Cryptotanshinone Inhibits the Growth of HCT116 Colorectal Cancer Cells Through Endoplasmic Reticulum Stress-Mediated Autophagy.

Among cancers, colorectal cancer (CRC) has one of the highest annual incidence and death rates. Considering severe adverse reactions associated with classical chemotherapy medications, traditional Chinese medicines have become potential drug candidates. In the current study, the effects of cryptotanshinone (CPT), a major component of Salvia miltiorrhiza Bunge (Danshen) on CRC and underlying mechanism were explored. First of all, data from in vitro experiments and in vivo zebrafish models indicated that CPT selectively inhibited the growth and proliferation of HCT116 and SW620 cells while had little effect on SW480 cells. Secondly, both ER stress and autophagy were associated with CRC viability regulation. Interestingly, ER stress inhibitor and autophagy inhibitor merely alleviated cytotoxic effects on HCT116 cells in response to CPT stimulation, while have little effect on SW620 cells. The significance of apoptosis, autophagy and ER stress were verified by clinical data from CRC patients. In summary, the current study has revealed the anti-cancer effects of CPT in CRC by activating autophagy signaling mediated by ER stress. CPT is a promising drug candidate for CRC treatment.

Endoplasmic reticulum stress, cell death and tumor: Association between endoplasmic reticulum stress and the apoptosis pathway in tumors (Review).

External and internal stimuli are often involved in the pathogenesis of tumors, and the deterioration of endoplasmic reticulum (ER) function within cells is also an important etiological factor of tumorigenesis resulting in the impairment of the endoplasmic reticulum, which is termed ER stress. The ER is an organelle that serves a crucial role in the process of protein synthesis and maturation, and also acts as a reservoir of calcium to maintain intracellular Ca2+ homeostasis. ER stress has been revealed to serve a critical role in tumorigenesis. In the present review, the association between ER stress­related pathways and tumor cell apoptosis is examined. Primarily, the role of ER stress in tumor cell apoptosis is discussed, and it is stipulated that ER stress, induced by drugs both directly and indirectly, promotes tumor cell apoptosis.

Crustal fingering facilitates free-gas methane migration through the hydrate stability zone.

Widespread seafloor methane venting has been reported in many regions of the world oceans in the past decade. Identifying and quantifying where and how much methane is being released into the ocean remains a major challenge and a critical gap in assessing the global carbon budget and predicting future climate [C. Ruppel, J. D. Kessler. Rev. Geophys. 55, 126-168 (2017)]. Methane hydrate ([Formula: see text]) is an ice-like solid that forms from methane-water mixture under elevated-pressure and low-temperature conditions typical of the deep marine settings (>600-m depth), often referred to as the hydrate stability zone (HSZ). Wide-ranging field evidence indicates that methane seepage often coexists with hydrate-bearing sediments within the HSZ, suggesting that hydrate formation may play an important role during the gas-migration process. At a depth that is too shallow for hydrate formation, existing theories suggest that gas migration occurs via capillary invasion and/or initiation and propagation of fractures (Fig. 1). Within the HSZ, however, a theoretical mechanism that addresses the way in which hydrate formation participates in the gas-percolation process is missing. Here, we study, experimentally and computationally, the mechanics of gas percolation under hydrate-forming conditions. We uncover a phenomenon-crustal fingering-and demonstrate how it may control methane-gas migration in ocean sediments within the HSZ.

Syphilis associated with recreational drug use, depression and high-risk sexual behaviour in men who have sex with men: a case-control study in China.

OBJECTIVE: We investigated syphilis prevalence among men who have sex with men (MSM) in China, as well as potential risk factors. Our principal hypothesis was that syphilis would be associated with the use of recreational drugs such as methamphetamines. METHODS: From April to October 2013, we used several methods to recruit MSM in Qingdao, collecting demographic/behavioural information via self-administrated questionnaires. Trained health workers collected blood for the Treponema pallidum particle assay (TPPA) with positives confirmed by a toluidine red unheated serum test. We used an unmatched case-control study to identify factors that might predict syphilis infection using multivariable logistic regression. RESULTS: We recruited 447 MSM who agreed to participate and who completed syphilis testing. Of 71 (15.9%) syphilis-positive MSM, 44 (62.0%) used drugs. Of 376 (84.1%) syphilis-negative MSM, 186 (49.5%) used drugs. We found a positive association with syphilis for any recreational drug use (crude OR (cOR) 1.7, 95 % CI 1.0 to 2.8), frequent methamphetamine use (cOR 2.4, 95% CI 1.1 to 5.3) and multiple drug use (adjusted OR (aOR) 3.4, 95% CI 1.3 to 9.2). Syphilis-positive men were more likely to have a higher physical depression score (aOR 5.2, 95% CI 1.1 to 24.4), be > 30 years old (aOR 2.7, 95% CI 1.5 to 4.8), report a prior STI (aOR 4.1, 95% CI 2.3 to 7.3) and report a sex party experience (aOR 2.2, 95% CI 1.1 to 4.4). CONCLUSIONS: Recreational drug use, depression and high-risk sexual behaviours were associated with syphilis infection among MSM in China. Only a multifaceted approach is likely be effective in control of both syphilis and HIV .

Nonequilibrium Thermodynamics of Hydrate Growth on a Gas-Liquid Interface.

We develop a continuum-scale phase-field model to study gas-liquid-hydrate systems far from thermodynamic equilibrium. We design a Gibbs free energy functional for methane-water mixtures that recovers the isobaric temperature-composition phase diagram under thermodynamic equilibrium conditions. The proposed free energy is incorporated into a phase-field model to study the dynamics of hydrate formation on a gas-liquid interface. We elucidate the role of initial aqueous concentration in determining the direction of hydrate growth at the interface, in agreement with experimental observations. Our model also reveals two stages of hydrate growth at an interface-controlled by a crossover in how methane is supplied from the gas and liquid phases-which could explain the persistence of gas conduits in hydrate-bearing sediments and other nonequilibrium phenomena commonly observed in natural methane hydrate systems.

Poor and enantioselective bioavailability of naftopidil enantiomers is due to extensive and stereoselective metabolism in rat liver.

Racemic naftopidil (NAF) is used to treat benign prostatic hyperplasia (BPH) and prostatic cancer (PCa). It exhibits greater efficacy but requires higher dose than other ɑ1-adrenoceptor blockers because of its poor bioavailability. It was previously shown that bioavailability of S(-)-NAF (14.5%) was twice that of R(+)-NAF (6.8%). The present study aimed to elucidate the major factors contributing to the poor and enantioselective bioavailability of NAF. First, absorption of NAF enantiomers was examined using a perfusated intestinal model. NAF enantiomers were found to be equally and highly permeable in all segments of the intestine. Second, the metabolites formed in different parts of the intestine and in bile were investigated. Glucuronidation of NAF enantiomers was found to occur primarily in the liver. Third, a new method consisting of ultra performance liquid chromatography coupled with triple-quadruple mass spectrometry (UPLC-MS/MS) was employed to quantify and calculate the pharmacokinetic parameters of NAF enantiomers and their glucuronides after the enantiomers were intravenously injected into rats. The amounts of R(+)-NAF glucuronide (R(+)-NAF-G) and S(-)-NAF glucuronide (S(-)-NAF-G) were six-fold higher than that of R(+)-NAF, and three-fold higher than that of S(-)-NAF. Glucuronidation of S(-)-NAF was faster than that of R(+)-NAF, but the conjugated amount was half of that of R(+)-NAF. Thus, bioavailability of S(-)-NAF was twice that of R(+)-NAF. In conclusion, extensive phase II metabolism in the liver significantly contributes to the low bioavailability of NAF enantiomers. Glucuronidation is the most important metabolic pathway for NAF enantiomers. Glucuronidation of S(-)-NAF is faster but occurs to a lesser extent than that of R(+)-NAF.

Enhancing HIV Testing and Treatment among Men Who Have Sex with Men in China: A Pilot Model with Two-Rapid Tests, Single Blood Draw Session, and Intensified Case Management in Six Cities in 2013.

OBJECTIVES: To explore models to improve HIV testing, linkage to care and treatment among men who have sex with men (MSM) in cooperation with community-based organizations (CBOs) in China. METHODS: We introduced a new model for HIV testing services targeting MSM in six cities in 2013.These models introduced provision of rapid HIV testing by CBO staff and streamlined processes for HIV screening, confirmation of initial reactive screening results, and linkage to care among diagnosed people. We monitored attrition along each step of the continuum of care from screening to treatment and compared program performance between 2012 and 2013. According to the providers of two rapid tests (HIV screening), four different services delivery models were examined in 2013: Model A = first screen at CDC, second at CDC (Model A = CDC+CDC), Model B = first and second screens at CBOs (Model B = CBO+CBO), Model C = first screen at CBO, second at Hospital (Model C = CBO+Hosp), and Model D = first screen at CBO, second at CDC (Model D = CBO+CDC). Logistic regressions were performed to assess advantages of different screening models of case finding and case management. RESULTS: Compared to 2012, the number of HIV screening tests performed for MSM increased 35.8% in 2013 (72,577 in 2013 vs. 53,455 in 2012). We observed a 5.6% increase in proportion of cases screened reactive receiving HIV confirmatory tests (93.9% in 2013 vs. 89.2% in 2012, χ2 = 48.52, p<0.001) and 65% reduction in loss to CD4 cell count tests (15% in 2013 vs. 43% in 2012, χ2 = 628.85, p<0.001). Regarding linkage to care and treatment, the 2013 pilot showed that the Model D had the highest rate of loss between screening reactive and confirmatory test among the four models, with 18.1% fewer receiving a second screening test and a further 5.9% loss among those receiving HIV confirmatory tests. The Model B and the Model C showed lower losses (0.8% and 1.3%) for newly diagnosed HIV positives receiving CD4 cell count tests, and higher rates of HIV positives referred to designated ART hospitals (88.0% and 93.3%) than the Model A and Model D (4.6% and 5.7% for CD4 cell count test, and 68.9% and 64.4% for referring to designated ART hospitals). The proportion of cases where the screening test was reactive that were commenced on ART was highest in Model C; 52.8% of cases commenced on ART compared to 38.9%, 34.2% and 21.1% in Models A, B and D respectively. Using Model A as a reference group, the multivariate logistic regression results also showed the advantages of Models B, C and D, which increased CD4 cell count test, referral to designated ART hospitals and initiation of ART, when controlling for program city and other factors. CONCLUSIONS: This study has demonstrated that involvement of CBOs in HIV rapid testing provision, streamlining testing and care procedures and early hospital case management can improve testing, linkage to, and retention in care and treatment among MSM in China.

Thermodynamic coarsening arrested by viscous fingering in partially miscible binary mixtures.

We study the evolution of binary mixtures far from equilibrium, and show that the interplay between phase separation and hydrodynamic instability can arrest the Ostwald ripening process characteristic of nonflowing mixtures. We describe a model binary system in a Hele-Shaw cell using a phase-field approach with explicit dependence of both phase fraction and mass concentration. When the viscosity contrast between phases is large (as is the case for gas and liquid phases), an imposed background flow leads to viscous fingering, phase branching, and pinch off. This dynamic flow disorder limits phase growth and arrests thermodynamic coarsening. As a result, the system reaches a regime of statistical steady state in which the binary mixture is permanently driven away from equilibrium.

Partner notification in cooperation with community-based organizations among HIV-positive men who have sex with men in two Chinese cities.

The epidemic of HIV/AIDS among Chinese men who have sex with men (MSM) is rapidly escalating. We implemented partner notification among HIV-infected MSM, cooperating with MSM-serving community-based organizations (CBOs) in two Chinese cities from June 2014 to May 2015. CBOs participated in identifying new HIV-positive MSM utilizing rapid HIV tests and partner notification among index cases. 253 index cases were recruited and 275 sexual partners were notified and tested with 10.5% screened positive. Compared with previously identified index cases, the proportion of contactable sexual partners of newly identified index cases was higher, but the testing rate was lower (p < 0.001). Overall, 83.7% of sexual partners were casual with a contactable rate of 24.9% and a HIV testing rate of 71.1%. Having no contact information for sexual partners and fear of disclosure of HIV status are the main reasons for declining partner notification. It is feasible and effective to perform partner notification in cooperation with CBOs serving Chinese MSM.

[The survival and development conditions of community-based organizations for HIV/AIDS prevention and control among men who have sex with men in three Chinese cities].

OBJECTIVE: To investigate the survival and development conditions of community-based organizations (CBOs) for HIV/AIDS prevention and control among men who have sex with men (MSM) in Chinese cities including Shanghai, Hangzhou, Chongqing. METHODS: This study employed both qualitative (focus groups) and quantitative (questionnaire survey) methods to obtain information from 15 MSM CBOs in three Chinese cities. RESULTS: The mean work time of the 15 CBOs for HIV/AIDS prevention and control among MSM was 6.7 years (2.1-11.3 years), and the majority of their funds was from international cooperation projects (80 447 000 RMB, 73.0%) from 2006 to 2013. The survival cost of MSM CBOs apart from expenditure of activities was 2 240-435 360 RMB per year. As it was shown in the graph, the survival and development of MSM CBOs was closely related to the development of international cooperation projects. There was a few small size MSM CBOs taking part in the prevention and control of HIV/AIDS and their work content was limited before 2006. From 2006 to 2008, some international cooperation projects were launched in China, such as the China Global Fund AIDS project and the China-Gates Foundation HIV Prevention Cooperation program. As a result, the number of MSM CBOs was increased sharply, and both the scale and 2012, the performance of these programs further promote the establishment of new MSM CBOs and the development of all MSM CBOs with regard to the work places, full-time staffs, work contents, work patterns and the specific targeted population. After 2012, most international cooperation programs were completed and the local department of disease prevention and control continued to cooperate with MSM CBOs. However, the degree of support funds from the local department was different among different regions. Where the funds were below the half of program funds, the development of MSM CBOs ceased and work slowed down. Besides, there were still some constraints for the survival and development of MSM CBOs, such as insufficient funds, no legitimate identity, the outflow of talents and the unsustainable development. CONCLUSION: The survival and development of MSM CBOs was closely related to the development of international cooperation projects in China. Some departments of disease prevention and control took over the cooperation with MSM CBOs when the international cooperation projects were completed. Given the survival cost of MSM CBOs and the constraints of MSM CBOs development, it needs further investigation on how to ensure the local departments of disease prevention and control to take over the cooperation with MSM CBOs and how to cooperate with MSM CBOs.

[Syphilis infection and its high risk factors among men who have sex with men by different recruitment channels].

OBJECTIVE: To understand the syphilis infection and its high risk factors among men who have sex with men (MSM) recruited from different channels. METHODS: Supported by the China-Gates Foundation HIV program from July to December 2011, we cooperated with community based organizations to conduct syphilis testing intervention among MSM from 14 cities (Beijing, Shanghai, Tianjin, Chongqing, Harbin, Shenyang, Qingdao, Xi'an, Nanjing, Wuhan, Hangzhou, Changsha, Kunming, and Guangzhou) and one province (Hainan province). Participants were recruited from different channels by the staff of local CBOs, Demographic (e.g. age, marital status, and education) and behavioral (e.g. condom use and sexual partners) data were collected using anonymous questionnaires. Blood samples were also collected to test for syphilis. A total of 34 100 MSM participated in the survey. Participants were excluded from data analysis (1 399, 4.1%) if they did not receive syphilis tests or they completed less than 80.00% of the key questions in the survey. Chi-square tests were used to understand the socio-demographic and behavioral differences between each group. Results of syphilis tests were also compared. Logistic regression models were used to test the statistical significance of these differences. RESULTS: A total of 32 701 MSM were enrolled and received syphilis testing. The average age of participates was 30.96 ± 9.57. And among them, 2 284 cases (7.0%) were recruited from gay bathhouses, 4 774 (14.6%) from gay bars, 6 266 (19.2%) from the internet, 1 997 (6.1%) from the parks/toilets and 17 380 (53.1%) from other channels. MSM recruited from the bathhouses had the highest syphilis infection rate than other 4 groups: gaybars (4.5%, 216/4 774), internet (6.7%, 422/6 266), parks/toilets (8.3%, 166/1 997), other channels (6.4%, 1 103/17 380) (χ² = 164.58, P < 0.001). The multivariate logistic regression analysis showed that being > 20 years of age (P < 0.001), having more than 2 homosexual partners in recent 3 months (8.0% (1 408/17 714), OR (95% CI) = 1.44 (1.04-1.98)), having no sex with females in past 3 months (6.8% (1 446/21 276), OR (95% CI) = 1.25 (1.07-1.46)), and not using condom at last anal sex (8.0% (769/9 668), OR (95% CI) = 1.13 (1.03-1.25)) were associated with a higher probability of being infected with syphilis. Whereas MSM married (7.2% (456/6 305), OR (95% CI) = 0.84 (0.73-0.98)), having a college or a higher education (5.3% (829/15 684), OR (95% CI) = 0.60 (0.53-0.67)), being local residents (6.5% (1 843/28 185), OR (95% CI) = 0.73 (0.61-0.87)) and living in the local province of project cities (6.6% (170/2 593), OR (95% CI) = 0.67 (0.53-0.85)) were protective factors. CONCLUSION: MSM who were recruited from gay bathhouses have a higher rate of syphilis infection than those in channels relatively. They are older, with low education levels and high-risk sexual behaviors. Tailored interventions are required in the future, especially for MSM from gay bathhouses.

Current insights into computer-aided immunotherapeutic design strategies.

Drug designing costs as well as design of immunotherapeutic agents could be nearly halved through the involvement of computer-aided drug designing methods in discovery and research. The inter-disciplinary, time-, and money-consuming process of drug discovery is amended by the development of drug designing, the technique of creating or finding a molecule that can render stimulatory or inhibitory activity upon various biological organisms. Meanwhile, the advancements made within this scientific domain in the last couple of decades have significantly modified and affected the way new bioactive molecules have been produced by the pharmaceutical industry. In this regard, improvements made in hardware solutions and computational techniques along with their efficient integration with biological processes have revolutionized the in silico methods in speeding up the lead identification and optimization processes. In this review, we will discuss various methods of recent computer-aided drug designing techniques that forms the basis of modern day drug discovery projects.

High risks of HIV transmission for men who have sex with men--a comparison of risk factors of HIV infection among MSM associated with recruitment channels in 15 cities of China.

OBJECTIVE: While the HIV epidemic varies greatly by region and population group throughout China, the HIV incidence among men who have sex with men (MSM) continues to rise at an alarmingly fast pace. We seek to analyze the risk factors associated with HIV infection among MSM recruited from different channels in large urban centers across China, in an attempt to shed light on the design of future targeted intervention strategies. METHODS: A total of 33,684 MSM from 14 cities and one province were recruited from July to December 2011. Demographic (e.g. age, marital status, education) and behavioral (e.g. condom use, HIV testing history) data were collected using information collection cards. Blood samples were also collected to test for HIV and Syphilis. RESULTS: Participants were recruited from five different channels, and all demonstrated distinct characteristics. The overall rate of positive HIV screening was 6.27% and the rate of syphilis infection was 6.50%. Participants recruited from bathhouses had the highest HIV (11.80%) and syphilis infection rates (11.20%). Participants who were infected with syphilis had the highest HIV-positive screening rate (13.75%; 95% CI OR, 2.33-3.06). living in the southwest region of the country (11.64%; OR=2.76, 95%CI OR 2.19-3.47), Being >20 years of age (P<0.001), living in the southwest region of the country (OR=2.76, 95%CI 2.19-3.47), not having sex with female over the previous 3 months (OR=1.27, 95%CI 1.09-1.48), no condom use during the last anal intercourse (OR=1.54, 95%CI 1.39-1.70) and other factors were all associated with a higher probability of having an HIV-positive test result. CONCLUSION: Depending on the way they are recruited, more targeted interventions are required to prevent the spread of HIV/AIDS among MSM with different characteristics and behaviors. Results from this study could provide evidence for researchers to conduct further studies and policy-makers to establish more effective and strategic interventions for MSM in China.

Promising Anti-influenza Properties of Active Constituent of Withania somnifera Ayurvedic Herb in Targeting Neuraminidase of H1N1 Influenza: Computational Study.

Neuraminidase (NA) is a membrane surface antigen which helps in the release of influenza viruses from the host cells after replication. Anti-influenza drugs such as zanamivir bind with eight highly conserved functional residues (R118, D151, R152, R224, E276, R292, R371, and Y406) in the active site of NA, thus restricting the viral release the from host cells. Binding of the drug in active site inhibits the ability of enzyme to cleave sialic acid residues on the cell membrane. Reports on the emergence of zanamivir-resistant strains of H1N1 Influenza virus necessitated a search for alternative drug candidates, preferably from plant source due to their known benefits such as less or no side effects, availability, and low cost. Withaferin A (WA), an active constituent of Withania somnifera ayurvedic herb, has been shown to have a broad range of medicinal properties including its anti-viral activity. The present study demonstrated that WA has the potential to attenuate the neuraminidase of H1N1 influenza. Our docking and simulation results predicted high binding affinity of the WA toward NA and revealed several interesting molecular interactions with the residues which are catalytically important during molecular dynamic simulations. The results presented in the article could be of high importance for further designing of target-specific anti-influenza drug candidates.

Case finding advantage of HIV rapid tests in community settings: men who have sex with men in 12 programme areas in China, 2011.

We sought to describe the advantage of rapid tests over ELISA tests in community-based screening for HIV among men who have sex with men (MSM) in urban areas of China. Data of 31,406 screening tests conducted over six months in 2011 among MSM across 12 areas were analyzed to compare the differences between those receiving rapid testing and ELISA. Rapid tests accounted for 45.8% of these screening tests. The rate of being screened positive was 7.2% among rapid tests and 5.3% for ELISA tests (χ(2 )= 49.161, p < 0.001). This advantage of rapid test in HIV case finding persisted even when socio-demographic, behavioural, screening recruitment channel and city were controlled for in logistic regression (exp[beta] = 1.42, p < 0.001, 95% CI = 1.27,1.59). MSM who received rapid tests, compared with those tested by ELISA, were less likely to use condoms during last anal sex (50.8% vs. 72.3%, χ(2 )= 1706.146, p < 0.001), more likely to have multiple sex partners (55.7% vs. 49.5%, χ(2 )= 238.188, p < 0.001) and less likely to have previously undergone HIV testing (38.8% vs. 54.7%, χ(2 )= 798.476, p < 0.001). These results demonstrate the robustness of the advantage of rapid tests over traditional ELISA tests in screening for MSM with HIV infection in cooperation with community-based organizations in urban settings in China.

[The feasibility of Community Health Service Center-based HIV prevention and intervention in China].

OBJECTIVE: To explore and analyze the feasibility of Community Health Service Center(CHSC)-based HIV prevention and intervention in China. METHODS: Data on case finding and case management indexes were collected from 42 CHSCs in 8 cities from November, 2011 to December, 2012, and complemented by questionnaires to investigate the willingness to accept community-based HIV services among health care providers and the service targets. RESULTS: During November, 2011 and December, 2012, 6 729 person-times HIV tests were carried out among MSM in the cooperation between CHSCs and CBOs, and 235 HIV positives were found. A total of 40 CHSCs among 42 have conducted HIV rapid tests. The sample sources were broad and the HIV screening positive detection rate from high-risk populations in key divisions of CHSCs 0.66% (38/5 769) was higher than that in outreach high-risk populations 0.41% (15/3 623) and people receiving physical check 0.31% (20/6 532). HIV positive detection rate in CHSCs was higher 0.4% (96/23 609) than that in conventional medical institutions 0.1% (11 870/9 644 944) and newly found positives among the confirmed positives was a little lower 73.7% (56/76) than conventional programs 80.1% (8 038/10 039). The case follow-up and CD4(+) T cell testing rates in CHSCs were 100.0% (1 046/1 046) and 99.1% (1 037/1 046), respectively. The testing cost was 6.1 RMB per person on average, and the cost of 1 case found positive was 2 727.3 RMB on average. Among 361 service providers, 68.1% (246)and 91.4% (330) service providers were willing to be involved in AIDS response and support HIV service in local CHSCs. Among 755 service targets including people who seek health care in key divisions of CHSCs, MSM, and high-risk populations in local communities, 77.3% (348), 73.9% (173) and 78.1% (57) were willing to accept free HIV tests in local CHSCs. CONCLUSION: The effect of case finding and case management in CHSCs was good and the cost of conducting HIV tests and finding new cases were relatively low, meanwhile, most of the service provides in CHSCs and service targets support HIV service in local CHSCs. The future CHSC-based HIV prevention and intervention was feasible.

Identification of human cytochrome P450 isozymes involved in the metabolism of naftopidil enantiomers in vitro.

OBJECTIVES: Naftopidil (NAF) is a chiral compound with two enantiomers (R(+)-NAF and S(-)-NAF) and is used as a racemic mixture in clinical practice. This study aims to investigate the metabolism of NAF enantiomers in pooled human liver microsomes (HLMs) and cytochrome P450 isozymes (CYPs) involved in their metabolism. METHODS: Metabolism studies were conducted in vitro using HLMs. Specific chemical inhibitors and recombinant human CYPs were used to confirm that the CYPs contributed to the metabolism of NAF enantiomers. KEY FINDINGS: Three metabolites were found and characterized in the HLMs incubations from R(+)-NAF and S(-)-NAF, respectively. The major metabolic pathways of R(+)-NAF and S(-)-NAF were demethylation and hydroxylation. CYP2C9 and CYP2C19 inhibitors strongly inhibited R(+)-NAF metabolism, and CYP1A2, CYP2C8, CYP2D6 and CYP3A4/5 inhibitors moderately inhibited R(+)-NAF metabolism. CYP2C9 inhibitors strongly inhibited S(-)-NAF metabolism, and CYP2C8, CYP2C19 and CYP3A4/5 inhibitors moderately inhibited S(-)-NAF metabolism. Consistent with the results of chemical inhibitors experiments, recombinant human CYP2C9 and CYP2C19 contributed greatly to R(+)-NAF metabolism, and CYP2C9 contributed greatly to S(-)-NAF metabolism. CONCLUSION: Both R(+)-NAF and S(-)-NAF are metabolized to three metabolites in HLMs. CYP2C9 plays the most important role in the demethylation and hydroxylation of both NAF enantiomers, CYP2C19 is another major CYP isoform that is involved in R(+)-NAF metabolism.

Attrition of MSM with HIV/AIDS along the continuum of care from screening to CD4 testing in China.

The aim of this study is to describe attrition of newly diagnosed men who have sex with men (MSM) living with HIV/AIDS from screening to CD4 testing and provide suggestions to improve HIV case management in China. Data from 15 China-Gates Program project cities were collected on number of MSM who underwent each step from HIV screening to CD4 testing. Descriptive statistics were calculated. A total of 76,628 HIV screening tests were performed among MSM, of which 4563 were HIV-positive. Most attrition occurred at confirmatory and CD4 testing. Within the same year, 21% (1065/4063) of MSM who screened HIV-positive did not receive confirmatory testing and 34% (1025/3024) of MSM newly diagnosed with HIV/AIDS did not receive CD4 testing. Marked differences were observed between project areas in attrition at these points of the care continuum. Marked differences were also observed across areas in the rate of CD4 counts <350 cells/mcl, ranging from 23% to 87%. In the current process for diagnosis and management of HIV infection in China, many MSM are lost to follow-up at HIV confirmation and CD4 testing. Actions should be taken to reduce complexity and time lag from screening to CD4 test and emphasize the importance of remaining in care during posttest counseling.

Experience of offering HIV rapid testing to at-risk patients in community health centers in eight Chinese cities.

OBJECTIVE: To explore the feasibility of offering HIV counseling and testing in community health centers (CHCs) and to provide evidence for the HIV/AIDS response in China. METHODS: Forty-two CHCs were selected from the eight cities that participated in the study. Rapid testing was mainly provided to: clients seeking HIV testing and counseling (HTC); outpatients with high-risk behavior of contracting HIV; inpatients and outpatients of key departments. Aggregate administrative data were collected in CHCs and general hospitals and differences between the two categories were compared. RESULTS: There were 23,609 patients who underwent HIV testing, accounting for 0.37% of all estimated clinic visits at the 42 sites (0.03%-4.35% by site). Overall, positive screening prevalence was 0.41% (95% confidence interval [CI] 0.33%-0.49%, range 0.00%-0.98%), which is higher than in general hospitals (0.17%). The identification efficiency was 0.22% (95% CI: 0.16%-0.27%) in pilot CHCs, 3.5 times higher than in general hospitals (0.06%) (Chi square test = 95.196, p<0.001). The percentage of those receiving confirmatory tests among those who screened positive was slightly lower in CHCs (73.7%) than in general hospitals (80.1%) (Chi-square test = 17.472, p<0.001). Composition of clients mobilized for testing was consistent with the usage of basic public health and medical services in CHCs. The rate of patients testing HIV positive was higher among patients from key CHC departments (0.68%) than among high-risk Voluntary Counseling and Testing (VCT) clients (0.56%), those participating in outreach activities (0.41%), pregnant women (0.05%), and surgical patients (0.00%). CONCLUSION: This project demonstrates that providing HIV testing services for patients who exhibit high risk behavior has a high HIV case detection rate and that CHCs have the capacity to integrate HTC into routine work. It provides concrete evidence supporting the involvement of CHCs in the expansion of HIV/AIDS testing and case finding.

[Social network analysis and high risk behavior characteristics of recreational drug users: a qualitative study].

OBJECTIVE: To understand the characteristics of recreational drug users' behaviors and social network, as well as their potential impact to the transmission of sexual transmitted infections (STI). METHODS: Qualitative interview was used to collect information on rough estimation of population size and behavior change before and after recreational drug use. A total of 120 participants were recruited by convenient sampling from April to October, 2013 in a community of Qingdao city. Blood specimens were taken for HIV/syphilis serological testing and social network analysis was performed to understand the characteristics of their behavior and social network. RESULTS: All participants used methamphetamine and 103 of them showed social connection. The prevalence of syphilis and HIV were 24.2% (29/120) and 2.5% (3/120) respectively. The estimated size of recreational drug users was big with a wide diversity of occupations and age range, and males were more frequent than females. Drug use may affect condom use and frequent drug users showed symptom of psychosis and neuro-toxicities. The size of social network was 2.45 ± 1.63 in the past 6 months, which indicated an increasing trend of the sexual partner number and risky behaviors. CONCLUSION: Recreational drug use could increase the size of social network among sex partners, the frequency of risky sexual behaviors and syphilis prevalence, which indicate a high risk of HIV/STI among this population as well as a huge burden of disease prevention and control in the future.