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Arrhythmia is the defective origin and conduction of heart activity leading to an abnormal frequency and rhythm of heartbeats. Arrhythmia can cause chest tightness, weakness, sinoatrial node blockages, tachycardia and even sudden death. Arrhythmia therefore seriously affects the safety of human life. An electrocardiogram (ECG) can record the changes in electrical activity produced in each heartbeat cycle. Due to its simplicity and noninvasiveness, ECGs are used clinically to diagnose arrhythmias. However, the diagnosis of arrhythmia by experts is an inefficient diagnostic method. Heart rate variability (HRV) analysis is a common method for analyzing heart-related diseases, especially for the automatic diagnosis of arrhythmia based on RR intervals. In this paper, we extracted the linear and nonlinear characteristics collected from the 5G-enabled medical Internet of Things to construct a time-frequency spectrogram from HRV sequences and used a deep learning model based on the combination of a deep convolutional neural network (CNN) and a long short-term memory (LSTM) network in order to classify normal sinus intervals and arrhythmia intervals. The average accuracy, sensitivity and specificity of this model were 99.06%, 98.29% and 99.73%, respectively, using a tenfold cross validation strategy. The united CNN-LSTM model can accurately detect arrhythmia and has potential value in clinical applications.

To learn whether and how lipid levels are associated with gestational hypertension and fetal growth in normal pregnancy.In a case-control study course, 464 patients with gestational hypertension were pooled into a case group; a total of 1077 women with full-term pregnancies and no pregnancy complications were selected as controls. In a cross-sectional study, whether maternal lipid levels were associated with fetal growth were evaluated in 1077 healthy controls.Maternal lipids and glucose levels and fetal measurements.Maternal levels of triglyceride (TG) were significantly higher in the case group than in controls at gestational weeks 12-16. Levels of TG, total cholesterol (TC) and low-densitylipoprotein (LDL-C) in control mothers increased gradually and significantly with increasing gestational week, however, these lipid concentrations lost these steady elevating trends with gestational week increases in the cases. Binary logistic regression showed that TG is a risk factor associated with hypertension at gestational weeks 12-16 and independent to maternal blood levels of LDL-C and glucose. Of the healthy mothers at gestational weeks 12-16, quantile regression showed that TG levels were not associated with real-time fetal growth measurements or final birthweight. The reference standards for maternal TG levels were estimated via the 10th, 25th, 50th, 75th, and 90th percentiles by gestational week.Maternal TG levels are associated with gestational hypertension, and a wide range of TG levels is sufficient for fetal growth within a given gestational week.

Background. Mitochondrial dysfunction and abnormal mitochondrial fission have been implicated in the complications associated with I/R injury as cardiomyocytes are abundant in mitochondria. SOCS6 is known to participate in mitochondrial fragmentation, but its exact involvement and the pathways associated are uncertain. Methods and Results. The expression of SOCS6 was analyzed by western blot in cardiomyocytes under a hypoxia and reoxygenation (H/R) model. A dual-luciferase reporter assay was used to confirm the direct interaction between miR-19b and the 3 ′ -UTR of Socs6. In the present study, we found that Socs6 inhibition by RNA interference attenuated H/R-induced mitochondrial fission and apoptosis in cardiomyocytes. A luciferase assay indicated that Socs6 is a direct target of miR-19b. The overexpression of miR-19b decreased mitochondrial fission and apoptosis in vitro. Moreover, the presence of miR-19b reduced the level of SOCS6 and the injury caused by I/R in vivo. There were less apoptotic cells in the myocardium of mice injected with miR-19b. In addition, we found that the RNA-binding protein, Quaking (QK), participates in the regulation of miR-19b expression. Conclusions. Our results indicate that the inhibition of mitochondrial fission through downregulating Socs6 via the QK/miR-19b/Socs6 pathway attenuated the damage sustained by I/R. The QK/miR-19b/Socs6 axis plays a vital role in regulation of mitochondrial fission and cardiomyocyte apoptosis and could form the basis of future research in the development of therapies for the management of cardiac diseases.

Atherosclerosis in diabetes is a leading cause of cardiovascular complications. Intermedin (IMD) is a calcitonin peptide that is known to inhibit macrophage phagocytosis in atherosclerosis, but the exact mechanism is unclear. We investigate genes that are differentially expressed in response to IMD in hyperglycemic conditions and determine whether they delay the progression of atherosclerosis. An atherosclerotic and diabetic-murine model was generated in 8-week-old male ApoE−/− mice receiving streptozotocin and a high-fat diet. The mouse model was treated with IMD and the expression levels of NF-κB, Dnm3os, miR-27b-3p, and SLAMF7 were detected in plaque tissue and macrophages cultured with high glucose concentrations. Phagocytosis was determined by oxidized-low-density lipoprotein (Ox-LDL) uptake and the interactions among Dnm3os, SLAMF7 and miR-27b-3p were assessed by dual-luciferase reporter assays. The expression of NF-κB, Dnm3os, and SLAMF7 was enhanced in atherosclerotic plaques but decreased by IMD. The suppression of Dnm3os reduced plaque formation in IMD-treated mice even further whereas increased by miR-27b-3p. Dnm3os and SLAMF7 were competitively bind to miR-27b-3p in vivo. In vitro, ox-LDL uptake is elevated in macrophages cultured in hyperglycemic conditions but reduced by IMD. Dual-luciferase assays indicate that Dnm3os positively regulates SLAMF7 through miR-27b-3p expression. In conclusion, Dnm3os is involved in macrophage phagocytosis through the competitive binding of SLAMF7 with miR-27b-3p. IMD induces the suppression of Dnm3os to inhibit macrophage phagocytosis and alleviate atherosclerosis in diabetes.

Pyroptosis has been implicated in the pathophysiology of myocardial infarction (MI) in rodents, but its contribution to reperfusion injury in MI patients is unclear. Here, we evaluated pyroptosis in MI patients in vitro and in vivo models of myocardial ischemia/reperfusion (I/R) injury. We also investigated the molecular mechanisms that regulate pyroptosis and myocardial I/R injury in these in vitro and in vivo models. The study showed that MI patients exhibited elevated serum concentrations of the pyroptosis-related pro-inflammatory cytokines IL-1β and IL-18. Increased levels of IL-1β and IL-18 as well as the pyroptosis-related inflammatory caspases (caspase-1 and 11) were detected in cultured cardiomyocytes after anoxia/reoxygenation (A/R) and in cardiac tissues after I/R. Circ-NNT and USP46 were upregulated while miR-33a-5p was downregulated in MI patients, as well as in cultured cardiomyocytes after A/R and cardiac tissues after I/R. Circ-NNT or USP46 knockdown or miR-33a-5p overexpression inhibited the expression of pro-caspase-1, cleaved caspase-1, pro-caspase-11, cleaved caspase-11, IL-1β, and IL-18 in A/R cardiomyocytes and attenuated myocardial infarction in I/R mice. The results from luciferase reporter assays and gene overexpression/knockdown studies indicated that miR-33a-5p directly targets USP46, and circ-NNT regulates USP46 by acting as a miR-33a-5p sponge. Direct association between circ-NNT and miR-33a-5p in cardiomyocytes was confirmed by pull-down assays. In summary, pyroptosis is activated during myocardial I/R and contributes to reperfusion injury. Circ-NNT promotes pyroptosis and myocardial I/R injury by acting as a miR-33a-5p sponge to regulate USP46. This circ-NNT→miR-33a-5p→USP46 signaling axis may serve as a potential target for the development of cardio-protective agents to improve the clinical outcome of reperfusion therapy.

Circular RNAs (circRNAs) are novel non-coding RNAs, which show abnormal expression in several diseases, such as atherosclerosis (AS). The purpose of the present study was to reveal the association between hsa_circ_0004543 and AS. In the present study, hsa_circ_0004543 was overexpressed in human umbilical vein endothelial cells (HUVECs) induced by oxidized low-density lipoprotein (oxLDL). Inhibition of hsa_circ_0004543 expression facilitated the proliferation, migration, and invasion of HUVECs and significantly reduced their apoptotic rate following treatment with oxLDL. Furthermore, silencing of hsa_circ_0004543 activated the PI3K/AKT/NOS3 pathway in oxLDL-induced HUVECs. Collectively, these results demonstrated that hsa_circ_0004543 may play a vital role in the development of AS and affect the proliferation of HUVECs, providing a potential target for treating endothelial cell damage in AS.

Background Ischemia/reperfusion (IR) injury following myocardial infarction can result in debilitating complications and morbidity. Mitochondrial dysfunction and abnormal mitochondrial fission have been implicated in the complications associated with IR injury as cardiomyocytes are abundant in mitochondria. SOCS-6 is known to participate in mitochondrial fragmentation but its exact involvement and the pathways associated are uncertain. Results In the present study, we examine the biological role and regulation of SOCS-6 in mitochondrial dynamics using hypoxia and reoxygenation (H/R) in cardiomyocytes and with a murine model of IR injury. We found that SOCS-6 inhibition by RNA interference attenuated H/R-induced mitochondrial fission and apoptosis in cardiomyocytes. A luciferase assay indicated that SOCS-6 is a direct target of miR-19b. The overexpression of miR-19b decreased mitochondrial fission and apoptosis in vitro . Moreover, the presence of miR-19b reduced the level of SOCS-6 and the injury caused by IR in vivo . There were less apoptotic cells in the myocardium of mice injected with miR-19b. In addition, we found that the RNA-binding protein, QKI, participates in the regulation of miR-19b expression. Conclusions Our results indicate that the inhibition of mitochondrial fission through downregulating SOCS-6 via the QKI/miR-19b/SOCS-6 pathway attenuated the damage sustained by IR. The QKI/miR-19b/SOCS-6 axis plays a vital role in regulation of mitochondrial fission and cardiomyocyte apoptosis and could form the basis of future research in the development of therapies for the management of cardiac diseases.

Background and aims Disorders in blood lipid metabolism and leukocyte-mediated inflammation are considered the main mechanisms of the pathogenesis of atherosclerosis. This study aims to show whether and how peripheral leukocyte counts are associated with serum lipid levels. Methods This is a cross-sectional study of 175,079 subjects from the healthy population. Results Age and sex are two key factors dictating the relationship between peripheral leukocyte counts and serum lipid levels. The log-transformed level of triglycerides (LnTG) was positively associated with all leukocyte counts in males except monocyte count in younger subjects. LnTG was positively associated with total leukocyte count in females regardless of age, and it was positively associated with lymphocyte and monocyte counts and neutrophil count only in elderly and young women, respectively. Total cholesterol levels were positively associated with total leukocyte, neutrophil and lymphocyte counts only in young males and with lymphocyte counts only in elderly women. LDL-C was negatively associated with monocyte count in males regardless of age; by contrast, it was positively associated with total leukocyte and lymphocyte counts in females regardless of age range and neutrophil and LnEosinophil counts only in young women. HDL-C was negatively associated with total leukocyte, lymphocyte and monocyte counts in both young men and young women; was negatively associated with monocyte count in elderly men and women; and was negatively associated with LnEosinophil count only in older men. Conclusions Peripheral leukocyte counts are extensively associated with serum lipid levels, with patterns differing by sex, age, lipid and leukocyte subset.

Objective To characterize the association pattern between blood pressure (BP), metabolism changes, and obstructive sleep apnea (OSA) severity within male OSA patients. Methods The association between systolic BP (SBP), diastolic BP (DBP), glucose, lipids, apnea-hypopnea index (AHI), oxygen desaturation index (ODI), and arousal index (ArI) was evaluated after adjustment for BMI and waist circumference/hip circumference ratio (WHR) in 1,370 male OSA patients. Results In the multiple linear regression models using SBP as an independent variable, SBP did not associate with the increase of any OSA indexes. BMI and glucose positively associated with AHI, ODI, and ArI elevation. WHR was also positively associated with increasing AHI and ODI. Total cholesterol levels increased with ODI and ArI increases. Triglyceride was associated with ArI. In the multiple linear regression models using DBP as an independent variable, DBP associated universally with AHI, ODI, and ArI with stable coefficients ranging from 0.19 to 0.20. The remaining independent variables were associated with AHI, ODI, and ArI with a similar trend to the models including SBP as an independent variable. Conclusions Apnea-hypopnea, hypoxemia, and arousal changed glycometabolism, fat metabolism, and BP profoundly in a particular pattern.

Understanding how blood lipid levels change with age in the general population is a precondition to defining dyslipidemia. To explore age-related trends in LDL-C and non-HDL-C levels in the general population, a large-scale cross-sectional study with 49,201 males and 35,084 females was adopted. Trends of non-HDL-C and LDL-C levels were plotted against each age (18 to 85 years old, one-year increments); the trends, as well as the influence of confounding factors on the trends, were validated and adjusted by linear regression modeling. The trajectory of LDL-C and non-HDL-C levels by age displayed a nonlinear correlation trend. Further multivariate linear regression modeling that incorporated sex-specific age phases showed that age was positively associated with LDL-C and non-HDL-C levels, with coefficients of 0.018 and 0.031, respectively, in females aged ≥18 to ≤56 years and negatively associated with LDL-C and non-HDL-C levels, with coefficients of -0·013 and -0.015, respectively, in females aged ≥57 years. The LDL-C and non-HDL-C levels increased with age in males ≥18 to ≤33 years of age, with coefficients of 0.025 and 0.053, respectively; the lipid levels plateaued at ≥34 to ≤56 years of age and subsequently decreased in those ≥57 years of age, with coefficients of -0.008 and -0.018, respectively. In contrast, pooled analyses without age stratification concealed these details. In conclusion, fluctuating increasing and decreasing lipid levels occurred with phases of aging in both sexes. Well-grounded age stratification is necessary to improve lipid-related pathophysiological studies.

Background: Evaluation of the lifetime trends of blood-lipid levels is needed to understand the role of dyslipidemia in the development and progression of diseases. Methods: The biannual physical examination results of 54,322 males and 37,851 females, comprising 167,542 data sets, were collected. Age-related trends in LDL-C and non-HDL-C levels were explored by age stratifications and valid by fitted linear logistic regression modeling. Findings: Among pooled females, age associated with LDL-C and non-HDL-C levels positively with coefficients of 0·016 and 0·026, respectively. After age stratification, age was positively associated with LDL-C and non-HDL-C levels with coefficients of 0·020 (95%CI: 0·020~0·021) and 0·033 (0·033~0·034), respectively in females aged 18 to 56 years; and negatively with coefficients of −0·013 (−0·010~−0·007) and −0·014 (−0·017~−0·011), respectively in females aged ≥57 years. Among pooled males, age associated with LDL-C and non-HDL-C levels positively with coefficients of 0·003 and 0·005, respectively. After age stratification, the LDL-C and non-HDL-C levels increased with age in males aged 18 to 33 years with coefficients of 0·026 (0·023~0·029) and 0·052 (0·049~0·055), respectively; plateaued between 34 to 56 years old with coefficients of 0·002 (0·001~0·003) and 0·005 (0·004~0·006), respectively; and subsequently decreased in males aged ≥57 years with coefficients of −0·008 (−0·010~−0·007) and −0·017 (−0·019~−0·015), respectively. Adjustments for covariates had little effect on the linear correlation patterns between age and lipids levels. Interpretation: In males and females, the LDL-C and non-HDL-C levels showed two (increase and decrease) and three (increase, plateau, and decrease) phases, respectively, with age. Funding Statement: The Major Projects of the Shanghai Municipal Commission of Health and Family Planning; the Shanghai Medical Key Specialty Construction Projects. Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: This study was conducted in accordance with the statement of ethical principles for medical research involving human subjects of the World Medical Association Declaration of Helsinki, and was approved by the Internal Review Board of Minhang Hospital, Fudan University, Shanghai, China. Written informed consent was obtained according to the guidelines of the National Ethics Regulation Committee.

Peroxiredoxin 2 (PRDX2) is an antioxidant and molecular chaperone that can be secreted from tumor cells. But the role of PRDX2 in acute myocardial infarction (AMI) is not clear. In the current study, we demonstrate the role of PRDX2 from clinical trials, H9c2 cells and in a mouse model. ELISA analysis shows that serum concentrations of VEGF and inflammatory factor IL-1β, TNF-α and IL-6 were increased in AMI patients compared to a control group. The expression of PRDX2 was also upregulated. In vivo experiments show that the expression of PRDX2 inhibits hypoxia-induced oxidative stress injury to H9c2 cells. However, PRDX2 expression promotes TLR4 mediated inflammatory factor expression and VEGF expression under hypoxia conditions. PRDX2 overexpression in H9c2 cells also promotes human endothelial cell migration, vasculogenic mimicry formation and myocardial hypertrophy related protein expression. The overexpression of PRDX2 inhibits ROS level and myocardial injury after AMI but promotes inflammatory responses in vivo. Immunocytochemistry and immunofluorescence analysis show that overexpression of PRDX2 promotes angiogenesis and myocardial hypertrophy. Taken together, our results indicate that PRDX2 plays two roles in acute infarction – the promotion of cell survival and inflammatory myocardial hypertrophy.