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Purpose: Research indicates that loneliness and emotional and behavioral problems increase the risk of suicidal ideation in adolescents, but less is known about the distinct contributions of these problems. This study aimed to distinguish the pathways through which loneliness, internalizing problems, and externalizing problems contribute to suicidal ideation in Chinese adolescents., Methods: We did a longitudinal mediation analysis with data collected at 3 time points (2021.05, 2021.10, and 2022.05) from 28 Taizhou high schools. Loneliness and suicidal ideation were assessed using the UCLA 3-Item Loneliness Scale and one suicide item from the Children's Depression Inventory, respectively. The Strength and Difficulties Questionnaire assessed internalizing (emotional and peer problems) and externalizing problems (conduct and hyperactivity problems). Structural equation modeling was used to construct complete longitudinal path models., Results: Using data from 2,190 adolescents in junior and senior high schools, we found that loneliness, internalizing problems, and externalizing problems separately contributed to subsequent higher levels of suicidal ideation. Most notably, loneliness predicted worse subsequent internalizing problems (β = 0.279, p < .001) and externalizing problems (β = 0.159, p < .001), which in turn predicted more severe suicidal ideation (β = 0.019, p < .001; β = 0.018, p < .001). Loneliness also partially mediated the association between internalizing or externalizing problems and suicidal ideation., Discussion: Loneliness, internalizing problems, and externalizing problems were strongly intertwined with suicidal ideation in adolescents. Public health initiatives could reduce loneliness and emotional and behavioral problems by implementing multifaceted interventions, thereby breaking the vicious circle and protecting against the development of suicidal ideation., (Copyright © 2024 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

The determinants of persistent human papillomavirus (HPV) infection remain largely unknown, and existing studies have predominantly focused on the female population. Individual genetic background may influence the persistence of HPV infection, we the evidence overall and among human immunodeficiency virus (HIV)-positive males are very limited. We conducted a genome-wide association study (GWAS) to identify single nucleotide polymorphisms (SNPs) associated with anal HPV persistence, based on a cohort designed to study the natural history of anal HPV infection among HIV-positive males in Taizhou, China from 2016 to 2022. A total of 322 HIV-positive males with anal HPV infection, with a mean age of 43.0 (standard deviation [SD]: 13.8) years, were included in this GWAS. The median follow-up time was 1.8 (interquartile range [IQR]: 1.5-2.0) years. The persistence of any type of HPV infection was 53.4%. After adjusting for age and sexual orientation, there were 2 SNPs with p < 1 × 10 -5 and 24 SNPs with p < 1 × 10 -4 . The most closely associated with HPV persistence in additive models were rs7359031 (LOC105370461, odds ratio [OR] T/C  = 0.36, 95% confidence interval [CI]: 0.24-0.56; p = 6.67 × 10 -6 ) located at 14q21.1, and rs11046048 (PYROXD1, OR C/A  = 0.41, 95% CI: 0.28-0.60; p = 7.80 × 10 -6 ) located at 12p12.1. Other SNPs were mainly located at 6q23.3 (HBS1L-MYB) and 6p21.33 (CCHCR1, PSORS1C3). LOC105370461, PYROXD1, HBS1L-MYB, CCHCR1, and PSORS1C3 may be susceptible genes for HPV persistence. We appeal further studies to validate these associations and examine the underlying mechanisms., (© 2024 Wiley Periodicals LLC.)

Background: COVID-19 threatened global health, however little is known about the long-term courses of loneliness and their effect on mental health in adolescents. This study aimed to explore the trajectories of loneliness among adolescents in Taizhou, Zhejiang Province, China, during the last phase of the pandemic. We also aimed to identify risk factors in each loneliness course and the impact of loneliness on emotional problems, peer problems, hyperactivity and conduct problems., Methods: The study employed multistage cluster sampling to collect four waves of data from 2347 Chinese adolescents (average baseline age of 14.7 years) covering a period of 20 months (October 2021 - May 2023). The UCLA 3-Item Loneliness Scale and the Strengths and Difficulties Questionnaire were utilized to assess loneliness and mental health problems, respectively. Growth mixture modelling was employed to identify latent classes of loneliness trajectories. Associated risk factors were investigated using multinomial logistic regression model. Mixed-effects logistic regression models were constructed to examine the long-term impact of loneliness classes on mental health outcomes., Results: The overall percentage of loneliness increased from 22.9% at baseline to 32.2% at the fourth wave in our sample. Three classes of loneliness were identified: Decreasing Low Loneliness (58.71%), Increasing Medium Loneliness (36.52%), and Increasing High Loneliness (4.77%). Risk factors for poorer loneliness trajectories included lack of physical exercise habits, poorer mental health literacy, medium or low perceived social support, having study difficulties, being female, higher grades, and lower economic status. Loneliness classes were associated with the severity and variability of emotional problems, peer problems, hyperactivity and conduct problems (ORs for the highest loneliness class: 10.24, 4.21, 3.87, 2.68, respectively). Individuals in the higher loneliness classes experienced a significant increase in these mental health problems over time (p < 0.05 for interactions between loneliness classes and time)., Conclusion: During the last phase of the pandemic, a large proportion of adolescents in our study endured medium to high levels of loneliness with no signs of improvement. Both unfavorable loneliness trajectories adversely affected internalizing and externalizing problems and displayed an upward trend in these difficulties. Results highlight the importance of tackling loneliness and improving mental health in adolescents., Competing Interests: The authors declare that they have no competing interests in this work., (© 2024 Wang et al.)

Introduction: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by the SFTS virus (SFTSV), which has a wide geographic distribution. The primary clinical manifestations of SFTS are fever and thrombocytopenia, with multiorgan failure being the leading cause of death. While most patients recover with treatment, little is known about the potential long-term metabolic effects of SFTSV infection., Objectives: This study aimed to shed light on dysregulated metabolic pathways and cytokine responses following SFTSV infection, which pose significant risks to the short-term and long-term health of affected individuals., Methods: Fourteen laboratory-confirmed clinical SFTS cases and thirty-eight healthy controls including 18 SFTSV IgG-positive and 20 IgG-negative individuals were recruited from Taizhou city of Zhejiang province, Eastern China. Inclusion criteria of healthy controls included residing in the study area for at least one year, absence of fever or other symptoms in the past two weeks, and no history of SFTS diagnosis. Ultrahigh-performance liquid chromatography-mass spectrometry (UHPLC-MS) was used to obtain the relative abundance of plasma metabolites. Short-term metabolites refer to transient alterations present only during SFTSV infection, while long-term metabolites persistently deviate from normal levels even after recovery from SFTSV infection. Additionally, the concentrations of 12 cytokines were quantified through fluorescence intensity measurements. Differential metabolites were screened using orthogonal projections to latent structures discriminant analysis (OPLS-DA) and the Wilcoxon rank test. Metabolic pathway analysis was performed using MetaboAnalyst. Between-group differences of metabolites and cytokines were examined using the Wilcoxon rank test. Correlation matrices between identified metabolites and cytokines were analyzed using Spearman's method., Results and Conclusions: We screened 122 long-term metabolites and 108 short-term metabolites by analytical comparisons and analyzed their correlations with 12 cytokines. Glycerophospholipid metabolism (GPL) was identified as a significant short-term metabolic pathway suggesting that the activation of GPL might be linked to the self-replication of SFTSV, whereas pentose phosphate pathway and alanine, aspartate, and glutamate metabolism were indicated as significant long-term metabolic pathways playing a role in combating long-standing oxidative stress in the patients. Furthermore, our study suggests a new perspective that α-ketoglutarate could serve as a dietary supplement to protect recovering SFTS patients., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The effects of prenatal element exposure on mothers and fetuses have generated concern. Profiles of trace and toxic elements in biological material are urgently desired, especially for women who reside near e-waste recycling facilities. The aim of this study was to investigate elements concentrations in placenta, cord blood, and maternal blood of women and to evaluate the influencing factors., Methods: A group of 48 women from an e-waste recycling site and a group of 31 women from a non-e-waste recycling site were recruited. Basic characteristics were collected by questionnaire and the concentrations of 17 elements in placenta, cord blood, and maternal blood samples were analyzed by inductively coupled plasma mass spectrometry (ICP-MS). Finally, the generalized linear model regression analysis (GLM) was used to test the association between element concentrations and possible factors., Results: Compared to the control group, the exposed group had significantly elevated cadmium (Cd), zinc (Zn), nickel (Ni), and antimony (Sb) in placenta, and higher lead (Pb) in maternal blood and cord blood (P<0.05). Sb concentration in maternal blood was significantly lower than in the control group (P<0.05). GLM analysis showed that element concentrations were mainly associated with maternal age [chromium (Cr), iron (Fe), selenium (Se), cobalt (Co), mercury (Hg) in placenta, copper (Cu) in maternal blood], education (Se, Sb in placenta), family income (Cu in maternal blood and Ni in placenta), passive smoking [Cu and Zn in placenta, Pb in maternal blood], and e-waste contact history (Hg in cord blood, Cu, Zn, and Cd in maternal blood)., Conclusions: Women in the e-waste recycling area had higher toxic element levels in the placenta and blood samples. More preventive measures were needed to reduce the risk of element exposure for mothers and fetuses in these areas., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yacui Luo reports financial support was provided by Taizhou Science and Technology Bureau. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Objectives: This study aims to estimate the incidence and persistence/clearance of anal human papilloma virus (HPV) infection and related factors among men with HIV in Taizhou, China., Design: A prospective cohort study., Methods: Men with HIV were recruited and followed up from 2016 to 2021. Questionnaire surveys were used to collect social-demographic and behavioral characteristics, and anal swabs were collected for HPV Genotyping., Results: A total of 675 men with HIV were recruited and followed up. After an average follow-up time of 1.75 years, HPV39 (3.8/100 person-years), HPV52 (3.6/100 person-years), HPV51 (3.1/100 person-years), HPV58 (2.5/100 person-years) and HPV16 (2.4 cases/100 person-years) in the high-risk types showed the highest incidence rate. In marriage with woman [adjusted hazard ratio (aHR) = 0.44, 95% confidence interval (CI) 0.20-0.99] showed an inverse association with HPV incidence, while bisexuality or undetermined sexual orientation (aHR = 2.62, 95% CI 1.08-6.36) showed a positive association. For those infected at baseline, the top three high-risk HPV with the lowest clearance density were HPV52 (32.2/100 person-years), HPV58 (38.1/100 person-years), and HPV16 (43.5/100 person-years). Daily consumption of 1-28 g alcohol (aHR = 0.62, 95% CI 0.41-0.95) showed an inverse association with HPV clearance, while illicit drug use (aHR = 3.24, 95% CI 1.59-6.59) showed a positive association., Conclusion: Anal HPV infection and clearance were both active in men with HIV in China. Marriage status and sexuality were associated with the incidence of HPV infection, while substance use including alcohol and illicit drug were associated with HPV clearance. More studies are needed to explore the risk factors of HPV persistence., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Severe fever with thrombocytopenia syndrome (SFTS) is a newly emerged tick-borne viral zoonosis and widely prevalent in China, Japan and South Korea. Most reported SFTS cases have been identified in mountainous and hilly areas, with a few in island areas. In this study, we conducted a systematic investigation about natural infection of SFTS virus (SFTSV) among humans, animals and ticks in a coastal endemic prefecture, containing island, plains and mountain settings, in Zhejiang Province, Southeastern China. From July 2020 to June 2021, 1117 participants completed a survey with questionnaire interview and serum testing. Meanwhile, 862 serum samples of domestic animals, 275 spleen tissue samples of wild animals and 829 ticks representing five species (predominantly Haemaphysalis longicornis and Rhipicephalus sanguineus sensu lato) were collected. The seroprevalence of anti-SFTSV total antibody and IgM antibody among the participants was 4.8 % (54/1117) and 0.6 % (7/1117), respectively. Multivariate logistic regression analysis indicated that living in the island area (OR=2.66; 95 %CI: 1.04-6.80; P = 0.041) was significantly associated with seropositivity of total antibody to SFTSV. Furthermore, a higher seroprevalence was observed in domestic animals (36.1 %), while the SFTSV-RNA infection rate was 0.4 % in wild animals and the minimum infection rate (MIR) was 0.8 % for all tick species combined. The only tick species infected with SFTSV was H. longicornis. The prevalence of SFTSV infection in the island area, manifested by anti-SFTSV total antibody (P = 0.012) and IgM antibody (P = 0.004) among humans, anti-SFTSV total antibody (P<0.001) among domestic animals, and SFTSV-RNA among ticks (P = 0.022), was significantly higher than that in the mountainous area and the plain area. Furthermore, phylogenetic analysis showed that SFTSV sequences obtained from ticks in the island area were clustered with reported strains in Japan and South Korea. These results suggest that islands in the study area might be an important natural focus of SFTSV., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

Background: Frailty is one of the major concerns among aging people with HIV (PWH). Evidence regarding the association between sleep disorders and physical frailty in PWH is limited., Methods: PWH and HIV-negative individuals aged ≥40 years were included and frequency-matched in a 1:2 ratio by sex and age. Logistic regression models were used to estimate the odds ratios (ORs) and 95% CIs of the association between sleep disorders and physical frailty, and restricted cubic splines were used to describe the dose-response association. The contribution of depression to the association was estimated by mediation analysis., Results: A total of 1526 PWH and 3052 HIV-negative individuals were included. Logistic regression indicated that insomnia (OR, 3.05; 95% CI, 1.63-5.72) and poor sleep quality (OR, 2.32; 95% CI, 1.21-4.45) were significantly associated with physical frailty in middle-aged and older PWH, especially in those with current CD4+ T-cell counts <350 cells/µL, but not in HIV-negative participants. A U-shaped and J-shaped dose-response relation between sleep duration and physical frailty was observed in PWH and HIV-negative participants, respectively. Shorter and longer sleep duration was associated with an increased risk of physical frailty in PWH. However, in HIV-negative participants, only longer sleep duration was associated with physical frailty. Mediation analysis revealed that depression mediated the relation between sleep disorders and frailty among PWH., Conclusions: Sleep disorders including insomnia, poor sleep quality, and short and long sleep duration were significantly associated with physical frailty among middle-aged and older PWH. Depression may play a mediating role in the sleep-frailty association., Competing Interests: Potential conflicts of interest. All authors: no reported conflicts., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Objectives: People with HIV (PWH) are more likely to develop ECG abnormalities. Substantial evidence exists for genetic contribution to ECG parameters among general population. However, whether and how would host genome associate with ECG parameters among PWH is unclear. Our research aims to analyze and compare genetic variants, mapped genes, and enriched pathways of ECG parameters among PWH and HIV-negative controls., Design: A cross-sectional study., Method: We performed a large original genome-wide association study (GWAS) of ECG parameters among PWH ( n  = 1730) and HIV-negative controls ( n =  3746). Genome-wide interaction analyses were also conducted., Results: A total of 18 novel variants were detected among PWH, six for PR interval including rs76345397 at ATL2 , 11 for QRS duration including rs10483994 at KCNK10 and rs2478830 at JCAD , and one for QTc interval (rs9815364). Among HIV-negative controls, we identified variants located at previously reported ECG-related genes ( SCN5A , CNOT1 ). Genetic variants had a significant interaction with HIV infection ( P  < 5 × 10 -8 ), implying that HIV infection and host genome might jointly influence ECG parameters. Mapped genes for PR interval and QRS duration among PWH were enriched in the biological process of viral genome replication and host response to virus, respectively, whereas enriched pathways for PR interval among HIV-negative controls were in the cellular component of voltage-gated sodium channel complex., Conclusion: The present GWAS indicated a distinctive impact of host genome on quantitative ECG parameters among PWH. Different from HIV-negative controls, host genome might influence the cardiac electrical activity by interfering with HIV viral infection, production, and latency among PWH., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Public restriction and school closure policies during the pandemic may have long-term effects on adolescents' mental health, and adolescents' feelings and needs may change as the pandemic progresses. This study was conducted to explore the network structure and differences in emotional and behavioral problems (EBPs), loneliness, and suicidal thoughts in adolescents during different pandemic periods in China., Methods: Based on two cross-sectional studies conducted in Taizhou, China, during school closure (April 16 to May 14, 2020) and reopening (May 25 to July 10, 2021) using online questionnaire, a total of 14,726 adolescents (school closure: 6,587, school reopening: 8,139) were recruited. EBPs were evaluated based on the student version of the Strengths and Difficulties Questionnaire (SDQ). Loneliness and suicidal thoughts were measured by item 20 and item 9 of the Chinese version of the Children's Depression Inventory (CDI), respectively. Network analysis was used to estimate the network connections and properties between EBPs, loneliness, and suicidal thoughts., Results: The prevalence of psychosocial problems significantly increased at the school reopening compared with the school closure: EBPs: 36.8% vs . 31.6%; loneliness: 40.3% vs . 33.9%; suicidal thoughts: 40.8% vs . 15.4%. Suicidal thoughts showed the closest connections with being unhappy and lonely. Being bullied was strongly connected with conduct problems of lying and stealing. The links between hyperactivity symptoms and the other domains of EBPs were stronger after the school reopened. Being unhappy and showing the hyperactivity symptoms of "nonpersistent, distractible, and fidgety" presented high network and bridge (increasing transference from one symptom domain to another) centrality. Loneliness showed high expected influence and bridge centrality., Conclusions: This study highlighted the high prevalence of EBPs, loneliness, and suicidal thoughts in Chinese adolescents. It also presented the network structure of these psychological problems over different pandemic stages. It is recommended that psychological support should be provided for adolescents, especially focusing on the central and bridge symptoms highlighted in this study., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tp.amegroups.com/article/view/10.21037/tp-23-33/coif). The authors have no conflicts of interest to declare., (2023 Translational Pediatrics. All rights reserved.)

Background: Few studies have explored the important role of different dimensions of emotional and behavioral problems (EBPs), perceived social support and loneliness in predicting suicidal ideation among Chinese adolescents. Based on a 6-month longitudinal study conducted in Taizhou high schools, we aimed to explore the associations between psychosocial problems and suicidal ideation in Chinese adolescents, and to ascertain whether co-occurring psychosocial problems increase suicidal ideation., Methods: A total of 3,267 students were eligible for this analysis. Perceived social support was assessed using the Multidimensional Scale of Perceived Social Support. Loneliness and suicidal ideation were assessed using the University of California, Los Angeles (UCLA) 3-Item Loneliness Scale and one item from the Children's Depression Inventory. The Strength and Difficulties Questionnaire assessed EBPs. Multivariable logistic regression models were used to estimate longitudinal associations between each psychosocial problem (lack of perceived social support from family, friends, and significant others, loneliness, emotional, conduct and peer problems, hyperactivity, and poor prosocial behavior) at baseline and suicidal ideation at follow-up. Multinomial logistic regression models were used to examine the association between the number of psychosocial problems at baseline and suicidal ideation at follow-up., Results: The multivariable logistic regression results showed that after adjusting for baseline suicidal ideation, sociodemographic covariates and depressive symptoms, low level of perceived social support from family (OR =1.78; 95% CI: 1.10-2.87), emotional problems (OR =2.35; 95% CI: 1.41-3.79), and poor prosocial behavior (OR =1.74; 95% CI: 1.08-2.79) were significant predictors of suicidal ideation among the adolescents. The risk of suicidal thoughts increased as the number of psychosocial problems increased. The participants with five or more psychosocial problems had a higher risk of having serious suicidal thoughts than those with no problem (relative risk ratio =4.50; 95% CI: 2.13-9.49)., Conclusions: The study confirmed the predictive role of multiple psychosocial problems on suicidal ideation, and the accumulative effect of co-occurring psychosocial problems in magnifying the risk of suicidal ideation. More integrated and holistic approaches need to be taken to identify high-risk groups and provide interventions of suicidality in adolescents., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tp.amegroups.com/article/view/10.21037/tp-22-676/coif). JW was sponsored by Shanghai Pujiang Program (No. 2020PJC005) and National Natural Science Foundation of China (No. 72104053); and reports that this work was also supported by the Shanghai Leading Academic Discipling Project of Public Health (No. GWV-10.1-XK18). TW was sponsored by Science and Technology Plan Projects of Taizhou (No. 22ywa62). HL was sponsored by Taizhou City Foundation for Talents (No. TZ2022-2). XC was sponsored by Taizhou City Foundation for Talents (No. TZ2022-2), and Science and Technology Plan Projects of Taizhou (No. 22ywa62). The other authors have no conflicts of interest to declare., (2023 Translational Pediatrics. All rights reserved.)

Objective: We aimed to examine whether HIV infection was independently associated with frailty status and its individual components., Methods: This cross-sectional investigation included people living with HIV (PLWH) and HIV-negative individuals from the baseline survey of the Comparative HIV and Aging Research in Taizhou (CHART) cohort, China. Frailty phenotype was based on five components: weight loss, low physical activity, exhaustion, weak grip strength and slow gait speed. Frailty was defined as the presence of at least three components, and prefrailty was defined as one or two components. Logistic regression models were used to analyse the factors associated with frailty and its components., Results: In all, 2475 people living with HIV (age 45.5 ± 14.9 years; 76.2% male) and 4948 HIV-negative individuals (age 45.5 ± 14.8 years; 76.3% male) were included. Among PLWH, median CD4 count was 395 cells/μL and 78% were currently on antiretroviral therapy (ART). Frailty and prefrailty were significantly more prevalent in PLWH (3.2% vs 1.9% and 32.9% vs 27.9%) overall and at ages 18-39 (1.4% vs 0.2% and 22.7% vs 19.0%), 40-59 (2.5% vs 0.9% and 30.9% vs 27.9%) and 60-90 years (8.4% vs 7.4% and 57.1% vs 45.8%). HIV infection was associated with frailty and prefrailty [adjusted odds ratio (aOR) = 1.48, 95% confidence interval (CI): 1.06-2.08; and aOR = 1.18, 95% CI: 1.05-1.33, respectively] after adjusting for confounding variables, but were strengthened with further adjustment for multimorbidity (aOR = 1.62, 95% CI: 1.14-2.28; and aOR = 1.22, 95% CI: 1.09-1.37), and were no longer significant with further adjustment for depressive symptoms and sleep disorders (aOR = 1.02, 95% CI: 0.71-1.46; and aOR = 1.06, 95% CI: 0.94-1.20). Among individual components, HIV infection was positively associated with weak grip strength and slow gait speed, but negatively associated with low physical activity and exhaustion in all the adjusted models described., Conclusions: Frailty and prefrailty occur more often and earlier in PLWH. However, grip strength and gait speed are affected to a greater extent, highlighting their potential as screening and intervention targets to prevent or slow frailty among PLWH., (© 2022 British HIV Association.)

Background: While psychosocial problems and their related factors in men who have sex with men (MSM) have been well documented in developed countries, there are still not many studies addressing this issue in China and the results are inconsistent. This study aimed to assess the prevalence of loneliness and depressive symptoms among MSM, examine their associated factors, and investigate potential factors moderating the link between depressive symptoms and loneliness., Methods: A cross-sectional study was conducted in Taizhou of Zhejiang Province in China between April and November 2021. Loneliness was assessed using the 3-item UCLA Loneliness Scale (UCLA-3), and depressive symptoms were measured using the Patient Health Questionaire-9 (PHQ-9). Data from 655 MSM were eligible for analysis. Logistic regression models were used to examine the associations between independent variables and the outcomes of loneliness and depression. The interaction terms were added in the models to assess the moderating effects., Results: Of the MSM sample, 13.28 and 7.48% perceived loneliness and reported moderate-to-severe depressive symptoms, respectively. We found that participants who experienced loneliness were more likely to have younger age (OR 0.44, 95% CI 0.21, 0.93, 15-32 years as reference group), low social support (OR 3.60, 95% CI 2.14, 6.04), low self-esteem (OR 3.03, 95% CI 1.45, 6.32) and moderate-to-severe depressive symptoms (OR 5.45, 95% CI 2.66, 11.15). The participants with moderate-to-severe depressive symptoms were more likely to have low self-esteem (OR 6.78, 95% CI 3.08, 14.95) and feelings of loneliness (OR 5.51, 95% CI 2.66, 11.40). Stratified analyzes showed that the magnitude of the associations between depressive symptoms and loneliness varied in MSM with different age, marital status, and self-esteem., Conclusion: Our study suggests that we need to pay attention to feelings of loneliness and depressive symptoms and their closely associated factors such as social support and self-esteem among MSM in China. The MSM who were young, not married, and had low self-esteem were especially vulnerable to the impact of depressive symptoms on loneliness., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Liu, Yang, Fu, Lin, Wang, Wang, Kuang, Chen and Wang.)

This study aims to understand MDR/RR-TB patients' experience from seeking TB-related health care to diagnosis and treatment completion, as well as the social determinants with the waiting time for DST and treatment, pre-treatment attrition, and treatment outcome based on a retrospective cohort study. Univariate and multi-variate logistic regressions were used to analyze the associated factors. The median time of waiting time for DST and treatment was 24.00 and 30.00 days, respectively. Non-residential patients (aOR: 2.89, 95% CI: 1.14-7.70), registered before 2018 (aOR: 19.93, 95% CI: 8.99-48.51), first visited a county-level hospital (aOR: 4.65, 95% CI: 1.08-21.67), sputum smear-negative (aOR: 3.54, 95% CI: 1.28-10.16), and comorbid with pneumoconiosis (aOR: 7.10, 95% CI: 1.23-47.98) had a longer DST delay. The pre-treatment attrition was 26.9% (82/305). Elderly, non-residential patients and patients registered before 2018 were more likely to refuse MDR/RR treatment. However, in housekeeping/unemployment and farmer/fisherman, recurrent patients tended to take therapeutic measures actively. The successful treatment rate was 62.1% (105/169). Elderly, comorbidity with diabetes and sputum smear conversion time >1 month may lead to poorer outcomes. Immediate interventions should be taken to smooth diagnosis and treatment pathways and improve the social protections further so as to encourage patients to cooperate with the treatment actively.

Background: Genome-wide association studies (GWAS) have identified some variants associated with subclinical atherosclerosis (SCA) in general population but lacking sufficient validation. Besides traditional risk factors, whether and how would genetic variants associate with SCA among people with HIV (PWH) remains to be elucidated., Method: A large original GWAS and gene-environment interaction analysis of SCA were conducted among Chinese PWH (n = 2850) and age/sex-matched HIV-negative controls (n = 5410). Subgroup analyses by age and functional annotations of variants were also performed., Results: Different from HIV-negative counterparts, host genome had a greater impact on young PWH rather than the elders: one genome-wide significant variant (rs77741796, P = 2.20 × 10 -9 ) and eight suggestively significant variants (P < 1 × 10 -6 ) were identified to be specifically associated with SCA among PWH younger than 45 years. Seven genomic loci and 15 genes were mapped to play a potential role on SCA among young PWH, which were enriched in the biological processes of atrial cardiac muscle cell membrane repolarization and molecular function of protein kinase A subunit binding. Furthermore, genome-wide interaction analyses revealed significant HIV-gene interactions overall as well as gene-environment interactions with alcohol consumption, tobacco use and obesity among PWH. The identified gene-environment interaction on SCA among PWH might be useful for discovering high-risk individuals for the prevention of SCA, particularly among those with tobacco use and alcohol consumption., Conclusion: The present study provides new clues for the genetic contribution of SCA among young PWH and is the starting point of precision intervention targeting HIV-related atherosclerosis., (© 2022. The Author(s).)

Ocular drug delivery has been significantly advanced for not only pharmaceutical compounds, such as steroids, nonsteroidal anti-inflammatory drugs, immune modulators, antibiotics, and so forth, but also for the rapidly progressed gene therapy products. For conventional non-gene therapy drugs, appropriate surgical approaches and releasing systems are the main deliberation to achieve adequate treatment outcomes, whereas the scope of "drug delivery" for gene therapy drugs further expands to transgene construct optimization, vector selection, and vector engineering. The eye is the particularly well-suited organ as the gene therapy target, owing to multiple advantages. In this review, we will delve into three main aspects of ocular drug delivery for both conventional drugs and adeno-associated virus (AAV)-based gene therapy products: (1) the development of AAV vector systems for ocular gene therapy, (2) the innovative carriers of medication, and (3) administration routes progression.

Purpose: To select individuals and families with a low genetic burden for age-related macular degeneration (AMD), to inform the clinical diagnosis of macular disorders, and to find novel genetic variants associated with maculopathies., Design: Genetic association study based on targeted and whole-exome sequencing., Participants: A total of 758 subjects (481 individuals with maculopathy and 277 controls), including 316 individuals in 72 families., Methods: We focused on 150 genes involved in the complement, coagulation, and inflammatory pathways. Single-variant tests were performed on 7755 variants shared among ≥ 5 subjects using logistic regression. Gene-based tests were used to evaluate aggregate effects from rare and low-frequency variants (at minor allele frequency [MAF] ≤ 5% or ≤ 1%) in a gene using burden tests. For families whose affected members had a low burden of genetic risk based on known common and rare variants related to AMD, we searched for rare variants (MAF < 0.001) whose risk alleles occurred in ≥ 80% of affected individuals but not in controls. Immunohistochemistry was performed to determine the protein expression of a novel gene ( coagulation factor II thrombin receptor-like 2 [ F2RL2 ]) in retinal tissues., Main Outcome Measures: Genotypes and phenotypes of macular degeneration., Results: We confirmed the association of a synonymous variant in complement factor H (Ala473, rs2274700, proxy to intronic rs1410996, r 2  = 1) with maculopathy (odds ratio, 0.64; P  = 4.5 × 10 -4 ). Higher AMD polygenic risk scores (PRSs) were associated with intermediate and advanced AMD. Among families with low PRSs and no known rare variants for maculopathy, we identified 2 novel, highly penetrant missense rare variants in ADAM15, A disintegrin and metalloprotease, metallopeptidase domain 15 (p.Arg288Cys) and F2RL2 (p.Leu289Arg). Immunohistochemistry analyses revealed F2RL2 protein expression in cone photoreceptor outer segments and Müller glia cells of human and pig retinas. Coagulation factor II thrombin receptor-like 2 expression appeared increased in fibrotic areas in advanced AMD samples with neovascularization, suggesting that F2RL2 may play a role in the progression to advanced macular disease., Conclusions: New missense rare variants in the genes ADAM15 and F2RL2 were associated with maculopathies. Results suggest that novel genes related to the coagulation and immune pathways may be involved in the pathogenesis of macular diseases., (© 2022 Published by Elsevier Inc. on behalf of the American Academy of Ophthalmology.)

Severe fever with thrombocytopenia syndrome (SFTS) virus has caused a large number of human infections since discovered in 2009. This study elucidated epidemiological features and fatal risk factors of SFTS cases accumulated up to ten years in Taizhou, a coastal prefecture of Zhejiang Province in Eastern China. A total of 188 hospitalised SFTS cases (including 40 deaths) reported to Taizhou Center for Disease Control and Prevention (CDC) during 2011-2020 were enrolled in the study. In the past decade, the annual incidence of SFTS increased over the years ( P < 0.001) along with an expanding epidemic area, and the case fatality of hospitalised cases has remained high (21.3%). Although most cases occurred in hilly areas, a coastal island had the highest incidence and case fatality. The majority of cases were over the age of 60 years (72.3%), and both incidence and case fatality of SFTS increased with age. Multivariate logistic regression analysis showed that age (OR 7.47, 95% CI 1.32-42.33; P = 0.023), and haemorrhagic manifestations including petechiae (OR 7.76, 95% CI 1.17-51.50; P = 0.034), gingival haemorrhage (OR 5.38, 95% CI 1.25-23.15; P = 0.024) and melena (OR 5.75, 95% CI 1.18-28.07; P = 0.031) were significantly associated with the death of SFTS cases. Five family clusters identified were farmers, among four of which the index patients were female with a history of hypertension. Based on the study, age is a critical risk factor for incidence and case fatality of SFTS. With an increased annual incidence over the last ten years, SFTS remains a public health threat that should not be ignored. Further study is needed to look at the natural foci in the coastal islands.

Background: Hemorrhagic fever with renal syndrome (HFRS) is endemic in Zhejiang Province, China, while few studies have concentrated on the influence of meteorological factors on HFRS incidence in the area., Methods: Data on HFRS and meteorological factors from January 1, 2008 to December 31, 2020 in Taizhou City, Zhejiang Province were collected. Multivariate analysis was conducted to the relationship between meteorological factors including minimum temperatures, relative humidity, and cumulative rainfall with HFRS., Results: The HFRS incidence peaked in November and December and it was negatively correlated with average and highest average temperatures. Compared with median of meteorological factors, the relative risks (RR) of weekly average temperature at 12 ℃, weekly highest temperature at 18 ℃relative humidity at 40%, and cumulative rainfall at 240 mm were most significant and RRs were 1.41 (95% CI: 1.09-1.82), 1.32 (95% CI: 1.05-1.66), 2.18 (95% CI: 1.16-4.07), and 1.91 (95% CI: 1.16-2.73), respectively. Average temperature, precipitation, relative humidity had interactions on HFRS and the risk of HFRS occurrence increased with the decrease of average temperature and the increase of precipitation., Conclusion: Our study results are indicative of the association of environmental factors with the HFRS incidence, probable recommendation could be use of environmental factors as early warning signals for initiating the control measure and response., (© 2022. The Author(s).)

Background: Atherosclerotic cardiovascular disease (CVD) is a common cause of morbidity among people with human immunodeficiency virus (PWH) who initiate antiretroviral therapy (ART). Little is known about the roles of inflammation in atherosclerotic CVD among PWH., Methods: This cross-sectional evaluation included 178 PWH between 40 and 70 years on stable (>3 months) ART who were derived from the ongoing, prospective cohort for Comparative HIV and Aging Research in Taizhou (CHART), China, from February 2017 to August 2018. Carotid intima-media thickness (cIMT) ≥1 mm was considered as cIMT thickening indicative of atherosclerotic CVD. Plasma inflammation and coagulation biomarkers were quantified by a multiplex bead cytokine assay for 27 cytokines and enzyme-linked immunosorbent assay (ELISA) for soluble CD14 and D-dimer, respectively. We performed a series of multiparametric analyses of biomarkers and developed a composite score for atherosclerotic CVD assessment among PWH., Results: Of 178 PWH, 53 (30.9%) had cIMT thickening. In multivariable logistic analysis adjusting for CVD and human immunodeficiency virus-specific risk factors, interleukin (IL)-4 (odds ratio [OR] = 19.0; 95% confidence interval [CI], 1.6-226.5), IL-7 (OR = 16.7; 95% CI, 1.8-151.7), IL-10 (OR = 11.9; 95% CI, 2.0-72.1), and D-dimer (OR = 3.1; 95% CI, 1.0-10.1) were significantly associated with cIMT thickening. We also developed a composite score incorporating markers (IL-7, IL-10, D-dimer, and hypertension) that accurately evaluated atherosclerotic CVD., Conclusions: The associations of IL-4, IL-7, IL-10, and D-dimer with atherosclerosis underscores research needs to further understand the inflammatory mechanisms in the pathogenesis of atherosclerosis CVD among treated PWH. The composite score for atherosclerotic CVD assessment could be useful for risk stratification in PWH., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Severe fever with thrombocytopenia syndrome (SFTS) is a newly emerging zoonotic infectious disease caused by the SFTS virus (SFTSV), which has been continuously circulating in Eastern Asia in recent years. Although the evolution of SFTSV has been investigated, the evolutionary changes associated with codon usage have not been reported. Thus, a comprehensive genetic and codon usage bias analysis of SFTSV was conducted to elucidate the genetic diversity and evolutionary relationships in a novel perspective. The study amplified and sequenced fifteen SFTSV strains from a prefecture of Zhejiang Province, Eastern China in 2020, where SFTS cases have been continuously reported in the past decade. Phylogenetic analysis was conducted based on the complete coding sequences of SFTSV segments. It suggested that all SFTSV strains circulating in Zhejiang were clustered with Japanese and Korean strains, which belonged to two different genotypes. Meanwhile, thirty-nine genetic reassortants classified into nineteen different reassortment forms were identified, while 45 recombination events in 41 SFTSV strains were found. Codon usage patterns were further analyzed to understand the evolutionary changes in relation to genotype and host. And it revealed that codon usage bias was mainly driven by natural selection rather than mutation pressure. In addition, the codon adaptation index (CAI) analysis demonstrated the strong adaptability of SFTSV to Gallus gallus and Homo sapiens. Similarity index (SiD) analysis indicated that Haemaphysalis longicornis posed a strong selection pressure to SFTSV. In conclusion, this study revealed that the genetic diversity of SFTSV is gradually increasing. The codon usage analysis suggested that codon usage bias of SFTSV was mainly driven by natural selection, and SFTSV has evolved host-specific codon usage patterns. This contributes to the development of control measures against SFTSV., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Neurocognitive impairment (NCI) persists among people living with HIV (PLWH) despite the success of combination antiretroviral therapy (cART). Although muscular waning or decreased handgrip strength has been widely reported to be associated with cognitive erosion in general elders, such association has not been examined in PLWH who commonly experience decreased handgrip strength and NCI. Furthermore, whether HIV infection modifies such association remains to be addressed. A cross-sectional analysis was conducted with 2808 HIV-positive and 5402 HIV-negative adults participating in the baseline survey of the CHART (Comparative HIV and Aging Research in Taizhou) cohort, China, 2017 - 2019. HIV-positive individuals showed weaker handgrip strength than HIV-negative controls (34.0 kg vs 37.7 kg). Multivariate logistic regression analysis indicated that both HIV infection (aOR = 4.35, p < 0.001) and every 5-kg decrease in "Handgrip strength" (aOR = 1.27, p < 0.001) were significantly associated with NCI, and there was a significant interaction between reduced handgrip strength and HIV infection on NCI (aOR = 1.14, p = 0.015). In stratified analyses adjusting for potential confounders, the association between reduced handgrip strength and NCI was significant among PLWH at all age groups but only significant among HIV-negative controls at 30 - 44 and 60 - 89 ages. Handgrip strength decline is significantly associated with the risk of NCI among PLWH. HIV infection may exacerbate the adverse effect of poor handgrip strength on NCI, especially at younger ages. Early detection of handgrip strength decline could facilitate delivery of compensatory strategies or assistive services to PLWH with or at high risk of NCI., (© 2021. Journal of NeuroVirology, Inc.)

Background: In the era of combination antiretroviral therapy (ART), the incidence, manifestations and severity of kidney diseases have dramatically changed in people living with HIV (PLWH). Little is known about the incidence of impaired kidney function (IKF) measured by serum creatine-based estimated glomerular filtration rate (eGFR) in PLWH., Methods: In this systematic review and meta-analysis, we searched PubMed, Ovid, Medline, Embase and Web of Science for studies published before May 7th, 2021, with estimates of incidence of IKF among PLWH. We independently reviewed each study for quality by using the Newcastle-Ottawa scale. The incidence and 95% confidence intervals (CIs) were calculated using random-effects model., Results: Sixty out of 3797 identifiable studies were eligible for the meta-analysis. A total of 19 definitions of IKF were described and categorized into three types: the threshold of eGFR, an absolute or percent decrease in eGFR, and certain eGFR threshold combined with decrement in eGFR. The eGFR< 60 ml/min/1.73m 2 was the most widely used definition or criterion for IKF, by which the pooled incidence rate of IKF was 12.50 (95%CI: 9.00-17.36) per 1000 person years (PYs). The second most-studied outcome was a > 25% decrease in eGFR, followed by eGFR< 90 ml/min/1.73m 2 , eGFR< 30 ml/min/1.73m 2 and a combination of eGFR threshold plus decreased eGFR. The reported incidence rates of IKF differ widely by different definitions of IKF. The highest pooled incidence was observed for those with > 25% decrease in eGFR, while the lowest was observed in those with eGFR < 30 ml/min/1.73m 2 . Substantial heterogeneity was identified across most estimates., Conclusion: Our study provides a comprehensive summary of eGFR-based definitions and incidence rates of IKF in PLWH, not only promoting our understanding of IKF, but also underscoring needs for a concerted action to unify definitions and outcomes of IKF and their applications in AIDS care., (© 2022. The Author(s).)

Objectives: This study aims to investigate the association between CD4 + T cell count and combined antiretroviral therapy (cART) with the prevalence of anal human papillomavirus (HPV) infection among HIV-positive male cohort in China., Methods: A survey was conducted in men from a HIV cohort in Taizhou, China between 2016 and 2019. A face-to-face questionnaire interview was administered, and an anal-canal swab was collected for HPV genotyping., Results: A total of 766 HIV-positive men were recruited. The HPV prevalence was lower among those with increased CD4 + T cell count than those with decreased or unchanged (46.5 vs. 56.6%, p = 0.033) from baseline. In multivariable models, having the current CD4 + T cell count of 350-499 cells/µL (aOR 0.28, 95% CI 0.13-0.64), and of ≥ 500 cells/µL (aOR 0.26, 95% CI 0.11-0.60) were associated with lower prevalence of any type HPV infection compared with those with < 200 cells/µL. Having taken NVP + 3TC + AZT was inversely associated with any high-risk (HR)-HPV (aOR 0.47, 95% CI 0.25-0.90) and any low-risk (LR)-HPV infection (aOR 0.40, 95% CI 0.18-0.88), compared with those taking EFV + 3TC + TDF., Conclusions: Increased CD4 + T cell count at follow-up was significantly associated with lower prevalence of anal HPV infection. Inverse associations between NVP + 3TC + AZT and HR-HPV or LR-HPV infecton were observed., (© 2022. The Author(s).)

Objective: Females are more vulnerable to renal impairment (RI) in people living with HIV (PLWH), but few studies have examined sex disparity in the association of HIV serostatus with RI., Methods: In total, 2,101 PLWH on antiretroviral treatment (ART) and 4,202 HIV-negative people were selected and frequency matched in 1:2 ratio by sex and age categories. RI was defined as estimated glomerular filtration rate (eGFR) <90 mL/min/1.73 m 2 . The interaction effect of sex with HIV serostatus and correlates of RI were assessed by logistic regression models., Results: In total, 78.2% of participants were males with median age 43.7 (IQR: 32.5-54.4) years. The prevalence of RI was comparable for PLWH and HIV-negative people overall (30.4% vs 30.1%) but significantly higher for HIV-positive females (37.1%) than HIV-negative females (30.1%). Multiple logistic regression identified an interaction between sex and HIV serostatus on RI (adjusted odds ratio [aOR] of the interaction term: 1.66, 95% CI: 1.23-2.26). HIV infection was significantly associated with RI in females (aOR: 1.55, 95% CI: 1.17-2.06) but not in males. Central obesity and nadir CD4 count were significantly associated with RI in HIV-infected females but not in HIV-infected males., Conclusions: Sex seems to modify the association between HIV infection and RI, suggesting a sex-specific mechanistic pathogenesis of RI in PLWH, which warrants further investigation and intervention., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Neurocognitive impairment (NCI) and gut microbiota dysbiosis are prevalent in patients with HIV infection. Docosahexanoic acid (DHA) supplementation may alleviate multiple neurocognitive diseases symptoms and plays important role in regulating gut microbiota. However, it is not known whether DHA algae oil supplements can alleviate neurocognitive impairment (NCI) and regulate gut microbiota and fecal metabolites. A randomized, double-blind, placebo-controlled trial was performed on 68 HIV-infected patients with NCI. Participants were randomized to receive a 3.15 g daily DHA algae oil supplement or placebo for 6 months. We collected blood and fecal samples from these patients before and after the trial. Mini mental state examination (MMSE) and neuropsychological tests (NP tests) were administered to assess the cognitive status of participants. The influence of DHA algae oil on the gut microbiota, fecal metabolomics, plasma proinflammatory, and oxidative stress factors was also investigated. There were no significant changes in NCI according to global diagnosis score (GDS) and MMSE score within the two groups, while patients receiving DHA had improvement in several blood lipids, pro-inflammatory and oxidative stress factors. The DHA supplement increased α-diversity indexes, increased abundances of Blautia, Bifidobacterium, Dorea, Lactobacillus, Faecalibacterium, Fusobacterium , and Agathobacter , and decreased abundances of Bacteroides and Prevotella&#95;9 . Furthermore, DHA supplement was correlated with improved fecal lipid metabolites as indicated by ceramides, bile acids, glycerophospholipids. In addition, the DHA supplement was associated with altered cholesterol metabolism and purine metabolism pathways. A daily supplement of DHA algae oil for 6 months has been shown to promote favorable transformations in gut microbiota, profiles of fecal metabolomic, and factors responsible for proinflammatory and oxidative stress, which might be beneficial for the prognosis of HIV-infected patients with NCI in the long-term., Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT04242004, identifier: NCT04242004., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Dong, Lin, Ding, Chen, Shi, Yuan, Li, Zhu, Xu, Shen, Wang, Ding and He.)

Background: Mitochondrial DNA (mtDNA) profiles and contributions of mtDNA variants to CD4+T-cell recovery in Euramerican people living with HIV (PLWH) may not be transferred to East-Asian PLWH, highlighting the need to consider more regional studies. We aimed to identify mtDNA characteristics and mutations that explain the variability of short-term CD4+T-cell recovery in East-Asian PLWH., Method: Eight hundred fifty-six newly reported antiretroviral therapy (ART)-naïve Chinese PLWH from the Comparative HIV and Aging Research in Taizhou (CHART) cohort (Zhejiang Province, Eastern China) were enrolled. MtDNA was extracted from peripheral whole blood of those PLWH at HIV diagnosis, amplified, and sequenced using polymerase chain reaction and gene array. Characterization metrics such as mutational diversity and momentum were developed to delineate baseline mtDNA mutational patterns in ART-naïve PLWH. The associations between mtDNA genome-wide single nucleotide variants and CD4+T-cell recovery after short-term (within ~48 weeks) ART in 724 PLWH were examined using bootstrapping median regressions., Results: Of 856 participants, 74.18% and 25.82% were male and female, respectively. The median age was 37 years; 94.51% were of the major Han ethnicity, and 69.04% and 28.62% were of the heterosexual and homosexual transmission, respectively. We identified 2,352 types of mtDNA mutations and mtDNA regions D-loop , ND5 , CYB , or RNR1 with highest mutational diversity or volume. Female PLWH rather than male PLWH at the baseline showed remarkable age-related uptrends of momentum and mutational diversity as well as correlations between CD4+T <200 (cells/μl) and age-related uptrends of mutational diversity in many mtDNA regions. After adjustments of important sociodemographic and clinical variables, m.1005T>C, m.1824T>C, m.3394T>C, m.4491G>A, m.7828A>G, m.9814T>C, m.10586G>A, m.12338T>C, m.13708G>A, and m.14308T>C (at the Bonferroni-corrected significance) were negatively associated with short-term CD4+T-cell recovery whereas m.93A>G, m.15218A>G, and m.16399A>G were positively associated with short-term CD4+T-cell recovery., Conclusion: Our baseline mtDNA characterization stresses the attention to East-Asian female PLWH at risk of CD4+T-cell loss-related aging and noncommunicable chronic diseases. Furthermore, mtDNA variants identified in regression analyses account for heterogeneity in short-term CD4+T-cell recovery of East-Asian PLWH. These results may help individualize the East-Asian immune recovery strategies under complicated HIV management caused by CD4+T-cell loss., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Liu, Wei, Lin, Ding, Sun, Zhao, He, Ma, Li, Zhou, Chen, Shen, Gao and He.)

Hypertension is highly prevalent among people living with HIV (PLWH). We sought to characterize the hypertension incidence among PLWH on antiretroviral therapy, focusing on the effect of change in general and abdominal obesity on hypertension during follow-up. This was a prospective analysis of 229 treated PLWH aged over 40 years without hypertension at baseline. Overall a median follow-up of 2.9 years, 26.2% PLWH developed hypertension. In multivariable models, compared to those without obesity measures at both baseline and follow-up visit, PLWH with general obesity at both occasions (adjusted odds ratio [aOR] = 3.83, P  = 0.006) or at baseline only (aOR = 5.45, P  = 0.003), abdominal obesity (measured as waist circumference) at both occasions (aOR = 3.87, P  = 0.001) or at follow-up only (aOR = 2.27; 9 P  = 0.060), abdominal obesity (measured as waist-to-hip ratio) at both occasions (aOR = 2.27, P  = 0.077) were at increased risk of incident hypertension. Our data show that both general and abdominal obesity especially in the persistent status increase the hypertension risk in treated PLWH.

Background: Most studies on mental health problems caused by COVID-19 crisis in children were limited to the period of home quarantine. It remained unclear what adverse impact of the psychosocial stressors caused by school reopening, as well as the transitions in daily activities and social interactions had on mental health in children. Methods: A total of 6400 students in primary schools were enrolled in a cross-sectional study conducted in East China, between June 26 and July 6, 2020, when schools reopened. Children's mental health status was assessed by the parent version of Strengths and Difficulties Questionnaire (SDQ). Ultimately, data on a total of 6017 children with completed information on mental health, psychosocial stressors, daily activities, and social interactions were eligible for analysis. The associations of mental health with psychosocial stressors, daily activities, and social interactions were determined by ordinal logistic regression models. Stratified analyses were conducted according to grade, gender, school level, area, and caregiver-child relationship to further observe the effects of stressors on mental status. Results: The prevalence of borderline, moderately abnormal, and prominently abnormal scores were 7.16, 3.34, and 1.96% for total difficulties, and 13.83, 13.45, and 17.85% for prosocial behavior, respectively. Children with psychological stressors had a significantly higher risk of being in a worse category of mental health status, with the maximum adjusted OR of 7.90 (95% CI 3.33-18.75) in those definitely afraid of inadaptation to study and life styles. Time used in home work and computer games was positively related to mental health problems, while physical exercises and frequency of communication with others was negatively related. The effects of psychological stressors on total difficulties were more evident in middle-high grade students (OR = 7.52, 95% CI 4.16-8.61), boys (OR = 6.95, 95% CI 4.83-8.55), those who lived in Taizhou (OR = 7.62, 95% CI 4.72-8.61) and with poor caregiver-child relationship (OR = 7.79, 95% CI 2.26-8.65). Conclusion: Emotional and behavioral difficulties, especially less prosocial behavior, were prevalent in primary school children after schools reopened. The Chinese government, communities, schools, and families need to provide more effective support for students' transition back into the school building and address emotional and behavioral problems for children with difficulties., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wang, Wang, Lin, Chen, Wang, Liang, Guo and Fu.)

Gut microbiota dysbiosis has been associated with many neurological diseases. However, how microbiota composition and metabolism relate to neurocognitive impairment (NCI) in HIV-infected individuals is largely unknown. In this study, a total of 102 HIV infected participants were classified into two groups-those with NCI and those without-using the global deficit score (GDS). Fecal samples were collected from the participants for 16S rRNA gene sequencing and untargeted metabolomics. The plasma level of 25 hydroxy-vitamin D (25(OH)D) was also evaluated. Although α-diversity and β-diversity were comparable, the HIV patients with NCI were significantly different from those without NCI in terms of abundance of several gut microbiota. The decreased abundance of butyrate-producing bacteria (BPB) and increased abundance of Klebsiella were related with NCI and carotid intima-media thickness (CIMT). Significant differences in fecal metabolites were also found between individuals with versus without NCI, including increased bile acids and bioactive lipids, decreased vitamin D, terpenoids, and resolvin D1 in the NCI group. Furthermore, the perturbed metabolic profile was closely related to BPB and Klebsiella . In addition, a low level of vitamin D was associated with NCI and CIMT. Both fecal and plasma vitamin D were positively correlated with BPB. Our results show that BPB and Klebsiella and the associated metabolites are associated with NCI in people with HIV. In addition, vitamin D, both in feces and blood, was associated with NCI and BPB, suggesting a protective effect of vitamin D on NCI., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Dong, Lin, Chen, Shi, Yuan, Li, Zhu, Xu, Shen, Wang, Shu, Ding and He.)

To investigate the prevalence of emotional and behavioral problems (EBPs) among children during the COVID-19 post-pandemic in China; examine associations between COVID-19-related knowledge and precautions and problems in children, and explore the potential explanatory value of the mental health status of caregivers on any associations observed. Based on a cross-sectional design, caregivers of 6,017 children from 12 primary schools in Shanghai and Taizhou, China, were invited to complete an online survey from June 26 to July 6, 2020. EBPs of the children were assessed using the Strengths and Difficulties Questionnaire (SDQ), while the emotional problems of caregivers were assessed using the Depression Anxiety Stress Scales-21 (DASS-21). Structural equation modeling was employed to estimate the direct and indirect associations (explained by the emotional problems of caregivers) between COVID-19-related knowledge and precautions and the EBPs among children. The overall prevalence of EBPs in the sample was 12.5%, and 5.3% of them had a high or very high SDQ total difficulties score during the COVID-19 post-pandemic. After adjustment for covariates, higher COVID-19-related knowledge (β = -0.83; P < 0.001) and precautions (β = -0.80; P < 0.001) were significantly associated with lower SDQ total difficulties score among children. There was an explanatory effect of emotional problems of caregivers on the aforementioned associations, which explained 31% and 41% of the total effect, respectively. Higher levels of knowledge and precautions of COVID-19 were associated with lower EBPs among children, and the relationship was partially explained by the emotional problems in caregivers. It may be beneficial to improve pandemic-related prevention education and adopt psychological interventions toward the emotional status of caregivers for the psychological health of children., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wang, Chen, Guo, Lin, Richards, Wang, Chen and Fu.)

Background: HIV infection and normal aging share immune and inflammatory changes that result in premature aging and non-communicable diseases (NCDs), but the exact pathophysiology is not yet uncovered. We identified the common metabolic pathways underlying various NCDs in treated HIV infection., Methods: We performed untargeted metabolomics including 87 HIV-negative (-) normal controls (NCs), 87 HIV-positive (+) NCs, and 148 HIV+ subjects with only one type of NCDs, namely, subclinical carotid atherosclerosis, neurocognitive impairment (NCI), liver fibrosis (LF) and renal impairment. All HIV+ subjects were virally suppressed., Results: HIV+ patients presented widespread alterations in cellular metabolism compared to HIV- NCs. Glycerophospholipid (GPL) metabolism was the only one disturbed pathway presented in comparisons including HIV- NCs across age groups, HIV+ NCs across age groups, HIV+ NCs vs HIV- NCs and each of HIV+ NCDs vs HIV+ NCs. D-glutamine and D-glutamate metabolism and alanine-aspartate-glutamate metabolism were presented in comparisons between HIV+ NCs vs HIV- NCs, HIV+ LF or HIV+ NCI vs HIV+ NCs. Consistently, subsequent analysis identified a metabolomic fingerprint specific for HIV+ NCDs, containing 42 metabolites whose relative abundance showed either an upward (mainly GPL-derived lipid mediators) or a downward trend (mainly plasmalogen phosphatidylcholines, plasmalogen phosphatidylethanolamines, and glutamine) from HIV- NCs to HIV+ NCs and then HIV+ NCDs, reflecting a trend of increased oxidative stress., Interpretation: GPL metabolism emerges as the common metabolic disturbance linking HIV to NCDs, followed by glutamine and glutamate metabolism. Together, our data point to the aforementioned metabolisms and related metabolites as potential key targets in studying pathophysiology of NCDs in HIV infection and developing therapeutic interventions., Funding: China National Science and Technology Major Projects on Infectious Diseases, National Natural Science Foundation of China, Yi-wu Institute of Fudan University, and Shanghai Municipal Health and Family Planning Commission., Competing Interests: Declaration of Competing Interest We declared no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: The COVID-19 related lockdown and home confinement might have an important impact on the quality of life in enterprise workers. We investigated the quality of life during the epidemic in enterprise workers who just returned to work, and assessed its potential influencing factors to have a better understanding of the impact of COVID-19 epidemic lockdown and home confinement., Methods: This was a cross-sectional study of enterprise workers conducted in Deqing and Taizhou, Zhejiang Province, China. The Chinese version of EQ5D was used to assess life quality, and information about general characteristics and COVID-19 related factors was collected by a structured questionnaire, which was distributed through the social application "WeChat". Multiple liner regression was used to investigate potential influencing factors., Results: A total of 2420 participants were enrolled, 59.5% of which worked in Deqing. About 50% of the participants reported worries about the COVID-2019 epidemic and 40.2% had a centralized or home quarantine during the epidemic. The mean EQ-5D score and VAS were 0.990 and 93.5. Multiple liner regression showed that the quality of life measures was related to physical activities (β = 0.006) and keeping home ventilation (β = 0.063) in Deqing, and were related to wearing a mask when going out (β = 0.014), keeping home ventilation (β = 0.061), other marital status (β = - 0.011), worry about the epidemic (β = - 0.005) and having a centralized or home quarantine (β = - 0.005) in Taizhou., Conclusions: The quality of life for returning enterprise workers in areas with different risks of COVID-19 was affected by different factors. Associated factors identified from this study would help develop proper intervention measures for enterprise workers to reduce the impact of large-scale public health events like the COVID-19 on their quality of life., (© 2021. The Author(s).)

Purpose: To determine the prevalence of depression and anxiety and associated factors among returning workers with different epidemic experience in East China., Methods: A cross-sectional study was conducted among 2435 employees from the enterprises located in Deqing (low-risk epidemic area) and Taizhou (high-risk epidemic area) of East China in March 2020. An online questionnaire covered information on sociodemographic and lifestyle factors as well as knowledge, attitude, behavior and experience about COVID-19. The Patient Health Questionnaire-9 (PHQ-9) and the Generalized Anxiety Disorder-7 (GAD-7) were applied to assess depression and anxiety symptoms, respectively. Logistic regression model was used to estimate adjusted odds ratios (aORs) and their 95% confidence intervals (CIs) for depression and anxiety symptoms associated with risk factors., Results: The participants were aged 36.3 ± 9.2 years on average, and nearly half of them were female. Overall, the prevalence of depression, anxiety and both were 19.4%, 12.3% and 9.8%, and decreased with age. After adjustment for covariates, 16 or more years of education, being a white-collar worker or working in the high-risk epidemic area were significantly associated with increased risks of both depression and anxiety, in contract regular physical exercise was associated with decreased risks of both mental disorders., Conclusion: The depression and anxiety problems were prevalent among returning workers during the COVID-19 period. Targeted psychological interventions should be developed and implemented to improve their mental health.

The wet form of age-related macular degeneration is characterized by neovascular pathologies that, if untreated, can result in edemas followed by rapid vision loss. Inhibition of vascular endothelial growth factor (VEGF) has been used to successfully treat neovascular pathologies of the eye. Nonetheless, some patients require frequent intravitreal injections of anti-VEGF drugs, increasing the burden and risk of complications from the procedure to affected individuals. Recombinant adeno-associated virus (rAAV)-mediated expression of anti-VEGF proteins is an attractive alternative to reduce risk and burden to patients. However, controversy remains as to the safety of prolonged VEGF inhibition in the eye. Here, we show that two out of four rAAV serotypes tested by intravitreal delivery to express the anti-VEGF drug conbercept lead to a dose-dependent vascular sheathing pathology that is characterized by immune cell infiltrates, reminiscent of vasculitis in humans. We show that this pathology is accompanied by increased expression in vascular cell adhesion molecule 1 (VCAM1) and intercellular adhesion molecule 1 (ICAM1), both of which promote extravasation of immune cells from the vasculature. While formation of the vascular sheathing pathology is prevented in immunodeficient Rag-1 mice that lack B and T cells, increased expression of VACM1 and ICAM1 still occurs, indicating that inhibition of VEGF function leads to expression changes in cell adhesion molecules that promote extravasation of immune cells. Importantly, a 10-fold lower dose of one of the vectors that cause a vascular sheathing pathology is still able to reduce edemas resulting from choroidal neovascularization without causing any vascular sheathing pathology and only a minimal increase in VCAM1 expression. The data suggest that treatments of neovascular eye pathologies with rAAV-mediated expression of anti VEGF drugs can be developed safely. However, viral load needs to be adjusted to the tropisms of the serotype and the expression pattern of the promoter.

Corneal neovascularization (CoNV) leads to visual impairment, affecting over 1.4 million people in the United States per year. It is caused by a variety of pathologies, such as inflammation, hypoxia, and limbal barrier dysfunction. Injection of the anti-vascular endothelial growth factor (VEGF) drug KH902 (conbercept) can inhibit CoNV but requires repeated dosing that produces associated side effects, such as cornea scar. To explore more efficacious and long-lasting treatment of CoNV, we employed recombinant adeno-associated virus (rAAV)2 and rAAV8 vectors to mediate KH902 expression via a single intrastromal injection and investigated its anti-angiogenic effects and safety in both alkali-burn- and suture-induced CoNV mouse models. Our results showed that rAAV-mediated KH902 mRNA expression in the cornea was sustained for at least 3 months after a single intrastromal injection. Moreover, the expression level of rAAV8- KH902 far exceeded that of rAAV2- KH902 . A single-dose rAAV8- KH902 treatment at 8 × 10 8 genome copies (GCs) per cornea dramatically inhibited CoNV for an extended period of time in mouse CoNV models without adverse events, whereas the inhibition of CoNV by a single intrastromal administration of the conbercept drug lasted for only 10-14 days. Overall, our study demonstrated that the treatment of CoNV with a single dose of rAAV8- KH902 via intrastromal administration was safe, effective, and long lasting, representing a novel therapeutic strategy for CoNV., Competing Interests: G.G. is a scientific co-founder of Voyager Therapeutics, Adrenas Therapeutics, and Aspa Therapeutics; holds equity in these companies; and is an inventor on patents with potential royalties licensed to Voyager Therapeutics, Aspa Therapeutics, and other biopharmaceutical companies. G.G., H.L., and P.W.L.T. are inventors on patents with potential royalties licensed to Kanghong Pharmaceutical Group. The remaining authors declare no competing interests., (© 2021 The Authors.)

Introduction: The perceived health benefits and effectiveness of electronic cigarettes (e-cigarettes) in quitting smoking may affect e-cigarette usage, however, research on the use of e-cigarettes among the Chinese, especially among the rural Chinse, is scarce. This study examined factors associated with perceptions of e-cigarette related harms, benefits, and addictiveness, among smoker and non-smoker households with children in rural China, to support the design of population-based interventions targeting rural Chinese households., Methods: In a cross-sectional study design, using a structured questionnaire, we collected data from the household members of children in two selected rural communities in China. Descriptive analyses were used to characterize respondents; χ 2 test and Fisher's exact probability test were used to compare the perceptions of e-cigarettes between different sociodemographic groups. Logistic regression was used to determine predictors for e-cigarette harms, benefits, and addictiveness, adjusting for demographic and other characteristics., Results: The overall participation rate was 81% (1211/1498). Of the participants, 668 (55%) were smokers and 543 (45%) were non-smokers; 53% knew about e-cigarettes. Participants from rural Dali (77% vs 59%), those who were ethnic minority (76% vs 59%), those who perceived increased COPD risks from smoking (mean score 4.37 vs 4.18) and concerned about harmful effects of secondhand smoke (SHS) exposure to children (mean score 4.48 vs 4.30) and adults (mean score 4.06 vs 3.87) were more likely to believe that e-cigarettes were less harmful (p<0.05). Participants with more knowledge about the harm of smoking were more likely to believe that e-cigarettes were helpful in quitting smoking (p<0.05). Of those participants who knew about e-cigarettes, females (19%) were significantly more likely to believe that e-cigarettes are addictive than males (10%). In the logistic regression analyses, believing e-cigarettes are helpful to quit smoking was the only variable associated with holding a higher knowledge about smoking and SHS exposure (OR=0.608; 95% CI: 0.450-0.820)., Conclusions: Our results showed that more than half of the rural household members who have a child at home were aware of e-cigarettes. Knowledge about health impacts of SHS exposure and perceptions about the benefits, harms and addictiveness of e-cigarette use varied among the participants, with a significant proportion of participants having wrong information. Public health campaigns to disseminate evidence-based information of e-cigarette benefits and harms are warranted. As knowledge about the harmfulness of smoking and SHS exposure was associated with perceived e-cigarette benefits, particular focus should be given to increasing knowledge about the health hazards related to smoking and SHS exposure., Competing Interests: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none was reported., (© 2021 Zhao D. et al.)

Background: Little is known about the prevalence of and risk factors for adolescent mental health problems during the COVID-19 outbreak. We aimed to investigate the prevalence of depressive symptoms, their association with study-relevant problems, and the moderating effect of parent-child relationship among Chinese adolescents during the school closures., Methods: We performed a cross-sectional analysis with data collected in middle and high schools in Taizhou, China. Students completed an online survey between April 16 and May 14, 2020. Depressive symptoms were assessed using the Children's Depression Inventory. Three types of study problems were recorded, including having difficulty in studying at home, dislike of remote learning, and excessive screen entertainment time. Parental relationships were categorized into good or normal relationship and poor relationship. Linear regression and logistic regression analyses were conducted to investigate the associations between study-relevant problems and depressive symptoms., Results: Using data from 6435 adolescents, we found that the prevalence of depressive symptoms was 17.7%. All the study problem measures were associated with more severe depressive symptoms. There was a moderating effect of the parental relationship on the associations between study problems and depressive symptoms. The association between number of study problems and depressive symptoms was stronger in adolescents with a poor parent-child relationship (regression coefficient 4.34 [95% CI 2.97, 5.72]) than those with a good or normal relationship (2.55 [2.35, 2.75]), p for interaction 0.002, on multivariable adjustment., Conclusions: Study problems due to school closures were particularly problematic for adolescents who had poor parent-child relationships. Public health initiatives could help students to adjust study habits and improve parent-child relationships, thereby protecting against the development of depression.

Metabolic syndrome (MS) is common among obese people. Little is known about the magnitude and characteristics of MS in people living with HIV (PLWH) in Asian countries in general and China in particular. Using baseline data collected between February 2017 through January 2020 from the Comparative HIV and Aging Research in Taizhou (CHART) cohort in China, we examined MS among 2,227 PLWH and 5,264 matched people without HIV, respectively. MS was defined using the criteria set forth by the International Diabetes Federation (IDF). Approximately 76.7% of PLWH had body mass index (BMI) < 24.0 kg/m 2 , significantly higher than people without HIV (50.3%). Among participants with BMI < 24.0 kg/m 2 , PLWH had a significantly higher prevalence of MS than people without HIV (20.6% vs. 14.5%; aOR: 1.41, 95% CI: 1.19-1.68) overall, and at an age of 18-29 (10.4% vs. 3.4%, aOR: 3.49, 95% CI: 1.99-6.11) and 30-44 years (17.3% vs. 8.5%, aOR: 2.03, 95% CI: 1.47-2.81), respectively. Among participants with BMI ≥ 24.0 kg/m 2 , MS prevalence was not significantly different between PLWH and people without HIV overall, but significantly lower in PLWH than people without HIV for those aged over 60 years (65.9% vs. 77.8%, aOR: 0.53, 95% CI: 0.32-0.88). Among PLWH, MS was significantly associated with older age and higher CD4 cell count, and with stavudine (d4T) use only in the group of BMI < 24.0 kg/m 2 . Our finding is indicative of a relatively higher risk for early onset of MS among HIV-infected young adults with lower BMI. Research is needed to elucidate the pathogenic mechanism for MS among PLWH.

Introduction: In less than two months, the COVID-19 outbreak in China was controlled through the stringent strategies of screening and isolation. This article aims to use empirical data from all cases from a prefecture-level city of China to introduce and examine the feasibility and efficiency of the screening and isolation strategies and how these were essential in combatting the COVID-19 outbreak., Methods: For this retrospective study, all confirmed COVID-19 patients were recruited from the Taizhou prefecture-level city of Zhejiang province, China., Results: Of the city's total population, 24% were screened for COVID-19 and isolated at home or designated locations for two weeks. From these, a total of 146 confirmed cases of COVID-19 were analysed. Of all cases, 51% were traced from Wuhan, and 21% of patients were in close contact with confirmed cases from outside of the city. Initially, 13% of all patients reported having no clear symptoms, while 42% of patients presented with fever and/or other symptoms. Compared with local patients, new arrivals to the city had fewer days between their exposure and the development of symptoms of COVID-19 ( P <0.001), and fewer days from the time they developed symptoms to the confirmation of COVID-19 ( P <0.001), respectively., Conclusion: This study has fully confirmed that controlling the COVID-19 outbreak through screening and isolation is effective, efficient, and essential. The evidence-based framework and implementation of China's strategy to combat COVID-19 can explain how China contained the COVID-19 outbreak in a short time period. This study offers important references and implications for containing the COVID-19 pandemic in the global community., Competing Interests: The authors report no conflicts of interest for this work., (© 2020 Zhao et al.)

Problem: On 21 January 2020, the city of Taizhou, China, reported its first imported coronavirus disease 2019 (COVID-19) case and subsequently the number of cases rapidly increased., Approach: To organize the emergency responses, the government of Taizhou established on 23 January 2020 novel headquarters for prevention and control of the COVID-19 outbreak, by coordinating different governmental agencies. People at high risk of acquiring COVID-19, as well as probable and confirmed cases, were identified and quarantined. The government closed public venues and limited gatherings. The Taizhou Health Commission shared information about identified COVID-19 patients and probable cases with affected agencies. To timely track and manage close contacts of confirmed cases, Taizhou Center for Disease Control and Prevention did epidemiological investigations. Medical institutions or local centers for disease control and prevention reported confirmed cases to the national Center for Disease Control and Prevention., Local Setting: Taizhou, a city in Zhejiang province with about 6 million residents, reported 18 confirmed COVID-2019 cases by 23 January 2020, which ranked it third globally in number of cases after Wuhan and Xiaogan cities in the Hubei province., Relevant Changes: In total, 146 confirmed cases (85 cases imported and 61 cases through community transmission) and no deaths due to COVID-19 had been reported in Taizhou by 1 June 2020. Between 16 February and 1 June 2020, no confirmed case had been reported., Lesson Learnt: Identifying and managing imported cases and people at risk for infection, timely information sharing, limiting gatherings and ensuring collaborations between different agencies were important in controlling COVID-19., ((c) 2020 The authors; licensee World Health Organization.)

Coronavirus disease 2019 (COVID-19), a newly identified acute respiratory disease caused by a strain of novel coronavirus (SARS-CoV-2), has become a worldwide pandemic. From December 2019 to present, millions of cases have been reported, bringing unprecedented pressure on both health and epidemic prevention services in every country. As frontline healthcare workers, ophthalmologists face an increased threat of viral infection, not only because of close contact with patients during examinations or operations, but also due to evidence showing that ocular fluids such as tears or conjunctival secretions may carry the virus. The risk that healthcare workers face is emphasized by the loss of our colleagues who have sacrificed themselves in combating the virus. As a result, it is necessary to have a comprehensive understanding of the threats that we face. In the first part of this review, we start by explaining the structure of SARS-CoV-2 and examining its transmission and means of infection. Next, we summarize the latest scientific advancements of epidemiology, clinical presentations, and current treatments of COVID-19. In the second half of the review, we emphasize the ocular transmission, symptomatic manifestations, and the essential knowledge in an ophthalmology clinic setting. As the pandemic of COVID-19 continues to pose a threat to global health, we hope that this review makes a contribution to combating COVID-19.

Objective/background: This study assessed the prevalence and correlates of various sleep disturbances in HIV-infected patients compared to sex- and age-frequency-matched HIV-uninfected controls in China., Methods: This cross-sectional analysis included 1469 HIV-infected cases and 2938 HIV-uninfected controls. Insomnia symptoms, poor sleep quality (Pittsburgh Sleep Quality Index [PSQI] >5) as well as their specific domains, were assessed., Results: Prevalence of insomnia symptoms, poor sleep quality, and long sleep duration were higher in HIV-infected vs uninfected participants (23.7% vs 19.8%, 24.1% vs 19.9%, and16.1% vs 8.7%, respectively; all p < 0.05), and remained significant after adjusting for age, sex and education. An Age-stratified analysis showed that such differences were significant only at ages 18-29 and 30-44 years for insomnia symptoms and poor sleep quality long sleep duration was significant across all age groups. Among HIV-infected patients, multivariate analysis indicated that older age, depressive symptoms and frailty score were the most consistent variables associated with sleep disorders (ie, insomnia symptoms, poor sleep quality, short and long sleep durations), as well as all associations (if significant) were positive, excluding the negative associations of older age and depressive symptoms with short sleep duration. Regarding HIV-specific factors, only current CD4 cell count ≥500 cells/μL was negatively associated with insomnia symptoms., Conclusions: The impact of HIV infection on sleep disturbances may differ across age groups and are more pronounced among young adults. Additionally, the phenomenon of prolonged sleep duration among HIV-infected patients should be noted, and its link to poor physical health warrants further investigation., (Copyright © 2019. Published by Elsevier B.V.)

Background: Norovirus (NoV) is recognized as a leading global cause of viral acute gastroenteritis (AGE). To better understand the prevalence and genotypic patterns of NoV infection in Southeast China, we conducted a retrospective study of diarrheal syndrome surveillance of NoV and analyzed the epidemiological characteristics of AGE cases and phylogenetic evolution of NoV strains., Methods: 1464 AGE patients in two diarrhea surveillance sentinel hospitals were sampled during 2016 and 2017. NoV Positive samples were genotyped by ORF1/ORF2 overlapping regional gene sequencing. Sequences analyses of the NoV genotypes were confirmed by online NoV Genotyping Tool and the phylogenetic analysis was constructed by MEGA 7.0., Results: 139 (9.49%) of the AGE specimens were NoV positive. The GII strain was the main geno-group in NoV infected patients. At least 12 NoV genotypes and seven recombinant strains were detected. Major NoV genotypic transformations were GII.Pe/GII.4, GII.P17/GII.17 and GII.Pe/GII.17 in 2016 to GII.P16/GII.2, GII.P17/GII.17 and GII.Pe/GII.4 in 2017. Phylogenetic analysis showed that GII.P16/GII.2 recombinant strains clustered with those detected in the USA, Russia and Japan in 2016., Conclusion: We characterized the molecular epidemiology of NoV infection in AGE patients during 2016-2017. The main three NoV GII genotypes circulating in the population of Taizhou were GII.P17/GII.17, GII.Pe/GII.4 and GII.P16/GII.2.The GII.P16/GII.2 genotype has become the predominant strain since first quarter 2017. Monitoring of the NoV genotypic shift is important for the prevention and control of AGE., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Although the use of mobile health (mHealth) to promote tobacco control and smoking cessation interventions has been available in developed countries, their use in low- and middle-income countries (i.e. in China) is lacking. This study examined the acceptance of text messaging and/or WeChat based tobacco control intervention among parents who smoke, in rural China., Methods: Using a structured questionnaire, we surveyed smoker households (n=668) of children aged ≤5 years in two rural regions of southern China. Descriptive analyses were used to characterize respondents; multivariate regression analysis was used to test the associations between participants' sociodemographic and other characteristics, and their acceptability of text messaging and/or WeChat intervention for tobacco control., Results: After adjusting for other variables (i.e. region, ethnicity, age, education level, occupation, attitudes towards smoking, perception of cigarettes addictiveness, and quitting smoking), the overall knowledge about smoking and secondhand smoke (SHS) exposure significantly predicted a higher acceptance to text messaging/WeChat intervention (OR=0.567; 95% CI: 0.457-0.704). Participants who thought smoking made people feel relaxed were less likely to accept text messaging/WeChat intervention than those who did not think so (OR=1.403; 95% CI: 1.080-1.822)., Conclusions: Our findings suggest that households in rural China that were more knowledgeable about the hazards of smoking and SHS exposure, and had negative feelings about the benefits of smoking, were more likely to accept text messaging/WeChat for tobacco control intervention. Understanding rural smokers' preferences to receive intervention and related characteristics can help with the design of targeted tobacco control intervention programs in rural China., Competing Interests: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none was reported., (© 2019 Chen X. et al.)

Background: Inconclusive results have been reported in studies evaluating the association between HIV infection and subclinical atherosclerosis. Unsolved issues include whether the increased atherosclerosis burden observed in some studies is attributed to greater prevalence of traditional risk factors or HIV infection. Therefore, we evaluated the association of HIV infection with subclinical atherosclerosis as assessed by carotid artery intima-media thickness, while controlling for the effects of traditional risk factors as operationalised by the Framingham risk score (FRS)., Methods: We did a cross-sectional evaluation of data derived from the baseline assessment of the Comparative HIV and Aging Research in Taizhou (CHART) cohort, an ongoing longitudinal study being done in Zhejiang province, China. HIV-positive and HIV-negative individuals aged 18 years and older were recruited between Feb 1, and Dec 10, 2017, and were frequency-matched for age and sex in a 1:2 ratio. Subclinical atherosclerosis was defined as carotid artery intima-media thickness of 780 μm or higher. Logistic regression was used to assess the associations of HIV-positive serostatus and FRS with subclinical atherosclerosis., Findings: 480 of 1425 (36·1%, 95% CI 33·6-38·6) HIV-positive and 784 of 2850 (27·5%, 95% CI 25·9-29·2) HIV-negative individuals had subclinical atherosclerosis (p<0·0001), and these patterns remained significant (adjusted odds ratio [adjOR] 1·72, 95% CI 1·47-2·01) in the adjusted model. After stratifying by age, higher prevalence of subclinical atherosclerosis was observed in HIV-positive than in HIV-negative individuals across the age groups 18-29 years (41 [16·0%] of 256 vs 13 [2·5%] of 512, p<0·0001), 30-44 years (128 [24·0%] of 533 vs 153 [14·4%] of 1066, p<0·0001), and 45-59 years (182 [46·6%] of 391 vs 294 [37·6%] of 782, p=0·0032), but not 60-75 years (163 [66·5%] of 245 vs 324 [66·1%] of 490, p=0·912). Significant negative interaction between HIV-positive serostatus and age on subclinical atherosclerosis was observed (p<0·0001). ORs adjusted for age, sex, and FRS were 8·84 (95% CI 4·50-17·34) for the age group 18-29 years, 2·09 (1·59-2·74) for 30-44 years, 1·54 (1·19-1·98) for 45-59 years, and 1·04 (0·75-1·44) for 60-75 years. Among HIV-positive individuals, none of the HIV-specific variables were significantly associated with carotid artery intima-media thickness estimates except for being antiretroviral therapy naive., Interpretation: HIV infection is associated with subclinical atherosclerosis, independent of classic risk factors. The association is stronger at younger ages, suggesting early onset of subclinical atherosclerosis among young adults. These findings highlight the need to modify HIV/AIDS treatment guidelines to incorporate cardiovascular evaluation in China., Funding: China National Science and Technology Major Projects on Infectious Diseases, National Natural Science Foundation of China, and Shanghai Municipal Health and Family Planning Commission., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Gut microbiota is closely related to age. Studies from Europe and the U.S. identified featured microbiota in different age groups for the elderly. Asian studies mainly focused on people living in longevity areas. Featured microbiota for the elderly people of different age groups, especially in the centenarian in the general population, has not been well investigated in China., Method: We conducted a comparative study by including 198 subjects of three age groups (65-70, 90-99, and 100+ years) in East China. Information regarding age, sex, height, weight, waist circumference, hip circumference, food preference, smoking status and alcohol consumption were collected by using a structured questionnaire. Fecal samples for each participant were collected as well. 16S rRNA gene sequencing were employed to analyze the gut microbiota composition. Logistic regression with LASSO feature selection was used to identify featured taxa in different age groups and to assess their potential interactions with other factors such as lifestyle., Result: The gut microbiota of the 90-99 year and 100+ year age groups showed more diversity, robustness, and richness compared with the 65-70 year age group. PCoA analysis showed a clear separation between the 65-70 and 100+ year age groups. At the species level, Bacteroides fragilis, Parabacteroides merdae, Ruminococcus gnavus, Coprococcus and Clostridium perfringens increased, but Bacteroides vulgatus, Ruminococcus sp.5139BFAA and Clostridium sp.AT5 decreased in the 90-99 year age group. The age differences in gut microbiota were similar across the strata of smoking, alcohol consumption status and food preference., Conclusion: Our study demonstrated age differences in many aspects of gut microbiota, such as overall diversity, microbiota structure, and relative abundance of key taxa. Moreover, the gut microbiota of centenarian was significantly different from those of younger age groups of the elderly., Competing Interests: The authors have declared that no competing interests exist.

HIV-infected (HIV+) women may be more vulnerable to neurocognitive impairment (NCI) due to psychological and physiological factors but previous studies show mixed findings. We investigated the neurocognitive performances in HIV+ versus HIV- women and men. This cross-sectional analysis included 669 HIV+ patients (223 women) and 1338 HIV-uninfected (HIV-) controls (446 women) which were frequency matched on sex, education, and 5-year age categories. NCI was screened using the Mini-mental State Examination. Psychomotor speed was assessed using timed alternating hand sequence test. Prevalence of NCI was higher among women versus men in the HIV+ group (16.1% vs 10.5%) but not the HIV- group (4.3% vs 3.5%). HIV+ women performed worse compared to men on psychomotor speed, orientation, attention, and calculation, whereas HIV- women performed worse compared to men on attention and calculation. Adjusted interaction effects of HIV status × sex (women vs men) were significant on orientation, attention, and calculation, and marginally significant on psychomotor speed (p = 0.053). In multivariable models, among both HIV+ women and men, less years of education and depressive symptoms were associated with NCI. Waist-to-hip ratio above the cut-off was strongly associated with NCI among HIV+ women. HIV+ women perform worse on cognitive measures compared to HIV+ men. The association of central obesity with NCI in HIV+ women should be noted.