Yancheng First People's Hospital

Esophageal cancer is a highly lethal malignancy of the digestive system, and its underlying molecular mechanisms remain incompletely understood. Protein palmitoylation, a critical lipid-based post-translational modification, has recently emerged as a key regulatory process implicated in various cancers. ZDHHC2, a prominent member of the palmitoyltransferase family, exhibits aberrant expression and functional dysregulation across multiple tumor types, suggesting its potential involvement in esophageal carcinogenesis. In this study, we utilized data from genome-wide association studies (GWAS) and applied a two-sample Mendelian randomization approach to systematically evaluate the causal relationship between ZDHHC2 and esophageal cancer. Moreover, we explored the indirect mediating role of metabolites in this association. Our analysis revealed a significant positive correlation between elevated ZDHHC2 expression and increased risk of esophageal cancer (OR = 1.178, P = 0.031). Notably, the metabolite N-acetylaspartylglutamate (NAAG) was identified as a partial mediator in this relationship, accounting for 6.1% of the total effect (P = 0.038). As a key derivative in glutamate metabolism, NAAG is implicated in tumor metabolism, immune suppression, and signal transduction. These findings suggest that the ZDHHC2–NAAG axis may represent a critical mechanism underlying metabolic reprogramming and immune evasion in esophageal cancer, providing new insights into its pathogenesis and potential therapeutic targets.

[Objective] To investigate the variations and clinical relevance of blood levels of β2-microglobulin (β2-MG), interleukin (IL)-2R, IL-10, and lactate dehydrogenase (LDH) in patients with lymphoma who have various circumstances. [Methods] A total of 200 lymphoma patients diagnosed in this hospital from 2021--2025 were selected as the lymphoma group. Serum samples and data such as age, sex, lymphoma tissue, immunological type, clinical stage, bone marrow infiltration, and Epstein–Barr virus (EBV) infection were collected. During the same period, serum samples and data from 80 healthy individuals who underwent physical examinations (the control group) were collected. The levels of serum LDH, β2-MG, IL-2R and IL-10. Changes in the levels of each index in lymphoma tissue, tissue immunological type, clinical stage, bone marrow infiltration, and Epstein–Barr virus (EBV) infection and after effective treatment were analyzed. [Results] The lymphoma group had greater levels of serum LDH, β2-MG, IL-2R, and IL-10 than the control group (P<0.05). Serum LDH, β2-MG, and IL-2R levels were higher in EBV+ patients than in EBV-patients (P<0.05). Patients with clinical stage III–IV disease and bone marrow infiltration had higher serum levels of LDH, β2-MG, and IL-2R as the disease progressed compared to those with clinical stage Ⅰ–II disease without bone marrow infiltration (P<0.05). Patients with lymphoma had lower serum levels of β2-MG, IL-2R, IL-10, and LDH after treatment than they had before. [Conclusion] Monitoring the changes in the serum levels of LDH, β2-MG, IL-2R and IL-10 has important clinical value for the auxiliary diagnosis of lymphoma patients, EBV infection, clinical staging, therapeutic effects and prognostic evaluation.

Spinal cord injury (SCI) causes severe trauma to the central nervous system (CNS), involving complex pathological processes such as oxidative stress, inflammation, demyelination, and scar formation. During SCI progression, ongoing myelin degeneration leads to the release of myelin debris, which directly inhibits neural regeneration and impairs functional recovery following the injury. Moreover, bone marrow-derived macrophages (BMDMs) infiltrate the injured site and extensively phagocytose myelin debris, transforming into lipid-laden foam cells. These foam cells accumulate at the lesion core, significantly promoting fibrotic scar formation. To address these challenges, we developed a composite scaffold consisting of a foam cell membrane-coated polycaprolactone (PCL) nanofiber membrane that was integrated with a dual-matrix human acellular amniotic membrane (HAAM) hydrogel. A comprehensive evaluation combining material characterization, in vitro assays, and in vivo assessment using a Sprague–Dawley rat spinal cord defect model demonstrated that the scaffold retains the bioactive properties of HAAM, effectively clearing myelin debris and mitigating foam cell accumulation while concurrently promoting neural regeneration following SCI. The proposed novel biomaterial-based strategy offers a promising approach to addressing the persistent accumulation of myelin debris after SCI.

Abstract Background: Sepsis is a leading cause of maternal mortality. Diagnosis in pregnancy is often delayed by non-specific presentation and legitimate caution regarding diagnostic imaging.This case illustrates a compounded diagnostic challenge: septic shock in a migrant patient, where unfamiliar, endemic comorbidities obscured the typical clinical picture. Case presentation: An 18-year-old primigravida at 27 weeks’ gestation presented with fever and mild respiratory symptoms, rapidly progressing to septic shock. Initial labs revealed severe microcytic anemia (Hb 59 g/L), marked hyperbilirubinemia, and leukocytosis. A low-dose abdominopelvic CT, crucial for source identification, revealed right-sided obstructive uropathy. This led to a diagnosis of obstructive pyelonephritis as the septic focus, managed with urgent ureteral stenting and antibiotics. Further investigation unmasked two underlying conditions contributing to her severe anemia: homozygous β-thalassemia intermedia and chronic Trichuris trichiura infection. The jaundice was attributed to sepsis-induced hepatocellular dysfunction. Following source control, transfusions, and supportive care, both maternal and fetal conditions stabilized. Conclusion: This case underscores that in pregnant patients with sepsis and atypical laboratory findings, timely imaging for source control is paramount. It also highlights the critical need to consider region-specific hereditary and parasitic diseases in the differential diagnosis for migrant populations, as these can significantly complicate the clinical presentation and management.

Primary central nervous system diffuse large B-cell lymphoma (PCNS-DLBCL) is a rare form of non-Hodgkin lymphoma with a notably poor prognosis. This study aimed to identify new prognostic factors for improved prognostic stratification in PCNS-DLBCL. A total of 85 PCNS-DLBCL cases from three hospitals were retrospectively analyzed. Disease progression within 24 months (POD24) and its risk factors were investigated, and a prognostic model for predicting POD24 was constructed. The median overall survival (mOS) and median progression-free survival (mPFS) for the entire cohort were 48.54 months and 39.09 months, respectively. Survival analysis indicated that age ≥ 65 years (HR = 4.05, P = 0.008), non-responsive disease (HR = 4.43, P = 0.004), and POD24 (HR = 25.22, P = 0.002) were independent poor prognostic factors for OS in PCNS-DLBCL. Further analysis revealed that independent risk factors for POD24 included elevated serum lactate dehydrogenase (LDH) levels (OR = 12.00, P = 0.03), elevated triglycerides (TG, OR = 4.88, P = 0.047), and non-responsive disease (OR = 9.39, P = 0.003). Subsequently, an “LDH-TG-Efficacy (LTE)” prognostic model for PCNS-DLBCL was constructed. The incidence of POD24 was significantly higher in the “LTE” high-risk group (≥ 1 point) compared to the low-risk group (0 points) (81.8% vs. 35%, P < 0.001). The receiver operating characteristic (ROC) curve determined that the area under the curve (AUC) for the “LTE” model was 0.828 (95% CI: 0.7282–0.927), with a sensitivity and specificity of 79.4% and 79.3%, respectively. Additionally, the prognosis of the “LTE” high-risk group was significantly worse. These findings demonstrated that POD24 might serve as an independent prognostic indicator for PCNS-DLBCL, and the “LTE” prognostic index may provide a reference for better identifying populations at risk for POD24.

Small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC) are the two main types of lung cancer. Signal transducer and activator of transcription 3 (STAT3) plays an oncogenic role in various malignancies, including lung cancer, and targeting STAT3 is currently being considered as a potential therapeutic approach. The expression of p-STAT3, STAT3, p-SRC, SRC, and apoptosis- and mitochondrial fission-related proteins was assessed through western blot analysis. The cellular events including cell proliferation, apoptosis and cell cycle, and cisplatin resistance were assessed via CCK8, colony formation assays, and flow cytometry. Mitochondrial oxidative stress was measured by DCFH-DA, JC-1, and oxygen consumption rate (OCR) kits. Network pharmacology combined with molecular docking was used to investigate the molecular targets of STAT3 inhibitor SH-4-54 in the treatment of SCLC. Xenograft mouse models were constructed to verify the in vivo impacts of SH-4-54, and related biochemical parameters were analyzed. STAT3 phosphorylation was upregulated in SCLC. The STAT3 inhibitor SH-4-54 inhibited cell proliferation, promoted cell apoptosis, induced cell cycle arrest, decreased cisplatin resistance, and reduced oxidative phosphorylation in mitochondria of SCLC cells. Additionally, it inhibited tumor growth in tumor-bearing mice. SRC functioned as a core target of SH-4-54, and its phosphorylation level was decreased by SH-4-54. YEEI peptide, an SRC activator, could reverse the in vitro impacts of SH-4-54 on ROS production, cell proliferation, apoptosis, and cell cycle. Our findings demonstrate that the STAT3 inhibitor SH-4-54 can target SRC to suppress the tumorigenesis and oxidative phosphorylation in SCLC.

BackgroundTriggering receptor expressed on myeloid cells 2 (TREM2) is a microglial receptor genetically linked to Alzheimer's disease (AD) and increasingly recognized as a key regulator of neuroinflammation, yet its global research landscape in AD remains unclear.ObjectiveIn the central nervous system, TREM2 expressed on microglia is closely related to the occurrence and development of AD and has been extensively studied in recent years. However, there is still a lack of bibliometric analysis regarding TREM2 and AD.MethodsWe searched in the Web of Science Core Collection (WoSCC) for articles published from January 1, 2000, to September 30, 2024. After a thorough screening process, we selected relevant information regarding TREM2 and AD. Subsequently, a comprehensive analysis was conducted on a total of 944 publications. The analysis utilized GraphPad Prism 9, CiteSpace6.1.6, VOSviewer1.6.19, the Online Analysis Platform of Literature Metrology, GeneMANIA and Metascape.ResultsA total of 944 publications from 2000 to 2024 met the inclusion criteria for this analysis. Over this period, research activity in TREM2 and AD has shown a consistent upward trend, with notable peaks in 2021 and 2022. The United States and China lead in the number of publications, with Washington University being the top research institution. Neurobiology of Aging is the most frequently cited journal in this field. Research has focused on key areas like molecular biology, genetics, and neuroimmunology. Critical keywords include microglia, inflammation, and genetic variants, while recent studies highlight emerging topics such as protein interactions, neurodegeneration, and cognitive impairment.ConclusionsThis study employs advanced bibliometric analysis tools and visualization techniques to clearly present the major research themes, development trends, and prospects of TREM2 in AD.

The online version contains supplementary material available at 10.1007/s13205-025-04663-1.

Folate receptor-⍺ (FR-⍺) is an attractive target for targeted therapy. Mirvetuximab soravtansine (MIRV) has been approved by the United States Food and Drug Administration (FDA) for treating adult patients with FR-⍺ positive, platinum-resistant epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer. Therefore, identifying and detecting FR-⍺ has become an essential part of precision medicine. This study aimed to evaluate the feasibility of detecting FR-⍺ protein expression in serous cavity effusions using cell blocks (CBs) and compare the results with surgical pathology biopsy or resection specimens. Furthermore, we investigated potential variations in FR-⍺ expression pre- and post-chemotherapy. Immunohistochemical (IHC) staining of FR-⍺ was performed on the serous cavity effusion specimens from 35 patients with epithelial ovarian cancer, along with matched surgical pathological (SP) biopsy or resection specimens, following the manufacturer's guidelines for IHC analysis. Positive staining was observed in 30 (85.7%) and 32 (91.4%) serous cavity effusion CB and tissue samples, respectively. A total of 31 (88.5%) tissue and 28 (80%) effusion CB samples exhibited moderate-to-strong FR-⍺ expression in at least 25% of tumor cells. A cutoff of 25% for FR-⍺ expression positivity was used to demonstrate high concordance (96.4%) between cytology CBs and tissue specimens. We recommend a cutoff of 75% viable tumor cells with moderate-to-strong membrane staining as "positive" in CBs for greater reliability, which aligns with FDA-approved criteria. A reasonable consistency was observed in FR-⍺ expression between the pre-treatment serous cavity effusion CB specimens and the new biopsy specimens obtained after multiline treatment. We demonstrated that serous effusion CB specimens may be effective for FR-⍺ biomarker detection; FR-⍺ maintains stable expression pre- and post-chemotherapy, and patients can benefit from MIRV.