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Icariside II (ICAII) is a bioflavonoid compound which has demonstrated anti‑oxidative, anti‑inflammatory and anti‑apoptotic biological activities. However, to the best of our knowledge, whether ICAII can alleviate myocardial ischemia and reperfusion injury (MIRI) remains unknown. The aim of the present study was to determine whether ICAII exerted a protective effect on MIRI and to investigate the potential underlying mechanism of action. A rat MIRI model was established by ligation of the left anterior descending coronary artery for 30 min, followed by a 24 h reperfusion. Pretreatment with ICAII with or without a PI3K/AKT inhibitor was administered at the beginning of reperfusion. Morphological and histological analyses were detected using hematoxylin and eosin staining; the infarct size was measured using Evans blue and 2,3,5‑triphenyltetrazolium chloride staining; and plasma levels of lactate dehydrogenase (LDH) and creatine kinase‑myocardial band (CK‑MB) were analyzed using commercialized assay kits. In addition, the cardiac function was evaluated by echocardiography and the levels of cardiomyocyte apoptosis were determined using a TUNEL staining. The protein expression levels of Bax, Bcl‑2, cleaved caspase‑3, interleukin‑6, tumor necrosis factor‑α, PI3K, phosphorylated (p)‑PI3K, AKT and p‑AKT were analyzed using western blotting analysis. ICAII significantly reduced the infarct size, decreased the release of LDH and CK‑MB and improved the cardiac function induced by IR injury. Moreover, ICAII pretreatment significantly inhibited myocardial apoptosis and the inflammatory response. ICAII also upregulated the expression levels of p‑PI3K and p‑AKT. However, the protective effects of ICAII were abolished by an inhibitor (LY294002) of the PI3K/AKT signaling pathway. In conclusion, the findings of the present study suggested that ICAII may mitigate MIRI by activating the PI3K/AKT signaling pathway.

Purpose: Computed tomography (CT) characteristics associated with critical outcomes of patients with coronavirus disease 2019 (COVID-19) have been reported. However, CT risk factors for mortality have not been directly reported. We aim to determine the CT-based quantitative predictors for COVID-19 mortality.Methods: In this retrospective study, laboratory-confirmed COVID-19 patients at Wuhan Central Hospital between December 9, 2019, and March 19, 2020, were included. A novel prognostic biomarker, V-HU score, depicting the volume (V) of total pneumonia infection and the average Hounsfield unit (HU) of consolidation areas was automatically quantified from CT by an artificial intelligence (AI) system. Cox proportional hazards models were used to investigate risk factors for mortality.Results: The study included 238 patients (women 136/238, 57%; median age, 65 years, IQR 51–74 years), 126 of whom were survivors. The V-HU score was an independent predictor (hazard ratio [HR] 2.78, 95% confidence interval [CI] 1.50–5.17; p = 0.001) after adjusting for several COVID-19 prognostic indicators significant in univariable analysis. The prognostic performance of the model containing clinical and outpatient laboratory factors was improved by integrating the V-HU score (c-index: 0.695 vs. 0.728; p < 0.001). Older patients (age ≥ 65 years; HR 3.56, 95% CI 1.64–7.71; p < 0.001) and younger patients (age < 65 years; HR 4.60, 95% CI 1.92–10.99; p < 0.001) could be further risk-stratified by the V-HU score.Conclusions: A combination of an increased volume of total pneumonia infection and high HU value of consolidation areas showed a strong correlation to COVID-19 mortality, as determined by AI quantified CT.

The aim of the current study was to investigate the effect and mechanism of schisandrin B (Sch B) on myocardial hypertrophy induced by pressure overload in mice. Male C57BL/6J mice were randomly divided into three groups: i) Sham (n=12); ii) transverse aortic constriction (TAC) (n=12); and iii) Sch B-treated (n=12; 80 mg·kg-1·d-1 per gavage). The model of myocardial hypertrophy was established by constricting the descending branch of the aortic arch. Following a 4-week treatment period, cardiac remodeling was evaluated using echocardiography and pathological and molecular analysis. Sch B improved cardiac function in the Sch B-treated group compared with the TAC group. Moreover, the Sch B-treated group had a smaller myocardial cell cross-sectional area and less fibrosis compared with the TAC group. The protein expression levels of cardiac hypertrophy and fibrosis markers in the TAC group were significantly higher compared with those in the sham group. The same markers in the Sch B-treated group were significantly lower compared with those in the TAC group. Additionally, the phosphorylation levels of the mitogen-activated protein kinase (MAPK) signaling pathway-associated proteins extracellular signal-regulated kinase 1/2, c-Jun N-terminal kinase 1/2 and P38 mitogen-activated protein kinase were significantly lower in the Sch B-treated group compared with the TAC group. Further in vitro investigation demonstrated that Sch B prevented the adverse effects of angiotensin II-induced hypertrophy and fibrosis by inhibiting the MAPK signaling pathway in H9c2 cells. In conclusion, Sch B may improve pathological myocardial remodeling and cardiac function induced by pressure overload, and its underlying mechanism may be associated with inhibition of the MAPK signaling pathway.

Inflammation parameters were verified to predict clinical outcomes of metastatic renal cell carcinoma (mRCC) patients treated with tyrosine kinase inhibitors (TKIs). Here, we developed a novel marker, lactate dehydrogenase (tumor burden marker) to lymphocytes (inflammation marker) ratio (LLR), aimed to reveal the prognostic role of LLR for mRCC patients treated with TKIs. We collected clinical data of mRCC patients treated with TKIs. Receiver operating curve analysis was used to determine the optimal cut-off value. The c-index method was used to determine the best predictive marker for overall survival (OS). Clinicopathological characteristics on OS and progression-free survival (PFS) were evaluated by univariate analysis, and multivariate analyses. LLR provided the greatest improvement in the c-index, and displayed the best marker of the prognostic accuracy for OS. Univariate analysis revealed that LLR, ECOG PS and IMDC risks were significant predictors of OS and PFS. However, multivariate analysis indicated that IMDC risks failed to predict PFS, and only showed predictor of OS. We finally stratifed patients into low LLR (

Endoplasmic reticulum stress (ERS)-induced apoptosis serves a crucial role in the pathogenesis of myocardial ischemia/reperfusion injury (MIRI). Previous studies have confirmed that pleckstrin homology-like domain family A member 3 (PHLDA3) is an important mediator in ERS-associated apoptosis. The aim of the current study focused on whether PHLDA3 served protective effects on hypoxia/reoxygenation (H/R)-injured cardiomyocytes by inhibiting ERS-induced apoptosis. Furthermore, the molecular mechanisms associated with the PI3K/AKT signaling pathway were investigated. Primary neonatal rat cardiomyocytes were isolated and randomized into four groups: i) Control + adenovirus encoding scrambled short hairpin RNA (AdshRNA); ii) control + adenoviral vectors encoding PHLDA3 shRNA (AdshPHLDA3); iii) H/R+ AdshRNA and iv) H/R+AdshPHLDA3. AdshPHLDA3 was used to knock down PHLDA3. An H/R injury model was constructed by treatment with hypoxia for 4 h followed by reoxygenation for 6 h. A PI3K/AKT inhibitor, LY294002, was supplemented in mechanistic studies. Cell viability and LDH/CK releases were detected to evaluate myocardial damage. Flow cytometry assays were used to assess apoptotic response. Western blotting assays were used to detect protein expression. The results demonstrated that H/R induced myocardial damage and increased PHLDA3 expression. ERS-induced apoptosis was significantly increased following H/R injury, as indicated by increased apoptotic rates and ERS-associated protein expression, including those of CHOP, 78 kDa glucose-regulated protein and caspase-12. However, PHLDA3 inhibition following AdshPHLDA3 transfection reversed cell damage and ERS-associated apoptosis on H/R injury. Studies for molecular mechanisms concluded that the apoptosis-inhibition effects and cardioprotective roles of PHLDA3 inhibition were induced partly by the activation of the PI3K/AKT pathway, which was verified by LY294002 treatment. In conclusion, in the process of H/R injury, PHLDA3 inhibition reduced ERS-induced apoptosis and H/R injury by activating the PI3K/AKT pathway. PHLDA3 may be a therapeutic target for the treatment of MIRI.

BackgroundThe recent emergence and rapid global spread of coronavirus disease 2019 (COVID-19) is leading to public health crises worldwide. Alcohol consumption and cigarette smoking (CS) are two known risk factors in many diseases including respiratory infections.MethodsWe performed a multi-center study in the four largest hospitals designated for COVID-19 patients in Wuhan. There are totally 1547 patients diagnosed with COVID-19 enrolled in the study, alcohol consumption and CS history were evaluated among these patients. The epidemiology, laboratory findings and outcomes of patients contracted COVID-19 were further studied.ResultsOur findings indicated that COVID-19 patients with a history of CS tend to have more severe outcomes than non-smoking patients. However, alcohol consumption did not reveal significant effects on neither development of severe illness nor death rates in COVID-19 patients.ConclusionCS is a risk factor for developing severe illness and increasing mortality during the SARS-CoV-2 infection. We believe that our findings will provide a better understanding on the effects of alcohol intake and CS exposure in COVID-19 patients.

Background The management of critically ill patients with coronavirus disease 2019 (COVID‐19), caused by a new human virus severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), is challenging. Recently, there have been several reports with inconsistent results after treatment with convalescent plasma (CP) on critically ill patients with COVID‐19, which was produced with a neutralizing antibody titer and tested in a P3 or P4 laboratory. However, due to the limitation of the conditions on mass production of plasma, most producers hardly had the capability to isolate the neutralizing antibody. Here, we report the clinical courses of three critically ill patients with COVID‐19 receiving CP treatments by total immunoglobulin G (IgG) titer collection. Methods Three patients with COVID‐19 in this study were laboratory confirmed to be positive for SARS‐CoV‐2, with radiographic and clinical features of pneumonia. CP was collected by total IgG titer of 160 (range, 200‐225 mL), and patients were transfused between 20 and 30 days after disease onset at the critical illness stage as a trial in addition to standard care. The clinical courses of these patients, including laboratory results and pulmonary functional and image studies after receiving convalescent plasma infusions, were reviewed. Results No therapeutic effect of CP was observed in any of the patients; instead, all three patients deteriorated and required extracorporeal membrane oxygenation treatment. A potential cytokine storm 4 hours after infusion of CP in Patient 2 was observed. No more patients were put on the trial of CP transfusion. Conclusions We recommend extreme caution in using CP in critically ill patients more than 2 weeks after the onset of COVID‐19 pneumonia.

Background: Our study investigated the diagnostic and prognostic role of serum antioxidant indexes in patients with acute pancreatitis (AP). Methods: This study included 708 AP patients from the Medical Information Mart for Intensive Care-III (MIMIC-III) database and 477 patients from the eICU Collaborative Research Database (eICU-CRD). X-tile software was applied to determine the best cutoff values for serum antioxidant indexes. Univariate and multivariate regression analyses were employed to select variables associated with severe AP (SAP) and in-hospital mortality. Finally, the nomograms were also externally validated in the eICU-CRD. Results: The best cutoff values for serum total bilirubin (TBIL) and albumin were 1.1 mg/dL and 2.1 g/dL in the training set, respectively. Multivariate logistical regression indicated that both TBIL (odds ratio [OR]=0.740, 95% confidence interval [CI]: 0.616-0.889, P=0.001) and albumin (OR=0.890, 95%CI: 0.819-0.967, P=0.006) were independent risk factors for SAP. Similarly, multivariate Cox analysis revealed that serum TBIL (hazard ratio [HR]=0.768, 95%CI:0.635-0.928, P=0.006) and albumin (HR=0.962, 95%CI:0.927-0.998, P=0.037) were independent risk factors for in-hospital mortality in AP patients. The diagnostic nomogram containing TBIL, albumin, Sequential Organ Failure Assessment (SOFA) score and urea nitrogen and prognostic nomogram combining TBIL, albumin, white blood count, SOFA score, and age obtained good discrimination, calibration and clinical utility in both the MIMIC-III and eICU-CRD. Conclusion: Serum TBIL and albumin were independent predictors for SAP and in-hospital mortality in AP patients. The nomograms combining serum TBIL and albumin with other significant features exerted favorable predictive performance for SAP and in-hospital mortality.

Background This present study aimed to investigate the correlation of long non‐coding RNA THRIL (lnc‐THRIL) with acute respiratory distress syndrome (ARDS) risk, disease severity, inflammation, and mortality in sepsis patients. Methods A total of 109 sepsis patients admitted to intensive care units were consecutively recruited, and their blood samples were collected. After admission, patients were supervised and screened daily to identify the occurrence of ARDS. Clinical characteristics, routine laboratory testing, and disease severity were recorded, and all enrolled patients were followed up until death in the hospital or discharge for mortality records. Lnc‐THRIL was detected by quantitative polymerase chain reaction, and inflammatory cytokine levels were measured by human enzyme‐linked immunoassay. Results A total of 32 (29.4%) sepsis patients occurred ARDS and 77 (71.6%) did not. Lnc‐THRIL was upregulated in ARDS group compared with non‐ARDS group, and it had good value in distinguishing ARDS from non‐ARDS in sepsis patients (AUC: 0.706; 95%CI: 0.602‐0.809). Besides, lnc‐THRIL, smoke, and chronic obstructive pulmonary disease independently predicted increased risk of ARDS. As for disease severity, lnc‐THRIL positively correlated with APACHE II score and SOFA score in sepsis patients. Regarding inflammation, lnc‐THRIL was positively associated with CRP, PCT, TNF‐α, and IL‐1β levels in sepsis patients. Additionally, the mortality rate was 30.2%, and lnc‐THRIL was upregulated in non‐survivors compared with survivors, presenting a good value (AUC: 0.780; 95%CI: 0.683‐0.876) in predicting mortality in sepsis patients. Conclusion Lnc‐THRIL predicts increased risk of ARDS and positively correlates with disease severity, inflammation, and mortality in sepsis patients.

The present study was undertaken to evaluate the cardioprotection potential and underlying molecular mechanism afforded by a selenium (Se) polysaccharide (Se-AVP) from Aloe vera in the ischemia-reperfusion (I/R) model of rats in vivo. Myocardial I/R injury was induced by occluding the left anterior descending coronary artery (LAD) for 30 min followed by 2-h continuous reperfusion. Pretreatment with Se-AVP (100, 200, and 400 mg/kg) attenuated myocardial damage, as evidenced by reduction of the infarct sizes, increase in serum and myocardial endogenous antioxidants (superoxide dismutase (SOD), glutathione peroxidase (GSH), and catalase (CAT)), and decrease in the malondialdehyde (MDA) level in the rats suffering I/R injury. This cardioprotective activity afforded by Se-AVP is further supported by the decreased levels of cardiac marker enzymes creatine kinase (CK) and lactate dehydrogenase (LDH), as well as the rise of myocardial Na+-K+-ATPase and Ca2+-Mg2+-ATPase activities in I/R rats. Additionally, cardiomyocytic apoptosis was measured by terminal-deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) staining and the result showed that the percent of TUNEL-positive cells in myocardium of Se-AVP-treated groups was lower than I/R rats. In conclusion, we clearly demonstrated that Se-AVP had a protective effect against myocardial I/R injury in rats by augmenting endogenous antioxidants and protecting rat hearts from oxidative stress-induced myocardial apoptosis.

BACKGROUND: To investigate the correlation of plasma lncRNA ANRIL expression with stroke risk, severity and inflammatory cytokines levels in acute ischemic stroke (AIS) patients. METHODS: A total of 126 AIS patients and 125 controls were consecutively recruited in this case‐control study. Blood samples from all participants were collected, and plasma was separated. Plasma lncRNA ANRIL expression was quantified by quantitative real‐time polymerase chain reaction (qRT‐PCR). Plasma tumor necrosis factor‐α (TNF‐α) and interleukin (IL)‐1β (IL‐1β), IL‐6, IL‐8, IL‐10, and IL‐17 levels were measured by enzyme‐linked immunosorbent assay (ELISA). National Institutes of Health Stroke Scale (NIHSS) scores were used to assess the stroke severity in AIS patients. RESULTS: Plasma lncRNA ANRIL expression was lower in AIS patients than in controls (P