Age-standardized incidence, prevalence, and mortality rates of autoimmune diseases in adolescents and young adults (15-39 years): an analysis based on the global burden of disease study 2021.

BACKGROUND: Autoimmune diseases (ADs) present significant health challenges globally, especially among adolescents and young adults (AYAs) due to their unique developmental stages. Comprehensive analyses of their burden are limited. This study leverages the Global Burden of Disease (GBD) 2021 data to assess the global, regional, and national burden and trends of major ADs among AYAs from 1990 to 2021. METHODS: Utilizing data from the Global Burden of Disease (GBD) Study 2021 for individuals aged 15-39 years, we employed a direct method for age standardization to calculate estimates along with 95% uncertainty intervals (UIs) for assessing the age-standardized incidence rates (ASIR), prevalence rates (ASPR), and mortality rates (ASMR) of ADs. The diseases analyzed included rheumatoid arthritis (RA), inflammatory bowel disease (IBD), multiple sclerosis (MS), type 1 diabetes mellitus (T1DM), Asthma, and Psoriasis. Trends from 1990 to 2021 were analyzed using Joinpoint regression, providing average annual percentage changes (AAPC) and 95% confidence intervals (CIs). RESULT: In 2021, the global ASIR, ASPR, and ASMR of RA among AYAs (per 100,000 population) were 9.46 (95% UI: 5.92 to 13.54), 104.35 (77.44 to 137.84), and 0.016 (0.013 to 0.019), respectively. For IBD, the corresponding rates were 4.08 (3.07 to 5.37), 29.55 (23.00 to 37.83), and 0.10 (0.07 to 0.12). MS exhibited rates of 1.40 (0.93 to 1.93), 16.05 (12.73 to 19.75), and 0.05 (0.04 to 0.05), respectively. T1DM had rates of 6.63 (3.08 to 11.84), 245.51 (194.21 to 307.56), and 0.54 (0.47 to 0.60). Asthma demonstrated rates of 232.22 (132.11 to 361.24), 2245.51 (1671.05 to 2917.57), and 0.89 (0.77 to 1.08). Psoriasis showed rates of 55.08 (48.53 to 61.93) and 426.16 (394.12 to 460.18) for ASIR and ASPR, respectively. From 1990 to 2021, the global ASIR of RA (AAPC = 0.47, 95% CI: 0.46 to 0.49), IBD (0.22 [0.12 to 0.33]), MS (0.22 [0.19 to 0.26]), T1DM (0.83 [0.80 to 0.86]), and Psoriasis (0.33 [0.31 to 0.34]) showed increasing trends, whereas Asthma (-0.96 [-1.03 to -0.88]) showed a decreasing trend. The global ASPR of RA (0.70 [0.68 to 0.73]), MS (0.35 [0.32 to 0.37]), T1DM (0.68 [0.66 to 0.69]), and Psoriasis (0.29 [0.27 to 0.32]) also showed increasing trends, whereas IBD (-0.20 [-0.27 to -0.13]) and Asthma (-1.25 [-1.31 to -1.19]) showed decreasing trends. Notably, the estimated global ASMR of RA (-2.35 [-2.57 to -2.12]), MS (-0.63 [-0.86 to -0.41]), T1DM (-0.35 [-0.56 to -0.14]), and Asthma (-1.35 [-1.44 to -1.26]) in AYAs declined. Additionally, the burden of disease for ADs in AYAs varies considerably across continents and between 204 countries and territories. CONCLUSION: ADs among AYAs present a substantial public health burden with notable regional disparities in incidence, prevalence, and mortality rates. Understanding these patterns is essential for developing targeted public health interventions and policies to mitigate the impact of ADs in this population.

Serum vitamin D levels and Sjogren's syndrome: bi-directional Mendelian randomization analysis.

BACKGROUND: Based on the results of existing observational studies, it can be found that the association between serum vitamin D levels and the risk of Sjogren's syndrome (SS) in humans is still controversial. Based on this situation, this study aimed to assess the causal relationship between serum vitamin D levels and SS by using the Mendelian randomization (MR) approach. METHODS: In this study, genome-wide association studies (GWAS) summary statistics on serum vitamin D levels [sample size = 417,580 (UK Biobank)] and SS [sample size = 416,757 (cases = 2495, controls = 414,262) (FinnGen)] were used. The bi-directional MR analysis was then used to assess possible causal relationships. The major analysis method of MR was performed using inverse-variance weighted (IVW), supplemented by MR-Egger and the weighted median approaches. In addition, sensitivity analyses were used to ensure the stability of the results, including Cochran's Q test, MR-PRESSO, MR-Egger intercept test, and the leave-one-out test. RESULTS: The MR suggested that no significant causal effects of serum 25(OH)D levels on SS risks were observed [odds ratio (OR) = 0.9824; 95% confidence interval (CI) = 0.7130 to 1.3538; P = 0.9137]. Similarly, no evidence supported the causal effects of SS on serum vitamin D levels (ß: 0.0076, 95% CI: - 0.0031 to 0.0183; P = 0.1640). CONCLUSION: This study found no obvious evidence that serum vitamin D level is causally associated with SS risks or vice versa. We call for larger sample size studies to further unravel the potential causal relationship and the exact mechanism.

Comparison of SARIMA model and Holt-Winters model in predicting the incidence of Sjögren's syndrome.

OBJECTIVE: To analyze the prevalence trend of Sjögren's syndrome in the Department of Immunology and Rheumatology of Nanjing Zhongda Hospital from January 2015 to December 2019, and compare the application of SARIMA model and Holt-Winters model in predicting the number of cases of Sjögren's syndrome. METHODS: All of the data from the Department of Immunology and Rheumatology of Nanjing Zhongda Hospital were collected. The number of monthly cases from January 2015 to December 2019 was regarded as the training set, and it was used to establish the SARIMA model and Holt-Winters model. The number of monthly incidences from January 2020 to December 2020 was regarded as the test set, and it was used to check the model performance. RESULTS: The optimal model of SARIMA is ARIMA (0,1,1) (2,1,1)12 model, and the optimal model of Holt-Winters model is Holt-Winters addition model. It was found that the Holt-Winters addition model produced the smallest error. CONCLUSION: Holt-Winters addition model produces better prediction accuracy of the model.

Association of PM2.5 and its components with lengths of hospital stay for hand foot and mouth disease in children.

Hand foot and mouth disease (HFMD) is a widespread public health concern but the studies on air pollution and the lengths of hospital stay (LOS) of HFMD are scarce nevertheless. Clinic demographic features among 5135 hospitalized HFMD cases in Nanjing, China, had been characterized from 2012 to 2017. Then, we had analyzed the association between PM2.5 short-term exposure as well as its components (OM, BC, SO42-, NH4+, NIT, SOIL, and SS) and the LOS of HFMD. Among these cases that were involved in our study, 98.62% were aged 0-6 years old, and 3772 (73.46%) were hospitalized within 1 week or less. The LOS of HFMD patients was different in various age ranges, illness onset years, and illness onset seasons (P < 0.01). For per IQR increase in PM2.5 concentrations, LOS of HFMD increased by 0.52 (0.33, 0.71), 0.50 (95% CI, 0.31-0.69) and 0.46 (95% CI, 0.28-0.65) day in adjusted models at lag 3 days, lag 7 days, and lag 14 days, respectively. In addition, per IQR increase of BC, SO42-, NH4+, NIT, and SOIL was also significantly associated with the LOS of HFMD. Our findings corroborated that short-term PM2.5 exposure was associated with the increased LOS of HFMD, and its components (BC, SO42-, NH4+, NIT, and SOIL) of PM2.5 might play a key role in prolonged LOS of HFMD.

The association of sex-biased ATRX mutation in female gastric cancer patients with enhanced immunotherapy-related anticancer immunity.

BACKGROUND: Genetic alterations have been proven to be the promising biomarkers for ICI response. However, sex biases in genetic alterations have been often ignored in the field of immunotherapy, which might specially influence the anticancer immunity and immunotherapy efficacy in male or female patients. Here, we have systematically evaluated the effect of the sex biases in somatic mutation of gastric cancer (GC) patients on the anticancer immunity and clinical benefit to immunotherapy. METHODS: Genomic and transcriptomic data of gastric cancer were downloaded from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC). We also obtained the genomic and clinical data of a MSKCC ICI-treated cohort from cbioportal database. GC male and female-derived tumor somatic mutation profiles were compared by maftools R package. Single sample gene set enrichment analysis (ssGSEA) was conducted to calculate the score of the anticancer immunity indicators including IFN-γ signaling, cytolytic activity (CYT) and antigen presenting machinery (APM). RESULTS: ATRX was found to mutate more frequently in female GC patients compared to male patients (FDR = 0.0108). Female GC patients with ATRX mutation manifested significantly more MSI-high subtypes, increased TMB and PDL1 expression as well as higher scores of IFN-γ signaling, CYT and APM. Gene set enrichment analysis (GSEA) has shown that ATRX mutation might enhance the immunogenicity and anticancer immunity through affecting DNA damage repair pathways. In the ICI-treated cohort from MSKCC, GC patients with ATRX mutation were associated with prolonged overall survival. When stratifying the entire ICI-treated cohort by sex, female patients with ATRX mutation obtained significantly better survival benefits than that of ATRX mutant male patients (Female patients, HR of ATRX MT vs WT = 0.636, 95%CI = 0.455-0.890, P = 0.023; Male patients, HR of ATRX MT vs WT = 0.929, 95%CI = 0.596-1.362, P = 0.712). CONCLUSIONS: ATRX mutation might serve as a potential predictive biomarker for favorable clinical benefit to ICI in female GC patients. ATRX mutation could be applied in combination with other biomarkers of ICI response to better identify the female GC patients who will derive greater benefits from ICI therapy.

Role of endothelin receptor type B (EDNRB) in lung adenocarcinoma.

BACKGROUND: The five-year survival rate of lung adenocarcinoma patients (LUAD) is very low,and the methods of predicting survival are a great obstacle for LUAD therapies. Endothelin receptor type B (EDNRB) gene is associated with tumorigenesis. In this study, we aimed to evaluate the predictive value of EDNRB on LUAD. METHODS: Survival analyses was performed to assess the correlation between EDNRB expression and survival of LUAD patients from the Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA) datasets. Gene set enrichment analysis (GSEA) was conducted to illustrate possible biological functions of EDNRB. Laboratory methods were used to verify the function of EDNRB in LUAD. RESULTS: The TCGA results showed that a low expression of EDNRB was found in LUAD patients which led to poor outcome and worse survival, compared with the high expression in GSEA results which suggested that expression of EDNRB might be associated with regulation of the ERK pathway. Laboratory results suggested that EDNRB could inhibit the proliferation and migration of LUAD H1299 cells. CONCLUSIONS: EDNRB is a potential prognostic marker for LUAD patients and might exert its functions by regulating the ERK pathway in LUAD.

The synergistic effect between adult weight changes and CYP24A1 polymorphisms is associated with pre- and postmenopausal breast cancer risk.

PURPOSE: Vitamin D (VD) metabolism regulates adipose tissue, lipogenesis inflammation, and tumor growth. CYP24A1 is the key enzyme for metabolic inactivation of active VD (1,25(OH)2D3). We examined whether common germline single nucleotide polymorphisms (SNPs) in the CYP24A1 gene could affect the association between adult weight gain and breast cancer (BC) risk. METHODS: The population-based case-control study included 818 patients with primary BC and 935 residence and age matched healthy controls. We studied the relationships between CYP24A1 gene SNPs (rs2209314, rs2585428, rs2762941, rs3787555, rs4809959, rs73913757, rs912505, and rs927a650), adult weight change and BC risk. Gene-weight change interactions were analyzed. RESULTS: Neither of CYP24A1 gene SNPs was associated with BC risk in the study participants. However, we found consistent gene-weight interactions with increasing adult weight gain for CYP24A1-rs2762941 (P-interaction = 0.0089) and CYP24A1-rs927650 (P-interaction = 0.0283). Adult weight gain has a higher premenopausal BC risk with double variant T alleles of rs927650 compared to women carrying at least one wild-type C allele (OR for TT = 1.82, 95% CI 1.10-3.01; for CT = 0.93, 95% CI 0.76-1.14; for CC = 1.12 95% CI 0.93-1.35). Women with double wild-type A alleles were at a higher postmenopausal BC risk compared to those carrying at least one variant-type G allele (OR for AA = 1.51, 95% CI 1.29-1.76; for AG = 1.13, 95% CI 0.98-1.30; for GG = 1.22 95% CI 0.95-1.57). When stratified by CYP24A1 SNPs genotypes, weight gain in adulthood increased postmenopausal BC risk of women with homozygous allele compared to women with heterozygotes allele. CONCLUSION: Significant interactions of weight change with CYP24A1 polymorphisms suggest CYP24A1 as a potential link between weight change and BC risk and the possibility that the impact of adult weight gain on postmenopausal BC risk may be enhanced by homozygous alleles of CYP24A1 SNPs.

Molecular characteristic of HIV-1 CRF01_AE in Nanjing from 2015 to 2017.

OBJECTIVE: To investigate the evolutionary dynamics and characteristic of the molecular transmission networks of HIV-1 CRF01_AE in Nanjing. METHODS: Viral samples were collected from 580 newly diagnosed HIV-1-infected patients. HIV-1 pol sequences were obtained and used for for molecular evolutionary analyses. The ML trees were constructed by MEGA 6.0 using under GTR+ G + I model with 1000 bootstrap replicates. The emergence and estimation of tMRCA and the evolutionary rate of the different CRF01_AE clusters were inferred using Bayesian phylogenetic analysis approaches implemented in the BEAST package. Pairwise genetic distances were calculated under the Tamura-Nei 93 model, a genetic distance threshold of ≤1.2% was used to identify potential transmission clusters. Network diagrams were plotted using Cytoscape 3.3.0. RESULTS: Of these HIV-1-infected patients, 551 (91.5%) were males. The largest number of infections were attributed to homosexual (462, 79.7%). A total of 518 full-length pol genes were successfully amplified, based on the phylogenetic analysis CRF01_AE was the most predominantly circulating strain (45.0%, 233/518). As shown in the ML tree, three distinct clusters were observed. The 'Nanjing lineage' 1, 2, 3 has an estimated tMRCA around1996.61, 1993.61, 1984.61 respectively. Of 233 Nanjing sequences, 123 (55.2%) distributed in 30 molecular clusters, average Links/node was 7.8 with range (1-33), most of Nanjing strains shared links with local strains. CONCLUSION: HIV-1 CRF01_AE was the most predominantly circulating strain, the epidemic of CRF01_AE in Nanjing was driven by multiple clusters of HIV-1 strains, and most CRF01_AE stains in our study were estimated to have originated in China in the 1990s.

Adult weight change and the risk of pre- and postmenopausal breast cancer in the Chinese Wuxi Exposure and Breast Cancer Study.

PURPOSE: The accumulating evidence indicates that weight gain in adulthood is more predictive of breast cancer risk than absolute body weight. However, the relative impact of timing of weight gain in adulthood on breast cancer as well as other characteristics of the association between weight and breast cancer has not been well documented. METHODS: This population-based case-control study of breast cancer included 818 patients with newly diagnosed primary breast cancer and 935 residence and age-matched healthy controls. The body weight values at 18 years old, 1 year before diagnosis, and at menopause were obtained during in-person interviews. Unconditional logistic regression was used to estimate the effects of the weight change over adulthood on breast cancer risk. Linear mixed-effects regression was also applied as a secondary analysis. RESULTS: We found that the increased risk of breast cancer was associated with the weight gain in adulthood among postmenopausal women (OR 1.23; 95% CI 1.10-1.37 per 5 kg increase) but not in the premenopausal women. The risk associated with weight gain since menopause (OR 1.65; 95% CI 1.28-2.14 a 5-kg increase) was higher than that from age 18 to menopause (OR 1.14; 95% CI 1.02, 1.28 a 5-kg increase). The association tended to be stronger in those with higher waist circumference and who had never used hormone replacement therapy (HRT). Women who had never used HRT, the increased risk of breast cancer associated with weight gain was more consistent in leaner women at age 18 (BMI < 18.5) or at menopause (BMI < 24). CONCLUSIONS: Our findings indicated that weight gain has significant impact on postmenopausal breast cancer risk. The time periods of weight gain, central body fat, and HRT may affect the observed association, which should be further studied.

Genetic transmission networks reveal the transmission patterns of HIV-1 CRF01_AE in China.

OBJECTIVES: The epidemic of HIV-1 CRF01_AE has become a major public health issue in China. This study aimed to characterise the transmission patterns of genetic networks for CRF01_AE nationwide and elucidate possible opportunities for prevention. METHODS: We isolated and conducted genetic transmission network analysis of all available CRF01_AE pol sequences (n=4704) from China in the Los Alamos HIV sequence database. RESULTS: A total of 1391 (29.6%) sequences were identified as belonging to 400 separate networks. Of men who have sex with men (MSM) in the networks, 93.8% were linked to other MSM and only 2.4% were linked to heterosexual women. However, 11.8% heterosexual women in the networks were linked to MSM. Lineages composed mainly of MSM had higher transmission than those that were mostly heterosexuals. Of the 1391 individuals in networks, 513 (36.9%) were linked to cases diagnosed in different provinces. The proportion of individuals involved in inter-province links was interrelated with the number of migrant people (Spearman's r=0.738, p=0.001). CONCLUSIONS: The outcome of this study could help improve our ability to understand HIV transmission among various regions and risk groups in China, and highlighted the importance of targeting MSM and migrants by prevention and intervention efforts.

Multiple introductions and onward transmission of HIV-1 subtype B strains in Shanghai, China.

OBJECTIVE: To investigate the viral genetic evolution, spatial origins and patterns of transmission of HIV-1 subtype B in Shanghai, China. METHODS: A total of 242 Shanghai subtype B and 1519 reference pol sequences were subjected to phylogenetic inference and genetic transmission network analyses. RESULTS: Phylogenetic analysis revealed that subtype B strains circulating in Shanghai were genetically diverse and closely associated with viral sequence lineages in Beijing (76 of 242 [31.4%]), Central China (Henan/Hebei/Hunan/Hubei) (43 of 242 [17.8%]), Chinese Taiwan (20 of 242 [8.3%]), Japan (6 of 242 [2.5%]), and Korea (7 of 242 [2.9%]), suggesting multiple introductions into Shanghai from mainland China and Taiwan, Japan, and Korea. Interestingly, a monophyletic Shanghai lineage (SH-L) (36 of 242 [14.9%]) of HIV-1 subtype B most likely originated from an Argentine strain, transferred through Liaoning infected individuals. In-depth analyses of 195 Shanghai subtype B sequences revealed that a total of 37.9% (n = 74) sequences contributed to 35 transmission networks, whereof 33.8% (n = 25) of the sequences associated with infected individuals from other provinces. CONCLUSIONS: Our new findings reflect the evolution complexity and transmission dynamics of HIV-1 subtype B in Shanghai, which would provide critical information for the design of effective prevention measures against HIV transmission.

A meta-analysis of the association between Behçet's disease and MICA-A6.

Behçet's disease (BD) is a multi-system inflammatory condition with unknown cause, characterized by a triple-symptom complex of recurrent oral aphthous ulcers, genital ulcers, and uveitis and skin lesions. It predominantly affects people living around the Mediterranean basin and in Japan. The effects of the major histocompatibility complex class I chain related gene A (MICA) A6 allele on susceptibility to Behçet's disease (BD) have been reported previously, however, their results have been unreliable. The present study aimed to determine whether an association between the MICA-A6 allele and BD susceptibility exists. A total of 12 case-control studies, examining the association between MICA-A6 and BD and involving 752 cases and 1,175 controls were included in the present meta-analysis. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. The results of meta-analysis revealed that the frequency of the MICA-A6 allele in the case group was significantly higher than those in the control groups (P<0.001, OR=2.43, 95% CI: 1.99-2.97). Sub-group analysis by ethnicity indicated that the association between of MICA-A6 gene to BD remained in Asian populations (5 cases and 731 controls) and Caucasian populations (242 cases and 444 controls) with OR=2.65, 95% CI: 2.07-3.38 and OR=2.23, 95% CI: 1.37-3.62, respectively. These findings demonstrate that MICA-A6 gene is associated with susceptibility to BD. The MICA-A6 gene may serve as an early diagnostic marker for BD in the future.