Asiatic acid alleviates ischemic myocardial injury in mice by modulating mitophagy- and glycophagy-based energy metabolism.

Myocardial infarction (MI) causes disturbances in myocardial energy metabolism, ultimately leading to a poor prognosis. Cytosolic glycogen autophagy (glycophagy) and mitochondrial autophagy (mitophagy) are upregulated in MI to optimize energy metabolism but to a limited extent. Asiatic acid (AA), a pentacyclic triterpene derived from the traditional Chinese herb Centella asiatica, displays anti-inflammatory, antioxidant, and antiapoptotic activities. AA has been found to alleviate focal cerebral and liver ischemic injury by reversing mitochondrial dysfunction. In this study, we investigated whether AA exerted cardioprotective effects against MI by activating glycophagy and mitophagy to improve the energy balance. In vitro cardioprotective effects were examined in neonatal mouse cardiomyocytes subjected to oxygen-glucose deprivation for 12 h. Treatment with AA (2-50 µM) significantly increased cell viability and improved the energy metabolism evidenced by increased ATP level and phosphocreatine/ATP ratio. In vivo cardioprotective effects were studied in a mouse model of MI. Administration of AA (5-125 mg·kg-1·d-1, ig) significantly reduced infarct size and ischemic myocardial injury, and improved cardiac function. AA treatment also promoted mitophagy and relieved mitochondrial edema evidenced by increased number of mitophagosomes in ischemic myocardium in vivo and increased mitochondria-light chain 3 (LC3)-II colocalization in ODG-treated cardiomyocytes in vitro. Mitophagy activation was accompanied by activation of the AMPK signaling pathway. Knockdown of AMPK abolished AA-activated mitophagy. Furthermore, we showed that glycophagy was upregulated in OGD cardiomyocytes evidenced by increased starch binding domain protein 1 (STBD1)-GABA type A receptor-associated protein-like 1(GABARAPL1) interaction and extracellular acidification rate, whereas AA treatment further promoted glycophagy accompanied by PI3K/Akt activation. PI3K inhibitor LY294002 or Akt inhibitor GSK690693 blocked the effects of AA on glycophagy and glycolysis. Finally, simultaneous inhibition of glycophagy and mitophagy abolished the cardioprotective effects and energy regulation of AA. These results demonstrate that AA protects ischemic cardiomyocytes by modulating glycophagy- and mitophagy-based energy metabolism through the PI3K/Akt and AMPK pathways.

Vasculopathy in the setting of cardiorenal syndrome: roles of protein-bound uremic toxins.

Chronic kidney disease (CKD) often leads to and accelerates the progression of cardiovascular disease (CVD), while CVD also causes kidney dysfunction. This bidirectional interaction leads to the development of a complex syndrome known as cardiorenal syndrome (CRS). CRS not only involves both the heart and the kidney but also the vascular system through a vast array of contributing factors. In addition to hemodynamic, neurohormonal, mechanical, and biochemical factors, nondialyzable protein-bound uremic toxins (PBUTs) are also key contributing factors that have been demonstrated through in vitro, in vivo, and clinical observations. PBUTs are ineffectively removed by hemodialysis because their complexes with albumins are larger than the pores of the dialysis membranes. PBUTs such as indoxyl sulfate and p-cresyl sulfate are key determinate and predictive factors for the progression of CVD in CKD patients. In CRS, both vascular smooth muscle cells (VSMCs) and endothelial cells (ECs) exhibit significant dysfunction that is associated with the progression of CVD. PBUTs influence proliferation, calcification, senescence, migration, inflammation, and oxidative stress in VSMCs and ECs through various mechanisms. These pathological changes lead to arterial remodeling, stiffness, and atherosclerosis and thus reduce heart perfusion and impair left ventricular function, aggravating CRS. There is limited literature about the effect of PBUT on the vascular system and their contribution to CRS. This review summarizes current knowledge on how PBUTs influence vasculature, clarifies the relationship between uremic toxin-related vascular disease and CRS, and highlights the potential therapeutic strategies of uremic vasculopathy in the setting of CRS.

Clinical and epidemiological features of the 2014 large-scale dengue outbreak in Guangzhou city, China.

BACKGROUND: Dengue virus is transmitted by mosquito around the tropical and sub-tropical regions. There was a large-scale dengue epidemic in Guangdong province, China during 2014 and around fifty thousands dengue fever cases, including six deaths, have been reported. In this study, we aimed to understand the clinical characteristics of hospitalized patients with laboratory-confirmed dengue virus (DENV) infection and determined the origin of the virus from the outbreak. METHODS: We have summarized the data from 138 hospitalized patients who were laboratory confirmed for dengue infection in Guangzhou city. Patients were classified as either non-severe dengue fever or severe dengue fever according to the guidelines from the WHO. Viral serotypes were determined by real time RT-PCR. Genetic sequences of the envelope and non-structural genes were amplified and analyzed from the serum samples of eleven patients. RESULTS: Co-circulation of dengue serotype 1 and 2 were identified from the outbreak. Patients infected by serotype 1 or 2 showed similar clinical features. Patients with severe dengue fever showed prolonged hospitalization and significant impairment of organ functions. Four samples from serotype 1 and five samples from serotype 2 were closely related respectively and clustered with Guangzhou isolates from previous years. The remaining isolates of serotype 1 were related to viruses found in Malaysia, India, Bangladesh and Singapore. CONCLUSION: The phylogenetic grouping of Guangdong isolates suggests that dengue is no longer an imported disease in China. Analysis of the isolates obtained in this study together with the size of the outbreak are suggestive of endemic circulation in Guangdong province.

Evaluation of Reflexology by "BIOCERAMIC Resonance" Operation producing Weak Force Field during Simultaneous Acupoint Stimulation of Urinary Bladder Point on Subject's Ear Resulting in Electric Current Change on Urinary Bladder reflex Point on Subject's Hands, and Related New Research Finding.

OBJECTIVE: It was postulated in our previous publications that the meridian channels as conceived in Traditional Chinese Medicine (TCM) are various standing waves arising from harmonic rhythmic sound frequencies originating from the human heart beat. BIOCERAMIC is an artificial material able to produce a weak force field causing different biophysical and systemic health benefits, with the key characteristics of hydrogen bonds weakening and microcirculation enhancement. Since discovering that the effects of a BIOCERAMIC field can be transmitted via sound waves propagation, we then also developed a BIOCERAMIC Resonance device to produce weak force field throughout the body, and achieve resonance with the body's meridian channels to reinforce microcirculation. METHODS: Since our previous research proved BIOCERAMIC can produces changes in ectodermal current levels, the present evaluation on reflexology is done by the application of Electric Current Detection (ECD) to the palmar surface of the hands matching correlative organs and glands loci to reflex points according to standard reflexology. The procedure will compare changes in the electrical current observed before and after a session of BIOCERAMIC Resonance treatment on the soles of the subjects' feet. We also conducted a procedure using corona discharge (Kirlian) photography of the hands to examine whether the coronal intensities could be affected by application of the BIOCERAMIC patch. Intensities are shown on the screen of a computer using special software that categorizes intensities into five zones. RESULTS: Under the continuous treatment of BIOCERAMIC Resonance on soles of the feet and simultaneous stimulation on the specific point on the surface of the ear representing the urinary bladder. The electrical current (Aji ampere) on the areas in the hands are decreased from the beginning of the experiment, but only the specific area on the surface of the ear representing the urinary bladder was exhibited increased of the electrical current (Aji ampere), with statistically significant difference (p<0.05). To the other study we evaluated the validity of reflexology and corona discharge (Kirlian) photography by applying BIOCERAMIC Resonance and small adhesive patches made from the BIOCERAMIC material. Significant differences were evident on four out of five different zones of the computerized images. CONCLUSION: Our findings suggest the existence of presupposed virtual channels or reflex points on the skin surface of the feet, hands, and ears that connect or somehow reflect back to specific internal organs, as mapped out on standard charts found in reflexology. Furthermore, the depicted corona intensities from five zones shown on a computer screen of corona discharge photography seem to indicate that the volunteer subjects are affected by the BIOCERAMIC patches. This study demonstrates the operation of the BIOCERAMIC Resonance device is able to produce weak force field through the body, which is objectively measurable and thereby scientifically integrating the concepts of reflexology, meridian channels and biofield therapy.

Effects of GRK5 and ADRB1 polymorphisms influence on systolic heart failure.

BACKGROUND: G-protein receptor kinase 5 (GRK5) Gln41 > Leu and ß1-adrenergic receptor (ADRB1) Arg389 > Gly polymorphisms presented the different distribution of genotype frequencies between Caucasian American and African American, and produced the difference in ß-blocker treatment effect among them with systolic heart failure (SHF). OBJECTIVE: This study sought to identify the distributed characteristics of these variant genotypes in Chinese population, and influence of GRK5 and ADRB1 polymorphisms on SHF morbidity and ß-blocker treatment effect in patients with SHF. METHODS: This study was based on cross-sectional survey data. 1794 and 1718 subjects' ADRB1 and GRK5 gene sequencing (sanger method) data were achieved respectively. Blood samples collection, clinical laboratory detection, electrocardiogram and echocardiography examinations were performed. Medication usage was confirmed at in-hospital visits or the questionnaire by personal interview. RESULTS: GRK5 Leu41Leu genotype was not found in our Chinese population. In non-SHF population, allele frequencies of GRK5 Gln41 and Leu41 were 2782 (0.992) and 22 (0.008) (Hardy-Weinberg equilibrium test χ(2) = 0.088, P = 0.767), and allele frequencies of ADRB1 Arg389 and Gly389 were 2127 (0.715) and 849 (0.285) (χ(2) = 0.272, P = 0.602). In SHF patients, allele frequencies of Gln41 and Leu41 were 446 (0.991) and 4 (0.009) (χ(2) = 0.018, P = 0.893), and allele frequencies of Arg389 and Gly389 were 331 (0.726) and 125 (0.274) (χ(2) = 1.892, P = 0.169). Further in logistic regression model, these ADRB1 and GRK5 variants were not significantly independently associated with the risk of SHF morbidity. Those carrying genotype ADRB1 Gly389Gly did not reduce significantly the risk of SHF morbidity after ß-blocker therapy. CONCLUSIONS: GRK5 Leu41Leu genotype was not found in our Chinese population, neither ADRB1 nor GRK5 variants presented independently associated with the risk of SHF morbidity, most ADRB1 and GRK5 polymorphisms did decrease significantly the risk of SHF morbidity after ß-blocker therapy except for those carrying genotype ADRB1 Gly389Gly.

Parthenolide-Induced Cytotoxicity in H9c2 Cardiomyoblasts Involves Oxidative Stress.

BACKGROUND: Cardiac cellular injury as a consequence of ischemia and reperfusion involves nuclear factor-κB (NF-κ B), amongst other factors, and NF-κ B inhibitors could substantially reduce myocardial infarct size. Parthenolide, a sesquiterpene lactone compound which could inhibit NF-κ B, has been shown to ameliorate myocardial reperfusion injury but may also produce toxic effects in cardiomyocytes at high concentrations. The aim of this study was to examine the cytotoxic effects of this drug on H9c2 cardiomyoblasts, which are precursor cells of cardiomyocytes. METHODS: Cell viability and apoptosis were examined by MTT and TUNEL assay, respectively, and protein expression was analyzed by western blot. Reactive oxygen species (ROS) production was measured using DCFH-DA as dye. Cytosolic Ca(2+) concentration and mitochondrial membrane potential were measured microfluorimetrically using, respectively, fura 2 and rhodamine 123 as dyes. RESULTS: Parthenolide caused apoptosis at 30 µ M, as judged by TUNEL assay and Bax and cytochrome c translocation. It also caused collapse of mitochondrial membrane potential and endoplasmic reticulum stress. Parthenolide triggered ROS formation, and vitamin C (antioxidant) partially alleviated parthenolide-induced cell death. CONCLUSIONS: The results suggested that parthenolide at high concentrations caused cytotoxicity in cardiomyoblasts in part by inducing oxidative stress, and demonstrated the imperative for cautious and appropriate use of this agent in cardioprotection. KEY WORDS: Cardiomyoblast; Endoplasmic reticulum stress; Oxidative stress; Parthenolide; Reperfusion injury.

Role of ZIC1 methylation in hepatocellular carcinoma and its clinical significance.

Hepatocellular carcinoma (HCC) is one of the most aggressive malignancies in humans, and its prognosis is generally poor even after surgery. The zinc finger of the cerebellum (ZIC1) gene is a novel tumor suppressor gene that plays a crucial role in vertebrate development. Altered expression of ZIC1 is observed in various types of human cancers. The aims of the present study were to investigate the methylation status of ZIC1 in HCC and evaluate its clinical implication. The methylation status of ZIC1 was analyzed in 132 pairs of HCC and corresponding noncancerous tissues by methylation-specific polymerase chain reaction (PCR) (MSP). The expression of ZIC1 messenger RNA (mRNA) in HCC tissues was examined by real-time PCR. Methylation frequency of ZIC1 in HCC was significantly higher than that in the corresponding noncancerous tissues (P < 0.001), and it was correlated with tumor size (P = 0.022), histological differentiation (P = 0.033), and tumor stage (P = 0.009). The downregulation of the ZIC1 mRNA expression in HCC was correlated with the ZIC1 methylation (P < 0.001). The patients with methylated ZIC1 had a poorer overall survival than those without methylated ZIC1 (P < 0.001). Taken together, our results suggested that the hypermethylation may lead to promoter silencing of ZIC1 mRNA and associated with poor survival in HCC. Overall, aberrant methylation is an important mechanism for ZIC1 inactivation in HCC, and ZIC1 methylation may be a promising biomarker for the diagnosis and prognosis of HCC.

Growth differentiation factor 15, ischemia modified albumin and pregnancy-associated plasma protein A in patients with coronary artery disease.

BACKGROUND: Growth differentiation factor 15 (GDF-15), ischemia modified albumin (IMA) might aid in the early diagnosis and risk stratification of patients with coronary artery disease (CAD), while pregnancy associated plasma protein-A (PAPP-A) can serve as a useful marker of vulnerable plaques and acute coronary syndrome (ACS). We sought to determine serum levels of GDF-15, IMA, PAPP-A and evaluate their diagnostic value in different types of CAD. METHODS: We detected serum levels of GDF-15, IMA and PAPP-A in 348 patients with CAD and 205 controls. Levels of high-sensitivity C reactive protein, creatine kinase isoenzyme MB, and high-sensitivity cardiac troponin-T, which represent biomarkers of inflammation, damage or necrosis, were also evaluated. RESULTS: There were significant differences of GDF-15, IMA and PAPP-A in patients with CAD compared with the controls, where GDF-15 seemed to be associated with severity of CAD. GDF-15 demonstrated a sensitivity of 84.0% and specificity of 84.8% for diagnosis of UAP, while the negative predictive value was 87.4%. The sensitivity and specificity, negative predictive value of IMA in the diagnosis of UAP were 70.0%, 69.5%, and 70.0%, respectively. PAPP-A had the lowest sensitivity and negative predictive value compared with other markers. CONCLUSIONS: GDF-15 demonstrated a significant improvement in earlier prediction and assessment of overall patient risk of UAP comparing to IMA and PAPP-A.

Age-specific 99th percentile cutoff of high-sensitivity cardiac troponin T for early prediction of non-ST-segment elevation myocardial infarction (NSTEMI) in middle-aged patients.

BACKGROUND: High-sensitivity cardiac troponin T (hs-cTnT) assay is used in the diagnosis and risk assessment of patients with symptoms of myocardial infarction. This study was undertaken to establish an age-specific 99th percentile cutoff value for hs-cTnT in Chinese population, and to evaluate its potential for early prediction of non-ST-segment elevation myocardial infarction (NSTEMI) in middle-aged patients. METHODS: Troponin T levels in blood obtained from healthy Chinese adults were assayed using hs-cTnT. The distribution was plotted and 99th percentiles were determined by nonparametric statistics. Prediction performance at the conventional cutoff (14 ng/L) recommended by the Roche company was compared with the age-specific cutoff for NSTEMI in 100 middle-aged patients (40-60 years of age) with acute chest pain. RESULTS: The 99th percentile for hs-cTnT was 14 ng/L for patients ≥60 years of age and 11 ng/L for those <60. Fifty of the 100 patients were finally diagnosed with NSTEMI. The age-specific 99th percentile cutoff value of 11 ng/L identified a higher number of patients with NSTEMI than the conventional 14 ng/L cutoff (46 vs. 40 patients), although the difference was not statistically significant (P = 0.084). In addition, the sensitivity of hs-cTnT increased from 80 to 92% and the negative predictive values increased from 82.4 to 91.8%. CONCLUSION: Using 11 ng/L as a decision-making cutoff point for hs-cTnT facilitated earlier prediction of NSTEMI in middle-aged patients than the conventional 14 ng/L cutoff. Further studies are needed to confirm this finding in larger group of patients.

Spatiotemporal alterations in the brain oscillations of Arctic explorers.

BACKGROUND: The limited understanding of the physiology and psychology of polar expedition explorers has prompted concern over the potential cognitive impairments caused by exposure to extreme environmental conditions. Prior research has demonstrated that such stressors can negatively impact cognitive function, sleep quality, and behavioral outcomes. Nevertheless, the impact of the polar environment on neuronal activity remains largely unknown. METHODS: In this study, we aimed to investigate spatiotemporal alterations in brain oscillations of 13 individuals (age range: 22 - 48 years) who participated in an Arctic expedition. We utilized electroencephalography (EEG) to record cortical activity before and during the Arctic journey, and employed standardized low resolution brain electromagnetic tomography to localize changes in alpha, beta, theta, and gamma activity. RESULTS: Our results reveal a significant increase in the power of theta oscillations in specific regions of the Arctic, which differed significantly from pre-expedition measurements. Furthermore, microstate analysis demonstrated a significant reduction in the duration of microstates (MS) D and alterations in the local synchrony of the frontoparietal network. CONCLUSION: Overall, these findings provide novel insights into the neural mechanisms underlying adaptation to extreme environments. These findings have implications for understanding the cognitive consequences of polar exploration and may inform strategies to mitigate potential neurological risks associated with such endeavors. Further research is warranted to elucidate the long-term effects of Arctic exposure on brain function.

GATA4 loss-of-function mutations underlie familial tetralogy of fallot.

Tetralogy of Fallot (TOF) represents the most common form of cyanotic congenital heart disease and accounts for significant morbidity and mortality in humans. Emerging evidence has implicated genetic defects in the pathogenesis of TOF. However, TOF is genetically heterogeneous and the genetic basis for TOF in most patients remains unclear. In this study, the GATA4 gene were sequenced in 52 probands with familial TOF, and three novel heterozygous mutations, including A9P and L51V both located in the putative first transactivational domain and N285S in the C-terminal zinc finger, were identified in three probands, respectively. Genetic analysis of the pedigrees demonstrated that in each family the mutation cosegregated with TOF with complete penetrance. The missense mutations were absent in 800 control chromosomes and the altered amino acids were highly conserved evolutionarily. Functional analysis showed that the GATA4 mutants were consistently associated with diminished DNA-binding affinity and decreased transcriptional activity. Furthermore, the N285S mutation completely disrupted the physical interaction between GATA4 and TBX5. To our knowledge, this report associates GATA4 loss-of-function mutations with familial TOF for the first time, providing novel insight into the molecular mechanism involved in TOF and suggesting potential implications for the early prophylaxis and allele-specific therapy of TOF.

Dual human iPSC-derived cardiac lineage cell-seeding extracellular matrix patches promote regeneration and long-term repair of infarcted hearts.

Human pluripotent stem cell-derived cardiovascular progenitor cells (hCVPCs) and cardiomyocytes (hCMs) possess therapeutic potential for infarcted hearts; however, their efficacy needs to be enhanced. Here we tested the hypotheses that the combination of decellularized porcine small intestinal submucosal extracellular matrix (SIS-ECM) with hCVPCs, hCMs, or dual of them (Mix, 1:1) could provide better therapeutic effects than the SIS alone, and dual hCVPCs with hCMs would exert synergic effects in cardiac repair. The data showed that the SIS patch well supported the growth of hCVPCs and hCMs. Epicardially implanted SIS-hCVPC, SIS-hCM, or SIS-Mix patches at 7-day post-myocardial infarction significantly ameliorated functional worsening, ventricular dilation and scar formation at 28- and 90-day post-implantation in C57/B6 mice, whereas the SIS only mildly improved function at 90-day post-implantation. Moreover, the SIS and SIS-cell patches improved vascularization and suppressed MI-induced cardiomyocyte hypertrophy and expression of Col1 and Col3, but only the SIS-hCM and the SIS-Mix patches increased the ratio of collagen III/I fibers in the infarcted hearts. Further, the SIS-cell patches stimulated cardiomyocyte proliferation via paracrine action. Notably, the SIS-Mix had better improvements in cardiac function and structure, engraftments, and cardiomyocyte proliferation. Proteomic analysis showed distinct biological functions of exclusive proteins secreted from hCVPCs and hCMs, and more exclusive proteins secreted from co-cultivated hCVPCs and hCMs than mono-cells involving in various functional processes essential for infarct repair. These findings are the first to demonstrate the efficacy and mechanisms of mono- and dual-hCVPC- and hCM-seeding SIS-ECM for repair of infarcted hearts based on the side-by-side comparison.

The analysis of the characteristics of imported COVID-19 cases from January to April in 2020: a cross-sectional study.

Background: Since the first case reported in December 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused an outbreak of coronavirus disease 2019 (COVID-19) worldwide. The global case count continued to rise and the WHO declared a Public Health Emergency of International Concern (PHEIC), causing a growing risk of imported COVID-19 infection. This study aimed to provide descriptive and quantitative epidemiological characteristics of imported COVID-19 cases in China. Methods: This cross-sectional study examined all imported COVID-19 cases in Mainland China from 22 January to 21 April 2020. Ratios, Median and percentile were used for descriptive analysis. Spearman's correlation analysis was performed between daily new imported cases in Mainland China and the country of origin. The chi-square test was used to evaluate the difference between home quarantine and compulsory centralized quarantine on native transmission. Results: A total of 1,610 cases of COVID-19 were imported from 49 countries to 27 provincial administrative regions in China; 79.8% were from European countries and the United States of America (the USA). Before 29 March 2020, the imported cases were mainly from the USA (27.7%) and United Kingdom (UK; 42.6%). After 29 March 2020, the daily newly imported cases from Russia rapidly grew. After 12 April 2020, the number of daily newly imported cases gradually decreased and remained at a low level (12±7 cases per day). Airport entry was encouraged, and ground border crossing was limited. Among the 1,610 cases, 54.0% were in the asymptomatic incubation period on arrival in Mainland China. Conclusions: The transmissions by imported COVID-19 were gradually and effectively curbed in Mainland China, despite a disproportionally high number of cases worldwide. Entry screening measures must be implemented universally to all inbound travelers at a point of entry or targeted to specific travel routes or to specific travelers. Compulsory centralized quarantine should be recommended in the prevention of the imported COVID-19 epidemic.

Well-organized zeolite nanocrystal aggregates with interconnected hierarchically micro-meso-macropore systems showing enhanced catalytic performance.

Preparation and characterization of well-organized zeolitic nanocrystal aggregates with an interconnected hierarchically micro-meso-macro porous system are described. Amorphous nanoparticles in bimodal aluminosilicates were directly transformed into highly crystalline nanosized zeolites, as well as acting as scaffold template. All pores on three length scales incorporated in one solid body are interconnected with each other. These zeolitic nanocrystal aggregates with hierarchically micro-meso-macroporous structure were thoroughly characterized. TEM images and (29)Si NMR spectra showed that the amorphous phase of the initial material had been completely replaced by nanocrystals to give a micro-meso-macroporous crystalline zeolitic structure. Catalytic testing demonstrated their superiority due to the highly active sites and the presence of interconnected micro-meso-macroporosity in the cracking of bulky 1,3,5-triisopropylbenzene (TIPB) compared to traditional zeolite catalysts. This synthesis strategy was extended to prepare various zeolitic nanocrystal aggregates (ZSM-5, Beta, TS-1, etc.) with well-organized hierarchical micro-meso-macroporous structures.

Relationship of arterial stiffness and early mild diastolic heart failure in general middle and aged population.

AIMS: The brachial-ankle pulse wave velocity (baPWV) has been recognized as a marker that reflects arterial stiffness. We conducted an investigation to evaluate whether baPWV is independently associated with early mild diastolic heart failure (DHF) in a general middle and aged population. METHODS AND RESULTS: From 1 July 2009 until 31 August 2009, we investigated 2095 subjects for the relevant factors of heart failure in the Lujiazui Community, Shanghai. The baPWV, echocardiography, and blood sampling were performed in the morning after a 12 h overnight fast. A total of 1929 subjects had the complete data, including questionnaire, age, gender, baPWV, brain natriuretic peptide, and E/A ratio. Early mild DHF was defined as a left ventricular ejection fraction >50%, E/A ratio <0.8, and E/E' ≤ 8; finally, 482 subjects with early mild DHF and 1282 subjects with non-DHF entered into analysis. Among 1764 subjects, 31.6% of the subjects were male (average age was 58.0 ± 12.3), 35.8% of the subjects had hypertension, the average body mass index (BMI) was 24.2 ± 3.3 kg/m(2), baPWV was 1513.0 (1329.1, 1763.5) cm/s, and the baPWV was significantly correlated with the E/A ratio (r = -0.39, P < 0.01). There was a difference of the baPWV [1456.0 (1295.3, 1698.3) vs. 1670.5 (1465.6, 1910.8) cm/s] between the non-DHF group and the early mild DHF group (P < 0.01). Multiple logistic-regression analyses demonstrated that age, male gender, BMI, baPWV, posterior left ventricular wall thickness (PVWT), interventricular septal thickness (IVST), E/E' ratio, left ventricular mass index (LVMI), systolic blood pressure (≥140 mmHg), and diastolic blood pressure (≥90 mmHg) were independently correlated with early mild DHF. CONCLUSIONS: The increased arterial stiffness is associated with early mild DHF in a general middle and aged population independently of age, male gender, BMI, PVWT, IVST, E/E' ratio, LVMI, and high blood pressure. The non-invasive techniques described may allow serial measurements to be made over time to monitor baPWV changes in arteries provided the introduction of anti-arteriosclerosis therapy.

An induced pluripotent stem cell line (EHTJUi003-A) generated from a neonate with c.1377delC mutation in the gene MYBPC3 causing hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is an autosomal dominant heart disease. An induced pluripotent stem cell line (EHTJUi003-A) was generated from umbilical cord blood mononuclear cells (UCBMCs) of a female neonate with heterozygous mutation of p.L460Wfs (c.1377delC) in the MYBPC3 gene. This iPSC model offers a very valuable resource to study the pathological mechanism of HCM in vitro.

An induced pluripotent stem cell line (EHTJUi004-A) generated from a neonate with c.4683_4684delCT:p.Leu1563fs mutation in the gene DSP causing Familial Arrhythmogenic Right Ventricular Dysplasia (ARVD).

Familial Arrhythmogenic Right Ventricular Dysplasia (ARVD) is a primary cardiomyopathy characterized by the abnormality of the right ventricular muscle. ARVD may be life-threatening due to the induction of paroxysmal refractory ventricular tachycardia or supraventricular arrhythmia. A human induced pluripotent stem cell line (EHTJUi004-A) was generated from human umbilical cord blood mononuclear cells (UCBMCs) of a female neonate with heterozygous mutation of p.Leu1563fs (c.4683_4684delCT) in the DSP gene. This iPS cell line resource provides an ideal in vitro model to study the pathological mechanism of ARVD.

CRISPR/Cas9 mediated generation of a iPSC line EHTJUi005-A-1 with homozygous knockout of the SUV39H1 gene.

SUV39H1 is a histone methyltransferase involve numerous biological processes, including of aging, embryo development, tumor growth and mitosis via catalysis of dimethylation and trimethylation of lysine 9 of histone H3. Here we report a human induced pluripotent stem cell line (EHTJUi005-A-1) which is generated from a wildtype human iPSC previously established in our laboratory, and this iPSC has a homozygous knockout of 8 bp in Exon 2 of SUV39H1. This iPSC model provides a valuable resource to study epigenetic regulation in extensive biological processes as mentioned above.

Generation of a laminopathies-specific iPSC line EHTJUi005-A-3 with homozygous knockout of the LMNA gene by CRISPR/Cas9 technology.

LAMIN A/C, encoded by the LMNA gene, supports the normal structure of the cell nucleus and regulates the connection between the nucleus and the cytoskeleton as a component of the nucleus envelope. The loss of expression and function of the LMNA gene would lead to the occurrence of congenital muscular dystrophy and Emery-Dreifuss muscular dystrophy which are collectively named as laminopathies. Here, we report a human induced pluripotent stem cell (iPSC) line (EHTJUi005-A-3) generated from a wild iPSC (EHTJUi005-A) with homozygous knockout of the gene LMNA through CRISPR/Cas9. This iPSC line provides a useful research model for studying laminopathies disease.

[Helicobacter pylori infection enhances atherosclerosis in high-cholesterol diet fed C57BL/6 mice].

OBJECTIVE: To evaluate the impacts of Helicobacter pylori (H. pylori) infection on atherosclerosis and plasma lipid levels in high-cholesterol diet fed C57BL/6 mice. METHOD: Female C57BL/6 mice were randomly divided into 4 groups (n = 12 each): fed with normal chow diet (A), infected with H. pylori (B), fed with high-cholesterol diet (C) and infected with H. pylori and fed with high-cholesterol diet (D). After 52 weeks, plasma levels of lipids were measured and aortic atherosclerosis was observed. The ureA, ureC, cagA and vacA DNA were also detected by PCR in the aortic arteries. RESULT: (1) Prevalence of atherosclerosis was similar between group C and D (91.6% vs. 100%, P > 0.05) while there was no atherosclerosis in group A and B. H. pylori infected mice showed more obvious inflammation in gastric mucosa than mice without H. pylori infection. (2) The plasma levels of triglyceride, total cholesterol and LDL were higher and HDL was lower in group B, C and D than those in group A and in group D than in group C (all P < 0.05). (3) Roberts & Thompson scores and number of foam cells in plaques were significantly higher in group D compared with those in group C (all P < 0.05). (4) ureC DNA was detected in 5 out of 12 aortic arteries of mice in group D but not in group A, B and C. CONCLUSION: Our results suggested that H. pylori infection might enhance the atherosclerotic lesion formation in this mouse model.