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Background: Long-term air pollution exposure and inflammation are considered to be associated with cognitive decline. However, whether air pollution exposure related cognitive decline is dependent on inflammation remains uncertain. Materials and methods: The present study collected data from China Health and Retirement Longitudinal Study (CHARLS) at baseline in 2011, with a follow up period in 2015. Concentration of air pollutants (particles with diameters ≤ 1.0 μm [PM1], ≤ 2.5 μm [PM2.5], ≤ 10 μm [PM10], nitrogen dioxide [NO2] and ozone [O3]) were obtained from China High Air Pollutants (CHAP) dataset. Hypersensitive C-reactive protein (hs-CRP), a systemic inflammation marker, was measured in blood of subjects and cognitive function was assessed by standardized questionnaire. Results: A total of 6434 participants were included in the study. Lower exposure to PM2.5, PM1, PM10 and NO2 were associated with mitigated cognitive decline. The odds ratios (ORs) for air pollutants changes and cognitive decline and 95% confidence intervals (CIs) were as follows: PM2.5-0.934(0.925, 0.943), PM1- 0.945 (0.935,0.955), PM10-0.977(0.972,0.982) and NO2-0.962(0.950,0.975), respectively. Hs-CRP showed no significant correlation with cognitive decline or change in levels of air pollution. The interaction regression analyses, both unadjusted and adjusted, did not uncover any significant correlation between hs-CRP and air pollution with respect to cognitive decline. Bootstrap test exhibited no significant mediating effect of hs-CRP on the relationship between any air pollutants and cognitive decline, the indirect effects of hs-CRP in conjunction with exposure to different air pollutants were all found to be non-significant, with the following bootstrap CIs and p-values: PM2.5-1.000([1.000,1.000], P = 0.480),PM1-1.000([1.000,1.000], P = 0.230),PM10-1.000([1.000,1.000], P = 0.650), O3-1.000([1.000,1.000], P = 0.470), ΔNO2-1.000([1.000,1.000], P = 0.830). Conclusion: Ambient air pollution exposure was linked to cognitive decline independent of hs-CRP level. [ABSTRACT FROM AUTHOR]

Mood disorders include a set of psychiatric manifestations of increasing prevalence in our society, being mainly represented by major depressive disorder (MDD) and bipolar disorder (BD). The etiopathogenesis of mood disorders is extremely complex, with a wide spectrum of biological, psychological, and sociocultural factors being responsible for their appearance and development. In this sense, immune system dysfunction represents a key mechanism in the onset and pathophysiology of mood disorders, worsening mainly the central nervous system (neuroinflammation) and the periphery of the body (systemic inflammation). However, these alterations cannot be understood separately, but as part of a complex picture in which different factors and systems interact with each other. Psychoneuroimmunoendocrinology (PNIE) is the area responsible for studying the relationship between these elements and the impact of mind–body integration, placing the immune system as part of a whole. Thus, the dysfunction of the immune system is capable of influencing and activating different mechanisms that promote disruption of the psyche, damage to the nervous system, alterations to the endocrine and metabolic systems, and disruption of the microbiota and intestinal ecosystem, as well as of other organs and, in turn, all these mechanisms are responsible for inducing and enhancing the immune dysfunction. Similarly, the clinical approach to these patients is usually multidisciplinary, and the therapeutic arsenal includes different pharmacological (for example, antidepressants, antipsychotics, and lithium) and non-pharmacological (i.e., psychotherapy, lifestyle, and electroconvulsive therapy) treatments. These interventions also modulate the immune system and other elements of the PNIE in these patients, which may be interesting to understand the therapeutic success or failure of these approaches. In this sense, this review aims to delve into the relationship between immune dysfunction and mood disorders and their integration in the complex context of PNIE. Likewise, an attempt will be made to explore the effects on the immune system of different strategies available in the clinical approach to these patients, in order to identify the mechanisms described and their possible uses as biomarkers. [ABSTRACT FROM AUTHOR]

Background: Systemic inflammation (SI) and insulin resistance (IR) are correlated to the progression of gastrointestinal (GI) cancer. Therefore, this study aimed to analyze the potential clinical value of the C-reactive protein-triglyceride-glucose index (CTI) in relation to SI and IR in patients with GI cancer. Methods: This prospective cohort study included patients with GI cancer. Patient data were collected from Fujian Cancer Hospital as an external validation cohort. Prognostic AUC, time-dependent ROC curve, C-index, and calibration curve analyses were used to predict the efficacy and accuracy of CTI survival prediction. Multivariate survival analysis was performed to evaluate the potential prognostic value of the CTI. Multiple logistic regression was performed to evaluate the relationship between the CTI and 90-day and 180-day mortalities. Results: We divided 1520 patients with GI cancer (mean age, 60.39 ± 11.3 years; male sex, 67%) into a training cohort and internal validation cohort; the external validation cohort included 476 patients. Prognostic AUC, time-dependent ROC curve, C-index, and calibration curve analyses of all cohorts indicated that the CTI could reliably and accurately predict the short- and long-term survival outcomes of patients with GI cancer. Multivariate survival analysis showed that for each standard deviation increase in the CTI, the risk of death increased by 32%, 21%, and 40% in the training, internal validation, and external validation cohorts, respectively. A high CTI was correlated to worse survival in patients with GI cancer (training cohort, hazard ratio [HR]=1.67, 95% confidence interval [CI]=1.35–2.08; internal validation cohort, HR=1.51, 95% CI=1.07–2.14, and external validation cohort, HR=1.59, 95% CI=1.18–2.13). In different tumor subgroups, a high CTI predicted worse survival outcomes for upper GI cancer (HR=1.54, 95% CI=1.18–2.01) and lower GI cancer (HR=1.98, 95% CI=1.36–2.86). Multivariate logistic regression analysis showed that a high CTI was positively correlated with 90-day (odds ratio [OR]=3.25, 95% CI=1.75–6.23) and 180-day mortalities (OR=2.66, 95% CI=1.72–4.15). Conclusions: The CTI is related to SI and IR and can predict the short- and long-term prognosis of patients with GI cancer. Evaluation of the CTI could provide clinicians with an effective tool for predicting the prognosis of patients with GI cancer. Clinical trial registration: https://www.chictr.org.cn/showproj.html?proj=31813 , identifier ChiCTR1800020329. [ABSTRACT FROM AUTHOR]

AbstractObjective: Physical exercise in treatment of asthma is scarcely studied with no clear exercise guidelines for asthmatics. We aimed to investigate the associations between physical exercise frequency, systemic inflammation and asthma control. This has not been previously studied in adult-onset asthma.Methods: This study is part of Seinäjoki Adult Asthma Study (SAAS), where 203 patients with adult-onset asthma were evaluated in 2012–2013. Exercise frequency was recorded with a structured lifestyle questionnaire. Study population was divided into two categories by exercise frequency: Low-frequency group exercised ≤2 times/week and high frequency group >2 times/week. Blood inflammatory markers were measured and IL-6 > 1.55 pg/ml and hs-CRP > 4.12 mg/l indicated systemic inflammation.Results: High-exercise frequency group had lower levels of hs-CRP (p = 0.007), IL-6 (p = 0.015), suPAR (p = 0.008) and adipsin (p = 0.031) and higher levels of adiponectin (p = 0.010) than low-exercise frequency group. In logistic multivariate regression models, higher-exercise frequency lowered odds for elevated hs-CRP (OR = 0.37, 95% CI 0.15–0.94) and IL-6 levels (OR = 0.43, 95% CI 0.20–0.91), after adjusting for possible confounding factors. There was no difference in lung function tests, asthma control test or airways questionnaire 20 scores between the exercise frequency groups. However, differences were found in single symptom questions; high-exercise frequency group had less symptoms during light housework and laughing but experienced more limitation of activity in self-reports.Conclusions: Higher-exercise frequency is associated with lower level of systemic inflammation in patients with adult-onset asthma but no clear association was found to asthma outcomes. Exercise frequency may be associated with lesser amount of some individual asthma symptoms. [ABSTRACT FROM AUTHOR]

Background: Obesity is associated with a systemic inflammatory state that contributes to neuroinflammation and increases the risk of stroke at an early age. Stroke is the third leading cause of death worldwide and the leading cause of permanent disability. This work aimed to assess whether obesity-induced neuroinflammation can be a prognostic stroke factor that can be improved with oral administration of silymarin, an anti-inflammatory and neuroprotective drug. Methods: Male C57/Bl6 mice were used to establish an obesity model through a high-fat diet (HFD) for 12 weeks. Cerebral ischemia was performed with photothrombosis in the left motor cortex at the end of the diet. Following the induction of ischemia, silymarin (100 mg/kg) was administered orally for 14 days. Levels of pro-inflammatory (IL1β, TNFα, and MCP1) and anti-inflammatory markers (IL4, IL10), neurotrophic factors (IGF1, BDNF), and CX3CL1 were assessed in the cortex and striatum using ELISA. Results: Mice on the HFD gained significantly more weight than control subjects and exhibited altered glucose metabolism, which was improved after silymarin treatment. The survival rate was significantly lower in HFD mice (52.2%) compared to control mice (86%). Silymarin treatment improved survival in both ischemic groups (non-diet control: 95.7%, HFD: 78.3%). Silymarin raised cortical TNFα, IL4, IL10, IGF1, BDNF, and CX3CL1 levels in the HFD group with stroke, while the striatum did not present relevant differences. Conclusion: Our findings suggest that silymarin improves glucose metabolism, possibly impacting post-stroke survival in obese mice. The increased levels of neurotrophic factors BDNF and IGF1, along with microglial regulatory factor CX3CL1, may contribute to the improved survival observed. These results indicate that silymarin could be a potential therapeutic option for managing neuroinflammation and enhancing post-stroke outcomes in obese individuals. [ABSTRACT FROM AUTHOR]

Background: Numerous studies have linked the inflammatory pathway in psoriasis and metabolic disease, while no specific marker defined it. It is worth exploring the association of β2-microglobulin (β2M) in psoriasis severity and comorbidities. Objectives: To investigate the correlation between blood β2M level and psoriasis severity, to explore the inflammatory factors influencing the occurrence of psoriasis comorbidities such as arthritis, diabetes, and hypertension. Methods: Ninety-seven psoriasis patients were analyzed in the cohort retrospective study during 12 weeks. Results: Significantly higher levels of blood β2M and ESR were observed in the group that patients' PASI ≥10 than in the group that PASI <10. Blood β2M level had strong significantly positive correlations with the PASI in Pearson's correlation analysis. In the model that systemic inflammatory factors to find psoriasis comorbidity risk factors, logistic regression analysis showed that blood β2M level was the significant risk factor associated with diabetes and hypertension. High-sensitivity C-reactive protein (hsCRP) was the significant risk factor associated with arthritis. Conclusions: Patients with a severer psoriasis tended to have higher blood β2M levels and severer inflammatory state. In the systemic inflammation indexes, the level of blood β2M affected the risk of hypertension and diabetes, and hsCRP affected the risk of arthritis in patients with psoriasis. [ABSTRACT FROM AUTHOR]

Background: The effect of air pollution, a major global health issue, on the immune system, particularly on white blood cell (WBC) counts, remains underexplored. Methods: This study utilized data from 54,756 participants in the Korean National Health and Nutrition Examination Survey to investigate the effects of short- (day of examination and 7-day averages), mid- (30- and 90-day averages), and long-term (one-, three-, and five-year averages) air pollutant exposure on WBC counts. We assessed exposure to particulate matter (PM10, PM2.5), sulfur dioxide (SO2), nitrogen dioxide (NO2), ozone (O3), and carbon monoxide (CO). Results: Linear regression with log-transformed WBC counts, adjusted for confounders, showed that PM10 was positively associated with long-term exposure, PM2.5 was negatively associated with short- and mid-term exposures, SO2 was consistently negatively associated with short- and mid-term exposures, NO2 and CO were positive across most periods, and O3 was negatively associated with short- and mid-term exposures. Logistic regression analysis confirmed these findings, showing that short- and mid-term exposure to PM10, PM2.5, and SO2 was negatively associated with the risk of belonging to the high-WBC group, while long-term exposure to PM10, PM2.5, NO2, and CO showed positive associations with risk. Conclusions: Our findings highlight the time- and pollutant-specific associations between air pollution exposure and WBC counts, underscoring air pollution's potential impact on systemic inflammation. [ABSTRACT FROM AUTHOR]

The list of standard abbreviations for JDS is available at adsa.org/jds-abbreviations-24. Nonstandard abbreviations are available in the Notes. The objective of this study was to assess the effects of prepartum administration of anti-inflammatory therapies on BCS, BHB concentration, haptoglobin (HP) concentration, milk yield, milk components, rumination time, clinical health events, and reproductive performance in Holstein dairy cows. At 14 d before the expected calving date, cows (parous [PAR]; n = 170) and heifers (nulliparous [NUL]; n = 63) were blocked by BCS group (optimal [OPT] = 3–3.5; over-conditioned cows [OVERC; BCS ≥3.75 points]) and parity (NUL; PAR) and randomly allocated to 1 of 3 treatment groups: (1) ASA (n = 78): receive one oral administration of acetylsalicylic acid (4 boluses; 480 grain/bolus); (2) MEL (n = 76): receive one oral administration with meloxicam (1 mg/kg BW), or (3) PLC (n = 77): receive one oral treatment with gelatin capsules filled with water. Body condition score was assessed, and blood samples were collected, weekly starting 1 wk before treatment until 3 wk after calving. Daily milk yields and daily rumination times were collected from on-farm computer records. Dairy Herd Improvement Association monthly test data were collected to assess milk yield, SCC, and milk components. Furthermore, health events, culling rate, and reproductive performance data were collected from on-farm computer records. The data were analyzed using MIXED, GLIMMIX, and LIFETEST procedures of SAS as a randomized complete block design. On average, MEL-NUL cows produced 4.77 ± 0.93 kg/d and 4.81 ± 0.92 kg/d more milk from wk 6 to 21 of lactation compared with ASA-NUL and PLC-NUL cows, respectively. Similarly, a week by treatment by body condition group interaction was present, where OVERC cows treated with MEL produced more milk from wk 10 to 15 of lactation compared with ASA-OVERC and PLC-VERC cows. Parous cows treated with ASA had lower BCS compared with PAR cows treated with MEL or PLC. A lower percentage of OVERC cows treated with ASA became sick in the first 60 DIM compared with MEL-OVERC and PLC-OVERC cows (ASA = 23.88% ± 7.26%, MEL = 46.36% ± 8.57%; PLC = 46.74% ± 8.53%). Parous cows treated with ASA had a higher hazard ratio to become pregnant by 300 DIM compared with PAR MEL cows. Although the study was not sized for finding treatment differences in blocking criteria groups, these results suggest that treatment with prepartum anti-inflammatory therapies may have positive effects on milk yield and postpartum health in specific groups of cows, such as NUL and OVERC cows, although it may not be recommended for other animal categories, such as parous cows and cows with optimal BCS. Larger studies are needed to strengthen the associations observed in this study. [ABSTRACT FROM AUTHOR]

Background: In this study, we aimed to investigate whether there is a relationship between aortic arch calcification (AAC) and hidradenitis suppurativa (HS) in HS patients without cardiovascular disease. Methods: In this study, patients over 18 years of age who applied to the dermatology outpatient clinic between January 2023 and February 2024 were followed up with the diagnosis of HS without cardiovascular disease, and a healthy control group matched in terms of age and gender were included retrospectively. Results: In total, 130 patients with HS without cardiovascular disease and 130 control patients were included in the study. AAC was significantly higher in the HS group compared to the control group (p = 0.028). In the multivariate analysis, we found that age and HS were independent predictors of AAC (OR: 1.048 (1.009–1.089); p = 0.015, OR: 3.158 (1.181–8.445); p = 0.022, respectively). When we divided the groups as having AAC (grade 1–3) and not having AAC (grade 0), the rate of HS disease was significantly higher in the group with AAC compared to the group without AAC (75.0% vs. 47.5% p = 0.010). Conclusions: AAC is observed more frequently in patients with HS without cardiovascular disease than in healthy individuals. Moreover, HS can be considered as an independent predictor of AAC. AAC may contribute to developing treatment strategies in HS patients without cardiovascular disease. [ABSTRACT FROM AUTHOR]

Background: Intestinal barrier dysfunction and systemic inflammation are common in obstructive sleep apnoea (OSA). We aimed to investigate the role of melatonin, an anti-inflammatory mediator, in mediating the relationships between OSA, intestinal barrier dysfunction and systemic inflammation. Methods: Two hundred and thirty-five male participants who complained with sleep problems and underwent whole night polysomnography at our sleep centre between 2017 and 2018 were enrolled. Polysomnographic data, anthropometric measurements and biochemical indicators were collected. Serum melatonin, intestinal barrier function biomarker zonula occludens-1 (ZO-1) and inflammatory biomarkers C-reactive protein (CRP) with lipopolysaccharide (LPS) were detected. Spearman's correlation analysis assessed the correlations between sleep parameters, melatonin and biomarkers (ZO-1, LPS and CRP). Mediation analysis explored the effect of OSA on intestinal barrier dysfunction and systemic inflammation in moderate-severe OSA patients. Results: As OSA severity increased, serum melatonin decreased, whereas ZO-1, LPS and CRP increased. Spearman's correlation analysis showed that serum melatonin was significantly negatively correlated with ZO-1 (r = -0.19, p < .05) and LPS (r = -0.20, p < .05) in the moderate-OSA group; serum melatonin was significantly negatively correlated with ZO-1 (r = -0.46, p < .01), LPS (r = -0.35, p < .01) and CPR (r = -0.30, p < .05) in the severe-OSA group. Mediation analyses showed melatonin explain 36.12% and 35.38% of the effect of apnoea-hypopnea index (AHI) on ZO-1 and LPS in moderate to severe OSA patients. Conclusions: Our study revealed that melatonin may be involved in mediating intestinal barrier dysfunction and systemic inflammation in moderate-to-severe OSA patients. [ABSTRACT FROM AUTHOR]

ABSTRACT Periodontal diseases, particularly periodontitis, are complex inflammatory conditions caused by interactions between oral microbiota and the host immune response. Lipopolysaccharides (LPSs) from Gram‐negative bacteria like Tannerella forsythia, Treponema denticola, and Porphyromonas gingivalis are key in pathogenesis. This review examines how LPS impacts systemic health through direct invasion, compromised oral barriers, increased vascular permeability, and immune cell transport. LPS triggers inflammation in periodontal tissues, leading to tissue destruction and disease progression. In the bloodstream, LPS contributes to conditions, such as cardiovascular diseases, diabetes, respiratory diseases, and rheumatoid arthritis. Current treatments include mechanical debridement, antibiotics, antimicrobial mouthwashes, and anti‐inflammatory therapies. Despite progress, gaps remain in understanding the molecular mechanisms of LPS in systemic diseases. Future research should focus on longitudinal studies, the gut–oral axis, biomarkers for early detection, and the lymphatic system's role in LPS dissemination. Maintaining periodontal health is crucial for overall systemic well‐being. [ABSTRACT FROM AUTHOR]

Although serum uric acid (SUA) is a risk factor for cardiometabolic outcome, but it remains unclear which patients with coronary artery disease (CAD) benefit the most from SUA lowering therapy (ULT). The association of SUA level, systemic inflammation and cardiometabolic risk is still unclear. The current study is aimed to examine whether SUA-associated cardiometabolic risk is modulated by systemic inflammation in CAD patients. A total of 16,598 CAD patients with baseline high-sensitivity C-Reactive Protein (hsCRP) and SUA available were included. Baseline and follow-up data were collected. The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE), including death, myocardial infarction and stroke. In patients with hsCRP ≥ 2 mg/L, increasing quintiles of SUA were significantly associated with increased rates of 2-year MACCE (adjusted p < 0.001 for trend, p = 0.037 for interaction). Each unit increase in SUA levels was associated with a 11.3% increased risk of MACCE (adjusted p < 0.001, p = 0.002 for interaction). However, in patients with hsCRP < 2 mg/L, increasing quintiles of SUA were not associated with increased MACCE (adjusted p = 0.120). Elevated SUA levels are related to MACCE when hsCRP levels are 2 mg/L or more but not less than 2 mg/L. This finding suggests a potential benefit of combined ULT and anti-inflammation therapy in patients with hyperuricemia and greater systemic inflammation. [ABSTRACT FROM AUTHOR]

Simple Summary: In this study we examined whether a specific blood test score, the Scottish Inflammatory Prognostic Score (SIPS), could help predict outcomes in people with advanced lung cancer receiving immunotherapy. Immunotherapy, which uses the body's immune system to fight cancer, is effective for some patients but not all. SIPS is based on two common blood measures: albumin (a protein) and neutrophils (a type of immune cell). Our findings suggest that patients with low SIPS scores, indicating lower inflammation, generally lived longer and had slower cancer progression. SIPS could become a helpful tool for doctors to decide on treatments and guide patients about their prognosis. Using SIPS alongside other health information may improve care by helping select the most suitable therapies for people with advanced lung cancer. Further studies could confirm these findings and support SIPS as a standard measure in clinical care. Background: The Scottish Inflammatory Prognostic Score (SIPS), combining albumin (≥/<35 g/L) and neutrophil count (≤/>7.5 × 109/L), has been identified as a prognostic biomarker for patients with non-small cell lung cancer (NSCLC) undergoing treatment with pembrolizumab monotherapy. We sought to validate this biomarker of systemic inflammation in an external cohort. Methods: Patients treated with first-line pembrolizumab for advanced NSCLC with programmed death-ligand 1 (PD-L1) expression ≥ 50% at an English cancer centre were identified. Pre-treatment clinicopathological characteristics and the SIPS were recorded. The relationship between these and progression-free survival (PFS) and overall survival (OS) was examined. Results: Among 257 patients evaluated, 56% (n = 144) were classified as SIPS 0, 36% (n = 93) as SIPS 1, and 8% (n = 20) as SIPS 2. Factors such as age, performance status (PS) and brain metastases presence were significantly correlated with SIPS categories. Multivariate analysis revealed that both SIPS and PD-L1 status were independently associated with PFS and OS. The combination of SIPS with either PS or PD-L1 expression enhanced the ability to detect patients with the most favourable or poorest survival. Conclusions: Our study confirms the prognostic significance of the SIPS in patients with advanced NSCLC treated with pembrolizumab in the context of high PD-L1 expression. SIPS offers a straightforward, clinically applicable approach to patient stratification, potentially guiding therapeutic decisions and enhancing outcomes in advanced NSCLC. Future research should focus on validating these findings in prospective studies and exploring the integration of SIPS into clinical practice, alongside other prognostic markers, to optimize treatment strategies. [ABSTRACT FROM AUTHOR]

The prevalence of adolescent myopia is remarkably increasing. Previous studies have indicated that an unhealthy diet is a risk factor for myopia. However, the link between diet-related inflammation and myopia is unclear. To explore their correlation, we used dietary inflammation index (DII) that is a parameter to quantify the inflammatory potential of diet, to reveal the relationship between DII and myopia in adolescents. We extracted sociodemographic data, information of diets and eye refractive status of adolescents from National Health and Nutrition Examination Survey (NHANES) for period 1999–2008. Dietary intake data was used to calculate DII scores, which were then categorized into quartiles. Multivariable regression models and subgroup analyses were conducted to investigate the association between DII and myopia. Subsequently, smoothed curve analyses were conducted to discern the trend of correlation between DII and myopia across diverse population. A total of 7191 juveniles aged at 12 to 18 years with complete information were included in our study, consisting 3367 participants with diagnosis of myopia. Among these participants, a trend towards an increasing prevalence of myopia was observed with a higher DII. After adjusting for all covariates, stratified logistic regression analyses showed that among the population aged in 16 to 18 years old or with 9-11th grade educational level, the prevalence of myopia was significantly increased with higher DII score (OR = 1.06, 95% CI = 1.01, 1.11, P = 0.006; OR = 1.06, 95% CI = 1.01, 1.11, P = 0.010). In the two subgroups, participants in the highest quartile of DII had a 31.00% higher risk of myopia and a higher 27.00% risk of myopia respectively, compared to those in the lowest quartile of DII. Our results revealed an increasing trend in the prevalence of myopia with increased DII score in adolescents. Particularly, DII was positively associated with the risk of myopia among the population aged in 16 to 18 years old and with 9-11th grade educational level. [ABSTRACT FROM AUTHOR]

Obstructive sleep apnea (OSA) syndrome is a prevalent form of respiratory sleep disorder, with an increasing prevalence among children. The consequences of OSA include obesity, diabetes, cardiovascular disease, and neuropsychological diseases. Despite its pervasive impact, a significant proportion of individuals especially children remain unaware that they suffer from OSA. Consequently, there is an urgent need for an accessible diagnostic approach. In this study, we conducted a bioinformatic analysis to identify potential biomarkers from a proteomics dataset comprising serum samples from children with OSA in the progression stage. In the Gene Set Enrichment Analysis (GSEA), we observed that the complement and immune response pathways persisted throughout the development of OSA and could be detected in the early stages. Subsequent to soft clustering and WGCNA analysis, it was revealed that the Hippo pathway, including ITGAL and FERMT3, plays a role in mild OSA. The analysis revealed a significant alteration of the complement and coagulation pathways, including TFPI and MLB2, in moderate OSA. In severe OSA, there was an association between hypoxia and the extracellular matrix (ECM) receptor interaction and collagen binding. In summary, it can be posited that the systemic inflammation may persist throughout the progression of OSA. Furthermore, severe OSA is characterized by abnormal vascular endothelial function, which may be attributed to chronic hypoxia. Finally, four potential biomarkers (ITGAL, TFPI, TTR, ANTXR1) were identified based on LASSO regression, and a prediction model for OSA progression was constructed based on the biomarkers. [ABSTRACT FROM AUTHOR]

Objective The aim of this study was to investigate the gut microbial signatures and related pathophysiological implications in patients with Cushing's disease (CD). Design and methods Twenty-seven patients with CD and 45 healthy controls were enrolled. Based on obtained metagenomics data, we performed correlation, network study, and genome interaction group (GIG) analysis. Fecal metabolomics and serum enzyme linked immunosorbent assay (ELISA) analysis were conducted in dichotomized CD patients. Caco-2 cells were incubated with gradient concentrations of cortisol for subsequent transepithelial electrical resistance (TEER) measurement, FITC-dextran transwell permeability assay, qPCR, and western blot analysis. Results Gut microbial composition in patients with CD was notably different from that in healthy controls. Network analysis revealed that Eubacterium siraeum might serve as the core specie in the gut microbial system of CD patients. Subsequent GIG analysis identified the positive correlations between GIG9 and UFC. Further serum ELISA and fecal metabolomics uncovered that CD patients with elevated UFC levels were characterized with increased lipopolysaccharide binding protein (LBP). Moreover, remarkable positive association was found between LBP level and relative abundance of E. siraeum. TEER and FITC-dextran transwell assays demonstrated that hypercortisolism induced increased gut permeability. Further qPCR and western blot analysis suggested that dysregulated AhR/Claudin 2 axis might be involved in the development of hypercortisolism-induced defective gut barrier function Conclusions Disease activity associated dysbiosis and defective gut barrier might jointly facilitate the development of systemic inflammation in patients with CD. [ABSTRACT FROM AUTHOR]

Background: Psoriasis is a chronic inflammatory disease often associated with serious cardiovascular comorbidities. The aim of this study was to investigate the systemic inflammatory burden in psoriasis by examining various inflammatory markers and to assess the relationship between these markers and the severity of the disease. Methods: This retrospective study was conducted on medical records of patients who visited the dermatology outpatient clinic between 1 January 2016 and 31 December 2022. The study included patients with psoriasis vulgaris and healthy volunteers. Demographic data, Psoriasis Area and Severity Index score, C‐reactive protein, monocyte‐high‐density lipoprotein cholesterol ratio, neutrophil‐to‐lymphocyte ratio, platelet‐to‐lymphocyte ratio, monocyte‐to‐lymphocyte ratio, systemic immune‐inflammation index, and Systemic Inflammation Response Index were analysed and compared. Results: A total of 278 psoriasis patients and 90 healthy volunteers were analysed. Compared to the control group, psoriasis patients showed significantly higher systemic immune‐inflammation index, Systemic Inflammation Response Index, neutrophil‐to‐lymphocyte ratio, monocyte‐high‐density lipoprotein cholesterol ratio, serum C‐reactive protein levels, neutrophil count, monocyte count, body mass index, and waist circumference (p < 0.001, p = 0.001, p < 0.001, p = 0.014, p < 0.001, p < 0.001, p = 0.046, p < 0.001, and p = 0.011, respectively). Among patients with severe psoriasis (Psoriasis Area and Severity Index >10), systemic immune‐inflammation index, neutrophil‐to‐lymphocyte ratio, platelet‐to‐lymphocyte ratio, and serum C‐reactive protein levels were significantly higher compared to patients with mild/moderate psoriasis (Psoriasis Area and Severity Index ≤10). In the ROC curve analysis, the optimal cut‐off (AUC, sensitivity, specificity) values for neutrophil‐to‐lymphocyte ratio, systemic immune‐inflammation index, and platelet‐to‐lymphocyte ratio were found to be 2.11 (0.592, 62%, 57%), 552.9 (0.579, 61%, 58%), and 111.9 (0.578, 64%, 46%), respectively. The inflammatory parameters that showed correlation with Psoriasis Area and Severity Index were systemic immune‐inflammation index, Systemic Inflammation Response Index, neutrophil‐to‐lymphocyte ratio, monocyte‐high‐density lipoprotein cholesterol ratio, monocyte‐to‐lymphocyte ratio, and C‐reactive protein. Conclusion: The findings of this study suggest that systemic immune‐inflammation index, Systemic Inflammation Response Index, neutrophil‐to‐lymphocyte ratio, monocyte‐high‐density lipoprotein cholesterol ratio, and C‐reactive protein values have the potential to serve as simple and cost‐effective markers for assessing the inflammatory burden in individuals with psoriasis. [ABSTRACT FROM AUTHOR]

Background and Objectives: Chronic kidney disease (CKD) is a growing public health problem and one of the leading causes of premature death worldwide. The progressive nature of CKD is associated with serious complications that can reduce the quality of life in CKD patients. Additional factors that can worsen well-being include dialysis treatment, malnutrition, inflammation, and lack of social support. The aim of our study was to analyze the quality of life of CKD patients undergoing hemodialysis and its association with certain biochemical and immunonutritional parameters, as well as with social support. Materials and Methods: This research was conducted as a cross-sectional study that included 170 patients, divided into two groups: a group of patients undergoing hemodialysis (HD group) (n = 85), and a control group of non-hemodialysis patients (group with CKD stage 3–4) (n = 85). The Health-Related Quality of Life (HRQoL) score was used to assess the quality of life of the study population. Measurement of biochemical and immunonutritional parameters was also performed in all patients. The Oslo-3 Social Support Scale (OSSS-3) was used to analyze social support. Results: The HRQoL score was significantly lower in HD patients compared to patients with CKD stage 3–4 (0.701 ± 0.137 vs. 0.832 ± 0.122, p < 0.001). It declined significantly as the concentrations of urea (β = −0.347, p < 0.001), creatinine (β = −0.699, p = 0.005), uric acid (β = −0.184, p = 0.016), β2-microglobulin (β = −0.432, p < 0.001), and parathormone (β = −0.209, p = 0.006) increased in HD patients. In addition to uremic toxins, an increase in glucose (β = −0.278, p = 0.010) and triglyceride (β = −0.354, p = 0.001) concentrations was associated with poor HRQoL in patients with CKD stage 3–4. There was a significant connection between the Hemoglobin, Albumin, Lymphocyte, and Platelet (HALP) score and HRQoL in HD patients (β = 0.229, p = 0.035). Additionally, C-reactive protein (β = −0.361, p < 0.001) and neutrophil-to-lymphocyte ratio (β = −0.288, p < 0.001), as markers of systemic inflammation, directly affected HRQoL in HD patients. In both study groups, perceived social support positively influenced the HRQoL scores (β = 0.192, p = 0.012 for hemodialysis; β = 0.225, p = 0.038 for non-hemodialysis). Conclusions: There is a decline in HRQoL in chronic hemodialysis patients, significantly affected by certain biochemical and immunonutritional parameters, along with perceived social support. [ABSTRACT FROM AUTHOR]

Purpose: Postoperative cognitive dysfunction (POCD) is a common postoperative complication. Studies have reported that lymphocyte-to-monocyte ratio (LMR) was a predictor of many diseases associated with inflammation. However, further examination of the relationship between preoperative LMR and POCD is needed. We aimed to investigate the association between POCD and preoperative LMR levels to examine the potential of LMR to predict POCD. Patients and Methods: This was a prospective cohort study that included patients who underwent elective major abdominal surgery at our hospital between January 2019 and January 2022. Multivariate logistic regression analysis was used to analyze the effects of preoperative LMR on POCD development. The optimal threshold of preoperative LMR for predicting POCD was determined by receiver operating characteristic (ROC) approach. A subgroup analysis was performed according to age, sex, type of surgery and hypertension. Results: Of 964 patients, 362 (37.6%) developed POCD. The preoperative LMR level in the Non-POCD group was higher than that in the POCD group. According to the ROC curve, a cutoff value of 3.758 of the preoperative LMR level could be used to predict POCD occurrence and the area under the curve (AUC) was 0.747 (95% CI: 0.715– 0.779, P < 0.001). The results of the subgroup analyses were consistent with the primary ones, and no heterogeneity was observed in the subgroup analyses (P for interaction > 0.05). Conclusion: LMR was significantly associated with the occurrence of POCD after major abdominal surgery. Preoperative low LMR levels can be used to identify patients who may be at high risk of POCD. [ABSTRACT FROM AUTHOR]

Background/Objectives: Cow's milk is a bioactive cocktail with essential nutritional factors that is widely consumed during early childhood development. However, it has been associated with allergic responses and immune cell activation. Here, we investigate whether cow's milk consumption regulates gut–brain axis functions and affects patterns of behaviors in BALB/c mice, previously described by present low sociability, significant stereotypes, and restricted interest features. The major objectives consist of to investigate cow's milk supplementation as possible triggers interfering with cellular niches of the gut–brain axis and behavioral patterns. Methods: Male BALB/c at 6 weeks were randomly divided into two groups, one supplemented with cow's milk processed at ultra-high temperature (UHT) and another group receiving water (controls) three times per day (200 μL per dose) for one week. Results: Milk consumption disturbed histological compartments of the small intestine, including niches of KI67+-proliferating cells and CD138+ Ig-secreting plasma cells. In the liver, milk intake was associated with pro-inflammatory responses, oxidative stress, and atypical glycogen distribution. Milk-supplemented mice showed significant increase in granulocytes (CD11b+SSChigh cells) and CD4+ T cells in the blood. These mice also had neuroinflammatory signals, including an enhanced number of cortical Iba-1+ microglial cells in the brain and significant cerebellar expression of nitric oxide synthase 2 by Purkinje cells. These phenotypes and tissue disorders in milk-supplemented mice were associated with atypical behaviors, including low sociability, high restricted interest, and severe stereotypies. Moreover, synaptic niches were also disturbed after milk consumption, and Shank-3+ and Drebrin+ post-synaptic cells were significantly reduced in the brain of these mice. Conclusions: Together, these data suggest that milk consumption interfered with the gut–brain axis in BALB/c mice and increased atypical behaviors, at least in part, linked to synapse dysfunctions, neuroinflammation, and oxidative stress regulation. [ABSTRACT FROM AUTHOR]

Chronic systemic inflammation caused by diseases such as ulcerative colitis (UC) and Crohn's disease (CD) increases the risk of developing colorectal cancer (CRC). Recent evidence indicates that patients with UC are more susceptible to prostate cancer (PCa), and individuals with PCa may also be at a higher risk of developing CRC. However, these relationships are not well defined. A better understanding of this phenomenon could improve the identification of high-risk populations. In this study, we characterized these relationships with experiments using preclinical mouse models of dextran sulfate sodium (DSS)-induced colitis (DSS-UC) and DSS/azoxymethane (AOM)-induced CRC (DSS/AOM-CRC) in wild-type and conditional transgenic mice of PCa. We showed that DSS-induced UC was more severe in mice with PCa and resulted in the development of CRC in the absence of AOM. We further showed that PCa-free mice that developed DSS-induced UC also showed histological changes in the normal prostate that resembled proliferative inflammatory atrophy. Finally, we used immunohistochemical immune profiling to show that mice with PCa-induced chronic systemic inflammation accumulated Gr1+ myeloid cells in the normal colon and exposure to DSS further enriched these cells in active colitis regions and colon tumors. Our study provides evidence to support a link between systemic chronic inflammation and cancer. [ABSTRACT FROM AUTHOR]

Central and systemic inflammation play pivotal roles in epileptogenesis and proepileptogenesis in temporal lobe epilepsy (TLE). The interplay between peripheral CD4+ T cells and central microglia orchestrates the "systemic‐central" immune response in TLE. However, the precise molecular mechanisms linking central and systemic inflammation in TLE remain unknown. This preliminary findings revealed an imbalance in Th1/Th2 subsets in the periphery，accompanied by related cytokines release in TLE patients. they proposed that this peripheral Th1/Th2 imbalance may influence central inflammation by mediating microglial state dynamics within epileptic foci and distant brain regions. In Li‐pilocarpine‐induced TLE rats, a peripheral Th1/Th2 imbalance and observed corresponding central and systemic responses is confirmed. Notably, CD4+ T cells infiltrated through the compromised blood‐brain barrierand are spatially close to microglia around epileptic foci. Intravenous depletion and reinfusion of CD4+ T cells modulated microglia state dynamics and altered neuroinflammatory cytokines secretion. Moreover, mRNA sequencing of the human hippocampus identified Notch1 as a key regulator of Th1/Th2 differentiation, CD4+ T cell recruitment to brain infiltration sites, and the regulation of microglial responses, seizure frequency, and cognition. This study underscores the significance of Th1/Th2 imbalance in modulating the "systemic‐central" response in TLE, highlighting Notch1 as a potential therapeutic target. [ABSTRACT FROM AUTHOR]

Background: Despite effective antiretroviral therapy, people with HIV (PWH) experience persistent systemic inflammation and increased morbidity and mortality. Modulating the gut microbiome through fecal microbiota transplantation (FMT) represents a novel therapeutic strategy. We aimed to evaluate proteomic changes in inflammatory pathways following repeated, low-dose FMT versus placebo. Methods: This double-masked, placebo-controlled pilot study assessed the proteomic impacts of weekly FMT versus placebo treatment over 8 weeks on systemic inflammation in 29 PWH receiving stable antiretroviral therapy (ART). Three stool donors with high Faecalibacterium and butyrate profiles were selected, and their individual stools were used for FMT capsule preparation. Proteomic changes in 345 inflammatory proteins in plasma were quantified using the proximity extension assay, with samples collected at baseline and at weeks 1, 8, and 24. Concurrently, we characterized shifts in the gut microbiota composition and annotated functions through shotgun metagenomics. We fitted generalized additive models to evaluate the dynamics of protein expression. We selected the most relevant proteins to explore their correlations with microbiome composition and functionality over time using linear mixed models. Results: FMT significantly reduced the plasma levels of 45 inflammatory proteins, including established mortality predictors such as IL6 and TNF-α. We found notable reductions persisting up to 16 weeks after the final FMT procedure, including in the expression of proteins such as CCL20 and CD22. We identified changes in 46 proteins, including decreases in FT3LG, IL6, IL10RB, IL12B, and IL17A, which correlated with multiple bacterial species. We found that specific bacterial species within the Ruminococcaceae, Succinivibrionaceae, Prevotellaceae families, and the Clostridium genus, in addition to their associated genes and functions, were significantly correlated with changes in inflammatory markers. Conclusions: Targeting the gut microbiome through FMT effectively decreased inflammatory proteins in PWH, with sustained effects. These findings suggest the potential of the microbiome as a therapeutic target to mitigate inflammation-related complications in this population, encouraging further research and development of microbiome-based interventions. 3bGeWVUV_8zBqrmtjgQWmW Video Abstract [ABSTRACT FROM AUTHOR]

Neurofilament light chain (NFL), a biomarker of neuroaxonal damage, has been linked to inflammation and depressive disorders, albeit with inconsistent results. We aimed to evaluate the association between serum NFL concentration and clinically relevant depressive symptoms in the general population and to examine the potential involvement of systemic inflammation in this association. The data of 1881 adults aged 20–75 years were extracted from the National Health and Nutrition Examination Survey (NHANES) 2013–2014 cycle. Serum NFL levels were quantified using a highly sensitive immunoassay. Further, markers of systemic inflammation, including systemic immune inflammation index (SII), system inflammation response index (SIRI), and white blood cell (WBC) counts were calculated based on whole blood cell counts. Clinically relevant depressive symptoms were evaluated using the 9-item Patient Health Questionnaire (PHQ-9) with a cut-off score of 10. After adjusting for potential confounders, we found that each one-unit increase in ln-transformed serum NFL concentration was significantly associated with a 1.37-fold increase in the risk of clinically relevant depressive symptoms (95 % confidence interval [CI]: 1.06, 1.77; p = 0.017). Serum NFL level was significantly related to increased SII (regression coefficient [β] = 0.04, 95%CI: 0.01, 0.08; p = 0.027), SIRI (β = 0.09, 95%CI: 0.05, 0.14; p < 0.001), and WBC (β = 0.05, 95%CI: 0.03, 0.07; p < 0.001), respectively. These significant associations were observed only in elderly participants. The cross-sectional study design is limited in causal inference. Our findings indicate that serum NFL levels are related to an increased risk of clinically relevant depressive symptoms and higher levels of markers of systemic inflammation. • Serum NFL concentration was associated with an increased risk of depressive symptoms • Serum NFL concentration was positively related to markers of systemic inflammation • Risk of depressive symptoms associated with serum NFL concentration was only observed in elderly people [ABSTRACT FROM AUTHOR]

Obstructive sleep apnea (OSA) syndrome is a prevalent form of respiratory sleep disorder, with an increasing prevalence among children. The consequences of OSA include obesity, diabetes, cardiovascular disease, and neuropsychological diseases. Despite its pervasive impact, a significant proportion of individuals especially children remain unaware that they suffer from OSA. Consequently, there is an urgent need for an accessible diagnostic approach. In this study, we conducted a bioinformatic analysis to identify potential biomarkers from a proteomics dataset comprising serum samples from children with OSA in the progression stage. In the Gene Set Enrichment Analysis (GSEA), we observed that the complement and immune response pathways persisted throughout the development of OSA and could be detected in the early stages. Subsequent to soft clustering and WGCNA analysis, it was revealed that the Hippo pathway, including ITGAL and FERMT3, plays a role in mild OSA. The analysis revealed a significant alteration of the complement and coagulation pathways, including TFPI and MLB2, in moderate OSA. In severe OSA, there was an association between hypoxia and the extracellular matrix (ECM) receptor interaction and collagen binding. In summary, it can be posited that the systemic inflammation may persist throughout the progression of OSA. Furthermore, severe OSA is characterized by abnormal vascular endothelial function, which may be attributed to chronic hypoxia. Finally, four potential biomarkers (ITGAL, TFPI, TTR, ANTXR1) were identified based on LASSO regression, and a prediction model for OSA progression was constructed based on the biomarkers. [ABSTRACT FROM AUTHOR]

Background: Beyond being a pulmonary disease, chronic obstructive pulmonary disease (COPD) presents with extrapulmonary manifestations including reduced cognitive, cardiovascular, and muscle function. While exercise training is the cornerstone in the non-pharmacological treatment of COPD, there is a need for new exercise training methods due to suboptimal adaptations when following traditional exercise guidelines, often applying moderate-intensity continuous training (MICT). In people with COPD, short-duration high-intensity interval training (HIIT) holds the potential to induce a more optimal stimulus for training adaptations while circumventing the ventilatory burden often associated with MICT in people with COPD. We aim to determine the effects of supramaximal HIIT and MICT on extrapulmonary manifestations in people with COPD compared to matched healthy controls. Methods: COPD-HIIT is a prospective, multi-centre, randomized, controlled trial with blinded assessors and data analysts, employing a parallel-group designed trial. In phase 1, we will investigate the effects and mechanisms of a 12-week intervention of supramaximal HIIT compared to MICT in people with COPD (n = 92) and matched healthy controls (n = 70). Participants will perform watt-based cycling two to three times weekly. In phase 2, we will determine how exercise training and inflammation impact the trajectories of neurodegeneration, in people with COPD, over 24 months. In addition to the 92 participants with COPD performing HIIT or MICT, a usual care group (n = 46) is included in phase 2. In both phases, the primary outcomes are a change from baseline in cognitive function, cardiorespiratory fitness, and muscle power. Key secondary outcomes include change from baseline exercise tolerance, brain structure, and function measured by MRI, neuroinflammation measured by PET/CT, systemic inflammation, and intramuscular adaptations. Feasibility of the interventions will be comprehensively investigated. Discussion: The COPD-HIIT trial will determine the effects of supramaximal HIIT compared to MICT in people with COPD and healthy controls. We will provide evidence for a novel exercise modality that might overcome the barriers associated with MICT in people with COPD. We will also shed light on the impact of exercise at different intensities to reduce neurodegeneration. The goal of the COPD-HIIT trial is to improve the treatment of extrapulmonary manifestations of the disease. Trial registration: Clinicaltrials.gov: NCT06068322. Prospectively registered on 2023-09-28. [ABSTRACT FROM AUTHOR]

Introduction: Inflammation and its associated factors play a pivotal role in the development and progression of cancer. Inflammation markers, such as neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, and the systemic immune-inflammation index can be readily calculated to gauge the level of inflammation. This study aimed to investigate the correlation between these inflammation markers and their role in the progression stages of endometrial cancer. Methods: A retrospective analysis was conducted on data collected from 154 patients. The patients were categorized into three groups: normal endometrium, hyperplasia with atypia, and endometrioid-type endometrial cancer. The differences in inflammation marker values among these groups were examined and identified. Results: The systemic immune-inflammation index (SII) findings revealed a nonsignificant trend in differentiation between the study groups; however, a significant inverse relationship was observed in the lymphocyte-to-monocyte ratio (LMR) values across the groups (P = 0.037). Post hoc analysis further demonstrated a significant difference in SII values between the group with normal endometrium and group with endometrial cancer (P = 0.042). Conclusion: These findings suggest that the SII and LMR show potential as biomarkers for distinguishing between endometrial pathologies in age-controlled patient cohorts. [ABSTRACT FROM AUTHOR]

The association of Healthy Eating Index 2020 (HEI‐2020), especially its components with systemic inflammatory biomarkers, has not been examined. The aim of this study was to investigate the relationship between HEI‐2020 and its components with systemic inflammatory biomarkers, and to provide a dietary pattern suggestion to combat systemic inflammation. Participants aged 20 years and older with complete information on two reliable dietary recalls, blood cell counts and demographic characteristics, were recruited from six NHANES cycles from 2007 to 2018. Weighted general linear methods showed that HEI‐2020 was negatively associated with systemic immune‐inflammation index (SII) and systemic inflammation response index (SIRI). Weighted quantile regression (WQS) models and quantile g‐computation (QGC) models supported the negative association between the mixed components and systemic inflammation. High intakes of whole fruits, whole grains, greens and beans, and seafood and plant proteins, along with a low intake of added sugars, were associated with reduced systemic inflammation. In contrast, the scores of sodium, dairy, total protein, and refined grains showed no significant effect. Briefly, our study provides an anti‐inflammatory dietary pattern suggestion based on the 13 components of HEI‐2020 and Dietary Guidelines for Americans. [ABSTRACT FROM AUTHOR]

SDIMMMER is an acronym intended for use in both clinical practice and medical research. It facilitates a comprehensive evaluation of a patient's metabolic profile and serves as a mnemonic for the following key assessment areas: Sleep, Diet, Microbiome, Metabolism, Medications, Exams, and Rehabilitation. In the clinical setting, SDIMMMER's primary objective is to monitor and manage the patient's metabolic status, particularly targeting low-grade chronic systemic inflammation, a hallmark of metabolic syndrome (MS). This inflammatory condition is characterized by elevated levels of circulating inflammatory cytokines and increased macrophage infiltration in peripheral tissues. SDIMMMER aims to enhance the effectiveness of ortho biological treatments by elevating growth factor levels, thereby enhancing patient outcomes. Additionally, SDIMMMER emphasizes guiding patients toward positive lifestyle changes to improve overall quality of life and foster a healthier metabolism. SDIMMMER introduces a patient metabolic profile quantification tool comprising 7 domains, totaling 35 items. Additionally, an instructional guide is provided to facilitate the application process. Its versatility spans various clinical and research domains, showcasing its potential to positively influence multiple fields. [ABSTRACT FROM AUTHOR]

Background: The pathophysiology of heart failure (HF) with preserved ejection fraction (HFpEF) is suggested to be influenced by inflammation. Leukocyte indices, including the neutrophil–lymphocyte ratio (NLR), the monocyte–lymphocyte ratio (MLR), and the pan-immune inflammation value (PIV), can be utilized as biomarkers of systemic inflammation. Their prognostic utility is yet to be fully understood. Methods: Between December 2010 and May 2023, patients presenting to a tertiary referral center for HFpEF were included into a prospective registry. The association of the NLR, MLR, and PIV with the composite endpoint of all-cause mortality and HF-related hospitalization was tested utilizing Cox regression analysis. Results: In total, 479 patients (median 74.3, interquartile range (IQR): 69.22–78.3 years, 27.8% male) were included. Patients were observed for 43 (IQR: 11–70) months, during which a total of 267 (55.7%) patients met the primary endpoint. In a univariate Cox regression analysis, an above-the-median NLR implied a hazard ratio (HR) of 1.76 (95%-confidence interval (CI): 1.38–2.24, p < 0.001), an MLR of 1.46 (95%-CI: 1.14–1.86, p = 0.003), and a PIV of 1.67, 95%-CI: 1.30–2.13, p < 0.001) for the composite endpoint. After adjustment in a step-wise model, the NLR (HR: 1.81, 95%-CI: 1.22–2.69, p = 0.003), the MLR (HR: 1.57, 95%-CI: 1.06–2.34, p = 0.026), and the PIV (HR: 1.64, 95%-CI: 1.10–2.46, p = 0.015) remained significantly associated with the combined endpoint. Conclusions: The NLR, the MLR, and the PIV are simple biomarkers independently associated with outcomes in patients with HFpEF. [ABSTRACT FROM AUTHOR]

Objectives To elucidate the longitudinal reciprocal association between RA and chronic obstructive pulmonary disease (COPD) and the mediating role of systemic inflammation in the association. Methods A total of 403 045 participants from UK Biobank were enrolled in this study. A cross-lagged panel model was used to investigate the longitudinal reciprocal association between RA and COPD. Cox proportional hazards regression and logistic regression models were also conducted to examine the association between baseline RA and COPD during follow-up, and vice versa. Causal mediation analysis was then performed to explore the mediating roles of 160 systemic inflammatory biomarkers in the bidirectional association. Results At baseline, 4755 (1.2%) and 6989 (1.7%) individuals were diagnosed with RA and COPD, respectively. After adjusting for the covariates, the result of a cross-lagged panel model revealed a bidirectional association between RA and COPD (β = 0.018, P  < 0.001 for the RA→COPD path; β = 0.010, P  < 0.001 for the COPD→RA path). In the non-COPD population, the risk of future COPD was increased in RA patients [Cox model: hazard ratio (HR) 1.65 (95% CI 1.50, 1.83); logistic model: odds ratio (OR) 1.85 (95% CI 1.66, 2.07)]. In the non-RA population, baseline COPD was associated with a higher risk of RA during follow-up [Cox model: HR 1.67 (95% CI 1.44, 1.92); logistic model: OR 1.70 (95% CI 1.47, 1.97)]. Five inflammatory factors mediated the RA→COPD path and CRP mediated the COPD→RA path (false discovery rate < 0.05). Conclusions A significant bidirectional association exists between RA and COPD and it is partially mediated by systemic inflammation. [ABSTRACT FROM AUTHOR]

• RA patients face an increased risk of CV diseases due to systemic inflammation and disease activity. • Other than traditional CV risk factors in RA patients, systemic inflammation and autoantibodies contribute to the heightened CV risk. • RA patients have low TC, LDL, and HDL but still experience high rates of CV events, known as the "lipid paradox," due to increased cholesterol breakdown and altered HDL function from inflammation. • In RA patients, inflammatory markers like CRP and cytokines promote atherosclerosis. • Early and aggressive intervention with DMARDs is crucial in achieving clinical remission, and potentially lowering the risk of CV events in RA patients. Rheumatoid arthritis (RA) is a chronic inflammatory disease mainly affecting the peripheral diarthrodial joints symmetrically and also presenting many extra-articular manifestations. Morbidity and mortality in RA patients are higher compared to the general population. Cardiovascular (CV) disease is one of the most common causes of death in these patients. Classical or traditional risk factors for atherosclerosis development occur more frequently in RA patients compared to those without this condition. Studies have showed that RA patients often present comorbidities such as hypertension, dyslipidemia, diabetes mellitus and obesity. However, the high incidence of CV events occurring in RA patients is not explained by the presence of traditional risk factors. Systemic inflammation, as it is expressed with the presence of proinflammatory cytokines and increased acute phase reactants, may contribute to the development of premature atherosclerosis in these patients. In this review, we explore the risk factors for CV disease, the generation of dyslipidemia, the lipid paradox and the role of systemic inflammation in the atherosclerotic process in RA. We discuss also the role of early therapeutic intervention that suppresses inflammation which may have beneficial effects on CV disease in RA patients. [ABSTRACT FROM AUTHOR]

Introduction/objectives: Changes in the stool metabolome have been poorly studied in the metabolic syndrome (MetS). Moreover, few studies have explored the relationship of stool metabolites with circulating metabolites. Here, we investigated the associations between stool and blood metabolites, the MetS and systemic inflammation. Methods: We analyzed data from 1,370 participants of the KORA FF4 study (Germany). Metabolites were measured by Metabolon, Inc. (untargeted) in stool, and using the AbsoluteIDQ® p180 kit (targeted) in blood. Multiple linear regression models, adjusted for dietary pattern, age, sex, physical activity, smoking status and alcohol intake, were used to estimate the associations of metabolites with the MetS, its components and high-sensitivity C-reactive protein (hsCRP) levels. Partial correlation and Multi-Omics Factor Analysis (MOFA) were used to investigate the relationship between stool and blood metabolites. Results: The MetS was significantly associated with 170 stool and 82 blood metabolites. The MetS components with the highest number of associations were triglyceride levels (stool) and HDL levels (blood). Additionally, 107 and 27 MetS-associated metabolites (in stool and blood, respectively) showed significant associations with hsCRP levels. We found low partial correlation coefficients between stool and blood metabolites. MOFA did not detect shared variation across the two datasets. Conclusions: The MetS, particularly dyslipidemia, is associated with multiple stool and blood metabolites that are also associated with systemic inflammation. Further studies are necessary to validate our findings and to characterize metabolic alterations in the MetS. Although our analyses point to weak correlations between stool and blood metabolites, additional studies using integrative approaches are warranted. [ABSTRACT FROM AUTHOR]

Scabies is a prevalent ectoparasitic infectious disease, caused by the mite Sarcoptes scabiei. As a consequence of the infestation, localised cutaneous inflammation, pruritus and polymorphic skin lesions develop. The primary symptoms of scabies manifest as hypersensitivity-like reactions and immune responses, the precise mechanisms of which remain poorly defined. The objective of this study was to evaluate the effects of oral ivermectin treatment in patients with scabies on the systemic immune response and the patient’s quality of life (QoL). Patients admitted to the dermatology outpatient clinic and diagnosed with scabies were administered oral ivermectin treatment following diagnosis at week 0 and 2. Laboratory tests were conducted to measure complete blood count (CBC), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) levels before treatment and at week 4. The systemic immune-inflammation index (SII) was calculated using the platelet, neutrophil and lymphocyte counts. Additionally, data pertaining to the Dermatological Life Quality Index (DLQI) were recorded. In 119 patients (51 males) diagnosed with scabies, increases in ESR, CRP, and SII values and decreases in inflammatory cell counts and DLQI scores were observed one month after treatment with oral ivermectin. The results of the study showed that the use of oral ivermectin, a scabicidal agent, triggered the inflammatory response and improved the QoL of the patients. [ABSTRACT FROM AUTHOR]

Background: The predictors associated with clinical outcomes in patients with tuberculous meningitis (TBM) remain unclear. We aimed to analyse the relationship between systemic inflammation and clinical outcomes, as well as to explore whether systemic inflammation level influences the effectiveness of dexamethasone on treatment. Methods: Between January 2011 and December 2021, TBM patients admitted to five hospitals were observed consecutively. Baseline and post-treatment systemic inflammation levels were calculated using the neutrophil-lymphocyte-ratio (NLR). Generalized linear mixed models were employed to identify predictors of clinical outcomes. Propensity score matching and subgroup analyses were conducted to evaluate the effect of dexamethasone on treatment outcomes across different NLR levels. Results: A total of 1203 TBM patients were included in the study. During the follow-up, 144 (13.6%) participants experienced early neurological deterioration within 7 days after admission, and 345 (28.67%) exhibited poor functional outcome at the 12-month follow-up. Multivariate analysis revealed that post-treatment NLR was significantly associated with early neurological deterioration (OR=1.25; 95% CI, 1.14– 1.33; P< 0.001), and poor outcome (OR=1.34; 95% CI, 1.26– 1.45; P< 0.001). After propensity score matching, dexamethasone treatment was not associated with early neurological deterioration (OR=0.83; 95% CI, 0.42– 1.66; P=0.610) or poor outcome (OR=1.22; 95% CI, 0.49– 2.11; P=0.490) in the highest quartile of post-treatment NLR. The effect of dexamethasone on treatment outcomes did not significantly vary with disease severity stratification. Conclusion: Elevated systemic inflammation is an independent risk factor for neurological outcome in TBM patients. Further studies are required to investigate systemic inflammation in more severely affected population to better predict the outcomes following anti-inflammatory therapies. [ABSTRACT FROM AUTHOR]

Introduction: Alcohol use disorder (AUD) is present in the majority of patients with alcohol-associated liver disease (ALD), which leads to about 50% of cirrhosis-related hospitalizations and over 25% of deaths worldwide. Patients with ALD often present at an advanced stage, like cirrhosis with its complications and alcohol-associated hepatitis (AH), which has high short-term mortality. Current treatments are limited, with the limited benefit of glucocorticoids only in the short-term among patients with AH, highlighting an urgent need for novel therapies. Areas covered: This review applies the PIRO (Predisposition, Injury, Response, Organ dysfunction) concept to ALD, understanding an ongoing process of liver damage, and opportunities to address and halt the progression. We also highlight the significance of treating AUD to improve long-term outcomes in ALD. Expert opinion: Personalized therapies targeting specific genetic profiles and multiple pathogenic pathways are crucial in managing ALD. Emerging therapies like gut-liver-brain axis modulators like fecal microbiota transplant and probiotics, interleukin-22, granulocyte-colony stimulating factor (G-CSF) and stem cells, epigenetic regulators of inflammation and regeneration are encouraging with the potential of efficacy in patients with ALD. Liver transplantation (LT) is a definitive therapy for advanced cirrhosis with increasing impetus on early LT select patients with active alcohol use. [ABSTRACT FROM AUTHOR]

The presence of Fusobacterium nucleatum is associated with an immunosuppressive tumor immune microenvironment (TIM) in primary colorectal cancer (CRC), contributing to tumor progression. Its persistence in CRC liver metastasis tissues raises questions about its role in modulating local and systemic immune responses and influencing recurrence patterns. This retrospective cohort study of 218 patients with CRC liver metastasis investigated the association of F. nucleatum in CRC liver metastasis tissues with systemic inflammation, TIM alterations, and the number of metastatic organs involved in recurrence. Two‐step polymerase chain reaction (PCR), including digital PCR, detected F. nucleatum in 42% (92/218) of fresh‐frozen specimens of CRC liver metastases. Compared with the F. nucleatum‐none group, the F. nucleatum‐high group showed higher C‐reactive protein levels (0.82 vs. 0.22 mg/dL; Ptrend = 0.02), lower numbers of CD8+ cells (33.2 vs. 65.3 cells/mm2; Ptrend = 0.04) and FOXP3+ cells (11.3 vs. 21.7 cells/mm2; Ptrend = 0.01) in the TIM, and a greater number of metastatic organs involved in recurrence (1.6 vs. 1.1; p < 0.001). The presence of F. nucleatum in CRC liver metastasis tissues was associated with increased systemic inflammation, TIM alterations, and a greater number of metastatic organs involved in recurrence. These findings suggest a potential contribution of F. nucleatum to the metastatic propensity of CRC cells and could inform future research to enhance understanding of the interaction between tumor, host, and microbes in the metastatic process. [ABSTRACT FROM AUTHOR]

In 2020, a revised definition of fatty liver disease associated with metabolic dysfunction (MAFLD) was proposed to replace non-alcoholic fatty liver (NAFLD). Liver steatosis and at least one of the three metabolic risk factors, including type 2 diabetes, obesity, or signs of metabolic dysregulation, are used to diagnose MAFLD. MAFLD, similarly to NAFLD, is characterized by a spectrum of disease ranging from simple steatosis to advanced metabolic steatohepatitis with or without fibrosis, and may progress to cirrhosis and liver cancer, including increased risk of other critical extrahepatic diseases. Even though the pathophysiology of MAFLD and potential therapeutic targets have been explored in great detail, there is yet no Food and Drug Administration approved treatment. Recently, gut microbiome-derived products (e.g., endotoxins and metabolites) involved in intestinal barrier disruption, systemic inflammation, and modification of intrahepatic immunity have been associated with MAFLD development and progression. Therefore, different strategies could be adopted to modify the gut microbiome to improve outcomes in early and progressive MAFLD. Here, we provide an overview of mechanisms that may link the gut microbiome and immune response during the onset of liver steatosis and progression to steatohepatitis and fibrosis in patients with MAFLD. Finally, gut microbiota-based approaches are discussed as potential personalized treatments against MAFLD. [ABSTRACT FROM AUTHOR]

Jiexin Chen,1,&ast; Ruiying Tang,1,&ast; Na Tian,2 Jihong Deng,1 Shuilian Ao,1 Fenfen Peng,3 Xiaojiang Zhan,4 Yueqiang Wen,5 Xiaoyang Wang,6 Xiaoran Feng,7 Ning Su,8 Xingming Tang,9 Xianfeng Wu,10 Qian Zhou,11 Qingdong Xu1 1Department of Nephrology, Jiangmen Central Hospital, Jiangmen, People’s Republic of China; 2Department of Nephrology, General Hospital of Ningxia Medical University, Yinchuan, People’s Republic of China; 3Department of Nephrology, Zhujiang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 4Department of Nephrology, The First Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China; 5Department of Nephrology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 6Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 7Department of Nephrology, Jiujiang No. 1 People’s Hospital, Jiujiang, People’s Republic of China; 8Department of Hematology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China; 9Department of Nephrology, Dongguan Songshan Lake Tungwah Hospital, Dongguan, People’s Republic of China; 10Department of Nephrology, Affiliated Sixth People’s Hospital, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 11Department of Medical Statistics, Clinical Trials Unit, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qingdong Xu, Department of Nephrology, Jiangmen Central Hospital, No. 23 Hai Bang Road, Jiangmen, 529000, People’s Republic of China, Tel +86 13427226923, Email xqd82@163.comPurpose: Systemic inflammation biomarkers, derived from routine blood tests, have been demonstrated to be associated with prognosis of patients undergoing peritoneal dialysis (PD). However, studies focusing on the comparisons of their role on predictive efficacy for prognosis of PD patient are limited and results are inconsistent. The purpose of this study was to evaluate the prognostic value of various systemic inflammation biomarkers and to identify the optimal one in PD patients.Patients and Methods: This longitudinal study involved 3,225 patients undergoing PD across China. The prognostic accuracy of systemic inflammatory biomarkers was evaluated using C-statistics. Independent prognostic biomarkers of outcomes were determined using multivariate Cox proportional hazards regression analysis.Results: During a 46-month follow-up, 829 (25.7%) patients died, with 458 (55.3%) deaths attributed to cardiovascular disease (CVD). The highest C-statistics were observed for the IBI, with 0.619 and 0.621 for all-cause and CVD mortality, respectively. The optimal threshold of the IBI for predicting prognosis in patients undergoing PD was 50.0. An elevated IBI was a significant independent predictor of all-cause mortality, with a 1-SD increase associated with higher risks of all-cause and CVD mortality. Participants in the upper two quartiles of IBI exhibited increased risks of all-cause mortality by 41.2% and 67.6%, respectively, compared to those in the lowest quartile. Similar results were observed for CVD mortality.Conclusion: The IBI is a superior prognostic indicator of survival and could be broadly applied for prognosis of patients undergoing PD. Elevated IBI is an independent risk factor for all-cause and CVD mortality.Keywords: biomarker, peritoneal dialysis, prognosis, systemic inflammation

Xu Sun,1– 3 Jun Zhu,2,3 Zhuyin Qian,4 Xiaowei Chen,5 Jie Zhang,6 Cheng Ji,7,&ast; Li Zhao1,&ast; 1China Pharmaceutical University, Nanjing, 211198, People’s Republic of China; 2Department of Pharmacy, Nanjing Luhe People’s Hospital, Nanjing, 211500, People’s Republic of China; 3Department of Pharmacy, Nanjing Luhe People’s Hospital, Yangzhou University, Nanjing, 211500, People’s Republic of China; 4Department of General Surgery, Nanjing Luhe People’s Hospital, Yangzhou University, Nanjing, 211500, People’s Republic of China; 5Department of Central Laboratory, Nanjing Luhe People’s Hospital, Yangzhou University, Nanjing, 211500, People’s Republic of China; 6Department of Endocrinology, Nanjing Luhe People’s Hospital, Yangzhou University, Nanjing, 211500, People’s Republic of China; 7Department of Pharmacy, Drum Tower Hospital Affiliated to Nanjing University Medical School, Nanjing, Jiangsu, 210000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Cheng Ji; Li Zhao, Email g6221230@163.com; 18806176799@163.comAim: To assess the potential association between the TyG index and the risk of abnormal UACR. Additionally, we aimed to determine the role and degree of influence of inflammatory biomarkers between the TyG index and abnormal UACR.Materials and Methods: A cross-sectional study recruited 1021 participants from a health management center between 2021 and 2022. Logistic or linear regression models, as well as mediation analysis, were employed to investigate the associations between the TyG index, inflammatory biomarkers (total and differential white blood cell counts, platelet, mean platelet volume(MPV), C-reactive protein(CRP)), and the risk of abnormal UACR.Results: The study included 1021 participants, of whom 55.0% were men. The median age (interquartile range [IQR]) was 61.0 (53, 70) years. In multivariable-adjusted logistic regression models, both with and without the inclusion of smoking, alcohol drinking, BMI, Lipid-lowering drugs using, TC, SUA, ALT, and AST as potential covariates, the TyG index was associated with the risk of UACR, both with the odds ratios (ORs) per 1-standard deviation (SD) increase were 1.32 (95% CI, 1.08– 1.62) and 1.27 (95% CI, 1.05– 1.52), respectively. This study also demonstrated a significant indirect effect of the TyG index on the risk of abnormal UACR through total white blood cell counts, neutrophil counts and platelet (P values < 0.05); The proportions mediated was 11.2%, 3.5% and 29.6% for each respective variable.Conclusion: Insulin resistance and inflammation are associated with an increased risk of kidney insufficiency. And indicators of inflammation weakly mediate insulin resistance and risk of kidney insufficiency.Keywords: TyG index, urinary albumin-to-creatinine ratio, UACR, white blood cell counts, systemic inflammation, neutrophil counts, platelet

ABSTRACT: The objective of this study was to assess the effects of prepartum administration of anti-inflammatory therapies on BCS, BHB concentration, haptoglobin (HP) concentration, milk yield, milk components, rumination time, clinical health events, and reproductive performance in Holstein dairy cows. At 14 d before the expected calving date, cows (parous [PAR]; n = 170) and heifers (nulliparous [NUL]; n = 63) were blocked by BCS group (optimal [OPT] = 3–3.5; over-conditioned cows [OVERC; BCS ≥3.75 points]) and parity (NUL; PAR) and randomly allocated to 1 of 3 treatment groups: (1) ASA (n = 78): receive one oral administration of acetylsalicylic acid (4 boluses; 480 grain/bolus); (2) MEL (n = 76): receive one oral administration with meloxicam (1 mg/kg BW), or (3) PLC (n = 77): receive one oral treatment with gelatin capsules filled with water. Body condition score was assessed, and blood samples were collected, weekly starting 1 wk before treatment until 3 wk after calving. Daily milk yields and daily rumination times were collected from on-farm computer records. Dairy Herd Improvement Association monthly test data were collected to assess milk yield, SCC, and milk components. Furthermore, health events, culling rate, and reproductive performance data were collected from on-farm computer records. The data were analyzed using MIXED, GLIMMIX, and LIFETEST procedures of SAS as a randomized complete block design. On average, MEL-NUL cows produced 4.77 ± 0.93 kg/d and 4.81 ± 0.92 kg/d more milk from wk 6 to 21 of lactation compared with ASA-NUL and PLC-NUL cows, respectively. Similarly, a week by treatment by body condition group interaction was present, where OVERC cows treated with MEL produced more milk from wk 10 to 15 of lactation compared with ASA-OVERC and PLC-VERC cows. Parous cows treated with ASA had lower BCS compared with PAR cows treated with MEL or PLC. A lower percentage of OVERC cows treated with ASA became sick in the first 60 DIM compared with MEL-OVERC and PLC-OVERC cows (ASA = 23.88% ± 7.26%, MEL = 46.36% ± 8.57%; PLC = 46.74% ± 8.53%). Parous cows treated with ASA had a higher hazard ratio to become pregnant by 300 DIM compared with PAR MEL cows. Although the study was not sized for finding treatment differences in blocking criteria groups, these results suggest that treatment with prepartum anti-inflammatory therapies may have positive effects on milk yield and postpartum health in specific groups of cows, such as NUL and OVERC cows, although it may not be recommended for other animal categories, such as parous cows and cows with optimal BCS. Larger studies are needed to strengthen the associations observed in this study.

Introduction. In psoriasis, plaque psoriasis is the most common kind. Patients may experience mild to severe symptoms, and while the sickness is not lethal, it is difficult to cure. Aim. The purpose of this study is to evaluate the efficacy of bee venom phonophoresis in treating mild to moderate plaque psoriasis of the knee. Materials and methods. Group A received bee venom phonophoresis in conjunction with conservative care, group B received bee venom topical application in conjunction with conservative care, and group C served as a control in a double-blind randomized controlled experiment including 96 patients with plaque psoriasis. Over the course of three months, every patient underwent a thorough evaluation that included blood tests to measure systemic inflammation (Neutrophil to lymphocyte ratio, C-reactive protein, and erythrocyte sedimentation rate), as well as PASI (Psoriasis Area and Severity Index) and Isokinetic knee proprioceptive. Results and disscusion. No statistically significant difference was found between the three groups at baseline measurement; however, a treatment effect was observed after 12 weeks of treatment (p = 0.001 and f-value = 50.718). In addition, both groups (A and B) showed a statistically significant interaction between pre- and post-treatment treatment and time; however, this interaction was much more pronounced and noticeable in group A. Conclusion. Phonophoresis with bee venom improves proprioception in the knee joint and decreases N/L ratio, CRP, ESR, and PASI. Registration: Clinicaltrials.gov identifier No. NCT06106230; registered 20.10.2023.

Abstract Although serum uric acid (SUA) is a risk factor for cardiometabolic outcome, but it remains unclear which patients with coronary artery disease (CAD) benefit the most from SUA lowering therapy (ULT). The association of SUA level, systemic inflammation and cardiometabolic risk is still unclear. The current study is aimed to examine whether SUA-associated cardiometabolic risk is modulated by systemic inflammation in CAD patients. A total of 16,598 CAD patients with baseline high-sensitivity C-Reactive Protein (hsCRP) and SUA available were included. Baseline and follow-up data were collected. The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE), including death, myocardial infarction and stroke. In patients with hsCRP ≥ 2 mg/L, increasing quintiles of SUA were significantly associated with increased rates of 2-year MACCE (adjusted p

Abstract The prevalence of adolescent myopia is remarkably increasing. Previous studies have indicated that an unhealthy diet is a risk factor for myopia. However, the link between diet-related inflammation and myopia is unclear. To explore their correlation, we used dietary inflammation index (DII) that is a parameter to quantify the inflammatory potential of diet, to reveal the relationship between DII and myopia in adolescents. We extracted sociodemographic data, information of diets and eye refractive status of adolescents from National Health and Nutrition Examination Survey (NHANES) for period 1999–2008. Dietary intake data was used to calculate DII scores, which were then categorized into quartiles. Multivariable regression models and subgroup analyses were conducted to investigate the association between DII and myopia. Subsequently, smoothed curve analyses were conducted to discern the trend of correlation between DII and myopia across diverse population. A total of 7191 juveniles aged at 12 to 18 years with complete information were included in our study, consisting 3367 participants with diagnosis of myopia. Among these participants, a trend towards an increasing prevalence of myopia was observed with a higher DII. After adjusting for all covariates, stratified logistic regression analyses showed that among the population aged in 16 to 18 years old or with 9-11th grade educational level, the prevalence of myopia was significantly increased with higher DII score (OR = 1.06, 95% CI = 1.01, 1.11, P = 0.006; OR = 1.06, 95% CI = 1.01, 1.11, P = 0.010). In the two subgroups, participants in the highest quartile of DII had a 31.00% higher risk of myopia and a higher 27.00% risk of myopia respectively, compared to those in the lowest quartile of DII. Our results revealed an increasing trend in the prevalence of myopia with increased DII score in adolescents. Particularly, DII was positively associated with the risk of myopia among the population aged in 16 to 18 years old and with 9-11th grade educational level.

Abstract Background Despite effective antiretroviral therapy, people with HIV (PWH) experience persistent systemic inflammation and increased morbidity and mortality. Modulating the gut microbiome through fecal microbiota transplantation (FMT) represents a novel therapeutic strategy. We aimed to evaluate proteomic changes in inflammatory pathways following repeated, low-dose FMT versus placebo. Methods This double-masked, placebo-controlled pilot study assessed the proteomic impacts of weekly FMT versus placebo treatment over 8 weeks on systemic inflammation in 29 PWH receiving stable antiretroviral therapy (ART). Three stool donors with high Faecalibacterium and butyrate profiles were selected, and their individual stools were used for FMT capsule preparation. Proteomic changes in 345 inflammatory proteins in plasma were quantified using the proximity extension assay, with samples collected at baseline and at weeks 1, 8, and 24. Concurrently, we characterized shifts in the gut microbiota composition and annotated functions through shotgun metagenomics. We fitted generalized additive models to evaluate the dynamics of protein expression. We selected the most relevant proteins to explore their correlations with microbiome composition and functionality over time using linear mixed models. Results FMT significantly reduced the plasma levels of 45 inflammatory proteins, including established mortality predictors such as IL6 and TNF-α. We found notable reductions persisting up to 16 weeks after the final FMT procedure, including in the expression of proteins such as CCL20 and CD22. We identified changes in 46 proteins, including decreases in FT3LG, IL6, IL10RB, IL12B, and IL17A, which correlated with multiple bacterial species. We found that specific bacterial species within the Ruminococcaceae, Succinivibrionaceae, Prevotellaceae families, and the Clostridium genus, in addition to their associated genes and functions, were significantly correlated with changes in inflammatory markers. Conclusions Targeting the gut microbiome through FMT effectively decreased inflammatory proteins in PWH, with sustained effects. These findings suggest the potential of the microbiome as a therapeutic target to mitigate inflammation-related complications in this population, encouraging further research and development of microbiome-based interventions. Video Abstract

Abstract Background Uric acid (UA), the terminal breakdown product of purine metabolism, possesses contradictory roles, functioning both as an inflammatory mediator and as an antioxidant. Its clinical relevance, particularly in geriatric populations, remains a topic of ongoing debate. Aiming to elucidate whether circulating UA is detrimental or beneficial to human health, we investigate the association between serum UA concentrations and the frailty index—a comprehensive measure of biological aging in a nationally representative cohort of community‐dwelling older adults. Methods We conducted a population‐based, cross‐sectional study utilizing data from the Korea National Health and Nutrition Examination Survey. The sample included 4268 participants aged 65 years and above. A deficit accumulation frailty index (FI) was constructed using 38 items that assess physical, cognitive, psychological, and social domains. Based on the FI, participants were categorized into non‐frail (FI ≤ 0.15), pre‐frail (0.15 0.25). Serum UA levels were quantified through a colorimetric enzymatic assay. Results After controlling for confounders such as age, sex, socioeconomic status (including income and education level), lifestyle factors (smoking status), and medical history (hypertension, diabetes, dyslipidemia, stroke, cardiovascular diseases), and body mass index, serum UA levels were observed to be significantly higher in frail participants compared with their non‐frail counterparts (P

Pineal cysts are benign, nonneoplastic lesions of the pineal gland, often identified incidentally on MRI scans. Although these cysts are usually asymptomatic, they can occasionally enlarge and compress adjacent structures, leading to neurological complications such as obstructive hydrocephalus and Parinaud's syndrome. The underlying mechanisms of pineal cyst development remain largely unclear, although inflammation - common in rheumatological conditions such as fibromyalgia - and mechanical stress have been suggested as contributing factors. In addition, the incomplete blood-brain barrier of the pineal gland raises the possibility that chronic lithium therapy, commonly used for psychiatric disorders and also known for its hyperplastic effects, could facilitate cysts formation through lithium accumulation and epithelial stimulation.We report the case of a 49-year-old woman with bipolar disorder on long-term lithium treatment who presented with a pineal cyst and clinical symptoms consistent with fibromyalgia. A review of the literature highlights possible links between pineal cyst formation, systemic inflammation associated with rheumatological disorders and prolonged lithium exposure.Although the hyperplastic properties of lithium in glandular tissue are well documented, there is no conclusive evidence directly linking lithium use to the development of pineal cysts in humans. The possibility of cystic growth driven by the pro-inflammatory environment of fibromyalgia remains plausible and warrants further investigation of the complex interactions between lithium therapy, systemic inflammation and pineal cystogenesis, particularly in patients with coexisting rheumatological and psychiatric disorders.