A novel internet sampling for HIV surveillance: feasibility of self-sampling and preparation of DBS for delivery detection of HIV total nucleic acid and complementarity to sentinel surveillance.

BACKGROUND: To propose a new mode of HIV test and surveillance among population of men who have sex with men (MSM): Internet-based Self-sampling at home plus Laboratory testing of HIV total nucleic acid (TNA) in dried blood spot (DBS) (ISL of DBS TNA). Feasibility of ISL of DBS TNA was studied. Characteristics of the new mode and that of conventional surveillance mode at HIV voluntary counseling and testing clinic (VCT) were compared. METHODS: A non-governmental organization (NGO) published the recruitment information on the WeChat public account. MSM filled in the questionnaire online, applied for self-sampling service package, and mailed the self made DBS to professional laboratory. The laboratory performed HIV TNA test and submitted the test results to online platform. Participants queried test results online with their unique ID. Center for Disease Control and Prevention (CDC) followed up participants with positive nucleic acid results using IDs and contact information. Rates were compared by using the Chi-Square test or Fisher's exact test. RESULTS: Four hundred twenty-three questionnaires were completed. 423 self-sampling service packages were sent out and 340 DBSs were returned to professional laboratory within one month with qualified rate of sampling as high as 95.0% (323/340). Seven samples were found to be TNA positive. Comparing ISL of DBS TNA with sentinel surveillance, it was found that there was a significant difference in the composition ratio of the two modes of surveillance population (P < 0.05). HIV prevalence of ISL of DBS as 2.17% was significantly lower than sentinel site as 8.96% (χ2 = 14.953, P = 0.000 < 0.05). CONCLUSIONS: ISL of DBS TNA proposed is feasible and has a high self-sampling qualification rate, good confidentiality. It is an effective supplement to routine sentinel surveillance and has important promotion value.

Surface-Anchored Nanogel Coating Endows Stem Cells with Stress Resistance and Reparative Potency via Turning Down the Cytokine-Receptor Binding Pathways.

Stem cell-based therapy has great potential in regenerative medicine. However, the survival and engraftment rates of transplanted stem cells in disease regions are poor and limit the effectiveness of cell therapy due to the fragility of stem cells. Here, an approach involving a single-cell coating of surface-anchored nanogel to regulate stem cell fate with anti-apoptosis capacity in the hypoxic and ischemic environment of infarcted hearts is developed for the first time. A polysialic acid-based system is used to anchor microbial transglutaminase to the external surface of the cell membrane, where it catalyzes the crosslinking of gelatin. The single-cell coating with surface-anchored nanogel endows mesenchymal stem cells (MSCs) with stress resistance by blocking the activity of apoptotic cytokines including the binding of tumor necrosis factor α (TNFα) to tumor necrosis factor receptor, which in turn maintains mitochondrial integrity, function and protects MSCs from TNFα-induces apoptosis. The administration of surface engineered MSCs to hearts results in significant improvements in engraftment, cardiac function, infarct size, and vascularity compared with using uncoated MSCs in treating myocardial infarction. The surface-anchored, biocompatible cell surface engineering with nanogel armor provides a new way to produce robust therapeutic stem cells and may explore immense potentials in cell-based therapy.

Use of Geosocial Networking Apps and HIV Risk Behavior Among Men Who Have Sex With Men: Case-Crossover Study.

BACKGROUND: HIV disproportionately affects men who have sex with men (MSM) in China. The HIV epidemic is largely driven by unprotected anal sex (ie, sex not protected by condoms or HIV pre-exposure prophylaxis [PrEP]). The possible association between unprotected anal sex and the use of geospatial networking apps has been the subject of scientific debate. OBJECTIVE: This study assessed whether users of a gay geospatial networking app in China were more likely to use condoms when they met their partners online versus offline. A case-crossover analysis, with each person serving as his own control, was employed to address the potential bias that men looking for sex partners through an online dating medium might have inherently different (and riskier) patterns of sexual behavior than men who do not use online dating media. METHODS: A cross-sectional survey was administered in 2018 to adult male users of Blued-a gay geospatial networking app-in Beijing, Tianjin, Sichuan, and Yunnan, China. A case-crossover analysis was conducted among 1311 MSM not taking PrEP who reported engaging in both unprotected and protected anal sex in the previous 6 months. Multivariable conditional logistic regression was used to quantify the association between where the partnership was initiated (offline or online) and the act of unprotected anal sex, controlling for other interval-level covariates. Four sensitivity analyses were conducted to assess other potential sources of bias. RESULTS: We identified 1311 matched instances where a person reported having both an unprotected anal sex act and a protected anal sex act in the previous 6 months. Of the most recent unprotected anal sex acts, 22.3% (292/1311), were initiated offline. Of the most recent protected anal sex acts, 16.3% (214/1311), were initiated offline. In multivariable analyses, initiating a partnership offline was positively associated with unprotected anal sex (odds ratio 2.66, 95% CI 1.84 to 3.85, P<.001) compared with initiating a partnership online. These results were robust to each of the different sensitivity analyses we conducted. CONCLUSIONS: Among Blued users in 4 Chinese cities, men were less likely to have unprotected anal sex in partnerships that they initiated online compared with those that they initiated offline. The relationship was strong, with over 2.5 times the likelihood of engaging in unprotected anal sex in partnerships initiated offline compared with those initiated online. These findings suggest that geospatial networking apps are a proxy for, and not a cause of, high-risk behaviors for HIV infection; these platforms should be viewed as a useful venue to identify individuals at risk for HIV transmission to allow for targeted service provision.

Bioinspired Shear-Flow-Driven Layer-by-Layer in Situ Self-Assembly.

Layer-by-layer (LbL) assembly is widely applied as a coating technique for the nanoscale control of architecture and related properties. However, its translational applications are limited by the time-consuming and laborious nature of the process. Inspired by the blood-clotting process, herein, we develop a shear-flow-driven LbL (SF-LbL) self-assembly approach that accelerates the adsorption rate of macromolecules by mechanically configuring the polymer chain via a coil-stretch transition, which effectively simplifies and speeds the diffusion-controlled assembly process. The structural characteristics and surface homogeneity of the SF-LbL films are improved, and diverse three-dimensional structures can be achieved. Functional SF-LbL-assembled surfaces for corneal modification are successfully fabricated, and the surface of wounded rat corneas and skin can be directly decorated in situ with SF-LbL nanofilms due to the advantages of this approach. Furthermore, in situ SF-LbL self-assembly has promise as a simple approach for the wound dressing for interventional therapeutics in the clinic, as illustrated by the successful in situ fabrication of drug-free layers consisting of chitosan and heparin on the dorsal skin of diabetic mice to rescue defective wound healing. This bioinspired self-assembly approach is expected to provide a robust and versatile platform with which to explore the surface engineering of nanofilms in science, engineering, and medicine.

Feasibility of an internet-based HIV testing service: anonymous urine collection from men who have sex with men.

A large proportion of people who are HIV positive do not know their serostatus because facility-based provider-initiated HIV testing and counseling, and voluntary counseling and testing, have not been efficiently implemented in China. Therefore, a new HIV testing strategy must be developed to improve testing services so that more HIV infections can be detected earlier. In this study, we established an anonymous internet-aided urine-based HIV testing service for men who have sex with men (MSM) from 1 April 2016 to 20 January 2017. In total, 3092 urine sample collection packs were distributed by grassroots organizations to MSM; 1977 (69.3%) packs were mailed back to the laboratory; and 1911 (96.7%) eligible samples were tested for HIV antibody. The rate of HIV antibody positivity was 7.1% (135/1901), excluding 10 previously-identified HIV infections. Of those tested, 65.4% (1243/1901) participants obtained their results from our website, 94 (69.6%) of 135 newly-identified urine HIV antibody-positive participants were contacted by CDC staff, and 61.7% (58/94) reported undergoing blood HIV antibody confirmation testing after learning of their urine HIV antibody test results. Of those who were tested for venous HIV antibody, 84.5% (49/58) reported being confirmed HIV antibody positive. Thirty-six of the newly diagnosed participants were successfully referred to a hospital to receive antiretroviral therapy. The rate of confirmed HIV antibody positivity was estimated to be 72.8-89.2 times of that of routine HIV antibody testing. In conclusion, this approach offers an alternative efficient HIV testing strategy to identify HIV positive persons in vulnerable populations.

Nanoparticle Counting by Microscopic Digital Detection: Selective Quantitative Analysis of Exosomes via Surface-Anchored Nucleic Acid Amplification.

Exosomes are nanosized vesicles secreted by cells, with a lipid bilayer membrane and protein and nucleic acid contents. Here, we present the first method for the selective and quantitative analysis of exosomes by digital detection integrated with nucleic acid-based amplification in a microchip. An external biocompatible anchor molecule conjugated with DNA oligonucleotides was anchored in the lipid bilayer membrane of exosomes via surface self-assembly for total exosome analysis. Then, specific antibody-DNA conjugates were applied to label selective exosomes among the total exosomes. The DNA-anchored exosomes were distributed into microchip chambers with one or fewer exosomes per chamber. The signal from the DNA on the exosomes was amplified by a rapid isothermal nucleic acid detection assay. A chamber with an exosome exhibited a positive signal and was recorded as 1, while a chamber without an exosome presented a negative signal and was recorded as 0. The 10100101 digital signals give the number of positive chambers. According to the Poisson distribution, the exosome stock concentration was calculated by the observed fraction of positive chambers. The findings showed that nanoscale particles can be digitally detected via DNA-mediated signal amplification in a microchip with simple microscopic settings. This approach can be integrated with multiple types of established nucleic acid assays and provides a versatile platform for the quantitative detection of various nanosomes, from extracellular vesicles such as exosomes and enveloped viruses to inorganic and organic nanoparticles, and it is expected to have broad applications in basic research areas as well as disease diagnosis and therapy.

An innovative HIV testing service using the internet: Anonymous urine delivery testing service at drugstores in Beijing, China.

Innovative human immunodeficiency virus (HIV) testing services will be needed to achieve the first 90 (90% of HIV-positive persons aware of their infection status) of the 90-90-90 target in China. Here, we describe an internet-based urine delivery testing service delivered through three pilot drugstores in Beijing that send specimens to a designated laboratory for HIV. From May 2016 to January 2017, we provided 500 HIV urine-testing service packs for display at the drugstores, and a total of 430 (86.0%) urine specimens were mailed back. All of the 430 urine specimens were of good quality and were tested. 70 urine specimens were HIV positive, showing a 16.3% (70/430) positivity rate. A total of 94.3% (66/70) of the HIV-positive participants obtained their test results through the internet, and 69.7% (46/66) of these participants received follow-up care. A total of 40 out of 46 (87.0%) participants agreed to have their results confirmed by a blood test, and 39 out of 40 (97.5%) participants were confirmed as HIV-1 positive, including two individuals that were previously diagnosed. Lastly, 28 out of 37 (75.7%) of the study participants were referred to the hospital and provided free antiviral treatment. Our data indicate that this innovative HIV testing service is effective and play an important role in HIV testing and surveillance.

[Analysis on factors associated with taking subsequent confirmation test among men who have sex with men after being tested positive in oral fluid HIV antibody test in Beijing].

OBJECTIVE: To analyze the proportion and associated factors of taking subsequent confirmation test among men who have sex with men (MSM) after being tested positive in oral fluid HIV antibody test. METHODS: By using successive sampling, 1 003 MSM, who were tested positive in oral fluid HIV antibody test in China-Bill & Melinda Gates Foundation AIDS prevention Program (Extension program) in Beijing during May 1 to December 31, 2013, were recruited. The inclusion criteria included: the objects were men who reported having sex with men; the objects aged more than 18 years old; the objects were tested positive in oral fluid HIV antibody test; the objects had not been reported as HIV positives in China Information System for Disease Control and Prevention previously. According to the program strategy, MSM grassroots organizations transferred the respondents to seek subsequent confirmation tests in specific Center for Disease Control and Prevention (CDCs) or hospitals. The subsequent confirmation tests included: fingertip blood HIV antibody rapid test, venous blood Enzyme Linked Immunosorbent Assay (ELISA) HIV antibody test and venous blood Western Blot (WB) HIV antibody test. Chi-square test was adopted to compare the proportion of taking subsequent confirmation tests in different groups. Nonconditional multivaritae binarylogistic regression analysis was taken to identify the associated factors with whether taking subsequent confirmation tests and to calculate the OR (95% CI) values. RESULTS: The 1 003 respondents were (30.9 ± 9.1) years old. Among all objects, 87.8% (881/1 003) of them took fingertip blood HIV antibody rapid tests and the positive rate was 85.4% (752/881). 98.0% (737/752) of those who were identified as positive in fingertip blood HIV rapid tests took ELISA and WB tests, and the positive rate was 94.4% (696/737). Comparing with those who were expected to seek subsequent confirmation tests in CDCs, the OR (95% CI) value of those who were expected to seek tests in hospitals was 5.10 (1.69-15.36). The OR (95% CI) values of those who used condom sometimes and those who never used condom in anal sex were 5.81 (2.14-15.77) and 3.45 (2.00-5.97) respectively, in comparison with those who reported not having anal sex or using condom consistently in anal sex during the past 6 months. Comparing with the respondents recruited from the internet, the OR (95% CI) values of those recruited in bathrooms, parks/toilets and bars were 0.17 (0.05-0.53), 0.10 (0.04-0.29) and 0.22 (0.06-0.79) respectively. The likelihood of taking subsequent confirmation test decreased with the increase of number of male sexual partners in the past 3 months, and the OR (95% CI) value was 0.92 (0.86-0.99). CONCLUSION: The potential HIV positive MSM in the bathroom, park/toilet and bars are less likely to take subsequent confirmation test. Those who do not use condom consistently during anal sex are more likely to seek subsequent confirmation test. Medical organization conducting subsequent confirmation tests is more likely to increase the confirmation test rate of potential HIV positive MSM. The number of male sexual partners has negative correlation with whether to accept the subsequent confirmation test.

Incidence of HIV and Syphilis among Men Who Have Sex with Men (MSM) in Beijing: An Open Cohort Study.

BACKGROUND: This study investigated HIV and syphilis incidence among men who have sex with men (MSM) in Beijing, China. METHODS: An open cohort was established from September 2009 to April 2012. Participants were followed up with every three to four months after recruitment and for thirty-one months in total. Chi-square tests were used to compare demographic and behavioral characteristics between participants who were followed up with and those lost to follow up. Univariate and multivariate Cox proportional hazards regression analyses were used to examine demographic and behavioral associations with HIV and syphilis incidence. RESULTS: 69.7% (699/1,003) of the participants finished at least two follow-up surveys during the study period. Variables which corresponded to increased loss to follow-up included younger age, less education, non-identification of homosexual identity, and migrant status. A total of 1,045 person-years (PYs) and 1,016.4 PYs were followed up for HIV and syphilis incidence estimation, respectively. The HIV incidence was 5.9 per 100 PYs and 7.8 per 100 PYs for syphilis. The predictors for the high HIV incidence included unsafe anal sex, sex after drinking alcohol and STI infection. CONCLUSION: HIV incidence increased rapidly within the cohort, but syphilis incidence remained stable and decreased. More research is needed to provide multi-pronged HIV prevention interventions among MSM in order to reduce the increasing burden of HIV and sexually transmitted infections (STIs) in China.

[Rate of retention and related factors on patients under methadone maintenance treatment in Beijing: a prospective cohort study].

OBJECTIVE: To study the rates of retention and associated factors on patients under methadone maintenance treatment (MMT) in Beijing. METHODS: A prospective cohort was conducted among 548 patients who enrolled in MMT clinics during 2004 - 2006 in Beijing. Log-rank method and Cox PH regression models were used to study related factors associated with long-term retention. RESULTS: Of the 548 patients, 463 (79.6%) were males, with 515 (94.0%) under Han ethnicity. 443 (80.8%) of them were unemployed with 449 (81.9%) as injecting drug users at the time of enrollment. The average age and duration of drug abuse at enrollment were 37.3 ± 6.7 and 9.1 ± 4.0 years, respectively. The median length of treatment was 2.1 years with five-year retention rate as 41.2%. The long-term retention rates between different dosages (Log-rank χ(2) = 10.527, P = 0.005), treatment ratio (Log-rank χ(2) = 19.027, P < 0.001) and illicit drug use (Log-rank χ(2) = 159.485, P < 0.001) showed significant differences, statistically. Factors as having high education level (HR = 0.76, P = 0.021), with daily dosage 60 mg/day or more (HR = 0.64, P = 0.002), having 1% - 9% times urine morphine positive result (HR = 0.32, P < 0.001) seemed to be able to predict the lower risk of dropout during the follow-up period. However, frequent illicit drug use (> 20%) (HR = 2.92, P < 0.001) could increase the risk of dropout. CONCLUSION: Treatment with higher dosage (≥ 60 mg/day) of methadone seemed to have decreased the possibility of dropout during the follow-up period, whereas frequent illicit drug use (≥ 20%) was important risk factor causing long-term retention.