Fuzhou Pulmonary Hospital of Fujian

Myocardial ischemia is the common etiology of heart failure (HF). However, the precise molecular mechanisms that govern the ischemic myocardium into HF remain poorly defined. Selective accumulation of succinate is a hallmark of ischemia. Succinate is a predominant regulator of protein succinylation modification. The present study unravels the novel role of succinate in ischemia-induced HF via succinylation. A clinical cohort study that was performed on 1554 Chinese patients with coronary artery disease (CAD) indicated that serum succinate levels were positively correlated with the increase of HF biomarker, decrease of left ventricular ejection fraction (LVEF), incidence of HF, and risk of death. In cardiomyocytes deprived of oxygen and glucose (OGD) and in mice subjected to ligation of the left anterior descending coronary artery (LAD), succinate levels and global protein succinylation were elevated. Succinylation proteomic analysis identified the α-subunit of mitochondrial ATP synthase (ATP5A1) as an important succinylated protein, and K531 was identified as the functional succinylation site. Ablation of succinylation by the ATP5A1-K531R mutant ameliorated OGD-induced cardiomyocyte death, mitochondrial dysfunction and energy metabolic dysfunction. K531R delivered by cardiac-specific adeno-associated virus (AAV9) achieved short-term cardioprotective effects against ischemic injury, and exerted prolonged protective effects against HF development. Sirtuin 5 was confirmed as a desuccinylase of ATP5A1, whereas carnitine palmitoyltransferase 1A (CPT1A) was recognized as a trans-succinylase. Mechanistically, succinylation of ATP5A1-K531 impeded the assembly of ATP synthase and impaired its activity. Elevated succinate potentially serves as a risk predictor of HF. Targeting desuccinylation of ATP5A1-K531 might be a promising therapeutic strategy.

<p>In the published version of this article [1], the author identified the error in the reported funding grant number. This has now been corrected. </p> <p> The original article can be found online at: https://www.eurekaselect.com/article/150528ss </p> <p> Details of the error and a correction are provided here. </p> <p> ORIGINAL: </p> <p> FUNDING </p> <p> This research was financially supported by the National Natural Science Foundation of China (grant number: 321600034), the Guangxi Natural Science Foundation of China (grant number: 2021GXNSFAA075026), and the Baise Science and Tech-nology project of Guangxi, China (grant numbers: 20212346 and 20224146). </p> <p> CORRECTED: </p> <p> FUNDING </p> <p> This research was financially supported by the National Natural Science Foundation of China (grant number: 32160034), the Guangxi Natural Science Foundation of China (grant number: 2021GXNSFAA075026), and the Baise Science and Tech-nology project of Guangxi, China (grant numbers: 20212346 and 20224146). The authors apologize for any inconvenience caused.</p>

Central nervous system tuberculosis (CNS-TB) remains a critical clinical challenge with high mortality, and its underlying immunopathological mechanisms have not been fully elucidated. This study aimed to investigate age-dependent variations in T lymphocyte subsets among CNS-TB patients and their clinical implications. In this retrospective study, we analysed 862 patients with extrapulmonary tuberculosis (EPTB) admitted to Fuzhou Pulmonary Hospital between April 2018 and April 2024. The cohort comprised 177 CNS-TB patients and a control group of 685 non-central nervous system extrapulmonary tuberculosis (non-CNS EPTB) patients. We comprehensively compared demographic characteristics, medical history, nutritional parameters, T lymphocyte subsets (CD3+, CD4+, CD8+, and CD45+), and neutrophil-to-lymphocyte ratio (NLR) between groups, with detailed age stratification and correlation analyses. Baseline characteristics, medical history, and nutritional parameters were not significantly different between the groups. CNS-TB patients exhibited markedly reduced T lymphocyte counts, which were most pronounced in the 25–54 year age group (CD3+: 735.5 vs 1010.0 cells/μL, P < 0.001; CD4+: 389.0 vs 576.0 cells/μL, P < 0.001; CD8+: 285.5 vs 358.0 cells/μL, P = 0.013; and CD45+: 1109.5 vs 1448.0 cells/μL, P < 0.001). These differences persisted but attenuated in the 55–64 years age group, with no significant disparities in the 18–24 years and ≥ 65 years age groups. Age-stratified analysis revealed a progressive NLR increase, peaking in patients ≥ 65 years (7.07 vs 4.67, P = 0.010), with diminishing intergroup differences. Correlation analysis revealed strong positive correlations among T-lymphocyte subsets (r = 0.52–0.96, P < 0.001), significant positive correlations with lymphocyte counts (r = 0.52–0.71, P < 0.001) and moderate negative correlations with the NLR (r = − 0.27– -0.37, P < 0.001). CNS-TB patients display characteristic T lymphocyte depletion and elevated NLRs, with dynamic age-dependent immune characteristics most prominent in immunocompetent adults. Lymphocyte counts can predict T-cell subset levels, whereas NLR values can predict inflammatory and immune response states. This study provides the first comprehensive demonstration of age-dependent immune characteristics in CNS-TB patients, offering a theoretical foundation for age-stratified immune monitoring strategies. Not applicable.

<title>Abstract</title> Background The prognostic role of nutrition–inflammation indices in esophageal squamous cell carcinoma (ESCC) requires further investigation. We developed the HALP–CONUT Integrated Score (HCIS) and evaluated its ability to predict survival and postoperative complications in locally advanced ESCC patients undergoing neoadjuvant therapy. Methods This multicenter retrospective study analyzed 410 patients. HCIS was calculated by integrating the HALP index and CONUT score. Patients were stratified into risk groups. Survival was analyzed using Kaplan–Meier and Cox regression. Logistic regression assessed associations with complications and pathologic complete response (pCR). Predictive performance was evaluated using ROC curves, C-index, and decision curve analysis. Results Patients with high HCIS scores had significantly worse overall survival (OS) compared with those in lower-risk groups (p &lt; 0.001). Multivariate Cox analysis confirmed HCIS as an independent prognostic factor for OS (HR 4.59, 95% CI 2.64–7.97, p &lt; 0.001). Higher HCIS scores were also independently associated with increased risk of major postoperative complications (OR 7.144, 95% CI 3.698–13.813, p &lt; 0.001) and a lower likelihood of achieving pCR (OR 6.470, 95% CI 3.577–12.40, p = 0.005). Predictive models incorporating HCIS demonstrated superior discrimination compared with models based on HALP or CONUT alone (AUC for OS: 0.789 vs 0.711 and 0.703, respectively). Conclusion HCIS is a robust biomarker that integrates hematologic, nutritional, and inflammatory parameters. It independently predicts survival, postoperative complications, and pCR, providing a valuable tool for risk stratification and individualized treatment planning in locally advanced ESCC.

Premature discontinuation and non-publication of clinical trials constitute a waste of limited public resources and create ethical dilemmas for trial participants, clinicians, and the public. This study investigated the rates of discontinuation and non-publication of clinical trials related to small-cell lung cancer (SCLC) treatment. We conducted a cross-sectional review of ClinicalTrials.gov to screen clinical trials examining anticancer therapies for SCLC between 2006 and 2020. Discontinuation was determined by recruitment status and a comparison between expected and actual enrollment sizes. The publication status was determined through a systematic search of PubMed, Embase, and Google Scholar. The study included 154 clinical trials. Of these, 79 (51.3%) were prematurely discontinued, and 27 were discontinued for preventable reasons (i.e., poor recruitment, organizational/strategic reasons, and limited resources). Multicenter recruitment (OR 0.227, 95% CI 0.077-0.673, P = 0.007) and Asian principal investigators (OR 0.324, 95% CI 0.114-0.924, P = 0.035) were independently associated with a reduced probability of premature discontinuation. In contrast, industry-funded clinical trials were independently associated with a reduced probability of preventable discontinuation (OR 0.237, 95% CI 0.080-0.698, P = 0.009). To date, 43 of the 154 trials (27.9%) remained unpublished. When considering reasons for discontinuation, preventable discontinuation (OR 0.044, 95% CI 0.014-0.144, P < 0.001) and industry funding (OR 0.118, 95% CI 0.031-0.448, P = 0.002) were independently associated with a reduced probability of publication, whereas multicenter (OR 6.302, 95% CI 1.783-22.271, P = 0.004) and international recruitment (OR 5.358, 95% CI 1.467-19.566, P = 0.011) were independently associated with an increased probability of publication. Premature discontinuation and non-publication are common in SCLC-related clinical trials and warrant further attention.

BackgroundPulmonary cryptococcosis (PC) can appear as nodules or masses on chest imaging, resembling lung cancer. Multiple nodules may be misdiagnosed as metastatic cancer, whereas solitary nodules may be mistaken for lung cancer and removed surgically. Reports of PC coexisting with lung cancer are rare, mostly limited to case reports. This retrospective case series study screened 46 cases of nodular PC coexisting with lung cancer from 22 tertiary hospitals across China to explore the potential imaging manifestations and clinical characteristics of this patient population.MethodsA total of 4,763 cases of PC were identified from the pathology systems of multiple hospitals. A further search for keywords such as “cancer” or “malignancy” from the above cases identified 70 cases that met the conditions simultaneously. The exclusion of cases that did not meet the screening criteria resulted in the final screening of 46 cases.ResultsWe observed four types of imaging manifestations of nodular PC coexisting with lung cancer—type I: solitary nodule (n=6), type II: ground-glass nodules + solid nodules (n=14), type III: multiple nodules (≥2) (n=18), and type IV: new nodules after lung cancer surgery (n=8). Most of the cases were coexisting with lung adenocarcinoma, had an insidious onset, and lacked typical clinical symptoms. The most common presenting symptoms included cough (15/46 cases, 32.6%), sputum production (8/46, 17.4%), and fever (3/46, 6.5%), whereas hemoptysis (1/46, 2.2%) and chest pain (2/46, 4.3%) were less frequent. Laboratory tests showed no significant differences in white blood cells (WBC, P=0.316), liver function (P=0.851), and serum creatinine (Scr, P=0.086) between the 2 based on the presence or absence of underlying diseases.ConclusionsMultiple pulmonary nodules should raise suspicion for PC alongside lung cancer, not just metastasis. New nodules after lung cancer surgery may indicate PC rather than recurrence.

Endoplasmic reticulum (ER) stress plays a pivotal role in tumor progression. As research in tumor biology advances, the relationship between ER stress and tumor initiation, development, and immune regulation has increasingly attracted attention. ER stress activates the unfolded protein response (UPR), thereby affecting key processes in tumor cells, including metabolism, proliferation, invasion, metastasis, and drug resistance. Moreover, it modulates tumor immune responses by regulating the functions of immune cells within the tumor microenvironment. This review consolidates the concept of ER stress as a central signaling hub that dictates cell fate and extensively remodels the tumor ecosystem. From a clinical perspective, this understanding provides a strong rationale for therapeutically targeting the UPR, suggesting that combining ER stress modulators with immunotherapy represents a promising strategy to overcome therapeutic resistance and improve patient outcomes.