Mechanism of DYRK1a in myocardial ischemia-reperfusion injury by regulating ferroptosis of cardiomyocytes.

This study aimed to explore the role and mechanism of DYRK1a regulating ferroptosis of cardiomyocytes during myocardial ischemia-reperfusion injury (MIRI). H9c2 cells treated with oxygen-glucose deprivation/reoxygenation (OGD/R) were used as MIRI cell models and transfected with sh-DYRK1a or/and erastin. Cell viability, apoptosis, and DYRK1a mRNA/protein expression were measured accordingly. The levels of reactive oxygen species (ROS), iron, malondialdehyde (MDA), and glutathione (GSH) were determined. The expression of ferroptosis-related proteins (GPX4, SLC7A11, ACSL4, and TFR1) was detected using western blotting. The MIRI rat model was established to explore the possible role of DYRK1a suppression in cell injury and ferroptosis. OGD/R cells showed elevated mRNA and protein expression for DYRK1a. OGD/R cells transfected with sh-DYRK1a showed elevated cell viability, GSH content, increased GPX4 and SLC7A11 expression, suppressed iron content, MDA, ROS, ACSL4, and TFR1 expression, and reduced apoptosis rate, whereas co-transfection of sh-DYRK1a with erastin reversed the attenuation of sh-DYRK1a on MIRI. The suppressive effect of sh-DYRK1a on MI/R injury was confirmed in an MIRI rat model. DYRK1a mediates ferroptosis of cardiomyocytes to deteriorate MIRI progression.

Long non-coding RNA XIST alleviates sepsis-induced acute kidney injury through inhibiting inflammation and cell apoptosis via regulating miR-155-5p/WWC1 axis.

Sepsis is characterized by a severe inflammatory response throughout the whole body and can induce acute kidney injury (AKI). This research aimed to investigate the regulatory mechanisms underlying miR-155-5p in sepsis-induced AKI. CLP-treated mice were used as an in vivo model of sepsis-induced AKI, and LPS-treated HK-2 and TCMK-1 cells were used as in vitro models. Bioinformatics analyses and mechanistic assays were utilized to reveal the relationships between molecules. H&E staining was used to reveal morphological changes in kidney tissues. ELISAs were conducted to detect the concentrations of proinflammatory cytokines. We discovered that miR-155-5p was prominently upregulated in sepsis-induced AKI in vivo and in vitro. MiR-155-5p inhibition alleviated kidney injury in mice. Moreover, WWC1 served as a direct target of miR-155-5p and was negatively regulated by miR-155-5p. WWC1 upregulation inhibited the productions of inflammatory cytokines and suppressed apoptosis in vivo and in vitro. In addition, rescue assays demonstrated that WWC1 knockdown counteracted the inhibitory effect of anti-miR-155-5p on inflammation and apoptosis. Moreover, miR-155-5p could bind to XIST. XIST expression was downregulated in LPS-stimulated HK-2 and TCMK-1 cells. XIST could negatively regulate miR-155-5p expression and positively regulate WWC1 expression. Rescue assays revealed that miR-155-5p overexpression significantly reversed the suppressive effects of XIST upregulation on inflammation and apoptosis. In conclusion, our study revealed that the XIST/miR-155-5p/WWC1 axis modulated sepsis-induced AKI progression, providing promising insight into therapeutic targets for sepsis-induced AKI.

The prognostic value of routine coagulation tests for patients with heat stroke.

OBJECTIVE: To evaluate the prognostic value of routine coagulation tests for patients with heat stroke. METHODS: This was a multi-center retrospective study. Patients who arrived at the hospital <24 h after the onset of Heat Stroke (HS) were included. The routine coagulation variables were detected within 24 h after the onset, including the lowest platelet count (PLC). RESULTS: 60-day mortality rate was 20.9%. The median Prothrombin Time-International Normalized Ratio (PT-INR) of the non-surviving patients was significantly higher than that of the survivors (P < 0.01). The median Activated Partial Thromboplastin Time (APTT) in non-surviving patients was significantly higher than in the surviving patients (P < 0.01). A Cox regression analysis revealed that 60-day mortality was associated with PT-INR (P = 0.032) and APTT (P = 0.004). The optimal PT-INR point for predicting 60-day mortality rate was 1.7. The optimal APTT point for predicting 60-day mortality was 51.45. Patients with increased PT-INR (≥1.7) levels had, overall, a significantly reduced survival time (P < 0.01). Patients with elevated APTT (≥51.45) also had a decrease in survival time (P < 0.01). The prognostic scoring, with increased PT-INR (≥1.7) and prolonged APTT (≥51.45) at one point each, was also demonstrated to be useful in predicting 60-day mortality. Patients whose temperature fell to 38.9 °C within 30 min had significantly lower levels of PT-INR and APTT within 24 h than those who took longer to cool down. CONCLUSIONS: A prolonged APTT and elevated PT-INR within 24 h are independent prognostic factors of 60-day mortality in HS.

Pathogens distribution and drug resistance in patients with acute cerebral infarction complicated with diabetes and nosocomial pulmonary infection.

BACKGROUND: This study aims to investigate the pathogen distribution and drug resistance in patients with acute cerebral infarction complicated with diabetes mellitus and nosocomial pulmonary infection. METHODS: From August 2015 to December 2017, 172 pathogenic bacterial strains from patients with acute cerebral infarction complicated with diabetes mellitus and nosocomial pulmonary infection in our hospital were identified, and the drug sensitivity was analyzed. RESULTS: Among these 172 strains of pathogenic bacteria, gram negative bacteria was the main cause of pulmonary infection in hospitalized patients with acute cerebral infarction, accounting for 75.6% of all pathogens. Furthermore, 80% of diabetic patients with cerebral infarction had lung infection induced by gram negative bacteria, which was significantly higher than that in non-diabetic patients (72.2%). Moreover, the drug resistance rate in the diabetic group (68.3%) was significantly higher than that in the non-diabetic group (54.3%). Gram positive bacteria accounted for 19.1% of all pathogenic bacteria. The infection rate of gram-positive bacteria in diabetic patients with cerebral infarction was 14.7%, which was lower than that in the non-diabetic group (22.6%). The drug-resistance rate was higher in the diabetic group (45.5%) than in the non-diabetic group (28.2%). Furthermore, the fungal infection rate in patients with lung infection in these two groups was 5.3 and 5.2%, respectively, and fungi presented with high sensitivity to commonly used antifungal agents. CONCLUSION: In patients with acute cerebral infarction complicated with diabetes mellitus and nosocomial pulmonary infection, the majority of pathogens are multidrug-resistant gram negative bacilli. Pathogen culture should be conducted as soon as possible before using antibiotics, and antimicrobial agents should be reasonably used according to drug sensitivity test results.

[The clinical evaluation of piperacillin and sulbactam sodium in treatment of respiratory, urinary tracts and other infections in 579 patients].

OBJECTIVE: To evaluate the clinical efficacy and safety of piperacillin and sulbactam sodium combinations in the treatment of common infections. METHODS: This was a multi-centre, prospective and open study. All subjects from 57 wards caught common infection like respiratory (RTI) or urinary diseases (UTI). The dosages of piperacillin and sulbactam sodium combinations 2.5 g injection were determined according to indications: for adult, 2.5 g or 5 g per time, 2 time/day; for severe or obstinate infection, 2.5 g or 5 g per time, 3 time/day. General information, clinical response pre- and post-treatment, infected locus, drug recipe and protocol, prognosis and adverse reaction were recorded. RESULTS: Data of 579 cases were collected with 388 males and 191 females. The average age was (66.8 ± 17.0) years. There were 500 patients who were suffering with RTI, with 362 cases of pneumonia, 102 of acute exacerbation of chronic bronchitis, and 36 of other infections. There were 50 cases with UTI, with 31 of simple urinary tract infection, and 19 of complex urinary tract infection. In addition, there were 9 cases of combined RTI and UTI, and 20 of other infections including peritonitis. The average duration of anti-microbial for RTI and UTI was (8.65 ± 3.78) days and (7.45 ± 3.46) days respectively with the total efficacy rate was 92.6% and 98.0% respectively for RTI and UTI. The incidence of adverse events was only 0.86% (5 cases), including nausea, rash, itching, ALT elevation and suspected drug induced fever in each one. CONCLUSION: Piperacillin and sulbactam sodium compound had high clinical efficacy and safety in the treatment of common infections including RTI and UTI.