ObjectiveTo evaluate the anti-inflammatory activity of the novel magnolol ester derivative YW and to investigate its effects on chondrocyte senescence and preliminary mechanisms. MethodsMagnolol and p-methylbenzoic acid were used as raw materials to synthesize the magnolol ester derivative YW （Molecular Formula： C₂₆H₂₄O₃， Molecular Weight： 384.17， HPLC Purity >96%） via DCC/DMAP-catalyzed esterification. Cytotoxicity was assessed using the CCK-8 assay. A lipopolysaccharide （LPS）-induced RAW264.7 macrophage activation model and an interleukin-1β （IL-1β）-induced rat primary chondrocyte model were established. The release and mRNA expression of inflammatory factors including nitric oxide （NO）， IL-1β， tumor necrosis factor-alpha （TNF-α）， and IL-6 were detected by enzyme-linked immunosorbent assay （ELISA）， Griess reagent method， and quantitative real-time PCR （RT-qPCR）. The expression of senescence markers such as inducible nitric oxide synthase （iNOS）， pro-interleukin-1β （pro-IL-1β）， lysine acetyltransferase 7 （KAT7）， cyclin-dependent kinase inhibitor 1A （p21）， and cyclin-dependent kinase inhibitor 2A （p16）， as well as proteins related to chondrocyte extracellular matrix synthesis and catabolism， were analyzed by Western blot （WB）. Molecular docking was performed using Discovery Studio 2019 to validate target binding. ResultsYW exhibited no significant cytotoxicity at concentrations ≤20 μmol/L. YW concentration-dependently inhibited LPS-induced macrophage inflammatory cytokine release， significantly downregulated iNOS， Pro-IL-1β protein， and inflammatory cytokine mRNA expression （P<0.01）. YW stably bound to KAT7 protein （binding energy： -94.2 kcal/mol）； YW downregulated KAT7 and aging marker protein expression in naturally aged and IL-1β-induced chondrocyte models （P<0.01）； YW regulated chondrocyte matrix synthesis and catabolic protein expression in IL-1β-induced chondrocytes （P<0.01）. ConclusionYW inhibits macrophage activation and inflammatory cytokine release while downregulating KAT7 and senescence marker protein expression in chondrocytes， thereby blocking chondrocyte senescence.

ObjectiveTo investigate the association between endothelin receptor type A gene （EDNRA） and congenital bilateral absence of the vas deferens （CBAVD）. MethodsThis case-control study consisted of 124 subjects with CBAVD and 100 fertile controls.Two single nucleotide polymorphisms （SNPs： rs5335 and rs1801708） in the EDNRA gene were genotyped via PCR， PCR-RFLP analysis， and direct sequencing. ResultsNo significant differences existed between EDNRA polymorphisms and CBAVD phenotype （rs1801708： P=0.220 2， 0.163 2； rs5335： P=0.805 8， 0.818 6）. However， the rs1801708-rs5335 haplotype AG was notably associated with an increased risk of CBAVD （P=0.008 6， OR=2.178， 95% CI： 1.207-3.929）. A significantly protective effect of rs1801708-rs5335 haplotype GG on CBAVD （P=0.038 5， OR= 0.671， 95% CI： 0.460-0.980） was observed. After Bonferroni correction， the result for haplotype A-G remained significant （P =0.008 6<0.012 5）， while haplotype G-G was not significant. ConclusionThe rs1801708-rs5335 AG haplotype of EDNRA is a potential risk factor for CBAVD development in Han Chinese.

Objective: To explore the related factors of college students social network addiction based on problem behavior theory, so as to provide a basis for improving social networking addiction in this population. Methods: From May to June 2023, a method combining convenient sampling and cluster random sampling was used to select 1 768 college students from five universities in Shanghai for a questionnaire survey on social networking addiction, self esteem, loneliness, depressive symptoms, social support, interpersonal needs, sense of distress and frustration; at the same time, the physical exercise, smoking and drinking of college students were investigated. Multivariate Logistic regression analysis was applied to explore the association between the three systems of the problem behavior theory (personality, behavior, and social environment) and social networking addiction among college students. Results: The score on the Social Network Addiction Tendency Scale was (21.08±6.29) among college students, and the detection rate of social networking addiction was 66.29%. After adjusting for gender, family economic status, parental divorce status, and whether being an only child, multivariate Logistic regression analysis showed that in the personality system, higher loneliness ( OR =1.66) and higher depressive symptoms ( OR =2.18) were associated with increased risk of social networking addiction among college students; in the behavior system, alcohol consumption ( OR =1.42) was associated with higher risk of soical networking addiction compared to non drinkers; and in the social environment system, low social support ( OR =1.43) was associated with increased risk of social networking addiction (all P <0.05). Conclusions The rate of social networking addiction among college students is relatively high, and the systems of personality, behavior, and social environment are all related to social network addiction. Providing social support, cultivating healthy lifestyle habits, and increasing interpersonal interactions may help reduce excessive dependence on social networking among college students.

Objective To evaluate the clinical efficacy of second-stage endovascular therapy for patients with aortic intramural hematoma (IMH) who developed progression of the distal hematoma into dissection-like changes after an initial procedure. Methods A retrospective analysis was conducted on patients at the University of Hong Kong-Shenzhen Hospital from July 2020 to December 2022. These patients had previously undergone a first-stage procedure to treat the proximal lesion of an IMH. However, follow-up examinations revealed a persistent distal hematoma, the presence of a distal entry tear, and progression of the hematoma into localized or extensive dissection-like changes, which could be accompanied by localized contrast enhancement. These patients then underwent a second-stage stent-graft intervention. The initial procedures included open surgery with total aortic arch replacement or endovascular stent-graft placement to seal the proximal entry tear. In the second-stage procedure, the aorta was divided into three zones based on its anatomy, and zonal stent-graft placement was performed to seal the entry tear and promote thrombosis of the false lumen. Results A total of 18 patients (15 males, 3 females) were included, with a mean age of (53.5±10.6) years (range, 39 to 76 years). The median operation time was 38.0 (29.5, 58.5) min, and the median intraoperative blood loss was 20.0 (20.0, 30.0) mL. The technical success rate was 100.0%. Intraoperative and postoperative imaging confirmed successful exclusion of the distal entry tear of the IMH, with no endoleak, stenosis or occlusion of visceral branches. There were no major perioperative complications, such as death, paraplegia, or visceral ischemia. During follow-up, complete thrombosis or resolution of the false lumen was observed in all patients. Conclusion For patients with residual entry tears and new-onset dissection-like changes in the distal aorta after the first-stage procedure for IMH, second-stage stent-graft placement can effectively seal the entry tear, promote false lumen thrombosis and hematoma resolution, and improve distal aortic remodeling, demonstrating favorable short- to mid-term outcomes.

Objective To analyze the characteristics and changing trends of lung cancer-related projects funded by National Natural Science Foundation of China (NSFC) during 2019–2023, providing a reference for researchers in topic selection and for optimizing scientific research management and resource allocation. Methods Relevant databases, including the NSFC Big Data Knowledge Management Service Platform, were systematically searched to collect information on lung cancer-related funded projects from 2019 to 2023. Quantitative methods were applied to evaluate project categories, funding amounts, and the distribution of host institutions. Project themes were classified according to their titles, keywords, and abstracts, and were subsequently compared with those of projects funded during 2014–2018. Results A total of 1 327 lung cancer-related projects were funded from 2019 to 2023, with total funding of 554.92 million yuan. The Young Scientists Fund and the General Program accounted for 90.3% (1 199/1 327) of the projects and 84.1% (46 675/55 492) of the total funding; the top 10 host institutions comprised approximately 32.0% of all funded projects. Thematic analysis revealed that the core funding directions in the lung cancer field during 2019–2023 focused on molecular mechanisms and signaling pathways. Major research themes included metastasis and recurrence, tumor microenvironment and immunity, and targeted therapy resistance and drug development. Compared with 2014–2018, the proportion of projects focused on tumor microenvironment and immunity, as well as artificial intelligence and medical engineering, increased substantially. Overall, the themes of funded lung cancer projects were dominated by mechanistic studies and demonstrated cross-cutting features intersecting with disease progression, therapeutic resistance, immune regulation, and clinical translation. Conclusion The number of NSFC-funded lung cancer-related projects has continued to grow. Research themes have evolved from pure mechanistic exploration toward immune regulation and translational research, exhibiting characteristics of interdisciplinary integration with emerging technologies and multi-theme cross-fertilization. Researchers are encouraged to align with policy orientations and to emphasize the innovation and translational value of their proposed topics.

Objective To explore the feasibility of magnetic compression technique (MCR) in the treatment of severe single mid-ureteral stricture in a rabbit model. Methods After 10 female New Zealand rabbits were selected, the distal end of the right ureter was ligated with silk thread. Two weeks after the operation, when the right ureter was dilated, the mid-ureter was ligated again with silk thread to create a severe single mid-ureteral stricture animal model. Longitudinal incisions were made at the upper and lower ends of the ligation site, and cylindrical NdFeB magnets with central holes (sub-magnets and main magnets) were placed to anastomose and recanalize the mid-ureteral stricture. The magnets were adjusted to the appropriate position to automatically align and attract each other. The longitudinal incision sites of the ureter were sutured with 6-0 Prolene thread, and the abdominal cavity was closed layer by layer. The operation time was recorded. X-ray films were taken every two days to confirm the position of the magnets and record the time of magnet detachment. Three weeks after the operation, the anastomotic specimens were obtained, and the formation of the anastomosis was evaluated with gross observation and histological staining. Results Two weeks after ligation, all experimental rabbits showed obvious dilation of the right ureter. The mid-ureteral ligation and placement of the male and female magnets were successfully completed in all 10 experimental rabbits, with an operation time of (24.00±5.15)minutes. The male and female magnets attracted each other well. X-ray examination showed that the magnets detached and entered the distal ureter (14.0±1.9) days after magnetic compression. The recanalization of the severe single mid-ureteral stricture was successfully achieved. The gross specimens and histological examination of the anastomosis showed that the anastomosis remained patent and the mucosal healing was good. All experimental rabbits survived well after the operation without serious complications. Conclusion MCT provides a new idea and novel method for the treatment of mid-ureteral stricture. This study confirmed the feasibility of this technique in treating severe single mid-ureteral stricture in a rabbit model. The operation is relatively simple and has potential for clinical application.

Objective To fabricate a large-diameter vascular graft with a pore size gradient structure mimicking that of natural blood vessels, using poly-L-lactic acid (PLLA) and polycaprolactone (PCL) as base materials through electrospinning and ultrasonic pore-forming techniques, and to evaluate its application potential. Methods A three-layered tubular graft was fabricated from a PCL/PLLA blend (mass ratio 6 : 4) via electrospinning, followed by an ultrasonic pore-forming process to create a gradient porosity. The resulting graft (diameter: 2 cm, length: 4 cm) was implanted into the descending thoracic aorta of an experimental pig using an end-to-end anastomosis. Graft patency and anastomotic sites were monitored by computed tomography angiography (CTA) at 1 and 6 weeks post-surgery. After 2 months, the graft was explanted for systematic evaluation of vascular regeneration and repair through gross examination, histopathology (H&E and elastic fiber staining), immunohistochemistry [for ETS-related gene (ERG), Actin, and Vimentin], and scanning electron microscopy (SEM). Results Postoperative CTA confirmed excellent graft patency at both 1 and 6 weeks, with no evidence of thrombosis or anastomotic stenosis. Gross examination of the 2-month explant revealed a smooth luminal surface covered by neotissue. Histopathological analysis demonstrated that the graft successfully induced the formation of a three-layered structure resembling a native vessel wall, comprising endothelial cells, smooth muscle cells, and fibroblasts. Immunohistochemistry further verified coverage of the luminal surface by endothelial cells (ERG-positive), along with the presence of neosmooth muscle (Actin-positive) and fibroblasts (Vimentin-positive). Endothelial cells were observed adhering to the inner surface of the artificial vessel under SEM. Conclusion The biomimetic, three-layered PLLA/PCL large-diameter vascular graft, constructed via electrospinning and ultrasonic pore-forming, exhibits excellent short-term patency and biocompatibility in a large animal model. More importantly, it demonstrates a significant potential to promote host cell infiltration and achieve in situ regeneration of a three-layered vascular wall structure, providing a promising experimental basis for the development of next-generation functional vascular substitutes.

Objective To systematically evaluate the efficacy and safety of traditional Chinese medicine (TCM) compound in treating pulmonary nodules, providing evidence-based medical evidence for TCM intervention in pulmonary nodules. Methods Computer search of PubMed, CNKI, Wanfang, VIP, and SinoMed was conducted to select randomized controlled trials (RCTs) of TCM compound intervention in pulmonary nodules, with the retrieval time from the inception to November 29, 2023. The Cochrane bias risk assessment tool was used to evaluate the quality of the included studies, and Review Manager 5.4 was used for Meta-analysis. Results A total of 18 RCTs were included, covering 8 provinces across the country, with a total sample size of 1301 patients. The TCM compounds used in the included studies all incorporated the method of dissolving phlegm and dissipating nodules. There was a high risk of bias uncertainty in the included studies. Meta-analysis results suggested that TCM compound could significantly reduce the diameter of pulmonary nodules [MD=−1.41, 95%CI (−1.70, −1.13), P<0.001], decrease the number of nodules [MD=−0.37, 95%CI (−0.73, −0.01), P=0.05], alleviate clinical symptoms [MD=−4.84, 95%CI (−6.04, −3.64), P<0.001], and improve lung function [forced expiratory volume in one second (FEV1), MD=0.55, 95%CI (0.09, 1.01), P=0.02; FEV1/forced vital capacity, MD=6.12, 95%CI (4.47, 7.78), P<0.001]. However, there was no statistically significant difference in the probability of malignancy between the experimental group and the control group [MD=−0.01, 95%CI (−0.01, 0.00), P=0.09]. Conclusion TCM compound can significantly reduce the diameter of pulmonary nodules, decrease the number of nodules, alleviate clinical symptoms, and improve lung function, but future multicenter, large-sample, high-quality RCTs are still needed to further explore and verify this conclusion.

Background/Aims: Liver transplantation (LT) following total hepatectomy is a life-saving treatment for hepatocellular carcinoma (HCC). The HCC recurrence after LT hinders the effectiveness of the procedure. The objective of this study is to develop a pre-operative risk stratification model based on a liquid biopsy. Methods: We conducted a comprehensive multi-omics study of 260 HCC patients from three centers, including clinical data, low-coverage whole-genome sequencing of cell-free DNA (cfDNA) from plasma, as well as whole-exome, single-nucleus RNA, and spatial transcriptomics from matched tumor and non-tumor tissues. Results: We identified cfDNA-derived copy number alteration (CNA) signatures associated with post-transplant recurrence. By integrating cfDNA-derived CNA profiles with single-cell transcriptomic data, we traced recurrence-associated cfDNA to a distinct subpopulation of malignant cells within the primary tumor. These cells were embedded in a pro-metastatic microenvironment of specialized endothelial subtypes and cancer-associated fibroblasts. Notably, most recurrence-associated lesions were detectable in cfDNA prior to liver transplantation (LT). Building on these insights, we developed the ZJU Criteria based on CNA fragments and tumor markers, a pre-LT risk prediction tool that integrates conventional clinical factors with cfDNA-derived CNA signatures, and validated it using internal and independent external cohorts. Conclusion Our findings suggest that post-transplant recurrence commonly originates from advanced subclones that emerge late during tumor evolution. The ZJU Criteria provides an accurate, non-invasive strategy that significantly improves pre-LT risk stratification and clinical decision-making for patients with HCC.

Background/Aims: Lenvatinib resistance remains a critical barrier in advanced hepatocellular carcinoma (HCC) therapy. However, the underlying mechanisms and strategies for reversing resistance remain incompletely understood. Methods: Integrated transcriptomics of lenvatinib-resistant patient tumors and an acquired-resistance murine model identified a novel macrophage subpopulation. Functional validation employed CRISPR-SAM screening, conditioned medium (CM) assays, subcutaneous/orthotopic xenografts, patient-derived organoids (PDOs), and patient-derived xenografts (PDXs). Mechanistic studies included ChIP-qPCR, co-immunoprecipitation, and pharmacologic targeting. Clinical relevance was assessed in a retrospective cohort. Results: Resistant HCC exhibited significant enrichment of a COLEC12high TAM subset , which correlated with poor survival and treatment response. These TAMs secreted neuregulin-1 (NRG1) , activating HER2/HER3-AKT signaling in tumor cells to drive cancer stemness and lenvatinib resistance. Mechanistically, in TAMs COLEC12 sequestered STAT1 in the cytoplasm, preventing its phosphorylation, and thereby derepressing STAT3-mediated NRG1 transcription. Depletion of NRG1 reversed the stemness phenotypes and resensitized tumors to lenvatinib both in vitro and in vivo. Clinically, high NRG1 expression predicted an inferior lenvatinib response and shorter survival. Crucially, the bispecific anti-HER2/HER3 antibody zenocutuzumab restored lenvatinib efficacy in PDOs, PDXs, and murine models. Conclusions Our work establishes the COLEC12high TAM/NRG1 axis as a master regulator of therapeutic resistance and identifies NRG1 as a predictive biomarker, providing a clinically actionable strategy to overcome lenvatinib resistance in HCC.