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Severe acute respiratory syndrome coronavirus 2 breakthrough infection in highly vaccinated populations raises study on the effectiveness for inactivated vaccine, including effectiveness of the vaccine dose, the continuance of effectiveness, the effectiveness against severe/critical coronavirus disease 2019 and against secondary attacks. A population of 10 870 close contacts were investigated in a Delta variant's epidemic. The effectiveness of vaccination was estimated in a test-negative case-control study. In addition, serum was used to detect neutralizing antibodies, to explore their correlation to effectiveness. The vaccine effectiveness (VE) values were estimated for populations aged 12 years or older. The overall adjusted VE was 56.2% and a two-dose vaccine was more effective than a one-dose vaccine (56.7% vs. 43.8%). In addition, the population that got the second dose vaccine within 2 months showed higher VE than the population vaccinated for longer than 2 months (61.5% vs. 52.3%). Among the population who vaccinated 2 doses or within 2 months, a higher level of neutralizing antibodies was observed. For infected cases, vaccinated populations showed lower rates of transmission (2.63% vs. 4.36%). Further, those vaccinated cases, who were not found causing transmission, had a higher level of antibodies. The study provided a full view of the effectiveness of inactivated vaccines in a real-world setting. The time-related VE against infection and lower transmission of breakthrough vaccinated cases were observed, which may indicate that a necessity of a booster vaccine to maintain the effectiveness and high level of neutralizing antibody.

Nucleic acid detection represents limitations due to its false-negative rate and technical complexity in the COVID-19 pandemic. Anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody tests are widely spread all over the world presently. However, there is no report on the effectiveness of anti-SARS-CoV-2 antibody testing methods in China.We gathered 10776 serum samples from close contacts of the SARS-CoV-2 infections in Fujian of China and used 2 chemiluminescence immunoassays (Wantai Bio., Yahuilong Bio.) and 2 lateral flow immunoassays (Lizhu Bio. and Dongfang Bio.) to perform the anti-SARS-CoV-2 antibody tests in China.The 4 antibody tests have great diagnostic value for infected or uninfected, especially in the neutralizing antibodies tests, the AUC can reach 0.939 (Wantai Bio.) and 0.916 (Yahuilong Bio.). Furthermore, we used pseudoviruses and euvirus neutralization assay to validate the effectiveness of these antibody test, the results of pseudoviruses neutralization assay or euvirus neutralization assay shows a considerable correlation with the 4 antibody detection respectively, particularly in euvirus neutralization assay, neutralizing antibodies detected by Wantai Bio. or Yahuilong Bio., the correlation can get the level of 0.93 or 0.82.The findings of this study demonstrate that the detections of antibodies have profound value in the diagnosis of COVID-19.

This meta-analysis was performed to clarify controversial associations of the

Since 1992, China has promoted hepatitis B vaccination. Concurrently, during this period, increasing use of immunoglobulins and nucleoside analogues might have exerted selective pressure on the hepatitis B virus (HBV) S gene, driving mutations in the HBsAg and changed the subtype. Using the National Center for Biotechnology Information database, we obtained gene sequence information for HBV strains from China and analysed changes in HBsAg subtypes and substitution mutations in HBsAg in 5-year intervals over 25 years to identify potential challenges to the prevention and treatment of hepatitis B. Most HBV sequences from China were genotype C (1996/2833, 70.46%) or B (706/2833, 24.92%). During the implementation of hepatitis B vaccination (recombinant hepatitis B vaccine was subgenotype A2 and HBsAg subtype adw2), the proportion of subtypes ayw1 and adw3 in genotype B and ayw2 in genotype C increased over the programme period. The overall mutation rate in HBsAg tended to decrease for genotype B, whereas, for genotype C, the rate increased gradually and then decreased slightly. Moreover, the mutation rate at some HBsAg amino acid sites (such as sG145 of genotype B and sG130 and sK141 of genotype C) is gradually increasing. HBV strains with internal stop codons of HBsAg (e.g., sC69*) and additional N-glycosylation (e.g., sG130N) mutations should be studied extensively to prevent them from becoming dominant circulating strains. The development of HBV vaccines and antiviral immunoglobulins and use of antiviral drugs may require making corresponding changes.

OBJECTIVE To quantitatively analyze the association between cholesterol efflux capacity (CEC) and the risk and prognosis of coronary artery disease (CAD). METHODS A systematic search of electronic databases for studies published until September 2019 was performed. Cohorts, case-control studies, and randomized controlled trials that examined the effect of CEC on the risk and prognosis of CAD were included. RESULTS Eighteen studies with 12 685 subjects met our inclusion criteria. Among them, 14 studies reported the CEC in non-CAD and CAD groups, and eight studies reported the association between CEC and risk of CAD. Four studies reported the prognosis of stable CAD or acute coronary syndrome (ACS). In the pooled analyses, significantly decreased CEC was found in patients with stable CAD as compared with those without CAD. Decreased CEC was also present in subgroup in patients with ACS. High CEC was significantly associated with decreased risk of CAD [odds ratio (OR) = 0.65, 95% confidence interval (CI): 0.55-0.75, P

It is widely accepted that circular RNA (circRNA) plays an important role in cardiovascular diseases. Therefore, this experiment aimed to investigate the pathogenesis of circMACF1 in acute myocardial infarction (AMI). qRT-PCR and immunoblotting were used to detect the expression levels of circMACF1, miR-500b-5p, and epithelial membrane protein 1 (EMP1). The role of circMACF1, miR-500b-5p, and EMP1 in cardiomyocyte apoptosis was assessed using annexin V-FITC/PI. Echocardiographic assessment, serum creatine kinase MB (CK-MB) and lactate dehydrogenase (LDH), myocardial infarct size, and TUNEL staining were applied in our research. In the MI group, the expression levels of circMACF1 and EMP1 were decreased with the increasing expression level of miR-500b-5p. CircMACF1 upregulated the expression of EMP1 as a sponge of miR-500b-5p, and circMACF1 was a direct target of miR-500b-5p. CircMACF1 impaired the progression of AMI by modulating the miR-500b-5p/EMP1 axis. CircMACF1 may be a potential therapeutic target for treating AMI. Graphical Abstract CircMACF1 upregulated EMP1 expression by sponge miR-500b-5p.

Urinalysis is often interfered by vitamin C and PH. This study was to evaluate the interference of vitamin C and PH in urinalysis, and minimize the risk to make the effective communication. 732 leftover urine samples in which the concentration of vitamin C was 0.0 mmol/L and either of the test-strip results (Glucose, Blood, Bilirubin, Leucocyte, Nitrite, Protein, Ketone) was positive that were collected. The interference test checked out using these leftover urine samples. When the chemical protein module was positive, the sulfosalicylic acid test performed to confirm the positive results. About 27% of urine samples were vitamin C positive. Adequate vitamin C would interfere with the chemical result of GLU, BIL, and BLD, but not KET, PRO, WBC, NIT (p-value < 0.05). False-positive protein occurred at any samples, but higher when urine PH is greater than or equal to 8.0. In summary, to minimize the risk of vitamin C and PH in urinalysis, the laboratory should pay more attention to its conditions. Also, do more to help guarantee the accuracy of the urinalysis results and to give more comments to doctors to achieve effective communication.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency, which is caused by pathogenic variants of G6PD that result in decreased G6PD activity, is an X-linked inherited inborn error of metabolism that occurs worldwide. Individuals with G6PD deficiency and heterozygous females with normal G6PD activity (i.e., all individuals with pathogenic G6PD variants) are at risk of developing hemolytic anemia under increased oxidative challenge. However, this risk can be minimized by timely diagnosis. Currently, two assays are used to diagnose G6PD deficiency in China: evaluation of enzymatic activity and targeted genotyping. In terms of identification of all individuals with pathogenic G6PD variants, the performance and cost of different diagnostic strategies (isolated or combined evaluation of G6PD activity and G6PD genotyping) can vary, and these factors should be comprehensively evaluated. In this study, we examined 555 infants (437 males and 118 females) who were positive for the newborn screening of G6PD deficiency. We first evaluated the diagnostic performances of enzymatic testing and targeted genotyping. Both assays attained 100% specificities and positive predictive values for both male and female infants. In contrast, the sensitivities and negative predictive values (NPVs) of the diagnostic tests were different for male and female infants. For male infants, the sensitivities were 99.8 and 98.3%, and the NPVs were 94.1% and 69.6%, for enzymatic testing and targeted genotyping, respectively. For female infants, the sensitivities were 62.5% and 97.9%, and the NPVs were 37.9% and 91.7%, for enzymatic testing and targeted genotyping, respectively. We also evaluated the cost of the five different diagnostic strategies. The combination of G6PD activity testing of all infants, followed by genotyping of female infants with normal G6PD activity, attained high diagnostic sensitivity (99.8%) at a low cost (8.60 USD per diagnosed case). In the future, simultaneous examination of G6PD activity and whole-exon or whole-gene G6PD sequencing could become a standard clinical practice. Our data provide references for clinical practice on the standardization of current and future interventions for G6PD deficiency in China.

Background: I kappa B kinase interacting protein (IKBIP) is dysregulated and closely correlated with prognosis in tumor. However, the potential functions of IKBIP have not been utterly revealed in hepatocellular carcinoma (HCC). Thus, we explored the clinical values of IKBIP and its correlation with immune infiltrates in HCC.Methods: IKBIP expression in different tumor types was analyzed through the Tumor Immunity Evaluation Resource (TIMER) database. IKBIP expression between HCC and normal tissues were readily available for retrospective analyses from GEPIA, UALCAN and the Cancer Genome Atlas (TCGA) databases. The association between clinical features and IKBIP expression in HCC was analyzed by the Wilcoxon signed-rank test and logistic regression. Human Protein Atlas (HPA) was used to analyze the protein expression of IKBIP. A receiver operating characteristic (ROC) curve was performed to explore diagnostic potential of IKBIP. Kaplan-Meier (K-M) method and Cox regression were conducted to evaluate the influence of IKBIP on the prognosis of HCC patients. Protein-protein interaction (PPI) networks were established using STRING. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used for gene functional enrichment analysis. The interrelation between IKBIP expression and immune infiltrates in HCC was analyzed through TIMER and tumor-immune system interaction database (TISIDB).Results: Our results revealed that IKBIP expression was abnormally upregulated in HCC, and ROC curve analysis confirmed the diagnostic power of IKBIP. High IKBIP expression was related to tumor sizes, pathologic stage and histologic grade. K-M plotter analysis showed that high IKBIP expression was correlated with poor prognosis of HCC patients. Moreover, multivariate Cox analysis further verified that high IKBIP expression was an independent risk factor in HCC patients. Correlation analysis found that IKBIP expression was associated with infiltrating immune cells.Conclusion: High IKBIP expression is associated with poor prognosis and immune infiltrates, which may serve as a prognostic biomarker and therapeutic target for HCC.

We analyzed the differences in serum homocysteine levels between patients with a history of recurrent spontaneous abortion (RSA) and those who had not experienced pregnancy-related complications. To this end, we retrieved literature and data on the association of RSA and serum homocysteine levels published before September 1st 2019 from the PubMed, EMBASE, China National Knowledge Infrastructure, and Wanfang databases. We further narrowed our literature review by focusing on peer-reviewed and full-text literature reporting on studies that used similar research methods and provided raw data or means and standard deviations while reporting results. Utilizing Stata 12.0 for a combined statistical analysis of the data, we assessed the quality of the included literature using the Newcastle Ottawa Scale. Patients who experienced RSA had higher serum homocysteine levels than the controls, with the difference being statistically significant (

Congenital heart disease (CHD) is a common structural birth defect worldwide, and defects typically occur in the walls and valves of the heart or enlarged blood vessels. Chromosomal abnormalities and genetic mutations only account for a small portion of the pathogenic mechanisms of CHD, and the etiology of most cases remains unknown. The role of epigenetics in various diseases, including CHD, has attracted increased attention. The contributions of DNA methylation, one of the most important epigenetic modifications, to CHD have not been illuminated. Increasing evidence suggests that aberrant DNA methylation is related to CHD. Here, we briefly introduce DNA methylation and CHD and then review the DNA methylation profiles during cardiac development and in CHD, abnormalities in maternal genome-wide DNA methylation patterns are also described. Whole genome methylation profile and important differentially methylated genes identified in recent years are summarized and clustered according to the sample type and methodologies. Finally, we discuss the novel technology for and prospects of CHD-related DNA methylation.

Schizandrin B exhibits prominent antioxidant and anti-inflammatory effects, and plays an important role in ameliorating myocardial ischemia/reperfusion injury. However, the underlying protective mechanisms remain to be elucidated. The aim of the present study was to explore the cardioprotective effects of schizandrin B against hypoxia/reoxygenation (H/R)-induced H9c2 cell injury, focusing on the role of the adenosine monophosphate-activated protein kinase (AMPK)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway in this process. The results showed that schizandrin B attenuated the H/R-induced decrease in cell viability and the increase in lactate dehydrogenase release, as well as the apoptosis rate in H9c2 cells. Schizandrin B also mitigated H/R-induced oxidative stress, as illustrated by the decrease in intracellular reactive oxygen species generation, malondialdehyde content and NADPH oxidase 2 expression, and the increase in antioxidant enzyme superoxide dismutase and glutathione peroxidase activities. In addition, schizandrin B reversed the H/R-induced upregulation of pro-inflammatory cytokines [interleukin (IL)-1β (IL-1β) tumor necrosis factor-α, IL-6 and IL-8] and the downregulation of anti-inflammatory cytokines (transforming growth factor-β and IL-10) in the culture supernatant. Notably, schizandrin B increased the expression of Nrf2, NAD(P)H: Quinone oxidoreductase (NQO-1) and heme oxygenase-1 (HO-1) in H/R-treated H9c2 cells, activating the Nrf2 signaling pathway. The cardioprotection of schizandrin B against H/R injury was inhibited by Nrf2 knockdown induced byNrf-2-specific small interfering RNA (siRNA; si-Nrf2) transfection. Furthermore, schizandrin B enhanced phosphorylated (p)-AMPK expression, while AMPK knockdown induced by AMPK-specific siRNA(si-AMPK) transfection remarkably eliminated schizandrin B-induced cardioprotection and reduced Nrf2 expression in H/R-treated H9c2 cells. Taken together, these results suggested that schizandrin B exerts cardioprotection on H/R injury in H9c2 cells due to its antioxidant and anti-inflammatory activities via activation of the AMPK/Nrf2 pathway.

Objective To investigate the association between DNA methylation and the stable warfarin dose through genome-wide DNA methylation analysis and pyrosequencing assay. Method This study included 161 patients and genome-wide DNA methylation analysis was used to screen potential warfarin dose-associated CpGs through Illumina Infinium HumanMethylation 450 K BeadChip; then, the pyrosequencing assay was used to further validate the association between the stable warfarin dose and alterations in the methylation of the screened CpGs. GenomeStudio Software and R were used to analyze the differentially methylated CpGs. Results The methylation levels of CpGs surrounding the xenobiotic response element (XRE) within the CYP1A1 promoter, differed significantly between the different dose groups (P 0, P Conclusion This is a novel report of the methylation levels of six CpGs surrounding the XRE within the CYP1A1 promoter and one differential CpG at the VKORC1 promoter associated with stable warfarin dosage; these methylation levels might be applied as molecular signatures for warfarin.

Background Cardiac hypertrophy is a common pathological process in many cardiac diseases, and persistent cardiac hypertrophy is the main cause of heart failure and sudden cardiogenic death. Thus, it is essential to elucidate the mechanism of cardiac hypertrophy to ensure better prevention and treatment. Methods The Human cardiac myocytes (HCMs) were incubated with 100 nmol/L Ang II (Sigma) for 48 hours to induce the in vitro cardiomyocyte hypertrophy model. The [(3H])-leucine incorporation assay was used to evaluate cardiomyocytes hypertrophy. The activities of oxidative stress related enzymes superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA) and nitric oxide (NO) were detected using corresponding detection kits following standard protocol. Targeting relationship was verified through Bioinformatics analysis and luciferase reporter gene assay. The morphological change of cardiomyocyte was observed through immunofluorescence staining. Expressions of message ribonucleic acid (mRNA) and proteins were detected by quantitative real-time polymerase chain reaction and western blot, respectively. Results In our study, the suppressed expression of micro ribonucleic acid (miRNA)-129-5p and the elevated expression of kelch-like ECH-associated protein 1 (keap-1) were found in the angiotensin II (Ang II)-induced cardiomyocyte hypertrophy model. MiR-129-5p effectively mimics suppressed Ang II-induced hypertrophic responses and oxidative stress. The results also showed that keap-1 was a target of miR-129-5p, and that the miR-129-5p inhibitor promoted cardiomyocyte hypertrophy and oxidative stress by elevating keap-1. Additionally, small interfering RNA (siRNA)-keap-1 activated the nuclear factor erythroid2-related factor 2 (Nrf2) pathway, while the miR-129-5p inhibitor inactivated the Nrf2 pathway by further elevating keap-1. The addition of the Nrf2 pathway activator NK-252 largely weakened the promoting effects of the miR-129-5p inhibitor on the progression of cardiomyocyte hypertrophy by suppressing oxidative stress. Conclusions In general, the results indicate that the overexpression of miRNA-129-5p protects against cardiomyocyte hypertrophy by targeting keap-1 via the Nrf2 pathway.

As a nutrient in body functions, folic acid (FA) plays a very important role for human health, and thus developing a highly sensitive method for its determination is of great significance. In the present work, carbon hollow nanospheres decorated with molybdenum disulfide nanosheets (CHN@MoS2) nanomaterials were produced through a simple method and adopted to modify a glassy carbon electrode for assembling a highly sensitive electrochemical sensor of FA. After characterizing the prepared nanomaterials using scanning-/transmission-electron microscopy and Raman spectra, as well as optimizing various testing conditions, including the pH value of the buffer solution, the accumulation time and amount of nanomaterials on electrode surface, and the electrochemical determination of FA was carried out using a CHN@MoS2 electrode. Owing to the coordinative advantages from CHN and MoS2, the results show that CHN@MoS2 exhibits excellent sensing responses for FA, and it has a wide linear range from 0.08 to 10.0 μM coupled with a low detection limit of 0.02 μM. Finally, the proposed method for FA detection was successfully applied in human urine analysis. The obtained results are satisfactory, revealing that the developed method based on CHN@MoS2 nanomaterials has important applications for FA determination.

Background We used bioinformatic analysis and quantitative reverse transcription polymerase chain reaction (RT-qPCR) assays to investigate the association between plasma microRNAs (miRNAs) and stable warfarin dosage in a Chinese Han population. Methods Bioinformatics analysis was used to screen out potential warfarin dose-associated miRNAs. Three plasma miRNAs were validated in 99 samples by RT-qPCR. Kruskal–Wallis test and multivariate logistic regression were used to compare differences in plasma miRNAs expression levels between three warfarin dosage groups. Results There were significant between-group differences among the three dose groups for hsa-miR-133b expression (p = 0.005), but we observed an “n-shaped” dose-dependent curve rather than a linear relationship. Expression levels of hsa-miR-24-3p (p = 0.475) and hsa-miR-1276 (p = 0.558) were not significantly different in the multivariate logistic regression. Conclusion miRNAs have received extensive attention as ideal biomarkers and possible therapeutic targets for various diseases. However, they are not yet widely used in precision medicine. Our results indicate that hsa-miR-133b may be a possible reference factor for the warfarin dosage algorithm. These findings emphasize the importance of a comprehensive evaluation of complex relationships in warfarin dose prediction models and provide new avenues for future pharmacogenomics studies.

Breast cancer (BC) is the leading cause of death in females worldwide. Although cisplatin is a strong-effect and broad-spectrum chemotherapy drug, resistance to cisplatin remains a significant factor effecting clinical efficacy. The underlying mechanism of cancer cell resistance to cisplatin is not fully understood. MicroRNAs (miRs/miRNAs), as a regulator, are involved in regulating chemosensitivity to numerous chemotherapeutic drugs. The present study aimed to investigate the function of miR-181a-5p as a potential tumor suppressor in improving the efficiency of cisplatin in BC. The IC50 of cisplatin and miR-181a-5p expression were determined in five BC cell lines, and HS578T was selected as an appropriate cell line for subsequent experiments. The sensitivity of HS578T cells to cisplatin was assessed using cell proliferation, migration and apoptosis assays. Western blotting was performed to detect the expression of vitamin D receptor (VDR) and autophagy in HS578T cells. It was found that the increase in autophagy resulted in increased apoptosis and sensitivity to cisplatin in HS578T cells. miR-181a-5p transfection also inhibited the proliferation and migration ability of HS578T cells and induced apoptosis. Meanwhile, HS578T cells have increased sensitivity to cisplatin. VDR, as a target gene and autophagy regulator of miR-181a-5p, was negatively regulated by miR-181a-5p. Upon the decrease in VDR expression, the autophagy in HS578T cells was increased. These results indicate that the increase in autophagy enhanced the chemosensitivity of cisplatin by inducing apoptosis of HS578T cells and by inhibiting proliferation and migration. The present study showed that miR-181a-5p increased the chemical sensitivity of HS578T cells to cisplatin by inhibiting VDR to promote autophagy. The use of miR-181a-5p/autophagy/VDR-based treatment strategies may be a potential method to overcome cisplatin resistance in BC.

Background YKL-40, a chitinase-like glycoprotein has been identified as a candidate tumor marker. The current study evaluated the clinical significance of plasma YKL-40 in esophageal cancer patients. Methods We enrolled 127 esophageal cancer patients, 29 healthy controls. Plasma YKL-40 levels were measured through enzyme linked immunosorbent assay. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic efficiency of plasma YKL-40 in esophageal cancer patients. The correlations between plasma YKL-40 and clinicopathological characteristics of esophageal were analyzed. Results Plasma YKL-40 levels were significantly higher in patients with lymph node metastasis than those that were non-metastatic (p = 0.005). Patients with tumor thrombus formation presented with significantly higher YKL-40 levels than those without thrombus formation (160.3 vs. 74.7 ng/mL, p = 0.012). YKL-40 levels in patients with advanced stage (III and IV) were significantly higher than those in the early stages (I and II, p = 0.016). ROC curve analysis showed that the area under curve was 0.909, and the best diagnostic threshold of YKL-40 for esophageal cancer was 80.6 ng/mL with 68.9% sensitivity and 96.6% specificity. Conclusions This study indicated that YKL-40 may be a biomarker for esophageal cancer and potential biomarker for identification of invasive esophageal cancer.

IntroductionPregnancy in patients with mechanical heart valves (MHVs) is associated with high maternal complications and fetal complications.Anticoagulation treatments serve to decrease their venous clotting risk. Although some anticoagulation regimens have been used for patients during pregnancy with MHVs, no one is definitively superior among different regimens in recent studies. For a better understanding of the clinical treatment which anticoagulation regimen is more effective and safer during the pregnancy in patients with MHVs, a Bayesian network meta-analysis is necessary.Methods and analysisThis protocol has been reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols. Related studies until April 2019 will be searched in the following databases: PubMed, Embase,SinoMed and the using the OVID interface to search for evidence-based medicine reviews. A clinical trial registry (www.ClinicalTrials.gov) was also searched for unpublished trials. Both experimental studies (randomised clinical trials) and observational studies (cohort studies, case–control studies and case series studies) will be included in this study. Quality assessment will be conducted using Cochrane Collaboration’s tool or Newcastle-Ottawa Scale based on their study designs. The primary outcomes of interest will be the frequencies of serious maternal and fetal events. The additional outcomes of interest will be adverse maternal events, mode of delivery and adverse fetal events. Pairwise and network meta-analysis will be conducted using R (V.3.4.4, R Foundation for Statistical Computing, Vienna, Austria) and Stata (V.14, StataCorp). The ranking probabilities will be estimated at each possible rank for each anticoagulation regimen using the surface under the cumulative ranking curve. Statistical inconsistency assessment, subgroup analysis, sensitivity analysis and publication bias assessment will be performed.Ethics and disseminationEither ethics approval or patient consent is not necessary, because this study will be based on literature. The results of this study will be published in a peer-reviewed journal.PROSPERO registration numberCRD42019130659

Background: Cardiac hypertrophy is a common pathological process of many cardiac diseases and persistent cardiac hypertrophy is the main cause of heart failure and sudden cardiogenic death. It is of great value to elucidate the mechanism of cardiac hypertrophy for better prevention and treatment. Methods: The protein levels were measured by western blotting or RT-qPCR. cardiomyocytes hypertrophy was evaluated by [3H]-leucine incorporation assay. oxidative stress was measured by corresponding detection kits. The target relationship was measured by Luciferase reporter gene assay. Morphological change of cardiomyocyte was measured by immunofluorescence staining. Results: In our study, we for the first time revealed the effects and regulatory mechanism of miR-296-5p in cardiac hypertrophy in vitro . We found suppressed expression of miR-129-5p and elevated expression of keap-1 in Ang II-induced cardiomyocyte hypertrophy model. MiR-129-5p mimic effectively suppressed Ang II-induced hypertrophic responses and oxidative stress. Further experiments showed that keap-1 is a target of miR-129-5p, and miR-129-5p inhibitor promoted cardiomyocyte hypertrophy and oxidative stress by elevating keap-1. Besides, si-keap-1 mediated the activation of Nrf2 pathway, while miR-129-5p inhibitor inactivated the Nrf2 pathway by further elevating keap-1. Conclusions: MiR-129-5p mimic protects against Ang II induced cardiomyocyte hypertrophy via activating Nrf2 pathway by targeting keap-1.

Background The association between cholesterol efflux capacity (CEC) with the occurrence and prognosis of coronary artery disease (CAD) remains unrevealed. In our study, a systematic review was performed to quantitively analyze the association between CEC and the risk of CAD and follow-up endpoint events of the patients with CAD.Methods A systematic search of electronic databases (PubMed, EMBASE, OVID, Web of Science and Cochrane Library) for studies published until September 2019 was performed. Cohort, case-control studies, and randomized controlled trials that examined the effect of CEC on risk and prognosis of CAD were included.Results Eighteen studies involving a total of 12615 subjects that met the inclusion criteria were included. Among them, 14 studies reported the CEC levels in control and CAD group and 8 of them analyzed the association of CEC with risk of CAD. Four studies reported the prognosis of CAD or acute coronary syndrome (ACS). From the pooled analyses, significantly decreased CEC level was shown in patients with stable CAD in comparison with the control. It was also true in subgroup analysis of the patients with ACS. The decreased CEC was significantly associated with increased risk of CAD (OR=0.65, 95% CI: 0.55-0.75, P

It is widely accepted that circular RNA (circRNA) plays an important role in cardiovascular diseases. Therefore, this experiment aimed to investigate the pathogenesis of circMACF1 in acute myocardial infarction (AMI). qRT-PCR and immunoblotting were used to detect the expression levels of circMACF1, miR-500b-5p, and epithelial membrane protein 1 (EMP1). The role of circMACF1, miR-500b-5p, and EMP1 in cardiomyocyte apoptosis was assessed using annexin V-FITC/PI. Echocardiographic assessment, serum creatine kinase MB (CK-MB) and lactate dehydrogenase (LDH), myocardial infarct size, and TUNEL staining were applied in our research. In the MI group, the expression levels of circMACF1 and EMP1 were decreased with the increasing expression level of miR-500b-5p. CircMACF1 upregulated the expression of EMP1 as a sponge of miR-500b-5p, and circMACF1 was a direct target of miR-500b-5p. CircMACF1 impaired the progression of AMI by modulating the miR-500b-5p/EMP1 axis. CircMACF1 may be a potential therapeutic target for treating AMI. Graphical Abstract CircMACF1 upregulated EMP1 expression by sponge miR-500b-5p.

Background This 4-year retrospective cohort study aimed to establish reference intervals for free triiodothyronine (FT3), free thyroxine (FT4), and thyrotropin (TSH) in premature infants using the Beckman Coulter Unicel DxI 800 automated immunoassay system. Methods Study subjects included 605 preterm infants with a gestational age of 26–36 weeks (corrected: 29–38 weeks). Pearson correlation was used to evaluate the association between hormone levels and gestational and corrected gestational ages. A nonparametric method was used to establish reference intervals based on corrected gestational age. Results FT3 and FT4 levels were positively correlated with gestational and corrected gestational ages, respectively. TSH levels were slightly negatively correlated with gestational and corrected gestational ages. FT3 significantly differed according to corrected gestational age (29–33 weeks vs 34–38 weeks); however, the difference was smaller than the reference change value (RCV) for the FT3 test. Thus, we combined the FT3 reference intervals into a single reference interval: 2.65–4.93 pmol/L (29–38 weeks). The reference intervals of FT4 and TSH were 11.20–24.97 pmol/L (29–38 weeks) and 1.01–10.14 mIU/L (29–38 weeks), respectively. Conclusions Unlike those of full-term infants or adults, the reference intervals established in this study are applicable in premature infants. These results highlight the importance and complexity of establishing instrument-specific thyroid hormone reference intervals for preterm infants.

Nucleic acids are considered as perfect programmable materials for cascade signal amplification and not merely as genetic information carriers. Among them, catalytic hairpin assembly (CHA), an enzyme-free, high-efficiency, and isothermal amplification method, is a typical example. A typical CHA reaction is initiated by single-stranded analytes, and substrate hairpins are successively opened, resulting in thermodynamically stable duplexes. CHA circuits, which were first proposed in 2008, present dozens of systems today. Through in-depth research on mechanisms, the CHA circuits have been continuously enriched with diverse reaction systems and improved analytical performance. After a short time, the CHA reaction can realize exponential amplification under isothermal conditions. Under certain conditions, the CHA reaction can even achieve 600 000-fold signal amplification. Owing to its promising versatility, CHA is able to be applied for analysis of various markers in vitro and in living cells. Also, CHA is integrated with nanomaterials and other molecular biotechnologies to produce diverse readouts. Herein, the varied CHA mechanisms, hairpin designs, and reaction conditions are introduced in detail. Additionally, biosensors based on CHA are presented. Finally, challenges and the outlook of CHA development are considered.

The aim of the study was to evaluate the role of human epididymal secretory protein (HE4), cancer antigen 125 (CA125), and the Risk of Ovarian Malignancy Algorithm (ROMA) in diagnosing benign pelvic masses in premenopausal women.Serum was collected from 391 premenopausal women with benign pelvic mass prior to surgery and from 45 healthy individuals. Serum HE4 and CA125 levels and ROMA scores were evaluated separately.Among the 391 women with benign pelvic mass, 2.3% (9/391) had elevated HE4 levels (70 pmol/L), while 37.1% (145/391) had elevated CA125 levels (35 U/mL) (p0001). Endometriosis provided false-positive results for CA125 levels in more than half of the cases but resulted in no significant change for HE4 level. In 13 gravid women with a mass, 30.8% (4/13) and 38.5% (5/13) had elevated HE4 and CA125 levels, respectively; however, the difference was not significant (p0.05). Moreover, serum levels and patient percentages for CA125 elevation significantly increased with increase in mass diameter, whereas those for HE4 did not.CA125 elevation showed random results for benign pelvic masses, while HE4 elevation showed a higher specificity. Thus, serum HE4 testing is a better approach than CA125 testing for diagnosing benign pelvic masses in premenopausal women.

The present study aimed to compare the effect of conservative pharmacotherapy (CP) and staged percutaneous coronary intervention (SPCI) on significant non-culprit vessels in patients with ST-segment elevation myocardial infarction (STEMI). A total of 266 male and 40 female patients were divided into two groups following their first successful PCI treatment: i) Patients in the complete revascularization (CR) group undergoing SPCI; and ii) patients in the CP group undergoing CP. Follow-up data were collected at 180 or 360 days after surgery to compare the rates of major adverse cardiovascular events (MACE), recurrent myocardial infarction, recurrent angina pectoris and MACE-free survival rates between the two groups. The rate of MACE in the CP group was higher compared with that in the CR group at the 360-day follow-up (6.1 vs. 12.7%; P=0.05), and the same was reflected in the rate of recurrent myocardial infarction (10.1 vs. 4.1%; P=0.04). The rate of recurrent angina pectoris in the CP group was significantly higher compared with that in CR group at the 180-day (13.9 vs. 5.4%; P=0.012) and 360-day follow-up (18.4 vs. 8.1%; P=0.009). The MACE-free survival rate of patients was significantly higher in the CR group compared with that in the CP group at the 360-day follow-up (93.9% vs. 87.3%, P

Background: The no-reflow phenomenon during primary percutaneous coronary intervention (pPCI) in patients with ST-elevation myocardial infarction (STEMI) can lead to poor outcomes. It has been shown that the monocytes may be involved in the pathogenesis of coronary artery disease and associated with high risk of myocardial infarction. Aim: To assess the relation between admission monocyte count and angiographic no-reflow after pPCI. Methods: A total of 236 patients with acute STEMI, who underwent pPCI, were enrolled. The patients were divided into two groups (no-reflow and normal reflow) based on post-pPCI Thrombolysis in Myocardial Infarction (TIMI) flow grade. No reflow was defined as TIMI flow grades ≤ 2, and normal reflow was defined as TIMI 3 flow grade. The monocyte count and other laboratory parameters were measured on admission before pPCI. Results: There were 43 (18.2%) patients in the no-reflow group and 193 (81.8%) patients in the normal-reflow group. Patients with no-reflow had significantly higher admission monocyte count (0.76 ± 0.48 × 109/L vs. 0.55 ± 0.29 × 109/L, p = 0.004). Also, white blood cell and neutrophil counts were significantly higher while haemoglobin was significantly lower in the no-reflow group. In multivariate analysis, monocyte count remained an independent predictor of angiographic no-reflow phenomenon (odds ratio [OR] 2.665, 95% confidence interwal [CI] 1.102–6.445, p = 0.030) together with low haemoglobin concentration (OR 0.978, 95% CI 0.961–0.995, p = 0.013). Conclusions: Monocyte count on admission and low haemoglobin concentration were independent clinical predictors of no-reflow following pPCI in patients with STEMI. Our findings suggest that admission monocyte count may be available for early risk stratification of no-reflow after pPCI and might allow the improvement of strategies to prevent this phenomenon.

The no-reflow phenomenon during primary percutaneous coronary intervention in patients with ST-segment elevation myocardial infarction (STEMI) can lead to poor outcomes. Increased neutrophil counts have been associated with an increased risk of adverse clinical events after acute myocardial infarction (AMI). The aim of this study was to assess the relation between admission neutrophil counts and angiographic no-reflow after PPCI.A total of 217 patients with acute STEMI who underwent PPCI, were enrolled. The patients were divided into two groups: no-reflow and normal-reflow. The neutrophil counts and other laboratory parameters were measured on admission before PPCI.There were 41 patients (18.9%) in the no-reflow group and 176 patients in the normal-reflow group. Patients with no-reflow were older (68.0 ± 11.7 years vs 60.7 ± 13.2 years, P = 0.019) and had significantly higher admission neutrophil counts (9.02 ± 3.97 × 109/L vs 7.57 ± 2.82 × 109/L, P = 0.007). Also, high-sensitivity C-reactive protein (hsCRP), white blood counts, monocyte counts were significantly higher while haemoglobin values were significantly lower in the no-reflow group. In multivariate analysis, neutrophil counts remained a strong independent predictor of angiographic no-reflow (odds ratio 1,200, 95% confidence interval 1.073-1.342, P = 0.001) together with age (odds ratio 1.041, 95% confidence interval 1.012-1.071, P = 0.005).Neutrophil counts on admission and age were independent clinical predictors of no-reflow following primary PCI in patients with STEMI. Our findings suggest that admission neutrophil counts may be available for early risk stratification of no-reflow after primary PCI and might allow the improvement of strategies to prevent this phenomenon.

Background Thyroid-stimulating hormone (TSH) levels are an important parameter in screening for congenital hypothyroidism (CH). This study aimed to analyze the effects of birth weight, gestational age, and delivery mode on the incidence of neonatal CH. Methods A retrospective cohort study of neonates born in 2015 at a maternity hospital in Xiamen, China and their mothers was conducted. Differences in TSH levels, CH positivity at baseline, and the incidence of CH according to gestational age, birth weight, and delivery mode were assessed using matched neonatal and maternal data. Results Of the 15,615 enrolled neonates, 150 had positive CH screening results at baseline and nine had confirmed CH. Premature and low-birth-weight neonates had a significantly higher incidence of CH and lower TSH levels when compared to full-term neonates and normal-to-high birth weight neonates, respectively. Neonates delivered vaginally had significantly lower TSH levels and a reduced incidence of baseline CH positivity; cesarean section delivery (odds ratio [OR] = 2.06, p = 0.006) and a maternal TSH level >2.5 mIU/L (OR = 2.37, p = 0.002) were risk factors for CH positivity at baseline. Conclusions In this study, the incidence of CH in neonates was associated with gestational age and birth weight. Neonatal baseline CH positivity was positively associated with cesarean delivery and an early-pregnancy maternal TSH level >2.5 mIU/L.

Acute heart failure (AHF) is a major public health issue due to its high incidence and poor prognosis; thus, efficient and timely diagnosis is critical for improving the prognosis and lowering the mortality rate. Amino-terminal pro-brain natriuretic peptide (NT-proBNP) is widely used in the diagnosis of AHF; however, its efficacy is controversial in diagnosing AHF with renal insufficiency. There were numerous studies reporting the association of adiponectin (ADPN) and heart diseases. Therefore, the present study aimed to investigate whether ADPN is helpful in identifying AHF with renal insufficiency. A total of 407 participants (218 AHF patients and 189 controls) were enrolled into the current study. The plasma levels of ADPN and NT-proBNP were measured using a sandwich enzyme-linked immunosorbent assay and an electrochemiluminescence immunoassay, respectively. In addition, these levels were compared among the various New York Health Association classes, as well as the ischemic and non-ischemic AHF cases. The correlation between the two biomarkers and the renal function was analyzed by Spearman's correlation, while the diagnostic efficiency of ADPN and NT-proBNP was evaluated in AHF patients with and without renal insufficiency. The results revealed that NT-proBNP exhibited a higher diagnostic efficiency as compared with ADPN in patients without renal insufficiency [area under the receiver operating characteristic curve (AUC), 0.905 vs. 0.775]. By contrast, the ADPN presented a better diagnostic value in comparison with NT-proBNP in AHF with renal insufficiency (AUC, 0.872 vs. 0.828). Therefore, a combination of these two biomarkers may provide an excellent efficacy in the diagnosis of AHF with renal insufficiency (AUC, 0.904; sensitivity, 71.2%; specificity, 98.3%). In conclusion, ADPN is a valuable biomarker for diagnosing AHF, particularly in patients with impaired renal function.

Background: The intracoronary high-thrombus burden during the primary percutaneous coronary intervention in patients with ST-elevation myocardial infarction (STEMI) can lead to poor outcomes. Monocytes have been described to play an important role in thrombotic disorders. Objectives: This study aimed to investigate the relationship between admission monocyte count and angiographic intracoronary thrombus burden in patients receiving primary percutaneous coronary intervention (PPCI). Methods: A total of 273 patients with acute STEMI who underwent PPCI were enrolled. The patients were divided into two groups according to the thrombolysis in myocardial infarction (TIMI) thrombus grade: low-thrombus burden group with a grade of 0-2 and high-thrombus burden group with a grade of 3-4. The monocyte count and other laboratory parameters were measured on admission before PPCI. P-value < 0.05 was considered significant. Results: There were 95 patients (34.8%) in the high-thrombus burden group, and 178 patients (65.2%) in the low-thrombus burden group. Patients with high-thrombus burden had significantly higher admission monocyte count (0.61 ± 0.29×109/L vs. 0.53 ± 0.24×109/L, p = 0.021). In multivariate analysis, monocyte count was the independent predictor of angiographic high-thrombus burden (odds ratio 3.107, 95% confidence interval [CI] 1.199-7.052, p = 0.020). For the prediction of angiographic high-thrombus burden, admission monocyte count at a cut-off value of 0.48×109/L yielded 0.59 ROC-AUC (71.9% sensitivity, 46.9% specificity). Conclusions: Monocyte count on admission was an independent clinical predictor of high-thrombus burden in patients with STEMI undergoing PPCI. Our findings suggest that admission monocyte count may be available for early risk stratification of high-thrombus burden in acute STEMI patients and might allow the optimization of antithrombotic therapy to improve the outcomes of PPCI.

Objectives To access the biocompatibility, effectiveness, and safety of biodegradable magnesium (Mg) alloy stent (BMAS) in the coronary artery and femoral artery. Background Atherosclerosis is a lesion of cardiovascular system, including the diseases in heart and blood vessels. Methods The aluminum (Al) and zinc (Zn)-based BMAS was designed by cold drawing methods. Forty healthy immunized mongrel dogs were randomly divided into 8 groups. Five dogs who have not been treated with stent were included in control group. The other dogs were implanted with an absorbable magnesium (Mg) alloy in the coronary and/or femoral artery, and their artery angiography were observed at 7 time points (1, 3, 5, 7, 14, 21, and 28 days; n = 5) follow-up. Dogs from each cohort were sacrificed following angiography for pathology assessment. The histological response including inflammatory response, thrombosis, and intimal hyperplasia were analyzed by hematoxylin-eosin staining. Lumen area (La), intimal hyperplasia area (IHa), and the ratio of IHa were calculated by image analysis software. Results The thin-walled BMAS were designed and produced by cold-drawing technology. Fifty-one devices were implanted into coronary artery of 35 dogs successfully. During the follow-up days, the angiography of coronary artery and femoral artery had confirmed that the lumen was clear and there were no elastic recoil and thrombosis. The stents were completely disappeared at 7 days after implantation. Moderate intimal hyperplasia was found at 14 days after implantation. Conclusion The BMAS stent proved to be of good biocompatibility, safety, and effectiveness. (J Interven Cardiol 2015;XXXX:XX–XX)