Probiotics combined with atorvastatin administration in the treatment of hyperlipidemia: A randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND: Hyperlipidemia is a common feature of chronic diseases. The aim of this work was designed to assess the role of probiotics (Lactobacillus casei Zhang, Bifidobactetium animalis subsp. lactis V9, and Lactobacillus plantarum P-8) in the treatment of hyperlipidemia. METHODS: Thirty three patients with hyperlipidemia were randomly divided into a probiotic group (n = 18) and a control group (n = 15). The probiotic group was administered probiotics (2 g once daily) and atorvastatin 20 mg (once daily), and the control group was administered a placebo (2 g once daily) and atorvastatin 20 mg (once daily). Serum and fecal samples were gathered for subsequent analyses. RESULTS: Time had a significant effect on the total cholesterol (TC), triglycerides (TG), and low-density lipoprotein-cholesterol (LDL-C) levels in the probiotic and control groups (P < .05). The gut microbial abundance in the probiotic group was markedly higher than that in the control group following 3-month probiotic treatment (P < .05). At the phylum level, probiotics exerted no notable effects on the relative abundance of Firmicutes, Bacteroidetes, and Actinobacteria but elevated that of Tenericutes and reduced Proteobacteria. At the genus level, probiotics increased the relative abundance of Bifidobacterium, Lactobacillus, and Akkermansia, and decreased that of Escherichia, Eggerthella, and Sutterella relative to the control group in months 1, 2, and 3 (P < .05). CONCLUSIONS: Probiotics optimize the gut microbiota structure and decrease the amount of harmful bacteria in patients with hyperlipidemia. Probiotics can influence the composition of gut microorganisms and increase their diversity and abundance in vivo. It is recommended to use probiotics combined with atorvastatin to treat patients with hyperlipidemia.

Bone marrow mesenchymal stem cells-derived exosomal lncRNA GAS5 mitigates heart failure by inhibiting UL3/Hippo pathway-mediated ferroptosis.

BACKGROUND: Exosomes (Exos) are involved in the therapeutic effects of bone marrow mesenchymal stem cells (BMSCs) on heart failure (HF). We investigated the molecular mechanisms underlying the involvement of BMSC-Exos in ferroptosis on HF. METHODS: A rat model of HF and cellular model of hypoxia were established. BMSC-Exos were injected into model rats or co-cultured with model cells. In model rats, the cardiac function (echocardiography), oxidative stress (commercial kits), pathological damage (HE staining), fibrosis (MASSON staining), iron deposition (Prussian blue staining), and cell apoptosis (TUNEL staining) were examined. Viability (cell counting kit-8; CCK-8), cell cycle (flow cytometry), oxidative stress, and Fe2+ levels were detected in the model cells. GAS5, UL3, YAP, and TAZ expression were detected using qRT-PCR, western blotting, and immunohistochemistry analyses. RESULTS: BMSC-Exos restored cardiac function and inhibited oxidative stress, apoptosis, pathological damage, fibrosis, and iron deposition in myocardial tissues of HF rats. In hypoxic cells, BMSC-Exos increased cell viability, decreased the number of G1 phase cells, decreased Fe2+ levels, and inhibited oxidative stress. Ferrostatin-1 (a ferroptosis inhibitor) exhibited a synergistic effect with BMSC-Exos. Additionally, GAS5 was upregulated in BMSC-Exos, further upregulating its target UL3 and Hippo pathway effectors (YAP and TAZ). The relieving effects of BMSC-Exos on HF or hypoxia-induced injury were enhanced by GAS5 overexpression, but weakened by UL3 silencing or verteporfin (a YAP inhibitor). CONCLUSIONS: GAS5-harbouring BMSC-Exos inhibited ferroptosis by regulating the UL3/Hippo pathway, contributing to HF remission in vivo and in vitro.

Variation and disparity in awareness of atrial fibrillation in China: A national cross-sectional study.

BACKGROUND: The latest information regarding the awareness of atrial fibrillation (AF) remains limited in China. OBJECTIVES: The present study aimed to understand the variation and disparity in awareness of AF in China. METHODS: The cross-sectional study used data from the 2020 nationwide epidemiology survey on AF among adults aged 18 years or older in mainland China to assess the prevalence of AF awareness. The awareness of AF diagnostic methods and outcomes was also assessed using an interviewer-administered questionnaire. RESULTS: Of the 114,039 adults responding to the survey, 1463 (age-standardized prevalence, 55.3% (95% confidence interval [CI], 47.7-62.9%) and 10,202 (8.2%, 95%CI 5.4-10.9%) were aware of AF in participants with and without AF, respectively. Of these, 36.4% (95%CI 30.0-42.9%) and 6.3% (95%CI 3.6-9.1%) considered electrocardiogram as a method of diagnosing AF, and 30.0% (95% CI 3.2-8.2%) and 5.2% (95%CI 2.7-7.6%) considered stroke as an outcome of AF. The proportion of participants who being aware of AF varied significantly across sociodemographic and cardiovascular disease subgroups, and was almost consistently lower in rural areas than those in urban areas. Overall, lack of AF awareness was associated with rural areas, geographical region, lower education levels, and without history and had no risk factors of cardiovascular disease. CONCLUSIONS: Nearly half of adults with AF, and >90% non-AF population are unaware of AF in China, with significant variation and disparity. Focused public health initiatives are needed to improve awareness and knowledge of AF among high-risk populations.

Factors associated with the delay in informed consent procedures of patients with ST-segment elevation myocardial infarction and its influence on door-to-balloon time: a nationwide retrospective cohort study.

Background and Objectives: ST-segment elevation myocardial infarction (STEMI) is the deadliest and most time-sensitive acute cardiac event. However, failure to achieve timely informed consent is an important contributor to in-hospital delay in STEMI care in China. We investigated the factors associated with informed consent delay in patients with STEMI undergoing percutaneous coronary intervention (PCI) and the association between the delay and door-to-balloon time. Methods: We conducted a nationally representative retrospective cohort study using patient data reported by hospital-based chest pain centers from 1 January 2016 to 31 December 2020. We applied generalized linear mixed models and negative binomial regression to estimate factors independently predicting informed consent delay time. Logistic regressions were fitted to investigate the association of the informed consent delay time and door-to-balloon time, adjusting for patient characteristics. Results: In total, 257, 510 patients were enrolled in the analysis. Mean informed consent delay time was 22.4 min (SD = 24.0), accounting for 39.3% in door-to-balloon time. Older age (≥65 years) was significantly correlated with informed consent delay time (RR: 1.034, P = 0.001). Compared with ethnic Han patients, the minority (RR: 1.146, P < 0.001) had more likelihood to extend consent giving; compared with patients who were single, longer informed consent time was found in married patients (RR: 1.054, P = 0.006). Patients with intermittent chest pain (RR: 1.034, P = 0.011), and chest pain relief (RR: 1.085, P = 0.005) were more likely to delay informed consent. As for transfer modes, EMS (RR: 1.063, P < 0.001), transfer-in (RR: 1.820, P < 0.001), and in-hospital onset (RR: 1.099, P = 0.002) all had positive correlations with informed consent delay time compared to walk-in. Informed consent delay was significantly associated with prolonged door-to-balloon time (OR: 1.002, P < 0.001). Conclusion: Informed consent delay is significantly associated with the door-to-balloon time which plays a crucial role in achieving better outcomes for patients with STEMI. It is essential to shorten the delay time by identifying and intervening modifiable factors that are associated with shortening the informed consent procedure in China and other countries.

SMOC2 plays a role in heart failure via regulating TGF-ß1/Smad3 pathway-mediated autophagy.

Heart failure (HF) is a major global cause of morbidity and mortality. This study aimed to elucidate the role of secreted protein acidic and rich in cysteine-related modular calcium-binding protein 2 (SMOC2) in HF development and its underlying mechanism. Using a rat HF model, SMOC2 expression was examined and then knocked down via transfection to assess its impact on cardiac function and damage. The study also evaluated the effects of SMOC2 knockdown on autophagy-related molecules and the transforming growth factor beta 1 (TGF-ß1)/SMAD family member 3 (Smad3) signaling pathway. Intraperitoneal injection of the TGF-ß agonist (SRI-011381) into the HF rat model was performed to explore the SMOC2-TGF-ß1/Smad3 pathway relationship. SMOC2 expression was elevated in HF rats, while its downregulation improved cardiac function and damage. SMOC2 knockdown reversed alterations in the LC3-II/I ratio, Beclin-1, and p62 levels in HF rats. Through transmission electron microscope, we observed that SMOC2 knockdown restored autophagosome levels. Furthermore, SMOC2 downregulation inhibited the TGF-ß1/Smad3 signaling pathway, which was counteracted by SRI-011381. In conclusion, SMOC2 knockdown inhibits HF development by modulating TGF-ß1/Smad3 signaling-mediated autophagy, suggesting its potential as a therapeutic target for HF.

Exosomes secreted from bone marrow mesenchymal stem cells suppress cardiomyocyte hypertrophy through Hippo-YAP pathway in heart failure.

Mesenchymal stem cells-derived exosomes (MSCs-exosomes) reportedly possess cardioprotective effects. This study investigated the therapeutic potential and mechanisms of MSCs-exosomes on heart failure (HF). H9c2 cells were used to establish a cardiomyocyte hypertrophy model by angiotensin II (Ang II) treatment. Isolated MSCs-exosomes were identified by transmission electron microscope and CD63 detection. Apoptosis rate was measured by terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End Labeling (TUNEL) assay. Levels of inflammatory factors [interleukin (IL)-1ß, IL-4, IL-6, and tumor necrosis factor (TNF)-α] and brain natriuretic peptide (BNP) were determined by ELISA. Expression of apoptosis-related proteins [Bax, B-cell lymphoma-2 (Bcl-2), and caspase 3] and Hippo-Yes-associated protein (YAP) pathway-related proteins [YAP, phosphor (p)-YAP, and tafazzin (TAZ)] was detected by western blotting. Cardiomyocyte hypertrophy of H9c2 cells induced by Ang II was ameliorated by MSCs-exosomes treatment. MSCs-exosomes downregulated Bax and caspase 3 levels and upregulated Bcl-2 level in Ang II-induced H9c2 cells. MSCs-exosomes also reduced the levels of BNP, IL-1ß, IL-4, IL-6, and TNF-α in Ang II-induced H9c2 cells. Meanwhile, p-YAP was downregulated and TAZ was upregulated after MSCs-exosomes administration. In conclusion, MSCs-exosomes alleviate the apoptosis and inflammatory response of cardiomyocyte via deactivating Hippo-YAP pathway in HF.

Prevalence and risk of atrial fibrillation in China: A national cross-sectional epidemiological study.

Background: Atrial fibrillation (AF) is the most common persistent cardiac arrhythmia. This study aimed to estimate its prevalence and explore associated factors in adults aged 18 years or older in China. Methods: Study data were derived from a national sample from July 2020 to September 2021. Participants were recruited using a multistage stratified sampling method from twenty-two provinces, autonomous regions, and municipalities in China. AF was determined based on a history of diagnosed AF or electrocardiogram results. Findings: A total of 114,039 respondents were included in the final analysis with a mean age of 55 years (standard deviation 17), 52·1% of whom were women. The crude prevalence of AF was 2·3% (95% confidence interval [CI] 1·7-2·8) and increased with age. The age-standardized AF prevalence was 1·6% (95% CI 1·6-1·7%) overall, and 1·7% (1·6-1·8%), 1·4% (1·3-1·5%), 1·6% (95% CI 1·5-1·7%), and 1·7% (1·6-1·9%) in men, women, urban areas, and rural areas, respectively. The prevalence was higher in the central regions (2·5%, 2·3-2·7%) than in the western regions (1·5%, 1·0-2·0%) and eastern regions (1·1%, 1·0-1·2%) in the overall population, either in the gender or residency subgroups. The associated factors for AF included age (per 10 years; odds ratio 1·41 [95% CI 1·38-1·46]; p < 0·001), men (1·34 [1·24-1·45]; p < 0·001), hypertension (1·22 [1·12-1·33]; p < 0·001), coronary heart disease (1·44 [1·28-1·62]; p < 0·001), chronic heart failure (3·70 [3·22-4·26]; p < 0·001), valvular heart disease (2·13 [1·72-2·63]; p < 0·001), and transient ischaemic attack/stroke (1·22 [1·04-1·43]; p = 0·013). Interpretation: The prevalence of AF was 1.6% in the Chinese adult population and increased with age, with significant geographic variation. Older age, male sex, and cardiovascular disease were potent factors associated with AF. It is crucial to increase the awareness of AF and disseminate standardized treatment in clinical settings to reduce the disease burden. Funding: This research was supported the Nature Science Foundation of Hubei province (No: 2017CFB204).

Diosmetin inhibits apoptosis and activates AMPK-induced autophagy in myocardial damage under hypoxia environment.

Inhibition of hypoxia-induced cardiomyocyte apoptosis is considered as an important treatment method for ischemic heart diseases, but related drugs are still insufficient. The present study aims to explore the protective function and mechanism of the key Chinese medicine monomer diosmetin (DIOS) on the injury of cardiomyocytes induced by hypoxia. Here, AC16 and HCM-a cells were treated with 40 µM of DIOS under hypoxic environment and a hypoxic rat model was built to study the role of DIOS. The viability and autophagy of cardiomyocytes were increased, but the apoptosis of cells was suppressed by 40 µM DIOS, under hypoxic environment. Intriguingly, 10 mM 3-methyladenine, an inhibitor of autophagy, reversed the effect of DIOS on autophagy and apoptosis of the cardiomyocytes under hypoxia. Furthermore, DIOS induced AMP-activated protein kinase (AMPK) activation and Compound C (5 µM), an AMPK inhibitor, attenuated the inhibition of DIOS on the apoptosis of cardiomyocytes under hypoxia environment. In isoprenaline-induced hypoxic rats, it was verified that DIOS inhibited apoptosis, accelerated autophagy, and activated AMPKα pathway in vivo. Our findings indicated that DIOS alleviated hypoxia-induced myocardial apoptosis via inducing the activation of AMPK-induced autophagy. In summary, the study suggested that DIOS inhibited the apoptosis and induced the autophagy of hypoxia-induced cardiomyocytes through AMPK activation.

Mechanism of miR-30b-5p-Loaded PEG-PLGA Nanoparticles for Targeted Treatment of Heart Failure.

Objective: Exploring the effectiveness of miR-30b-5p-loaded PEG-PLGA nanoparticles (NPs) for the treatment of heart failure and the underlying mechanism. Methods: PEG-PLGA characteristics with different loading amounts were first examined to determine the loading, encapsulation, and release of miR-30b-5p from NPs. The effects of miR-30b-5p NPs on cardiac function and structure were assessed by immunofluorescence, echocardiography, HE/Masson staining, and TUNEL staining. The effects of NPs on the expression of factors related to cardiac hypertrophy and inflammation were examined by RT-PCR and western blotting, and the mechanism of miR-30b-5p treatment on heart failure was explored by dual luciferase reporter assay and RT-PCR. Results: The size of PEG-PLGA NPs with different loading amounts ranged from 200 to 300 nm, and the zeta potential of PEG-PLGA NPs was negative. The mean entrapment efficiency of the NPs for miR-30b-5p was high (81.8 ± 2.1%), and the release rate reached 5 days with more than 90% release. Distribution experiments showed that NPs were mainly distributed in the heart and had a protective effect on myocardial injury and cardiac function. Compared with a rat model of cardiac failure and miR-30b-5p-non-loaede NP groups, the expression of cardiac hypertrophy markers (ANP, BNPß-MHC) and inflammatory factors (IL-1ß, IL-6) were significantly decreased. Dual luciferase reporter assay assays indicated that miR-30b-5p exerted its effects mainly by targeting TGFBR2. Conclusion: PEG-PLGA NPs loaded with miR-30b-5p improved cardiac function, attenuated myocardial injury, and regulated the expression of factors associated with cardiac hypertrophy and inflammation by targeting TGFBR2.

The mechanism of myocardial fibrosis is ameliorated by myocardial infarction-associated transcript through the PI3K/Akt signaling pathway to relieve heart failure.

OBJECTIVE: This study aimed to investigate the role of long noncoding RNA (LncRNA) myocardial infarction-associated transcript (MIAT) in a heart failure (HF) model in vivo and in vitro by regulating the PI3K/Akt signaling pathway. METHODS: We established HF models in vivo and in vitro and evaluated the collagen content of these models and other factors. RESULTS: We found that when LncRNA MIAT was silenced, vascular endothelial growth factor, phosphorylated protein kinase B (Akt), and phosphorylated phosphoinositide 3-kinase (PI3K) mRNA and protein levels were significantly downregulated, which suggested that MIAT activated the PI3K/Akt signaling pathway. Akt and PI3K expression was not significantly changed. We also found that when LncRNA MIAT was silenced, collagen expression was significantly downregulated. This finding suggested that MIAT promoted myocardial fibrosis during the development of HF. The levels of inflammatory factors were also significantly reduced with silencing of LncRNA MIAT. This finding suggested that MIAT promoted the expression of inflammatory factors in myocardial fibrosis by activating the PI3K/Akt signaling pathway. CONCLUSION: This study indicates that silencing LncRNA MIAT may improve myocardial fibrosis and alleviate HF through the PI3K/Akt signaling pathway, which may be helpful for patients with HF to obtain a better therapeutic effect.

Apoptosis in HUVECs induced by microRNA-616-3p via X-linked inhibitor of apoptosis protein targeting.

Atherosclerosis causes stroke and coronary heart disease and is associated with a high mortality rate worldwide. However, the pathogenesis of atherosclerosis remains unclear. Endothelial cell apoptosis is one of the early changes observed in atherosclerosis. Previous studies have found that microRNA (miR)-616-3p may be involved in the development of atherosclerosis, but the specific mechanism is not clear. The present study aimed to investigate whether miR-616-3p is involved in endothelial cell apoptosis and its underlying mechanism. The present study demonstrated that compared with normal HUVECs, HUVECs treated with oxidized low-density lipoprotein expressed higher miR-616-3p and lower X-linked inhibitor of apoptosis protein (XIAP) levels. In the present study, HUVECs were transfected with miR-616-3p mimic and Cell Counting Kit-8 (CCK-8), flow cytometry and TUNEL staining assays demonstrated that compared with miR-616-3p mimic control, the miR-616-3p mimic promoted HUVEC apoptosis. In addition, using StarBase 3.0 for bioinformatics analysis it was predicted that miR-616-3p may bind to the 3'untranslated region (UTR) of XIAP mRNA. The present study performed the CCK-8, flow cytometry, TUNEL staining and dual-luciferase reporter assays and demonstrated that miR-616-3p binds to the 3'UTR of the XIAP mRNA and inhibits its expression and that this further promotes apoptosis in HUVECs. In addition, western blotting demonstrated that compared with miR-616-3p mimic control, the miR-616-3p mimic increases the level of cleaved caspase-3 in HUVECs. In summary, the present study demonstrated that miR-616-3p can directly inhibit the expression of XIAP mRNA by targeting its 3'UTR which promoted apoptosis in HUVECs. miR-616-3p and XIAP may be used as therapeutic targets of atherosclerosis in the future.

An Adaptive Roller Speed Control Method Based on Monitoring Value of Real-Time Seed Flow Rate for Flute-Roller Type Seed-Metering Device.

In order to obtain desirable crop yields, grain seeds need to be sown at the optimal seed amount per hectare with uniform distribution in the field. In previous grain sowing processes, the seeding rates are controlled by the rotational speed of the flute roller which significantly effects the uniform distribution of the seeds due to disturbances, such as the reduction of the seeds' mass in the hopper and the change of working length of the flute roller. In order to overcome the above problem, we developed an adaptive roller speed control system based on the seed flow rate sensor. The developed system can monitor and feedback actual seeding rates. In addition, based on the monitoring value of the real-time seeding rates, an adaptive roller speed control method (ARSCM), which contains an algorithm for calculating the seeding rate with a compensation, was proposed. Besides, the seeding performance of the ARSCM and that of the conventional roller speed control method (CRSCM) were compared. The results of constant-velocity experiments demonstrated that the accuracy (SA) and the coefficient of variation (SCV) of the seeding rates controlled by the ARSCM were 94.12% and 6.77%, respectively. As for the CRSCM, the SA and SCV were 89.00% and 8.95%, respectively. Under variable-velocity conditions, the SA and SCV of the proposed system were 91.58% and 11.08%, respectively, while those of the CRSCM were 88.48% and 13.08%, respectively. Based on the above results, this study concluded that the ARSCM is able to replace the CRSCM in practical sowing processes for the optimal and uniform seed distribution in the field.

Quality of Respiratory Infection Disease Prevention in Outpatient and Emergency Departments in Hospitals in Inner Mongolia, China: An Exit Poll Survey.

PURPOSE: Measures to prevent respiratory infection diseases (RIDs) in hospitals are important to protect both patients and physicians. In 2003, an outbreak of severe acute respiratory syndrome occurred in Inner Mongolia Autonomous Region (IMAR) of China. We aimed to evaluate competency in RID prevention procedures in terms of hospital performance and physician behavior. PATIENTS AND METHODS: We conducted a cross-sectional study in 10 tertiary general public hospitals in 3 cities of IMAR. In each hospital, we chose the respiratory and ear-nose-throat outpatient departments (OPDs) and the emergency department (ED) to invite patients with symptoms of cough to join the study before they consulted a physician. After their consultation, we asked the patients to complete a checklist to score the performance of the departments and the behavior of their physicians in terms of RID prevention practices according to international professional guidelines. RESULTS: From 711 respondents, in the domain of hospital performance, display of posters on directive to wash hands after coughing/sneezing had an average score of 0.452 (range 0-1), while other cough etiquette items had scores averaging between 0.33 and 0.39. The average score for air ventilation was 0.66. For physicians' performance, informing patients the location of handwashing facilities scored the highest (0.62), while low scores were seen for offering a mask to coughing patients (0.14) and encouraging coughing patients to distance themselves from others (0.17). Most RID prevention procedures received low scores in EDs in both hospital performance and physician behavior domains. CONCLUSION: Hospitals in IMAR should improve their performance in RID prevention procedures, especially in giving information to RID patients through the display of posters. The practice of physicians in preventing respiratory infection spread was suboptimum. ED staff and hospital administrators should improve their procedures to prevent the spread of respiratory infections, especially given the increasing occurrences of global pandemics such as COVID-19.

Assessment of adequacy of respiratory infection prevention in hospitals of Inner Mongolia, China: a cross-sectional study using unannounced standardized patients.

INTRODUCTION: Recent respiratory infectious disease (RID) outbreaks of influenza and the novel coronavirus have resulted in global pandemics. RIDs can trigger nosocomial infections if not adequately prevented. OBJECTIVE: The objective of this study was to rate the adequacy of healthcare workers (HCWs) and hospital settings on RID prevention using unannounced standardized patients (USP) in clinical settings of hospital gateways. METHODS: Trained USPs visited 5 clinical settings: information desks, registration desks, two outpatient departments and the emergency departments in 10 hospitals across 3 cities of Inner Mongolia, China. USPs observed the hospital air ventilation and distance from the nearest hand-washing facilities to each clinical setting, then mimicked symptoms of either tuberculosis or influenza before observing the HCW's behavior. A total of 480 clinical-setting assessments were made by 19 USPs. RESULTS: The overall adequacy of triage services was 86.7% and for prevention of the spread of airborne droplets was 83.5%. Almost all hospitals offered adequate air ventilation. Compared to the information desk, adequacy of triage and preventing the spread of airborne droplets by physicians in the three clinical departments was less likely to be adequate. Triage services for USPs simulating symptoms of influenza were 2.6 times more likely to be adequate than for those simulating symptoms of tuberculosis but there was no significant difference in the prevention of the spread of airborne droplets. CONCLUSIONS: There is a need to improve respiratory infectious disease procedures in our study hospitals, especially in outpatient and emergency departments.

A Novel Mechanism of BAM8-22 Inhibiting Microglia Activation: Represses CX3CR1 Expression via Upregulating miR-184.

Bone cancer pain (BCP) is the most common type of pain in cancer patients, during which microglia cells were activated. A previous study showed BAM8-22 had the ability to alleviate BCP via inhibiting microglia activation while the mechanism was not clear. This study aims to investigate the specific mechanism of BAM8-22 inhibiting microglia activation. This study was mainly investigated in BCP mice or LPS-treated microglia BV-2 cells. The behavior tests of mice were performed at 0, 1, 2, 12, and 24 h after BAM8-22 treatment. The expression of miR-184 and CX3CR1 mRNAs was detected by quantitative RT-PCR. The expression of CX3CR1 protein and microglia activation marker, Iba-1, was measured by western blot analysis. The levels of TNF-α and IL-1ß were detected by ELISA. Dual-luciferase assay was performed to verify the combination between miR-184 and CX3CR1. After BAM8-22 treatment, increased miR-184 level was observed in both BCP mice and LPS-treated BV-2 cells, with the downregulated expression of Iba-1 and inflammatory cytokines, namely the inhibition of microglia activation. The inhibition of miR-184 reversed the inhibitory effect of BAM8-22 on microglia activation. Further, in vitro studies showed that miR-184 bound to the 3'UTR of CX3CR1 and inhibited microglia activation via repressing CX3CR1 expression. What's more, the suppression of CX3CR1 expression eliminated the reversal effect of the miR-184 inhibitor on BAM8-22-induced microglia activation and decreased Iba-1 expression and pro-inflammatory cytokine secretion. In BCP models, miR-184 was upregulated by BAM8-22 and the elevated level of miR-184 bound to the 3'UTR region of CX3CR1 and repressed CX3CR1 expression, thus inhibiting the microglia activation, suggesting the potential application of miR-184/CX3CR1 for BCP treatment.

LINC01140 Alleviates the Oxidized Low-Density Lipoprotein-Induced Inflammatory Response in Macrophages via Suppressing miR-23b.

Our previous study has demonstrated that miR-23b enhances oxidized low-density lipoprotein (oxLDL)-induced inflammatory response of macrophages through the A20/NF-κB signaling pathway, thus contributing to atherosclerosis. This study aims to further investigate the upstream regulators of miR-23b in mediating oxLDL-induced inflammatory response. Human monocyte cell line THP1 was induced to differentiate into macrophages followed by the oxLDL stimulation of inflammatory response. The expression of miR-23b, LINC01140, and p53 mRNA was detected by quantitative PCR. The combination of miR-23b and LINC01140 was confirmed by luciferase reporter assay and RNA immunoprecipitation. The binding of p53 and LINC01140 promoter was determined by luciferase reporter assay. The level of inflammatory cytokines, including MCP-1, TNF-α, and IL-1ß, was assessed by enzyme-linked immunosorbent assay. LINC01140 was downregulated, while p53 and miR-23b were upregulated in oxLDL-induced inflammatory response of macrophages. Overexpression of LINC01140 reduced NF-κB activity by reducing miR-23b and increasing A20. The transcription of LINC01140 was inhibited by binding of p53 and the LINC01140 promoter region. Knockdown of p53 significantly reduced NF-κB activity and level of inflammatory cytokines by promoting LINC01140 expression. Our findings demonstrated that LINC01140 acts as an anti-inflammatory factor through negatively regulating miR-23/A20 axis. In addition, p53 is identified as a transcriptional repressor of LINC01140.

Development and Experimental Analysis of a Seeding Quantity Sensor for the Precision Seeding of Small Seeds.

Having the correct seeding rate for a unit area is vital to crop yields. In order to assess the desirable seeding rate, the number of discharged seeds needs to be monitored in real-time. However, for small seeds, the miscounting of seeds during monitoring happens frequently when using conventional seeding quantity sensors, which have wide light beam intervals. Thus, a seeding quantity sensor, which enables small seeds to pass through the light beam steadily, was developed. Based on the seed-shading time, a seed-counting algorithm was proposed. Moreover, the key structure parameters of the proposed sensor were ascertained using an optimization experiment. Finally, the developed seeding quantity sensor was tested against a photoelectric sensor and a fiber sensor to compare the seed monitoring accuracies. The results show that the average monitoring accuracy of the developed sensor, photoelectric sensor, and fiber sensor were 97.09%, 56.79%, and 91.10%, respectively. Furthermore, the factorial analysis shows that the forward velocity of the experimental apparatus and the rotational speed of the seeding plate did not significantly change the monitoring accuracies obtained by the developed sensor. Therefore, the developed sensor can be applied to monitor the seed quantity for the precision seeding of small seeds accurately and robustly.

Protocol of the China ST-segment elevation myocardial infarction (STEMI) Care Project (CSCAP): a 10-year project to improve quality of care by building up a regional STEMI care network.

INTRODUCTION: Successful ST-segment elevation myocardial infarction (STEMI) management is time-sensitive and is based on prompt reperfusion mainly to reduce patient mortality. It has evolved from a single hospital care to an integrated regional network approach over the last decades. This prospective study, named the China STEMI Care Project (CSCAP), aims to show how implementation of different types of integrated regional STEMI care networks can improve the reperfusion treatment rate, shorten the total duration of myocardial ischaemia and lead to mortality reduction step by step. METHODS AND ANALYSIS: The CSCAP is a prospective, multicentre registry study of three phases. A total of 18 provinces, 4 municipalities and 2 autonomous regions in China were included. Patients who meet the third universal definition of myocardial infarction and the Chinese STEMI diagnosis and treatment guidelines are enrolled. Phase 1 (CSCAP-1) focuses on the in-hospital process optimisation of primary percutaneous coronary intervention (PPCI) hospitals, phase 2 (CSCAP-2) focuses on the PPCI hospital-based regional STEMI care network construction together with emergency medical services and adjacent non-PPCI hospitals, while phase 3 (CSCAP-3) focuses on the whole-city STEMI care network construction by promoting chest pain centre accreditation. Systematic data collection, key performance index assessment and subsequent improvement are implemented throughout the project to continuously improve the quality of STEMI care. ETHICS AND DISSEMINATION: The study has been reviewed and approved by the Ethics Committee of Peking University First Hospital. Ranking reports of quality of care will be generated available to all participant affiliations. Results will be disseminated via peer-reviewed scientific journals and presentations at congresses. TRIAL REGISTRATION NUMBER: NCT03821012.

The Effect of Diuretics on Patients with Heart Failure: A Network Meta-Analysis: Diuretics Effect on Heart Failure Patients.

PURPOSE: We aimed to comprehensively evaluate the curative effect of torasemide, tolvaptan, furosemide and azosemide on patients with heart failure. METHODS: Relevant studies were retrieved by searching the electronic databases until May 2018. Quality assessment and data extraction of selected studies were evaluated by two reviewers. Heterogeneity across studies was assessed utilizing the I2 statistic and Q- test, and appropriate effect model was selected to calculate the pooled effect size. Network meta-analysis was conducted and the convergence degree of model was evaluated. RESULTS: A total of 12 studies were enrolled in this study. Significant heterogeneity was not identified across the studies. Significantly greater differences were found in left ventricular ejection fraction (LVEF) for furosemide VS. azosemide, in brain natriuretic peptide (BNP) for furosemide VS. azosemide and furosemide VS. torasemide, and in adverse effects for furosemide VS. torasemide through Meta-analysis of direct comparison. In addition, network meta-analysis results suggested there were no significant differences in adverse effects, mortality, BNP and LVEF among these groups. However, the relatively low mortality and small improvement of BNP and LVEF were found in HF patients treated with torasemide. CONCLUSION: Torasemide might be an optimal treatment for HF patients considering its comprehensive curative effect.

Correlation between sleep duration and hypertension: a dose-response meta-analysis.

To deeply investigate the correlation between sleep duration and hypertension. The electronic databases Cochrane Library, Pubmed and Embase updated to December 2017 were retrieved, and manual searching for paper-based documents was also performed. After studies were selected according to the predefined screening criteria, their qualities were assessed using Newcastle-Ottawa Scale. Based on R 3.43 software, the association between sleep duration and hypertension was analyzed by dose-response meta-analysis, using relative risk (RR) and 95% confidence interval (95% CI) as effect indexes. Furthermore, publication bias of the eligible studies was evaluated using Egger's test. In addition, sensitivity analysis was conducted through ignoring one study per time and then observing its influences on the pooled results. A total of 9 studies (involving 48525 objects) were included in this dose-response meta-analysis, which had high qualities. The differences in ≤5 h vs. 7 h, 6 h vs. 7 h, and 9 h vs. 7 h groups had statistical significances, suggesting that hypertension risk was higher for shorter sleep duration (P < 0.05). There was no significant difference in >9 h vs. 7 h group. No publication bias was found for the eligible studies, indicating that our results were highly credible (t = 0.030, P = 0.9766). However, the pooled results were reversed after ignoring each included study per time. Dose-response meta-analysis showed that the hypertension risk reduced for 0.3207% when the sleep duration increased by 1 h. Shorter sleep duration contributes to the increase of hypertension risk.