Intervertebral disc degeneration （IVDD） is the core cause of chronic low back pain， which severely impairs patients’ quality of life and imposes a heavy social and medical burden. The hypoxia-pyroptosis-inflammation cascade mediated by hypoxia-inducible factor-1α （HIF-1α） is the core pathological mechanism driving the initiation and progression of IVDD. Natural active ingredients derived from traditional Chinese medicine （TCM） have become a research hotspot in the field of IVDD prevention and treatment due to their advantages of multi-target effects， favorable efficacy， and low toxicity. This paper systematically reviews the mechanism of HIF-1α-mediated hypoxia-pyroptosis-inflammation cascade in degenerative nucleus pulposus tissue and the intervention of related active ingredients. It is found that natural active ingredients such as baicalein， curcumin and resveratrol can intervene in the HIF-1α-mediated pathological cascade through four core links to delay IVDD progression： targeting the HIF-1α oxygen sensing pathway to block the initiation of pyroptosis cascade， inhibiting NOD-like receptor protein 3 inflammasome activation to cut off the cascade amplification of inflammatory signals， intervening in the Gasdermin D-mediated pyroptosis execution stage to protect cell membrane integrity， and regulating extracellular matrix metabolism to reconstruct intervertebral disc homeostasis.

There is a substantial unmet need for treatments in the field of pediatric rare diseases, and investigator initiated trial(IIT) provide a critical pathway for testing and developing new drugs or treatment strategies. However, healthcare institutions, when conducting such research, must address compliance risks related to project approval, contract management, data protection, and conflict of interest management. This study aims to analyze the particularities and challenges of IIT in pediatric rare diseases, review relevant regulations and regulatory requirements, and provide healthcare institutions with a reference framework for compliance risk management to maximize the benefits of IIT. Based on literature review, analysis of laws and regulations, practical work experience, and frameworks from other institutions, we summarize the unique aspects of pediatric rare disease IIT in terms of participant characteristics, innovative technologies, and organizational structures.On this basis, targeted compliance management recommendations are proposed, which include establishing a risk rating and full-cycle risk monitoring mechanism, a consent and ethical review mechanism tailored to pediatric participants, a robust contract management mechanism, a comprehensive data security management mechanism, and a multidisciplinary team and multi-channel compensation mechanism. The study concludes that healthcare institutions, funders, and other collaborating entities should implement compliance management in line with the characteristics of IIT to ensure the safety and effectiveness of research and facilitate innovation and development in the treatment of pediatric rare diseases.

With the rapid development of minimally invasive techniques in surgery, arti-ficial intelligence (AI), particularly deep learning, is playing an increasingly important role in mini-mally invasive surgery. By automated analysis of surgical videos, AI can efficiently perform key tasks such as instrument recognition, surgical phase identification, action analysis, anatomical structure recognition, intraoperative diagnosis, adverse event monitoring and smart desmoking. These appli-cations provide essential support for real-time monitoring, surgical navigation and skill assessment during surgery. The authors summarize the current research progress of AI in minimally invasive surgery, including its applications in the fields of hepatobiliary and pancreatic surgery, as well as gastrointestinal surgery. It also explores the potential of AI in enhancing surgical safety, efficiency and skill assessment. By synthesizing the latest research achievements of AI technology in the field of surgery, as well as analyzing its technical challenges and risks, it aims to provide guidance for future innovations and clinical applications, promoting the advancement and implementation of AI in minimally invasive surgery.

Objective:To investigate the current status of knowledge, attitude, and practice (KAP) of intensive care unit (ICU) medical staff for post-intensive care syndrome (PICS) and explore its influencing factors.Methods:The cross-sectional investigation study with stratified sampling was conducted. From June to September 2024, ICU medical staff from general hospitals in 5 regions (Chongqing, Beijing, Shaanxi, Jiangsu, and Gansu) were selected as the research subjects. The KAP of PICS questionnaire was distributed in the form of an electronic questionnaire. Observation indicators: (1) results of the questionnaire survey; (2) general information of ICU medical staff; (3) KAP scores of PICS and the correlation among various dimensions; (4) analysis of influencing factors for KAP of PICS. Comparison of measurement data with normal distribution between groups was conducted using the independent samples t test. One-way analysis of variance (ANOVA) was applied for com-parison among multiple groups, and post-hoc LSD test was used for pairwise comparison. Comparison of count data between groups was conducted using the chi-square test. Pearson correlation analysis was adopted for correlation analysis. Multiple linear regression analysis was used for univariate and multivariate analyses. Results:(1) Results of questionnaire survey. A total of 410 questionnaires were distributed and retrieved, among which 408 were valid, with an effective rate of 99.512%(408/410). (2) General information of ICU medical staff. Among the 408 ICU medical staff, there were 79 males and 329 females. Eight cases were under 25 years old, 248 cases were 25-35 years old, 132 cases were 36-40 years old, and 20 cases were over 40 years old. In terms of professional title, there were 10 junior nurses, 130 junior nurse practitioners, 228 intermediate nurse practitioners, and 40 senior nurse practitioners. About the educational background, 34 cases had a junior college degree, 347 cases had a bachelor's degree, and 27 cases had a master's degree or above. Regarding the hospital level, 25 nurses worked in secondary hospitals and 383 cases in tertiary hospitals. In terms of ICU type, 181 cases were from specialized ICU and 227 cases from general ICU. About working experience in ICU, 41 nurses had less than 5 years, 207 cases had 5-10 years, and 160 cases had more than 10 years. (3) KAP scores of PICS and the correlation among various dimensions. The total KAP score of PICS among the 408 ICU medical staff was 88.7±14.2, with 40.2±9.2 for the knowledge dimension, 22.0±5.6 for the attitude dimension, and 26.5±6.3 for the practice dimension. Pearson correlation analysis showed that the knowledge dimension of PICS among ICU medical staff was significantly positively correlated with both the attitude dimension and the practice dimension ( r=0.15, 0.69, P<0.05); the attitude dimension was positively correlated with the practice dimension ( r=0.23, P<0.05).(4) Analysis of influencing factors for KAP of PICS. Results of multivariate analysis showed that age (25-35 years old, 36-40 years old, over 40 years old), educational background and hospital level were independent influencing factors for the KAP of PICS among ICU medical staff ( t=2.23, 1.97, 2.84, 0.15, 2.04, P<0.05). Conclusions:The KAP of PICS among ICU medical staff is relatively good, while their practical ability still needs to be improved. Age, educational background, and hospital level are independent influencing factors for the KAP of PICS among ICU medical staff.

Objective:To explore the clinical distribution characteristics and changes of common inhalant allergens and food allergens in all outpatient and inpatient children visiting Shanghai Children′s Hospital from 2020 to 2024, and to provide a basis for the diagnosis, treatment and prevention of allergic diseases in children.Methods:A retrospective cohort study was conducted to retrospectively enroll all outpatient and inpatient children who visited Shanghai Children′s Hospital and underwent serum allergen-specific IgE (sIgE) antibody testing from January 2020 to August 2024, and the characteristics and changing trends of allergens in the past 5 years were analyzed. A total of 127 310 tests were included. There were 76 776 male tests (60.31%) and 50 534 female tests (39.69%). There were 27 392 tests (21.52%) aged 0-3 years (infant group), 51 596 tests (40.53%) aged 4-6 years (preschool group), 44 574 tests (35.01%) aged 7-12 years (school-age group), and 3 748 tests (2.94%) aged 13-18 years (adolescent group). The χ2 test was used for statistical analysis. Results:The difference in total positivity rate between different years was statistically significant ( χ2=2 907.478, P<0.001). The positive rates of inhalant allergens such as house dust, Dermatophagoides pteronyssinus/ Dermatophagoides farinae, cockroach, cat dander, mugwort, Humulus scandens, mold fungi mix, and food allergens such as beef and mutton increased significantly with age (The χ2 values were 649.496, 3 414.686, 303.247, 1 277.408, 40.477, 189.952, 600.737, 203.198, and 15.301, respectively, and the P values were <0.001, <0.001, <0.001, <0.001, <0.001, <0.001,<0.001,<0.001, and 0.002, respectively). The positive rates of inhalant allergen such as Ambrosia elatior (1.59%) and food allergens such as egg white (17.36%), milk (30.48%), shrimp (8.27%), crab (8.13%), codfish (2.61%), salmon (0.66%), mytilus edulis (2.89%), lobster/scallop (5.27%), cashew nuts (5.09%), peanuts (3.54%), and soybean (1.73%) were highest at the age of 0-3 years and decreased significantly with age (The χ2 values were 10.365, 2 407.443, 139.085, 872.548, 870.245, 106.823, 47.674, 47.244, 559.422, 369.800, 384.788, 153.660, respectively, and the P values were 0.016, 0.000,<0.001,<0.001,<0.001,<0.001,<0.001,<0.001,<0.001,<0.001,<0.001,<0.001, respectively). Inhaled allergens mainly have a greater impact on children with respiratory-related diseases such as allergic rhinitis and asthma, while food allergens mainly have a greater impact on children with atopic dermatitis/eczema. The positive rate of sIgE of various allergens in the allergic rhinitis combined asthma group were higher than that of allergic rhinitis alone, and the sIgE positive rate of total allergens and inhaled allergens was significantly higher than that of allergic rhinitis alone ( χ2=20.851, 39.155, the P values were both<0.001). Among them, the sIgE positive rate of Ambrosia elatior and cashew nuts showed significant difference ( χ2=5.044, 8.420, P=0.025, 0.004); and the sIgE positive rate of Dermatophagoides pteronyssinus/ Dermatophagoides farinae, cat dander, grass pollens mix and mold fungi mix had extremely significant difference ( χ2=26.409, 25.990, 21.283, 16.411, the P values were all <0.001). The inhaled allergens and food allergens with the highest positive rates in the 5 years were Dermatophagoides pteronyssinus/ Dermatophagoides farinae (56.21%) and milk (47.47%), and as time went by, the positive rates gradually decreased. There is a moderate correlation between the three allergens of Ambrosia elatior, Amaranthus retroflexus, and tree pollens mix (0.55, 0.70, 0.63), and there is a moderate correlation between mango and tree pollens mix (0.50). Conclusion:Dermatophagoides pteronyssinus/ Dermatophagoides farinae, cat dander, dog dander, egg white, and milk may be important allergens for children in Shanghai City from 2020 to 2024. The positive rates vary among different genders, age groups, and disease groups, but the positive rates of Dermatophagoides pteronyssinus/ Dermatophagoides farinae, milk and cat dander allergens remain in the top three.

Objective To observe the changes in the serum level of tumor necrosis factor-α(TNF-α)during pegylated interferon-alpha(PEG-IFN-α)treatment in inactive HBsAg carriers(IHCs),to investigate the association between the dynamic changes of TNF-α and HBsAg clearance,and to assess the value of TNF-α as a potential biomarker for predicting the therapeutic efficacy of PEG-IFN-α.Methods A prospective study was conducted among 455 IHCs who attended our hospital from January 2018 to March 2023,and they were divided into treatment group and IHC control group.The 210 IHCs in the treatment group voluntarily received PEG-IFNα-2b treatment for 48 weeks,followed by follow-up for 24 weeks,and the 245 IHCs in the IHC control group were followed up for 72 weeks without treatment.The serum level of TNF-α was measured at baseline(week 0)and at weeks 12,24,48,and 72,and at week 72,the treatment group was further divided into HBsAg clearance group and non-clearance group.The serum level of TNF-α at different time points was compared between groups.The logistic regression analysis was used to assess the value of TNF-α in predicting HBsAg clearance.The t-test was used for comparison of normally distributed continuous data between two groups,and a one-way analysis of variance used for comparison between multiple groups;the repeated measures analysis of variance was used for comparison of normally distributed repeated measurement data within each group and between groups;the chi-square test or the Fisher's exact test was used for comparison of categorical data between groups.Univariate and multivariate logistic regression analyses were used to investigate the predictive factors for HBsAg clearance,and the receiver operating characteristic(ROC)curve was used to determine the cut-off value of TNF-α in predicting HBsAg clearance.Results At week 72,compared with the IHC control group,the treatment group had significantly higher HBsAg clearance rate(46.2%vs 1.2%,χ2=133.333,P<0.001)and seroconversion rate(34.8%vs 0.8%,χ2=94.650,P<0.001).The HBsAg clearance group and the non-clearance group had a significant increase in the serum level of TNF-α during treatment,which gradually returned to the baseline level after drug withdrawal(F=351.733 and 76.434,both P<0.001).Comparisons between groups showed that the HBsAg clearance group had the highest serum level of TNF-α at weeks 12,24,and 48,followed by the non-clearance group and the IHC control group(all P<0.001).The multivariate logistic regression analysis showed that baseline HBsAg level(odds ratio[OR]=0.329,95%confidence interval[CI]:0.189-0.571,P<0.001),baseline HBV DNA<20 IU/mL(OR=1.414,95%CI:1.057-1.787,P=0.045),ALT≥2×upper limit of normal at week 12(OR=1.127,95%CI:1.028-1.722,P=0.043),TNF-α level at week 12(OR=1.336,95%CI:1.018-1.754,P=0.037),and TNF-α level at week 24(OR=1.879,95%CI:1.477-2.391,P<0.001)were independent predictive factors for HBsAg clearance.The ROC analysis showed that TNF-α level at week 12 had an area under the ROC curve(AUC)of 0.846(95%CI:0.814-0.889)in predicting HBsAg clearance at week 72,with a sensitivity of 76.3%and a specificity of 81.0%,while TNF-α level at week 24 had an AUC of 0.912(95%CI:0.758-0.972),with a sensitivity of 81.4%and a specificity of 96.2%.Conclusion PEG-IFN-α can increase the serum level of TNF-α in IHCs,and the serum level of TNF-α at weeks 12 and 24 can effectively predict HBsAg clearance induced by PEG-IFN-α.

Objective To investigate the value of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid(Gd-EOB-DTPA)enhanced MRI radiomics and signal intensity in hepatobiliary phase(HBP)in predicting the pathological differentiation degree of hep-atocellular carcinoma(HCC).Methods The clinical and imaging data of 224 patients pathologically confirmed with HCC were col-lected.All patients were randomly divided into test group(68 cases)and training group(156 cases)at a ratio of 7︰3.The ITK-SNAP software was used to delineate region of interest(ROI)on arterial phase(AP),portal venous phase(PVP)and HBP,the radiomics features of the tumor tissues were extracted and the radiomics models were established using the FAE software.Logistic regression analysis was used to determine the clinical independent predictors associated with the pathological differentiation degree of HCC and to construct clinical model and clinical-radiomics model.Receiver operating characteristic(ROC)curve was plotted for each model and the area under the curve(AUC)was calculated to compare the diagnostic efficacy of the models.Results Age,alpha-fetoprotein(AFP),and r-glutamyltransferase(r-GT)were independent risk factors for predicting the degree of pathological differentiation of HCC.The AUC of the clinical-radiomics model in the training group and test group were 0.825 and 0.779,respectively,which were higher than those of the radiomics model(0.812 and 0.771)and the clinical model(0.687 and 0.666).Conclusion Gd-EOB-DTPA enhanced MRI radiomics have certain value in predicting the degree of pathological differentiation of HCC,while the predictive value of the signal intensity on HBP and the signal intensity ratio(SIR)on HBP is limited.

Objective To observe the changes in the serum level of tumor necrosis factor-α(TNF-α)during pegylated interferon-alpha(PEG-IFN-α)treatment in inactive HBsAg carriers(IHCs),to investigate the association between the dynamic changes of TNF-α and HBsAg clearance,and to assess the value of TNF-α as a potential biomarker for predicting the therapeutic efficacy of PEG-IFN-α.Methods A prospective study was conducted among 455 IHCs who attended our hospital from January 2018 to March 2023,and they were divided into treatment group and IHC control group.The 210 IHCs in the treatment group voluntarily received PEG-IFNα-2b treatment for 48 weeks,followed by follow-up for 24 weeks,and the 245 IHCs in the IHC control group were followed up for 72 weeks without treatment.The serum level of TNF-α was measured at baseline(week 0)and at weeks 12,24,48,and 72,and at week 72,the treatment group was further divided into HBsAg clearance group and non-clearance group.The serum level of TNF-α at different time points was compared between groups.The logistic regression analysis was used to assess the value of TNF-α in predicting HBsAg clearance.The t-test was used for comparison of normally distributed continuous data between two groups,and a one-way analysis of variance used for comparison between multiple groups;the repeated measures analysis of variance was used for comparison of normally distributed repeated measurement data within each group and between groups;the chi-square test or the Fisher's exact test was used for comparison of categorical data between groups.Univariate and multivariate logistic regression analyses were used to investigate the predictive factors for HBsAg clearance,and the receiver operating characteristic(ROC)curve was used to determine the cut-off value of TNF-α in predicting HBsAg clearance.Results At week 72,compared with the IHC control group,the treatment group had significantly higher HBsAg clearance rate(46.2%vs 1.2%,χ2=133.333,P<0.001)and seroconversion rate(34.8%vs 0.8%,χ2=94.650,P<0.001).The HBsAg clearance group and the non-clearance group had a significant increase in the serum level of TNF-α during treatment,which gradually returned to the baseline level after drug withdrawal(F=351.733 and 76.434,both P<0.001).Comparisons between groups showed that the HBsAg clearance group had the highest serum level of TNF-α at weeks 12,24,and 48,followed by the non-clearance group and the IHC control group(all P<0.001).The multivariate logistic regression analysis showed that baseline HBsAg level(odds ratio[OR]=0.329,95%confidence interval[CI]:0.189-0.571,P<0.001),baseline HBV DNA<20 IU/mL(OR=1.414,95%CI:1.057-1.787,P=0.045),ALT≥2×upper limit of normal at week 12(OR=1.127,95%CI:1.028-1.722,P=0.043),TNF-α level at week 12(OR=1.336,95%CI:1.018-1.754,P=0.037),and TNF-α level at week 24(OR=1.879,95%CI:1.477-2.391,P<0.001)were independent predictive factors for HBsAg clearance.The ROC analysis showed that TNF-α level at week 12 had an area under the ROC curve(AUC)of 0.846(95%CI:0.814-0.889)in predicting HBsAg clearance at week 72,with a sensitivity of 76.3%and a specificity of 81.0%,while TNF-α level at week 24 had an AUC of 0.912(95%CI:0.758-0.972),with a sensitivity of 81.4%and a specificity of 96.2%.Conclusion PEG-IFN-α can increase the serum level of TNF-α in IHCs,and the serum level of TNF-α at weeks 12 and 24 can effectively predict HBsAg clearance induced by PEG-IFN-α.

Objective To investigate the value of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid(Gd-EOB-DTPA)enhanced MRI radiomics and signal intensity in hepatobiliary phase(HBP)in predicting the pathological differentiation degree of hep-atocellular carcinoma(HCC).Methods The clinical and imaging data of 224 patients pathologically confirmed with HCC were col-lected.All patients were randomly divided into test group(68 cases)and training group(156 cases)at a ratio of 7︰3.The ITK-SNAP software was used to delineate region of interest(ROI)on arterial phase(AP),portal venous phase(PVP)and HBP,the radiomics features of the tumor tissues were extracted and the radiomics models were established using the FAE software.Logistic regression analysis was used to determine the clinical independent predictors associated with the pathological differentiation degree of HCC and to construct clinical model and clinical-radiomics model.Receiver operating characteristic(ROC)curve was plotted for each model and the area under the curve(AUC)was calculated to compare the diagnostic efficacy of the models.Results Age,alpha-fetoprotein(AFP),and r-glutamyltransferase(r-GT)were independent risk factors for predicting the degree of pathological differentiation of HCC.The AUC of the clinical-radiomics model in the training group and test group were 0.825 and 0.779,respectively,which were higher than those of the radiomics model(0.812 and 0.771)and the clinical model(0.687 and 0.666).Conclusion Gd-EOB-DTPA enhanced MRI radiomics have certain value in predicting the degree of pathological differentiation of HCC,while the predictive value of the signal intensity on HBP and the signal intensity ratio(SIR)on HBP is limited.

Objective:To investigate the value of habitat radiomic features based on gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI in establishing a predictive model for cytokeratin 19 (CK19) expression in hepatocellular carcinoma (HCC) and to evaluate its role in prognostic risk stratification.Methods:This multicenter case-control study retrospectively enrolled 489 patients with pathologically confirmed HCC who underwent Gd-EOB-DTPA-enhanced MRI between June 2016 and June 2024. Among them, 346 patients from the First Affiliated Hospital of Soochow University were divided into a training cohort ( n=245) and an internal test cohort ( n=101) via stratified sampling at a 7∶3 ratio. And 143 patients from Nantong Third Hospital Affiliated to Nantong University served as an external validation cohort. The training cohort included 53 CK19-positive and 192 CK19-negative patients. The internal test cohort included 21 CK19-positive and 80 CK19-negative patients. The external validation cohort included 30 CK19-positive and 113 CK19-negative patients. Univariate logistic regression analysis was performed to identify potential factors associated with CK19 expression, and a clinical-radiologic model was constructed. The k-means clustering algorithm was applied to segment target HCC lesions into 3 subregions. Radiomic features were extracted and selected from these habitat subregions. Habitat radiomics models were constructed for the arterial phase (AP), portal venous phase, hepatobiliary phase (HBP), and combined phases (CP). Multivariate logistic regression analysis identified independent clinical and radiologic predictors of CK19 expression, and the optimal habitat model score was integrated to build a clinical-radiologic-habitat combined model. The area under the receiver operating characteristic curve (AUC) was used to evaluate model predictive performance. Recurrence-free survival (RFS) was analyzed using the Kaplan-Meier method and the differences in survival curves were compared with the log-rank test. Results:Univariate logistic regression analysis revealed that alpha-fetoprotein (AFP) ( OR=2.629, 95% CI 1.412-4.896, P=0.002), AP enhancement ( OR=3.636, 95% CI 1.642-8.052, P=0.001), AP peritumoral enhancement ( OR=2.219, 95% CI 1.084-4.542, P=0.029), and HBP peritumoral hypointensity ( OR=2.010, 95% CI 1.004-4.021, P=0.049) were potential factors associated with CK19 expression, which were incorporated into the clinical-radiologic model. In the internal and external validation cohorts, the AUC of the clinical-radiologic model was 0.690 (95% CI 0.590-0.778) and 0.650 (95% CI 0.565-0.727), respectively. The habitat radiomics model based on CP images demonstrated the highest performance. It achieved AUC of 0.729 (95% CI 0.622-0.836) and 0.725 (95% CI 0.607-0.842) in the internal and external validation cohorts, respectively. Multivariate analysis identified AFP ( OR=2.494, 95% CI 1.163-5.348, P=0.019), AP enhancement ( OR=5.230, 95% CI 1.868-14.643, P=0.002) and habitat radiomics model score ( OR=4.105, 95% CI 2.643-6.368, P<0.001) as independent predictors of CK19 positivity. Based on these factors, a combined clinical-radiologic-habitat combined model was established. The clinical-radiologic-habitat combined model achieved AUCs of 0.767 (95% CI 0.671-0.846) and 0.730 (95% CI 0.649-0.801) in the internal and external validation cohorts, respectively. Significant differences in RFS were observed between the CK19-positive group (25.1 month) and CK19-negative group (51.0 month) as predicted by the clinical-radiologic-habitat model ( χ2=4.17, P=0.041). Conclusion:The clinical-radiologic-habitat combined model based on Gd-EOB-DTPA-enhanced MRI habitat radiomics demonstrates good predictive performance for CK19 expression in HCC and offers valuable prognostic stratification for clinical practice.