Gastrointestinal (GI) cancers are a leading cause of cancer morbidity and mortality worldwide. Despite advances in treatment, cancer relapse remains a significant challenge, necessitating novel therapeutic strategies. In this study, we engineered nanobody-based chimeric antigen receptor (CAR) natural killer (NK) cells targeting cadherin 17 (CDH17) for the treatment of GI tumors. In addition, to enhance the efficacy of CAR-NK cells, we also incorporated CV1, a CD47-SIRPα axis inhibitor, to evaluate the anti-tumor effect of this combination. We found that CDH17-CAR-NK cells effectively eliminated GI cancers cells in a CDH17-dependent manner. CDH17-CAR-NK cells also exhibit potent in vivo anti-tumor effects in cancer cell-derived xenograft and patient-derived xenograft mouse models. Additionally, the anti-tumor activity of CDH17-CAR-NK cells is synergistically enhanced by CD47-signal regulatory protein α (SIRPα) axis inhibitor CV1, likely through augmented macrophages activation and an increase in M1-phenotype macrophages in the tumor microenvironment. Collectively, our findings suggest that CDH17-targeting CAR-NK cells are a promising strategy for GI cancers. The combination of CDH17-CAR-NK cells with CV1 emerges as a potential combinatorial approach to overcome the limitations of CAR-NK therapy. Further investigations are warranted to speed up the clinical translation of these findings.

Objective:To understand the incidence trend of meningococcal meningitis from 1990 to 2023 and major pathogenic serogroups of Neisseria ( N.) meningitidis from 2006 to 2023 in China and the time trend of the incidence of meningococcal meningitis caused by main pathogenic serogroups, and provide reference for the prevention and control of meningococcal meningitis. Methods:The study used the data from "National Epidemic Data Compile" from 1990 to 2003 and the data from China Notifiable Infectious Disease Reporting System from 2004 to 2023 to analyze the incidence trend of meningococcal meningitis in China from 1990 to 2023 by Joinpoint regression method. Based on the data of the national meningococcal meningitis surveillance information reporting and management system from 2006 to 2023, the incidence of meningococcal meningitis caused by different serogroups of N. meningitidis was described and analyzed, and the trend χ2 test was performed to analyze the change of the incidence of meningococcal meningitis caused by N. meningitidis A, B, and C. Results:The overall incidence of meningococcal meningitis in China showed a downward trend from 1990 to 2023 [average annual percent change (AAPC)=-14.80%, P<0.001], with the most obvious decline from 2005 to 2012 [annual percent change (APC)=-31.01%, P<0.001]. The incidence of meningococcal meningitis decreased in both men and women (AAPC=-14.69% and -15.05%, both P<0.001). A total of 1 178 serogroup specific cases of meningococcal meningitis were reported in China from 2006 to 2023, the proportion of serogroup C was highest (32.5%), followed by unclassified (22.3%), B (20.1%), A (18.4%), W (4.5%), Y (2.0%) and X (0.2%). The results of trend χ2 test indicated that the incidence of meningococcal meningitis caused by N. meningitidis A and C showed downward trends (both P<0.001) and the incidence of meningococcal meningitis caused by N. meningitidis B showed an upward trend in general population and young children (0-4 years old group) from 2006 to 2023 (both P<0.05). Conclusion:The incidence of meningococcal meningitis showed a downward trend in China from 1990 to 2023, but it is still necessary to pay more attention to the incidence of meningococcal meningitis caused by N. meningitidis B in age group aged 0-4 years and by multi serogroups at same time in general population.

Cockayne syndrome(CS)group B(CSB),which results from mutations in the excision repair cross-complementation group 6(ERCC6)genes,which produce CSB protein,is an autosomal recessive disease characterized by multiple progressive disorders including growth failure,microcephaly,skin photosensitivity,and premature aging.Clinical data show that brain atrophy,demyelination,and calcification are the main neurological manifestations of CS,which progress with time.Neuronal loss and calcification occur in various brain areas,particularly the cerebellum and basal ganglia,resulting in dyskinesia,ataxia,and limb tremors in CSB patients.However,the understanding of neurodevelopmental defects in CS has been constrained by the lack of significant neurodevelopmental and functional abnormalities observed in CSB-deficient mice.In this review,we focus on elucidating the protein structure and distribution of CSB and delve into the impact of CSB mutations on the development and function of the nervous system.In addition,we provide an overview of research models that have been instrumental in exploring CS disorders,with a forward-looking perspective on the substantial contributions that brain organoids are poised to further advance this field.

Objective:To investigate the effect of nuclear factor-erythroid 2-related factor 2 (Nrf2) gene on the proliferation and apoptosis of colorectal adenocarcinoma cells in vitro, and the role of Nrf2 gene in regulation of epithelial-mesenchymal transition (EMT) pathway.Methods:Three Nrf2 small interfering RNA (siRNA) sequences were designed and synthesized, namely siRNA-223, siRNA-538 and siRNA-756, and the unrelated sequences were designed and synthesized. The plasmids carrying various siRNA sequences of Nrf2 were constructed, and the plasmids carrying siRNA sequences and the plasmids carrying unrelated sequences were transfected into human colorectal adenocarcinoma Caco-2 cells, namely interference group and empty vector group, respectively. Additionally, Caco-2 cells without any treatment were used as the control group. Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and Western blotting (WB) methods were used to detect the relative expression of Nrf2 gene in transcription and translation levels in each group of cells, in order to verify the interference effect of Nrf2; the siRNA with the best interference effect was selected for subsequent experiments. CCK-8 method was used to detect the proliferation ability of each group of cells (expressed as absorbance value); RT-qPCR was used to detect the relative expression of EMT pathway-related factors [vimentin (Vim), N-cadherin (N-cad) and E-cadherin (E-cad)] in transcription level in each group of cells; WB method was used to detect the expression of pro-apoptotic protein Bax in each group of cells.Results:The results of RT-qPCR and WB methods showed that compared with the control group and the empty group, the relative expression of Nrf2 gene in transcription and translation levels in Caco-2 cells of the siRNA-756 interference group were the lowest, and the differences were statistically significant (all P < 0.05). The CCK-8 results showed that the absorbance values of Caco-2 cells in the control group, empty group and siRNA-756 interference group after 48 hours of culture were (100±5)%, (94±4)% and (82±5)%, respectively; compared with the control group and the empty group, the siRNA-756 interference group had lower absorbance value, and the differences were statistically significant (all P < 0.05). The results of RT-qPCR method showed that the relative expression of Vim and N-cad in transcription level in the siRNA-756 interference group were higher than those in the control group and the empty vector group, and the differences were statistically significant (all P < 0.05); the relative expression of E-cad in transcription level was lower than those in the control group and the empty vector group, and the differences were statistically significant (both P < 0.05). The results of WB method showed that the relative expression of Bax protein in the siRNA-756 interference group was higher than that in the control group, and the difference was statistically significant ( P < 0.05). Conclusions:Interference with Nrf2 expression in vitro can weaken the proliferation and anti-apoptotic abilities of human colorectal adenocarcinoma Caco-2 cells. The mechanism may be that Nrf2 regulates the expression of Vim, N-cad and E-Cad in the EMT pathway to enhance the EMT ability of tumor cells.

Skin wounds are global public problems,especially in terms of the difficult healing of chronic wounds,which may seriously affect patients'lives.Most skin-wound animal models are currently established by physical method,and different animal models have different biological characteristics.This review therefore classifies mouse,rat,and other animal models of skin wounds according to the literature,summarizes and analyzes the construction of skin-wound animal models based on physical method and evaluation indicators,and considers the advantages and disadvantages of different animal models,to provide a basis for the rational construction of skin-wound animal models and drug research and development.

Objective:To develop the training syllabus of palliative care for general practitioners.Methods:Twenty-nine experts in fields of general practice and hospice care from different teaching hospitals and community health service centers were invited to participate in two rounds of Delphi consultation from April 2022 and August 2022. Based on results of Delphi consultation a preliminary training syllabus was established through data analysis, synthesis and process.Results:Of the 29 experts, 11 (37.9%) were male with age of (52.9±8.9) years and working experience of (17.0±7.2) years. The expert activity coefficient of the two rounds of consultation was 100.0% (29/29) and 96.6% (28/29), authority coefficient was 0.815 and 0.870, and opinion coordination coefficient was 0.359 and 0.515, respectively ( P<0.05). The training syllabus comprised of 4 first-grade indicators, 19 second-grade indicators and 58 third-grade indicators. The weight coefficients of the 4 first-grade indicators, namely objective of training, theory courses and theoretical knowledge, clinical base rotation contents and requirements, community base rotation content and requirements, were 0.251, 0.251, 0.250 and 0.248, respectively. Conclusions:A preliminary training syllabus of palliative care for general practitioner has been developed in this study, which provide a basis for standardized training of community palliative care.

Objective:To develop standards of hospice care specialized clinical training base for general practitioners.Methods:Twenty nine experts in fields of general practice and hospice care were invited to participate in two rounds of Delphi expert consultation from April 2022 to August 2022. Based the results of Delphi consultations the standards of clinical training base for general practitioner hospice care specialized training were developed through data analysis, synthesis and process.Results:The age of 29 consulting experts was (52.9±8.9) years old, and their working years were (17.0±7.2) years, 69.0% (20/29) of them had senior professional titles. In the two rounds of expert consultation, the expert positive coefficient was 100.0% (29/29) and 96.6% (28/29), the expert authority coefficient was 0.791 and 0.830, and the expert opinion coordination coefficient W of the importance of all indicators was 0.177 and 0.296, respectively ( χ2=133.54 , 223.46; P<0.01). Finally, a set of clinical base standards for general practitioner hospice care specialized training was established, which consisted of 4 first-level indicators and 23 second-level indicators. The 4 first-level indicators were basic conditions, teaching conditions, teacher conditions and teaching management, with the weight coefficients of 0.250, 0.250, 0.251 and 0.253, respectively. Conclusions:The clinical training base standards of hospice care specialized training for general practitioners have been established in this study, which will be helpful in selecting appropriate hospitals as the specialized clinical training base for general practitioners.

Objective:To develop standards of hospice care community training base for general practitioners.Methods:Twenty-nine experts in general practice and hospice care from different teaching hospitals and community health service centers were invited to participate in two rounds of Delphi consultation from April to August 2022. Based on the consultations a set of standards of hospice care community training base was developed.Results:The age of experts was 38-75 (52.9±8.9) years, and their working years were 5-32 (17.0±7.2)years. In the two rounds of expert consultation, the expert positive coefficient was 100.0% (29/29) and 96.6% (28/29), the expert authority coefficient was 0.791 and 0.830, and the expert opinion coordination coefficient W of the importance of all indicators was 0.137 and 0.289, respectively ( χ2=114.83, 226.94; P<0.05). A set of hospice care community training base standards for general practitioner was established, which consisted of 4 first-level indicators and 27 second-level indicators. The 4 first-level indicators were basic conditions, teaching conditions, teacher conditions and teaching management, with the weight coefficients of 0.247, 0.248, 0.250 and 0.252, respectively. Conclusion:The standards developed in this study may be used for constructing and evaluating hospice care community training base for general practitioners.

Objective:To construct an evaluation index system for community hospice comfort care.Methods:This was a cross-sectional study. Two rounds of expert consultations were conducted using modified Delphi method from June to September 2023, 14 experts in the field of palliative care nursing were invited to participate in the consultations. Based on the consultation results, an evaluation index system for comfort care of community hospice was preliminarily developed.Results:All consultation experts were females, with an average age of (48±8) years; 9 held senior professonal titles, and 12 had more than 5 years of palliative care-related working experiencs. The positive coefficient of correspondence in two rounds of consultations was 100%, and the degree of authority was 0.841 and 0.834, respectively. The expert coordination coefficients for the importance of secondary indicators were 0.281 (χ 2=182.65) and 0.284 (χ 2=132.98), and the expert coordination coefficients for the operability of secondary indicators were 0.231 (χ 2=150.12) and 0.252 (χ 2=118.01), respectively. The constructed evaluation index system of hospice comfort care consisted of 5 primary indexes and 32 secondary indexes. The five primary indexes were environmental comfort, physiological comfort, psychological comfort, spiritual comfort and social comfort with a weight coefficient of 0.202 3, 0.205 3, 0.205 3, 0.199 4 and 0.187 7, respectively. Conclusion:An evaluation index system for comfort care in community hospice has been preliminarily developed in this study, after validation it would provide a reference for assessing the comfort needs of patients with palliative care.

Objective:To establish a global health talent competency index system in China as a scientific basis for improving the global health talent team construction.Methods:Such keywords as global health, competence, global competence and public health talent competence, were used to search for literature published from 2012 to 2022 in the China National Knowledge Infrastructure database. Through literature research and job responsibility analysis and the competency iceberg theory model, the authors established the initial Index set. In October 2022, the expert consultation method was used to identify indexes, with their weight evaluated. Based on the results of expert consultation, a survey questionnaire was developed to evaluate the importance of global health talent competency indexes. A questionnaire survey was conducted in November 2022 through random convenient sampling to select relevant personnel from domestic medical institutions, universities, and pharmaceutical enterprises, and exploratory factor analysis and regression analysis on questionnaire data were made to explore the internal structure, weights and quantitative relationships between indexes of the index system.Results:The global health talent competency index system consisted of 8 level-1 indexes and 28 level-2 indexes. The 8 level-1 indexes were professional accumulation, foreign language communication, international exchange, self-management and growth, influence, achievement drive, globalization literacy, and professionalism. The weights of the level-1 indexes were 0.110, 0.104, 0.153, 0.121, 0.106, 0.171, 0.139, and 0.096, respectively. Knowledge and skill related competencies included professional accumulation and foreign language communication; Behavioral competencies included international communication, self-management and growth, and influence; Personality traits and competencies included internal drive by achievements, global literacy, and professionalism. The regression analysis results showed that all the level-2 indexes, except for creativity, team collaboration, and independent thinking, had a significant predictive effect on their level-1 indexes ( P<0.01). Conclusions:The global health talent competency index system established in this study proves scientific, and practical for the selection, training, and evaluation of global health talents.