Objective Cirrhotic cardiomyopathy(CCM)refers to cardiac dysfunction and electrophysiological disorder caused by liver cirrhosis and is closely associated with the prognosis of patients with liver cirrhosis.Endothelial cell-specific molecule 1(endocan)can be used as a diagnostic marker for cardiovascular diseases,and it remains unclear whether it is involved in the pathogenesis of CCM.The aim of this study is to investigate the expression of serum endocan in patients with CCM and its possible role in the development of CCM.Methods This cross-sectional study was conducted among the patients with liver cirrhosis who were consecutively admitted to Beijing YouAn Hospital,Capital Medical University,from January 2019 to January 2021,and according to the presence or absence of CCM,the patients were divided into CCM group with 19 patients and non-CCM group with 106 patients.ELISA was used to measure the serum level of endocan,and its correlation with liver function and cardiac function was analyzed.The independent-samples t test was used for comparison of normally distributed continuous data between two groups,and the Mann-Whitney U rank sum test was used for comparison of continuous data with skewed distribution between two groups;the chi-square test was used for comparison of categorical data between groups.A Pearson or Spearman correlation analysis was used to investigate the correlation between indicators,and the receiver operating characteristic(ROC)curve was used to assess the CCM predictive model.Results The CCM group had a significantly higher expression level of serum Endocan than the non-CCM group(2.69±0.43 ng/mL vs 2.23±0.52 ng/mL,t=2.247,P=0.034).The patients with compensated cirrhosis had a significantly lower expression level of serum endocan than those with decompensated cirrhosis(2.41±0.37 ng/mL vs 2.72±0.49 ng/mL,t=3.214,P=0.02).In the CCM group,the serum level of endocan was positively correlated with Child-Pugh score(r=0.509,P=0.026)and MELD-Na score(r=0.484,P=0.036)and was negatively correlated with mean arterial pressure(r=-0.591,P=0.013)and mitral ratio of peak early to late diastolic filling velocity(r=-0.515,P=0.042).The serum endocan had an area under the ROC curve of 0.658(95%CI:0.522～0.781)in predicting CCM,when the cut-off value was 2.61 ng/mL,the sensitivity was 67.1%and the specificity was 73.7%.Conclusion There is a certain association between serum endocan and CCM,and serum endocan may be involved in the pathogenesis of CCM.

Objective:To explore the possibility of hepatitis B core antibody (anti-HBc) in predicting hepatitis B virus surface antigen (HBsAg) clearance.Methods:Sixty cases with chronic hepatitis B who were previously treated with peginterferon α-2a combined with nucleos(t)ide analogues (NAs) antiviral therapy were divided according to the HBsAg clearance or non-clearance; 41 cases in the clearance group and 19 cases in the non-clearance group. Double antigen sandwich method was used to detect patients anti-HBc quantitative levels during the course of treatment and at baseline, 24, 48, 72 and 96 weeks. Logistic regression analysis and receiver operating characteristic curve (ROC) were used to evaluate the predictive ability of related influencing factors for HBsAg clearance.Results:With antiviral treatment prolongation, anti-HBC quantitative levels in the overall population showed a progressive downward trend in the clearance group and the non-clearance group, but the anti-HBC level in the clearance group was significantly higher than non-clearance group at the baseline and successive detection time points during the antiviral treatment ( P < 0.05). Multivariate logistic regression showed that baseline quantitative anti-HBC level, HBsAg decline at week 24 (log10 IU / ml), and alanine aminotransferase (ALT) > 1.5 times the upper limit of normal value (ULN) were all influencing factors for HBsAg clearance during the treatment ( OR = 0.156, P = 0.026; OR = 0.134, P = 0.023; OR = 0.239, P = 0.028). Among them, the baseline quantitative anti-HBc level was the best independent predictor for HBsAg clearance ( OR = 0.235; P = 0.004), and the sensitivity and specificity for predicting HBsAg clearance at > 3.40 log10 IU/ mL were 56.1% and 89.5%, respectively. Logistic regression model was used as a reference to construct combined predictors in order to improve the prediction accuracy. Among them, the combined factor 3 had the highest predictive value (the area under the ROC curve had reached up to 0.870; 95%CI was 0.781 ~ 0.960; P < 0.001). The cut-off value of combined factor 3 was > 0.386, and the sensitivity and specificity were 80.5% and 78.9%, respectively. In addition, the combined index had further improved the predictive value, which is the combination of any two or more indexes based on the baseline quantitative anti-HBC level, and HBsAg clearance predictive rate had reached 94.12% ~ 100%. Conclusion:The baseline quantitative anti-HBC level has the highest predictive value for HBsAg clearance. The combination of ALT > 1.5×ULN and HBsAg decline at 24 weeks during the treatment can more precisely predict HBsAg clearance. Therefore, it is a reliable non-invasive biomarker.

OBJECTIVE： To study the effects of Wuzhi soft capsule and imatinib mesylate tablet on the pharmacokinetics of imatinib in rats. METHODS： The rats were divided into single administration group and consecutive administration group. The single administration group was divided into imatinib group one （ig administration of blank soybean oil+imatinib suspension 10   mg/kg）， low-dose， medium-dose and high-dose of Wuzhi soft capsule+imatinib group （ig administration of Wuzhi soft capsule solution 134， 268， 536 mg/kg+imatinib suspension 10 mg/kg）， with 6 rats in each group. Each group was given imatinib suspension intragastrically 30 min after intragastric administration of blank soybean oil/Wuzhi soft capsule solution. The consecutive administration group was divided into imatinib group two （ig administration of blank soybean oil+imatinib suspension 10 mg/kg）， Wuzhi soft capsule low-dose+imatinib group （ig administration of Wuzhi soft capsule solution 134 mg/kg+imatinib suspension 10 mg/kg）， with 6 rats in each group. Each group was given blank soybean oil/Wuzhi soft capsule solution intragastrically for consecutive 14 d， once a day； 30 min after last administration， ig imatinib suspension. About 100 μL blood was collected before imatinib， 0.5， 1， 2， 2.5， 3， 4， 5， 6， 8， 12， 24 and 36 h after medication. The plasma concentration of imatinib was determined by HPLC-MS/MS. The pharmacokinetic parameters were fitted by using DAS 2.0 software. RESULTS： After single administration， compared with imatinib group one， cmax， t1/2， AUC0-36 h and AUMC0-36 h in low-dose， medium-dose and high-dose of Wuzhi soft capsule+imatinib group were increased significantly （P＜0.05 or P＜0.01）. After consecutive administration， compared with imatinib group two， cmax， t1/2 and AUMC0-36 h of imatinib+low-dose of Wuzhi soft capsule group were increased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS： Single administration and consecutive administration of Wuzhi soft capsule influence the pharmacokinetics of imatinib， increase plasma concentration of imatinib and prolong half-time.

Objective: To observe the changes of liver function, virology and serology and the safety of drug withdrawal in pregnant women who are chronic hepatitis B virus (HBV) carriers. Methods: A prospective clinical cohort was established to enroll pregnant women who are chronic HBV carriers and they were divided into the nucleoside/nucleotide analogs (NAs) intervention group and the non-NAs intervention group according to patients' wishes. Liver function, HBV DNA and HBV serological markers were detected at gestation, postpartum 6 weeks, 12 weeks, 24 weeks, 36 weeks and 48 weeks. Results: 351 patients were enrolled, 320 in the NAs intervention group and 31 in the non-NAs intervention group. The proportion of postpartum hepatitis flares in both groups was higher than that in pregnancy (39.4% vs 12.5%, P < 0.001; 38.7% vs 3.2%, P = 0.001). Six weeks postpartum was the peak period of hepatitis flares, and 96.0% (121/126) of the hepatitis flares occurred within 24 weeks postpartum. At 6 weeks postpartum, there were 6 cases of alanine aminotransferase (ALT) ≥ 10 times upper limit of normal (ULN) in the NAs intervention group. The rate of the hepatitis flare after drug withdrawal was 16.7% (34/203). Conclusion Regardless of the presence or absence of NAs intervention, pregnant women who are chronic HBV carriers have a certain proportion of hepatitis flares during pregnancy and postpartum, and the hepatitis flare even have a tendency to be severe. Therefore, drug withdrawal after delivery is not always safe, which requires close observation and classification. At 6 weeks postpartum, the incidence of hepatitis flares was high, and those who meet the treatment indications can get better therapeutic effects if given appropriate treatment. The vast majority (96%) of postpartum hepatitis flares occur within 24 weeks, so it is recommended to follow up to at least 24 weeks postpartum after discontinuation.

Objective: To analyze the therapeutic effect on HBeAg-negative chronic hepatitis B patients treated with Peg-IFNα-2a combined with NAs to obtain the influencing factors for predicting HBsAg clearance. Methods: A retrospective study was conducted to investigate the effect of pegylated interferon alpha-2a combined with nucleoside analogues (lamivudine/adefovir dipivoxil) on HBeAg-negative chronic hepatitis B. The treatment course was 96 weeks. Patients were followed up 120 weeks after the treatment. HBsAg clearance at 120 weeks was taken as the objective of the study. Logistic regression and receiver operating characteristic curve analysis screened the related factors affecting HBsAg clearance. χ ² test was used to compare count data. Results: 111 patients were treated with pegylated interferon alpha-2a combined with nucleoside analogues, and 107 patients completed the scheduled course of treatment and follow-up. HBsAg clearance rate at120 week was 29.0% (31/107). The influencing factors for analysis were: (1) gender had no effect on HBsAg clearance rate; age and baseline levels of HBV DNA and alanine aminotransferase had no significant effect on HBsAg clearance; low baseline level of HBsAg (< 3.023 lgIU/ml) was beneficial to HBsAg clearance. The area under the working characteristic curve of the subjects was 0.746, the positive predictive value was 44.4%, and the negative predictive value was 86.8%. (2) HBsAg quantification or decline in 24 weeks and 48 weeks of treatment had a good predictive effect on HBsAg clearance, and the 48 weeks predicted value was higher than 24 weeks. When the HBsAg quantification was≤2.070 lgIU/ml at 48 weeks, the area under the receiver operating characteristic curve was 0.931, the positive predictive value was 52.8%, and the negative predictive value was 94.4%. When HBsAg decreased from baseline to≥0.991 lgIU/ml, the area under the receiver operating characteristic curve was 0.888, the positive predictive value was 50.8%, and the negative predictive value was 97.9%. (3) The analysis of HBsAg subgroup levels at 48 weeks suggested that the "interval analysis" can forecast HBsAg clearance more exactly than "nodal analysis" .The final HBsAg clearance rate of 100 IU/ml < HBsAg≤1 000 IU/ml, 10 IU/ml < HBsAg≤100 IU/ml and HBsAg≤10 IU/ml groups reached 6.7%, 31.8% and 67.7%, respectively. (4) The ALT abnormal group in the course of treatment obtained a higher HBsAg clearance rate (48.0%, 12/25). Conclusion 96-weeks long-term treatment with pegylated interferon-alpha -alpha-2a combined with nucleoside analogues for HBeAg-negative chronic hepatitis B has a good predictive value for HBsAg clearance at baseline and during treatment. The "interval level" of HBsAg at 48-weeks is more accurate in predicting HBsAg clearance, suggesting that HBeAg-negative chronic hepatitis B patients with low HBsAg levels at 48-weeks are the advantageous populations with HBsAg clearance. These patients are worthy of prolonged treatment to pursue "clinical cure".

Objective To evaluate the feasibility and safety profile of pegylated-interferonα-2a (Peg IFNα-2a) combined with adefovir dipivoxil (ADV) in inactive hepatitis B surface antigen (HBsAg) carriers (IHC).Methods This was a single center, prospective and open-label study.IHC were divided into therapeutic group (T, 112 subjects) and control group (C, 72 subjects) according to personal willingness.Patients with hepatitis B virus (HBV) DNA<20 IU/mL were treated with Peg IFNα-2a monotherapy, and those with HBV DNA ≥20-<2 000 IU/mL were treated with Peg IFNα-2a combined with ADV.Total therapy duration was 96 weeks.For patients who achieved HBsAg seroconversion and continued consolidation treatment for 24 weeks, the treatment duration could be less than 96 weeks.t test was used for continuous variable comparison between the two groups, while chi-square test or Fisher′s exact probability method was used for counting data analysis.The related factors affecting HBsAg clearance was analyzed by univariate or multivariate logistic regression analysis.Results A total of 194 patients were enrolled with 112 in therapeutic group and 72 in control group.The HBsAg clearance rate and seroconversion rate at week 48 in therapeutic group were 30.8% (32/104) and 26.0% (27/104), respectively.The rates at week 96 increased to 45.2% (47/104) and 38.5% (40/104), respectively.The HBsAg clearance rates at weeks 48 and 96 in control group were both 1.5% (1/68).HBsAg seroconversion was not achieved in control group.The HBsAg clearance rate in treatment group was significantly higher than that in control group (χ2=39.066, P<0.01).The quantitative HBsAg levels at baseline (OR=2.313, 95%CI: 1.258-4.251, P=0.007), week 12 (OR=3.159, 95%CI: 1.826-5.466, P<0.01) and week 24 (OR=3.347, 95%CI: 2.050-5.465, P<0.01), the decline of HBsAg at week 12 (OR=5.343, 95%CI: 2.085-13.689, P<0.01), and week 24 (OR=4.855, 95%CI: 2.380-9.902, P<0.01), and alanine transaminase (ALT) elevation at week 12 (OR=3.520, 95%CI: 1.369-9.052, P=0.009) were independent predictors for HBsAg clearance.Conclusions Peg IFNα-2a-based treatment for IHC could achieve higher HBsAg clearance rate and seroconversion rate, and has a safety profile.Decline of HBsAg at week 12 and week 24 with ALT elevation at week 12 could predict a higher HBsAg clearance rate.

Objective To evaluate initial results of Ivor Lewis minimally invasive esophagectomy (MIE) for esophageal carcinoma using a diamond-shaped anastomosis with 45 mm linear-stapler.Methods Clinical data of 12 patients diagnosed middle to distal esophageal carcinoma and undergoing Ivor Lewis minimally invasive esophagetomy using a diamond-shaped anastomosis technique during Dec.2015 and Nov.2016 in Peking Union Medical College Hospital were collected and analyzed retrospectively.Results The mean operation time was (378 ± 56) min,the mean blood loss was (280 ± 120) ml,and the mean postoperative hospital stay was (12.2 ± 2.0) days.No positive margin,no peri-operative death occurred.Postoperative complication included atelectasis and pulmonary infection in 1 patient,paresis of left recurrent laryngeal nerve in 1 patient.No anastomotic leak or constriction occurred.Median follow up was 7 months,11 patients had no evidence of disease progress,1 patient had subcutanecous metastasis and was reoperated.Conclusion The diamond anastomosis technique utilizing in Ivor Lewis MIE for esophageal carcinoma is feasible,easy to manipulate,safe and reliable.

Objective:To review the chemical and pharmacological activities of Codonopsis lanceolata in order to provide reference for the further development of C. lanceolata. Methods:The related literatures at home and abroad in the past 40 years were reviewed and analyzed, and then the chemical components and pharmacological actions of C. lanceolata were summarized. Results: The major chemical constiturents in C. lanceolata were terpenoids, alkaloids, phenylethanoid glycoside and flavonoids. The pharmacological ac-tivities were antioxidation, anti-inflammatory, anti-tumor, antiplatelet aggregation, hypoglycemic and hypolipidemic effects, etc. Con-clusion:The review provides reference for the further development and comprehensive utilization of C. lanceolata. The development of relevant safe and effective agents is still needed, and at present, the definition of mechanism and the extension of clinical application remain as the primary tasks of the exploration of C. lanceolata.

ObjectiveTo investigate the association between HBsAg clearance and serum level of interleukin-17 (IL-17) in HBeAg-negative chronic hepatitis B (CHB) patients treated by pegylated interferon (PEG-IFN). MethodsA total of 13 HBeAg-negative CHB patients who visited Beijing YouAn Hospital from January 2012 to January 2015 were enrolled. After the 24-week treatment with PEG-IFN, 6 achieved HBsAg clearance (R group) and 7 did not achieve HBsAg clearance (NR group). The Luminex technology was used to measure the serum level of IL-17 at baseline and weeks 12 and 24 of treatment. Ten healthy controls and 6 patients with acute hepatitis B (AHB) were enrolled and serum level of IL-17 was measured. An analysis of variance was used for comparison of continuous data between multiple groups, and the SNK-q test was used for further pairwise comparison; the t-test was used for comparison of continuous data between any two groups; the chi-square test was used for comparison of categorical data between groups. ResultsThe AHB group had the highest serum level of IL-17 at baseline, followed by the CHB group and healthy control group, and the serum level of IL-17 at baseline showed significant differences between the three groups (P＜0.05). After the PEG-IFN treatment for 24 weeks, HBeAg-negative CHB patients showed a significant reduction in serum level of IL-17 (P=0.044). R group had a significantly higher serum level of IL-17 than NR group and showed a significant reduction in the serum level of IL-17 after PEG-IFN treatment, while NR group showed no significant increase or reduction in the serum level of IL-17. ConclusionIn the PEG-IFN treatment for HBeAg-negative CHB patients, a high serum level of IL-17 at baseline and a significant reduction in serum level of IL-17 helps with HBsAg clearance.

OBJECTIVETo investigate the inhibitory effect of salinomycin on human breast cancer cells in vitro, and to explore the related molecular mechanism.

METHODSHuman breast cancer MDA-MB-231 cells were treated with salinomycin at different concentrations and at various time points. The effect of salinomycin on MDA-MB-231 cells proliferation was studied by CCK-8 method. The cell cycle status was examined by flow cytometry. RT-PCR and Western blot were used to detect the expression of Shh, Smo and Gli1 in the Hedgehog pathway at mRNA and protein levels.

RESULTSProliferation of MDA-MB-231 cells treated with salinomycin was markedly inhibited in a concentration and time dependent manner. Salinomycin at concentrations of 0, 0.4, 0.8 and 1.6 µmol/L inhibited the growth at the rates of 11.18%, 25.88%, 50.03%, 92.65%, respectively. Salinomycin prevented MDA-MB-231 cells from G1 into S phase. Salinomycin at concentrations of 0, 0.8 and 1.6 µmol/L resulted in S-phase percentage of 25.03%, 11.85% and 35.21%, respectively (P < 0.05). RT-PCR and Western blot showed that the expression of key elements Shh, Smo and Gli1 in the Hedgehog pathway was inhibited by salinomycin in a concentration dependent manner (P < 0.05).

CONCLUSIONSalinomycin prevents breast cancer cell transition from G1 to S phase through downregulation of the target genes of Hedgehog signaling pathway, leading to an effective inhibition of MDA-MB-231 cells.