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.

Objective To develop a machine learning(ML)-based prediction model for assessing the therapeutic effects of resveratrol(RES)on the pathological damage of acute pancreatitis(AP),and to optimize RES administration strategies for AP through validation using an animal model.Methods AAn ML-based prediction model was constructed using published data.Interpretability analysis was applied to identify high-efficacy zones within the parameter space of administration dose and frequency,which was followed by rigorous screening to select the optimal dosing strategy that balanced therapeutic efficacy and experimental feasibility.A total of 32 C57BL/6 mice were randomly assigned to 4 groups(n=8 per group),including a control group(Ctrl),an AP model group induced by caerulein(CER)and referred to as CER-AP,a treatment group receiving RES via intraperitoneal injection(RES i.p.),and a treatment group receiving RES via intragastric gavage(RES i.g.).The Ctrl group received intraperitoneal injection of normal saline.The CER-AP and the treatment groups were induced with 10 intraperitoneal injections of CER at 50 μg/kg.RES was administered to the RES i.p.and RES i.g.groups according to the optimal dose and timing predicted by the ML model.Blood and tissue samples were collected 12 hours after the experiment started.Results The gradient boosting decision tree model,optimized via Hyperopt,yielded the best performance,predicting that the optimal dose and administration frequency were 19.992 mg/kg and 3.828 times,respectively.Accordingly,a regimen of 20 mg/kg RES,administered four times,was used in the animal experiments.Compared with the Ctrl group,the CER-AP group exhibited higher pancreatic pathology scores and elevated levels of serum amylase,lipase,pancreatic myeloperoxidase,and trypsin,with all differences reaching statistical significance(all P<0.05).The administration of 20 mg/kg RES via both intraperitoneal injection and intragastric gavage mitigated pancreatic inflammatory cell infiltration and necrosis,improved the overall pathology score,and reduced serum amylase,lipase,and pancreatic myeloperoxidase levels to varying degrees(all P<0.05).Conclusion A regimen of 20 mg/kg RES administered four times effectively alleviates the severity of CER-induced AP.The therapeutic benefits appear to arise from a multi-target regulatory network that simultaneously suppresses inflammatory cascades,mitigates oxidative stress,and reduces apoptosis,thereby reducing pancreatic tissue damage and systemic inflammatory responses.

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.

Objective:To explore the value of the deep learning model based on gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) enhanced MRI in preoperatively predicting vessels completely encapsulating tumor clusters (VETC) in hepatocellular carcinoma (HCC).Methods:This study adopted a case-control design to retrospectively analyze 420 patients with HCC confirmed by postoperative pathology who underwent Gd-EOB-DTPA enhanced MRI between June 2016 and March 2023. A total of 420 patients were divided into a training set ( n=305) from the First Affiliated Hospital of Soochow University and an external validation set ( n=115) from Affiliated Nantong Hospital 3 of Nantong University. Based on postoperative pathological findings, patients were stratified into VETC-positive and VETC-negative groups. The training set comprised 161 VETC-positive cases and 144 VETC-negative cases, while the external validation set included 55 VETC-positive cases and 60 VETC-negative cases. Tumor regions of interest in arterial, portal venous, and hepatobiliary phases were manually delineated using ITK-SNAP software. Pre-trained Vgg19, Densenet121, and Vision Transformer (ViT) models were employed for transfer learning, extracting deep learning features from each image. Feature data were processed using FAE software, and 12 logistic regression models (arterial phase, portal venous phase, hepatobiliary phase, and combined three-phase models) were constructed to select the optimal deep learning model. Independent predictors in clinical characteristics were identified through univariate and multivariate logistic analyses to establish a clinical model for predicting VETC pattern. Subsequently, a clinical-deep learning fusion model was developed by integrating these clinical predictors with the optimal deep learning features. Model performance in predicting VETC-positive HCC was evaluated using receiver operating characteristic curves, calibration curves, and decision curve analysis (DCA). Results:In the external validation set, the area under the curve (AUC) of the Vgg19 model in the arterial phase, portal venous phase, hepatobiliary phase, and combined three-phase, respectively were 0.799,0.756,0.789,0.821, which were higher than those of Densenet121 (AUC: 0.544,0.581,0.544,0.583) and ViT (AUC: 0.740,0.752,0.785,0.767) model. The three-phase combined Vgg19 model achieved the highest AUC of 0.821 (95% CI 0.746-0.897). Multivariate logistic regression identified alpha-fetoprotein level ( OR=1.826,95% CI 1.069-3.120, P=0.028) and tumor diameter ( OR=1.329,95% CI 1.206-1.466, P<0.001) as independent predictors of VETC-positive HCC, forming the clinical model with an AUC of 0.789 (95% CI 0.703-0.859). The clinical-deep learning fusion model further achieved the AUC of 0.825 (95% CI 0.749-0.900). Calibration curves confirmed high concordance between predicted and actual probabilities for the three-phase Vgg19 model, while DCA revealed greater net clinical benefit for the combined Vgg19 and fusion models compared with the clinical model alone. Conclusions:The deep learning model based on Gd-EOB-DTPA enhanced MRI can be used to predict VETC of HCC preoperatively, among which the three-phase combined Vgg19 model and the clinical-deep learning model provide high predictive value.

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.

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.

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.

BACKGROUND:Linagliptin exhibits the capacity to regulate macrophage polarization,shifting them from the pro-inflammatory M1 phenotype towards the anti-inflammatory M2 phenotype. This alteration results in a dampened release of inflammatory mediators,thereby mitigating local inflammation.OBJECTIVE:To explore the effects of linagliptin on macrophage polarization,osteoclast activation,and inflammatory osteolysis elicited by wear particles.METHODS:(1) Cell experiments:For macrophage polarization,RAW264.7 cells were cultured and divided into four groups:the control group received high-glucose culture medium;the M1-induced group received M1-inducing culture medium (high-glucose culture medium containing 100 ng/mL lipopolysaccharide and 20 ng/mL interferon-γ) to simulate an inflammatory environment;the low-and high-dose linagliptin groups were treated with 50 and 200 nmol/L linagliptin,respectively,for 4 hours before exposure to M1-inducing culture medium. After 24 hours of macrophage polarization induction,immunofluorescence staining and RT-PCR were performed. For osteoclast activation,RAW264.7 cells were cultured and divided into four groups:the control group was cultured with high-glucose culture medium,the osteoclast-induced group and low-and high-dose linagliptin groups were subjected to osteoclast induction. After osteoclast formation,cells were treated with linagliptin (50 and 200 nmol/L) for 3 days. Subsequently,cell tartrate-resistant acid phosphatase staining and RT-PCR were performed. (2) Animal experiments:Twenty-four male C57BL/6J mice were randomly divided into four groups:sham operation group,model group,low-dose linagliptin group,and high-dose linagliptin group. The model group,low-dose linagliptin group,and high-dose linagliptin group were induced to establish a cranial bone resorption model by injecting titanium particle suspension onto the surface of the skull. Starting from the 2nd day after modeling,the low-and high-dose linagliptin groups were orally administered linagliptin (2 and 10 mg/kg,respectively) once daily. After modeling for 3 weeks,serum macrophage polarization marker protein and inflammatory factor levels were detected;skull samples were collected for micro-CT scanning,bone parameter analysis,and hematoxylin-eosin staining to evaluate osteolysis and morphological changes.RESULTS AND CONCLUSION:(1) Cell experiments:Both low and high doses of linagliptin significantly suppressed M1 polarization while promoting M2 polarization compared to the M1-induced group (P<0.01). Notably,the high-dose group exhibited a more pronounced inhibitory effect (P<0.01). Inflammatory factor mRNA expression was elevated in the M1-induced group compared with the control group (P<0.01),whereas inflammatory factor mRNA expression was significantly lower in the low-and high-dose linagliptin groups compared with the M1-induced group (P<0.01). There was a significant upregulation of mRNA expression of osteoclast functional markers in the osteoclast-induced group compared with the control group (P<0.01). Conversely,both low and high doses of linagliptin led to a substantial downregulation of mRNA expression of these markers compared with the osteoclast-induced group (P<0.01),with the high-dose group exhibiting a more pronounced reduction. (2) Animal experiments:Titanium particle implantation induced cranial bone resorption damage in mice. Treatment with linagliptin effectively mitigated this bone resorption,with the high-dose group showing superior efficacy. To conclude,linagliptin has been shown to modulate macrophage polarization,inhibit osteoclast activation,and have a protective effect on the skeletal system.

Simultaneous management of intestinal mucosal barrier dysfunction and gut microbiota dysregulation represents a significant challenge in the treatment of inflammatory bowel disease (IBD). Herein, we report a novel system that integrates multi-enzyme mimicking cerium single-atom nanocatalysts (CeSACs) with Lactobacillus reuteri probiotics (LR@CeSACs) for multipronged management of IBD. In this system, CeSACs demonstrate robust multi-enzyme activities across a broad pH range, effectively scavenging elevated reactive oxygen species, downregulating pro-inflammatory cytokines, and suppressing the expression of fibrosis-related genes. Moreover, probiotics promote the targeting and retention of the CeSACs for sustained catalytic antioxidant therapy. In turn, the inflammation relief enabled by CeSACs promotes bacterial viability, allowing for the rapid reshaping of intestinal barrier function and the restoration of gut microbiota. Therefore, LR@CeSACs exhibit excellent catalytic anti-inflammatory and anti-fibrotic therapeutic effects, as well as a certain prophylactic effect, as demonstrated in several murine models.