The Long Noncoding RNA LnRPT Is Regulated by PDGF-BB and Modulates the Proliferation of Pulmonary Artery Smooth Muscle Cells.

Pulmonary artery hypertension (PAH) is a rare and fatal disorder that involves extensive remodeling of the pulmonary arteries mediated by hyperproliferation of pulmonary artery smooth muscle cells (PASMCs). Aberrant platelet-derived growth factor (PDGF) activity can lead to hyperproliferation of PASMCs; however, little is known about the role of long noncoding RNA (lncRNA) in this process. Using RNA sequencing, we identified 725 lncRNAs in rat PASMCs, 95 of which were expressed differentially in response to PDGF-BB treatment. Depletion of four lncRNAs affected the proliferation of rat PASMCs as measured by 5-ethynyl-2'-deoxyuridine incorporation assay. Among these, one lncRNA, named LnRPT (lncRNA regulated by PDGF and transforming growth factor ß), was found to be the most potent in promoting the proliferation of PASMCs when knocked down. In contrast, proliferation of PASMCs was repressed when LnRPT was overexpressed. Mechanistically, LnRPT inhibited the expression of two genes involved in the Notch signaling pathway (notch3 and jag1) as well as the cell-cycle-regulating gene ccna2. In addition, downregulation of LnRPT induced by PDGF-BB was abrogated when phosphatidylinositol 3'-kinase activity was inhibited with pictilisib. Downregulation of LnRPT was also observed in the pulmonary arteries of rats with monocrotaline-induced PAH. This study provides novel insights into the effects of PDGF-BB on lncRNA expression in PASMCs, and identifies one lncRNA, LnRPT, that plays a role in PAH development as a regulator of PASMC proliferation by mediating the Notch signaling pathway and cell cycle.

Multi-omics analysis reveals regulators of the response to PDGF-BB treatment in pulmonary artery smooth muscle cells.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a lethal disease with pronounced narrowing of pulmonary vessels due to abnormal cell proliferation. The platelet-derived growth factor BB (PDGF-BB) is well known as a potent mitogen for smooth muscle cell proliferation. To better understand how this growth factor regulates pulmonary arterial smooth muscle cells (PASMCs) proliferation, we sought to characterize the response to PDGF-BB stimulation at system-wide levels, including the transcriptome and proteome. RESULTS: In this study, we identified 1611 mRNAs (transcriptome), 207 proteins (proteome) differentially expressed in response to PDGF-BB stimulation in PASMCs based on RNA-sequencing and isobaric tags for relative and absolute quantification (iTRAQ) assay. Transcription factor (TF)-target network analysis revealed that PDGF-BB regulated gene expression potentially via TFs including HIF1A, JUN, EST1, ETS1, SMAD1, FOS, SP1, STAT1, LEF1 and CEBPB. Among them, SMAD1-involved BMPR2/SMADs axis plays a significant role in PAH development. Interestingly, we observed that the expression of BMPR2 was decreased in both mRNA and protein level in response to PDGF-BB. Further study revealed that BMPR2 is the direct target of miR-376b that is up-regulated upon PDGF-BB treatment. Finally, EdU incorporation assay showed that miR-376b promoted proliferation of PASMCs. CONCLUSION: This integrated analysis of PDGF-BB-regulated transcriptome and proteome was performed for the first time in normal PASMCs, which revealed a crosstalk between PDGF signaling and BMPR2/SMADs axis. Further study demonstrated that PDGF-BB-induced miR-376b upregulation mediated the downregulation of BMPR2, which led to expression change of its downstream targets and promoted proliferation of PASMCs.

[Assessment on Minnesota Living with Heart Failure Questionnaire in the Principle of Chinese Civilization and Traditional Medicine Characteristics].

Objective To assess Minnesota living with heart failure questionnaire in the principle of Chinese civilization and Traditional Medicine characteristics (C-MLHF). Methods A survey was con- ducted in 124 heart failure ( HF) patients using C-MLHF and Minnesota living with heart failure question- naire (MLHF). Reliability, validity, feasibility, and the correlation of New York Heart Association (NYHA) classification was compared between the two questionnaires. Results The recovery of C-MLHF was 95. 2% (118/124) ,the effective rate was 97. 5% (115/118), Cronbach's α was 0. 896, and the validity ranged 0. 505 -0. 875. The correlation with MLHF was 0. 946 (P <0. 01) , the correlation with NYHA classi- fication was 0. 524 (P <0. 05). The recovery of MLHF was 95. 2% (118/124) , the effective rate was 88. 1%(104/118) , Cronbach's a was 0. 889, and the validity ranged 0. 487 -0. 787. The correlation with NYHA classification was 0. 468 (P <0. 05). Conclusions The C-MLHF had better feasibility, reliability, validity, and relativity between feasibility/reliability and NYHA classification, as compared with MLHF. In conclusion C-MLHF was more suitable for assessing quality of life for Chinese HF patients.

Analysis of the fatigue status of medical security personnel during the closed-loop period using multiple machine learning methods: a case study of the Beijing 2022 Olympic Winter Games.

Using machine learning methods to analyze the fatigue status of medical security personnel and the factors influencing fatigue (such as BMI, gender, and wearing protective clothing working hours), with the goal of identifying the key factors contributing to fatigue. By validating the predicted outcomes, actionable and practical recommendations can be offered to enhance fatigue status, such as reducing wearing protective clothing working hours. A questionnaire was designed to assess the fatigue status of medical security personnel during the closed-loop period, aiming to capture information on fatigue experienced during work and disease recovery. The collected data was then preprocessed and used to determine the structural parameters for each machine learning algorithm. To evaluate the prediction performance of different models, the mean relative error (MRE) and goodness of fit (R2) between the true and predicted values were calculated. Furthermore, the importance rankings of various parameters in relation to fatigue status were determined using the RF feature importance analysis method. The fatigue status of medical security personnel during the closed-loop period was analyzed using multiple machine learning methods. The prediction performance of these methods was ranked from highest to lowest as follows: Gradient Boosting Regression (GBM) > Random Forest (RF) > Adaptive Boosting (AdaBoost) > K-Nearest Neighbors (KNN) > Support Vector Regression (SVR). Among these algorithms, four out of the five achieved good prediction results, with the GBM method performing the best. The five most critical parameters influencing fatigue status were identified as working hours in protective clothing, a customized symptom and disease score (CSDS), physical exercise, body mass index (BMI), and age, all of which had importance scores exceeding 0.06. Notably, working hours in protective clothing obtained the highest importance score of 0.54, making it the most critical factor impacting fatigue status. Fatigue is a prevalent and pressing issue among medical security personnel operating in closed-loop environments. In our investigation, we observed that the GBM method exhibited superior predictive performance in determining the fatigue status of medical security personnel during the closed-loop period, surpassing other machine learning techniques. Notably, our analysis identified several critical factors influencing the fatigue status of medical security personnel, including the duration of working hours in protective clothing, CSDS, and engagement in physical exercise. These findings shed light on the multifaceted nature of fatigue among healthcare workers and emphasize the importance of considering various contributing factors. To effectively alleviate fatigue, prudent management of working hours for security personnel, along with minimizing the duration of wearing protective clothing, proves to be promising strategies. Furthermore, promoting regular physical exercise among medical security personnel can significantly impact fatigue reduction. Additionally, the exploration of medication interventions and the adoption of innovative protective clothing options present potential avenues for mitigating fatigue. The insights derived from this study offer valuable guidance to management personnel involved in organizing large-scale events, enabling them to make informed decisions and implement targeted interventions to address fatigue among medical security personnel. In our upcoming research, we will further expand the fatigue dataset while considering higher precisionprediction algorithms, such as XGBoost model, ensemble model, etc., and explore their potential contributions to our research.

Identification and validation of lipid metabolism-related key genes as novel biomarkers in acute myocardial infarction and pan-cancer analysis.

BACKGROUND: Acute myocardial infarction (AMI) is associated with high morbidity and mortality, and is associated with abnormal lipid metabolism. We identified lipid metabolism related genes as biomarkers of AMI, and explored their mechanisms of action. METHODS: Microarray datasets were downloaded from the GEO database and lipid metabolism related genes were obtained from Molecular Signatures Database. WGCNA was performed to identify key genes. We evaluated differential expression and performed ROC and ELISA analyses. We also explored the mechanism of AMI mediated by key genes using gene enrichment analysis. Finally, immune infiltration and pan-cancer analyses were performed for the identified key genes. RESULTS: TRL2, S100A9, and HCK were identified as key genes related to lipid metabolism in AMI. Internal and external validation (including ELISA) showed that these were good biomarkers of AMI. In addition, the results of gene enrichment analysis showed that the key genes were enriched in inflammatory response, immune system process, and tumor-related pathways. Finally, the results of immune infiltration showed that key genes were concentrated in neutrophils and macrophages, and pan-cancer analysis showed that the key genes were highly expressed in most tumors and were associated with poor prognosis. CONCLUSIONS: TLR2, S100A9, and HCK were identified as lipid metabolism related novel diagnostic biomarkers of AMI. In addition, AMI and tumors may be related through the inflammatory immune response.

miR-199b-5p-AKAP1-DRP1 Pathway Plays a Key Role in ox-LDL-induced Mitochondrial Fission and Endothelial Apoptosis.

BACKGROUND: Atherosclerosis (AS) remains prevalent despite hyperlipidemia-lowering therapies. Although multiple functions of miR-199b-5p have been implicated in cancers, its role in endothelial apoptosis and AS remains unclear. This study aimed to examine the role of miR-199b-5p in mitochondrial dynamics and endothelial apoptosis. METHODS: Human umbilical vein endothelial cells (HUVECs) treated with oxidized low-density lipoprotein (ox-LDL) were subjected to other treatments, followed by a series analysis. We found that ox-LDL-treated HUVECs were associated with miR-199b-5p downregulation, increased reactive oxygen species level, reduced adenosine triphosphate (ATP) production, mitochondrial fission, and apoptosis, whereas enhanced miR-199b-5p expression or applied mitochondrial division inhibitor 1 (Mdivi-1) markedly reversed these changes. RESULTS: Mechanistically, A-kinase anchoring protein 1 (AKAP1) was confirmed as a downstream target of miR-199b-5p by dual-luciferase activity reporter assay. AKAP1 overexpression reversed the anti-apoptotic effects of miR-199b-5p through the enhanced interaction of AKAP1 and dynamin protein 1 (DRP1) in ox-LDL-treated HUVECs. Moreover, miR-199b-5p downregulation, AKAP1 upregulation, and excessive mitochondrial fission were verified in human coronary AS endothelial tissues. CONCLUSION: The miR-199b-5p-dependent regulation of AKAP1/DRP1 is required to inhibit hyperlipidemia- induced mitochondrial fission and endothelial injury and may be a promising therapeutic target for AS.

[Early reperfusion strategy selection and prognosis analysis in patients with acute ST segment elevation myocardial infarction: based on the data of 49 hospitals in Hebei Province].

OBJECTIVE: To explore the selection of strategies for early reperfusion therapy and its impact on prognosis in patients with acute ST segment elevation myocardial infarction (STEMI). METHODS: The treatment data and 3-year follow-up results of acute myocardial infarction (AMI) patients in 49 hospitals in Hebei Province from January to December 2016 were collected. Patients with STEMI who received either intravenous thrombolytic therapy (ITT) or primary percutaneous coronary intervention (PPCI) within 12 hours of onset were enrolled. Baseline data, the time from the first diagnosis to the start of reperfusion (FMC2N for ITT patients and FMC2B for PPCI patients), vascular recanalization rate, in-hospital mortality, 1-year mortality, and 3-year mortality were compared between ITT and PPCI groups. The efficacy and prognosis of ITT and PPCI at different starting time of reperfusion (FMC2N ≤ 30 minutes, FMC2N > 30 minutes, FMC2B ≤ 120 minutes, FMC2B > 120 minutes) were analyzed. RESULTS: A total of 1 371 STEMI patients treated with ITT or PPCI were selected, including 300 patients in the ITT group and 1 071 patients in the PPCI group. 1 055 patients were actually followed up (205 patients in the ITT group and 850 patients in the PPCI group), with a rate of 79.4%. There were no significant differences in age, gender, and previous history between the two groups. The time from the first diagnosis to the start of reperfusion in the ITT group was shorter than that in the PPCI group [minutes: 63 (38, 95) vs. 95 (60, 150), U = -9.286, P = 0.000], but was significantly longer than the guideline standard. Compared with the ITT group, the vascular recanalization rate in the PPCI group was higher [95.5% (1 023/1 071) vs. 88.3% (265/300), P < 0.01], and in-hospital mortality was lower [2.1% (22/1 071) vs. 6.7% (20/300), P < 0.01], but there were no significant differences in the 1-year mortality and 3-year mortality [5.3% (45/850) vs. 4.4% (9/205), 9.5% (81/850) vs. 9.3% (19/205), both P > 0.05]. Between ITT group and PPCI group with different reperfusion starting time, the FMC2N > 30 minutes group had the lowest vascular recanalization rate and the highest in-hospital mortality. Pairwise comparison showed that the vascular recanalization rate of the FMC2B ≤ 120 minutes group and the FMC2B > 120 minutes group were significantly higher than those of the FMC2N > 30 minutes group [95.5% (654/685), 95.6% (369/386) vs. 88.0% (220/250), both P < 0.008], the in-hospital mortality was significantly lower than that of the FMC2N > 30 minutes group [2.0% (14/685), 2.1% (8/386) vs. 7.6% (19/250), both P < 0.008]. There was no significant difference in 1-year mortality (χ2 = 2.507, P = 0.443) and 3-year mortality (χ2 = 2.204, P = 0.522) among the four groups. CONCLUSIONS: For STEMI patients within 12 hours of onset, reperfusion therapy should be performed as soon as possible. PPCI showed higher infarct related artery opening rate and lower in-hospital mortality compared with ITT, and had no effect on 1-year and 3-year mortality.

The effects of ω-3 fish oil emulsion-based parenteral nutrition plus combination treatment for acute paraquat poisoning.

OBJECTIVE: To investigate the effects of parenteral nutrition (PN) including ω-3 fish-oil emulsion on nutritional state, inflammatory response, and prognosis in patients with acute paraquat poisoning. METHODS: Patients randomized to receive medium chain triglycerides (MCT)/long chain triglycerides (LCT)-based PN (control group) or MCT/LCT-based PN containing ω-3 fish-oil emulsion (intervention group) were compared for 90-day survival and short-term treatment efficacy. RESULTS: Tumour necrosis factor-α levels were significantly lower in the intervention group ( n = 101) versus controls ( n = 73) on treatment days 4 and 7. Intervention group C-reactive protein (CRP) levels were significantly increased on day 4, decreased to baseline (day 1) levels on day 7, and were significantly lower than baseline on day 10. Control group CRP levels were significantly increased on days 4 and 7 versus baseline, and returned to baseline levels on day 10. On day 7, retinol binding protein had recovered to baseline levels in the intervention group only. Intervention group mortality rate (36.6%) was significantly lower than controls (57.5%). ω-3 fish-oil PN was associated with reduced risk of death (hazard ratio 0.52; 95% confidence interval 0.33, 0.82). CONCLUSION: In patients with acute paraquat poisoning, MCT/LCT with ω-3 fish-oil emulsion PN plus combination treatment advantageously attenuated the inflammatory response, modified the nutritional state, and was associated with significantly improved 90-day survival versus treatment without ω-3 fish oil.

A wide-range operating synaptic device based on organic ferroelectricity with low energy consumption.

In this work, a wide-range operating synaptic device based on organic ferroelectricity has been demonstrated. The device possesses a simple two-terminal structure by using a ferroelectric phase-separated polymer blend as the active layer and gold/indium tin oxide (ITO) as the top/bottom electrodes, and exhibits a distinctive history-dependent resistive switching behavior at room temperature. And the device with low energy consumption (∼50 fJ µm-2 per synaptic event) can provide a reliable synaptic function of potentiation, depression and the complex memory behavior simulation of differential responses to diverse stimulations. In addition, using simulations, the accuracy of 32 × 32 pixel image recognition is improved from 76.21% to 85.06% in the classical model Cifar-10 with 1024 levels of the device, which is an important step towards the higher performance goal in image recognition based on memristive neuromorphic networks.

Band-Gap Tuning of Organic-Inorganic Hybrid Palladium Perovskite Materials for a Near-Infrared Optoelectronics Response.

Organic-inorganic hybrid material is a recent hot topic in the scientific community. The best band gap for the entire solar absorption spectrum is about 1.1 eV. However, the lead perovskite band gap is about 1.5 eV. Therefore, developing organic-inorganic hybrid material toward the broader light harvesting of the solar spectrum is extremely urgent. In this study, we prepare three kinds of organic-inorganic hybrid palladium perovskite materials, including (CH3NH3)2PdCl4, (CH3NH3)2PdCl4-x Br x , and CH3NH3PdI3, for an optoelectronic response. The absorption cut offs of (CH3NH3)2PdCl4, (CH3NH3)2PdCl4-x Br x , and CH3NH3PdI3 are approximately 600, 700, and 1000 nm, respectively. The band gaps of (CH3NH3)2PdCl4, (CH3NH3)2PdCl4-x Br x , and CH3NH3PdI3 are determined to be approximately 2.15, 1.87, and 1.25 eV, respectively. To the best of our knowledge, this is the first study that discusses adsorption properties and photoelectric behavior of organic-inorganic hybrid palladium perovskite materials. Interestingly, the photoelectric response of the devices based on CH3NH3PdI3 reaches 950 nm. The results will attract attention in the fields of optical recorders, optical memory, security, light capture, and light treatment.

MiR-339 inhibits proliferation of pulmonary artery smooth muscle cell by targeting FGF signaling.

Pulmonary artery hypertension (PAH) is a fatal disorder. Recent studies suggest that microRNA (miRNA) plays an important role in regulating proliferation of pulmonary artery smooth muscle cells (PASMC), which underlies the pathology of PAH However, the exact mechanism of action of miRNAs remains elusive. In this study, we found that miR-339 was highly expressed in the cardiovascular system and was downregulated by a group of cytokines and growth factors, especially PDGF-BB and FGF2. Functional analyses revealed that miR-339 can inhibit proliferation of PASMC Also, miR-339 inhibited FGF2-induced proliferation, but had no effect on proliferation induced by PDGF-BB The fibroblast growth factor receptor substrate 2 (FRS2) was identified as a potential direct target of miR-339. Consistent with the actions of miR-339, knockdown of FRS2 only inhibited FGF2- but not PDGF-BB-induced proliferation of PASMC In addition, our results showed that inhibition of ERK and PI3K abrogated the downregulation of miR-339 induced by PDGF-BB Finally, miR-339 expression was found to be decreased in the pulmonary arteries of rats with MCT-induced PAH Our study is the first report on the biological role of miR-339 in regulating proliferation of PASMC by targeting FGF signaling, providing new mechanistic insights into PASMC proliferation and pathogenesis of PAH.

Hydrazinium Salt as Additive To Improve Film Morphology and Carrier Lifetime for High-Efficiency Planar-Heterojunction Perovskite Solar Cells via One-Step Method.

One-step solution process is the simplest method to fabricate organic-inorganic metal halide perovskite thin films, which however does not work well when employed in the planar-heterojunction (PHJ) solar cells due to the generally poor film morphology. Here we show that hydrazinium chloride can be used as an additive in the precursor solution to produce perovskite films featuring higher coverage and better crystallinity. The light absorption ability and charge carrier lifetime are both significantly improved accordingly. Under the optimal additive ratio, the average power conversion efficiency (PCE) of the inverted PHJ perovskite solar cells greatly increases by as much as 70%, and the champion device shows a satisfying PCE of 12.66%. These results suggest that N2H5Cl is a promising additive for fabricating high-efficiency perovskite solar cells via one-step method, which could be of interest in the future commercial solar cell industry.

Western medication plus Traditional Chinese Medicine preparations in patients with chronic heart failure: a prospective, single-blind, randomized, controlled, and multicenter clinical trial.

OBJECTIVE: To assess the efficacy and safety in patients with chronic heart failure (CHF) of Western medication plus Traditional Chinese Medicine (TCM) preparations. METHODS: This prospective, single-blind, randomized, controlled, and multicenter clinical trial began on September 17, 2008, and was completed on June 25, 2011. A total of 340 inpatients, aged 40-79 years, with exacerbating CHF from 10 hospitals were enrolled and randomly allocated within 24 h of admission. The trial included three intervention periods. During hospitalization, the control group received western medication for CHF and the treatment group received Danhong injection with Shenfu injection or Shenmai injection. After discharge, all patients were treated with Qiliqiangxin capsules and Buyiqiangxin tablets or a placebo for 6 months. After the 6-month intervention, both groups received only continuous western medication. The primary endpoint was all-cause mortality. The efficacy assessments were as follows: B-type natriuretic peptide (BNP), Lee's HF score, the 6-minute walking test (6MWT), left ventricular ejection fraction (LVEF), and the Minnesota Living with Heart Failure Questionnaire (MLHFQ). The safety assessments were as follows: blood and urine routine examination, hepatic and renal function, electrolytes in blood and adverse events. RESULTS: Compared with the control group, the treatment group showed a 30.99% reduction in all-cause mortality and an improved survival rate. The treatment group showed greater improvement in 6MWT (P = 0.02) than the control group on discharge, after 12-month follow-up, there was a time-group interaction for MLHFQ (P = 0.03). Incidence rate of adverse events and other relevant safety indexes were not statistically significant between the two groups. CONCLUSION: Western medication plus TCM treatment can increase 6-minute walking distance (improve exercise tolerance) and quality of life with heart failure patients.