SGLT2i improves kidney senescence by down-regulating the expression of LTBP2 in SAMP8 mice.

Senescent kidney can lead to the maladaptive repairment and predispose age-related kidney diseases. Here, we explore the renal anti-senescence effect of a known kind of drug, sodium-dependent glucose transporters 2 inhibitor (SGLT2i). After 4 months intragastrically administration with dapagliflozin on senescence-accelerated mouse prone 8 (SAMP8) strain mice, the physiologically effects (lowering urine protein, enhancing glomerular blood perfusion, inhibiting expression of senescence-related biomarkers) and structural changes (improving kidney atrophy, alleviating fibrosis, decreasing glomerular mesangial proliferation) indicate the potential value of delaying kidney senescence of SGLT2i. Senescent human proximal tubular epithelial (HK-2) cells induced by H2 O2 also exhibit lower senescent markers after dapagliflozin treatment. Further mechanism exploration suggests LTBP2 have the great possibility to be the target for SGLT2i to exert its renal anti-senescence role. Dapagliflozin down-regulate the LTBP2 expression in kidney tissues and HK-2 cells with senescent phenotypes. Immunofluorescence staining show SGLT2 and LTBP2 exist colocalization, and protein-docking analysis implies there is salt-bridge formation between them; these all indicate the possibility of weak-interaction between the two proteins. Apart from reducing LTBP2 expression in intracellular area induced by H2 O2 , dapagliflozin also decrease the concentration of LTBP2 in cell culture medium. Together, these results reveal dapagliflozin can delay natural kidney senescence in non-diabetes environment; the mechanism may be through regulating the role of LTBP2.

Predicting prognosis in patients with stroke treated with intravenous alteplase through blood pressure changes: A machine learning-based approach.

The use of machine learning (ML) in predicting disease prognosis has increased, and researchers have adopted different methods for variable selection to optimize early screening for AIS to determine its prognosis as soon as possible. We aimed to improve the understanding of the predictors of poor functional outcome at three months after discharge in AIS patients treated with intravenous thrombolysis and to construct a highly effective prognostic model to improve prediction accuracy. And four ML methods (random forest, support vector machine, naive Bayesian, and logistic regression) were used to screen and recombine the features for construction of an ML prognostic model. A total of 352 patients that had experienced AIS and had been treated with intravenous thrombolysis were recruited. The variables included in the model were NIHSS on admission, age, white blood cell count, percentage of neutrophils and triglyceride after thrombolysis, tirofiban, early neurological deterioration, early neurological improvement, and BP at each time point or period. The model's area under the curve for predicting 30-day modified Rankin scale was 0.790 with random forest, 0.542 with support vector machine, 0.411 with naive Bayesian, and 0.661 with logistic regression. The random forest model was shown to accurately evaluate the prognosis of AIS patients treated with intravenous thrombolysis, and therefore they may be helpful for accurate and personalized secondary prevention. The model offers improved prediction accuracy that may reduce rates of misdiagnosis and missed diagnosis in patients with AIS.

Effectiveness and safety of early postpyloric feeding during therapeutic hypothermia in patients with large hemispheric infarction: A retrospective cohort study.

BACKGROUND: What kind of feeding should be provided during therapeutic hypothermia (TH) in patients with large hemispheric infarction (LHI) is not clear. Therefore, we conducted a retrospective observational study to determine whether providing early postpyloric feeding (PPF) (<24 h after admission) is beneficial or harmful for patients with this condition. METHODS: This study retrospectively screened 78 patients with LHI who were treated with TH from one neurological intensive care unit (ICU). The patients were receiving either early PPF (n = 52) or early parenteral nutrition (PN) (n = 26). Data regarding 30-day mortality, neurological outcome, nutrition-related laboratory indicators, ICU hospitalization time, mechanical ventilation (MV) duration, and complications were collected. RESULTS: A greater number of patients who received early PPF had favorable neurologic outcome than those who received early PN (57.7% vs 30.7%, P = 0.025). The early PPF group had a lower severity of pulmonary infection than the early PN group, as measured by the Clinical Pulmonary Infection Score (7.33 ± 0.96 vs 9.42 ± 2.11, P = 0.006). The total protein and hemoglobin levels in the early PPF group were higher than those in the early PN group (59.56 ± 5.09 vs 56.52 ± 7.94 g/L, P = 0.046; 131.06 ± 19.58 vs 122.07 ± 17.72 g/L, P = 0.045). The MV duration and ICU hospitalization time were shorter in the early PPF group (13 [9;21] vs 21 [14;30] days, P = 0.006; 28 [22;36] vs 34 [33;51] days, P = 0.014). There were no significant differences in the incidence of catheter-related bloodstream infections, 30-day mortality, or nutrition intolerance between the two groups. CONCLUSION: Early PPF is an effective and safe enteral nutrition method for patients with LHI receiving TH.

Association between blood ethylene oxide levels and the prevalence of hypertension.

The relationship of blood ethylene oxide levels with hypertension and blood pressure has not been addressed. A total of 5005 participants from the National Health and Nutrition Examination Survey (NHANES) 2013-2016 were enrolled. Hypertension was defined as a mean systolic blood pressure (SBP) of at least 140 mmHg, a mean diastolic blood pressure (DBP) of at least 90 mmHg, or both, and/or the self-reported use of prescription drugs for diagnosed hypertension. Generalized linear regression models and restricted cubic spline plots were performed to explore the associations of ethylene oxide levels with hypertension and blood pressure. The prevalence of hypertension in the study sample was 27.6%. After adjusting for confounding factors, compared with the lowest quantile, the odds ratios (ORs) with 95% confidence intervals (CIs) of hypertension across the quantiles of ethylene oxide levels were 0.80 (0.63, 1.03), 0.91 (0.71, 1.16), and 1.39 (1.06, 1.82), respectively (P-value for trend = 0.001). Compared with the lowest quantile, the highest quantile of blood ethylene oxide levels was significantly associated with the worst DBP profile by approximately 2.67 mmHg. Blood ethylene oxide levels showed a strong nonlinear and positive association with DBP, while no significant association was observed between blood ethylene oxide levels and SBP. These results provide epidemiological evidence of elevated blood levels of ethylene oxide in relation to a higher prevalence of hypertension and higher DBP. Further study is warranted to address these issues.

Case Report: Use of Liposomal Amphotericin B in Low Doses in Patients With Visceral Leishmaniasis.

Background: No consensus has been reached regarding the optimal therapy for visceral leishmaniasis (VL), which affects ~12 million people worldwide. Case Presentation: This report described four cases of VL encountered in the First Affiliated Hospital of Xi'an Jiaotong University between October 2019 and December 2020. Of the four patients, one patient experienced relapse after antimonial treatment, and the remaining patients had primary VL (including one patient with impaired kidney function and one patient with hemophagocytic syndrome). All patients received a novel treatment protocol, namely the low-dose L-AmB therapy, which was characterized by a low initial dose, cautious dose escalation, and low-dose therapy as maintenance. All patients were cured without severe complications, and there was no further recurrence during follow-up. Conclusions: This case series demonstrated the safety and efficacy of the low-dose L-AmB therapy for VL patients, providing novel treatment protocol for the VL.

The risk factors for delayed recovery in patients with cardiopulmonary bypass: Why should we care?

ABSTRACT: Cardiopulmonary bypass (CPB) is very commonly performed among the cardiovascular surgeries, and delayed recovery (DR) is a kind of serious complications in patients with CPB. It is necessary to assess the risk factors for DR in patients with CPB, to provide evidence into the management of CPB patients.Patients undergoing CPB in our hospital from January 2018 to March 2020 were included. Cases that consciousness has not recovered 12 hours after anesthesia were considered as DR. The preoperative and intraoperative variables of CPB patients were collected and analyzed. Logistic regressions were conducted to analyze the potential influencing factor.A total of 756 CPB patients were included, and the incidence of DR was 9.79%. There were significant differences on the age, aspartate aminotransferase (AST), glutamic pvruvic transaminase (ALT), blood urea nitrogen (BUN), and serum creatinine (SCr) between patients with and without DR (all P < .05); there were no significant differences in the types of surgical procedure (all P > .05); there were significant differences on the duration of CPB, duration of aortic cross clamp (ACC), duration of surgery, minimum nasopharyngeal temperature, and transfusion of packed red blood cells between patients with and without DR (all P < .05). Logistic regression analysis indicated that duration of CPB ≥132 minutes (odds ratio [OR] 4.12, 1.02-8.33), BUN ≥9 mmol/L (OR 4.05, 1.37-8.41), infusion of red blood cell suspension (OR 3.93, 1.25-7.63), duration of surgery ≥350 minutes (OR 3.17, 1.24-5.20), age ≥6 (OR 3.01, 1.38-6.84) were the independent risk factors for DR in patients with CPB (all P < .05).Extra attention and care are needed for those CPB patients with duration of CPB ≥132 minutes, BUN ≥9 mmol/L, infusion of red blood cell suspension, duration of surgery ≥350 minutes, and age ≥60.