Clinical presentation of early syphilis and genomic sequences of Treponema pallidum strains in patient specimens and isolates obtained by rabbit inoculation.

BACKGROUND: The global resurgence of syphilis necessitates vaccine development. METHODS: We collected ulcer exudates and blood from 17 primary syphilis (PS) participants and skin biopsies and blood from 51 secondary syphilis (SS) participants in Guangzhou, China for Treponema pallidum subsp. pallidum (TPA) qPCR, whole genome sequencing (WGS), and isolation of TPA in rabbits. RESULTS: TPA DNA was detected in 15 of 17 ulcer exudates and 3 of 17 blood PS specimens. TPA DNA was detected in 50 of 51 SS skin biopsies and 27 of 51 blood specimens. TPA was isolated from 47 rabbits with success rates of 71% (12/17) and 69% (35/51), respectively, from ulcer exudates and SS bloods. We obtained paired genomic sequences from 24 clinical samples and corresponding rabbit isolates. Six SS14- and two Nichols-clade genome pairs contained rare discordances. Forty-one of the 51 unique TPA genomes clustered within SS14 subgroups largely from East Asia, while 10 fell into Nichols C and E subgroups. CONCLUSIONS: Our TPA detection rate was high from PS ulcer exudates and SS skin biopsies and over 50% from SS blood, with TPA isolation in over two-thirds of samples. Our results support the use of WGS from rabbit isolates to inform vaccine development.

The incidence of new cases of syphilis has skyrocketed globally in the twenty-first century. This global resurgence requires new strategies, including vaccine development. As part of an NIH funded Cooperative Research Center to develop a syphilis vaccine, we established a clinical research site in Guangzhou, China to better define the local syphilis epidemic and obtain samples from patients with primary and secondary syphilis for whole genome sequencing (WGS) of circulating Treponema pallidum strains. Inoculation of rabbits enabled us to obtain T. pallidum genomic sequences from spirochetes disseminating in blood, a compartment of immense importance for syphilis pathogenesis. Collectively, our results further clarify the molecular epidemiology of syphilis in southern China, enrich our understanding of the manifestations of early syphilis, and demonstrate that the genomic sequences of spirochetes obtained by rabbit inoculation accurately represent those of the spirochetes infecting the corresponding patients.

HIV self-testing adoption and post-test linkage to care among men who have sex with men in China: a nationwide cross-sectional survey.

BACKGROUND: HIV self-testing (HIVST) was recommended to improve HIV testing services. China initiated some of the first HIVST pilots in the world, providing a unique opportunity for implementation research. We aim to investigate HIVST adoption and its following linkage to care among Chinese men who have sex with men (MSM). METHODS: Data were collected using an online questionnaire distributed on major social media platforms in 2018, one year after HIVST was officially endorsed and allowed for sale. MSM who were at least 16 years old, assigned as male at birth, and ever tested for HIV were eligible. Primary outcome, adoption was defined as ever use of HIVST. Bivariate and multivariable logistic regressions were performed to explore the association between HIVST adoption and sociodemographic and behavioral factors. Linkage to care was also described via the following sequential events as indicators: (1) receiving result after recent test (2), seeking care from healthcare facility if test result was positive or indeterminate, and (3) delayed time before seeking care. RESULTS: A total of 540 participants were included with an average age of 27.4 ± 6.6. Most were never married (87.4%) and half completed college (52.2%). Overall, 75.2% had adopted HIVST. Self-test kits were commonly obtained from community-based organizations (54.4%) and from online (46.6%). HIVST adoption was positively associated with having college or higher education (OR = 1.66, 95%CI: 1.07-2.57), and negatively associated with age older than 30 (AOR = 0.52, 95%CI: 0.32-0.84). Adoption was not associated with other socio-demographic or behavioral factors. After receiving HIV-positive or indeterminate results, 25/25 of HIVST adopters sought care while 3 out of 7 (42.9%) non-adopters sought care (p < 0.001). Delays before seeking care were not significantly different between HIVST adopters compared to non-adopters (P = 0.366). CONCLUSION: Many MSM adopted HIVST shortly after its launch. Our findings suggested that HIVST linkage to care is promising among MSM in China. Integration of HIVST with other essential sexual health services is needed.

Total flavone of Abelmoschus manihot regulates autophagy through the AMPK/mTOR signaling pathway to treat intestinal fibrosis in Crohn's disease.

BACKGROUND AND AIM: Drug therapy is the treatment of choice for Crohn's disease because it effectively controls or prevents intestinal inflammation. The purpose was to research the molecular mechanism of the total flavones of Abelmoschus manihot (TFA) on intestinal fibrosis in Crohn's disease. METHODS: A 2,4,6-Trinitrobenzenesulfonic acid (TNBS)-induced colitis model and IGF-1-treated intestinal fibroblasts were established. Then, TFA, 3-MA, and compound C were used treatments. Hematoxylin and eosin, Masson, and Picrosirius red staining were performed to observe the colon tissue. Immunohistochemical staining was used to detect α-SMA expression. Flow cytometry, CCK8, wound healing, and Transwell assays were conducted to determine apoptosis, proliferation, invasion, and migration. Col1a1 and Col3a1 levels were detected using quantitative polymerase chain reaction. Proteins related to autophagy and apoptosis were detected using western blotting. RESULTS: TFA treated intestinal fibrosis in chronic Crohn's disease. Colon length was the shortest in the ethanol + TNBS group, and TFA treatment significantly improved the situation. Intestinal fibrosis and the percentage of collagen area decreased after TFA treatment. TFA reduced fibrosis by enhancing autophagy stimulation, whereas an autophagy inhibitor reversed the TFA effect. TFA also inhibited migration, proliferation, and collagen synthesis in intestinal fibroblasts. Moreover, it enhanced autophagy and apoptosis of intestinal fibroblasts. TFA upregulated p-AMPK expression and decreases p-mTOR levels. Compound C partially rescued the effect of TFA, indicating that TFA affected intestinal fibroblasts via the AMPK/mTOR pathway in vitro and in vivo. TFA also downregulated Col1a1 and Col3a1 expression. CONCLUSION: TFA regulates autophagy through AMPK/mTOR signaling pathway to treat intestinal fibrosis, which may provide a new therapy for Crohn's disease treatment.

Changing trends in Chlamydia and gonorrhea infections among female sex workers in Southern China: a surveillance data analysis spanning 2019 to 2022.

BACKGROUND: Female sex workers (FSW) are particularly vulnerable to chlamydia and gonorrhea infections. However, there were few studies that detail the evolving patterns of chlamydia and gonorrhea among Chinese FSW. Therefore, our study endeavors to assess the prevalence of chlamydia and gonorrhea epidemics within FSW, investigate their changing trends and scrutinize associated factors. METHODS: In 2019, China instituted a sentinel surveillance network focused on FSW in Guangdong Province. This network conducted an annual serial cross-sectional survey spanning from April to August. All analyses are predicated on surveillance data accumulated between 2019 and 2022. RESULTS: The prevalence of chlamydia increased from 10.1 to 12.3%, exhibiting an annual percentage shift of 6.8%. Conversely, the prevalence of gonorrhea dwindled from 2.0 to 1.3%, marking an annual percentage decline of 13.4% (P < 0.001). After adjusting for covariates, chlamydia exhibited associations with having household registration in other provinces (adjusted odds ratio (aOR = 0.55)), displaying symptoms of sexually transmitted infections (STIs) (aOR = 1.65) and infected with gonorrhea (aOR = 5.68). In parallel, gonorrhea demonstrated associations with providing oral sex to clients (aOR = 3.74), manifesting STIs symptoms (aOR = 4.27) and those infected with chlamydia (aOR = 5.43). CONCLUSIONS: Our observations underscore the imperative to implement a comprehensive intervention strategy concentrating on chlamydia, while simultaneously fortifying endeavors to expand the scope of gonorrhea prevention services.

Expanding hepatitis C virus test uptake using self-testing among men who have sex with men in China: two parallel randomized controlled trials.

BACKGROUND: HCV self-testing (HCVST) may be an effective strategy to address low rates of HCV test uptake among men who have sex with men (MSM). We evaluated the effectiveness and cost of providing HCVST to increase HCV test uptake among MSM in China. METHODS: Two parallel, unmasked, individual-level randomized controlled trials were conducted. HIV-negative MSM and MSM living with HIV were enrolled from 22 cities in China. Men in both trials were randomly assigned (1:1) into standard-of-care (SOC) or HCVST arms. The primary outcome was the proportion of participants who tested for HCV during the trial period. Intervention effects were estimated using multiply imputed data in the main analysis. Costs were measured using a micro-costing approach. RESULTS: A total of 84 men who were HIV-negative (trial 1) and 84 men living with HIV were enrolled (trial 2). Overall, the proportion of individuals who underwent HCV testing during the trial period was higher in the HCVST arm compared to SOC in trial 1 (estimated risk difference (RD): 71.1%, 95% CI: 54.6 to 87.7%) and trial 2 (estimated RD: 62.9%, 95% CI: 45.7 to 80.1%). Over half (58.6%, 34/58) of HCV self-testers reported the self-test was their first HCV test. The cost per person tested in trial 1 was $654.52 for SOC and $49.83 for HCVST, and in trial 2 was $438.67 for SOC and $53.33 for HCVST. CONCLUSIONS: Compared to the standard of care, providing HCVST significantly increased the proportion of MSM testing for HCV in China, and was cheaper per person tested. TRIAL REGISTRATION: Chinese Clinical Trial Registry. REGISTRATION NUMBER: ChiCTR2100048379.

HCV knowledge and attitudes among HIV-negative MSM and MSM living with HIV in China: results from a cross-sectional online survey.

BACKGROUND: Men who have sex with men (MSM) are at high risk of hepatitis C virus (HCV) infection, especially for those living with human immunodeficiency virus (HIV). Learning about knowledge of and attitudes towards HCV is essential to inform health promotion interventions development. This is one of very limited studies to examine the level of knowledge and attitudes towards HCV and their determinants among HIV-negative MSM and MSM living with HIV in China. METHODS: A cross-sectional survey was conducted across seven provinces in China from December 2021 to January 2022. All the MSM living with HIV were recruited offline, whereas the recruitment ratio for HIV-negative MSM was half online and half offline. Data on socio-demographic characteristics, sexual behaviors, knowledge about HCV, and attitude towards HCV from participants were collected through the online survey. Univariate and multivariable logistic regressions were used to determine the associated factors. RESULTS: Only 39.3% (33/84) of HIV-negative men and 44.0% (37/84) of men living with HIV had a good level knowledge about HCV. Nearly one-third (32.1%, 27/84) of HIV-negative men and 41.7% (35/84) of men living with HIV reported a positive attitude towards HCV. For HIV-negative men, positive attitude towards HCV was associated with the multiple sexual partners (aOR: 5.8, 95%CI:1.9-18.1) and the use of recreational substances (aOR: 3.1, 95%CI: 1.0-9.4). For men living with HIV, knowledge about HCV was associated with disclosing sexual orientation to healthcare providers, family or friends (aOR: 7.0, 1.9-26.0), the multiple sexual partners (aOR: 0.2, 0.1-1.0), the use of recreational substances (aOR: 3.7, 95%CI: 1.1-13.1) and the HBV testing history (aOR: 7.3, 95%CI: 1.6-32.7); positive attitude towards HCV was associated with the use of recreational substances (aOR: 3.1, 95%CI: 1.1-9.0). CONCLUSIONS: The majority of Chinese MSM showed an inadequate knowledge of and negative attitude towards HCV irrespective of HIV infection status. More tailored education campaigns and multicomponent interventions are required to be targeted on MSM, and more researches are also needed to inform how best to address the negative attitudes of this population towards HCV.

HIV/STD prevalence and test uptake among african in Guangzhou, China: an analysis of data from hospital-based surveillance.

Human immunodeficiency virus (HIV) and sexually transmitted diseases (STDs) cause substantial morbidity and mortality both in African and China. However, there is limited data available on the prevalence of HIV/STDs and the uptake of testing experience ever during in China among African migrants. A venue-based survey was conducted at a tertiary hospital in Guangzhou to investigate the prevalence of HIV/STDs through laboratory testing and identify the associated factors. A total of 200 eligible participants completed the survey and bring into the analysis from April to October 2019, and the temporary visitors were excluded. The prevalence rates of HIV, syphilis, NG, CT, and HBsAg among the participants were 1.0%, 2.5%, 1.0%, 1.5%, and 5.5%, respectively. The overall reported rate of HIV/STD testing was 37.0%, with rates of 23.0% for HIV, 16.5% for syphilis, 12.5% for NG, 6.5% for genital herpes, 5.0% for condyloma acuminata, and 2.5% for CT. HIV/STD testing was associated with living environment in Guangzhou, having medical insurance in China, and utilizing health services in China in the past year. HIV/STDs are prevalent among Africans in Guangzhou, and the epidemic is likely to spread due to a significant proportion of unprotected sexual behaviors and low rates of HIV/STD testing. Urgent interventions, including targeted health education, promotion of health service utilization, and active surveillance of HIV/STDs, are needed to reduce the risk of HIV/STD transmission.

Online commercial sex-seeking among female sex workers in south China: a cross-sectional study.

BACKGROUND: Online communication platforms have the potential to facilitate commercial sex among female sex workers (FSW), increasing the risk of contracting sexually transmitted diseases (STD). This study aimed to describe the patterns of online commercial sex-seeking and examine the associated factors among FSW in China. METHODS: A venue-based cross-sectional study was conducted in five cities in Guangdong Province, China, between April and October 2020. Data on socio-demographic characteristics, sexual behaviors, and online commercial sex-seeking patterns were collected through face-to-face interviews. Venous blood and urine samples were collected for STD testing. Univariate and multivariable logistic regressions were used to explore the factors associated with online commercial sex-seeking. RESULTS: A total of 1155 FSW were recruited in physical venues for this study. Among them, 33.42% reported ever using online applications to seek commercial sex. The prevalence of HIV, syphilis, gonorrhea, chlamydia, and STD was 0.26%, 1.30%, 4.40%, 15.54%, and 18.39%, respectively, among FSW who had ever used both physical and online venues to seek commercial sex, which was higher than among FSW who had never sought commercial sex online. Multivariable logistic regression indicated that FSW who used online platforms to seek commercial sex were more likely to have STD (adjusted odds ratio (aOR) = 1.48, 95%CI: 1.05-2.09), experience unintended pregnancies due to commercial sex (aOR = 1.78, 95%CI: 1.21-2.62), be diagnosed as infertile (aOR = 3.20, 95%CI: 1.42-7.21), and undergo abortions (aOR = 1.69, 95%CI: 1.29-2.20). CONCLUSION: A significant proportion of FSW who practiced in physical venues in China engaged in seeking commercial sex online, and this behavior is positively correlated with both STD and reproductive health outcomes. Given the high prevalence of online sex-seeking, it is crucial to provide a wide range of internet-based healthcare interventions and reproductive health services to Chinese FSW.

Exploring causal mechanisms and essential factors in the prevention and control of chlamydia in Guangdong, Southern China: a study protocol.

BACKGROUND: Chlamydia Trachomatis (CT) is among the most prevalent sexually transmitted diseases (STDs) globally. According to the World Health Organization, more than 131 million people get infected with CT annually. CT is usually transmitted via sexual contact or perinatal exposure and can result in severe long-term complications. In developing nations, particularly, the prevention and control of CT is challenging. Hence, this study will explore the feedback mechanisms of chlamydia prevention and control, as well as identify the essential factors affecting the control and prevention of this infection in China. METHODS: Our study will employ a mixed-methods research design that encompasses both qualitative and quantitative methods. Firstly, we will develop a causal loop diagram (CLD) based on the literature review and optimize it via in-depth interviews with stakeholders. Additionally, we will utilize a quantitative method called MICMAC(Impact Matrix Cross-Reference Multiplication Applied to a Classification tool) to obtain consensus among different stakeholders and pinpoint the key information. Next, the CLD will be transformed into a system dynamics model (SDM) to evaluate the feedback mechanisms within the CLD. The causality in the CLD will be modeled using mathematical equations, which facilitate the transformation into an SDM. As such, we will be able to analyze the dynamic behavior of the system and its response to different decisions. DISCUSSION: Our study offers a systematic perspective on the control and prevention of chlamydia infection through system dynamics modeling, examining the dynamic properties and background factors of the system. The creation of the CLD affords stakeholders the chance to comprehend the functionality of their relationships and improve cooperation. Consequently, by evaluating the outcomes of these simulations, it will be possible to analyze and determine potential interventions and their effects on chlamydia infections. This modeling approach can help us gain insight into the dynamic characteristics of the system, evaluate the potential outcomes of different decisions, and design control strategies to either stabilize the system or adjust its behavior.

Optimizing Peer Distribution of Syphilis Self-Testing Among Men Who Have Sex with Men in China: A Multi-City Pragmatic Randomized Controlled Trial.

Syphilis testing uptake is low among men who have sex with men (MSM) around the world. Syphilis self-testing (SST) may complement facility-based testing; the distribution model is yet to be explored. This study aimed to investigate the effectiveness of peer distribution of syphilis self-testing on promoting syphilis testing. We conducted a three-arm, unblinded, parallel individually randomized controlled trial among MSM in three cities in Guangdong, China. Inclusion criteria were: men who were born biologically male, aged 18 or above, have ever had sex with a man, will refer the interventions to peers, and will take the three-month follow-up survey. Enrolled indexes were randomly assigned in a 1:1:1 ratio into standard-of-care arm (SOC arm), standard SST delivery arm (S-SST arm), and a web-based referral link SST delivery arm (RL-SST arm). The primary outcome was the number of returned photograph-verified syphilis testing results per index. A total number of 300 indexes were enrolled, with 100 indexes in each arm. The number of verified syphilis tests per index conducted by alters was 0.05 in the control arm, 0.51 in the S-SST arm, and 0.31 in the RL-SST arm. The cost per alter tested was $760.60 for SOC, $83.78 for S-SST, and $93.10 for RL-SST. Minimal adverse event was reported among both indexes and alters during the study. This study showed that peer distribution of SST could improve syphilis testing uptake among MSM in China compared to facility-based testing. This approach warrants further consideration as part of expanding syphilis self-testing.

Analyses of human papillomavirus, Chlamydia trachomatis, Ureaplasma urealyticum, Neisseria gonorrhoeae, and co-infections in a gynecology outpatient clinic in Haikou area, China.

BACKGROUND: The purpose of this study was to study the infection rates of Chlamydia trachomatis (CT), Ureaplasma urealyticum (UU), Neisseria gonorrhoeae (NG), and co-infections with human papillomavirus (HPV) in a hospital gynecology outpatient clinic in the Haikou region in 2021. METHODS: From January to December 2021, the Women and Children Medical Center of Hainan Province collected 2389 samples of cervical exfoliated cells and vaginal swab specimens from gynecologic outpatients. The samples were then analyzed descriptively for data, and the detection rate of each pathogen was tallied. All vaginal swabs were obtained for CT, UU, and NG DNA testing, and cervical exfoliated cells for HPV genotyping. Analyses were performed on the detection rate of each group. RESULTS: In 2389 samples, the frequencies of pathogen identification among the 2389 samples were as follows: UU (58.43%); HPV (17.29%); CT (7.99%); and NG (0.38%). HPV, CT, UU, and NG were detected in 33.33%, 22.55%, 77.45%, and 2.94% of individuals between 15 and 20 years of age, respectively. The detection rates of CT, UU, and NG were substantially greater in the HPV-positive group than the the HPV-negative group (P < 0.05). CONCLUSION: Among gynecologic outpatients at a hospital in the Haikou area, the probability of mixed infections with genital tract pathogens in HPV-positive patients was higher compared to HPV-negative patients. Reproductive tract infections are becoming more prevalent in younger people, hence adolescent sexual health education needs improvement.

Molecular identification and functional analysis of Niemann-Pick type C2 proteins，carriers for semiochemicals and other hydrophobic compounds in the brown dog tick, Rhipicephalus linnaei.

Ticks are important vectors of many pathogens with tremendous impact on human and animal health. Studies of semiochemical interactions and mechanisms underlying chemoreception can provide important tools in tick management. Niemann-Pick type C2 (NPC2) proteins have been proposed as one type of chemoreceptor in arthropods. Here, we cloned two NPC2 genes in the brown dog tick, Rhipicephalus linnaei, the tropical lineage previously named R. sanguineus sensu lato and characterized them functionally. R.linNPC2a and R.linNPC2b genes were found to be expressed at each developmental stage with the highest level in adult males. By using quantitative real-time PCR we revealed expression in multiple tissues, including midgut, ovary, salivary glands and legs. Ligand binding analysis revealed that R.linNPC2b bound a wide spectrum of compounds, with ß-ionone, α-amylcinnamaldehyde, 2-nitrophenol and benzaldehyde displaying the strongest binding affinity (Ki < 10 µM), whereas R.linNPC2a showed a more narrow ligand binding range, with intermediate binding affinity to α-amylcinnamaldehyde and 2-nitrophenol (Ki < 20 µM). Molecular docking indicated that the amino acid residue Phe89, Leu77 and Val131 of R.linNPC2a and Phe70, Leu132 and Phe73 of R.linNPC2b could bind multiple ligands. These residues might thus play a key role in the identification of the volatiles. Our results contribute to the understanding of olfactory mechanisms of R. linnaei and can offer new pathways towards new management strategies.

BEXCIS: Bayesian methods for estimating the degree of the skewness of X chromosome inactivation.

BACKGROUND: X chromosome inactivation (XCI) is an epigenetic phenomenon that one of two X chromosomes in females is transcriptionally silenced during early embryonic development. Skewed XCI has been reported to be associated with some X-linked diseases. There have been several methods measuring the degree of the skewness of XCI. However, these methods may still have several limitations. RESULTS: We propose a Bayesian method to obtain the point estimate and the credible interval of the degree of XCI skewing by incorporating its prior information of being between 0 and 2. We consider a normal prior and a uniform prior for it (respectively denoted by BN and BU). We also propose a penalized point estimate based on the penalized Fieller's method and derive the corresponding confidence interval. Simulation results demonstrate that the BN and BU methods can solve the problems of extreme point estimates, noninformative intervals, empty sets and discontinuous intervals. The BN method generally outperforms other methods with the lowest mean squared error in the point estimation, and well controls the coverage probability with the smallest median and the least variation of the interval width in the interval estimation. We apply all the methods to the Graves' disease data and the Minnesota Center for Twin and Family Research data, and find that SNP rs3827440 in the Graves' disease data may undergo skewed XCI towards the allele C. CONCLUSIONS: We recommend the BN method for measuring the degree of the skewness of XCI in practice. The R package BEXCIS is publicly available at https://github.com/Wen-YiYu/BEXCIS .

Expanding syphilis test uptake using rapid dual self-testing for syphilis and HIV among men who have sex with men in China: A multiarm randomized controlled trial.

BACKGROUND: Low syphilis testing uptake is a major public health issue among men who have sex with men (MSM) in many low- and middle-income countries. Syphilis self-testing (SST) may complement and extend facility-based testing. We aimed to evaluate the effectiveness and costs of providing SST on increasing syphilis testing uptake among MSM in China. METHODS AND FINDINGS: An open-label, parallel 3-arm randomized controlled trial (RCT) was conducted between January 7, 2020 and July 17, 2020. Men who were at least 18 years of age, had condomless anal sex with men in the past year, reported not testing for syphilis in the last 6 months, and had a stable residence with mailing addresses were recruited from 124 cities in 26 Chinese provinces. Using block randomization with blocks of size 12, enrolled participants were randomly assigned (1:1:1) into 3 arms: standard of care arm, standard SST arm, and lottery incentivized SST arm (1 in 10 chance to win US$15 if they had a syphilis test). The primary outcome was the proportion of participants who tested for syphilis during the trial period and confirmed with photo verification and between arm comparisons were estimated with risk differences (RDs). Analyses were performed on a modified intention-to-treat basis: Participants were included in the complete case analysis if they had initiated at least 1 follow-up survey. The Syphilis/HIV Duo rapid test kit was used. A total of 451 men were enrolled. In total, 136 (90·7%, 136/150) in the standard of care arm, 142 (94·0%, 142/151) in the standard of SST arm, and 137 (91·3%, 137/150) in the lottery incentivized SST arm were included in the final analysis. The proportion of men who had at least 1 syphilis test during the trial period was 63.4% (95% confidence interval [CI]: 55.5% to 71.3%, p = 0.001) in the standard SST arm, 65.7% (95% CI: 57.7% to 73.6%, p = 0.0002) in the lottery incentivized SST arm, and 14.7% (95% CI: 8.8% to 20.7%, p < 0.001) in the standard of care arm. The estimated RD between the standard SST and standard of care arm was 48.7% (95% CI: 37.8% to 58.4%, p < 0.001). The majority (78.5%, 95% CI: 72.7% to 84.4%, p < 0.001) of syphilis self-testers reported never testing for syphilis. The cost per person tested was US$26.55 for standard SST, US$28.09 for the lottery incentivized SST, and US$66.19 for the standard of care. No study-related adverse events were reported during the study duration. Limitation was that the impact of the Coronavirus Disease 2019 (COVID-19) restrictions may have accentuated demand for decentralized testing. CONCLUSIONS: Compared to standard of care, providing SST significantly increased the proportion of MSM testing for syphilis in China and was cheaper (per person tested). TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR1900022409.

Correction: Expanding syphilis test uptake using rapid dual self-testing for syphilis and HIV among men who have sex with men in China: A multiarm randomized controlled trial.

[This corrects the article DOI: 10.1371/journal.pmed.1003930.].

Robust association tests for quantitative traits on the X chromosome.

The genome-wide association study is an elementary tool to assess the genetic contribution to complex human traits. However, such association tests are mainly proposed for autosomes, and less attention has been given to methods for identifying loci on the X chromosome due to their distinct biological features. In addition, the existing association tests for quantitative traits on the X chromosome either fail to incorporate the information of males or only detect variance heterogeneity. Therefore, we propose four novel methods, which are denoted as QXcat, QZmax, QMVXcat and QMVZmax. When using these methods, it is assumed that the risk alleles for females and males are the same and that the locus being studied satisfies the generalized genetic model for females. The first two methods are based on comparing the means of the trait value across different genotypes, while the latter two methods test for the difference of both means and variances. All four methods effectively incorporate the information of X chromosome inactivation. Simulation studies demonstrate that the proposed methods control the type I error rates well. Under the simulated scenarios, the proposed methods are generally more powerful than the existing methods. We also apply our proposed methods to data from the Minnesota Center for Twin and Family Research and find 10 single nucleotide polymorphisms that are statistically significantly associated with at least two traits at the significance level of 1 × 10-3.

Coerced syphilis self-testing among men who have sex with men: a nationwide cross-sectional study in China.

BACKGROUND: Syphilis testing uptake remains low among men who have sex with men (MSM) in many low-and middle-income countries. Syphilis self-testing is an efficacious approach on increasing syphilis testing coverage. However, one unintended consequence is the syphilis self-testing coercion from others (including partners, healthcare providers, friends, etc.). This study aimed to examine the prevalence, pattern and correlates of coerced syphilis self-testing among MSM in China. METHODS: A nationwide online cross-sectional study was conducted from 14 to 28 July 2018. Sociodemographic characteristics, sexual behaviors and coerced syphilis self-testing variables were collected through a questionnaire that targeted MSM in China. Multivariable logistic regression was used to explore associated factors with syphilis self-testing coercion. RESULTS: Overall, 174 MSM were recruited in this study, 31 men (17.8%) reported ever experiencing syphilis self-testing coercion. The most common types of coercion before syphilis self-testing were verbal abuse (38.7%, 12/31) and threatening to end a relationship (38.7%, 12/31). After obtaining the self-test results, men were mostly subjected to end a relationship (45.2%, 14/31) and threaten of violence (35.5%, 11/31). Multivariable logistic regression indicated that men who used condoms inconsistently in the past three months, ever used substances before or during sex, ever had group sex with males and commercial sex were more likely to experience syphilis self-testing coercion. CONCLUSIONS: Coerced syphilis self-testing was prevalent among MSM in China. Innovative intervention to reduce coerced syphilis self-testing is necessary among MSM in China.

Sexual uses of drug and alcohol among men who have sex with men in China: implications for HIV prevention.

BACKGROUND: Sexual uses of alcohol and drugs are pervasive among men who have sex with men (MSM) and associated with increased risk of HIV infection. However, there are limited studies related to sexual uses of alcohol and drugs among MSM in China. This study aims to describe the pattern of alcohol use, drug use, and multi-drug use during sex among Chinese MSM and to examine the association between condomless anal intercourse, group sex, commercial sex and HIV infection. METHODS: We conducted an online cross-sectional survey in China. Characteristics on social-demographic, sexual behaviors, and sexual uses of alcohol and drugs were collected. The associations with high-risk sexual behaviors and HIV infection were analyzed with multivariable logistic regression. RESULTS: A total of 699 MSM were included in this study. About 39.5% (230/582) of men reported sexual alcohol use in the past three months and 50.8% (355/699) reported sexual drug use. Of those reporting sexual drug use, around 10.7% (38/355) reported having multi-drug use. Factors associated with both sexual uses of alcohol and drugs included: reporting more male sexual partners (alcohol: adjusted odds ratio [aOR] = 1.77; drug: aOR = 2.12), reporting condomless anal intercourse in the past three months (alcohol: aOR = 2.08; drug: aOR = 2.08), having ever engaged in group sex (alcohol: aOR = 2.04; drug: aOR = 5.22; multi-drug: aOR = 3.52) and commercial sex (alcohol: aOR = 4.43; drug: aOR = 4.22 multi-drug: aOR = 5.07). Sexual drug use was also correlated with reported HIV-positive status (drug: aOR = 2.53, 95% CI:1.31-4.90). CONCLUSION: Sexual uses of alcohol and drugs are prevalent among Chinese MSM. Interventions to reduce the sexual use of alcohol and other drugs may be warranted among MSM in China.

Community engagement on-site rapid test for chlamydia and gonorrhea among men who have sex with men: a pioneering study in Guangzhou, China.

BACKGROUND: Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections are prevalent among men who have sex with men (MSM) in China. However, compared to syphilis and HIV, the testing rate for chlamydia and gonorrhea remains low. The purpose of this pilot study was to evaluate the feasibility for conducting rapid nucleic acid test for chlamydia and gonorrhea in MSM community-based organizations (CBO). METHOD: We recruited our participants through an MSM CBO where free HV and syphilis testing were routinely provided. We collected data including social-demographic background, sexual history, chlamydia and gonorrhea testing history, and reasons for accepting this on-site rapid testing. Urine and/or anorectal swab samples were collected and tested for chlamydia and gonorrhea on-site and the testing results were delivered in about 1.5 h. Positive cases received on-site free treatment. RESULTS: From August 2020 to October 2020, 634 MSM visited the CBO for syphilis and HIV testing and 158 (158/634, 24.9%) accepted the on-site chlamydia and gonorrhea rapid test, 135 were finally enrolled. The positive rate fo chlamydia was 16.3% (22/135) and 3.0% (4/135) for gonorrhea, respectively. Only 19.3% participants had previously undergone chlamydia and gonorrhea testing and 68.9% (93/135) participants reported that they had heard of gonorrhea, 47.4% (64/135) had heard of chlamydia. The main reason for testing was "free for charge" (66.2%), followed by "convenient, 'shorter waiting time" (45.2%) and "had high-risk sexual behavior recently" (16.3%). CONCLUSIONS: This pilot study showed that the chlamydia and gonorrhea infection rate remains high among MSM, while the testing rate was low. On-site rapid testing is feasible and potentially preferred by MSM.

MicroRNA-101-3p, MicroRNA-195-5p, and MicroRNA-223-3p in Peripheral Blood Mononuclear Cells May Serve as Novel Biomarkers for Syphilis Diagnosis.

OBJECTIVES: Syphilis is a sexually transmitted disease of global prevalence. Current diagnostic methods lack sensitivity and specificity, which limits the early diagnosis and prognosis of the disease. MiRNAs hold great promise as potential biomarkers for infectious diseases diagnosis. We previously profiled the expression of miRNAs in PBMCs from patients with different stages of syphilis. We aimed to further confirm the miR-101-3p, miR-195-5p, and miR-223-3p expression profiles and evaluate their diagnostic value in syphilis infection. METHODS: The expression levels of PBMC-derived miR-101-3p, miR-195-5p, and miR-223-3p were analyzed in 133 syphilis patients, 18 non-syphilis patients, and 23 healthy controls by RT-qPCR. ROC analysis was used to evaluate the differentiation power of these miRNAs in syphilis diagnosis, while the correlation between the expression of these miRNAs and TRUST titer was also statistically analyzed. RESULTS: These miRNAs were significantly upregulated in syphilis patients in a stage-specific manner. ROC analysis indicated that miR-223-3p was powerful in discriminating between controls and patients with early, primary, secondary, and latent syphilis, as well as serological cure; the miR-195-5p/miR-223-3p panel showed an improved capacity to differentiate between syphilis patients, primary, or serofast-stage syphilis and controls, while the three miRNAs combined showed an improved capacity to differentiate latent syphilis or serological cure from controls. Importantly, miR-101-3p and miR-223-3p singly or jointly could specifically distinguish syphilis from non-syphilis patients. Moreover, TRUST titer was significantly correlated with miR-101-3p expression. CONCLUSIONS: MiR-101-3p, miR-195-5p, and miR-223-3p might singly or jointly be potential diagnostic biomarkers at different stages of syphilis.