Xīn Gào

Musculoskeletal (MSK) disorders are a leading cause of disability worldwide, particularly prevalent among women of childbearing age (WCBA). Our aim is to comprehensively assess the global, regional, and national burden of MSK disorders in WCBA, and examine the burden of MSK disorders among WCBA at varying levels of the Socio-demographic Index (SDI), then to project the burden of these disorders through to 2045. This study utilized data from the Global Burden of Disease (GBD) 2021 project, focusing on MSK disorders among WCBA (15-49 years). Age-standardized rate was calculated using the World Standard Population proportions. Descriptive analysis was conducted at global, regional, and national levels. SDI associations were explored using smoothing spline models. Projections to 2045 employed age-period-cohort models using R software. In 2021, the estimated global age-standardized incidence, prevalence, deaths, Years of Life Lost, Years Lived with Disability, and Disability-Adjusted Life Years (DALYs) rates per 100 000 population of MSK disorders in WCBA were 4933.9 (95% UI 3683.7-6454.4), 20145.9 (17 082.6-23 564.4), 0.7 (0.6-0.8), 40.7 (34.1-45.7), 2090.4 (1414.8-2896.2), and 2131.1 (1455.8-2936.8), respectively. From 1990 to 2021, a total of 183 countries exhibited an increase in prevalence rate and 166 countries showed an upward trend in DALYs rate. Between 1990 and 2021, there was a positive association between the SDI and age-standardized DALYs rate for MSK disorders in WCBA, both globally and regionally. By 2045, the age-standardized number of DALYs for MSK disorders in WCBA is expected to reach 48.8 million, with an age-standardized DALYs rate of 2160 per 100,000 population. The burden of MSK disorders among WCBA is already substantial and is expected to increase further in the future. Despite the observed decline in age-standardized incidence rate of MSK disorders among WCBA in half of the regions and countries globally, the age-standardized prevalence and DALYs rates have shown an adverse increasing trend. By 2045, the global number of DALYs for MSK disorders in WCBA is projected to exceed 48 million. To mitigate the future burden of MSK disorders in WCBA, stratified and targeted healthcare strategies are essential to improve early diagnosis and treatment.

Background: In China, the 2022–2023 influenza season began earlier and was characterized by higher levels of influenza activity and co-circulation of various respiratory pathogens compared with seasons before the coronavirus disease 2019 (COVID-19) pandemic. Timely and precise estimates of influenza vaccine effectiveness (IVE) against infections can be used to guide public health measures. Methods: A test-negative study was conducted to estimate IVE against laboratory-confirmed influenza using data from the CHinese Electronic health Records Research in Yinzhou (CHERRY) study that prospectively integrated laboratory, vaccination, and health administrative data in Yinzhou, southern China. We included patients who presented influenza-like illness and received nucleic acid tests and/or antigen tests between October 2023 and March 2024. Estimates of IVE were adjusted for age, gender, month of specimen submitted, chronic comorbidities, and hospitalization status. Results: A total of 205 028 participants, including 96 298 influenza cases (7.6% vaccinated) and 108 730 influenza-negative controls (13.4% vaccinated), were eligible for this analysis. The estimates of IVE were 49.4% (95% CI, 47.8%–50.9%), 41.9% (95% CI, 39.8%–44.0%), and 59.9% (95% CI, 57.9%–61.9%) against overall influenza, influenza A, and influenza B, respectively. A lower IVE was observed for individuals aged 7–17 years (38.6%), vs 45.8% for 6 months–6 years, 46.7% for 18–64 years, and 46.1% for ≥65 years. Vaccination reduced the risk of infection by 44.4% among patients with chronic comorbidities. IVEs varied by epidemic weeks with the changes in influenza activity levels and the switch of dominant influenza strains. Conclusions: Influenza vaccination in the 2023–2024 season was protective against infection for the entire population.

Objectives To estimate the global, regional, and national burden and trends of Guillain-Barré Syndrome (GBS), and to explore the impact of the COVID-19 pandemic and related public health measures on the GBS burden. Design Observational study. Setting 204 countries and territories. Data sources Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 and Our World in Data. Main outcome measures All-cause and COVID-19-specific age-standardized years lived with disability (YLD) rates and estimated annual percentage change (EAPC). Results Globally, the burden of GBS significantly increased during the COVID-19 pandemic, age-standardized YLD rates were 0.86 (95% uncertainty interval (UI): 0.56 to 1.24) per 100,000 people in 2020, rising to 1.75 (95% UI: 1.12 to 2.54) per 100,000 people in 2021, reflecting an EAPC of 70.35% (95% UI: 38.73 to 109.06) from 2019 to 2021. Regionally, the highest age-standardized YLD rates in 2020 and 2021 were observed in the high-income Asia Pacific and central Latin America, respectively, while the lowest rates were found in East Asia for both years. Age-standardized YLD rates rose 3.7 times faster in countries with a low socio-demographic index (SDI) versus countries with a high SDI (103.21% per year (95% UI: 71.10 to 141.35%) vs 28.02% per year (11.46 to 47.03)). Males generally had higher YLD rates across all age groups, with the highest disparity in those aged 80 and above. During the first two years of the pandemic, the increase in YLD rates was more pronounced in females and younger populations aged 15-29 years. A statistically negative correlation was observed between COVID-19 vaccination coverage and the GBS burden, with increases in full vaccination coverage per 100 people leading to decreases in all-cause YLD rates by 0.0070 and COVID-19-specific YLD rates by 0.0128 per 100,000 people. Conclusion Predominantly driven by the surge of COVID-19 cases, the burden of GBS significantly increased during the first two years of the pandemic, especially in those countries with lower SDI levels. Greater increases in the GBS burden were observed in females and younger populations (15-29 years). Importantly, the benefits of vaccination outweighed the risks in controlling the post-COVID-19 GBS burden, although significant disparities in vaccination coverage existed between countries. These findings offer robust evidence facilitating public education and transparent communication on COVID-19 vaccination and highlight the urgency for targeted control measures to manage the burden of post-infection complications, such as GBS, during future COVID-19 waves or other potential pandemics. WHAT IS ALREADY KNOWN ON THIS TOPIC Guillain-Barré syndrome (GBS) is an autoimmune disease, and respiratory and gastrointestinal infections are the major triggering factors. From 1990 to 2019, the burden of GBS was relatively low, with negligible changes observed in most countries and territories. The impact of the COVID-19 pandemic and vaccination on the burden of GBS remains not fully understood. WHAT THIS STUDY ADDS During the COVID-19 pandemic, the global age-standardized years lived with disability (YLD) related to GBS increased by 70.30% annually, and low socio-demographic index (SDI) regions experienced the most rapid GBS burden increment (103.21%). The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was the primary factor contributing to the increased burden of GBS during the COVID-19 pandemic. Improving vaccination coverage was the most effective measure to reduce the post-COVID-19 burden of GBS, and each additional fully vaccinated person (per hundred people) decreased the COVID-19-specific age-standardized YLD of GBS by 0.0128 per 100,000 population.

We performed a multi-ethnic Epigenome Wide Association study on 22,774 individuals to describe the DNA methylation signature of chronic low-grade inflammation as measured by C-Reactive protein (CRP). We find 1,511 independent differentially methylated loci associated with CRP. These CpG sites show correlation structures across chromosomes, and are primarily situated in euchromatin, depleted in CpG islands. These genomic loci are predominantly situated in transcription factor binding sites and genomic enhancer regions. Mendelian randomization analysis suggests altered CpG methylation is a consequence of increased blood CRP levels. Mediation analysis reveals obesity and smoking as important underlying driving factors for changed CpG methylation. Finally, we find that an activated CpG signature significantly increases the risk for cardiometabolic diseases and COPD.

Chronic kidney disease is a major public health burden. Elevated urinary albumin-to-creatinine ratio is a measure of kidney damage, and used to diagnose and stage chronic kidney disease. To extend the knowledge on regulatory mechanisms related to kidney function and disease, we conducted a blood-based epigenome-wide association study for estimated glomerular filtration rate (n = 33,605) and urinary albumin-to-creatinine ratio (n = 15,068) and detected 69 and seven CpG sites where DNA methylation was associated with the respective trait. The majority of these findings showed directionally consistent associations with the respective clinical outcomes chronic kidney disease and moderately increased albuminuria. Associations of DNA methylation with kidney function, such as CpGs at JAZF1, PELI1 and CHD2 were validated in kidney tissue. Methylation at PHRF1, LDB2, CSRNP1 and IRF5 indicated causal effects on kidney function. Enrichment analyses revealed pathways related to hemostasis and blood cell migration for estimated glomerular filtration rate, and immune cell activation and response for urinary albumin-to-creatinineratio-associated CpGs.

Elevated serum urate levels, a complex trait and major risk factor for incident gout, are correlated with cardiometabolic traits via incompletely understood mechanisms. DNA methylation in whole blood captures genetic and environmental influences and is assessed in transethnic meta-analysis of epigenome-wide association studies (EWAS) of serum urate (discovery, n = 12,474, replication, n = 5522). The 100 replicated, epigenome-wide significant (p < 1.1E–7) CpGs explain 11.6% of the serum urate variance. At SLC2A9, the serum urate locus with the largest effect in genome-wide association studies (GWAS), five CpGs are associated with SLC2A9 gene expression. Four CpGs at SLC2A9 have significant causal effects on serum urate levels and/or gout, and two of these partly mediate the effects of urate-associated GWAS variants. In other genes, including SLC7A11 and PHGDH, 17 urate-associated CpGs are associated with conditions defining metabolic syndrome, suggesting that these CpGs may represent a blood DNA methylation signature of cardiometabolic risk factors. This study demonstrates that EWAS can provide new insights into GWAS loci and the correlation of serum urate with other complex traits.

We performed a trans-ethnic Epigenome Wide Association study on 22,774 individuals to describe the DNA methylation signature of chronic low-grade inflammation as measured by C-Reactive protein (CRP). We found 1,511 independent differentially methylated loci associated with CRP. These CpG sites showed correlation structures across chromosomes, and were primarily situated in euchromatin, depleted in CpG islands and enriched in transcription factor binding sites and genomic enhancer regions. Mendelian randomisation analysis suggests altered CpG methylation is a consequence of increased blood CRP levels. Mediation analysis revealed obesity and smoking as important underlying driving factors for changed CpG methylation. Finally, we found that a fully activated CpG signature, meaning that if all novel discovered CpGs would either be fully methylated or unmethylated depending on their CRP associated direction of effect, the risk of myocardial infarction would be increased by 20.3%, risk of T2D by 11.3% and the risk of COPD by 5.6%.

Red and processed meat consumption and obesity are established risk factors for colorectal adenoma (CRA). Adverse changes in biomarkers of body iron stores (total serum iron, ferritin, transferrin and transferrin saturation), inflammation (high-sensitivity C-reactive protein [hs-CRP]) and anti-oxidative capacity (total of thiol groups (-S-H) of proteins [SHP]) might reflect underlying mechanisms that could explain the association of red/processed meat consumption and obesity with CRA. Overall, 100 CRA cases (including 71 advanced cases) and 100 CRA-free controls were frequency-matched on age and sex and were selected from a colonoscopy screening cohort. Odds ratios (OR) and 95% confidence intervals (95%CI) for comparisons of top and bottom biomarker tertiles were derived from multivariable logistic regression models. Ferritin levels were significantly positively associated with red/processed meat consumption and hs-CRP levels with obesity. SHP levels were significantly inversely associated with obesity. Transferrin saturation was strongly positively associated with overall and advanced CRA (ORs [95%CIs]: 3.05 [1.30–7.19] and 2.71 [1.03–7.13], respectively). Due to the high correlation with transferrin saturation, results for total serum iron concentration were similar (but not statistically significant). Furthermore, SHP concentration was significantly inversely associated with advanced CRA (OR [95%CI]: 0.29 [0.10–0.84]) but not with overall CRA (OR [95%CI]: 0.65 [0.27–1.56]). Ferritin, transferrin, and hs-CRP levels were not associated with CRA. High transferrin saturation as a sign of iron overload and a low SHP concentration as a sign of redox imbalance in obese patients might reflect underlying mechanisms that could in part explain the associations of iron overload and obesity with CRA.

Leukocytes are involved in the progression of colorectal cancer (CRC). The proportion of six major leukocyte subtypes can be estimated using epigenome-wide DNA methylation (DNAm) data from stored blood samples. Whether the composition of circulating leukocytes can be used as a prognostic factor is unclear. DNAm-based leukocyte proportions were obtained from a prospective cohort of 2206 CRC patients. Multivariate Cox regression models and survival curves were applied to assess associations between leukocyte composition and survival outcomes. A higher proportion of lymphocytes, including CD4+ T cells, CD8+ T cells, B cells, and NK cells, was associated with better survival, while a higher proportion of neutrophils was associated with poorer survival. CD4+ T cells outperformed other leukocytes in estimating the patients’ prognosis. Comparing the highest quantile to the lowest quantile of CD4+ T cells, hazard ratios (95% confidence intervals) of all-cause and CRC-specific mortality were 0.59 (0.48, 0.72) and 0.59 (0.45, 0.77), respectively. Furthermore, the association of CD4+ T cells and prognosis was stronger among patients with early or intermediate CRC or patients with colon cancer. In conclusion, the composition of circulating leukocytes estimated from DNAm, particularly the proportions of CD4+ T cells, could be used as promising independent predictors of CRC survival.