Cold tumors have a poor response to tumor immunotherapy due to low immune cell infiltration and the ability to evade immune attacks. Converting cold tumors into hot tumors can enhance the clinical effectiveness of anti-tumor immunotherapy. High-intensity focused ultrasound (HIFU) as a non-invasive treatment can damage tumors through mechanical effects, but there is a lack of research on its cytotoxic mechanisms at the cellular level and its role in inducing anti-immune responses. In this study, the role of HIFU in triggering tumor ferroptosis by disrupting the GSH/GSSG balance through mechanochemical action and the associated anti-tumor immune priming effect were investigated. The use of a nano-enhancer loaded with PFOB combined with HIFU could enhance ferroptosis in triple-negative breast cancer at a specific stage of tumor growth (UTGR = 0) while promoting the conversion of a cold tumor into a hot tumor, thereby improving the immune response. Overall, this provides valuable guidance for the clinical application of HIFU in tumor immunotherapy.

Purpose The current study aims to elucidate the interrelationships among IREB2,FBXL5,iron ho-meostasis,and the therapeutic efficacy of neoadjuvant chemotherapy.Methods A total of 97 samples,classified into colorectal cancer neoadjuvant chemotherapy-resistant and-sensitive groups,along with their corresponding paracancer-ous normal mucosa were collected.The expression levels of FBXL5,IREB2,TFRC and FTH1 were detected by immu-nohistochemistry,Werstern blot and RT-qPCR.The contents of ferroptosis-related markers Fe2+,MDA,ROS and GSH were detected by applying the kit,and the levels of these markers were analyzed.The relationship between each factor in different colorectal cancer tissues and tumor regression rate and prognosis of neoadjuvant chemotherapy were ana-lyzed.Results(1)The expression of IREB2,FBXL5,TFRC and FTH1 in colorectal cancer was higher than that in normal intestinal mucosa(P＜0.05),and the expression of FBXL5 and FTH1 in colorectal cancer drug-resistant group was lower than that in the sensitive group,whereas the expression of IREB2 and TFRC was higher than that in the sen-sitive group(P＜0.05);(2)The correlation analysis showed a positive correlation between the expression of IREB2 and TFRC in the drug-resistant group,and a negative correlation with the expression of FBXL5 and FTH1 in the drug-resistant group.TFRC expression in the colorectal cancer resistance group were positively correlated(P＜0.05)and negatively correlated with the expression of FBXL5 and FTH1(P＜0.05);(3)the content of Fe2+and GSH was high-er than that of the sensitivity group in the colorectal cancer resistance group,and the level of ROS was lower than that of the sensitivity group(P＜0.05);(4)Fe2+was positively correlated with the expression of IREB2,TFRC,and neg-atively correlated with the expression of FBXL5 and FTH1,and was negatively correlated with the expression of FBXL5 and FTH1.FTH1 expression were both negatively correlated(P＜0.05);(5)tumor regression rate was positively cor-related with the expression of FBXL5 and FTH1,and negatively correlated with the expression of IREB2 and TFRC,as well as positively correlated with the level of ROS,and negatively correlated with Fe2+and GSH(P＜0.05);(6)The expression of IREB2 and TFRC was positively correlated with tumor diameter and lymph node metastasis,and the ex-pression of FBXL5 and FTH1 was negatively correlated with tumor diameter and lymph node metastasis,and the expres-sion of FBXL5 was also negatively correlated with the depth of tumor infiltration(P＜0.05);(7)Kaplan-Meier analy-sis showed that lymph node metastasis,FBXL5,IREB2,TFRC,FTH1,and TRG grading were closely related to the prognosis of colorectal cancer patients(P＜0.05).Cox multivariate regression analysis indicated that lymph node me-tastasis,high expression of IREB2 and TFRC,low expression of FBXL5 and FTH1,and low tumor regression grade(TRG)were risk factors for the ineffectiveness of neoadjuvant chemotherapy in colorectal cancer patients.Conclusion FBXL5 and IREB2 are not only associated with high iron homeostasis,but also closely related to the efficacy and prognosis of neoadjuvant chemotherapy for colorectal cancer.In the future,they may become new targets for the treat-ment of colorectal cancer and improve the prognosis of patients.

Objective:To compare the efficacy of body posture combined with pharmacotherapy and pharmacotherapy alone in the treatment of chronic subdural hematoma(CSDH).Methods:Firstly, retrospective case series study was conducted. Thirty cases of CSDH that had received body posture combined with pharmacotherapy at Department of Neurosurgery, Huashan Hospital Affiliated to Fudan University from December 2016 to October 2020 were studied retrospectively. Twenty-seven patients were male, and 3 patients were female. The age of patients ( M(IQR)) was 66(16) years (range:28 to 84). Nineteen patients had unilateral hematoma, and 11 patients had bilateral hematoma. All patients received pharmacotherapy and body posture therapy that was to raise their lower limbs 20 to 30 cm with leg lift pad and get abdominal compressed with customized abdominal belt in supine position. Patients were required to maintain the body posture as much as possible, with the maximum to 16 to 18 hours per day. Patients with unilateral hematoma should tilt the head to the affected side and avoid tilting it to the opposite side. For patients with bilateral hematoma, there was no need for head lateralization. Patient were treated with oral dexamethasone and atorvastatin simultaneously. The preliminary efficacy of body posture combined with pharmacotherapy was determined by hematoma improvement rate which was analyzed by Clopper-Pearson method. Then, the multi-center, prospective, randomized controlled trial had carried out in 9 medical centers from August 2020 to November 2021. The stratified block randomization method was adopted. Patients were randomized in a ratio of 1∶1 to either receive pharmacotherapy alone(the control group) or body posture combined with pharmacotherapy(the experiment group) for 3 months and followed up for 6 months. Effective treatment was defined as complete absorption of hematoma, or the hematoma volume decreased by more than 10 ml and Markwalder grading scale score had improved by more than 1 point compared to the baseline. The efficacy rate and surgery conversion rate at 3 months and recurrence at 6 months were observed. Comparison between groups was performed with paired sample t test, Mann-Whitney U test, χ2 test, corrected χ2 test, or Fisher exact probability method. Logistic regression was used to compare the effective rate and operation rate between the two groups. Results:In the respective study, 30 patients completed follow-up 13 to 353 days after treatment. At the last follow-up, the incidence of almost complete absorption or significantly absorption of hematoma (hematoma volume was significantly reduced accompanied by symptom improvement) was 93.3%. The 95% CI for the incidence that analyzed by the Clopper-Pearson method was 77.9% to 99.2%. One hundred and six patients were enrolled in the multicenter study. Fifty-five patients underwent body posture combined with pharmacotherapy. The age was 74(17) years (range:26 to 92). Thirty-nine patients were males and 16 were females. Fifty-one patients underwent pharmacotherapy alone. The age was 69(12) years (range:48 to 84). Thirty-seven patients were males and 14 were females. The length of body posture recorded in diary card was (15.7±2.3) hours(range:7.6 to 19.3 hours). The efficacy rate in the body posture combined with pharmacotherapy group and pharmacotherapy alone group were 83.6% (46/55) and 56.9% (29/51), respectively at 3 months. The result of the logistic regression analysis showed that the efficacy of body posture combined with pharmacotherapy group was better than that of pharmacotherapy alone group ( OR=3.88,95% CI:1.57 to 9.58, P=0.003). Surgery rate in the body posture combined with pharmacotherapy group and pharmacotherapy alone group were 5.5% (3/55) and 21.6% (11/51) respectively. The result of Logistic regression showed that the pharmacotherapy alone group was more likely to be converted to surgery ( OR=0.21,95% CI:0.05 to 0.80, P=0.023). At the 6 months, no recurrence of cases was found in the body posture combined with pharmacotherapy group. However, the recurrence rate of pharmacotherapy alone group was 6.3% (3/48), there was no significant difference between the two groups ( P>0.05). Conclusion:The effect of body posture combined with pharmacotherapy for chronic subdural hematoma is better than that of pharmacotherapy alone.

Objective To explore the impact of organizational innovation climate in public hospitals on doctors'innovation performance,providing a reference for improving doctors'innovation performance.Methods A questionnaire survey was conducted with practicing(assistant)physicians in 22 hospitals in Beijing,and 1 859 questionnaires were effectively recovered.The scores of hospital organizational innovation climate,physicians'individual innovation performance,innovation behavior,and innovation self-efficacy were analyzed by Pearson correlation;the partial least squares structural equation modeling was further used to explore the role of the organizational innovation climate of hospitals on physicians'innovation performance.Results The path of hospital organizational innovation climate on physicians'innovation performance.The difference in path coefficients for the mediating effect of hospital organizational innovation climate significantly affecting physicians'innovation performance,and physicians'innovation self-efficacy between hospital innovation climate and physicians'innovation behavior and innovation performance was statistically significant(P＜0.001).Conclusion The innovation performance of practicing(assistant)physicians in Beijing municipal hospitals is influenced by the organizational innovation climate,physicians'innovation self-efficacy and innovation behaviors,and physicians'innovation self-efficacy and innovation behaviors play a chain-mediated role.It is suggested that public hospitals should strengthen doctors'self-efficacy and consider the fit between the construction of innovation atmosphere and actual needs to stimulate innovation behavior and ultimately improve inno-vation performance.

Purpose The current study aims to elucidate the interrelationships among IREB2,FBXL5,iron ho-meostasis,and the therapeutic efficacy of neoadjuvant chemotherapy.Methods A total of 97 samples,classified into colorectal cancer neoadjuvant chemotherapy-resistant and-sensitive groups,along with their corresponding paracancer-ous normal mucosa were collected.The expression levels of FBXL5,IREB2,TFRC and FTH1 were detected by immu-nohistochemistry,Werstern blot and RT-qPCR.The contents of ferroptosis-related markers Fe2+,MDA,ROS and GSH were detected by applying the kit,and the levels of these markers were analyzed.The relationship between each factor in different colorectal cancer tissues and tumor regression rate and prognosis of neoadjuvant chemotherapy were ana-lyzed.Results(1)The expression of IREB2,FBXL5,TFRC and FTH1 in colorectal cancer was higher than that in normal intestinal mucosa(P＜0.05),and the expression of FBXL5 and FTH1 in colorectal cancer drug-resistant group was lower than that in the sensitive group,whereas the expression of IREB2 and TFRC was higher than that in the sen-sitive group(P＜0.05);(2)The correlation analysis showed a positive correlation between the expression of IREB2 and TFRC in the drug-resistant group,and a negative correlation with the expression of FBXL5 and FTH1 in the drug-resistant group.TFRC expression in the colorectal cancer resistance group were positively correlated(P＜0.05)and negatively correlated with the expression of FBXL5 and FTH1(P＜0.05);(3)the content of Fe2+and GSH was high-er than that of the sensitivity group in the colorectal cancer resistance group,and the level of ROS was lower than that of the sensitivity group(P＜0.05);(4)Fe2+was positively correlated with the expression of IREB2,TFRC,and neg-atively correlated with the expression of FBXL5 and FTH1,and was negatively correlated with the expression of FBXL5 and FTH1.FTH1 expression were both negatively correlated(P＜0.05);(5)tumor regression rate was positively cor-related with the expression of FBXL5 and FTH1,and negatively correlated with the expression of IREB2 and TFRC,as well as positively correlated with the level of ROS,and negatively correlated with Fe2+and GSH(P＜0.05);(6)The expression of IREB2 and TFRC was positively correlated with tumor diameter and lymph node metastasis,and the ex-pression of FBXL5 and FTH1 was negatively correlated with tumor diameter and lymph node metastasis,and the expres-sion of FBXL5 was also negatively correlated with the depth of tumor infiltration(P＜0.05);(7)Kaplan-Meier analy-sis showed that lymph node metastasis,FBXL5,IREB2,TFRC,FTH1,and TRG grading were closely related to the prognosis of colorectal cancer patients(P＜0.05).Cox multivariate regression analysis indicated that lymph node me-tastasis,high expression of IREB2 and TFRC,low expression of FBXL5 and FTH1,and low tumor regression grade(TRG)were risk factors for the ineffectiveness of neoadjuvant chemotherapy in colorectal cancer patients.Conclusion FBXL5 and IREB2 are not only associated with high iron homeostasis,but also closely related to the efficacy and prognosis of neoadjuvant chemotherapy for colorectal cancer.In the future,they may become new targets for the treat-ment of colorectal cancer and improve the prognosis of patients.

Objective To explore the impact of organizational innovation climate in public hospitals on doctors'innovation performance,providing a reference for improving doctors'innovation performance.Methods A questionnaire survey was conducted with practicing(assistant)physicians in 22 hospitals in Beijing,and 1 859 questionnaires were effectively recovered.The scores of hospital organizational innovation climate,physicians'individual innovation performance,innovation behavior,and innovation self-efficacy were analyzed by Pearson correlation;the partial least squares structural equation modeling was further used to explore the role of the organizational innovation climate of hospitals on physicians'innovation performance.Results The path of hospital organizational innovation climate on physicians'innovation performance.The difference in path coefficients for the mediating effect of hospital organizational innovation climate significantly affecting physicians'innovation performance,and physicians'innovation self-efficacy between hospital innovation climate and physicians'innovation behavior and innovation performance was statistically significant(P＜0.001).Conclusion The innovation performance of practicing(assistant)physicians in Beijing municipal hospitals is influenced by the organizational innovation climate,physicians'innovation self-efficacy and innovation behaviors,and physicians'innovation self-efficacy and innovation behaviors play a chain-mediated role.It is suggested that public hospitals should strengthen doctors'self-efficacy and consider the fit between the construction of innovation atmosphere and actual needs to stimulate innovation behavior and ultimately improve inno-vation performance.

Objective:To compare the efficacy of body posture combined with pharmacotherapy and pharmacotherapy alone in the treatment of chronic subdural hematoma(CSDH).Methods:Firstly, retrospective case series study was conducted. Thirty cases of CSDH that had received body posture combined with pharmacotherapy at Department of Neurosurgery, Huashan Hospital Affiliated to Fudan University from December 2016 to October 2020 were studied retrospectively. Twenty-seven patients were male, and 3 patients were female. The age of patients ( M(IQR)) was 66(16) years (range:28 to 84). Nineteen patients had unilateral hematoma, and 11 patients had bilateral hematoma. All patients received pharmacotherapy and body posture therapy that was to raise their lower limbs 20 to 30 cm with leg lift pad and get abdominal compressed with customized abdominal belt in supine position. Patients were required to maintain the body posture as much as possible, with the maximum to 16 to 18 hours per day. Patients with unilateral hematoma should tilt the head to the affected side and avoid tilting it to the opposite side. For patients with bilateral hematoma, there was no need for head lateralization. Patient were treated with oral dexamethasone and atorvastatin simultaneously. The preliminary efficacy of body posture combined with pharmacotherapy was determined by hematoma improvement rate which was analyzed by Clopper-Pearson method. Then, the multi-center, prospective, randomized controlled trial had carried out in 9 medical centers from August 2020 to November 2021. The stratified block randomization method was adopted. Patients were randomized in a ratio of 1∶1 to either receive pharmacotherapy alone(the control group) or body posture combined with pharmacotherapy(the experiment group) for 3 months and followed up for 6 months. Effective treatment was defined as complete absorption of hematoma, or the hematoma volume decreased by more than 10 ml and Markwalder grading scale score had improved by more than 1 point compared to the baseline. The efficacy rate and surgery conversion rate at 3 months and recurrence at 6 months were observed. Comparison between groups was performed with paired sample t test, Mann-Whitney U test, χ2 test, corrected χ2 test, or Fisher exact probability method. Logistic regression was used to compare the effective rate and operation rate between the two groups. Results:In the respective study, 30 patients completed follow-up 13 to 353 days after treatment. At the last follow-up, the incidence of almost complete absorption or significantly absorption of hematoma (hematoma volume was significantly reduced accompanied by symptom improvement) was 93.3%. The 95% CI for the incidence that analyzed by the Clopper-Pearson method was 77.9% to 99.2%. One hundred and six patients were enrolled in the multicenter study. Fifty-five patients underwent body posture combined with pharmacotherapy. The age was 74(17) years (range:26 to 92). Thirty-nine patients were males and 16 were females. Fifty-one patients underwent pharmacotherapy alone. The age was 69(12) years (range:48 to 84). Thirty-seven patients were males and 14 were females. The length of body posture recorded in diary card was (15.7±2.3) hours(range:7.6 to 19.3 hours). The efficacy rate in the body posture combined with pharmacotherapy group and pharmacotherapy alone group were 83.6% (46/55) and 56.9% (29/51), respectively at 3 months. The result of the logistic regression analysis showed that the efficacy of body posture combined with pharmacotherapy group was better than that of pharmacotherapy alone group ( OR=3.88,95% CI:1.57 to 9.58, P=0.003). Surgery rate in the body posture combined with pharmacotherapy group and pharmacotherapy alone group were 5.5% (3/55) and 21.6% (11/51) respectively. The result of Logistic regression showed that the pharmacotherapy alone group was more likely to be converted to surgery ( OR=0.21,95% CI:0.05 to 0.80, P=0.023). At the 6 months, no recurrence of cases was found in the body posture combined with pharmacotherapy group. However, the recurrence rate of pharmacotherapy alone group was 6.3% (3/48), there was no significant difference between the two groups ( P>0.05). Conclusion:The effect of body posture combined with pharmacotherapy for chronic subdural hematoma is better than that of pharmacotherapy alone.

Objective To explore the dyad coping experience of stress in pregnant women with undifferentiated connective tissue disease and their spouses,providing a basis for developing dyadic coping intervention measures.Methods By purposive sampling,15 pairs of pregnant women and their spouses who visited the outpatient clinic for pregnancy complicated with immune diseases in a matemity hospital in Jiangsu Province from April to August 2023 were selected as the research subjects for semi-structured interviews.Content analysis was conducted using the Colaizzi 7-step method,and an interview outline and integrated themes were developed based on the Developmental Contextual Coping Model.Results 3 themes(coexistence of positive and negative stress experiences;diverse approaches to dyadic coping with stress;growth and challenges following stress adaptation)and 11 subthemes were identified.Conclusion Healthcare professionals should attach importance to the stress coping issues of pregnant women with undifferentiated connective tissue disease and their spouses,take measures to regulate the negative emotions of couples,ensure multi-faceted support,help the couple adopt positive coping strategies,and promote good stress adaptation.

Purpose To investigate the effect of autophagy intervention on ferroptosis and drug resistance of colorectal canc-er cells and its molecular mechanism.Methods The human colorectal cancer cell lines HCT-8,COLO205,HCT-116,SW620,and SW480 were cultured.HCT-116 cells with moder-ate expression of LC3 were screened,and the expression differ-ences of LC3,p62,Keap1,Nrf2,GPX4 proteins,Fe2+,GSH,and MDA between them and OXA-resistant HCT-116/OXA cell lines were detected.The expression levels of LC3,p62,Keap1,Nrf2,GPX4,Fe2+,GSH and MDA were assessed in HCT-116/OXA cells through the intervention of autophagy and ferroptosis intervention agent combined with oxaliplatin.The proliferative activity and sensitivity to oxaliplatin in each group were detected by CCK-8 assay.Cell growth and invasion ability of each group were detected by plate cloning and Trans well assay.Results LC3,p62 and GPX4 expression levels of HCT-116 cells in the 5 groups were moderate.Compared with HCT-116 cells,HCT-116/OXA was less sensitive to oxaliplatin,and the proteins of p62,Nrf2 and GPX4 were highly expressed,LC3 and Keap1 were lowly expressed,and the expression of Fe2+,GSH and MDA were increased(P＜0.05).The levels of LC3,Keap1 protein,Fe2+and MDA in Rapa and Rapa+Fer-1 groups were higher than those in Fer-1 and control groups,while p62,Nrf2,GPX4 and GSH levels were lower.The expressions of GPX4 pro-tein and GSH in Rapa+Fer-1 group were lower than those in Rapa group(P＜0.05).In the autophagy inhibitor group,LC3,p62,Nrf2,GPX4 and GSH were highly expressed in the CQ and CQ+Erastin groups compared with the control and Eras-tin groups,while Keap1 protein,Fe2+and MDA were low.The levels of GPX4 protein and GSH in Erastin group were lower than those in the other three groups,and the levels of Fe2+and MDA were higher than those in the other three groups(P＜0.05).The combination of autophagy activator OXA showed that Rapa intervention group had higher chemical sensitivity to OXA,less number of migrating cells and lower cell proliferation activity than the other three groups.The sensitivity of Rapa+Fer-1 group to oxaliplatin was lower than that of Rapa group,but higher than that of Fer-1 group and control group(P＜0.05).There was no significant difference between Fer-1 group and con-trol group(P＜0.05).Compared with the control group,the cell activity,migration capacity and clonogenesis capacity of Erastin,CQ+Erastin and CQ groups were decreased when auto-phagy inhibitor was combined with OXA,and the Erastin group was the lowest,while the CQ+Erastin group was higher than the Erastin group,and lower than the CQ group(P＜0.05).Con-clusion In colorectal cancer,autophagy is involved in the regu-lation of ferroptosis,and intervention in autophagy can regulate ferroptosis in colorectal cancer cells through the p62-Keap1/Nrf2-GPX4 pathway,thereby reversing oxaliplatin resistance.

Target trail emulation is an observational research method, which can use real-world data (such as observational data and historical data) to carry out research design according to the design principles of randomized controlled trials (RCT) when RCT cannot be carried out. The intervention group and the control group were classified by simulating random grouping. Finally a high-reliable conclusion similar to RCT can be obtained. This paper summarizes the basic concepts and application process of target trail emulation based on the effect of statins on the prognosis of myocardial infarction in diabetic patients to provide reference for the application of this method in real world.