2023 Chinese expert consensus on the impact of COVID-19 on the management of cardiovascular diseases.

The primary site of infection in COVID-19 exhibit is the respiratory system, but multiple organ systems could be affected. The virus could directly invade cardiomyocytes. Alternatively, cytokine storm could lead to myocardial injury. More importantly, the management of existing cardiovascular diseases must be re-examined in COVID-19 due to, for example, interaction between antiviral agents and with a wide variety of pharmacological agents. The Branch of Cardiovascular Physicians of Chinese Medical Doctor Association organized a panel of experts in cardiovascular and related fields to discuss this important issue, and formulated the "2023 Chinese Expert Consensus on the Impact of COVID-19 on the Management of Cardiovascular Diseases." The Consensus was drafted on the basis of systematic review of existing evidence and diagnosis and treatment experience, and covers three major aspects: myocardial injury caused by COVID-10 and COVID-19 vaccine, the impact of COVID-19 on patients with cardiovascular disease, and the impact of COVID-19 on the cardiovascular system of healthy people, and rehabilitation guidance recommendations. The Consensus involves 11 core clinical issues, including incidence, pathogenesis, clinical manifestations, treatment strategies, prognosis, and rehabilitation. It is our hope that this Consensus will provide a practical guidance to cardiologists in the management of cardiovascular diseases in the new era of COVID-19 pandemic.

Qishen Yiqi dropping pills improve cardiomyocyte hypertrophy via the lncRNA TINCR/miR-193b-3p/RORA axis.

Background: This study was designed to explore the therapeutic effect and mechanism of action of Qishen Yiqi dropping pills (QYDP) in chronic heart failure (CHF) via a long non-coding RNA (lncRNA)-microRNA (miRNA)-messenger RNA (mRNA) axis. Here, the mechanism of action of the lncRNA terminal differentiation-induced non-coding RNA (TINCR), miR-193b-3p, and RAR-related orphan receptor A (RORA) mRNA was analyzed in an angiotensin (Ang) II-induced H9C2 cardiomyocyte hypertrophy model treated with QYDP. Methods: Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to analyze the gene expression changes of lncRNA, miRNA, and mRNA in H9C2 induced by QYDP on Ang II. The Gene Expression Omnibus (GEO) was used to analyze differentially expressed genes (DEGs) potentially affecting CHF progression. Cell Counting Kit-8 (CCK-8) was used to analyze the effect of QYDP on the proliferation of H9C2, RNA pull-down was used to analyze the binding of lncRNA and miRNA, and dual luciferase was used to analyze the targeting of miRNA and lncRNA or mRNA. Results: Ang II induced TINCR and RORA downregulation, miR-193b-3p upregulation, and hypertrophy in the H9C2 cardiomyocytes, which were alleviated by QYDP. In contrast, TINCR inhibition reversed the effects of QYDP by increasing miR-193b-3p expression and downregulating RORA expression. According to subsequent double luciferase and RNA pull-down experiments, TINCR adsorbed miR-193b-3p by acting as a competitive endogenous RNA sponge and miR-193b-3p directly targeted RORA. Lastly, we showed that the Ang-II-induced inhibition of TINCR and RORA expression and promotion of cardiac hypertrophy were both reversed by a TINCR overexpression plasmid (ov-TINCR), whereas the effects of ov-TINCR were suppressed by a miR-193b-3p mimic. Conclusions: Administration of QYDP improves Ang II-induced H9C2 cardiomyocyte hypertrophy and increase cell proliferation rate through the TINCR/miR-193b-3p/RORA axis.

Qishen Yiqi dropping pills improve isoproterenol-induced cardiomyocyte hypertrophy by regulating X-inactive specific transcript (XIST) expression in rats.

Background: This study aimed to explore the potential mechanism of Qishen Yiqi dropping pills (QYDPs) in the treatment of chronic heart failure (CHF) by regulating the expression of lncRNAs during CHF. Methods: Differences in the expression of the long non-coding RNA (lncRNA), X-inactive specific transcript (XIST), in an isoproterenol (ISO)-induced cardiomyocyte hypertrophy model treated with QYDPs was analyzed by reverse transcription quantitative polymerase chain reaction (RT-qPCR). A cell counting kit-8 (CCK8) assay, flow cytometry (FCM), and enzyme linked immunosorbent assay (ELISA) were used to analyze the protective effects of QYDPs on the proliferation rate, apoptosis, myocardial enzyme, oxidative stress, and inflammation of cardiomyocytes, as well as the molecular mechanism of XIST. Results: Our results showed that in the ISO-induced cardiomyocyte hypertrophy model, XIST expression and apoptosis were increased, the cell proliferation rate was decreased, and myocardial enzyme levels increased [i.e., increased lactate dehydrogenase (LDH) and creatine kinase (CK) levels]. Furthermore, cellular oxidative stress [i.e., increased malondialdehyde (MDA) levels and decreased superoxide dismutase (SOD) levels] and inflammatory response [i.e., increased interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α protein secretion] were also promoted. QYDP treatment effectively mitigated the effects of ISO induction. Subsequently, we found that suppressing XIST expression reversed the effect of ISO induction, whereas overexpression (ov) of XIST enhanced the effect of ISO induction. Finally, this study confirmed that QYDP treatment improved the ISO-induced decrease in proliferation, apoptosis, and promotion of oxidative stress and inflammatory response in cardiomyocytes, whereas ov of XIST partially negated the effect of QYDPs. Conclusions: QYDPs protected H9c2 cells from ISO-induced damage by downregulating XIST expression.

Comparative Analysis and Identification of Differentially Expressed microRNAs in the Hypothalamus of Kazakh Sheep Exposed to Different Photoperiod Conditions.

MicroRNAs (miRNA) plays an important role in several mammalian biological regulatory processes by post-transcriptionally regulating gene expression. However, there is little information on the miRNAs involved in the photoperiodism pathway that controls seasonal activity. To enhance our knowledge on the effect of different photoperiod conditions on miRNA, we divided Kazakh sheep into two groups: one exposed to a long photoperiod (LP, 16L:8D) and another with exposed to a short photoperiod (SP, 8L:16D) under supplemental feeding conditions. Further we compared the related miRNAs and target genes between the two groups. Fifteen differentially expressed miRNAs were identified, which were associated with 310 regulatory pathways covering photoperiodism, reproductive hormones, and nutrition. The miR-136-GNAQ pair was selected and validated as a differentially expressed, and a dual-luciferase reporter assay showed that the negative feedback loop existed between them. Examination of the expression profile revealed that the GNAQ expression was low in the estrous females both under LP and SP conditions, but high expression of GNAQ was observed in the anestrous females under LP conditions. Moreover, functional analysis revealed that KISS1 and GnRH expression was upregulated when GNAQ expression was downregulated in the hypothalamic cells, whereas DIO2 and TSHB expression was downregulated. Thus, miR-136-GNAQ might act as a switch in the regulation of seasonal estrus under different photoperiod conditions. These findings further enrich our understanding of the relationship between miRNAs and seasonal regulation of reproductive activity. Furthermore, our study provides novel insights into the miRNA-mediated regulatory mechanisms for overcoming photoinhibition in the seasonally breeding mammals, such as Kazakh sheep.

LncRNA kcnq1ot1 promotes lipid accumulation and accelerates atherosclerosis via functioning as a ceRNA through the miR-452-3p/HDAC3/ABCA1 axis.

Kcnq1 overlapping transcript 1 (kcnq1ot1), an imprinted antisense lncRNA in the kcnq1 locus, acts as a potential contributor to cardiovascular disease, but its role in atherosclerosis remains unknown. The aim of this study was to explore the effects of kcnq1ot1 on atherogenesis and the underlying mechanism. Our results showed that kcnq1ot1 expression was significantly increased in mouse aorta with atherosclerosis and lipid-loaded macrophages. Lentivirus-mediated kcnq1ot1 overexpression markedly increased atherosclerotic plaque area and decreased plasma HDL-C levels and RCT efficiency in apoE-/- mice fed a Western diet. Upregulation of kcnq1ot1 also reduced the expression of miR-452-3p and ABCA1 but increased HDAC3 levels in mouse aorta and THP-1 macrophages. Accordingly, kcnq1ot1 overexpression inhibited cholesterol efflux and promoted lipid accumulation in THP-1 macrophages. In contrast, kcnq1ot1 knockdown protected against atherosclerosis in apoE-/- mice and suppressed lipid accumulation in THP-1 macrophages. Mechanistically, kcnq1ot1 enhanced HDAC3 expression by competitively binding to miR-452-3p, thereby inhibiting ABCA1 expression and subsequent cholesterol efflux. Taken together, these findings suggest that kcnq1ot1 promotes macrophage lipid accumulation and accelerates the development of atherosclerosis through the miR-452-3p/HDAC3/ABCA1 pathway.

Association of S100B 3'UTR polymorphism with risk of chronic heart failure in a Chinese Han population.

To study the correlation between single nucleotide polymorphism (SNP) of the 3' untranslated region (UTR) rs9722 locus in S100B and the risk of chronic heart failure (CHF), plasma levels of S100B protein as well as has-miR-340-3p in a Chinese Han population.A total of 215 patients with CHF (124 ischemic cardiomyopathy (ICM) and 91 dilated cardiomyopathy (DCM)) and 215 healthy controls were recruited to analyze the S100B rs9722 genotype by Sanger sequencing. The levels of hsa-miR-340-3p in the plasma were detected by RT-PCR, and S100B levels were detected by ELISA.The risk of CHF in S100B rs9722 locus T allele carriers was 4.24 times higher than that in those with the C allele (95% CI: 2.84-6.33, P < .001). The association of S100B rs9722 locus SNP with ICM and DCM risk was not affected by factors such as age, gender, and body mass index (BMI). The levels of plasma S100B and hsa-miR-340-3p in patients with ICM and DCM were significantly higher than those in the control group (P < .001). There was no significant difference in plasma S100B levels between patients with ICM and DCM (P > .05). Among ICM, DCM, and control subjects, TT genotype carriers had the highest levels of plasma S100B and hsa-miR-340-3p, followed by the CT genotype and TT genotype, and the difference was statistically significant (P < .05). Plasma hsa-miR-340-3p levels were positively correlated with S100B levels in the control subjects and patients with ICM and DCM.The S100B rs9722 locus SNP is associated with CHF risk in a Chinese Han population.

MHC-DRB1 exon 2 polymorphism and its association with mycoplasma ovipneumonia resistance or susceptibility genotypes in sheep.

Major histocompatibility complex (MHC) polymorphisms are associated with animal and human diseases. However, only a few studies have reported an association between MHC polymorphisms and mycoplasma ovipneumonia (MO). In the present study, three resistance/susceptibility genotypes associated with MO were identified by polymerase chain reaction-restriction fragment length polymorphism genotyping, assessing the clinical and pathological features, and examining the immune factors. The current results showed that MvaI bb and HaeIII ee were dominant genotypes in the susceptible Hu population, while MO-resistant populations, Dorper and D 9 H hybrids, were dominated by the MvaI cc and HaeIII dd genotypes, suggesting that MvaI cc and HaeIII dd genotypes might be associated with the trait of MO resistance. Further, the clinical symptoms and pathological morphology in the susceptibility group infected with MO were more severe than those in the resistant groups infected similarly. The data on the changes in the immune factor responses were utilized to deduce the molecular mechanism underlying the MO resistance/susceptibility. The results showed that the susceptible genotypes promote the inflammatory responses by inducing a high expression of TNFa, IFNc, IL-4, IL-6, and IL-1b, while the resistant genotypes inhibit the inflammatory response by increasing the expression of IL-2 and IL-10 significantly. This finding would provide the theoretical guidance for propagating sheep breeds that are highly resistant to MO.

The long noncoding RNA XIST protects cardiomyocyte hypertrophy by targeting miR-330-3p.

Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) are implicated in numerous kinds of cardiovascular diseases, and their vital role in regulating cardiac hypertrophy still needs to be explored. In this study, we demonstrated that lncRNA X-inactive specific transcript (XIST) was upregulated in hypertrophic cardiac of mice and phenylephrine (PE)-treated cardiomyocytes. Next, we observed that inhibition of XIST induced hypertrophic response of cardiomyocyte and overexpression of XIST attenuated cardiomyocyte hypertrophy induced by PE. Furthermore, through online predictive tools and functional experiments, we demonstrated that XIST and S100B were targets of miR-330-3p. XIST and miR-330-3p suppressed each other in a reciprocal way in cardiomyocytes. Additionally, XIST promoted S100B expression through harboring the complementary binding sites with miR-330-3p, eventually prevented cardiac hypertrophy. In conclusion, our findings revealed a novel molecular mechanism that XIST/miR-330-3p/S100B pathway modulates the progression of cardiomyocyte hypertrophy.

Associations between polymorphisms of the CXCL12 and CNNM2 gene and hypertension risk: A case-control study.

BACKGROUND: Hypertension is the most important risk factor for cardiovascular and cerebrovascular diseases. The study found that CXCL12 and CNNM2 gene affects the risk of coronary heart disease, but the relationship with hypertension is unclear. The aim of this research is to explore the association between CXCL12 and CNNM2 gene and hypertension in Chinese Han population. METHODS: Genotypes at 11 CHD-relevant SNPs were determined in 350 Hypertension patients and 483 controls in Chinese Han population using χ2 test, genetic model analysis and haplotype analysis. RESULTS: In the allele model, CXCL12 rs1065297 "G" allele, CXCL12 rs4948878 "G" allele and CXCL12 rs10793538 "T" allele were associated with decreased risk of hypertension (rs1065297: OR = 0.53, p = 0.005; rs4948878: OR = 0.51, p = 0.004; rs10793538: OR = 0.58, p = 0.005). CNNM2 rs12413409 "A" allele and CNNM2 rs11191514 "T" allele were also associated with reduced risk of hypertension (rs12413409: OR = 0.71, p = 0.003; rs11191514: OR = 0.70, p = 0.002). Further stratified analysis by sex and age found that CXCL12, CNNM2 gene also influence the risk of hypertension. Model analysis found that CXCL12 rs1093538 TA-TT genotype was associated with decreased risk of hypertension in the dominant model (OR = 0.57, p = 0.0015); Log-additive model revealed that rs1065297 and rs4948878 in CXCL12 gene have a potential association with essential hypertension (rs1065297: OR = 0.54, p = 0.005; rs4948878: OR = 0.52, p = 0.0038). For CNNM2 gene, rs12413409 GA-AA genotype and rs11191514 CT-TT genotype was associated with reduced risk of hypertension in the dominant model (rs12413409: OR = 0.64, p = 0.012; rs11191514: OR = 0.63, p = 0.0082). CXCL12 "GCGCCGT" and CNNM2 "ATAG" haplotype were associated with reduced risk of hypertension with 0.57-fold and 0.75-fold. CONCLUSIONS: Our analysis suggests that CXCL12, CNNM2 gene influence the risk of hypertension in Chinese Han population.

Identification and analysis of microRNAs-mRNAs pairs associated with nutritional status in seasonal sheep.

Given the important role of nutritional status for reproductive performance, we aimed to explore the potential microRNA (miRNA)-mRNA pairs and their regulatory roles associated with nutritional status in seasonal reproducing sheep. Individual ewes were treated with and without 0.3 kg/day concentrates, and the body condition score, estrus rate, and related miRNAs and target genes were compared. A total of 261 differentially expressed miRNAs were identified, including 148 hypothalamus-expressed miRNAs and 113 ovary-expressed miRNAs, and 349 target genes were predicted to be associated with nutritional status and seasonal reproduction in sheep. Ultimately, the miR-200b-GNAQ pair was screened and validated as differentially expressed, and a dual luciferase reporter assay showed that miR-200b could bind to the 3'-untranslated region of GNAQ to mediate the hypothalamic-pituitary-ovarian axis. Thus, miR-200b and its target gene GNAQ likely represent an important negative feedback loop, providing a link between nutritional status and seasonal reproduction in sheep toward enhancing reproductive performance and productivity.

Using Mobile Health Intervention to Improve Secondary Prevention of Coronary Heart Diseases in China: Mixed-Methods Feasibility Study.

BACKGROUND: Coronary heart disease (CHD) is the leading cause of cardiovascular mortality worldwide, yet implementation of evidence-based strategies for secondary prevention remains suboptimal. OBJECTIVE: This study aimed to evaluate the feasibility, specifically the usability and acceptability, and estimate the preliminary effectiveness of a mobile health (mHealth) intervention targeting both physicians and patients to improve adherence to evidence-based medications and lifestyle modifications. METHODS: We conducted a 12-week pre-post interventional pilot study at two sites in Shanghai and Hainan, China. Physicians used the app designed in this study to prescribe evidence-based medicines and record patient information. Eligible and consenting patients received automatic text messages or voice calls 4 to 5 times per week for 12 weeks on medication adherence and healthy behaviors. Interviews were conducted among 10 physicians and 24 patients at the two sites for their thoughts on medication adherence and feedback on the usability and acceptability. Questions on usability and acceptability were also asked in a patient follow-up survey. With regard to estimating effectiveness, the primary outcome was medication adherence (as estimated by the Morisky Green Levine Scale) at 12 weeks. Secondary outcomes included physical activity, smoking status, fruits and vegetables consumption, and facility visit frequency. RESULTS: Interview findings and patient survey showed the good usability and acceptability of the intervention. Among 190 patients who completed the intervention, there was a significant increase in medication adherence (odds ratio [OR] 1.80, 95% CI 1.14-2.85). The study also showed decrease of smokers' percentage (-5%, P=.05), increase of daily vegetables consumption frequency (+0.3/day, P=.01), and community health care center visit frequency (+3 in 3 months, P=.04). The following site-specific differences were noted: medication adherence appeared to increase in Hainan (OR 14.68, 95% CI 5.20-41.45) but not in Shanghai (OR 0.61, 95% CI 0.33-1.12). CONCLUSIONS: Our study demonstrated that the intervention was feasible in both a tertiary care center and an urban community health center in China. Preliminary results from pre-post comparison suggest the possibility that provider and patient-linked mHealth interventions may improve medication adherence and lifestyle modifications among CHD patients, especially in resource-scarce settings. Randomized controlled trials are needed to verify the findings.

The seroprevalence of Mycobacterium avium subspecies paratuberculosis in dairy cattle in Xinjiang, Northwest China.

BACKGROUND: Mycobacterium avium subspecies paratuberculosis (MAP) causes chronic, wasting, and progressive enteritis in cattle, bringing significant economic losses in livestock industries. MAP has spread worldwide mainly due to movement of animals. The objective of this study was to determine the MAP seroprevalence in cattle in the Xinjiang Uygur Autonomous Region, Northwest China, and evaluate the difference between intensive farming herds (cattle number in a herd is more than 200, and the cattle cannot have access to pasture) and free-range herds (the cattle are bred by individual households, a herd is defined as the cattle are bred in a village or town in this study). RESULTS: A total of 3157 serum specimens were collected from 42 herds in nine different regions. This included 1481 specimens from 18 intensive farming herds in four regions and 1676 specimens from 24 free-range herds in six regions. Antibody against MAP was tested with commercial ELISA test kits. The results showed that the overall apparent prevalence was 4.8% (95% CI, 4.1 to 5.6%) at animal level, and 50.0% (21/42) at herd level. The apparent prevalence in intensive farming herds and free-range herds were 9.5% (141/1481) and 0.7% (11/1676) at the animal-level, 88.9%(16/18) and 20.8% (5/24) at herd level, respectively, with a significant statistical difference between these two farming modes (p < 0.01). Cattle in intensive farming herds had a relatively higher risk to be infected with MAP than those in free-range herds (RR = 14.4). CONCLUSION: This study demonstrates that apparent prevalence of MAP infection in dairy cattle differs with farming modes at the animal level and herd level, and farming density could be an important risk factor associated with the presence of MAP infected cattle. This study provides important epidemiological data for bovine MAP control in Xinjiang, Northwest China.

Development of a mobile phone-based intervention to improve adherence to secondary prevention of coronary heart disease in China.

Coronary heart disease (CHD) is a major disease burden globally and in China, but secondary prevention among CHD patients remains insufficient. Mobile health (mHealth) technology holds promise for improving secondary prevention but few previous studies included both provider-facing and patient-directed measures. We conducted a physician needs assessment survey (n = 59), physician interviews (n = 6), one focus group and a short cellphone message validation survey (n = 14) in Shanghai and Hainan, China. Based on these results, we developed a multifaceted mHealth intervention that includes: (1) a provider-facing bilingual mobile app guiding prescription of evidence-based medications for secondary prevention and (2) a patient-directed short messaging system automatically sending reminders to patients regarding medication adherence and lifestyle changes (4-5 messages per week for 12 weeks). This combined intervention has the potential to improve secondary prevention of CHD and to be adapted to other countries and healthcare conditions.

Gene Expression Profile in the Liver of Sheep Infected with Cystic Echinococcosis.

BACKGROUND: Cystic Echinococcosis (CE), caused by infection with the Echinococcus granulosus (E. granulosus), represents considerable health problems in both humans and livestock. Nevertheless, the genetic program that regulates the host response to E. granulosus infection is largely unknown. Previously, using microarray analysis, we found that the innate immunity played a vital role in the E. granulosus defense of the intestine tissue where E. granulosus first invaded. Subsequently, we turned our attention to investigating the molecular immune mechanism in its organ target, the liver, which is where the E. granulosus metacestodes are established and live for very long periods. In this work, the microarray-based methodology was used to study gene expression profiles in the liver of sheep infected with E. granulosus at 8 weeks post infection, corresponding to the early cystic established phase. METHODS: A total of 6 female-1-year-old healthy Kazakh sheep were used for the experiments. Three Kazakh sheep were orally infected with E. granulosus eggs, and the others remained untreated and served as controls. Sheep were humanely euthanized and necropsized at 8 weeks post-infection (the early stage of cyst established). The microarray was used to detect differential hepatic gene expression between CE infection sheep and healthy controls at this time point. Real-time PCR was used to validate the microarray data. RESULTS: We found that E. granulosus infection induces 153 differentially expressed genes in the livers of infected sheep compared with healthy controls. Among them, 87 genes were up-regulated, and 66 genes were notably down-regulated. Functional analysis showed that these genes were associated with three major functional categories: (a) metabolism, (b) the immune system and (c) signaling and transport. Deeper analysis indicated that complement together with other genes associated with metabolism, played important roles in the defense of E. granulosus infection. CONCLUSION: The present study identified genes profiling in the liver tissue of E. granulosus infection in sheep. The expression pattern obtained here could be helpful for understanding the molecular immunity mechanisms of host responses to E. granulosus infection. However, it is necessary to carry out further studies to evalute the role of these genes.