Association of TyG index with hypertension in Chinese adults: the China Health Examination Collaborative Study (CHEC Study).

BACKGROUND AND OBJECTIVES: We aimed to investigate the association of triglyceride-glucose (TyG) index with hypertension and compare the discriminative power of the TyG index, lipid, glycemic parameters for hypertension using the China Health Examination Collaborative study (CHEC Study). METHODS AND STUDY DESIGN: Data were collected at Ningbo Mingzhou Hospital and Beijing physical examination center from the CHEC Study during 2014 and 2021. Participants with ≥2 medical check-up times were included. The TyG index is the logarithmized product of fasting triglyceride and glucose. Generalised estimation equation (GEE) model was used to evaluate the association between the TyG index, lipid parameters, glycemic parameters and hypertension. Receiver operating characteristic (ROC) analysis was performed to explore the predictive ability of TyG index on hypertension at different years of medical check-up. RESULTS: 112,902 participants with an average age of 42.8 years were recruited in the study, 36,839 participants developed hypertension over the 8-year period. GEE model analysis showed that the ORs with 95% CI of hypertension were 3.35 (3.15-3.57), 1.86 (1.76-1.95), 1.67 (1.58-1.78), 1.45 (1.33-1.58), 1.24 (1.19-1.29), 0.92 (0.86-0.99), and 1.90 (1.83-1.97) in the highest versus lowest quintiles of TyG index, TG/HDL-C ratio, TG, TC, LDL-C, HDL-C and FPG in model 2. The area under the ROC curve of the overall years of medical check-up was signifi-cantly higher than a particular year in predicting hypertension (AUC: 0.883, p < 0.05). CONCLUSIONS: TyG index is associated with hypertension and shows the superior discriminative ability for hypertension compared with lipid and glycemic parameters.

ß-Catenin promotes long-term survival and angiogenesis of peripheral blood mesenchymal stem cells via the Oct4 signaling pathway.

Stem cell therapy has been extensively studied to improve heart function following myocardial infarction; however, its therapeutic potency is limited by low rates of engraftment, survival, and differentiation. Here, we aimed to determine the roles of the ß-catenin/Oct4 signaling axis in the regulation of long-term survival and angiogenesis of peripheral blood mesenchymal stem cells (PBMSCs). These cells were obtained from rat abdominal aortic blood. We showed that ß-catenin promotes the self-renewal, antiapoptotic effects, and long-term survival of PBMSCs by activating the Oct4 pathway through upregulation of the expression of the antiapoptotic factors Bcl2 and survivin and the proangiogenic cytokine bFGF and suppression of the levels of the proapoptotic factors Bax and cleaved caspase-3. ß-Catenin overexpression increased Oct4 expression. ß-Catenin knockdown suppressed Oct4 expression in PBMSCs. However, ß-catenin levels were not affected by Oct4 overexpression or knockdown. Chromatin immunoprecipitation assays proved that ß-catenin directly regulates Oct4 transcription in PBMSCs. In vivo, PBMSCs overexpressing ß-catenin showed high survival in infarcted hearts and resulted in better myocardial repair. Further functional analysis identified Oct4 as the direct upstream regulator of Ang1, bFGF, HGF, VEGF, Bcl2, and survivin, which cooperatively drive antiapoptosis and angiogenesis of engrafted PBMSCs. These findings revealed the regulation of ß-catenin in PBMSCs by the Oct4-mediated antiapoptotic/proangiogenic signaling axis and provide a breakthrough point for improving the long-term survival and therapeutic effects of PBMSCs.

Oct4 cooperates with c-Myc to improve mesenchymal-to-endothelial transition and myocardial repair of cardiac-resident mesenchymal stem cells.

BACKGROUND: Cardiac-resident mesenchymal stem cells (cMSCs) can exhibit fibrotic, proinflammatory, and proangiogenic phenotype in response to myocardial ischemia (Isch). How their phenotypic fate decisions are determined remains poorly understood. Here, we demonstrate that the cooperation of Oct4 and c-Myc in cMSCs creates a preferable mesenchymal-to-endothelial transition (MEndoT) to promote angiogenesis and consequent myocardial repair. METHODS: We collected MSCs from cardiac and peripheral blood of rat with left ventricular Isch (LV Isch) 30 days after myocardial infarction (MI) or sham operation. After a comparison of characterization between cMSCs and peripheral blood MSCs (pbMSCs), we conducted transcriptome analysis and RNA sequencing of cMSCs. Using loss/gain-of-function approaches to understand the cooperation of c-Myc and Oct4 on MEndoT of cMSCs under hypoxic condition, we explored the mechanisms through transcriptome and functional experiment, and chromatin immunoprecipitation. Next, we transplanted male cMSCs with overexpression or inhibition of c-Myc/Oct4 into the infarcted myocardium of female rats and evaluated infarct size, cell retention, inflammation, remodeling, and function after 30 days. RESULTS: LV Isch switched cMSCs toward both inflammatory and proangiogenic phenotypes, with increased secretion of inflammatory cytokines as well as decreased expression of proangiogenic factors. The effect of LV Isch on pbMSCs was less remarkable. Gene expression heatmap showed imbalance in expression of Oct4 and c-Myc regulating genes associated with remodeling of cMSCs. We provided evidence that cMSCs-specific c-Myc- versus Oct4-overexpression showed divergent genomic signatures, and their corresponding target genes play an important role in regulating cMSCs phenotypic changes. In particular, Oct4 accelerated angiogenesis induced by c-Myc overexpression in cMSCs and inhibited their phenotypic transition into inflammatory cells and fibroblast. Mechanistically, exogenous Oct4 caused c-Myc to translocate from the nucleus to the cytoplasm and activated some of its target signalings including VEGF signaling. Although transplantation of cMSCs alone did not improve LV remodeling and function, cMSCs co-transfected with c-Myc and Oct4 promoted a more positive effect in their survival and reparative properties, increased animal survival, reduced infarct size, decreased scar thickness, inhibited LV remodeling, and improved heart function 30 days after MI. Significantly, Oct4 promoted MEndoT ("Rescue me" signal) of cMSCs after both c-Myc stimulation in vitro and transplantation into the infarcted heart. CONCLUSIONS: Myocardial Isch drives resident cMSCs toward multiple phenotypes. Oct4 interacts with c-Myc to promote MEndoT capacity of cMSCs and improve their survival and reparative effects through upregulation of angiogenesis-related signaling pathways. These findings may identify novel targets for stem cell therapy.

Chief Financial Officer Functional Diversity and the Timeliness of Annual Reports: A Comparative Study of Firms With Different Ownership Types.

Functional diversity is related to functional areas in which CFOs are experienced. It reflects their number of general managerial skills or social ties to some extent. In this paper, we try to examine whether there is an association between CFO functional diversity and the timeliness of annual reports. Using data on Chinese listed firms from 2009 to 2017, we found that in state-owned enterprises, there is a negative relationship between this diversity and timeliness. However, the promotion incentive of CFOs with functionally diverse experience can weaken this negative relationship. We also found that there is a positive relationship between the two factors in private enterprises whose offices are headquartered in regions with a low degree of marketization. We use difference-in-differences method to test the hypotheses again. The conclusions remain robust.

Diagnostic and prognostic value of serum Chitinase 3-like protein 1 in hepatocellular carcinoma.

The serum Chitinase 3-like protein 1 (CHI3L1) protein level can distinguish the stages of liver fibrosis to a great extent. However, the diagnostic and prognostic significance of serum CHI3L1 in hepatocellular carcinoma (HCC) is not clarified. To evaluate the diagnostic and prognostic value of CHI3L1 in HCC, a total of 128 HCC patients treated in the HwaMei Hospital, University of Chinese Academy of Sciences, from December 2018 to April 2020 were collected retrospectively. Matched age and gender subjects, 40 patients with liver cirrhosis, 40 patients with chronic hepatitis, and 40 healthy subjects were enrolled in the control group. The relevant clinical laboratory and examination data and the overall survival time (OS) of the HCC patients were collected. The serum CHI3L1 expression level is related to α-fetoprotein (AFP), tumor-node-metastasis (TNM) stage, maximum tumor diameter, liver cirrhosis, and HCC patient's OS (p < 0.05). The area under the curve (AUC) of CHI3L1 was 0.7875 with the cutoff value of 91.36 ng/ml. Combining the serum CHI3L1 and α-fetoprotein (AFP) by a binary logistic regression model can increase the diagnostic sensitivity to 97.5%. Multivariate Cox regression analysis indicated that CHI3L1 is an independent prognostic factor in patients with HCC.

Oct4-dependent FoxC1 activation improves the survival and neovascularization of mesenchymal stem cells under myocardial ischemia.

BACKGROUND: The administration of mesenchymal stem cells (MSCs) remains the most promising approach for cardiac repair after myocardial infarct (MI). However, their poor survival and potential in the ischemic environment limit their therapeutic efficacy for heart repair after MI. The purpose of this study was to investigate the influence of FoxC1-induced vascular niche on the activation of octamer-binding protein 4 (Oct4) and the fate of MSCs under hypoxic/ischemic conditions. METHODS: Vascular microenvironment/niche was induced by efficient delivery of FoxC1 transfection into hypoxic endothelial cells (ECs) or infarcted hearts. MSCs were cultured or injected into this niche by utilizing an in vitro coculture model and a rat MI model. Survival and neovascularization of MSCs regulated by Oct4 were explored using gene transfer and functional studies. RESULTS: Here, using gene expression heatmap, we demonstrated that cardiac ECs rapidly upregulated FoxC1 after acute ischemic cardiac injury, contributing to an intrinsic angiogenesis. In vitro, FoxC1 accelerated tube-like structure formation and increased survival of ECs, resulting in inducing a vascular microenvironment. Overexpression of FoxC1 in ECs promoted survival and neovascularization of MSCs under hypoxic coculture. Overexpression of Oct4, a FoxC1 target gene, in MSCs enhanced their mesenchymal-to-endothelial transition (MEndoT) while knockdown of Oct4 by siRNA altering vascularization. In a rat MI model, overexpression of FoxC1 in ischemic hearts increased post-infarct vascular density and improved cardiac function. The transplantation of adOct4-pretreated MSCs into these ischemic niches augments MEndoT, enhanced vascularity, and further improved cardiac function. Consistently, these cardioprotective effects of FoxC1 was abrogated when Oct4 was depleted in the MSCs and was mimicked by overexpression of Oct4. CONCLUSIONS: Together, these studies demonstrate that the FoxC1/Oct4 axis is an essential aspect for survival and neovascularization of MSCs in the ischemic conditions and represents a potential therapeutic target for enhancing cardiac repair.

Surface modification of manganese monoxide through chemical vapor deposition to attain high energy storage performance for aqueous zinc-ion batteries.

Surface modification of the manganese-based oxide electrode is considered to be a viable strategy to improve electrochemical property in aqueous zinc-ion batteries (ZIBs). However, the modification method through traditional wet-chemical technology can hardly to satisfy high rate capability for aqueous ZIBs due to unhomogeneous and nonconformal coating originates from surface energy mismatch. Herein, a surface modification strategy based on chemical vapor deposition is developed to enhance the electrochemical property of the inactive MnO in aqueous ZIBs. The constructed carbon coating modified MnO electrode shows excellent reversible capacity and superior rate capability with remarkable energy density of 351 Wh kg-1 at 625 W kg-1. The energy storage mechanism of the electrode during the charge and discharge processes is elucidated according to the ex-situ measurements of X-ray diffraction and photoelectron spectroscopy, Fourier transform infrared spectra, and galvanostatic intermittent titration techniques. Moreover, soft-packaged batteries are fabricated with the carbon coating modified MnO, which shows great promises for the practical application of the material. The work paves the way for the exploitation of high performance surface-modified electrode through chemical vapor deposition for aqueous ZIBs.

FoxC1-Induced Vascular Niche Improves Survival and Myocardial Repair of Mesenchymal Stem Cells in Infarcted Hearts.

AIMS: Forkhead box C1 (FoxC1) is essential for maintaining the hair follicle stem cell niche. The role of FoxC1 in maintaining mesenchymal stem cell (MSC) niches after myocardial infarction (MI) has not been directly determined to date. In this study, we determined to explore the possible roles and mechanisms of FoxC1 on MSC survival and function in the ischemic niche. METHODS AND RESULTS: MI model was established in this study, and expression level of FoxC1 was overexpressed or knocked down through efficient delivery of FoxC1 transfection or siFoxC1. Fifteen days later, the animals were allocated randomly to receive phosphate-buffered saline (PBS) injection or MSC transplantation. We identified FoxC1 as a key regulator of maintaining the vascular niche in the infarcted hearts (IHs) by driving proangiogenic and anti-inflammatory cytokines while repressing inflammatory and fibrotic factor expression. This vascular niche improved MSC survival and capacity in the IHs. Importantly, FoxC1 interacted with MSCs and was required for vessel specification and differentiation of engrafted MSCs in the ischemic niches, promoting myocardial repair. Inhibiting FoxC1 abolished these effects. CONCLUSION: These results definitively implicate FoxC1 signaling in maintaining ischemic vascular niche, which may be helpful in myocardial repair induced by MSC therapy.

TERT assists GDF11 to rejuvenate senescent VEGFR2+/CD133+ cells in elderly patients with myocardial infarction.

Growth differentiation factor 11 (GDF11) is a transforming growth factor ß superfamily member with a controversial role in rejuvenating old stem cells after acute injury in the elderly population. This study aimed to evaluate the effects of telomerase reverse transcriptase (TERT) on GDF11-mediated rejuvenation of senescent late-outgrowth endothelial progenitor cells (EPCs), defined as VEGFR2+/CD133+ cells, in elderly patients with acute myocardial infarction (AMI). We compared the quantity and capabilities of VEGFR2+/CD133+ cells from old (>60 years), middle-aged (45-60 years), and young (<45 years) AMI patients. The decline in circulating count and survival of VEGFR2+/CD133+ cells with age was accompanied by decrease in their TERT and GDF11 expression levels in patients with AMI. Further, upregulation of TERT could trigger GDF11-mediated rejuvenation of old VEGFR2+/CD133+ cells by renewing their survival and angiogenic abilities through activation of canonical (Smad2/3) and noncanonical (eNOS) signaling pathways. Depletion of GDF11 or TERT caused senescence of young VEGFR2+/CD133+ cells leading to impaired vascular function and angiogenesis in vitro and in vivo, whereas adTERT and rhGDF11 rescued this senescence. TERT cooperates with GDF11 to enhance regenerative capabilities of old VEGFR2+/CD133+ cells. When combined with TERT, GDF11 may represent a potential therapeutic target for the treatment of elderly patients with MI.

Effect of Intracoronary Plus Low-Dose Intravenous Tirofiban in Elderly Patients with Acute Myocardial Infarction.

BACKGROUND: To investigate the efficacy and safety of low-dose tirofiban in elderly patients undergoing primary percutaneous coronary intervention (PPCI) for acute myocardial infarction (AMI). METHODS: One hundred and four patients aged 70 years and above undergoing PPCI for AMI were divided into control (n=52) and study (n=52) groups. All patients received bolus intracoronary injection of tirofiban (10µg/kg), which was followed by intravenous infusion at 0.15µg/kg/min in the control group and at 0.075µg/kg/min in the study group for 24h. RESULTS: There was no statistically significant difference between the study group and the control group in patients with complete ST segment resolution (84.2% vs. 85.7%, P=0.851), peak high-sensitive cardiac troponin T level (5.1±1.9 vs. 5.8±2.6µg/L, P=0.123), scores of thrombus in the infarct-related artery (0.98±0.51 vs. 1.12±0.59, P=0.214), and patients with TIMI grade 3 flow (86.0% vs. 88.2%, P=0.737) after PPCI. There were no statistically significant differences between the two groups in left ventricular ejection fraction (57.1±6.3 vs. 57.7±6.1, P=0.611) and composite major adverse cardiovascular events rate (P =0.778) at 90 days after PCI. The total bleeding rate in the study group was lower than in the control group (P=0.048). CONCLUSION: In elderly patients with AMI undergoing primary PCI, low and standard dose of tirofiban exerts similar effects on platelet aggregation, coronary flow, infarct size, left ventricular systolic function and short-term clinical outcomes. Low dose regimen is associated with a lower bleeding rate than the standard dose.

Therapeutic efficacy of a modified method with splints in correction of cryptotia / 中华整形外科杂志

<p><b>OBJECTIVE</b>To explore the therapeutic efficacy of a modified method with splints in correction of cryptotia.</p><p><b>METHODS</b>From Oct. 2012 to Jan. 2014, 3 cases with unilateral cryptotia were treated with the modified method with splints. The muscles attached to the periosteum of cartilage were dissected. The muscles between the ear and temper were cut off. Then one silicon tube was put around the ear through cranioauricular sulcus. The other tube was placed within the cavum conchae and fixed with the tube around the ear.</p><p><b>RESULTS</b>No flap necrosis happened. The patients were followed up for six months to one year with satisfied and stable results.</p><p><b>CONCLUSIONS</b>The modified method is easy to perform with less morbidity. It is one of the ideal correction for cryptotia.</p>

Effect of intracoronary tirofiban in patients undergoing percutaneous coronary intervention for acute coronary syndrome.

BACKGROUND: To investigate the efficacy of intracoronary tirofiban during primary percutaneous coronary intervention (PCI) for patients with acute coronary syndrome (ACS). METHODS AND RESULTS: The 118 patients aged 70 years and above (average age 75+/-2) were divided into study (n = 58, intracoronary bolus tirofiban) and control (n = 57, intravenous tirofiban) groups. The culprit vessels were targeted with primary PCI in all patients. Compared with the control group, the study group showed better Thrombolysis In Myocardial Infarction (TIMI) flow grades and TIMI myocardial perfusion grades (TMPG) immediately after PCI (p = 0.016 and 0.026, respectively). The 14-day composite major adverse cardiac events rate was lower in the study group (3.5% vs 17.5%, p = 0.030), but was similar between the 2 groups at 30 days following PCI (7.0% vs 1.7%, p = 0.350). The left ventricular ejection fraction in the study group was higher than in the control group 30 days following PCI (67.4+/-6.2% vs 60.7+/-4.6%, p = 0.033). The 14-day bleeding complication (p = 0.201) and platelet reduction rates (p = 0.984) were similar between the 2 groups. CONCLUSION: In patients with ACS undergoing primary PCI, intracoronary bolus administration of tirofiban is superior to intravenous bolus injection for improving coronary flow, myocardial perfusion and short-term clinical outcomes.