Bile acid coordinates microbiota homeostasis and systemic immunometabolism in cardiometabolic diseases

Cardiometabolic disease (CMD), characterized with metabolic disorder triggered cardiovascular events, is a leading cause of death and disability. Metabolic disorders trigger chronic low-grade inflammation, and actually, a new concept of metaflammation has been proposed to define the state of metabolism connected with immunological adaptations. Amongst the continuously increased list of systemic metabolites in regulation of immune system, bile acids (BAs) represent a distinct class of metabolites implicated in the whole process of CMD development because of its multifaceted roles in shaping systemic immunometabolism. BAs can directly modulate the immune system by either boosting or inhibiting inflammatory responses via diverse mechanisms. Moreover, BAs are key determinants in maintaining the dynamic communication between the host and microbiota. Importantly, BAs via targeting Farnesoid X receptor (FXR) and diverse other nuclear receptors play key roles in regulating metabolic homeostasis of lipids, glucose, and amino acids. Moreover, BAs axis per se is susceptible to inflammatory and metabolic intervention, and thereby BAs axis may constitute a reciprocal regulatory loop in metaflammation. We thus propose that BAs axis represents a core coordinator in integrating systemic immunometabolism implicated in the process of CMD. We provide an updated summary and an intensive discussion about how BAs shape both the innate and adaptive immune system, and how BAs axis function as a core coordinator in integrating metabolic disorder to chronic inflammation in conditions of CMD.

Chinese medicine (Q-14) in the Treatment of Patients with Coronavirus Disease 2019 (COVID-19): A Single-center, Open label, Randomised Controlled Trial

OBJECTIVETo evaluate the efficacy and safety of Chinese medicine (Q-14) plus standard care compared with standard care alone in adult with coronavirus disease 2019 (COVID-19). Study DESIGNSingle-center, open label, randomised controlled trial. SETTINGWuhan Jinyintan Hospital, Wuhan, China, February 27 to March 27, 2020. PARTICIPANTS204 patients with laboratory confirmed COVID-19 were randomised in to treatment group and control group, which was 102 patients each group. INTERVENTIONSIn treatment group, Q-14 was administrated at 10g (granules), twice daily for 14 days and plus standard care. In control group, patients were given standard care alone for 14 days. MAIN OUTCOME MEASUREThe primary outcome was conversion time of SARS-CoV-2 viral assay. Adverse events were analyzed in the safety population. RESULTSAmong 204 patients, 195 were analyzed according to the intention to treat principle. There were 149 patients (71 vs. 78 in treatment group and control group respectively) turning to negative via SARS-CoV-2 viral assay. No statistically significance showed in conversion time between treatment group and control group (FAS: Median (IQR): 10.00 (9.00-11.00) vs. 10.00 (9.00-11.00); Mean rank: 67.92 vs. 81.44; P=0.051.). Time to recovery of fever was shorter in treatment group as compared in control group. The disappearance rate of symptom in cough, fatigue, chest discomfort was significantly higher in treatment group. In chest computed tomography (Chest CT) examinations, overall evaluation of chest CT examination after treatment compared with baseline showed more patients improved in treatment group .There were no significant differences in the other outcomes. CONCLUSIONAdministration of Q-14 on standard care for COVID-19 was useful for improvement of symptoms (such as fever, cough, fatigue and chest discomfort), while did not result in a significantly higher probability of negative conversion of SARS-CoV-2 viral assay. No serious adverse events were reported. TRIAL REGISTRATIONChiCTR2000030288

Preventive effects of ulinastatin on acute respiratory distress syndrome / 北京大学学报(医学版)

Objective:To explore the effect of ulinastatin on prevention of acute respiratory distress syn-drome (ARDS).Methods:A prospective multicentral cohort study was conducted.The patients from three intensive care units (ICUs)of grade A tertiary hospitals in Beijing and a ICU of grade A tertiary hospitals in Cangzhou from January 2012 to December 2014,included 77 ARDS at-risk patients with uli-nastatin treatment and 108 ARDS at-risk patients without ulinastatin treatment (control)were eligible. Both groups received normal treatment;additionally,the intervention group received 600 000 units of uli-nastatin via intravenous infusion for 5 days.The control group received the same amount of saline via in-travenous infusion for 5 days.Venous blood human neutrophil elastase (HNE)and peptidase inhibitor 3 (PI3)levels were measured on days 1,3,and 7,respectively.Other outcomes included acute physiolo-gy and chronic health evaluation scoring Ⅱ (APACHE Ⅱ),body temperature,respiratory rate,heart rate,mean arterial pressure,white blood cell counts,PaO2 /FiO2 ,ARDS incident,mechanical ventila-tion time,ICU treatment and hospitalization duration,28 days mortality.Results:The PI3 levels showed no statistical difference on day 1,but significant differences on day 3 and day 7 between the two groups (P <0.01).HNE /PI3 ratio showed no statistical difference on day 1,but significant differences on day 3 and day 7 (P <0.05).PaO2 /FiO2 was significantly higher in ulinastatin group on day 3 and day 7 (P <0.05).The incident rate for ulinastatin group was 15.58%,lower than that for the control group (33.33%),and the difference was statistically significant (P <0.05).The mechanical ventilation time and ICU treatment time in ulinastatin group was shorter than that in the control group,and the difference was statistically significant (P <0.05).There were no significant effects in other factors.Conclusion:Increased dose of ulinastatin can recover the balance of HNE and its antagonist,lower the HNE’s damage to lungs,and further reduce the ARDS incident rate.

Risk factors of the occurence and death of acute respiratory distress syndrome:a prospective multicenter cohort study / 中华危重病急救医学

Objective To explore the risk factors of the occurence and 28-day death of acute respiratory distress syndrome (ARDS) in intensive care unit (ICU). Methods A prospective multicentral cohort study was conducted. The patients from five ICUs of grade A tertiary hospitals in Beijing from July 2009 to March 2014, including sepsis,septic shock,trauma,pneumonia,aspiration,massive blood transfusion,bacteremia and pulmonary contusion,were enrolled. Researchers in each center reported the records with uniform tables,which included demographic,systemic conditions,the primary disease,and the severity within 24 hours,past history and so on. According to the admission diagnosis in ICU,these patients were divided into ARDS group and other severe disease control group. The risk factors of occurence and prognosis of ARDS were analyzed by univariate analysis,multivariate logistic regression and multivariate COX regression analysis. Kaplan-Meier method was applied to draw the 28-day survival curves of the two groups. Results There were 343 critical patients included in this prospective multicenter cohort study,of which 163 patients who developed ARDS were considered as ARDS group(2 case lost to follow-up, and 49 died)and 180 patients who did not developed ARDS regarded as severe control group(1 case lost to follow-up, and 34 died). The 28-day mortality of ARDS group was significantly higher than that of severe control group〔30.43%(49/161)vs. 18.99%(34/179),χ2=6.013,P=0.014〕. Multivariate logistic analysis showed that aspiration〔odds ratio(OR)=6.390,95% confidence interval(95%CI)=2.046-19.953,P=0.001〕,history of alcohol (OR=4.854,95%CI=1.730-13.617,P=0.003),sepsis(OR=2.859,95%CI=1.507-5.425,P=0.001), pneumonia(OR=2.822,95%CI=1.640-4.855,P30 beats/min(OR=3.305,95%CI=1.910-5.721,P100 beats/min(OR=2.101,95%CI=1.048-4.213,P=0.037)happened in critically ill patients, it highly suggested ARDS would happen. The proportion of the patients whose serum creatinine>176.8 μmol/L in ARDS group was lower than that in control group(OR=0.387,95%CI=0.205-0.733,P=0.004). Multivariate COX regression analysis showed that old age and septic shock were significantly associated with the increased risk of in 28-day death of ARDS〔advanced age:hazard ratio(HR)=1.040,95%CI=1.018-1.064,P30 beats/min and heart rate>100 beats/min could predict the occurrence of ARDS in critical patients. Old age and septic shock were the risk factors of 28-day death of ARDS.

Study on the Regulatory Effect of Xinchuan Capsules on the Excessive Aactivation of Neuroendocrine of Dogs with Experimental Heart Failure / 中国中医药信息杂志

Objective To investigate the regulatory effect of Xinchuan capsules on the excessive activation of neuroendocrine with heart failure.Methods The heart failure animal model was built up using dogs by intravenous pumping of sodium pentobarbital.Water extract of Xinchuan capsules was given through duodenum.Indicators relating to the excessive activation of neuroendocrine changes of each group were observed.Results Xinchuan capsules could significantly increase the density of beta receptors of failure myocardial cells and lower the level of plasma norepinephrine and epinephrine,and remarkbly decrease the activity of plasma angiotensin converting enzyme.This played the similar role as the positive control drug metoprolol plus captopril.Conclusion Xinchuan capsules have the regulatory effect on the excessive activation of neuroendocrine with heart failure.TCM treatment for heart failure should not only target the functional disorder of the heart dominating blood circulation and vessels,but also the functional disorder of the heart stores the spirit,that is uneasy mental state.