Objective: To explore the expression characteristics of complement C3 in childhood asthma and its mechanism of regulating macrophage migration and polarization in immune inflammatory responses. Methods: (1) Clinical research section:a total of 200 children hospitalized and diagnosed with acute asthma exacerbation at Children's Hospital of Soochow University from January 2020 to December 2023 were retrospectively enrolled, including 135 males and 65 females with a mean age of (7.0±3.0) years. According to clinical symptoms on admission, patients were divided into mild group (n=89), moderate group (n=71) and severe group (n=40). Meanwhile, 100 healthy children receiving physical examination during the same period were recruited as healthy control group, consisting of 64 males and 36 females with a mean age of (6.6±3.5) years. Clinical characteristics were compared between the asthma group and healthy control group as well as among asthma subgroups of different severities. Multivariate logistic regression model was applied to analyze relevant factors associated with asthma severity. (2) Animal experiment section:Female C3 knockout (C3^-/-) mice aged 6 to 8 weeks and weighing (20±2) g were selected. Female wild-type C57BL/6J mice aged 6 to 8 weeks with a body weight of (20±2) g served as the control group. There were 10 mice in each group. All mice were randomly divided into 4 groups using a random number table method: wild-type control group, wild-type asthma group, C3^-/- control group and C3^-/- asthma group, with 5 mice in each group. Asthma mouse models were established by airway instillation sensitization and challenge with cockroach extract, while phosphate buffered saline (PBS) was administered in control groups. All mice were anesthetized and sacrificed on day 14. Bronchoalveolar lavage fluid (BALF) was collected for classification and counting of inflammatory cells. Enzyme-linked immunosorbent assay was used to detect levels of Th2 cytokines including interleukin-4 (IL-4) and interleukin-5 (IL-5) in BALF, as well as serum total immunoglobulin E (IgE) and immunoglobulin G1 (IgG1). Lung tissues were harvested, and quantitative real-time polymerase chain reaction (qRT-PCR) was performed to assess the distribution and polarization of M1-type (iNOS⁺) and M2-type (Arg-1⁺) macrophages. (3) Cell experiment section: murine macrophage cell line RAW264.7 was cultured in vitro and treated with different concentrations of recombinant C3 protein to observe macrophage migration ability. Cells were divided into PBS group, recombinant C3 protein group, and recombinant C3 protein combined with SB290157 (C3a receptor antagonist) group according to interventions. Cells were stimulated with PBS, IL-4 and lipopolysaccharide (LPS), respectively. The polarization of M1 (iNOS⁺) and M2 (Arg-1⁺) macrophages was detected via qRT-PCR. Results: (1) Clinical sample results: the level of complement C3 in the asthma group was significantly higher than that in the healthy control group [(1.20±0.20) vs (0.98±0.18) g/L, P<0.001]. Children with moderate and severe asthma had elevated complement C3 levels compared with those with mild asthma [(1.27±0.19) vs (1.13±0.20) g/L, (1.22±0.16) vs (1.13±0.20) g/L, both P<0.05]. Multivariate logistic regression analysis indicated that complement C3 was positively correlated with moderate-severe asthma (OR=12.373, 95%CI: 1.756-87.153). (2) Animal experimental results: the total number of inflammatory cells, counts of neutrophils, eosinophils, macrophages and lymphocytes, as well as levels of IL-4 and IL-5 in BALF were lower in the C3^-/- asthma group than those in the wild-type asthma group. Serum total IgE and IgG1 levels were also decreased (all P<0.05). qRT-PCR results revealed that the relative mRNA expression of iNOS and Arg-1, together with the M2/M1 ratio in lung tissues were lower in the C3^-/- asthma group (all P<0.05). (3) Cell experimental results: compared with the PBS group, recombinant C3 protein significantly enhanced macrophage migration ability, and the absorbance (A) increased with the elevation of recombinant C3 protein concentration (all P<0.05). After LPS stimulation, macrophage differentiation toward M1 phenotype was markedly higher in the recombinant C3 protein+SB290157 group than in the PBS group and recombinant C3 protein group (all P<0.001). Following treatment with PBS, IL-4 or LPS, M2 polarization level was higher in the recombinant C3 protein group relative to the PBS group, while the recombinant C3 protein+SB290157 group presented lower M2 polarization than the other two groups (all P<0.01). Conclusions: Complement C3 is markedly elevated in children with asthma and positively correlated with moderate and severe asthma. Complement C3 may enhance macrophage migration and promote M2 polarization, thereby participating in and aggravating immune inflammatory responses in asthma.

The global burden of chronic kidney disease (CKD) is rapidly increasing due to the rising prevalence of metabolic diseases. However, the epidemiological characteristics of CKD in women and its epidemiological association with metabolic disorders and cardiovascular diseases (CVDs) remain unclear.

Based on data from the Global Burden of Disease study 2021, this research used Joinpoint regression analysis to identify the global trends of CKD in women. A comprehensive assessment of CKD burden in women was conducted across multiple dimensions, such as age stratification, five CKD subtypes, sociodemographic index, decomposition analysis, risk factors, and CVD attributable to kidney function impairment.

In 2021, the global number of women with CKD reached 359 million, an increase of 90.65% compared to 1990, with the absolute number of diabetic kidney disease cases nearly doubling. Nearly two-thirds of patients were postmenopausal women, and their age-standardized mortality rate and age-standardized disability-adjusted life-years (DALYs) rate had significantly increased to 64.03 and 1493.31 per 100,000, respectively. The age-standardized prevalence rate among women of reproductive age demonstrated a continuous upward trend (average annual percentage change, 0.13%). Regionally, the age-standardized mortality rate and age-standardized DALY rate of women with CKD were highest in the regions with low and low-middle sociodemographic index (SDI), while the age-standardized prevalence rate was highest in low-middle SDI regions. Metabolic risk factors constituted the main attributable risk factors for CKD in women, with risks owing to high fasting glucose and high body mass index rapidly increasing among women of reproductive age (by 40.66% and 112.17%, respectively). CVD attributable to kidney function impairment accounted for 18.19 million DALYs, representing 46.70% of the total disease burden, with ischemic heart disease being the main contributor. Population growth (58.63%) and aging (26.64%) were the main drivers of the increasing burden of CKD in women.

In the future, women will face severe metabolic-renal-cardiac health challenges related to metabolic disorders.

Insufficient physical activity (IPA) is a well-established cardiovascular risk factor. Iran has one of the highest cardiovascular disease (CVD) burdens in the Middle East and North Africa region. This study estimated prevalence-based, scenario-driven population-attributable fractions (PAFs) of prevalent CVD, coronary heart disease (CHD), and stroke statistically associated with insufficient non-occupational physical activity among Iranian adults aged ≥ 40 years under a counterfactual model of sufficient physical activity.

We analyzed data from 16,552 adults aged ≥ 40 years from the nationally representative Iran STEPS 2021 survey. IPA was defined as < 600 MET-minutes/week of non-occupational physical activity. PAFs were estimated using Miettinen's formula combining the prevalence of IPA among cases with sex-specific relative risks from a prospective meta-analysis after transformation to reflect IPA versus sufficient activity. Analyses incorporated sampling weights and complex survey design; 95% confidence intervals (CIs) were estimated via bootstrap.

Weighted prevalence was 11.48% (95% CI: 10.95, 12.04) for CVD, 10.43% (95% CI: 9.91, 10.96) for CHD, and 2.17% (95% CI: 1.94, 2.43) for stroke. Under a counterfactual scenario of sufficient activity, the estimated PAF was 19.2% (95% CI: 15.1, 23.2) for CVD, 15.9% (95% CI: 11.2, 20.5) for CHD, and 17.1% (95% CI: 11.5, 22.5) for stroke. Higher fractions were observed among women (25.2% for CVD) and adults aged ≥ 60 years (19.7% for CVD).

These scenario-driven estimates suggest that a substantial proportion of prevalent CVD would be statistically associated with IPA under a counterfactual model. Due to the cross-sectional design, reverse causation is likely and may upwardly bias estimates. Findings highlight women and older adults as priority subgroups for physical activity promotion. The PAF estimates should be interpreted as policy-oriented scenario measures rather than direct causal effects.

Not applicable.

The online version contains supplementary material available at 10.1007/s40200-026-01992-7.

ObjectivesThe Coronavirus Disease-2019 (COVID-19) pandemic had indirect impacts on healthcare provided to critically ill intensive care unit (ICU) non-COVID patients and their outcomes. Therefore, we examined the effect of the COVID-19 pandemic on patients with non-COVID critical illness during the pandemic and pre-pandemic epochs.DesignRetrospective, population-based, observational cohort study.SettingAll adult patients admitted to general ICUs in Alberta, Canada, from March 2017-2020 (pre-pandemic period) and March 2020-2023 (pandemic period).Data sourcesData was captured from an integrated critical care clinical information system (eCritical Alberta) and Alberta Health Services (AHS) administrative databases were utilized.Measurements and main resultsA total of 80 540 non-COVID patients were admitted to ICUs in Alberta in the period between March 2017 and March 2023, equally distributed between the pandemic (40,196, 50.1%) and pre-pandemic (40,344, 49.9%) periods. For pandemic versus pre-pandemic cohorts, patient mean age was 57.7 ± 16.2 versus 58.5 ± 16.6 years and mean APACHE II score was 19.5 ± 8.8 versus 18.8 ± 8.5, respectively. ICU mortality was higher during the pandemic compared with pre-pandemic (14.2% vs 11.2%, mean difference [MD]: +3.1%, adjusted odds ratio [OR]: 1.21; 95% CI: 1.14-1.28, p < 0.001) after logistic regression adjustment. The hospital mortality was significantly higher in the pandemic versus the pre-pandemic period (23.6% vs 15.9%; MD: +7.7%, adjusted OR: 2.06, 95% CI: 1.97-2.16, p < 0.001). There was greater ICU (5.95 ± 9.4 vs 5.35 ± 8.5 days, MD: +0.63 days, 95% CI: 0.47 to 0.72 days, p < 0.001), and lower hospital (18.0 ± 28.0 vs 19.9 ± 33.3 days, MD: -1.89 days, 95% CI: -1.45 to -2.32 days p < 0.001) lengths of stay (LOS) during the pandemic compared with pre-pandemic.ConclusionDuring the pandemic period, non-COVID patients had worse outcomes, greater adjusted ICU and hospital mortality, with increased ICU lengths of stay, but shorter hospital lengths of stay, when compared with pre-pandemic periods.

Most diabetes care is managed in primary care settings, which represent a critical yet underutilized site for continuous glucose monitoring (CGM) adoption. Whether CGM initiation by primary care clinicians improves glycemic outcomes and reduces acute health care utilization remains understudied.

To evaluate the association of primary care-initiated CGM with changes in hemoglobin A1c (HbA1c) levels and rates of hospitalizations and emergency department (ED) visits among adults with insulin-treated diabetes.

This cohort study was performed at 18 primary care clinics within Montefiore Medical Center, a large safety-net health system in the Bronx, New York. Adults 18 years or older with any insulin-treated diabetes who had at least 1 primary care visit between August 1, 2022, and August 1, 2025, were included. Patients were excluded if they were uninsured, if they had a CGM prescription in the prior 2 years, or if their first CGM during follow-up was prescribed outside primary care.

First CGM prescription by a primary care clinician.

The primary outcomes were HbA1c level trajectories, which were analyzed using mixed-effects models, and hospitalizations and ED visits, which were analyzed using recurrent event frailty models.

The study included 8502 insulin-treated CGM-naive adult patients with diabetes (mean [SD] age, 62.3 [14.6] years; 4764 [56.0%] female; 3618 [42.6%] with Medicare and 2854 [33.6%] with Medicaid coverage). Of these, 2392 patients (28.1%) were prescribed CGM by primary care clinicians. Patients who initiated CGM were younger, more often English-speaking and commercially insured, and had higher baseline HbA1c levels and more microvascular complications. At 12 months, HbA1c levels decreased by 0.66 (95% CI, 0.57-0.75) percentage points (pp) in patients who initiated CGM vs 0.17 (95% CI, 0.08-0.27) pp in those who did not, with a between-group difference of -0.49 (95% CI -0.62 to -0.35) pp. CGM initiation was associated with lower risk of recurrent hospitalizations (hazard ratio, 0.87 [95% CI, 0.77-0.98]) and ED visits (hazard ratio, 0.82 [95% CI, 0.74-0.91]).

In this cohort study of adults with insulin-treated diabetes, initiation of CGM by primary care clinicians was associated with clinically meaningful improvements in HbA1c and significant reductions in recurrent hospitalizations and ED visits. These findings support expanding CGM implementation in primary care settings as a scalable strategy to improve diabetes outcomes and reduce acute care utilization, particularly in underserved populations.

To evaluate the prevalence of comorbidities preceding the diagnosis of psoriatic arthritis (PsA) compared with the general population. We identified all adult patients granted a special reimbursement (SR) for disease-modifying anti-rheumatic drugs for PsA between 2002 and 2014 from the Finnish Social Insurance Institution register (N = 6077). Three general population controls were matched to each case. Visits to specialized medical care (Classification of Disease 10th revision coded), and prescription drug purchases categorized by Anatomical Therapeutic Chemical codes were collected for cases and controls between 2000 and 2014. We evaluated the period from 24 months before to 3 months after the index date (ID), defined as the date when the SR was granted. SRs granted for other chronic diseases prior to the ID were additionally collected. PsA patients had three times more visits to specialized medical care and increased overall drug use compared with controls. Based on SRs valid at the time of PsA diagnosis, new-onset PsA patients had significantly higher prevalence of diabetes mellitus (women: 11% vs. 7%; men: 14% vs. 10%; all p < 0.001), cardiovascular diseases (women: 19% vs. 14%; men: 23% vs. 18%; all p < 0.001), and obstructive lung diseases (women: 12% vs. 7%; men: 8% vs. 6%; all p < 0.001) compared with controls. PsA patients demonstrate increased morbidity already at the time of PsA diagnosis. Screening for comorbidities should therefore be considered when joint disease is clinically apparent.

Diabetes is a growing global health concern. Environmental exposure to airborne particles has recently been identified as a risk factor for type 2 diabetes. Despite hundred- or thousandfold concentrations in many occupational settings, epidemiological studies in workers are very scarce. This study aims to quantify the association between occupational inorganic particle exposure and incident type 2 diabetes among Swedish construction workers.

This was a retrospective cohort analysis in the Swedish Construction Workers' Cohort (Bygghälsokohorten), with data from occupational health examinations between 1971 and 1993. Exposure assessment was based on a cohort-specific job-exposure matrix. Data from the National Patient Register, the National Diabetes Register, and the National Prescribed Drug Register were combined to identify incident type 2 diabetes cases. Longitudinal, multivariable Cox proportional hazards regression models were fit to estimate adjusted hazard ratios (aHR).

We included 275,941 male workers with a mean follow-up time of 31 years. Slightly more than half were exposed to inorganic dusts or fumes. In crude analyses, workers exposed to inorganic dust and fumes were at an increased risk of type 2 diabetes. After confounder adjustment, only workers exposed to high levels of cement, concrete, and quartz dust were associated with an increased risk of type 2 diabetes (strongest for high levels of cement dust, aHR 1.12, 95% CI 1.02‒1.24).

In this large cohort of construction workers with long follow-up, workers with high exposure to cement, concrete, and quartz dust were at a moderately increased risk of type 2 diabetes.

Diabetes mellitus (DM) represents an increasing global health burden with type 2 diabetes mellitus (T2DM) accounting for most cases. T2DM is associated with microvascular and macrovascular complications including myocardial ischemia and contributes to the development of a distinct form of cardiac dysfunction referred to as diabetic cardiomyopathy (DCM). Importantly, DCM contributes to 50-80% of mortality in patients with diabetes independent of other vascular comorbidities and is characterized by structural and functional alterations of the myocardium. Notably, these outcomes exhibit sex-specific differences in patients with T2DM. Despite this, most preclinical rodent studies fail to incorporate female subjects. This is truly the case of the Zucker diabetic fatty (ZDF) rat model, where the left ventricular contractile and morphological properties have been investigated almost exclusively in males. This review aims to: a) synthesize existing data on myocyte shortening and morphology in ZDF male and female rats; b) identify critical gaps in current knowledge and define priorities for future experiments; and c) emphasize the urgent need for longitudinal studies assessing cardiomyocyte contractility and structural remodeling in both sexes. Cardiac myocyte contractility and calcium dynamics data are entirely lacking in ZDF female rats, while findings in males remain limited and, in some cases, inconsistent. For morphological and ultrastructural alterations in cardiac myocytes information is scarce for both ZDF males and females. Overall, this review highlights the need for comprehensive longitudinal investigations spanning the early and advanced stages of DCM including progression to heart failure in both male and female ZDF rats.

Age-related eye diseases (AREDs)-including age-related macular degeneration (AMD), glaucoma, and diabetic retinopathy-are leading causes of permanent blindness. Current treatments manage clinical manifestations but do not halt the molecular processes that drive disease progression. This limitation has shifted attention toward "geroscience," a strategy that targets the fundamental biology of aging rather than treating each disease in isolation. Four key hallmarks of aging-mitochondrial dysfunction, loss of proteostasis, cellular senescence, and epigenetic drift-are widely implicated in AREDs. We review evidence that these hallmarks do not act independently; instead, they form an interactive, self-reinforcing network. The way this network engages differs from tissue to tissue. In the high-energy environment of the retinal pigment epithelium, mitochondrial dysfunction dominates and drives AMD. In the mechanically stressed trabecular meshwork (TM), senescence and epigenetic drift take precedence, leading to glaucoma. In the neurovascular unit, chronic hyperglycemia routes the same network into a metabolic-epigenetic amplification loop that sustains diabetic retinopathy. The same aging mechanisms, routed through distinct tissue contexts, thus produce divergent clinical phenotypes. We also evaluate emerging therapies, including senolytics, mitochondria-targeted agents, and partial epigenetic reprogramming, and identify key intervention nodes such as NLRP3, p62, and NAD⁺ metabolism. Dismantling these pathological feedback loops offers a path beyond symptom management toward combination strategies that restore tissue resilience.

Imeglimin is a first-in-class oral antidiabetic agent that improves glycemia through dual actions on insulin secretion and sensitivity. However, real-world data on its long-term metabolic effects, particularly on endogenous insulin secretion, remain limited. We aimed to evaluate 12-month longitudinal changes in glycemic indices, an insulin secretion index, and treatment intensity during imeglimin therapy in routine clinical practice.

This retrospective observational study included 73 Japanese patients with type 2 diabetes mellitus who continued imeglimin therapy for approximately 12 months. Hemoglobin A1c (HbA1c) and glycated albumin (GA) were assessed at baseline and follow-up. Fasting plasma glucose and C-peptide levels obtained between 10 and 14 months after initiation were used to calculate the fasting C-peptide index (fCPI). Overall glucose-lowering treatment intensity was quantified using the medication effect score (MES).

HbA1c significantly decreased from 8.55% ± 1.38% to 7.67% ± 0.99% over 12 months (p < 0.0001). GA also declined from the early phase after initiation, whereas the GA/HbA1c ratio showed only transient change without sustained differences. The fCPI increased from 1.14 [0.65-1.84] to 1.21 [0.79-2.01] (n = 69, p = 0.003), and an early increase was observed within 1-2 months. Despite frequent adjustments to background therapies, treatment intensity as assessed by MES did not change significantly.

In a real-world setting, long-term imeglimin therapy was associated with sustained glycemic improvement and early as well as sustained numerical changes in an insulin secretion index without an increase in overall treatment intensity.