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Defining a non-eosinophilic inflammatory subtype in COPD: the role of CXCL9 and type 1 immune responses

Front Immunol. 2025 Apr 17;16:1576849. doi: 10.3389/fimmu.2025.1576849. eCollection 2025.

ABSTRACT

BACKGROUND: C-X-C motif chemokine ligand 9 (CXCL9) is induced by the interferon-γ response, and its receptor, C-X-C motif chemokine receptor 3, is a well-established marker of T-helper 1 (Th1) cells, which play an essential role in type 1 immune responses. CXCL9 expression is upregulated in patients with interstitial lung disease (ILD), COVID-19, and asthma. Although type 1 inflammation and CD8+ T cell activation are considered central to the inflammatory pathophysiology of chronic obstructive pulmonary disease (COPD), the relationship between blood levels of Th1 chemokines and this pathophysiology remains unclear. This study aimed to investigate the relationship between CXCL9 and chronic respiratory diseases.

METHODS: We conducted a retrospective cohort study. The serum levels of CXCL9, surfactant protein A (SP-A), Krebs von den Lungen-6 (KL-6), and C-reactive protein (CRP) were analyzed in 165 patients with ILD and COPD. COPD was diagnosed using pulmonary function tests according to the Global Initiative for Chronic Obstructive Lung Disease criteria. Statistical analyses included Fisher’s exact test, Steel-Dwass test, Mann-Whitney U, and Wilcoxon test. An unsupervised hierarchical cluster analysis using complete linkage and Euclidean distance was performed for data clustering.

RESULTS: CXCL9 levels were significantly higher in patients with COPD and interstitial ILD than in healthy smokers and non-smokers. The median serum CXCL9 levels in patients with ILD, COPD, healthy smokers, and healthy nonsmokers were 61.6, 69.3, 37.0, and 32.5pg/mL, respectively. CXCL9 levels in patients with COPD significantly correlated with KL-6, SP-A, blood eosinophil ratio, lactate dehydrogenase (LDH), and CRP levels, with correlation coefficients of 0.243, 0.381, 0.225, 0.369, and 0.293, respectively. Additionally, CXCL9 levels were negatively correlated with FEV1%. Levels of LDH and KL-6 and the neutrophil ratio were significantly elevated in non-eosinophilic COPD patients with high CXCL9 levels.

CONCLUSIONS: Our results highlight the potential role of CXCL9 in the inflammatory pathophysiology of COPD.

PMID:40313944 | PMC:PMC12043484 | DOI:10.3389/fimmu.2025.1576849

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A new predictive factor VGF based on IHC experiments, gene pathways and molecular functional groups for tumor immune microenvironment and prognosis of adrenocortical carcinoma

Front Immunol. 2025 Apr 17;16:1542780. doi: 10.3389/fimmu.2025.1542780. eCollection 2025.

ABSTRACT

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy with a poor prognosis, and its clinical management remains a significant challenge due to the high recurrence rates and limited treatment options. Despite advances in understanding the molecular mechanisms underlying ACC, no reliable biomarkers have been validated for routine clinical use.

METHODS: We analyzed RNA sequencing data from The Cancer Genome Atlas (TCGA) database (n=79) and Genotype Tissue Expression (GTEx) database (n=128) to investigate the expression of VGF in ACC and normal adrenal tissues. Gene expression levels of VGF were quantified and correlated with clinicopathological features and survival outcomes. Statistical methods included Cox proportional hazards models and Kaplan-Meier analysis, while Gene Set Enrichment Analysis (GSEA) was utilized to identify relevant biological pathways associated with VGF expression. Clinical data from 7 ACC patients from YANTAI YUHUANGDING Hospital were also analyzed. The expression of VGF in ACC and normal adrenal gland tissue was further validated through IHC experiments.

RESULTS: Our results demonstrate that VGF expression is elevated in ACC tissues compared to normal adrenal tissues and is significantly associated with advanced disease stages, lymph node involvement, metastasis and poor overall survival. VGF levels also correlate with immune cell infiltration, including Th2 cells, T helper cells, and Neutrophils. Importantly, our study establishes VGF as a potential prognostic biomarker for ACC and highlights its role in tumor progression and immune modulation. Additionally, GSEA analysis suggests that VGF is involved in cytokine receptor interaction and the P13K-Akt signaling pathway, possibly relating to tumor immunity.

CONCLUSIONS: VGF could serve as a valuable marker for patient stratification, monitoring disease progression, and predicting responses to immunotherapies. Future studies should focus on investigating circulating VGF levels as a non-invasive biomarker for ACC to improve clinical management and treatment outcomes.

PMID:40313932 | PMC:PMC12043488 | DOI:10.3389/fimmu.2025.1542780

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Prevalence and Associated Risk Factors of Intestinal Parasitic Infections Among Patients Requesting Stool Examination at Kidus Harvey Health Center, Ayna Bugina District, North Wollo, Ethiopia

J Parasitol Res. 2025 Apr 23;2025:5596158. doi: 10.1155/japr/5596158. eCollection 2025.

ABSTRACT

Intestinal parasitic infections (IPIs) remain a significant global health burden, disproportionately affecting developing nations. This cross-sectional study aimed to determine the prevalence and associated risk factors of IPIs among patients visiting Kidus Harvey Health Center in North Wollo, Ethiopia, from February to April 2023. Stool samples and questionnaire data were collected from 404 voluntary participants. Data were analyzed using SPSS version 20, employing descriptive statistics and logistic regression. The overall prevalence of IPIs was 41.09% (166/404). E. histolytica/dispar (16.34%) and A. lumbricoides (7.2%) were the predominant parasitic species. Significant risk factors identified included marital status (married: AOR = 3.536, 95%CI = 1.515-8.250, p = 0.003), occupation (farmers: AOR = 2.447, 95%CI = 0.816-7.337, p = 0.04), family size (> 9 members: AOR = 2.860, 95%CI = 0.619-13.206, p = 0.008), infrequent handwashing before meals, infrequent shoe wearing, contact with water bodies, untreated water sources, and raw meat consumption. The high prevalence of IPIs underscores the need for targeted public health interventions. These interventions should prioritize promoting personal and environmental sanitation, reducing raw meat consumption, and preventing unprotected contact with soil and water. Comprehensive public health campaigns delivering specific hygiene education to high-risk groups, emphasizing handwashing, shoe wearing, and safe water practices, are essential to mitigate the burden of IPIs in this population.

PMID:40313928 | PMC:PMC12043435 | DOI:10.1155/japr/5596158

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Thromboembolic Events in Castration-Resistant Prostate Cancer Patients With and Without Cardiovascular Comorbidities Receiving Oral Androgen Receptor Pathway Inhibitors

Prostate. 2025 May 1. doi: 10.1002/pros.24902. Online ahead of print.

ABSTRACT

BACKGROUND: This study investigates the association between thromboembolic events (TE) and castration-resistant prostate cancer (CRPC) patients receiving oral androgen receptor pathway inhibitors (ARPi) compared to those undergoing chemotherapy, both with and without a pre-existing history of cardiovascular disease (CVD).

METHODS: A total of 2779 men diagnosed with CRPC were identified using the Surveillance, Epidemiology, and End Results (SEER) Medicare Linked Database from 2012 to 2016. Patients were stratified based on their CVD history. Within each CVD stratum (pre-existing CVD vs. no pre-existing CVD), patients were further categorized into two treatment groups: those receiving oral ARPi and those undergoing chemotherapy. Unadjusted and inverse probability treatment weight (IPTW)-adjusted proportional hazards models, using Fine and Gray’s method, were applied to evaluate the potential association between ARPi treatment and TE.

RESULTS: Patients with pre-existing CVD treated with ARPi exhibited a significantly lower crude hazard ratio (HR) for TE compared to chemotherapy (HR 0.39, 95% CI 0.27-0.58, p < 0.001). However, after adjustment using IPTW, this association was no longer significant (adjusted hazard ratio [AHR] 1.00, 95% CI 0.75-1.32, p = 0.99). For patients without CVD, ARPi use was also associated with a reduced risk of TE in the crude analysis (HR 0.53, 95% CI 0.32-0.87, p = 0.01), but this effect was not statistically significant after IPTW adjustment (HR 0.99, 95% CI 0.69-1.41, p = 0.94).

CONCLUSION: ARPi demonstrated no significant effect on TE risk compared to chemotherapy, regardless of pre-existing CVD status. Similarly, when excluding patients with a prior history of TE, ARPi use remained non-significantly associated with new TE in the IPTW-adjusted competing risk analysis, highlighting the need for further investigation.

PMID:40312772 | DOI:10.1002/pros.24902

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Autologous umbilical cord blood mononuclear cell therapy for hypoplastic left heart syndrome: a nonrandomized control trial of the efficacy and safety of intramyocardial injections

Stem Cell Res Ther. 2025 May 1;16(1):215. doi: 10.1186/s13287-025-04316-3.

ABSTRACT

BACKGROUND: Preliminary phase I clinical trial results revealed that autologous umbilical cord blood-derived mononuclear cells (UCB-MNCs) preserved right ventricular cardiac function. To establish the efficacy of intramyocardial injections of an autologous UCB-MNC product at the time of stage II palliation surgery in patients with hypoplastic left heart syndrome (HLHS).

METHODS: A phase IIb, multicenter, open-label, nonrandomized study was conducted. Ninety-five children (fifty treated and forty-five controls) with HLHS and its variants, a history of stage I palliation surgery, and planned stage II palliation surgery at less than thirteen months were enrolled. We assessed coprimary efficacy endpoints for changes in right ventricular cardiac function through fractional area changes and longitudinal and circumferential strain, both in the short term (three months) and long term (twelve months). Second, we assessed changes in biomarkers of cardiac injury. Safety endpoints included severe adverse events (SAEs), changes in overall health through vital signs, and cumulative hospitalization.

RESULTS: Assessment of our coprimary efficacy endpoints revealed an unfavorable change in longitudinal cardiac strain in the treatment group compared with an improvement in strain in the control group (unadjusted p =.032) in the short term. No differences were observed between the groups in terms of other coprimary efficacy endpoints in the short or long term. A secondary assessment of biomarkers of cardiac injury revealed higher troponin T levels in the treatment group at three and six hours postsurgery. Regarding safety, no deaths related to the administered product or delivery procedure were reported. The treatment group presented a greater incidence (20%) of at least one SAE than the control group at three months (p =.048). Additionally, no statistically significant differences were found for the other safety endpoints.

CONCLUSION: Intramyocardial injections of autologous UCB-MNC products into the right ventricular myocardium during stage II palliation surgery failed to enhance cardiac function in patients with hypoplastic left heart syndrome. REGISTERED ON CLINICALTRIALS.GOV: Registered on ClinicalTrials.gov (NCT03779711) on 12/04/2018; URL: https://clinicaltrials.gov/ct2/show/NCT0377971 .

PMID:40312733 | DOI:10.1186/s13287-025-04316-3

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Burden of disease in the Belt and Road countries from 1990 to 2021: analysis of estimates from the Global Burden of Disease 2021

Glob Health Res Policy. 2025 May 1;10(1):20. doi: 10.1186/s41256-025-00403-3.

ABSTRACT

BACKGROUND: As a newly emerging collaborative platform to boost regional growth and prosperity, the Belt and Road Initiative (BRI) has great potential to promote global health development. However, the overall health status of BRI countries remains unclear. We analyzed the health patterns and its geographical distribution in 149 BRI countries from 1990 to 2021.

METHODS: Using the Global Burden of Disease 2021 (GBD 2021) online database, we examined time trends, country and income variations in death rate and disability-adjusted life years (DALY) rate, and compared the trends and projected 2030 values for ten key health-related Sustainable Development Goals (SDGs) indicators among the 149 BRI countries.

RESULTS: The number of deaths and DALYs of BRI countries represented 62.9-66.0% of global deaths and 64.8-66.8% of global DALYs between 1990 and 2021, and both the overall age-standardized death rate and DALY rate continued to be higher in BRI countries than in non-BRI countries throughout the time period studied. Great variations existed across the 149 BRI countries for both level of and changes in age-standardized death rate and DALY rate. The 2030 targets for six health-related SDGs indicators will not be reached in over 70% of BRI countries according to the previous changing speed trajectory.

CONCLUSIONS: Our findings demonstrate that BRI countries face a heavy burden of disease that varies across countries, although health outcomes have improved since 1990. Progress toward 2030 targets for six key health-related SDGs indicators in most BRI countries was slow. These findings support calls for more health collaborations, aid programs, and other health service to reduce health disparities across the BRI countries.

PMID:40312730 | DOI:10.1186/s41256-025-00403-3

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Cardiovascular-kidney-metabolic syndrome modifies smoking-related risk for cardiovascular diseases: findings from an observational cohort study in UK Biobank

BMC Public Health. 2025 May 1;25(1):1609. doi: 10.1186/s12889-025-22865-3.

ABSTRACT

BACKGROUND: The present study aims to investigate the association of smoking behaviors and cardiovascular-kidney-metabolic (CKM) syndrome with incident cardiovascular disease (CVD), and to evaluate whether the cardiovascular benefits of smoking cessation vary across different CKM conditions.

METHODS: This study included 242,636 white European participants from the UK Biobank who were classified as CKM syndrome Stages 0 to 3 and free of CVD at baseline. Covariates adjusted Cox proportional hazards models were employed to evaluate the associations of CKM syndrome with the risks of total CVD, stroke, coronary heart disease (CHD), major adverse cardiovascular events (MACE), and 13 CVD subtypes. The impact of smoking behavior across different CKM stages and the joint effect of smoking and CKM syndrome on CVD risk were also evaluated. To investigate the potential effect modification by CKM syndrome, we examined the multiplicative scale by interaction terms in Cox models, and quantified the additive scale using statistics such as the relative excess risk due to interaction (RERI).

RESULTS: The risk of total CVD, stroke, and CHD increased progressively with advancing CKM stages, with Stage 3 associated with hazard ratios (HRs) of 3.38 (95% CI: 3.05-3.74), 3.01 (2.49-3.64), and 3.65 (3.25-4.10), respectively (P for trend < 0.001). The time required to reduce CVD risk to a level not significantly different from that of never smokers tends to be longer for individuals with advancing CKM stage: smokers at Stages 0-1 achieved this after approximately 10 years of cessation, whereas those at Stages 2-3 required more than 25 years. Compared with never smokers at CKM Stage 0, current smokers at CKM Stage 3 had substantially higher risk of total CVD (HR = 4.14, 95% CI: 3.54-4.83) and several subtypes, particularly abdominal aortic aneurysm (HR = 17.68, 95% CI: 6.33-49.43) and peripheral vascular disease (HR = 10.53, 95% CI: 6.79-16.34). CKM syndrome appeared to act as a positive additive effect modifier in smoking-related risk of total CVD (RERI = 0.20, 95% CI: 0.05-0.32), as well as several CVD subtypes, suggesting that the combined effect of smoking and CKM progression exceeds the sum of their individual effects.

CONCLUSIONS: Our finding emphasizes the importance of smoking cessation among individuals with advanced CKM syndrome, as they face heightened CVD risk. However, compared to those at earlier CKM stages, the short-term benefits of smoking cessation may be less pronounced in this population. Interventions that combine smoking cessation promotion with CKM syndrome management may yield greater reductions in the risk of several CVD outcomes.

PMID:40312716 | DOI:10.1186/s12889-025-22865-3

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The effect of community-based palliative supportive care integrated with primary health care (PHC) on the outcomes of terminally ill cancer patients

BMC Prim Care. 2025 May 1;26(1):139. doi: 10.1186/s12875-025-02831-z.

ABSTRACT

BACKGROUND: Cancer is increasing worldwide. Palliative care can help reduce the suffering of patients with cancer. Providing palliative care with a primary health care (PHC) approach can lead to greater patient access to palliative services. Given the lack of studies in this area, the present study aimed to determine the impact of community-based palliative care integrated with PHC on outcomes of terminally ill cancer patients.

METHODS: This was a randomized controlled trial. Research population included 120 cancer patients in Khorramabad in 2023. A convenience sampling method was conducted, and then subjects were allocated to the intervention and control groups through randomization blocks with size of four. Subjects in the intervention group received PHC-integrated community-based palliative support for two months, while their control peers received their routine health care programs during the same period. The data were gathered using the Palliative Care Outcome Scale before and two months after the intervention and then were analyzed using SPSS 22 software and descriptive and inferential statistics.

RESULTS: The mean scores of all dimensions of palliative outcomes, including physical, psychological, emotional, and social, as well as the overall palliative care outcome, improved after the intervention in the experimental group, and these changes were statistically significant (p < 0.001). Before the intervention, the mean score of overall palliative care outcome was 22.21 ± 2.89 in the intervention group and 21.88 ± 2.55 in the control group (P = 0.51), While after the intervention, the mean scores in the experimental and control groups changed to 17.98 ± 2.88 and 21.83 ± 2.69, respectively, and this difference was statistically significant (p < 0.001). The mean changes in the overall palliative outcome score before and after the intervention in the experimental and control groups were 4.23 ± 2.83 and 0.5 ± 0.72, respectively, and this difference was statistically significant (p < 0.001).

CONCLUSION: The community-based palliative care integrated into the PHC structure could positively affect all aspects of palliative care. It is recommended that policymakers create conditions where cancer patients can receive care through the PHC structure. More studies are required to designate the strengths and weaknesses of this care approach.

TRIAL REGISTRATION NUMBER: IRCT20180721040540N5, 2023-06-07, Registered on June 7,2023. https://irct.behdasht.gov.ir/user/trial/68288/view .

PMID:40312691 | DOI:10.1186/s12875-025-02831-z

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A systematic review and meta-analysis of the effectiveness of high-intensity interval training for physical fitness in university students

BMC Public Health. 2025 May 1;25(1):1601. doi: 10.1186/s12889-025-22829-7.

ABSTRACT

BACKGROUND: Extensive research has demonstrated the effectiveness of high-intensity interval training (HIIT) in children and adults; however, evidence specific to university students remains limited. This study aimed to evaluate the effects of HIIT on promoting physical health in university students and to identify potential factors influencing intervention outcomes.

METHOD: A systematic search was conducted across five electronic databases (Web of Science, Scopus, PubMed, SportDiscus, and MEDLINE) up to December 2024 using Boolean operators and keywords related to HIIT and university students.

INCLUSION CRITERIA: (1) Experimental studies; (2) Physical-related outcomes; (3) Intervention duration of at least 3 weeks; (4) Meets the definition of high-intensity activity; (5) Participants are general university students. A meta-analysis was conducted using RevMan 5.4 software, comparing intervention and control groups. Effect sizes were calculated using Cohen’s d, and heterogeneity was assessed with the I² statistic. Subgroup analyses were performed based on intervention duration and rest interval duration.

RESULTS: Results showed that HIIT significantly reduced BMI, body fat percentage, waist-to-hip ratio, and heart rate, while significantly improving VO2max and muscle strength in university students. Interventions lasting longer than eight weeks demonstrated greater improvements in muscle strength compared to those lasting eight weeks or less. However, there are no significant differences in rest interval across any of the groups. Notably, HIIT also has positive effects on agility and speed with varying effect sizes.

CONCLUSION: The unique characteristics of university students make HIIT a time-efficient and effective intervention strategy for this population. Future studies should consider the specific needs of the university environment, incorporating the latest technological advancements and developing tailored intervention strategies that align with students’ preferences.

PMID:40312686 | DOI:10.1186/s12889-025-22829-7

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Perception of quality and adoption of health-preventive measures in gym-goers after the COVID-19 pandemic peak in Italy

BMC Public Health. 2025 May 1;25(1):1621. doi: 10.1186/s12889-025-22870-6.

ABSTRACT

BACKGROUND: The aim of this study was to assess the sociodemographic characteristics, physical activity and exercise patterns among gym-goers in Italy and their health-related behaviours at the gym after COVID-19 restrictions were lifted in Italy. In addition to that, their perception of the hygiene standards and safety of gyms, according to several individual variables, was evaluated.

METHODS: A self-administered questionnaire was used to collect the data of individuals who were recruited from gyms between May and June 2023. Descriptive statistics were carried out to describe the sociodemographic and behavioural characteristics of the sample and the perceived quality of the gyms. Each association between variables was assessed by using bivariate analysis, and after verifying its statistical significance, two logistic regression models were performed using the perceived quality of the gym and the likelihood of adoption of health-preventive measures as dependent variables.

RESULTS: The study involved 1321 participants, with a nearly equal gender distribution. Most of the sample was aged between 18 and 25, unmarried, and approximately 45% were students. Most engaged in moderate physical activity, mainly free-weight lifting and machine exercises, 3-5 times a week for 1-2 h in the evening. Participants generally rated the gym positively, with 34.49% considering it “Good” and 39.23% rating it “Very good.” Ratings from females were slightly lower compared to those from males. The age group 18-25 rated the gym higher, while higher education levels were associated with slightly lower ratings. The analysis of health-preventive behaviours, including practices such as using personal towels, sanitising equipment, respecting safety distances, revealed that approximately 41.3% of the participants were likely to adopt those measures, with an additional 23.3% categorised as “very likely.” Males showed a greater inclination towards these behaviours compared to females. In particular, the perceived quality of the gym influenced individuals’ likelihood of adopting health-preventive measures. This indicates that factors such as hygiene, adequacy, and safety of the environment can influence individuals’ motivation to engage in health-preventive behaviours.

CONCLUSIONS: Italian gym-goers generally perceived the quality of the gyms positively, with safety and cleanliness impacting their satisfaction and the adoption of health-preventive behaviours. Sociodemographic factors significantly influence these perceptions and behaviours, highlighting the need for safer, health-focused fitness facilities to promote physical activity, public health, and sustainable fitness habits and emphasising the need to understand user preferences for enhanced customer satisfaction, loyalty, and well-being through tailored management strategies and preventive measures.

PMID:40312661 | DOI:10.1186/s12889-025-22870-6