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Wen-Qi Xu,1,2 Jing-Wei Liu,1,2 Xiao-Yu Zhu,1,2 Xiao-Li Zheng,1,2 Kai Chen,1,2 Xiang-Sheng Chen,1,2 Yue-Ping Yin1,2 1STD Reference Laboratory, Institute of Dermatology and Hospital for Skin Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing, People’s Republic of China; 2STD Reference Laboratory, National Center for Sexually Transmitted Diseases Control, Chinese Center for Disease Control and Prevention, Nanjing, People’s Republic of ChinaCorrespondence: Yue-Ping YinSTD Reference Laboratory, Institute of Dermatology and Hospital for Skin Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 12, Jiangwangmiao Street, Nanjing, 210042, People’s Republic of ChinaTel/Fax +86 258 547 8024Email yinyp@ncstdlc.orgPurpose: Neisseria gonorrhoeae, resistant to the first-line treatment option ceftriaxone, is widespread in China from 2016. Nowadays, diverse reagents of disks and strips for rapid gonococcal antimicrobial susceptibility tests used in clinics are culture-based disks diffusion and gradient strips methods. This study aimed to evaluate the accuracy, quality, and availability of almost all disks and strips acquired in the Chinese market and serve as a reference for clinical selection.Methods: We tested the performance of 15 commercial disks and 9 commercial gradient strips acquired in China, compared with traditional agar dilution method. The overall performance was evaluated by the categorical agreement. The reagent accuracy of gradient strips was assessed by the essential agreement.Results: A total of 167 gonococcal isolates were used to evaluate antimicrobial disks from three brands. The overall categorical agreements were 71.7% to 81.8% for ceftriaxone, less than 58% for cefixime, 100% for spectinomycin, over 98% for ciprofloxacin, below 70.5% for penicillin, and 73.3% to 81.8% for tetracycline. A total of 81 isolates were tested for different gradient strips. Categorical agreements were over 96% for ceftriaxone, 86.2% for azithromycin, 62.3% to 67.1% for penicillin, 41.9% to 67.5% for tetracycline, and 95% for ciprofloxacin. Essential agreements were 57.7% to 87.3% for ceftriaxone, 70% for azithromycin, 64.9% to 68.4% for penicillin, 51.8% to 71.2% for tetracycline, and 91.3% for ciprofloxacin.Conclusion: Rapid test reagents of disks and strips based on gonococcal culture have suboptimal performance. Disk diffusion for spectinomycin or ciprofloxacin can be recommended for clinical individualized prescription. The gradient strips are of great value to identify ceftriaxone-resistant gonococcal strains. Furthermore, abundant improvements are required for many reagents to further optimize their accuracy till the fulfillment of molecular detection.Keywords: Neisseria gonorrhoeae, disk diffusion test, gradient strip test, antimicrobial susceptibility

Wen-Qi Xu,1,2 Xiao-li Zheng,1,2 Jing-Wei Liu,1,2 Qian Zhou,1,2 Xiao-Yu Zhu,1,2 Jin Zhang,1,2 Yan Han,1,2 Kai Chen,1,2 Shao-Chun Chen,1,2 Xiang-Sheng Chen,1,2 Yue-Ping Yin1,2 1STD Reference Laboratory, Institute of Dermatology and Hospital for Skin Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, People’s Republic of China; 2STD Reference Laboratory, National Center for Sexually Transmitted Diseases Control, Chinese Center for Disease Control and Prevention, Nanjing, People’s Republic of ChinaCorrespondence: Yue-Ping YinSTD Reference Laboratory, Institute of Dermatology and Hospital for Skin Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, People’s Republic of ChinaTel/Fax +86 258 547 8024Email yinyp@ncstdlc.orgPurpose: This study aimed to determine the minimum inhibitory concentrations (MICs) of ertapenem on Neisseria gonorrhoeae collected from eight Chinese provinces in 2018.Methods: The MICs of ertapenem on 503 Neisseria gonorrhoeae isolates (415 isolates selected randomly and 88 isolates selected with preference) were measured using the agar dilution method. For comparison, the MICs of ceftriaxone and azithromycin were detected.Results: Among 415 randomly selected isolates, the MIC range for ertapenem was from ≤ 0.008 mg/L to 0.5 mg/L. The corresponding MIC50 and MIC90 were 0.06 and 0.125 mg/L, respectively. Twelve of 415 isolates (2.9%) exhibited MIC values ≥ 0.25 mg/L, and only one isolate (0.2%) had a MIC of 0.5 mg/L. By comparing all 503 tested isolates, a correlation of r = 0.487 (P < 0.001) between ertapenem and ceftriaxone MIC was observed, and the correlation between MICs of ertapenem and azithromycin was low (r = − 0.12, P = 0.007). In 24 ceftriaxone-decreased susceptibility isolates, four isolates (16.7%) showed a MIC ≥ 0.25 mg/L for ertapenem. In 85 azithromycin resistant isolates, three isolates (3.5%) showed a MIC ≥ 0.25 mg/L for ertapenem.Conclusion: The in vitro results suggest that ertapenem has satisfactory susceptibility in isolates collected from eight provinces in China; hence, it might be a promising treatment option for resistant gonococcal infections.Keywords: Neisseria gonorrhoeae, treatment, ertapenem, antimicrobial resistance

Yan Han,1,2 Yue-Ping Yin,1,2 Jing-Wei Liu,1,2 Kai Chen,1,2 Bang-Yong Zhu,3 Ke Zhou,1,2 Mei-Qin Shi,1,2 Wen-Qi Xu,1,2 Tulip A Jhaveri,4 Xiang-Sheng Chen1,2 1Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, People’s Republic of China; 2National Center for STD Control, Chinese Center for Disease Control and Prevention, Nanjing, People’s Republic of China; 3Institute of Dermatology, Guangxi Autonomous Region, Nanning, People’s Republic of China; 4Division of Medical Microbiology, Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USACorrespondence: Yue-Ping YinInstitute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, 12 Jiangwangmiao Street, Nanjing, 210042, People’s Republic of ChinaTel/Fax +86 258 547 8024Email yinyp@ncstdlc.orgBackground: Previous studies have investigated rectal Mycoplasma genitalium (MG) in men who have sex with men (MSM), while little is known about the prevalence of rectal MG infection in individuals attending sexually transmitted disease (STD) clinics in China. We aimed to estimate the prevalence of rectal MG infection in this population and identified the potential risk factors for rectal MG infection.Methods: A cross-sectional study was conducted among individuals attending STD clinics located in China from June 2018 to August 2020. Univariate and multivariate logistic regression analyses were conducted to explore the association of different risk factors for rectal MG infection.Results: A total of 1,382 patients were included in the final analyses. A total of 30 of 1377 rectal swabs (2.2%) and 77 of 1374 urogenital samples (5.6%) were positive for MG. In Guangxi, 18 of 47 patients (38.3%) infected with urogenital MG and 5 of 19 patients (26.3%) infected with rectal MG received the recommended treatment. Factors found to be significantly associated with rectal MG infection included: male (adjusted odds ratio (AOR) 0.232, [95% CI: 0.072– 0.745]) compared to female, homosexual or bisexual (AOR 40.427, [95% CI: 3.880– 421.196]) compared to heterosexual, and those infected with urogenital MG (AOR 7.215, [95% CI: 2.898– 17.965]) compared to those who did not get infected with urogenital MG.Conclusion: Rectal MG infection should be thought of not only in MSM population but also in STD clinic patients, especially females who have urogenital MG infection. Appropriate strategy for rectal MG screening and treatment needs to be developed for these patients in China.Keywords: Mycoplasma genitalium, rectal infection, sexually transmitted disease clinics

Xiao-Li Zheng,1,2 Wen-Qi Xu,1,2 Jing-Wei Liu,1,2 Xiao-Yu Zhu,1,2 Shao-Chun Chen,1,2 Yan Han,1,2 Xiu-Qin Dai,1,2 Isabelle Griffin Goodman,3 Christoph Budjan,4,5 Xiang-Sheng Chen,1,2 Yue-Ping Yin1,2 1Institute of Dermatology and Hospital for Skin Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, People’s Republic of China; 2National Center for Sexually Transmitted Diseases Control, Chinese Center for Disease Control and Prevention, Nanjing, People’s Republic of China; 3Boston University, Boston, MA, USA; 4Department of Data Sciences, Dana-Farber Cancer Institute, Boston, MA, USA; 5Department of Systems Biology, Harvard Medical School, Boston, MA, USACorrespondence: Yue-Ping YinInstitute of Dermatology and Hospital for Skin Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 12, Jiangwangmiao Street, Nanjing 210042, People’s Republic of ChinaTel/Fax +86 258 547 8024Email yinyp@ncstdlc.orgPurpose: The study aimed to evaluate meropenem, fosfomycin, berberine hydrochloride, and doxycycline minimum inhibitory concentrations (MICs) of Neisseria gonorrhoeae collected from eight provinces in China in 2018.Methods: The MICs of 540 Neisseria gonorrhoeae isolates (451 isolates selected randomly and 89 isolates selected with preference) were determined to meropenem, fosfomycin, berberine hydrochloride, and doxycycline using the agar dilution method, and the MICs of ceftriaxone and azithromycin were detected for comparison.Results: Among 451 randomly selected isolates, the MIC90 was 0.06 mg/L for meropenem, 64 mg/L for fosfomycin, 64 mg/L for berberine hydrochloride, and 16 mg/L for doxycycline. All isolates showed the MIC ≤ 0.125 mg/L to meropenem, 13 isolates (2.9%) showed MIC > 64 mg/L to fosfomycin, 8 isolates (1.8%) demonstrated MIC > 64 mg/L to berberine hydrochloride, and 271 isolates (60.1%) demonstrated MIC > 1 mg/L to doxycycline. Comparing all 540 tested isolates, a correlation of r = 0.50 (P < 0.001) between meropenem and ceftriaxone MIC was observed. In 24 ceftriaxone-decreased susceptibility isolates, all isolates showed an MIC ≤ 0.125 mg/L for meropenem, 1 isolate (4.2%) showed an MIC > 64 mg/L for fosfomycin, 1 isolate (4.2%) showed an MIC > 64 mg/L for berberine hydrochloride, and 13 isolates (54.2%) showed an MIC > 1 mg/L for doxycycline. In 87 azithromycin resistant isolates, all isolates showed an MIC ≤ 0.125 mg/L for meropenem, 2 isolates (2.3%) showed an MIC > 64 mg/L for fosfomycin, 4 isolates (4.6%) showed an MIC > 64 mg/L for berberine hydrochloride, and 64 isolates (73.6%) showed an MIC > 1 mg/L for doxycycline.Conclusion: The in vitro results suggest that meropenem might be a promising treatment option for resistant gonococcal infections, while the effects of fosfomycin and berberine hydrochloride should be further evaluated as potential therapeutic agents. The effectiveness of these drugs in animal experiments and clinical use may need further study.Keywords: Neisseria gonorrhoeae, treatment, antimicrobial resistance, meropenem, fosfomycin

Yan Han,1,2 Yue-Ping Yin,1,2 Wen-Qi Xu,1,2 Xiao-Yu Zhu,1,2 Shao-Chun Chen,1,2 Xiu-Qin Dai,1,2 Li-Gang Yang,3,4 Bang-Yong Zhu,5 Na Zhong,6 Wen-Ling Cao,7 Xiao-Hui Zhang,3,4 Zhi-Zhou Wu,8 Liu-Feng Yuan,9 Zhong-Jie Zheng,10 Jun Liu,11 Xiang-Sheng Chen1,2 1Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, Jiangsu, People’s Republic of China; 2National Center for STD Control, Chinese Center for Disease Control and Prevention, Nanjing, Jiangsu, People’s Republic of China; 3Dermatology Hospital, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China; 4Guangdong Provincial Dermatology Hospital, Guangzhou, Guangdong, People’s Republic of China; 5Institute of Dermatology, Nanning, Guangxi Autonomous Region, People’s Republic of China; 6Hainan Provincial Center for STD/Skin Disease Control and Prevention, Haikou, Hainan, People’s Republic of China; 7Guangzhou Institute of Dermatology, Guangzhou, Guangdong, People’s Republic of China; 8Jiangmen Dermatology Hospital, Jiangmen, Guangdong, People’s Republic of China; 9Beijing Ditan Hospital Capital Medical University, Beijing, People’s Republic of China; 10Tianjin Center for Disease Control and Prevention, Tianjin, People’s Republic of China; 11Harvard Medical School, Boston, MA, USACorrespondence: Yue-Ping YinInstitute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, 12 Jiangwangmiao Street, Nanjing 210042, People’s Republic of ChinaTel/ Fax +86 258 547 8024Email yinyp@ncstdlc.orgPurpose: Injectable ceftriaxone and oral cefixime are the last agents effective against Neisseria gonorrhoeae. In vitro antimicrobial-susceptibility testing (AST) is done to identify the most efficacious antibiotic needed to combat the infection in that particular individual. The objective of this study was to evaluate whether Kirby–Bauer (KB) disk-diffusion tests can detect N. gonorrhoeae isolates that have decreased susceptibility to ceftriaxone and cefixime for appropriate clinical management.Methods: A total of 1,633 consecutive clinical isolates of N. gonorrhoeae were collected from January 1, 2013 to December 31, 2017 from seven dermatology clinics located in five provinces in China. Consistency between KB disk-diffusion tests and the agar-dilution method, as well as sensitivity of the KB test for detecting N. gonorrhoeae isolates with decreased susceptibility to ceftriaxone and cefixime, were determined using 1,306 clinical isolates that had been recovered to complete agar-dilution AST.Results: The prevalence of isolates with decreased susceptibility to ceftriaxone and cefixime was 12.1% (198 of 1,633) and 12.7% (208 of 1,633), respectively, using KB disk-diffusion tests. The prevalence of isolates with decreased susceptibility was 9.9% (129 of 1,306) for ceftriaxone and 9.9% (129 of 1,305) for cefixime using agar-dilution AST. The categorical agreement of these two methods was 80.9% for both ceftriaxone and cefixime. Compared to agar-dilution AST, the sensitivity of the KB test for detecting N. gonorrhoeae isolates with decreased susceptibility was 22.5% (29 of 129) for ceftriaxone and 29.5% (38 of 129) for cefixime, and its specificity 87.3% (1,028 of 1,177) for ceftriaxone and 86.7% (1,018 of 1,176) for cefixime.Conclusion: Although KB tests are easy to carry out in clinical practice, their ability to detect cephalosporin-resistant gonorrhoea strains is limited. This method is not an appropriate selection for screening cephalosporin-resistant gonorrhoea strains in clinical practice in China.Keywords: Neisseria gonorrhoeae, Kirby–Bauer disk-diffusion tests, agar-dilution method, susceptibility, screen

Shao-Chun Chen,1,2,* Jing-Wei Liu,1,2,* Xing-Zhong Wu,3 Wen-Ling Cao,4 Feng Wang,5 Jin-Mei Huang,3 Yan Han,1,2 Xiao-Yu Zhu,1,2 Bang-Yong Zhu,6 Quan Gan,6 Xiao-Zheng Tang,7 Xing Shen,8 Xiao-Lin Qin,3 Yu-Qi Yu,3 He-Ping Zheng,3 Yue-Ping Yin1,2 1Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, People’s Republic of China; 2National Center for STD Control, Chinese Center for Disease Control and Prevention, Nanjing, People’s Republic of China; 3Clinical Laboratory, Guangdong Provincial Dermatology Hospital, Guangzhou, Guangdong, People’s Republic of China; 4Clinical Laboratory, Guangzhou Dermatology Hospital, Guangzhou, Guangdong, People’s Republic of China; 5Shenzhen Center for Chronic Diseases Control, Shenzhen, Guangdong, People’s Republic of China; 6Clinical Laboratory, Guangxi Provincial Dermatology Hospital, Nanning, Guangxi, People’s Republic of China; 7Clinical Laboratory, Hainan Provincial Dermatology Hospital, Haikou, Hainan, People’s Republic of China; 8Zhuhai Center for Chronic Diseases Control, Zhuhai, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yue-Ping YinNational Center for STD Control,Chinese Center for Disease Control and Prevention, 12 Jiangwangmiao Street, Nanjing 210042, People’s Republic of ChinaTel +86-25-85478024Email yinyp@ncstdlc.orgHe-Ping ZhengGuangdong Provincial Dermatology Hospital, 2 Lujing Road, Guangzhou 510091, People’s Republic of ChinaEmail zhhpf@hotmail.comIntroduction: Antimicrobial resistance (AMR) of Neisseria gonorrhoeae (N. gonorrhoeae) becomes a grave public health problem in the world. A strengthened Antimicrobial Resistance Surveillance Program is needed to track the trend of AMR development. However, the lack of a proper antimicrobial susceptibility test (AST) method is a barrier to expand the AMR surveillance in China. Traditional agar dilution (AD) method is laborious and E-test strips have no approval license for clinical use. Herein, a Chinese group modified the microdilution (MD) method for clinical ASTs. The objective of this study is to compare the MD method with the AD method for N. gonorrhoeae AST.Materials and Methods: A total of 166 clinical isolates were tested for antimicrobial susceptibility of ceftriaxone, spectinomycin, azithromycin, ciprofloxacin, tetracycline, and penicillin using MD and AD method simultaneously. Results of MD method were read manually or automatically. Rates of essential agreement (EA), category agreement (CA), minor error, and very major error were compared.Results: The total EAs (compared with results read manually) of penicillin, tetracycline, ciprofloxacin, spectinomycin, ceftriaxone, and azithromycin were 90.4%, 97.0%, 85.5%, 100.0%, 94%, and 72.3%; and CAs were 82.5%, 94.0%, 100%, 100%, 95.2%, and 94%, respectively.Conclusion: We conclude that the MD method might be an alternative for clinical AST of N. gonorrhoeae in China. In particular, MD method has the potency of accurate differentiation of isolates resistant to ceftriaxone or azithromycin, which were empirically recommended for gonococcal treatment, but its quality remained suboptimal, and further improvement is needed for clinical use.Keywords: Neisseria gonorrhoeae, antimicrobial susceptibility test

Jing-Wei Liu,1,2 Wen-Qi Xu,1,2 Xiao-Yu Zhu,1,2 Xiu-Qin Dai,1,2 Shao-Chun Chen,1,2 Yan Han,1,2 Jun Liu,3 Xiang-Sheng Chen,1,2 Yue-Ping Yin1,21Institute of Dermatology and Hospital for Skin Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, People’s Republic of China; 2National Center for Sexually Transmitted Diseases Control, Chinese Center for Disease Control and Prevention, Nanjing, People’s Republic of China; 3SYNAPSE Center, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USAPurpose: Gentamicin is a promising antimicrobial for the treatment of gonorrhea. The study aimed to evaluate gentamicin minimum inhibitory concentrations (MICs) of Neisseria gonorrhoeae isolates in China.Methods: In this study, the agar dilution method was used to determine the MICs of 470 isolates collected in 2016 to four effective antimicrobials (gentamicin, azithromycin, ceftriaxone, and spectinomycin).Results: Gentamicin MICs ranged from 1 to 8 mg/L. No isolate was resistant to gentamicin. Of seven isolates simultaneously resistant to azithromycin and ceftriaxone, 6 isolates demonstrated MICs of 4 mg/L or less to gentamicin. No cross relationships were found between MICs of gentamicinand susceptibility profiles of azithromycin, ceftriaxone, and spectinomycin.Conclusion: The in vitro results suggest that gentamicin can be a promising treatment option for gonococcal infections in China. Clinical trials to evaluate the therapeutic efficacy of gentamicin are required.Keywords: Neisseria gonorrhoeae, agar dilution method, gentamicin, antimicrobial surveillance

Feng Wang,1,* Jingwei Liu,2,* Hongye Liu,2 Jing Huang,1 Shaochun Chen,2 Xiangsheng Chen,2 Yueping Yin2 1Department of STD Control Laboratory, Shenzhen Center for Chronic Disease Control, Shenzhen, China; 2Department of Reference STD Lab, National Center for STD Control, Chinese Center for Disease Control and Prevention, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China *These authors contributed equally to this work Background: Neisseria gonorrhoeae resistance to azithromycin has become a significant public health concern globally, and high-level azithromycin-resistant (HL-AzmR) isolates have emerged frequently. However, high-level azithromycin resistance is considered to be caused by mutated alleles of 23S rRNA gene at position 2059, and identification of HL-AzmR isolates mainly relies on agar dilution method or E-test method. This study aimed to assess the accuracy of the molecular assays targeting the mutation A2059G for identifying HL-AzmR isolates and thereby determine the association between the mutation and high-level azithromycin resistance. Methods: Two researchers independently searched six databases to identify studies published from the launch of each database to October 15, 2017. The fixed effects model was used to estimate the pooled sensitivity rate, specificity rate, positive predictive value (PPV), and negative predictive value (NPV). Summary receiver operating characteristic curves were generated, and the area under the curve (AUC) was determined to estimate the overall performance of the assays. The Deeks’ test was conducted to evaluate potential publication bias. Results: Ten relevant studies were included in the meta-analysis to assess the synthetic accuracy of the molecular assays. The molecular assays had the synthetic sensitivity rate of 97.8% and the synthetic specificity rate of 99.1%. And the aggregated PPV and NPV were 96.4% and 99.5%, respectively. AUC was 0.99, suggesting a close relation existing between the mutation A2059G and high-level azithromycin resistance. This indicated that the molecular assays targeting the mutation A2059G have relatively high overall accuracy for identifying HL-AzmR N. gonorrhoeae isolates. Publication bias was statistically significant. Conclusion: The mutation A2059G is the critical factor causing high-level azithromycin resistance. Hence, molecular methods are recommended to be put into clinical practice by commercialization, which will assist clinicians to prescribe more precisely. Keywords: Neisseria gonorrhoeae, 23S rRNA, A2059G, azithromycin resistance, systematic review

Background: It has been demonstrated that thymosin β4 (Tβ4) could inflect the severity of acute-on-chronic hepatitis B liver failure (ACHBLF), but the relationship between its methylation status and the prognosis of liver failure is not clear. This study aimed to determine Tβ4 promoter methylation status in patients with ACHBLF and to evaluate its prognostic value., Methods: The study recruited 115 patients with ACHBLF, 80 with acute-on-chronic hepatitis B pre-liver failure (pre-ACHBLF), and 86 with chronic hepatitis B (CHB). In addition, there were 36 healthy controls (HCs) from the Department of Hepatology, Qilu Hospital of Shandong University. The 115 patients with ACHBLF were divided into three subgroups: 33 with early stage ACHBLF (E-ACHBLF), 42 with mid-stage ACHBLF (M-ACHBLF), and 40 with advanced stage ACHBLF (A-ACHBLF). Tβ4 promoter methylation status in peripheral blood mononuclear cells (PBMCs) was measured by methylation-specific polymerase chain reaction, and mRNA was detected by quantitative real-time polymerase chain reaction., Results: Methylation frequency of Tβ4 was significantly higher in patients with ACHBLF than in those with pre-ACHBLF, CHB or HCs. However, expression of Tβ4 mRNA showed the opposite trend. In patients with ACHBLF, Tβ4 promoter methylation status correlated negatively with mRNA levels. The 3-month mortality of ACHBLF in the methylated group was significantly higher than that in the unmethylated group. Also, Tβ4 promoter methylation frequency was lower in survivors than in non-survivors. When used to predict the 1-, 2-, and 3-month incidence of ACHBLF, Tβ4 methylation status was better than the model for end-stage liver disease (MELD) score. The predictive value of Tβ4 methylation was higher than that of MELD score for the mortality of patients with E-ACHBLF and M-ACHBLF, but not for A-ACHBLF., Conclusions: Tβ4 methylation might be an important early marker for predicting disease incidence and prognosis in patients with ACHBLF., (Copyright © 2022. Published by Elsevier B.V.)

Background: Chlamydia trachomatis (CT) infection has an increased risk for fertility-related and pregnancy adverse outcomes partly due to mechanisms related to a pro-inflammatory response to CT-, or cHSP60-induced delayed hypersensitivity. This study aimed to assess the evidence on the association between CT serology and adverse outcomes., Methods: PubMed/Medline, Embase and Web of Science databases were searched for observational studies on the association of CT-specific antibodies (e. g. IgG, IgA, IgM, etc.) with infertility, tubal factor infertility (TFIF), ectopic pregnancy (EP), spontaneous abortion (SA), or preterm labor (PL) that were published from database inception to 31 August 2022. Pooled adjusted odds ratios or relative risks with corresponding 95% confidence intervals were calculated using a random effects model. This study was registered with PROSPERO (CRD42022368366)., Findings: We identified 128 studies that met the inclusion criteria, comprising 87 case-control, 34 cross-sectional and 7 cohort studies, for a total of 167 records involving 128,625 women participants included into the meta-analyses. Based on the adjusted estimates, it was found that CT-specific IgG was significantly associated with TFIF (pooled adjusted OR = 2.09, 95% CI 1.33-3.27, I 2  = 63.8%) or EP (pooled adjusted OR = 3.00, 95% CI 1.66-5.40, I 2  = 93.0%). Analyses of the unadjusted estimates indicated significant associations between CT-specific IgG and infertility, TFIF, EP or SA (four pooled unadjusted ORs ranging between 1.60 and 5.14, I 2 ranging between 40% and 83%); IgA and infertility, TFIF, EP (three pooled unadjusted ORs ranging between 3.64 and 4.91, I 2 ranging between 0% and 74%); IgM and TFIF (pooled unadjusted OR = 5.70, 95% CI 1.58-20.56, I 2  = 56%); or cHSP60 and TFIF (pooled unadjusted OR = 7.83, 95% CI 5.42-11.31, I 2  = 49%)., Interpretation: A broad range of CT-specific antibodies have been studied in association with fertility-related and pregnancy adverse outcomes. However, our study identified a low- or moderate-quality evidence for an association of CT serology with the outcomes. There are substantial research gaps in relation to the clinical implications of CT serological biomarkers., Funding: The work was supported by the Chinese Academy of Medical Sciences Initiative for Innovative Medicine (2016-I2M-3-021)., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Actively screening for Chlamydia trachomatis (CT) is important for young people because of a high prevalence of asymptomatic infection in this population. This study aimed to investigate knowledge on CT and preference to the screening services for CT among young students in China., Methods: From June to July 2022, a web-based questionnaire survey was conducted to collect information on sociodemographic characteristics, sexual behaviors, knowledge of CT, previous testing for CT, and preference to platform of testing for CT among Chinese young students. An online home-based self-sampling test (HBSST) service was offered free of charge if the participant was willing to be tested for CT. Statistical analyses included descriptive analysis, χ 2 test, and multivariable logistic regression., Results: Of 520 participants, 419 (80.6%) were aged between 16 and 24 years, 235 (45.2%) reported having sexual experience in the past, and 27 (5.2%) being tested before for CT. Slightly higher than 10% (57/520) of students were knowledgeable about CT. About one-third (36.9%) expressed their willingness to have a testing for CT but majority of them (63.1%) preferred to a free testing. Having sexual experience was significantly associated with the willingness to take the HBSST service (adjusted odds ratio, 2.96; 95% confidence interval, 1.92-4.58). A total of 139 (26.7%) participants requested the HBSST service online and 43.2% (60/139) returned the specimen for testing, in which 2 positives (3.3%) were found., Conclusions: The knowledge on CT and the previous uptake or current willingness to have a testing for CT was low among Chinese young students., Competing Interests: Conflict of Interest: None declared., (Copyright © 2022 American Sexually Transmitted Diseases Association. All rights reserved.)

Objectives: Screening for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) at both urogenital and extragenital sites has been recommended in many countries. Testing of the infections using pooled specimens from urogenital and extragenital sites offer the opportunity to shorten the testing time and reduce the testing cost. Ex-ante pooling is placing the original single-site specimens in a tube with transport media, while ex-post pooling is making a pool of the transport media from both anorectal and oropharyngeal specimens and the urine. This study aimed to conduct a multisite performance evaluation of two pool-specimen approaches (ex-ante and ex-post) in detection of CT and NG using the Cobas 4800 platform among men who have sex with men (MSM) in China., Design: Diagnostic accuracy study., Setting, Participants and Outcome Measures: Participants were recruited from MSM communities at six cities in China. Two oropharyngeal and anorectal swabs collected by clinical staff and 20 mL first-void urine collected by the participant himself were used for evaluating sensitivity and specificity., Results: A total of 1311 specimens were collected from 437 participants in six cities. The sensitivities of ex-ante pooling approach as compared with single-specimen approach (reference standard) were 98.7% (95% CI, 92.7% to 100.0%) for detection of CT and 89.7% (95% CI, 75.8% to 97.1%) for NG, and the specificities were 99.5% (95% CI, 98.0% to 99.9%) and 98.7% (95% CI, 97.1% to 99.6%), respectively. The sensitivities of ex-post pooling approach were 98.7% (95% CI, 92.7% to 100.0%) for CT and 100.0% (95% CI, 91.0% to 100.0%) for NG, and the specificities were 100.0% (95% CI, 99.0% to 100.0%) and 100.0% (95% CI, 99.1% to 100.0%), respectively., Conclusions: The ex-ante and ex-post pooling approaches show good sensitivity and specificity in detecting urogenital and extragenital CT and/or NG, indicating that these approaches can be used in epidemiological surveillance and clinical management of CT and NG infections, particularly among MSM population., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The response rate of topotecan, as a second-line chemotherapeutic drug for small cell lung cancer, is ~20%. DNA/RNA helicase SLFN11 (schlafen family member 11), a member of the Schlafen (SLFN) family, is a crucial determinant of response to many DNA damaging agents, expression of SLFN11 tends to augment the antitumor effects of the commonly used DNA-targeting agents. In the present study we investigated how SLFN11 expression regulated the sensitivity of small cell lung cancer to topotecan. We showed that SLFN11 expression levels were positively associated with the sensitivity to topotecan in a panel of seven SCLC cell lines. Topotecan treatment induced different patterns of the DNA response network in SCLC cells: DNA damage response (DDR) was more prominently activated in SLFN11-deficient SCLC cell line H82 than in SLFN11-plentiful SCLC cell line DMS273, whereas topotecan induced significant accumulation of p-Chk1, p-RPA2 and Rad51 in H82 cells, but not in DMS273 cells. We unraveled that SLFN11 expression was highly negatively correlated to the methylation of the SLFN11 promoter. HDAC inhibitors FK228 and SAHA dose-dependently increased SLFN11 expression through suppressing DNA methylation at the SLFN11 promoter, thereby sensitizing SCLC cells to topotecan. Finally, we assessed the methylation status of the SLFN11 promoter in 27 SCLC clinical specimens, and found that most of the clinical samples (24/27) showed DNA methylation at the SLFN11 promoter. In conclusion, it is feasible to combine topotecan with FK228 to improve the response rate of topotecan in SCLC patients., (© 2021. The Author(s), under exclusive licence to CPS and SIMM.)

Introduction: Chlamydia trachomatis (CT) causes the most prevalent bacterial sexually transmitted infection in the world, and men who have sex with men (MSM) are considered as a high-risk population for this infection. Data regarding the prevalence of CT infection in China are limited and fragmented. In this study, we aim to determine at the national level the anatomically specific CT prevalence and genotype distribution of CT strains among MSM, recruiting from the venues where MSM commonly seek sexual partners., Methods and Analysis: The study will be a nationwide cross-sectional survey to estimate the prevalence of chlamydial infections among MSM who meet the inclusion criteria over a period of 6 months (May-October 2022). A total of 2429 participants will be recruited from the venues where MSM most often seek sex partners in 14 cities of the 7 geographical regions in China. A mobile phone app-based anonymous self-administered questionnaire will be used to collect sociodemographic and behavioural data, and specimens of urine, anorectal and pharyngeal swabs will be collected for identifying the infections of CT and Neisseria gonorrhoeae and genotypes of CT. The data will be analysed using the IBM SPSS program V.20 ETHICS AND DISSEMINATION: The study protocol has been approved by the Medical Ethics Committee of the Chinese Academy of Medical Sciences Institute of Dermatology and the National Center for STD Control on 9 October 2021 (approval number 2021-KY-037). The study is based on voluntary participation and a written informed consent process. The study results will be submitted for publication in peer-reviewed journals and reported in conferences. The relevant data will be made available to development of control programmes and used as health education materials to disseminate to the community. The dataset will be deposited in a public repository., Trial Registration Number: ChiCTR2100052869., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: We aimed to evaluate the clinical performance of the GeneXpert ® (Xpert) CT/NG assay for the detection of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) using urine and cervical swabs collected from patients in China., Methods: This study was conducted from September 2016 to September 2018 in three Chinese urban hospitals. The results from the Xpert CT/NG test were compared to those from the Roche cobas ® 4800 CT/NG test. Discordant results were confirmed by DNA sequence analysis., Results: In this study, 619 first void urine (FVU) specimens and 1,042 cervical swab specimens were included in the final dataset. There were no statistical differences between the results of the two tests for the detection of CT/NG in urine samples ( p  > 0.05), while a statistical difference was found in cervical swabs ( p  < 0.05). For CT detection, the sensitivity and specificity of the Xpert test were 100.0% (95%CI = 96.8-99.9) and 98.3% (95%CI = 96.6-99.2) for urine samples and 99.4% (95%CI = 96.5-100.0) and 98.6% (95%CI 97.5-99.2) for cervical swabs, respectively. For NG detection, the sensitivity and specificity of the Xpert test were 99.2% (95%CI = 94.9-100.0) and 100.0% (95%CI = 99.0-100.0) for urine and 100% (95%CI = 92.8-100.0) and 99.7% (95%CI = 99.0-99.9) for cervical swabs, respectively., Conclusion: The Xpert CT/NG test exhibited high sensitivity and specificity in the detection of CT and NG in both urine and cervical samples when compared to the reference results. The 90-min turnaround time for CT and NG detection at the point of care using Xpert may enable patients to receive treatment promptly., Competing Interests: FT and YT are employees of Cepheid, the commercial manufacturer of the Xpert® CT/NG test. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Han, Shi, Jiang, Le, Qin, Xiong, Zheng, Tenover, Tang and Yin.)

Background: Little is known about rectal Chlamydia trachomatis (CT) infection in outpatients attending sexually transmitted disease (STD) clinics in China. In this study, we aimed to explore the clinical and epidemiologic features of rectal CT infection in this population., Methods: A cross-sectional study was conducted among patients attending STD clinics in Tianjin and Guangxi provinces of China from June 2018 to August 2020. Bivariate and multivariate logistic regression analysis were developed to explore the association of different risk factors for urogenital and rectal CT infection., Results: The prevalence of urogenital and rectal CT was 11.2% (154/1374) and 4.9% (68/1377), respectively. The rectal CT prevalence among female and male patients was 7.8% (60/767) and 1.3% (8/610), respectively. The most common genotype in urogenital CT-positive samples was genotype E (29.9%), while the most common genotype among rectal CT-positive samples was genotype J (23.4%). More than 85% (52/60) of women infected with rectal CT were co-infected with urogenital CT. About 90.0% (36/40) of women shared similar genotypes between rectal and urogenital samples. Females and patients infected with urogenital CT were deemed to be at an increased risk for rectal CT infection. A high proportion of rectal CT infection had concurrent urogenital CT infection, especially in women, and most of the co-infections were shared among the same genotypes., Conclusions: It would be prudent to encourage awareness and introduce detection tests and treatment strategies for rectal CT infection particularly in female patients visiting STD clinics in China., (© The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Rhein, belonging to anthraquinone compounds, is one of the main active components of rhubarb and Polygonum multiflorum . Rhein has a variety of pharmacological effects, such as cardiocerebral protective effect, hepatoprotective effect, nephroprotective effect, anti-inflammation effect, antitumor effect, antidiabetic effect, and others. The mechanism is interrelated and complex, referring to NF- κ B, PI3K/Akt/MAPK, p53, mitochondrial-mediated signaling pathway, oxidative stress signaling pathway, and so on. However, to some extent, its clinical application is limited by its poor water solubility and low bioavailability. Even more, rhein has potential liver and kidney toxicity. Therefore, in this paper, the pharmacological effects of rhein and its mechanism, pharmacokinetics, and safety studies were reviewed, in order to provide reference for the development and application of rhein., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Gang-Min Li et al.)

Proteasome inhibitors, bortezomib (BTZ), and carfilzomib (CFZ) are approved drugs for hematological malignancies, but lack anticancer activities against most solid tumors. Small cell lung cancer (SCLC) is a very aggressive neuroendocrine carcinoma of the lungs demanding effective therapy. In this study we investigated whether BTZ or CFZ combined with obatoclax (OBX), an antagonist for MCL-1 and a pan-BCL family inhibitor, could cause synergistic growth inhibition of SCLC cells. We showed that combined application of BTZ or CFZ with OBX caused synergistic growth inhibition of human SCLC cell lines (H82, H526, DMS79, H196, H1963, and H69) than single agent alone. Both BTZ-OBX and CFZ-OBX combinations displayed marked synergism on inducing apoptosis (~50% increase vs BTZ or CFZ alone). A comprehensive proteomics analysis revealed that BTZ preferentially induced the expression of MCL-1, an antiapoptotic protein, in SCLC cells. Thus, proteasome inhibitor-OBX combinations could specifically induce massive growth inhibition and apoptosis in SCLC cells. Subsequent proteome-wide profiling analysis of activated transcription factors suggested that BTZ- or CFZ-induced MCL-1 upregulation was transcriptionally driven by FOXM1. In nude mice bearing in SCLC H82 xenografts, both BTZ-OBX, and CFZ-OBX combinations exhibited remarkable antitumor activities against SCLC tumors evidenced by significant reduction of tumor size and the proliferation marker Ki-67 signals in tumor tissues as compared with single agent alone. Thus, proteasome inhibitor-OBX combinations are worth immediate assessments for SCLC in clinical settings., (© 2020. CPS and SIMM.)

Background: Chlamydia trachomatis (CT) is one of the most prevalent bacterial sexually transmitted infections (STIs) globally but has been inadequately detected for intervention. Introduction of point-of-care tests (POCTs) for CT is critical for filling the intervention gaps. We conducted a systematical review and meta-analysis on diagnostic performance of POCTs for CT to assist in guiding the application of these assays in CT screening and detection., Methods: We searched PubMed/Medline and Embase databases, from January 2004 to May 2021, for studies reporting the performance of POCTs for identifying CT using specimens collected from urethral, vaginal, cervical, anorectal, or pharyngeal site or of urine. Two investigators independently screened and extracted data for controlling the quality of data extraction. Any discrepancies in study selection and data extraction were resolved through consensus. We only included studies with sufficient data to estimate sensitivity and specificity, and used laboratory-based nucleic acid amplification test (NAAT) as the reference standard. The main outcomes were pooled sensitivity, specificity, and diagnostic odds ratio (DOR) and their corresponding 95% confidence intervals (CIs). Summary estimates were calculated using a random-effects model and summary receiver operator curves (SROCs) were generated using the Moses-Littenberg method. STATA 14.0 and Meta-DiSc 1.4 were used for statistical analysis. The study protocol is registered with PROSPERO, number CRD42019140544., Findings: Of 3,038 records identified, 39 studies (42,336 specimens) were included in the study, including 14 studies on evaluation of antigen detection (AD)-based and 25 on NAAT-based POCTs. The overall pooled sensitivity, specificity and DOR were 56% (95% CI 45%-67%), 99% (95% CI 98%-99%) and 86 (95% CI 46-163), respectively, for AD-based POCTs and corresponding values for NAAT-based POCTs were 94% (95% CI 91%-96%), 99% (95% CI 99%-99%) and 1,933(95% CI 1,018-3,669), respectively. The pooled sensitivity of AD-based POCTs varied across the types of specimens, indicating 46% for cervical swabs (95% CI 37%-56%; range 22.7%-71.4%), 52% for vaginal swabs (95% CI 34%-70%; range 17.1%-86.8%) and 57% for male urine (95% CI 36%-75%; range 20.0%-82.6%). For NAAT-based POCTs, the pooled sensitivity was 94% (95% CI 90%-96%) for cervical swabs, 94% (95% CI 86%-98%) for vaginal swabs, 95% (95% CI 91%-97%) for urine specimens and 93% (95% CI 87%-96%) for anorectal swabs., Interpretation: NAAT-based POCTs for CT have a significantly better performance particularly in sensitivity for diagnosing the infection with CT than the AD-based POCTs. Screening strategy with AD-based POCTs may potentially result in a substantial under-detection of the infections., Competing Interests: We declare no competing interests., (© 2021 The Authors.)

The p53-like transcription factor (TF) NDT80 plays a vital role in the regulation of pathogenic mechanisms and meiosis in certain fungi. However, the effects of NDT80 on entomopathogenic fungi are still unknown. In this paper, the NDT80 orthologue BbTFO1 was examined in Beauveria bassiana, a filamentous entomopathogenic fungus, to explore the role of an NDT80-like protein for fungal pest control potential. Disruption of BbTFO1 resulted in impaired resistance to oxidative stress (OS) in a growth assay under OS and a 50% minimum inhibitory concentration experiment. Intriguingly, the oxidation resistance changes were accompanied by transcriptional repression of the two key antioxidant enzyme genes cat2 and cat5. ΔBbTFO1 also displayed defective conidial germination, virulence and heat resistance. The specific supplementation of BbTFO1 reversed these phenotypic changes. As revealed by this work, BbTFO1 can affect the transcription of catalase genes and play vital roles in the maintenance of phenotypes associated with the biological control ability of B. bassiana., Competing Interests: The authors have declared that no competing interests exist.

Global dissemination of the Neisseria gonorrhoeae ceftriaxone-resistant FC428 clone jeopardizes the currently recommended ceftriaxone-based first-line therapies. Ceftriaxone resistance in the FC428 clone has been associated with the presence of its mosaic penA allele 60.001. Here we investigated the contribution penA allele 60.001 to ceftriaxone resistance and its impact on biological fitness. Gonococcal isolates expressing penA allele 60.001 and mosaic penA allele 10.001, which is widespread in the Asia-Pacific region and associated with reduced susceptibility to ceftriaxone and cefixime, were genetic engineered to exchange their penA alleles. Subsequent antimicrobial susceptibility analyses showed that mutants containing penA 60.001 displayed 8- to 16-fold higher ceftriaxone and cefixime minimal inhibitory concentrations (MICs) compared with otherwise isogenic mutants containing penA 10.001. Further analysis of biological fitness showed that in vitro liquid growth of single strains and in the competition was identical between the isogenic penA allele exchange mutants. However, in the presence of high concentrations of palmitic acid or lithocholic acid, the penA 60.001-containing mutants grew better than the isogenic penA 10.001-containing mutants when grown as single strains. In contrast, the penA 10.001 mutants outcompeted the penA 60.001 mutants when grown in competition at slightly lower palmitic acid or lithocholic acid concentrations. Finally, the penA 60.001 mutants were outcompeted by their penA 10.001 counterparts for in vivo colonization and survival in a mouse vaginal tract infection model. In conclusion, penA allele 60.001 is essential for ceftriaxone resistance of the FC428 clone, while its impact on biological fitness is dependent on the specific growth conditions.

Objectives: The development and emergence of antimicrobial resistance in Neisseria gonorrhoeae (NG) have become a major public-health problem worldwide. This study aimed to analyse the antimicrobial susceptibility and molecular characteristics of NG isolates in Shenzhen, China., Methods: A total of 1282 NG isolates were consecutively collected between 2010 and 2017. Patient demographic information was also collected. MICs of ceftriaxone, spectinomycin, ciprofloxacin, azithromycin and penicillin were determined by agar dilution. Isolates were genotyped using N. gonorrhoeae multi-antigen sequence typing (NG-MAST)., Results: Among the isolates, 97.4% were resistant to ciprofloxacin and 68.2% to penicillin. Moreover, 5.0% showed decreased susceptibility to ceftriaxone (CRO D ) and 17.3% were resistant to azithromycin (AZM-R); 1.3% were simultaneously CRO D and AZM-R. All isolates were susceptible to spectinomycin. Increasing ceftriaxone MICs were found from 2010 to 2017. A total of 427 sequence types (STs) and 68 genogroups were identified from 724 isolates. ST5061, ST3741 and ST1766 were observed across the study years. ST14638 (n = 3) was predominant among 32 CRO D isolates. Prevalent STs were ST5061 (n = 6), ST1866 (n = 5) and ST11133 (n = 5) among 96 AZM-R isolates., Conclusions: A high prevalence of isolates resistant to ciprofloxacin and penicillin was found in this study. Azithromycin, one antimicrobial of dual antimicrobial therapy recommended by the WHO, showed a high prevalence of resistance. The other, ceftriaxone, can be used continuously in this region owing to lower resistance levels. However, the emergence of CRO D and decreasing susceptibility to ceftriaxone indicate that continuous antimicrobial resistance surveillance is essential., (Copyright © 2020. Published by Elsevier Ltd.)

Objectives: China has a high burden of gonorrhea, but an imbalanced male-to-female (M/F) ratio of reported cases. Therefore, the prevalence of gonorrhea in China may be underestimated due to inadequate testing of potentially infected females. The objective of this study is to investigate the cause of this imbalanced M/F ratio and develop strategies to enhance gonorrhea surveillance, particularly among females., Methods: The national center for STD control (NCSTDC) of China CDC collected data in Zhongshan city over the year 2018 from the National Notifiable Disease Report System (NNDRS) and the Hospital and Laboratory Information Systems (HIS and LIS) that obtains information from 24 hospitals., Results: Analysis of 1,542 reported cases of gonorrhea and the case distribution among different hospitals showed that most of the female cases (80.31%) were reported by gynecological clinics. The M/F ratio of reported cases varied between different hospitals and was dependent on the intensity of testing of females by their gynecological clinics., Conclusions: This study showed a significant correlation between M/F ratios and the relative contribution of female gonorrhea testing, especially in gynecology clinics. Enhancing gonorrhea testing among females should be advocated to improve surveillance in China., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Inappropriate use of antibiotics to treat gonorrhoea can lead to antibiotic resistance. Education programmes may be helpful for improving physician prescribing behaviours in accordance with treatment guidelines. As traditional education based on printed materials may have limited effect on guideline-based treatment, innovative education strategies are needed. The current trial aims to assess the effectiveness of a novel education intervention to increase guideline-based treatment of gonorrhoea in China., Methods and Analysis: We will conduct a two-arm cluster randomised control trial at 144 hospitals (clusters) in eight Chinese provinces. The intervention will include an online training video developed on the WenJuanXing platform that covers workflows and requirements for managing a patient with uncomplicated gonorrhoea. Outpatient physicians in dermatology (dermatovenerology), urology, andrology and gynaecology will be given access to the video via a quick response code. In hospitals allocated to the control arm, physicians will continue to participate in their standard of care training programme. The primary outcome is the proportion of gonorrhoea antibiotic prescriptions adherent to Chinese national guidelines at the cluster level. In addition, to understand the reasons of physician's non-adherence to the intervention by conducting a questionnaire survey will be considered as the secondary outcome of the study., Ethics and Dissemination: Ethical approval was obtained from the Medical Ethics Committee of the Chinese Academy of Medical Sciences Institute of Dermatology (2020-LS-004). All physicians will provide an informed consent prior to participating in the study. Findings of the trial will be disseminated through conferences and peer-reviewed journals, and will be used to develop training programmes for physicians., Trial Registration Number: ChiCTR2000029591., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Current point-of-care tests (POCT) for syphilis, based on the detection of Treponema pallidum (TP) total antibodies, have limited capacity in distinguishing between active and past/treated syphilis. We report the development and early evaluation of a new prototype POCT based on the detection of TP-IgA antibodies, a novel biomarker for active syphilis., Methods: The TP-IgA POCT (index test) was developed in response to the World Health Organisation (WHO) target product profile (TPP) for a POCT for confirmatory syphilis testing. Two sub-studies were conducted consecutively using 458 pre-characterised stored plasma samples in China (sub-study one, addressing the criteria for the WHO TPP), and 503 venous blood samples collected from pregnant/postpartum women in South Africa (sub-study two, addressing potential clinical utility). Performance of the index test was assessed against standard laboratory-based serology using a combination of treponemal (TPHA) and non-treponemal (rapid plasma reagin [RPR]) tests., Findings: In sub-study one, the index test demonstrated 96·1% (95%CI=91·7%-98·5%) sensitivity and 84·7% (95%CI=80·15-88·6%) specificity for identification of active syphilis (TPHA positive, RPR positive). It correctly identified 71% (107/150) samples of past-treated syphilis (TPHA positive, RPR negative). In sub-study two, the index test achieved 100% (95%CI=59%-100%) sensitivity for active syphilis and correctly identified all nine women with past syphilis., Interpretation: The TP-IgA POCT has met the WHO TPP for a POCT for diagnosis of active syphilis and demonstrated its potential utility in a clinical setting. Future studies are warranted to evaluate field performance of the final manufactured test., Funding: Saving Lives at Birth: Grand Challenge for Development, Thrasher Research Fund, and the Victorian Government Operational Infrastructure Scheme., Competing Interests: MLG, HV, DAA and SZ developed the syphilis IgA test at the Burnet Institute in Australia and DAA is also employed at Nanjing BioPoint Diagnostics, a spinoff company of the Burnet Institute, which will manufacture the final syphilis IgA POCT device. MLG, HV, DAA, SZ, MDP, YM and SL report grants from Saving Lives at Birth - A Grand Challenge for Development managed by USAID (award number AID-OAA-F-13-00,011) and from the Thrasher Research Fund via a project grant (award number: 12617). AW and KT report funding from the Burnet Institute, Australia, during the conduct of the study. MDP, YM, SL work at the Burnet Institute but were not involved in the development of the test. All other authors report no conflict., (© 2020 The Authors.)

Background: Chlamydia trachomatis (CT) infection is one of the most pervasive sexually transmitted infections and has high prevalence in urogenital and extra-urogenital sites among men who have sex with men (MSM). This study investigated anatomical site-specific prevalence and genotypes of CT among MSM recruited from three geographic areas in China., Methods: We collected urine specimens and anorectal, pharyngeal swab specimens from 379 MSM. CT infection was identified using polymerase chain reaction and CT genotyping was determined by sequences of the ompA gene., Results: The results indicated that the overall prevalence of CT infection was 18.2% (95% confidence intervals [CIs], 13.9-22.5%) and significantly different between the cities (p = 0.048). The infection was most common at the anorectal site (15.6, 95%CIs 11.6-19.5%) followed by urethral (3.2, 95%CIs 1.4-5.0%) and oropharyngeal sites (1.6, 95%CIs 0.3-2.9%). Genotypes D and G were the most common CT strains in this population but genotype D was significantly predominated in Nanjing while genotype G was in Wuhan. No genotype related to lymphogranuloma venereum was found. CT infection was significantly related to the infection of Neisseria gonorrhoeae (adjusted odds ratio [aOR] 14.27, 95%CIs 6.02-33.83, p < 0.001) and age. Men older than 40 years old were less likely to have a CT infection as compared to men under 30 years old (aOR 0.37, 95% CIs 0.15-0.93, p = 0.03)., Conclusion: The high CT infection prevalence, particularly in the anorectal site, among MSM suggests the necessity to development an integrated CT screening and treatment program specifically focusing on this high-risk population. Surveillance of CT infections should be improved by including both infection and genotype based surveys into the current surveillance programs in China.

In 2016, we identified a ceftriaxone-resistant Neisseria gonorrhoeae isolate in China. The strain genotype was identical to the resistant clone FC428 that originated in Japan. Enhanced international collaborative surveillance programs are crucial to track the transmission of the ceftriaxone-resistant clones.

Background: Tracking the spread of the Neisseria gonorrhoeae strains with decreased susceptibility or resistance to cephalosporins is a major priority for global surveillance programmes. Whole-genome sequencing (WGS) has been widely used by increasing countries in North America, Europe, and Pacific to determine the decreased susceptible or resistance determinants of Neisseria gonorrhoeae , track the spread of these determinants throughout the gonococcal population at national or regional level. However, no studies to date have examined the genomic epidemiology of gonorrhea in Asia where the antimicrobial resistant strains of Neisseria gonorrhoeae appears to have emerged before disseminating the strains globally., Methods: We obtained clinical isolates and data from the China Gonococcal Resistance Surveillance Programme (China-GRSP) from 2012 to 2013. We sequenced the genomes of 435 clinical isolates of Neisseria gonorrhoeae , including 112 (25.6%) isolates with decreased susceptibility to ceftriaxone (Cfx-DS). We assessed the association between antimicrobial resistance genotype and phenotype. We also compared our data with the whole genome data of the isolates from the USA and the UK in the GenBank., Findings: The most prevalent MLST STs in our gonococcal population were MLST ST7827 (n = 74), followed by ST7365 (n = 58), ST1600 (n = 38), ST7367 (n = 35), and ST7363 (n = 29). MLST ST1901 which was reported as the predominant ST in the US was not found in our population. A total of 2512 strains, including additional 2077 published NG strains, were further included for phylogenetic analysis. It generated two distinct lineages - lineage 1 and lineage 2. Analysis of MLST ST1901 in the database indicate that most of MLST ST1901 isolates in the lineage2.6 were Cfx-DS isolates while all isolates in the lineage 2.1 were sensitive to ceftriaxone (77/110 vs. 0/13; p < 0.001). ST1901/lineage 2.6 is a ceftriaxone resistant clone which cannot distinguished by MLST genotyping. In the isolates from our study, the MICs of ceftriaxone for ST7363/lineage 2.6 isolates ranged from 0.008-0.125 mg/L (mean ± SD; 0.054 ± 0.043 mg/L) while those for ST7363/lineage 2.8 isolates ranged from 0.032-0.250 mg/L (0.134 ± 0.085 mg/L). All ST7363/lineage 2.8 isolates contained penA mosaic alleles., Interpretation: To our knowledge, current study is the first WGS-based analysis of gonococcal population at national level in Asia. China harbors the different predominant clones associated with decreased susceptibility to ceftriaxone from those clones circulated in other regions. The findings from the study can be not only used as baseline data for future studies in China but also contributable to our understanding on spread of N . gonorrhoeae and its resistant strains at regional and global levels., Funding: The Chinese Academy Medical Sciences (CAMS) Initiative for Innovative Medicine.

Background: Provider adherence to the national treatment guidelines for gonorrhea is critical to assuring effective treatment. It is also an important means of limiting antibiotic overuse, which can lead to development of resistant bacteria. The Chinese treatment guidelines recommend the monotherapy with ceftriaxone or spectinomycin in accordance with the World Health Organization guidelines for treatment of uncomplicated gonorrhea. We evaluated adherence to the guidelines among treatment providers in China., Methods: The study was a nationwide cross-sectional study. In each of the 6 geographic regions in China, at least 1 province was selected. In each selected province, cities with elevated incidence of reported gonorrhea were purposively selected. Using a questionnaire, 2121 physicians recruited from 512 different categories and levels of health sectors from July to September 2017 were investigated., Results: Of the participants, more than 99% diagnosed gonorrhea using one of the laboratory tests including Gram stain, culture, nucleic acid amplification test, or other tests. Culture was the predominant assay of the choice for the diagnosis. Of the 1890 physicians who provided information on prescription behaviors, 62.2% were not adherent to the regimens for treatment of uncomplicated gonorrhea recommended by the National Sexually Transmitted Disease (STD) Treatment Guidelines (National STD Guidelines). Physicians working in the areas located in Northern China (adjusted odds ratio [AOR], 3.06; 95% confidence intervals [CIs], 1.77-5.31), in general hospitals or departments of urology (AOR, 1.54; 95% CIs, 1.08-2.19), diagnosing more cases in the past 6 months (AOR, 1.82; 95% CIs, 1.25-2.67), or unfamiliar with the treatment regimens in the National STD Guidelines (AOR, 3.48; 95% CIs, 2.76-4.37) were significantly more likely to be nonadherent to the National STD Guidelines., Conclusions: It can be concluded from our study that nonadherence to the national guidelines and empirical treatment with high doses of ceftriaxone occurred frequently in China. Further studies on the impacts of the empirical treatment on antimicrobial resistance of gonorrhea are needed.

Cephalosporin-resistant Neisseria gonorrhoeae is a major public health concern. N. gonorrhoeae of multiantigen sequence type G1407 and multilocus sequence type 1901 is an internationally spreading cephalosporin-resistant clone. We detected 4 cases of infection with this clone in China and analyzed resistance determinants by using N. gonorrhoeae sequence typing for antimicrobial resistance.

Background: Gonorrhea remains one of the most common sexually transmitted diseases worldwide. Successful treatment has been hampered by emerging resistance to each of the antibiotics recommended as first-line therapies. We retrospectively analyzed the susceptibility of gonorrhea to azithromycin and ceftriaxone using data from the China Gonococcal Resistance Surveillance Programme (China-GRSP) in order to provide evidence for updating the treatment recommendations in China., Methods and Findings: In this study, we included 3,849 isolates collected from patients with a confirmed positive Neisseria gonorrhoeae (N. gonorrhoeae) culture at clinic visits during the period of 1 January 2013 through 31 December 2016 in 7 provinces. Antimicrobial susceptibility testing of gonorrhea isolates using agar dilution was conducted to determine minimum inhibitory concentration (MIC). Resistance to azithromycin (RTA) was defined as MIC ≥ 1.0 mg/l, and decreased susceptibility to ceftriaxone (DSC) was defined as MIC ≥ 0.125 mg/l. The prevalence of isolates with RTA was 18.6% (710/3,827; 95% CI 17.4%-19.8%). The percentage of patients with DSC fluctuated between 9.7% and 12.2% over this period. The overall prevalence of isolates with both RTA and DSC was 2.3% (87/3,827; 95% CI 1.9%-2.8%) and it increased from 1.9% in 2013 to 3.3% in 2016 (chi-squared test for trend, P = 0.03). Study limitations include the retrospective study design and potential biases in the sample, which may overrepresent men with symptomatic infection, coastal residents, and people reporting as heterosexual., Conclusions: To our knowledge, this is the first national study on susceptibility of N. gonorrhoeae to azithromycin and ceftriaxone in China. Our findings indicate high rates of RTA and DSC from 2013 to 2016. Although dual therapy with azithromycin and ceftriaxone has been recommended by WHO and many countries to treat gonorrhea, reevaluation of this therapy is needed prior to its introduction in China.

The onion maggot, Delia antiqua , is a worldwide subterranean pest and can enter diapause during the summer and winter seasons. The molecular regulation of the ontogenesis transition remains largely unknown. Here we used high-throughput RNA sequencing to identify candidate genes and processes linked to summer diapause (SD) induction by comparing the transcriptome differences between the most sensitive larval developmental stage of SD and nondiapause (ND). Nine pairwise comparisons were performed, and significantly differentially regulated transcripts were identified. Several functional terms related to lipid, carbohydrate, and energy metabolism, environmental adaption, immune response, and aging were enriched during the most sensitive SD induction period. A subset of genes, including circadian clock genes, were expressed differentially under diapause induction conditions, and there was much more variation in the most sensitive period of ND- than SD-destined larvae. These expression variations probably resulted in a deep restructuring of metabolic pathways. Potential regulatory elements of SD induction including genes related to lipid, carbohydrate, energy metabolism, and environmental adaption. Collectively, our results suggest the circadian clock is one of the key drivers for integrating environmental signals into the SD induction. Our transcriptome analysis provides insight into the fundamental role of the circadian clock in SD induction in this important model insect species, and contributes to the in-depth elucidation of the molecular regulation mechanism of insect diapause induction., (Copyright © 2018 Ren et al.)

Background: Parenteral penicillin is the first-line regimen for treating syphilis, but unsuitable for some patients due to penicillin allergy and lacking health resources. Unfortunately, the efficacy of penicillin alternatives remains poorly understood. This study aimed to assess the efficacy of ceftriaxone and doxycycline/tetracycline in treating early syphilis relative to that of penicillin, and thereby to determine which antibiotic is a better replacement for penicillin., Method: By searching literature from PubMed, Cochrane Central Register of Controlled Trials, Embase, the Web of Science, and ClinicalTrials.gov and systematically screening relevant studies, eligible randomized controlled trials (RCTs) and observational studies on treatments with penicillin, doxycycline/tetracycline, and ceftriaxone for early syphilis were identified and combined in this systematic review. Estimated risk ratios (RRs) and 95% confidence intervals (CIs) were utilized to compare their serological response and treatment failure rates. At 12-month follow up, serological response rates were compared by a direct meta-analysis and network meta-analysis (NMA), while treatment failure rates were compared with a direct meta-analysis., Result: Three RCTs and seven cohort studies were included in this research. The results of NMA demonstrated that no significant differences existed in serological response rate at 12-month follow-up between any two of the three treatments (doxycycline/tetracycline vs. penicillin RR = 1.01, 95%CI 0.89-1.14; ceftriaxone vs. penicillin RR = 1.00, 95%CI 0.89-1.13; ceftriaxone vs. doxycycline/tetracycline RR = 0.99, 95%CI 0.96-1.03), which was consistent with the outcomes of the direct meta-analysis. In addition, the direct meta-analysis indicated that, at 12-month follow-up, penicillin and ceftriaxone treatment groups had similar treatment failure rates (RR = 0.92, 95%CI 0.12-6.93), while treatment failure rate was significantly lower among penicillin recipients than among doxycycline/tetracycline recipients (RR = 0.58, 95%CI 0.38-0.89)., Conclusion: Ceftriaxone is as effective as penicillin in treating early syphilis with regard to serological response and treatment failure rate. Compared with doxycycline/tetracycline, ceftriaxone appears to be a better choice as the substitution of penicillin.

Transition metal oxides with a perovskite crystal structure exhibit a variety of physical properties associated with the lattice. Among these materials, strontium ruthenate (SrRuO 3 ) displays unusually strong coupling of charge, spin and lattice degrees of freedom that can give rise to the photostriction, that is, changes in the dimensions of material due to the absorption of light. In this study, we observe a photon-induced strain as high as 1.12% in single domain SrRuO 3 , which we attribute to a nonequilibrium of phonons that are a result of the strong interaction between the crystalline lattice and electrons excited by light. In addition, these light-induced changes in the SrRuO 3 lattice affect its electrical resistance. The observation of both photostriction and photoresistance in SrRuO 3 suggests the possibility of utilizing the mechanical and optical functionalities of the material for next-generation optoelectronics, such as remote switches, light-controlled elastic micromotors, microactuators and other optomechanical systems.

Objective: To determine whether intramural administration of rapamycin (RPM)-loaded polylactic-polyglycolic acid (PLGA) nanoparticles (NPs) can reduce intimal thickening and affect the mRNA expressions of matrix metalloproteinase (MMP)-2, tissue inhibitor of metalloproteinase (TIMP)-2 and p27(kipl) in a coronary injury-stenosis model of minipigs., Methods: Twenty eight minipigs were randomly separated into four groups: saline group (n=7), blank PLGA NPs group (5.0 mg/ml)(n=7), RPM group (1.0 mg/ml)(n=7), and RPM-PLGA NPs(5.0 mg/ml)group (n=7), respectively. Different treatments were intracoronary locally delivered via a Dispatch™ catheter for 10 minutes. Serial angiography was performed pre-and post-modeling 30 days and the percent stenosis degree was assessed. Hematoxylin-Eosin (HE) staining, Weigert's resorcin fuchsin staining and picric acid-sirius red staining were used for morphometric analysis. Immunohistochemistry was performed to assess the levels of proliferating cell nuclear antigen (PCNA), MMP-2, and TIMP-2 at early and late time points, respectively. The expression of p27(kip1) mRNA was detected by in situ hybridization staining., Results: Data from 21 minipigs had been collected at the end of the experiment with 6, 4, 5, and 6 from the former mentioned 4 groups, respectively. For the instant injury index, there was no significant difference among the four groups. The percent stenosis degree of RPM-PLGA NPs group was significantly lower than that of the other three groups respectively (all P< 0.05). The neointima area, net external elastic lamina area to external elastic laminal area ratio, and proliferative index of RPM-PLGA NPs group were significantly less than those of the other three groups, with all the P values less than 0.05. The mean value of integral optical density of p27(kip1)mRNA expression of RPM-PLGA group was 0.35 ± 0.06, higher than that of blank PLGA NPs group (0.12 ± 0.05, P< 0.01), saline group (0.16 ± 0.03, P< 0.05), and RPM group (0.15 ± 0.03, P< 0.05), respectively. The MMP-2/TIMP-2 ratio and the positive expression index of PCNA in RPM-PLGA group were lower than that of the other groups (P< 0.05)., Conclusions: Locally delivered rapamycin-loaded PLGA NPs significantly reduces MMP-2/TIMP-2 ratio and PCNA expression, increases p27(kip1) mRNA expression and significantly relieves percent stenosis degree and shows excellent acute procedural results in the minipig interventional coronary artery oversized balloon injury model. The results from minipig model further support that this approach could be a potential clinical procedure for vascular proliferative disease.

The equilibrium structures, vibrational frequencies, and bond characteristics of NpO2(m+) ions and NpO2(H2O)n(m+) (m = 1-2, n = 1-6) complexes have been studied by carrying out ab initio calculations in the gas phase and aqueous solution. The geometries have been obtained at the B3LYP level with the use of the polarized continuum model (PCM). The computed structural parameters that are in reasonably good agreement with the available data show that the solvation effect leads to a red shift of the IR spectra and the weakness of interaction strengths in neptunyl ions. By comparing the structural properties and the density of states (DOS) of these aqua complexes in the gas phase and aqueous solution, it is found that the solvation effect can be simulated approximately with the calculations of these aqua complexes in the gas phase. In addition, the DOS of these aqua complexes together with the binding energies between the neptunyl ion and water molecule reveal that the penta-aqua complex is preferred for neptunyl ions in aqueous solution.

Background: In China, the HIV/AIDS epidemic is expanding among men who have sex with men (MSM). As independent risk factors of HIV infection, the epidemics of Chlamydia (CT) and Gonorrhea (NG) in MSM were not well studied, particular for the risk factors of these infectious. The objectives of current reported study were to understand the dynamics of HIV and other sexual transmitted infections (STIs) among MSM in Jiangsu, China, and to measure factors that correlated with STIs., Methods: In order to gain more participants, a multisite cross-sectional study design was used in our study, by using convenience-sampling to recruit MSM in two Changzhou and Yangzhou, Jiangsu, China, between the July and October of 2009., Results: In this comprehensive survey involving MSM in two cities of Jiangsu province of China, the prevalence of STIs of CT (6.54%), NG (3.63%), syphilis (20.34%) and HIV (11.62%) were measured. Overall, the STIs prevalence (CT, NG or syphilis) for the participants in our study was 26.39%, meanwhile, 3.4% (14 out of the 413) participants had at least two kinds of STIs. Meeting casual partners at parks, public restrooms or other public areas, having had anal sex with men in the past six months, having had STI symptoms in the past year were positively correlated with STIs positive, with adjusted ORs of 4.61(95%CI 1.03-20.75), 1.91(95%CI 1.14-3.21) and 2.36(95%CI 1.07,5.24)., Conclusion: Our study findings reiterate the fact that Chinese MSM are highly susceptible to acquiring syphilis, CT, NG and HIV, and there is an urgent need for intervention targeted towards this population. Behavioral measures should constitute an important part of the targeted intervention. Furthermore, the already implemented preventive and diagnostic services for HIV should be expanded to include syphilis CT and NG, too.

Introduction: In China, the prevalence and incidence of HIV among men who have sex with men (MSM) in large-sized cities have drawn much attention. In contrast, there has been a paucity of research focussing on the sexual health of MSM of medium-sized cities. This study fills this important gap in the knowledge by investigating the sexual health of MSM in a medium-sized city (Yangzhou) and a large-sized city (Guangzhou)., Methods: A baseline survey and a prospective cohort study were conducted among MSM in Yangzhou and Guangzhou from July 2009 to September 2010. A total of 622 MSM (317 from Yangzhou and 305 from Guangzhou) were screened for eligibility. Prevalence and incidence of HIV infection, as well as its risk factors, were investigated., Results: Baseline HIV prevalence was 14.5%, and overall HIV incidence density was 6.78 per 100 person-years (PY) among Yangzhou MSM. Risk factors for HIV prevalence that were significant in multivariate models were older age, married status, unprotected sex with female partners, sexually transmitted disease (STD)-associated symptoms and syphilis positivity. Risk factors for HIV incidence that were significant in multivariate models were STD-associated symptom and syphilis positivity. Compared to Yangzhou MSM, Guangzhou MSM had a lower HIV prevalence (6.2%; p<0.05) and lower overall HIV incidence density (5.77 per 100 PY). Risk factors for HIV prevalence that were significant in multivariate models were married status, unprotected anal sex with men and syphilis positivity. The single risk factor for HIV incidence that was significant in multivariate models was unprotected anal sex with men., Conclusions: This study showed a high prevalence and incidence of HIV among Yangzhou MSM, which suggest a more serious HIV epidemic than that in large-sized cities. Further investigation targeting MSM in medium-sized cites is urgently needed to prevent the spread of the HIV epidemic in China.

Background: An increasing incidence of anal cancer among men, especially men who have sex with men (MSM) suggests a need to better understand anal human papillomavirus (HPV) infection among this group., Methods: A cross-sectional study was conducted among MSM in Shenzhen, China. Blood was collected for HIV serological testing and syphilis serological screening, and anal swabs were collected for HPV genotyping. Difference of HPV prevalence between HIV seropositive and HIV seronegative MSM was assessed by chi-square test. Factors associated with anal canal HPV infection were assessed by univariate and multivariate logistic regression., Results: A total of 408 MSM were recruited. HIV and HPV prevalence were 6.9% and 36.4%, respectively. HPV was detected in the anal canal in 71.4% of the HIV-positive MSM and in 33.8% of the HIV-negative MSM (P<0.001). Oncogenic types were seen more often in anal specimens of HIV-positive MSM than in specimens of HIV-negative MSM (P = 0.001). The HPV genotypes detected most frequently were HPV06 (8.2%), HPV16 (7.2%), HPV11 (6.4%), HPV18 (4.7%), HPV58 (4.7%), and HPV52 (4.2%)., Conclusions: In this study, HIV positive MSM had a higher burden of HPV infection, especially oncogenic HPV infection. HPV types 52 and 58 were as popular as those types designed for the currently available vaccine (HPV6, 11, 16, 18).

Objectives: To estimate the prevalence of HIV and syphilis, incidence of syphilis and to identify the correlates of syphilis infection among heterosexual male attendees of sexually transmitted infection (STI) clinics (MSC)., Methods: A cohort study of one-year duration was conducted in Yangzhou and Changzhou cities in Jiangsu province of China. The baseline survey commenced in June 2009, recruited 1225 consenting adult MSCs (609 in Yangzhou and 617 in Changzhou) through STI-clinic based convenience sampling., Results: Baseline HIV and syphilis prevalence were 0.49% and 17.29% respectively. Syphilis incidence rate was 7.22 per 100 person-years (6.53 in Yangzhou and 7.76 in Changzhou) during the 6-month follow-up with retention fractions of 27.38% and 35.15% for Yangzhou and Changzhou respectively. Majority of the participants were middle-aged, high school educated, married, living with partners and non-migrants. Very few subjects reported recent and consistent condom-use with regular partners. Although considerable number of MSCs reported recent sexual exposure with female sex workers (FSW) and non-FSW casual partners, the proportion of reported condom use was very low during those exposures. In multivariate analyses higher age, having recent sex with FSWs and being HIV-positive were associated with higher syphilis sero-positivity while higher education was protective. In bivariate analyses, being married, divorced/widowed, official residency of the study cities and non-use of condom with regular partners predicted higher risk., Conclusions: Considering the potential bridging role of MSCs between high and low-risk populations, effective intervention strategies among them targeting the correlates of syphilis infection are urgently called for in Jiangsu province of China.

Small GTPases, RacA and Cdc42, act as molecular switches in fungi, regulating cell signaling, cytoskeletal organization, polar growth and reactive oxygen species (ROS) generation, the latter by influencing the activity of the NADPH oxidase complex. In this study, the racA and cdc42 genes from Nomuraea rileyi were cloned and shown to encode 218 and 184 amino acid proteins, respectively. To determine the functions of racA and cdc42, gene-silencing mutants (racARM, cdc42RM and racA&cdc42RM, respectively) were generated using RNA silencing technology. In racARM and cdc42RM, the conidial and microsclerotium (MS) yields, ROS production and virulence were reduced, the hyphal extension rate was decreased and the dimorphic switch was delayed. On the other hand, the double-silencing mutants showed growth retardation and virtually no conidia, MS or ROS production. The transcription levels of the noxA and noxR genes that regulate ROS generation were reduced in the three RNAi-silenced strains. Interestingly, when compared with the controls, racARM exhibited thicker hyphae and bigger conidia; moreover, the MS produced by racARM were bigger than those of the control and smaller than those of cdc42RM. Thus RacA and Cdc42 appear to share some essential functions in N. rileyi, including hyphal growth, conidiation, MS formation, ROS generation and virulence. Yet RacA appears to play a more pivotal role in the polar growth of N. rileyi., (Copyright © 2014 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)

Background: To evaluate the performance of the Abbott RealTime CT/NG assay for detection of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) among female sex workers (FSWs) in China., Methods: Cervical swabs from 997 participants were blindly detected by the Abbott RealTime CT/NG assay on the automated m2000 molecular platform and Roche Cobas Amplicor CT/NG assay. Discrepant analysis were confirmed by the Qiagen care CT PCR assay. The sample was defined as candidate nvCT-positive if it was CT positive in the Abbott m2000 assay, but CT negative in the other two assays., Results: 25 specimens that were discordant for CT and 26 specimens that were discordant for NG between the two assays were resolved by Qiagen care CT & NG PCR assays. The sensitivity and specificity, respectively, for Abbott m2000 assay were 92.59% and 100% for CT and 95.45% and 99.90% for NG. The positive predictive value (PPV) and negative predictive value (NPV) of Abbott m2000 assay were100% and 98.52% for CT and 95.5% and 99.90% for NG, respectively. No candidate new-variant CT(nvCT)specimens were identified., Conclusion: Abbott RealTime CT/NG assay were more specify for CT and NG detection, however, its sensitivity for CT and NG were a little bit lower than Roche Cobas Amplicor CT/NG assay. Abbott RealTime CT/NG assay had higher PPV for NG detection than Roche Cobas Amplicor CT/NG assay; it would be more suitable for screening for population with low-prevalence NG. There is currently no evidence that nvCT is present in FSWs in China.

Background: Although Mycoplasma genitalium (MG) is a common sexually transmitted infection (STI), very little information regarding the prevalence of MG among MSM (men who have sex with men) is available in China. The objective of this study was to determine the prevalence of MG among MSM in the city of Shenzhen, Guangdong Province, China, and to identify the potential risk factors associated with MG infection in this population., Methods: Between January and May 2010, a total of 409 MSM were recruited in Shenzhen, Guangdong Province, China. An anonymous questionnaire was used to collect information regarding their sociological and sexual behaviors. In addition, their first-void urine (FVU) samples and rectal swabs were collected for PCR-based MG testing., Results: Among the 406 FVU and 405 rectal swab samples were collected from 409 MSM, the overall MG prevalence was 8.1% (33/406, 95% CI 5.7%-10.6%), with a FVU positivity of 3.4% (95% CI 1.7%-5.4%) and a rectal positivity of 5.4% (95% CI 3.5%-7.7%). Using both univariate and multivariable logistic regression analyses, urethral MG infection was significantly associated with having more heterosexual behaviors (AOR 7.16, 95% CI 1.89-27.13), and with having unprotected anal intercourse in the past six months (AOR 4.80, 95% CI 1.40-16.47). Rectal MG infection was significantly associated with HIV infection based on univariate logistic regression analysis (OR = 4.49, 95% CI 1.18-17.12)., Conclusions: In this study, we investigated the prevalence of MG infection in the population of interest, as determined from both urethral and rectal specimen. We showed that MG was more prevalent in MSM who had bisexual behaviors compared to those who engaged only in homosexual behaviors. Further work is needed to establish the mode of MG transmission and to identify its role in HIV transmission. Meanwhile, more attention should be paid to MG infection among MSMs, and especially bisexual MSMs, which might have critical implications for effective HIV/STD control in China.