The impact of smoking and alcohol consumption on rosacea: a multivariable Mendelian randomization study.

Backgrounds: Observational studies have shown that cigarette smoking is inversely associated with risk of rosacea, However, it remains uncertain whether this association is causal or it is a result of reverse causation, and whether this association is affected by drinking behaviors. Methods: This study utilized the summary-level data from the largest genome-wide association study (GWAS) for smoking, alcohol consumption, and rosacea. The objective was to investigate the effect of genetically predicted exposures to smoking and alcohol consumption on the risk of developing rosacea. Two-sample bidirectional Mendelian randomization (MR) was applied, accompanied by sensitive analyses to validate the robustness of findings. Furthermore, multivariable MR was conducted to evaluate the direct impact of smoking on rosacea. Results: A decreased risk of rosacea was observed in individuals with genetically predicted lifetime smoking [odds ratio (OR)MR - IVW = 0.53; 95% confidence interval (CI), 0.318-0.897; P = 0.017], and number of cigarettes per day (ORMR - IVW = 0.55; 95% CI, 0.358-0.845; P = 0.006). However, no significant associations were found between initiation of regular smoking, smoking cessation, smoking initiation, alcohol consumption and rosacea. Reverse MR analysis did not show any associations between genetic liability toward rosacea and smoking or alcohol drinking. Importantly, the effect of lifetime smoking and the number of cigarettes per day on rosacea remained significant even after adjusting for alcohol consumption in multivariable MR analysis. Conclusion: Smoking was causally related to a lower risk of rosacea, while alcohol consumption does not appear to be associated with risk of rosacea.

Development of an environmentally sensitive fluorescent peptide probe for MrgX2 and application in ligand screening of peptide antibiotics.

Mast cells (MCs) are primary effector cells involved in immediate allergic reactions. Mas-related G protein-coupled receptor-X2 (MrgX2), which is highly expressed on MCs, is involved in receptor-mediated drug-induced pseudo-anaphylaxis. Many small-molecule drugs and peptides activate MrgX2, resulting in MC activation and allergic reactions. Although small-molecule drugs can be identified using existing MrgX2 ligand-screening systems, there is still a lack of effective means to screen peptide ligands. In this study, to screen for peptide drugs, the MrgX2 high-affinity endogenous peptide ligand substance P (SP) was used as a recognition group to design a fluorescent peptide probe. Spectroscopic properties and fluorescence imaging of the probe were assessed. The probe was then used to screen for MrgX2 agonists among peptide antibiotics. In addition, the effects of peptide antibiotics on MrgX2 activation were investigated in vivo and in vitro. The environment-sensitive property of the probe was revealed by the dramatic increase in fluorescence intensity after binding to the hydrophobic ligand-binding domain of MrgX2. Based on these characteristics, it can be used for in situ selective visualization of MrgX2 in live cells. The probe was used to screen ten types of peptide antibiotics, and we found that caspofungin and bacitracin could compete with the probe and are hence potential ligands of MrgX2. Pharmacological experiments confirmed this hypothesis; caspofungin and bacitracin activated MCs via MrgX2 in vitro and induced local anaphylaxis in mice. Our research can be expected to provide new ideas for screening MrgX2 peptide ligands and reveal the mechanisms of adverse reactions caused by peptide drugs, thereby laying the foundation for improving their clinical safety.

The relationship between social support and depression among HIV-positive men who have sex with men in China: the chain mediating role of psychological flexibility and hope.

Introduction: HIV and mental health problems are a global syndemic. One key issue is that the significant mental health problems among people vulnerable to acquiring or living with HIV have not been fully addressed. Access to social support has been one of the biggest challenges for HIV-positive men who have sex with men (HIV+ MSM). Lower social support has been linked to more severe depression symptoms. However, the mechanisms underlying the association between social support and depression in HIV+ MSM are unclear. Two possible mediators include hope and psychological flexibility. This study aimed to examine the relationship between social support and depression in HIV+ MSM and to explore the single mediating effects of hope and psychological flexibility and the chain mediating effect of these two variables on this relationship. Methods: A convenience sample was used to recruit participants from the designated HIV/AIDS hospital in Changsha city, Hunan Province of China. A total of 290 HIV+ MSM completed questionnaires. Results: Our findings showed that hope mediated the relationship between social support and depression in HIV+ MSM. Furthermore, the chain mediation model confirmed a direct negative association between social support and depression, but this relationship was largely mediated by the chain effects of hope and psychological flexibility. Conclusions: Integrating hope and psychological flexibility into interventions may provide better mental health support for HIV+ MSM and improve their wellbeing and quality of life.

Effect of remote ischemic preconditioning on postoperative gastrointestinal function in patients undergoing laparoscopic colorectal cancer resection.

PURPOSE: Patients undergoing laparoscopic colorectal cancer resection have a high incidence of postoperative gastrointestinal dysfunction (POGD). Remote ischemic preconditioning (RIPC) is an organ protection measure. The study investigated the effect of RIPC on postoperative gastrointestinal function. METHODS: In this single-center, prospective, double-blinded, randomized, parallel-controlled trial, 100 patients undergoing elective laparoscopic colorectal cancer resection were randomly assigned in a 1:1 ratio to receive RIPC or sham RIPC (control). Three cycles of 5-min ischemia/5-min reperfusion induced by a blood pressure cuff placed on the right upper arm served as RIPC stimulus. Patients were followed up continuously for 7 days after surgery. The I-FEED score was used to evaluate the patient's gastrointestinal function after the surgery. The primary outcome of the study was the I-FEED score on POD3. Secondary outcomes include the daily I-FEED scores, the highest I-FEED score, the incidence of POGD, the changes in I-FABP and the inflammatory markers (IL-6 and TNF-α), and the time to first postoperative flatus. RESULTS: A total of 100 patients were enrolled in the study, of which 13 patients were excluded. Finally, 87 patients were included in the analysis, 44 patients in the RIPC group and 43 patients in the sham-RIPC group. Patients assigned to the RIPC group had a lower I-FEED score on POD3 compared with the sham-RIPC group (mean difference 0.86; 95% CI: 0.06 to 1.65; P = 0.035). And patients in the RIPC group were also associated with a lower I-FEED score on POD4 vs the sham-RIPC group (mean difference 0.81; 95% CI: 0.03 to 1.60; P = 0.043). Compared with the sham-RIPC group, the incidence of POGD within 7 days after surgery was lower in the RIPC group (P = 0.040). At T1, T2, and T3 time points, inflammatory factors and I-FABP were considerably less in the RIPC group compared to the sham-RIPC group. The time to the first flatus and the first feces was similar in both groups. CONCLUSION: RIPC reduced I-FEED scores, decreased the incidence of postoperative gastrointestinal dysfunction, and lowered concentrations of I-FABP and inflammatory factors.

HIV knowledge, sexual practices, condom use and its associated factors among international students in one province of China: a cross-sectional study.

OBJECTIVE: China has seen an increasing number of international students in recent years, mostly from Africa and Asia. However, little is known about these students' HIV knowledge, sexual practices and potential HIV risk. This study aimed to describe HIV-related risk among international students. DESIGN: An online cross-sectional survey. SETTING: 10 universities situated in one province of China. PARTICIPANTS: 617 international students filled out the questionnaire and 607 international students were included in this study. PRIMARY AND SECONDARY OUTCOME MEASURES: Socio-demographic and programme-related characteristics, HIV-related knowledge, sexual practices and other HIV/sexually transmitted infection-related variables. Logistic regression analyses were performed to examine factors associated with inconsistent condom use among international students. RESULT: The results showed that in total, only 51.6% (313/607) of international students had adequate HIV-related knowledge, and 64.9% (394/607) reported not receiving any HIV related education or training while studying in China. Moreover, 32.3% (196/607) reported having penetrative sex including oral, vaginal and anal sex during the period in which they studied in China and among them. The proportions of inconsistent condom use in vaginal and oral intercourse while studying in China were 52.6% (50/95) and 79.5% (35/44), respectively, with casual partners, and 60% (80/129) and 91.2% (52/57) with regular partners, respectively. Female gender, being married and having multiple sexual partners were associated with inconsistent condom use. CONCLUSION: The present study indicated that international students in one province of China have suboptimal HIV-related knowledge, significant unprotected sex, less HIV testing and less safe sex education, which highlights an urgent need to provide HIV education and related health services to international students in China.

Post-lockdown Rebounding High-risk Behaviors and HIV Testing Among MSM in China in the Era of the COVID-19 Pandemic.

BACKGROUND: Lockdown measures for controlling the COVID-19 epidemic were enforced in China between January and May 2020. Previous studies showed a decrease in HIV high- Risk Behaviors (HRBs) and updated testing during the lockdown, but little is known about these behaviors during the post-lockdown period. OBJECTIVE: We conducted quantitative and qualitative assessments of HIV-related behaviors among MSM during the lockdown and post-lockdown periods in Changsha, south-central China. METHODS: Face-to-face structured interviews with open-ended questions were conducted using the TimeLine Follow Back (TLFB) method for collecting retrospective data on frequencies of HRBs and testing. McNemar's Chi-square test and Wilcoxon signed-rank test were used to comparing frequencies of behaviors between lockdown (January-May 2020) and post-lockdown periods (June- October 2020). Content analysis was used to analyze qualitative data on the reasons for rebounding HRBs and testing. RESULTS: Of 159 MSM participants, 64% had at least one HRB during the post-lockdown period. Men had increased condomless sex (from 24% to 35%), multiple partners (23% to 35%), and substance abuse (16% to 27%) between the two study periods due to the negative emotions and increased use of social networks during the lockdown. HIV testing frequency also increased from 37% to 66% due to resuming routine testing services in the community-based organizations and increased HRBs among MSM during post-lockdown. CONCLUSION: After lifting the lockdown measures, MSM had rebounding HRBs and uptake of testing. Effective preventive measures and healthcare services should be available to MSM after the lockdown measures are lifted.