Efficacy of Voluntary Medical Male Circumcision to Prevent HIV Infection Among Men Who Have Sex With Men : A Randomized Controlled Trial.

BACKGROUND: Observational studies suggest that voluntary medical male circumcision (VMMC) may lower HIV risk among men who have sex with men (MSM). A randomized controlled trial (RCT) is needed to confirm this. OBJECTIVE: To assess the efficacy of VMMC in preventing incident HIV infection among MSM. DESIGN: An RCT with up to 12 months of follow-up. (Chinese Clinical Trial Registry: ChiCTR2000039436). SETTING: 8 cities in China. PARTICIPANTS: Uncircumcised, HIV-seronegative men aged 18 to 49 years who self-reported predominantly practicing insertive anal intercourse and had 2 or more male sex partners in the past 6 months. INTERVENTION: VMMC. MEASUREMENTS: Rapid testing for HIV was done at baseline and at 3, 6, 9, and 12 months. Behavioral questionnaires and other tests for sexually transmitted infections were done at baseline, 6 months, and 12 months. The primary outcome was HIV seroconversion using an intention-to-treat analysis. RESULTS: The study enrolled 124 men in the intervention group and 123 in the control group, who contributed 120.7 and 123.1 person-years of observation, respectively. There were 0 seroconversions in the intervention group (0 infections [95% CI, 0.0 to 3.1 infections] per 100 person-years) and 5 seroconversions in the control group (4.1 infections [CI, 1.3 to 9.5 infections] per 100 person-years). The HIV hazard ratio was 0.09 (CI, 0.00 to 0.81; P = 0.029), and the HIV incidence was lower in the intervention group (log-rank P = 0.025). The incidence rates of syphilis, herpes simplex virus type 2, and penile human papillomavirus were not statistically significantly different between the 2 groups. There was no evidence of HIV risk compensation. LIMITATION: Few HIV seroconversions and limited follow-up period. CONCLUSION: Among MSM who predominantly practice insertive anal intercourse, VMMC is efficacious in preventing incident HIV infection; MSM should be included in VMMC guidelines. PRIMARY FUNDING SOURCE: The National Science and Technology Major Project of China.

Factors associated with immunological non-response after ART initiation: a retrospective observational cohort study.

BACKGROUND: Among people living with HIV (PLHIV) on antiretroviral therapy (ART), the mortality of immunological non-responders (INRs) is higher than that of immunological responders (IRs). However, factors associated with immunological non-response following ART are not well documented. METHODS: We obtained data for HIV patients from the National Free Antiretroviral Treatment Program database in China. Patients were grouped into IRs (CD4 cell count ≥ 350 cells/µl after 24 months' treatment), immunological incomplete responders (ICRs) (200-350 cells/µl) and INRs (< 200 cells/µl). Multivariable logistic regression was used to assess factors associated with immunological non-response. RESULTS: A total of 3900 PLHIV were included, among whom 2309 (59.2%) were IRs, 1206 (30.9%) ICRs and 385 (9.9%) INRs. In multivariable analysis, immunological non-response was associated with being male (2.07, 1.39-3.09), older age [40-49 years (vs. 18-29 years): 2.05, 1.29-3.25; 50-59 years: 4.04, 2.33-7.00; ≥ 60 years: 5.51, 2.84-10.67], HBV co-infection (1.63, 1.14-2.34), HCV co-infection (2.01, 1.01-4.02), lower CD4 + T cell count [50-200 cells/µl (vs. 200-350 cells/µl): 40.20, 16.83-96.01; < 50 cells/µl: 215.67, 85.62-543.26] and lower CD4/CD8 ratio (2.93, 1.98-4.34) at baseline. Compared with patients treated with non-nucleoside reverse transcriptase inhibitors (NNRTIs) based regimens, those receiving protease inhibitors (PIs) based regimens were less likely to be INRs (0.47, 0.26-0.82). CONCLUSIONS: We found a sizable immunological non-response rate among HIV-infected patients. Being male, older age, coinfection with HBV and HCV, lower CD4 + T cell count and lower CD4/CD8 ratio are risk factors of immunological non-response, whereas PIs-based regimens is a protective factor.

Paraptosis: a non-classical paradigm of cell death for cancer therapy.

Due to the sustained proliferative potential of cancer cells, inducing cell death is a potential strategy for cancer therapy. Paraptosis is a mode of cell death characterized by endoplasmic reticulum (ER) and/or mitochondrial swelling and cytoplasmic vacuolization, which is less investigated. Considerable evidence shows that paraptosis can be triggered by various chemical compounds, particularly in cancer cells, thus highlighting the potential application of this non-classical mode of cell death in cancer therapy. Despite these findings, there remain significant gaps in our understanding of the role of paraptosis in cancer. In this review, we summarize the current knowledge on chemical compound-induced paraptosis. The ER and mitochondria are the two major responding organelles in chemical compound-induced paraptosis, which can be triggered by the reduction of protein degradation, disruption of sulfhydryl homeostasis, overload of mitochondrial Ca2+, and increased generation of reactive oxygen species. We also discuss the stumbling blocks to the development of this field and the direction for further research. The rational use of paraptosis might help us develop a new paradigm for cancer therapy.

The mystery of phospho-Drp1 with four adaptors in cell cycle: when mitochondrial fission couples to cell fate decisions.

Recent study had deepened our knowledge of the mitochondrial dynamics to classify mitochondrial fission into two types. To further clarify the relationship between the two distinct fission machinery and the four major adaptors of Drp1, we propose a model of mechanism elucidating the multiple functions of phospho-Drp1 with its adaptors during cell cycle and providing in-depth insights into the molecular basis and evolutionary implications in depth. The model highlights not only the clustering characteristics of different phospho-Drp1 with respective subsets of mitochondrial pro-fission adaptors but also the correlation, crosstalk and shifting between different clustering of phosphorylated Drp1-adaptors during different key fission situations. Particularly, phospho-Drp1 (Ser616) couples with Mff/MiD51 to exert mitochondrial division and phospho-Drp1 (Ser637) couples with MiD49/Fis1 to execute mitophagy in M-phase. We then apply the model to address the relationship of mitochondrial dynamics to Parkinson's disease (PD) and carcinogenesis. Our proposed model is indeed compatible with current research results and pathological observations, providing promising directions for future treatment design.

Changes in HPV prevalence, incidence, and clearance following the use of HIV pre-exposure prophylaxis (PrEP) among MSM in Xinjiang, China: An observational cohort study.

The association between HIV pre-exposure prophylaxis (PrEP) and the natural history of human papillomavirus (HPV) has not been well documented. Our objective was to evaluate the impact of PrEP on the prevalence, incidence, and clearance of anal HPV among men who have sex with men (MSM). Sexually active, HIV-negative MSM aged 18 years and older in Xinjiang, China since September 1, 2016, were enrolled in an ongoing observational cohort study of HPV. At baseline and every 6 months, an anal swab was taken to test for HPV and a questionnaire on sociodemographic characteristics and sexual behaviors was collected. Those who consented to receive PrEP were enrolled in an open-label PrEP intervention study from November 1, 2019, to June 30, 2021. This study analyzed data from participants present in the HPV cohort between November 1, 2019, and June 30, 2021. We compared the prevalence, incidence, and clearance of anal HPV between men who received PrEP (PrEP users) and those who did not (non-PrEP users), and compared men before and after initiating PrEP. We calculated prevalence ratios (PRs), incidence rate ratios (IRRs), and clearance rate ratios (CRRs) for both comparisons. Of the 870 participants present in the HPV cohort during the period between November 1, 2019, and June 30, 2021, 859 had adequate ß-globin for HPV genotype testing and were included in our study. Among them, 429 were PrEP users, while 430 were non-PrEP users. Median age was 32 years (interquartile range [IQR]: 26-38). Among PrEP users, 217 were tested for anal HPV before PrEP initiation. PrEP users had lower prevalence of HPV 45, 51, and 54 (PRs: 0.27 [95% CI: 0.09-0.80], 0.42 [0.21-0.85], and 0.41 [0.17-0.99], respectively) and lower clearance of HPV 16 (CRR: 0.31 [0.10-0.91]) compared with non-PrEP users. PrEP users exhibited lower prevalence of HPV 51 (PR: 0.31 [0.12-0.84]), lower incidence of HPV 6, 11, 16, 39 and 61 (IRRs: 0.34 [0.13-0.90], 0.26 [0.08-0.87], 0.44 [0.21-0.91], 0.21 [0.05-0.93], and 0.19 [0.04-0.82], respectively), as well as higher clearance of HPV 52 (CRR: 2.17 [1.08-4.35]) after PrEP initiation. PrEP use may lower the risk of HPV infection among MSM in Xinjiang, China. Our findings further extend the knowledge of the impact of PrEP on sexually transmitted infections.

Global patterns and trends in Kaposi sarcoma incidence: a population-based study.

BACKGROUND: Kaposi sarcoma is a rare, possibly angioproliferative, tumour. Kaposi sarcoma is one of the most common cancers in people living with HIV and poses a serious public health challenge in regions with high HIV burden. We aim to describe global patterns and population-wide trends in the burden of Kaposi sarcoma. METHODS: In this population-based study, the incidence and mortality estimates of Kaposi sarcoma from 185 countries and regions in 2020 were extracted from the GLOBOCAN 2020 database. The time trends in Kaposi sarcoma incidence were evaluated using the cancer registry data from Cancer Incidence in Five Continents plus from 1998 to 2012. We did not apply any inclusion or exclusion criteria to the data used in this study. Joinpoint regression was used to evaluate the average annual percentage change (AAPC) to quantify trends in the age-standardised incidence rate (ASIR) of Kaposi sarcoma. Correlation analysis was used to evaluate the relationship between the ASIR or age-standardised mortality rate (ASMR) and Human Development Index (HDI). FINDINGS: In 2020, the global estimated ASIR of Kaposi sarcoma was 0·39 (per 100 000 people), with an estimated 34 270 newly diagnosed cases (23 413 males and 10 857 females). An estimated 15 086 Kaposi sarcoma deaths were reported (9929 males and 5157 females), corresponding to an ASMR of 0·18 (per 100 000 people). In 2020, Africa accounted for 73·0% (25 010 of 34 270) of the incidence and 86·6% (13 066 of 15 086) of the deaths from Kaposi sarcoma worldwide. There was a significant correlation between the ASIR or ASMR and HDI. The incidence of Kaposi sarcoma increased in males in both Türkiye and the Netherlands. The AAPC was 11·5% (95% CI 3·2-20·4) for males in Türkiye and 2·5% (1·1-3·9) for males in the Netherlands from 1998 to 2012. The incidence of Kaposi sarcoma decreased in White Americans, Israel, Uganda, Costa Rica, Colombia, Canada, and Denmark, from 1998 to 2012. INTERPRETATION: Kaposi sarcoma is a relatively rare cancer worldwide but is endemic in some countries in southern and eastern Africa. Addressing disparities in health-care resource allocation and improving HIV/AIDS care across different HDI regions might contribute to the prevention of Kaposi sarcoma. FUNDING: The Natural Science Foundation of China Excellent Young Scientists Fund and the Natural Science Foundation of China International/Regional Research Collaboration Project. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Electrocardiographic Characteristics of Ventricular Arrhythmias Originating from Different Areas Adjacent to the Mitral Annulus.

BACKGROUND: This study aimed to explore the electrocardiographic (ECG) characteristics of ventricular arrhythmias (VAs) arising from epicardial and endocardial areas adjacent to the mitral annulus (MA). METHODS: This study involved 283 patients with MA-VAs who received radiofrequency catheter ablation at the center. The ECG characteristics of these patients were analyzed retrospectively. RESULTS: The origin of MA-VAs was judged based on the ECG variables. Among all MA-VAs, intrinsicoid deflection time (IDT) > 77 ms or maximum deflection index (MDI) > 0.505 predicted the VAs arising from the epicardium (sensitivity of 70.20% and 73.51%, specificity of 94.70% and 82.58%, positive predictive value (PPV) of 93.81% and 82.84%, and negative predictive value (NPV) of 73.53% and 73.15%). Among all epicardial MA-VAs, the RV1/RV2 ratio > 0.87 predicted the VAs originating from the epicardial anteroseptal wall adjacent to the MA. It had a sensitivity, specificity, PPV, and NPV of 62.86%, 98.06%, 91.67%, and 88.60%, respectively. Among all endocardial MA-VAs, Q(q)R(r) morphology in lead V1 predicted the VAs arising from the endocardial septal wall adjacent to the MA. It had a sensitivity, specificity, PPV, and NPV of 92.98%, 100%, 100%, and 94.94%, respectively. Among all endocardial septal MA-VAs, a predominant positive wave in lead II and a predominant negative wave in lead III predicted the VAs arising from the endocardial midseptal portion adjacent to the MA. It had a sensitivity, specificity, PPV, and NPV of 86.04%, 100%, 100%, and 70.00%, respectively. CONCLUSION: the ECG characteristics of VAs from the different sites adjacent to the MA can enable judging the arrhythmia's origin and designing the ablation plan accordingly.

Diagnosis of neurosyphilis in HIV-negative patients with syphilis: development, validation, and clinical utility of a suite of machine learning models.

Background: The ability to accurately identify the absolute risk of neurosyphilis diagnosis for patients with syphilis would allow preventative and therapeutic interventions to be delivered to patients at high-risk, sparing patients at low-risk from unnecessary care. We aimed to develop, validate, and evaluate the clinical utility of simplified clinical diagnostic models for neurosyphilis diagnosis in HIV-negative patients with syphilis. Methods: We searched PubMed, China National Knowledge Infrastructure and UpToDate for publications about neurosyphilis diagnostic guidelines in English or Chinese from database inception until March 15, 2023. We developed and validated machine learning models with a uniform set of predictors based on six authoritative diagnostic guidelines across four continents to predict neurosyphilis using routinely collected data from real-world clinical practice in China and the United States (through the Dermatology Hospital of Southern Medical University in Guangzhou [659 recruited between August 2012 and March 2022, treated as Development cohort], the Beijing Youan Hospital of Capital Medical University in Beijng [480 recruited between December 2013 and April 2021, treated as External cohort 1], the Zhongshan Hospital of Xiamen University in Xiamen [493 recruited between November 2005 and November 2021, treated as External cohort 2] from China, and University of Washington School of Medicine in Seattle [16 recruited between September 2002 and April 2014, treated as External cohort 3] from United States). We included all these patients with syphilis into our analysis, and no patients were further excluded. We trained eXtreme gradient boosting (XGBoost) models to predict the diagnostic outcome of neurosyphilis according to each diagnostic guideline in two scenarios, respectively. Model performance was measured through both internal and external validation in terms of discrimination and calibration, and clinical utility was evaluated using decision curve analysis. Findings: The final simplified clinical diagnostic models included neurological symptoms, cerebrospinal fluid (CSF) protein, CSF white blood cell, and CSF venereal disease research laboratory test/rapid plasma reagin. The models showed good calibration with rescaled Brier score of 0.99 (95% CI 0.98-1.00) and excellent discrimination (the minimum value of area under the receiver operating characteristic curve, 0.84; 95% CI 0.81-0.88) when externally validated. Decision curve analysis demonstrated that the models were useful across a range of neurosyphilis probability thresholds between 0.33 and 0.66 compared to the alternatives of managing all patients with syphilis as if they do or do not have neurosyphilis. Interpretation: The simplified clinical diagnostic models comprised of readily available data show good performance, are generalisable across clinical settings, and have clinical utility over a broad range of probability thresholds. The models with a uniform set of predictors can simplify the sophisticated clinical diagnosis of neurosyphilis, and guide decisions on delivery of neurosyphilis health-care, ultimately, support accurate diagnosis and necessary treatment. Funding: The Natural Science Foundation of China General Program, Health Appropriate Technology Promotion Project of Guangdong Medical Research Foundation, Department of Science and technology of Guangdong Province Xinjiang Rural Science and Technology（Special Commissioner）Project, Southern Medical University Clinical Research Nursery Garden Project, Beijing Municipal Administration of Hospitals Incubating Program.

Incidence, persistence, and clearance of anogenital human papillomavirus among men who have sex with men in Taiwan: a community cohort study.

Background: Men who have sex with men (MSM) have an increased risk of human papillomavirus (HPV) infection. This study aimed to assess the incidence, persistence, and clearance of anogenital HPV infections among MSM and the correlates in a 3-year community cohort study. Methods: From 2015 to 2019, MSM were recruited and followed up at 6, 12, 24, and 36 months in Taiwan. Questionnaires and anogenital swabs were collected at baseline and each follow-up visit. Thirty-seven HPV genotypes were tested and genotyped using the linear array HPV genotyping test. The incidence, persistence, and clearance rates of anogenital HPV infection and 95% confidence intervals (CIs) were estimated through Poisson regression. Correlates of the incidence and clearance rates were examined using a generalized estimating equations (GEE) model. Results: A total of 201 MSM were retained in the cohort study with a median age of 27 years (interquartile range [IQR]: 24-32) at baseline. The incidence, persistence, and clearance rates of any anal HPV infection among MSM were 43.6 (95% CI: 33.7-55.6), 23.4 (17.7-30.2), and 58.3 (45.1-74.1) per 1,000 person months (pms), respectively. The incidence, persistence, and clearance rates of any penile HPV infection among MSM were 26.8 (20.1-34.9), 13.4 (8.0-20.9), and 51.5 (37.8-68.5) pms, respectively. MSM who did not consistently use a condom in receptive sex (adjusted odds ratio [AOR]: 2.06, 95% CIs: 1.14-3.72) were more likely to acquire any anal HPV infection. Age at recruitment (1.05, 1.01-1.09) was positively associated with any penile HPV incidence. MSM with over one sex partner in receptive anal sex (0.53, 0.30-0.94) were less likely to clear any anal HPV infection. MSM who were unemployed/students (0.55, 0.30-0.98) were less likely to clear any penile HPV infection. Conclusion: High incidence and low clearance of anogenital HPV infection among MSM in the study serve as a reminder that this population needs to be targeted for HPV vaccination. It is essential for MSM to scale up HPV screening and adhere to safe sex.

Effectiveness and cost-effectiveness of human papillomavirus vaccination strategies among men who have sex with men in China: a modeling study.

Introduction: The health and economic benefits of human papillomavirus (HPV) vaccination targeted at men who have sex with men (MSM) in developing settings have been rarely assessed. This study aimed to evaluate the effectiveness and cost-effectiveness of different HPV vaccination strategies among MSM in China. Methods: A Markov model was developed to simulate HPV transmission dynamics among a total of 30.73 million MSM in China. The corresponding natural history included 6 states: susceptible, infected with low-risk subtypes, high-risk subtypes, anogenital warts and anal cancer, and deaths from anal cancer. MSM were divided into three age groups with cut-off points of 27 and 45 years. Alternative vaccination strategies were built by allocating bivalent, quadrivalent, nine-valent, or no vaccine to each of the groups. We generated the prevented infections and deaths by vaccination compared with baseline (no vaccination) and calculated incremental cost-effectiveness ratios (ICERs) to determine the optimal strategy. Results: The model showed that in 10 years, at baseline, the existing cases of anogenital warts would reach 5,464,225 (IQR, 4,685,708-6,174,175); that of anal cancer would reach 1,922.95 (1,716.56-2,119.93), resulting in 940.55 (732.27-1,141.87) deaths. Under 50% vaccination coverage among one age group, the prevented cases of anogenital warts were maximized with quadrivalent vaccines allocated to MSM aged 27-45 years; that of anal cancer were maximized when offering nine-valent vaccines to the same group. Under 50% vaccination coverage among all groups, the lowest ICER (34,098.09 USD/QALY, 31,146.54-37,062.88) was reached when only quadrivalent vaccines were provided. Based on this strategy, when the annual vaccination rate increased by 30%, the ICER (33,521.75 USD/QALY, 31,040.73-36,013.92) would fall below three times China's per capita GDP. When the vaccine price decreased by 60%, the ICER was reduced to 7,344.44 USD/QALY (4,392.89-10,309.23), indicating good cost-effectiveness taking China's per capita GDP as a threshold. Conclusions: HPV vaccination can effectively reduce the prevalence and mortality of related diseases among MSM in China, especially quadrivalent vaccines for anogenital warts and nine-valent vaccines for anal cancer. MSM aged 27-45 years were the optimal group for vaccination. Annual vaccination and appropriate adjustment of vaccine price are necessary to further improve the cost-effectiveness.

Changes in human papillomavirus prevalence, incidence, and clearance among men who have sex with men in Xinjiang, China after implementation of nonpharmaceutical interventions to control COVID-19: An interrupted time series analysis.

OBJECTIVES: This study aimed to assess the effects of COVID-19 nonpharmaceutical interventions (NPIs) on the human papillomavirus (HPV) epidemic among men who have sex with men (MSM) in Xinjiang, China. METHODS: In our cohort study, we enrolled and followed HIV-negative MSM in Xinjiang, China, between 2016 and 2022. Anal swab samples were collected to test for HPV DNA. We used interrupted time series analysis to characterize the temporal trends in HPV prevalence, incidence, and clearance before (September 01, 2016, to July 16, 2020) and during the implementation of COVID-19 NPIs in Xinjiang (July 17, 2020, to March 31, 2022). We used binomial segmented regression models to estimate the impact of COVID-19 NPIs on HPV prevalence, incidence, and clearance. RESULTS: We recruited 1296 MSM who contributed to a total of 5374 HPV tests in our study. COVID-19 NPIs were associated with a 37.9% decrease in the prevalence (prevalence ratio, 0.621; 95% confidence interval, 0.465-0.830), 52.2% decrease in the incidence (risk ratio, 0.478; 0.377-0.606), and 40.4% increase in the clearance (risk ratio, 1.404; 1.212-1.627) of HPV of any genotype after the implementation of COVID-19 NPIs in Xinjiang. CONCLUSION: COVID-19 NPIs may lead to lower transmission and higher clearance of HPV among MSM. Future studies are needed to clarify the longer-term impact of COVID-19 on the transmission and natural history of HPV among MSM.

Corrigendum: Incidence, persistence, and clearance of anogenital human papillomavirus among men who have sex with men in Taiwan: a community cohort study.

[This corrects the article DOI: 10.3389/fimmu.2023.1190007.].

Voluntary Medical Male Circumcision and Incident HIV Infection Among Men Who Have Sex With Men in China (The CoM Study): Protocol for a Randomized Controlled Trial.

BACKGROUND: Systematic reviews and meta-analyses based on observational studies have shown voluntary medical male circumcision (VMMC) may reduce HIV risk among men who have sex with men (MSM). There is a lack of randomized controlled trial (RCT) data assessing the efficacy of VMMC. OBJECTIVE: The primary objective of this study was to assess the efficacy of VMMC for preventing HIV acquisition among MSM who primarily engage in insertive anal sex. METHODS: A multicenter RCT will be conducted among MSM in 8 cities in China. Eligible participants are men aged 18-49 years who self-report ≥2 male sex partners in the past 6 months, predominantly practice insertive anal sex, and are willing to undergo circumcision. Interested men who satisfy inclusion criteria will be tested for HIV 1 month before enrollment and at enrollment, and only those who are HIV negative will be enrolled. At baseline, all enrolled participants will be asked to report sociodemographic characteristics and sexual behaviors; provide a blood sample for HIV, syphilis, and herpes simplex virus type 2 testing; and provide a penile swab for human papillomavirus testing. Participants will be randomly assigned to the intervention or control group. Those in the intervention group will receive VMMC and undergo a web-based weekly follow-up assessment of postsurgery healing for 6 consecutive weeks. All participants will be tested for HIV at 3-, 6-, 9-, and 12-month follow-ups. All participants will also be asked to report sexual behaviors and undergo repeat herpes simplex virus type 2 and human papillomavirus testing at 6- and 12-month follow-ups. The primary end point is HIV seroconversion. Secondary end points are the safety and satisfaction with VMMC and the changes in sexual behaviors after VMMC. The grouped censored data will be analyzed by intention-to-treat approach. RESULTS: Recruitment for the RCT began in August 2020 and continued through July 2022. Data collection is expected to be completed by July 2023, and full data analysis is going to be completed by September 2023. CONCLUSIONS: This study will be the first RCT to assess the efficacy of VMMC in preventing HIV infection among MSM. Results from this trial will provide preliminary evidence for the potential efficacy of VMMC to reduce incident HIV infection among MSM. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000039436; https://www.chictr.org.cn/showproj.html?proj=63369. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/47160.

Combating breast cancer progression through combination therapy with hypomethylating agent and glucocorticoid.

Breast cancer is the leading cause of cancer-related death in women. Among breast cancer types, triple-negative breast cancer (TNBC) accounts for 15% of all breast cancers with aggressive tumor behavior. By using bioinformatic approaches, we observed that the microRNA-708 promoter is highly methylated in breast carcinomas, and this methylation is linked to a poor prognosis. Moreover, microRNA-708 expression correlates with better clinical outcomes in TNBC patients. Combination treatment with the hypomethylating agent decitabine and synthetic glucocorticoid significantly increased the expression of microRNA-708, reactivated DNMT-suppressed pathways, and decreased the expression of multiple metastasis-promoting genes such as matrix metalloproteinases (MMPs) and IL-1ß, leading to the suppression of breast cancer cell proliferation, migration, and invasion, as well as reduced tumor growth and distant metastasis in the TNBC xenograft mouse model. Overall, our study reveals a therapeutic opportunity in which a combined regimen of decitabine with glucocorticoid may have therapeutic potential in treating TNBC patients.

Perception of and Vaccine Readiness towards Mpox among Men Who Have Sex with Men Living with HIV in China: A Cross-Sectional Study.

BACKGROUND: Men who have sex with men (MSM) living with HIV make up the majority of cases in the current Mpox outbreak. We aimed to investigate the perception of and vaccine readiness towards Mpox among MSM living with HIV in China. METHODS: This cross-sectional online study was conducted from 10 August to 9 September 2022. Participants responded to survey questions about their socio-demographic information, HIV status, sexual behaviors, knowledge of Mpox, and attitudes towards Mpox vaccines. RESULTS: A total of 577 MSM living with HIV participated in the study. A total of 37.6% expressed concerns about the Mpox epidemic in China, and 56.8% were willing to get the Mpox vaccine. Men who had > four sexual partners in the previous three months (aOR = 1.9 95% CI: 1.2-2.8 Ref: 0), had close contact with > four individuals in a day (3.1, 1.5-6.5 Ref: 0-3), were worried about the Mpox epidemic in China (1.6, 1.1-2.3 Ref: No), and believed that Mpox vaccines are safe (6.6, 2.7-16.4 Ref: No or not sure) and effective (1.9, 1.1-3.3 Ref: No) for people living with HIV were more likely to be willing to get the Mpox vaccine. MSM living with HIV with a high school education or below (0.5, 0.3-0.9 Ref: Postgraduate diploma), and sometimes (0.5, 0.3-0.8 Ref: Often), seldom, or never (0.5, 0.3-0.9 Ref: Often) followed news about Mpox were unwilling to get the Mpox vaccine. CONCLUSION: The ongoing Mpox pandemic has not attracted widespread concerns among MSM living with HIV in China. Having more sexual partners and close contacts, worrying about the Mpox epidemic, and believing in the vaccine's safety and efficacy were predictors of their willingness to get the Mpox vaccine. Efforts should be made to raise awareness of the potential risk of Mpox in this at-risk population. Public health strategies should fully address predictors of vaccination willingness.

Altered gut microbiota is associated with different immunologic responses to antiretroviral therapy in HIV-infected men who have sex with men.

The association between gut microbiota and immunologic nonresponse among people living with HIV (PLHIV) on antiretroviral therapy (ART) is not well documented. This study aimed to characterize gut microbiota among HIV-infected men who have sex with men (MSM) with different immunologic responses. We recruited HIV-infected MSM and HIV-uninfected MSM (healthy controls, HC) in Guangzhou, June-October 2021. HIV-infected MSM were grouped into good immunological responders (GIR) (CD4 + T cell count ≥ 350 cells/µL) and poor immunological responders (PIR) (<350 cells/µL). Blood and stool samples were collected. Microbial translocation in serum was performed using enzyme-linked immunosorbent assay (ELISA). Bacterial 16S ribosomal DNA sequencing was performed on stool samples, and microbial metabolites were obtained through gas chromatography-mass spectrometry. 56 GIR, 41 PIR, and 51 HC were included. Microbial translocation marker soluble cluster of differentiation 14 (sCD14) in both GIR and PIR groups was significantly higher than that in HC. Compared with PIR or HC groups, the genera of Coprococcus, Blautia, Clostridium, and SMB53 were decreased, whereas Megamonas and Megasphaera were more abundant in GIR group. Compared with GIR or PIR groups, Bifidobacterium, Collinsella, Faecalibacterium, Oscillospira, and Roseburia were more abundant, whereas Escherichia was decreased in HC group. The levels of benzenoids, imidazoles, phenylpropanoic acids, phenylpropanoids, and pyridines showed strongly significant correlations between differential genera. This study presented a comprehensive landscape of gut microbiota in PLHIV with different treatment outcomes. Megamonas, Coprococcus and Blautia were the major genera correlated with different immunologic responses in PLHIV.

Knowledge of Human Mpox (Monkeypox) and Attitude towards Mpox Vaccination among Male Sex Workers in China: A Cross-Sectional Study.

BACKGROUND: Re-emerging human mpox (previously known as monkeypox) is spreading around the world. According to existing studies, the current mpox pandemic mainly affects men who have sex with men (MSM), including male sex workers (MSW). Our study aimed to assess mpox knowledge and attitude towards mpox vaccination among MSW in China. METHODS: A web-based, cross-sectional survey was conducted in August 2022. We collected participants' socio-demographic characteristics and knowledge with 15 knowledge items related to mpox. Modified Bloom's cut-off points of 80% (total score > 12) was used to indicate good knowledge. Multivariable regression analysis was used to assess factors of mpox knowledge and attitude towards mpox vaccination. RESULTS: A total of 154 MSW were recruited (age: median = 22, interquartile range, IQR = 12). Of the 154 MSW, 49.4% had good knowledge of mpox, and 63.0% were willing to be vaccinated against mpox. We found that good knowledge was associated with being single [adjusted odds ratio (AOR) = 2.46, 95% confident interval (CI) (1.22-4.87)], being unemployed [5.01, 1.21-20.70] and willingness to be vaccinated [2.51, 1.14-5.54]. Willingness to get vaccinated was related to age [1.06, 1.00-1.12], chronic diseases history [8.53, 1.01-71.68], and agreement with "priority for high-risk groups if mpox vaccine is in short supply" [2.57, 1.01-6.54]. CONCLUSIONS: We found that MSW had suboptimal mpox knowledge and a high willingness to be vaccinated against mpox. MSW who are single and willing to be vaccinated may have good knowledge of mpox. These findings underscore the necessity of providing health education on mpox among MSW. When the mpox vaccine is in short supply, priority should be given to high-risk groups, such as MSW.

Monkeypox awareness and low vaccination hesitancy among men who have sex with men in China.

Men who have sex with men (MSM) have been recommended for targeted monkeypox vaccination. We aimed to investigate monkeypox awareness and explore the correlates of monkeypox vaccination hesitancy among MSM in China. We conducted a cross-sectional survey from August 10 to September 9, 2022. Awareness related to monkeypox and attitude toward monkeypox vaccination among MSM aged ≥18 years were collected. Multivariable logistic regression was applied to evaluate correlates of vaccination hesitancy. The discrepancy in awareness between subgroups regarding HIV status was assessed. A total of 1090 MSM were included (age: median 30 years, interquartile range [IQR], 25-35; HIV-infected: 53.12%). Only 13.85% of respondents expressed high monkeypox vaccination hesitancy. Hesitancy was associated with no fixed income (adjuster odds ratio [aOR], 2.46, 95% confidence interval [CI], 1.48-4.11), infrequent information following (sometimes, 3.01, 1.55-5.83; seldom or never, 5.66, 2.58-12.45), and lack of worries about monkeypox endemic (1.78, 1.11-2.87). Participants who believed that HIV-infected cases accounted for a smaller proportion (1.62, 1.01-2.60), disagreed that monkeypox virus could be detected in semen (2.21, 1.26-3.88), and considered either replication-competent (1.84, 1.14-2.96) or replication-deficient (4.80, 2.26-10.21) monkeypox vaccine unsuitable for HIV-infected people were generally more hesitant. Compared with HIV-uninfected MSM, HIV-infected MSM supported more for vaccination promotion. MSM in China had low hesitancy toward monkeypox vaccination. Safety and affordability of vaccine and availability of information were essential aspects to reduce hesitancy. Education on vaccination benefits should be encouraged to promote future vaccination plans.

Perceptions and worries about monkeypox, and attitudes towards monkeypox vaccination among medical workers in China: A cross-sectional survey.

BACKGROUND: The World Health Organization (WHO) declared monkeypox a "public health emergency of international concern" on 23 June 2022. However, there is a lack of data on monkeypox perceptions among medical workers. The purposes of this study were to evaluate perceptions, worries about monkeypox, attitudes towards monkeypox vaccination and their correlates among medical workers in China. METHODS: Data were collected from medical practitioners using an online survey questionnaire between September 1 and September 30, 2022 in China. All the subjects completed an online questionnaire including general characteristics, perceptions/knowledge/worries about monkeypox, and attitudes towards monkeypox vaccination. Logistic regression was employed to examine the correlates of perceptions, worries about monkeypox, and attitudes toward monkeypox vaccination. RESULTS: In total, this study sample included 639 medical workers. The mean age was 37.9 ± 9.4 years old. Approximately 71.8% of individuals reported perceptions of monkeypox, 56.7% worried about monkeypox, and 64.9% supported the promotion of monkeypox vaccination. Medical workers who were older than 50 years (aOR 3.73, 95%CI 1.01-13.85), worked in the Infectious Diseases/Dermatology/Venereal Diseases departments (3.09, 1.61-5.91), and provided correct answer to monkeypox transmission route (10.19, 5.42-19.17) were more likely to know about monkeypox/monkeypox virus before investigation. 30.7% reported that they were more worried about monkeypox than the coronavirus (COVID-19). Participants reported that the key population most in need of monkeypox vaccination were health practitioners (78.2%) and people with immunodeficiency (74.3%), followed by children (65.4%) and older adults (63.2%). CONCLUSION: Awareness of monkeypox was high and attitude towards the promotion of monkeypox vaccination was positive among medical staff in China. Further targeted dissemination of monkeypox common knowledge among health care providers might improve their precaution measures and improve the promotion of monkeypox vaccination among key populations.

The Impact of COVID-19 Lockdown on Cases of and Deaths From AIDS, Gonorrhea, Syphilis, Hepatitis B, and Hepatitis C: Interrupted Time Series Analysis.

BACKGROUND: China implemented a nationwide lockdown to contain COVID-19 from an early stage. Previous studies of the impact of COVID-19 on sexually transmitted diseases (STDs) and diseases caused by blood-borne viruses (BBVs) in China have yielded widely disparate results, and studies on deaths attributable to STDs and BBVs are scarce. OBJECTIVE: We aimed to elucidate the impact of COVID-19 lockdown on cases, deaths, and case-fatality ratios of STDs and BBVs. METHODS: We extracted monthly data on cases and deaths for AIDS, gonorrhea, syphilis, hepatitis B, and hepatitis C between January 2015 and December 2021 from the notifiable disease reporting database on the official website of the National Health Commission of China. We used descriptive statistics to summarize the number of cases and deaths and calculated incidence and case-fatality ratios before and after the implementation of a nationwide lockdown (in January 2020). We used negative binominal segmented regression models to estimate the immediate and long-term impacts of lockdown on cases, deaths, and case-fatality ratios in January 2020 and December 2021, respectively. RESULTS: A total of 14,800,330 cases of and 127,030 deaths from AIDS, gonorrhea, syphilis, hepatitis B, and hepatitis C were reported from January 2015 to December 2021, with an incidence of 149.11/100,000 before lockdown and 151.41/100,000 after lockdown and a case-fatality ratio of 8.21/1000 before lockdown and 9.50/1000 after lockdown. The negative binominal model showed significant decreases in January 2020 in AIDS cases (-23.4%; incidence rate ratio [IRR] 0.766, 95% CI 0.626-0.939) and deaths (-23.9%; IRR 0.761, 95% CI 0.647-0.896), gonorrhea cases (-34.3%; IRR 0.657, 95% CI 0.524-0.823), syphilis cases (-15.4%; IRR 0.846, 95% CI 0.763-0.937), hepatitis B cases (-17.5%; IRR 0.825, 95% CI 0.726-0.937), and hepatitis C cases (-19.6%; IRR 0.804, 95% CI 0.693-0.933). Gonorrhea, syphilis, and hepatitis C showed small increases in the number of deaths and case-fatality ratios in January 2020. By December 2021, the cases, deaths, and case-fatality ratios for each disease had either reached or remained below expected levels. CONCLUSIONS: COVID-19 lockdown may have contributed to fewer reported cases of AIDS, gonorrhea, syphilis, hepatitis B, and hepatitis C and more reported deaths and case-fatality ratios of gonorrhea, syphilis, and hepatitis C in China.