Min Zhu

Lung adenocarcinoma (LUAD), a leading cause of cancer mortality, involves incompletely understood epigenetic-metabolic crosstalk. We identified ANP32E as a key regulator through multi-omics (TCGA, scRNA-seq) and clinical analyses, finding its overexpression correlates with poor prognosis. Functionally, ANP32E knockdown suppressed proliferation, migration, and glycolysis in LUAD cells (A549/H1975) and attenuated xenograft growth, while overexpression promoted tumorigenesis. Mechanistically, ANP32E transcriptionally upregulates histone demethylase KDM3B, reducing repressive H3K9me2 marks at the EGFR promoter to enhance EGFR transcription. This activates PI3K/AKT signaling, inducing inhibitory GSK3β phosphorylation. Combined with ANP32E-mediated GSK3β suppression, this dual inactivation liberates oncogenic glycolysis. Crucially, KDM3B silencing or EGFR inhibition (Cetuximab) abrogated ANP32E-driven phenotypes. High-throughput screening identified Penta-O-galloyl-β-D-glucose (PGG) as an ANP32E-targeting compound, with molecular dynamics confirming binding. PGG dose-dependently inhibited the ANP32E/KDM3B/EGFR axis in vitro and suppressed tumor growth in vivo. Thus, ANP32E drives LUAD progression via KDM3B/EGFR-mediated GSK3β inactivation, representing a prognostic biomarker and therapeutic target validated by PGG.

Myelolipoma is a rare benign tumor composed of mature adipose and hematopoietic tissue, most commonly occurring in the adrenal glands. Thoracic myelolipoma is extremely uncommon, particularly when originating in the lung or chest wall, and is frequently misdiagnosed due to its nonspecific clinical and radiological features. This study aimed to retrospectively characterize the clinical, imaging, pathological, and surgical features of thoracic myelolipoma and to conduct a comprehensive literature review to improve understanding of this rare entity. Thirteen cases of thoracic myelolipoma diagnosed at Tongji Hospital between October 2015 and January 2025 were retrospectively reviewed. Data collected included patient demographics, clinical presentation, imaging characteristics, surgical approach, histopathology, and outcomes. Additionally, a comprehensive literature review was conducted using PubMed, Web of Science, and the Cochrane Library, covering reports published from 1960 to 2025. Descriptive statistics were used for data analysis. Thirteen patients were included (mean age: 57.2 ± 8.0 years; 6 men). Nine patients (69.2%) presented with tumors in the posterior mediastinum, and four (30.8%) had tumors in the lung. Most lesions were well-circumscribed and incidentally detected. Eleven patients (84.6%) underwent uniportal video-assisted thoracoscopic surgery (VATS), and all cases were histopathologically confirmed as myelolipoma. No recurrence or metastasis was observed over a mean follow-up period of 40.5 ± 31.0 months. The literature review identified 71 additional cases with comparable clinical characteristics. Among the 33 patients with available follow-up, no recurrence or metastasis was reported. Thoracic myelolipoma is a rare, indolent tumor that is often discovered incidentally and is generally associated with a favorable prognosis following complete surgical resection. VATS represents a minimally invasive and effective approach, offering both diagnostic and therapeutic benefits. Conservative observation may be appropriate for asymptomatic patients with characteristic imaging findings. However, surgical intervention is recommended when clinical symptoms are present or malignancy cannot be ruled out. Further large-scale studies with extended follow-up are warranted to refine management strategies.

Despite advances in understanding the metabolic mechanisms of ferroptosis, the molecular events following lipid peroxide accumulation on the plasma membrane (PM) remain unclear. Herein, we identify TMEM16F as a ferroptosis suppressor at the executional phase. TMEM16F-deficient cells display heightened sensitivity to ferroptosis. Mechanistically, TMEM16F-mediated phospholipids (PLs) scrambling orchestrates extensive remodeling of PM lipids, translocating PLs at the lesion sites to reduce membrane tension, therefore mitigating the membrane damage. Unexpectedly, failure of PL scrambling in TMEM16F-deficient cells leads to lytic cell death, exhibiting PM collapse and unleashing substantial danger-associated molecule patterns. TMEM16F-deficient tumors exhibit decelerated progression. Notably, lipid scrambling inhibition synergizes with PD-1 blockade to trigger robust tumor immune rejection. The antiparasitic drug ivermectin enhances the responsiveness to PD-1 blockade by suppressing TMEM16F. Our findings uncover TMEM16F-mediated lipid scrambling as an anti-ferroptosis regulator by relocating PLs on the PM during the final stages of ferroptosis. Targeting TMEM16F-mediated lipid scrambling presents a promising therapeutic strategy for cancer treatment.

Background: Pulmonary benign metastasizing leiomyoma (PBML) is a rare condition characterized by histologically benign smooth muscle tumors occurring at extrauterine sites, often in women with a history of uterine leiomyoma. While PBML generally exhibits indolent behavior, its pathogenesis, management, and malignant potential remain unclear. Methods: This study retrospectively analyzes the clinical characteristics, imaging features, diagnostic approaches, pathological findings, treatment strategies, and outcomes of seven patients with PBML treated at our institution between January 2016 and May 2025. Results: Seven patients were included, with a mean age at diagnosis of 48.9 ± 5.6 years. Two patients presented with respiratory symptoms. Imaging revealed multiple bilateral pulmonary nodules in four patients and solitary nodules in three. Six patients were diagnosed via video-assisted thoracoscopic surgery, and one through computed tomography-guided percutaneous biopsy. Immunohistochemistry revealed positivity for SMA and Desmin in all cases, ER in six, and PR in five, with the Ki-67 labeling index ≤3% in six patients. One patient had a coexisting in situ mucinous adenocarcinoma within the PBML lesion. All had a history of uterine leiomyoma. After diagnosis, one patient received hormonal therapy, and another underwent right adnexectomy. The remaining patients were managed with surveillance without additional treatment. During follow-up, one patient developed distant organ metastasis. Conclusions: PBML is a rare, typically indolent condition with potential for metastasis. Accurate diagnosis relies on imaging, histopathology, and immunohistochemistry. This study reports a unique case of PBML coexisting with intratumoral in situ mucinous adenocarcinoma, a previously unreported finding that may broaden the known histopathological spectrum.

Background: Heart failure (HF) is a serious public health concern. Baicalin is one of the major active ingredients of a traditional Chinese herbal medicine, Huang Qin, which is used to treat patients with chest pain or cardiac discomfort. However, the underlying mechanism(s) of the cardioprotective effect of baicalin are still not fully understood. Methods: Isoprenaline injection or transverse aortic constriction-induced animal models and isoprenaline or angiotensin 2 administration-induced cell models of heart failure were established. Baicalin (15 mg/kg/day or 25 mg/kg/day) was administered in vivo, and 10 μM baicalin was administered in vitro. Potential pharmacological targets of baicalin and genes related to heart failure were identified via different databases, which suggested that PI3K–Akt may be involved in the effects of baicalin. Molecular docking was carried out to reveal the effect of baicalin on p85a. Results: We observed significant antihypertrophic and antifibrotic effects of baicalin both in vivo and in vitro. The mean cross-sectional area of cardiomyocytes recovered from 390 μm² in the HF group to 195 μm² in the baicalin-treated group. The area of fibrosis was reduced from 2.8-fold in the HF group to 1.62-fold in the baicalin-treated group. Baicalin displayed a significant cardioprotective effect via the inhibition of the PI3K signaling pathway by binding with five amino acid residues of the p85a regulatory subunit of PI3K. The combination treatment of baicalin and an inhibitor of PI3K p110 demonstrated a stronger cardioprotective effect. The mean ejection fraction increased from 54% in the baicalin-treated group to 67% in the combination treatment group. Conclusions: Our work identified baicalin as a new active herbal ingredient that is able to treat isoprenaline-induced heart dysfunction and suggests that p85a is a pharmacological target. These findings reveal the significant potential of baicalin combined with an inhibitor of PI3K p110 for the treatment of heart failure and support more clinical trials in the future.

Diabetic nephropathy (DN) is a renal microvascular complication caused by diabetes mellitus. One of the most typical characteristics of DN is glomerular mesangial cells (GMCs) proliferation. Stromal interaction molecule 1 (STIM1), a Ca²⁺ channel, is involved in many diseases. In this study, we investigated the role of STIM1 in the proliferation and fibrosis in high glucose (HG)-induced HBZY-1 cells. We found that the expression of STIM1 was increased in renal tissues of diabetic rat and HBZY-1 cells stimulated by HG. Downregulation of STIM1-mediated SOCE suppressed hyperglycemic cell proliferation and fibrosis by activating autophagy. In addition, the inhibitory effect of downregulating STIM1 on cells was blocked by autophagy inhibitor Bafilomycin A1 (BafA1). Moreover, this experiment also showed that STIM1 regulated autophagy, cell proliferation and fibrosis via PI3K/AKT/mTOR signal pathway. These results clarify the role of STIM1 in HBZY-1 cells and its mechanism, and provide a new target for the treatment of DN.

Background: Upper esophageal cancer (UEC) is rare in both Eastern and Western countries. The epidemiological characteristics and long-term survival of UEC patients are less known. In addition, the choice of optimal treatment for UEC has been controversial.Methods: Cases of UEC (C15.3 and C15.0) arising during the period from 1973 to 2013 were identified and selected using the SEER database. Student's t-test and Pearson's chi-square test were used to compare the differences in parameters among different groups. Esophageal cancer-specific survival (ECSS) and overall survival (OS) rates were calculated by using the Kaplan–Meier method. Cox proportional hazard regression was used to analyze predictive factors.Results: In the past 40 years, the cases of UEC have gradually increased, and the proportion of adenocarcinoma (AD) has gradually increased (from 3.6% to 11.8%, p < 0.001). There has been a significant increase (1973–1982 vs. 2004–2013) in median OS (7 months vs. 10 months, p < 0.001) and median ECSS (7 months vs. 11 months, p < 0.001) among UEC patients from 1973 to 2013. For the impact of different treatments, the results showed that the ECSS and OS of surgery without radiation (SWR) and radiation plus surgery (R+S) were superior to those of radiation without surgery (RWS). Subgroup analysis showed that ECSS and OS were highest among patients treated with SWR compared with R+S and RWS for patients with localized disease. For regional disease, ECSS and OS were highest among patients with R+S compared with SWR or RWS. Among patients with regional-stage squamous cell carcinoma (SCC), OS was higher with neoadjuvant radiotherapy or adjuvant radiotherapy compared with SWR. Multivariate analysis showed that radiotherapy sequence was dependently associated with OS among patients with regional-stage SCC.Conclusion: Although the long-term survival of UEC remains poor, it has gradually increased since 1973. This should be closely related to the improvement of medical care over the past 40 years. Different treatment methods have a great influence on the long-term survival of UEC. For localized diseases, surgery may be a better choice. For regional disease, surgery plus adjuvant or neoadjuvant radiotherapy may be more beneficial to improve the long-term prognosis of UEC patients.