Nonalcoholic steatohepatitis (NASH) is a spectrum of chronic liver disease characterized by hepatic lipid metabolism disorder. Recent reports emphasized the contribution of triglyceride and diglyceride accumulation to NASH, while the other lipids associated with the NASH pathogenesis remained unexplored. The specific purpose of our study was to explore a novel pathogenesis and treatment strategy of NASH via profiling the metabolic characteristics of lipids. Herein, multi-omics techniques based on LC-Q-TOF/MS, LC-MS/MS and MS imaging were developed and used to screen the action targets related to NASH progress and treatment. A methionine and choline deficient (MCD) diet-induced mouse model of NASH was then constructed, and Schisandra lignans extract (SLE) was applied to alleviate hepatic damage by regulating the lipid metabolism-related enzymes CES2A and CYP4A14. Hepatic lipidomics indicated that MCD-diet led to aberrant accumulation of phosphatidylethanolamines (PEs), and SLE could significantly reduce the accumulation of intrahepatic PEs. Notably, exogenous PE (18:0/18:1) was proved to significantly aggravate the mitochondrial damage and hepatocyte apoptosis. Supplementing PE (18:0/18:1) also deteriorated the NASH progress by up regulating intrahepatic proinflammatory and fibrotic factors, while PE synthase inhibitor exerted a prominent hepatoprotective role. The current work provides new insights into the relationship between PE metabolism and the pathogenesis of NASH.

Patients with severe or critical coronavirus disease 2019 (COVID-19) are at high risk of death primarily due to respiratory failure caused by the cytokine storm in pulmonary tissues. The treatment response of these patients remains limited. Recently, low-dose radiation therapy (LDRT) has been clinically adopted to treat severe or critical COVID-19 patients in multiple medical centers abroad, indicating high feasibility and effectiveness. However, the mechanism and optimal radiation dose are still incompletely clear. This paper reviews the radiobiological mechanism, effectiveness, adverse reactions, and radiotherapy dose of LDRT in the treatment of severe or critical COVID-19 patients, aiming to better understand the clinical benefits and adverse reactions of LDRT.

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.

Objective To observe the clinical effect of Mirabegron combined with Silodosin on detrusor hyperactivity with impaired contractile (DHIC).Methods From September, 2019 to December, 2021, 40 patients with DHIC in the Department of Urology of Beijing Bo'ai Hospital were selected and randomly divided into control group and experimental group, with 20 cases in each group. The control group took Silodosin only, and the experimental group took Mirabegron in addition, for four weeks. The urinary diary, residual urine volume, Overactive Bladder Symptom Score (OABSS) and quality of life (QOL) score were compared before and after treatment.Results A total of 18 patients in the control group and 19 in the experimental group finished the trial. After treatment, the number of night urination per day, the residual urine volume and QOL score improved in the control group (P<0.01); the number of urination per 24 hours, the number of night urination per day, the volume per urination, the residual urine volume, the daily urgency score, the OABSS score and QOL score improved in the experimental group (P<0.01). The number decrease of urination per 24 hours, the volume decrease of per urination, the daily urgency score decrease, the OABSS score decrease and QOL score decrease were more in the experimental group than in the control group (P<0.01). The adverse reactions included palpitations, increased heart rate, dyspareunia, increased blood pressure, gastric discomfort, postural hypotension, and retrograde ejaculation, and there was no significant difference between two groups (P > 0.05).Conclusion The efficacy of Mirabellone combined with Silodosin on DHIC is better than Silodosin only, and there was no significant increase in drug-related adverse effects.

Aim To evaluate the pharmacokinetics and bioequivalence of two osmotic pump tablets of hydrochloride venlafaxine in Chinese healthy volunteers.Methods The fed test each enrolled twenty-six Chinese healthy volunteers in a randomized-sequence, open-label, two-period crossover single-dose oral test and reference preparations of hydrochloride venlafaxine extended-release tablets.The plasma concentrations of venlafaxine and its active metabolites O-desmethylvenlafaxine were determined by a validated liquid chromatography-tandem mass spectrometry(LC-MS/MS)method, and the pharmacokinetic parameters and bioequivalence of the two tablets were analyzed using PhoenixTM WinNonlin 6.4 software.Results The pharmacokinetic parameters of venlafaxine after single dose for the test and reference tablets were as follows: Cmax(58.50±19.47)vs(60.14±22.18)μg•L-1, AUC0-t(1 074.1±526.7)vs(1 057.9±539.7)μg•h•L-1, AUC0-∞(1 084.7±536.8)vs(1 067.8±554.0)μ g•h•L-1.The pharmacokinetic parameters of O-desmethylvenlafaxine were as follows: Cmax(101.63±29.64)vs(101.45±31.62)μg•L-1, AUC0-t(2 694.0±834.5)vs(2 702.9±946.4)μg• h•L-1, AUC0-∞(2 753.9±885.5)vs(2 753.2±988.4)μg•h•L-1.The 90% confidence intervals of the geometric mean ratios of Cmax, AUC0-t, AUC0-∞ for the test preparation and the reference preparationwere all within the equivalent interval of 80.00%-125.00%.Conclusion The test and reference preparations of hydrochloride venlafaxine extended-release tablets are bioequivalent in Chinese healthy volunteers under fed conditions.

Invitation of patients and their families as advisors in medical activities is conducive to enhancing patient safety and medical quality, as an innovative way for hospital reform and development. By analysis of such practice of overseas hospitals, the authors recommended on introducing this practice into China. The specific recommendations included creating a social support atmosphere for patient and family as advisors, promoting patient and family engagement by hospitals, establishing a management evaluation system for the patient and family engagement, improving the comprehensive literacy level of patient and family advisors, and building an internet platform for patient and family engagement.

Ulcerative colitis(UC)is a chronic inflammatory bowel disease caused by many factors including colonic inflammation and microbiota dysbiosis.Previous studies have indicated that celastrol(CSR)has strong anti-inflammatory and immune-inhibitory effects.Here,we investigated the effects of CSR on colonic inflammation and mucosal immunity in an experimental colitis model,and addressed the mechanism by which CSR exerts the protective effects.We characterized the ther-apeutic effects and the potential mechanism of CSR on treating UC using histological staining,intestinal permeability assay,cytokine assay,flow cytometry,fecal microbiota transplantation(FMT),16S rRNA sequencing,untargeted metabolomics,and cell differentiation.CSR administra-tion significantly ameliorated the dextran sodium sulfate(DSS)-induced colitis in mice,which was evidenced by the recovered body weight and colon length as well as the decreased disease activity index(DAI)score and intestinal permeability.Meanwhile,CSR down-regulated the production of pro-inflammatory cytokines and up-regulated the amount of anti-inflammatory mediators at both mRNA and protein levels,and improved the balances of Treg/Thl and Treg/Th1 7 to maintain the colonic immune homeostasis.Notably,all the therapeutic effects were exerted in a gut microbiota-dependent manner.Furthermore,CSR treatment increased the gut microbiota diversity and changed the compositions of the gut microbiota and metabolites,which is probably associated with the gut microbiota-mediated protective effects.In conclusion,this study provides the strong evidence that CSR may be a promising therapeutic drug for UC.

Objective :To analyze correlation among fasting (FBL) and postprandial blood lipids (PBL) ,blood lipid fluctuation (absolute value of PBL‐FBL) and severity of coronary artery disease .Methods :Cross‐sectional study was performed among 264 patients undergoing coronary angiography (CAG) in our hospital .According to percutaneous coronary intervention (PCI) or not based on CAG results ,patients were divided into plaque group (n＝128) and PCI group (n＝136).Gensini score was used to assess severity of coronary artery disease .Blood lipid levels and its fluctu‐ation were compared between two groups .Correlation among blood lipid levels ,blood lipid fluctuation and severity of coronary artery disease were analyzed .Results :Compared with plaque group ,there were significant rise in per‐centages of men and smokers ,waist circumference ,levels of postprandial‐fasting (P‐F ) serum LDL‐C (ΔLDL‐C ) and P‐F plasma apolipoprotein B (ΔApoB ) , and significant reduction in plasma level of P‐F apolipoprotein A1 (ΔApoA1) in PCI group , P＜0. 05 or ＜ 0. 01. Pearson correlation analysis indicated that serum fasting and post‐prandial HDL‐C levels ,plasma fasting and postprandial levels of ApoA1 and ΔApoA1 were significant inversely cor‐related with Gensini score ( r＝ －0. 130～ －0.218 , P＜0. 05 or ＜0. 01) ,and levels of plasma fasting lipoprotein a (Lp (a)) ,serum fasting and postprandial levels of free fatty acid (FFA) ,serum P‐F FFA (Δ FFA) were significant positively correlated with Gensini score ( r＝0. 139－0. 176 , P＜0.05 or ＜0.01).Multifactor linear regression anal‐ysis indicated that postprandial serum HDL‐C was protective factor for Gensini score (B＝ －22.274 , P＝0.002 ) , while postprandial serum FFA ,Δ FFA ,waist circumference and hyperlipidemia history were its influencing factors (B＝0. 388～24. 135 , P＜0. 05 or ＜0.01).Conclusion :Measurements of fasting and postprandial blood lipid levels and their fluctuation contribute to more comprehensively and objectively assessing blood lipid levels and severity of coronary disease in patients with coronary artery disease .

Objective To explore the clinical characteristics of Mycoplasma pneumoniae pneumonia (MPP) complicated with "top of the basilar" syndrome (TOBS) in children. Method The clinical data of MPP complicated with TOBS in a child were retrospectively analyzed, and the related literature was reviewed. Results A 6-year-old girl developed fever and inflexible movement in unilateral limb, and serum Mycoplasma pneumoniae antibody increased gradually. Lung CT showed a large area of inflammatory consolidation. Brain magnetic resonance imaging (MRI) showed multiple cerebral infarctions. After the symptomatic treatment of anti-infection, anticoagulation, thrombolysis and intracranial pressure reduction, the girl's condition continued to worsen and she presented with coma, cough weakness, dysphagia, facial nerve paralysis and bilateral pupillary inequality. Although the vital signs of the child were stable, she could not take care of herself and was still recovering. Conclusion MPP is often accompanied by hypercoagulative state and autoimmune abnormalities, and the prognosis of patients combined with TOBS is poor.

Objective To test the the reliability and validity of the Chinese version of the adult haemophilia activities list (HAL).Methods A Chinese version of the HAL was prepared by translation,back-translation and revision.Adult hemophilia patients were used to test it and a short-form arthritis impact measurement scale (AIMS-SF) simultaneously.A total of 98 valid questionnaires were collected.The internal consistency,reliability,split-half reliability,content validity,construct validity and convergent validity were tested.Results The Cronbach's α coefficients for the total questionnaire and its dimensions were all 0.7 or more.The half-reliability test produced a Spearman.correlation coefficient of 0.97.The Pearson correlation coefficients relating each dimension score with the total score and each dimension's entry score with the dimension score were all greater than 0.6.The correlation coefficient between the dimensions of the two questionnaires was smaller than the correlation coefficients relating each dimension with the total scale.There was relatively good correlation between the HAL sum score and the AIMS2-SF sum score (r=0.640,P≤0.01),as well as between the HAL sum score and the AIMS2-SF physical score (r=0.576,P≤0.01).Conclusion The Chinese version of the adult HAL has good reliability and validity.