Objective To discuss the relationship between various T lymphocyte subsets apoptosis and disease progression in chronic antiretroviral-naive HIV/AIDS patients. Methods Thirty-six chronic antiretrovi-ral-naive HIV-infected individuals as well as 16 healthy HIV-negative controls were performed in this study. Ac-cording to the CD4~+ T cell counts, all the patients were divided three groups: < 200/μl, 200-350/μl and > 350/μl. After the peripheral blood mononuclear cells(PBMC) were isolated, T lymphocyte subpopulations were determined by the expression of CD45RO and CD27, and the apoptosis of different T cell subsets were measured by Annexin V staining, then analyzed by flow cytometry. To investigate whether the apoptosis of T cells varied with the culture time in vitro, 4 healthy controls and 4 patients were chosen as subjects, and the lev-els of cell apoptosis were analyzed at the culture time points of 0, 3, 6, 12, 24 h. Results (1)The percenta-ges of the AnnexinV expression on CD4~+ and CD8~+ T cells and all the subsets in HIV/AIDS patients were sig-nificantly higher than that in the healthy controls (P<0.05), but there were no significant differences among the three HIV-infected patient groups(P>0.05). (2) No significant correlations were observed between the levels of apoptosis of all the T cells and subsets and total CD4~+ T cell counts(P>0.05) ,nor with the HIV viral load (P>0.05). (3)As the culture time prolonged in vitro, the levels of apoptosis and necrosis of CD4~6 T cells in HIV/AIDS patients were significantly higher than those in the healthy conlrols, and the CD4~+ T cells were more susceptible to apoptosis and necrosis compared with CD8~+ T cells. Conclusion The levels of T cell apoptosis in HIV/AIDS patients was significantly higher than those in the healthy controls, at the same time, CD4~+ T cells were more susceptible to apoptosis and necrosis compared with CD8~+ T cells, but no correlation was found between the T cell apoptsis and disease progression.

Objective To study the relationship of proliferation and activation of T lymphocyte subsets and disease progression in antiretroviral-naive human immunodeficiency virus(HIV)-1-infected individuals.Methods Forty-nine antiretroviral-naive,chronically HIV-1 infected patients and 16 healthy,HIV-1 negative controls were enrolled in this study.The patients were divided into 3 groups according to their CD4+T cell counts:<200×106/L,(200-350)×106/L and>350×106/L.Peripheral blood mononuclear cells(PBMC)were isolated.T cell proliferation index was measured by Ki-67 staining.T cell activation was detected by CD38 staining.The samples were analyzed by flow cytometry.The data were compared by one-way ANOVA.Results The percentage of Ki-67+cells in CIM+T ceils was 7.92%±4.37%in CD4+T cell<200×106/L group,which was significantly higher than those 0.39%d:0.24%in control group,2.61%±2.12%in(200-350)×106/k group and 2.65%±2.13%in>350 X106/L group(F=21.961,P<0.01).The percentage of Ki-67+cells in CD8+T ceils in CD4+T cells<200×106/L group was 2.87%±1.13%,which was also much higher than those in other 3 groups(0.15%±0.90%,1.40%±1.17%,1.22%±0.80%,respectively F=19.203,P<0.01).The Ki-67'CD4'T cells and Ki-67+CD8+T cells were inversely correlated with CD4+T cell counts(r=-0.654,r=-0.539,respectively;P350×106/L group(F=14.333,F=15.412,respectively;P<0.01).The expressions of Ki-67+ on CD4+ and CD8+T cells were positively correlated with CD38 expression(r=0.527,r=0.391,respectively;P=0.002).Conclusions The proliferation and activation of T lymphoeytes are enhanced during HIV/AIDS disease progression.And T eell activation may be the result of persistent immune activation.

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.

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.

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 summarize the scientific research management response strategies and practices of designated hospitals under the prevention and control of new coronary pneumonia, provide reference for the scientific and technological management of public health emergencies in domestic hospitals.Methods:Take the hospital scientific research management response under the prevention and control of the new coronavirus pneumonia epidemic in 2020 as an example, discuss and summarize the response strategies and mechanism establishment, work practice and existing problems of designated hospitals in the research management of prevention and control of public health emergencies represented by COVID-19 from the aspects of management system, resource integration, project operation, and scientific and technological service.Results:As a designated hospital of COVID-19 in Beijing, Youan hospital has actively carried out scientific and technological research on epidemic prevention and control while successfully completing patient treatment, established a scientific and efficient scientific and technological research management system, and integrated resources to form an efficient project operation mechanism, Providing a full range of scientific management services, providing policy and material guarantee for the rapid and high-quality completion of scientific and technological research on epidemic prevention and control.Conclusions:The scientific and technological research on public health emergencies has the characteristics of demand-driven, focused on key points, collaborative research, scientific decision-making, In order to carry out the research work smoothly, it is particularly important to form a benign interaction, straighten out the system, do a good job in long-term planning and layout, and establish a scientific and efficient research and management mechanism.

ObjectiveCirrhotic 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. MethodsThis 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. ResultsThe 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%. ConclusionThere is a certain association between serum endocan and CCM， and serum endocan may be involved in the pathogenesis of CCM.

OBJECTIVE：To establish a method for the determination of pyrrotinib concentration in plasma ，and apply it in clinic. METHODS ：After precipitated with methanol ，the plasma sample was determined by LC-MS/MS using imatinib as internal standard. The determination was performed on Ultimate AQ-C 18 column with mobile phase consisted of methanol （containing 0.1％ formic acid ）and water （containing 0.1％ formic acid ）（gradient elution ）at the flow rate of 0.4 mL/min. The column temperature was 40 ℃，and the sample size was 5 µL. The ion source was electrospray ionization source ，and the positive ion scanning was carried out in multiple reaction mode. The ion pairs for quantitative analysis were m/z 583.4→138.3（pyrrotinib）and m/z 494.5→ 393.4（internal standard ），respectively. Thirty breast cancer patients taking pyrrotinib were collected from the Affiliated Hospital of Qingdao University during Jun.-Nov. 2020 to determine their steady-state trough concentrations of pyrrotinib after a week of treatment. RESULTS ：The linear range of pyrrotinib were 5-300 ng/mL（r＝0.999 3）. The lower limit of quantification was 5 ng/mL. RSDs of intra-day and inter-day were not higher than 9.30％，and relative errors （REs）ranged －6.70％-5.04％. REs of stability tests were in the range of －1.92％-5.42％. The extraction method ，matrix effect and residual effect did not affect the quantitative analysis of the substance to be tested. The steady-state trough concentrations of pyrrotinib were 32.6-82.8 ng/mL，with an average plasma concentration of 53.8 ng/mL；there was about 2.54 fold individual difference. CONCLUSIONS ：Established LC-MS/MS method is simple ，sensitive and accurate ，and can be used for the plasma concentration monitoring of pyrrotinib in breast cancer patient.

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.