[Bidirectional regulation of Pam3CSK4?induced inflammatory response by ATP?binding cassette transporter A1 knockdown in mouse mononuclear macrophages in vitro].

OBJECTIVE: To investigate the regulatory effect of ATP?binding cassette transporter A1 (ABCA1) knockdown on inflammatory response induced by Pam3CSK4 in mouse mononuclear macrophage RAW264.7 cell line. METHODS: A mouse mononuclear macrophage RAW264.7 cell line with stable ABCA1 knockdown was constructed and stimulated with Toll?like receptor 2 (TLR2) ligand Pam3CSK4, and the changes in the transcriptional levels of the proinflammatory and anti-inflammatory cytokines were analyzed in this cell model. RESULTS: In RAW264.7 cells, ABCA1 knockdown significantly up-regulated Pam3CSK4 stimulation?induced expressions of IL?1ß, TNF?α and IL?6 and also enhanced the expression of transcription factor cAMP?dependent transcription factor 3 (ATF3) without obviously affecting the expressions of the transcription factors ATF1, ATF2, ATF4 or ATF5. CONCLUSION: ABCA1 knockdown in macrophages may have both proinflammatory and anti?inflammatory effects. ABCA1 knockdown up?regulates the transcription of ATF3 possibly through a mechanism that is different from that for the other members of the ATF protein family.

[HCV prevalence among the populations under the HIV sentinel surveillance data from 2009 to 2012 in China].

OBJECTIVE: To analyze the hepatitis C virus (HCV) prevalence among 8 populations in 2009-2012 in China, using the HIV sentinels surveillance data. METHODS: Cross-sectional studies had been repeatedly conducted on HIV Sentinel Surveillance with uniformed questionnaire and collection of venous blood specimen among 8 populations including drug users (DUs), men who have sex with men(MSM), female sex workers(FSW), male STD clinic attendees, male long distance truck drivers, male mobile populations, pregnant women and young students from April to June 2009 to 2012 on the yearly base. Blood testing for HIV, syphilis and HCV infections have been routinely performed on all participants of 8 populations recruited during the surveillance period. RESULTS: HCV prevalence among drug users had been relatively high, between 40.0%-43.0% in 2009-2012. HCV prevalence of injection drug users(IDUs)showing a slight increasing trend in the past four years from 55.0% in 2009 to 65.0% in 2012. HCV prevalence rates among other 7 populations maintained low remained less than 1.0% in the past three years. CONCLUSION: Data from sentinel surveillance programs showed that HCV prevalence of DUs maintained high but the other 7 populations at low levels in the HIV sentinel surveillance areas in China. Blood-borne was the most common transmission pathways of HCV. IDU was one of the predominant models of HCV transmission in China and continued to fuel the HCV epidemics throughout the country.

HIV prevalence and influencing factors analysis of sentinel surveillance among men who have sex with men in China, 2003 - 2011.

BACKGROUND: Men who have sex with men (MSM) have been impacted by HIV and now as an important driver of the HIV/AIDS epidemic in China. This study collected HIV sentinel surveillance system data on the MSM population to describe the characteristics and trends of the HIV epidemic among MSM in China from 2003 to 2011. METHODS: Data on HIV prevalence and risk behaviors from 2003 to 2011 were obtained from the national HIV sentinel surveillance database. RESULTS: MSM sentinel surveillance data for 2011 showed that proportions of MSM who consistently used condoms during anal sex in the last six months and at last anal sex encounter were 43.3% and 74.1%, respectively. Between 2005 and 2011 there were no significant changes in the proportion of consistent condom use. The proportion of MSM who had multiple male sex partners in the last six months increased. Overall HIV prevalence over the years showed a rising trend from 0.9% in 2003 to 6.3% in 2011. The syphilis antibody positive rate was 7.8% in 2011. In addition, the proportion of MSM in heterosexual marriages was rising, AIDS awareness was also increasing, and the proportion of MSM who had taken an HIV test in the last year and was aware of the results rose. The proportion who had received intervention services in the last year stabilized. CONCLUSIONS: HIV prevalence in MSM populations is rapidly and widely distributed. MSM who are in heterosexual marriages may be a bridge group transmitting HIV to their heterosexual partners. The risky sexual behavior among MSM will remain a serious and important driver of China's AIDS epidemic over the next period of time. Intervention need to be strengthened, as does the effective implementation of measures to control AIDS and prevent it from spreading further.

[Epidemic characteristics of HIV/AIDS among men who have sex with men from 2006 to 2010 in China].

OBJECTIVE: To analyze the epidemic characteristics of HIV/AIDS among men who have sex with men (MSM) from 2006 to 2010 in China, and to provide evidence for the development of prevention and control measures. METHODS: Through the network reporting information system. The distribution of MSM transmission was analyzed. Through sentinel surveillance system from 2006 to 2010, data was gathered and analyzed for HIV/AIDS positive rates and condom use to describe the epidemic characteristics of HIV/AIDS among MSM. RESULTS: Data from HIV/AIDS case reporting system showed that the proportion of MSM transmission was on the rise (from 1.5% in 2006 to 10.8% in 2010), becoming the fastest growth of spreading. Compared with other routes of spreading, MSM transmission showed the following obvious characteristics: 15 to 29 years olds (54.6%), having higher culture background (senior high school graduated or above accounting for 69.8%), unmarried (64.8%), being cadres/teacher/doctor/retirees and students (accounted for 14.3% and 7.9%), with high mobility floating population (36.2%), being urban population (72.6%), having history of blood donation without payment (26.7% and 6.4%). In terms of location, they mainly lived in provinces as Beijing, Sichuan, Guangdong, Chongqing, Jiangsu, Zhejiang, Shanghai and Liaoning where economics were more developed. Data from HIV/AIDS sentinel surveillance system showed that, from 2006 to 2010, the HIV positive anti-body detection rate (median) was 3.4% among MSM in this country, much higher than among the female sex workers. Rate on condom usage (median) was 73.2%, lower than among the female sex workers. CONCLUSION: The proportion of HIV transmission among MSM was on the rapid rise from 2006 to 2010 in China. Through HIV/AIDS sentinel surveillance system, we found that the infection rate was high but the rate of condom usage was low among MSM. Factors as being 15 to 29 years olds, students and blood donors should be under major concern.

[HIV prevalence among populations at risk, using sentinel surveillance data from 1995 to 2009 in China].

OBJECTIVE: To effectively monitor the time trend of HIV prevalence and epidemic among injecting drug users (IDUs), female sex workers (FSWs), sexually transmitted disease (STD) clinic attendants, men who have sex with men (MSM) and pregnant women etc., to provide information for evaluation on strategies regarding comprehensive HIV prevention and effectiveness of intervention, in China. METHODS: Cross-sectional studies had been repeatedly conducted on sentinel surveillance program with uniformed questionnaire and collection of venous blood specimen among IDUs, FSWs, STD clinic attendants, MSM and pregnant women, from 1995 to 2009. RESULTS: HIV prevalence (median) among IDUs had been increasing rapidly since 1996, reaching the plateau (19.2%) in 1999-2000, then gradually decreasing in 2001-2003, and leveling off since 2004 in those relatively hard-hit epidemic provinces. HIV prevalence among drug users had increased a bit since 2001, achieving high level (2.9%) in 2004 before leveling off, showing a slight downward trend in the past two years among the medially-hit epidemic provinces, while it maintained at a low level in those low epidemic provinces. HIV prevalence (median) among FSWs had been slightly increasing, reaching a high level (1.5%) in 1999, then decreased and maintained at a low level in relatively hard-hit provinces. HIV prevalence among FSWs maintained at a low level in medially-hit and low epidemic provinces. HIV prevalence (median) among STD clinic attendants had been maintained at a lower level, lower than 0.7%. HIV prevalence among MSM had been consistently greater than 1%, and was increasing year by year, becoming one of the most important drivers of the HIV/AIDS epidemic over the past years. HIV prevalence (median) among pregnant women had slightly been increasing since 1997, then leveling off over the past years in those relatively hard-hit provinces (0.3%). HIV prevalence among pregnant women had maintained at a low level in the medial and low epidemic provinces. CONCLUSION: Data from sentinel surveillance programs showed a leveling-off situation on HIV prevalence rates among IDUs, FSWs, sexually transmitted infections clinic patients and pregnant women. However, HIV prevalence among MSM had increased significantly since 2005, indicating the high speed of transmission among this population. Epidemic among IDUs had still been concentrated in those relatively hard-hit epidemic provinces. As for FSWs and STD patients, the overall epidemic remained at low level, but the areas of epidemic kept expanding.

[Study on the HIV infection status, characteristics of AIDS-related behaviors and risk factors among men attending the sexually transmitted disease clinics].

OBJECTIVE: To understand the status on AIDS awareness, AIDS-related behaviors, risk factors on HIV infection status among 15 - 90 years or older men at the sexually transmitted disease clinics. METHODS: Data from the 2009 and 2010 national sentinel surveillance system, regarding men attending sexually transmitted disease clinics was collected from Guangdong, Guangxi, Henan, Sichuan, Yunnan and Jiangxi provinces, where the AIDS epidemic among 15 - 90 years or older population was serious. Data was uploaded to National Center for AIDS/STD Control and Prevention (NCAIDS) through the comprehensive AIDS control and prevention information system. Data was then analyzed by SPSS 18.0. RESULTS: A total of 64 003 pieces of data were collected. Among them, 8783 (13.7%) were related to men at ≥ 50 years or older, and to men 15 - 49 years older were 55 220. The rates on the awareness of AIDS knowledge were from 69.6% vs. 80.1%, on frequently having had commercial sexual contacts in the last three months were between 34.1% vs. 36.6%, on having had casual sexual contact in the last three months were 18.7% vs. 28.4%, on having had homosexual anal intercourse as 0.7% vs. 1.4%. The rates of taking HIV antibody testing in the last year (14.3% vs. 17.1%) among this population were all significantly lower than the rate among the 15 to 49 years age group. However, the HIV-positive rate among the older age group (fifty years of age or older) was significantly higher than the rate among 15 to 49 year age group (1.1% vs. 0.7%). Regard the fifty years of age or older men. Data from the multivariate logistic regression analysis demonstrated that factors as: having regular partner (OR = 0.588, P = 0.034), having homosexual anal intercourse (OR = 5.226, P = 0.006) were associated with positivities of HIV antibody. CONCLUSION: High-risk sexual behaviors, including homosexual anal intercourse were the major risk factors for men at ≥ 50 years or older age, related to the infection of HIV.

[Study on the natural history of HIV among former commercial plasma donors caused by contaminated plasma donation in central China].

OBJECTIVE: To investigate the natural history of HIV infection caused by contaminated plasma donation among former commercial plasma donors in China. METHODS: Ambispective cohort study among HIV/AIDS cases and suspected AIDS deaths was conducted from January 1, 1995 to March 31, 2008 in 7 administrative villages in Shangcai county of Henan province. Information regarding diagnostic criteria, deaths and anti-retrovirus treatment was collected. Incubation and survival time were calculated using Kaplan-Meier and life-tables method. Sensitive analysis on the time of outcome was conducted. RESULTS: A total number of 2569 cases of HIV infection including 483 suspected AIDS deaths were involved in a cohort. 200 patients with rapid progress (7.8%) and 337 long-term but non-progressive patients (13.1%) were identified. Results from the sensitive analysis showed that the median incubation period from HIV infection to AIDS was between 8.5 and 8.9 years, with incidence as 11.7 - 12.0 cases/100 person-years and the median survival time for HIV progression to death was from 8.8 to 10.7 years, with the death rate as 6.9 - 8.3 cases/100 person-years. The median survival time for AIDS patient was from 1.2 to 2.0 years, with death rate as 34.9 - 51.5 cases/100 person-years. CONCLUSION: According to sensitive analysis, the incubation period for HIV progression to AIDS, the median survival time for HIV progression to death and the median survival time for AIDS patient to death were 8.8 years, 1.2 years and 9.8 years, respectively.

[Situations and trends of HIV and syphilis infections among drug users in China, 1995 - 2009].

OBJECTIVE: To understand the characteristics and trends of HIV and syphilis infections among drug users. METHODS: Information was collected regarding HIV and syphilis epidemics, as well as on high risk behaviors from the HIV/AIDS surveillance system. Source of information was from HIV/AIDS case-reporting, sentinel surveillance and trend estimation, related to the changes of distribution among HIV positive drug users prevalence rates on HIV and syphilis together with their high risk behaviors. RESULTS: Scale number on drug users remained stable in the past six year (from 2003 - 2009), while the proportion of drug users decreased from 44.2% in 2005 to 25.8% in 2009. Based on the information from HIV/AIDS case reporting system, HIV sentinel surveillance data showed that the HIV prevalence of drug users was quite different from those of Southwestern to Northeastern parts of China. The HIV prevalence in Southwestern China was much higher than that of the Northeastern areas. Sentinel surveillance data showed that the average positive rates were 6.2% and 3.7% on HIV and syphilis, among the drug users. As for injecting drug users (IDU), the average rates on HIV antibody syphilis and HCV were 9.2% and 4.0% respectively. Series surveillance data indicated that the HIV epidemic expanded quickly among drug users from 1995 - 1999 but became plateaued after 2000 among the IDUs. HIV antibody positive rate remained at 9.0% - 10.0% in the past three years while syphilis fluctuated between 3.5% - 4.5% in the past three years. CONCLUSION: Drug users and IDUs still remained an important driven factor for HIV/AIDS epidemic in China, suggesting more specific strategies and methods should be developed, based on the characteristics and trends of HIV epidemic, to optimize the allocation HIV prevention and control resources.

[HIV/AIDS epidemic situation and data analysis among young students from 2006-2009 in China].

OBJECTIVE: To analyze the HIV/AIDS epidemic situation and related behavioral components among young students in the last years and to provide information for integrated control and prevention programs. METHODS: Data on young students (15 - 24 years) through case reporting system was collected from 2006 to 2009 and continuous sentinel surveillance data regarding 6 national sentinel sites carried out from 2006 to 2009 was also collected. The sentinel sites would include universities, junior college and secondary vocational colleges registered students, using cluster sampling phases method. Self-administered questionnaire survey and blood (HIV antibody testing and syphilis antibody testing) tests were carried out, with the sample size was about 800 cases per site per year. RESULTS: The number of case report on HIV/AIDS among the young students of 15 - 24 years age group had been rising. Similar trend was also observed on the number of reported cases over the years, accounting for the proportions of the total number of reported cases, as 0.39%, 0.50%, 0.83% and 1.02% respectively from 2006 to 2009. Sexual contacts continued to be the major route of transmission, with the increasing proportion of homosexual transmission. In the 6 national sentinel sites of young students which continuous surveillance was conducted during the period from 2006 to 2009, data showed the following facts as: proportion (median) of objects who admitted to have had sex, were: 4.3%, 4.5% and 6.1%, proportions (median) of commercial sex occurred in the past year were: 0.3%, 0.2% and 0.3%; proportions (median) of MSM occurred in the past year were: 0.7%, 0.2% and 0.2%; median of HIV antibody positive rate and syphilis antibody positive rate were 0%; median of awareness rate on HIV/AIDS were: 49.0%, 75.0% and 80.5%; proportion (median) of monitor objects who received intervention services in the past year were: 44.2%, 54.3% and 50.2% respectively. CONCLUSION: In recent years, the HIV/AIDS number through case reporting system on the young students under 15 - 24 years age group, was increasing, but the HIV prevalence among young students was still relatively low, in general. The main transmission was sexual. Some young students had been engaged in commercial sex and MSM activities. Health education should be strengthened to increase the awareness of young students on AIDS/STD prevention. It is necessary to take more effective intervention measures to decrease new infection and control HIV/AIDS epidemic among young students.

[Data analysis of national HIV comprehensive surveillance sites among female sex workers from 2004 to 2008].

OBJECTIVE: To monitor the time trend of behaviors change related to HIV/AIDS epidemic and HIV prevalence, and to provide information and basis for comprehensive HIV prevention responses and evaluation of intervention effectiveness among female sex workers in China. METHODS: During the year of 2004 to 2008, a series of cross-sectional surveys were conducted among female sex workers in community recruited in both entertainment places and in street, during the defined timeframe, a face-to-face interview was conducted with uniformed questionnaire; while, the venous blood specimen was collected. The sample size was 400 per site per survey. RESULTS: In 15 continuous national HIV comprehensive surveillance sites among female sex workers from 2004 to 2008, the median of HIV prevalence was 0.0%; Prevalence (median) of syphilis respectively: 0.5%, 1.8%, 1.6%, 1.8% and 1.0%. The median of target subjects who used condom in the last commercial sex was: 81.8%, 80.5%, 84.6%, 87.0% and 88.9% respectively; the median of always used condom in commercial sex during the last month: 65.8%, 59.6%, 60.3%, 59.8% and 73.7%. The median of awareness rate on HIV/AIDS transmission of female sex workers was: 74.3%, 84.1%, 65.2%, 66.0% and 74.3%. The median of target subjects who attended HIV VCT services were: 12.4%, 20.4%, 25.8%, 25.3% and 31.7%. The median of the proportion of female sex workers who reached intervention in last year respectively: 46.4%, 76.1%, 72.1%, 95.0% and 90.8%. CONCLUSION: Condom use and HIV awareness rate need to enhance further among female sex workers. The proportion of female sex workers who attended VCT and knew their HIV testing result and the proportion of female sex workers who reached intervention in last year both increase. HIV prevalence rate among female sex workers is generally low, but high risk behaviors are still alarming. It is necessary to take more comprehensive and effective prevention measures and intervention.

[Retrospective research on proportion of HIV related death causes in nine counties in China].

OBJECTIVE: To investigate the proportion of HIV related death cause, and its years of potential life lost (YPLL) and work years of potential life lose (WYPLL) in project counties. METHOD: According to the protocol of the third national death causes surveillance and HIV related death causes surveillance, retrospective study was implemented including baseline investigation of deaths' name list, demography information, door-to-door interview and death causes deduction in Gejiu, Ruili and Longchuan county in Yunnan province, Yangdong county in Guangdong province, Luzhai county in Guangxi zhuang Autonomous Region, Weishi and Zhecheng county in Henan province, Xishui county in Hubei province and Gu'an county in Hebei province. RESULTS: The study was conducted among nine counties located in seven provinces. A total of 118 719 cases were included, raw mortality was 5.83 per thousand, 2002 death cases were related to HIV, which contributed 1.67% of total deaths. The average age of HIV death was 38.03 yearsow, which was earlier than the non-HIV-related life-span (63.10 years). The YPLL and WYPLL of HIV death was 33.80 years and 20.50 years, respectively, which had contributed the second highest average YPLL. CONCLUSION: HIV has an important proportion among all death causes, and has contributed severe average YPLL and WYPLL.

Caspase-3 antisense oligodeoxynucleotides inhibit apoptosis in gamma-irradiated human leukemia HL-60 cells.

To study the inhibitory effects of caspase-3 mRNA antisense oligodeoxynucleotides (ASODNs) on apoptosis, we designed four ASODNs targeting different regions of caspase-3 mRNA and transfected them into human leukemia HL-60 cells. The transfected cells were given 10 Gy gamma-irradiation followed by incubation for 18 h and measurement of apoptosis and caspase-3 expression. Our results showed that ASODN-2 targeting the 5' non-coding region of sites -62 to -46, and ASODN-3 targeting the 5' coding region of sites -1 to 16, both reduced apoptosis measured by gel electrophoresis and flow cytometry. Hoechst 33258 staining and TUNEL assay revealed that apoptotic indexes in the ASODN-2 and ASODN-3 groups were significantly lower than those in the untransfected and mismatched oligodeoxynucleotide (MODN) groups. Immunocytochemistry, Western blotting and RT-PCR showed that expression levels of caspase-3 protein and mRNA in both ASODN-2 and ASODN-3 groups were decreased compared with those in the untransfected and MODN groups. In conclusion, caspase-3 mRNA ASODNs can inhibit gamma-radiation-induced apoptosis of HL-60 cells and reduce expression of caspase-3 protein and mRNA. The results suggest that antisense approach may be useful for therapeutic treatment of certain neurodegenerative diseases in which apoptosis is involved.

Overexpression of PTEN suppresses growth and induces apoptosis by inhibiting the expression of survivin in bladder cancer cells.

The tumor suppressor gene PTEN, which encodes a multifunctional phosphatase protein, is mutated in a variety of human cancers. Several reports have indicated that it has growth-suppressive and proapoptosis properties and displayed an altered expression pattern during human oncogenesis. Overexpression of PTEN leads to decreasing cell growth and tumorigenicity in vitro and in vivo. In the present study, we further demonstrated that overexpression of PTEN mediated by adenovirus suppressed bladder cancer cell growth and significantly induced apoptosis, through downregulating of survivin and activating of caspase cascades. Our results indicate that Ad-PTEN exerts its tumor suppressive effect on bladder cancer cells through inhibiting survivin and upregulating caspase-related proteins. Thus Ad-PTEN may be potentially therapeutic for the treatment of bladder cancers.

[Caspase-3 antisense oligodeoxynucleotides inhibit caspase-3 expression and apoptosis of gamma-irradiated HL-60 cells].

It has been shown that gamma -irradiation induces apoptosis of the human promyeloid leukemia cell line HL-60, but the mechanism remains unclear. To explore the effect of caspase-3 in this apoptotic model, antisense oligodeoxynucleotides (ASODNs) targeting 5'-noncoding region (ASODN-1) and initial translation region (ASODN-2) of caspase-3 mRNA were designed, synthesized and introduced into HL-60 cells by means of liposome-mediated transfection followed by gamma-irradiation in the present study. The TUNEL assay was used for morphological analysis of HL-60 cell apoptosis. Immunocytochemical staining, Western blotting and RT-PCR were, respectively, performed for detecting expression of caspase-3 and its mRNA. HL-60 cells transfected with mismatched oligodeoxynucleotide (MODN) or untransfected were taken as the control groups. The TUNEL assay showed that the percentages of HL-60 cell apoptosis induced by gamma-Irradiation in both ASODN-1 and ASODN-2 groups were significantly reduced compared with those in the control group (P<0.01) when the final transfection concentration was > or = 3 micromol/L. Immunocytochemistry demonstrated that in the ASODN-1 and ASODN-2 groups, caspase-3 positive cell percentages were reduced and average gray values of the positive cells increased significantly compared with those in the control group (P<0.01). Western blotting found that procaspase-3 expression in HL-60 cells of the ASODNs groups was decreased,and it was lower in the ASODN-1 group than in the ASODN-2 group. RT-PCR revealed marked expression of caspase-3 mRNA in HL-60 cells of the control group. Expression of caspase-3 mRNA was decreased after ASODNs transfection. Furthermore, ASODN-1 was more effective in inhibiting HL-60 cell apoptosis (P<0.05) and caspase-3 expression (P<0.01) than ASODN-2. These results indicate that caspase-3 mRNA ASODNs prevent HL-60 cells from apoptosis induced by gamma-radiation,and reduce expression of caspase-3 and its mRNA. These effects are dose dependent in a certain range.

[A retrospective cohort study on the natural history of human immunodeficiency virus among formal plasma donors in central China].

OBJECTIVE: To study the time span from human immunodeficiency virus (HIV) infection to full bloom AIDS and to death. METHODS: Among formal plasma donors (FPD) from 2 counties in central China, 178 HIV cases were confirmed by western blot method but received no ARV treatment under a retrospective cohort study. Data on personal information, history on plasma donation, as well as dates regarding HIV diagnostic confirmation, onset of AIDS and death was collected through reviewing laboratory and medical records thus the course of disease for each case was identified. Incubation and survival time were calculated, using Kaplan-Meier method. RESULTS: The incubation period was 8.31 years on average (95% CI: 8.04 - 8.58 years). The cumulative incidence rate of AIDS was 6.41/100 person-years after HIV infection. The survival time was 9.90 (95% CI: 8.20 - 11.60) months after the onset of AIDS. CONCLUSION: According to the findings from this study, the average incubation was shorter than 9.5 years which was reported by UNAIDS. Comparing with figures that had been reported by UNAIDS, AIDS incidence rate among this population was lower within 6 years but higher since the 7th year on after being infected but the survival time was shorter.