BACKGROUND:The inflammatory response of microglia is closely related to neuronal survival,regeneration,and functional recovery after spinal cord injury.Peroxiredoxin 1 is not only involved in the regulation of oxidative stress,but also has an important effect on cell proliferation,apoptosis,and inflammatory response.OBJECTIVE:To investigate the role and mechanism of peroxiredoxin 1 in the inflammatory response of microglia following spinal cord injury.METHODS:(1)Twelve female C57BL/6 mice were randomly divided into sham-operated(n=6)and spinal cord injury(n=6)groups.The sham-operated group was not modeled and acute spinal cord injury models were constructed in the spinal cord injury group using the modified Allen's method.Spinal cord tissue at the injured site was taken at 7 days after modeling and transcriptome sequencing was performed to identify differentially expressed genes.The expression of peroxiredoxin 1 in spinal cord tissues was verified using western blot and RT-qPCR.(2)Mouse microglia BV2 were divided into two groups:the control group was stimulated with lipopolysaccharide for 6 hours,and in the knockout group,lipopolysaccharide stimulation was applied for 6 hours at 24 hours after peroxiredoxin 1 was knocked down in the cells.RT-qPCR was performed to detect mRNA expression of peroxiredoxin 1,inflammatory factors(interleukin 1β,interleukin 6,inducible nitric oxide synthase,tumor necrosis factor α,C-C motif chemokine ligand 2,and C-X-C motif chemokine ligand 2),and western blot was performed to detect the expression of peroxiredoxin 1,inducible nitric oxide synthase,and reactive oxygen/mitogen-activated protein kinase signaling pathway proteins.Mouse microglia BV2 were treated in two groups:the control group was stimulated by hydrogen peroxide for 4 hours,and the knockout group was stimulated by hydrogen peroxide for 4 hours at 24 hours after knockdown of peroxiredoxin 1.The level of reactive oxygen species was detected by 2,7-dichlorodihydrofluorescein diacetate probe.RESULTS AND CONCLUSION:(1)Results from transcriptome sequencing,western blot and RT-qPCR confirmed that peroxiredoxin 1 expression levels in mouse spinal cord tissues were significantly higher in the spinal cord injury group than the sham-operated group(P＜0.05).(2)Peroxiredoxin 1 knockdown in microglial cells led to decreased expression of peroxiredoxin 1 mRNA and protein(P＜0.05),increased mRNA expression of interleukin 1β,interleukin 6,inducible nitric oxide synthase,tumor necrosis factor α,C-C motif chemokine ligand 2,and C-X-C motif chemokine ligand 2(P＜0.05),increased protein expression of inducible nitric oxide synthase,P-P38,P-JNK and P-ERK proteins(P＜0.05),and increased level of reactive oxygen species(P＜0.05).To conclude,peroxiredoxin 1 regulates microglial inflammation by targeting the reactive oxygen species/mitogen-activated protein kinase signaling pathway.

BACKGROUND:The inflammatory response of microglia is closely related to neuronal survival,regeneration,and functional recovery after spinal cord injury.Peroxiredoxin 1 is not only involved in the regulation of oxidative stress,but also has an important effect on cell proliferation,apoptosis,and inflammatory response.OBJECTIVE:To investigate the role and mechanism of peroxiredoxin 1 in the inflammatory response of microglia following spinal cord injury.METHODS:(1)Twelve female C57BL/6 mice were randomly divided into sham-operated(n=6)and spinal cord injury(n=6)groups.The sham-operated group was not modeled and acute spinal cord injury models were constructed in the spinal cord injury group using the modified Allen's method.Spinal cord tissue at the injured site was taken at 7 days after modeling and transcriptome sequencing was performed to identify differentially expressed genes.The expression of peroxiredoxin 1 in spinal cord tissues was verified using western blot and RT-qPCR.(2)Mouse microglia BV2 were divided into two groups:the control group was stimulated with lipopolysaccharide for 6 hours,and in the knockout group,lipopolysaccharide stimulation was applied for 6 hours at 24 hours after peroxiredoxin 1 was knocked down in the cells.RT-qPCR was performed to detect mRNA expression of peroxiredoxin 1,inflammatory factors(interleukin 1β,interleukin 6,inducible nitric oxide synthase,tumor necrosis factor α,C-C motif chemokine ligand 2,and C-X-C motif chemokine ligand 2),and western blot was performed to detect the expression of peroxiredoxin 1,inducible nitric oxide synthase,and reactive oxygen/mitogen-activated protein kinase signaling pathway proteins.Mouse microglia BV2 were treated in two groups:the control group was stimulated by hydrogen peroxide for 4 hours,and the knockout group was stimulated by hydrogen peroxide for 4 hours at 24 hours after knockdown of peroxiredoxin 1.The level of reactive oxygen species was detected by 2,7-dichlorodihydrofluorescein diacetate probe.RESULTS AND CONCLUSION:(1)Results from transcriptome sequencing,western blot and RT-qPCR confirmed that peroxiredoxin 1 expression levels in mouse spinal cord tissues were significantly higher in the spinal cord injury group than the sham-operated group(P＜0.05).(2)Peroxiredoxin 1 knockdown in microglial cells led to decreased expression of peroxiredoxin 1 mRNA and protein(P＜0.05),increased mRNA expression of interleukin 1β,interleukin 6,inducible nitric oxide synthase,tumor necrosis factor α,C-C motif chemokine ligand 2,and C-X-C motif chemokine ligand 2(P＜0.05),increased protein expression of inducible nitric oxide synthase,P-P38,P-JNK and P-ERK proteins(P＜0.05),and increased level of reactive oxygen species(P＜0.05).To conclude,peroxiredoxin 1 regulates microglial inflammation by targeting the reactive oxygen species/mitogen-activated protein kinase signaling pathway.

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 analyze the association between healthcare workers mental health,institu-tional supplies and facilities,inter-organizational coordination during infectious disease outbreaks,and the healthcare institution resilience.Methods:An online questionnaire survey was conducted among the healthcare workforce from 146 institutions in Beijing from January 13,2023 to February 9,2023,and a total of 1 434 eligible respondents were included.The sample comprised 408 responses from tertiary hos-pitals,117 from secondary hospitals,and 909 from primary care institutions.The resilience indicator for healthcare institutions was defined as the degree to which medical services met patient demands,with in-fluencing factors including physical factors,such as material shortages and facility space adaptation or ex-pansion,organizational factors such as information sharing and patient referral,and psychological factors were evaluated using job satisfaction(extrinsic satisfaction,intrinsic satisfaction),burnout(emotional exhaustion,depersonalization,reduced personal accomplishment),and depression status.Ordered mul-ticlassification Logistic regression was used to examine the impact of various factors on the degree to which healthcare services met patient needs;additionally,demographic factors that might influence institutional resilience were controlled.Results:During the emergency response phase,93％of hospitals maintained the capacity to meet patient needs,though tertiary hospitals demonstrated significantly higher rates of service inadequacy(21.05％).Material shortages were reported across all institutions,with tertiary hos-pitals experiencing more frequent multi-item shortages.Inter-institutional collaboration patterns revealed substantial variation:87.50％of primary care facilities,42.86％of secondary hospitals,and 31.58％of tertiary hospitals.Healthcare workers across all levels reported mild depressive symptoms and moderate-to-severe burnout levels.Regression analysis showed high satisfaction(overall satisfaction β=0.04,ex-trinsic satisfaction β=0.06,and intrinsic satisfaction β=0.08),low degree of job burnout(emotional exhaustion β=-0.04,depersonalization β=-0.07 and reduced personal accomplishment β=0.01),low degree of depression(β=-0.06)were significantly associated with higher healthcare institution re-silience.In addition,material shortages were significantly associated with lower resilience,and renova-tion and expansion of treatment spaces,and information sharing,were all associated with higher resilience.Demographic factors(age,gender,marital status,educational background,etc.)had no sig-nificant impact on resilience.Conclusion:Mental health status significantly influences healthcare institu-tion resilience.As human resources constitute the core asset of healthcare institutions,strategic optimiza-tion of workforce allocation and psychological support interventions can effectively strengthen resilience.Moreover,healthcare institution resilience is positively impacted by orderly material supply chains,timely resource distribution,and adaptive reconfiguration of clinical spaces.Finally,facilitating information sharing also enhances institutional resilience.

Objective:To formulate a community teacher standard for the training of general practitioner program (direction in hospice care).Methods:This was a qualitative study. Twenty-nine experts in general practice and hospice care from various 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 results of the consultation, a standard for community faculty training in comprehensive care and end-of-life care for general practitioners was formulated, and the weight coefficients of the indicators were calculated.Results:Of the 29 experts, 11 (37.9%) were male, their age was (52.9±8.9) years, and their working life was (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 0.789 and 0.851, and the expert opinion coordination coefficient W of the importance of all indicators was 0.124 and 0.131, respectively ( χ2=123.01, 131.71, P<0.05). Finally, a set of community-based teacher standard for general practitioner specialty training (direction in hospice care) was established, which consisted of 4 first-level indicators and 30 second-level indicators. The four first-level indicators were basic literacy, clinical qualification and ability, teaching qualification and ability, and scientific research ability, all with the weight coefficients of 0.254, 0.254, 0.252 and 0.240, respectively. Conclusion:The standard of teachers in the community base of general practitioner specialty training (direction in hospice care) established in this study is more scientific, which is conducive to the comprehensive evaluation of teachers in the community training base.

Objective:To develop accreditation standards for clinical faculty in general practitioner specialized training of hospice care.Methods:This was a qualitative study. Twenty nine experts in fields of general practice and hospice care were invited for two rounds of Delphi consultation from April 2022 to August 2022. Based on the consultation results, the accreditation standards for clinical faculty in general practitioner training bases of hospice care specialty was preliminarily developed.Results:The mean age of the consulting experts was (52.9±8.9) years with a mean working year of (17.0±7.2), and 69.0% (20/29) of them held senior professional titles. In the two rounds of consultation, the expert positive coefficient was 100.0% (29/29) and 96.6% (28/29), the expert authority coefficient was 0.765 and 0.813, and the expert opinion coordination coefficient W for the importance of all indicators was 0.112 and 0.196, respectively. The expert opinions tended to be consistent. Finally, a set of clinical base faculty standards for general specialty training was developed, which consisted of 4 first-level indicators and 24 second-level indicators. The 4 first-level indicators were basic literacy, clinical qualification and ability, teaching qualification and ability, scientific research ability, with the weight coefficients of 0.253, 0.255, 0.254 and 0.241, respectively. Conclusion:The standards for clinical teaching faculty in general practitioner specialty training base of hospice care has been established in this study, which is conducive to the comprehensive quality evaluation for training faculty.

Objective:To construct a set of admission evaluation indicators for terminal patients in community hospice wards.Methods:This qualitative study employed a mixed-methods approach. From January to June 2023, 10 physicians working in community hospice wards in Shanghai participated in one-on-one, semi-structured, in-depth interviews. Based on the interview findings and literature review, a preliminary set of admission evaluation indicators was drafted. Subsequently, from July to December 2023, 18 national experts in hospice/palliative care were selected for a two-round Delphi expert consultation to refine the indicators. The final indicator system was established based on the consultation results, and the weight coefficients for each indicator were determined.Results:Sixteen experts completed both rounds of consultation. The experts had a mean age of (52.0±8.3) years and a mean working experience of (14.4±6.8) years. The response rates for the two rounds were 88.9% and 100.0%, respectively. The authority coefficients were 0.875 and 0.894, and the Kendall′s W coordination coefficients were 0.338 (χ2=471.737, P<0.001) and 0.349 (χ2=398.230, P<0.001), respectively. After two rounds of Delphi consultation, a final admission evaluation indicator system was established, comprising 4 first-level indicators and 63 second-level indicators. The first-level indicators and their weight coefficients were: Underlying Disease (0.256 7), Survival Prognosis (0.256 7), Holistic Needs (0.256 6), and Social Environment (0.240 0). Conclusion:The admission evaluation indicator system for terminal patients in community hospice wards developed in this study facilitates the standardized development of community hospice/palliative care services and contributes to providing high-quality care for patients and their families.

Objective:To analyze the awareness of and factors influencing the adjusted national immunization schedule for the diphtheria-tetanus-acellular pertussis (DTaP) vaccine among grassroots immunization service personnel in China.Methods:Based on the snowball sampling method from January to February 2025, immunization service personnel from all provinces of China were selected from the "Tingting Experts Talk" WeChat platform, with concurrent dissemination through the "National Vaccine-Preventable Diseases Communication Group" WeChat group. The questionnaire included basic demographic characteristics and knowledge of the DTaP vaccine immunization policy (13 questions in total). Respondents who answered ≥10 questions correctly were defined as being aware of the policy adjustment. The multivariable logistic regression analysis was performed to identify factors influencing awareness.Results:A total of 8 030 valid questionnaires were collected from 29 provinces, with a valid response rate of 92.91%. The overall awareness accuracy rates among the Centers for Disease Control and Prevention (CDC) personnel and the point of vaccination (POV) staff were 74.1% and 62.5%, respectively. The awareness rate of the core points of policy adjustment among the research subjects exceeded 90%. Among the questions regarding the operational details of policy implementation, the correct rate of answering questions related to the catch-up vaccination principles was relatively low (37.1%-74.0%). The multivariate logistic regression analysis showed that, compared with those with primary titles, CDC personnel with senior titles had higher mastery of the policy adjustment, with an OR (95% CI) value of 2.238 (1.343-3.730). Compared with those engaged in disease surveillance and immunization strategy research, CDC personnel with other work types had lower awareness of the policy adjustment, with an OR (95% CI) value of 0.404 (0.195-0.833). Compared with those in western regions, with primary titles, and without relevant training, POV staff in central regions, eastern regions, with intermediate titles, with senior titles, with one relevant training session, and with ≥2 relevant training sessions had better awareness of the program adjustment, with OR (95% CI) values of 1.214 (1.085-1.358), 1.412 (1.246-1.600), 1.606 (1.446-1.784), 1.737 (1.443-2.091), 2.254 (1.509-3.366), and 2.674 (1.769-3.981), respectively. Compared with those engaged in information registration/recipient notification, POV staff with vaccination services and other work types had lower awareness of the program adjustment, with OR (95% CI) values of 0.713 (0.633-0.803) and 0.508 (0.427-0.604), respectively. Conclusion:Although grassroots immunization service personnel show an insufficient mastery of certain catch-up vaccination knowledge, they demonstrate a good understanding of overall principles and routine immunization schedules shortly after the policy adjustment, which can effectively ensure an orderly transition between old and new immunization strategies.

Objective:To analyze the awareness of and factors influencing the adjusted national immunization schedule for the diphtheria-tetanus-acellular pertussis (DTaP) vaccine among grassroots immunization service personnel in China.Methods:Based on the snowball sampling method from January to February 2025, immunization service personnel from all provinces of China were selected from the "Tingting Experts Talk" WeChat platform, with concurrent dissemination through the "National Vaccine-Preventable Diseases Communication Group" WeChat group. The questionnaire included basic demographic characteristics and knowledge of the DTaP vaccine immunization policy (13 questions in total). Respondents who answered ≥10 questions correctly were defined as being aware of the policy adjustment. The multivariable logistic regression analysis was performed to identify factors influencing awareness.Results:A total of 8 030 valid questionnaires were collected from 29 provinces, with a valid response rate of 92.91%. The overall awareness accuracy rates among the Centers for Disease Control and Prevention (CDC) personnel and the point of vaccination (POV) staff were 74.1% and 62.5%, respectively. The awareness rate of the core points of policy adjustment among the research subjects exceeded 90%. Among the questions regarding the operational details of policy implementation, the correct rate of answering questions related to the catch-up vaccination principles was relatively low (37.1%-74.0%). The multivariate logistic regression analysis showed that, compared with those with primary titles, CDC personnel with senior titles had higher mastery of the policy adjustment, with an OR (95% CI) value of 2.238 (1.343-3.730). Compared with those engaged in disease surveillance and immunization strategy research, CDC personnel with other work types had lower awareness of the policy adjustment, with an OR (95% CI) value of 0.404 (0.195-0.833). Compared with those in western regions, with primary titles, and without relevant training, POV staff in central regions, eastern regions, with intermediate titles, with senior titles, with one relevant training session, and with ≥2 relevant training sessions had better awareness of the program adjustment, with OR (95% CI) values of 1.214 (1.085-1.358), 1.412 (1.246-1.600), 1.606 (1.446-1.784), 1.737 (1.443-2.091), 2.254 (1.509-3.366), and 2.674 (1.769-3.981), respectively. Compared with those engaged in information registration/recipient notification, POV staff with vaccination services and other work types had lower awareness of the program adjustment, with OR (95% CI) values of 0.713 (0.633-0.803) and 0.508 (0.427-0.604), respectively. Conclusion:Although grassroots immunization service personnel show an insufficient mastery of certain catch-up vaccination knowledge, they demonstrate a good understanding of overall principles and routine immunization schedules shortly after the policy adjustment, which can effectively ensure an orderly transition between old and new immunization strategies.

Objective:To analyze the association between healthcare workers mental health,institu-tional supplies and facilities,inter-organizational coordination during infectious disease outbreaks,and the healthcare institution resilience.Methods:An online questionnaire survey was conducted among the healthcare workforce from 146 institutions in Beijing from January 13,2023 to February 9,2023,and a total of 1 434 eligible respondents were included.The sample comprised 408 responses from tertiary hos-pitals,117 from secondary hospitals,and 909 from primary care institutions.The resilience indicator for healthcare institutions was defined as the degree to which medical services met patient demands,with in-fluencing factors including physical factors,such as material shortages and facility space adaptation or ex-pansion,organizational factors such as information sharing and patient referral,and psychological factors were evaluated using job satisfaction(extrinsic satisfaction,intrinsic satisfaction),burnout(emotional exhaustion,depersonalization,reduced personal accomplishment),and depression status.Ordered mul-ticlassification Logistic regression was used to examine the impact of various factors on the degree to which healthcare services met patient needs;additionally,demographic factors that might influence institutional resilience were controlled.Results:During the emergency response phase,93％of hospitals maintained the capacity to meet patient needs,though tertiary hospitals demonstrated significantly higher rates of service inadequacy(21.05％).Material shortages were reported across all institutions,with tertiary hos-pitals experiencing more frequent multi-item shortages.Inter-institutional collaboration patterns revealed substantial variation:87.50％of primary care facilities,42.86％of secondary hospitals,and 31.58％of tertiary hospitals.Healthcare workers across all levels reported mild depressive symptoms and moderate-to-severe burnout levels.Regression analysis showed high satisfaction(overall satisfaction β=0.04,ex-trinsic satisfaction β=0.06,and intrinsic satisfaction β=0.08),low degree of job burnout(emotional exhaustion β=-0.04,depersonalization β=-0.07 and reduced personal accomplishment β=0.01),low degree of depression(β=-0.06)were significantly associated with higher healthcare institution re-silience.In addition,material shortages were significantly associated with lower resilience,and renova-tion and expansion of treatment spaces,and information sharing,were all associated with higher resilience.Demographic factors(age,gender,marital status,educational background,etc.)had no sig-nificant impact on resilience.Conclusion:Mental health status significantly influences healthcare institu-tion resilience.As human resources constitute the core asset of healthcare institutions,strategic optimiza-tion of workforce allocation and psychological support interventions can effectively strengthen resilience.Moreover,healthcare institution resilience is positively impacted by orderly material supply chains,timely resource distribution,and adaptive reconfiguration of clinical spaces.Finally,facilitating information sharing also enhances institutional resilience.