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Background: Helicobacter pylori (H. pylori) virulence factors, particularly the cagA and vacA genotypes, play important roles in the pathogenic process of gastrointestinal disease., Methods: The cagA and vacA genotypes of 87 H. pylori strains were determined by PCR and sequencing. The EPIYA and CM motif patterns were analyzed and related to clinical outcomes. We examined the associations between the virulence genes of H. pylori and gastrointestinal diseases in Shandong, and the results were analyzed via the chi-square test and logistic regression model., Results: Overall, 76 (87.36%) of the strains carried the East Asian-type CagA, with the ABD types being the most prevalent (90.79%). However, no significant differences were observed among the different clinical outcomes. The analysis of CagA sequence types revealed 8 distinct types, encompassing 250 EPIYA motifs, including 4 types of EPIYA or EPIYA-like sequences. Additionally, 28 CM motifs were identified, with the most prevalent patterns being E (66.67%), D (16.09%), and W-W (5.75%). Notably, a significant association was discovered between strains with GC and the CM motif pattern D (P < 0.01). With respect to the vacA genotypes, the strains were identified as s1, s2, m1, m2, i1, i2, d1, d2, c1, and c2 in 87 (100%), 0 (0), 26 (29.89%), 61 (70.11%), 73 (83.91%), 14 (16.09%), 76 (87.36%), 11 (12.64%), 18 (20.69%), and 69 (79.31%), respectively. Specifically, the vacA m1 and c1 genotypes presented a significantly greater prevalence in strains from GC compared to CG (P < 0.05). Following adjustment for age and sex, the vacA c1 genotype demonstrated a notable association with GC (OR = 5.174; 95% CI, 1.402-20.810; P = 0.012). This association was both independent of and more pronounced than the correlations between vacA m1 and GC., Conclusions: CagA proteins possessing CM motif pattern D were more frequently observed in patients with GC (P < 0.01), implying a potentially higher virulence of CM motif pattern D than the other CM motif patterns. Moreover, a strong positive association was identified between the vacA c1 genotype and GC, indicating that the vacA c1 genotype is a robust risk indicator for GC among male patients aged ≥55 years in Shandong., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Xue et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

In order to predict the global potential distribution range of Ixodes pacificus (I. pacificus) under different climate scenario models in the future, analyze the major climate factors affecting its distribution, and provide references for the transformation of passive vector surveillance into active vector surveillance, the maximum entropy model (MaxEnt) was used in this study to estimate the global potential distribution range of I. pacificus under historical climate scenarios and different future climate scenarios. The global distribution data of I. pacificus were screened by ENMtools and ArcGIS 10.8 software, and a total of 563 distribution data of I. pacificus were obtained. Maxent 3.4.1 and R 4.0.3 were used to screen climate variables according to the contribution rate of environmental variables, knife cutting method and correlation analysis of variables. R 4.0.3 was used to calculate model regulation frequency doubling and feature combination to adjust MaxEnt parameters. The model results showed that the training omission rate was in good agreement with the theoretical omission rate, and the area under ROC curve (AUC) value of the model was 0.978. Among the included environmental variables, the Tmin2 (minimum temperature in February) and Prec1 (precipitation in January) contributed the most to the model, providing more effective information for the distribution of I. pacificus. MaxEnt model revealed that the distribution range of I. pacificus was dynamically changing. The main potential suitable areas are distributed in North America, South America, Europe, Oceania and Asia. Under the future climate scenario model, the potential suitable areas show a downward trend, but the countries and regions ieeeeeeenvolved in the suitable areas do not change much. Therefore, the invasion risk of the potential suitable area of I. pacificus should be paid attention to., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Chlamydia psittaci-a zoonotic pathogen in birds-may be transmitted to humans, causing severe respiratory disease. Individuals working in or living near poultry farms are highly susceptible to C. psittaci infection. In this study, we assessed the prevalence and genotypes of C. psittaci in poultries and humans in three cities of China by collecting fecal samples from different poultry species and throat swab samples and serum samples from workers in poultry farms and zoos. These samples were screened by real-time fluorescence quantitative PCR (qPCR) targeting C. psittaci ompA. The positive samples were subjected to PCR amplification and sequencing of ompA. The strains detected in the samples were genotyped on the basis of the phylogenetic analysis of ompA sequences. In total, 3.13% (40/1278) poultry fecal samples were positive in the qPCR assay, whereas 3.82% (6/157) of throat swab samples and 42.59% (46/108) of serum samples from the workers were positive in the qPCR and indirect fluorescent antibody assays, respectively. The strains detected in the 32 poultry samples and 6 human samples were genotyped as type A, indicating that the workers were infected with C. psittaci that originated in poultry birds in farms. Additionally, eight peacocks showed strains with the genotype CPX0308, which was identified in China for the first time. Elucidating the distribution of C. psittaci in animals and poultry-related workers may provide valuable insights for reducing the risk of C. psittaci infection within a population., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Hou et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

To analyze the results of proficiency testing for anti-tuberculosis drug susceptibility testing (DST) in China. Number of laboratory participating the proficiency testing performed DST, and the sensitivity, specificity, reproducibility, and accordance rate were calculated from data of 13 rounds proficiency testing results for DST from 2008 to 2021. A total of 30 and 20 strains of Mycobacterium tuberculosis with known susceptibility results were sent to each laboratory in 2008 to 2019, 2020 and 2021, respectively. The number of participating laboratories ranged from 30 in 2009 to 546 in 2021. L-J DST was the predominant method. The specificity presented relatively higher than sensitivity. Improvement of specificity were observed for all drugs through the years, while sensitivity did not show improvement for amikacin and capreomycin. Accordance rate of pyrazinamide and kanamycin and reproducibility of capreomycin and pyrazinamide were not significantly improved through the years. Most of the participating laboratories significantly improved the quality of their DST through the consecutive rounds of proficiency testing except for second-line injectable drugs and pyrazinamide. The results highlight the importance of developing novel and/or improving existing methods for phenotypic DST for certain drugs., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Song et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The WHO has issued a call to action urging countries to accelerate the rollout of new WHO-recommended shorter all-oral treatment regimens for drug-resistant TB (DR-TB), which remains a public-health crisis. The all-oral, 6-month BPaL/M regimen comprises 3-4 drugs: pretomanid used in combination with bedaquiline and linezolid, with or without moxifloxacin. This regimen has been recommended by the WHO for use in DR-TB patients instead of ≥9-month (up to 24-month) regimens. This study aims to project this regimen's use, along with its components bedaquiline, pretomanid and linezolid, and other treatments for DR-TB globally through 2026. It is intended to guide global health stakeholders in planning and budgeting for DR-TB interventions. Projected usage could help estimate cost of the individual components of DR-TB regimens over time., Methods: Semi-structured interviews were conducted with national TB programme participants in key countries to gather intelligence on established plans and targets for use of various DR-TB treatment regimens from 2023 to 2026. These data informed development of projections for the global use of regimens and drugs., Results: Consistent global growth in the use of shorter regimens in DR-TB treatment was shown: BPaLM reaching 126,792 patients, BPaL reaching 43,716 patients, and the 9-11-month all-oral bedaquiline-based regimen reaching 13,119 patients by 2026. By 2026, the longer all-oral regimen is projected to be used by 19,262 patients, and individualised treatment regimens by 15,344 patients., Conclusion: The study shows BPaL/M will be used in majority of DR-TB patients by 2024, reaching 78% by 2026. However, national efforts to scale-up, case-finding, monitoring, drug-susceptibility testing, and implementation of new treatments will be essential for ensuring they are accessible to all eligible patients in the coming years and goals for ending TB are met. There is an urgent need to engage communities in capacity building and demand generation., Competing Interests: Authors, Aastha Gupta and Sandeep Juneja, are employed by TB Alliance, the non-profit product development partnership that developed pretomanid and the BPaL regimen for the treatment of drug-resistant tuberculosis. Author, Suvanand Sahu, serves on the Access Advisory Committee (an unpaid role) for TB Alliance, the non-profit product development partnership that developed pretomanid and the BPaL regimen for the treatment of drug-resistant tuberculosis. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Gupta et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Previous studies showed that physical activity (PA) is concerned with hypertension (HTN). However, the mediation and interaction role of the obesity index: body mass index (BMI), waist-hip ratio (WHR), body fat rate (BFR) and visceral fat index (VFI) between PA and HTN has never been studied. Therefore, the purpose of this study was to assess the mediation and interaction of the obesity index between moderate-vigorous recreational physical activity (MVRPA) and HTN. We conducted a cross-sectional study of 4710 individuals aged 41 or older in Torch Development Zone, Zhongshan City. The mediation and interaction of the obesity index were evaluated by a four-way decomposition. 48.07% of participants had HTN among these groups. In the adjusted linear regression model, MVRPA was significantly correlated with WHR (β±SE = -0.005±0.002; P<0.05). Compared to sufficient MVRPA (odds ratio (OR) = 1.35), 95% (confidence interval (CI) = 1.17-1.56), insufficient MVRPA increased the risk of developing HTN. Furthermore, there were associations between BMI, WHR, BFR, VFI and HTN where the adjusted ORs and 95% CIs were 1.11 (1.09-1.13), 6.23 (2.61-14.90), 1.04 (1.03-1.06), 1.07 (1.06-1.09), respectively. The mediation analyses suggested that the impact of MVRPA on HTN risk may partly be explained by changes in obesity index, with a pure indirect mediation of WHR between MVRPA and HTN (P<0.05). Therefore, weight control, especially reducing abdominal obesity and maintaining adequate MVRPA, may lead to more proper control of HTN., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Du et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

To investigate incidence of pregnancy-related low back pain (LBP), evaluate physical fitness objectively during pregnancy and analyze the correlation between LBP and physical fitness of pregnant women, 180 pregnant women including 101 in mid-gestation (14-28 gestational weeks) and 79 in late-gestation (28-37 gestational weeks) were recruited and self-reported their LBP. The aerobic ability such as cardiorespiratory fitness and anaerobic ability including strength, endurance, speed, flexibility, and balance were evaluated by a novel materal physical fitness test system. The correlation between LBP and each component in physical fitness test system was analyzed in SPSS. As the results, 135 out of 180 participants (75% of total) had pregnancy-related LBP. Physical fitness of participants in late-gestation was significantly weaker including weaker back strength (p<0.05), less resistance band pullbacks in 30s (p<0.01), less stretching in sit-and-reach test (p<0.001), shorter duration in left legged blind balance test (p<0.05) and weaker bird dog balance(p<0.05) than those in mid-gestation. Correlation analysis indicated that LBP was negatively associated with standing heel raises in 20s (p<0.01) and standing glute kickbacks in 30s (left p<0.01, right p<0.05). Thus, it is concluded that LBP is in high prevalence throughout the entire pregnant course. The pregnant women are prone to have weakened strength of core muscle groups and poorer flexibility and balance along the pregnancy. In addition, their LBP was negatively correlated to strength of back muscle groups of lower limbs., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Zhou et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Backgrounds: The therapeutic efficacy studies of DHA-PIP for uncomplicated Plasmodium falciparum patients were implemented from 2012 to 2016 along China (Yunnan province)-Myanmar border, which verified the high efficacy of DHA-PIP. With the samples collected in these studies, the genetic characteristics of P. falciparum parasites based on in vivo parasite clearance time (PCT) was investigated to explore if these parasites had developed resistance to DHA and PIP at molecular level., Methods: The genetic characteristics were investigated based on K13 genotypes, copy numbers of genes pfpm2 and pfmdr1, and nine microsatellite loci (Short Tandem Repeats, STR) flanking the K13 gene on chromosome 13. The PCT 50s were compared based on different K13 genotypes, sites, periods and copy numbers., Results: In the NW (North-West Yunnan province bordering with Myanmar) region, F446I was the main K13 genotype. No significant differences for PCT 50s presented among three K13 genotypes. In SW (South-West Yunnan province bordering with Myanmar) region, only wild K13 genotype was detected in all parasite isolates whose PCT 50s was significantly longer than those in NW region. For the copy numbers of genes, parasite isolates containing multiple copies of pfmdr1 gene were found in both regions, but only single copy of pfpm2 gene was detected. Though the prevalence of parasite isolates with multiple copies of pfmdr1 gene in SW region was higher than that in NW region, no difference in PCT 50s were presented between isolates with single and multiple copies of pfmdr1 gene. The median He values of F446I group and Others (Non-F446I K13 mutation) group were 0.08 and 0.41 respectively. The mean He values of ML group (Menglian County in SW) and W (wild K13 genotype in NW) group were 0 and 0.69 respectively. The mean Fst values between ML and W groups were significantly higher than the other two K13 groups., Conclusions: P. falciparum isolates in NW and SW regions had very different genetic characteristics. The F446I was hypothesized to have independently appeared and spread in NW region from 2012 and 2016. The high susceptibility of PIP had ensured the efficacy of DHA-PIP in vivo. Multiple copy numbers of pfmdr1 gene might be a potential cause of prolonged clearance time of ACTs drugs along China-Myanmar border., Trial Registration: Trial registration: ISRCTN, ISRCTN 11775446. Registered 17 April 2020-Retrospectively registered, the registered name was Investigating resistance to DHA-PIP for the treatment of Plasmodium falciparum malaria and chloroquine for the treatment of Plasmodium vivax malaria in Yunnan, China. http://www.isrctn.com/ISRCTN11775446., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Clathrin is a key protein for viruses to enter host cells. Previous studies often use clathrin inhibitors or gene knockdown technology to partially inhibit the function of clathrin, but whether SFTSV can infect host cells without clathrin expression remains unclear. In this research, a clathrin heavy chains (CLTC) knockout A549 cell line was established by CRISPR/Cas9 technology, and the knockout of CLTC was verified by PCR, Western blot, immunofluorescence and T7E1 analysis. The off-target effect was evaluated by PCR combined with Sanger sequencing. Furthermore, this research verified that SFTSV infection was significantly inhibited, but not completely blocked, due to the deletion of CLTC protein. Our research also found that lipid raft inhibitor Filipin, other than macropinocytosis inhibitor EIPA, could significantly reduce SFTSV infection, and the inhibition was more obviously observed when Filipin was used in CLTC knockout cells. These result indicated that clathrin-dependent and lipid raft mediated endocytosis are the major two mode used by SFTSV entry. In conclusion, this study constructed a CLTC knockout cell line, which, for the first time, established a cell model for the study of the function of CLTC protein, and provided direct evidence that SFTSV pendent could still infect cells without clathrin. Additionally, we confirmed that lipid raft mediated endocytosis, as a clathrin-independent pathway, could be another key mode for SFTSV entry., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Streptococcus suis is a zoonotic pathogen that causes invasive infections in humans and pigs. Herein, we performed genomic analysis of seven S. suis serotype 4 strains belonging to clonal complex (CC) 94 that were recovered from a human patient or from diseased and clinically healthy pigs. Genomic exploration and comparisons, as well as in vitro cytotoxicity tests, indicated that S. suis CC94 serotype 4 strains are potentially virulent. Genomic analysis revealed that all seven strains clustered within minimum core genome group 3 (MCG-3) and had a high number of virulence-associated genes similar to those of virulent serotype 2 strains. Cytotoxicity assays showed that both the human lung adenocarcinoma cell line and HeLa cells rapidly lost viability following incubation for 4 h with the strains at a concentration of 106 bacterial cells. The human serotype 4 strain (ID36054) decreased cell viability profoundly and similarly to the control serotype 2 strain P1/7. In addition, strain ST1689 (ID34572), isolated from a clinically healthy pig, presented similar behaviour in an adenocarcinoma cell line and HeLa cells. The antimicrobial resistance genes tet(O) and ermB that confer resistance to tetracyclines, macrolides, and lincosamides were commonly found in the strains. However, aminoglycoside and streptothricin resistance genes were found only in certain strains in this study. Our results indicate that S. suis CC94 serotype 4 strains are potentially pathogenic and virulent and should be monitored., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Hatrongjit et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

THP-1 monocyte, which can be differentiated into macrophages by PMA, is widely used in researches on pathogen infection and host innate immunity, but reports on the induction methods of PMA are different and lack a unified standard, and the transcriptome characteristics of macrophage compared with THP-1 cells remains unclear. In this research, we examined the differentiation effect of three factors including induction time, cell seeding density and PMA concentration by detecting the positive rate of CD14 expression. The concentration of 80ng/ml of PMA, the induction time of 24h, and the cell seeding density of 5×105 cells/ml, could respectively facilitates a relatively higher CD14 positive rate in THP-1 cells. Under this optimized conditions, the CD14 positive rate of THP-1 cells can reach 66.52%. Transcriptome sequencing showed that after the above induction, the mRNA expression of 3113 genes which were closely related to cell communication, signal transduction, cell response to stimulus, signaling receptor binding and cytokine activity were up-regulated, and the top 10 genes were RGS1, SPP1, GDF15, IL-1B, HAVCR2, SGK1, EGR2, TRAC, IL-8 and EBI3. While the mRNA expression of 2772 genes which were associated with cell cycle process, DNA binding and replication and cell division, were down-regulated, and the top genes were SERPINB10, TRGC2, SERPINB2, TRGC1, MS4A3, MS4A4E, TRGJP1, MS4A6A, TRGJP2, MS4A4A. This research optimized the induction method on THP-1 cell differentiation from three aspects and delineated the transcriptomic profile of PMA-induced THP-1 cells, laying a foundation for the construction method of cell model and for the functional study of macrophage., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: Reducing the prevalence of treatment failure among people living with HIV (PLHIV) on highly active antiretroviral therapy (HAART) is crucial for improving individual health and reducing disease burden. This study aimed to assess existing evidence on treatment failure and its associated factors among PLHIV in mainland China., Methods: We conducted a comprehensive search of PubMed, Web of Science, Cochrane Library, WanFang, China National Knowledge Infrastructure, and SinoMed databases. Relevant studies on treatment failure among PLHIV in mainland China until September 2022 were searched, including cross-sectional, case-control, and cohort studies. The primary outcome was treatment failure, and secondary outcomes were the potential influencing factors of treatment failure. We performed a meta-analysis to pool each outcome of interest, including meta-regression, subgroup, publication bias, and sensitivity analyses., Results: A total of 81 studies were deemed eligible and included in the final meta-analysis. The pooled treatment failure prevalence among PLHIV in mainland China was 14.40% (95% confidence interval [CI]:12.30-16.63), of which the virological and immunological failure prevalence was 10.53% (95%CI:8.51-12.74) and 18.75% (95%CI:15.44-22.06), respectively. The treatment failure prevalence before and after 2016 was 18.96% (95%CI:13.84-24.67) and 13.19% (95%CI:10.91-15.64). Factors associated with treatment failure included good treatment adherence (odds ratio [OR] = 0.36, 95%CI:0.26-0.51), baseline CD4 counts>200 cells/μL (OR = 0.39, 95%CI:0.21-0.75), HAART regimens containing Tenofovir Disoproxil Fumarate (TDF) (OR = 0.70, 95%CI:0.54-0.92), WHO clinical stage III/IV (OR = 2.02, 95%CI:1.14-3.59) and age≥40 years (OR = 1.56, 95%CI:1.23-1.97)., Conclusion: The prevalence of treatment failure among PLHIV receiving HAART in mainland China was low and tended to decline. Poor adherence, low baseline CD4 count, HAART regimens without TDF, advanced clinical stage, and old age were contributing factors for treatment failure. Relevant intervention programs are needed with increasing treatment adherence through behavioral intervention or precise intervention targeting older adults., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Niu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: In Guangxi province of China, there is a high prevalence of HIV in the general population and in men who have sex with men (MSM). However, there is still a low proportion of MSM among people living with HIV. This apparent contradiction could be due to the high proportion of potential non-disclosed MSM (pnMSM) among reported heterosexual men. We analyzed the genetic linkage of HIV specimens to address this problem aiming to (1) identify the optimal genetic distance threshold, which gave the highest number of genetic clusters, (2) document the proportion of potential non-disclosed MSM (pnMSM) among self-reported heterosexual men, and (3) determine predictors for pnMSM., Methods: Pairwise genetic distances were computed among all samples. The genetic distance threshold giving the highest number of genetic clusters was identified. Self-reported heterosexual men were identified as belonging to the pnMSM group if they could be linked to any MSM in their cluster. Multinomial logistic regression was used to determine associated factors of being pnMSM., Results: The optimal genetic distance threshold was 0.75% substitutions/site. Among 896 self-reported heterosexual men, the frequency (percentage and 95% confidence interval) was 62 (6.9%, 5.2-8.6%) for pnMSM, 779 (86.9%, 84.7-89.1%) for indeterminate men and 55 (6.1%, 4.5-7.7%) for potential heterosexual men, respectively. Self-reported heterosexual men who were younger, single and more educated were more likely to be pnMSM., Conclusion: Based on these findings, there is a need to pay more attention to sexually active, young and educated self-reported heterosexual men and provide them with voluntary counselling and testing and specific HIV prevention services., Competing Interests: NO authors have competing interests, (Copyright: © 2023 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: Growing evidence suggests that alcohol consumption is a risk factor for hearing loss; however, the evidence has been inconsistent. This systematic review and meta-analysis aimed to evaluate the effect of alcohol consumption on hearing loss., Methods: We searched several databases up to November 2021, for published articles using the keywords "alcohol drinking" and "hearing loss". Two investigators independently conducted the study selection and data extraction. Based on the results of the heterogeneity analysis (Q statistic and I2 statistic), a fixed- or random-effects model was used to calculate the pooled odds ratios (ORs). Subgroup and sensitivity analyses were performed to assess the potential sources of heterogeneity and robustness of the pooled estimation. Publication bias in the literature was evaluated using Egger's test., Results: In total, 18 (9 cross-sectional, 5 case-control, and 4 cohort) observational studies were identified in this search; 27,849 participants were included. Compared with non-drinkers, the pooled OR of drinkers was 1.22 (95% confidence interval: 1.09-1.35)., Conclusion: Evidence suggests a positive association between alcohol consumption and hearing loss. Drinkers were at a higher risk than non-drinkers. Drinking limitations may be useful for preventing hearing loss., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Qian et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Hepatitis B is a major global public health threat. According to China's National Notifiable Disease Reporting System (NNDRS), Gannan Tibetan Autonomous Prefecture (Gannan) had the highest incidence of hepatitis B in Gansu Province during 2004 to 2016. We evaluated NNDRS hepatitis B case reports from Gannan to determine accuracy of diagnosis and to understand factors associated with inaccuracy. We reviewed medical records with hepatitis B diagnosis hospitalized in seven county hospitals in Gannan between January 1, 2016 and July 31, 2017. Using national "Classification and Diagnostic Procedures for Hepatitis B," we independently reclassified the diagnoses. We determined the positive predictive value (PPV) of reported hepatitis B cases. We investigate clinicians' understanding of the diagnostic and reporting criteria for hepatitis B by questionnaire. We reviewed and re-categorized 400 inpatients reported. Sixteen cases had been reported as acute hepatitis B, but on re-categorization, none were acute hepatitis B cases. PPVs for chronic hepatitis B and unclassified hepatitis B cases were 66% and 15% respectively; 327 (82%) of the reported hepatitis B cases were inaccurately classified; 261 were carriers, 59 were reported previously, and 7 did not have hepatitis B. The actual incidence of hepatitis B in Gannan in 2016 was estimated to be 19/100,000, significantly below the reported incidence of 106/100,000. Among reported cases, 81% had been tested for Alanine aminotransferase, 52% for hepatitis C antibody, 80% with liver ultrasound, 32% for hepatitis A antibody, and 7% for hepatitis B virus (HBV) DNA. Not all cases were tested for anti-HBc IgM or hepatitis E antibody or had a liver biopsy. In the knowledge test, 56% of clinicians accurately diagnosed three simulated cases of acute hepatitis B, and 17% correctly diagnosed two simulated cases chronic hepatitis B; 22% knew that "a client with only HBsAg positivity need not be reported." The falsely high incidence in Gannan was due to diagnostic and reporting inaccuracies. We recommend that clinicians and laboratorians receive additional training in hepatitis B diagnostic criteria and reporting standards, including appropriate use of IgM anti-HBc tests. Hepatitis B surveillance data should be periodically reviewed and evaluated for accuracy., Competing Interests: he authors have declared that no competing interests exist.

Objective: Smoking and obesity are established risk factors of dyslipidemia, however, the interplay between them has not been well studied. This study aims to explore the joint effect of smoking and body mass index (BMI) on serum lipid profiles., Methods: The study consisted of 9846 Chinese adults (mean age = 49.9 years, 47.6% males, 31.2% ever smokers), based on the China Health and Nutrition Survey. Serum lipid profiles included total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein A (APO-A), and apolipoprotein B (Apo-B). The joint effect of smoking and BMI on serum lipids were examined by the four-way decomposition analysis and multivariate linear regression models., Results: The four-way decomposition showed that the interplay between smoking and BMI was complicated. There was only indirect effect (the mediated effect) between smoking and BMI on TC, LDL-C and APO-B. The pure indirect effect was -0.023 for TC, -0.018 for LDL-C, and -0.009 for APO-B. For TG, HDL-C and APO-A, the interaction effect was dominant. The reference interaction (the interactive effect when the mediator is left to what it would be in the absence of exposure) was 0.474 (P < 0.001) for TG, -0.245 (P = 0.002) for HDL-C, and -0.222 (P < 0.001) for APO-A, respectively. The effect of BMI on TG, HDL-C and APO-A were significantly higher in smokers than in nonsmokers (TG: 0.151 in smokers versus 0.097 in nonsmokers, HDL-C: -0.037 versus -0.027, APO-A: -0.019 versus -0.009, P for difference < 0.001 for all)., Conclusion: These findings illustrate the joint effects of smoking and BMI on serum lipid profiles. There were significant interaction effects of smoking and BMI on TG, HDL-C and APO-A, while BMI maybe a mediator for the association of smoking with TC, LDL-C and APO-B. The effects between them were rather complex. Smoking cessation is necessary, especially for those overweight., Competing Interests: The authors have declared that no competing interests exist.

To control the HIV/AIDS epidemics in Guangxi Zhuang Autonomous Region in China, Guangxi government launched the 5-year Guangxi AIDS Conquering Project (GACP, Phase I: 2010-2014, Phase II: 2015-2020). In the project, three measures are implemented, such as great improvements of the coverage of HIV/AIDS education, promotion of HIV voluntary counseling and testing, and enhancement of antiretroviral treatment. In this paper, we explore the effects of the three measures of GACP by construction of a Susceptible-Infected-Diagnosed-Treated population compartments model and via evaluation of the basic reproduction number derived from the model. A computational framework is developed for estimating the model parameters based on the HIV surveillance data, with application of the Markov-Chain Monte-Carlo method and Nonlinear Least Squares method. By estimating the new infections and evaluating the basic reproduction number, we find that the implementation of the three measures of GACP has a significant effect on controlling the rise of HIV/AIDS cases and the epidemic trend. Compared with HIV voluntary counseling and testing, strengthening HIV/AIDS education and expanding the coverage of antiretroviral treatment show a greater impact on HIV/AIDS epidemic control, which provides a reference project for other provinces with a similar epidemic situation in Guangxi Zhuang Autonomous Region. At the same time, our research fills the current research gap for the evaluation of large-scale AIDS prevention and control projects in developing areas., Competing Interests: The authors have declared that no competing interests exist.

Background: Helicobacter pylori (H. pylori) encodes numerous outer membrane proteins (OMPs), with considerable geographic heterogeneity and related to different clinical outcomes. This study aimed to investigate the distribution characteristics of five important OMP genes (sabA, hofC, homA, homB and frpB-4) in different regions of China., Materials and Method: A total of 266 strains were isolated from 348 stomach biopsy specimens in Shandong, Guangxi, Heilongjiang, Hunan, and Qinghai provinces. The presence of sabA, hofC, homA, homB and frpB-4 gene was detected by polymerase chain reaction (PCR) from H. pylori genomic DNA., Results: Among the strains in five regions, the prevalence of frpB-4 was 100% and that of hofC was 97.7%. The prevalence of homB in the isolates from Qinghai (45.5%) was significantly lower than that in Shandong (75.3%), Guangxi (76.9%) and Hunan (69.6%) (P<0.05). The frequency of homA in Shandong (30.1%) was significantly lower than in Guangxi (57.7%) and Qinghai (63.6%) (P<0.05). The prevalence of the sabA gene in Shandong, Guangxi, Heilongjiang, Hunan and Qinghai provinces was 21.9%, 59.7%, 45.9%, 52.2%, and 18.2%, respectively (P<0.05). The sabA "on" status was significantly more frequent in isolates from Guangxi (46.8%), Heilongjiang (37.8%), and Hunan (47.8%) than Qinghai (3.0%) (P<0.05). The presence of homA and sabA genes may be negatively correlated with the development of gastritis. There was no significant association between the frpB-4, hofC, homB gene and clinical outcomes., Conclusion: The prevalence of homA, homB, and sabA genes and the sabA "on" or "off" status have significant geographical differences among five provinces in China. The presence of homA and sabA genes may be protective factors of gastritis., Competing Interests: The authors have declared that no competing interests exist.

The prevalence and molecular characteristics of Bartonella infections in small rodents in the Zhongtiao Mountain, China have been explored. In this study, the liver, spleen and kidney tissues of captured rodents were used for Bartonella spp. detection and identification by combination of real-time PCR of transfer-mRNA (ssrA) gene and traditional PCR and sequencing of citrate synthase (gltA) gene. It was shown that 49.52% of the rodents (52/105) were positive for Bartonella spp.. The infection rate in different gender (χ2 = 0.079, P = 0.778) and tissues (χ2 = 0.233, P = 0.890) of small rodents did not have statistical difference, but that in different small rodents (Fisher's exact test, P < 0.001) and habitats (χ2 = 5.483, P = 0.019) had statistical difference. And, the sequencing data suggests that Bartonella sequences (n = 31) were identified into three species, including 14 of B. grahamii, 3 of B. queenslandensis and 14 of unknown Bartonella species. Phylogenetic analysis showed that B. grahamii sequences were clustered with the isolates from South Korea and China, and B. queenslandensis sequences were mainly closely related to the isolates from China and Thailand. The genetic diversity analysis showed that B. grahamii and B. queenslandensis sequences exhibited noticeable intraspecies diversity. Taken together our data demonstrates the high prevalence and genetic diversity of Bartonella infections in small rodents in the Zhongtiao Mountain, especially a potential novel Bartonella specie was detected, which could benefit the prevention and control of rodent-Bartonella species in this area., Competing Interests: The authors have declared that no competing interests exist.

The development of human respiratory syncytial virus (hRSV) vaccine has been hampered by the risk of enhanced respiratory disease (ERD) which was induced by highly skewed toward Th2 immune response. In our previous study, we expressed the recombinant pre-F protein using Escherichia coli BL21, called RBF. To verify if the RBF protein could cause ERD, we tested the immunogenicity and safety of RBF with a commercial alum adjuvant (GMP-grade Adju-Phos). RBF alone and RBF/Adju-Phos elicited long-lasting protective antibodies and a cellular immune response in mice after three immunizations. Unfortunately, compared with the mice in RBF group, mice in RBF/Adju-Phos generated a serious Th2 humoral immune response that elicited Th2-mediated lung pathology. From the IL-4+:IFNγ+ ratio, there was also a robust Th2 cellullar immunologic response in the RBF/Adju-Phos group. This study demonstrates that it may not be enough for RBF to increase the titer of neutralizing antibodies. A balanced immune response must be induced for hRSV vaccine safety., Competing Interests: The authors have declared that no competing interests exist.

Objectives: This study intends to build and compare two kinds of forecasting models at different time scales for hemorrhagic fever incidence in China., Methods: Autoregressive Integrated Moving Average (ARIMA) and Long Short-Term Memory Neural Network (LSTM) were adopted to fit monthly, weekly and daily incidence of hemorrhagic fever in China from 2013 to 2018. The two models, combined and uncombined with rolling forecasts, were used to predict the incidence in 2019 to examine their stability and applicability., Results: ARIMA (2, 1, 1) (0, 1, 1)12, ARIMA (1, 1, 3) (1, 1, 1)52 and ARIMA (5, 0, 1) were selected as the best fitting ARIMA model for monthly, weekly and daily incidence series, respectively. The LSTM model with 64 neurons and Stochastic Gradient Descent (SGDM) for monthly incidence, 8 neurons and Adaptive Moment Estimation (Adam) for weekly incidence, and 64 neurons and Root Mean Square Prop (RMSprop) for daily incidence were selected as the best fitting LSTM models. The values of root mean square error (RMSE), mean absolute error (MAE) and mean absolute percentage error (MAPE) of the models combined with rolling forecasts in 2019 were lower than those of the direct forecasting models for both ARIMA and LSTM. It was shown from the forecasting performance in 2019 that ARIMA was better than LSTM for monthly and weekly forecasting while the LSTM was better than ARIMA for daily forecasting in rolling forecasting models., Conclusions: Both ARIMA and LSTM could be used to build a prediction model for the incidence of hemorrhagic fever. Different models might be more suitable for the incidence prediction at different time scales. The findings can provide a good reference for future selection of prediction models and establishments of early warning systems for hemorrhagic fever., Competing Interests: The authors have declared that no competing interests exist.

Huangjiu is a national alcoholic beverage in China. Millet has congenital advantages in development and utilization of nutrient. Brewing Huangjiu with millet can increase the value of millet. Microbial community plays crucial roles in millet Huangjiu fermentation. Flavor compounds reflect the quality and health function of Huangjiu. The flavor compounds of Huangjiu are complex and their formation is closely associated with microorganisms, but the relationship between them during fermentation has been unknown. In this research, this relationship during millet Huangjiu fermentation were deeply investigated. Totally 86 volatile compounds were detected. Bacillus, Weissella, Paenibacillus, Klebsiella, Prevotella was investigated as the dominant microbes through high-throughput sequencing. 537 correlations between major flavor compounds and microbes were established to reflect the dynamic change during millet Huangjiu fermentation. The top five dominant genus of flavor producing microbes were Chryseobacterium, Sporolactobacillus, Psychrobacter, Sphingobium and Anoxybacillus. The content of malic acid and citric acid was gradually improved all through the millet Huangjiu fermentation. Malic acid and citric acid generated from millet Huangjiu fermentation shows healthy properties as liver protection and eliminating fatigue. Our research provides essential information on microbial community succession and the flavor formation during millet Huangjiu fermentation, and beneficial for development of Huangjiu products., Competing Interests: The authors have declared that no competing interests exist.

Background: China's National Free Antiretroviral Treatment Program (NFATP) has substantially reduced morbidity and HIV/AIDS incidence since 2003. However, HIV resistance to antiretroviral drugs (ARVs) has been a major challenge for the current treatment of HIV/AIDS in China., Methods: In the current study, we established a nested dynamic model to predict the multi-drug resistance dynamics of HIV among the heterosexual population and evaluated the impact of intervention measures on the transmission of drug resistance. We obtained an effective reproductive number [Formula: see text] from each sub-model held at different stages of the dynamic model. Meanwhile, we applied Bayesian phylogenetic methods to infer the weighted average effective reproductive number [Formula: see text] from four HIV subtypes that sampled from 912 HIV-positive patients in China. It is an original and innovative method by fitting [Formula: see text] to [Formula: see text] by Markov Chain Monte Carlo (MCMC) to generate unknown parameters in [Formula: see text]., Results: By analyzing the HIV gene sequences, we inferred that the most recent common ancestor of CRF01AE, CRF07BC, CRF08BC, and CRFBC dated from 1994, 1990, 1993 and 1990, respectively. The weighted average effective reproductive number [Formula: see text] dropped from 1.95 in 1994 to 1.73 in 2018. Considering different interventions, we used a macro dynamic model to predict the trend of HIV resistance. The results show that the number of new infections and total drug resistance under the baseline parameter (S1) are 253,422 and 213,250 in 2025, respectively. Comparing with the numbers under the target treatment rate (S2), they were 219,717 and 236,890, respectively. However, under the ideal treatment target (S3, the treatment rate reaches 90% and the treatment success rate reaches 90%), the number of new infections shows a declining trend and will decrease to 46,559 by 2025. Compared with S1 and S2, the total number of resistance also decreased to 160,899 in 2025., Conclusion: With the promotion of NFATP in China, HIV resistance to ARVs is inevitable. The strategy of increasing the treatment rate would not only ineffectively curb the epidemic, but also deteriorate drug resistance issue. Whereas, a combination of intervention strategies (the treatment rate reaches 90% and the treatment success rate reaches 90%) can greatly reduce both infection and drug resistance rate than applying one strategy alone., Competing Interests: We declare there is no conflict of interest.

Background: China is vulnerable to zoonotic disease transmission due to a large agricultural work force, sizable domestic livestock population, and a highly biodiverse ecology. To better address this threat, representatives from the human, animal, and environmental health sectors in China held a One Health Zoonotic Disease Prioritization (OHZDP) workshop in May 2019 to develop a list of priority zoonotic diseases for multisectoral, One Health collaboration., Methods: Representatives used the OHZDP Process, developed by the US Centers for Disease Control and Prevention (US CDC), to prioritize zoonotic diseases for China. Representatives defined the criteria used for prioritization and determined questions and weights for each individual criterion. A review of English and Chinese literature was conducted prior to the workshop to collect disease specific information on prevalence, morbidity, mortality, and Disability-Adjusted Life Years (DALYs) from China and the Western Pacific Region for zoonotic diseases considered for prioritization., Results: Thirty zoonotic diseases were evaluated for prioritization. Criteria selected included: 1) disease hazard/severity (case fatality rate) in humans, 2) epidemic scale and intensity (in humans and animals) in China, 3) economic impact, 4) prevention and control, and 5) social impact. Disease specific information was obtained from 792 articles (637 in English and 155 in Chinese) and subject matter experts for the prioritization process. Following discussion of the OHZDP Tool output among disease experts, five priority zoonotic diseases were identified for China: avian influenza, echinococcosis, rabies, plague, and brucellosis., Conclusion: Representatives agreed on a list of five priority zoonotic diseases that can serve as a foundation to strengthen One Health collaboration for disease prevention and control in China; this list was developed prior to the emergence of SARS-CoV-2 and the COVID-19 pandemic. Next steps focused on establishing a multisectoral, One Health coordination mechanism, improving multisectoral linkages in laboratory testing and surveillance platforms, creating multisectoral preparedness and response plans, and increasing workforce capacity., Competing Interests: The authors have declared that no competing interests exist.

Sales data in China indicate that slim cigarette consumption has increased dramatically over the last few years. This study examined who smoked slim cigarettes and the reasons for adopting these new products. A survey of an online panel from 19 Chinese cities was conducted from October 2018 to April 2019 with 20,055 members aged 16 and older. Among the 31.7% [95% confidence interval (CI) = 30.1-33.4] of panel members who reported currently smoking, 37.7% (95% CI = 34.8-40.5) smoked slim cigarettes. Among smokers, women were significantly more likely to smoke slim cigarettes than men [56.5% (95% CI = 50.8-62.2) vs. 35.5% (95% CI = 32.8-38.1)]. Smokers with a bachelor's degree were more likely to smoke slim cigarettes than those without [41.3% (95% CI = 38.1-44.4) vs. 33.1% (95% CI = 30.0-36.1)]. Most slim cigarette smokers were dual smokers [77.7% (95% CI = 75.3-80.1)], smoking both regular and slim cigarettes. Among dual smokers, 97.5% (95% CI = 96.7-98.3) started smoking regular cigarettes before slim cigarettes. Of the many reasons given for smoking slim cigarettes, 37.0% (95% CI = 34.3-39.7) directly related to harm reduction with another 10.1% (95% CI = 8.4-11.7) reporting their reason as wanting "to reduce consumption of regular cigarettes," a plausible indication of harm reduction. These findings suggest strong interest in harm reduction among the current Chinese smoking population and that the popularity of slim cigarettes is likely to increase, with the more educated as the early adopters. Given the absence of any evidence that these products actually reduce harm, it is urgent that the public health community be on high alert in order to avoid repeating the sad history of low-tar cigarettes, when a supposed harm-reduction product misled the field of tobacco control., Competing Interests: The authors have declared that no competing interests exist.

Japanese encephalitis (JE) is an acute infectious disease caused by the Japanese encephalitis virus (JEV) and is transmitted by mosquitoes. Meteorological conditions are known to play a pivotal role in the spread of JEV. In this study, a zero-inflated generalised additive model and a long short-term memory model were used to assess the relationship between the meteorological factors and population density of Culex tritaeniorhynchus as well as the incidence of JE and to predict the prevalence dynamics of JE, respectively. The incidence of JE in the previous month, the mean air temperature and the average of relative humidity had positive effects on the outbreak risk and intensity. Meanwhile, the density of all mosquito species in livestock sheds (DMSL) only affected the outbreak risk. Moreover, the region-specific prediction model of JE was developed in Chongqing by used the Long Short-Term Memory Neural Network. Our study contributes to a better understanding of the JE dynamics and helps the local government establish precise prevention and control measures., Competing Interests: The authors have declared that no competing interests exist.

Background: In October 2016, a senior high school student was diagnosed with sputum-smear positive [SS(+)] pulmonary tuberculosis (TB). We conducted an investigation of an outbreak in the school, including among students and teachers diagnosed with latent TB, who we followed until July 2019., Methods: We defined latent TB infection (LTBI) as a tuberculin skin test (TST) induration of 15mm or larger; probable TB as a chest radiograph indicative of TB plus productive cough/hemoptysis for at least 2 weeks, or TST induration of 15mm or larger; and confirmed TB as two or more positive sputum smears or one positive sputum smear plus a chest radiograph indicative of TB or culture positive with M. tuberculosis. We conducted mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) typing based on 24 loci in the isolates., Results: Between October 2016 and July 2019, we identified 52 cases, including nine probable, six confirmed, and 37 LTBI cases. The index case-student had attended school continuously despite having TB symptoms for almost three months before being diagnosed with TB. We obtained three isolates from classmates of the index case in 2016; all had identical MIRU-VNTR alleles with the index case. The LTBI rate was lower among students (7.41%, 30/405) than among teachers (26.92%, 7/26) (rate ratio [RR] = 0.28, 95% confidential interval [CI]: 0.13-0.57). Among the 17 students who had latent TB and refused prophylaxis in October 2016, 23.53% (4/17) became probable/confirmed cases by July 2019. None of the six teachers who also refused prophylaxis became probable or confirmed cases. Of the 176 students who were TST(-) in October 2016, 1.70% (3/176) became probable/confirmed cases, and among the 20 teachers who were TST(-), 1 became a probable case., Conclusions: Delayed diagnosis of TB in the index patient may have contributed to the start of this outbreak; lack of post-exposure chemoprophylaxis facilitated spread of the outbreak. Post-exposure prophylaxis is strongly recommended for all TST-positive students; TST-negative students exposed to an SS(+) case should be followed up regularly so that prophylaxis can be started if LTBI is detected., Competing Interests: The authors have declared that no competing interests exist.

Background: The effects of multiple meteorological factors on influenza activity remain unclear in Chongqing, the largest municipality in China. We aimed to fix this gap in this study., Methods: Weekly meteorological data and influenza surveillance data in Chongqing were collected from 2012 to 2019. Distributed lag nonlinear models (DLNMs) were conducted to estimate the effects of multiple meteorological factors on influenza activity., Results: Inverted J-shaped nonlinear associations between mean temperature, absolute humidity, wind speed, sunshine and influenza activity were found. The relative risks (RRs) of influenza activity increased as weekly average mean temperature fell below 18.18°C, average absolute humidity fell below 12.66 g/m3, average wind speed fell below 1.55 m/s and average sunshine fell below 2.36 hours. Taking the median values as the references, lower temperature, lower absolute humidity and windless could significantly increase the risks of influenza activity and last for 4 weeks. A J-shaped nonlinear association was observed between relative humidity and influenza activity; the risk of influenza activity increased with rising relative humidity with 78.26% as the break point. Taking the median value as the reference, high relative humidity could increase the risk of influenza activity and last for 3 weeks. In addition, we found the relationship between aggregate rainfall and influenza activity could be described with a U-shaped curve. Rainfall effect has significantly higher RR than rainless effect., Conclusions: Our study shows that multiple meteorological factors have strong associations with influenza activity in Chongqing, providing evidence for developing a meteorology-based early warning system for influenza to facilitate timely response to upsurge of influenza activity., Competing Interests: The authors have declared that no competing interests exist.

Enterovirus A71 (EV-A71) has emerged as a clinically important neurotropic virus following poliovirus eradication. Recent studies have shown that human tonsillar epithelial cell lines (UT-SCC-60A and UT-SCC-60B) were susceptible to EV-A71, suggesting that human tonsillar crypt epithelium could be important in EV-A71 pathogenesis. However, the mechanism about how EV-A71 infects the upper oro-digestive tract remains largely unclear. In this study, we demonstrated that the human tonsillar epithelial cells infected with EV-A71 underwent apoptotic, in which cytochrome c was released from the mitochondria to the cytosol and caspase-9 was activated, while caspase-2 and -8 were not cleaved or activated during the infection. A selective inhibitor of caspase-9, Z-LEHD-FMK, inhibited the cleavage of the executioner caspase-3 and -7, indicating that only mitochondria-mediated intrinsic apoptotic pathway was activated in EV-A71-infected tonsillar epithelial cells. No evidence of pyroptosis or necroptosis was involved in the cell death. EV-A71 infection induced interferon, pro-inflammatory cytokines and chemokines, including IFN-β, IL-6, CCL5, and TNF-α in tonsillar epithelial cells, which may play a critical role in EV-A71-caused herpangina. Our data indicated that the induction of the cytokines was partially regulated by the mitogen-activated protein kinases (MAPKs) signaling pathway. The findings unveiled the host response to EV-A71 and its regulation mechanism, and will further our understanding the significance about the tonsillar crypt epithelium as the initial and primary portal in viral pathogenesis for EV-A71 infection., Competing Interests: We have read the journal’s policy and there is no competing conflict of interest.

Introduction: The ST-4821 complex (cc4821) is a leading cause of serogroup C and serogroup B invasive meningococcal disease in China where diverse strains in two phylogenetic groups (groups 1 and 2) have acquired fluoroquinolone resistance. cc4821 was recently prevalent among carriage isolates in men who have sex with men in New York City (USA). Genome-level population studies have thus far been limited to Chinese isolates. The aim of the present study was to build upon these with an extended panel of international cc4821 isolates., Methods: Genomes of isolates from Asia (1972 to 2017), Europe (2011 to 2018), North America (2007), and South America (2014) were sequenced or obtained from the PubMLST Neisseria database. Core genome comparisons were performed in PubMLST., Results: Four lineages were identified. Western isolates formed a distinct, mainly serogroup B sublineage with alleles associated with fluoroquinolone susceptibility (MIC <0.03 mg/L) and reduced penicillin susceptibility (MIC 0.094 to 1 mg/L). A third of these were from anogenital sites in men who have sex with men and had unique denitrification gene alleles. Generally 4CMenB vaccine strain coverage was reliant on strain-specific NHBA peptides., Discussion: The previously identified cc4821 group 2 was resolved into three separate lineages. Clustering of western isolates was surprising given the overall diversity of cc4821. Possible association of this cluster with the anogenital niche is worthy of monitoring given concerns surrounding antibiotic resistance and potential subcapsular vaccine escape., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: JL, XB and RB perform contract research on behalf of Public Health England for GlaxoSmithKline, Pfizer, and Sanofi Pasteur. GT has performed contract research on behalf of the School of Public Health, University of West Attica for GlaxoSmithKline and Pfizer. This does not alter our adherence to PLOS ONE policies on sharing data and materials. BZ, JJG, YG, RM, KJS, AS, PS, BS, PT, LX, ZS declare no conflicts of interest.

Background: In China, an indigenously developed electronic medication monitor (EMM) was used. EMM recorded each time the device was opened (no real time data), offering an indirect measure of tuberculosis treatment adherence. Previous study in China showed that the EMM uptake was satisfactory, missing adherence data were common in the information management system (25%) and shift to directly observed therapy (DOT) based on poor adherence documented by EMMs were seldom., Objectives: Among people with tuberculosis notified in 30 counties (July-December 2018) where EMM supported self-administered therapy (SAT) was suggested to all eligible (no communication impairment, ambulatory), we assessed the relative differences in unfavourable outcomes and deaths among those started on EMM at baseline (within first month of diagnosis) when compared to SAT alone., Methods: This was a cohort study using secondary data. We employed an intention to treat analysis, and used modified Poisson regression with robust variance estimates to assess the association., Results: Of 1810 eligible people, 1047 used EMM at baseline and of them, 216 (20.1%) stopped using EMM midway. Of 763 people who did not use EMM at baseline, 267 (35.0%) started using EMM later during the treatment. Among those who started using EMM at baseline, 6.3% [95% CI: 4.9, 8.0] had unfavourable outcomes compared to 6.7% [95% CI: 5.1, 8.8] among those who did not (p = 0.746). Lesser deaths were observed in people who started EMM at baseline when compared to those who did not: 2.5% [95% CI: 1.7, 3.7] versus 3.5% [95% CI: 2.4, 5.2], p = 0.191. The lack of association remained after adjusting for potential confounders (occupation, TB classification and TB category)., Conclusion: Under programmatic settings, we did not find significant differences in the outcomes. Optimization of EMMs by shifting to DOT when indicated, addressing the issue of missing data and ensuring continuous use is required., Competing Interests: The authors have declared that no competing interests exist.

Background: Border areas are at high risk of measles epidemics. This study aimed to evaluate the effectiveness of the implementation of the routine two-dose measles containing vaccine (MCV) program in border counties of Southwest China., Methods: Data used in the study were derived from a cross-sectional survey among 1,467 children aged 8 to 84 months from five border counties of Yunnan Province, Southwest China in 2016. The participants were recruited using a multistage sampling method. Primary guardians of the children were interviewed to collect information on vaccination history, socio-economic status, and knowledge about immunization. Both coverage and timely coverage for the first (MCV1) and the second (MCV2) dose of MCV were calculated. The Kaplan-Meier method was performed to estimate the cumulative coverage of MCV, and Log-rank tests were adopted to compare the differences across counties and birth cohorts. Univariate and multivariate logistic regression models were used to investigate the predictors of delayed MCV1 vaccination., Results: The coverage for MCV1 and MCV2 were 97.5% and 93.4%, respectively. However, only 63.8% and 84.0% of the children received MCV1 or MCV2 on time. Significant differences in the cumulative coverage were detected across counties and birth cohorts. Results of the multivariate logistic regression analysis indicated that children whose primary guardian knew the schedule of MCV were less likely to receive MCV1 late (OR = 0.63, P<0.01). For the guardians, doctors at vaccination units were the primary and also the most desired source of vaccination information., Conclusions: Although the coverage for MCV is high in border areas of Southwest China, the timeliness of MCV vaccination seems suboptimal. Tailored information from local health professionals may help to reduce untimely vaccination., Competing Interests: The authors have declared that no competing interests exist.

Background: The correlation between the infection of H. pylori and the occurrence of gastric MALT lymphoma (GML) has been well documented. However, the mechanism of how GML is caused by this bacterium is not well understood, although some immunologic mechanisms are thought to be involved., Materials and Methods: In this study, we performed both transcriptomic and proteomic analyses on gastric cancer cells infected by H. pylori isolates from GML patients and the gastric ulcer strain 26695 to investigate the differentially expressed molecular signatures that were induced by GML isolates., Results: Transcriptomic analyses revealed that the differentially expressed genes (DEGs) were mainly related to binding, catalytic activity, signal transducer activity, molecular transducer activity, nucleic acid binding transcription factor activity, and molecular function regulator. Fifteen pathways, including the Wnt signaling pathway, the mTOR signaling pathway, the NOD-like receptor signaling pathway and the Hippo signaling pathway, were revealed to be related to GML isolates. Proteomic analyses results showed that there were 116 differentially expressed proteins (DEPs). Most of these DEPs were associated with cancer, and 29 have been used as biomarkers for cancer diagnosis. We also found 63 upstream regulators that can inhibit or activate the expression of the DEPs. Combining the proteomic and transcriptomic analyses revealed 12 common pathways. This study provides novel insights into H. pylori-associated GML. The DEPs we found may be good candidates for GML diagnosis and treatment., Conclusions: This study revealed specific pathways related to GML and potential biomarkers for GML diagnosis., Competing Interests: The authors have declared that no competing interests exist.

EV-B93 is a novel serotype within the Enterovirus B species and is uncommon worldwide. Currently, only one full-length genomic sequence (the prototype strain) has been deposited in the GenBank database. In this study, three EV-B93 were identified, including one from an acute flaccid paralysis (AFP) patient (named 99052/XZ/CHN/1999, hereafter XZ99052) and two from healthy children (named 99096/XZ/CHN/1999 and 99167/XZ/CHN/1999, hereafter XZ99096 and XZ99167, respectively) from Tibet in 1999 during the polio eradication program. The identity between the nucleotide and amino acid sequences of the Tibet EV-B93 strain and the EV-B93 prototype strain is 83.2%-83.4% and 96.8%-96.9%, respectively. The Tibet EV-B93 strain was found to have greater nucleotide sequence identity in the P3 region to another enterovirus EV-B107 as per a phylogenetic tree analysis, which revealed that recombination occurred. Seroepidemiology data showed that EV-B93 has not produced an epidemic in Tibet and there may be susceptible individuals. The three Tibet EV-B93 strains are temperature-resistant with prognosticative virulence, suggesting the possibility of a potential large-scale outbreak of EV-B93. The analyzed EV-B93 strains enrich our knowledge about this serotype and provide valuable information on global EV-B93 molecular epidemiology. What is more, they permit the appraisal of the serotype's potential public health impact and aid in understanding the role of recombination events in the evolution of enteroviruses., Competing Interests: The authors have declared that no competing interests exist.

Background: Brief assessments of functional status for community-dwelling older adults are needed given expanded interest in the measurement of functional decline., Methods: As part of a 2015 prospective cohort study of older adults aged 60-89 years in Jiangsu Province, China, 1506 participants were randomly assigned to two groups; each group was administered one of two alternative 20-item versions of a scale to assess activities of daily living (ADL) and instrumental activities of daily living (IADL) drawn from multiple commonly-used scales. One version asked if they required help to perform activities (ADL-IADL-HELP-20), while the other version provided additional response options if activities could be done alone but with difficulty (ADL-IADL-DIFFICULTY-20). Item responses to both versions were compared using the binomial test for differences in proportion (with Wald 95% confidence interval [CI]). A brief 9-item scale (ADL-IADL-DIFFICULTY-9) was developed favoring items identified as difficult or requiring help by ≥4%, with low redundancy and/or residual correlations, and with significant correlations with age and other health indicators. We repeated assessment of the measurement properties of the brief scale in two subsequent samples of older adults in Hong Kong in 2016 (aged 70-79 years; n = 404) and 2017 (aged 65-82 years; n = 1854)., Results: Asking if an activity can be done alone but with difficulty increased the proportion of participants reporting restriction on 9 of 20 items, for which 95% CI for difference scores did not overlap with zero; the proportion with at least one limitation increased from 28.6% to 34.2% or an absolute increase of 5.6% (95% CI = 0.9-10.3%), which was a relative increase of 19.6%. The brief ADL-IADL-DIFFICULTY-9 maintained excellent internal consistency (α = 0.93) and had similar ceiling effect (68.1%), invariant item ordering (H trans = .41; medium), and correlations with age and other health measures compared with the 20-item version. The brief scale performed similarly when subsequently administered to older adults in Hong Kong., Conclusions: Asking if tasks can be done alone but with difficulty can modestly reduce ceiling effects. It's possible that the length of commonly-used scales can be reduced by over half if researchers are primarily interested in a summed indicator rather than an inventory of specific types of deficits., Competing Interests: The authors have read the journal’s policy and the authors of this manuscript have the following competing interests: BJC has received research funding unrelated to this study from Sanofi Pasteur (https://www.sanofi.com/en/your-health/vaccines). RP is a paid employee of Abt Associates (https://www.abtassociates.com/). There are no patents, products in development or marketed products associated with this research to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Little evidence from developing countries on dietary transition demonstrates the effects of comprehensive childhood obesity interventions on dietary diversity and food variety among younger children. This study aimed to evaluate the effects of comprehensive childhood obesity interventions on dietary diversity among younger children., Methods: A total of 4846 children aged 7-13 years were included based on a multicenter randomized controlled trial for childhood obesity interventions in 38 primary schools. Nutrition education intervention (NE), physical activity intervention (PA) and comprehensive intervention including both NE and PA (CNP) were carried out separately for 2 semesters. Dietary Diversity Score (DDS9 and DDS28 for 9 and 28 food groupings, respectively), Food Variety Score (FVS, the number of food items) and the proportions of different foods consumed were calculated according to the food intake records collected with the 24-h dietary recall method., Results: The intervention effects per day of comprehensive intervention group were 0 (95% Confidence Interval (CI): 0, 0.1; p = 0.382) on DDS9, 0.1 (95% CI: -0.1, 0.2; p = 0.374) on DDS28 and 0.1 (95% CI: -0.1, 0.3; p = 0.186) on FVS of overall diet, which was 0.1 (95% CI: 0, 0.1; p < 0.001) on DDS9, 0 (95% CI: 0, 0.1; p = 0.168) on DDS28 and 0.1 (95% CI: 0, 0.1; p = 0.067) on FVS of dietary scores of breakfast only. Additionally, CNP group had greater increases in cereals, meat and fruits, and more decreases in eggs, fish and dried legumes consumption proportions as compared with the control group. Decreasing side effect on dietary diversity and food variety were found for PA intervention, but not for NE intervention only., Conclusions: Though the comprehensive obesity intervention didn't improve the overall dietary diversity per day, the positive intervention effects were observed on breakfast foods and some foods' consumption., Competing Interests: The authors have declared that no competing interests exist.

Background and Objective: China carries a heavy burden of cervical cancer and has an alarmingly low cervical cancer screening rate. In order to achieve the goal of cervical cancer elimination, there is an urgent need for suitable methods and strategies in China., Materials and Methods: A total 9972 woman who received cervical cancer screening services of National Cervical Cancer Screening Program in Rural Areas (NCCSPRA) in 8 project counties participated in this study. TruScreen, HPV test and LBC test were performed in all participants. A total of 1945women had one or more than one positive or abnormal screening results of the above three screening tests subsequently received colposcopy. The detection rate of CIN2+ between the three tests were compared., Results: No matter what kind of screening method is used, the CIN2+ detection rate in the eastern regions was much higher than that in the central and western regions. The total detection rate of CIN2+ in HPV group was highest (0.73%), following in LBC group (0.44%) and TS group (0.31%). There was statistically significant difference in the total detection rate of CIN2+ between TS and HPV groups, LBC and HPV groups, respectively. There was no statistical difference in the total detection rate of CIN2+ between TS and LBC screening groups. Moreover, except for the eastern regions, there was no statistical difference in the detection rate of CIN2+ between TS group and the other two groups in central and western regions., Conclusion: If it can meet the requirements of the laboratory and personnel, HPV test seems to be the preferred method for cervical cancer screening in rural areas of China. The characteristics of minimal training requirements, simple operation, real-time results obtained without the collection of cervical cell samples and the help of laboratory equipment and cytologists of TS make it ideal for cervical cancer screening in low-resource regions., Competing Interests: The authors have declared that no competing interests exist.

Background: Measures to effectively expand tracing and testing to identify undiagnosed HIV infections are significant for the control of HIV/AIDS epidemic among men who have sex with men (MSM). We piloted a choice-based tracing and testing package aimed at improving partner tracing, uptake, and yield of HIV testing for sexual partners of newly diagnosed HIV-positive MSM., Methods: This package was piloted in the cities of Hangzhou and Ningbo, Zhejiang province, China from June 2014 to June 2016. The package adopted four modes: couples' HIV counseling and testing (CHCT), information assisted partner notification (IAPN), assisted HIV self-testing (HIVST) and patient referral. Data regarding sociodemographic factors and sexual behaviors between HIV-positive MSM and their sexual partners, as well as tracing and testing outcomes of each mode, were collected., Results: Among 2,495 newly diagnosed HIV-positive MSM, 446(18%) were enrolled as index cases (ICs) through two rounds of contact tracing. The ICs disclosed a total of 4,716 sexual partners, of whom 548 (12%) were reachable. The pilot study resulted in a testing uptake of 87% (478/548), and a yield of 16% (74/478) among sexual partners. The generalized linear mixed model showed that the odds of a reachable sexual partner enrolled via IAPN taking an HIV test were 290% greater than that of a partner traced via CHCT (95% CI: 1.6, 9.3)., Conclusions: A choice-based tracing and testing package can feasibly expand HIV testing uptake and case finding among sexual partners of HIV-positive MSM. IAPN may be an acceptable option to reach sexual partners for whom limited contact information is available., Competing Interests: The authors have declared that no competing interests exist.

To update the landscape analysis of vaccine injuries no-fault compensation programmes, we conducted a scoping review and a survey of World Health Organization Member States. We describe the characteristics of existing no-fault compensation systems during 2018 based on six common programme elements. No-fault compensation systems for vaccine injuries have been developed in a few high-income countries for more than 50 years. Twenty-five jurisdictions were identified with no-fault compensation programmes, of which two were recently implemented in a low- and a lower-middle-income country. The no-fault compensation programmes in most jurisdictions are implemented at the central or federal government level and are government funded. Eligibility criteria for vaccine injury compensation vary considerably across the evaluated programmes. Notably, most programmes cover injuries arising from vaccines that are registered in the country and are recommended by authorities for routine use in children, pregnant women, adults (e.g. influenza vaccines) and for special indications. A claim process is initiated once the injured party or their legal representative files for compensation with a special administrative body in most programmes. All no-fault compensation programmes reviewed require standard of proof showing a causal association between vaccination and injury. Once a final decision has been reached, claimants are compensated with either: lump-sums; amounts calculated based on medical care costs and expenses, loss of earnings or earning capacity; or monetary compensation calculated based on pain and suffering, emotional distress, permanent impairment or loss of function; or combination of those. In most jurisdictions, vaccine injury claimants have the right to seek damages either through civil litigation or from a compensation scheme but not both simultaneously. Data from this report provide an empirical basis on which global guidance for implementing such schemes could be developed., Competing Interests: The authors have declared that no competing interests exist.

Human adenovirus (HAdV-7) is a highly contagious pathogen that causes severe respiratory illnesses. However, the epidemic patterns and genetic variability of HAdV-7 circulating in mainland China have not been well elucidated. In this study, we used Chinese HAdV sentinel surveillance data obtained from 2012-2015 to investigate the clinical features of 122 HAdV-7-positive cases and performed amplification and sequence determination of three capsid genes (penton base, hexon, and fiber) from 69 isolated viruses covering from seven provinces of China. Additionally, we compared with data from representative sequences of 21 strains covering seven more provinces in China and 32 international HAdV-7 strains obtained from GenBank database to determine the phylogenetic, sequence variations, and molecular evolution of HAdV-7. The results indicated that HAdV-7 infection occurred throughout the year, and a high proportion of severe cases (27 cases, 22.1%) exhibited infantile pneumonia. Moreover, phylogenetic analysis showed that all HAdV-7 strains could be divided into two major evolutionary branches, including subtype 1 and subtype 2, and subtype 3 was also formed according to analysis of the penton base gene. Subtypes 1 and 2 co-circulated in China before 2008, and HAdV-7 strains currently circulating in China belonged to subtype 2, which was also the predominant strain circulating worldwide in recent years. Further sequence variation analysis indicated that three genes of HAdV-7 were relatively stable across time and geographic space, particularly for viruses within subtypes, which shared almost the same variation sites. Owing to continuous outbreaks caused by HAdV-7, resulting in increased illness severity and fatality rates in China, the establishment of a national HAdV surveillance system is urgently needed for the development of effective preventive and infection-control interventions for adenovirus respiratory infections in China., Competing Interests: The authors have declared that no competing interests exist.

Background: China piloted a digital adherence technology called electronic medication monitor (EMM) to support self-administered treatment for tuberculosis. EMM is a portable plastic box that records each time the device is opened, offering an indirect measure of treatment adherence. During the monthly patient visits to tuberculosis designated hospitals, the doctors access the data from the EMM., Objectives: Among people with tuberculosis notified in 30 counties in China (July-December 2018) where EMM supported self-administered treatment was suggested to all those eligible (no communication impairment, ambulatory care), we assessed the i) proportion eligible for using EMM ii) uptake of EMM and factors associated and iii) treatment adherence, including the proportion shifted to DOT., Methods: This was an observational study using secondary programme data. Single instance of ≥50% or continued instance of 20-49% monthly missed doses was the eligibility criteria to shift to DOT. We used log binomial regression to identify factors associated with not using EMM within first month., Results: Of 2227 with EMM eligibility data, 1810 (81%) were eligible for EMM. Of 1810 people, 1314 (73%) ever used EMM anytime during treatment, among them, 134 (10%) were eligible for shift to DOT (based on EMM data), and 29 (22%) were shifted. In addition, 70 were shifted while the EMM data was missing. Of 1047 people who started using EMM within first month, we observed 6381 person-months of follow up and there were 1526(25%) instances of missing EMM data. Children (<15 years), elderly (≥65 years), semi-skilled or unemployed people, people with tuberculosis pleurisy and previous tuberculosis treatment were less likely to use EMM within first month., Conclusion: The EMM uptake was satisfactory but shift to DOT has to be ensured based on adherence data from EMM. The subsequent follow-up action when EMM data is missing has to be clarified in the guidelines., Competing Interests: The authors have declared that no competing interests exist.

Background: Maternal mortality remains a major challenge to health systems in low and middle-incoming countries. Some pregnant women develop potentially life-threatening complications during childbirth. Therefore, home delivery is a precursor for maternal mortality. In this study, we aimed at not only estimating the percentage of deliveries occurring at home and examining the factors associated with home delivery, but we also explored the reasons for home delivery among women in rural Ghana., Methods: The study was conducted among mothers with delivery experience in selected communities in the Builsa South district located in the Upper East Region of Ghana. Both quantitative and qualitative data were collected using semi-structured questionnaires and Focus Group Discussion (FGD) guide respectively. A total of 456 mothers participated in this study. Regression models were used in the quantitative analysis whereas a thematic analysis approach was used to analyze the qualitative data., Results: Of the 423 mothers in the quantitative research, 38.1% (95% CI: 33.5-42.8) delivered their index child at home. In adjusted analysis, women who were not exposed to information (AOR = 13.64, p<0.001) and women with 2 (AOR = 4.64, p = 0.014), 3 (AOR = 4.96, p = 0.025) or at least 4 living children (AOR = 9.59, p = 0.001) had higher odds of delivering at home. From the qualitative analysis, the poor attitude of nurses (midwives), lack of, and cost of transportation, cost of delivery kits, and traditional beliefs and practices were cited as reasons for home delivery., Conclusion: Despite the government's efforts to provide free maternal care services to women in Ghana, a significant proportion of rural women still deliver at home due to other 'hidden costs'. Addressing poor staff attitude, transportation challenges, and negative traditional beliefs and practices through awareness creation may contribute to improving health facility delivery by rural pregnant women in Ghana., Competing Interests: The authors have declared that no competing interests exist

The performance of VereMTBTM Detection Kit for detection of multidrug-resistant tuberculosis (MDR-TB) was validated by using 124 sputum samples. Comparing with MGIT culture, the sensitivity and specificity of VereMTB Detection Kit for MTBC detection were 97.0% and 98.3%, respectively. Compared with MGIT DST, the sensitivity and specificity of VereMTB Detection Kit for RIF resistance detection were 85.7% and 93.9%, respectively, and the sensitivity and specificity of VereMTB Detection Kit for INH resistance detection were 75.0% and 95.7%, respectively. 6 NTM samples were also detected and identified correctly. The VereMTB Detection Kit can detect MDR-TB rapidly and accurately in sputum samples from TB suspects., Competing Interests: We have the following competing interests: Veredus Laboratories Pte Ltd provided support for this study in the form of VereMTB Detection Kit training, machine adjustment and maintenance. There are no patents, products in development or marketed products to declare. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials.

Background: In the World Health Organization Western Pacific Region (WHO WPRO), most adolescents enroll in secondary school. Safe, healthy and nurturing school environments are critical for adolescent health and development. Yet, there were no systematic reviews found on the efficacy of school-based interventions among adolescents living in low and middle income countries (LMIC) in the Region. There is an urgent need to identify effective school-based interventions and facilitating factors for successful implementation in adolescent health in WPRO., Methods: For this systematic review, we used five electronic databases to search for school-based interventions to promote adolescent health published from January 1995 to March 2019. We searched RCT and non-RCT studies among adolescents between 10 to 19 years old, done in LMIC of WHO WPRO, and targeted health and behaviour, school environment and academic outcomes. Quality of studies, risk of bias and treatment effects were analyzed. Effective interventions and implementation approaches were summarized for consideration in scale-up., Results: Despite a broad key term search strategy, we identified only eight publications (with 18,774 participants). Most of the studies used knowledge, attitudes and behaviours as outcome measures. A few also included changes in the school policy and physical environment as outcome measures while only one used BMI, waist circumference and quality of life as their outcome measures. The topics in these studies included: AIDS, sexual and reproductive health, de-worming, nutrition, obesity, tobacco use, and suicide. Some interventions were reported to be successful in improving knowledge, attitudes and behaviours, but their impact and scale were limited. The interventions used by the different studies varied from those that addressed a single action area (e.g. developing personal skills) or a combination of action areas in health promotion, e.g. developing a health policy, creating a supportive environment and developing personal skills. No intervention study was found on other important issues such as screening, counseling and developing safe and nurturing school environments., Conclusions: Only eight school-based health interventions were conducted in the Region. This study found that school-based interventions were effective in changing knowledge, attitudes, behaviors, healthy policies and environment. Moreover, it was clarified that policy support, involving multiple stakeholders, incorporating existing curriculum, student participation as crucial factors for successful implementation., Competing Interests: The authors have declared that no competing interests exist. The authors alone are responsible for the views expressed in this article and they do not necessarily represent the views, decisions or policies of the institutions with which they are affiliated.

Background: The development of a schistosome vaccine has proved challenging but we have suggested that characterisation of the self-cure mechanism in rhesus macaques might provide a route to an effective product. The schistosome esophagus is a complex structure where blood processing is initiated by secretions from anterior and posterior glands, achieved by a mixture of ~40 unique proteins. The mechanism of self-cure in macaques involves cessation of feeding, after which worms slowly starve to death. Antibody coats the esophagus lumen and disrupts the secretory processes from the glands, potentially making their secretions ideal vaccine targets., Methodology/principal Findings: We have designed three peptide arrays comprising overlapping 15-mer peptides encompassing 32 esophageal gland proteins, and screened them for reactivity against 22-week infection serum from macaques versus permissive rabbit and mouse hosts. There was considerable intra- and inter-species variation in response and no obvious unique target was associated with self-cure status, which suggests that self-cure is achieved by antibodies reacting with multiple targets. Some immuno-dominant sequences/regions were evident across species, notably including: MEGs 4.1C, 4.2, and 11 (Array 1); MEG-12 and Aspartyl protease (Array 2); a Tetraspanin 1 loop and MEG-n2 (Array 3). Responses to MEGs 8.1C and 8.2C were largely confined to macaques. As proof of principle, three synthetic genes were designed, comprising several key targets from each array. One of these was expressed as a recombinant protein and used to vaccinate rabbits. Higher antibody titres were obtained to the majority of reactive regions than those elicited after prolonged infection., Conclusions/significance: It is feasible to test simultaneously the additive potential of multiple esophageal proteins to induce protection by combining their most reactive regions in artificial constructs that can be used to vaccinate suitable hosts. The efficacy of the approach to disrupt esophageal function now needs to be tested by a parasite challenge., Competing Interests: The authors have declared that no competing interests exist.

Objective: Cognitive impairment is common among hemodialysis patient, but still lack adequate screening in clinical settings. The Montreal Cognitive Assessment (MoCA) is reportedly to be a sensitive screening tool for cognitive impairment, but its clinical value in patients undergoing hemodialysis is not well established. We aimed to validate the utility of the Beijing version of the MoCA (MoCA-BJ) for detecting cognitive impairment in comparison to a detailed neuropsychological battery as the gold standard., Methods: We assessed 613 patients undergoing hemodialysis using the MoCA-BJ, the Mini-Mental State Examination (MMSE), and a comprehensive neuropsychological battery. Cognitive dysfunction was defined by the fifth version of the Diagnostic and Statistical Manual of Mental Disorders (DSM-V). Spearman's correlation and linear regression were used to estimate the performance of the MoCA-BJ and MMSE in predicting cognitive impairment. A receiver operating characteristic (ROC) curve analysis was used to evaluate the utility of various cutoffs of the MoCA-BJ and MMSE for predicting cognitive impairment., Results: Cognitive impairment was diagnosed in 80.91% (496/613), 75.69% (464/613), and 61.34% (376 /613) of the patients using the DSM-V, MoCA-BJ, and MMSE, respectively. Spearman's rank correlation analysis indicated that the MoCA-BJ was significantly correlated with the neuropsychological battery (rs = 0.639, p<0.001), whereas the MMSE had a weaker correlation with the battery. The area under the ROC curve for cognitive impairment diagnosis using the MoCA-BJ was 0.891 (95% confidence interval: 0.859-0.924) while using the MMSE was 0.823 (95% confidence interval: 0.786-0.860). The optimal MoCA-BJ cutoff score in discriminating patients with and without cognitive impairment was 24 points with a sensitivity of 0.877 and specificity of 0.752., Conclusion: The MoCA-BJ offers good sensitivity and specificity levels in detecting cognitive impairment in hemodialysis patients. These findings support the utility of the MoCA-BJ as a screening tool for cognitive impairment in Chinese patients undergoing hemodialysis., Competing Interests: The authors have declared that no competing interests exist.

Tick-borne encephalitis (TBE) is endemic to Europe and some Asian countries and is prevalent in northeast China. We analyzed the epidemiology of TBE in China from 2007 to 2018. A total of 3,364 TBE cases were reported in mainland China from 2007 to 2018, for an annual incidence of 0.09 to 0.44/100,000. Among the TBE cases, 89.92% were reported in forest areas (41.94% in DaXingAnLing, 8.70% in XiaoXingAnLing, and 39.21% in ChangBaiShan) in northeast China. The TBE cases were primarily male with a proportion of 67.15% (2,259/3,364 cases) and in 40-49-year age group with a proportion of 31.89% (1,073/3,364 cases). The epidemiology of TBE differed slightly among the three forest regions. Domestic workers and forestry workers accounted for the most of the TBE cases in DaXingAnLing, and domestic workers and farmers in XiaoXingAnLing and ChangBaiShan, respectively. The TBE cases mainly occurred from April to August with a peak in June. The TBE laboratory confirmed rate in DaXingAnLing (84.14%, 1,189/1,413 cases) was highest, compared with XiaoXingAnLing and ChangBaiShan (13.99% and 11.37%, respectively). Moreover, the hospital with the highest laboratory confirmed rate (88.01%, 1,336/1,518 cases) was Inner Mongolia Forestry General Hospital of DaXingAnling region. Systematic enhanced TBE surveillance and a vaccination program are needed to improve the laboratory confirmed rate and reduce the incidence of TBE in northeast China., Competing Interests: The authors have declared that no competing interests exist.

Background: In recent decades, hypertension has become a popular public health problem in China. In 2017, a cross-sectional survey about hypertension and sodium intake measured by 24-hour (24-h) urine was launched in Zhejiang Province, to provide the basis of the Chinese population to develop a salt reduction intervention and prevention of hypertension strategy., Methods: Cross-sectional data were obtained from 7512 participants aged 18 to 69 years in Zhejiang Province of China by complex, multistage sampling methods. The survey included face-to-face questionnaires and physical examination among all participants. Blood pressures and the use of anti-hypertension medications were used to determine hypertension. One thousand five hundred participants of them were asked to collect 24-h urine to measure sodium and potassium levels to assess intake. All rates and means were weighted by sampling weight and population structure of the province., Results: The weighted means of systolic blood pressure (SBP) and diastolic blood pressure (DBP) were 127.78 mm Hg (95% confidence interval [CI], 127.21-128.36) and 79.40 mm Hg (95%CI, 79.04-79.76). The weighted hypertension prevalence was 30.41% (95%CI, 28.91-31.91). Among those classified as having hypertension, 43.55% (95%CI, 40.77-46.34) were aware of the fact that they were suffering from hypertension, 32.05% (95%CI, 29.49-34.61) of them reported taking anti-hypertension medications, only 14.48% (95%CI, 12.54-16.42) had their blood pressure controlled. The weighted means of 24-h urinary sodium was 165.52 mmol (standard deviation [SD], 2.92), representing that the mean intake of sodium chloride was 9.68g (SD, 0.17) through conversion., Conclusion: These cross-sectional survey results show that hypertension and excessive sodium intake in adults are prevalent in Zhejiang Province, China. Salt reduction and prevention of hypertension is still an urgent public health work., Competing Interests: The authors have declared that no competing interests exist.

Objectives: To assess the prevalence of human immunodeficiency virus (HIV) infection and the correlated risk factors among male clients of female sex workers (FSWs) in a Chinese-Vietnamese border region in Yunnan Province, China., Methods: A cross-sectional survey was conducted between 2014 and 2015 in Hekou County, Yunnan Province, China. Convenience sampling and snowball sampling methods were used to recruit male clients for a questionnaire survey to collect information on demographics, sexual behavior, and drug use. Blood and urine samples were collected for testing of HIV/sexually transmitted infections (STIs) and drug use. Multivariate logistic regression was used to examine factors correlated with HIV infection., Results: Of 776 respondents who participated in the study, 721 (92.91%) were Chinese and 55 (7.09%) were Vietnamese. Overall HIV prevalence in male clients of FSWs was 2.06%, 128 (16.49%) were infected with HSV-2, and five (0.64%) tested syphilis-positive. Two-thirds (68.81%) of respondents reported always using condoms with FSWs, and 89.05% reported condom use in the last episode of commercial sex. Male clients from Vietnam were significantly more likely to take morphine (9.09%) compared with Chinese male clients of FSWs. Age ≥50 years (OR: 8.11, 95%CI: 1.26-52.16) and morphine positivity (OR: 7.35, 95%CI: 1.42-38.06) were associated with HIV infection in the multivariate logistic regression model., Conclusion: The relatively high proportion of male clients of FSWs who have numerous sexual partners and use condoms less frequently make them serve as important bridges for HIV transmission from FSWs to the low-risk general population. The positive association between morphine positivity and HIV infection confirmed illegal drug use as another important route for acquiring HIV infection in addition to sexual transmission, indicating that innovative interventions addressing both drug use and risky sexual behaviors are greatly required for male clients. Respondents aged ≥50 years have a higher risk of HIV infection, which emphasizes that older male clients of FSWs should be focused in future HIV prevention interventions in the border regions of China., Competing Interests: The authors have declared that no competing interests exist.