Cuproptosis, a recently identified form of regulated cell death triggered by excess intracellular copper, has emerged as a promising cytotoxic strategy for cancer therapy. However, the therapeutic efficacy of copper ionophores such as elesclomol (ES) is often hindered by cellular copper homeostasis mechanisms that limit copper influx and cuproptosis induction. To address this challenge, we developed a nanoagent utilizing outer membrane vesicle (OMV) derived from Akkermansia muciniphila (Akk) for co-delivery of antioxidant 1 copper chaperone (Atox1)-targeting siRNA and ES (siAtox1/ES@OMV) to tumors. In vitro, we demonstrated that Atox1 knockdown via siRNA significantly disrupted copper export mechanisms, resulting in elevated intracellular copper levels. Simultaneously, ES facilitated efficient copper influx and mitochondrial transport, leading to Fe-S cluster depletion, increased proteotoxic stress, and robust cuproptosis. In vivo, siAtox1/ES@OMV achieved targeted tumor delivery and induced pronounced cuproptosis. Furthermore, leveraging the immunomodulatory properties of OMVs, siAtox1/ES@OMV promoted T-cell infiltration and the activation of tumor-reactive cytotoxic T cells, enhancing tumor immune responses. The combination of siAtox1/ES-induced cuproptosis and immunogenic cell death synergistically suppressed tumor growth in both subcutaneous breast cancer and orthotopic rectal cancer mouse models. This study highlights the potential of integrating copper homeostasis disruption with a copper ionophore using an immunomodulatory OMV-based vector, offering a promising combinatorial strategy for cancer therapy.

Objective:To explore the genotype and the clinical phenotype of SCN2A-related developmental delay in children. Methods:A case series study was adopted. Collect clinical data from 10 cases of children with SCN2A gene variants diagnosed with global developmental delay/intellectual disability who were admitted to the Children′s Hospital between July 2019 and March 2023. Summarize the clinical phenotype and genotype based on clinical data such as general information, clinical manifestations, imaging examinations, laboratory tests, genetic testing results, and comprehensive pediatric neuropsychological development assessment. Results:A total of 10 patients were recruited, including 7 males and 3 females, with an age range of 27 days to 5 years and 9 months. 9 patients underwent children′s neuropsychological and behavioral assessments, and the results were consistent with global developmental delay, including 2 mild cases, 4 moderate cases, and 3 severe cases. 3 cases had autism spectrum disorder, and 2 cases had epilepsy. 6 patients underwent complete head MRI examination, and 4 of them showed abnormalities, including delayed myelination, widening of the local extra brain space in the frontal lobe, and abnormal frontal lobe morphology. All 10 cases had point variants. Among them, 9 cases are de novo and 1 case is maternal inheritance. Out of 10 cases, there were 5 cases with copy number variations, but all of them were of unknown significance. Among the 10 variants, 8 have been reported and 2 have not been reported, namely c.4145A>T(p.N1382I) and c.4937T>A(p.I1646N). In this study, 4 out of 10 patients with SCN2A variants had variation sites located in the S4 segment of domain which constitute Nav1.2, the sodium ion channel encoded by SCN2A. The developmental quotient level was lower when the variation sites were located in the S4 segment of domain, and the difference was statistically significant ( t=-3.101, P=0.017), indicating that the severity of developmental delay may be related to the localization of amino acids corresponding to variant sites within the protein domain. Conclusion:SCN2A mutations are strongly associated with diverse neurodevelopmental disorders. In this study, the phenotypic spectrum of SCN2A variants encompassed epilepsy, global developmental delay, and autism spectrum disorder. Affected individuals exhibited early-onset developmental delays, predominantly moderate to severe in severity. Voltage-sensing domain dysfunction in sodium channels may constitute a critical pathomechanism underlying neurodevelopmental impairments. Further electrophysiological characterization and molecular mechanistic studies are warranted todelineate the genotype-phenotype correlations between specific variant loci and clinical severity.

Objective:To search, evaluate, and synthesize the best evidence for the management of diabetes in patients after heart transplantation, in order to provide reference for blood glucose management in subsequent patients within transplant teams.Methods:Following the "6S" model, a systematic search was conducted for guidelines, expert consensus, systematic reviews, and primary studies on the management and prevention of diabetes mellitus after heart transplantation. The search period was from database inception to May 22, 2024. The articles were assessed for quality and evidence grading using the Joanna Briggs Institute Evidence-Based Health Care Center's quality appraisal standards and evidence grading and recommendation grading system.Results:A total of 11 articles were included, consisting of three guidelines, six expert consensus papers, and two systematic reviews. These studies covered six key areas: early risk factor assessment, expansion of post transplantation diabetes mellitus screening trials, management of modifiable risk factors, lifestyle changes, implementation of personalized blood sugar reduction plans, and microvascular complication management. A total of 33 relevant pieces of evidence were summarized.Conclusions:The transplant team should formulate personalized blood glucose management plans based on clinical contexts, and heart transplant recipients should also actively engage in blood glucose monitoring and management to improve prognosis.

Objective:To explore the genotype and the clinical phenotype of SCN2A-related developmental delay in children. Methods:A case series study was adopted. Collect clinical data from 10 cases of children with SCN2A gene variants diagnosed with global developmental delay/intellectual disability who were admitted to the Children′s Hospital between July 2019 and March 2023. Summarize the clinical phenotype and genotype based on clinical data such as general information, clinical manifestations, imaging examinations, laboratory tests, genetic testing results, and comprehensive pediatric neuropsychological development assessment. Results:A total of 10 patients were recruited, including 7 males and 3 females, with an age range of 27 days to 5 years and 9 months. 9 patients underwent children′s neuropsychological and behavioral assessments, and the results were consistent with global developmental delay, including 2 mild cases, 4 moderate cases, and 3 severe cases. 3 cases had autism spectrum disorder, and 2 cases had epilepsy. 6 patients underwent complete head MRI examination, and 4 of them showed abnormalities, including delayed myelination, widening of the local extra brain space in the frontal lobe, and abnormal frontal lobe morphology. All 10 cases had point variants. Among them, 9 cases are de novo and 1 case is maternal inheritance. Out of 10 cases, there were 5 cases with copy number variations, but all of them were of unknown significance. Among the 10 variants, 8 have been reported and 2 have not been reported, namely c.4145A>T(p.N1382I) and c.4937T>A(p.I1646N). In this study, 4 out of 10 patients with SCN2A variants had variation sites located in the S4 segment of domain which constitute Nav1.2, the sodium ion channel encoded by SCN2A. The developmental quotient level was lower when the variation sites were located in the S4 segment of domain, and the difference was statistically significant ( t=-3.101, P=0.017), indicating that the severity of developmental delay may be related to the localization of amino acids corresponding to variant sites within the protein domain. Conclusion:SCN2A mutations are strongly associated with diverse neurodevelopmental disorders. In this study, the phenotypic spectrum of SCN2A variants encompassed epilepsy, global developmental delay, and autism spectrum disorder. Affected individuals exhibited early-onset developmental delays, predominantly moderate to severe in severity. Voltage-sensing domain dysfunction in sodium channels may constitute a critical pathomechanism underlying neurodevelopmental impairments. Further electrophysiological characterization and molecular mechanistic studies are warranted todelineate the genotype-phenotype correlations between specific variant loci and clinical severity.

Objective:To search, evaluate, and synthesize the best evidence for the management of diabetes in patients after heart transplantation, in order to provide reference for blood glucose management in subsequent patients within transplant teams.Methods:Following the "6S" model, a systematic search was conducted for guidelines, expert consensus, systematic reviews, and primary studies on the management and prevention of diabetes mellitus after heart transplantation. The search period was from database inception to May 22, 2024. The articles were assessed for quality and evidence grading using the Joanna Briggs Institute Evidence-Based Health Care Center's quality appraisal standards and evidence grading and recommendation grading system.Results:A total of 11 articles were included, consisting of three guidelines, six expert consensus papers, and two systematic reviews. These studies covered six key areas: early risk factor assessment, expansion of post transplantation diabetes mellitus screening trials, management of modifiable risk factors, lifestyle changes, implementation of personalized blood sugar reduction plans, and microvascular complication management. A total of 33 relevant pieces of evidence were summarized.Conclusions:The transplant team should formulate personalized blood glucose management plans based on clinical contexts, and heart transplant recipients should also actively engage in blood glucose monitoring and management to improve prognosis.

Objective:To explore the characteristics and typology of self-care behavior among patients with chronic heart failure (CHF), and analyze their influencing factors.Methods:A cross-sectional study was used. A total of 318 patients with CHF who were hospitalized in the Heart Center of Zhongshan Hospital, Fudan University from November 2022 to July 2023 were selected by continuous enrollment method. The General Information Questionnaire, Heart Failure Self-care Index Scale, Brief Illness Perception Questionnaire, Self-efficacy for Managing Chronic Disease 6-item Scale, Perceived Social Support Scale, Atlanta Heart Failure Knowledge Test-V2 and Self-Care Confidence Scale were used to investigate. Latent profile analysis was utilized to delineate the characteristics and subtypes of self-care behaviors in CHF patients and examine the influencing factors.Results:A total of 291 patients were included in this study, including 190 males and 101 females, aged 67 (61, 74) years old. The analysis identified three latent categories of self-care behaviors among CHF patients: 26 cases in high self-care group, 131 cases in moderate self-care with deficiencies in maintenance and symptom perception group, and 134 cases in low self-care group.Ordered multicategorical Logistic regression analysis revealed that age ( OR=1.023, 95% CI 1.001-1.046, P<0.05), self-care confidence ( OR=0.859, 95% CI 0.817-0.904, P<0.01), and social support ( OR=0.966, 95% CI 0.940-0.993, P<0.05) were the factors influencing the potential categories of self-care behavior in CHF patients. Conclusions:The study identifies distinct categorical characteristics of self-care behaviors in patients with CHF. Healthcare professionals can leverage these findings to identify the self-care behavior characteristics and influencing factors for each patient category at an early stage, thereby providing personalized and precise support strategies to help patients enhance self-care behaviors.

This paper systematically analyzed the understanding of qi from the perspectives of matter， energy， information and relationship reality， introduced the original holistic principle of systematic traditional Chinese medicine （TCM）， and considered the latest research results of qi （three-layer material theory）， trying to optimize the structure framework of the qi theoretical system and exhibit the occurrence and development rules of original qi. It emphasizes the hierarchical order of qi transformation following the original holistic principle， and takes this to guide the clinical understanding of “qi diseases”， helping doctors grasp the basic pathogenesis of the disease， that is abnormal qi movement， and helping them establish the awareness of providing systematic TCM treatment to patients by taking qi regulation as the key. At the same time， it discusses people within the structure of time and space， and points out that the treatment of diseases must comply with the principle of “the harmony of heaven， earth， and human beings”.

The human resource management of organ donation coordinators in China is still in its infancy stage, plagued by such problems as unclear career orientation, poor management and unclear career planning. In March 2010, a tertiary public hospital was approved as a medical institution in a national pilot province for organ donation. In recent years, the hospital had kept exploring human resource management of coordinators and established a relatively complete management mode for organ donation coordinators. This mode featured the establishment of full-time recruitment positions, development of human resource management plans, refinement of job descriptions, establishment of performance evaluation plans, optimization of assessment and incentive mechanisms, and innovation of talent cultivation modes. The management practice had achieved certain results, ensuring the sustainable development of hospital organ donation operation, and providing a reference for the scientific and standardized development of organ donation and transplantation in China.

ObjectiveTo explore the macroscopic medication pattern of traditional Chinese medicine （TCM） in treating esophageal cancer （EC） and provide medication references for the clinical application of TCM in EC treatment. MethodRelevant literature on TCM treatment of EC was retrieved from three major Chinese databases： China National Knowledge Infrastructure （CNKI）， Wanfang Data， and VIP. Information about Chinese herbal medicines was entered into Excel to establish a prescription database for EC. The data were standardized， summarized， and subjected to frequency analysis， association rules， and cluster analysis of medication in the prescriptions. Based on the TCM classification of EC syndromes， clinical indications corresponding to each syndrome were identified， and high-frequency drugs and drug pairs were analyzed correspondingly with syndromes. ResultA total of 136 prescriptions containing 240 Chinese herbal medicines were screened， with a cumulative frequency of 1 853 times. The top 5 frequently used Chinese herbal medicines were Glycyrrhizae Radix et Rhizoma， Poria， Atractylodis Macrocephalae Rhizoma， Astragali Radix， and Pinelliae Rhizoma. In terms of functions， the Chinese herbal medicines were mainly deficiency-tonifying， urination-promoting and dampness-draining， deficiency-tonifying， deficiency-tonifying， and phlegm-resolving and cough and dyspnea-relieving ones. The statistical analysis of flavor， property， and meridian tropism showed that Chinese herbal medicines were mainly bitter and sweet， warm， cold， and neutral， and acted on the spleen， lung， and stomach meridians. Association rule analysis yielded nine potential drug combinations， and cluster analysis of high-frequency drugs resulted in four combination categories. The four TCM syndromes for EC corresponded to respective clinical indications， treatment drugs， and drug pairs. ConclusionTonifying deficiency， reinforcing healthy Qi， descending adverse Qi， resolving phlegm， activating blood， and resolving stasis are the basic principles of TCM treatment for EC， which are supplemented by clearing heat and dissipating mass while focusing on regulating and smoothing the qi movement. The drug combinations obtained from high-frequency drug and association rule analysis provide references for different TCM syndrome treatments of EC， offering valuable insights for clinical medication.

OBJECTIVE: To investigate the serum microRNA (miRNA) expression and examine the impact of miRNA expression profiles on T helper type 17 (Th17)/regulatory T cells (Treg) imbalance among patients with cystic echinococcosis, so as to provide insights into the illustration of the mechanisms underlying chronic Echinococcus granulosus infections, and long-term pathogenesis. METHODS: Total RNA was extracted from the sera of cystic echinococcosis patients and healthy controls, and subjected to high-throughput sequencing with the Illumina sequencing platform. Known miRNAs were annotated and new miRNAs were predicted using the miRBase database and the miRDeep2 tool, and differentially expressed miRNAs were identified. The target genes of differentially expressed miRNAs were predicted using the software miRanda and TargetScan, and the intersection was selected for Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Among the differentially expressed miRNAs with the 20 highest fold changes, miRNAs that targeted genes relating to key transcription factors RORC and FOXP3 that determine the production of Th17 and Treg cells or their important regulatory pathways (PI3K-Akt and mTOR pathways) were matched. RESULTS: A total of 53 differentially expressed miRNAs were screened in sera of cystic echinococcosis patients and healthy controls, including 47 up-regulated miRNAs and 6 down-regulated miRNAs. GO enrichment analysis showed that these differentially expressed miRNA were involved DNA transcription and translation, cell components, cell morphology, neurodevelopment and metabolic decomposition, and KEGG pathway analysis showed that the differentially expressed miRNA were mainly involved in MAPK, PI3K-Akt and mTOR signaling pathways. Among the differentially expressed miRNAs with the 20 highest fold changes, there were 3 miRNAs that had a potential for target regulation of RORC, and 15 miRNAs that had a potential to target the PI3K-Akt and mTOR signaling pathways. CONCLUSIONS Significant changes are found in serum miRNA expression profiles among patients with E. granulosus infections, and differentially expressed miRNAs may lead to Th17/Treg imbalance through targeting the key transcription factors of Th17/Treg or PI3K-Akt and mTOR pathways, which facilitates the long-term parasitism of E. granulosus in hosts and causes a chronic disease.
Echinococcosis/genetics* ; Gene Expression Profiling ; Humans ; MicroRNAs/metabolism* ; Phosphatidylinositol 3-Kinases/genetics* ; Proto-Oncogene Proteins c-akt/genetics* ; T-Lymphocytes, Regulatory ; TOR Serine-Threonine Kinases/genetics* ; Th17 Cells ; Transcription Factors/genetics*