Activation of the Vascular Smooth Muscle GLP-1/NCX1 Pathway Regulates Cytoplasmic Ca2+ Homeostasis and Improves Blood Pressure Variability in Hypertension.

BACKGROUND: Hypertension is the most common cardiovascular disease, and its main harmful effect is chronic damage to target organs. In some patients with well-controlled blood pressure, target organ damage still occurs. GLP-1 agonists have significant cardiovascular benefits, but their antihypertensive effect is limited. The cardiovascular protective effect of GLP-1 is worth studying. METHODS: The ambulatory blood pressure of spontaneously hypertensive rats (SHRs) was detected by ambulatory blood pressure monitoring, and the characteristics of blood pressure and the effect of subcutaneous intervention with a GLP-1R agonist on blood pressure were observed. To explore the mechanism of the cardiovascular benefit of GLP-1R agonists in SHRs, we evaluated the effects of GLP-1R agonists on vasomotor function and calcium homeostasis in vascular smooth muscle cells (VSMCs) in vitro. RESULTS: Although the blood pressure of SHRs was significantly higher than that of WKY rats, the blood pressure variability of SHRs was also significantly higher than that of the control group. The GLP-1R agonist significantly reduced blood pressure variability in SHRs, but the antihypertensive effect was not obvious. GLP-1R agonists can significantly improve the cytoplasmic calcium overload of VSMCs in SHRs by upregulating the expression of NCX1, improving the systolic and diastolic functions of arterioles, and reducing blood pressure variability. CONCLUSIONS: Taken together, these results provide evidence that GLP-1R agonists improved VSMC cytoplasmic Ca2+ homeostasis through upregulated NCX1 expression in SHRs, which plays a key role in blood pressure stability and broad cardiovascular benefits.

TRPC6 inhibits renal tubular epithelial cell pyroptosis through regulating zinc influx and alleviates renal ischemia-reperfusion injury.

Canonical transient receptor potential-6 (TRPC6) has been reported to be involved in cell damage after ischemia/reperfusion (I/R) injury in target organs. While the effect and of TRPC6 on pyroptosis in renal I/R injury remain unclear. In our study, we first established the renal I/R mouse model and oxygen-glucose deprivation and re-oxygenation (OGD/R) cell model, and investigated the impacts of TRPC6 on the pyroptosis-related proteins using CCK-8, western blot, ELISA, and immunofluorescence probes. Besides, we also explored the mechanism of TRPC6 in pyroptosis of renal tubular epithelial cells through A20 knockdown or overexpression and zinc chloride (ZnCl2 ) or a zinc ion chelator (TPEN) treatment. Our results indicated that I/R injury could cause downregulation of TRPC6 both in vivo and in vitro. In the I/R injury murine model, TRPC6 inhibition exacerbated tissue damage and upregulated NLRP3, ASC, caspase-1, IL-18, and IL-1ß, which could be alleviated by the administration of ZnCl2 . In the OGD/R cell model, inhibitor of TRPC6 (SAR7334) reduced zinc ion influx, aggravated cell death and upregulated pyroptosis-related protein. The pyroptosis phenotype also could be alleviated by ZnCl2 and intensified by TPEN. Overexpression of A20 reduced the expression of pyroptosis-related protein, increased cell viability in the sh-TRPC6 and TPEN-treated OGD/R cell models, while A20 deficiency impaired the protective effect of zinc ion. Therefore, our results indicate that TRPC6 could promote zinc ion influx in renal tubular epithelial cells, thereby upregulating intracellular A20, inhibiting the activation of inflammasome NLRP3, and ultimately attenuating renal I/R injury.

Emergency trauma care during the outbreak of corona virus disease 2019 (COVID-19) in China.

BACKGROUND: A novel coronavirus pneumonia outbreak began in Wuhan, Hubei Province, in December 2019; the outbreak was caused by a novel coronavirus previously never observed in humans. China has imposed the strictest quarantine and closed management measures in history to control the spread of the disease. However, a high level of evidence to support the surgical management of potential trauma patients during the novel coronavirus outbreak is still lacking. To regulate the emergency treatment of trauma patients during the outbreak, we drafted this paper from a trauma surgeon perspective according to practical experience in Wuhan. MAIN BODY: The article illustrates the general principles for the triage and evaluation of trauma patients during the outbreak of COVID-19, indications for emergency surgery, and infection prevention and control for medical personnel, providing a practical algorithm for trauma care providers during the outbreak period. CONCLUSIONS: The measures of emergency trauma care that we have provided can protect the medical personnel involved in emergency care and ensure the timeliness of effective interventions during the outbreak of COVID-19.

[A new warning scoring system establishment for prediction of sepsis in patients with trauma in intensive care unit].

OBJECTIVE: To analyze the risk factors of patients with trauma in intensive care unit (ICU), a new warning scoring system is established for predicting the incidence of sepsis in traumatic patients; and to provide a new simple method of clinical score, which could provide a reference for clinical prevention and treatment of sepsis. METHODS: The clinical data of 591 patients with trauma in the ICU of the Army Specialized Medical Center of Army Medical University and Affiliated Hospital of Zunyi Medical University from January 2012 to December 2017 were retrospectively analyzed. The patients were divided into sepsis group (n = 382) and non-sepsis group (n = 209) according to their clinical outcome. The basic clinical data of all ICU trauma patients were collected, and the differences in gender, age, underlying diseases, and vital signs, critical illness scores, blood culture results and laboratory biochemical examinations within 24 hours of ICU admission between the two groups were analyzed. Univariate Logistic regression analysis was used to screen the related factors leading to sepsis. The indexes with P < 0.12 analyzed by univariate Logistic regression analysis were included in multivariate Logistic regression analysis. The risk factors of sepsis in traumatic patients were screened and assigned, and the total score was sepsis early warning score. The receiver operating characteristic (ROC) curve was plotted to evaluate the predictive value of the warning score of sepsis in patients with trauma. RESULTS: The incidence of sepsis in ICU trauma patients was 64.6% (382/591), and the ICU mortality was 10.5% (40/382). The traffic accident was a common cause of ICU trauma patients. Compared with non-sepsis patients, Glasgow coma score (GCS), proportion of past history, red blood cell (RBC), platelet (PLT), albumin (Alb) were lower in patients with sepsis, and body temperature, pulse, acute physiology and chronic health evaluation II (APACHE II), sequential organ failure assessment (SOFA), injury severity score (ISS), new injury severity score (NISS), fraction of inspired oxygen (FiO2), blood sodium, activated partial thromboplastin time (APTT), prothrombin time (PT), procalcitonin (PCT), C-reactive protein (CRP) levels were higher, blood transfusion, central venous catheterization, mechanical ventilation, shock, multiple organ dysfunction syndrome (MODS), open injury and multiple injuries were more common, the duration of mechanical ventilation, ICU days and total hospital days were longer, and all the differences were statistically significant. Most of the traumatic patients with sepsis were undergone with multiple trauma. Compared with non-sepsis patients, the proportion of multiple position trauma was significantly higher than patients without sepsis. And most traumatic patients were insulted in head, face and neck. The risk factors were screened by univariate and multivariate Logistic stepwise regression analysis, the indexes into the regression model were pulse > 100 bpm [odds ratio (OR) = 1.617, 95% confidence interval (95%CI) = 0.992-2.635, P = 0.044], APTT > 36 s (OR = 2.164, 95%CI = 1.056-4.435, P = 0.035), shock (OR = 1.798, 95%CI = 1.056-3.059, P = 0.031), mechanical ventilation (OR = 5.144, 95%CI = 2.302-11.498, P < 0.001), APACHE II > 21 (OR = 3.348, 95%CI = 1.724-6.502, P < 0.001), NISS > 25 (OR = 3.332, 95%CI = 1.154-9.624, P = 0.026), assigning scores were 0.5, 1.0, 0.5, 1.5, 1.5, 1.5, respectively, which were included in the new warning score of sepsis. ROC curve analysis showed that the area under ROC curve (AUC) of warning score for predicting sepsis in patients with trauma was 0.782, which was significantly higher than the APACHE II (AUC = 0.672), APTT (AUC = 0.574) and NISS (AUC = 0.515) with significant difference (all P < 0.01). When the cut-off value of sepsis warning score was 4.0, the sensitivity and specificity were 71.7% and 61.9%, respectively. CONCLUSIONS: Close monitoring and stabilization of vital signs of traumatic patients within 24 hours of ICU admission and reduction of unreasonable invasive mechanical ventilation time are expected to reduce the incidence of sepsis in traumatic patients. New warning score of sepsis consisted of six factors: pulse, APTT, shock, mechanical ventilation, APACHE II and NISS. Rational use of warning score of sepsis would help us to assess the prognosis of traumatic patients more easily and effectively, and the predicted effect is much better than APACHE II, APTT and NISS.

Umbilical cord-derived mesenchymal stem (stromal) cells for treatment of severe sepsis: aphase 1 clinical trial.

The aim of this phase 1 clinical trial was to test the safety and feasibility of a single dose of allogeneic umbilical cord-derived mesenchymal stem cells (MSCs) in patients with severe sepsis. This is a single-center, open-label, dose-escalation phase 1 clinical trial of a single dose of intravenous MSCs in patients with severe sepsis. We enrolled 15 patients who averagely divided into low (1 × 106 cells/kg), intermediate (2 × 106 cells/kg), and high (3 × 106 cells/kg) dosing cohorts. Primary outcomes included the incidence of infusion-associated events and serious adverse events. Secondary outcomes included systemic endpoints, mortality, and inflammation biologic markers. A historical case-matched comparison group was set as the control. This study enrolled 15 patients (10 male and 5 female), with a median age of 58. Compared to those in the historical, case-matched group, neither there were infusion-associated serious events or treatment-related adverse events in any of the 15 patients in this trial, nor were there any safety or efficacy signals for serious adverse events or the measured cytokines. A single intravenous infusion of allogeneic MSCs up to a dose of 3 × 106 cells/kg was safe and well tolerated in 15 patients with severe sepsis.

Study of intra-abdominal hypertension prevalence and awareness level among experienced ICU medical staff.

BACKGROUND: Intra-abdominal hypertension (IAH) is a disease with high morbidity and mortality among critically ill patients. The study's objectives were to explore the prevalence of IAH and physicians' awareness of the 2013 World Society of Abdominal Compartment Syndrome (WSACS) guidelines in Chinese intensive care units (ICUs). METHODS: A cross-sectional study of four ICUs in Southwestern China was conducted from June 17 to August 2, 2014. Adult patients admitted to the ICU for more than 24 h, with bladder catheter but without obvious intravesical pressure (IVP) measurement contraindications, were recruited. Intensivists with more than 5 years of ICU working experience were also recruited. Epidemiological information, potential IAH risk factors, IVP measurements and questionnaire results were recorded. RESULTS: Forty-one patients were selected. Fifteen (36.59 %) had IVP ≥ 12 mmHg. SOFA (Sequential Organ Failure Assessment) hepatic and neurological sub-scores were utilized as independent predictors for IAH via logistic backward analysis. Thirty-seven intensivists participated in the survey (response rate: 80.43 %). The average score of each center was less than 35 points. All physicians believed the IAH prevalence in their departments was no more than 20.00 %. A significant negative correlation was observed between the intensivists' awareness of the 2013 WSACS guidelines and the IAH prevalence in each center (r = -0.975, P = 0.025). CONCLUSIONS: The prevalence and independent predictors of IAH among the surveyed population are similar to the reports in the literature. Intensivists generally have a low awareness of the 2013 WSACS guidelines. A systematic guideline training program is vital for improving the efficiency of the diagnosis and treatment of IAH.

The effect of different types of abdominal binders on intra-abdominal pressure.

OBJECTIVES: To investigate the effect of non-elastic/elastic abdominal binders on intra-vesical pressure (IVP), physiological functions, and clinical outcomes in laparotomy patients at the perioperative stage.  METHODS: This prospective study was conducted from May to October 2014 at the Trauma Surgery Department, Daping Hospital, Chongqing, China. Laparotomy patients were randomly divided into non-elastic abdominal binder group (28 patients), and elastic abdominal binder group (29 patients). Binders were applied for 14 days following the operation, or until discharge. Demographic information, Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation  II (APACHE-II) scores (prior to the operation, on the first day after operation, the day IVP measurement was stopped, and one day before discharge), and outcomes were recorded. The IVP was measured before the operation to postoperative day 7. RESULTS: There were no significant differences in the demographic information, outcomes, SOFA or APACHE-II scores between the 2 groups. Initial out-of-bed mobilization occurred earlier in the elastic binder group (3.2 ± 2.0 versus 5.0 ± 3.7 days, p=0.028). A greater increase in IVP was observed in the non-elastic binder group than in the elastic binder group (2.9 ± 1.1 versus 1.1 ± 0.7 mm Hg, p=0.000). CONCLUSION: Elastic binders have relatively little effect on IVP and are more helpful at promoting postoperative recovery than non-elastic binders. Therefore, elastic binders are more suitable for clinical use.

Prevalence and diagnosis rate of intra-abdominal hypertension in critically ill adult patients: A single-center cross-sectional study.

PURPOSE: To investigate the prevalence and diagnosis rate of intra-abdominal hypertension (IAH) in a mixed-population intensive care unit (ICU), and to investigate the knowledge of ICU staff regarding the guidelines published by the World Society of Abdominal Compartment Syndrome (WSACS) in 2013. METHODS: A one-day cross-sectional study based on the WSACS 2013 guidelines was conducted in the general ICU of a tertiary teaching hospital in Chongqing, China. The included patients were divided into intravesical pressure (IVP) measured group and IVP unmeasured group. The epidemiologic data were recorded, and potential IAH risk factors (RFs) were collected based on the guidelines. IVP measurements were conducted by investigators every 4 h and the result was compared to that measured by the ICU staff to evaluate the diagnosis rate. Besides, a questionnaire was used to investigate the understanding of the guidelines among ICU staff. RESULTS: Thirty-two patients were included, 14 in the IVP measured group and 18 in the IVP unmeasured group. The prevalence of IAH during the survey was 15.63% (5/32), 35.71% (5/14) in IVP measured group. Only one case of IAH had been diagnosed by the ICU physician and the diagnosis rate was as low as 20.00%. Logistic regression analysis showed that sequential organ failure assessment (SOFA) score was an independent RF for IAH (OR: 1.532, 95% CI: 1.029-2.282, p=0.036. Fourteen doctors and 5 nurses were investigated and the response rate was 67.86%. The average scores of the doctors and nurses were 27.14±20.16 and 16.00±8.94 respectively. None of them had studied the WSACS 2013 guidelines thoroughly. CONCLUSION: Patients with a higher SOFA score has a higher incidence of IAH. The IAH prevalence in 14 ICU patients with indwelling catheter was 35.71%. Strengthening the wide and rational use of WSACS guideline is important to improve the diagnosis of IAH.