Optimization of genetic distance threshold for inferring the CRF01_AE molecular network based on next-generation sequencing.

Introduction: HIV molecular network based on genetic distance (GD) has been extensively utilized. However, the GD threshold for the non-B subtype differs from that of subtype B. This study aimed to optimize the GD threshold for inferring the CRF01_AE molecular network. Methods: Next-generation sequencing data of partial CRF01_AE pol sequences were obtained for 59 samples from 12 transmission pairs enrolled from a high-risk cohort during 2009 and 2014. The paired GD was calculated using the Tamura-Nei 93 model to infer a GD threshold range for HIV molecular networks. Results: 2,019 CRF01_AE pol sequences and information on recent HIV infection (RHI) from newly diagnosed individuals in Shenyang from 2016 to 2019 were collected to construct molecular networks to assess the ability of the inferred GD thresholds to predict recent transmission events. When HIV transmission occurs within a span of 1-4 years, the mean paired GD between the sequences of the donor and recipient within the same transmission pair were as follow: 0.008, 0.011, 0.013, and 0.023 substitutions/site. Using these four GD thresholds, it was found that 98.9%, 96.0%, 88.2%, and 40.4% of all randomly paired GD values from 12 transmission pairs were correctly identified as originating from the same transmission pairs. In the real world, as the GD threshold increased from 0.001 to 0.02 substitutions/site, the proportion of RHI within the molecular network gradually increased from 16.6% to 92.3%. Meanwhile, the proportion of links with RHI gradually decreased from 87.0% to 48.2%. The two curves intersected at a GD of 0.008 substitutions/site. Discussion: A suitable range of GD thresholds, 0.008-0.013 substitutions/site, was identified to infer the CRF01_AE molecular transmission network and identify HIV transmission events that occurred within the past three years. This finding provides valuable data for selecting an appropriate GD thresholds in constructing molecular networks for non-B subtypes.

Riemerella anatipestifer UvrC is required for iron utilization, biofilm formation and virulence.

UvrC is a subunit of excinuclease ABC, which mediates nucleotide excision repair (NER) in bacteria. Our previous studies showed that transposon Tn4531 insertion in the UvrC encoding gene Riean_1413 results in reduced biofilm formation by Riemerella anatipestifer strain CH3 and attenuates virulence of strain YZb1. In this study, whether R. anatipestifer UvrC has some biological functions other than NER was investigated. Firstly, the uvrC of R. anatipestifer strain Yb2 was in-frame deleted by homologous recombination, generating deletion mutant ΔuvrC, and its complemented strain cΔuvrC was constructed based on Escherichia coli - R. anatipestifer shuttle plasmid pRES. Compared to the wild-type (WT) R. anatipestifer strain Yb2, uvrC deleted mutant ΔuvrC significantly reduced biofilm formation, tolerance to H2O2- and HOCl-induced oxidative stress, iron utilization, and adhesion to and invasion of duck embryonic hepatocytes, but not its growth curve and proteolytic activity. In addition, animal experiments showed that the LD50 value of ΔuvrC in ducklings was about 13-fold higher than that of the WT, and the bacterial loads in ΔuvrC infected ducklings were significantly lower than those in Yb2-infected ducklings, indicating uvrC deletion in R. anatipestifer attenuated virulence. Taken together, the results of this study indicate that R. anatipestifer UvrC is required for iron utilization, biofilm formation, oxidative stress tolerance and virulence of strain Yb2, demonstrating multiple functions of UvrC.RESEARCH HIGHLIGHTSDeletion of uvrC in R. anatipestfer Yb2 significantly reduced its biofilm formation.uvrC deletion led to reduced tolerance to H2O2- and HOCl-induced oxidative stress.The iron utilization of uvrC deleted mutant was significantly reduced.The uvrC deletion in R. anatipestifer Yb2 attenuated its virulence.

Trajectories of anxiety and depression among Chinese men who have sex with men on pre-exposure prophylaxis: a group-based trajectory model approach.

BACKGROUND: Anxiety and depression can influence adherence to Pre-exposure Prophylaxis (PrEP). However, there is limited research on the temporal dynamics of anxiety and depression among men who have sex with men (MSM) using PrEP. METHODS: From December 2018 to November 2020, we administered the Hospital Anxiety and Depression Scale (HADS) to participants in the China Real-World Oral Intake of PrEP (CROPrEP) to measure their anxiety and depression levels. The group-based trajectory model (GBTM) depicted the dynamic changes of anxiety and depression scores over time. RESULTS: A total of 1023 MSM were included, with 4523 follow-up assessments. The GBTM categorized the trajectories into three distinct patterns: consistently low (54.8% for anxiety, 60.7% for depression), consistently moderate (39.3% for anxiety, 31.4% for depression), and high but bell-shaped (5.9% for anxiety, 7.9% for depression). Higher anxiety levels were associated with being aged 18-30 years old, earning less than US$619 per month, female-identifying, adopting the bottom sexual role with men, and having two or more anal sex partners in the past three months; similarly, higher depression levels correlated with a monthly income under US$619, female-identifying, sexual behavior as bottom and a positive syphilis at baseline. PrEP adherence was notably lower in the high but bell-shaped anxiety and depression group compared to the other groups, particularly at the 12th-month follow-up. CONCLUSIONS: Close monitoring of anxiety and depression levels in MSM on PrEP is crucial. Provision of targeted mental health support is essential to enhance PrEP effectiveness.

Willingness to take long-acting injectable pre-exposure prophylaxis among men who have sex with men who participated in the CROPrEP study: a cross-sectional online study.

INTRODUCTION: Evidence on the willingness of men who have sex with men (MSM) with oral pre-exposure prophylaxis (PrEP) experience, especially those with suboptimal adherence, to take long-acting injectable PrEP (LAI-PrEP) is critical to guide future LAI-PrEP implementation. OBJECTIVE: The objective was to assess the willingness of MSM with oral PrEP experience to take LAI-PrEP. METHODS: MSM who participated in the China Real-world Study of Oral PrEP (CROPrEP) were enrolled in this study. Information on the willingness of MSM to take LAI-PrEP and potential correlates was collected using a structured online questionnaire. The main outcomes were the willingness of MSM to take LAI-PrEP and its association with HIV-related behaviours, sexually transmitted infections, and oral PrEP history. Logistic regression was used to identify correlates of the willingness of MSM to take LAI-PrEP. RESULTS: A total of 612 former CROPrEP participants (FCPs) were included in this study. There were 315 (51.5%) daily oral PrEP (D-PrEP) users and 297 (48.5%) event-driven oral PrEP (ED-PrEP) users at the last follow-up. Most FCPs (77.8%) were willing to take free LAI-PrEP. FCPs with no less than two sexual male partners (aOR = 1.54, [95% CI: 1.04, 2.29], P = 0.031), those with male partners with unknown HIV statuses (aOR = 2.04, [95% CI: 1.31, 3.18], P = 0.002), those with recreational drug use (aOR = 1.58, [95% CI: 1.05, 2.40], P = 0.030), and those with HSV-2 positivity (aOR = 2.15, [95% CI: 1.30, 3.57], P = 0.003) were more willing to take LAI-PrEP, while ED-PrEP users (aOR = 0.66, [95% CI: 0.45, 0.98], P = 0.037) and FCPs with suboptimal oral PrEP adherence (aOR = 0.58, [95% CI: 0.36, 0.94], P = 0.026) were less willing to take LAI-PrEP. CONCLUSION: LAI-PrEP has good prospects for expanding PrEP coverage. However, FCPs with suboptimal oral PrEP adherence are less likely to take LAI-PrEP. Further intervention and implementation efforts are needed to improve the willingness of MSM to use LAI-PrEP, and sexual health should be considered during the discussion about PrEP initiation.

Inhibitory receptor CD47 binding to plasma TSP1 suppresses NK-cell IFN-γ production via activating the JAK/STAT3 pathway during HIV infection.

BACKGROUND: Natural killer (NK) cells play an important first-line role against tumour and viral infections and are regulated by inhibitory receptor expression. Among these inhibitory receptors, the expression, function, and mechanism of cluster of differentiation 47 (CD47) on NK cells during human immunodeficiency virus (HIV) infection remain unclear. METHODS: Fresh peripheral blood mononuclear cells (PBMCs) were collected from people living with HIV (PLWH) and HIV negative controls (NC) subjects. Soluble ligand expression levels of CD47 were measured using ELISA. HIV viral proteins or Toll-like receptor 7/8 (TLR7/8) agonist was used to investigate the mechanisms underlying the upregulation of CD47 expression. The effect of CD47 on NK cell activation, proliferation, and function were evaluated by flow cytometry. RNA-seq was used to identify downstream pathways for CD47 and its ligand interactions. A small molecule inhibitor was used to restore the inhibition of NK cell function by CD47 signalling. RESULTS: CD47 expression was highly upregulated on the NK cells from PLWH, which could be due to activation of the Toll-like receptor 7/8 (TLR7/8) pathway. Compared with NC subjects, PLWH subjects exhibited elevated levels of CD47 ligands, thrombospondin-1 (TSP1), and counter ligand signal regulatory protein-α (SIRPα). The TSP1-CD47 axis drives the suppression of interferon gamma (IFN-γ) production and the activation of the Janus kinase signal transducer and activator of transcription (JAK-STAT) pathway in NK cells. After treatment with a STAT3 inhibitor, the NK cells from PLWH showed significantly improved IFN-γ production. CONCLUSIONS: The current data indicate that the binding of the inhibitory receptor CD47 to plasma TSP1 suppresses NK cell IFN-γ production by activating the JAK/STAT3 pathway during HIV infection. Our results suggest that CD47 and its related signalling pathways could be targets for improving NK cell function in people living with HIV.

Online distribution of HIV self-testing kits to promote HIV testing among men who have sex with men discontinuing pre-exposure prophylaxis after demonstration project completion in China: a multicentre open-label randomized controlled trial.

Background: HIV self-testing (HIVST) offers potential solutions to challenges associated with site-based HIV testing (SBHT). However, the effectiveness of HIVST as an HIV prevention strategy for men who have sex with men (MSM) discontinuing pre-exposure prophylaxis (PrEP) after the completion of PrEP demonstration project has rarely been assessed. Methods: The China Real-world Study of Oral PrEP (CROPrEP) project was conducted in four cities in China. Participants were directed to community resources to continue their PrEP medication after the discontinuation of project-provided PrEP at the last CROPrEP visit. We conducted a multicentre open-label randomized controlled trial among MSM who had discontinued PrEP induced by the completion of CROPrEP. Eligible participants were randomly assigned to either the intervention group or the control group (1:1). Participants received regular health education and behavioural interventions throughout the trial. The intervention group was given a link to order free HIVST kits online, while the control group received information about free SBHT. Both groups completed internet-based follow-up surveys at three and six months. The primary outcome was the proportion of participants who underwent HIV testing during the six-month follow-up period. This trial was registered at chictr.org.cn (ChiCTR2000038416). Findings: Between November 2020 and January 2021, we recruited a total of 620 participants (300 in the intervention group and 320 in the control group). The follow-up completion rates were 99·0% and 95·0% in the intervention and control groups, respectively. At baseline, the median age of participants was 32 (interquartile range: 26-37), and 77·7% underwent HIV testing in the past three months. The proportion of participants who underwent HIV testing in the past three months was higher in the intervention group than in the control group at both the three-month (adjusted risk difference [RD]: 36·7, 95% confidence interval [CI]: 35·1-38·5, p < 0·001) and six-month (RD: 26·7, 95% CI: 24·6-28·7 p < 0·001) follow-up periods. Interpretation: Our study suggests that providing online distribution of HIVST kits for MSM with PrEP discontinuation induced by completion of the PrEP project effectively promoted HIV testing. This digital approach improves access to HIV testing for MSM and can be applicable to other settings where MSM turn to online public health services. Funding: The study was funded by the Fund of National Natural Science Foundation of China; the Mega-Projects of National Science Research for the 13th Five-Year Plan; and the Liaoning Revitalization Talents Program, China.

Effectiveness and safety of community-led assisted partner service among HIV-diagnosed men who have sex with men: a multicentre, randomized controlled trial in China.

Background: No randomized controlled trials have involved established HIV-diagnosed men who have sex with men (MSM) diagnosed for more than 6 months into the assisted partner service (aPS). We compared voluntary aPS involving community-based organizations (CBOs) and HIV self-testing (aPSST) with regular partner service (rPS) in HIV-diagnosed MSM irrespective of diagnosis time. Methods: In this unblinded, multicentre trial, we enrolled HIV-diagnosed MSM irrespective of diagnosis time in three cities in northern China. Index patients were randomly assigned to aPSST or rPS. Index patients in the aPSST group were additionally provided a comprehensive intervention package including HIV self-testing and CBO-based aPS compared with rPS group. The primary outcome was the number of index patients whose any sexual partner tested for HIV during the 6-month study. Completion of HIV testing was defined as sexual partners taking a clinic-based HIV test or HIV self-testing. Safety was assessed preliminary at the end of the 6-month follow-up. This study has been registered at chictr.org.cn (ChiCTR2000038784). Findings: From March to December 2021, 325 of HIV-diagnosed MSM were enrolled (90⋅2% were established HIV-diagnosed MSM) and randomly assigned to receive aPSST (n = 167) or rPS (n = 158). At 6 months, 110 (65⋅9%) index patients in the aPSST group had at least one sexual partner tested for HIV compared with 50 (31⋅6%) in the rPS group (hazard ratio 2⋅86; 95% confidence interval 2⋅03-4⋅03; p < 0⋅001). No significant difference was observed in effects of aPSST on HIV testing promotion between established and newly HIV-diagnosed MSM. Self-reported harms were infrequently observed in both groups (approximately 2⋅0%). Interpretation: Among HIV-diagnosed MSM regardless of diagnosis time, voluntary aPS involving CBOs and HIV self-testing was effective and safe for promoting partner HIV testing. Funding: This work was supported by the Mega-Projects of National Science Research, the National Natural Science Foundation of China and the Liaoning Revitalization Talents Program, China.

Impact of different industrial activities on heavy metals in floodplain soil and ecological risk assessment based on bioavailability: A case study from the Middle Yellow River Basin, northern China.

Understanding the impact of different industrial activities on heavy metals and conducting scientific ecological risk assessments are critical to the management of heavy metal pollution. The present study compared soils affected by different industrial activities in three types of industrial cities (coal city, oil-gas city, and economic city) to control samples and examined the ecological risk based on bioavailability in the Middle Yellow River Basin. The findings revealed that the impact characteristics of different industrial activities on soil heavy metals in the research area were different. Both coal-based and oil-gas industry activities had a minor impact on soil heavy metals, whereas economic industry activities in the southern part had a major impact, as evidenced by significant enrichment of Cd, Hg, Cu, Pb, and Zn. In principal component analysis, the soil heavy metals affected by economic industry activities designated a distinct source from the control samples, particularly the anthropogenic sources represented by Hg and Cd. In the context of heavy metals in chemical form, three types of industrial activities all had an effect on bioavailability (0.72-24.27%) and could increase migratory activity in the environment. Furthermore, both traditional and improved assessments, based on total content and bioavailability, showed a low ecological risk near coal cities and oil-gas cities in the middle and northern parts, while there was a medium-high ecological risk near economically developed cities in the south, particularly Tianshui, Baoji, Qishan, Xianyang, Xi'an, and Tongchuan. In comparison, improved risk assessment based on bioavailability tends to not only compensate for an overestimation in traditional risk assessment from the perspective of total content, but additionally achieve a more reasonable, effective, and advanced assessment of heavy metal risks in scientific research. The outcome of this study has significance for the ecological conservation and high-quality development of the Yellow River Basin.

Spatial-temporal variability and influence factors of Cd in soils of Guangxi, China.

In this study, the regional spatial-temporal variability of cadmium (Cd) in the topsoil of Guangxi, China from 2010 to 2016 was studied from data obtained from the China Geochemical Baseline Project (CGB Ⅰ and CGB Ⅱ). The driving forces of natural and anthropogenic variables were quantitatively analyzed using a geographically and temporally weighted regression model. The results showed that 1) soil Cd was highly enriched in 2010 and in soils of Hechi city in northwest Guangxi, a non-ferrous metal mining and metallurgy area, ~17% of the samples exceeded the soil contamination risk limit. In contrast, in 2016, the topsoil Cd content decreased significantly, with 7% of sites exceeding the soil risk limit. 2) Multiple factors jointly influenced the regional spatial variability of Cd. pH and organic carbon were found to be the main factors influencing Cd content and were strongly spatially correlated with Cd. Anthropogenic activities, including mining and industrial emissions, resulted in significant Cd enrichment in local areas, whereas agricultural and domestic pollutants were relatively weakly correlated with Cd. The weathering products of carbonates were significantly enriched in Cd; thus, the geological background played a significant role in the spatial variability of Cd. Soil-forming factors, including temperature, precipitation, and elevation influenced the spatial distribution of Cd, especially in the Cd background area. 3) Anthropogenic activities were the key factors influencing temporal changes in Cd. Mining caused significant enrichment of Cd in CGB Ⅰ, while industrial emissions were the primary factor for Cd enrichment in CGB Ⅱ. In addition, natural factors also played an important role; the increased Normalized Difference Vegetation Index suggested reduced desertification and reduction of soil erosion in the watershed and in pollutants transported from upstream.

DEAD Box Protein DhR1 Is a Global Regulator Involved in the Bacterial Fitness and Virulence of Riemerella anatipestifer.

DEAD box proteins perform diverse cellular functions in bacteria. Our group previously reported that the transposon Tn4531 insertion in Riean_0395 (designated dhR1), which encodes a putative DEAD box helicase, attenuated the virulence of R. anatipestifer strain YZb1. Here, we show that, compared to the wild-type (WT) R. anatipestifer strain Yb2, the growth or survival of the ΔdhR1 mutant in tryptic soy broth (TSB) was significantly decreased in response to cold, pH, osmotic stress, ethanol, Triton X-100, and oxidative stress, and the dhR1 deletion significantly reduced biofilm formation and the adhesion capacity to Vero cells, whereas the growth of ΔdhR1 was less impaired in iron-limited TSB. Moreover, the virulence of ΔdhR1 in ducklings was attenuated by about 80-fold, compared to the WT. In addition, a transcriptome analysis showed that the dhR1 deletion in the strain Yb2 affected the expression of 58 upregulated genes and 98 downregulated genes that are responsible for various functions. Overall, our work reveals that the deletion of DhR1 results in a broad effect on the bacterial fitness, biofilm formation, iron utilization, and virulence of R. anatipestifer, which makes it a global regulator. IMPORTANCE R. anatipestifer infection has been a continued and serious problem in many duck farms, but little is known about the mechanism underlying the pathogenesis of R. anatipestifer and how R. anatipestifer adapts to the external environment and thereby persists in duck farms. The results of this study demonstrate that the DEAD box protein DhR1 is required for the tolerance of R. anatipestifer to cold, pH, and other stresses, and it is also necessary for biofilm formation, iron utilization, and virulence in ducklings, demonstrating multiple functions of DhR1.

Double spiral chip-embedded micro-trapezoid filters (SMT filters) for the sensitive isolation of CTCs of prostate cancer by spectral detection.

Circulating tumor cells (CTCs) are cancer cells that are released from the original tumor and circulate in the blood vessels, carrying greatly similar constituents as the original tumor. Therefore, CTCs have a significant value in cancer prognosis, early diagnosis, and anti-cancer therapy. However, their rarity and heterogeneity make the isolation of CTCs an arduous task. In the present research, we propose a double spiral chip-embedded micro-trapezoid filter (SMT filter) for the sensitive isolation of the CTCs of prostate cancer by spectral detection. SMT filters were elongated to effectively capture CTCs and this distinctive design was conducive to their isolation and enrichment. The SMT filters were verified with tumor cells and artificial patient blood with a capture efficiency as high as 94% at a flow rate of 1.5 mL h-1. As a further validation, the SMT filters were validated in isolating CTCs from 10 prostate cancers and other cancers in 4 mL blood samples. Also, the CTCs tested positive for each patient blood sample, ranging from 83-114 CTCs. Significantly, we advanced hyperspectral imaging to detect the characteristic spectrum of CTCs both captured in situ on SMT filters and enriched after isolation. The CTCs could be positively identified by hyperspectral imaging with complete integrity of the cell morphology and an improved characteristic spectrum. This represents a breakthrough in the conventional surface-enhanced Raman scattering (SERS) spectroscopy of nanoparticles. Also, the characteristic spectrum of the CTCs would be highly beneficial for distinguishing the cancer type and accurate for enumerating tumor cells with varied intensities. Furthermore, a novel integrated flower-shaped microfilter was presented with all these aforementioned merits. The success of both the SMT filters and characteristic spectral detection indicated their feasibility for further clinical analysis, the evaluation of cancer therapy, and for potential application.

CD38+CD39+ NK cells associate with HIV disease progression and negatively regulate T cell proliferation.

The ectonucleotidases CD38 and CD39 have a critical regulatory effect on tumors and viral infections via the adenosine axis. Natural killer (NK) cells produce cytokines, induce cytotoxic responses against viral infection, and acquire immunoregulatory properties. However, the roles of CD38 and CD39 expressed NK cells in HIV disease require elucidation. Our study showed that the proportions of CD38+CD39+ NK cells in HIV-infected individuals were positively associated with HIV viral loads and negatively associated with the CD4+ T cell count. Furthermore, CD38+CD39+ NK cells expressed additional inhibitory receptors, TIM-3 and LAG-3, and produced more TGF-ß. Moreover, autologous NK cells suppressed the proliferation of CD8+ T and CD4+ T cells of HIV-infected individuals, and inhibiting CD38 and CD39 on NK cells restored CD8+ T and CD4+ T cell proliferation in vitro. In conclusion, these data support a critical role for CD38 and CD39 on NK cells in HIV infection and targeting CD38 and CD39 on NK cells may be a potential therapeutic strategy against HIV infection.

CD160 Promotes NK Cell Functions by Upregulating Glucose Metabolism and Negatively Correlates With HIV Disease Progression.

Natural killer (NK) cells are crucial for immune responses to viral infections. CD160 is an important NK cell activating receptor, with unknown function in HIV infection. Here, we found that CD160 expression was reduced on NK cells from HIV-infected individuals and its expression was negatively correlated with HIV disease progression. Further, GLUT1 expression and glucose uptake were higher in CD160+ NK cells, and the results of RNA-seq and flow cytometry demonstrated that CD160 positively regulated glucose metabolism through the PI3K/AKT/mTOR/s6k signaling pathway, thereby enhancing NK cell function. Moreover, we determined that reduced CD160 expression on NK cells could be attributed to the higher plasma levels of TGF-ß1 in HIV-infected individuals. Overall, these results highlight the vital role of CD160 in HIV disease progression and regulation of glucose metabolism, indicating a potential target for HIV immunotherapy.

Patterns of Sexually Transmitted Co-infections and Associated Factors Among Men Who Have Sex With Men: A Cross-Sectional Study in Shenyang, China.

Background: Men who have sex with men (MSM) are disproportionately affected by sexually transmitted infections (STIs). We sought to describe patterns of sexually transmitted co-infections and explore factors associated with increased acquisition of STIs among MSM. Methods: We enrolled MSM in Shenyang, China, between July and December 2020 to test for four STIs, including human papillomavirus (HPV), Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and Treponema pallidum (TP). Data regarding demographic and behavioral characteristics of participants were collected through a self-administered digital questionnaire. We adopted the ordinal logistic regression model to identify factors associated with acquiring more STIs. Results: Overall, 177 participants with completed test results for all four STIs were analyzed. These participants had a median age of 29.0 (interquartile range: 23.0-38.0) years. The prevalence of STI co-infections was 23.7% [42/177; 95% confidence interval (CI), 17.8%-30.8%], among which HPV/CT (47.1%) and HPV/CT/NG (50.0%) co-infection were the predominant types among participants with dual and multiple infections, respectively. Participants who had a higher educational background [adjusted odds ratio (aOR), 0.46; 95% CI, 0.24-0.85; P = 0.014] and had a history of STIs (aOR, 2.53; 95% CI, 1.24-5.18; P = 0.011) were positively associated with acquiring more STIs. Conclusions: MSM in Shenyang suffer a substantial burden of sexually transmitted co-infections. An optimized multi-STI integration strategy targeting prevention, surveillance, screening, and treatment is warranted to reduce the prevalence of sexually transmitted co-infections, especially in less-educated MSM.

Medication Non-adherence and Condomless Anal Intercourse Increased Substantially During the COVID-19 Pandemic Among MSM PrEP Users: A Retrospective Cohort Study in Four Chinese Metropolises.

Background: The coronavirus disease (COVID-19) pandemic has impacted HIV prevention strategies globally. However, changes in pre-exposure prophylaxis (PrEP) adherence and HIV-related behaviors, and their associations with medication adherence among men who have sex with men (MSM) PrEP users remain unclear since the onset of the COVID-19 pandemic. Methods: A Retrospective Cohort Study of HIV-negative MSM PrEP users was conducted in four Chinese metropolises from December 2018 to March 2020, assessing the changes in PrEP adherence and HIV-related behaviors before and during the COVID-19. The primary outcome was poor PrEP adherence determined from self-reported missing at least one PrEP dose in the previous month. We used multivariable logistic regression to determine factors correlated with poor adherence during COVID-19. Results: We enrolled 791 eligible participants (418 [52.8%] in daily PrEP and 373 [47.2%] in event-driven PrEP). Compared with the data conducted before the COVID-19, the proportion of PrEP users decreased from 97.9 to 64.3%, and the proportion of poor PrEP adherence increased from 23.6 to 50.1% during the COVID-19 [odds ratio (OR) 3.24, 95% confidence interval (CI) 2.62-4.02]. While the percentage of condomless anal intercourse (CAI) with regular partners (11.8 vs. 25.7%) and with casual partners (4.4 vs. 9.0%) both significantly increased. The proportion of those who were tested for HIV decreased from 50.1 to 25.9%. Factors correlated with poor PrEP adherence during the COVID-19 included not being tested for HIV (adjusted odds ratio [aOR] = 1.38 [95% CI: 1.00, 1.91]), using condoms consistently with regular partners (vs. never, aOR = 2.19 [95% CI: 1.16, 4.13]), and being married or cohabitating with a woman (vs. not married, aOR = 3.08 [95% CI: 1.60, 5.95]). Conclusions: Increased poor PrEP adherence and CAI along with the decrease in HIV testing can lead to an increase in HIV acquisition and drug resistance to PrEP. Targeted interventions are needed to improve PrEP adherence and HIV prevention strategies.

Association of HIV Preexposure Prophylaxis Use With HIV Incidence Among Men Who Have Sex With Men in China: A Nonrandomized Controlled Trial.

Importance: Evidence on HIV preexposure prophylaxis (PrEP) among Chinese men who have sex with men (MSM) is critical to guide its large-scale implementation in low- and middle-income countries. Objective: To evaluate incident HIV infection, adherence, safety, and changes in sexual behaviors among MSM using daily PrEP (D-PrEP) and event-driven PrEP (ED-PrEP) in 4 cities in China. Design, Setting, and Participants: This nonrandomized controlled trial was conducted among HIV-seronegative MSM from December 11, 2018, to November 30, 2020, in Beijing, Shenyang, Chongqing, and Shenzhen. Participants self-chose D-PrEP or ED-PrEP regimens at baseline and could switch regimens during the 12-month study period. HIV-negative MSM who declined to initiate PrEP (nonusers) in the same cities joined a separate parallel prospective cohort and served as control individuals. Interventions: PrEP consisted of coformulated tenofovir disoproxil fumarate, 300 mg, and emtricitabine, 200 mg. Main Outcomes and Measures: The main outcome was incident HIV infection. Poisson regression was used to obtain the HIV incidence rate ratio (IRR). Results: A total of 1530 MSM were included in the analysis (median age, 30 [IQR, 25-37] years). At baseline, 520 MSM chose D-PrEP (median age, 29 [IQR, 25-35] years) and 503 chose ED-PrEP (median age, 29 [IQR, 25-36] years). The median HIV Risk Index score was 18 (IQR, 12-22) among D-PrEP users and 18 (IQR, 11-22) among ED-PrEP users. Among 507 PrEP nonusers, the median age was 33 (IQR, 27-43) years, and the median HIV Risk Index score was 12 (IQR, 7-18). Although PrEP users had more baseline behaviors associated with HIV risk, the HIV incidence was lower among all PrEP users (adjusted IRR, 0.09 [95% CI, 0.04-0.21]), ED-PrEP users (adjusted IRR, 0.05 [95% CI, 0.01-0.22]), and D-PrEP users (adjusted IRR, 0.12 [95% CI, 0.04-0.33]) compared with PrEP nonusers. There was no difference in HIV incidence between D-PrEP users and ED-PrEP users (IRR, 0.33 [95% CI, 0.06-2.04]). Event-driven PrEP users consumed 40% fewer tablets than D-PrEP users during the study period. Adherence, defined as the proportion of self-reported days with sexual intercourse in which PrEP was taken according to prescription of at least 90%, increased over time among ED-PrEP users (from 57.4% to 77.8%; P < .001 for trend) and decreased over time among D-PrEP users (from 75.1% to 72.1%; P = .02 for trend). Daily PrEP users reported fewer adverse events than ED-PrEP users (193 of 520 [37.1%] vs 241 of 503 [47.9%]). Conclusions and Relevance: The findings of this study suggest that D-PrEP and ED-PrEP regimens are associated with lower incidence of HIV and a good safety profile among high-risk MSM in China. Trial Registration: Chinese Clinical Trial Registry number: ChiCTR-IIN-17013762.

PaR1 secreted by the type IX secretion system is a protective antigen of Riemerella anatipestifer.

Riemerella anatipestifer mainly infects domestic ducks, geese, turkeys, and other birds, and causes considerable economic losses to the global duck industry. Previous studies have shown that concentrated cell-free culture filtrates of R. anatipestifer induce highly significant protection against homologous challenge. In this study, 12 immunogenic proteins were identified in the culture supernatant of R. anatipestifer strain Yb2 with immunoproteomic analysis. Of these, three immunogenic proteins, AS87_RS06600 (designated "PaR1" in this study), AS87_RS09020, and AS87_RS09965, which appeared in more than three spots on the western-blotted membrane, were expressed in Escherichia coli and purified. Animal experiments showed that the recombinant PaR1 (rPaR1) protein protected 41.67% of immunized ducklings against challenge with virulent Yb2, whereas rAS87_RS09020 or rAS87_RS09965 did not, and that ducklings immunized once with rPaR1 were 20, 40, and 0% protected from challenge with R. anatipestifer strains WJ4 (serotype 1), Yb2 (serotype 2), and HXb2 (serotype 10), respectively. In addition, rPaR1 immunized rabbit serum showed bactericidal activity against strain Yb2 at a titer of 1:8. These results indicate that rPaR1 of strain Yb2 protects against homologous challenge. Amino acid homology analysis show that PaR1 is a non-serotype-specific protein among different R. anatipestifer serotypes. Furthermore, PaR1 is mainly secreted outside the cell through the T9SS. Overall, our results demonstrate that R. anatipestifer PaR1 is a non-serotype-specific protective protein secreted by the T9SS.

High Human Papillomavirus Vaccine Acceptability and Cost-Effectiveness of the Chinese 2-Valent Vaccine Among Men Who Have Sex With Men: A Cross-Sectional Study in Shenyang, China.

Background: Despite the insupportable burden caused by the human papillomavirus (HPV) and high vaccine acceptability, vaccination programs are not currently available for men who have sex with men (MSM). We aimed to assess HPV infection by examining the willingness for vaccination among MSM and cost-effectiveness of the Chinese 2-valent HPV vaccine. Methods: We recruited MSM in Shenyang, China between July and December 2020 to conduct anal HPV testing and an online survey regarding HPV-related knowledge and vaccine acceptability. We performed a cost-effectiveness analysis to evaluate the incremental cost-effectiveness ratios (ICERs) of the Chinese 2-valent HPV vaccine. Results: A total of 234 participants completed the online survey; of those, 203 were successfully tested for HPV. The median age was 30 years [interquartile range (IQR): 23-38 years]. Most participants had at least undergraduate education (136/234, 58.1%). The acceptability rate for the free HPV vaccine was 57.7% (135/234). The prevalence of HPV types 16 and 18 was 14.9% (18/121) and 26.8% (22/82) in the willing and unwilling to vaccinate groups, respectively (P > 0.05). The prevalence of high-risk HPV among participants aged <30 and ≥50 years was 48.6 and 38.9%, respectively. Using the Chinese per capita gross domestic product (GDP) as a threshold, the Chinese 2-valent HPV vaccine would be a "very cost-effective" strategy, with an ICER value of USD 4,411. This evidence showed that the Chinese 2-valent HPV vaccine was more cost-effective than other imported vaccines. Conclusions: Targeted strategies should be utilized in MSM with different rates of vaccine acceptability. A pilot HPV vaccination program based on the Chinese 2-valent HPV vaccine for MSM is urgently warranted to reduce the burden of HPV and anal cancer.

In-hospital Mortality and Causes of Death in People Diagnosed With HIV in a General Hospital in Shenyang, China: A Cross-Sectional Study.

Background: Acquired immune deficiency syndrome (AIDS), caused by human immunodeficiency virus (HIV) infection, is a serious public health issue. This study investigated the correlated factors and possible changing trend of in-hospital death in patients diagnosed with HIV in the past decade in our hospital. Methods: We retrospectively collected data of firstly hospitalized patients with HIV in the Department of Infectious Disease in the First Affiliated Hospital of China Medical University from January 1, 2010 to December 31, 2019, and compared various factors that correlated with in-hospital death, including age, sex, opportunistic infections, and antiretroviral therapy (ART) status. Cox regression analysis was used to identify the risk factors for death. Results: In total, 711 patients were recruited for this study, and 62 patients died in the hospital. The in-hospital mortality rate was 8.72%. Tuberculosis (TB), malignancies, and thrombocytopenia were associated with mortality. Antiviral treatment before admission was found to be a protective factor. There was a declining trend in in-hospital mortality from 19.2% in 2010 to 6.3% in 2019 (linear-by-linear association test, p < 0.001), partly due to intensified medical care strategy. Conclusions: Till date, AIDS-defining illnesses remain the major cause of hospital admission and in-hospital mortality. TB and malignancies were correlated risk factors for in-hospital mortality. ART before admission was found to be beneficial, and considering the decreasing rate of in-hospital mortality, the implementation of intensified medical care strategy requires further effort.