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Jinquan Liu,1 Ruihua Zhang,1 Tingting Lian,2 Zuoxi Chen,1 Rui-Li Zhang,3 Qianqiu Wang1 1Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, National Center for STD Control, China Centers for Disease Control and Prevention, Nanjing, 210042, People’s Republic of China; 2Department of Dermatology, Zhongshan Hospital, Fudan University, Shanghai, 200032, People’s Republic of China; 3Department of Dermatology, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, 210003, People’s Republic of ChinaCorrespondence: Rui-Li Zhang; Qianqiu Wang, Email reallyvictor@126.com; wangqianqiunj@126.comPurpose: Syphilis is a sexually transmitted bacterial infection caused by Treponema pallidum (T. pallidum), which can lead to chronic morbidity and adverse complications. In clinical practice, serofast status (SF) patients present with clinical symptoms that are very similar to those of healthy individuals or syphilis-cured patients, and often require prolonged follow-up for diagnosis. Currently, there is increasing interest in the potential of plasma exosome-derived miRNA as a biomarker for the detection of infectious diseases. In this study, we aimed to explore the diagnostic potential of miRNA in SF and its possible biological implications.Patients and Methods: Exosome-derived miRNAs were isolated from peripheral plasma samples obtained from 20 patients with secondary syphilis (SS), SF, serologically cured syphilis (SC), and healthy controls (HC), and differentially expressed miRNAs (DEmiRNAs) were identified by microarray analysis. Prediction of potential target genes, functional annotation, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were then performed. The expression of selected miRNAs was confirmed in 37 patients by quantitative reverse transcription polymerase chain reaction (RT-qPCR). A receiver operating characteristic (ROC) analysis was performed to evaluate the diagnostic performance of these miRNAs in differentiating syphilis from HC or SC.Results: The expression profile of plasma exosome-derived miRNA was discovered in individuals with SF through microarray analysis. The targeted genes of DEmiRNAs were found to be involved in diverse biological processes according to GO and KEGG analysis, such as regulation of transcription, mitochondria, Golgi, immune system, apoptosis, Ras signaling pathway, etc. Using RT-qPCR validation, miR-1273g-3p, miR-4485-5p, miR-197-3p, and miR-1908-3p showed significant upregulation in patients with SF. These miRNAs exhibited a superior diagnostic ability, either individually or combined, to distinguish SF from SC or HC.Conclusion: The DEmiRNAs in plasma exosomes may play a role in the pathogenesis of SF and have the potential to become a noble and effective diagnostic method.Keywords: serofast status, syphilis, microRNA, exosome, biomarker

Background Syphilis is a bacterial STI caused by Treponema pallidum that results in substantial morbidity and mortality. Currently, it has been suggested that exosomes (Exo) may play a possible role as novel biomarkers for the detection of infectious diseases. Here, we investigated the exosomal miRNA derived from plasma in syphilis, aimed to help in the diagnosis and prognosis of serofast syphilis. Methods A discovery cohort was used to investigate exosomal miRNAs that vary across the different subjects of participants. Exosomal miRNAs were isolated from peripheral plasma obtained at secondary syphilis(SS,n=5), serofast(SF,n=6),healthy control(HC,n=5) and serologically cured syphilis patients(SC,n=4), and microarray analysis was performed. A validation cohort was used to confirm the selected differential expression of exosomal miRNAs by real-time fluorescence quantitative PCR (RT-qPCR). ROC analysis was used to evaluate the differentiation power of these miRNAs in syphilis diagnosis. Results The microarray result revealed a specific plasma exosomal miRNA expression profile in serofast syphilis. 44 miRNAs showed significant differences between serofast and secondary syphilis, and 12 miRNAs were differentially expressed between serofast and serologically cured syphilis patients. MiR-1273g-3p, miR-4485-5p, miR-197-3p, miR- 1908-3p were significantly upregulated in syphilis patients in a stage-specific manner. These miRNAs singly or jointly displayed an improved diagnostic capability to differentiate serological cure patients or healthy people from serofast syphilis. Conclusions In practical work, differently-expressed exosomal miRNAs may be of great clinical significant utility in the diagnosis and prognosis of serofast syphilis. According to the data, miR-197-3p, miR- 1908-3p, miR-1273g-3p, miR-4485-5p within exosomes might singly or jointly be potential diagnostic biomarkers at serofast syphilis.

BACKGROUND The tp0548 gene, hypothesized to encode for an outer-membrane protein, was originally used in the enhanced Centers for Disease Control and Prevention typing for molecular typing of Treponema pallidum. It plays an important role in the molecular epidemiology of Treponema because it is not only an important locus of multiple typing approaches but also suitable for strain typing of multiple Treponema subspecies. METHODS A 27-year-old Chinese man attended the Institute of Dermatology, Chinese Academy of Medical Sciences Sexually Transmitted Disease Clinic in Nanjing, China, because of a genital ulcer and inguinal lymphadenopathy for 1 week. Workup consisted of microbiological and hematological investigations, and sequences analysis. The aims of this study were to describe a novel tp0548 sequence type "Qn" of this syphilis strain and to review all previously reported novel tp0548 genotypes. RESULTS We identified a novel tp0548 gene type in a genital ulcer in a patient with primary syphilis in Nanjing, China. Using sequence alignment, we further found that this novel sequence was closely similar to "Q." Following the nomenclature used in the enhanced Centers for Disease Control and Prevention typing methodology, the letters "Qn" was assigned to the new sequence type. CONCLUSION The novel tp0548 sequence type of T. pallidum not only expands the database up to 27 different sequence types but also indicates the substantial genetic diversity of the tp0548 gene sequence.

The correlation between polymorphisms at the tumor necrosis factor (TNF) gene and generalized pustular psoriasis (GPP) has rarely been reported. The goal of this study is to investigate whether TNF polymorphisms (-238 A/G, -308 A/G, -857C/T) are associated with susceptibility to GPP in a Han population from Eastern China and to perform subgroup analysis to explore the influence of age onset. Polymorphisms were assessed by polymerase chain reaction amplification and resequencing in 91 GPP patients and 102 healthy controls. The frequencies of the TNF -238A allele and GA+AA genotypes were significantly higher in GPP patients than in those of healthy controls. The subgroup analysis revealed that these significant associations were still present between -238A variants and pediatric-onset GPP patients who developed GPP at less than 18 years old (PGPP), but not for patients with adult-onset GPP who developed GPP at 18 years old or more. There were no significant differences in genotype or allele frequencies of TNF -308 A/G and -857C/T polymorphisms between GPP and controls. In conclusion, individuals carrying TNF -238A may be more susceptible to PGPP.

Objectives The objective of this study was to investigate risk factors of microvascular involvement and survival in Chinese patients with primary antiphospholipid syndrome. Methods In this single-center, retrospective study, we enrolled 112 patients with a confirmed diagnosis of primary antiphospholipid syndrome who were admitted to Peking Union Medical College Hospital from January 2004 to December 2016. Demographic data, clinical characteristics, laboratory results, and follow-up records were collected. Results A total of 112 patients with primary antiphospholipid syndrome were studied. Microvascular involvement was identified in 21 patients (18.75%). Patients with microvascular involvement experienced fewer episodes of arterial or venous thrombosis (28.6% vs. 84.6%) and a higher incidence of thrombocytopenia (85.7% vs. 54.9%), respectively. Low complement and elevated high-sensitivity CRP levels were observed more frequently in the microvascular group compared with the non-microvascular group (complement 38.1% vs. 18.7%; high-sensitivity CRP 71.4% vs. 31.9%, respectively). Anti-β2-glycoprotein I antibodies were more prevalent in patients with microvascular involvement than in patients without (66.7% vs. 33.0%, respectively). Multivariate logistic regression analysis revealed that thrombocytopenia (odds ratio = 4.523, 95% confidence interval 1.139–17.962), elevated high-sensitivity CRP levels (odds ratio = 6.385, 95% confidence interval 1.969–20.704), and anti-β2-glycoprotein I antibody positivity (odds ratio = 5.042, 95% confidence interval 1.555–16.352) were independent risk factors for microvascular involvement. A Kaplan–Meier analysis revealed that survival was significantly poorer in patients with microvascular involvement compared with patients without ( p = 0.0278). Conclusions In addition to arterial and venous thrombosis, antiphospholipid syndrome can affect the microvasculature of select organs. It is thus important for clinicians to be aware that antiphospholipid syndrome-associated microvascular involvement has a unique pathogenesis and can be a life-threatening condition.

Recent studies have shown that exosomes play a role in pathogenesis and in the treatment of inflammatory diseases and tumours. We explored the effects of Treponema pallidum-induced macrophage-derived exosomes on vascular endothelial cells to determine whether they are involved in the pathogenesis of syphilis. A syphilis infection model was established using rabbits to harvest T. pallidum at the peak of proliferation. Exosomes derived from macrophages were extracted using commercial kits and characterized by transmission electron microscopy, western blot assays, and nanoparticle tracking analysis. Secreted cytokine levels and the adhesion and permeability of human umbilical vein endothelial cells were evaluated in a co-culture model using the extracted exosomes. The results of this study revealed that exosomes derived from T. pallidum-infected macrophages enhanced cell adhesion and permeability. The levels of the secreted cytokines, including ICAM-1, VCAM-1, VEGF, and IL-8 were higher in the experimental group than in the control group. Our findings suggest that exosomes derived from T. pallidum-infected macrophages affect the cell adhesion and permeability of vascular endothelial cells. These changes may play important roles in syphilis pathogenesis. This study is the first to reveal the effects of exosomes derived from T. pallidum-infected macrophages on the adhesion, permeability, and secreted cytokines of human umbilical vein endothelial cells.

Neurosyphilis (NS) is a neurological disorder caused by Treponema pallidum subspecies pallidum (T. pallidum), but how T. pallidum attach to and cross the blood−brain barrier (BBB) and how BBB response to this bacteria remain unclear. To explore how the human brain microvascular endothelial cells (HBMECs) response to T. pallidum, the Agilent SurePrint G3 Human Gene Expression 8×60K microarray was used. The results revealed that 249 genes were differentially expressed in HBMECs infected with T. pallidum. In particular, genes encoding proteins involved in bacterial adhesion, endothelial cell activation and immune response were regulated by T. pallidum. Furthermore, Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed to determine the biological functions of differentially expressed genes. In summary, T. pallidum changes the gene expression profile in HBMECs, and differentially expressed genes are associated with widespread biological and pathophysiological functions. Above all, this is the first paper reporting the effects of T. pallidum on HBMECs. These data develop a new platform for further molecular experiments on the pathogenesis of NS.

The incidence of syphilis caused by Treponema pallidum subsp pallidum (T pallidum) infection is accompanied by inflammatory injuries of vascular endothelial cells. Studies have revealed that T pallidum infection could induce inflammasome activation and pyroptosis in macrophages. MicroRNA‐223‐3p (miR‐223‐3p) was reported to be a negative regulator in inflammatory diseases. The present study aimed to explore whether miR‐223‐3p regulates T pallidum‐induced inflammasome activation and pyroptosis in vascular endothelial cells, and determine the mechanisms which underlie this process. MiR‐223‐3p levels in syphilis and control samples were determined. The biological function of miR‐223‐3p in the NLRP3 inflammasome and pyroptosis was evaluated in T pallidum‐infected human umbilical vein endothelial cells (HUVECs). We observed a dramatic decrease in miR‐223‐3p levels in syphilis patients (n = 20) when compared to healthy controls (n = 20). Moreover, miR‐223‐3p showed a notable inhibitory effect on recombinant Tp17 (rTP17)‐induced caspase‐1 activation, resulting in decrease in IL‐1β production and pyroptosis, which was accompanied by the release of lactate dehydrogenase (LDH) in HUVECs. Additionally, the dual‐luciferase assay confirmed that NLRP3 is a direct target of miR‐223‐3p. Moreover, NLRP3 overexpression or knockdown largely blocked the effects of miR‐223‐3p on T pallidum‐induced inflammasome activation and pyroptosis in HUVECs. Most importantly, a notable negative correlation was observed between miR‐223‐3p and NLRP3, caspase‐1, and IL‐1β, respectively, in the serum of syphilis patients and healthy controls. Taken together, our results reveal that miR‐223‐3p targets NLRP3 to suppress inflammasome activation and pyroptosis in T pallidum‐infected endothelial cells, implying that miR‐223‐3p could be a potential target for syphilis patients.

TprK is a key virulence factor of Treponema pallidum subsp. pallidum (T. pallidum) due to its ability to undergo intra-strain antigenic variation through gene conversion. This mechanism can generate millions of tprK gene and protein variants to allow immune evasion and pathogen persistence during infection. In silico structural modeling supports that TprK is an outer membrane β-barrel with porin function and with several surface-exposed loops, seven of which corresponding to the variable regions. No definitive structural of functional data, however, exist for this protein aside from its role in immune evasion. Studies to elucidate TprK biological function as a porin, are hindered by the evidence that TprK is not abundant on T. pallidum outer membrane, and by the fragility of T. pallidum envelope. To gain insight onto TprK structure and possible function as a porin, we used an Escherichia coli - based expression system that yielded highly pure full-length TprK without any intermediate denaturation step, and proceeded to reconstitute it in detergents and lipid nanodiscs. Visualization of TprK in nanodiscs using negative staining electron microscopy supported that TprK is a monomeric porin in an artificial lipid environment mimicking T. pallidum membrane. Our work provided evidence that TprK is a possible porin transporter of T. pallidum, a biological function compatible with its structural models. These results bring us closer to a comprehensive understanding of the function of this important virulence factor in syphilis pathogenesis and T. pallidum biology.

Background The aim of this study was to assess the efficacy of ceftriaxone and benzathine penicillin G (BPG) in nonpregnant, immunocompetent adults with early syphilis because there is a lack of clinical evidence supporting ceftriaxone as an alternative treatment for early syphilis without an human immunodeficiency virus coinfection. Methods A randomized, open-label controlled study evaluating the efficacy of ceftriaxone and BPG was conducted in 4 hospitals in Jiangsu Province. Treatment comprised either ceftriaxone (1.0 g, given intravenously, once daily for 10 days) or BPG (2.4 million units, given intramuscularly, once weekly for 2 weeks). A serological response was defined as a ≥4-fold decline in the rapid plasma reagin (RPR) titer. Results In all, 301 patients with early syphilis were enrolled in this study; 230 subjects completed the follow-ups. The serological response at 6 months of follow up was observed in 90.2% in ceftriaxone group and 78.0% in BPG group (P = .01). There was no significant difference between treatment groups in patients with primary or early latent syphilis, but among patients with secondary syphilis the difference was highly significant (95.8% vs 76.2%; P < .01). Moreover, patients exhibiting a Jarisch-Herxheimer reaction after treatment might have a shorter period before a serological response (P = .03). Conclusions In this study, ceftriaxone regimen was noninferior to the BPG regimen in nonpregnant, immunocompetent patients with early syphilis. Clinical Trials Registration ChiCTR-TQR-13003624.

Rural-to-urban migrants are at high risk of HIV infection. The goal of this survey was to explore the commercial sexual behavior and condom use among male rural-to-urban migrants in western China. A cross-sectional survey on male rural-to-urban migrants in western China was conducted. Among all the subjects surveyed, 140 (7.4%) had commercial sexual behavior, which is associated with being aged older than 24 years, being of Han or other ethnic minorities, being divorced, separated, or widowed, having experienced drug abuse, having had heterosexual behavior, having had casual sexual partners, having had sex with a homosexual, and being from Xinjiang. A total of 31.4% of them never use condoms when buying sex. Not using condoms is associated with being from Chongqing, having a high school or above education, and having commercial sex monthly. Commercial sexual behavior and not using condoms are common among male rural-to-urban migrants in western China. Strategies and appropriate education should be developed to prevent HIV transmission due to high-risk sexual behaviors.

Sexually transmitted infections (STIs) are not new to China. However, a resurgence, particularly of syphilis, has been observed in the 1980s and 1990s. Driven by the sweeping political, economic, and social reforms of the late 1970s, syphilis has emerged as the third most-commonly reported infectious disease. Although inexorably linked to the emergence and expansion of China’s HIV epidemics, China’s syphilis response has lagged and been plagued by lack of recognition and lack of funding. Nevertheless, prevention and control efforts have grown with advances in treatment, testing, surveillance, and case reporting. Over the past decade, new national policies have prioritized syphilis prevention and control, and observational studies have improved our understanding of the syphilis epidemic among key, at-risk populations. Yet, many challenges remain—late presentation to testing and treatment is all too common, clinical services are not fully standardized, STI screening coverage still needs to be expanded, sexual health education should be improved, human resource and laboratory capacity needs to be increased, and stigma and discrimination must be eliminated. The syphilis response could benefit greatly from being more integrated into the HIV response, and China should look for opportunities to provide its citizens integrated prevention, testing, treatment, and care services.

Background Patients with neurospyphilis have been increasingly reported from clinics in China. Symptomatic neurosyphilis is more common among HIV-positive than HIV-negative patients. Clinical data of neurosyphilis among HIV-negative patients are limited. Methods Socio-demogeaphic and clinical data of the patients diagnosed with neurosyphilis and hospitalized at the Suzhou 5th People’s Hospital in China during January 2012 to November 2018 were collected and clinical and laboratory characteristics of these patients were analysed. Results Of the 58 patients enrolled into the analysis, majority (84.5%) were males. Two cases (3.4%) were diagnosed with asymptomatic neurosyphilis by evidence of only increases of protein and white blood cell count in their cerebrospinal fluids (CSF). The clinical charactistics were presented to be meningeal vascular type (defined as presentation of hemiplegia, headache, tinnitus, or epileptic attack) among 6, paralytic dementia (defined as decline in intelligence and memory, decreas of judgement sense and cognition, or mental symptoms) among 30, tabes dorsalis (defined as having manifestation such as walking instability of lower limbs, lightning pain, numbness, abnormal urination, or Arrow pupil) among 8, and ocular syphilis (defined as choroiditis,iritis, retinitis, or optic atrophy) among 12 patients, respectively. Most of the patients (84.5%) had serum RPR titers of ≥ 1:8 and two-thirds (75.9%) were positive for RPR in CSF (ranging 1:1 to 1:16). Additional CSF evaluations indicated an elevated protein in 55 and leukopenia in 57 patients. Among 30 patients with paralytic dementia, 16 (53.3%) shown a multiple lacunar foci in their brain CT or MRI, and 7 (23.3%) had cerebral atrophy. Conclusion Symptomatic neurosyphilis is common among HIV-negative patients and clinical features charactierislized majorly as neurological, psychiatric or phthalmic symptoms have call for attendtion of the relevant departments to detect these patients for interventions timely. Disclosure No significant relationships.

World Health Organization (WHO) and Joint United Nations Program on AIDS (UNAIDS) recommend male circumcision (MC) as an additional HIV prevention measure. This study aimed to assess three models of promoting MC and their effects on preventing HIV infection among drug users in western China. We carried out a cohort study in three provinces of western China. HIV seronegative male drug users were recruited from methadone maintenance therapy clinics and cluster randomized into three intervention models. At baseline, 6, and 9 months of follow-up, changes in MC knowledge, the acceptability of MC, MC surgery uptake, and the costs of model implementation were analyzed. Of 1,304 male drug users who were screened, 1,218 were enrolled in the study. The participants' knowledge about MC was significantly increased after interventions by all three models. The one-stage model led to the highest increase in MC acceptability and the greatest increase in MC uptake. Multivariable Cox regression analysis showed that the one-stage model was also the most effective method to promote MC uptake, compared with the two-stage model [rate ratio (RR) = 0.602; 95% confidence interval (CI), 0.420-0.862] and three-stage model (RR = 0.555; 95% CI, 0.382-0.807). The HIV incidence rate in the MC group was lower than that in the non-MC group (RR = 0.234; 95% CI, 0.056-0.974). Moreover, the one-stage model required the lowest cost per circumcision. The one-stage model is the most effective and the most cost-effective intervention to increase MC uptake among male drug users in western China and could decrease the HIV incidence rate, based on a short follow-up investigation.

Exosomal microRNAs (miRNAs) transferred between cells have been implicated in modulating the host immune response in microbial infections. In this study, we isolated exosomes from Treponema pallidum (T. pallidum)-stimulated macrophages and detected differential exosomal miRNA expression using both microarrays, and RT-qPCR. A total of 65 differentially expressed miRNAs (35 upregulated and 30 downregulated) were identified. Of all identified miRNAs, miR-146a-5p was one of the most significantly changed miRNAs with high expression in exosomes from T. pallidum-stimulated macrophages. Furthermore, we isolated plasma exosomes from early syphilis patients and healthy controls, and confirmed miR-146a-5p upregulation in the former group. We also show that exosomal miR-146a-5p is efficiently transported into endothelial cells, reducing monocyte transendothelial migration and endothelial permeability by targeting junctional adhesion molecule C (JAM-C). Luciferase reporter assays confirmed binding of exosomal miR-146a-5p to the 3'untranslated region (3'UTR) of JAM-C. We then demonstrated that also exosomes derived from macrophages stimulated by T. pallidum expressed high levels of miR-146a-5p which could be delivered to endothelial cells, and decreased monocyte transendothelial migration by targeting JAM-C. Overall, this work provides novel insights into the mechanism by which T. pallidum hampers inflammatory reactions of the host via a blockade of leukocytes transendothelial migration and endothelial permeability.

Introduction The aim of this study was to assess the efficacy of ceftriaxone and benzathine penicillin in non-pregnant, immunocompetent adults with early syphilis since there is a lack of clinical evidence supporting ceftriaxone as an alternative treatment for early syphilis without an HIV co-infection. Methods A randomised, open-label controlled study evaluating the efficacy of ceftriaxone and benzathine penicillin was performed in four hospitals in Jiangsu Province. Treatment comprised either ceftriaxone (1.0 g, intravenously, once daily for 10 days) or benzathine penicillin (2.4 million units, intramuscularly, once per week for two weeks). Serological response was defined as at least a 4-fold decline in rapid plasma regain(RPR) titer. Results In all, 301 patients with early syphilis were enrolled in this study; 230 subjects completed the follow-ups. The median follow-up period was 9 months. Among these 230 patients, a serological response was observed in 83.9% and 86.5% at the 6- and 12 month follow-ups, respectively. There were significant differences between the ceftriaxone- and penicillin-treated groups at both the 6- (90.2% vs 80.0%; p=0.012) and 12 month follow-ups (92.0% vs 81.4%; p=0.021), especially in patients with secondary syphilis (p Conclusion Our serological data demonstrate that this ceftriaxone regimen is more effective than the currently recommended benzathine penicillin regimen for early syphilis in non-pregnant, immunocompetent patients, especially for secondary syphilis.

Objective This article aims to determine the serological biomarkers which can be considered as risk factors of systemic lupus erythematosus (SLE)-associated pulmonary arterial hypertension by a systematic review and meta-analysis. Methods This study was conducted in accordance with the PRISMA statement. The search database included MEDLINE, EMBASE, Cochrane Library and Scopus. The Newcastle–Ottawa scale was used for the quality assessment. The odds ratio was the primary measure of effect of the risk factors. Results Twelve studies were included in this meta-analysis. The results identified the anti-RNP antibody and anti-Sm antibody as risk factors for SLE-associated pulmonary arterial hypertension with the pooled odds ratios 3.68 (95% confidence interval 2.04–6.63, P Conclusion Pulmonary arterial hypertension is a serious complication of SLE with a worse prognosis than SLE patients without pulmonary arterial hypertension. The early recognition of pulmonary arterial hypertension with transthoracic echocardiography routinely performed in SLE patients with risk factors is necessary, especially in Asian patients.

Doxycycline is an alternative antibiotic drug for the treatment of syphilis, but data on its efficacy, especially data on its efficacy against late latent syphilis, are limited. A retrospective study was conducted to evaluate the effectiveness of doxycycline for the treatment of patients with different stages of syphilis. Patients who received doxycycline treatment between June 2011 and June 2014 were involved. The serological response to doxycycline was defined as either a negative toluidine red unheated serum test (TRUST) result or a ≥4-fold decrease in titer at 12 months following the treatment. Univariate and multivariate logistic regression analyses were performed to identify factors associated with the serological response. During the study period, a total of 163 syphilis patients were treated with doxycycline, and 118 patients completed doxycycline treatment and the 12-month follow-up. Among the 118 patients, the serological response rate at 12 months was 100.0% (7/7) in patients with primary syphilis, 96.9% (62/64) in patients with secondary syphilis, 91.3% (21/23) in patients with early latent syphilis, and 79.2% (19/24) in patients with late latent syphilis. The total serological response rates were 92.4% (109/118) for preprotocol (PP) patients and 66.9% (109/163) for all intention-to-treat (ITT) patients. In multivariate analysis, patients who serologically responded at 12 months following treatment were positively associated with a higher baseline TRUST titer and an earlier syphilis stage than nonresponders. Our study showed excellent treatment outcomes in patients with different stages of syphilis. Our data, along with those from other reports, support the usage of doxycycline as a good alternative therapeutic option in the treatment of syphilis.

Previously, a small study showed that 14f was the predominant subtype of Treponema pallidum in Shanghai, China. The result was quite different from the genotype distribution in other areas of China. This study aimed to identify the strain types of Treponema pallidum in samples collected over a 5-year period in Shanghai. From 2007 to 2011, genital swabs were collected from patients with syphilis from the Shanghai Skin Disease Hospital. Positive specimens were typed by the enhanced typing method by adding a tp0548 gene to the existing arp and tpr genotype system. In total, 304 of the 372 enrolled patients yielded fully typeable DNA. Ten arp types (4, 6, 8, 9, 11, 12, 13, 14, 15, and 19), 3 tpr types (a, d, and o), and 5 tp0548 types (a, c, f, g, and i) were identified. In total, 12 subtypes were identified with a combination of the arp and tpr genes. Subtype 14d was found in 270 samples (88.8%). When the combination included the tp0548 gene, the 12 CDC subtypes identified were divided into 14 strain types. The predominant type was 14d/f (88.8%), followed by 15d/f (3.6%), 13d/f (1.3%), and 19d/c (1.3%). Two of the 44 14d/f-infected patients and both of the 19d/c-infected patients who underwent a lumbar puncture were diagnosed with neurosyphilis. This study showed that the predominant type in Shanghai was 14d/f. While this is in keeping with data from other areas in China, it is different from an earlier report showing that 14f is the most common genotype in Shanghai. Further studies are needed to better understand the association between strain types and neurosyphilis.

Epidermodysplasia Verruciformis is a rare skin disease due to human papillomavirus (HPV) infection. We report here a male patient of 39 years with severe giant lesion of hands and feet leading to disability for 20 years. The function of the hands was almost lost. We treated the case with the shaving technique and a satisfactory result without recrudescence in the following two years. No apparent scarring resulted.

Background Male circumcision (MC) has been shown to reduce the risk of female to male transmission of HIV. The goal of this survey was to explore MC's acceptability and the factors associated with MC among college students in medical universities in western China. Methods A cross-sectional study was carried out in three provinces in western China (Guangxi, Chongqing and Xinjiang) to assess the acceptability of MC as well as to discover factors associated with the acceptability among college students in medical universities. A total of 1,790 uncircumcised male students from three medical universities were enrolled in this study. In addition, 150 students who had undergone MC were also enrolled in the survey, and they participated in in-depth interviews. Results Of all the uncircumcised participants (n = 1,790), 55.2% (n = 988) were willing to accept MC. Among those who accepted MC, 67.3% thought that MC could improve their sexual partners' hygiene, 46.3% believed that HIV and sexually transmitted diseases (STDs) could be partially prevented by MC. The multivariable logistic regression indicates that MC's acceptability was associated with three factors: the redundant foreskin (OR = 10.171, 95% CI = 7.629-13.559), knowing the hazard of having a redundant foreskin (OR = 1.597, 95% CI = 1.097-2.323), and enhancing sexual pleasure (OR = 1.628, 95% CI = 1.312-2.021). The in-depth interviews for subjects who had undergone MC showed that the major reason for having MC was the redundant foreskin (87.3%), followed by the benefits and the fewer complications of having MC done. In addition, most of these participants (65.3%) said that the MC could enhance sexual satisfaction. Conclusions MC's acceptance among college students in medical universities is higher than it is among other populations in western China. An implementation of an MC programme among this population is feasible in the future.

The objectives were to address the role of men who have sex with men (MSM) in the human immunodeficiency virus (HIV)/sexually transmitted disease (STD) epidemic in China. Goal: To explore the prevalence of risky sexual behaviors and the existing prevention efforts among men who have sex with men (MSM) in China. Review of behavioral and STD/HIV prevention studies addressing MSM in China. Sexual risk behaviors including unprotected group sex anal sex casual sex and commercial sex were prevalent among Chinese MSM. Many Chinese MSM also engaged in unprotected sex with both men and women. Most MSM either did not perceive that they were at risk of HIV/AIDS or underestimated their risk of infection. Surveillance and intervention research among these men are still in the preliminary stages. Chinese MSM are at risk for HIV/STD infection and potential transmission of HIV to the general population. In addition to sexual risk reduction among MSM reduction of homosexuality-related stigma should be part of effective intervention efforts. Volunteers from the MSM community and health care workers in primary health care system may serve as valuable resources for HIV/STD prevention and control among MSM. (authors)

We investigated Chlamydia trachomatis strains from Nanjing, China, and whether these strains differed from Amsterdam, the Netherlands. C. trachomatis type was determined with multilocus sequence typing. Most strains were specific to Nanjing, but some clustered with strains from Amsterdam. This demonstrates a geographical variation in C. trachomatis previously left undetected.

We conducted a cross-sectional study on prevalence of human immunodeficiency virus (HIV) and syphilis among female sex workers (FSWs) recruited from different types of venues in 6 cities in China. Among 5322 FSWs (1379 were from high-tier venues, 2482 from middle-tier venues, and 1461 from low-tier venues, respectively), overall HIV prevalence was 0.54% (95% confidence interval [CI], 0.37%- 0.76%). By typology of venues where FSWs solicited clients, the prevalence was 1.37% (95% CI, 0.89%-2.11%) in low-tier venues, 0.28% (95% CI, 0.14%- 0.58%) in middle-tier venues, and 0.07% (95% CI, 0.01%-0.41%) in high-tier venues. The final logistic regression model showed an association of having had HIV infection with working in low-tier venues (adjusted odds ratio 2.73; 95% CI, 1.12-6.67) and coming from Guangxi Province (adjusted odds ratio, 7.89; 95% CI, 1.65-37.64). It can be concluded that FSWs working in low-tier venues (on the streets or public outdoor places) had higher risk of HIV infection than other venues. Such subgroup of FSWs should be efficiently covered by the current HIV/STD surveillance and intervention programs in China.

Objectives 1. To determine the aetiologies of genital ulcers in China. 2. To evaluate a modified WHO syndromic management algorithm for genital ulcer disease (GUD). Methods: Patients with genital ulcers were enrolled at their first visit to STD clinics in the cities of Shanghai and Chengdu. They were managed according to a modified WHO algorithm for GUD, in which no treatment was given for chancroid. A multiplex polymerase chain reaction was used to detect Treponema pallidum, Herpes simplex and Haemophilus ducreyi. Dark field examination and serology (rapid plasma reagin and Treponema pallidum particle agglutination assay (TPPA) were also used to diagnose syphilis. Results: A total of 227 male and female patients were enrolled. Syphilis alone was diagnosed in 78 (35%), genital herpes alone in 43 (19%), and both infections were present in 28 (12%). No diagnosis was made in 76 (34%). No case of chancroid was identified. The sensitivity of the algorithm for syphilis and herpes was 88.7% and 69.0% respectively, the specificity 95.0% and 50.0%. 12/106 cases of syphilis were incorrectly classified as herpes (11%), and did not receive treatment. More than 97% of patients followed up responded clinically to treatment. Conclusion: Further validation and revision of the WHO flowchart for GUD are needed.

The objective of the study is to evaluate the efficacy and safety of oral inosine pranobex as compared with acyclovir in the treatment of recurrent herpes labialis (RHL) and recurrent herpes genitalis (RHG). A multicenter double-blind, double-dummy, randomized, controlled, parallel group trial was conducted in 144 patients with RHL and 144 RHG. Patients were assigned to treatment in one of two groups: (i) inosine pranobex group (active inosine pranobex, 1 g four times daily, and acyclovir placebo); or (ii) acyclovir group (active acyclovir, 200 mg five times daily, and inosine pranobex placebo). The total symptom score (TSS) of patients with RHL did not differ in the inosine pranobex and acyclovir group on the 3rd or 7th day of treatment. There was also no difference in the efficacy rates between the two groups. No difference of TSS was observed between patients with RHG taking inosine pranobex and acyclovir on days 3 or 5 of the treatment, respectively. The short-term clinical recurrence rate of RHG at 3-month follow-up was much lower in the inosine pranobex group than acyclovir group. The incidence of hyperuricemia was higher in the inosine pranobex group than acyclovir group. In conclusion, inosine pranobex was as effective as acyclovir in treating RHL and RHG with significantly greater reduction of the short-term recurrence rate of herpes genitalis at 3-month follow up. Long-term recurrence rates at 6 months or longer remain to be determined. Hyperuricemia should be monitored during the treatment.

To describe the acceptability of male circumcision (MC) and explore potential factors associated with MC acceptability among male rural-to-urban migrants in western China, a cross-sectional survey of MC acceptability was conducted with 1,904 subjects in three western provinces with high HIV prevalence (Guangxi, Chongqing, and Xinjiang) in China between June 2009 and November 2009. Through face-to-face interviews, the participants completed a self-administered questionnaire about demographics, MC knowledge, willingness and reasons to accept or refuse MC, sexual behaviors, and other psychosocial variables. Factors associated with acceptability of MC were identified by multiple logistic regression analysis. Of the participants (n=1,904), 710 men were willing to accept MC (37.3%); the reasons included promotion of the partners' genital hygiene (54.9%), redundant prepuce or phimosis (43.1%), enhancement of sexual pleasure (40.6%), prevention of penile inflammation or cancer (35.5%), and protection against HIV and sexual transmitted diseases (STDs)(31.1%). A multivariable logistic regression showed that four factors were associated with acceptability of MC, including education level (OR=1.286, 95% CI=1.025∼1.614), redundant prepuce or phimosis (OR=13.751, 95% CI=10.087∼18.745), having one or more circumcised friends (OR=2.468, 95% CI=1.953∼3.119), and having sexual intercourse with a temporary partner in the past year (OR=1.543, 95% CI=1.101∼2.162). Compared with previously published data among the general population in China or worldwide, the acceptability of MC (37.3%) was low among the male rural-to-urban migrants in western China. Nevertheless, appropriate education could greatly improve the acceptability of MC. More public campaigns and health education on MC are needed to increase the rate of MC in China.

Wei-wei Tian,1 Qian-qiu Wang,1 Wei-da Liu,2 Jian-ping Shen,1 Hong-sheng Wang11Laboratory of Mycobacterial Disease, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Nanjing, Jiangsu, People’s Republic of China; 2Department of Mycology, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Nanjing, Jiangsu, People’s Republic of ChinaPurpose: The aim of the present study was to investigate the immune response induced by Mycobacterium marinum infection in vitro and the potential of M. marinum as an immunotherapy for M. tuberculosis infection.Methods: The potential human immune response to certain bacillus infections was investigated in an immune cell–bacillus coculture system in vitro. As a potential novel immunotherapy, M. marinum was studied and compared with two other bacilli, Bacillus Calmette-Guérin (BCG) and live attenuated M. tuberculosis. We examined the changes in both the bacilli and immune cells, especially the time course of the viability of mycobacteria in the coculture system and host immune responses including multinuclear giant cell formation by Wright–Giemsa modified staining, macrophage polarization by cell surface antigen expression, and cytokines/chemokine production by both mRNA expression and protein secretion.Results: The M. marinum stimulated coculture group showed more expression of CD209, CD68, CD80, and CD86 than the BCG and M. tuberculosis (an attenuated strain, H37Ra) groups, although the differences were not statistically significant. Moreover, the M. marinum group expressed more interleukin (IL)-1B and IL-12p40 on day 3 (IL-1B: P = 0.003 and 0.004, respectively; IL-12p40: P = 0.001 and 0.011, respectively), a higher level of CXCL10 on day 1 (P = 0.006 and 0.026, respectively), and higher levels of chemokine (C-X-C motif) ligand (CXCL) 8 and chemokine (C motif) ligand (XCL) 1 on day 3 (CXCL8: P = 0.012 and 0.014, respectively; XCL1: P = 0.000 and 0.000, respectively). The M. marinum stimulated coculture group also secreted more tumor necrosis factor (TNF)-α, IL-1ß, and IL-10 on day 1 (TNF-α: P = 0.000 and 0.000, respectively; IL-1ß: P = 0.000 and 0.000, respectively; IL-10: P = 0.002 and 0.019, respectively) and day 3 (TNF-α: P = 0.000 and 0.000, respectively; IL-1ß: P = 0.000 and 0.001, respectively; IL-10: P = 0.000 and 0.000, respectively). In addition, the colony-forming units (an index of viability) of M. marinum in the M. marinum stimulated coculture group was significantly less than that of BCG and H37Ra in their corresponding bacillus stimulated groups (P = 0.037 and 0.013, respectively).Conclusion: Our results indicated that M. marinum could be a potentially safe and effective immunotherapy.Keywords: immunotherapy, Mycobacterium marinum, bacilli, immunity

OBJECTIVE: Three models for promoting male circumcision (MC) as a preventative intervention against HIV infection were compared among migrant worker populations in western China. METHODS: A cohort study was performed after an initial cross-sectional survey among migrant workers in three provincial level districts with high HIV prevalence in western China. A total of 1,670 HIV seronegative male migrants were cluster-randomized into three intervention models, in which the dissemination of promotional materials and expert- and volunteer-led discussions are conducted in one, two, and three stage interventions. Changes in knowledge of MC, acceptability of MC, MC surgery uptake, and the costs of implementation were analyzed at 6-month and 9-month follow-up visits. RESULTS: All three models significantly increased the participants' knowledge about MC. The three-stage model significantly increased the acceptability of MC among participants and led to greatest increase in MC uptake. At the end of follow-up, 9.2% (153/1,670) of participants underwent MC surgery; uptake among the one-, two-, and three-stage models were 4.9%, 9.3%, and 14.6%, respectively. Multivariable Cox regression analysis showed that three-stage model was the most effective method to scale up MC, with RR = 2.0 (95% CI, 1.3-3.1, P=0.002) compared to the on-site session model. The two-stage intervention model showed no significant difference with either the on-site session model (RR=1.5, 95% CI, 0.92-2.4, P=0.12) or three-stage model (P=0.10). CONCLUSIONS: A three-stage intervention with gradual introduction of knowledge led to the significantly increase in MC uptake among migrant workers in western China, and was also the most cost-effective method among the three models.

The prevalence and correlates of sexual risk behaviors among drug users in western China and the implications for HIV transmission in this population are described. A cross-sectional survey of male drug users was conducted in methadone maintenance therapy clinics and detoxification centers in three western provinces of China between September 2009 and December 2010. Participants in the study completed a questionnaire about demographics, HIV/AIDS knowledge, drug use history, sexual risk behaviors, and other psychosocial variables. Factors associated with HIV sexual risk behaviors were identified by multiple logistic regression analysis. Of 1,304 drug users surveyed, nearly 54% never used condoms during sexual intercourse with a spouse or cohabitant, and this behavior was associated with coming from Chongqing (OR=1.86, p

The authors of the paper “Scheduling Optimization of the RFID Tagged Explosive Storage Based on Genetic Algorithm” (Xiaoling Wu, Huawei Fu, Xiaomin He, Guangcong Liu, Jianjun Li, Hainan Chen, Qianqiu Wang, and Qing He), DOI: 10.1007/978-3-642-38027-3_38, appearing on pages 358-366 of this publication, have decided to retract the paper, because there are serious flaws in both the data and some steps of the algorithm. This makes the data unreliable.

In the view of the large scale and increasing kinds of service of space information networks, a service- oriented topology control algorithm is proposed. According to demands of existing service, the topology of network is divided into several logical sub-topologies, on which construct the corresponding topology. Taking the communication pattern as an example, the augmentation-based approach is adopted to construct topologies which can meet the requirements of one-to-many communication. The augmentation-based approach calculates the weight of links, according to the requirements of service on bandwidth, delay, delay jitter and reliability. After that, the augmentation-based approach use the free links as most as possible, establish a nearest neighbor graph that meets the requirement of fault tolerance, then augment to be the ultimate topology. The simulation results indicate that the proposed algorithm can remove redundant links effectively, improve the effectiveness of data transmission and also ensure the fault tolerance of the network, can adapt to the multiple application requirement of space information networks.

Children may acquire syphilis as a consequence of nonsexual close contact if family members or caregivers are infected by active syphilis. We described 3 cases of acquired secondary syphilis in Chinese preschool children who contracted the disease from their caregivers to draw attention to the potential for syphilis patients to transmit Treponema pallidum to the children they are caretakers for.