Objective To explore the clinical efficacy of single-branch intraoperative stent combined with modified bilateral cerebral perfusion in type A aortic dissection. Methods A retrospective analysis was conducted on the clinical data of patients who underwent surgery for type A aortic dissection at the First Affiliated Hospital of Anhui Medical University from January 2021 to May 2024. Patients were divided into a test group (single branch stent+modified bilateral cerebral perfusion) and a control group (traditional surgical method, straight stent+unilateral cerebral perfusion) according to the surgical method. Propensity score matching analysis was used to match the two groups of patients with a ratio of 1:1, and the perioperative data and clinical efficacy after matching were compared. Results A total of 14 patients were included in the test group, including 13 males and 1 female, with an average age of (46.6±16.4) years. There were 56 patients in the control group, including 38 males and 18 females, with an average age of (52.1±11.7) years. After propensity score matching, 14 patients were included in each group. Compared with the control group, the ventilator support time [(27.4±24.3) h vs. (93.4±88.0) h, P=0.018], length of stay in the intensive care unit [(2.8±1.8) d vs. (8.7±6.5) d, P=0.009], and postoperative awakening time [(5.4±2.2) h vs. (8.8±4.8) h, P=0.047] in the test group were shorter than those in the control group, with statistically significant differences. There was no statistical difference in neurological complications between the two groups (P=1.000). Conclusion Single-branch intraoperative stent combined with modified bilateral cerebral perfusion can effectively shorten ventilator support time, length of stay in the intensive care unit, and postoperative awakening time, and is safe and effective for the treatment of type A aortic dissection, which is worth further promotion.

Definitive chemoradiotherapy (dCRT) has become a cornerstone in the treatment of locally advanced esophageal cancer; however, local control remains suboptimal, and persistent lesions or locoregional recurrences after treatment are not uncommon. For patients without distant metastases but with local failure, whether surgical intervention can still offer curative potential remains a major clinical dilemma. Salvage esophagectomy (SE) offers potential long-term survival for selected patients, but this procedure is performed in the context of severe fibrosis, impaired local blood supply, and obscured anatomical planes following chemoradiotherapy, resulting in significantly higher perioperative risk compared to primary esophagectomy. Consequently, controversies exist regarding patient selection, preoperative restaging, choice of surgical approach, extent of lymphadenectomy, gastrointestinal reconstruction, and perioperative management. In recent years, with the refinement of restaging modalities such as PET/CT, the accumulation of experience in high-volume centers, and emerging evidence from clinical studies, the clinical role of SE has gradually shifted from a "high-risk salvage measure" to a "selective curative strategy aimed at achieving long-term survival in carefully selected patients". Nevertheless, standardized guidelines for patient selection, technical approaches, and perioperative management are still lacking. Based on current evidence and clinical experience, experts organized by the Integrated Esophageal Cancer Committee of Chinese Anti-Cancer Association systematically reviewed key issues regarding SE, including its definition, indications, preoperative evaluation, choice of surgical approach, lymphadenectomy, gastrointestinal reconstruction, and perioperative management, and formulated a Chinese expert consensus. This consensus aims to provide guidance for standardized assessment, appropriate referral, individualized surgical decision-making, and optimized perioperative management of patients with locoregional failure after dCRT. Ultimately, this will increase the likelihood of R0 resection, reduce the risk of severe complications, and promote the safer, more judicious, and standardized implementation of SE in high-risk scenarios.

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.

ObjectiveHepatocellular carcinoma (HCC) represents 90% of all primary liver cancers. The main risk factors associated with HCC include viral hepatitis (B and/or C), alcohol abuse, and metabolic dysfunction-associated steatotic liver disease (MASLD), which progressively advance to liver fibrosis, cirrhosis, and ultimately evolve into HCC. Surgical resection represents the most effective treatment for HCC, while recent advances in immunotherapy, including immune checkpoint inhibitors and adoptive cell therapies, have provided improved treatment prospects for patients with unresectable HCC. However, the complex metabolic heterogeneity of HCC limits the therapeutic efficacy. Metabolic intermediates acyl-CoA not only provide energy and substrates for numerous biochemical reactions but also serve as donors for protein lysine acylation, a major class of post-translational modification (PTM). Therefore, a deeper understanding of the molecular mechanisms underlying protein lysine acylation and hepatocarcinogenesis is urgently needed. MethodsThe levels of protein lysine acylation and silence information regulator 5 (SIRT5) expression levels in clinical HCC samples were analyzed by Western blot. Quantitative malonylome and succinylome of HCC samples were analyzed by antibody-based affinity enrichment coupled with tandem mass spectrometry. The proliferation of HCC cells was analyzed with Cell Counting Kit-8 (CCK-8) assays, the apoptosis was quantified by Annexin V-FITC/propidium iodide (PI) staining coupled with flow cytometry, and the ability of cells to migrate was assayed by Transwell assays. The enzymatic activity of glutathione S-transferase Mu 1 (GSTM1) was quantified. Transgenic mice with hepatic overexpression of SIRT5 were constructed using CRISPR-Cas9, and primary hepatocarcinogenesis was induced by administration of diethylnitrosamine. ResultsWestern blot analysis indicated that the expression level of SIRT5 was elevated in clinical samples from HCC patients, and the levels of lysine malonylation, glutarylation, and succinylation were significantly reduced in HCC tissues. Knockout of SIRT5 in MHCC-97H and MHCC-97L hepatoma cells suppressed cell proliferation, and increased the percentage of apoptotic cells significantly. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the differentially malonylome and succinylome of HCC samples revealed significant enrichment in two major classes of biological processes: core energy metabolism (e.g., glycolysis/gluconeogenesis, tricarboxylic acid metabolic process, fatty acid beta oxidation) and detoxification and oxidative stress response (e.g., response to toxic substance, chemical carcinogenesis, reactive oxygen species (ROS)). SIRT5 removes malonylation from lysine residues in GSTM1 and restores its detoxification activity, which is crucial for the survival of hepatocytes under stressed conditions. More importantly, in vivo experiment indicated that hepatic-specific overexpression of SIRT5 in mice accelerated diethylnitrosamine-induced liver fibrosis and hepatocarcinogenesis, indicating the critical role of SIRT5 in HCC progression. ConclusionThis study highlights the previously unrecognized SIRT5-GSTM1 axis as a key regulator in hepatocarcinogenesis, and suggests a potential target for the treatment of patients with HCC.

BACKGROUND:Sarcopenia is an age-related systemic skeletal muscle disease,which is associated with a variety of adverse outcomes such as falls,functional decline,frailty,and death.Postmenopausal women are one of the high-risk groups for sarcopenia.OBJECTIVE:To develop a predictive model for assessing the risk of sarcopenia in Chinese postmenopausal women based on high-quality database.METHODS:Data for this study were derived from 2 370 postmenopausal women from the China Health and Retirement Longitudinal Study(CHARLS),and sarcopenia was assessed using the Asian Working Group on Sarcopenia 2019(AWGS2019)recommended metrics.The study cohort was randomized into a training set(70％)and a validation set(30％).Risk factors for sarcopenia in postmenopausal women were screened using the least absolute shrinkage and selection operator,ten-fold cross-validation,and logistic regression.Nomogram predicting the risk of sarcopenia in postmenopausal women was constructed based on the risk factors,and the model efficacy was evaluated by the receiver operating characteristic curve and area under the curve(AUC),calibration curve,and decision curve analysis.RESULTS AND CONCLUSION:The prevalence of sarcopenia in this study was 23.50％and age,place of residence,sleep quality,cognitive function,depression,and the number of chronic diseases were selected as predictors of sarcopenia in postmenopausal women.The nomogram model showed good discrimination between the training and validation sets,with an AUC value of 0.751(95％confidence interval=0.724-0.778,P＜0.001),a specificity of 72.2％,and a sensitivity of 63.2％in the training set,and an AUC value of 0.763(95％confidence interval=0.721-0.805,P＜0.001),with a specificity of 69.6％and a sensitivity of 70.8％.The calibration curve showed a relatively significant agreement between the nomogram model and the actual observations,and the decision curve analysis demonstrated broad and good clinical utility.To conclude,the nomogram to assess the risk of sarcopenia constructed based on age,place of residence,sleep quality,cognitive function,depression,and number of chronic diseases,provides an effective tool for identifying and eliminating risk factors for sarcopenia in Chinese postmenopausal women,and helps to reduce the incidence of sarcopenia.

BACKGROUND:Ammonia poisoning is considered to be the main hypothesis for the pathogenesis of hepatic encephalopathy.Ammonia can lead to psychiatric and cognitive behavioral disorders,although the specific pathological molecular mechanisms remain unclear.OBJECTIVE:To investigate the effects of ammonia poisoning on cognitive behavior and hippocampal neuronal synapses in mice.METHODS:Thirty-two C57BL/6J mice were randomly divided into a normal control group and an ammonium chloride group,with 16 mice in each group.Normal saline was injected intraperitoneally in the control group,and ammonium chloride(10 mmol/kg)was injected intraperitoneally in the ammonium chloride group to construct a model of ammonia poisoning,once a day.After 7 days of ammonium chloride intervention,blood samples were collected from the hearts of six mice in each group for blood ammonia concentration detection.Behavioral experiments,including the open field test,novel object recognition test,and Y-maze test,were performed to assess mental and cognitive-behavioral changes in mice.Finally,hippocampal tissues were extracted for western blot analysis to detect the expression levels of synaptophysin and postsynaptic density protein-95 in hippocampal neurons.RESULTS AND CONCLUSION:The blood ammonia concentration was significantly elevated in the ammonium chloride group compared with the control group(P＜0.05).Mice in the ammonium chloride group showed anxiety-like behavior and disinhibition phenomenon,and a significant decrease in recognition memory and working memory ability.Western blot results revealed that the expression of synaptophysin and postsynaptic density protein-95 protein in hippocampal neurons in the ammonium chloride group was lower than that in the control group(P＜0.05).To conclude,ammonia poisoning can induce hippocampal neuronal synaptic damage,leading to psychiatric and cognitive behavioral abnormalities in mice.

BACKGROUND:Peripheral nerve axon rupture seriously affects patients' physical function and mental health.Microsurgery,nerve autograft,nerve allograft,fibrin glue and catheter technology are the main treatments for peripheral nerve injury,each of which has its own advantages and disadvantages,but the overall treatment effect is not satisfactory.Despite the clinical success of Schwann cells in promoting axonal regeneration,there are still many challenges in the treatment with Schwann cells,such as slow expansion of Schwann cells,immune rejection,and low survival rate of transplanted cells.OBJECTIVE:To summarize the role and mechanism of Schwann cells in promoting the regeneration of peripheral nerve axons,and the difficulties and challenges of Schwann cells in the process of nerve regeneration treatment.METHODS:PubMed,Medline,WanFang,VIP,and CNKI were searched by computer using the search terms of"Schwann cells,synaptic Schwann cell,macrophage,peripheral nerve axon rupture,Wallerian degeneration,Peripheral nerve axon regeneration,Central nervous system repair"in English and Chinese.Literature related to Schwann cell proliferation and differentiation,promotion of peripheral nerve regeneration,and clinical applications was retrieved from database inception to October 2024,and a total of 95 articles were finally included for review.RESULTS AND CONCLUSION:Schwann cells interact with macrophages,T cells and other cells,to initiate the regeneration process through signaling pathways,including Krox20/C-Jun,NRG-1/ErbB,Notch,MAPK,and PI3K/Akt/mTOR,synthesize and release nerve growth factors,and thus promote regeneration of the peripheral nervous system.Schwann cells have been experimentally demonstrated to have great potential in peripheral nerve repair and are expected to become the key target of therapeutic intervention.However,there are still problems such as difficulties in cell harvest and culture,as well as the occurrence of other diseases during the treatment process.

Organoid-on-a-chip technology represents a promising interdisciplinary advancement that merges two cutting-edge biomedical platforms: stem cell-derived organoids and microfluidics-based organ-on-a-chip systems. Organoids are self-organizing three-dimensional (3D) cell cultures that mimic the key structural and functional features of in vivo organs. However, traditional organoid culture systems are often static, lacking dynamic environmental cues and suffering from limitations such as batch-to-batch variability, low stability, and low throughput. Organ-on-a-chip platforms, by contrast, utilize microfluidic technologies to simulate the dynamic physiological microenvironment of human tissues and organs, enabling more controlled cell growth and differentiation. By integrating the advantages of organoids and organ-on-a-chip technologies, organoid-on-a-chip systems transcend the limitations of conventional 3D culture models, offering a more physiologically relevant and controllable in vitro platform. In organoid-on-a-chip systems, stem cells or pre-formed organoids are cultured in micro-engineered environments that mimic in vivo conditions, enabling precise control over fluid flow, mechanical forces, and biochemical cues. Specifically, these platforms employ advanced strategies including bio-inspired 3D scaffolds for structural support, precise spatial cell patterning via 3D bioprinting, and integrated biosensors for real-time monitoring of metabolic activities. These synergistic elements recreate complex extracellular matrix signals and ensure high structural fidelity. Based on structural complexity, organoid-on-a-chip systems are classified into single-organoid and multi-organoid types, forming a trajectory from unit biomimicry to systemic simulation. Single-organoid chips focus on highly biomimetic units by integrating vascular, immune, or neural functions. Multi-organoid chips simulate inter-organ crosstalk and systemic homeostasis, advancing complex disease modeling and PK/PD evaluation. This emerging technology has demonstrated broad application potential in multiple fields of biomedicine. Organoid-on-a-chip systems can recapitulate organ developmentin vitro, facilitating research in developmental biology. They mimic organ-specific physiological activities and mechanisms, showing promising applications in regenerative medicine for tissue repair or replacement. In disease modeling, they support the reconstruction of models for neurodegenerative, inflammatory, infectious, metabolic diseases, and cancers. These platforms also enable in vitro drug testing and pharmacokinetic studies (ADME). Patient-derived chips preserve genetic and pathological features, offering potential for precision medicine. Additionally, they reduce species differences in toxicology, providing human-relevant data for environmental, food, cosmetic, and drug safety assessments. Despite progress, organoid-on-a-chip systems face challenges in dynamic simulation, extracellular matrix (ECM) variability, and limited real-time 3D imaging, requiring improved materials and the integration of developmental signals. Current bottlenecks also include the high technical threshold for automation and the lack of standardized validation frameworks for regulatory adoption. Meanwhile, the concept of a “human-on-a-chip” has been proposed to mimic whole-body physiology by integrating multiple organoid modules. This approach enables systemic modeling of drug responses and toxicity, with the potential to reduce animal testing and revolutionize drug development. Future advancements in bio-responsive hydrogels and flexible biosensors will further empower these platforms to bridge the gap between bench-side research and personalized clinical interventions. In conclusion, organoid-on-a-chip technology offers a transformative in vitro model that closely recapitulates the complexity of human tissues and organ systems. It provides an unprecedented platform for advancing biomedical research, clinical translation, and pharmaceutical innovation. Continued development in biomaterials, microengineering, and analytical technologies will be essential to unlocking the full potential of this powerful tool.

Chinese hamster ovary (CHO) cells are the most established and versatile mammalian expression system for the large-scale production of recombinant therapeutic proteins, owing to their genetic stability, adaptability to serum-free suspension culture, and ability to perform human-like post-translational modifications. More than 70% of biologics approved by the U.S. Food and Drug Administration rely on CHO-based production platforms, underscoring their central role in modern biopharmaceutical manufacturing. Despite these advantages, CHO systems continue to face three persistent bottlenecks that limit their potential for high-yield, reproducible, and cost-efficient production: excessive metabolic burden during high-density culture, heterogeneity of glycosylation patterns, and progressive loss of long-term expression stability. This review provides an integrated analysis of recent advances addressing these challenges and proposes a forward-looking framework for constructing intelligent and sustainable CHO cell factories. In terms of metabolic regulation, excessive lactate and ammonia accumulation disrupts energy balance and reduces recombinant protein synthesis efficiency. Optimization of culture parameters such as temperature, pH, dissolved oxygen, osmolarity, and glucose feeding can effectively alleviate metabolic stress, while supplementation with modulators including sodium butyrate, baicalein, and S-adenosylmethionine promotes specific productivity (qP) by modulating apoptosis and chromatin structure. Furthermore, genetic engineering strategies—such as overexpression of MPC1/2, HSP27, and SIRT6 or knockout of Bax, Apaf1, and IGF-1R—have demonstrated significant improvements in cell viability and product yield. The combination of multi-omics metabolic modeling with artificial intelligence (AI)-based prediction offers new opportunities for building self-regulating CHO systems capable of dynamic adaptation to environmental stress. Regarding glycosylation uniformity, which determines therapeutic efficacy and immunogenicity, gene editing-based glycoengineering (e.g., FUT8 knockdown or ST6Gal1 overexpression) has enabled the humanization of CHO glycan profiles, minimizing non-human sugar residues and enhancing drug stability. Process-level strategies such as galactose or manganese co-feeding and fine control of temperature or osmolarity further allow rational regulation of glycosyltransferase activity. Additionally, in vitro chemoenzymatic remodeling provides a complementary route to construct human-type glycans with defined structures, though industrial applications remain constrained by cost and scalability. The integration of model-driven process design and AI feedback control is expected to enable real-time prediction and correction of glycosylation deviations, ensuring batch-to-batch consistency in continuous biomanufacturing. Long-term expression stability, another critical challenge, is often impaired by promoter silencing, chromatin condensation, and random genomic integration. Molecular optimization—such as the use of improved promoters (CMV, EF-1α, or CHO endogenous promoters), Kozak and signal peptide refinement, and incorporation of chromatin-opening elements (UCOE, MAR, STAR)—helps maintain durable transcriptional activity, while site-specific integration systems including Cre/loxP, Flp/FRT, φC31, and CRISPR/Cas9 can enable single-copy, position-independent gene insertion at genomic safe-harbor loci, ensuring stable, predictable expression. Collectively, this review highlights a paradigm shift in CHO system optimization driven by the convergence of genome editing, synthetic biology, and artificial intelligence. The transition from empirical optimization to rational, data-driven design will facilitate the development of programmable CHO platforms capable of autonomous regulation of metabolic flux, glycosylation fidelity, and transcriptional activity. Such intelligent cell factories are expected to accelerate the transformation from laboratory-scale research to industrial-scale, high-consistency, and economically sustainable biopharmaceutical manufacturing, thereby supporting the next generation of efficient and customizable biologics manufacturing.