Xinqiao Hospital

Mitochondrial dysfunction is a hallmark of heart failure (HF), but its upstream regulatory pathways remain incompletely understood. Sirtuin 3 (SIRT3), a mitochondrial deacetylase, is crucial for maintaining enzymatic activity through deacetylation. This study investigates whether SIRT3 downregulation leads to mitochondrial metabolic impairment in HF by enhancing acetylation of tricarboxylic acid (TCA) cycle enzymes. A chronic HF model was established in male C57BL/6J mice via transverse aortic constriction (TAC). Cardiac function and morphology were evaluated by echocardiography, histological staining, and transmission electron microscopy. Mitochondrial function was assessed using ATP quantification, Seahorse XF analysis, and enzymatic activity assays. Protein acetylation and SIRT3 expression were examined through Western blotting and acetyl-proteomics. Angiotensin II-treated cardiomyocytes served as an in vitro model. TAC-induced HF led to cardiac remodeling and mitochondrial damage. Proteomic analysis revealed increased global protein acetylation, especially in mitochondrial proteins related to the TCA cycle. SIRT3 was significantly downregulated, corresponding with hyperacetylation and suppressed activity of pyruvate dehydrogenase (PDH), succinate dehydrogenase (SDH), and citrate synthase (CS), which was associated with impaired respiration and reduced ATP output. Ang II-treated cells showed similar changes. SIRT3 downregulation in HF drives TCA enzyme hyperacetylation and metabolic dysfunction, suggesting a key mechanism linking protein acetylation imbalance to mitochondrial impairment in disease progression.

Immune reconstitution (IR) is a critical factor influencing the quality of life and long-term prognosis in hematopoietic stem cell transplant (HSCT) recipients. But delayed IR post-transplant may lead to infections and disease recurrence, while impaired reconstitution is closely associated with graft-versus-host disease (GVHD). To formulate strategies that promote immune recovery, it is crucial to understand the fundamental principles and influencing factors of IR. The emergence of technologies such as single-cell sequencing enables researchers to reveal the specific patterns and mechanisms of immune reconstitution under different conditions, which has given us a better understanding of immune reconstitution than before. Current evidence indicates that delayed IR is related to several aspects, mainly the strength of the conditioning regimen, the composition of the graft, and the occurrence of GVHD. This review summarizes the main characteristics of immune reconstitution after allogeneic hematopoietic stem cell transplantation, combined with the latest research progress Carefully explore the influencing factors of immune reconstitution and the existing monitoring methods.

The expanding clinical use of helical tomotherapy (HT) has raised concerns regarding its potential to increase low-dose lung exposure and the risk of radiation pneumonitis (RP) in thoracic radiotherapy. While a few retrospective studies have compared dosimetric parameters and RP rates between HT and fixed-field intensity-modulated radiation therapy (IMRT), their findings remain inconsistent, necessitating a prospective randomized controlled trial for clarification. To prospectively compare dosimetric parameters and the incidence of RP between HT and IMRT in patients with lung or esophageal cancer. Patients eligible for thoracic radiotherapy were enrolled. Both HT and IMRT plans were designed and optimized for each patient, with a prescription equivalent dose in 2Gy /fraction (EQD2) ≥50Gy to the gross tumor volume (GTV). Plans were evaluated based on target dose coverage, dose-volume histograms, and other dosimetric indices. RP was diagnosed and graded according to the Common Terminology Criteria for Adverse Events (version 5.0). Risk factors for RP were identified using univariate analysis. Between February and September 2022, 110 consecutive patients with lung or esophageal cancer were enrolled and randomly assigned in a 1:1 ratio to either the HT group (n=54) or the IMRT group (n=56). Compared with IMRT, HT had a significant reduction in lung V20 (p=0.002) and mean lung dose (p=0.013). Furthermore, the HT group exhibited a superior conformity index for the planning gross tumor volume of the primary lesion (PGTVp) (p=0.004) and a lower homogeneity index for all planning target volumes (PTVs) (p<0.001). At a median follow-up of 14.0 months, the rate of grade≥2 RP for the entire cohort was 14.5%, with no significant differences between the HT and IMRT groups (p=0.61). Compared with fixed-field IMRT, HT provided superior dose distribution to the PTVs while maintaining a comparable incidence of RP in patients undergoing thoracic radiotherapy.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative therapy for severe aplastic anemia (SAA), with donor sources including matched sibling donors (MSDs), haploidentical donors (HIDs), and unrelated donors (URDs). However, the optimal criteria for donor selection remain undefined. We performed a multicenter retrospective study of 795 consecutive SAA patients who underwent allo-HSCT between 2012 and 2020 across 11 transplant centers in China. The overall survival (OS), failure-free survival (FFS), and GVHD-free/FFS (GFFS) rates were 85.2%, 83.6%, and 76.1%, respectively. Donor-related variables including relationship, age, sex match, blood type, and HLA mismatches were evaluated. Multivariable Cox regression identified donor age ≥50years as an independent risk factor for inferior GFFS (HR=2.13), OS (HR=2.09), and FFS (HR=2.18) (all P<0.001). To directly compare the prognostic weight of donor age versus HLA compatibility, we stratified patients into four subgroups according to donor type (HID vs. MSD) and donor age (<50 vs. ≥50years). Kaplan-Meier analysis with log-rank testing revealed that recipients of haploidentical grafts from younger donors achieved superior OS and FFS compared with those transplanted from older HLA-matched sibling donors. These findings demonstrate that donor age has a greater influence on transplant outcomes than HLA matching. With continuous improvements in haploidentical transplantation techniques, selecting younger haploidentical donors may represent a more favorable strategy than choosing older matched sibling donors.

Single-Metal-Doped Nanoplatforms In their Research Article (10.1002/adfm.202520463), Malcolm Xing, Shiming Yang, and co-workers present manganese-doped metal–organic frameworks that induce ferroptosis-mediated release of endogenous mitochondrial DNA, thereby synergistically activating the manganese-specific cGAS-STING signaling pathway to promote dendritic cell maturation and remodel the immunosuppressive tumor microenvironment in liver cancer.