[摘 要] 目的：评估放疗作为原位疫苗的联合治疗模式在晚期软组织肉瘤（STS）患者中的有效性和安全性。方法：回顾性分析2020年12月至2024年9月期间在南京大学医学院附属鼓楼医院肿瘤中心接受联合治疗模式的12例晚期STS患者的临床资料。12例患者均接受了联合治疗。放疗主要以大分割为主。靶向治疗：安罗替尼10例、阿帕替尼2例。免疫治疗以PD-1抗体为主。主要研究终点为疾病控制率（DCR），次要研究终点为客观有效率（ORR）及安全性。结果：接受联合治疗的12例STS患者中有0例CR，4例PR，7例SD，1例PD。ORR为33%，DCR为91.7%，其中靶病灶的DCR为100%。12例患者中，9例出现Ⅰ~Ⅱ级不良反应。最常发生的血液学不良反应是贫血（6例）、肝功能检查结果异常（3例）。最常发生的非血液学不良反应是尿蛋白（5例）、高血压（4例）、甲状腺功能异常（3例）、厌食（3例）、恶心呕吐（2例）；仅2例发生Ⅲ级血液毒性，有1例发生Ⅲ级气胸。结论：放疗作为原位疫苗的联合治疗模式在晚期STS患者中展现出较高的DCR，且未出现严重不良反应。该联合治疗模式具有良好的有效性与安全性。

Studies on specific transient receptor potential melastatin 2 (TRPM2) channel inhibitors can deepen our understanding of the pathological mechanism of related diseases, and allow discovery of novel, effective targets and drugs for therapy. The development of TRPM2 channel inhibitors can be broadly classified into four categories with distinct characteristics: reutilization and structural modification of homologous ion channel modulators to produce a diverse array of TRPM2 channel inhibitors with strong inhibitory effects; TRPM2 channel inhibitors based on channel gating mechanism with high specificity; inhibitors identified through high-throughput screening with novel chemical structures; inhibitors developed from natural antioxidants with higher safety. In recent years, the application of computer-aided drug design has significantly accelerated the development of TRPM2 channel inhibitors. Several promising compounds such as ZA18, A1 and D9 have been discovered, and it is expected that more potent and selective TRPM2 channel inhibitor scaffolds will be discovered in the future. This article reviews the advances on the studies of TRPM2 channel inhibitors, aiming to provide insights for further research and clinical application of TRPM2 channel inhibitors.
TRPM Cation Channels/antagonists & inhibitors* ; Humans ; Drug Design

CRISPR/Cas9-based therapeutics face significant challenges in penetrating the dense microenvironment of solid tumors, resulting in insufficient gene editing and compromised treatment efficacy. Current nanostrategies, which mainly focus on the paracellular pathway attempted to improve gene editing performance, whereas their efficiency remains uneven in the heterogenous extracellular matrix. Here, the nanoCRISPR system is prepared with self-cascading mechanisms for gene editing-mediated robust apoptosis and transcellular penetration. NanoCRISPR unlocks its self-cascade capability within the matrix metallopeptidase 2-enriched tumor microenvironment, initiating the transcellular penetration. By facilitating cellular uptake, nanoCRISPR triggers robust apoptosis in edited malignancies, promoting further transcellular penetration and amplifying gene editing in neighboring tumor cells. Benefiting from self-cascade between robust apoptosis and transcellular penetration, nanoCRISPR demonstrates continuous gene transfection/tumor killing performance (transfection/apoptosis efficiency: 1st round: 85%/84.2%; 2nd round: 48%/27%) and homogeneous penetration. In xenograft tumor-bearing mice, nanoCRISPR treatment achieves remarkable anti-tumor efficacy (∼83%) and significant survival benefits with minimal toxicity. This strategy presents a promising paradigm emphasizing transcellular penetration to enhance the effectiveness of CRISPR-based antitumor therapeutics.

Objective To explore the mediating effect of psychological resilience between perceived spousal support and dignity loss in breast cancer patients.Methods A convenience sampling method was employed,involving 377 breast cancer patients who met the study criteria and received treatment at a tertiary oncology hospital in Yunnan Province from March to September 2023.Data were collected using a general information questionnaire,the Dignity Scale,the Perceived Spousal Support Scale,and the Psychological Resilience Scale.Data analysis was conducted using IBM SPSS 26.0 software.Results The scores for dignity loss,perceived spousal support,and psychological resilience of breast cancer patients were(41.72±6.77),(100.42±6.93),and(75.27±8.50),respectively.Pearson correlation analysis showed that dignity loss was negatively correlated with both perceived spousal support and psychological resilience(r1=-0.568,r2=-0.640,both P＜0.05).Mediation effect analysis indicated that psychological resilience had a mediating effect between perceived spousal support and dignity loss,with a value of-0.320(95％CI-0.409 to-0.246),accounting for 57.1％of the total effect.Conclusion The dignity of breast cancer patients in this study is in a state of mild loss,and psychological resilience plays a partial mediating role between perceived spousal support and dignity loss.This suggests that clinical medical staff should pay attention to the spousal support situation of breast cancer patients,provide timely guidance and health education to spouses,enhance the level of support from spouses,and strengthen the confidence and capability of couples in jointly coping with the disease,thereby alleviating dignity loss in breast cancer patients and improving their quality of life.

Objective To systematically evaluate the incidence and influencing factors of falls in adult cancer patients,and provide evidence support for early identification and prevention of falls.Methods Eight Chinese and English databases,including PubMed,Embase,CNKI,and Wanfang Database,were searched by computer.The databases were established until January 2024 and included in cross-sectional,cohort,and case-control studies based on the incidence and/or influencing factors of falls in adult cancer patients.Two researchers independently screened and reviewed literature,evaluated literature quality,and extracted data before conducting meta-analysis using RevMan 5.4 software.Results A total of 19 articles were incorporated into the research,with a total sample population size of 70508 cases.The results showed that the incidence of comorbid falls in adult tumor patients was 23.0%(95%CI 0.23,0.24).Age,female,low education level,fall history,fall fear,middle and late stage of tumor,tumor type(breast cancer,reproductive system tumor,prostate cancer),comorbidity,chemotherapy,radiotherapy,multiple drugs(n≥5),drugs(antidepressants,antipsychotics,sedatives and hypnotics),related symptoms(fever,peripheral neuropathy,fatigue,depression),malnutrition,low weight,cognitive dysfunction,balance disorders,gait abnormalities,and low ability of daily living were the influencing factors for falls of adult tumor patients.Conclusion Cancer professionals should identify the influencing factors of falls early and take targeted measures to reduce the occurrence of falls.

Objective To explore the current status of oncology nurses'medical narrative competence and to analyze its influencing factors.Methods 931 nurses from the oncological departments of 17 3A grade hospitals in Yunnan Province were selected from June to August 2023 and were surveyed using the Medical Narrative Competence Scale,the General Self-Efficacy Scale,and the Humanistic Care Scale.Results The score of medical narrative competence of oncology nurses was(151.52±14.61).The results of multiple linear regression showed that general self-efficacy,humanistic competence,years of experience,department,peer support,family support,familiarity with medical narratives,and job satisfaction were the factors influencing oncology nurses'competence in medical narratives(P<0.05),which explained 38.0%of the total variation.Conclusion The medical narrative competence of oncology nurses,moderately level,is influenced by multiple factors.

Objective To explore the different latent class and characteristics of the cognitive ability level of undergraduate nursing students in hospice care based on the individual-centered perspective,and analyze its influencing factors to provide the reference for the formulation of targeted nursing education.Methods Nursing students in a medical university in Yunnan Province were selected from March 2023 to June 2023.The general data questionnaire and hospice care knowledge questionnaire were used to conduct a cross-sectional survey.SPSS and Mplus were used for the data analysis.Results Three latent class of hospice care cognitive ability were identified,which were named as hospice care high cognitive ability group,general cognitive ability group,and low cognitive ability group,accounting for 28.74%,57.29%,and 13.97%,respectively;Nursing students'gender,nationality,place of residence,earning and practice experience of hospice care(whether they had the contact with end-stage cancer patients,whether they had received the hospice care related training),and whether they were willing to engage in the hospice care related work were the influencing factors of different potential categories of cognitive ability of hospice care among nursing students(P<0.05).Conclusion There are three latent class of hospice care cognitive ability of nursing students.Male minority nursing students who have not been exposed to end-stage cancer patients and have not received the hospice care-related training,are unwilling to engage in the hospice care-related work.Male ethnic minority nursing students residing in rural areas have the weaker cognitive levels of hospice care.Scholars in the future can formulate targeted training strategies according to different latent class of hospice care cognitive ability to improve nursing students'hospice care cognitive ability and reserve talents for hospice care teams.

The "pre-disease" theory of traditional Chinese medicine focuses on the dynamic and continuous evolution from health to disease, and emphasizes early identification and intervention in the complex and gradual process of evolution from health to disease. The "pre-disease" theory and complexity science share the same perspective on health and disease from the standpoint of features of the dynamic evolution and holism, i. e., life is considered as a complex system with ongoing dynamic changes, which exhibit the nonlinear features of " homeostasis-destabilization-phase transition-another homeostasis". In this paper, from the perspective of nonlinear dynamics in complexity science, we explain the scientific connotation of the evolution law of "pre-disease"-disease based on the theory of critical slowing down in traditional Chinese medicine. Based on the theory of critical slowing down and the dynamic network biomarker method generated by its development, combined with the macro signs of comprehensive analysis of data gained by four diagnostic method and the micro features including transcriptomics and the microbiomics, this paper proposes to integrate macro and micro multi-hierarchy information to construct a "pre-disease" critical slowing down identification model with the characteristics of traditional Chinese medicine diagnosis and treatment, which provides a new perspective and method for the early warning of complex diseases.

Objective To investigate the expression of Nanog and its regulatory relationship with MMP-2/MMP-9 proteins in esophageal squamous cell carcinoma(ESCC).Methods We detected Nanog and MMP-2/MMP-9 protein expressions in 127 ESCC tissues and 82 adjacent normal tissues using immunohistochemistry and explored their correlations with the clinicopathological parameters and prognosis of the patients.GEO database was utilized to analyze the pathways enriched with the stemness-related molecules including Nanog,and TIMER online tool was used to analyze the correlations among TβR1,MMP-2,and MMP-9 in esophageal cancer.Results Nanog and MMP-2/MMP-9 proteins were significantly upregulated in ESCC tissues and positively intercorrelated.Their expression levels were closely correlated with infiltration depth and lymph node metastasis of ESCC but not with age,gender,or tumor differentiation.The patients with high expressions of Nanog and MMP-2/MMP-9 had significantly shorter survival time.Bioinformatics analysis showed enrichment of stemness-associated molecules in the TGF-β signaling pathway,and the expressions of MMP-2/MMP-9 and TβR1 were positively correlated.In cultured ESCC cells,Nanog knockdown significantly decreased the expression of TβR1,p-Smad2/3,MMP-2,and MMP-9 and strongly inhibited cell migration.Conclusion The high expressions of Nanog,MMP-2,and MMP-9,which are positively correlated,are closely related with invasion depth,lymph node metastasis,and prognosis of ESCC.Nanog regulates the expressions of MMP-2/MMP-9 proteins through the TGF-β signaling pathway,and its high expression promotes migration of ESCC cells.