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.

Deep brain stimulation(DBS)has witnessed rapid advancement as a neurosurgical intervention over the past four decades,addressing movement disorders and a spectrum of neuropsychiatric conditions.Notably,subthalamic nucleus deep brain stimulation(STN-DBS)is widely implemented in the management of Parkinson's disease(PD)patients experiencing refractory motor fluctuations and complications,and has shown promise in ameliorating non-motor symptoms(NMS).However,the long-term efficacy of STN-DBS on NMS remains a subject of scholarly discourse.This review endeavors to synthesize current knowledge regarding the long-term impacts,underlying mechanisms,and future research directions of STN-DBS in the context of NMS in Parkinson's disease.

Objective:To analyze the clinical characteristics of anti-melanoma differentiation associated gene 5 (MDA5) antibody-positive juvenile dermatomyositis (JDM) patients.Methods:A retrospective case-control study was conducted. The positive group included 18 children with anti-MDA5 antibody-positive JDM who were admitted to the Department of Rheumatology and Immunology at Capital Center for Children′s Health with Capital Medical University between January 2016 and January 2023. Another 36 children with anti-MDA5 antibody-negative JDM hospitalized during the same period were enrolled as the negative group. Based on the extent of pulmonary involvement and pulmonary CT scores, the MDA5-positive group was further divided into severe pulmonary involvement and non-severe pulmonary involvement subgroups. Chi-square test and Kruskal-Wallis test were used to compare clinical features, laboratory test results between groups.Results:Among the 18 patients in the MDA5-positive group, 7 were male and 11 were female, with an age of onset of 5.0 (2.6, 9.4) years and disease duration of 6.0 (4.0, 9.3) months. The MDA5-negative group included 36 cases (14 male, 22 female), with an age of onset of 4.9 (2.0, 7.0) years and disease duration of 5.0 (1.8, 7.0) months. The MDA5-positive group exhibited significantly higher rates of arthritis, skin ulcers, and interstitial lung disease (ILD), along with elevated serum ferritin (SF) and erythrocyte sedimentation rate levels compared to the MDA5-negative group (9/18 vs. 11% (4/36), 6/18 vs. 3% (1/36), 16/18 vs. 33% (12/36), 327 (141, 518) vs. 131 (68, 257) μg/L, 17.5 (12.5, 26.8) vs. 11.0 (5.0, 13.0) mm/1 h, χ2=7.92, 7.41, 14.84, Z=2.50, 2.87, all P<0.05). Conversely, the MDA5-positive group had lower rates of muscle weakness and lower creatine kinase levels (5/18 vs. 75% (27/36), 58.5 (49.3, 97.5) vs. 225.0 (68.0, 695.5) U/L, χ2=11.08, Z=-2.94, both P<0.05). Severe pulmonary involvement 6 cases and non-severe pulmonary involvement subgroups 12 cases. Among the MDA5-positive patients, those in the severe pulmonary involvement subgroup had an older age at onset and higher rates of muscle weakness as well as hydroxybutyrate dehydrogenase (HBDH), lactate dehydrogenase (LDH), SF, and Krebs von den Lungen-6 (KL-6) compared to the non-severe subgroup (all P<0.05). In the MDA5-positive group, 17 patients improved after treatment with glucocorticoids combined with immunosuppressants, while One died due to rapidly progressive ILD. Conclusions:Anti-MDA5 antibody-positive JDM is characterized by typical skin rashes, a high incidence of arthritis and skin ulcers, relatively mild muscle involvement, but is prone to ILD. Among MDA5-positive patients, those with older age at onset, muscle involvement (manifested as muscle weakness and elevated muscle enzymes (LDH, HBDH)), or significantly elevated KL-6 and SF levels are more likely to develop severe pulmonary complications.

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.

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.

Immunotherapy has become a pivotal treatment regimen for hepatocellular carcinoma (HCC); however, its efficacy is influenced by various factors. Hepatitis B virus (HBV) infection is one of the primary etiological factors leading to HCC. HBV DNA replication can alter the immune microenvironment through multiple mechanisms, notably by upregulating the expression of programmed cell death protein 1 (PD-1) and its ligand (PD-L1), thereby facilitating tumor immune escape. Paradoxically, this upregulation of PD-1/PD-L1 may enhance the response rate to PD-1/PD-L1 inhibitors and potentiate the antitumor effect. This review aims to summarize current research progress on the relationship between HBV DNA load and the efficacy of PD-1/PD-L1 inhibitors, explore the underlying mechanisms, and provide a scientific basis for promoting personalized treatment strategies for patients with HBV-related HCC.

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 investigate the effects of acute sleep deprivation (ASD) on hippocampal glucose metabolism and neuroinflammation in rat models.Methods:Twenty SD rats (10 males and 10 females) were divided into four groups (five in each group) by random sampling method: female ASD group, male ASD group, female control group, and male control group. Among them, the ASD group constructed the ASD model. After 72h sleep deprivation, all rats underwent 18F-FDG and N, N-diethyl-2-(2-(4-(2- 18F-fluoroethoxy)phenyl)-5, 7-dimethylpyrazolo[1, 5-a]pyrimidin-3-yl)acetamide ( 18F-DPA-714) microPET/CT brain imaging in 2d to compare the changes of 18F-FDG and 18F-DPA-714 SUV mean in the hippocampus of rats. Brain histopathology, immunohistochemistry and immunofluorescence staining were detected in rats. Independent-sample t test was used to analyze the data. Results:18F-FDG imaging showed the hippocampal SUV mean between ASD group and control group (female: 4.11±0.35 vs 1.89±0.28; male: 3.43±0.47 vs 2.02±0.54) were statistically significant ( t values: 9.65, 3.92, P values: <0.001, 0.002). 18F-DPA-714 imaging showed the hippocampal SUV mean between ASD group and control group (females: 0.28±0.01 vs 0.28±0.02; male: 0.26±0.02 vs 0.31±0.04) were not statistically significant ( t values: -0.18, -2.24, P values: 0.859, 0.056). The 18×10 3 translocator protein (TSPO) immunohistochemistry showed the expression in the hippocampal region of the brain between ASD group and control group (female: 0.19±0.02 vs 0.19±0.01; male: 0.21±0.01 vs 0.20±0.01) were not statistically different ( t values: -0.48, -1.67, P values: 0.651, 0.139). Immunofluorescence staining showed that microglial cytosol in the hippocampal region of the brain decreased after 72h of ASD, and the protrusion points and surrounding branches were significantly reduced. Conclusion:Increased hippocampal glucose metabolism in rats is observed after 72 h of ASD without significant neuroinflammation.