Hypertension-specific association of cardio-ankle vascular index with subclinical left ventricular function in a Chinese population: Danyang study.

The association of cardio-ankle vascular index (CAVI), with subclinical cardiac dysfunction in hypertensive patients is unclear. We aim to examine their relationship in hypertensive patients compared with that in normotensive subjects. Our study included 1887 subjects enrolled from Danyang between 2018 and 2019. CAVI was measured using VaSera VS-1500A device. We performed conventional echocardiography to measure ejection fraction (EF) and E/A, tissue Doppler to measure mitral annular early diastolic velocities (e'), and speckle-tracking to estimate left ventricular (LV) global longitudinal strain (GLS). LV mass index (76.3, 80.0, and 84.0 g/m2), and E/e' (7.6, 8.2, and 8.8) were increased and GLS (21.1, 21.0, and 20.4%), E/A (1.2, 1.0, and 0.8) and e' velocity (11.2, 9.4, and 8.2 cm/s) was decreased from tertiles 1-3 of CAVI on unadjusted analyses (P < .001). After adjustment for covariates, GLS, E/A, and e' were still significantly decreased from tertiles 1-3 of CAVI (P ≤ .04). Further sensitive analyses revealed a similar association pattern for diastolic function but not systolic function. Compared with the lowest tertile, subjects with a top tertile of CAVI were at higher risk of subclinical LV systolic dysfunction in hypertensive patients (OR = 2.61; P = .005). Increased CAVI is associated with worse subclinical diastolic function. However, this relationship of CAVI to subclinical systolic function was more prominent in hypertensive patients.

Association of epicardial and visceral adipose tissue in relation to subclinical cardiac dysfunction in Chinese: Danyang study.

OBJECTIVE: Our study aims to examine the associations of visceral adipose tissue (VAT) and epicardial adipose tissue (EAT) with subclinical cardiac dysfunction in a Chinese population. DESIGN: Cross-sectional. BACKGROUND: EAT and VAT are the most important ectopic fat pools which were previously shown to be associated with subclinical cardiac dysfunction. However, few studies simultaneously measured both EAT thickness and VAT area, and explored their associations with cardiac dysfunction. Our study aims to examine the associations of VAT and EAT with subclinical cardiac dysfunction in a Chinese population. METHODS: The study subjects were recruited from Danyang County from 2018 to 2019. Using Philips CX50, we recorded EAT thickness at the end-systole in a long-axis view. The subclinical systolic and diastolic function were assessed by two-dimensional speckle tracking, and transmitral and tissue Doppler imaging, respectively. Using Omron HDS-2000, we measured VAT area by dual bioelectrical impedance analysis. RESULTS: The 1558 participants (age, 52.3±12.8 years) included 930 (59.7%) women. Compared with women, men had higher VAT area (99.4 vs 70.1 cm2; p<0.0001) but lower EAT thickness (4.02 vs 4.46 mm; p<0.0001). In simple correlation analyses, EAT thickness and VAT area were positively associated with E/e' ratio (r=0.16 to 0.20; all p<0.0001) and negatively with global longitudinal strain (GLS) and e' (r=-0.12 to -0.37; all p<0.0001). Furthermore, VAT area was associated with left ventricular ejection fraction (LVEF) (r=-0.14; p<0.0001). After adjustment for confounding factors, the association of EAT with GLS and that of VAT with e' and E/e' ratio remained significant (all p≤0.001), whereas the associations of EAT with subclinical diastolic dysfunction and that of VAT with systolic function became non-significant (all p≥0.11). Analyses on further adjustment for LVEF showed similar results. CONCLUSIONS: Increased EAT thickness was associated with worse subclinical systolic dysfunction, while greater VAT area was associated with early diastolic dysfunction.

Combined associations of obesity and metabolic health with subclinical left ventricular dysfunctions: Danyang study.

AIMS: The association of strictly defined metabolic healthy obese (MHO) with subclinical cardiac function was unclear. Our study aims to examine the role of MHO in subclinical cardiac dysfunction in a Chinese population. METHODS AND RESULTS: The study subjects were recruited from Danyang from 2017 to 2019. Obesity was defined by body mass index (BMI) categories (normal weight, overweight and obesity). Metabolic health was strictly defined as having neither any of the guidelines recommended metabolic syndrome components nor insulin resistance. Thus, subjects were grouped by BMI categories and metabolic health status as six groups. Preclinical systolic (global longitudinal strain [GLS]) and diastolic function were assessed by 2D speckle tracking, and transmitral and tissue Doppler imaging, respectively. The 2757 participants (mean age ± standard deviation, 52.7 ± 11.7 years) included 1613 (58.5%) women, 999 (36.2%) obese, 2080 (75.4%) metabolically unhealthy and 93 (3.4%) MHO participants. After adjustment for covariates, the trend was similar for left ventricular (LV) ejection fraction (Ptrend  ≥ 0.07) but significantly worse for GLS, e' and E/e' (Ptrend  ≤ 0.02) across the six groups or passing from normal weight to obese individuals irrespective of metabolic status. MHO participants had lower GLS (20.4 vs. 21.4%) and e' (9.6 vs. 10.6 cm/s) compared with controls (P < 0.0001) but had similar GLS (P = 0.47) compared with metabolically unhealthy obese (MUO). Regardless of obesity status, metabolically unhealthy participants had worse diastolic function compared with their metabolically healthy counterparts (P ≤ 0.0004). Compared with controls, MHO individuals were at higher risk of subclinical LV systolic dysfunction (OR = 3.44, 95% CI = 1.25-9.49, P = 0.02). These results were robust to sensitivity analysis. CONCLUSIONS: MHO was substantially associated with worse subclinical systolic function although early diastolic dysfunction seemed to be more accentuated in MUO.

Yin-xing-tong-mai decoction attenuates atherosclerosis via activating PPARγ-LXRα-ABCA1/ABCG1 pathway.

Atherosclerosis is now the major cause of mortality and morbidity worldwide. Formation of macrophage-derived foam cells is a hallmark of atherosclerosis, which is regulated by cholesterol uptake, intracellular metabolism, and efflux. PPARγ-LXRα-ABCA1/ABCG1 pathway plays an important part in regulating cholesterol efflux and this pathway could be a promising target for treating atherosclerosis. However, due to undesirable systemic effects, PPARγ agonist therapy for atherosclerosis remains challenging. Many traditional Chinese medicine has been well accepted and applied in atherosclerosis treatment. Yin-xing-tong-mai decoction (YXTMD) has been applied for treating atherosclerosis for decades. However, the mechanism remains to be explored. Here, we showed that YXTMD effectively attenuated atherosclerosis in ApoE-/- mice. YXTMD increased cholesterol efflux of foam cell by upregulation of ABCA1 and ABCG1 in vivo and in vitro. Through bioinformatic analysis and experimental validation, we found that PPARγ was an important downstream effector of YXTMD in macrophages. Reduction of PPARγ significantly decreased LXRα, ABCA1, and ABCG1 expression in macrophages, with reduced cholesterol efflux. In conclusion, these findings confirmed that YXTMD attenuated atherosclerosis by activating the PPARγ-LXRα- ABCA1/ABCG1 pathway to enhance cholesterol efflux.

Association of urine albumin-to-creatinine ratio with subclinical systolic dysfunction in hypertensive patients but not normotensive subjects: Danyang study.

The association of albuminuria, as measured by urine albumin-to-creatinine ratio (UACR) concentration, with subclinical cardiac dysfunction in hypertensive patients is unclear. Our study aimed to examine its relationship in hypertensive patients compared with that in normotensive patients. The study participants were recruited from Danyang, a city of Jiangsu Province from 2017 to 2019. Categorical and continuous analyses were performed with sex-specific UACR tertiles and natural logarithmically transformed UACR, respectively. Comprehensive echocardiography including conventional imaging, tissue Doppler imaging, and 2D speckle tracking was performed using Philips CX50 device. The 2857 participants (mean age = 52.7 ± 11.8 years) included 1673 (58.6%) women, 1125 (39.4%) hypertensive patients, 546 (19.1%) patients with microalbuminuria, and 38 (1.3%) patients with macroalbuminuria. Comorbidities were increasingly prevalent across the tertiles of UACR. Increased left ventricular (LV) mass index, decreased global longitudinal strain (GLS) and LV ejection fraction, lower E/A ratio and e' velocity, and higher E/e' ratio were significantly associated with higher UACR on unadjusted analyses (p ≤ .01). After adjustment for covariates, UACR was only independently associated with lower GLS (tertile 3 = 20.7% vs. tertile 1 = 20.9%; p = .04). The results of hypertensive patients (p ≤ .04) but not normotensive patients (p ≥ .16) were similar to those of the total cohort. Subgroup analyses revealed similar results in patients without coronary artery disease, or without LV hypertrophy, or without diabetes. In conclusion, increased UACR is associated with worse subclinical systolic function in Chinese hypertensive patients but not in normotensive participants.

Increased Circulating Chemerin in Relation to Chronic Microvascular Complications in Patients with Type 2 Diabetes.

OBJECTIVE: Type 2 diabetes (T2DM) is a global epidemic and increases mortality due to its vascular complications. Chemerin has been found to exert a major role in glucose and lipid metabolism. The aim of this study was to explore the correlation between plasma chemerin levels and microangiopathy in patients with T2DM. METHODS: A total of 598 T2DM patients were classified into two groups: with and without microvascular complications. Anthropometric parameters and blood pressure were taken. The amounts of glycosylated hemoglobin, glucose, lipid profiles, creatinine, and chemerin concentrations in the blood were determined. The presence and severity of nephropathy, retinopathy, and neuropathy were also evaluated by specific tests. RESULTS: Plasma levels of chemerin in diabetic subjects with microvascular complications were markedly elevated compared to those without. The number of microvascular complications increased with high plasma chemerin levels. Patients with high chemerin levels had an increased incidence of nephropathy and retinopathy. Furthermore, the chemerin plasma concentrations increased with the progression of diabetic nephropathy with highest values in macroalbuminuria groups. In contrast, no significant difference was observed in plasma chemerin levels between subjects with and without peripheral neuropathy. Pearson correlation analysis showed that plasma chemerin levels were positively related to duration of diabetes, serum creatinine, and 24-hour urine albumin excretion, even after multiple adjustments. Using logistic regression analysis, plasma chemerin concentrations were independently associated with the presence of nephropathy and retinopathy, not neuropathy. CONCLUSION: This study elucidated a positive correlation between increased chemerin levels and the development of some subtypes of diabetic microangiopathy.

Competing endogenous RNA network of endometrial carcinoma: A comprehensive analysis.

Competing endogenous RNA (ceRNA) network is dysregulated in the initiation and progression of tumors. In the present study, we explored the regulatory mechanism of ceRNA in endometrial carcinoma (EC) and the potential key molecules with potential value in the diagnosis, treatment, and prognosis of EC. The long noncoding RNAs (lncRNAs) and messenger RNAs (mRNAs) expression profiles (552 EC tissues and 35 nontumor tissues) and microRNAs (miRNAs) expression profiles (546 EC tissues and 33 nontumor tissues) were downloaded from The Cancer Genome Atlas database to identify differentially expressed RNAs (DERNAs) in EC. An integrated bioinformatics analysis was used to construct an EC-specific ceRNA network and select key molecules. As a result, 96 differentially expressed lncRNAs (DElncRNAs), 29 differentially expressed miRNAs (DEmiRNAs), and 77 differentially expressed mRNAs (DEmRNAs) were identified. An EC-specific ceRNA network was built based on nine DElncRNAs significantly associated with overall survival. CCNB1 was found as a key gene in EC through the weighted gene coexpression network analysis and protein-protein interaction network analysis. Our ceRNA network showed C2orf48 and LINC00483 might upregulate CCNB1 via competing with miR-183. In addition, we found a subnetwork which contained survival-associated DERNAs (AC110491.1, LINC00483-miR-192-GRHL1). The results of reverse transcription quantitative polymerase chain reaction supported the relative expressions of C2orf48, LINC00483 were upregulated and that of AC110491.1 was downregulated in EC. We further found C2orf48 was upregulated in serous EC, endometrioid EC, and mixed serous and endometrioid EC. LINC00483 was upregulated in mixed serous and endometrioid EC compared with that in the normal tissues according to UALCAN database. In addition, candidate small molecular drugs were screened out by ConnectivityMap based on the 77 DEmRNAs in the ceRNA network. Eventually, C2orf48, LINC00483, and AC110491.1 were identified as three key lncRNAs in EC.

ITLNI identified by comprehensive bioinformatic analysis as a hub candidate biological target in human epithelial ovarian cancer.

BACKGROUND: Epithelial ovarian cancer (EOC) is a female malignant tumor. Bioinformatics has been widely utilized to analyze genes related to cancer progression. Targeted therapy for specific biological factors has become more valuable. MATERIALS AND METHODS: Gene expression profiles of GSE18520 and GSE27651 were downloaded from Gene Expression Omnibus. We used the "limma" package to screen differentially expressed genes (DEGs) between EOC and normal ovarian tissue samples and then used Clusterprofiler to do functional and pathway enrichment analyses. We utilized Search Tool for the Retrieval of Interacting Genes Database to assess protein-protein interaction (PPI) information and the plug-in Molecular Complex Detection to screen hub modules of PPI network in Cytoscape, and then performed functional analysis on the genes in the hub module. Next, we utilized the Weighted Gene Expression Network Analysis package to establish a co-expression network. Validation of the key genes in databases and Gene Expression Profiling Interactive Analysis (GEPIA) were completed. Finally, we used quantitative real-time PCR to validate hub gene expression in clinical tissue samples. RESULTS: We analyzed the DEGs (96 samples of EOC tissue and 16 samples of normal ovarian tissue) for functional analysis, which showed that upregulated DEGs were strikingly enriched in phosphate ion binding and the downregulated DEGs were significantly enriched in glycosaminoglycan binding. In the PPI network, CDK1 was screened as the most relevant protein. In the co-expression network, one EOC-related module was identified. For survival analysis, database and clinical sample validation of genes in the turquoise module, we found that ITLN1 was positively correlated with EOC prognosis and had lower level in EOC than in normal tissues, which was consistent with the results predicted in GEPIA. CONCLUSION: In this study, we exhibited the key genes and pathways involved in EOC and speculated that ITLN1 was a tumor suppressor which could be used as a potential biomarker for treating EOC, Gene Expression Omnibus, prognosis.

Association of serum lipids and severity of epithelial ovarian cancer: an observational cohort study of 349 Chinese patients.

While obesity and fat intake have been associated with the risk and prognosis of epithelial ovarian cancer, the association between the lipid levels and epithelial ovarian cancer phenotype remains controversial. We conducted a retrospective study of 349 epithelial ovarian cancer patients who received treatment at Jiangsu Cancer Hospital, China between 2011 and 2017. We analyzed age at diagnosis, blood pressure, plasma glucose content, body mass index (BMI), lipid levels and clinical parameters. Severity of epithelial ovarian cancer was classified according to the International Federation of Gynecology and Obstetrics (FIGO) grading system. Univariate analysis of the clinical factors according to the severity of epithelial ovarian cancer was followed by logistic regression analysis to identify clinical factors significantly associated with epithelial ovarian cancer severity. Univariate analysis indicated that age, BMI, triglyceride (TG), and high density lipoproteins (HDL) differed significantly among different stages of epithelial ovarian cancer (P<0.05). In the logistic regression model, elevated TG (OR: 1.883; 95% CI= 1.207-2.937), and low HDL (OR: 0.497; 95% CI= 0.298-0.829) levels were significantly associated with the high severity epithelial ovarian cancer. Our data indicate that high TG and low HDL levels correlate with a high severity of epithelial ovarian cancer. These data provide important insight into the potential relationship between the lipid pathway and epithelial ovarian cancer phenotype and development.

Twisted bio-nanorods serve as a template for constructing chiroptically active nanoflowers.

Using biomacromolecule-based nanorods as a chiral source is a creative way to fabricate broadband chiroptically active nanoarchitectures. Herein, right-handedly twisted cellulose nanocrystal (CNC) nanorods, serving simultaneously as a chiral template and a building block, were combined with CuO for constructing composite nanoflowers that showed broadband chiroptical activity. Through calcination, the CuO/CNC nanoflowers can transform into chiral CuO with a flower-like architecture. The established preparation technology is expected to provide various novel broadband chiroptically active nanoarchitectures originating from CNCs and metal oxides.

Epigenetic modifications in KDM lysine demethylases associate with survival of early-stage NSCLC.

Background: KDM lysine demethylase family members are related to lung cancer clinical outcomes and are potential biomarkers for chemotherapeutics. However, little is known about epigenetic alterations in KDM genes and their roles in lung cancer survival. Methods: Tumor tissue samples of 1230 early-stage non-small cell lung cancer (NSCLC) patients were collected from the five independent cohorts. The 393 methylation sites in KDM genes were extracted from epigenome-wide datasets and analyzed by weighted random forest (Ranger) in discovery phase and validation dataset, respectively. The variable importance scores (VIS) for the sites in top 5% of both discovery and validation sets were carried forward for Cox regression to further evaluate the association with patient's overall survival. TCGA transcriptomic data were used to evaluate the correlation with the corresponding DNA methylation. Results: DNA methylation at sites cg11637544 in KDM2A and cg26662347 in KDM1A were in the top 5% of VIS in both discovery phase and validation for squamous cell carcinomas (SCC), which were also significantly associated with SCC survival (HRcg11637544 = 1.32, 95%CI, 1.16-1.50, P = 1.1 × 10-4; HRcg26662347 = 1.88, 95%CI, 1.37-2.60, P = 3.7 × 10-3), and correlated with corresponding gene expression (cg11637544 for KDM2A, P = 1.3 × 10-10; cg26662347 for KDM1A P = 1.5 × 10-5). In addition, by using flexible criteria for Ranger analysis followed by survival classification tree analysis, we identified four clusters for adenocarcinomas and five clusters for squamous cell carcinomas which showed a considerable difference of clinical outcomes with statistical significance. Conclusions: These findings highlight the association between somatic DNA methylation in KDM genes and early-stage NSCLC patient survival, which may reveal potential epigenetic therapeutic targets.

Construction of Molecularly Imprinted Polymer Microspheres by Using Helical Substituted Polyacetylene and Application in Enantio-Differentiating Release and Adsorption.

Chiral molecularly imprinted polymer microspheres (MIPMs) reported so far are majorly limited to being constructed by using achiral polymer together with chiral template. The present contribution reports on a unique type of chiral MIPMs consisting of chirally helical substituted polyacetylene, which are prepared through suspension polymerization by using (a)chiral acetylenics as monomer and chiral Boc-d/l-proline as template. The resulting MIPMs after removing the template show optical activity that is derived from the chirally helical structures of substituted polyacetylene. The microspheres demonstrate enantio-differentiating ability in releasing the enantiopure templates. A complete release of the template provides the chiral MIPMs. Worthy to mention is that the two chiral sources (chirally helical conformation and chiral template configuration) work in a synergistic way, obviously increasing the MIPMs' enantiodiscrimination ability. The present study develops a strategy for preparing chiral MIPMs, which are expected to find significant applications in chiral separation, enantioselective release of chiral drugs, etc.

Chiral porous hybrid particles constructed by helical substituted polyacetylene covalently bonded organosilica for enantioselective release.

Hybrid materials are interesting because they combine the advantages of multiple components in one material entity. This article reports on a new type of chiral porous hybrid particle constructed by helical substituted polyacetylene and silica. To prepare the hybrid particles, chirally helical substituted acetylene copolymers containing pendent Si-O-Et groups were first synthesized and subsequently used as macromolecular silane couplers to perform a sol-gel reaction with TEOS. After aging, the designed hybrid particles were fabricated. Phase separation in the sol-gel reaction endowed the hybrid particles with abundant pores. In the resulting hybrid particles, inorganic silica constituted the rigid framework, whereas the organic helical substituted polyacetylene bonded with the framework and offered optical activity. SEM images confirmed the formation of spherical particles with regular morphology and porous structure. Circular dichroism and UV-vis absorption spectra demonstrated that the helical polymer chains had a preferential helicity and considerable optical activity in the hybrid particles. The hybrid materials demonstrated the capability of enantioselectively releasing cinchona alkaloid, which was used to model chiral drugs. The release process was found to be influenced by temperature: low temperature was more favorable for enantio-differentiating release.

Optically Active Porous Materials Constructed by Chirally Helical Substituted Polyacetylene through a High Internal Phase Emulsion Approach and the Application in Enantioselective Crystallization.

This article reports the first optically active macroporous materials constructed by helical substituted polyacetylene and prepared by a high internal phase emulsion (HIPE) technique. The macroporous (∼3 µm) materials were fabricated simply through polymerization of the continuous phase in HIPEs. The porous structures of the resulting materials can be adjusted by varying the fraction of the dispersed phase. The obtained materials were characterized by regular pore morphology, high porosity, and low density. Circular dichroism and UV-vis absorption spectra demonstrated that the substituted polyacetylene forming the materials adopted chirally helical conformations, which endowed the materials with considerable optical activity. The optically active porous materials were used as chiral inducers and efficiently induced enantioselective crystallization of threonine and alanine racemates. l-Threonine and l-alanine were preferably induced to form crystals from the respective racemic solutions. The prepared materials open a new type of functional chiral materials with potential applications in asymmetric catalysis, chiral resolution, etc.

Optically active microspheres constructed by helical substituted polyacetylene and used for adsorption of organic compounds in aqueous systems.

This article reports optically active microspheres consisting of chiral helical substituted polyacetylene and ß-cyclodextrin-derivative (ß-CD-A). The microspheres showed remarkable adsorption toward various organic compounds in water. To prepare the microspheres, an acetylenic-derived helical macro-monomer was synthesized and then underwent aqueous suspension copolymerization with octadecyl acrylate and butyl acrylate by using azobis(isobutyronitrile) as initiator and ß-CD-A simultaneously as comonomer and cross-linking agent. The helical macro-monomer chains enabled the microspheres to exhibit desirable enantio-differentiating adsorption capacity toward chiral compounds respectively dissolved in organic solvent, dispersed in water, and dissolved in water. The saturated absorbency toward (R)-(+)- and (S)-(-)-1-phenylethylamine was 29 and 12 mg · g(-1), respectively. The microspheres also showed large oil absorbency (e.g., 22 g · g(-1) CCl4) and a large adsorption toward methyl red (as a model for organic dyes) dispersed in water. The presence of ß-CD-A moieties improved the adsorption performance of the microspheres. The present optically active microspheres open a new approach for preparing adsorbents particularly chiral adsorbents with potentials for wastewater treatment.

Chiral functionalization of graphene oxide by optically active helical-substituted polyacetylene chains and its application in enantioselective crystallization.

This article reports an original, versatile strategy to chirally functionalize graphene oxide (GO) with optically active helical-substituted polyacetylene. GO was first converted into alkynyl-GO containing polymerizable -C≡C moieties, which took part in the polymerization of another chiral acetylenic monomer, yielding the expected GO hybrid covalently grafted with chiral helical polyacetylene chains. Transmission electron microscopy, atomic force microscopy, X-ray diffraction, Fourier transform infrared spectroscopy, Raman spectroscopy, X-ray photoelectron spectroscopy, and thermogravimetric analyses verified the successful attachment of substituted polyacetylene chains on GO by covalent chemical bonding. Moreover, circular dichroism effects and UV-vis absorption demonstrated that the GO hybrid possessed fascinating optical activity. It also largely improved the dispersibility of GO in tetrahydrofuran. The GO-derived hybrid was further used as a chiral inducer toward enantioselective crystallization of alanine enantiomers. l-Alanine was preferably induced to crystallize, forming rodlike crystals.