Although a single nucleotide polymorphism for N-acetyltransferase 10 (NAT10) has been identified in patients with early-onset stroke, the role of NAT10 in ischemic injury and the related underlying mechanisms remains elusive. Here, we provide evidence that NAT10, the only known RNA N4-acetylcytidine (ac4C) modification "writer", is increased in the damaged cortex of patients with acute ischemic stroke and the peri-infarct cortex of mice subjected to photothrombotic (PT) stroke. Pharmacological inhibition of NAT10 with remodelin on Days 3-7 post-stroke or astrocytic depletion of NAT10 via targeted virus attenuates ischemia-induced infarction and improves functional recovery in PT mice. Mechanistically, NAT10 enhances ac4C acetylation of the inflammatory cytokine tissue inhibitor of metalloproteinase 1 (Timp1) mRNA transcript, which increases TIMP1 expression and results in the accumulation of microtubule-associated protein 1 light chain 3 (LC3) and progression of astrocyte autophagy. These findings demonstrate that NAT10 regulates astrocyte autophagy by targeting Timp1 ac4C after stroke. This study highlights the critical role of ac4C in the regulation of astrocyte autophagy and proposes a promising strategy to improve post-stroke outcomes via NAT10 inhibition.

Cerebral blood flow directly affects the metabolism of substances and neural activity in the brain, and is closely associated with the occurrence and development of cerebral small vessel disease (CSVD). Multiple studies have revealed that various imaging biomarkers in patients with CSVD, such as lacunar infarction, enlarged perivascular spaces, cerebral microbleeds, cerebral atrophy, and white matter hyperintensities, are closely associated with cerebral autoregulation (CA) function. Therefore, understanding the regulatory mechanism of CA in patients with CSVD is of great significance for delaying the further development of CSVD, improving cerebral ischemia and cognitive impairment. This article reviews the correlation and mechanism between CA and CSVD.

Objective:To develop a Pain Management Nursing Competency Evaluation Index System for surgical nurses, providing a framework for assessing their pain management competency and guiding in-service training programs.Methods:From December 2023 to July 2024, a research team employed literature analysis, semi-structured interviews, expert consultations, and the analytic hierarchy process (AHP) to determine the content and weight of the competency evaluation index system. A cross-sectional survey was subsequently conducted using convenience sampling on 788 surgical nurses to test the internal consistency, test-retest reliability, and content validity of the index system.Results:The response rates for the two rounds of expert consultations were both 100% (46/46), with an expert authority coefficient of 0.921; the Kendall′s coefficients of expert opinions for the primary indicators were 0.106 and 0.245, respectively. The final index system included seven primary indicators (routine pain assessment, assessment and management of active and unexpected pain, pharmacological pain management, patient-controlled analgesia nursing, non-pharmacological pain management, pain related education for patients and their families, and professional development), 23 secondary indicators, and 78 tertiary indicators. The overall Cronbach α was 0.991, the test-retest reliability was 0.493, the item-level content validity index ranged from 0.96 to 1.00, and the scale-level content validity index was 0.98.Conclusions:The pain management nursing competency evaluation index system for surgical nurses is scientifically valid, reliable, and practical. It offers a solid foundation for evaluating the pain management competencies of surgical nurses and designing targeted in-service training programs.

Purpose To investigate the predictive value of nomogram based on preoperative CT imaging for predicting programmed cell death receptor ligand 1(PD-L1)expression in patient with lung adenocarcinoma.Materials and Methods A total of 158 patients with lung adenocarcinoma were enrolled in Shenzhen people's Hospital from January 2021 to July 2022,of which 82 were negative for PD-L1 and 76 were positive for PD-L1.They were randomly divided into training set(n=119)and verification set(n=39)according to the proportion of 7:3.The significant characteristics between PD-L1 negative and PD-L1 positive were screened by univariate and multivariate Logistic regression to construct a clinical model.Radiomics features were extracted from preoperative CT images,and then features were screened and modeled.Finally,the combined model was established by clinical factors and radiomics features,which was visualized by nomogram.The diagnostic performance of the model was evaluated using receiver operating characteristic curves and area under the curve(AUC).Results The area under the curve(AUC)of the clinical model composed of carcinoembryonic antigen and vascular convergence sign was 0.774(95%CI 0.687-0.860)and 0.808(95%CI 0.670-0.947)in the training set and validation set,respectively.Through feature screening,the radiomics model was composed of 17 radiomics features,and the AUC of the training and validation sets was 0.837(95%CI 0.764-0.910)and 0.778(95%CI 0.633-0.923).The training set and validation set of the combined model composed of carcinoembryonic antigen,vascular convergence sign and radiomics score were AUC 0.892(95%CI 0.832-0.952)and 0.853(95%CI 0.737-0.968).In the training set,the AUC of the combined model was higher than that of the other two models(Z=-2.640,-2.855,P＜0.05).Conclusion Based on preoperative CT radiomics nomogram,it had high predictive efficacy on the expression of PD-L1 in lung adenocarcinoma and could provide decision-making support for the selection of clinical treatment regimens for lung adenocarcinoma patients.

Objective:To explore the prognosis after radical resection for stage Ⅰ gastric cancer and the application value of adjuvant chemotherapy.Methods:The retrospective cohort study was conducted. The clinicopathological data of 3 353 patients with stage Ⅰ gastric cancer who were admitted to Fudan University Shanghai Cancer Center from January 2000 to December 2022 were collected. There were 2 369 males and 984 females, aged 60(range, 21-91) years. All patients underwent radical R 0 resection. Observation indicators: (1) clinicopathological characteristics of patients; (2) influencing factors for postoperative prognosis of patients; (3) prognostic analysis of patients; (4) construction and validation of a predictive model for the efficacy of postoperative adjuvant chemotherapy. Comparison of count data between groups was conducted using the chi-square test. Univariate and multivariate analyses were performed using the Cox proportional hazards regression model. The Kaplan-Meier method was used to calculate survival rates and draw survival curves, and the Log-rank test was used for survival analysis. Based on the multivariate analysis result, a nomogram prediction model was constructed to predict survival benefit. Results:(1) Clinicopatho-logical characteristics of patients. The highly, moderately, and poorly differentiated tumors were observed in 16, 234, 396 cases of 646 patients aged <50 years and 279, 1 617, 811 cases of 2 707 pati-ents aged ≥50 years, respectively, showing a significant difference in degree of tumor differentiation between them ( P<0.05). For 297 patients in stage T1N1M0, cases aged <50 years and ≥50 years were 71 and 226, cases of males and females were 184 and 113, cases with negative and positive vascular invasion were 37 and 260, cases with negative and positive nerve invasion were 275 and 22, cases without and with postoperative adjuvant chemotherapy were 222 and 75, respectively. The above indicators for 678 patients in stage T2N0M0 105, 573, 533, 145, 517, 161, 526, 152, 563, 115, respectively. There were significant differences in the above indicators between the two groups ( P<0.05). (2) Influencing factors for postoperative prognosis of patients. Results of multivariate analysis showed that age ≥50 years, stage T2, moderately differentiated tumor, the number of lymph nodes dissected <16, positive vascular invasion, carcinoembryonic antigen (CEA) ≥5 μg/L, and CA19-9 ≥37 U/mL were independent risk factors for disease-free survival (DFS) after surgery for stage Ⅰ gastric cancer ( hazard ratio=4.600, 1.555, 1.835, 1.362, 1.451, 1.571, 2.134, 95% confidence interval as 2.806-7.541, 1.205-2.006, 1.016-3.314, 1.059-1.753, 1.057-1.993, 1.100-2.243, 1.257-3.625, P<0.05). Age ≥50 years, stage T2, the number of lymph nodes dissected <16, positive vascular invasion, CEA ≥5 μg/L, and CA19-9 ≥37 U/mL were independent risk factors for overall survival (OS) after surgery for stage Ⅰ gastric cancer ( hazard ratio=5.208, 1.597, 1.373, 1.520, 1.464, 2.356, 95% confidence interval as 3.028-8.955, 1.231-2.072, 1.060-1.777, 1.099-2.104, 1.004-2.134, 1.385-4.009, P<0.05). Postoperative adjuvant chemotherapy was an independent protective factor for both DFS and OS after surgery for stage I gastric cancer ( hazard ratio=0.361 0.297, 95% confidence interval as 0.177-0.736, 0.131-0.674, P<0.05). (3) Prognostic analysis of patients. According to the results of multi-variate analysis, among 3 353 patients, there were significant differences in 5-year DFS rate and 10-year OS rate between patients aged <50 years and ≥50 years ( P<0.05). There were significant differences in 5-year DFS rate and 10-year OS rate among patients in TNM stage ⅠA and ⅠB ( P<0.05). There were significant differences in 5-year DFS rate and 10-year OS rate among patients in stage T1N0M0, T1N1M0, T2N0M0 ( P<0.05). There were significant differences in 5-year DFS rate and 10-year OS rate among patients with the highly, moderately, and poorly differentiated tumors ( P<0.05). There were significant differences in 5-year DFS rate and 10-year OS rate among patients with the number of lymph lodes dissected <16 and ≥16 ( P<0.05). There were significant differences in 5-year DFS rate and 10-year OS rate between patients with negative and positive vascular invasion ( P<0.05). There were significant differences in 5-year DFS rate and 10-year OS rate between patients with and without postoperative adjuvant chemotherapy ( P<0.05), among patients in stage T1N0M0, T1N1M0, T2N0M0 who received no postoperative adjuvant chemotherapy ( P<0.05). For patients in stage T1N1M0, there was no significant difference in 5-year DFS rate and 10-year OS rate between patients with and without postoperative adjuvant chemotherapy ( P>0.05).Results of stratified analysis showed that for patients aged ≥ 50 years, there were significant differences in 5-year DFS rate and 10-year OS rate between patients with and without postoperative adjuvant chemotherapy ( P<0.05). For patients in stage T2N0M0, there were significant differences in 5-year DFS rate and 10-year OS rate between patients with and without postoperative adjuvant chemotherapy ( P<0.05). For patients with positive vascular invasion, there were significant differences in 5-year DFS rate and 10-year OS rate between patients with and without postoperative adjuvant chemotherapy ( P<0.05). (4) Construction and validation of a predictive model for the efficacy of adjuvant chemotherapy. A nomogram predictive model was constructed based on the multivariate analysis results of OS and used for calculating net benefits and distribution. Among the 3 096 patients without postoperative adjuvant chemotherapy, 1 009 cases had a predicted net benefit of >5%-10%, and 250 patients had a predicted net benefit >10%. The predicted survival analysis further verified that the predicted benefit of adjuvant chemotherapy was consistent with the prognosis of patients. Conclusions:Patients with age ≥50 years, stage T2 tumors, moderately differentiated tumor, the number of lymph nodes dissected <16, positive vascular invasion have worse survival prognosis postoperative. Postoperative adjuvant chemotherapy provides better prognosis in high-risk patients. Patients in stage T1N1M0 have lower recurrence and survival risks, of whom with 1 metastatic lymph node is more suitable for follow-up rather than postoperative adjuvant chemotherapy.

Objective:To explore the prognosis after radical resection for stage Ⅰ gastric cancer and the application value of adjuvant chemotherapy.Methods:The retrospective cohort study was conducted. The clinicopathological data of 3 353 patients with stage Ⅰ gastric cancer who were admitted to Fudan University Shanghai Cancer Center from January 2000 to December 2022 were collected. There were 2 369 males and 984 females, aged 60(range, 21-91) years. All patients underwent radical R 0 resection. Observation indicators: (1) clinicopathological characteristics of patients; (2) influencing factors for postoperative prognosis of patients; (3) prognostic analysis of patients; (4) construction and validation of a predictive model for the efficacy of postoperative adjuvant chemotherapy. Comparison of count data between groups was conducted using the chi-square test. Univariate and multivariate analyses were performed using the Cox proportional hazards regression model. The Kaplan-Meier method was used to calculate survival rates and draw survival curves, and the Log-rank test was used for survival analysis. Based on the multivariate analysis result, a nomogram prediction model was constructed to predict survival benefit. Results:(1) Clinicopatho-logical characteristics of patients. The highly, moderately, and poorly differentiated tumors were observed in 16, 234, 396 cases of 646 patients aged <50 years and 279, 1 617, 811 cases of 2 707 pati-ents aged ≥50 years, respectively, showing a significant difference in degree of tumor differentiation between them ( P<0.05). For 297 patients in stage T1N1M0, cases aged <50 years and ≥50 years were 71 and 226, cases of males and females were 184 and 113, cases with negative and positive vascular invasion were 37 and 260, cases with negative and positive nerve invasion were 275 and 22, cases without and with postoperative adjuvant chemotherapy were 222 and 75, respectively. The above indicators for 678 patients in stage T2N0M0 105, 573, 533, 145, 517, 161, 526, 152, 563, 115, respectively. There were significant differences in the above indicators between the two groups ( P<0.05). (2) Influencing factors for postoperative prognosis of patients. Results of multivariate analysis showed that age ≥50 years, stage T2, moderately differentiated tumor, the number of lymph nodes dissected <16, positive vascular invasion, carcinoembryonic antigen (CEA) ≥5 μg/L, and CA19-9 ≥37 U/mL were independent risk factors for disease-free survival (DFS) after surgery for stage Ⅰ gastric cancer ( hazard ratio=4.600, 1.555, 1.835, 1.362, 1.451, 1.571, 2.134, 95% confidence interval as 2.806-7.541, 1.205-2.006, 1.016-3.314, 1.059-1.753, 1.057-1.993, 1.100-2.243, 1.257-3.625, P<0.05). Age ≥50 years, stage T2, the number of lymph nodes dissected <16, positive vascular invasion, CEA ≥5 μg/L, and CA19-9 ≥37 U/mL were independent risk factors for overall survival (OS) after surgery for stage Ⅰ gastric cancer ( hazard ratio=5.208, 1.597, 1.373, 1.520, 1.464, 2.356, 95% confidence interval as 3.028-8.955, 1.231-2.072, 1.060-1.777, 1.099-2.104, 1.004-2.134, 1.385-4.009, P<0.05). Postoperative adjuvant chemotherapy was an independent protective factor for both DFS and OS after surgery for stage I gastric cancer ( hazard ratio=0.361 0.297, 95% confidence interval as 0.177-0.736, 0.131-0.674, P<0.05). (3) Prognostic analysis of patients. According to the results of multi-variate analysis, among 3 353 patients, there were significant differences in 5-year DFS rate and 10-year OS rate between patients aged <50 years and ≥50 years ( P<0.05). There were significant differences in 5-year DFS rate and 10-year OS rate among patients in TNM stage ⅠA and ⅠB ( P<0.05). There were significant differences in 5-year DFS rate and 10-year OS rate among patients in stage T1N0M0, T1N1M0, T2N0M0 ( P<0.05). There were significant differences in 5-year DFS rate and 10-year OS rate among patients with the highly, moderately, and poorly differentiated tumors ( P<0.05). There were significant differences in 5-year DFS rate and 10-year OS rate among patients with the number of lymph lodes dissected <16 and ≥16 ( P<0.05). There were significant differences in 5-year DFS rate and 10-year OS rate between patients with negative and positive vascular invasion ( P<0.05). There were significant differences in 5-year DFS rate and 10-year OS rate between patients with and without postoperative adjuvant chemotherapy ( P<0.05), among patients in stage T1N0M0, T1N1M0, T2N0M0 who received no postoperative adjuvant chemotherapy ( P<0.05). For patients in stage T1N1M0, there was no significant difference in 5-year DFS rate and 10-year OS rate between patients with and without postoperative adjuvant chemotherapy ( P>0.05).Results of stratified analysis showed that for patients aged ≥ 50 years, there were significant differences in 5-year DFS rate and 10-year OS rate between patients with and without postoperative adjuvant chemotherapy ( P<0.05). For patients in stage T2N0M0, there were significant differences in 5-year DFS rate and 10-year OS rate between patients with and without postoperative adjuvant chemotherapy ( P<0.05). For patients with positive vascular invasion, there were significant differences in 5-year DFS rate and 10-year OS rate between patients with and without postoperative adjuvant chemotherapy ( P<0.05). (4) Construction and validation of a predictive model for the efficacy of adjuvant chemotherapy. A nomogram predictive model was constructed based on the multivariate analysis results of OS and used for calculating net benefits and distribution. Among the 3 096 patients without postoperative adjuvant chemotherapy, 1 009 cases had a predicted net benefit of >5%-10%, and 250 patients had a predicted net benefit >10%. The predicted survival analysis further verified that the predicted benefit of adjuvant chemotherapy was consistent with the prognosis of patients. Conclusions:Patients with age ≥50 years, stage T2 tumors, moderately differentiated tumor, the number of lymph nodes dissected <16, positive vascular invasion have worse survival prognosis postoperative. Postoperative adjuvant chemotherapy provides better prognosis in high-risk patients. Patients in stage T1N1M0 have lower recurrence and survival risks, of whom with 1 metastatic lymph node is more suitable for follow-up rather than postoperative adjuvant chemotherapy.

Objective:To develop a Pain Management Nursing Competency Evaluation Index System for surgical nurses, providing a framework for assessing their pain management competency and guiding in-service training programs.Methods:From December 2023 to July 2024, a research team employed literature analysis, semi-structured interviews, expert consultations, and the analytic hierarchy process (AHP) to determine the content and weight of the competency evaluation index system. A cross-sectional survey was subsequently conducted using convenience sampling on 788 surgical nurses to test the internal consistency, test-retest reliability, and content validity of the index system.Results:The response rates for the two rounds of expert consultations were both 100% (46/46), with an expert authority coefficient of 0.921; the Kendall′s coefficients of expert opinions for the primary indicators were 0.106 and 0.245, respectively. The final index system included seven primary indicators (routine pain assessment, assessment and management of active and unexpected pain, pharmacological pain management, patient-controlled analgesia nursing, non-pharmacological pain management, pain related education for patients and their families, and professional development), 23 secondary indicators, and 78 tertiary indicators. The overall Cronbach α was 0.991, the test-retest reliability was 0.493, the item-level content validity index ranged from 0.96 to 1.00, and the scale-level content validity index was 0.98.Conclusions:The pain management nursing competency evaluation index system for surgical nurses is scientifically valid, reliable, and practical. It offers a solid foundation for evaluating the pain management competencies of surgical nurses and designing targeted in-service training programs.

Purpose To investigate the predictive value of nomogram based on preoperative CT imaging for predicting programmed cell death receptor ligand 1(PD-L1)expression in patient with lung adenocarcinoma.Materials and Methods A total of 158 patients with lung adenocarcinoma were enrolled in Shenzhen people's Hospital from January 2021 to July 2022,of which 82 were negative for PD-L1 and 76 were positive for PD-L1.They were randomly divided into training set(n=119)and verification set(n=39)according to the proportion of 7:3.The significant characteristics between PD-L1 negative and PD-L1 positive were screened by univariate and multivariate Logistic regression to construct a clinical model.Radiomics features were extracted from preoperative CT images,and then features were screened and modeled.Finally,the combined model was established by clinical factors and radiomics features,which was visualized by nomogram.The diagnostic performance of the model was evaluated using receiver operating characteristic curves and area under the curve(AUC).Results The area under the curve(AUC)of the clinical model composed of carcinoembryonic antigen and vascular convergence sign was 0.774(95%CI 0.687-0.860)and 0.808(95%CI 0.670-0.947)in the training set and validation set,respectively.Through feature screening,the radiomics model was composed of 17 radiomics features,and the AUC of the training and validation sets was 0.837(95%CI 0.764-0.910)and 0.778(95%CI 0.633-0.923).The training set and validation set of the combined model composed of carcinoembryonic antigen,vascular convergence sign and radiomics score were AUC 0.892(95%CI 0.832-0.952)and 0.853(95%CI 0.737-0.968).In the training set,the AUC of the combined model was higher than that of the other two models(Z=-2.640,-2.855,P＜0.05).Conclusion Based on preoperative CT radiomics nomogram,it had high predictive efficacy on the expression of PD-L1 in lung adenocarcinoma and could provide decision-making support for the selection of clinical treatment regimens for lung adenocarcinoma patients.

BACKGROUND:The biological behavior of mesenchymal stem cells is influenced by the survival microenvironment.Pre-treatment of the microenvironment is an important means of regulating the function of mesenchymal stem cells. OBJECTIVE:To compare the differences in paracrine function of umbilical cord mesenchymal stem cells and adipose mesenchymal stem cells under oxidative stress and hypoxia,and to provide a theoretical basis for selecting appropriate pretreatment of mesenchymal stem cells to treat different diseases. METHODS:Umbilical cord mesenchymal stem cells and adipose mesenchymal stem cells were cultured by H2O2 or O2 oxygen,respectively,and cell morphology,proliferation,viability and paracrine factor expression were examined. RESULTS AND CONCLUSION:(1)The expression levels of brain-derived neurotrophic factor and transforming growth factor-β were higher in umbilical cord mesenchymal stem cells than in adipose mesenchymal stem cells under a normal culture environment,while the expressions of stromal cell-derived factor-1α and tumor necrosis factor stimulating factor-6 in the adipose mesenchymal stem cells were significantly higher than those in the umbilical cord mesenchymal stem cells.(2)There was no significant difference in the effect of low and moderate levels(≤100 μmol/L)of H2O2 on the viability of the two mesenchymal stem cells.However,increasing the H2O2 concentration from 50 μmol/L to 100 μmol/L resulted in a distinct increase in vascular endothelial growth factor expression in umbilical cord mesenchymal stem cells.The expression of basic fibroblast growth factor,vascular endothelial growth factor,stromal cell-derived factor-1α and interleukin-10 in adipose mesenchymal stem cells was greatly increased by increasing H2O2 concentration in this range.(3)1%O2 hypoxia promoted mesenchymal stem cell proliferation.After 24 hours of culture in 1%O2,gene expression levels were elevated in both mesenchymal stem cells,but the expression levels of vascular endothelial growth factor,interleukin-10 and tumor necrosis factor stimulating factor-6 were significantly higher in adipose mesenchymal stem cells than in umbilical cord mesenchymal stem cells.(4)It is concluded that hypoxia and oxidative stress preconditioning enhances the paracrine function of mesenchymal stem cells.However,mesenchymal stem cells respond differently to hypoxia and oxidative stress.Treating diseases can choose suitable mesenchymal stem cells for appropriate pretreatment to further enhance their therapeutic potential.

Objective To analyze the value of magnetic resonance proton density-weighted fat-saturated(PDWI-FS)sequence in the diagnosis of bone marrow edema(BME)in osteoarticular injury.Methods A total of 150 patients with bone and joint trauma were enrolled in the study.All patients underwent sagittal PDWI-FS sequence scan and conventional MRI sequence scan.The BME detection,signal intensity,image quality,and the signal-to-noise ratio and contrast-to-noise ratio of the lesions were compared between two methods.Results Both methods revealed that there were 225 sites of BME signs in 134 out of the 150 patients,with a higher prevalence in knee joint trauma patients.The signal intensity of the lesions was mainly grade 3 on PDWI-FS sequence and grade 2 on conventional MRI sequence,accounting for 97.78%(220/225)and 43.11%(97/225),indicating that the two methods graded signal intensity differently(Z=15.919,P<0.05).PDWI-FS sequence and conventional sequence had scores of 4.09±0.45 vs 3.88±0.39,3.65±0.42 vs 3.41±0.36,3.25±0.37 vs 3.14±0.35 and 4.21±0.38 vs 3.97±0.34 on lesion clarity,spatial resolution,anamorphosis and diagnostic confidence,and the former scored higher(t=4.319,5.314,2.645,5.765;P<0.05).The signal-to-noise ratio and contrast-to-noise ratio of the lesions on PDWI-FS sequence were 2.07±0.23 and 5.52±0.64,higher than 2.01±0.22 and 5.17±0.59 on conventional sequence,and the differences were statistically significant(t=2.309,4.925;P<0.05).Conclusion Compared with conventional MRI sequence,magnetic resonance PDWI-FS sequence can effectively enhance image quality and display lesions more clearly,providing more accurate information for the diagnosis of BME in osteoarticular injury.