[摘 要] 目的：探讨胰岛素样生长因子2 mRNA结合蛋白3（IGF2BP3）、尿苷二磷酸-葡萄糖醛酸脱羧酶1（UXS1）在肝细胞癌（HCC）中的表达特征、预后价值及两者协同作用的分子机制。方法：整合UALCAN、cBioPortal、ENCORI、TISCH2、GDSC等公共数据库的转录组数据，对IGF2BP3和UXS1进行表达、预后评估、功能富集及药物敏感性等分析。收集GEO数据库的单细胞RNA测序（scRNA-seq）数据，分析细胞通信、单细胞代谢评分，系统解析IGF2BP3-UXS1轴在HCC中的具体作用。结果：IGF2BP3、UXS1在HCC组织中均显著高表达，且高表达患者总生存期显著缩短（均P < 0.05）。采用CRISPP技术敲除IGF2BP3或UXS1后，多种HCC细胞的增殖能力受到明显抑制。scRNA-seq分析揭示了IGF2BP3、UXS1在肝细胞等细胞类型中的广泛表达分布，前者在细胞分化晚期上调，后者则在细胞分化早、中期高表达。IGF2BP3、UXS1高表达组均显著激活了MIF通路，同时IGF2BP3的高表达削弱了成纤维细胞的相互作用，而UXS1的高表达则增强了T细胞的信号转导功能。IGF2BP3与UXS1在表达相关性中存在显著的正相关（r = 0.432，P < 0.05）。沉默IGF2BP3结合位点会导致UXS1表达水平变化（F = 0.333）。功能富集分析提示，IGF2BP3与UXS1协同调控能量代谢、蛋白质翻译等生物学过程。在IGF2BP3或UXS1高表达的细胞亚群中，发现两者与多个糖代谢相关通路存在显著关联。IGF2BP3、UXS1高表达的患者对优普色替等药物表现出显著的敏感性，还对药物那维托克等表现出显著的耐药性。结论： IGF2BP3、UXS1在HCC中高表达，两者通过调控糖代谢重编程的协同作用促进HCC恶性生物学行为。

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:Parkinson's disease has the main pathological changes in the midbrain,especially in the dense substantia nigra,leading to impaired motor and non-motor function in patients.At present,research is limited by cellular heterogeneity,and its pathogenesis still needs to be further elucidated.In recent years,single-cell RNA sequencing(scRNA-seq)has gradually been applied in neurodegenerative diseases,which is of great significance for understanding intercellular heterogeneity,disease development mechanisms,and treatment strategies. OBJECTIVE:To review the research progress of scRNA-seq technology applied to Parkinson's disease in recent years,providing a theoretical basis for the application of scRNA-seq in the treatment and diagnosis of Parkinson's disease. METHODS:The first author used a computer system to search for relevant literature in the CNKI,WanFang,PubMed,and Web of Science databases,with the Chinese search terms"single-cell RNA sequencing,Parkinson's disease,cell heterogeneity,cell subtypes,dopaminergic neurons,glial cells"and English search terms"single-cell RNA seq,Parkinson disease,heterogenicity,subtypes,dopaminergic neurons,glial cells."71 articles were ultimately included for review and analysis. RESULTS AND CONCLUSION:(1)scRNA-seq is a high-throughput experimental technique that utilizes RNA sequencing at the single-cell level to quantify gene expression profiles in specific cell populations,revealing cellular mysteries at the molecular level.Compared with traditional sequencing techniques,scRNA-seq technology is used to reveal the diversity of cell types and changes in specific gene expression in complex tissues under various physiological and pathological conditions through automatic clustering analysis of cell transcriptome.(2)By using scRNA-seq,the development process of dopaminergic neurons and the unique functional characteristics of various cell subtypes are elucidated,in order to better understand potential therapeutic molecular targets.(3)The use of scRNA-seq analysis has improved our understanding of the response of Parkinson's disease glial cells,enabling us to comprehensively map and characterize different cell type populations,identify specific glial cell subpopulations related to neurodegeneration,and draw valuable single cell maps as reference data for future research.(4)The application of scRNA-seq to detect embryonic mice and stem cells will help improve the in vitro differentiation protocol and quality control of cell therapy,as well as evaluate the overall cell quality and developmental stage of dopaminergic neurons derived from stem cells.

Objective To evaluate the safety and effectiveness of different doses of epidural oxycodone injection for traction reaction during cesarean sections to determine the optimal dose.Methods Totally 119 cases of parturients who underwent cesarean sections from October 2023 to May 2024 were selected and randomly divided into groups A,B,C and D.All four groups of lying-in women received epidural injection after the umbilical cord was cut.Groups A,B and C were given oxycodone 3 mg,5 mg and 7 mg respectively,and group D was given an equal amount of normal saline.The primary outcomes were documentation of maternal vital signs and traction reaction during the surgery.Secondary outcomes included patient-controlled intravenous analgesia(PCIA)times within 48 hours and documentation of any postoperative adverse events within 24 hours.Results The comparison of in-tra?operative vital signs among the four groups of patients revealed no statistically significant differences.In groups A,B and C the incidence of traction reactions was significantly lower at 20％,17.2％and 3.3％,respectively,compared to group D at 53.3％,showing statistically significant differences(P<0.05).Additionally,the inci?dence of traction reaction in group C was significantly lower than in group A(P<0.05).Groups A,B and C pro?duced significantly better results than group D in terms of the duration of anesthesia.PCIA presses were substan?tially less in groups A and C than in group D(P<0.05),and group C had a significantly higher total incidence of adverse events than group A and group D(P<0.05).Conclusions Epidural injection of 3 mg,5 mg and 7 mg oxycodone has been proved to significantly reduce traction reaction during cesarean sections while minimally im?pacting intraoperative vital signs.This intervention has the potential to extend the duration of anesthesia,decrease the frequency of PCIA presses.Among these,7 mg is the most effective but has the highest incidence of adverse effects,requiring carefully post?operative monitoring.

OBJECTIVES: The integrated endoplasmic reticulum stress inhibitor (ISRIB) is a selective inhibitor of the protein kinase R-like endoplasmic reticulum kinase (PERK) signaling pathway within endoplasmic reticulum stress (ERS) and can improve spatial and working memory in aged mice. Although ERS and oxidative stress are tightly interconnected, it remains unclear whether ISRIB alleviates cognitive impairment by restoring the balance between ERS and oxidative stress. This study aims to investigate the effects and mechanisms of ISRIB on lipopolysaccharide (LPS)-induced cognitive impairment in mice. METHODS: Eight-week-old male ICR mice were randomly divided into 3 groups: Normal saline (NS) group, LPS group, and ISRIB+LPS group. NS and LPS groups received daily intraperitoneal injections of normal saline for 7 days; on day 7, LPS group mice received intraperitoneal LPS (0.83 mg/kg) to establish a cognitive impairment model. ISRIB+LPS group received ISRIB (0.25 mg/kg) intraperitoneally for 7 days, with LPS injected 30 minutes after ISRIB on day 7. Cognitive ability was evaluated by the novel place recognition test (NPRT). Real-time fluorogenic quantitative PCR (RT-qPCR) was used to detect changes in nitric oxide synthase (NOS), superoxide dismutase-1 (SOD-1), and catalase (CAT) gene expression in the hippocampus and prefrontal cortex. Oxidative stress markers malondialdehyde (MDA), glutathione (GSH), and oxidized glutathione (GSSG), were measured in hippocampal and prefrontal cortex tissues. RESULTS: Compared with the NS group, mice in LPS group showed a significant reduction in novel place recognition ratio, upregulation of hippocampal NOS-1 and NOS-2 mRNA, downregulation of SOD-1 and CAT mRNA, increased MDA and GSSG, decreased GSH, and reduced GSH/GSSG ratio (all P<0.05). Compared with the LPS group, mice in ISRIB+LPS group exhibited significantly improved novel place recognition, downregulated NOS-1 and NOS-2 mRNA, upregulated SOD-1 and CAT mRNA, decreased MDA and GSSG, increased GSH, and an elevated GSH/GSSG ratio in the hippocampus (all P<0.05). No significant changes were observed in the prefrontal cortex. CONCLUSIONS ISRIB improves LPS-induced cognitive impairment in mice by restoring the oxidative/antioxidant balance in the hippocampus.
Animals ; Lipopolysaccharides ; Male ; Mice, Inbred ICR ; Cognitive Dysfunction/drug therapy* ; Mice ; Oxidative Stress/drug effects* ; Endoplasmic Reticulum Stress/drug effects* ; Hippocampus/drug effects* ; Nitric Oxide Synthase Type II/genetics* ; Guanidines/pharmacology* ; eIF-2 Kinase/antagonists & inhibitors* ; Signal Transduction/drug effects* ; Superoxide Dismutase/metabolism*

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

Objective To investigate the current status of pain crisis in patients with advanced colorectal cancer(CRC)and analyze its influencing factors.Methods A total of 186 patients with advanced CRC who were hospitalized in the Oncology Department,the Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine from June 2024 to March 2025 were selected as the subjects of the investigation.General information questionnaires numerical rating scale,distress tolerance scale,self-rating anxiety scale,self-rating depression scale and quality of life assessment scales were used for the investigation.Logistic regression was used to analyze the influencing factors of pain crisis in patients with advanced CRC.Results Among the 186 CRC patients,87 experienced pain crises,with an incidence rate of 46.8％.The results indicated that pain type,use of analgesics,traditional Chinese medicine adjuvant therapy,metastasis radiotherapy and chemotherapy,pain intensity and pain tolerance were important influencing factors for pain crises in advanced CRC patients.Conclusion The incidence of pain crisis in patients with advanced CRC is relatively high.Nursing staff should promptly identify patients with pain crisis and implement targeted intervention strategies for high-risk patients to reduce the risk of pain crisis.

Objective:To investigate the efficacy of botulinum toxin type A (BTX-A) injections in treating motor tics in adult patients with tic disorders.Methods:A retrospective analysis was conducted on the baseline and clinical data of 25 adult tic disorder patients who received BTX-A treatment at the Movement Disorders Clinic of the Department of Neurology, Peking Union Medical College Hospital, from January 2019 to July 2023. Before the treatment, the Yale Global Tic Severity Scale (YGTSS) was used to assess the severity of motor and vocal tics. The injection sites and dosage of BTX-A were determined based on the distribution and severity of tic symptoms. Post-treatment improvement was evaluated via telephone follow-up.Results:Among the 25 patients, 18 were male and 7 were female, with an age of 27.0 (23.5, 31.0) years and a disease duration of 10.0 (5.5, 18.5) years. The pre-treatment YGTSS score was 41.3±12.3. After treatment, the time to onset of effect was 2.0 (1.0, 5.0) days, the peak efficacy was achieved at (15.5±9.4) days, and the duration of efficacy was 4.0 (2.5, 6.0) months. Post-treatment YGTSS score decreased to 14.7±11.3, with an improvement rate of 63.7%±24.9%. Significant efficacy was observed in 68.0% (17/25) of patients, 28% (7/25) showed moderate improvement, and 4% (1/25) had no response. Anxiety symptoms were alleviated in 91% (21/24) of patients, and premonitory urges were reduced in 90% (18/20) of patients. Retreatment in 13 patients with symptom recurrence remained effective. Adverse effects included facial stiffness in 4 patients, scalp tightness in 1, and mild neck muscle weakness in 5, all of which resolved spontaneously within 3-14 days; 16 patients reported no adverse effects.Conclusion:BTX-A is safe and effective in controlling motor tics in adult patients with tic disorders.

The prevalence of suicidal ideation (SI) and suicide behavior (SB) has gradually risen among adolescents with major depressive disorders in recent years, yet the underlying neurological mechanisms remain unknown. With the advancement of neuroimaging technology, multimodal magnetic resonance imaging (MRI) methods show fundamental value in detecting structural and functional brain abnormalities associated with these conditions. Preliminary studies have revealed alterations in key brain regions, such as the prefrontal cortex, amygdala, and anterior cingulate cortex, in adolescents with major depressive disorders. These findings provide critical insights into the neuropathological basis and underlying mechanisms of SI and SB in adolescent major depressive disorders. This review summarizes recent advances in brain structure and function in adolescents with major depressive disorder who exhibit SI and/or SB using diverse MRI techniques. This paper will provide new insights for the investigation of the neurobiological mechanisms underlying suicidality in adolescents with major depressive disorder, and provide objective neuroimaging evidence for the early identification and individualized intervention for at-risk adolescents.

Objective To explore the identification of adverse reactions of type 1 diabetes during lung cancer treat-ment with cardonilimab and the pharmaceutical monitoring of patient's blood glucose management,and to accumulate ex-perience for the prevention,treatment,and pharmaceutical services of related diseases.Methods The clinical pharmacist assisted doctors in judging adverse drug reactions and identifying suspicious drugs in a patient with lung cancer who devel-oped type 1 diabetes.At the same time,the clinical pharmacist provided suggestions for clinical treatment by referring to clinical evidence,and providing medication education,pharmaceutical care,and long-term follow-up for the patient's blood glucose management.Results After intensive insulin therapy and dietary control,the patient's high glucose symptoms were relieved,and the blood glucose gradually stabilized.The patient continued to be challenged using cardonilimab immu-notherapy,and the condition was stable.Conclusions Clinical pharmacists assist physicians in identifying adverse drug reactions on time and participate in the full process management of patient medication.They play an active therapeutic role in the medical team and reflect the value of pharmaceutical services.