CSF3 aggravates acute exacerbation of pulmonary fibrosis by disrupting alveolar epithelial barrier integrity.

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive respiratory disorder characterized by poor prognosis, often presenting with acute exacerbation. The primary cause of death associated with IPF is acute exacerbation of IPF (AE-IPF). However, the pathophysiology of acute exacerbation has not been clearly elucidated yet. This study aims to investigate the underlying pathophysiological molecular mechanism in a mouse AE-PF model. C57BL/6J mice were intratracheally administered bleomycin (BLM, 5 mg/kg) to induce pulmonary fibrosis. After 14 days, lipopolysaccharide (LPS, 2 mg/kg) was injected via the trachea route. Histological assessments, including H&E and Masson staining, as well as inflammatory indicators, were included to evaluate the induction of AE-PF by BLM and LPS in mice. Transcriptomic profiling of pulmonary tissues identified CSF3 as one of the top 10 upregulated DEGs in AE-PF mice. Indeed, administration of exogenous CSF3 protein exacerbated AE-PF in mice. Mechanistically, CSF3 disrupted alveolar epithelial barrier integrity and permeability by regulating specialized cell adhesion complexes such as tight junctions (TJs) and adherens junctions (AJs) via PI3K/p-Akt/Snail pathway, contributing to the aggravation of AE-PF in mice. Moreover, the discovery of elevated sera CSF3 indicated a notable increase in IPF patients during the exacerbation of the disease. Pearson correlation analysis in IPF patients revealed significant positive associations between CSF3 levels and KL-6 levels, LDH levels, CRP levels, respectively. These results provide mechanistic insights into the role of CSF3 in exacerbating of lung fibrotic disease and indicate monitoring CSF3 levels may aid in early clinical decisions for alternative therapy in the management of rapidly progressing IPF.

Identification of key molecules in the formation of portal vein tumor thrombus in hepatocellular carcinoma based on single cell transcriptomics and in vitro experiments.

Background: The presence of portal vein tumor thrombus (PVTT) is a significant indicator of advanced-stage hepatocellular carcinoma (HCC). Unfortunately, the prediction of PVTT occurrence remains challenging, and there is a lack of comprehensive research exploring the underlying mechanisms of PVTT formation and its association with immune infiltration. Methods: Our approach involved analyzing single-cell sequencing data, applying high dimensional weighted gene co-expression network analysis (hdWGCNA), and identifying key genes associated with PVTT development. Furthermore, we constructed competing endogenous RNA (ceRNA) networks and employed weighted gene co-expression network analysis (WGCNA), as well as three machine-learning techniques, to identify the upstream regulatory microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) of the crucial mRNAs. We employed fuzzy clustering of time series gene expression data (Mfuzz), gene set variation analysis (GSVA), and cell communication analysis to uncover significant signaling pathways involved in the activation of these important mRNAs during PVTT development. In addition, we conducted immune infiltration analysis, survival typing, and drug sensitivity analysis using The Cancer Genome Atlas (TCGA) cohort to gain insights into the two patient groups under study. Results: Through the implementation of hdWGCNA, we identified 110 genes that was closely associated with PVTT. Among these genes, TMEM165 emerged as a crucial candidate, and we further investigated its significance using COX regression analysis. Furthermore, through machine learning techniques and survival analysis, we successfully identified the upstream regulatory miRNA (hsa-miR-148a) and lncRNA (LINC00909) that targeted TMEM165. These findings shed light on the complex regulatory network surrounding TMEM165 in the context of PVTT. Moreover, we conducted CIBERSORT analysis, which unveiled correlations between TMEM165 and immune infiltration in HCC patients. Specifically, TMEM165 exhibited associations with various immune cell populations, including memory B cells and CD8+ T cells. Additionally, we observed implications for immune function, particularly in relation to immune checkpoints, within the context of HCC. Conclusions: The regulatory axis involving TMEM165, hsa-miR-148a, and LINC00909 emerges as a crucial determinant in the development of PVTT in HCC patients, and it holds significant implications for prognosis. Furthermore, alterations in the TMEM165/hsa-miR-148a/LINC00909 regulatory axis exhibit a strong correlation with immune infiltration within the HCC tumor microenvironment, leading to immune dysfunction and potential failure of immunotherapy.

Association between triglyceride-glucose index and hypertension: a cohort study based on the China Health and Nutrition Survey (2009-2015).

AIM: Insulin resistance (IR) may participate in the pathogenesis of hypertension by mediating low-grade systemic inflammation. The triglycerides-glucose (TyG) index has recently been suggested as a reliable alternative biochemical marker of IR compared with traditional methods. Herein, we speculated TyG index may also be associated with hypertension. METHODS: Data of adults were extracted from the China Health and Nutrition Survey (CHNS) in 2009-2015 in this retrospective cohort study. The TyG index was calculated using the formula: TyG = Ln [fasting triglycerides (mg/dL) ×fasting glucose (mg/dL)/2]. Associations between TyG index and hypertension were evaluated by univariate and multivariate logistic regression analyses with odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup analyses of age and gender were also performed. In addition, we assessed the interaction effect between TyG index and body mass index (BMI) on hypertension in participants with different age and gender. RESULTS: Among 3,413 eligible participants, 1,627 (47.67%) developed hypertension. The average TyG index in hypertension group and non-hypertension group was 8.58 and 8.39 respectively. After adjusting for covariates, we found that compared with participants with TyG index ≤ 8.41 (median value), those who had higher TyG index seemed to have higher odds of hypertension [OR = 1.17, 95%CI: (1.01-1.37)]. Similarly, this association was also discovered in participants who aged ≤ 65 years old [OR = 1.19, 95%CI: (1.01-1.39)] or were female [OR = 1.35, 95%CI: (1.10-1.65)]. Additionally, there was a potential additive interaction effect between obesity and TyG index on hypertension. CONCLUSION: High TyG index was associated with high odds of hypertension in general population in China, but the causal relationship between them needed further exploration.

A rapid expansion of hospitals: the adaptation of multi-campus hospitals under the Chinese healthcare system.

In recent years, China's healthcare system has undergone significant changes to meet the increasing demands of its growing population. One notable development is the rapid expansion of hospitals, particularly the adaptation of multi-campus hospitals. These multi-campus hospitals have become increasingly popular due to the many advantages that single-campus hospitals lack, including the ability to; improve medical service quality, reduce operating costs, and facilitate the development of healthcare services in rural areas. In this study, we discuss the advantages that this type of medical facility offers and identify existing and potential problems that could hinder the development of multi-campus hospitals. Additionally, we propose appropriate solutions to mitigate these problems. Overall, we propose that there should be more communication between multi-campus hospitals and other healthcare providers.

Efficacy of two hemodialyses in patients with chronic renal failure complicated by massive intracerebral hemorrhage.

OBJECTIVE: To compare the efficacy of intermittent hemodialysis (IHD) and continuous veno-venous hemofiltration (CVVH) in patients with chronic renal failure complicated by massive intracerebral hemorrhage. METHODS: Sixty-two patients were randomly and equally divided into IHD and CVVH groups. The clinical variables were compared, including National Institutes of Health Stroke Scale (NIHSS) score as the primary indicator, cerebral edema volume, hospital-acquired pneumonia (HAP) incidence, acute heart failure (AHF) incidence, rehemorrhage incidence, hospital stay length, and modified Rankin Scale (mRS) score. RESULTS: The CVVH group had lower NIHSS scores and edema volumes than the IHD group on postoperative days 7 and 14. Moreover, in the CVVH group, (i) the NIHSS scores on postoperative days 3 and 7 were higher than those on postoperative day 1; (ii) there was no significant difference in NIHSS scores between days 14 and 1; and (iii) no significant difference in cerebral edema volume was found between postoperative days 1 and 3, 7, and 14. In the IHD group, the NIHSS scores and cerebral edema volume on postoperative days 7 and 14 were significantly higher than those on postoperative day 1. The CVVH group had a lower incidence of HAP, AHF, and adverse events and shorter hospital stay length than the IHD group. The proportions of patients with mRS scores of 1 and 2 in the CVVH group were higher than those in the IHD group on day 30 after discharge. INTERPRETATION: CVVH is more effective than IHD in the treatment of patients with chronic renal failure complicated by massive intracerebral hemorrhage.

Trend analysis of mortality rates and causes of death in children under 5 years of age in Xuzhou, China from 2016 to 2020.

Objectives: To analyze the trends in mortality and causes of death among children under 5 years of age in Xuzhou, China between 2016 and 2020, in order to protect children's health and provide a basis for formulating child survival, development, and protection strategies. Methods: A population-based epidemiological study was conducted. Data were obtained from the Xuzhou Center for Disease Control Prevention. We input the data into the excel database and analyzed with SPSS20.0. Results: There were 1,949 children under 5 years of age died in Xuzhou, The number of deaths from 2016 to 2020 were 573 (29.40%), 577 (29.60%), 371 (19.04%), 334 (17.14%), and 94 (4.82%) respectively, mortality in children showed a downward trend. The number of deaths was relatively high in January (195 cases, 10.01%), February (190 cases, 9.75%), and May (180 cases, 9.24%), while was relatively small in July (147 cases, 7.54%), August (139 cases, 7.13%), and September (118 cases, 6.05%). The leading causes of death (COD) in children under 5 years of age were neonatal suffocation and hypoxia (323 cases, 16.57%). Pizhou (528 cases, 27.09%) showed the highest number of deaths in children under 5 years of age in China, and the Kaifa (25 cases, 1.28%) zone showed the lowest death toll. Conclusions: Our research suggested that the current strategies for reducing child mortality should prioritize the actions on neonatal deaths and conduct targeted interventions for the main cause.

An interpretable machine learning approach for predicting 30-day readmission after stroke.

BACKGROUND: Stroke is the second leading cause of death worldwide and has a significantly high recurrence rate. We aimed to identify risk factors for stroke recurrence and develop an interpretable machine learning model to predict 30-day readmissions after stroke. METHODS: Stroke patients deposited in electronic health records (EHRs) in Xuzhou Medical University Hospital between February 1, 2021, and November 30, 2021, were included in the study, and deceased patients were excluded. We extracted 74 features from EHRs, and the top 20 features (chi-2 value) were used to build machine learning models. 80% of the patients were used for pre-training. Subsequently, a 20% holdout dataset was used for verification. The Shapley Additive exPlanations (SHAP) method was used to explore the interpretability of the model. RESULTS: The cohort included 6,558 patients, of whom the mean (SD) age was 65 (11) years, 3,926 were males (59.86 %), and 132 (2.01 %) were readmitted within 30 days. The area under the receiver operating characteristic curve (AUROC) for the optimized model was 0.80 (95 % CI 0.68-0.80). We used the SHAP method to identify the top 10 risk factors (i.e., severe carotid artery stenosis, weak, homocysteine, glycosylated hemoglobin, sex, lymphocyte percentage, neutrophilic granulocyte percentage, urine glucose, fresh cerebral infarction, and red blood cell count). The AUROC of a model with the 10 features was 0.80 (95 % CI 0.69-0.80) and was not significantly different from that of the model with 20 risk factors. CONCLUSIONS: Our methods not only showed good performance in predicting 30-day readmissions after stroke but also revealed risk factors that provided valuable insights for treatments.

Effect of preoperative intensive statin on the efficacy and inflammatory response of acute ST-segment elevation myocardial infarction after emergency percutaneous coronary intervention.

It was to explore the application value of individualized nursing oriented by solution-focused nursing mode in postoperative nursing of patients with pelvic fractures. 90 patients with ST-segment elevation myocardial infarction (STEMI) undergoing emergency percutaneous coronary intervention (PCI) were enrolled. They were randomly grouped into a control group and an experimental group, with 45 cases in each group. Patients in the general group were treated with conventional treatment, and patients in the enhancement group were treated with high-dose rosuvastatin based on conventional treatment. The experimental group was compared for indicators such as serum inflammatory factors, cardiac function, overall efficacy, and follow-up prognosis before and after the operation. After treatment, the total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) in the enhancement group were better as against the control group (P<0.05). Through treatment, the concentration of high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in the enhancement group was lower compared to the general group. The total effective rate of the enhancement group (95.56%) was higher relative to the general group (86.67%) (P<0.05). In patients with STEMI, preoperative intensive statin therapy can improve the efficacy of PCI, and reduce the inflammatory response and the incidence of cardiovascular events.

Predictive Value of Arterial Blood Lactic Acid Concentration on the Risk of in-Hospital All-Cause Death in Patients with Acute Heart Failure.

The study aims to examine the predictive value of arterial blood lactic acid concentration for in-hospital all-cause mortality in the intensive care unit (ICU) for patients with acute heart failure (AHF). We retrospectively analyzed the clinical data of 7558 AHF patients in the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. The exposure variable of the present study was arterial blood lactic acid concentration and the outcome variable was in-hospital all-cause death. The patients were divided into those who survived (n = 6792) and those who died (n = 766). The multivariate logistic regression model, restricted cubic spline (RCS) plot, and subgroup analysis were used to evaluate the association between lactic acid and in-hospital all-cause mortality. In addition, receiver operating curve (ROC) analysis also was performed. Finally, we further explore the association between NT-proBNP and lactic acid and in-hospital all-cause mortality. Compared with the lowest quartiles, the odds ratios with 95% confidence intervals for in-hospital all-cause mortality across the quartiles were 1.46 (1.07-2.00), 1.48 (1.09-2.00), and 2.36 (1.73-3.22) for lactic acid, and in-hospital all-cause mortality was gradually increased with lactic acid levels increasing (P for trend <0.05). The RCS plot revealed a positive and linear connection between lactic acid and in-hospital all-cause mortality. A combination of lactic acid concentration and the Simplified Acute Physiology Score (SAPS) II may improve the predictive value of in-hospital all-cause mortality in patients with AHF (AUC = 0.696). Among subgroups, respiratory failure interacted with an association between lactic acid and in-hospital all-cause mortality (P for interaction <0.05). The correlation heatmap revealed that NT-proBNP was positively correlated with lactic acid (r = 0.07) and positively correlated with in-hospital all-cause mortality (r = 0.18). There was an inverse L-shaped curve relationship between NT-proBNP and in-hospital all-cause mortality, respectively. Mediation analysis suggested that a positive relationship between lactic acid and in-hospital all-cause death was mediated by NT-proBNP. For AHF patients in the ICU, the arterial blood lactic acid concentration during hospitalization was a significant independent predictor of in-hospital all-cause mortality. The combination of lactic acid and SAPS II can improve the predictive value of the risk of in-hospital all-cause mortality in patients with AHF.

[Influence of posttraumatic blood pressure variability on post-traumatic stress disorder].

OBJECTIVE: To investigate the relationship between blood pressure variability (BPV) and incidence of post-traumatic stress disorder (PTSD) in trauma patients. METHODS: Patients admitted to the department of emergency medicine of the Affiliated Hospital of Xuzhou Medical University for acute trauma from January 2018 to December 2021 were enrolled. The clinical data and blood pressure at admission (T1), 10 minutes before anesthesia (T2), 60 minutes after surgery (T3), and 24 hours after surgery (T4) were collected. Coefficient of variation of blood pressure variation [CV-BP, including coefficient of variation of systolic blood pressure (CV-SBP), coefficient of variation of diastolic blood pressure (CV-DBP), coefficient of variation of mean arterial pressure (CV-MAP)] and its quartile were calculated. Patients were divided into Q1 group (CV-MAP ≤ 7.27), Q2 group (7.27 < CV-MAP ≤ 9.50), Q3 group (9.50 < CV-MAP ≤ 14.05) and Q4 group (CV-MAP > 14.05) according to CV-MAP quartile. The PTSD symptoms of the patients were evaluated using the PTSD scale (PCL-5) one month later, and the patients were divided into the PTSD group and the non-PTSD group according to whether PCL-5 score higher than 38. Then the differences of the above indicators were compared and analyzed. Spearman correlation analysis was used to analyze the relationship between each index and PCL-5 score; the risk factors of PTSD were analyzed by univariate binary Logistic regression. Variables with P < 0.05 were included in the multivariate binary Logistic regression model. The receiver operator characteristic curve (ROC curve) was drawn to analyze the predictive value of CV-MAP on the incidence of PTSD. RESULTS: A total of 112 patients were enrolled, including 24 in PTSD group and 88 in non-PTSD group. Compared with non-PTSD group, the proportion of women, T1 shock index, proportion of intraoperative and postoperative blood transfusion in PTSD group was higher. Besides, PTSD group also had longer PT, more intraoperative and postoperative blood transfusion, and lower postoperative hemoglobin (Hb) level (all P < 0.05). The T1 SBP, DBP, MAP and T4 MAP of patients in PTSD group were significantly lower than those in non-PTSD group [T1 SBP (mmHg, 1 mmHg ≈ 0.133 kPa): 105.0 (86.3, 121.3) vs. 122.0 (112.0, 132.8), T1 DBP (mmHg): 62.5 (50.0, 77.3) vs. 76.0 (68.5, 82.8), T1 MAP (mmHg): 77.8 (60.4, 91.3) vs. 93.3 (82.5, 99.0), T4 MAP (mmHg): 83.8±9.1 vs. 88.7±10.4, all P < 0.05], CV-SBP, CV-DBP and CV-MAP were higher than those in the non-PTSD group [CV-SBP: 12.80 (10.12, 19.16) vs. 9.30 (6.07, 12.95), CV-DBP: 16.62±6.47 vs. 12.40±5.61, CV-MAP: 14.10 (9.25, 18.85) vs. 8.90 (6.93, 13.29), all P < 0.05]. Spearman correlation analysis showed that there was a positive correlation between CV-MAP and PCL-5 scores in patients with acute trauma (r = 0.429, P < 0.001); multivariate binary Logistic regression analysis showed that only CV-MAP [odds ratio (OR) = 1.128, 95% confidence interval (95%CI) was 1.015-1.254, P = 0.025] and CV-DBP (OR = 1.114, 95% confidence interval (95%CI) was 1.016-1.221, P = 0.022) was the risk factor for PTSD in acute trauma patients. Compared with Q1 group, Q4 group was significantly more likely to develop PTSD (OR = 18.6, 95%CI was 1.9-179.1, P = 0.012). CV-SBP, CV-DBP and CV-MAP had certain predictive value on PTSD diagnosis in patients with acute trauma according to ROC curve analysis results [area under the ROC curve (AUC) was 0.713, 0.682 and 0.726, respectively], among which CV-MAP has the highest predictive value. When the cut-off value of CV-MAP was 12.158, the sensitivity was 75.0% and the specificity was 69.3%. CONCLUSIONS: Higher BPV after trauma is a risk factor for PTSD. Maintaining stable blood pressure in trauma patients is of great significance for prevention and treatment of PTSD.

The Association between Standardized Serum 25-Hydroxyvitamin D Concentration and Risk of Anemia: A Population-Based Cross-Sectional Study.

The relationship between standardized serum 25-hydroxyvitamin D (25(OH)D) concentration and incident anemia in the United States (U.S.) is unclear. The purpose of our study was to examine the association between serum 25(OH)D and anemia risk. We performed a cross-sectional analysis of the U.S. population participating in the National Health and Nutrition Examination Survey (NHANES) between 2001 and 2018. A generalized linear model and restricted cubic spline (RCS) plot curve were constructed to assess the relationship between serum 25(OH)D concentration and anemia incidence. Additionally, the association between serum 25(OH)D concentration and red blood cell (RBC) count and hemoglobin (HB) levels was investigated using generalized additive models with smooth functions. Subgroup analysis also was performed. A total of 29933 individuals were included in our research. After adjusting for known confounding variables, compared with the lowest quartile, the odds ratios (ORs) with 95% confidence intervals (CIs) for association of serum 25(OH)D with anemia across the second, third, and fourth quartiles were 0.735 (0.651, 0.829), 0.527 (0.461, 0.602), and 0.696 (0.611, 0.792), respectively. Serum 25(OH)D concentration was associated with anemia risk in a U-shaped pattern, as shown by an RCS plot (P for nonlinearity <0.001). In addition, RBC count and Hb levels initially increased and then decreased as serum 25(OH)D levels increased. Serum 25(OH)D concentration and risk of anemia are associated with a U-shaped curve in the U.S. general population. Serum 25(OH)D concentration in the range 59.7-70.3 nmol/l was associated with anemia incidence <1. Therefore, the risk of anemia can be reduced by close monitoring and appropriate vitamin D supplementation.

Palliative radiotherapy combined with stent insertion to relieve dysphagia in advanced esophageal carcinoma patients: A systematic review and meta-analysis.

Introduction: Esophageal cancer is one of the most aggressive malignancies with limited treatment options, thus resulting in high morbidity and mortality. For patients with advanced esophageal cancer, the median survival is 3-6 months, with the majority requiring intervention for dysphagia. Objective: To compare the relief of dysphagia in patients with incurable esophageal cancer treated with stenting alone or a combination of stenting and palliative radiotherapy. Methods: The protocol of this study was pre-registered on PROSPERO (CRD42022337481). We searched PubMed, Wan Fang, Cochrane Library, Embase, and Web of Science databases. The literature search, quality assessment, and data extraction were conducted by two reviewers independently. The primary endpoints included median overall survival and dysphagia scores. Bleeding events, stent migration, and pain events were secondary outcomes. The meta-analysis results (the primary and secondary outcomes) were pooled by means of a random-effect model or a fixed-effects model. Results: Nine studies with a total of 851 patients were included in this meta-analysis, consisting of 412 patients in the stenting alone group and 439 patients in the palliative radiotherapy after esophageal cancer stenting (ROCS) group. The ROCS group could significantly improve dysphagia scores (SMD: -0.77; 95% CI: -1.02 to -0.51) and median overall survival (SMD: 1.70; 95% CI: 0.67-2.72). Moreover, there were no significant differences between the two groups in bleeding events, pain events, and stent migration. Conclusion: Patients with dysphagia in advanced esophageal cancer may benefit further from ROCS in median overall survival and dysphagia scores. However, there was no significant advantage in improving bleeding events, pain events, and stent migration. Therefore, it is urgent to find a better therapy to improve adverse events in the future. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022337481.

Diagnostic performance of coronary computed tomography (CT) angiography derived fractional flow reserve (CTFFR) in patients with coronary artery calcification: insights from multi-center experiments in China.

Background: Coronary computed tomography angiography (CCTA) is affected by calcification artifacts, which reduces its diagnostic efficacy. CT-derived fractional flow reserve (CTFFR) based on CCTA has been proven to be accurate in the diagnosis of non-calcified patients, but its clinical use in patients with calcified coronary artery disease remains to be investigated. The purpose of this study was to determine the effect of coronary artery calcification on CTFFR. Methods: CCTA, coronary angiography, and FFR were performed on 128 patients in three clinical medical centers. Local investigators performed an assessment of stenosis for CCTA and the core laboratory performed the CTFFR calculations. CTFFR ≤0.8 and diameter stenosis ≥50% for CCTA was identified as lesion-specific ischemia. The diagnostic performance of CTFFR in identifying the diagnostic sensitivity, specificity, and accuracy was analyzed using an invasive FFR ≤0.8 as the gold standard. We compared the diagnostic performances between CTFFR and CCTA according to the level of calcification. We divided patients into four groups based on the coronary artery calcification score [coronary artery calcification score (CACS) =0, >0 to <100, ≥100 to <400, and ≥400]. Results: The Youden index indicated an optimal threshold of 0.80 for CTFFR to identify functionally ischemic lesions. The sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV), and area under receiver operating characteristic curve (AUC) for CTFFR on a per-patient basis were 90% (80-96%), 98% (92-99%), 94% (89-97%), 98% (91-99%), 92% (83-97%), and 96.9% (94.2-99.6%), respectively. Compared to CCTA, CTFFR had a higher specificity, accuracy, PPV, NPV, and AUC in both the low to intermediate calcification group and the high calcification group. The diagnostic efficacy of CTFFR was higher than that of CCTA without the influence of calcification. Conclusions: This Chinese multi-center study showed that CTFFR based on novel computational fluid dynamics (CFD) modeling demonstrated very high diagnostic efficacy compared to the invasive measurement of FFR in all lesions suspected coronary artery disease (CAD). Of particular note are the high specificity, sensitivity, and accuracy of CTFFR, even in patients with calcification, which were significantly better than previous CCTA assessments.

The sST2 level is an independent influencing factor associated with atrial fibrillation in heart failure patients: a case-control study.

Background: Most heart failure (HF) patients were complicated with atrial fibrillation (AF). Previous study has reported a correlation between soluble suppression of tumorigenicity 2 (sST2) and HF. While the association between sST2 and AF in HF patients remains elusive, which will strengthen our understanding of sST2 in HF patients. Methods: In the study, a case-control study was conducted with 306 HF patients enrolled from June 2019 to June 2020 at Beijing Anzhen Hospital. All the patients were divided into the following two groups, based on whether they AF complications prior to admission: (I) the HF group (patients with HF alone) and the HF-AF group (HF patients complicated with AF). Baseline data and sST2 levels were assessed and compared between the two groups, and the influencing factors associated with AF in HF patients were screened. Results: The sST2 level in the HF-AF group was 40.6 (25.9-53.6) ng/mL, which was significantly higher than that in the HF group [23.7 (16.3-35.9) ng/mL] (P<0.001). Correlation analysis showed that sST2 level in the HF-AF group was positively correlated with age (r=0.287, P=0.001), New York Heart Association (NYHA) grade (r=0.470, P<0.0001), left ventricular diameter (LVD) (r=0.311, P=0.001), serum creatinine (r=0.320, P<0.0001), NT-pro-brain natriuretic peptide (r=0.540, P<0.0001), and D-dimer (r=0.322, P<0.0001), and negatively correlated with left ventricular ejection fraction (LVEF) (r=-0.259, P=0.004), hemoglobin (r=-0.188, P=0.039), and glomerular filtration rate (r=-0.283, P=0.002). Logistic regression analysis results indicated that history of coronary heart disease [odds ratio (OR): 0.176, 95% confidence interval (CI): 0.081-0.380, P<0.0001], LVEF (OR: 0.956, 95% CI: 0.915-0.998, P=0.039), LVD (OR: 1.156, 95% CI: 1.059-1.261, P=0.001), left arterial diameter (OR: 0.761, 95% CI: 0.695-0.833, P<0.0001), and sST2 (OR: 0.942, 95% CI: 0.917-0.967, P<0.0001) were independent influencing factors associated with AF in HF patients. Conclusions: The sST2 level is an independent influencing factor associated with AF in HF patients, which may favor to optimize the clinical strategies in the management of HF patients complicated with AF.

[Design and application of a portable cardiopulmonary resuscitation protection device].

Standardized cardiopulmonary resuscitation (CPR) of patients prior to the arrival of emergency medical services can significantly improve survival rate after out-of-hospital cardiac arrest (OHCA). According to statistics, about 40% to 85% of CPR led to chest fractures, making bystanders alarm, and reducing the willingness of rescuing by CPR. Therefore, there is an urgent need to develop a CPR protection device that is convenient for placing in public places outside the hospital and conforms to the operation habit of freehand CPR. In view of the above problems, medical students majored in emergency and rescue medicine and anesthesiology in Xuzhou Medical University, together with students majored in product design in Southeast University, designed a portable CPR protection device under the guidance of doctors working in department of emergency medicine of the Affiliated Hospital of Xuzhou Medical University, and obtained the national invention patent authorization of China (patent number: ZL 2021 1 0309001.4) and the national utility model patent authorization of China (patent number: ZL 2021 2 0591084.6). The device is composed of a foldable frame, support components, guide slide rails and compression body, which provides guidance and guarantee for the implementation of CPR, thus users can accurately grasp the implementation process, compression amplitude, strength and frequency, and effectively prevent accidental injuries such as rib fractures caused by CPR compression. The device is small, easy to store and move, with low manufacturing cost, making it suitable for social popularization.

Effect of S-Nitrosylation of RIP3 Induced by Cerebral Ischemia on its Downstream Signaling Pathway.

OBJECTIVES: Our preliminary experiments indicate that receptor-interacting protein 3 (RIP3) is S-nitrosylated and contributes to its autophosphorylation (activation) after 3 h of rat brain ischemia/reperfusion mediated by activation of the N-methyl-D-aspartate receptor (NMDAR)-dependent neuronal NO synthase (nNOS) and is involved in the process of neuronal injury. Here, we will to demonstrate whether S-nitrosylation of RIP3 facilitates the activation of the downstream signaling pathway and finally exacerbates ischemic neuron death. MATERIALS AND METHODS: Adult male Sprague-Dawley rat transient brain ischemia/reperfusion and cortical neurons oxygen and glucose deprivation (OGD)/reoxygenation models were performed. The hippocampal CA1 regions or cultured cells were homogenized and the cytosolic fraction were collected as tissue samples. Coimmunoprecipitation and western blot analysis were carried out for detecting phosphorylation of RIP1 and mixed lineage kinase-like domains (MLKL) and the Cleaved-Caspase8 (Cl-Caspase8). The activities of Glycogen phosphorylase (PYGL), Glutamate-ammonia ligase (GLUL) and Glutamate dehydrogenase (GLUD1) were detected with ultraviolet absorption method. RESULTS: This study showed that active RIP3 could phosphorylate RIP1 and MLKL through its kinase activity, promote the conversion of Caspase8 to active Cl-Caspase8, enhance the activities of PYGL, GLUL and GLUD1, and finally aggravate neuronal injury in cerebral ischemia/reperfusion. The inhibition of RIP3 S-nitrosylation inhibited the phosphorylation of RIP1 and MLKL, inhibited the activities of Caspase8, PYGL, GLUL, and GLUD1, and alleviated neuronal damage in cerebral ischemia/reperfusion. CONCLUSIONS: S-nitrosylation of RIP3 increased RIP1 and MLKL phosphorylation levels, Cl-Caspase8 content and PYGL, GLUL and GLUD1 activities and aggravated neuronal damage during cerebral ischemia/reperfusion and regulating the S-nitrosylation of RIP3 and its downstream signaling pathway might be a therapeutic target for stroke.

Hydrostatic pressure stimulates the osteogenesis and angiogenesis of MSCs/HUVECs co-culture on porous PLGA scaffolds.

In native bone tissue regeneration, blood vessels, providing oxygen and nutrition for tissues, can promote the regeneration of bone and accelerate the repair of a defected area. In this study, Poly(D, L-lactic-co-glycolic acid) (PLGA) inverse opal scaffolds with high pore interconnectivity were fabricated and further modified with vascular endothelial growth factor (VEGF). The rat bone marrow derived mesenchymal stem cells (rMSCs) and human umbilical vein endothelial cells (HUVECs) were co-cultured onto the scaffolds to enhance vascularization for bone tissue regeneration. Cell attachment, viability, proliferation, and morphology were detected by cell counting kit-8 (CCK-8) assay, live and dead staining and scanning electron microscopy (SEM). Hydrostatic pressure with 0-279 KPa and 1 Hz one hour per day for 7 days was applied to tissue engineered bone constructs to investigate whether the loading stimulation can promote osteogenesis and angiogenesis mutually evaluated in parallel by multiple in vitro assays and in an in vivo chicken chorioallantoic membrane (CAM) model. The results indicated that the immobilization of VEGF can improve biocompatibility of PLGA scaffolds and promote cell attachment and proliferation. The cell-scaffold constructs showed higher CD31 expression because of the angiogenic differentiation of rMSCs in hydrostatic loading culture condition in vitro. The in vivo CAM model experiment demonstrated that hydrostatic loading stimulated angiogenic differentiation of rMSCs can accelerate tubulogenesis. Furthermore, the new capillaries formed in cell-scaffold constructs were conducive to calcium deposition in vivo.

Biomechanics of the lead straight punch and related indexes between sanda fighters and boxers from the perspective of cross-border talent transfer.

Objective: To bridge the technical gaps in reserve athletes in China's national boxing program and to rapidly improve the overall level of boxing, the Wushu Sports Administration Center of the General Administration of Sports of China has sent outstanding Sanda players to boxing events through cross-border talent transfer. This was done to widely improve the strengths and resources in various fields to prepare for the Tokyo Olympic Games. In view of this, we analyzed and compared differences in biomechanical parameters of the lead straight punch and index of force developments of the lower extremities between Sanda and boxing. The results provide information and insights to bridge the technical gaps in cross-border talent transfer from Sanda to boxing. Methods: We employed a Vicon infrared 3D motion capture system, two Kistler platforms, a Kistler target, and a synchronous instrument. Eleven boxers and sixteen Sanda athletes were recruited, and their lead straight punch techniques were compared and analyzed. Three indexes of punch velocity, six indexes of strength measurement, and four indexes of lower extremity strength were analyzed. Results: Significant differences in the peak punch velocity and contact velocity were found between the two groups. Furthermore, significant differences were noted in the peak impulse, peak strength, relative strength, and the rate of force development (RFD). Among the kinetics indexes of lower limbs, the front leg strength index was higher in the boxing group than in the Sanda group, namely the RFD index and RFD/body mass. Conclusion: Based on the disparity in the effects of the lead straight punch and biomechanical parameters of both lower extremities, we can conclude that, compared to the boxers, most Sanda athletes lack standard punching technique. Therefore, it is advised that coaches and practitioners carefully consider selecting Sanda athletes with higher technical standards of punching.

Blood lead level in Chinese adults with and without coronary artery disease.

BACKGROUND: The Trial to Assess Chelation Therapy study found that edetate disodium (disodium ethylenediaminetetraacetic acid) chelation therapy significantly reduced the incidence of cardiac events in stable post-myocardial infarction patients, and a body of epidemiological data has shown that accumulation of biologically active metals, such as lead and cadmium, is an important risk factor for cardiovascular disease. However, limited studies have focused on the relationship between angiographically diagnosed coronary artery disease (CAD) and lead exposure. This study compared blood lead level (BLL) in Chinese patients with and without CAD. METHODS: In this prospective, observational study, 450 consecutive patients admitted to Beijing Anzhen Hospital with suspected CAD from November 1, 2018, to January 30, 2019, were enrolled. All patients underwent coronary angiography, and an experienced heart team calculated the SYNTAX scores (SXscore) for all available coronary angiograms. BLLs were determined with atomic absorption spectrophotometry and compared between patients with angiographically diagnosed CAD and those without CAD. RESULTS: In total, 343 (76%) patients had CAD, of whom 42% had low (0-22), 22% had intermediate (23-32), and 36% had high (≥ 33) SXscore. BLLs were 36.8 ± 16.95 µg/L in patients with CAD and 31.2 ± 15.75 µg/L in those without CAD (P = 0.003). When BLLs were categorized into three groups (low, middle, high), CAD prevalence increased with increasing BLLs (P < 0.05). In the multivariate regression model, BLLs were associated with CAD (odds ratio (OR): 1.023, 95% confidence interval (CI): 1.008-1.039; P = 0.0017). OR in the high versus low BLL group was 2.36 (95% CI: 1.29-4.42,P = 0.003). Furthermore, BLLs were independently associated with intermediate and high SXscore (adjusted OR: 1.050, 95% CI: 1.036-1.066; P < 0.0001). CONCLUSION: BLLs were significantly associated with angiographically diagnosed CAD. Furthermore, BLLs showed excellent predictive value for SXscore, especially for complex coronary artery lesions.

p-Coumaric acid regulates macrophage polarization in myocardial ischemia/reperfusion by promoting the expression of indoleamine 2, 3-dioxygenase.

Macrophage infiltration is a hallmark pathological change observed in early stage myocardial ischemia/reperfusion (MI/R) injury and one of the main causes of myocardial damage. Here, we investigated the effects of p-Coumaric acid (p-CA) on macrophage polarization following MI/R injury and its mechanisms. In vitro, p-CA decreases the expression of LPS/IFN-γ-induced M1 macrophage markers (TNF-α, IL-6, iNOS and CCL2) and increases IL-4-induced M2 macrophage markers (IL-10, CD206, Arg1 and Mrc) in mouse bone marrow-derived macrophages (BMDMs). Additionally, p-CA elevated indoleamine 2, 3-dioxygenase (IDO) protein expression levels, M2 macrophage polarization and M2 macrophage markers through IL-4. In contrast, repression of IDO attenuated p-CA functions regulating BMDMs through IL-4. In vivo, IDO expression was downregulated in mouse hearts subjected to MI/R injury. Treatment of p-CA increased IDO expression in the hearts of MI/R mice. Functionally, p-CA decreases M1 macrophage markers, the number of M1 macrophages and inflammation around heart tissue following MI/R injury. Importantly, p-CA reduces cardiomyocyte apoptosis caused by MI/R. Altogether, our study identified that p-CA modulates macrophage polarization by promoting IDO expression and that p-CA attenuates macrophage-mediated inflammation following MI/R by promoting M2 macrophage polarization through IDO.