Background::A more comprehensive understanding of the trends of incidence, prevalence, and mortality in human immunodeficiency virus (HIV), and their complex interrelationships, may provide important evidence for decision-making related to HIV prevention and control. The variances in these indices between different population groups, genders, and ages are critical to decipher evolving patterns of the HIV epidemic in specific populations.Methods::A secondary analysis of relevant data was conducted using data extracted from the Global Burden of Disease study of 2019. HIV/acquired immune deficiency syndrome (AIDS) incidence, prevalence, AIDS-related mortality, and mortality-to-prevalence ratio (MPR) for annual percentage change, average annual percentage change (AAPC), and corresponding 95% confidence intervals (CIs) were calculated using joinpoint regression statistical analysis.Results::The AAPC of HIV/AIDS incidence, prevalence, AIDS-related mortality rate, and MPR were -1.4 (95% CI: -1.6, -1.2), 4.1 (95% CI: 4.0, 4.3), 2.0 (95% CI: 1.7, 2.3), and -2.1 (95% CI: -2.3, -1.8) between 1990 and 2019 globally, and were 3.5 (95% CI: 2.2, 4.8), 6.9 (95% CI: 6.8, 7.0), 8.1 (95% CI: 7.1, 9.1), and 1.2 (95% CI: 0.1, 2.3) in China during the same period. In terms of differences in the preceding indicators by gender, we observed a similar pattern of trends for male and female genders both globally and in China during the entire study period. Each specific age group exhibits a distinct pattern in terms of incidence, prevalence, mortality rate, and MPR both globally and in China.Conclusions::Prevalence and mortality rates of HIV/AIDS have increased between 1990 and 2019 globally and in China. While the incidence rate and MPR have declined globally over the past three decades, these two indicators are observed to present an increasing trend in China. There is a high HIV burden among young and middle-aged adults globally; however, the elderly have a high HIV burden in China. HIV screening at older age should be scaled up, and patients with advanced HIV disease should be provided early with additional care and health resources.

Objective:To explore the effects of BCR-ABL downstream pathway inhibitors, such as RAF inhibitor SB590885, JAK inhibitor AZD1480, PI3K-mTOR double target inhibitor BEZ235 on chronic myelogenous leukemia (CML) cells, and the effect of BEZ235 on the proliferation, apoptosis of CML cells and the sensitivity of imatinib in vitro.Methods:K562 cells were treated with different concentrations of the drugs. MTS method was applied to detect the proliferation inhibition rate of K562 cells, and 50% inhibitory concentration (IC 50) of all drugs for 48 h was calculated. The cell apoptosis rate was tested by using flow cytometry with Annexin V-FITC/PI double staining. The cell cycle was tested by using flow cytometry with PI staining. K562 cells, imatinib-resistant and T315I-mutant human CML KBM7R cells and imatinib-resistant CML primary cells of patients were treated with different concentrations of the drugs. MTS method was used to test the proliferation inhibition of cells, and IC 50 of all drugs for 48 h was evaluated. KBM7R cells or primary cells of CML patients were treated with 1.0 μmol/L BEZ235, 1.0 μmol/L imatinib or the combination of both, respectively. Flow cytometry with PI staining was used to detect the cell cycle of KBM7R cells. Flow cytometry with Annexin V-FITC/PI double staining was used to detect the cell apoptosis rate in CML primary cells. The expressions of p-AKT, cleaved Caspase-3 and Cyclin D1 proteins were detected by using Western blot. Results:SB590885, AZD1480 and BEZ235 could inhibit the proliferation of K562 cells, and the IC 50 after the treatment of K562 cells for 48 h was (11.49±3.14), (4.83±1.26) and (0.37±0.21) μmol/L, respectively. SB590885, AZD1480 and BEZ235 could promote the apoptosis of K562 cells. The cell apoptosis rates were increased compared with the control group without drug treatment (all P < 0.01). SB590885 and BEZ235 induced G 0/G 1 block (both P < 0.05). AZD1480 induced G 2/M block ( P < 0.05). BEZ235 could inhibit the proliferation of K562 cells, KBM7R cells and CML primary cells, and their IC 50 for 48 h was (0.37±0.21), (0.43±0.27) and (0.49±0.24) μmol/L, respectively. Compared with imatinib alone, the different concentrations of imatinib combined with 0.2 μmol/L BEZ235 could increase the proliferation inhibition of K562 cells, KBM7R cells and CML primary cells, and could reduce the IC 50 of imatinib. After the treatment of imatinib alone and combination with BEZ235 for 48 h, the imatinib IC 50 of K562 cells was (0.14±0.05) and (0.09± 0.04) μmol/L ( t = 1.531, P = 0.249), the imatinib IC 50 of KBM7R cells was (3.93±2.29) and (0.44±0.22) μmol/L ( t = 2.837, P = 0.047), the imatinib IC 50 of the primary cells was (3.12±1.53) and (0.39±0.23) μmol/L ( t = 3.925, P = 0.042). The cell apoptotic rate of the primary cells was (4.9±1.4)%, (13.1±3.2)%, (8.8±2.0)% and (40.6±6.0)%, respectively in the control group without drug treatment, 1.0 μmol/L BEZ235, 1.0 μmol/L imatinib and the combination of 1.0 μmol/L BEZ235 and 1.0 μmol/L imatinib after the treatment of 24 h ( F = 71.031, P < 0.01). Compared with imatinib alone, the expressions of p-AKT and Cyclin D1 proteins were decreased, and the expression of cleaved Caspase-3 protein was increased after the treatment of KBM7R cells for 12 h in the combination group of both BEZ235 and imatinib. Conclusions:BCR-ABL downstream pathway inhibitors can effectively inhibit the proliferation and promote the apoptosis of K562 cells. BEZ235 can inhibit the proliferation and promote the apoptosis of K562 cells, imatinib-resistant and T315I-mutant human KBM7R cells and imatinib-resistant CML primary cells of patients, which has a synergistic effect to imatinib.

Objective:To observe the effects of Shexiang Baoxin Pill (SBP) on isoprenaline (Iso)-induced changes in myocardial cell volume,shape,and connexin 43 (Cx43) expression.Methods:HgC2 myocardial cells were randomly divided into a control group,a Iso group and a Iso+SBP group.After 72 h of culture,the average surface area of HgC2 cells was measured under phase contrast microscope.Bicinchoninic acid (BCA) protein assay was carried out to determine the concentration of proteins.The survival rate of myocardial cells was measured by methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay,and the Cx43 expression was detected by Western blot.Results:The mean surface area and Cx43 concentration in Iso-treated myocardial cells were increased under the phase contrast microscope (P<0.05).Compared with the Iso group,the mean surface area was decreased,and the Cx43 concentration was reduced in the Iso+SBP group (both P<0.05).Compared with the control group,the Cx43 expression was obviously down-regulated in the H9C2 cells of the Iso group (P<0.05);while compared with the Iso group,the Cx43 expression was obviously up-regulated in the Iso+SBP group (P<0.05).Conclusion:Shexiang Baoxin Pills can prevent Iso-induced myocardial hypertrophy and down-regulate Cx43 expression.

Objective To explore the recuperative effect of immunological function and nutritional status on the patients treated by immune enteral nutrition in early stage after severe multiple injury (SMI). Method The patients with SMI,in department of Trauma Surgery,Tongji Hospital,Tongji Medical College, Huazhong University of Science and Technology,between January 2006 to May 2007 were randomly divided into 2 groups: immune enteral nutrition group (IEN group, 20 cases), enteral nutrition group (EN group, 20 cases). The health persons served as the control group(15 cases) .Since 1st postinjury day, all patients were treated with nutritional support. The T-cell subgroup in periphera blood were detected by FCM and the level of PA, RBP, IL-2 and IL-4 in blood serum were detected by ELASA on the 1st, 3rd,5th, 8th postinjury day. Results After the treatment of IEN and EN,the serum levels of PA, RBP and the proportion of T-cell subgroup were significantly increased on the 8th postinjury day compared with on 1st postinjury day (P ＜ 0.01), but there were no differences between IEN group and EN group. The level of IL-4 were significantly decreased and the level of IL-2 were significantly increased in each group on 8th postinjury day, at same time, the level of IL-2 were significantly increased in IEN group compared with EN group (P ＜ 0.05), and the level of IL-4 were significantly decreased in IEN group compared with EN group (P ＜ 0.05). The duration of SIRS was transient and the infected complication was low on the patients treatment by IEN than EN. Conclusions On the patients with severe multiple injury, IEN was most ascendant than EN to improve the immunosuppression and clinical prognosis.

Objective To determine the effect of nanochemotherapy drug on Survivin and p53 ex-pressed by human biliary traet carcinoma cell line QBC939.Methods Culturing the human biliary tract carcinoma cell line QBC939 in vitro and it was divided into five groups including saline,nanochemotherapy drug,nanopartiele withoul nanochemotherapy drug,5-FU and gemcitabine.Using the methods of MTT and flow cytometry to observe the growth of QBC939 which was dealt with different drugs.In addition,RT-PCR and Western blot were used to delect the expression of mRNA and protein by Survivin or p53.Results The expression of mRNA and protein by Survivin decreased in the following set:saline,nanoparlicle withoul nanochemotherapy drug,5-FU,gemcitabine and nanochemotherapy drug,respeclively.However,the ex-pression of mRNA and protein by p53 were in reverse order.The inhibiting action to QBC939 was obvious in nanochenmtherapy drng and the apoplotic rate was higher than others except for gemcitabine(P＜0.05). Conclusion Nanochemotherapy drug has significant effect on treatment cholangiocarcinoma in vilro,which may attribute to the down regulation of Survivin and up regulation of p53.

Hypermethylation of the promoter region is an important mean for the transcriptional repression of a number of cancer-associated genes, and over-expression and/or increased activity of DNA methyltransferase are considered to be the main cause of promoter hypermethylation. In order to further explore the epigenetic mechanism of tumor suppressor gene RASSF1A inactivation,5-aza-2'-deoxycytidine (5-Aza-CdR), a DNA methyltransferase inhibitor, was used to treat the human biliary tract carcinoma cell line QBC-939 at the concentration of 5 μmol/L for 24 h in this study. After the chemical intervention with 5-Aza-CdR, the methylation status in the promoter region of RASSF1A gene was detected by methylation specific PCR (MS-PCR), and the expression alteration of RASSF1A mRNA and protein were observed by RT-PCR and Western Blot respectively. Following the treatment with 5-Aza-CdR, methylaiton status in the promoter region of RASSF1A gene was reversed from methylation to unmethylation. A 280 bp DNA band which represented RASS1FA expression at transcriptional level and a 40 kDa (1kDa=0.9921 ku) protein band which represented RASSF1A expression at protein level were detected by RT-PCR and Western Blot respectively in the experimental group cells and there were no corresponding bands in the control group cells. The experimental results suggest that 5-Aza-CdR can induce demethylation in the promoter region of RASSF1A. It can also reverse epigenetic transcriptional silencing caused by DNA methylation and induce the re-expression of RASSF1A in QBC-939. This study also suggest that the mechanism of RASSF1A inactivation is very closely related to the methylation of the promoter region, which may provide a new epigenetic understanding for tumor related gene inactivation and the pathogenesis of biliary tract carcinoma.

Hypermethylation of the promoter region is an important mean for the transcriptional repression of a number of cancer-associated genes, and over-expression and/or increased activity of DNA methyltransferase are considered to be the main cause of promoter hypermethylation. In order to further explore the epigenetic mechanism of tumor suppressor gene RASSF1A inactivation, 5-aza-2'-deoxycytidine (5-Aza-CdR), a DNA methyltransferase inhibitor, was used to treat the human biliary tract carcinoma cell line QBC-939 at the concentration of 5 micromol/L for 24 h in this study. After the chemical intervention with 5-Aza-CdR, the methylation status in the promoter region of RASSF1A gene was detected by methylation specific PCR (MS-PCR), and the expression alteration of RASSF1A mRNA and protein were observed by RT-PCR and Western Blot respectively. Following the treatment with 5-Aza-CdR, methylation status in the promoter region of RASSF1A gene was reversed from methylation to unmethylation. A 280 bp DNA band which represented RASS1FA expression at transcriptional level and a 40 kDa (1 kDa=0.9921 ku) protein band which represented RASSF1A expression at protein level were detected by RT-PCR and Western Blot respectively in the experimental group cells and there were no corresponding bands in the control group cells. The experimental results suggest that 5-Aza-CdR can induce demethylation in the promoter region of RASSF1A. It can also reverse epigenetic transcriptional silencing caused by DNA methylation and induce the re-expression of RASSF1A in QBC-939. This study also suggest that the mechanism of RASSF1A inactivation is very closely related to the methylation of the promoter region, which may provide a new epigenetic understanding for tumor related gene inactivation and the pathogenesis of biliary tract carcinoma.

OBJECTIVETo detect the regulative effects of IFN-gamma on the expression of Fas and FasL of cholangiocarcinoma cells.

METHODSWe studied that the expression of Fas and FasL gene by the human cholangiocarcinoma cell line QBC939 by RT-PCR, Western blot, immunohistochemistry. At the same time, we investigated the regulative effect of IFN-gamma on them.

RESULTSFas and FasL mRNA and protein were expressed by cholangiocarcinoma cells. We also found IFN-gamma could upregulate the expression of the two genes (P < 0.01). However, IFN-gamma could also downregulate the ability of them to make Jurkat cells apoptotic. With the increasing of dosage and time, the effect was enhanced.

CONCLUSIONSIFN-gamma could regulate the expression of Fas and FasL by cholangiocarcinoma cells, therefore it could reduce the ability of cholangiocarcinoma to occur immune escape. This provides new theoretical basis for immunological therapy of cholangiocarcinoma.

Apoptosis ; drug effects ; Bile Duct Neoplasms ; Bile Ducts, Intrahepatic ; Cholangiocarcinoma ; Humans ; Membrane Glycoproteins ; RNA, Messenger ; genetics ; fas Receptor

OBJECTIVETo clarify the relationship between the loss of expression of the deleted in pancreatic carcinoma locus 4 (DPC4) proteins and the pathogenesis of biliary tract carcinoma.

METHODS71 primary biliary tract carcinoma (BTCa), including 38 common bile duct (CBD) carcinomas, 18 gallbladder carcinomas, 15 hilar bile ducts (HBD) carcinomas were examined by immunohistochemical staining. In addition, the CBD carcinomas were divided into two groups: tumors with metastasis (M(+) group, 27 cases) and tumors without metastasis (M(-) group, 11 cases).

RESULTSThe frequency of loss of the expression of DPC4 protein was 32.8% in BTCa, 47.3% in CBD carcinoma, 11% in gallbladder carcinoma, 13% in HBD carcinoma. Comparison of the frequency of loss expression of DPC4 was significant statistical difference in CBD carcinoma versus gallbladder carcinoma and HBD carcinoma (P < 0.01). The frequency of loss expression of DPC4 was 48.1% in the M(+) group and 45.4% in the M(-) group.

CONCLUSIONThere are a close relationship between pathogenesis of BTCa and inactivation of DPC4 and different frequencies of DPC4 gene alternation in various locations of the biliary tract, which are not significantly increased with tumor metastasis in BTCa.

Bile Duct Neoplasms ; Biliary Tract ; Carcinoma ; DNA-Binding Proteins ; metabolism ; Humans ; Pancreatic Neoplasms ; Smad4 Protein ; Trans-Activators