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Background. Leukemia is a common malignancy that has four main subtypes and is a threat to human health. Understanding the epidemiological status of leukemia and its four main subtypes globally is important for allocating appropriate resources, guiding clinical practice, and furthering scientific research. Methods. Average annual percentage changes (AAPCs) were calculated to estimate the change trends of age-standardized rates (ASRs) from 1990 to 2019 in 204 countries and territories. The risk factors for leukemia death and disability-adjusted life-year (DALY) were also analyzed. In addition, the future trends in ASRs were projected through 2030. Results. The total number of incident cases, deaths, and DALYs from leukemia in 2019 was 0.64, 0.33, and 11.66 million, respectively. Decreasing trends in age-standardized incidence rate (ASIR), the age-standardized death rate (ASDR), and age-standardized DALY rate were detected on a global level while increasing trends in ASIR were detected in the high-sociodemographic index (SDI) regions. The leukemia burden was heavier in males than in females. By cause, acute myeloid leukemia (AML), chronic myeloid leukemia (CML), and chronic lymphocytic leukemia (CLL) were more likely to impose a burden on the elderly, while acute lymphoblastic leukemia (ALL) showed a greater impact in the younger population. A significant positive correlation was observed between SDI and AAPC in ASIR, while SDI was negatively correlated with AAPCs in both ASDR and age-standardized DALY rate. Smoking remained the most significant risk factor associated with leukemia-related death and DALY, especially in males. Similar deaths and DALYs were caused by smoking and high body mass index (BMI) in females. Future projections through 2030 estimated that ASIR and ASDR will continue to increase, while the DALY rate is predicted to decline. Conclusions. Patterns and trends of leukemia burden are correlated with SDI. The estimated contributions to leukemia deaths indicate that timely measures are needed to reduce smoking and obesity. [ABSTRACT FROM AUTHOR]

The emergence of various variants of concern (VOCs) necessitates the development of more efficient vaccines for COVID-19. In this study, we established a rapid and robust production platform for a novel subunit vaccine candidate based on eukaryotic HEK-293 T cells. The immunogenicity of the vaccine candidate was evaluated in pigs. The results demonstrated that the pseudovirus neutralizing antibody (pNAb) titers reached 7751 and 306 for the SARS-CoV-2 Delta and Omicron variants, respectively, after the first boost. Subsequently, pNAb titers further increased to 10,201 and 1350, respectively, after the second boost. Additionally, ELISPOT analysis revealed a robust T-cell response characterized by IFN-γ (171 SFCs/106 cells) and IL-2 (101 SFCs/106 cells) production. Our study demonstrates that a vaccine candidate based on the Delta variant spike protein may provide strong and broad protection against the prototype SARS-CoV-2 and VOCs. Moreover, the strategy for the efficient and stable expression of recombinant proteins utilizing HEK-293 T cells can be employed as a universal platform for future vaccine development. [ABSTRACT FROM AUTHOR]

A comprehensive overview of the associations between air pollution and the risk of gastrointestinal (GI) diseases has been lacking. We aimed to examine the relationships of long-term exposure to ambient particulate matter (PM) with aerodynamic diameter ≤2.5 μm (PM 2.5), 2.5–10 μm (PM c oarse), ≤10 μm (PM 10), nitrogen dioxide (NO 2), and nitrogen oxides (NO x), with the risk of incident GI diseases, and to explore the interplay between air pollution and genetic susceptibility. A total of 465,703 participants free of GI diseases in the UK Biobank were included at baseline. Land use regression models were employed to calculate the residential air pollutants concentrations. Cox proportional hazard models were used to evaluate the associations of air pollutants with the risk of GI diseases. The dose-response relationships of air pollutants with the risk of GI diseases were evaluated by restricted cubic spline curves. We found that long-term exposure to ambient air pollutants was positively associated with the risk of peptic ulcer (PM 2.5 : Q4 vs. Q1: hazard ratio (HR) 1.272, 95% confidence interval (CI) 1.179–1.372, NO 2 : 1.220, 1.131–1.316, and NO x : 1.277, 1.184–1.376) and chronic gastritis (PM 2.5 : 1.454, 1.309–1.616, PM 10 : 1.232, 1.112–1.366, NO 2 : 1.456, 1.311–1.617, and NO x : 1.419, 1.280–1.574) after Bonferroni correction. Participants with high genetic risk and high air pollution exposure had the highest risk of peptic ulcer, compared to those with low genetic risk and low air pollution exposure (PM 2.5 : HR 1.558, 95%CI 1.384–1.754, NO 2 : 1.762, 1.395–2.227, and NO x : 1.575, 1.403–1.769). However, no significant additive or multiplicative interaction between air pollution and genetic risk was found. In conclusion, long-term exposure to ambient air pollutants was associated with increased risk of peptic ulcer and chronic gastritis. • A comprehensive overview of the associations between air pollution and the risk of GI diseases has been lacking. • Long-term exposure to air pollution was associated with increased risks of peptic ulcer and chronic gastritis. • Our study highlights the importance of controlling air pollution as a preventive measure for GI diseases. [ABSTRACT FROM AUTHOR]

The 38 kDa protein is a major antigen of mycobacterium tuberculosis and has been widely used in TB serodiagnosis, due to its highly sensitivity and specificity. Here we attempt to establish a production platform of recombinant 38 kDa protein in mammalian cells and to evaluate the potential value of 38 kDa protein in TB serodiagnosis. The 38 kDa gene is synthesized and cloned into a lentiviral expressing vector. Recombinant lentiviral vector LV-CMV-38 kDa-eGFP was packaged, titered, and then transduced into HEK 293 T cells. Recombinant cell lines were selected by limiting dilution. Supernatants were collected and purified by HisTrapTM HP column. Western blot showed a molecular weight of approximate 38 kDa in cell supernatants as expected. ELISA assay confirmed the immunological specificity of the obtained protein in the presence of MTB-infected human serum samples. In all, we have obtained a stable cell line with long-term and robust expression of secretory MTB 38 kDa protein, which may provide a promising candidate antigen for the development of TB serological diagnosis. [ABSTRACT FROM AUTHOR]

Clinicians are advised caution in reducing serum urate for gout management due to observational associations with risk of neuropsychiatric diseases. We examined the causal effect of genetically predicted serum urate levels on the risk of major depressive disorder (MDD), anxiety, and related psychiatric disorders using two-sample Mendelian randomization (MR). We identified single-nucleotide polymorphisms (SNPs) associated with serum urate from a genome-wide association study (GWAS) of 110,347 European-descent individuals. The causal effect of serum urate on MDD was tested using summary data from a GWAS of 135,458 cases and 344,901 controls of European descent. MR was performed using random-effects inverse variance-weighted method and a series of sensitivity analyses. This approach was repeated using summary GWAS data for anxiety, bipolar disorder, post-traumatic stress disorder, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, schizophrenia, and anorexia nervosa. We identified 30 SNPs associated with serum urate. Genetically predicted urate levels were not causally associated with risk of MDD (OR 0.98; 95% CI 0.94, 1.03), anxiety (OR 0.90; 95% CI 0.80, 1.02), or the other psychiatric conditions (OR range 0.95 to 1.06). Results were similar in sensitivity analyses. We found no evidence that genetically predicted serum urate has a causal effect on risk of MDD, anxiety, or other psychiatric disorders. Key Points • Clinicians are advised to be cautious about reducing the serum urate level too far in gout management, citing observational associations between low serum urate levels and various neuropsychiatric diseases. • In this two-sample Mendelian randomization study, we found no evidence for a causal link between genetically predicted serum urate level and the development of major depressive, anxiety, or other related psychiatric disorders. • Future revisions of clinical guidelines may need to reconsider recommendations regarding lower limits for serum urate levels. [ABSTRACT FROM AUTHOR]

Purpose: China was affected by an outbreak of coronavirus disease 2019 (COVID-19) in 2019–2020. Research data are needed to develop evidence-driven strategies to reduce the adverse psychological and occupational impacts on healthcare workers (HCWs). Methods: From March 1, 2020, to March 8, 2020, 946 HCWs in China completed a survey consist of sociodemographic data, precautionary measures against COVID-19, and concerns about COVID-19. Self-administered questionnaire were collected to assess psychological and occupational adverse outcomes of HCWs. Multivariable logistic regression analysis was performed to identify factors associated with the outcomes. Results: A total of 55.0%, 56.0% and 48.3% of the HCWs experienced burnout, psychological distress and posttraumatic stress, respectively. A total of seven factors were independently associated with burnout: good health status (OR 0.51, 95% CI 0.36–0.71), fear of contagion (OR 1.31, 95% CI 1.003–1.79), avoiding contact with children (OR 1.40, 95% CI 1.03–1.91), enough staff support at the workplace (OR 0.59, 95% CI 0.38–0.92), having to work overtime (OR 1.37, 95% CI 1.03–1.83), maladaptive coping (OR 3.28, 95% CI 2.42–4.45) and adaptive coping (OR 0.47, 95% CI 0.35–0.62). A total of 11 factors were independently associated with high psychological distress: having one child (OR 0.54, 95% CI 0.38–0.77), good health status (OR 0.57, 95% CI 0.39–0.83), alcohol abuse (OR 1.51, 95% CI 1.02–2.25), thinking the epidemic would continue for quite a long time (OR 1.59, 95% CI 1.08–2.34), wearing extra-work clothes (OR 1.51, 95% CI 1.06–2.15),effective protective equipment (OR 0.45, 95% CI 0.22–0.90), enough staff support at the workplace (OR 0.55, 95% CI 0.34–0.89), unable to take care of families (OR 1.99, 95% CI 1.42–2.78), economic losses (OR 1.62, 95% CI 1.14–2.31), maladaptive coping (OR 6.88, 95% CI 4.75–9.97),and adaptive coping (OR 0.29, 95% CI 0.21–0.41). These factors were independently associated with posttraumatic stress: living with the elderly (OR 1.46, 95% CI 1.04–2.05), alcohol abuse (OR 1.41, 95% CI 1.002–1.98), working at a 3A hospital(OR 0.66, 95% CI 0.49–0.88), acquaintances confirmed COVID-19 (OR 2.14, 95% CI 1.20–3.84), fear of contagion (OR 1.87, 95% CI 1.40–2.50), believing they would survive if infected (OR 0.63, 95% CI 0.46–0.86), self-disinfected after arriving home (OR 1.43, 95% CI 1.01–2.02), interpersonal isolation (OR 1.65, 95% CI 1.21–2.26), unable to take care of families (OR 1.41, 95% CI 1.05–1.88) and maladaptive coping (OR 3.09, 95% CI 2.32–4.11). Conclusion: The variance in adverse outcomes was explained by the effect of various factors, which will help policymakers better prepare for subsequent potential outbreaks of COVID-19. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to quantitatively summarize the available evidence on the association of breastfeeding with the risk of childhood cancer. Methods: A literature search of PubMed and Embase databases was performed to identify eligible observational studies published from inception to July 17, 2020. The categorical and dose-response meta-analysis was conducted by pooling relative risk (RR) or odds ratio (OR) estimates with 95% confidence intervals (CIs). Potential sources of heterogeneity were detected by meta-regression and stratification analysis. Sensitivity analysis and publication bias test were also carried out. Results: Forty-five articles involving 475,579 individuals were included in the meta-analysis. Among the thirty-three studies on the association between breastfeeding and risk of childhood leukemia, the pooled risk estimates were 0.77 (95% CI, 0.65–0.91) and 0.77 (95% CI 0.63–0.94) for ever versus non/occasional breastfeeding and longest versus shortest breastfeeding duration group, respectively. There was clear indication for non-linear dose-response relationship between breastfeeding duration and the risk of childhood leukemia (P non-linear < 0.001). The most protective effect (OR, 0.66, 95% CI 0.62–0.70) was observed at a breastfeeding duration of 9.6 months. Four studies examined, the association between breastfeeding and risk of childhood neuroblastoma, and significant inverse associations were consistently observed in both the comparisons of ever breastfeeding versus non/occasional breastfeeding (OR = 0.59, 95% CI 0.44–0.81) and longest versus shortest breastfeeding (OR = 0.61, 95% CI 0.44–0.83). However, no associations of breastfeeding with risk of other cancers were found. Conclusions: Our study supports a protective role of breastfeeding on the risk of childhood leukemia, also suggesting a non-linear dose-response relationship. Further studies are warranted to confirm the association between breastfeeding and risk of childhood neuroblastoma. [ABSTRACT FROM AUTHOR]

• Milk products are a major part of western diet, but their role in rheumatoid arthritis (RA) is controversial. • Based on National Health and Nutrition Examination Survey, a negative association of milk products with RA was observed. • The protective effect of the milk products on RA was stronger in several subgroups, such as Mexican Americans and highly educated participants. Milk products are a major part of the western diet, but the role of their effect in rheumatoid arthritis (RA) is controversial. The objective of this study was to explore the relationship between milk products and RA in the United States (US) population. In the cross-sectional study, a total of 12,813 participants aged 20 years or older were selected from the National Health and Nutrition Examination Survey (NHANES). Consumption of milk products was collected by personal interview, and RA status was obtained by self-reported questionnaires. The association between milk products and RA was estimated by using the weighted logistic regression model. We found a negative association of once a day or more milk products intake with self-reported RA prevalence (odds ratio [OR]: 0.68; 95% confidence interval [CI]: 0.53 to 0.86; P < 0.001). A linear trend between consumption of milk products and the prevalence of RA (P < 0.01) was also observed. In subgroup analysis, protective effects of milk products on RA were more pronounced in several groups (i.e., Mexican Americans, highly educated and drinking individuals, etc.). However, no interaction effect of stratification variables and the frequency of milk products intake with RA was detected. After imputing missing data, the sensitivity analysis showed the same association. This study suggested a negative association between consumption of milk products and RA among US population. Further investigations are warranted to validate the causal association and the underlying mechanism. [ABSTRACT FROM AUTHOR]

Keywords: Bibliometric analysis; Incidental gallbladder cancer; Research hotspots; Scientific cooperation EN Bibliometric analysis Incidental gallbladder cancer Research hotspots Scientific cooperation 821 824 4 03/10/21 20210301 NES 210301 Introduction Incidental gallbladder cancer (IGBC) was occasionally detected during operations intended for benign gallbladder diseases.[1] Over the last decade, high-quality evidence was more likely to be achieved by cooperative researches, rather than single-center experiences. Various synonyms of IGBC were used including "incidental gallbladder cancer", "incidental gallbladder malignancy", "incidental gallbladder tumor", "unexpected gallbladder cancer", "unexpected gallbladder malignancy", and "unexpected gallbladder tumor." To explore research hotspots, keywords co-occurrence analysis[3] was performed by using VOSviewer 1.6.13.[4] On the co-occurrence map, keywords clusters were identified and summarized as research hotspots. [Extracted from the article]

Background: The disability rate associated with rheumatoid arthritis (RA) ranks high among inflammatory joint diseases. However, the cause and potential molecular events are as yet not clear. Here, we aimed to identify differentially expressed genes (DEGs), pathways and immune infiltration involved in RA utilizing integrated bioinformatics analysis and investigating potential molecular mechanisms. Materials and methods: The expression profiles of GSE55235, GSE55457, GSE55584 and GSE77298 were downloaded from the Gene Expression Omnibus database, which contained 76 synovial membrane samples, including 49 RA samples and 27 normal controls. The microarray datasets were consolidated and DEGs were acquired and further analyzed by bioinformatics techniques. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of DEGs were performed using R (version 3.6.1) software, respectively. The protein-protein interaction (PPI) network of DEGs were developed utilizing the STRING database. Finally, the CIBERSORT was used to evaluate the infiltration of immune cells in RA. Results: A total of 828 DEGs were recognized, with 758 up-regulated and 70 down-regulated. GO and KEGG pathway analyses demonstrated that these DEGs focused primarily on cytokine receptor activity and relevant signaling pathways. The 30 most firmly related genes among DEGs were identified from the PPI network. The principal component analysis showed that there was a significant difference between the two tissues in infiltration immune. Conclusion: This study shows that screening for DEGs, pathways and immune infiltration utilizing integrated bioinformatics analyses could aid in the comprehension of the molecular mechanisms involved in RA development. Besides, our study provides valuable data related to DEGs, pathways and immune infiltration of RA and may provide new insight into the understanding of molecular mechanisms. [ABSTRACT FROM AUTHOR]

Background: The early life risk factors of childhood obesity among preterm infants are unclear and little is known about the influence of the feeding practices. We aimed to identify early life risk factors for childhood overweight/obesity among preterm infants and to determine feeding practices that could modify the identified risk factors.Methods: A total of 338,413 mother-child pairs were enrolled in the Jiaxing Birth Cohort (1999 to 2013), and 2125 eligible singleton preterm born children were included for analyses. We obtained data on health examination, anthropometric measurement, lifestyle, and dietary habits of each participant at their visits to clinics. An interpretable machine learning-based analytic framework was used to identify early life predictors for childhood overweight/obesity, and Poisson regression was used to examine the associations between feeding practices and the identified leading predictor.Results: Of the eligible 2125 preterm infants (863 [40.6%] girls), 274 (12.9%) developed overweight/obesity at age 4-7 years. We summarized early life variables into 25 features and identified two most important features as predictors for childhood overweight/obesity: trajectory of infant BMI (body mass index) Z-score change during the first year of corrected age and maternal BMI at enrollment. According to the impacts of different BMI Z-score trajectories on the outcome, we classified this feature into the favored and unfavored trajectories. Compared with early introduction of solid foods (≤ 3 months of corrected age), introducing solid foods after 6 months of corrected age was significantly associated with 11% lower risk (risk ratio, 0.89; 95% CI, 0.82 to 0.97) of being in the unfavored trajectory.Conclusions: The trajectory of BMI Z-score change within the first year of life is the most important predictor for childhood overweight/obesity among preterm infants. Introducing solid foods after 6 months of corrected age is a recommended feeding practice for mitigating the risk of being in the unfavored trajectory. [ABSTRACT FROM AUTHOR]

Purpose: Psychological well-beings of left-behind children (LBC) in rural areas of China remain under-studied. In this cross-sectional study, we aimed to explore the subjective well-being (SWB) in LBC and its associated factors in a rural area in eastern China. Methods: Stratified random cluster sampling was used to select middle school and high school students in Qingyuan County of Zhejiang Province. Relevant information including sociodemographic characteristics was collected from each participant using an organized questionnaire. SWB was measured using the modified scale developed for Chinese adolescents. Univariable and multivariable regression analyses were performed using R version 3.3.0. Results: A total of 1086 children were recruited and examined in the current analysis, with 365 (33.61%) being left-behind. Compared with non-left-behind children (NLBC), LBC had significantly lower scores in family satisfaction (P = 0.003) and environment satisfaction (P = 0.020). Multivariable regression analysis uncovered that frequent parent–child communication was associated with high positive affect (P = 0.003) and life satisfaction (P < 0.001), and the type of caregivers was associated with negative affect among LBC (P = 0.037). Conclusions: Our results suggest SWB was lower in LBC, and targeted interventions including strengthening parental-child communication should be developed and implemented to improve LBC's SWB in rural areas of China. [ABSTRACT FROM AUTHOR]

Background This study aimed to investigate the associations of selected polymorphisms in RP 11-650 L 12.2 with the risk of colorectal cancer (CRC) in a Chinese population. Methods A total of 821 CRC cases (test set: 320, validation set: 501) and 857 healthy controls (test set: 319, validation set: 538) were enrolled in this study. Demographic characteristics and lifestyle information were collected by a validated questionnaire. A sample of 5 ml venous blood was collected from each subject for DNA isolation, and the selected polymorphisms (rs144182521, rs514743, rs76071148, rs149941240) were genotyped by MassArray technique. Results The rs149941240 polymorphism was significantly associated with the risk of CRC, with ORs of 1.50 (95% CI: 1.15–1.96) by co-dominant model and 1.45 (95% CI: 1.21–1.87) by dominant model in the test set, respectively. Correspondingly, the ORs were 1.48 (95% CI: 1.19–1.82) and 1.41 (95% CI: 1.15–1.73) in the validation set, respectively. The crossover analysis showed that non-smokers with the variant genotypes in rs149941240 had a significantly increased risk of CRC than those with wild genotype by dominant model in the validation set (OR 1.42, 95% CI 1.04–1.96). However, no gene-environment multiplicative interactions of rs149941240 with tobacco smoking were found on risk of CRC. Conclusions Our findings suggest that rs149941240 polymorphism was associated with the risk of CRC, and might contribute to the susceptibility to CRC. The effects of this polymorphism should be validated in a larger sample and require further mechanistic investigations to determine the nature of its influence on CRC. [ABSTRACT FROM AUTHOR]

Background: We aimed to probe the association of serum 25-hydroxyvitamin D [25(OH)D] concentrations with all-cause and cause-specific mortality among patients with gout and hyperuricemia (HUA)., Methods: The study included 1169 gout patients and 7029 HUA patients from the National Health and Nutrition Examination Survey (NHANES) 2007-2018 and 2001-2018, respectively. The association between serum 25(OH)D and mortality was evaluated by Cox proportional hazard and restricted cubic spline models., Results: Among participants with gout and HUA, the weighted mean concentrations of serum 25(OH)D were 71.49 ± 30.09 nmol/L and 64.81 ± 26.92 nmol/L, respectively. Vitamin D deficiency occurred in 29.68% of gout patients and 37.83% of HUA patients. During 6783 person-years of follow-up among gout patients, 248 all-cause deaths occurred, among which 76 died from cardiovascular disease (CVD) and 49 died from cancer. 1375 HUA patients were recorded for all-cause mortality during 59,859 person-years of follow-up, including 427 CVD deaths and 232 cancer deaths. After multifactorial adjustment, per one-unit increment in natural log-transformed 25(OH)D was associated with lower risk of 55% all-cause mortality and 61% CVD mortality among gout patients, and a 45% reduced risk of cancer mortality among HUA patients. Restricted cubic splines showed a U-shaped relationship with all-cause and CVD mortality among HUA patients, with inflection points of 72.7 nmol/L and 38.0 nmol/L, respectively. The results were robust in subgroup and sensitivity analyses., Conclusions: Serum 25(OH)D was negatively linearly correlated with mortality among gout patients, whereas U-shaped correlated with mortality in HUA patients. These results indicate that adequate vitamin D status could prevent premature death., (© 2024. The Author(s).)

Irritable bowel syndrome (IBS) patients exhibit significantly lower levels of serum selenium (Se) compared to healthy controls. This study integrates a prospective cohort analysis and animal experiments to investigate Se deficiency as a potential risk factor for IBS. Using data from the UK Biobank, a longitudinal analysis was conducted to explore the associations between dietary Se intake and the risk of incident IBS. In animal study, C57BL/6 mice were fed diets with normal (0.2 ppm) or low (0.02 ppm) Se levels to assess the impacts of Se deficiency on IBS symptoms. Furthermore, we performed 16 S rRNA sequencing, untargeted colonic fecal metabolomics analysis, and colon transcriptome profiling to uncover the regulatory mechanisms underlying Se deficiency-induced IBS. The analysis of UK Biobank data revealed a significant correlation between low dietary Se levels and an increased incidence of IBS. In the experimental study, a low Se diet induced IBS symptoms, evidenced by elevated abdominal withdrawal reflex scores, colon inflammation, and severe pathological damage to the colon. Additionally, the low Se diet caused disturbances in gut microbiota, characterized by an increase in Faecalibaculum and Helicobacter, and a decrease in Bifidobacterium and Akkermansia. Combined colonic fecal metabolomics and colon transcriptome analysis indicated that Se deficiency might trigger IBS through disruptions in pathways related to "bile excretion", "steroid hormone biosynthesis", "arachidonic acid metabolism", and "drug metabolism-cytochrome P450". These findings underscore the significant adverse effects of Se deficiency on IBS and suggest that Se supplementation should be considered for IBS patients., Competing Interests: Declaration of Competing Interest The authors 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 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Although previous studies have explored the association of drinking with gout risk, we sought to explore the dose-response relationship and the evidence between subtypes of alcoholic beverages and gout risk., Methods: The weekly alcoholic beverage consumption of patients in the UK Biobank was collected and calculated. The Cox regression model was applied to assess the effects of drinking alcohol in general and its subtypes on gout risk by calculating the hazard ratio (HR) and 95% CIs. Additionally, the restricted cubic splines were used to estimate the dose-response relationship between alcohol consumption and gout risk. To evaluate the robustness, we performed subgroup analysis across various demographic characteristics., Results: During a mean follow-up period of 11.7 years, a total of 5728 new incident gout cases were diagnosed among 331,865 participants. We found that light alcohol consumption was linked to a slight decrease in gout incidence among female individuals (HR 0.78, 95% CI 0.65-0.94, P = 0.01), whereas there was no significant association in male individuals. Moreover, the dose-response relationship showed that drinking light red wine and fortified wine could reduce the gout risk, whereas beer or cider, champagne or white wine, and spirits increased the gout risk at any dose., Conclusion: Our study suggested a J-shaped dose-response relationship between drinking and gout risk in female individuals, but not in male individuals. For specific alcoholic beverages, light consumption of red wine and fortified wine was associated with reduced gout risk. These findings offer new insights into the roles of alcoholic beverages in gout incidence risk, although further validation is warranted., (Copyright © 2024 by the Journal of Rheumatology.)

Background: The investigation of dietary micronutrient intakes and risk of alcoholic liver disease (ALD) based on observational studies was limited., Objectives: Our study aimed to explore the associations of 30 dietary micronutrients intakes with risk of ALD, interactions between dietary micronutrients and genetic variation, and mediation effects of blood and urinary biomarkers on the associations between dietary micronutrients and risk of ALD., Methods: A case-control study was conducted within the UK Biobank cohort, with 231 incident ALD cases and 1386 controls. Dietary data were collected using a dietary questionnaire that relied on a 24-h dietary recall of the previous day. Logistic regression models were employed to assess the associations of dietary micronutrient intakes with risk of ALD. We conducted stratified analyses on the associations between dietary micronutrient intakes and risk of ALD by PNPLA3 rs738409 and tested the interactions between dietary micronutrients and genetic variation. In addition, we conducted mediation analyses to investigate the mediating effects of biomarkers on the associations between dietary micronutrients and risk of ALD., Results: Our findings indicated significant inverse associations of thiamin, riboflavin, niacin equivalent, pantothenic acid, vitamin B-6, folate, vitamin E, calcium, magnesium, phosphorus, potassium, copper, iodine, and manganese with risk of ALD (all false discovery rate-P trend < 0.050). We also found a significant interaction between PNPLA3 rs738409 and magnesium (P interaction = 0.028). Creatinine (enzymatic) in urine, aspartate aminotransferase, and insulin-like growth factor 1 were the top 3 biomarkers with the highest number of significant mediation effects on the associations between the dietary micronutrients and risk of ALD., Conclusions: Dietary intakes of thiamin, riboflavin, niacin equivalent, pantothenic acid, vitamin B-6, folate, vitamin E, calcium, magnesium, phosphorus, potassium, copper, iodine, and manganese were inversely associated with risk of ALD., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Background: Modifiable factors were found to be associated with the risk of irritable bowel syndrome (IBS) in observational studies, but whether these associations are causal is uncertain. We conducted a Mendelian randomization (MR) study to systematically explore the causal associations of modifiable factors with IBS., Methods: Summary-level statistical data for IBS was obtained from a genome-wide association study (GWAS) meta-analysis of UK Biobank (40,548 cases and 293,220 controls) and the international collaborative Bellygenes initiative (12,852 cases and 139,981 controls). Genetic instruments associated with the exposures at the genome-wide significance ( p  < 5 × 10 -8 ) level were selected from previous GWASs. Mendelian randomization was performed using inverse-variance weighted (IVW) method, supplemented with several sensitivity analyses to evaluate potentially causal relationships between identified contributing factors and IBS. Furthermore, we applied another database from FinnGen (8,116 IBS cases and 276,683 controls) to testify the reliability of the significant associations., Results: Seven convincing modifiable factors were significantly associated with IBS after correction for multiple testing. Genetically predicted smoking initiation (OR = 1.12, 95% CI = 1.06-1.18, p  = 1.03 × 10 -4 ), alcohol consumption (OR = 0.47, 95% CI = 0.34-0.64, p  = 3.49 × 10 -6 ), sedentary behavior (OR = 1.17, 95% CI = 1.07-1.28, p  = 4.02 × 10 -4 ), chronotype (OR = 0.92, 95% CI = 0.88-0.96, p  = 4.42 × 10 -4 ), insomnia (OR = 1.19, 95% CI = 1.15-1.24, p  = 7.59 × 10 -19 ), education (OR = 0.80, 95% CI = 0.74-0.88, p  = 5.34 × 10 -7 ), and visceral adiposity (OR = 1.15, 95% CI = 1.06-1.24, p  = 7.96 × 10 -4 ). We additionally identified several suggestive factors, including serum magnesium, serum phosphorus, physical activity, lifetime smoking, intelligence, lean body mass, and body mass index (BMI). After pooling the effect estimates from FinnGen, the associations remained significant except for chronotype., Conclusion: This MR analysis verified several modifiable risk factors for IBS, thus prevention strategies for IBS should be considered from multiple perspectives on these risk factors., 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 © 2024 Chen, Yang, Song, Chen, Liu, Liu, Luo, Sun, He, Mao and Ye.)

Few prospective studies have investigated the joint effect of lifestyle factors and genetic susceptibility on the risk of irritable bowel syndrome (IBS). This study aims to evaluate the associations of lifestyle and genetic factors with incident IBS in the UK Biobank. We analyzed data from 481,057 participants (54% female) without prevalent IBS at enrollment in the UK Biobank. An overall healthy lifestyle was defined using six modifiable lifestyle factors, including smoking, body mass index (BMI), sleep duration, diet, physical activity, and alcohol consumption, and hence categorized into 'favorable', 'intermediate', and 'unfavorable' lifestyles. A Cox proportional hazard model was used to investigate the association between a healthy lifestyle and incident IBS. Furthermore, we constructed a polygenic risk score (PRS) for IBS and assessed whether lifestyle modified the effect of genetics on the development of IBS. During a median follow-up of 12.1 years, 8645 incident IBS were ascertained. Specifically, among the six modifiable lifestyle factors, adequate sleep demonstrates the greatest protective effect (hazard ratio [HR]: 0.72, 95% CI: 0.69,0.75) against IBS. Compared with a favorable lifestyle, an unfavorable lifestyle was associated with a 56% (95% CI: 46%-67%) increased risk of IBS (P = 8.99 × 10 -40 ). The risk of incident IBS was 12% (95% CI: 4%-21%) higher among those at high genetic risk compared with those at low genetic risk (P = 0.005). When considering the joint effect of lifestyle and genetic susceptibility, the HR nearly doubled among individuals with high genetic risk and unfavorable lifestyle (HR: 1.80; 95% CI:1.51-2.15; P = 3.50 × 10 -11 ) compared to those with low genetic risk and favorable lifestyle. No multiplicative or addictive interaction was observed between lifestyle and genetics. The findings from this study indicated that lifestyle and genetic factors were independently associated with the risk of incident IBS. All these results implicated a possible clinical strategy of lowering the incidence of IBS by advocating a healthy lifestyle., Competing Interests: Conflict of interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: Limited research has been conducted on the association between long-term exposure to air pollutants and the incidence of gout., Objectives: This study aims to assess the individual and combined effects of prolonged exposure to five air pollutants (NO 2 , NO x , PM 10 , PM coarse and PM 2.5 2 ) on the incidence of gout among 458,884 initially gout-free participants enrolled in the UK Biobank., Methods: Employing a land use regression model, we utilized an estimation method to ascertain the annual concentrations of the five air pollutants. Subsequently, we devised a weighted air pollution score to facilitate a comprehensive evaluation of exposure. The Cox proportional hazards model was utilized to investigate the association between ambient air pollution and gout risk. Interaction and stratification analyses were conducted to evaluate age, sex, BMI, and genetic predisposition as potential effect modifiers in the air pollution-gout relationship. Furthermore, mediation analyses were conducted to explore the potential involvement of biomarkers in mediating the association between air pollution and gout., Results: Over a median follow-up time of 12.0 years, 7,927 cases of gout were diagnosed. Significant associations were observed between the risk of gout and a per IQR increase in NO 2 (HR 3 : 1.05, 95 % CI 4 : 1.02-1.08, p = 0.003), NO x (HR: 1.04, 95 % CI: 1.01-1.06, p = 0.003), and PM 2.5 (HR: 1.03, 95 % CI: 1.00-1.06, p = 0.030). Per IQR increase in the air pollution score was associated with an elevated risk of gout (p = 0.005). Stratified analysis revealed a significant correlation between the air pollution score and gout risk in participants ≥60 years (HR: 1.05, 95 % CI: 1.02-1.09, p = 0.005), but not in those <60 years (p = 0.793), indicating a significant interaction effect with age (p-interaction=0.009). Mediation analyses identified five serum biomarkers (SUA:15.87 %, VITD: 5.04 %, LDLD: 3.34 %, GGT: 1.90 %, AST: 1.56 % 5 ) with potential mediation effects on this association., Conclusions: Long-term exposure to air pollutants, particularly among the elderly population, is associated with an increased risk of gout. The underlying mechanisms of these associations may involve the participation of five serum biomarkers., Competing Interests: Declaration of competing interest The authors 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 Inc. All rights reserved.)

Objective: To explore the associations between metabolic syndrome (MetS) and its individual components and the risk of rheumatoid arthritis (RA)., Methods: A total of 369,065 individuals were included in the present study based on the UK Biobank. Multivariable Cox proportional hazards regression models were applied to estimate the associations between MetS and its individual components and the risk of RA. Mediation analysis was performed to further assess the potential mediating role of C-reactive protein (CRP) in the relationship between MetS and RA., Results: During a median follow-up period of 12.04 years, a total of 4901 incident RA cases were documented. MetS (hazard ratio [HR] 1.22, 95% CI 1.14-1.30) and 4 of its 5 components (elevated waist circumference [WC; HR 1.21, 95% CI 1.12-1.32], elevated triglyceride [TG] level [HR 1.12, 95% CI 1.05-1.19], reduced high-density lipoprotein cholesterol [HDL-C] level [HR 1.31, 95% CI 1.23-1.39], and hyperglycemia [HR 1.15, 95% CI 1.05-1.25]) were associated with an increased risk of RA. In addition, the risk of RA increased as the number of diagnosed MetS components increased, with the highest risk in participants with all 5 components. Mediation analysis showed that CRP might mediate the association between MetS and RA, accounting for 9.27% of the total effect., Conclusion: These findings indicated positive associations between MetS and 4 of its components (WC, TG, HDL-C, and hyperglycemia) and the risk of RA, highlighting the importance of MetS management in the prevention of RA., (Copyright © 2024 by the Journal of Rheumatology.)

Background and Aims: The causal relationship between gut microbiota and gout and hyperuricemia (HUA) has not been clarified. The objective of this research was to evaluate the potential causal effects of gut microbiota on HUA and gout using a two-sample Mendelian randomization (MR) approach., Methods and Results: Genetic instruments were selected using summary statistics from genome-wide association studies (GWASs) comprising a substantial number of individuals, including 18,473 participants for gut microbiome, 288,649 for serum urate (SU), and 763,813 for gout. Two-sample MR analyses were performed to determine the possible causal associations of gut microbial genera with the risk of HUA and gout using the inverse-variance weighted (IVW) method, and robustness of the results was confirmed by several sensitivity analyses. A reverse MR analysis was conducted on the bacterial taxa that were identified in forward MR analysis. Based on the results of MR analyses, Escherichia-Shigella (OR = 1.05; 95% CI, 1.01-1.08; P = 0.009) exhibited a positive association with SU levels, while Lachnospiraceae NC2004 group (OR = 0.95; 95% CI, 0.92-0.98; P = 0.001) and Family XIII AD3011 group (OR = 0.94; 95% CI, 0.90-0.99; P = 0.015) were associated with a reduced HUA risk. Moreover, Coprococcus 3 (OR = 1.17, 95% CI: 1.01-1.34, P = 0.031) was causally associated with a higher gout risk. In reverse MR analysis, no causal relationships were identified between these bacterial genera and HUA or gout., Conclusion: This study provides evidence for a causal association between gut microbial genera and HUA or gout, and further investigations of the underlying mechanism are warranted., Competing Interests: Declaration of competing interest The authors have declared no conflicts of interest., (Copyright © 2024 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Periodontitis drives irreversible destruction of periodontal tissue and is prone to exacerbating inflammatory disorders. Systemic immunomodulatory management continues to be an attractive approach in periodontal care, particularly within the context of 'predictive, preventive, and personalized' periodontics. The present study incorporated genetic proxies identified through genome-wide association studies for circulating immune cells and periodontitis into a comprehensive Mendelian randomization (MR) framework. Univariable MR, multivariable MR, subgroup analysis, reverse MR, and Bayesian model averaging (MR-BMA) were utilized to investigate the causal relationships. Furthermore, transcriptome-wide association study and colocalization analysis were deployed to pinpoint the underlying genes. Consequently, the MR study indicated a causal association between circulating neutrophils, natural killer T cells, plasmacytoid dendritic cells, and an elevated risk of periodontitis. MR-BMA analysis revealed that neutrophils were the primary contributors to periodontitis. The high-confidence genes S100A9 and S100A12 , located on 1q21.3, could potentially serve as immunomodulatory targets for neutrophil-mediated periodontitis. These findings hold promise for early diagnosis, risk assessment, targeted prevention, and personalized treatment of periodontitis. Considering the marginal association observed in our study, further research is required to comprehend the biological underpinnings and ascertain the clinical relevance thoroughly., Competing Interests: XY, YB, ML, YY, YC, BL, YD, SW, WP, ZW, YM, QC No competing interests declared, (© 2023, Ye et al.)

Purpose: This study aimed to explore the clinical characteristics of male breast cancer (MBC) patients and the factors influencing their prognosis., Methods: We conducted a retrospective case series analysis of 117 MBC cases who were treated at Zhejiang Cancer Hospital from 2009 to 2022. Cox proportional hazard model was used to identify prognostic factors of MBC. Nomogram was constructed based on these factors, which was further evaluated by C-index and calibration curves., Results: A total of 115 MBC cases were finally included in our analyses, with median diagnosis age of 59 years. Of these cases, 80.0% were estrogen receptor (ER) positive, 79.2% were progesterone receptor (PR) positive, 48.7% were human epidermal growth factor receptor 2 (HER2) negative, and 42.6% had Ki67 levels higher than 15%. 108 (93.9%) cases underwent radical mastectomy, while only 3 (2.6%) received breast-conserving surgery. The Logrank test suggested that lymphocyte-to-monocyte ratio (LMR) was negatively associated with both overall survival (OS) and disease-free survival (DFS) of MBC, while platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) were only positively associated with OS (all P-values < 0.05). Multivariate regression analysis showed that age (HR 1.08, 95% CI 1.03-1.13) was significant prognostic factors for OS. Meanwhile, age (HR 1.06, 95% CI 1.02-1.10), histological differentiation grade (poorly differentiated/undifferentiated vs. well-differentiated: HR 2.55, 95% CI 1.05-6.17), and TNM stage (IV vs . I: HR 31.59, 95% CI 6.01-165.93) were also significant prognostic factors for DFS. Nomograms were developed for DFS, with C-indexes of 0.782, indicating good predictive performance., Conclusion: Increased age, bigger tumor size, higher TNM stage, and lower histological differentiation grade were associated with poor MBC prognosis, and LMR, PLR, and NLR might be potential predictors for MBC prognosis., 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 © 2024 Lei, Hua, Mao, Cui, Mao, Yang and Li.)

Background: Observational studies have suggested the potential role of inflammatory factors in the risk of coronary artery disease (CAD). We aimed to perform 2-sample Mendelian randomization (MR) analyses to assess the causal association between circulating cytokines/growth factors and CAD., Methods and Results: The instrumental variables for 28 circulating cytokines and growth factors were identified from a genome-wide association study of 8293 European participants. Summary-level data on CAD were derived from a large genome-wide association study (71 602 cases and 260 875 controls). We used the inverse-variance-weighted and Wald ratio methods as our main MR methods. The weighted median, simple median, maximum likelihood, MR pleiotropy residual sum and outlier, and MR-Egger methods were performed as sensitivity analyses. Genetic colocalization analyses were conducted to validate the robustness of our MR findings. We found that genetically predicted circulating levels of macrophage migration inhibitory factor were associated with an increased risk of CAD at the Bonferroni-adjusted level of significance ( P <1.79×10 -3 ). The odds ratio was 1.20 (95% CI, 1.08-1.33; P =6.83×10 -4 ) per 1-SD increase in macrophage migration inhibitory factor. Colocalization analyses supported our MR findings. Additionally, we found suggestive evidence between the genetic effects of stem cell growth factor-β and the risk of CAD (odds ratio, 0.95 [95% CI, 0.91-0.98]; P =0.007)., Conclusions: Our findings suggested a risk-increasing effect of macrophage migration inhibitory factor level on the development of CAD. The roles of these inflammatory factors for CAD warrant further investigation.

Evidence from epidemiological literature on the association of circulating micronutrients with risk of nonalcoholic fatty liver disease (NAFLD) is inconsistent. We aimed to elucidate the causal relationships using Mendelian randomization (MR). Single-nucleotide polymorphisms associated with 14 circulating micronutrients (β-carotene, calcium, copper, folate, iron, magnesium, phosphorus, selenium, vitamin B6, B12, C, D, K1 and zinc) were employed as instrumental variables. Summary level data for NAFLD were obtained from a genome-wide association study (GWAS) meta-analysis of 8434 cases and 770,180 controls (discovery stage) and another two datasets including 1483 NAFLD cases and 17,781 controls (replication stage 1) and 2134 NAFLD cases and 33,433 controls (replication stage 2). Inverse variance-weighted method (IVW) was used as primary analysis, supplemented with a series of sensitivity analysis. Genetically predicted higher β‑carotene levels were suggestively associated with reduced NAFLD risk [odds ratio (OR) 0.81, 95% confidence interval (CI) 0.66-0.99; P = 0.047], whereas the association did not survive the false discovery rates (FDR) correction (P FDR  = 0.164). Genetically predicted circulating iron (OR 1.16, 95% CI 1.05-1.29; P = 0.006, P FDR  = 0.028), selenium (OR 1.11, 95% CI 1.03-1.20; P = 0.005, P FDR  = 0.028) and vitamin B12 (OR 1.08, 95% CI 1.03-1.13; P = 0.002, P FDR  = 0.028) were significantly associated with increased risk of NAFLD. Moreover, the findings were consistent in individual datasets (P heterogeneity  > 0.05) and confirmed in sensitivity analysis. Our study provided evidence that circulating iron, selenium and vitamin B12 might be causally linked to the risk of NAFLD, which deserves further exploration of the potential biological mechanism., (© 2024. The Author(s).)

Existing reporting checklists lack the necessary level of detail and comprehensiveness to be used in guidelines on Chinese patent medicines (CPM). This study aims to develop a reporting guidance for CPM guidelines based on the Reporting Items of Practice Guidelines in Healthcare (RIGHT) statement. We extracted information from CPM guidelines, existing reporting standards for traditional Chinese medicine (TCM), and the RIGHT statement and its extensions to form the initial pool of reporting items for CPM guidelines. Seventeen experts from diverse disciplines participated in two rounds of Delphi process to refine and clarify the items. Finally, 18 authoritative consultants in the field of TCM and reporting guidelines reviewed and approved the RIGHT for CPM checklist. We added 16 new items and modified two items of the original RIGHT statement to form the RIGHT for CPM checklist, which contains 51 items grouped into seven sections and 23 topics. The new and revised items are distributed across four sections (Basic information, Background, Evidence, and Recommendations) and seven topics: title/subtitle (one new and one revised item), Registration information (one new item), Brief description of the health problem (four new items), Guideline development groups (one revised item), Health care questions (two new items), Recommendations (two new items), and Rationale/explanation for recommendations (six new items). The RIGHT for CPM checklist is committed to providing users with guidance for detailed, comprehensive and transparent reporting, and help practitioners better understand and implement CPM guidelines., Competing Interests: Declaration of Competing Interest The authors have declared no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Prior epidemiological studies have established a correlation between inflammatory cytokines and inflammatory bowel disease (IBD). However, the nature of this relationship remains uncertain. Mendelian randomization (MR) study has the advantages of avoiding confounding and reverse causality compared with traditional observational research., Objective: We aimed to evaluate whether genetically determined circulating levels of cytokines are associated with the risk of IBD by using the MR approach., Materials and Methods: We selected genetic variants associated with circulating levels of 28 cytokines at the genome-wide significance level from a genome-wide association study (GWAS) including 8,293 individuals. Summary-level data for IBD (including Crohn's disease and ulcerative colitis) were obtained from the International Inflammatory Bowel Disease Genetics Consortium and UK Biobank. We performed the primary analysis using the inverse-variance weighted method, as well as sensitivity analyses to test the stability of our results. We subsequently replicated the results of IBD in the UK Biobank dataset. A reverse MR analysis was also conducted to evaluate the possibility of reverse causation., Results: Genetically predicted elevated levels of interleukin-17 (IL-17) and monokine induced by interferon-gamma (MIG) were associated with an increased risk of IBD[odds ratio (OR): 1.52, 95% confidence interval (CI):1.10-2.08, P =0.010 for IL-17 and OR: 1.58, 95% CI: 1.24-2.00, P = 1.60×10 -4 for MIG]. Moreover, we observed suggestive associations between β-NGF and MIP-1β with the risk of Crohn's disease (OR: 0.71, 95% CI: 0.52-0.98, P = 0.039) and ulcerative colitis (OR: 1.08, 95% CI: 1.01-1.15, P = 0.019). In the reverse MR study, there was no evidence of causal effects of IBD and these cytokines., Conclusion: Our study suggests the potential causal associations of IL-17 and MIG with IBD. Further studies are needed to determine whether IL-17 and MIG or their downstream effectors could be useful in the management of IBD., 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, Qian, Li, Shen, Ye, Mao and Sun.)

Background: Sepsis-associated encephalopathy (SAE) is frequently present at the acute and chronic phase of sepsis, which is characterized by delirium, coma, and cognitive dysfunction. Despite the increased morbidity and mortality of SAE, the pathogenesis of SAE remains unclear. This study aims to discover the potential biomarkers, so as to clear the pathogenesis potentially contributing to the development of SAE and provide new therapeutic strategies for the treatment of SAE., Methods: The GSE135838 dataset was obtained from the Gene Expression Omnibus (GEO) database and utilized for analysis the differentially expressed genes (DEGs). The DEGs were analyzed by limma package of R language and the extracellular protein-differentially expressed genes (EP-DEGs) were screened by the Human Protein Atlas (HPA) and UniProt database. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were carried out to analyze the function and pathway of EP-DEGs. STRING, Cytoscape, MCODE and Cytohubba were used to construct a protein-protein interaction (PPI) network and screen key EP-DEGs. Key EP-DEGs levels were detected in the cerebrospinal fluid (CSF) of SAE patients and non-sepsis patients with critical illness. ROC curve was used to evaluate the diagnostic of SAE., Results: We screened 82 EP-DEGs from DEGs. EP-DEGs were enriched in cytokine-cytokine receptor interaction, IL-17 signaling pathway and NOD-like receptor signaling pathway. We identified 2 key extracellular proteins IL-1B and IL-8. We clinically verified that IL-6 and IL-8 levels were increased in CSF of SAE patients and CSF IL-8 (AUC = 0.882, 95 % CI = 0.775-0.988) had a higher accuracy in the diagnosis of SAE than CSF IL-6 (AUC = 0.824, 95 % CI = 0.686-0.961). Furthermore, we found that the IL-8 levels in CSF might not associated with Glasgow Coma Scale (GCS) scores of SAE patients., Conclusion: IL-8 may be the key extracellular cytokine in the pathogenesis of SAE. Bioinformatics methods were used to explore the biomarkers of SAE and validated the results in clinical samples. Our findings indicate that the IL-8 in CSF might be the potential diagnostic biomarker and therapeutic target in SAE., Competing Interests: Declaration of Competing Interest The authors 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 © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

To investigate the association of long-term exposure to ambient air pollution with the risk of allergic rhinitis (AR), we performed a longitudinal analysis of 379,488 participants (47.4% women) free of AR at baseline in the UK Biobank. The annual average concentrations of PM 2.5 , PM coarse , PM 10 , NO 2 , and NO x were estimated by land use regression models. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). A weighted polygenic risk score was constructed. During a median follow-up period of 12.5 years, 3095 AR cases were identified. We observed significant associations between the risk of AR and PM 2.5 (HR: 1.51, 95% CI: 1.27-1.79, per 5 μg/m 3 ), PM coarse (HR: 1.28, 95% CI: 1.06-1.55, per 5 μg/m 3 ), PM 10 (HR: 1.45, 95% CI: 1.20-1.74, per 10 μg/m 3 ), NO 2 (HR: 1.14, 95% CI: 1.09-1.19, per 10 μg/m 3 ), and NO x (HR: 1.10, 95% CI: 1.05-1.15, per 20 μg/m 3 ). Moreover, participants with high air pollution combined with high genetic risk showed the highest risk of AR, although no multiplicative or additive interaction was observed. In conclusion, long-term exposure to air pollutants was associated with an elevated risk of AR, particularly in high-genetic-risk populations, emphasizing the urgent need to improve air quality.

The association between circulating copper and the risk of liver cancer has been investigated by previous studies, while the findings were inconsistent. Thus, we aimed to evaluate the association between circulating copper and liver cancer by using meta-analysis and Mendelian randomization (MR). For meta-analysis, PubMed and Web of Science were searched to identify eligible studies published before April 4, 2022. Standardized mean difference (SMD) with 95% confidence interval (CI) in circulating copper level between liver cancer patients and controls were pooled. Furthermore, we selected genetic instruments for circulating copper from a genome-wide association study (GWAS) to conduct MR analysis. The summary statistics related to liver cancer were obtained from two large independent cohorts, UKBB and FinnGen, respectively. MR analysis was performed mainly by inverse-variance weighted (IVW) approach, followed by maximum-likelihood method as sensitivity analysis. In meta-analysis of eight studies, circulating copper was found to be higher in liver cancer patients (SMD: 1.65; 95% CI: 0.65 to 2.65) with high heterogeneity (I 2  = 96.40%, P = 0.001). However, inconsistent findings were observed among subgroups with high evidence. In MR analysis, genetically predicted circulating copper was not significantly associated with the risk of liver cancer by IVW in UKBB (OR: 1.38; 95% CI: 0.72 to 2.65) and FinnGen (OR: 1.10; 95% CI: 0.69 to 1.73) separately, and the pooled results produced similar results (OR: 1.18, 95% CI: 0.81 to 1.72). Moreover, non-significant finding was confirmed by using maximum-likelihood method. There is no sufficient evidence to demonstrate that high levels of circulating copper increase the risks of liver cancer., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Rabies continues to be a huge threat to public health. The rabies virus envelope glycoprotein (RABV G) is a major rabies virus antigen and contains neutralizing epitopes, which are primary candidates for subunit vaccines and diagnostic antigens. However, the production and purification of rRABV G while retaining its antigenic and immunogenic remains to be a challenge. Here, we aimed to establish a platform for rRABV G production and purification, and determine the immunogenicity and antigenicity of rRABV G. The cDNA fragment encoding the soluble form of RABV G was synthesized and cloned into a lentiviral expressing vector. Recombinant lentiviral vector LV-CMV-RABV G-eGFP was packaged, titered, and then transduced into HEK 293T cells. The cell culture supernatant was purified using nickel affinity chromatography and subsequently confirmed through Western Blot analysis and indirect enzyme-linked immunosorbent assay (ELISA). The ELISA utilized human sera obtained from individuals who had been vaccinated with the human commercial Purified Vero Cells Rabies Vaccine (PVRV). Notably, we observed a neutralizing antibody response in immunized pigs rather than in mice. This discrepancy could potentially be attributed to factors such as the instability of the rRABV G protein, variations in host responses, and variances in the adjuvant used. Taking all these findings into account, the rRABV G protein generated in this study exhibits promise as a potential vaccine candidate for the prevention of rabies., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: Evidence from observational studies on the association of folate and vitamin B 12 with autoimmune diseases are conflicting., Objective: We aimed to investigate the relationship of folate and vitamin B 12 with autoimmune diseases using Mendelian randomization (MR)., Materials and Methods: We selected single-nucleotide polymorphisms associated with folate and vitamin B 12 at the genome-wide significance level. Summary-level data for four common autoimmune diseases (vitiligo, inflammatory bowel disease, rheumatoid arthritis, and systemic lupus erythematosus) were obtained from large-scale genome-wide association studies, with a sample size of 44,266, 86,640, 58,284, and 23,210, respectively. MR analyses were conducted using the inverse variance weighted (IVW) approach, and sensitivity analyses were further performed to test the robustness., Results: We found that a higher genetically determined serum folate level per one standard deviation (SD) was associated with a decreased risk of vitiligo by the IVW method [odds ratios (OR) = 0.47; 95% confidence interval (CI): 0.32-0.69; P = 1.33 × 10 -4 ]. Sensitivity analyses using alternative methods showed similar associations, and no evidence of pleiotropy was detected by MR-Egger regression ( P = 0.919). In addition, we observed that vitamin B 12 per one SD was positively associated with IBD (IVW: OR = 1.14, 95% CI: 1.03-1.26, P = 0.010; maximum likelihood: OR = 1.14, 95% CI: 1.01-1.29, P = 0.035; MR-PRESSO: OR = 1.14, 95% CI:1.01-1.28, P =0.037), while the association was not significant after Bonferroni correction., Conclusion: The study provides convincing evidence for an inverse association between serum folate level and risk of vitiligo. Further studies are warranted to elucidate the possible association between vitamin B 12 and risk of IBD., 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 Yang, Song, Li, Lv, Sun, Mao and Ye.)

Background: Early weaning-induced stress impairs the intestinal barrier function and adversely affects the health of piglet. Probiotics can be used to prevent and treat various intestinal diseases. Lactobacillus rhamnosus GG (LGG) has an LuxS/AI-2 quorum sensing (QS) system that senses environmental changes through chemical signaling molecules. The aim of the study was to explore whether luxS mutant affects the protective role of LGG in the gut barrier of weaned piglets by comparing the luxS mutant (ΔluxS) with its wild-type (WT)., Methods: Newborn piglets were orally administered with WT and ΔluxS at dosage of 10 9 CFU, respectively. Accordingly, newborn piglets in the Con group were orally administered with PBS. Piglets were weaned on day 21 and euthanized on day 24, three days following weaning., Results: Supplementation of ΔluxS in advance significantly boosted the relative abundances of healthy microbes (including Catenibacterium , Eubacterium , Lachnospiraceae and Bifidobacterium ). WT and ΔluxS maintain intestinal barrier function mainly by promoting intestinal villus to crypt ratio (VCR), occludin protein expression and mucus secretion ( P <0.05). Furthermore, LGG reduces pro-inflammatory mediators by inhibiting TLR4 and MAPK signal transduction ( P <0.05)., Conclusion: Both WT and ΔluxS were shown to resist weaning stress by enhancing the intestinal barrier function of piglets. It has to be said that the ability of ΔluxS to maintain intestinal tissue morphology and promote mucus secretion significantly decreased compared with that of WT., 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 Deng, Dai, Wei, Ma, Mao, Zhang, Hua and Wang.)

Introduction: Observational studies have reported a relationship between iron status and the risk of prostate cancer. However, it remains uncertain whether the association is causal or due to confounding or reverse causality. To further clarify the underlying causal relationship, we conducted a Mendelian randomization (MR) analysis., Methods: We selected three genetic variants (rs1800562, rs1799945, and rs855791) closely correlated with four iron status biomarkers (serum iron, log-transformed ferritin, transferrin saturation, and transferrin) as instrumental variables. Summary statistics for prostate cancer were obtained from the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome consortium including 79,148 cases and 61,106 controls of European ancestry. The inverse-variance weighted (IVW) method was conducted primarily to estimate the association of genetically predicted iron status and the risk of prostate cancer, supplemented with simple-median, weighted-median and maximum-likelihood methods as sensitivity analysis. MR-Egger regression was used to detect directional pleiotropy. We also conducted a meta-analysis of observational studies to assess the associations between iron status and the risk of prostate cancer., Results: Genetically predicted increased iron status was associated with the decreased risk of prostate cancer, with odds ratio of 0.91 [95% confidence interval (CI): 0.84, 0.99; P = 0.035] for serum iron, 0.81 (95% CI: 0.65, 1.00; P = 0.046) for log- transformed ferritin, 0.94 (95% CI: 0.88, 0.99; P = 0.029) for transferrin saturation, and 1.15 (95% CI: 0.98, 1.35; P = 0.084) for transferrin (with higher transferrin levels representing lower systemic iron status), using the inverse-variance weighted method. Sensitivity analyses produced consistent associations, and MR-Egger regression indicated no potential pleiotropy. Our replication analysis based on FinnGen research project showed compatible results with our main analysis. Results from our meta-analysis similarly showed that serum ferritin [standardized mean difference (SMD): -1.25; 95% CI: -2.34, -0.16; P = 0.024] and transferrin saturation (SMD: -1.19; 95% CI: -2.34, -0.05; P = 0.042) were lower in patients with prostate cancer compared with that in controls., Discussion: Our study suggests a protective role of iron in the risk of prostate cancer, further investigations are required to clarify the underlying mechanisms., 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 Ying, Wang, Han, Song, Liu, Chen, Sun, Mao and Ye.)

Childhood is an important period for individuals’ psychological development. Due to long-term separation from the parents, left-behind children (LBC) more easily develop deviation in cognition and abnormal personality. In this study, we aimed to explore the status of psychological resilience among LBC in a rural area of eastern China. We carried out a cross-sectional survey including middle and high school students from Qingyuan County of Zhejiang Province. Psychological resilience was measured using a modified scale developed for Chinese children. Data from a total of 1086 participants were collected, and the mean ± standard deviation score of psychological resilience was 4.11 ± 0.42. Multivariable linear regression analyses revealed that being a class leader (p = 0.010) and having high self-evaluation of academic performance (p < 0.001) were related with psychological resilience. Moreover, high contact frequency between parents and children (p = 0.019) was associated with better psychological resilience among LBC. In conclusion, we found that being a class leader and having high self-evaluation of academic performance were associated with better psychological resilience among the children in this rural area and contact between parent and child was an essential factor associated with psychological resilience among LBC.

Objective: The objective of the study was to provide an overview of the existing evidence on non-genetic biomarkers for ankylosing spondylitis (AS)., Methods: In this umbrella review, we searched PubMed and Web of Science from database inception to October 31, 2020. Systematic reviews and meta-analyses of observational studies investigating the associations between any non-genetic biomarkers and AS were included. We estimated summary standardized mean difference (SMD) along with 95% confidence interval (CI), I 2 statistic, 95% prediction interval (PI), and assessed small-study effects and excess significance bias. The study was registered in PROSPERO with registration number of CRD42020218240., Results: A total of 1276 publications were identified, of which 21 articles covering 43 non-genetic biomarkers were eligible for inclusion. Evidence of 22 (51%) non-genetic biomarkers exhibited a nominally significant effect (p < 0.05) on AS, and 7 associations (14%) showed small-study effects. The associations of platelet count (SMD: 0.53, 95% CI: 0.36 to 0.71) and serum interleukin (IL)-23 levels (SMD = 2.03, 95% CI: 1.27 to 2.79) with AS presented highly suggestive evidence, while circulating IL-17 levels (SMD = 2.36, 95% CI: 1.71, 3.01) and Treg/PBMC ratio (SMD = -0.75, 95% CI: -1.06 to -0.44) presented suggestive evidence. However, these associations showed large or very large between-study heterogeneity, suggesting an indefinite direction for the effect when 95% PIs were considered., Conclusion: No convincing evidence supported the existence of a non-genetic biomarker for AS. Some highly suggestive associations might be affected by bias, therefore, promising non-genetic biomarkers for AS remain limited at least based on the current evidence from observational studies., (© 2022 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

Gene therapy's entrance into clinical settings has made it an ever more attractive field of study for various diseases. However, relatively little progress has been made in targeting kidney diseases due to poor gene delivery efficiency in renal cells. The development of novel gene therapy vectors for medical intervention to treat kidney diseases is needed. In this study, we designed and produced a pseudotyped lentiviral vector with envelope glycoproteins of Zika virus (ZIKV), and evaluated its potential use in viral vector entry, neutralization assay, and gene delivery especially in the renal context. The lentiviral vector, simplified as ZIKV-E, is pseudotyped with Env/G-TC representing the transmembrane (TM) and cytoplasmic ( C Y) domains of Env replaced with the TM and CY domains of the glycoprotein (G) of the vesicular stomatitis virus. In vivo results show that ZIKV-E induced efficient transduction in tubular epithelial cells in mouse kidneys, demonstrating >100-fold higher expression of exogenous green fluorescent protein gene compared with that achieved by vesicular stomatitis virus G (VSV-G) protein pseudotyped lentiviral vector. The results also showed that the vector ZIKV-E transduced cells in a pH-independent manner and the transduction was inhibited by anti-ZIKV Env domain III antibodies. Results also show that ZIKV-E can be used as a surrogate for studies of ZIKV entry mechanisms and neutralization antibody assay. In all, this study successfully demonstrated a novel pseudotyped lentiviral vector ZIKV-E for inducing high transduction efficiency in renal tubular epithelial cells that could serve as a foundation for gene therapy for the treatment of inherited renal diseases in humans.

Object: Prostate cancer is one of the leading malignancies in men worldwide. Previous observational studies have linked amino acids and transaminase with altered risk of prostate cancer. However, whether these associations were causal remained unclear. Therefore, we conducted a Mendelian randomization (MR) to assess their potential causal associations., Methods: Summary-level data for prostate cancer were obtained from a meta-analysis of genome-wide association studies (GWAS) including 79,148 prostate cancer cases and 61,106 controls of European descent. Instrumental variables (IVs) of amino acids and alanine aminotransferase (ALT) were obtained from a GWAS of 86,507 European individuals and a GWAS of 312,572 participants from the UK Biobank, respectively. MR analyses were performed using inverse-variance-weighted (IVW), likelihood-based, MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) test and MR-Egger regression., Results: Genetically predicted circulating concentrations of alanine were associated with an increased risk of prostate cancer (odds ratio (OR): 1.16, 95% confidence interval (CI): 1.01-1.33, P =0.037 by IVW). Consistently, genetically predicted ALT was inversely associated with the risk of prostate cancer (OR: 0.43, 95% CI: 0.27-0.68, P =3.28×10 -4 by IVW). MR-Egger regression did not indicate evidence of directional pleiotropy and sensitivity analyses yielded consistent associations., Conclusion: Our study revealed that genetically predicted circulating alanine and ALT levels were associated with an altered risk of prostate cancer, suggesting their potential roles in the development of prostate cancer. Whether targeting alanine, ALT or its downstream effectors are helpful in reducing prostate cancer incidence warrants further investigation., Competing Interests: The authors declare that they have no competing interests., (© 2022 Yang et al.)

Background: Previous observational studies have provided inconsistent evidence for the association between alcohol consumption and the risk of colorectal cancer (CRC). To assess this potential causal effect, we performed bidirectional Mendelian randomization (MR) analysis. Methods: We selected six single nucleotide polymorphisms (SNPs) as instrumental variables (IVs) associated with alcohol consumption (ever versus never drinker) and two SNPs representing the number of drinks per week from a genome-wide association study (GWAS) of the Japanese population. Summary data for CRC were obtained from a GWAS meta-analysis in the Japanese population of 6,692 CRC cases and 27,178 controls. MR analysis was performed by the inverse-variance weighted (IVW) method primarily, supplemented with several sensitivity methods including the weighted median method, maximum likelihood method, MR pleiotropy residual sum and outlier (MR-PRESSO) test, MR-Egger regression, Causal Analysis Using Summary Effect estimates (CAUSE) method, as well as constrained maximum likelihood and model averaging and Bayesian information criterion (cML-MA-BIC) method. Multivariable Mendelian randomization (MMR) analyses were used to adjust for potential confounders. Reverse MR analyses were also performed to assess the potential causal effect of CRC on alcohol consumption. Results: Genetically predicted alcohol consumption (ever versus never drinker) was positively associated with the risk of CRC (odds ratio (OR) = 1.08, 95% confidence interval (CI): 1.05-1.12, p = 1.51 × 10 -5 by IVW). The number of alcoholic drinks per week was also associated with an increased risk of CRC (OR = 1.39, 95%CI: 1.27-1.52, p = 5.29 × 10 -13 by IVW). Sensitivity analysis yielded similar results. Reverse MR analyses found no evidence that CRC contributes to either ever drinkers (OR = 1.00, 95%CI: 0.99-1.00, p = 0.339 by IVW) or added number of drinks per week (OR = 1.01, 95%CI: 0.98-1.05, p = 0.545 by IVW). Conclusion: Our study suggested a potential causal association between alcohol consumption and the risk of CRC among Asians. Reducing drinking may be beneficial to the prevention and management of CRC., 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 Li, Ye, Zhou, Liu, Mao and Sun.)

Background: Beef is common in daily diet, but its association with the risk of rheumatoid arthritis (RA) remains uncertain. The objective of this study is to explore the relationship between beef intake and the risk of RA., Materials and Methods: We investigated the association between beef intake and risk of RA by multivariate logistic regression, based on the National Health and Nutrition Examination Survey (NHANES) 1999-2016 involving 9,618 participants. The dose-response relationship between beef intake and RA was explored as well. Furthermore, we performed Mendelian randomization (MR) analysis to examine the causal effect of beef intake on RA. Genetic instruments for beef intake were selected from a genome-wide association study (GWAS) including 335,576 individuals from the UK Biobank study, and summary statistics relating to RA were obtained from a GWAS meta-analysis of 14,361 RA patients and 43,923 controls. The inverse-variance weighted (IVW) approach was used to estimate the causal association, and MR-Egger regression and Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) test were applied to evaluate the pleiotropy and outliers., Results: Compared with the lowest quintile (0 to ≤33.50 g/d), beef intake was found to be significantly associated with the risk of RA [odds ratio (OR): 1.94; 95% confidence interval (CI): 1.20-3.12] in the third quintile (50.26 to ≤76.50 g/d). Moreover, a reversed "U" dose-response relationship between beef and RA ( P non-linearity = 0.023) was found. In the MR analysis, beef intake was associated with an increased risk of RA (OR: 3.05; 95% CI: 1.11-8.35; P = 0.030) by the IVW method. The results from MR-Egger regression and MR-PRESSO test showed that there were no pleiotropic variations and outliers., Conclusion: This study indicated that there is suggestive evidence to support the causal effect of beef intake on the risk of RA, while further studies are warranted to elucidate the exact association., 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 Chen, Liu, Huang, Mao, Wen, Ye and He.)

Chronic hepatitis B virus (HBV) infection remains a global health problem and current treatments are insufficient due to immune tolerance to hepatitis B surface antigen (HBsAg). RNA interference (RNAi) is a more promising approach for antiviral therapy. Here, 17 single artificial microRNAs (amiRNAs) targeting the highly conserved regions of HBV genome were screened to inhibit HBV replication. In addition, we compared three tandem amiRNAs, each containing 3 different amiRNAs, out of which amiRNA135 was selected to be studied in detail. In vitro data showed that amiRNA135 significantly inhibited the replication of different HBV genotypes (including resistant and mutant). In vivo study was carried out by adeno-associated virus 8-mediated gene delivery, we found that the anti-HBV effects of AAV8-amiRNA135 were time and dose-dependent. Serum HBsAg and HBeAg in high dose groups were significantly reduced at 7 days after a single intravenous vector injection, and maintained at low levels throughout a 15-month experiment. Immunohistochemical staining and HBV core particle DNA analysis confirmed that HBV replication in the liver was strongly inhibited by AAV8-amiRNA135. Taken together, our data suggest that AAV8-mediated trimeric amiRNA expression is a promising therapeutic approach for chronic HBV infection., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: The burden of gout is substantial in the United States (US). Most gout cases can be attributed to modifiable risk factors, while systematic evidence-based assessment of gout cases and incidence attributable to the risk factors in the US is limited., Methods: The estimated cases and incidence of gout in the US was obtained from global burden of disease (GBD) study 2019. We calculated the exposure rate of risk factors from National Health and Nutrition Examination Survey (NHANES) 2009-2010, since we estimated an average induction time of 10 years for risk factors and gout. We also conducted a meta-analysis to evaluate the associations of modifiable risk factors and gout in the US population. Furthermore, the population attributable fraction (PAF) was calculated using based on the prevalence of risk factors and relative risk (RR) from the meta-analysis., Results: The weighted prevalence of hypertension was 14.37%, and the average body mass index (BMI) and alcohol consumption was 28.50 kg/m 2 and 7.14 g/d, respectively. Meta-analysis showed that individuals with hypertension had a higher risk of gout (2.12, 95% CI 1.88 to 2.40). For every five units of increase in BMI, the risk of gout increased by 1.48-fold (95% CI 1.26 to 1.75). The pooled RR was 1.21 (95% CI 1.13 to 1.29) for every 10 g/day increment of alcohol consumption. BMI, hypertension and alcohol consumption accounted for 53.58%, 13.85% and 12.66% of gout cases, respectively. Overall, 65.05% of gout incidence was attributable to the joint effects of these three risk factors., Conclusion: Hypertension, excess BMI and high alcohol consumption were responsible for approximately 65% of gout incidence in the US in 2019. Reducing the exposure to these factors can effectively reduce the incidence of gout., (Copyright © 2022. Published by Elsevier Inc.)

Classical swine fever virus (CSFV) is a major animal pathogen threatening the global pork industry. To date, numerous anti-CSFV monoclonal antibodies (mAbs) and their recognizing epitopes have been reported. However, few mAbs were systematically characterized for the capacity to differentiate field CSFV isolates from CSF vaccine strains, and the molecular basis associated with antigenic differences between vaccines and field isolates is still largely unknown. In the present study, recombinant CSFV structural glycoproteins E2 of both virulent and vaccine strains and E rns of vaccine strain were expressed using eukaryotic cells and murine mAbs generated against E2 and E rns . After serial screening and cloning of the hybridomas, the viral spectra of mAbs were respectively determined by indirect fluorescent antibody assay (IFA) using 108 CSFVs, followed by Western blot analysis using expressed glycoproteins of all CSFV sub-genotypes including vaccine strains. The antigenic structures recognized by these mAbs were characterized by epitope mapping using truncated, chimeric, and site-directed mutated E2 and E rns proteins. We have identified two vaccine-specific, one field isolate-specific, and two universal CSFV-specific mAbs and five novel conformational epitopes with critical amino acid (aa) motifs that are associated with these five mAbs: 213 EPD 215 , 271 RXGP 274 , and 37 LXLNDG 42 on E2 and 38 CKGVP 42 , W 81 , and D 100 /V 107 on E rns . Particularly, E 213 of E2 is field isolate-specific, while N 40 of E2 and D 100 /V 107 of E rns are vaccine strain-specific. Results from our study further indicate that N 40 D of E2 mutation in field strains was likely produced under positive selection associated with long-term mass vaccination, leading to CSFV evasion of host immune response. Taking together, this study provides new insights into the antigenic structure of CSFV E2 and E rns and the differentiating mAbs will contribute to the development of a diagnostic strategy to differentiate C-strain vaccination from natural infection (DIVA) of CSFV in terms of elimination of CSF in China., Competing Interests: Author RY is employed by Guangzhou Bioneeds Biotechnology Co., Ltd., China. The remaining 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 Mi, Wang, Li, Bao, Madera, Shi, Zhang, Mao, Yan, Xia, Gong, Shi and Tu.)

Background: Inflammation plays a pivotal role in the pathogenesis of cancer. Though previous studies have reported a link between several inflammatory biomarkers and risk of certain types of cancer, there is a lack of systematic investigation. Therefore, we aimed to assess the role of circulating cytokines on the risk of cancer using a two-sample Mendelian randomization (MR) approach., Method: We used genetic variants associated with circulating levels of cytokines from a meta-analysis of genome-wide association studies (GWASs) of 8,293 Finns as instrumental variables. Summary level data of 20 site-specific cancer were obtained from the UK BioBank including up to 456,348 participants of European ancestry. We performed two-sample MR analyses using inverse-variance weighted (IVW) method as the main method, followed by weighted-median and likelihood-based methods as sensitivity analysis. Pleiotropic and outlier variants were assessed by MR-Egger regression and MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) test., Results: 224 genetic variants associated with 27 circulating cytokines achieving genome-wide significance ( P <5×10 -8 ) were used as IVs. After Bonferroni correction, genetically predicted high levels of interleukin-18 (IL-18) were associated with a decreased risk of acute myeloid leukemia (odds ratio (OR) per 1 standard deviation (SD) increase = 0.55, 95% confidence interval (CI):0.43-0.69, P =5.39×10 -7 ), and circulating levels of IL-17 were associated with altered stomach cancer risk (OR per 1 SD increase = 0.15, 95% CI: 0.07-0.36, P =1.25×10 -5 ) by IVW. Results were stable across sensitivity analyses, and MR-Egger regression did not suggest the presence of directional pleiotropy. Additionally, we found suggestive evidence for 48 cytokine-cancer associations including tumor necrosis factor related apoptosis-inducing ligand (TRAIL) and cutaneous T-cell attracting chemokine (CTACK) with the risk of several types of cancer (9.26×10 -5 ≤ P <0.05)., Conclusions: By using a genetic epidemiological approach, our study systematically evaluated the role of circulating cytokines on the risk of cancer, and provided clues for potential therapeutic targets. However, the exact underlying biological mechanism warrants further investigation., 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 Song, Li, Qian, Liu, Lv, Ye, Sun and Mao.)

Background: Intestinal dysbiosis is associated with inflammatory bowel disease (IBD). Ulcerative colitis (UC) and Crohn's disease (CD), two subtypes of IBD, are characterized by unique microbial signatures, respectively. However, it is unclear whether UC or CD has a specific causal relationship with gut microbiota., Objective: To investigate the potential causal associations between gut microbial genera and IBD, UC, or CD, two-sample Mendelian randomization (MR) analyses were conducted., Materials and Methods: We obtained genome-wide association study (GWAS) summary statistics of gut microbiota and IBD, UC, or CD from published GWASs. Two-sample MR analyses were performed to identify potential causal gut microbial genera for IBD, UC, and CD using the inverse-variance weighted (IVW) method. Sensitivity analyses were also conducted to validate the robustness of the primary results of the MR analyses. Finally, a reverse MR analysis was performed to evaluate the possibility of reverse causation., Results: Combining the results from the primary and sensitivity analyses, six bacterial genera were associated with the risk of IBD, UC, or CD in the IVW method. Briefly, Eubacterium ventriosum group was associated with a lower risk of IBD ( P =0.011) and UC ( P =1.00×10 -4 ), whereas Coprococcus 2 was associated with a higher risk of IBD ( P =0.022) and UC ( P =0.007). In addition, we found a positive association between Oxalobacter with IBD ( P =0.001) and CD ( P =0.002), and Ruminococcaceae UCG014 with IBD ( P =0.005) and CD ( P =0.007). We also noticed a negative association between Enterorhabdus ( P =0.044) and IBD, and between Lachnospiraceae UCG001 ( P =0.023) and CD. We did not find causal effects of IBD, UC, or CD on these bacterial genera in the reverse MR analysis., Conclusion: This study expanded gut microbial genera that were causally associated with the risk of IBD, and also revealed specificity-gut microbial genera for UC or CD., 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 Liu, Ye, Yang, Song, Sun, Mao and He.)

An increasing number of studies investigated the association between air pollution during pregnancy and the risk of eczema in offspring. However, no meta-analysis has confirmed the existence and size of their association to date. We systematically searched PubMed, Web of Science, Cochrane Library, and Embase databases to select the observational controlled studies published from the inception date to October 16, 2021. Quality evaluation was guided by the Newcastle-Ottawa Scale (NOS). Sensitivity analysis was applied to assess the impact of each included study on the combined effects, and publication bias was examined by Begg's tests and Egger's tests. A total of 12 articles involving 69,374 participants met our eligibility criteria. A significant association between the maternal exposure to NO 2 (per 10 μg/m 3 increased) and childhood eczema was observed, with a pooled risk estimate of 1.13 (95% CI: 1.06-1.19), but no association was observed between exposure to PM 10 , PM 2.5 , and SO 2 and the risk of eczema in offspring. Besides, the effect of maternal NO 2 exposure on childhood eczema was significant in the first and second trimesters, but not in the third trimester. There was notable variability in geographic location (p = 0.037) and air pollutant concentration (p = 0.031) based on meta-regression. Our findings indicated that prenatal exposure to NO 2 was a risk factor for elevated risk of eczema in childhood, especially in the first and second trimesters. Further studies with larger sample sizes considering different constituents of air pollution and various exposure windows are needed to validate these associations., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Colorectal cancer (CRC) is the third-most frequently diagnosed cancer globally. Studies have linked low serum albumin with increased risk of CRC, but the causal nature of the association remains unclear. In the present study, we explored the potential causal relationship using bidirectional Mendelian randomization (MR)., Methods: Instrumental variants for albumin were obtained from a genome-wide association study (GWAS) on 102,223 Eastern Asian participants to investigate the effect of albumin on CRC. Summary statistics of CRC were obtained from a GWAS on 7,062 CRC cases and 195,745 controls of Eastern Asian ancestry. Bidirectional MR analysis was performed using inverse variance weighting (IVW) for primary analysis, supplemented with a maximum likelihood-based method, MR-PRESSO test, leave-one-out analysis, and MR-Egger regression. Stratification analyses were further performed., Results: We found that genetically predicted serum albumin per unit was associated with a lower risk of CRC (OR 0.75, 95% CI 0.59-0.95 with IVW). No evidence of pleiotropy was observed. Sex-stratified MR analysis showed that serum albumin was inversely associated with risk of CRC in men (OR 0.71, 95% CI 0.53-0.96), but not in women (OR 0.81, 95% CI 0.55-1.19) using IVW. Reverse MR analysis suggested a genetic predisposition toward CRC was not associated with serum albumin., Conclusion: Our study revealed a suggestive sex disparity in the effect of albumin, which deserves further exploration of the potential biological mechanism., Competing Interests: The authors have no relevant financial or nonfinancial interests to disclose., (© 2022 Lv et al.)

Aim: The prevalence of the use of electronic cigarettes (e-cigarettes) has grown rapidly in the past decade in the United States. While numerous studies have demonstrated combustible cigarette is closely associated with an increased risk of arthritis diseases, little is known about the effect of e-cigarette usage on inflammatory arthritis diseases. We aimed to determinate if e-cigarette usage is associated with an increased risk of inflammatory arthritis. Methods: Data were obtained from the Behavioral Risk Factor Surveillance System, which is the largest national telephone-based survey of randomly sampled adults in the United States. A total of 924,882 participants with information on e-cigarette usage and inflammatory arthritis were included. We used multivariable logistic regression to estimate the risk of arthritis associated with e-cigarette usage. Results: Of the 924,882 participants, there were 30,569 (3.3%) current e-cigarette users, and 314,190 (25.9%) reported to have inflammatory arthritis diseases. In the fully adjusted model, we observed that the odds ratio (OR) (95% confidence interval) of inflammatory arthritis diseases was 1.81 (95% CI, 1.70-1.93) for current e-cigarette users compared with never e-cigarette users. The ORs of inflammatory arthritis diseases were 1.31 (95% CI, 1.18-1.47), and 1.55 (95% CI, 1.42-1.69) among sole e-cigarette and dual users compared with never e-cigarette users, respectively. Conclusions: This is the first study to observe a cross-sectional association between e-cigarette usage and inflammatory arthritis diseases, and the findings were consistent in both sole-e-cigarette users and dual users. Our findings provide evidence that e-cigarette usage might be an important risk factor for arthritis diseases, which may have regulatory implications for e-cigarette control., 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 Tian, Jiao, Mao and Zhang.)