Objectives:Fenofibric acid is extracted from the widely used hypolipemic fenofibrate,nowadays being approved for marketing around numerous nations and regions,nonetheless not in China.Present trial evaluated the efficacy and safety in the Chinese hypertriglyceridemia population. Methods:This is a multi-center,randomized,double-blind,placebo-controlled phase Ⅲ clinical trial.Patients from 3 different cohorts,including severe hypertriglyceridemia(HTG),moderate HTG and mixed-dyslipidemia(MD),were randomized at 1:1 ratio to receive fenofibric acid 135 mg or placebo daily for 12 weeks.The primary endpoint was the percentage change of triglyceridemia(TG)from baseline at week 12.Secondary endpoints were the percentage changes of other blood lipid indexes.At the same time,the incidence of medical adverse events was observed. Results:Among the three cohorts of patients with severe HTG(n=52),moderate HTG(n=23)and MD(n=52),the TG levels in the fenofibric acid-treated group decreased by(49.12±29.19)%,(49.95±25.19)%and(49.79±19.28)%,respectively from baseline to 12 weeks,while the corresponding placebo groups decreased by(18.88±40.69)%,(8.11±29.86)%and increased by(10.42±73.04)%,respectively from baseline to 12 weeks.The differences between treatment and placebo groups were statistically significant(P<0.017 for severe HTG cohort,P<0.05 for moderate and MD cohort).The high-density lipoprotein cholesterol(HDL-C)in the fenofibric acid-treated group increased by(25.51±21.45)%,(24.55±24.73)%,and(23.60±27.38)%,and the placebo group increased by(1.91±20.42)%,(2.40±9.32)%and(7.13±19.12)%,respectively,the differences between the two groups were statistically significant(all P<0.05).In the fenofibric acid group,adverse events with incidence>5%included upper respiratory tract infection(10.9%),abdominal pain(6.3%),and increased serum creatinine levels(6.3%),rates of adverse events were similar between the two groups(P>0.05). Conclusions:Fenofibric acid can significantly reduce triglycerides and elevate HDL-C levels safely in Chinese patients with severe to moderate HTG without statin or MD patients on top of statin therapy.

Heart failure is the leading cause of death worldwide. Compound Danshen Dripping Pill (CDDP) or CDDP combined with simvastatin has been widely used to treat patients with myocardial infarction and other cardiovascular diseases in China. However, the effect of CDDP on hypercholesterolemia/atherosclerosis-induced heart failure is unknown. We constructed a new model of heart failure induced by hypercholesterolemia/atherosclerosis in apolipoprotein E (ApoE) and LDL receptor (LDLR) dual deficient (ApoE^-/-LDLR^-/-) mice and investigated the effect of CDDP or CDDP plus a low dose of simvastatin on the heart failure. CDDP or CDDP plus a low dose of simvastatin inhibited heart injury by multiple actions including anti-myocardial dysfunction and anti-fibrosis. Mechanistically, both Wnt and lysine-specific demethylase 4A (KDM4A) pathways were significantly activated in mice with heart injury. Conversely, CDDP or CDDP plus a low dose of simvastatin inhibited Wnt pathway by markedly up-regulating expression of Wnt inhibitors. While the anti-inflammation and anti-oxidative stress by CDDP were achieved by inhibiting KDM4A expression and activity. In addition, CDDP attenuated simvastatin-induced myolysis in skeletal muscle. Taken together, our study suggests that CDDP or CDDP plus a low dose of simvastatin can be an effective therapy to reduce hypercholesterolemia/atherosclerosis-induced heart failure.

Objective:To explore the prognostic value of lymphocyte subsets in adult hemophagocytic syndrome (HPS).Methods:A total of 172 adult HPS patients diagnosed in 8 medical centers from January 2013 to August 2020 were selected for the study, of whom 87 were male (50.6%, 87/172), and 85 were female (49.4%, 85/172), with 68 survivors and 104 deaths. The clinical data were summarized, and variables such as lymphocyte subsets, immunoglobulin characteristics and fibrinogen were retrospectively analyzed, and the correlation between the mentioned variables and patient prognosis was analyzed. The optimal cut-off values of continuous variables were calculated by MaxStat, and the prognostic factors of HPS patients were screened based on the Cox proportional hazard regression model.Results:The median age of HPS patients was 56 (42, 66) years old, and the 5-year cumulative survival rate was 37.4% (37.4/100). The median age, platelet and albumin were 48 (27, 63) years, 84×10 9/L and 32.3 g/L in the survival group, and 59 years, 45.5×10 9/L, and 27.3 g/L in the death group, respectively. The differences between the two groups was statistically significant ( Z=?3.368, P=0.001; Z=?3.156, P=0.002; Z=?3.431, P=0.001). Patients with differentiated cluster 8+(CD8+)<11.1%, CD3+<64.9%, CD4+>51%, and CD4/CD8 ratio>2.18 had poor prognosis (χ 2=7.498, P=0.023; χ 2=4.169, P=0.041; χ 2=4.316, P=0.038; χ 2=9.372, P=0.002). Multivariable analysis showed that CD4/CD8 ratio, age, fibrinogen and hemoglobin were independent prognostic factors in HPS patients ( HR=2.435, P=0.027; HR=5.790, P<0.001; HR=0.432, P=0.018; HR=0.427, P=0.018). Conclusion:Peripheral blood lymphocyte subsets can be used to evaluate the prognosis of patients with HPS; CD4/CD8 ratio, age, fibrinogen, and hemoglobin are independent prognostic factors in HPS patients.

Ferroptosis is a non-apoptotic regulated cell death caused by iron accumulation and subsequent lipid peroxidation. Currently, the therapeutic role of ferroptosis on cancer is gaining increasing interest. Baicalin an active component in

Objective:Factors influencing the prognosis of hemophagocytic lymphohistiocytosis (HLH) in adults were analyzed based on multicentric data.Methods:Clinical data of 124 adult patients with HLH diagnosed in eight medical centers in the Huaihai Lymphoma Working Group from March 2014 to July 2020 were collected. The optimal truncation value of continuous variables was obtained based on the Maxstat algorithm, X-Tile software, and restricted cubic spline. Cox proportional risk regression model was used to construct the adult HLH risk prediction model, and the visualization of the model was realized through the histogram. The bootstrap resampling method was used to verify the model, C-index and calibration curve was used to verify the histogram, and the prediction accuracy was checked. Kaplan-Meier analysis was used to calculate the survival rate and draw the survival curve. Furthermore, the differences between groups were tested by log-rank.Results:The median age of the 124 patients was 55 (18-84) years, including 61 (49.19%) males. The most common etiology was infection. Serum ferritin increased in 110 cases (88.71%) , hepatosplenomegaly in 57 cases (45.97%) . Of the 124 patients, 77 (62.10%) died, and the median survival time of the patients was 7.07 months. Univariate results showed that the prognosis of adult HLH was influenced by sex, age, fibrinogen, serum creatinine, alanine aminotransferase, and albumin ( P<0.05) . The results of multivariate analysis showed that gender, platelet, albumin, alanine aminotransferase, and treatment regimens were independent influencing factors for prognosis. Based on the above five risk factors, the prediction model of the histogram was established, and the C-index of the model was 0.739. Finally, the calibration chart showed good consistency between the observed and predicted values of HLH. Conclusion:The prognosis of the adult hemophagocytic syndrome is influenced by many factors. Gender, platelet, albumin, alanine aminotransferase, and treatment regimens are independent risk factors. Therefore, the established histogram provides a visual tool for clinicians to evaluate the prognosis of adult HLH.

Objective To investigate the risk factors of death and to establish an early multi-index predictive model for mortality moderately of severe acute pancreatitis (MSAP) and severe acute pancreatitis (SAP) in elderly patients.Methods Clinical data of 58 digible elderly patients of MSAP and SAP between January 2014 and May 2017 in First Affiliated Hospital of Harbin Medical University were analyzed retrospectively,including 18 cases (31.0％) in the death group and 40 cases in the control group (69.0％).Univariate analysis and logistic regression analysis were used to screen out the independent risk factors related to death,combined with these independent risk factors,the unweighted predictive model (unwScore) and weighted predictive model (wScore) for mortality were established.The receiver-operating characteristic (ROC) curves of independent risk factors and predictive models were drawn to determine the cut-off value,to calculate the area under the curve (AUC),sensitivity,specificity,positive predictive value and negative predictive value and to observe the clinical predictive effectiveness.Student's t-test was used to analyze continuous variables that complied with a normal distribution expressed as ((x) ± s).Mann-Whitney U test was used to analyze abnormally distributed variables expressed as median (quartile range) [M(P25,P75)].chi-square test or Fisher's exact test was used to analyze categorical data expressed by rate (％).Univariate analysis was used to screen out data with statistically significant difference,and then Logistic regression analysis was performed to determine independent predictors.Results Univariate analysis showed that there were statistically significant differences in pro-calcitonin,serum albumin (ALB),serum calcium,D-dimers,mean arterial pressure,pleural effusion and peritoneal effusion between the two groups (P ＜0.05);multivariate analysis showed that ALB,pleural effusion and peritoneal effusion were independent risk factors for mortality of MSAP,SAP in early patients,which AUC were 0.815,0.678,0.696,sensitivity were 0.611,0.556,0.667,specificity were 0.825,0.800,0.725,the positive predictive values were 61.1％,55.6％,52.2％,and the negative predictive values were 82.5％,80.0％,89.9％,respectively.The AUC of unwScore and wScore were 0.852 and 0.863,the sensitivity were 0.667 and 0.778,the specificity were O.875 and 0.800,the positive predictive values were 70.6％ and 63.6％,and the negative predictive values were 85.4％ and 88.9％,respectively.Conclusion ALB,pleural effusion and peritoneal effusion were independent risk factors for mortality of MSAP,SAP in elderly patients.The multi-index predictive model had good clinical predictive effectiveness,which could provide clinical references for the treatment of MSAP and SAP in elderly patients.

Objective To evaluate the early predictive and diagnostic value of procalcitonin (PCT) in abdominal infection after pancreatoduodenectomy(PD).Methods The clinical data of 62 patients with PD in the First Affiliated Hospital of Harbin Medical University from April 2016 to April 2017 were retrospectively analyzed.The general data and postoperative conditions of the patients were recorded.Serum PCT,C-reactive protein (CRP) levels and WBC counts were measured before and 1,3,and 5 days after surgery.According to the postoperative abdominal infection,the patients were divided into abdominal infection group (n =10) and control group(n =52).The area under the ROC curve (AUC) was calculated by plotting the receiver operating characteristic (ROC) curve,and the cut-off value was determined to compare the sensitivity and specificity of the two groups of patients.Results There were no significant difference between two groups on age,gender,BMI,diabetes mellitus,preoperative laboratory indicators,anesthetic time,operation time,intraoperative bleeding and blood transfusion,surgical procedures and Braun anastomosis,which were comparable.The incidence of postoperative hyperglycemia,surgical incision infection,pancreatic fistula,biliary fistula,mortality,postoperative hospital stay and total medical costs of abdominal infection group were significantly higher than those of control group (P ＜ 0.05).There were no significant differences on PCT,CRP,and WBC between the two groups before surgery.The PCT level of the abdominal infection group was significantly higher than that of the control group at the 1st postoperative day and the difference was statistically significant (P ＜0.05).The sensitivity of predicting abdominal infection was 90％ and the specificity was 75％,which was significantly higher than those of CRP and WBC.There were no significant differences on the sensitivity and specificity of PCT,CRP and WBC for postoperative abdominal infection at 3 and 5 days after surgery,but the sensitivity of the combined diagnosis was as high as 100％ and 90％,significantly higher than 3 indicators alone,respectively.Conclusions Serum PCT level may predict in advance or diagnose early abdominal infection after PD.The combination of PCT,CRP and WBC might be more valuable for the diagnosis of abdominal infection after PD.

Objective To investigate the spatial distribution and growing trend of 438 human infection with the H7N9 avian influenza virus in mainland China,and to provide evidence for developing scientific prevention and control strategies.Methods 438 human infection with the avian influenza A (H7N9) cases from February 2013 to May 2014 in mainland China were studied and data collected to establish a database for the development of geographic information system.Trend surface analysis and spatial autocorrelation analysis were used to study the spatial distribution.Descriptive epidemiological method was utilized to analyze the demographic characteristic.Results From June 2013 to May 2014,cases had an overall national increase,but significantly decreasing in Shanghai.A trend surface was established for human infection with avian influenza A (H7N9) in the mainland of China,showing that the incidence was increasing obviously from north to south and the line slope declined from west to east.Distribution pattern of the cases varied within different time series and regional levels.The overall Moran' s I coefficient of the provincial level from February to May in 2013 and the coefficient of the city level from June 2013 to May 2014 were 0.144 718 and 0.117 468,respectively,with the differences statistically significant (P＜0.05).According to the analysis of the local autocorrelation and hot spot,northern Zhejiang and southern Guangdong showed high spatial clusters of human infection with avian influenza A(H7N9) (Z＞2.58).Conclusion From February 2013 to May 2014,the spatial correlation at the provincial level decreased.However,the spatial correlation and the numbers of hot spots at the city level were both increasing.Effective measures should be taken accordingly,following the distributive characteristics.

Ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF/MS) was developed to identify the absorbed parent components and metabolites in rat bile, plasma and urine after oral administration of Radix Paeoniae Alba extract (RPAE). A total of 65 compounds were detected in rat bile, plasma and urine samples, including 11 parent compounds and 54 metabolites. The results indicated that glucuronidation, hydroxylation and methylation were the major metabolic pathways of the components of RPAE. Furthermore, the results of this work demonstrated that UPLC-Q-TOF/MS combined with MetaboLynx? software and mass defect filtering (MDF) could provide unique high throughput capabilities for drug metabolism study, with excellent MS mass accuracy and enhanced MSE data acquisition. With the MSE technique, both precursor and fragment mass spectra can be simultaneously acquired by alternating between high and low collision energy during a single chromatographic run.

Objective To investigate the level of platelet activating factor (PAF) in acute myocardial infarction (AMI) in minipig model and patients, and to study the relationship between PAF and lethal arrhythmia referring to ventricular fibrillation and ventricular tachycardia. Method ( 1 ) The levels of PAF in minipig models ( n = 20) were measured by using ELISA before and 1h after occlusion of left anterior descending coronary artery with balloon at the junction of 1/3 middle and distal portion. The lethal arrythmia was recorded by using electrocardiography. (2) In patients with AMI (n = 72), the levels of PAF were measured on arrival, and 24 h,48 h and 72 h later. The lethal arrythmia, acute heart failure and cardiogenic shock were documented. Results ( 1 ) In minipigs with occlusion of coronary artery for one hour, the mean level of PAF increased from (4.66± 2.89)ng/mL to (6.00±2.82) ng/mL,and thus the increment in PAF was (1 .34± 1.40) ng/mL (P ＜ 0.05). In 13 minipigs with lethal anythmia after occlusion of coronary artery for one hour, the increment in mean level of PAF was ( 1.92 ± 1 .34) ng/mL, whereas the increment in mean level of PAF in other 7 minipigs without lethal arrythmia after occlusion of coronary artery for one hour was as low as (0.28 ± 0. 74 ) ng/mL ( P ＜ 0. 05 ). ( 2 ) In patients, the mean levels of PAF on arrival, 24 h,48 h,and 72 hous after admission were (0.47 ± 0.05) ng/mL,(2.38±0.12) ng/mL,(3.65±0.15) ng/mL and (3.02±0.10) ng/mL, respectively. Of 72 ACI patients, 40 (55%) had complication of lethal arrythnia, heart failure or cardiogenic shock and their mean level of PAF 48 h after admission was (4.72 ± 0.16) ng/mL, whereas mean level of PAF in other 32 (44.44%) without complications was (2.31 ±0.03) ng/mL ( P ＜0.05). Conclusions The level of PAF increased after acute myocardial infarction, and the minipigs and AMI patients complicated with lethal arrythmia had higher levels of PAF.