Concentrations and influencing factors of 17 elements in placenta, cord blood, and maternal blood of women from an e-waste recycling area.

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.

Seroprevalence and transmission of severe fever with thrombocytopenia syndrome virus in a coastal endemic area in Southeastern China.

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.

Incidence, clearance, and factors associated with anal human papilloma virus infection among men with HIV.

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.

Association of Insomnia, Sleep Quality, and Sleep Duration With Risk of Physical Frailty in Middle-aged and Older People With HIV.

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.

Network structure of emotional and behavioral problems, loneliness, and suicidal thoughts in adolescents at the school closure and reopening stage in China.

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.

Psychosocial problems and suicidal ideation in Chinese adolescents: findings from a longitudinal study.

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.

Differential genome-wide associated variants and enriched pathways of ECG parameters among people with versus without HIV.

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.

Loneliness and depressive symptoms among men who have sex with men in China: A cross-sectional study.

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.

Diagnosis and Treatment Pathway of MDR/RR-TB in Taizhou, Zhejiang Province, China.

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.

Associations between HIV infection and frailty status and its individual components: Are frailty components disproportionally affected?

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.

Identifying Novel Genes and Variants in Immune and Coagulation Pathways Associated with Macular Degeneration.

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.

Associations between educational burden and depression and anxiety symptoms among middle school students in Taizhou City / 中国学校卫生

Objective@#To investigate the prevalence of depression and anxiety symptoms among middle school students in Taizhou, Zhejiang Province, and its associations with their educational burden, so as to provide a theoretical reference for making more targeted psychological interventional measures.@*Methods@#A cross sectional study was conducted by multi stage cluster sampling from September to November 2022 from 30 schools in five districts and counties of Taizhou, with a final sample of 8 128 junior and senior high school students completing the online surveys on the Questionnaire Star platform. The Educational Stress Scale for Adolescents (ESSA) was used to measure academic stress; the Child Depression Inventory (CDI) and the Generalized Anxiety Disorder Scale (GAD-7) were used to screen students depression and anxiety, respectively. The relationships between educational burden and depression and anxiety symptoms were analyzed by Logistic regression models.@*Results@#The prevalence of depression and anxiety were 19.3% and 11.1%, respectively. The average score of middle school students study pressure was (52.8±11.5). The number of extracurricular classes was <1, the time length of extracurricular courses was <1 hour per day, and students averagely spend 3.6 hours per day on homework assigned by school teachers. Nearly 30.0% students had ≤0.5 of discretionary time school days and 28.5% students had ≤2 on weekends. About 30.8% students though they do worse in their academic performance. According to the results of binary Logistic regression analysis, after controlling the demographic variables, the score in Study Pressure Scale, the number of extracurricular classes, the volume of homework and the time length of extracurricular courses were positively associated with depression and anxiety ( OR =1.09, 1.07, 1.08, 1.05, 1.04, 1.08, 1.08, 1.08, 1.06, 1.09, 1.07, 1.47, 1.34, 2.84 ; 1.08, 1.06, 1.08, 1.04, 1.03, 1.05, 1.05, 1.05, 1.05, 1.07, 1.06, 1.48, 1.23, 1.75, P <0.05). Students with overage grades had a higher risk of depression symptoms ( OR=1.34, P <0.05).@*Conclusions@#Academic burden has negative effects on depression and anxiety of students in Taizhou. It is advisable to alleviate academic stress, so as to improve the mental health of students.

Genome-wide associated variants of subclinical atherosclerosis among young people with HIV and gene-environment interactions.

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.

Ocular Drug Delivery: Advancements and Innovations.

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.

Association Between Inflammation and Coagulation Biomarkers and Carotid Atherosclerosis Among Treated People With Human Immunodeficiency Virus.

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.

Analysis of the effect of meteorological factors on hemorrhagic fever with renal syndrome in Taizhou City, China, 2008-2020.

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.

A ten-year assessment of the epidemiological features and fatal risk factors of hospitalised severe fever with thrombocytopenia syndrome in Eastern China.

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.

Increased CD4+ T cell count is associated with lower anal human papillomavirus prevalence among HIV-positive male cohort in Taizhou, China: a cross-sectional study.

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.

Incidence of impaired kidney function among people with HIV: a systematic review and meta-analysis.

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/1.73m2 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/1.73m2, eGFR< 30 ml/min/1.73m2 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/1.73m2. 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.