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A novel goose astrovirus (GAstV) has broken out across China in recent years, causing widespread damage to the poultry industry. In goslings infected with GAstV, the leading cause of death is visceral gout. However, our understanding of themechanismof gout formation in GAstV infection is largely inadequate. The aim of this study was to examine the pathogenicity of a GAstV strain and explore the molecular mechanisms of visceral gout caused by viral infection in goslings. The virulent GAstV strain HR2105/1 was effectively isolated from the visceral tissue of goslings in gout-affected areas. The whole genome of the HR2105/1 strain was sequenced and analyzed. Subsequently, we established a gosling goutmodels with experimental GAstV infection. Finally, we conducted a study on the mechanism of GAstV induced acute kidney injury. Phylogenetic analysis of the complete genome sequence showed that it was closely related to the strain circulating in China since 2016, and it was grouped within the GAstV-1 cluster. The clinical signs were reproduced by experimental infection of healthy goslings with the isolated strain andwere found to be similar to those reported in clinical cases. Moreover, the virus exhibits strong renal tropism. Infection with the GAstV strain HR2105/1 was found to cause acute kidney injury, as evidenced by increased levels of uric acid and creatinine as well as severe pathological damage. Mechanistic experiments with Masson and Picrosirius Red staining revealed fibrosis in renal tissues after GAstV infection. Furthermore, TUNEL staining revealed that GAstV infection triggered renal cell apoptosis. Additionally, RT-qPCR revealed that GAstV infection caused an excessive inflammatory response by upregulating the expression of IL-1b, IL-6, IL-10, TGF-b, and iNOS in renal tissues. Overall, our findings demonstrate that GAstV infection causes renal damage by inducing renal cell apoptosis, fibrosis, and excessive inflammatory response, which subsequently leads to hyperuricemia and lethal visceral gout formation. This is the first systematic study on the etiology of lethal gout in goslings caused by GAstV infection, and we believe that the findings can guide vaccine development and therapeutic targets for GAstVassociated renal diseases. [ABSTRACT FROM AUTHOR]

Introduction: The host immune response determines the differential outcome of acute or chronic viral infections. The comprehensive comparison of lymphoid tissue immune cells at the single-cell level between acute and chronic viral infections is largely insufficient. Methods: To explore the landscape of immune responses to acute and chronic viral infections, single-cell RNA sequencing(scRNA-seq), scTCR-seq and scBCRseq were utilized to evaluate the longitudinal dynamics and heterogeneity of lymph node CD45+ immune cells in mouse models of acute (LCMV Armstrong) and chronic (LCMV clone 13) viral infections. Results: In contrast with acute viral infection, chronic viral infection distinctly induced more robust NK cells and plasma cells at the early stage (Day 4 postinfection) and acute stage (Day 8 post-infection), respectively. Moreover, chronic viral infection exerted decreased but aberrantly activated plasmacytoid dendritic cells (pDCs) at the acute phase. Simultaneously, there were significantly increased IgA+ plasma cells (MALT B cells) but differential usage of B-cell receptors in chronic infection. In terms of T-cell responses, Gzma-high effector-like CD8+ T cells were significantly induced at the early stage in chronic infection, which showed temporally reversed gene expression throughout viral infection and the differential usage of the most dominant TCR clonotype. Chronic infection also induced more robust CD4+ T cell responses, including follicular helper T cells (Tfh) and regulatory T cells (Treg). In addition, chronic infection compromised the TCR diversity in both CD8+ and CD4+ T cells. Discussion: In conclusion, gene expression and TCR/BCR immune repertoire profiling at the single-cell level in this study provide new insights into the dynamic and differential immune responses to acute and chronic viral infections. [ABSTRACT FROM AUTHOR]

Epigenetic regulation of inflammatory macrophages governs inflammation initiation and resolution in the pathogenesis of rheumatoid arthritis (RA). Nevertheless, the mechanisms underlying macrophage-mediated arthritis injuries remain largely obscure. Here, we found that increased expression of lysine acetyltransferase 2A (KAT2A) in synovial tissues was closely correlated with inflammatory joint immunopathology in both RA patients and experimental arthritis mice. Administration of MB-3, the KAT2A-specific chemical inhibitor, significantly ameliorated the synovitis and bone destruction in collagen-induced arthritismodel. Both pharmacological inhibition and siRNAsilencing ofKAT2A, not only suppressed innate stimuli-triggered proinflammatory gene (such as Il1b and Nlrp3) transcription but also impaired NLR family pyrin domain containing 3 (NLRP3) inflammasome activation in vivo and in vitro. Mechanistically, KAT2A facilitated macrophage glycolysis reprogramming through suppressing nuclear factor-erythroid 2-related factor 2 (NRF2) activity as well as downstream antioxidant molecules, which supported histone 3 lysine 9 acetylation (H3K9ac) and limited NRF2-mediated transcriptional repression of proinflammatory genes. Our study proves that acetyltransferase KAT2A licenses metabolic and epigenetic reprogramming for NLRP3 inflammasome activation in inflammatory macrophages, thereby targeting KAT2A represents a potential therapeutic approach for patients suffering from RA and relevant inflammatory diseases. [ABSTRACT FROM AUTHOR]

Spinocerebellar ataxia (SCA) is an autosomal dominant neurodegenerative disease (ND) with a high mortality rate. Symptomatic treatment is the only clinically adopted treatment. However, it has poor effect and serious complications. Traditional diagnostic methods [such as magnetic resonance imaging (MRI)] have drawbacks. Presently, the superiority of RNA interference (RNAi) and extracellular vesicles (EVs) in improving SCA has attracted extensive attention. Both can serve as the potential biomarkers for the diagnosing and monitoring disease progression. Herein, we analyzed the basis and prospect of therapies for SCA. Meanwhile, we elaborated the development and application of miRNAs, siRNAs, shRNAs, and EVs in the diagnosis and treatment of SCA. We propose the combination of RNAi and EVs to avoid the adverse factors of their respective treatment and maximize the benefits of treatment through the technology of EVs loaded with RNA. Obviously, the combinational therapy of RNAi and EVs may more accurately diagnose and cure SCA. [ABSTRACT FROM AUTHOR]

Background: The identification of high-risk population patients is key to the personalized treatment options for the stage II colorectal cancers. The use of proteomics in the prognosis of patients with stage II colorectal cancer remains unclear. Methods: Using quantitative proteomics, we analyzed proteins that are differentially expressed in the tumor and adjacent normal tissues of 11 paired colorectal cancer patients with and without recurrence selected by a nested case-control design. Of the 21 identified proteins, we selected one candidate protein. The association of the corresponding gene of the selected protein with overall survival (OS) and adjuvant chemotherapy was analyzed using two independent cohorts of patients with stages II colorectal cancer. Results: Sterile a motif and histidine-aspartate domain-containing protein 1 (SAMHD1) was selected as the candidate biomarker. A group of 124 patients (12.5%) were stratified into SAMHD1-high subgroup. The 5-year OS rate of SAMHD1-high patients was lower than that of SAMHD1-low patients with stage II colorectal cancer (discovery cohort: hazard ratio [HR] = 2.89, 95% confidence interval [CI], 1.17-7.18, P = 0.016; validation cohort: HR = 2.25, 95% CI, 1.17-4.34, P = 0.013). The Cox multivariate analysis yielded similar results. In a pooled database, the 5-year OS rate was significantly different between patients with and without adjuvant chemotherapy among stage II SAMHD1-low tumors than in patients with stage II SAMHD1-high tumors (88% vs. 77%, P = 0.032). Conclusions: SAMHD1-high expression could help in identifying patients with stage II colorectal cancer with poor prognosis and less benefit from adjuvant chemotherapy. [ABSTRACT FROM AUTHOR]

9 For instance, the early-rising group also included patients with elevated preoperative CEA, normal CEA within 9 months of surgery, elevated CEA at 10thmonthsaftersurgery,andunknownCEAlevelsfrom then. Notably, we found that the patients with early-rising and later-rising CEA had lower OS and RFS. Received:10December2020 Revised:5January2021 Accepted:7January2021 Publishedonline:20January2021 DOI:10.1002/ctm2.293 LETTER TO EDITOR Trajectoriesofperioperativeserumcarcinoembryonic antigenandcolorectalcanceroutcome:Aretrospective, multicenterlongitudinalcohortstudy DearEditor, Carcinoembryonic antigen (CEA) is regarded as an important tumor marker for colorectal cancer (CRC). [Extracted from the article]

Growing evidence suggests that HIV infection may accelerate biological aging. Insomnia symptoms, particularly in later life, exacerbate cellular aging. We examined the association between insomnia symptoms and leukocyte telomere length (LTL), and further explored how this association was affected by HIV serostatus and age. Data were assessed from 244 HIV-infected individuals ≥40 years and 244 HIV-uninfected individuals who were frequency-matched by age, gender and education level. Insomnia symptoms were assessed by responses to four sleep-related questions covering the past month. We performed multivariable linear regression with logarithmically transformed LTL and reported exponentiated coefficients. HIV-infected individuals had shorter LTL compared to uninfected individuals (geometric mean 0.82 vs 0.89, P=0.052), and this association remained after adjustment for gender, education level, and smoking history (-7.4%, P=0.051) but markedly attenuated after additional adjustment for insomnia and depressive symptoms (-3.7%, P=0.367). Significant interactions between age group (55-82 vs 40-54 years) and insomnia symptoms on LTL were observed in the HIV-infected individuals (-28.4%, P=0.033) but not the uninfected (-17.9%, P=0.250). After stratifying by age group, LTL was independently associated with insomnia symptoms in those 55 years and older among the HIV-infected individuals (-24.5%, P=0.026) but not those 40-54 years old (-9.8%, P=0.428). Our findings suggest that elevated insomnia and depressive symptoms may partly explain the correlation between HIV serostatus and shorter LTL. Significant association between insomnia and shorter LTL observed in elderly HIV-infected but not in uninfected individuals suggest that such adverse effect may begin at an earlier age or is more pronounced in HIV-infected individuals but requires further investigation. [ABSTRACT FROM AUTHOR]

Objective: To estimate the prevalence of ever, current and heavy tobacco and alcohol use and their correlates among patients undergoing methadone maintenance treatment (MMT). Design: Cross-sectional study. Setting: The study was conducted in all of the 5 MMT clinics in Dehong Prefecture, China. Participants: 2121 (81.6%) eligible MMT participants were included in the study population. Analysis: Ordinal logistic regression was used to estimate the ORs and their 95% CIs. Results: The overall prevalence of ever, current and heavy smoking was 98.6%, 97.8% and 66.3%, respectively; while that of ever, current and hazardous alcohol drinking was 86.6%, 58.6% and 16.6%, respectively. Among HIV-infected participants, the proportions of those experiencing harmful effects of tobacco and alcohol on AIDS were 53.6% and 72.5%, respectively, and 16.9% and 49.3% had ever tried to quit after diagnosis with HIV. After adjusting for potential confounders, heavier smokers and more hazardous drinkers were more likely to be men, older and less educated. Ethnic minorities were less likely to heavily smoke, but more likely to engage in hazardous drinking. In addition, hazardous drinking was negatively associated with longer years of MMT and HIV infection. Moreover, heavier smoking (OR≥2=2.08, 95% CI 1.16 to 3.73) and more hazardous drinking (OR≥2=2.46, 95% CI 1.53 to 3.97) were positively associated with having multiple sexual partners, and both were positively associated with each other. Conclusions: The prevalence of tobacco and alcohol consumption was extraordinarily high among MMT participants in China, suggesting the urgent need of enhancing MMT patients' awareness of the harmful effects of tobacco and alcohol consumption and implementing comprehensive education and effective intervention programmes. [ABSTRACT FROM AUTHOR]

We investigated the prevalence and correlates of prefrailty/frailty, determined on the basis of the Fried criteria, in Chinese patients with and those without human immunodeficiency virus (HIV) infection. HIV-infected patients were more likely to be frail or prefrail than controls, and this association remained significant after adjustment for potential confounders (odds ratio, 3.79). After additional adjustment for neurocognitive impairment and depressive and insomnia symptoms, this association remained significant but attenuated (odds ratio, 2.16). In the HIV-infected group, these 3 variables were independently associated with prefrailty/frailty. These findings suggest that neurocognitive impairment and depressive and/or insomnia symptoms may account for a higher prevalence of prefrailty/frailty in HIV-infected patients but require further longitudinal investigation. [ABSTRACT FROM AUTHOR]

Objectives: Identification of risk factors is essential for developing herpes simplex virus type 2 (HSV-2) prevention interventions that could also reduce HIV-1 transmission, particularly among HIV-1-discordant couples.Methods: A prospective cohort study was conducted among HIV-1-discordant couples from June 2009 to March 2011 in Yunnan province, China. 413 HIV-1-infected partners and 517 HIV-1-uninfected partners who were HSV-2 seronegative or equivocal at enrolment and who had a study partner completing the baseline survey and HSV-2 testing were included in the analysis.Results: HSV-2 incidence was 2.9 per 100 person-years (PY) for HIV-1-infected partners and 4.5 per 100 PY for HIV-1-uninfected partners. At least 36% of incident HSV-2 infections were from outside sexual partner. Among HIV-1-infected partners, multivariate analysis indicated that HSV-2 incidence was significantly higher among those with baseline equivocal HSV-2 result, having an initially HSV-2 seropositive or equivocal partner, reporting no sex with study partner and initiating antiretroviral therapy (ART) during follow-up. Among HIV-1-uninfected partners, multivariate analysis indicated that HSV-2 incidence was significantly higher among those having an initially HSV-2 seropositive partner and reporting sex with study partner ≥5 times/month, but was lower among those having a partner with baseline CD4(+) count ≥350 cells/μL.Conclusions: Our findings underscore the importance of developing prevention and intervention programmes to reduce HSV-2 transmission among this population. The relationship between ART initiation and HSV-2 seroconversion requires further investigation. [ABSTRACT FROM AUTHOR]

Background: We conducted a systematic review and meta-analysis to determine the association between serum lipid levels and suicidality, as evidence from previous studies has been inconsistent. Methods: We identified relevant studies by searching Medline, Web of Science, EMBASE, and the Cochrane Database of Systematic Reviews (1980 to Dec. 5, 2014). Studies assessing the association between serum total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and/or triglycerides (TG) levels and suicidality were included. We used a random-effects model to take into account heterogeneity among studies. Results: We included 65 studies with a total of 510 392 participants in our analysis. Compared with the nonsuicidal patients, suicidal patients had significantly lower serum TC (weighted mean difference [WMD] -22.35, 95% confidence interval [CI] -27.95 to -16.75), LDL-C (WMD -19.56, 95% CI -26.13 to -12.99) and TG (WMD -23.40, 95% CI -32.38 to -14.42) levels, while compared with the healthy controls, suicidal patients had significantly lower TC (WMD -24.75, 95% CI -27.71 to -21.78), HDL-C (WMD -1.75, 95% CI -3.01 to -0.48) and LDL-C (WMD -3.85, 95% CI -7.45 to -0.26) levels. Furthermore, compared with the highest serum TC level category, a lower serum TC level was associated with a 112% (95% CI 40%-220%) higher risk of suicidality, including a 123% (95% CI 24%-302%) higher risk of suicide attempt and an 85% (95 CI 7%-221 %) higher risk of suicide completion. The cut-off values for low and high serum TC level were in compliance with the categories reported in the original studies. Limitations: A major limitation of our study is the potential heterogeneity in most of the analyses. In addition, the suicidal behaviour was examined using different scales or methods across studies, which may further explain heterogeneity among the studies. Conclusion: We identified an inverse association between serum lipid levels and suicidality. More mechanistic studies are needed to further explain this association. [ABSTRACT FROM AUTHOR]

Background: This research aimed to study the role of ezrin, CD44, and VEGF in invasion, metastasis, recurrence, and prognosis of giant cell tumor of bone (GCTB) and its association with the clinical and pathological features of GCTB. Methods: Expression status of ezrin, CD44, and VEGF in 80 GCTB tissues and its adjacent noncancerous tissue samples were measured with immunohistochemical and Elivison staining. Their correlation with the clinical and pathologic factors was statistically analyzed by chi-square test. Results: The expression status of ezrin, CD44, and VEGF were significantly higher in GCTB tissue samples than in its adjacent noncancerous tissue samples and in GCTB at Campanacci stage III than in Campanacci stages I and II (P < 0.05). No significant difference was found in age and sex of the patients and locations of the tumor (P > 0.05). Survival analysis showed that the expression status of ezrin, CD44, VEGF, and Campanacci clinical stages of GCTB were positively associated with the survival rate of GCTB patients and negatively associated with ezrin and Campanacci stages of GCTB, indicating that ezrin, CD44, VEGF, and Campanacci clinical stages of GCTB are the independent factors for GCTB. Conclusions: Ezrin, CD44, and VEGF are over-expressed in GCTB tissue and its adjacent noncancerous tissue samples and may play an important role in the occurrence, invasion, metastasis, and recurrence of GCTB. Measurement of ezrin, CD44, and VEGF expression status may contribute to the judgment of prognosis of GCTB patients. [ABSTRACT FROM AUTHOR]

Background This study aimed to investigate the prevalence of abdominal obesity and its association with the health-related quality of life (HRQOL) in a randomly selected Chinese sample. Methods A population-based sample of 3,600 residents aged 18-80 years was selected randomly from 5 Chinese cities. Demographic information, and waist and hip circumference measurements were obtained. The Mandarin version of the Short Form 36 Health Survey questionnaire (SF- 36) was used to assess the HRQOL. Waist circumference (WC) and waist-to-hip ratio (WHR) were used as measures of abdominal obesity, and the prevalence of abdominal obesity and its association with HRQOL were analysed. Results Among the 3,184 participants included in the analysis, the prevalence of abdominal obesity was about 45% in both women and men as evaluated by WC, and about 40% in women and 33% in men as evaluated by WHR. The prevalence varied by city, region, age, marital status, education level, family income, smoking, and the presence of chronic diseases. Both WC and WHR increased with age, and men had larger WC and WHR than women in most age groups. In women, abdominal obesity, as determined by both WC and WHR, was associated with meaningful impairments in 4 physical health scales and 2 mental health scales. In men, abdominal obesity, as determined by WC, was associated with 1 physical health scale and 1 mental health scale, and it was associated with 2 physical health scales based on WHR. Conclusions Physical health, but not mental health, was more vulnerable to impairment with abdominal obesity, and the impairments varied between genders. Public health agencies should emphasize that abdominal obesity impairs physical health. [ABSTRACT FROM AUTHOR]

Background: Contact tracing is especially useful for identifying an infection with few cases in the population, such as HIV in China. Little such research is available in China. Methods: Every newly diagnosed HIV case from 2008-2010 in Taizhou Prefecture, Zhejiang Province in China, was invited to participate as an "index case" in a contact tracing survey by providing contact information for up to eight sexual contacts who themselves were approached for voluntary HIV counseling and testing (VCT). Those who tested HIV-positive were then subjected to another contact tracing survey. This process was repeated until no more sexual contacts were reported or tested positive. Results: A total of 463 HIV-infected individuals were newly identified during the study period, including 338 cases who were identified from routine surveillance programs and 125 cases who were identified from the present contact tracing survey. Among these 463 cases, 398 (86.0%) served as 'index cases' in the survey, including 290 (85.8%) out of the 338 cases identified from routine surveillance programs and 108 (86.4%) out of the 125 cases identified from the present survey. These 398 'index cases' reported a total of 1,403 contactable sexual contacts, of whom 320 (22.8%) received HIV testing and 125 (39.1%) tested positive for HIV. Willingness to receive HIV testing was high among spouses and long term heterosexual or homosexual partners but extremely low among casual and commercial sex partners of 'index cases'. Consistent condom use was rare for all participants. A total of 290 independent sexual network components were constructed, with high complexity. Conclusion: Contact tracing is useful for identifying new HIV infections from spouses or long term sexual partners of HIV-infected individuals. The complicated sexual networks existing between and beyond HIV-infected persons provide opportunities for rapid spread of HIV in such areas. [ABSTRACT FROM AUTHOR]

The primary objective was to examine prevalence and correlates of social support and depressive symptoms among male sex workers (known as 'money boys' (MBs)) and general men who have sex with men (MSM) in Shanghai. The Social Provision Scale (SPS), which consists of 24 items, scored out of 4 for social provision, was used to evaluate the functions of social relationships. The score for each item ranges from 1 to 4, with a higher score indicating more social provision. The overall mean SPS score was 68.1 (s.d. = 6.53) for MBs and 69.3 (s.d. = 6.99) for general MSM. Depression was measured with a 12-item version of the Center for Epidemiological Studies Depression Scale (CES-D), where a score of 9 has been recommended as the cutoff score to indicate possible depressive symptoms. The prevalence of depressive symptoms was 57.9%, with MBs having a higher level of depressive symptoms than general MSM (70.0% v. 46.1%) (odds ratio = 1.86, 95% confidence interval = 1.07-3.24). Social support was a protective factor for depressive symptoms (odds ratio = 0.92, 95% confidence interval = 0.89-0.96). MSM in China, particularly MBs, are vulnerable to low social support and high depressive symptoms, highlighting the need for tailored psychological programs targeting this population. [ABSTRACT FROM AUTHOR]