The First Affiliated Hospital of Chengdu Medical College

The aim of our study was to investigate neurobiological markers and gender difference for diagnosing anxious major depressive disorder (aMDD) through a meta-analysis.

We systematically searched multiple databases for whole-brain neuroimaging studies comparing anxious major depression disorder (aMDD), pure MDD, and healthy controls, with publication dates through December 2024. We extracted brain coordinates and their corresponding peaks, for further analysis using the Seed-based d Mapping software package.

A total of 11 studies were included in this study, encompassing 829 aMDD patients, 681 MDD patients, and 865 healthy controls. The meta-analysis revealed that aMDD patients exhibited increased functional alteration in the left middle temporal gyrus compared to individuals diagnosed with MDD. In the comparison between individuals with aMDD and healthy controls, the meta-analysis revealed increased functional alteration in the anterior commissure and decreased functional alteration the right middle frontal gyrus. Furthermore, the meta-regression analysis revealed heightened neural activity of the left middle cingulate gyrus and right anterior thalamic regions, as well as weakened neural activity of the left rolandic operculum in females with aMDD compared to the control group.

We identified specific functional alterations in brain regions that may serve as potential neurobiological markers for aMDD and associated differences.

Acute lymphoblastic leukemia (ALL) is characterized by metabolic reprogramming, including elevated glycolysis and lactate production. Monocarboxylate transporter 1 (MCT1/SLC16A1) is frequently overexpressed in ALL, sustaining glycolytic flux to promote cell proliferation. While the natural flavonoid deguelin is known to induce necroptosis at high concentrations, the mechanisms underlying its anti-leukemic effects at lower, potentially more therapeutically relevant doses remain unclear.

Nalm6 cells were treated with deguelin (0.08-10 µM) for up to 72 h. Cell viability, apoptosis, cell cycle, reactive oxygen species (ROS), mitochondrial membrane potential (ΔΨm) were analyzed. We found that low concentration of deguelin significantly inhibited proliferation by inducing G2/M phase cell cycle arrest. This was associated with reduced ROS levels and loss of ΔΨm. Mechanistically, low concentration of deguelin activated the GSK-3β/AKT signaling pathway without inducing NF-κB/p70S6K phosphorylation. Furthermore, it concurrently downregulated lactate dehydrogenase A (LDHA) and MCT1 expression, leading to decreased intracellular lactate synthesis and influx, extracellular lactate accumulation, and ultimately, severe intracellular ATP depletion.

Our study reveals the mechanism of low concentration of deguelin in ALL. It acts not through classic necroptosis, but via coordinated cell cycle arrest and a unique "metabolic trap" caused by dual inhibition of lactate synthesis and transport. These findings reposition deguelin as a promising candidate for targeted therapy against metabolic vulnerabilities in B-ALL.

To evaluate trends and disparities in the rates of mortality from chronic obstructive pulmonary disease (COPD) among adults aged 65 years or more in the United States from 1999 to 2020, and to make near-term projections.

Population-based ecological time-trend analysis using mortality data from the Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research database.

Age-adjusted mortality rates (AAMR) per 10⁵ adults, stratified by sex, age, race and ethnicity, census region, urbanization, and state. Joinpoint regression estimated annual percent changes, autoregressive integrated moving average (ARIMA) models projected rates to 2030, and Socio-Demographic Index (SDI) correlations and stochastic frontier analysis assessed state-level disparities and performance gaps.

Among 2,564,672 COPD deaths, overall AAMR declined from 303.5 to 238.6 per 10⁵ over the period 1999-2017 (APC -0.45%), with a further decline observed over 2017-2020 (APC -4.40%). Male AAMR declined significantly in both periods (APC -1.36% and - 3.97%), whereas female AAMR remained relatively stable during 1999-2017 (APC 0.18%) before declining significantly during 2017-2020 (APC -4.90%), suggesting an acceleration in mortality reduction in recent years. Despite the overall decline, mortality remained unevenly distributed, with the highest AAMRs observed in the Midwest (301.1) and South (297.3), nonmetro areas (339.4), and low-SDI states, particularly West Virginia (401.3). ARIMA projections suggested that the overall AAMR would continue to fall to 223.3 by 2030, mainly because of an 18.6% projected decline among males; in contrast, female rates were projected to plateau at approximately 246.4. Frontier analysis further indicated that several high-burden states had excess mortality relative to benchmark states with comparable SDI levels, highlighting opportunities for targeted improvement.

Mortality risk declined, but the burden remained concentrated among the oldest adults (≥85 years), women, rural residents, and socially disadvantaged states. Sex-, geriatric-, and place-based strategies are needed to reduce persistent inequities.