BACKGROUND: Many diseases accompany with changes of gene expression which can provide a valuable clue for pathogenesis and therapy of cognitive diseases.OBJECTIVE: To screen expression of different genes in lung tissue of model rats with chronic obstructive pulmonary disease (COPD) by gene expression profiling technique. DESIGN: Open study. SETTING: Affiliated Hospital of Shandong University of Traditional Chinese Medicine; Radiation Medical Institute of Academy of Military Medical Sciences of Chinese PLA; Shangdong University of Traditional Chinese Medicine.MATERIALS: The experiment was carried out in the Central Laboratory of Affiliated Hospital, Shandong University of Traditional Chinese Medicine from April to October 2005. ① Fifteen healthy male Wistar rats of SPF grade and aged 50 days were randomly divided into normal group, model control group and Chinese herb group with 5 in each group. ② Type of gene chip was BiostarR-40S and provided by Shanghai Boxing Gene Chip Company Limited (batch number: G050510010052).METHODS: ① COPD models in model control group and Chinese herb group were established with modified smoking-fumigated method plus adding lipopolysaccharide in windpipe. Pathological changes of airway were observed under optic microscope. Models were established successfully based on the following phenomenon: hyperemia and edema in mucous membrane of airway; degeneration and necrosis of epithelial cells; infiltration of bronchial cavity in lung tissue and surrounding chronic inflammatory cells; proliferation of smooth muscle and fibrocyte surrounding dissepiment; thin and broken interval; amplifying confluence of pulmonary alveolus; thickness of vascular wall of arteriole; decrease of vaso-cavity; infiltration of surrounding inflammatory cells. ② At 30 days after modeling,0.65 g/mL self-made Chinese herb (mahuang, xingren, huangqi, etc.) wasperfused into rats in Chinese herb group with 2 mL each time, once a day,for successive 14 days. Rats in model control group were perfused with 2 mLsaline; however, rats in normal group were untouched. All rats drank freely under the same internal environment. ③ After administration, rats in each group were sacrificed to extract total RNA, label and hybridizated with probe, wash pieces, analyze gray value of clip with clip imaging software,obtain original signal of each gene point (signal values of foreground and background) and determine differently expressed genes. If size of test was more than 2.0, genes were regarded as up-regulation genes; otherwise, if ratio was less than 0.5, they were regarded as down-regulation genes. In this study, based on reliability, if size of test was more than 2.5, they were regarded as up-relation genes; however, if ratio was less than 0.375, they were regarded as down-regulation genes.MAIN OUTCOME MEASURES: ① Comparisons of differently expressed genes in normal and model control groups; ② Comparisons of differently expressed genes in normal and Chinese herb groups; ③Comparisons of differently expressed genes in model control and Chinese herb groups.RESULTS: Fifteen rats were all involved in the final analysis. ① As compared with those in normal group, there were 57 differently expressed genes in model control group, involving in immunity, metabolism, signal transduction, adjusting of gene expression, cell cycle, cell transport, cell migration, fibrosis, etc. ② Gene expression in Chinese herb group reached normal level and there were 11 differently expressed genes as compared with those in normal group, involving in stress, signal transduction, cytoskeleton, etc. ③ As compared with those in model control group, there were 7 differently expressed genes in Chinese herb group, involving in immunity and excretion of neurotransmitter.CONCLUSION: Changes of gene expression may be one of reasons of COPD pathogeneses; moreover, most differently expressed genes can recover the normal level after drug therapy which is beneficial to correct pathological changes of COPD.

Adult ; Aged ; Aged, 80 and over ; Antiviral Agents ; therapeutic use ; Carcinoma, Hepatocellular ; epidemiology ; virology ; Female ; Hepatitis B ; drug therapy ; epidemiology ; Humans ; Liver Neoplasms ; epidemiology ; virology ; Male ; Middle Aged ; Retrospective Studies ; Young Adult

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 protective mechanism of Ginsenoside Rb1 on apoptosis of primary cultured cerebral cortical neurons caused by hypoxia.MethodsThe anti apoptosis effect of Ginsenoside Rb1 on primary cultured neurons was observed by methods of the primary culture of cerebral neurons of postnatal rats in free serum with neurobasal medium supplied with 2% B27 supplement, trypan blue exclusion, hypoxic culture of neurons, Hoechst 33342 staining and immunocytochemistry.ResultsAt concentrations of 10μg/ml,50μg/ml and 100μg/ml, the Ginsenoside Rb1 dropped apoptosis rate of cerebral cortical neurons induced by hypoxia (in 100 μg/ml,P<0.05),and increased Bcl-2 protein expression (except 10μg/ml,P<0.05) and decreased Bax protein expression (except 10μg/ml,P<0.05—P<0.001) in the cerebral cortical neurons induced by hypoxia, improved the ratio of Bcl-2/Bax (except 10 μg/ml,P<0.05).ConclusionGinsenoside Rb1 is able to prevent hypoxic neurons from apoptosis in primary cultured cerebral cortical neurons from 50—100 μg/ml. The effect of anti apoptosis is through up regulation of Bcl-2 protein expression and down regulation of Bax-2 protein expression.

Animals ; Biocatalysis ; Cattle ; Enteropeptidase ; chemistry ; metabolism ; Humans ; Models, Molecular ; Oryzias ; metabolism ; Structure-Activity Relationship ; Substrate Specificity

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 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 investigate the clinical characteristics, treatment and prognosis of newly-treated patients with primary central nervous system lymphoma (PCNSL).Methods:Clinical data of 117 newly-treated PCNSL patients who were admitted to the First Hospital of Jilin University, the Fifth Medical Center of Chinese PLA General Hospital, Harbin Medical University Cancer Hospital, and Cancer Hospital of Chinese Academy of Medical Sciences & Peking Union Medical College from August 2009 to February 2018 were retrospectively analyzed. The patients' age, sex, Eastern Cooperative Oncology Group (ECOG) physical status (PS) score, pathological type, involvement of deep brain tissue, number of lesions, cerebrospinal fluid protein concentration, International Extranodal Lymphoma Study Group (IELSG) score, Memorial Sloan Kettering Cancer Center (MSKCC) score, treatment strategy, and response after the first-line therapy were analyzed using univariate and multivariate Cox proportional hazards models to identify the independent influencing factors for progression-free survival (PFS) and overall survival (OS) of PCNSL patients. Kaplan-Meier method was used for survival analysis.Results:In 117 newly-treated PCNSL patients, 59 cases (50.4%) presented with increased intracranial pressure or focal neurological symptoms at diagnosis; there were 65 cases (55.6%) with single lesions and 52 cases (44.4%) with multiple lesions; 1 patient (0.9%) had lymphoma of T-cell origin, and 116 cases (99.1%) had diffuse large B-cell lymphoma (DLBCL). Among 95 evaluable patients, 41 patients (43.2%) achieved complete remission (CR), 20 patients (21.1%) achieved partial remission (PR), 16 patients (16.8%) achieved stable disease (SD), and 18 patients (18.9%) had progressive disease (PD). In 117 patients with median follow-up of 66.0 months (95% CI 57.9-74.1 months), the median PFS and OS were 17.4 months (95% CI 11.5-23.3 months) and 45.6 months (95% CI 20.1-71.1 months), respectively. The 2-, 3- and 5-year PFS rates were 41.2%, 28.6% and 19.3%, and OS rates were 63.7%, 52.4% and 46.3%, respectively. Univariate Cox regression analysis showed that baseline high-risk MSKCC score group was an adverse prognostic factor for PFS ( P = 0.037), and the first-line chemotherapy with ≥4 cycles of high-dose methotrexate (HDMTX), HDMTX in combination with rituximab, ≥4 cycles of rituximab in combination with HDMTX, and achieving CR or ≥PR after the first-line treatment reduced the risk of disease progression and prolonged the PFS time (all P <0.01); age >60 years old, ECOG-PS score of 2-4 points, elevated cerebrospinal fluid protein concentration, high-risk IELSG score, and high-risk MSKCC score were adverse prognostic factors for OS, and ≥4 cycles of HDMTX and achieving CR or ≥PR after the first-line treatment were favorable factors for OS. Multivariate Cox regression analysis verified that rituximab in combination with HDMTX (yes vs. no: HR = 0.349, 95% CI 0.133-0.912, P = 0.032) and achieving ≥PR after the first-line chemotherapy (yes vs. no: HR = 0.028, 95% CI 0.004-0.195, P < 0.001) were independent favorable factors for PFS; age >60 years old (>60 years old vs. ≤60 years old: HR = 10.878, 95% CI 1.807-65.488, P = 0.009) was independent unfavorable factor for OS, while ≥4 cycles of HDMTX treatment (≥4 cycles vs. <4 cycles: HR = 0.225, 95% CI 0.053-0.947, P = 0.042) was independent favorable factor for OS. Conclusions:The older the PCNSL patients at initial treatment, the worse the prognosis. Intensive and continuous treatment for achieving deeper remission may be the key for improving the outcome of PCNSL patients.

Objective:To improve the prognosis stratification, especially early mortality(EM), of elderly patients with newly diagnosed multiple myeloma(NDMM).Methods:In this retrospective study, univariate and multivariate Cox regression analysis were conducted to identify the independent prognostic factors associated with overall survival(OS)and the chi-square test and multivariate Logistic analysis were used to identify the prognostic factors associated with EM in 223 elderly patients(age≥65 years)with NDMM from three centers in the country.Results:Increased NT-pro-BNP(≥300 pg/ml), ECOG-PS≥2 and stage Ⅲ R-ISS were identified as three independent adverse prognostic factors of OS.The rates of EM3, EM6, EM12 and EM24 were 12.1%, 20.1%, 32.2% and 60%, respectively.The most common cause for EM6(particularly EM3)was disease-related complications resulting from ineligibility for treatment due to poor physical performance, severe organ dysfunction or treatment discontinuation due to treatment intolerance, while the most common cause for EM12(particularly EM24)was disease progression or relapse mainly as a result of inadequate treatment.R-ISS staging failed to predict EM, while decreased eGFR, ECOG-PS≥2, and increased NT-pro-BNP were able to estimate the risk of EM, with increased NT-pro-BNP as a common independent factor for EM12( P=0.03)and EM24( P=0.015). Conclusions:R-ISS staging, which primarily reflects MM biology, cannot predict EM.However, factors such as NT-pro-BNP, eGFR and ECOG-PS associated with frailty and impairment of organ functions can be used to estimate the risk of EM, among which NT-pro-BNP may be the most important independent factor for EM.Therefore, incorporation of these frailty-related biomarkers into R-ISS staging may be able to more precisely estimate the prognosis and particularly early death of elderly patients with NDMM.