1) gene with type 2 diabetes in Chinese population from Jiangsu province.Subjects consisting of 2925 cases and 3281 controls were enrolled from a community based cohort study of type 2 diabetes in Wuxi in 2007 and a community based cross-sectional survey on chronic non-communicable disease in Nantong in 2009. Epidemiological questionnaire survey and physical examinations were conducted and 10 h overnight fasting blood samples of 5 ml were drawn for all subjects.Genotypes were determined by TaqMan OpenArray Genotyping System and i-PLEX Sequenom MassARRAY platform. The relationship between KCNQ1 gene polymorphism and risk of type 2 diabetes after adjustment for age,sex and body mass index (BMI) was analyzed.The C allele of rs2237897, rs2237892 and rs2237895 at KCNQ1 increased the risk of type 2 diabetes with adjusted OR (95%CI) value being 1.41(1.30-1.54), 1.35(1.24-1.47), 1.22(1.12-1.33) respectively (all P value0.05) under the additive genetic model after adjusted by age,sex and BMI. Stratification analyses in additive genetic model showed that the C allele of rs2237897 increased the risk of type 2 diabetes in subgroups stratified by age ( ≤ 56 years and56 years), sex (females and males), BMI (24 kg/m(2) and ≥ 24 kg/m(2)) with OR (95%CI) value being 1.39(1.22-1.59), 1.43(1.28-1.60), 1.40(1.26-1.55), 1.44(1.26-1.66), 1.48(1.33-1.66), 1.34(1.17-1.53) respectively (all P value0.05).Polymorphisms of rs2237897, rs2237892 and rs2237895 in the KCNQ1 gene were associated with occurrence of type 2 diabetes among Jiangsu province population.

By using RS/GIS techniques and the method of multiple objective grey situation decision, and in considering the forest economic benefits (biomass and stand productivity) and ecological benefits (water and soil conservation) , an optimal spatial allocation of the present forest types in Qingyuan County of Liaoning, Northeast China was approached in this study. After the optimization of spatial allocation, the structural proportions of different forest types in Qingyuan County changed obviously, with the area of coniferous forests reduced from 43% to 23% , the area of broadleaved forests reduced from 51% to 31% , the area of mixed coniferous-broadleaf forests increased from 3% to 43% , and the area of shrubs remained unchanged. As compared with the results before optimization, the biomass, stand productivity, and water conservation function of the forest ecosystem in Qingyuan County after optimization increased by 0.6%, 2.1% , and 31.7%, respectively, and the soil conservation function remained unchanged. It could be concluded that after the optimization of spatial allocation, the forest ecosystem of Qingyuan County could maintain its soil conservation function, and, at the time of keeping higher timber production, fully exert waler conservation function, realizing the maximization of the economic and ecological benefits of the forest ecosystem.

To investigate the effect of a common polymorphism rs928508(A/G) in flanking region of miR-30c on the expression of pri, pre and mature miR-30c, and discuss the effect of this polymorphism on the maturing process of miR-30c in lung carcinoma.The pGL3-promoter-miR-30c-A and pGL3-promoter-miR-30c-G luciferase plasmids were created containing A or G allele of miR-30c flanking region. Taqman assay was used to genotype rs928508 polymorphism in 50 lung cancer tissues. RT-PCR was performed to determine the expression of pri-miR-30c, pre-miR-30c, mature miR-30c and miR-30c host gene NFYC in the 50 lung cancer tissues.The luciferase expression level of the pGL3-promoter-miR-30c-A construct group was not significantly different compared with that in the the pGL3-promoter-miR-30c-G construct group (A549 cells, P = 0.758; 293A cells, P = 0.554; CHO cells, P = 0.175). The results demonstrated that rs928508(A/G) variant had no effect on the transcriptional regulation of pri-miR-30c. In the genotype-phenotype collection analysis of the 50 lung cancer tissues, the expression of pre-miR-30c and mature miR-30c for rs928508 AG/GG genotypes showed significantly lower levels compared with those in the AA genotype (P = 0.009, P = 0.011). However, the expression of pri-miR-30c showed no significant difference between AG/GG genotypes and AA genotype. Similarly, the expression of host NFYC gene was correlated with pri-miR-30c, showed no significant difference between AG/GG genotypes and AA genotype.The rs928508(A/G) polymorphism in flanking region of miR-30c could influence the processing from pri-miR-30c to mature miR-30c, but does not influence the transcription of pri-miR-30c.

To investigate the performance of random forest method as a SNP screening procedure in high dimensional case-control data of lung cancer.This study included 500 lung cancer patients and 517 controls. A total of 5 ml venous blood sample was collected from each participant. The genotypes were classified by GoldenGate platform, and 399 SNPs were selected. The random forest method was first applied to reduce the dimension, and then the traditional logistic regression method was used to analyze the variables and the genetic susceptibility between lung cancer and multiple SNPs was analyzed by AUC (areas under receiver operation characteristics (ROC) curves).Fifty important variables, whose average importance scores were highest and whose error rates were lowest, were selected by random forest method. The importance scores of environmental variables (smoking, age and gender) were all listed at top 20, which were respectively 4.05, 3.12 and 1.16. After adjusting 3 environmental variables and false discovery rate (FDR), 6 SNPs were still significantly associated with lung cancer (FDR-P0.05). However, if traditional logistic regression analysis were directly applied, no significant SNPs were found. The likelihood testing result of AUC of the 2 ROC (one curve only included environmental variables and the other curve included environmental variables and SNPs) were 0.6491 ± 0.0172 and 0.6811 ± 0.0166 respectively; showed statistical significance of the association between the 6 SNPs and lung cancer (χ² = 43.82, P = 3.6×10⁻¹¹).Random forest analysis could first remove the turbulent SNPs and then make the analysis by logistic regression method. This could improve the testing efficacy, which is significantly better than single logistic regression analysis.

The key components of metabolic syndrome (MS) are waist circumference, blood pressure, fast blood glucose, high density lipoprotein cholesterol (HDL-c) and triglycerides (TG). These components have, separately and jointly, been associated with an increased risk of cardiovascular diseases. In this study, we aimed to explore the association between MS components and cancer risk in a population-based cohort in China.We established a population-based cohort with 17 779 individuals aged 35 and above at baseline in 2004 and 2005 in Changzhou, Jiangsu Province, China. All participants were face-to-face interviewed to complete a questionnaire and were accepted physical examinations including blood tests for glucose and lipids and physical measurements for obesity and blood pressure. In 2009, a total of 16 284 subjects (6886 men and 9398 women, 91.6%) attended the flow-up interviews and the participants or their family members reported all the hospitalizations and diseases including cancer occurred during the follow-up period. Multivariate Cox regression was used to estimate the hazard ratios (HRs) of metabolic syndrome components and cancer incidence.There was a dose-response association between cancer risk and the number of MS components presented at baseline (P for trend = 0.012) and the HR (95% confidence interval (CI)) was 2.63 (1.27 - 5.45) for subjects carrying 3 or more metabolic syndrome components after adjustment for possible confounding factors. Specifically, the multivariate-adjusted HRs (95%CIs) for cancer risk in subjects with central obesity, high fasting glucose, low HDL-c were 1.94 (1.01 - 3.74), 2.04 (1.10 - 3.77) and 2.05 (1.09 - 3.88), respectively.In this population-based, prospective cohort study in China, we found MS components, e.g., central obesity, high fasting glucose, low HDL-c were risk factors for cancer development. Early intervention of MS components may be also beneficial to reduce cancer burden.

A recent genome-wide association study in Caucasians revealed that three loci (rs174547 in fatty acid desaturase 1 (FADS1), rs2338104 near mevalonate kinase/methylmalonic aciduria, cobalamin deficiency, cblB type (MVK/MMAB) and rs10468017 near hepatic lipase (LIPC)) influence the plasma concentrations of high-density lipoprotein-cholesterol (HDL-C) and triglycerides (TG). However, there are few reports on the associations between these polymorphisms and plasma lipid concentrations in Chinese individuals. This study aimed to evaluate the associations between these three polymorphisms with HDL-C and TG concentrations, as well as coronary heart disease (CHD) susceptibility in Chinese individuals.We conducted a population-based case-control study in Chinese individuals to evaluate the associations between these three polymorphisms and HDL-C and TG concentrations, and also evaluated their associations with susceptibility to CHD. Genotypes were determined using polymerase chain reaction-restriction fragment length polymorphism assays and TaqMan genotyping assays.We found significant differences in TG and HDL-C concentrations among the TT, TC and CC genotypes of FADS1 rs174547 (P=0.017 and 0.003, respectively, multiple linear regression). The CC variant of rs174547 was significantly associated with hyperlipidemia compared with the TT variant (adjusted odds ratio (OR)=1.71, 95% confidence intervals (CI): 1.16-2.54). The FADS1 rs174547 CC variant was also associated with significantly increased CHD risk compared with the TT and TC variant (adjusted OR=1.53, 95%CI: 1.01-2.31), and the effect was more evident among nonsmokers and females. The polymorphisms rs2338104 and rs10468017 did not significantly influence HDL-C or TG concentrations in this Chinese population.rs174547 in FADS1 may contribute to the susceptibility of CHD by altering HDL-C and TG levels in Chinese individuals.

The purpose of this study was to discuss the relationship between genetic polymorphism of promoter region let-7 and genetic susceptibility to hepatocellular carcinoma (HCC) in Chinese population.In this case-control study, 1300 cases of HBV positive patients were recruited in case group and another 1344 cases of persistent chronic HBV carriers were selected as control. 5 ml of blood sample was collected from each subject, from which the DNA was extracted; and rs10877887 and rs13293512 in promoter region let-7 were selected as the study sites. The polymorphism was detected by TaqMan allelic discrimination assay and the OR value (95%CI) was evaluated by Logistic Regression Method to analyze the relationship between susceptibility to HCC and different genotypes.The frequencies of genotype TT, CT and CC in site rs10877887 were 43.0% (542/1261), 44.7% (564/1261) and 12.3% (155/1261) respectively in case group; while separately 44.0% (581/1319), 44.4% (585/1319) and 11.6% (153/1319)in control group. The frequencies of genotype TT, CT and CC in site rs13293512 were 32.0% (406/1270), 48.1% (611/1270) and 19.9% (253/1270) respectively in case group; while separately 33.1% (427/1291), 49.4% (638/1291) and 17.5% (226/1291) in control group. The results of multifactor logistic regression analysis showed no statistical significance in the relationship between different genotype TT, mutated genotype C in site rs10877887 and susceptibility to HCC (CC + CT vs TT, adjusted OR = 1.05, 95%CI: 0.90 - 1.23); and either no statistical significance in the relationship between different genotype TT, mutated genotype C in site rs13293512 and susceptibility to HCC (CC + CT vs TT, adjusted OR = 1.06, 95%CI: 0.89 - 1.25). The united-analysis of the two sites showed the frequencies of 0, 1, 2 and 3-4 mutated-genotype C were 13.3% (164/1235), 36.2% (447/1235), 33.0% (408/1235) and 17.5% (216/1235) respectively in case group; and separately 14.2% (181/1269), 37.0% (469/1269), 33.1% (420/1269) and 15.7% (199/1269) in control group. The susceptibility to HCC in 1,2,3-4 mutated-genotype C carriers were 1.05 (0.81 - 1.34), 1.07 (0.83 - 1.38) and 1.22 (0.91 - 1.62) times of the non-mutated genotype subjects; but there was no statistical significance (Wald χ(2) = 1.79, P = 0.181).The polymorphism of study sites rs10877887 and rs13293512 may not be the biomarker of susceptibility to HCC in Chinese.

To explore the correlation between single-nucleotide polymorphisms (SNPs) of telomerase reverse transcriptase (TERT) rs2736098 and rs2736100 and the susceptibility to hepatocellular carcinoma (HCC).This case-control study design included 1300 diagnosed HCC patients with HBsAg positive and 1344 HBsAg positive people as control-group.rs2736098 and rs2736100 on TERT were selected as research sites, whose polymorphisms were detected by TaqMan allelic discrimination assay. The OR values (95%CI) were calculated by logistic regression to compare the correlation between different genotype and susceptibility to HCC.The distribution frequencies of three genotypes as GG, AG and AA on rs2736098 were separately 39.3% (500/1273), 44.2% (563/1273) and 16.5% (210/1273) in case group; while respectively 39.6% (526/1328), 45.5% (604/1328) and 14.9% (198/1328) in control group. The distribution frequencies of three genotypes as AA, AC and CC on rs2736100 were separately 33.7% (428/1269), 49.9% (633/1269) and 16.4% (208/1269) in case group; while respectively 34.0% (449/1322), 49.2% (651/1322) and 16.8% (222/1322) in control group. The multi-variates logistic regression analysis showed that there was no significant difference between rs2736098 mutated A carriers and genotype GG carriers in the susceptibility to HCC after adjusting by age, sex, smoking and drinking factors (rs2736098, AA + AG vs GG: adjusted OR = 1.00 (95%CI: 0.86 - 1.18)); and there was no significant different between rs2736100 mutated C carriers and genotype AA carriers in the susceptibility to HCC either (AC + CC vs AA: adjusted OR = 1.03 (95%CI: 0.87 - 1.22)).The polymorphisms of rs2736098 and rs2736100 on TERT may not play a landmark role in susceptibility to HCC among Chinese population.

To investigate the relationship between genetic polymorphism in microRNAs (miRNAs) precursor and genetic predisposition of hepatocellular carcinoma (HCC) in Chinese population.A case-control study including 963 HCC cases and 829 HBsAg positive controls and 852 HBsAg negative controls was conducted. hsa-mir-146a rs2910164 C→G and hsa-mir-196-a2 rs11614913 T→C were selected, where the genotypes were determined by the primer introduced restriction analysis-PCR (PIRA-PCR) assay. Odd ratios (ORs) and 95% confidence intervals (CIs) were evaluated by logistic regression analysis to investigate the relationship between onset risk of HCC and different genotypes.The genotype frequencies of CC, CG and GG at rs2910164 gene locus were separately 34.5% (319/925), 48.6% (450/925) and 16.9% (156/925) in cases; 36.4% (274/753), 45.0% (339/753) and 18.6% (140/753) in HBsAg positive controls; and 36.1% (303/840), 46.0% (386/840) and 18.0% (151/840) in HBsAg negative controls. The genotype frequencies of TT, CT and CC at rs11614913 were respectively 29.7% (277/934), 48.1% (449/934) and 22.3% (208/934) in cases; 30.3% (238/785), 51.0% (400/785) and 18.7% (147/785) in HBsAg positive controls; and 28.6% (239/837), 49.8% (417/837) and 21.6% (181/837) in HBsAg negative controls. No significant relationships were observed between these two single nucleotide polymorphisms (SNPs) and onset risk of HCC after adjusting the factors as age, gender, smoking and drinking status in comparison with HBsAg positive controls: hsa-mir-146a rs2910164 (CG + GG vs CC): adjusting OR = 1.10, 95%CI: 0.90 - 1.36; hsa-mir-196-a2 rs11614913 (CC + CT vs TT): adjusting OR = 1.01, 95%CI: 0.81 - 1.25; as well as in comparison with HBsAg negative controls: hsa-mir-146a rs2910164 (CG + GG vs CC): adjusting OR = 1.06, 95%CI: 0.87 - 1.29; hsa-mir-196-a2 rs11614913 (CC + CT vs TT): adjusting OR = 0.94, 95%CI: 0.76 - 1.16. As well, no significant relationships were observed between these two SNPs and onset risk of HCC in the subgroups stratified by age, gender, smoking and drinking status.hsa-mir-146a rs2910164 C→G and hsa-mir-196-a2 rs11614913 T→C may not play an important role in the HCC predisposition among Chinese populations.

Historical range of variability (HRV) characterizes the fluctuations of ecosystem structure and processes under natural disturbances, and is helpful in understanding the causes and consequences of ecosystem change, providing the researchers and managers a reference to evaluate the present status of ecosystems and guiding managers to develop effective management strategies to ultimately drive ecosystems to a sustainable state. In recent years, HRV has played an increasingly important role in forest ecosystem management, and has been successfully used in indicating the causes of ecosystem change, conservation of biological diversity and endangered species, and restoration of ecosystem function, etc. This paper outlined the concept of HRV, and discussed the applications, limitations (lack of data, environmental change, and human impacts, etc.), and challenges of applying HRV in forest ecosystem management. Strengthening data mining, focusing on the changes of natural environment and human society, and increasing the public's recognition of HRV would benefit the improvement of the application efficacy of HRV in forest ecosystem management, and make the forest ecosystem ultimately achieve a sustainable state.

Based on the fuzzy logic knowledge database designed by NetWeaver tools, and using ecosystem management decision support system (EMDS), a quantitative evaluation was made on the landscape change in the upper reaches of Minjiang River from 1986 to 2000. The results showed that the type, area, amount, and spatial distribution of landscape patches in the reaches changed greatly, and the changing direction was in favor of ecosystem restoration. The changes of forest landscape mainly occurred in the north part of study area (Songpan County and Heishui County), while those of grass landscape mainly occurred both in the north part and in the furthest south part (Wenchuan County). The joint effect of increasing human activities and nature change was the driving force of the landscape changes.

According to the topography, land type suitability and human activity, the urban area of Shenyang City was regionalized into four landscape functional regions, i.e., economic and cultural supporting region, ecological equilibrium region (including northern high plain equilibrium sub-region and southern low plain equilibrium sub-region), ecological supporting region (including eastern ecological supporting sub-region and western ecological supporting sub-region), and ecological barrier region. In economic and cultural supporting region, the radiation of function in economy and culture should be strengthened, and the natural and artificial green space system should be preserved. In ecological supporting region, environmentally friendly industries should be developed to provide diverse ecological service well. As a combination of natural and man-made ecological system, the ecological equilibrium region could balance and steady the other regional services. To keep the balance between artificial and natural landscapes in this region, it was needed to control the expansion of construction land, maintain the natural and semi-natural system, and build the ecological corridors to connect various natural system. In ecological barrier region, the ecological environment was in instability, where the protection and production should be dealt with equally.

To investigate the association of polymorphisms of CDT1 and GMNN gene, two important genes participating in DNA replication, with the risk of sporadic breast cancer.Using polymerase chain reaction-restriction fragment length polymorphism (PCR - RFLP) and the primer-introduced restriction analysis (PIRA)-PCR assay to genotype the CDT1 838G/A and GMNN 387C/A polymorphisms in a case-control study of 427 breast cancer cases and 477 cancer-free controls in a Chinese population.No significant association of the CDT1 838G/A and GMNN 387C/A polymorphisms with the risk of breast cancer was found (adjusted OR:1.16, 95% CI:0.88-1.54 for CDT1 GA+AA genotypes and adjusted OR:0.90, 95% CI:0.67-1.21 for GMNN CA+AA genotypes). However, in the stratified analyses, a significant association of CDT1 GA+AA genotypes with breast cancer risk among subjects with family history of cancer was found (adjusted OR:2.21, 95% CI:1.20-4.09).These findings suggest that the CDT1 838G/A and GMNN 387C/A polymorphisms may not play a major role in the etiology of breast cancer, but CDT1 variant may have a potential role only in genetically susceptible women.

To explore the relationship between two exonic polymorphisms of DNA repair gene XPC and the susceptibility to lung cancer.Genotypes were determined by the primer introduced restriction analysis-PCR(PIRA-PCR) and the PCR-restriction fragment length polymorphism(PCR-RFLP) approaches, respectively, in 320 histologically-confirmed lung cancer cases and 322 age and sex frequency-matched cancer-free controls.Multivariate logistic regression analysis revealed that individuals carrying at least one 499Val variant allele (Ala/Val + Val/Val genotypes) had a significantly increased risk for lung cancer (adjusted OR=1.54; 95%CI: 1.11-2.14), compared with the wild-type genotype (499Ala/Ala). Furthermore, individuals with both putative risk genotypes had a significantly higher risk (adjusted OR=2.55; 95%CI: 1.45-4.52), compared with those with both wild-genotypes. In addition, a potential super multiplicative gene-environment interaction between Ala499Val genotypes and smoking on lung cancer risk was unveiled. The odds ratios of lung cancer for individuals with both putative risk genotypes were 2.63 (95%CI=1.23-5.62) in nonsmokers and 7.36 (95%CI=3.19-17.0) in smokers, respectively.These findings support the hypothesis that these two XPC variants may contribute to the risk of developing lung cancer.

To investigate the association of R219K and M883I polymorphisms of ATP binding cassette transporter 1 gene with lipid metabolism and the susceptibility to coronary atherosclerotic heart disease in Chinese population.Genotypes were determined by PCR-restriction fragment length polymorphism and Primer introduced restriction analysis-PCR techniques, respectively, in 248 unrelated CHD-free controls and 224 CHD cases.Smoking, high blood pressure and high serum glucose were independent risk factors for CHD. Multivariate logistic regression analysis revealed that individuals carrying at least one 219K variant allele (RK + KK genotypes) had a significantly decreased risk for CHD (adjusted OR = 0.41; 95% CI = 0.27-0.61) compared with the wild-type genotype (219RR) and only 883II homozygotes displayed a decreased risk for CHD (adjusted OR = 0.54; 95% CI = 0.26-1.11) compared with 883MM and 883MI genotypes. Furthermore, compared with individuals with both wild genotypes (219 RR and 883 MM or 883 MI) other individuals with all other assembly genotypes had a significantly decreased risk (adjusted OR = 0.39, 95% CI = 0.26-0.60). Plasma HDL-C in 219K allele carriers were markedly higher than those in 219 K non-carriers in controls (P = 0.037).The ABCA1 R219K polymorphism may be involved in the variability of serum HDL-C and the susceptibility to coronary artery disease.

To investigate whether the mitochondrial ATP-sensitive potassium channel (mitoK(ATP)) opener diazoxide as an additive to cardioplegia solution could enhance myocardial protection during hypothermic preservation of the rat heart.The Langendorff model of isolated rat heart was used. After equilibrium, the hearts were stored in Celsior cardioplegia solution at 4 degree with or without supplement of diazoxide for 3 or 8 h followed by 60 minutes reperfusion. The recovery of cardiac contractile function, myocardial enzyme leakage in the coronary effluent, and myocardial water content were determined. The myocardial ultrastructure was also observed.(1) Treatment of diazoxide improved the recovery of left ventricular developed pressure and decreased the leakage of myocardial enzymes, lactate dehydrogenase (LDH) and creatine kinase (CK), at the 2nd and 4th minute of reperfusion of rat heart after hypothermic preservation for 3 h. (2) After hypothermic preservation for 8 h, diazoxide improved the recovery of left ventricular developed pressure and decreased the leakage of myocardial enzymes (LDH, CK and glutamic oxalic transaminase) during reperfusion. Moreover, left ventricular end-diastolic pressure was significantly lower in diazoxide-treated hearts than that of hearts in Celsior solution. (3) Diazoxide significantly decreased the water content of myocardium and increased coronary flow of the hearts compared with those in control after hypothermic preservation for 8 h. (4) Impairment of myocardial ultrastructure after 8 h hypothermic preservation was alleviated in hearts treated with 30 mol/L diazoxide. (5) The cardiac effects of 30 mol/L diazoxide were attenuated by a mitoK(ATP) blocker 5-hydroxydecanoate (100 micromol/L).Diazoxide as a supplementation in cardioplegia solution could enhance myocardial protection during hypothermic heart preservation via opening of mitochondrial K(ATP) channel.

To study the relationship between two potential functional polymorphisms in exon 2 of the p73 gene and the susceptibility of lung cancer.Genotypes were determined by polymerase chain reaction-single stand conformation polymorphism (PCR-SSCP) method in 425 histologically-confirmed lung cancer cases and 588 cancer-free controls, frequency-matched by age and sex.The two polymorphisms were in complete linkage disequilibrium and the frequencies of variant p73 AT haplotype (A4T14) were less commonly seen in the cases (0.225) than in the controls (0.287) (P = 0.0018). Compared with the p73 GC/GC homozygotes, both the AT/AT variant homozygotes and GC/AT heterozygotes were associated with a significantly decreased risk [adjusted odds ratio (OR) = 0.45, 95% confidence interval (CI) = 0.26 - 0.80 and OR = 0.70, 95% CI = 0.53-0.92, respectively].These results suggested that this p73 dinucleotide polymorphism might have had a role to play in the susceptibility of lung cancer.

Prolongation of the duration of heart preservation in vitro is very important in clinical heart transplantation. Previous studies have shown that mitochondrial ATP-sensitive potassium channel (mitoK(ATP)) plays an important role in cardioprotective effect. The purpose of this study was to assess whether the mitoK(ATP) opener diazoxide as an additive to cardioplegia solution could enhance myocardial protection during long-term hypothermic preservation of the rat heart. Langendorff model of isolated rat heart was used. After 30 min stabilization of perfusion, the hearts were stored in Celsior cardioplegia solution at 4 degrees C with (15, 30 and 45 micromol/L) or without diazoxide, a mitoK(ATP) channel opener, for 10 h followed by 60 min reperfusion. The recovery of cardiac contractile function, myocardial enzyme leakage in the coronary effluent, and myocardial water content were determined. The myocardial ultrastructure was also observed. We found that: (1) Diazoxide treatment improved the recovery of left ventricular developed pressure and +/-dp/dt(max) dose-dependently. Left ventricular end-diastolic pressure was significantly lower in diazoxide-treated hearts than that of hearts in Celsior solution after hypothermic preservation for 10 h. (2) Diazoxide at 30 and 45 micromol/L significantly decreased the water content of myocardium and increased coronary flow of the hearts compared to those in control. (3) The leakage of myocardial enzymes (lactate dehydrogenase, creatine kinase and glutamate-oxaloacetate transaminase) in the coronary effluent was significantly reduced in diazoxide-treated hearts. (4) Impairment of myocardial ultrastructure after 10 h hypothermic preservation was alleviated in hearts treated with 30 micromol/L diazoxide. (5) The cardiac effects of 30 micromol/L diazoxide were attenuated by a mitoK(ATP) blocker 5-hydroxydecanoate (5-HD, 100 micromol/L). These results indicate that diazoxide as a supplementation in cardioplegia solution could enhance myocardial protection during long-term hypothermic heart preservation via opening of mitochondrial K(ATP) channel.