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Epidemiological studies consistently show that decreases in serum testosterone level are observed more frequently in men with type 2 diabetes mellitus (T2DM), while clinical investigations have demonstrated that an increased level of circulating growth differentiation factor-15 (GDF-15) are also related closely to T2DM. The aim of this study was to examine the potential relationship between serum GDF-15 levels and hypogonadism in Chinese male patients with T2DM.A total of 305 T2DM men were recruited between July 2020 and August 2021. GDF-15 and total testosterone concentrations were quantified by an enzyme-linked immunosorbent assay and LC/MS mass spectrometry, respectively. Multiple linear regression analysis, logistic regression, and restricted cubic splined models were used to examine the correlation between GDF-15 levels and hypogonadism in these patients.When compared with T2DM patients without hypogonadism circulating GDF-15 levels were significantly higher in the hypogonadism group [1081.83 (746.79,1539.94) versus 779.49 (548.46,1001.27), p 0.001] and were associated positively with hypogonadism in unadjusted and fully adjusted multivariate regression models (p 0.01). The fully adjusted regression coefficients with 95% confidence intervals for circulating GDF-15 and testosterone deficiency were -1.795 (-2.929, -0.661). Serum GDF-15 levels were also associated positively with testosterone deficiency in each logistic regression model (p 0.05), while after adjustment for all risk factors, the same findings were obtained in the restricted cubic splined models (p 0.01).In hypogonadal men with T2DM, an elevated serum GDF-15 level is associated negatively with serum testosterone concentration. GDF-15 may be a novel cytokine related to T2DM men with hypogonadism.

Background The prenatal test of cell-free fetal DNA (cffDNA) is also known as noninvasive prenatal testing (NIPT) with high sensitivity and specificity. This study is to evaluate the performance of NIPT and its clinical relevance with various clinical indications. Methods A retrospective analysis was conducted on 14,316 pregnant women with prenatal indications, including advanced maternal age (≥35 years), maternal serum screening abnormalities, the thickened nuchal translucency (≥2.5 mm) and other ultrasound abnormalities, twin pregnancy/IVF-ET pregnancy, etc. The whole-genome sequencing (WGS) of maternal plasma cffDNA was employed in this study. Results A total of 189 (1.32%) positive NIPT cases were identified, and 113/189 (59.79%)cases were confirmed by invasive prenatal testing. Abnormal serological screening (53.14%) was the most common indication, followed by elderly pregnancy (23.02%). The positive prediction value for T21, T18, T13, sex chromosome abnormalities, other autosomal aneuploidy abnormalities, and CNV abnormalities were 91.84, 68.75,37.50, 66.67, 14.29, and 6.45%, respectively. The positive rate and the true positive rate of nuchal translucency (NT) thickening were the highest (4.17 and 3.33%), followed by the voluntary requirement group (3.49 and 1.90%) in the various prenatal screening indications. The cffDNA concentration was linearly correlated with gestational age (≥10 weeks) and the positive NIPT group’s Z-score values. Conclusions whole-genome sequencing of cffDNA has extremely high sensitivity and specificity for T21, high sensitivity for T18, sex chromosome abnormalities, and T13. It also provides evidence for other abnormal chromosomal karyotypes (CNV and non-21/18/13 autosomal aneuploidy abnormalities). The cffDNA concentration is closely related to the gestational age and determines the specificity of NIPT. Our results highlight NIPT’s clinical significance, which is an effective prenatal screening tool for high-quality care of pregnancy., Highlights The whole-genome sequencing of cell-free fetal DNA from maternal plasma is an effective prenatal screening tool for pregnancies with various prenatal indications.The concentration of cffDNA was linear with gestational age and the Z-score values of the positive NIPT group.NIPT has a significant positive predictive value for pregnancies with prenatal indications.

BACKGROUND Angiopoietinlike protein 5 (ANGPTL5) is an adipocytokine and has an important role in metabolic processes including lipid metabolism, obesity, and type 2 diabetes mellitus. On the basis of these roles, the present study aimed to investigate the level and role of plasma ANGPTL5 in metabolic syndrome (MS) patients. MATERIAL AND METHODS A total of 139 participants was enrolled in this study; 69 of them were diagnosed with MS. Plasma ANGPTL5 levels were measured by enzyme-linked immunosorbent assay. Sex, age, and other laboratory tests were compared statistically. Correlations between ANGPTL5 and biochemical parameters such as lipid levels and insulin resistance were all evaluated statistically. RESULTS In patients with MS, plasma ANGPTL5 levels were higher than in those without MS (P

Purpose. Our previous research has confirmed that the addition of nano-amorphous calcium phosphate (ACP) materials can improve the support of poly-L-lactic acid (PLLA) vascular scaffolds. Based on this, we continued to explore the effect of novel bioresorbable scaffold composed of PLLA and ACP nanoparticles on inflammation and calcification of surrounding tissues after scaffold implantation in porcine coronary artery. Methods. PLLA/ACP scaffolds in the experimental group and PLLA scaffolds in the control group were implanted into the coronary arteries of small pigs. Serum levels of C-reactive protein (CRP), calcium (Ca), and alkaline phosphatase (ALP) were measured before implantation and at 1, 6, 12, and 24 months after operation. Intravascular ultrasonography (IVUS) was performed to evaluate the vascular calcification score. The scaffold and surrounding tissues were hematoxylin-eosin staining for inflammation score. The scaffold and surrounding tissues were stained with NF-κB and ALP, and the positive expression index was calculated. Western blot was used to detect the expression of IL-6 and BMP-2 in the tissues around the scaffold. Results. There was no statistically significant difference between the two groups in CRP, calcium, and ALP at preimplant, 1 month, 6 months, 12 months, and 24 months ( P > 0.05 ). The inflammation score, NF-κB positive expression index, and calcification score in the PLLA/ACP group were lower than that in the PLLA group at 12 months and 24 months ( P < 0 05 ). The ALP positive expression index in the PLLA/ACP group was lower than that in the PLLA group at 6 months, 12 months, and 24 months ( P < 0 05 ). Western blot results showed that the IL-6 expression level in the PLLA/ACP group was significantly lower than that in the control group at 6 months, 12 months, and 24 months ( P < 0.05 ). The expression of BMP-2 in the PLLA/ACP group was significantly lower than that in the control group at 12 months and 24 months ( P < 0.05 ). Conclusion. The PLLA/ACP composite scaffold has good biocompatibility. The incorporation of nanoscale ACP can reduce the inflammatory response caused by the acid metabolites of PLLA scaffolds, reduce the expression of procalcification factors in the body, and inhibit tissue calcification. The PLLA/ACP composite scaffold provides reliable guidance for the application and development of degradable vascular scaffold.

Background: The aging process is accompanied by the gradual development of chronic systemic inflammation (inflamm-aging). Growth differentiation factor-15 (GDF-15) is associated with inflammation and known to be a stress-induced factor. The present study aimed to explore the association of GDF-15 with aging.Methods: In this cross-sectional study, serum GDF-15, hematological parameters, and biomedical parameters were determined in 120 healthy individuals (23-83 years old, males). Three telomere related parameters, including telomere length, telomerase activity, and the expression of human telomerase reverse transcriptase (hTERT) mRNA were also quantified.Results: The older group has a higher levels of GDF-15 and lower expression of hTERT mRNA, and PBMC telomerase activity (ppr=0.664, pr=-0.434, pr=-0.231, p=0.012), and hTERT mRNA (r=-0.206, p=0.024). Furthermore, in multivariate regression analysis, GDF-15 levels showed a statistically significant linear and negative relationship with PBMC telomerase activity (β-coefficient=-0.583, 95% CI -1.044 to -0.122, p=0.014), telomere length (β-coefficient=-0.200, 95% CI -0.305 to -0.094, pβ-coefficient=-0.207, 95% CI -0.312 to -0.102, pConclusions: In conclusion, our results show that circulating GDF-15 is the potential biomarkers of aging that may influence the risk and progression of multiple aging conditions.

Objective Using coronary angiography and intravascular ultrasound methods to evaluate the performance of the novel fully bioabsorbable scaffold (NFBS) composed of poly-L-lactic acid/amorphous calcium phosphate (PLLA/ACP) at six-month follow-up by comparing with PLLA scaffolds Methods Twelve PLLA/ACP scaffolds and 12 PLLA scaffolds were implanted into the coronary arteries of 12 miniature pigs. Quantitative coronary angiography (QCA) was used to measure the reference vessel diameter (RVD), mean lumen diameter (MLD) and late lumen loss (LLL). According to IVUS images, we calculated the strut malapposition rate (SMR) at post implantation, strut overlap rate (SOR), reference vessel area (RVA), mean stent area (MSA), mean lumen area (MLA) and luminal patency rate (LPR) at six-month follow-up. The radial strength of the scaffold was evaluated using a catheter tensile testing machine. Results QCA results indicated that, at six month, MLD of PLLA/ACP scaffolds was greater than those of PLLA scaffolds (2.47 ± 0.22 mm vs. 2.08 ± 0.25 mm, P 2 vs. 5.35 ± 0.51 mm2, P 2 vs. 3.77 ± 0.46 mm2, P Conclusion The NFBS had less stent recoil, better lumen patency rate and greater radial strength than PLLA scaffolds. The results suggest the NFBS scaffolds can maintain the structural strength and functional performance, which are effective for up to six months when implanted in porcine coronary arteries.

Additional file 1: Table S1. Serum concentrations of GDF-15 and testosterone among SA, UA and AMI groups.

The ageing process is accompanied by the gradual development of chronic systemic inflammation (inflamm-ageing). Growth differentiation factor 15 (GDF15) is associated with inflammation and known to be a stress-induced factor. The present study aimed to explore the association of GDF15 with ageing. In this cross-sectional study, serum GDF15, hematological parameters, and biomedical parameters were determined in 120 healthy individuals (23-83 years old, males). Three telomere related parameters, including telomere length, telomerase activity, and the expression of human telomerase reverse transcriptase (hTERT) mRNA were also quantified. Our results showed that the older group has a higher levels of GDF15 and lower expression of hTERT mRNA, and PBMC telomerase activity (p 0.001). In individuals with high GDF15 levels, they were older, and presented with the lower level of hTERT mRNA and T/S ratio (p 0.01). Spearman correlation analysis shows that GDF15 positively correlated with age (r = 0.664, p 0.001), and negatively correlated with telomere length (r = -0.434, p 0.001), telomerase activity (r = -0.231, p = 0.012), and hTERT mRNA (r = -0.206, p = 0.024). Furthermore, in multivariate regression analysis, GDF15 levels showed a statistically significant linear and negative relationship with PBMC telomerase activity (β-coefficient = -0.583, 95% CI -1.044 to -0.122, p = 0.014), telomere length (β-coefficient = -0.200, 95% CI -0.305 to -0.094, p 0.001), and hTERT mRNA (β-coefficient = -0.207, 95% CI -0.312 to -0.102, p 0.001) after adjusting for confounders. These results support that circulating GDF15 is the potential biomarker of ageing that may influence the risk and progression of multiple ageing conditions.

BACKGROUND The role of renal sympathetic denervation (RSD) in ameliorating post-myocardial infarction (MI) left ventricular (LV) fibrosis via microRNA-dependent regulation of connective tissue growth factor (CTGF) remains unknown. MATERIAL AND METHODS MI and RSD were induced in Sprague-Dawley rats by ligating the left coronary artery and denervating the bilateral renal nerves, respectively. Norepinephrine, renin, angiotensin II and aldosterone in plasma, collagen, microRNA21, microRNA 101a, microRNA 133a and CTGF in heart tissue, as well as cardiac function were evaluated six weeks post-MI. RESULTS In the RSD group, parameters of cardiac function were significantly improved as evidenced by increased LV ejection fraction (p

New Findings What is the central question of this study? The enzyme system that is responsible for extracellular matrix (ECM) turnover is the matrix metalloproteinases (MMPs), which can be blocked by the tissue inhibitors of MMPs (TIMPs). Whether renal sympathetic denervation (RSD) is able to ameliorate post-myocardial infarction left ventricular remodelling through attenuation of ECM via regulation of MMP activity and/or the MMP–TIMP complex remains unknown. What is the main finding and its importance? Renal sympathetic denervation has therapeutic effects on post-myocardial infarction left ventricular remodelling, probably by attenuating the ECM through regulation of the MMP9–TIMP1 complex in the transforming growth factor-β1 (a profibrotic cytokine that accelerates ECM remodelling after ischaemia) signalling pathway. Whether renal sympathetic denervation (RSD) is able to ameliorate post-myocardial infarction (post-MI) left ventricular (LV) remodelling by attenuation of the extracellular matrix via regulation of matrix metalloproteinase (MMP) activity and/or the MMP–tissue inhibitor of matrix metalloproteinase (TIMP) complex remains unknown. Sixty-five Sprague–Dawley rats were randomly divided into the following four groups: normal (N, n = 15), RSD (RSD, n = 15), myocardial infarction (MI, n = 15) and RSD 3 days after MI (MI3d+RSD, n = 20). The bilateral renal nerves were surgically denervated 3 days after MI had been induced by coronary artery ligation. Left ventricular function was assessed using echocardiography and a Millar catheter at 6 weeks post-MI. Plasma noradrenaline, angiotensin II and aldosterone, collagen volume fraction, transforming growth factor-β1 (TGF-β1), MMP2, MMP9 and TIMP1 in heart tissue were measured 6 weeks after MI. In rats with MI3d+RSD compared with MI rats, RSD improved systolic and diastolic function, resulting in an improvement in ejection fraction (P

This study aimed to explore the association between growth differentiation factor-15 (GDF-15), a stress-induced factor, and sex hormones in male patients with coronary artery disease (CAD). In this study, we recruited 253 male patients with CAD and 205 male controls. Patients were divided into three groups in accordance with GDF-15 tertiles. Serum levels of GDF-15, testosterone, estradiol and other biochemical variables were measured. Serum levels of GDF-15 were significantly increased and serum testosterone and testosterone/estradiol ratio (T/E2 ratio) were significantly decreased in CAD patients compared with controls. Patients with high GDF-15 levels had lower testosterone (203.97, 95% CI 154.67–328.30 vs. 303.98, 95% CI 246.93–345.66; P = 0.001) and T/E2 ratio (8.82, 95% CI 5.77–11.41 vs. 11.07, 95% CI 7.91–14.32; P = 0.013). Correlation analyses showed that serum GDF-15 levels inversely correlated with testosterone levels (r = −0.339) and T/E2 ratio (r = −0.365) (both P

Current assessment tools for patients with acute chest pain are either traumatic (coronary angiography) or unreliable (measurement of cardiac troponin concentrations). We investigated whether the novel cardiovascular stress markers, serum growth differentiation factor-15 (GDF-15), Krüppel-like factor 4 (KLF4) and growth arrest-specific 6 (gas6) may be useful biomarkers of coronary artery disease (CAD).A total of 350 male patients were enrolled, 198 with CAD and 152 controls, based on coronary angiography. GDF-15, KLF4 and gas6 concentrations were measured using commercial enzyme-linked immunosorbent assay kits. Multivariate logistic regression and multivariate linear regression were performed to evaluate potential associations of GDF-15, KLF4 and gas6 with risk of CAD or CAD severity.Serum GDF-15, KLF4 and gas6 concentrations were significantly higher in male patients with CAD than in control subjects (P .05), and they correlated significantly with involvement of coronary vessels (P .05). After adjusting for confounding factors, we found that circulating GDF-15 concentrations remained positively associated with the presence of CAD (odds ratio [OR] per 1-standard deviation [SD] increase, 3.182; 95% confidence interval [CI] 1.586 to 6.382; P = .001), as did KLF4 concentrations (OR per 1-SD increase, 13.05; 95% CI 2.940 to 57.921, P = .001). Moreover, circulating GDF-15 concentrations were positively associated with the Gensini score (estimated SD change per 1-SD increase, 22.091; 95% CI 9.147 to 35.035, P = .001), as were KLF4 concentrations (estimated SD change per 1-SD increase, 27.996; 95% CI 10.082 to 45.910, P = .002). Gas6, in contrast, showed no relationship to presence of CAD or Gensini score.In this case-control study, increased concentrations of circulating GDF-15 and KLF4 were significantly associated with the presence and severity of CAD.

Objectives. Our previous studies have confirmed the superior biocompatibility of the poly-L-lactic acid/amorphous calcium phosphate (PLLA/ACP) scaffolds compared to PLLA scaffolds at 1-month. In the present study, the long-term inflammatory responses of PLLA/ACP scaffolds in a porcine coronary model have been explored. Methods. The 24 PLLA scaffolds and 24 PLLA/ACP scaffolds were implanted into the coronary arteries of 24 miniature pigs. Serum levels of ALT, AST, and CRP were measured before operation, as well as 1-month, 6-months, 12-months, and 24-months. The vascular segments were taken for pathomorphological observation. HE staining was used for the inflammatory score and fibrosis score. Immunohistochemical staining detected positive expression indexes of MMP-9 and NF-κB. The expression of inflammation-related proteins of IL-1 and IL-6 was detected by Western Blot in surrounding tissues of scaffolds. Results. There was no significant difference between the two groups in ALT, AST, and UR at different time points (P<0.05). The inflammation score in the PLLA/ACP group was lower than that in the PLLA group at 6-months, 12-months, and 24-months (P<0.05), and the fibrosis score was reduced in the PLLA/ACP group than that in the PLLA group at 12-months and 24-months (P<0.05). The expression of MMP-9 and NF-κB in the PLLA/ACP group was significantly less than that in the PLLA group at 6-months, 12-months, and 24-months (P<0.05). The protein expression of IL-1 in the PLLA/ACP group was decreased than that in the PLLA group at 12-months and 24-months (P<0.05). Furthermore, the protein expression of IL-1 was significantly lower than that in the PLLA group at 6-months, 12-months, and 24-months (P<0.01). Conclusions. The supplement of ACP nanoparticles can effectively reduce the long-term inflammatory reaction caused by PLLA and has good safety and biocompatibility. The novel bioabsorbable PLLA/ACP scaffold provides reliable guidance for the development and clinical application of bioabsorbable scaffolds in the future.

Coronary atherosclerotic heart disease (CHD) is currently regarded as a chronic inflammatory disease. The inflammatory cytokine neopterin (NP) is a new predictor of the stable type of atherosclerotic plaque, and this study focused on the relationship between neopterin, Gensini score and high-sensitivity C-reactive protein (Hs-CRP) to explore the important role of neopterin in patients with CHD. This study enrolled 176 patients into the control group and 266 patients into the experimental group. The Gensini score was used to assess the severity of the coronary lesions, enzyme-linked immunosorbent assays (ELISAs) were used to measure the serum NP level, and other indicators were assessed using a fully automatic biochemical analyzer. The data were analyzed using SPSS19.0 statistical software. The serum NP level was higher in the experimental group than in the control group (132.23 ± 6.40 ng/mL vs. 40.95 ± 2.67 ng/mL, P < 0.001). Compared with the stable angina (SA) group, the serum NP level was significantly increased in the unstable angina (UA) group (135.99 ± 12.45 ng/mL) and the acute myocardial infarction (AMI) group (173.66 ± 13.59 ng/mL) (P < 0.05). In addition, the serum NP level was positively correlated with the Gensini score (r = 0.687, P < 0.001) as well as with the level of Hs-CRP (r = 0.190, P < 0.001). The serum level of NP was significantly higher in patients with CHD and was positively correlated with the severity of CHD. Thus, NP may become a new indicator for the assessment of the inflammatory response in coronary atherosclerosis.

Dilated cardiomyopathy arises from mutations in many genes. TTN, the gene encoding the sarcomere protein titin, has been insufficiently analyzed for cardiomyopathy mutations because of its enormous size. In this study, we report a Chinese family with two members affected by TTN. Blood samples were collected from all family members. Genomic DNA was isolated from blood, and all coding exons and adjacent intronic sequences of the TTN gene were examined for mutation analysis using polymerase chain reaction (PCR)-based sequencing. The proband (III3) and his sister (III2) carry a TTN c.100126A>G (p.Thr33376Ala) missense mutation. The proband currently exhibits decreased cardiac function accompanied by malignant arrhythmia, and his sister has no obvious clinical symptoms and no abnormal ultrasound findings. The study found that there is a missense mutation in the TTN gene, c.100126A>G (p.Thr33376Ala), in a family whose members suffer from familial dilated cardiomyopathy in Hubei province. TTN is closely related to dilated cardiomyopathy and is an important causative gene of familial dilated cardiomyopathy.

Biodegradable polymers used as vascular stent coatings and stent platforms encounter a major challenge: biocompatibility in vivo, which plays an important role in in-stent restenosis (ISR). Co-formulating amorphous calcium phosphate (ACP) into poly(lactic-co-glycolic acid) (PLGA) or poly-L-lactic acid (PLLA) was investigated to address the issue. For stent coating applications, metal stents were coated with polyethylene-co-vinyl acetate/poly-n-butyl methacrylate (PEVA/PBMA), PLGA or PLGA/ACP composites, and implanted into rat aortas for one and three months. Comparing with both PEVA/PBMA and PLGA groups after one month, the results showed that stents coated with PLGA/ACP had significantly reduced restenosis (PLGA/ACP vs. PEVA/PBMA vs. PLGA: 21.24 +/- 2.59% vs. 27.54 +/- 1.19% vs. 32.12 +/- 3.93%, P < 0.05), reduced inflammation (1.25 +/- 0.35 vs. 1.77 +/- 0.38 vs. 2.30 +/- 0.21, P < 0.05) and increased speed of re-endothelialization (1.78 +/- 0.46 vs. 1.17 +/- 0.18 vs. 1.20 +/- 0.18, P < 0.05). After three months, the PLGA/ACP group still displayed lower inflammation score (1.33 +/- 0.33 vs. 2.27 +/- 0.55, P < 0.05) and higher endothelial scores (2.33 +/- 0.33 vs. 1.20 +/- 0.18, P < 0.05) as compared with the PEVA/PBMA group. Moreover, for stent platform applications, PLLA/ACP stent tube significantly reduced the inflammatory cells infiltration in the vessel walls of rabbit iliac arteries relative to their PLLA cohort (NF-kappaB-positive cells: 23.31 +/- 2.33/mm2 vs. 9.34 +/- 1.35/mm2, P < 0.05). No systemic biochemical or pathological evidence of toxicity was found in either PLGA/ACP or PLLA/ACP. The co-formulation of ACP into PLGA and PLLA resulted in improved biocompatibility without systemic toxicity.