Central Hospital of Wuhan

Lung cancer (LC) causes large amount of cancer death worldwide. As the most common and aggressive type of LC, the molecular mechanisms in LUAD (Lung Adenocarcinoma) remain unclear. In order to find novel potential molecular targets for improving the prognosis of LUAD, we obtained gene information of LUAD patients from The Cancer Genome Atlas (TCGA) and identified hub genes through weighted gene co-expression network analysis (WGCNA). We selected the top 25% of total 5945 differently expressed genes (DEGs) and established 16 modules. The purple module was highly associated with tumor stage and chosen as key module. Further analysis revealed that the level of 6 hub genes (TRIM31, DKK1, FAM83A, RHOV, S100P and TSKU) were negatively relevant to survival rate but positively correlated with advanced tumor stage. Immunohistochemistry (IHC), western blot (WB) and reverse transcription-quantitative PCR (RT-qPCR) verified the high expression of TRIM31 in LUAD. Loss-of-function assays indicated TRIM31 accelerated viability, proliferation and metastasis of LUAD cells. According to the UbiBrowser website, TRIM31, as an E3 ubiquitin ligase, may be involved in the ubiquitination of P53, an important tumor suppressor. Co-immunoprecipitation verified the interaction between TRIM31 and P53. More importantly, the degradation rate of P53 was slowed when TRIM31 was knockdown. Further immunoblot assays revealed that TRIM31 promoted the ubiquitination and degradation of P53. P53 could inhibit the expression of SLC7A11 and was regarded as an important regulator of ferroptosis. Ferroptosis analysis showed that TRIM31 knockdown decreased cell viability and GSH, but increased ROS, MDA and iron, which could reverse by knockdown of P53. Above results displayed that TRIM31 effected ferroptosis level via P53. In addition, website prediction showed that BATF was a transcription factor of TRIM31, and experiments confirmed that BATF could indeed promote the transcription of TRIM31. Taken together, the data demonstrated that TRIM31 promoted LUAD progression by inhibiting ferroptosis via the TRIM31/P53/SLC7A11 axis.

Kinesio taping, as a non-invasive, non-pharmacological elastic taping technique, has become increasingly popular in sports injury management due to its safety, non-restrictive nature, and lack of interference with joint movement. This study aims to evaluate whether conventional comprehensive rehabilitation combined with kinesio taping can more effectively improve rehabilitation outcomes in military personnel following surgery for recurrent shoulder dislocation caused by training injuries. Sixty military personnel with recurrent shoulder dislocation caused by training injury were selected and randomly divided into a study group and a control group, with 30 cases in each group.The control group received conventional rehabilitation therapy, including physical agent modalities (ultrasound), cryotherapy and exercise therapy. The study group received, in addition to all treatments administered to the control group, shoulder-specific kinesio taping (using I-strip, Y-strip, and fan-cut strips applied over the supraspinatus muscle, deltoid muscle, and glenohumeral joint area, changed daily). After 6 weeks of treatment, shoulder joint range of motion, UCLA(The university of California at Los Angeles shoulder rating scale)score, and Constant-Murley score were compared between the two groups. After treatment, the range of motion for shoulder flexion, abduction, internal rotation, external rotation, and extension increased in both groups compared to pre-treatment values (P < 0.05). Similarly, the UCLA and Constant-Murley scores also improved significantly in both groups (P < 0.05). The study group demonstrated significantly greater improvements in shoulder joint mobility (P < 0.05), UCLA score (P < 0.05), and Constant-Murley score (P < 0.05) compared to the control group. Conventional comprehensive rehabilitation therapy combined with kinesio taping can better improve the range of motion and activities of daily living in postoperative military personnel with recurrent shoulder dislocation caused by training injury.

Community-acquired pneumonia (CAP), particularly severe CAP (SCAP), poses a significant clinical challenge with high mortality. MicroRNAs, including miR-342-3p, have been implicated in various pulmonary diseases, suggesting a potential role in SCAP. To examine the expression, functional mechanisms, and clinical relevance of miR-342-3p in SCAP. Bioinformatic analysis was performed on two independent GEO datasets (GSE196399 and GSE136390). Serum miR-342-3p levels were measured in a clinical cohort of 109 SCAP patients and 109 healthy controls by RT-qPCR, and its correlation with clinical prognosis was analyzed. An in vitro pneumonia model was established using LPS-stimulated MRC-5 cells. Gain-of-function experiments of miR-342-3p were achieved through mimic transfection. MiR-342-3p's involvement in inflammation, cytotoxicity, and pyroptosis was assessed via ELISA, western blot, CCK-8, and LDH assays. The interaction between miR-342-3p and EP300 was confirmed by dual-luciferase reporter and RNA pull-down assays, and its functional role was confirmed through rescue experiments. The downregulation of miR-342-3p in SCAP patient serum correlated with increased mortality. In vitro, miR-342-3p overexpression reduced LPS-induced inflammation and pyroptosis. Bioinformatics analysis confirmed that histone acetyltransferase EP300 is a candidate target gene for miR-342-3p. Mechanistically, miR-342-3p directly targeted and negatively regulated EP300. Overexpression of EP300 abolished the anti-inflammatory and anti-pyroptotic effects of miR-342-3p through the activation of NF-κB p65. MiR-342-3p acts as a protective factor in SCAP by targeting EP300 to inhibit inflammation and pyroptosis. These results indicate the potential of miR-342-3p as a biomarker and therapeutic target in SCAP.

BackgroundNuclear protein in testis (NUT) carcinoma is an extremely rare and highly aggressive epithelial malignancy driven by NUTM1 rearrangements. Sinonasal involvement is uncommon and often presents with non-specific clinical and radiologic features, leading to delayed diagnosis. Optimal management remains undefined, and outcomes are poor when complete resection is not feasible.Case presentationA 31-year-old man developed progressive numbness and swelling of the left cheek after tooth extraction. Imaging revealed a soft-tissue mass involving the left maxillary sinus with adjacent maxillofacial soft-tissue extension. Endoscopic biopsy demonstrated a poorly differentiated carcinoma with diffuse punctate nuclear NUT expression, high proliferative index (Ki-67 ~50%), and PD-L1 expression in both tumor cells and immune cells. ^18F-FDG PET-CT showed no regional or distant metastases. Given unresectability, the patient received toripalimab (240 mg) combined with docetaxel and cisplatin every 3 weeks. MRI after three cycles showed early radiologic improvement, and further tumor regression was observed after six cycles, consistent with a partial response. The patient subsequently continued on toripalimab-based maintenance therapy with ongoing stable residual disease at the latest follow-up (approximately 5 months after therapy initiation and 6 months from diagnosis).ConclusionTo our knowledge, this is the first reported case of toripalimab-based chemoimmunotherapy demonstrating an early partial response and short-term disease control in unresectable maxillary sinus NUT carcinoma. It supports the potential role of PD-1 blockade integrated with platinum–taxane chemotherapy as a component of multimodal management for sinonasal NUT carcinomas.

Axial spondyloarthritis (axSpA) is an inflammatory disease marked by chronic low back pain, with a global average diagnostic delay of 6.7 years. Early diagnosis is crucial for improving prognosis and reducing disability rates, yet primary care physicians (PCPs) may find it challenging to ensure timely recognition and referrals. This study developed and validated Spondyloarthritis Agents (SpAgents), an early diagnostic system based on a multi-agent framework integrating large language models (LLMs) and imaging models. The SpAgents framework includes PlannerAgent, DataAgent, ToolAgent, and DoctorAgent, supported by long-term memory for dynamic knowledge updates. We enrolled 596 patients, dividing 545 from one hospital into a training dataset (n = 359) and a validation dataset (n = 186), along with an independent cohort of 51 patients from five additional hospitals for testing. SpAgents demonstrated strong diagnostic performance, achieving sensitivity of 0.8615 and specificity of 0.8000 during validation, and 0.9375 and 0.7368 during testing. SpAgents exhibited significantly higher sensitivity (0.9400) and accuracy (0.8600) than both PCPs and junior rheumatologists, with overall performance equivalent to that of senior rheumatologists. Under SpAgents-assisted diagnosis, both PCPs and junior rheumatologists showed marked improvements in sensitivity and accuracy. SpAgents effectively enhance early axSpA identification among PCPs, offering an innovative solution to reduce diagnostic delays.

Initially characterized as a component of the extracellular matrix (ECM) in cartilage, cartilage intermediate layer protein 2 (CILP2) is now recognized as a pleiotropic secretory protein with far-reaching roles in physiology and disease. This review synthesizes evidence establishing CILP2 as a key modulator at the nexus of metabolic dysfunction, cancer, and other pathologies. Genomic studies have firmly established the NCAN-CILP2 locus as a hotspot for genetic variants influencing dyslipidemia and cardiovascular risk. Functionally, CILP2 is upregulated by metabolic stress, including high glucose and oxidatively modified LDL (oxLDL), and actively contributes to pathologies such as dyslipidemia, diabetes, and sarcopenia by impairing glucose metabolism and mitochondrial function. Its role extends to fibrosis and neurodevelopment, promoting hypertrophic scar formation and neurogenesis through interactions with ATP citrate lyase (ACLY) and Wnt3a, respectively. More recently, CILP2 has emerged as an oncoprotein, overexpressed in multiple cancers, including pancreatic ductal adenocarcinoma and colorectal cancer. It drives tumor proliferation and metastasis and correlates with tumor microenvironment remodeling through mechanisms involving Akt/EMT signaling and immune infiltration. The dysregulation of CILP2 in patient serum and its correlation with disease severity and poor prognosis highlight it as a promising biomarker and a compelling therapeutic target across a spectrum of human diseases.

Circadian rhythms have been reported in a variety of physiological processes that may influence cardiovascular disease, while little is known about the effects of circadian rhythm-related genes (CRRGs) on acute myocardial infarction (AMI). The genome-wide association study (GWAS) data of AMI (ukb-a-533) and expression quantitative trait loci (eQTL) data of CRRGs were downloaded from the integrative epidemiology unit Open GWAS database. The relationship between the CRRGs and AMI was assessed by the two-sample Mendelian randomization (TSMR) analysis. The hub genes that could directly affect AMI were identified based on the inverse variance weighted (IVW) algorithms. Subsequently, the TSMR results were evaluated via sensitivity analyses and MR-Steiger filtering. Then, the expression in immune cells and tissues was predicted from the Human Protein Atlas and Genotype-Tissue Expression databases. Finally, the molecular regulatory networks were generated based on the hub genes. In TSMR results, NR1H3 (IVW: odds ratio (OR) = 1.0009, 95% confidence interval (CI) = 1.0005–1.0013), SREBF1 (IVW: OR = 1.0015, 95% CI = 1.0007–1.0022), SIRT1 (IVW: OR = 1.0007, 95% CI = 1.0001–1.0013), and HIF1A (IVW: OR = 1.0022, 95% CI = 1.0004–1.0039) were risk factors for AMI patients, while NCOA1 (IVW: OR = 0.9984, 95% CI = 0.9969–0.9998) was a protective factor for AMI patients (P < .05). Importantly, the 5 hub genes could affect AMI occurrence in one direction. The expression levels of HIF1A, NCOA1, and SREBF1 were highest in neutrophils than the other immune cells. Also, HIF1A and SREBF1 had higher expression in the heart (left ventricle and atrial appendage) and artery (aorta, tibial, and coronary). Moreover, the transcription factor, NFKB1, might regulate the hub genes except for NCOA1. Generally, 4 risk genes (NR1H3, SREBF1, SIRT1, and HIF1A) and 1 protective gene (NCOA1) associated with circadian rhythm for AMI patients were identified, providing new insights into the diagnosis and treatment of AMI.

Ligustilide is a natural benzoquinone derivative with many pharmacological properties, including anticancer and anti-inflammatory activities. Here, we investigated the antitumor efficacy of ligustilide in gastric cancer. MKN74 and AGS cells were treated with 20, 60, and 100 µM ligustilide. The antitumor efficacy of ligustilide was studied with MTT assays, colony formation assays, and flow cytometry. Apoptosis-, endoplasmic reticulum stress-, and autophagy-associated proteins were examined by immunoblotting and immunofluorescence. JC-1 staining was used to detect mitochondrial membrane potential in cancer cells. Tumor-bearing mice were intraperitoneally injected with 5 mg/kg ligustilide. Tumor weight and tumor volume were measured after 20 days of administration. We demonstrated that ligustilide suppressed gastric cancer cell proliferation by inducing cell cycle arrest and apoptosis. Mechanistically, ligustilide disrupted mitochondrial function by increasing the Bax/Bcl-2 ratio, triggering cytochrome c release into the cytoplasm, and activating caspase-3 and PARP cleavage, ultimately leading to mitochondrial membrane potential loss. Furthermore, ligustilide enhanced autophagy, as evidenced by elevated LC3-II/LC3-I ratio and ATG5 expression, accompanied by reduced p62 levels. This autophagic response was mediated through endoplasmic reticulum stress via the PERK-eIF2α-CHOP pathway. Notably, the proapoptotic effects of ligustilide were attenuated by 4-phenylbutyric acid (an ER stress inhibitor) or 3-methyladenine (an autophagy inhibitor). Consistent with in vitro findings, 4-phenylbutyric acid also abrogated the antitumor efficacy of ligustilidein vivo by concurrently suppressing apoptosis and autophagy.Overall, ligustilide triggers mitochondrial dysfunction, autophagy, and endoplasmic reticulum stress, collectively promoting gastric cancer cell death and suppressing survival.