Cannabidiol mitigates radiation-induced intestine ferroptosis via facilitating the heterodimerization of RUNX3 with CBFß thereby promoting transactivation of GPX4.

Radiation enteritis remains a major challenge for radiotherapy against abdominal and pelvic malignancies. Nevertheless, there is no approved effective therapy to alleviate irradiation (IR)-induced gastrointestinal (GI) toxicity. In the current study, Cannabidiol (CBD) was found to mitigate intestinal injury by GPX4-mediated ferroptosis resistance upon IR exposure. RNA-sequencing was employed to investigate the underlying mechanism involved in the radio-protective effect of CBD, wherein runt-related transcription factor 3 (RUNX3) and its target genes were changed significantly. Further experiment showed that the transactivation of GPX4 triggered by the direct binding of RUNX3 to its promoter region, or by stimulating the transcriptional activity of NF-κB via RUNX3-mediated LILRB3 upregulation was critical for the anti-ferroptotic effect of CBD upon IR injury. Specially, CBD was demonstrated to be a molecular glue skeleton facilitating the heterodimerization of RUNX3 with its transcriptional chaperone core-biding factor ß (CBFß) thereby promoting their nuclear localization and the subsequent transactivation of GPX4 and LILRB3. In short, our study provides an alternative strategy to counteract IR-induced enteritis during the radiotherapy on abdominal/pelvic neoplasms.

The association between adverse pregnancy outcomes with genital Chlamydia Trachomatis infection among pre-pregnancy couples in Shenzhen, China: A cross-sectional study.

Objectives: To investigate the prevalence of adverse pregnancy outcomes (APOs) in women and the impact of pre-pregnancy couples' genital Chlamydia Trachomatis (GCT) infection and other infections on APOs. Study design: Data on genital infections were collected from the Free Pre-pregnancy Health Check (FPHC) in Shenzhen, China. Data on APOs were collected from a 1-year telephone follow-up of pregnancy status and subsequent pregnancy outcomes. Methods: APO data were used to count adverse outcomes, and logistic regression was conducted to determine the association between APOs and GCT infection. Results: From December 2018 to December 2019, among 4,429 couples who underwent FPHC; 1,925 were pregnant, and 1,816 couples were tracked for pregnancy outcomes, including 1,471 normal pregnancies and 345 (19.00%) APOs. The rest of 109 pregnant couples did not answer the phone or refused to answer the pregnancy outcome during the follow-up. Among APOs, the number of spontaneous abortions was 122 (35.36%), the number of macrosomia was 85 (24.64%), the number of low birth weight (LBW) & preterm births (PTB) was 39 (11.30%), the number of LBW was 34 (9.86%), and the number of PTB was 31 (8.99%). The prevalence of GCT infection in females and males was 4.24% [95% Confidence Interval, (CI): 3.41-5.27%] and 3.58% (95% CI: 2.79-4.57%), respectively. More than half (52.69%, 49/93) of the couples were GCT-concordant. The prevalence of APOs in couples without GCT infection was 18.74% (332/1,772). The prevalence of APOs in female GCT-discordant was 32.14% (9/28), and the prevalence of APOs in male GCT-discordant was 25% (4/16). The prevalence of APOs in GCT-concordant was 12.24% (6/49). Multivariable analysis indicated that females 30-35 years old [adjusted Odds Ratio (aOR) = 1.08, 95% CI: 1.01-1.17] and over 35 years old (aOR = 1.16, 95% CI: 1.03-1.32) were more likely to experiencing APOs. Conclusion: Although only women's age was found to be associated with APOs, the prevalence of APOs with GCT-discordant in couples, especially female GCT-discordant, was higher than in those without infection or who were GCT-concordant, suggesting that these groups, especially in older women, should be paid more attention to in follow-ups to improve reproductive health.

Distribution of Chlamydia trachomatis ompA genotypes and its association with abnormal cervical cytology among women of reproductive age in Shenzhen, China.

Background: Many studies have focused on the distribution and specific clinical symptoms caused by Chlamydia trachomatis. Still, relatively few studies have focused on the associations between Chlamydia trachomatis genotypes and cervical intraepithelial lesions. Objectives: This study was conducted to determine the distribution of Chlamydia trachomatis genotypes and its associations with cervical intraepithelial lesions among women of reproductive age. The presence of other STIs coinfection was also evaluated. Method: 375 Chlamydia trachomatis positive cervical swabs collected from women of reproductive age were analyzed though molecular assay. Multivariate logistic regression analyses (covariates include contraception, gravidity (≥1), abnormal vaginal discharge, adverse pregnancy outcomes, reproductive tract symptoms and abnormal cervical cytology) were performed to evaluate the associations between Chlamydia trachomatis genotypes and cervical intraepithelial lesions and genital clinical symptoms. Results: Among 375 Chlamydia trachomatis positive cervical swabs, the prevalence of coinfection with Neisseria gonorrhoeae, Candida albicans, Trichomonas vaginitis, Vulvovaginal candidiasis, and HPV were 0.8%, 2.7%, 2.4%, 10.1% and 15.5%, respectively. 306 were genotyped successfully, and nine genotypes were identified. The most common genovar was E (25.16%, 77/306), followed by J (22.55%, 69/306), F (17%, 52/306), D (14.4%, 44/306), K (7.2%, 22/306), G (6.9%, 21/306), H (5.2%, 16/306), B (1.0%, 3/306), Ia (0.7%, 2/306). Genotype H was associated with abnormal cervical cytology [p = 0.006, aOR = 8.16 (1.86-36.6)]. However, this study observed no association between Chlamydia trachomatis genotypes and any genital clinical symptoms. Conclusions: Chlamydia trachomatis genotype H may be a high risk factor for cervical intraepithelial lesions, which is useful for treatment and management measures for patients with cervical intraepithelial lesions.

Predictors of Seronegative Conversion After Centralized Management of Syphilis Patients in Shenzhen, China.

Objective: The aim of this study was to explore the seronegative conversion status of syphilis patients after centralized management and to analyze potential determinants. Materials and Methods: A retrospective population-based cohort study was conducted, and data for individuals who had been diagnosed with syphilis between 2011 and 2019 were retrieved from the Shenzhen Nanshan Center for Chronic Disease Control. Seroconversion statuses were summarized as percentages. Univariable and multiple Cox proportional hazard regression models were used to analyze the factors associated with seronegative conversion among syphilis patients. Results: During the study period, 1,545 patients with syphilis participated in the syphilis convergence case management program on a voluntary basis, of whom 290 were excluded due to missing follow-up data. A total of 27.6% (346/1255) of patients with syphilis showed seronegative conversion. Multivariable analysis revealed that the following significantly determined syphilis seroconversion from positive to negative: younger age (15-19 years vs. ≥30 years: HR = 2.18), male gender (HR = 1.45), lower baseline toluidine red unheated serum test (TRUST) titer of ≤ 1:8 (HR = 2.23), and different disease stages, including latent syphilis (HR = 1.98), primary syphilis (HR = 7.67), and secondary syphilis (HR = 4.83). Conclusions: Few patients with syphilis tested negative after treatment at the end of the study. Seronegative conversion in the patients was associated with age, sex, baseline TRUST titer, and syphilis stage.

Predictors of serological cure after penicillin therapy in HIV-negative patients with early syphilis in Shenzhen, China.

BACKGROUND: Syphilis is a common infectious disease worldwide. Serological monitoring is important for syphilis management. We currently know little about the characteristics of this seronegative response. The aim of this study was to explore the factors associated with serological cure after treatment of early syphilis. METHODS: A retrospective cohort study was conducted and the data of patients with early syphilis in a clinic in Shenzhen from 2011 to 2019 were retrieved. Univariable and multiple Cox proportional hazard regression models were utilized to identify factors associated with a serological cure state among syphilis patients with early syphilis two years after treatment. RESULTS: A total of 346 (85.9%) syphilis patients achieved serological cure. The multivariate analysis results revealed that having a baseline TRUST titer >1:8 was associated with an increased probability of serological cure, compared with having a baseline TRUST titer ≤1:8 (HR = 1.43, 95% CI = 1.10-1.85, P<0.01); primary syphilis was positively associated with serological cure, compared with participants with latent early syphilis (HR = 1.72, 95% CI = 1.27-2.33, P<0.001). CONCLUSIONS: Two years after treatment, a higher percentage of early syphilis patients achieved serological cure. The study indicated that the syphilis stage and baseline serum titer were crucial factors associated with serological cure.

Correction: Associations of sexually transmitted infections and bacterial vaginosis with abnormal cervical cytology: A cross-sectional survey with 9090 community women in China.

[This corrects the article DOI: 10.1371/journal.pone.0230712.].

Associations of sexually transmitted infections and bacterial vaginosis with abnormal cervical cytology: A cross-sectional survey with 9090 community women in China.

BACKGROUND: Although it is well acknowledged that persistent infection with high-risk human papillomavirus types in genital sites plays a crucial role in the development of squamous cell cervical carcinoma, there is no unanimous consensus on the association between non-HPV sexually transmitted infections and abnormal cervical cytology. METHODS: In the present study, we evaluated cervical cytology status, sexually transmitted infections and bacterial vaginosis status, and collected social-demographic information among recruited participants to explore the association of STIs and bacterial vaginosis with abnormal cervical cytology. RESULTS: 9,090 women's specimens were successfully tested, with a total of 8,733 (96.1%) women had normal cytology and 357 (3.9%) women exhibited abnormal cytology. The prevalence of HPV, Chlamydia trachomatis, Neisseria gonorrhoeae, and bacterial vaginosis was significantly higher in the ≥ASC-US group than the NILM group (P<0.05). Women with Neisseria gonorrhoeae infection (AOR = 5.30, 95% CIs = 1.30-21.51, P = 0.020) or bacterial vaginosis (AOR = 1.94, 95% CIs = 1.08-3.47, P = 0.026) exhibited an increased risk of abnormal cervical cytology after adjusted for carcinogenic HPV-positive status. CONCLUSIONS: Our results demonstrated that Neisseria gonorrhoeae infection in genital sites and/or bacterial vaginosis may independently increase the risk for cervical cytology abnormalities after adjusted for carcinogenic HPV-positive status. Besides, these results improved our understanding of the etiology of abnormal cervical cytology and may be useful for the management of women with ASC-US cytology.

Correction: Population-based study of chlamydial and gonococcal infections among women in Shenzhen, China: Implications for programme planning.

[This corrects the article DOI: 10.1371/journal.pone.0196516.].

Population-based study of chlamydial and gonococcal infections among women in Shenzhen, China: Implications for programme planning.

This study was aimed to estimate the prevalences of chlamydia (CT) and gonococcal (NG) infections and explore risk factors associated with the CT infection among women in Shenzhen, China. We collected socio-demographic and clinical data from women (aged 20-60) and determined positivity of CT or NG by nucleic acid amplification test (NAAT) with self-collected urine specimens. We estimated prevalence of CT and NG and determined risk factors associated with CT infection. Among 9,207 participants, 4.12% (95% confidence interval [CI], 3.71%-4.53%) tested positive for CT and 0.17% (95% CIs, 0.09%-0.25%) for NG. Factors significantly associated with CT infection included being an ethnic minority (ethnicity other than Han China) (Adjusted odds ratio [AOR], 1.9; 95% CI, 1.2-3.0), using methods other than condom for contraception (AOR, 1.5; 95% CI, 1.2-1.8), having a history of adverse pregnancy outcomes (AOR, 1.4; 95% CI, 1.1-1.8), and experiencing reproductive tract symptoms in the past three months (AOR, 1.3; 95% CI, 1.0-1.7). we found that CT infection is prevalent among women in Shenzhen, China and associated with both demographic and behavioral factors. A comprehensive CT screening, surveillance and treatment programme targeting this population is warranted.

Factors associated with syphilis treatment failure and reinfection: a longitudinal cohort study in Shenzhen, China.

BACKGROUND: The treatment failure and reinfection rates among syphilis patients are high, and relevant studies in China are limited. The aim of this study was to detect the rates of treatment failure and reinfection after syphilis treatment and to explore the potential associated factors. METHODS: We conducted a longitudinal cohort study in a sexually transmitted disease clinic, the Department of Dermatology and Venereology in Nanshan Center for Chronic Disease Control. Serological testing was performed at baseline and throughout the 2-year follow-up for syphilis patients. To identify potential predictors of treatment outcomes, multivariate logistics analyses were utilized to compare the demographic and clinical characteristics of patients with serological failure/reinfection to those with serological cure/serofast. RESULTS: From June 2011 to June 2016, a total of 1133 patients were screened for syphilis. Among the 770 patients who completed the 2-year follow-up, 510 first-diagnosed patients were included in the final analysis. Multivariate logistics analysis revealed the stage of syphilis (secondary syphilis VS. primary syphilis: adjusted odds ratio, 3.50; 95% confidence interval, 1.11-15.47; p = 0.04), HIV status (positive VS. negative: adjusted odds ratio, 3.06; 95% confidence interval, 1.15-8.04; p = 0.02) and frequency of condom use (always use VS. never use: adjusted odds ratio, 0.28; 95% confidence interval 0.08-0.75; p = 0.02) were significantly associated with the serological outcome. CONCLUSIONS: The clinical implications of our findings suggest that it is very important to perform regular clinical and serologic evaluations after treatment. Health counseling and safety education on sex activity should be intensified among HIV-infected patients and secondary syphilis patients after treatment.

Congenital syphilis: refining newborn evaluation and management in Shenzhen, southern China.

INTRODUCTION: Consistent definitions of congenital syphilis are critical for determining true incidences and setting up targets of elimination. This study aimed to assess the evaluation and management of infants at high risk of congenital syphilis with an antenatal syphilis-screening programme in the Shenzhen SEZ and to develop feasible definitions for the detection of congenital syphilis in China. METHODS: A retrospective study was conducted of all standardised records of pregnant women with positive syphilis between 2003 and 2007. Infants at high risk of congenital syphilis were evaluated by laboratory tests at birth and longitudinal follow-up. A screening test-positive congenital syphilis case was defined based on a positive 19S-IgM-FTA-ABS result at birth. Assuming that 19S-IgM-FTA-ABS was the gold standard, the sensitivity and specificity of the ascertainment methods were calculated. RESULTS: During the study period, 1010 live infants were born to women with active syphilis during pregnancy. 19S-IgM-FTA-ABS detected 42 screening-positive congenital syphilis cases and another nine cases were identified by longitudinal follow-up only. Using 19S-IgM-FTA-ABS as the gold standard, 'fourfold rapid plasma reagin (RPR) titres' had the highest sensitivity and specificity compared with the other two follow-up methods. DISCUSSION: 19S-IgM-FTA-ABS makes congenital syphilis case classification simpler and faster for newborns. In areas where 19S-IgM-FTA-ABS is not available, comparing newborn RPR titres with maternal titres can be an alternative method. Meanwhile, positive follow-up results act as treatment indicators for older infants. As congenital syphilis definitions vary over the country, the Shenzhen programme suggested a practical model for surveillance and treatment in areas with or without available 19S-IgM-FTA-ABS testing.