Targeting endothelial PDGFR-ß facilitates angiogenesis-associated bone formation through the PAK1/NICD axis.

The intricate orchestration of osteoporosis (OP) pathogenesis remains elusive. Mounting evidence suggests that angiogenesis-driven osteogenesis serves as a crucial foundation for maintaining bone homeostasis. This study aimed to explore the potential of the endothelial platelet-derived growth factor receptor-ß (PDGFR-ß) in mitigating bone loss through its facilitation of H-type vessel formation. Our findings demonstrate that the expression level of endothelial PDGFR-ß is reduced in samples obtained from individuals suffering from OP, as well as in ovariectomy mice. Depletion of PDGFR-ß in endothelial cells ameliorates angiogenesis-mediated bone formation in mice. The regulatory influence of endothelial PDGFR-ß on H-type vessels is mediated through the PDGFRß-P21-activated kinase 1-Notch1 intracellular domain signaling cascade. In particular, the endothelium-specific enhancement of PDGFR-ß facilitates H-type vessels and their associated bone formation in OP. Hence, the strategic targeting of endothelial PDGFR-ß emerges as a promising therapeutic approach for the management of OP in the near future.

Injectable Ozone-Rich Nanocomposite Hydrogel Loaded with D-Mannose for Anti-Inflammatory and Cartilage Protection in Osteoarthritis Treatment.

Osteoarthritis (OA) is a dynamic condition characterized by cartilage damage and synovial inflammation. Ozone (O3) shows potential therapeutic effects owing to its anti-inflammatory properties; however, its high reactivity and short half-life substantially limit its effectiveness in OA treatment. In this study, an ozone-rich thermosensitive nanocomposite hydrogel loaded with D-mannose is developed for OA treatment. Briefly, O3 is encapsulated in nanoparticles (NPs) composed of perfluorotributylamine and fluorinated hyaluronic acid to improve its stability. Next, D-mannose is conjugated with α-amino of the hydroxypropyl chitin (HPCH) via Schiff base to prepare MHPCH. These nanoparticles are encapsulated in MHPCH to produce O3 NPs@MHPCH. In vitro cell experiments demonstrate that the O3 NPs@MHPCH treatment significantly reduced VEGF and inflammation levels, accompanied by a decrease in inflammatory factors such as IL-1ß, IL-6, TNF-α, and iNOS. Furthermore, O3 NPs@MHPCH promotes the expression of collagen II and aggrecan and stimulates chondrocyte proliferation. Additionally, in vivo studies show that O3 NPs@MHPCH significantly alleviated OA by reducing synovial inflammation, cartilage destruction, and subchondral bone remodeling. O3 NPs@MHPCH offers a promising option for improving the efficacy of O3 therapy and reducing the risk of synovial inflammation and cartilage degeneration in OA.

Cascade analysis of awareness, willingness, uptake and adherence with regard to PrEP among young men who have sex with men (YMSM) in China: A comparison between students and non-students.

INTRODUCTION: In China, young men who have sex with men (YMSM) are one of the groups most at risk of HIV/AIDS. The uptake of pre-exposure prophylaxis (PrEP) among YMSM has not been well documented. A cascade analysis of awareness, willingness, use and adherence with regard to PrEP was conducted separately among YMSM students and non-students. METHODS: From 20 October to 30 December 2021, all adolescents aged 16-24 years were selected for the study from among MSM recruited from 31 provincial administrative regions in mainland China. Participants were included in a cross-sectional study of awareness, willingness, use and adherence with regard to PrEP among YMSM. Logistic regression modelling was used to identify factors associated with the four outcomes. RESULTS: Among 1014 student and 866 non-student YMSMs, respectively, 88.07% and 81.64% had heard of PrEP; 58.16% and 50.35% were willing to use PrEP; 7.59% and 7.62% had used PrEP; and 3.16% and 3.58% had adhered to PrEP. Among students, those living in high-risk areas and pilot cities and those who had engaged in commercial sex and group sex had a positive effect on PrEP use, and the same trends were found among non-students living in high-risk areas and pilot cities and those who had engaged in group sex. 'Daily oral' and 'flexible' PrEP use positively influenced adherence among both groups. CONCLUSIONS: A differentiation strategy of PrEP promotion should be implemented among YMSM. Material support for students, such as financial resources, should increase, while non-students should increase their level of perception of HIV risk.

Lag effect of ambient temperature on respiratory emergency department visits in Beijing: a time series and pooled analysis.

BACKGROUND: Although the association between ambient temperature and mortality of respiratory diseases was numerously documented, the association between various ambient temperature levels and respiratory emergency department (ED) visits has not been well studied. A recent investigation of the association between respiratory ED visits and various levels of ambient temperature was conducted in Beijing, China. METHODS: Daily meteorological data, air pollution data, and respiratory ED visits data from 2017 to 2018 were collected in Beijing. The relationship between ambient temperature and respiratory ED visits was explored using a distributed lagged nonlinear model (DLNM). Then we performed subgroup analysis based on age and gender. Finally, meta-analysis was utilized to aggregate the total influence of ambient temperature on respiratory ED visits across China. RESULTS: The single-day lag risk for extreme cold peaked at a relative risk (RR) of 1.048 [95% confidence interval (CI): 1.009, 1.088] at a lag of 21 days, with a long lag effect. As for the single-day lag risk for extreme hot, a short lag effect was shown at a lag of 7 days with an RR of 1.076 (95% CI: 1.038, 1.114). The cumulative lagged effects of both hot and cold effects peaked at lag 0-21 days, with a cumulative risk of the onset of 3.690 (95% CI: 2.133, 6.382) and 1.641 (95% CI: 1.284, 2.098), respectively, with stronger impact on the hot. Additionally, the elderly were more sensitive to ambient temperature. The males were more susceptible to hot weather than the females. A longer cold temperature lag effect was found in females. Compared with the meta-analysis, a pooled effect of ambient temperature was consistent in general. In the subgroup analysis, a significant difference was found by gender. CONCLUSIONS: Temperature level, age-specific, and gender-specific effects between ambient temperature and the number of ED visits provide information on early warning measures for the prevention and control of respiratory diseases.

Significant insights from a National survey in China: PrEP awareness, willingness, uptake, and adherence among YMSM students.

INTRODUCTION: Few studies focused on the Pre-Exposure Prophylaxis (PrEP) -related aspects, and the applicability of prior evidence to young men who have sex with men (YMSM) students was unknown. This study aimed to assess the awareness, willingness, uptake, and adherence (AWUA) to PrEP among YMSM students in China and to explore the associated factors with these stages. METHODS: A cross-sectional survey with a sizable sample of 1151 was conducted among YMSM students aged 16 and above, who self-identified as men who have sex with men(MSM) and resided in mainland China between October 20 and December 20, 2021. The chi-square test and Fisher's exact test were used for univariate analysis, followed by multivariable logistic regression analysis of influencing factors at all levels. RESULTS: According to the cascade analysis approach, 88.71% of the participants were aware of PrEP, among which 66.7% expressed willingness to use it. Among those who were willing to use PrEP, only 13.80% took it, and of those who took it, 44.68% adhered to it. The students taking PrEP were those with higher education (OR = 4.239, 95% CI: 1.334-13.467), residence in pilot cities (OR = 2.791, 95% CI: 1.498-5.198), residence in high-risk areas (OR = 5.082, 95% CI: 2.224-11.612), engagement in multi-person sexual behavior (OR = 2.186, 95% CI: 1.236-3.867), and substance use (OR = 1.908, 95% CI: 1.167-3.118). Furtherly, students with higher adherence to PrEP were likely to have receptive sexual behaviors (OR = 8.702, 95% CI: 2.070-36.592), absence of substance use (OR = 4.468, 95% CI: 1.371-14.561), and uptake of PrEP through daily oral route. (OR = 7.065, 95% CI: 1.699-29.371). CONCLUSION: YMSM students exhibit distinct patterns of "high awareness, low willingness, low uptake, and low adherence" to PrEP. Strategies for reduction in the acquisition of HIV prioritizing the current features of utilizing PrEP were urgently warranted.

Correlates of oral pre-exposure prophylaxis cessation among men who have sex with men in China: implications from a nationally quantitative and qualitative study.

BACKGROUND: Several studies have demonstrated the population-level effectiveness of oral PrEP in reducing the risk of HIV infection. However, oral PrEP utilization among MSM in China remains below 1%. While existing literature has primarily focused on oral PrEP preference and willingness, there is limited exploration of the underlying factors contributing to oral PrEP cessation in China. This study aims to fill this gap by investigating the factors associated with oral PrEP cessation among MSM in China. METHODS: Assisted by MSM community organizations, we collected 6,535 electronic questionnaires from 31 regions across China, excluding Taiwan, Hong Kong, and Macau. The questionnaire focused on investigating MSM's awareness, willingness, usage, and cessation of oral PrEP. Additionally, 40 participants were randomly chosen for key informant interviews. These qualitative interviews aimed to explore the reasons influencing MSM discontinuing oral PrEP. RESULTS: We eventually enrolled 6535 participants. Among the 685 participants who had used oral PrEP, 19.70% (135/685) ceased oral PrEP. The results indicated that individuals spending > ¥1000 on a bottle of PrEP (aOR = 2.999, 95% CI: 1.886-4.771) were more likely to cease oral PrEP compared to those spending ≤ ¥1000. Conversely, individuals opting for on-demand PrEP (aOR = 0.307, 95% CI: 0.194-0.485) and those using both daily and on-demand PrEP (aOR = 0.114, 95% CI: 0.058-0.226) were less likely to cease PrEP compared to those using daily PrEP. The qualitative analysis uncovered eight themes influencing oral PrEP cessation: (i) High cost and low adherence; (ii) Sexual inactivity; (iii) Lack of knowledge about PrEP; (iv) Trust in current prevention strategies; (v) Poor quality of medical service and counseling; (vi) PrEP stigma; (vii) Partner and relationship factors; (viii) Access challenges. CONCLUSIONS: The cessation of oral PrEP among MSM in China is associated with various factors, including the cost of oral PrEP medication, regimens, individual perception of HIV risk, stigma, and the quality of medical services. It is recommended to provide appropriate regimens for eligible MSM and develop tailored combinations of strategies to enhance PrEP awareness and acceptance among individuals, medical staff, and the MSM community. The findings from this study can support the refinement of HIV interventions among MSM in China, contributing to efforts to reduce the burden of HIV in this population.

The risk of acute and early HIV (AEH) infection among MSM with different behaviour trajectories: an open cohort study in Tianjin, China, 2011-2019.

BACKGROUND: Acute and early HIV (AEH) infection is characterized by a high viral load and infectivity. Approximately 50% of cases of HIV-1 transmission occur during AEH. Understanding sexual behaviour trajectories would be useful for predicting changes in the risk of HIV acquisition. However, few studies have investigated sexual behaviour trajectories and their association with AEH acquisition. This study identified behaviour trajectories among men who have sex with men (MSM), determined the risk of AEH infection, and compared risk factors between different behaviour trajectories. METHODS: The study was based on an ongoing prospective open cohort of voluntary HIV counselling and testing (VHCT) among MSM in Tianjin, China. From 2011 to 2019, 1974 MSM were recruited. Group-based trajectory modelling (GBTM) was used to identify behaviour trajectories by constructing a sexual risk behaviour score. Logistic regression and generalized estimating equation (GEE) were used to compare the risk of AEH infection and risk factors for different behaviour trajectories. All data analyses were performed using SAS 9.4. RESULTS: The incidence of AEH infection was 1.76/100 person-years, with 64 AEH infections documented in 3633 person-years of follow-up. Three sexual behaviour trajectories were identified: CL (consistently low risk, 35.46%), CH (consistently high risk, 42.71%) and HTL (high to low risk, 21.83%). MSM in the HTL and CH groups had higher AEH infection rates than MSM in the CL group (6.73%, 3.08% and 1.28%, respectively), with ORs of 5.54 (2.60, 11.82) and 2.44 (1.14, 5.25), respectively. MSM aged 30-50 years old and MSM who underwent HIV testing in the last year were more likely to be in the CH group and HTL group. In addition, the HTL group was characterized by a lower likelihood of local registration and a higher likelihood of working as a MSW. CONCLUSION: MSM in the CH group and the HTL group had a higher risk of AEH infection. In the future, VHCT should be performed more often among younger MSM, and HIV counselling should be given the same priority as HIV testing. In addition, VHCT combined with PrEP may have a better preventive impact on MSM with a high risk of AEH infection.

The association between air pollutants, meteorological factors and tuberculosis cases in Beijing, China: A seven-year time series study.

BACKGROUND: Tuberculosis (TB) is a severe public health problem globally. Previous studies have revealed insufficient and inconsistent associations between air pollutants, meteorological factors and TB cases. Yet few studies have examined the associations between air pollutants, meteorological factors and TB cases in Beijing. OBJECTIVE: The purpose of this study was to explore the impact of air pollutants and meteorological factors on TB in Beijing, and to provide novel insights into public health managers to formulate control strategies of TB. METHODS: Data on the daily case of TB in Beijing during 2014-2020 were obtained from Chinese tuberculosis information management system. Concurrent data on the daily PM10, PM2.5, SO2, NO2, CO and O3, were obtained from the online publication platform of the Chinese National Environmental Monitoring Center. Daily average temperature, average wind speed, relative humidity, sunshine duration and total precipitation were collected from the China Meteorological Science Data Sharing Service System. A distributed lag non-linear model was fitted to identify the non-linear exposure-response relationship and the lag effects between air pollutions, meteorological factors and TB cases in Beijing. RESULTS: In the single-factor model, the excess risk (ER) of TB was significantly positively associated with every 10 µg/m3 increase in NO2 in lag 1 week (ER: 1.3%; 95% confidence interval [CI]: 0.4%, 2.3%) and every 0.1 m/s increase in average wind speed in lag 5 weeks (ER: 0.3%; 95% CI: 0.1%, 0.5%), and was negatively associated with every 10 µg/m3 increase in O3 in lag 1 week (ER: -1.2%; 95% CI: -1.8%, -0.5%), every 5 °C increase in average temperature (ER: -1.7%; 95% CI: -2.9%, -0.4%) and every 10% increase in average relative humidity (ER: -0.4%; 95% CI: -0.8%, -0.1%) in lag 10 weeks, respectively. In the multi-factor model, the lag effects between TB cases and air pollutants, meteorological factors were similar. The subgroup analysis suggests that the effects of NO2, O3, average wind speed and relative humidity on TB were greater in male or labor age subgroup, while the effect of CO was greater in the elderly. In addition, no significant associations were found between PM2.5, SO2, sunshine duration and TB cases. CONCLUSION: Our findings provide a better understanding of air pollutants and meteorological factors driving tuberculosis occurrence in Beijing, which enhances the capacity of public health manager to target early warning and disease control policy-making.

A five-parameter score for predicting saphenous vein graft degenerative and/or occlusive disease in recurring ischemic symptoms after one year post coronary artery bypass grafting.

BACKGROUND: The recurrence rate of ischemic symptoms after coronary artery bypass grafting (CABG) is increasing in recent years. How to prevent and treat saphenous vein graft disease (SVGD [symptomatic ⩾50% stenosis in at least one Saphenous vein graft]) has been a clinical challenge to date. Different pathogenesis may exist in SVGD of different periods. There are currently few available scores for estimating the risk of SVGD after one year post CABG. OBJECTIVE: We sought to develop and validate a simple predictive clinical risk score for SVGD with recurring ischemia after one year post CABG. METHODS AND RESULTS: This was a cross-sectional study and the results were validated using bootstrap resampling on a separate cohort. A nomogram and risk scoring system were developed based on retrospective data from a training cohort of 606 consecutive patients with recurring ischemia >1 year after CABG. Logistic regression model was used to find the predictive factors and to build a nomogram. To assess the generalization, models were validated using bootstrap resampling and an external cross-sectional study of 187 consecutive patients in four other hospitals. In multivariable analysis of the primary cohort, native lesion vessel number, SVG age, recurring ischemia type, very low-density lipoprotein level, and left ventricular end-diastolic diameter were independent predictors. A summary risk score was derived from nomogram, with a cut-off value of 15. In internal and external validation, the C-index was 0.86 and 0.82, indicating good discrimination. The calibration curve for probability of SVGD showed optimal agreement between actual observations and risk score prediction. CONCLUSION: A simple-to-use risk scoring system based on five easily variables was developed and validated to predict the risk of SVGD among patients who recurring ischemia after one year post CABG. This score may be useful for providing patients with individualized estimates of SVGD risk.

Sexual Behavior Transition and Acute and Early HIV Infection Among Men Who Have Sex With Men: Evidence from an Open Cohort in China, 2011-2019.

The present study examined how sexual behaviors transit over time among men who have sex with men (MSM) and whether these transitions were associated with acute and early HIV (AEH) infection. An open cohort study was conducted using snowball sampling to recruit MSM via physical venues and Internet venues from 2011 to 2019, in China. Cox models were used to estimate the correlates of risk factors and AEH infection. We used Latent Transition Analysis (LTA) to describe behavioral profile and explore latent behavioral "trans-phenotypes," then examined the effect between different "trans-phenotypes" and AEH infection risk and explored the effect of characteristics as possible predictors of sexual behavior transition. Of 6502 MSM, a total of 1974 individuals with negative human immunodeficiency virus (HIV) tests at baseline and at least 2 visit records were included in the final analysis from 2011 to 2019. During an average 1.84 years of follow-up, 64 AEH infections were documented. In the multivariable Cox model, the association between condom use in last anal sex (HR: 0.095, 0.038-0.205), fewer sexual partners (HR: 0.375, 0.205-0.712), low frequency of condom use (HR: 3.592, 1.186-11.272), and AEH acquisition were found. The percentage of MSM with "maintain/develop safety-profile," "consistent risky-profile," and "safety-profile to risky-profile" were 52.48, 40.17, and 7.35%, respectively. Compared with "maintain\develop safety-profile," "consistent or develop risky-profile" had an increasing likelihood of AEH infection. Meanwhile, male sex workers (MSWs) or older MSM were more likely to consist or transit in "risky-profile." Having middle education is a risk factor to transit in "risky-profile" for MSM with "safety-profile" at baseline. In addition, MSM who accept health services in the past year engaged in higher proportion of developing safety-profile. Approximately half of MSM maintain or develop risky behavior with the increasing likelihood of AEH acquisition in China, which suggested that targeted and intensive interventions should be prioritized to maintain safety-profile. Clinical Trial Number: ChiCTR2000039500.

High risks of HIV transmission for men sex worker - a comparison of profile and risk factors of HIV infection between MSM and MSW in China.

BACKGROUND: Although men who have sex with men (MSM) and male sex workers (MSWs) both represent the high-risk groups for the transmission of HIV/AIDS and syphilis, the comparison between them have not yet been well studied in China. We aimed to evaluate the prevalence of HIV among MSM and MSW, and then identify the difference of risk factors of HIV infection. METHODS: A snowball sampling was employed to recruit patrons attending the Tianjin bathhouse from March 2011 to October 2018. A questionnaire covering sociodemographic characteristics, sexual behaviors, HIV-related and HIV awareness was completed by 5166 patrons from all parts of China. Bivariate analyses were done using the Chi-square test to investigate the association between factors and HIV infection among MSM and MSWs. Subsequently, we studied the different impact of risk factors on HIV infections among the two groups using multiple logistic regression with the adjusted odds ratio (aOR) being derived. RESULTS: From 2011 to 2018, 235 MSWs and 4931 MSM were included into our study. HIV prevalence among the MSWs was 17.8% (95%CI: 13.2% ~ 23.4%) while 6.5% (95%CI: 5.8% ~ 7.2%) for MSM (P < 0.01). MSWs tends to be younger (26.50% in MSWs vs. 8.64% in MSM, P < 0.05), live alone (84.68% in MSWs vs. 47.98 in MSM, P < 0.05), get poor education (41.28% in MSWs vs. 28.45 in MSM, P < 0.05), use drug (8.09% in MSWs vs. 0.89% in MSM, P < 0.05), have more proportion of always use condom during anal sex (56.50% in MSWs vs. 41.95% in MSM, P < 0.05) but less proportion during commercial sex (81.28% in MSWs vs. 98.48% in MSM, P < 0.05), access HIV-related health services (65.96% in MSWs vs. 47.80% in MSM, P < 0.05) and have a HIV test last year(60.85% in MSWs vs. 41.27% in MSM, P < 0.05). The significant associations between risk factors with HIV infection in MSM were not observed in MSWs and vice versa. CONCLUSIONS: High HIV prevalence needs urgent intervention targeting MSWs as a higher susceptible to HIV in comparison to MSM owing to their unique characteristics. The discrepancies of profiles and risk factors between MSM and MSWs should be consider in design and development of strategies.

Prostate Cancer Risk Prediction and Online Calculation Based on Machine Learning Algorithm.

Objective To build a prostate cancer (PCa) risk prediction model based on common clinical indicators to provide a theoretical basis for the diagnosis and treatment of PCa and to evaluate the value of artificial intelligence (AI) technology under healthcare data platforms. Methods After preprocessing of the data from Population Health Data Archive, smuothly clipped absolute deviation (SCAD) was used to select features. Random forest (RF), support vector machine (SVM), back propagation neural network (BP), and convolutional neural network (CNN) were used to predict the risk of PCa, among which BP and CNN were used on the enhanced data by SMOTE. The performances of models were compared using area under the curve (AUC) of the receiving operating characteristic curve. After the optimal model was selected, we used the Shiny to develop an online calculator for PCa risk prediction based on predictive indicators. Results Inorganic phosphorus, triglycerides, and calcium were closely related to PCa in addition to the volume of fragmented tissue and free prostate-specific antigen (PSA). Among the four models, RF had the best performance in predicting PCa (accuracy: 96.80%; AUC: 0.975, 95% CI: 0.964-0.986). Followed by BP (accuracy: 85.36%; AUC: 0.892, 95% CI: 0.849-0.934) and SVM (accuracy: 82.67%; AUC: 0.824, 95% CI: 0.805-0.844). CNN performed worse (accuracy: 72.37%; AUC: 0.724, 95% CI: 0.670-0.779). An online platform for PCa risk prediction was developed based on the RF model and the predictive indicators. Conclusions This study revealed the application value of traditional machine learning and deep learning models in disease risk prediction under healthcare data platform, proposed new ideas for PCa risk prediction in patients suspected for PCa and had undergone core needle biopsy. Besides, the online calculation may enhance the practicability of AI prediction technology and facilitate medical diagnosis.

Effects of daily mean temperature and other meteorological variables on bacillary dysentery in Beijing-Tianjin-Hebei region, China.

BACKGROUND: Although previous studies have shown that meteorological factors such as temperature are related to the incidence of bacillary dysentery (BD), researches about the non-linear and interaction effect among meteorological variables remain limited. The objective of this study was to analyze the effects of temperature and other meteorological variables on BD in Beijing-Tianjin-Hebei region, which is a high-risk area for BD distribution. METHODS: Our study was based on the daily-scale data of BD cases and meteorological variables from 2014 to 2019, using generalized additive model (GAM) to explore the relationship between meteorological variables and BD cases and distributed lag non-linear model (DLNM) to analyze the lag and cumulative effects. The interaction effects and stratified analysis were developed by the GAM. RESULTS: A total of 147,001 cases were reported from 2014 to 2019. The relationship between temperature and BD was approximately liner above 0 °C, but the turning point of total temperature effect was 10 °C. Results of DLNM indicated that the effect of high temperature was significant on lag 5d and lag 6d, and the lag effect showed that each 5 °C rise caused a 3% [Relative risk (RR) = 1.03, 95% Confidence interval (CI): 1.02-1.05] increase in BD cases. The cumulative BD cases delayed by 7 days increased by 31% for each 5 °C rise in temperature above 10 °C (RR = 1.31, 95% CI: 1.30-1.33). The interaction effects and stratified analysis manifested that the incidence of BD was highest in hot and humid climates. CONCLUSIONS: This study suggests that temperature can significantly affect the incidence of BD, and its effect can be enhanced by humidity and precipitation, which means that the hot and humid environment positively increases the incidence of BD.

Low awareness of and willingness to use PrEP in the Chinese YMSM: An alert in YMSM HIV prevention.

OBJECTIVES: Despite being a key population in whom to initiate pre-exposure prophylaxis (PrEP), the awareness of and willingness to use PrEP are still unclear in Chinese young men who have sex with men (YMSM). We report factors associated with PrEP awareness and willingness in the population. METHODS: From 1 August to 31 December 2018, 495 participants aged 15-24 years were included in a cross-sectional study about awareness of and willingness to use PrEP among YMSM. Logistic regression models were used to identify factors associated with two outcomes: awareness of PrEP; and willingness to use PrEP. RESULTS: Among 495 eligible participants, 129 participants (26.1%) knew about PrEP. PrEP awareness among YMSM was associated with higher education level [adjusted odds ratio (aOR) = 1.812, 95% CI: 1.113-2.951] and previous HIV testing (aOR = 3.507, 95% CI: 1.261-9.752). YMSM with shorter local residence time (aOR = 0.317, 95% CI: 0.101-0.992) and internet-based partner-seeking (aOR = 0.171, 95% CI: 0.096-0.305) were less likely to be aware of PrEP. In those with previous knowledge of PrEP, 36 (27.9%) conveyed their willingness to use it. PrEP willingness was associated with internet-based partner-seeking (aOR = 9.593, 95% CI: 1.965-46.844). The main barriers influencing those who knew about PrEP but refused to use it were the high price of PrEP (69.9%), the need to use condoms consistently (52.7%), and concerns about side effects (39.8%) and effectiveness of prevention (22.6%). CONCLUSIONS: Chinese YMSM have low awareness of and willingness to use PrEP. Adequate PrEP promotions should be implemented, especially on the Internet and dating software.

The associations of gut microbiota and fecal short-chain fatty acids with bone mass were largely mediated by weight status: a cross-sectional study.

PURPOSE: We aimed to investigate whether the gut microbiota and fecal short-chain fatty acids (SCFAs) are associated with bone mass in healthy children aged 6-9 years. METHODS: In this study, 236 healthy children including 145 boys and 91 girls were enrolled. 16S rRNA gene sequencing was used to characterize the composition of their gut microbiota. Total and 10 subtypes of SCFAs in the fecal samples were determined by high-performance liquid chromatography. Dual X-ray absorptiometry was used to measure the bone mineral density (BMD) and bone mineral content (BMC) for total body (TB) and total body less head (TBLH). Z score of TBLH BMD was calculated based on the recommended reference. RESULTS: Four gut microbiota principal components (PCs) were identified by the compositional principal component analysis at the genus level. After adjustment of covariates and controlling for the false discovery rate, multiple linear regression analysis showed that PC3 score (positive loadings on genera Lachnoclostridium and Blautia) was significantly negatively associated with TBLH BMD/BMC/Z score, TB BMC and pelvic BMD (ß: - 0.207 to - 0.108, p: 0.002-0.048), whereas fecal total and several subtypes of SCFAs were correlated positively with TBLH BMD/Z score and pelvic BMD (ß: 0.118-0.174, p: 0.038-0.048). However, these associations disappeared after additional adjustment for body weight. Mediation analysis suggested that body weight significantly mediated 60.4% and 78.0% of the estimated association of PC3 score and SCFAs with TBLH BMD Z score, respectively. CONCLUSIONS: The associations of gut microbiota composition and fecal SCFA concentrations with bone mass in children were largely mediated by body weight.

Pcsk9 is associated with severity of coronary artery lesions in male patients with premature myocardial infarction.

BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (Pcsk9) correlated with incidence and prognosis of coronary heart disease. However, it is unclear whether Pcsk9 contributed to coronary artery lesion severity in patients with premature myocardial infarction (PMI). The present study investigated associations between Pcsk9 and coronary artery lesion severity in PMI patients who underwent coronary angiography (CAG). METHODS: This prospective cohort study included young men (age ≤ 45 years, n = 332) with acute MI who underwent CAG between January 2017 and July 2019. Serum Pcsk9 levels and clinical characteristics were evaluated. SYNTAX scores (SYNergy between percutaneous coronary intervention with [paclitaxel-eluting] TAXUS stent and cardiac surgery) were calculated to quantify coronary artery lesions. RESULTS: Serum Pcsk9 levels were positively associated with SYNTAX scores (r = 0.173, P < 0.05). The diagnostic cutoff value of PSCK9 level was 122.9 ng/mL, yielding an area under the curve (AUC) of 0.63, sensitivity 81%, and specificity 40%. Serum Pcsk9, LDL-C, Apob, NT-proBnp, CK level, and diabetes history were independent predictors of high SYNTAX scores (P < 0.05). After stratifying by serum LDL-C level (cutoff = 2.6 mmol/L), medium-high Pcsk9 levels had increased risk of high SYNTAX scores in patients with high LDL-C (P < 0.05), and higher serum Pcsk9 levels had increased risk of major adverse cardiac events (MACE) after adjusting for confounding factors (P < 0.05). CONCLUSION: Serum Pcsk9 levels correlates with severity of coronary artery lesion in PMI patients and may serve as a biomarker for severity of coronary artery stenosis in this patient population, which may contribute to risk stratification.

Factors related to HIV testing frequency in MSM based on the 2011-2018 survey in Tianjin, China: a hint for risk reduction strategy.

BACKGROUND: In recent years, HIV testing has become one of the effective strategies to reduce the risk of the infection. Frequent quarterly HIV testing can be cost effective. Therefore, an in-depth study of factors related to the testing behavior of men who have sex with men (MSM) were analyzed to optimize intervention strategies. METHODS: From March 2011 to October 2018, the project was implemented in a Tianjin (China) bathhouse, and 5165 MSM were surveyed using snowball sampling. Factors related to HIV testing behavior were analyzed by ordinal logistic regression analysis after grouping according to testing frequency, and comprehensive analysis was performed. RESULTS: The multivariate logistic analysis showed that 6 variables including young MSM (OR = 0.67, 95% CI: 0.49-0.92, p = 0.01), low-educated MSM (OR = 0.60, 95% CI: 0.48-0.77, p < 0.0001), low HIV/AIDS knowledge (95% CI: 0.57-0.83, p < 0.0001), marital status (OR = 1.30, 95% CI: 1.07-1.57, p = 0.007), acceptance of condom promotion and distribution (OR = 14.52, 95% CI: 12.04-17.51, p < 0.0001), and frequency of condom use (p < 0.05) could link to HIV testing behaviors. CONCLUSIONS: In order to achieve the 95-95-95 goal, target publicity, HIV/AIDS education and promotion of HIV self-testing kits should be carried out to encourage frequent HIV testing among MSM who are young (especially students), married to women, poorly educated and who are reluctant to always use condoms.

Specific inhibition of FAK signaling attenuates subchondral bone deterioration and articular cartilage degeneration during osteoarthritis pathogenesis.

Osteoarthritis (OA), a disease of the entire joint, is characterized by abnormal bone remodeling and coalescent degradation of articular cartilage. We have previously found that elevated levels of H-type vessels in subchondral bone correlate with OA and that focal adhesion kinase (FAK) is critical for H-type vessel formation in osteoporosis. However, the potential role of FAK in OA remains unexplored. Here, we demonstrate that the p-FAK level was dramatically elevated in subchondral bone following anterior cruciate ligament transection (ACLT) in rats. Specific inhibition of FAK signaling with Y15 in subchondral bone resulted in the suppression of subchondral bone deterioration and this effect was mediated by H-type vessel-induced ectopic bone formation. Further, articular cartilage degeneration was also alleviated after Y15 treatment. In vitro, the p-FAK level was significantly elevated in mesenchymal stem cells (MSCs) from vehicle-treated ACLT rats as compared to that in MSCs from sham controls and Y15-treated ACLT rats. Elevated p-FAK level in MSCs promoted vascular endothelial growth factor (VEGF) expression, as demonstrated from the high VEGF level in the blood, subchondral bone, and conditioned medium (CM) of MSCs from vehicle-treated ACLT rats. The CM of MSCs from vehicle-treated ACLT rats might promote the angiogenesis of endothelial cells and the catabolic response of chondrocytes through the FAK-growth factor receptor-bound protein 2-mitogen-activated protein kinase-mediated expression of VEGF. The effect of the CM from MSCs of Y15-treated ACLT rats or that treated with a VEGF-neutralizing antibody on vessel formation and the catabolic response was lowered. Thus, the specific inhibition of FAK signaling may be a promising avenue for the prevention or early treatment of OA.

Effect of 650-nm low-level laser irradiation on c-Jun, c-Fos, ICAM-1, and CCL2 expression in experimental periodontitis.

This study was designed to investigate the effect of 650-nm low-level laser irradiation (LLLI) as an adjunctive treatment of experimental periodontitis. To investigate possible LLLI-mediated anti-inflammatory effects, we utilized an experimental periodontitis (EP) rat model and analyzed c-Jun, c-Fos, ICAM-1, and CCL2 gene expressions on PB leukocytes and in the gingival tissue. Total RNA was isolated from the gingivae and peripheral blood (PB) leukocytes of normal, EP, scaling, and root planing (SRP)-treated EP and LLLI + SRP-treated EP rats, and gene expressions were analyzed by real-time PCR. The productions of c-Jun, c-Fos, ICAM-1, and CCL2 in gingivae were analyzed immunohistochemically. Tartrate-resistant acid phosphatase (TRAP) staining was used to determine osteoclast activity in alveolar bone. The c-Jun and ICAM-1 messenger RNA (mRNA) levels were significantly decreased in the EP rat gingival tissue treated by SRP + LLLI than by SRP, the c-Jun, ICAM-1, and c-Fos mRNA levels on PB leukocytes reduced after LLLI treatment but did not show any significant differences in both groups. There was no significant difference in CCL2 mRNA levels on PB leukocytes and in gingivae between the SRP + LLLI and the SRP groups. The c-Fos mRNA levels in gingivae did not show significant difference in both groups. Immunohistochemistry showed that the CCL2, ICAM-1, c-Jun, and c-Fos productions were significantly reduced in rats of the SRP + LLLI group compared with the only SRP group. LLLI significantly decreased the number of osteoclasts as demonstrated by TRAP staining. The 650-nm LLLI might be a useful treatment modality for periodontitis.

Correction to: Effect of 650-nm low-level laser irradiation on c-Jun, c-Fos, ICAM-1, and CCL2 expression in experimental periodontitis.

After publication of our article [1] we realized that we had not acknowledged that some of the text overlaps with a previous publication [2]. We apologize to readers for this error.