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.

OBJECTIVE To investigate the effect and potential mechanism of toosendanin in enhancing the antileukemic activity of cytosine arabinoside against acute myeloid leukemia （AML） based on the mammalian target of rapamycin complex 1 （mTORC1） signaling pathway.METHODS Female NSG immunodeficient mice were used to establish an AML model via a single γ-ray irradiation followed by a single tail-vein injection of a U937 cell suspension. The effects of cytosine arabinoside （2.5 mg/kg）， toosendanin （1.0 mg/kg）， and cytosine arabinoside+toosendanin （2.5 mg/kg+1.0 mg/kg） on body weight， survival time， peripheral blood routine indicators， histopathological morphology， and the expressions of autophagy-related proteins were explored. Using U937 cells as the subject， the effects of cytosine arabinoside （1 μmol/L）， toosendanin （160 nmol/L）， and cytosine arabinoside+toosendanin （1 μmol/L+160 nmol/L） on the expressions of autophagy-related proteins， mTORC1 signaling pathway-related proteins and mRNAs were investigated. The targeting relationship between toosendanin and the selective autophagy ligand 1 （also known as p62） was validated， and the Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analyses， as well as molecular docking， were performed. A p62 -knockdown U937 stable cell line was constructed， and the underlying mechanism of toosendanin-induced sensitization was verified.RESULTS Animal experiments confirmed that the combination of toosendanin and cytosine arabinoside significantly improved body weight， survival time and peripheral blood routine indicators in AML mice （ P ＜0.05）， alleviated pathological changes such as leukemic cell infiltration and focal necrosis in bone marrow， liver， and spleen tissues， and modulated the expressions of autophagy-related proteins. Cell experiments confirmed that toosendanin could reverse cytosine arabinoside-induced activation of the autophagy cascade （manifested by downregulation of the protein expressions of microtubule-associated protein 1 light chain 3B and Beclin-1， upregulation the protein expression of p62）， and might inhibit the expression of the downstream Unc-51-like autophagy activating kinase 1 （ULK1） complex （including ULK1， ULK2， autophagy-related protein 13， and FAK family interacting protein of 200 kDa） by activating the mTORC1 signaling pathway （ P ＜0.05）. The sensitizing effect of toosendanin was associated with the inhibition of autophagy and the regulation of the mTORC1 signaling pathway； it could stably bind to p62 via hydrophobic interactions. Mechanism verification experiments indicated that upon p62 knockdown， toosendanin was no longer able to activate the mTORC1 signaling pathway or inhibit autophagy.CONCLUSIONS Toosendanin may enhance chemo-sensitivity of AML cells to cytosine arabinoside by directly targeting the p62 protein， which subsequently activates the mTORC1 signaling pathway， and thereby suppresses cytosine arabinoside-induced protective autophagy.

OBJECTIVE To compare the short-term efficacy and safety of small-caliber polyvinyl alcohol （PVA） microsphere-based transcatheter arterial chemoembolization （TACE） versus conventional iodized oil emulsion-based TACE in the treatment of unresectable hepatocellular carcinoma （HCC）.METHODS Clinical data of 146 patients with unresectable HCC who underwent TACE at Gansu Provincial Second People’s Hospital （Affiliated Hospital of Northwest Minzu University） from June 1， 2024， to June 30， 2025， were retrospectively collected. According to the treatment strategy， the patients were divided into the control group （conventional iodized oil emulsion-based TACE， n ＝79） and the observation group （small-caliber PVA microsphere-based TACE， n ＝67）. One-to-one propensity score matching （PSM） was performed， and the matched cohort （62 patients in each group） was used for the primary analysis. The objective response rate （ORR） and disease control rate （DCR） at 1 and 3 months post-treatment， serum levels of tumor markers （alpha-fetoprotein， alpha-fetoprotein lectin-binding fraction L3， and protein induced by vitamin K absence or antagonist-Ⅱ） before treatment and at 1 and 3 months post-treatment， the occurrence of adverse events， progression-free survival （PFS）， and overall survival （OS） were compared between the two groups. Sensitivity and interaction analyses were also performed.RESULTS After PSM， the ORRs in the observation group at 1 and 3 months post-treatment were both 59.7%， and the DCRs were 91.9% and 93.5%， respectively， significantly higher than those in the control group （ORRs： 41.9% and 38.7%； DCRs： 77.4% and 75.8%； P ＜0.05）. At 1 and 3 months post-treatment， the serum levels of tumor markers decreased significantly from baseline in both groups， with significantly lower levels in the observation group than in the control group （ P ＜0.05）. No statistically significant differences were observed in the overall incidence of adverse events or the incidence of grade≥3 adverse events between the two groups （ P ＞0.05）. The median PFS was 10.6 months in the control group and 14.3 months in the observation group， with no statistically significant difference [hazard ratio （HR） of 0.69， 95% confidence interval （CI） of 0.44-1.09， P ＝0.111]. During follow-up， 8 and 9 patients died in the control and observation groups， respectively， and the median OS was not reached in either group. The 12-month OS rates were 88.8% and 87.3%， respectively， with no statistically significant difference （HR of 0.88， 95%CI of 0.35-2.24， P ＝0.790）. After adjustment for potential confounding factors in the original cohort， the ORR at 3 months post-treatment remained significantly higher in the observation group than in the control group （adjusted odds ratio of 2.67， 95%CI of 1.28-5.56， P ＝0.009）. Additionally， the interaction between treatment modality and Barcelona Clinic Liver Cancer staging had no statistically significant impact on the ORR at 3 months post-treatment （ P ＝0.391）.CONCLUSIONS For patients with unresectable HCC， compared with conventional iodized oil emulsion-based TACE， small-caliber PVA microsphere-based TACE demonstrates superior efficacy in terms of early radiological response and improvement in tumor markers， and the two regimens are comparable in terms of safety.

As the application of immune checkpoint inhibitors(ICIs)in the perioperative treatment of melanoma is increasingly introduced at earlier stages,it presents a critical opportunity for the development and clinical translation of neoadjuvant therapy.The results of phaseⅠ/Ⅱ clinical trials on neoadjuvant ICI therapy for melanoma demonstrate that neoadjuvant ICIs effectively improve the pathologic re-sponse rate in melanoma patients.Recent studies have shown that combining ICIs with other treatment modalities,including radiotherapy,chemotherapy,and targeted therapies,can enhance antitumor efficacy of neoadjuvant treatment for patients with melanoma.Optimizing treatment regimens,managing adverse events,identifying and addressing pseudoprogression,and handling cases of oligoprogression have become key areas of research in incorporating ICI regimens into neoadjuvant treatment for patients with melanoma.The search for bio-markers to monitor immunotherapy efficacy is expected to become a major focus of future research.This article provides a review of the re-search progress,controversies,and challenges in the application of ICIs in the neoadjuvant treatment of melanoma,and discusses future re-search directions,aiming to offer insights into the clinical application and development of ICIs in melanoma neoadjuvant therapy.

Cervical spinal cord injury without fracture-dislocation (CSCIWFD) is referred to as a special type of cervical spinal cord injury characterized by traumatic spinal cord dysfunction and no significant bony structural abnormalities on imagines. Duo to the high risk of missed diagnosis during the initial consultation, CSCIWFD may lead to progressive neurological deterioration or even complete paralysis, severely impacting patients′ prognosis. Currently, there are no established consensuses over the diagnosis and treatment of CSCIWFD, such as the lack of evidence-based standards for indications of non-surgical treatment and risk of secondary neurological injury, as well as debates over the optimal timing for surgical intervention and indications for different surgical approaches. To address these issues, the Spine Trauma Group of the Orthopedic Branch of the Chinese Medical Doctor Association organized experts in the relevant fields to formulate Diagnosis and treatment guideline for acute cervical spinal cord injury without fracture- dislocation in adults ( version 2025) . Based on evidence-based medicine and the principles of scientific rigor and clinical applicability, the guidelines proposed 11 recommendations covering terminology, diagnosis, evaluation treatment, and rehabilitation, etc., aiming to standardize the management of CSCIWFD.

Vertebral refracture following percutaneous vertebral augmentation (PVA) is commonly seen in elderly patients with osteoporotic thoracolumbar compression fractures (OTLCF). It can lead to recurrent pain, loss of vertebral height, progression of kyphosis, and even neurological dysfunction, significantly impairing patients′ quality of life. Current diagnosis and treatment face multiple challenges, including high misdiagnosis rate, difficulty in choosing between surgical and non-surgical treatment options, lack of standardized surgical protocols, interference from intralesional bone cement during procedures, inadequate stability of internal fixation in osteoporotic bone, and suboptimal compliance of anti-osteoporotic therapy. Establishing a standardized diagnostic and therapeutic framework is urgently needed. To standardize the management process and improve outcomes for vertebral refractures after PVA in elderly OTLCF patients, Spinal Trauma Group of the Orthopedic Branch of Chinese Medical Doctor Association organized experts in the field to develop Guideline for the diagnosis and treatment of vertebral refracture after percutaneous vertebral augmentation in elderly patients with osteoporotic thoracolumbar compression fractures ( version 2025), based on current literature and clinical experience, and adhering to principles of scientific rigor and clinical applicability. A total of 11 recommendations were proposed, encompassing diagnosis, treatment, and rehabilitation of vertebral refracture after PVA in elderly patients with OTLCF, aiming to provide a foundation for a standardized management.

Objective:To explore the clinicopathological and molecular genetic characteristics of anaplastic lymphoma kinase (ALK)-rearranged renal cell carcinoma (RCC), including a rare case with the TPM1-ALK gene subtype.Methods:Three cases of ALK-rearranged RCC diagnosed in the Department of Pathology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China from January 2020 to December 2024 were collected. Their clinical pathological and next-generation sequencing (NGS) data were analyzed. Relevant literature was also reviewed, and follow-ups were carried out.Results:Among the three patients, there were 1 female (case 1) and 2 males (cases 2 and 3), with the ages of 29,41 and 44 years, respectively. All of them were presented with space-occupying renal lesions. Case 1 (KIAA1217-ALK RCC) showed mixed cystic and solid components under the microscope, with tubular, papillary, and cribriform arrangements. The tumor cells had clear boundaries, and were cubic or low columnar, arranged in a single layer, pseudostratified or in sheets. The cytoplasm was abundant and eosinophilic, and part of the cytoplasm was vacuolated, as if there was accumulation of mucoid substances. The tumor cell nuclei were oval with prominent nucleoli. A large amount of mucus and inflammatory cell infiltration were noted in the stroma. Case 2 (TPM1-ALK RCC) showed a papillary growth pattern, with small, slender papillae accompanied by branches. The cells were arranged in a single layer, and the cytoplasm was either eosinophilic or clear. Foamy cells were aggregated in the stroma, accompanied by psammoma body-like calcifications. Case 3 (EML4-ALK RCC) was characterized by papillary and tubulocystic structures. The cytoplasm was abundant and eosinophilic. The tumor cell nuclei were large, with prominent nucleoli. There was conspicuous infiltration of lymphocytes and neutrophils in the fibromuscular stroma. The tumor cells all expressed epithelial markers, PAX8, GATA3, P504s and FH. ALK (5A4) staining showed diffuse strong expression in the cytoplasm, while TFE-3 was positive (nuclear stain) only in case 1 and case 3. The fluorescence in situ hybridization showed that ALK gene rearrangement was present in all three cases, while TFE-3 gene rearrangement/mutation was not detectable in case 1 and case 3. NGS showed the KIAA1217::ALK fusion (the fusion site in the exon 11 of KIAA1217 and exon 18 of ALK) in case 1, the TPM1::ALK fusion (the exon 8 of TPM1 and exon 20 of ALK) in case 2, and the EML4::ALK fusion (the exon 2 region of EML4 and the exon 20 region of ALK) in case 3.Conclusions:ALK-rearranged RCC has unique molecular characteristics. Its histological morphology is easily confused with that of papillary RCC and TFE3-rearranged RCC. Both immunohistochemistry and gene rearrangement tests should be used to confirm the diagnosis.

Nonunion of osteoporotic vertebral fractures (OVF), predominantly affecting the elderly, can lead to intractable pain, vertebral collapse, progressive kyphotic deformity, and neurological impairment, significantly compromising patients′ quality of life. There exists considerable debate on diagnosis and management of OVF, encompassing key issues such as clinical diagnosis and staging criteria for nonunion, surgical indications and procedure selection, and postoperative rehabilitation planning. Currently, there lacks standardized clinical guideline and expert consensus on the diagnosis and management of OVF nonunion in China. To address this gap, Minimally Invasive Surgery Group of Chinese Orthopedic Association, Osteoporosis Committee of Chinese Association of Orthopedic Surgeons, Prevention and Rehabilitation Committee for Osteoporosis of Chinese Association of Rehabilitation Medicine and Minimally Invasive Orthopedic Surgery Branch of China Association for Geriatric Care jointly organized domestic experts in spinal surgery, endocrinology, and rehabilitation to formulate the Clinical guideline for the diagnosis and treatment for nonunion of osteoporotic vertebral fractures ( version 2025), based on existing literature and clinical experience and adhering to principles of scientific rigor and practicality. The guideline provided 13 evidence-based recommendations encompassing diagnosis and treatment of OVF nonunion, aiming to standardize its clinical management.

With the development of science and technology worldwide, the blooming of artificial intelligence (AI) and big data has brought new opportunities and challenges to the promotion of the research capacity of professional master's students in oncology. The construction of the new medical education in China aims to cultivate high-level medical talents with comprehensive multidisciplinary skills and innovative abilities to flexibly solve complex problems at the frontier of medicine. In this context, professional master's students in oncology, who are facing problems such as low scientific research output and uneven quality and needing improving scientific research literacy, have been required to develop into compound talents with both clinical and research prowess. To cultivate and promote the research capacity of professional master's students in oncology, the key steps include accelerating the construction of AI education and databases, highlighting the cultivation of their scientific research capacity, implementing and fostering the cultivation of innovative ability and scientific research thinking, piloting joint cultivation models by engineering universities and medical universities, emphasizing the construction of the curriculum and teacher team for oncology, piloting the multidisciplinary mode and COME mode, and establishing a multidisciplinary cooperation network.

Turning to critical illness is a common stage of various diseases and injuries before death. Patients usually have complex health conditions, while the treatment process involves a wide range of content, along with high requirements for doctor′s professionalism and multi-specialty teamwork, as well as a great demand for time-sensitive treatments. However, this is not matched with critical care professionals and the current state of medical care in China. Telemedicine, which shortens the distance of medical professionals and the gap of disease diagnosis and treatments in various regions through electronic information, can effectively solve the current problem. Therefore, there is an urgent need to develop a standardized, high-quality visualization telemedicine round system .Therefore, experts have been organized to search domestic and foreign literature on telemedicine round for critically ill patients and to form this consensus based on clinical experiences so as to further improve the level of critical care treatments in regions.