Objective The study aimed to investigate whether montelukast sodium could alleviate airway inflammatory responses in asthmatic mice by affecting the PHD2/HIF-1α pathway.Methods An allergic asthma model was established by ovalbumin(OVA)induction,and 18 female BALB/c mice were randomly divided into a control group(Con group),an asthma group(OVA group),and an asthma group with montelukast sodium intervention(30 mg/kg montelukast sodium by oral administration 1 h before OVA challenge,Mon group).HE staining was used to analyze the pathological changes in the lungs of mice.Blood cell analyzer and kits were used to determine the number of inflammatory cells and the levels of cytokines,the content of lactic acid and pyruvic acid in the lungs,respectively.RT-PCR and Western blot were used to detect the mRNA and protein expression of HIF-1α,PHD2,E-cad and p120 in the lungs of mice.Results Compared with the Con group,there was a significant increase in the number of eosinophils,lymphocytes,neutrophils and monocytes,the levels of IL-5,IL-13,complement factor D(CFD)and contents of lactate and pyruvate in the lungs of mice in the OVA group.Lung HIF-1α,PHD2,p120 and E-cad mRNA levels were reduced,meanwhile HIF-1α and PHD2 protein expression were upregulated but E-cad and p120 protein expression were downregulated(all with P<0.05).After montelukast sodium intervention,the number of eosinophils and monocytes and CFD expression were significantly decreased in the lungs of Mon group,the contents of lactate and pyruvate were basically restored to normal,and the mRNA and protein expression of HIF-1α,PHD2,p120 and E-cad were effectively improved.Conclusion Montelukast sodium could alleviate the airway inflammatory responses in the lungs of asthmatic mice by regulating the PHD2/HIF-1α signaling pathway.

Objective:To investigate the inhibitory effect of Huqizhengxiao decoction (HQZXD) on subcutaneous tumor in H22 hepatoma-bearing mice and its potential mechanism.Methods:Twenty-five healthy male BALB/c inbred mice aged 4 to 6 weeks and weighing (20±2) g were taken. One of them was used for the amplification of H22 hepatoma cells. The amplified H22 hepatoma cells were inoculated subcutaneously at the left posterior axillary line of the remaining mice for modeling. After subcutaneous tumor formation, the mice were randomly divided into four groups: model group, HQZXD group, sorafenib group and combined (HQZXD+ sorafenib) group, with 6 mice in each group. Tumor inhibition rates, and serum levels of aspartate transaminase (AST) and alanine transaminase (ALT) were observed. The expression of interleukin (IL)-6, signal transducer and activator of transcription 3 (STAT3), phosphorylated STAT3 (p-STAT3), and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) in tumor tissues was detected using immunohistochemistry and Western blotting. Enzyme-linked immunosorbent assay was used to quantify the levels of IL-6, tumor necrosis factor-alpha (TNF-α), and IL-1β in tumor tissues. Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to assess the mRNA levels of IL-6, STAT3, and C-X-C motif chemokine ligand 1 (CXCL1) in tumor tissues.Results:The general condition of mice in all treatment groups improved compared to the model group. Notably, the tumor weight (0.50±0.22) g and tumor volume (0.37±0.18) cm 3 in the combined group were significantly lower than those in the model group [tumor weight: (1.63±0.26) g, tumor volume: (0.98±0.83) cm 3] with statistical significance (both P<0.05). The tumor inhibition rates for the sorafenib, HQZXD, and combination groups were 35.4%, 48.6%, and 69.7%, respectively. Compared to the model group, serum levels of AST and ALT were reduced in all treatment groups, with the combined group showing the most significant decrease [AST: (48.81±2.82) U/L vs. (188.12±6.51) U/L; ALT: (34.14±1.25) U/L vs. (116.62±4.72) U/L], and the differences were statistically significant (both P<0.05). The protein expression levels of IL-6, STAT3, p-STAT3, IL-1β, TNF-α, and NLRP3 in tumor tissues were reduced in all treatment groups compared to the model group, with the combined group showing the most marked reduction, and the differences were statistically significant (all P<0.05). Similarly, the mRNA levels of IL-6, STAT3, and CXCL1 in tumor tissues were lower in all treatment groups compared to the model group, with the combined group showing lower levels than the single treatment groups, and these differences were statistically significant (all P<0.05). Conclusion:HQZXD can inhibit the activation of IL-6/STAT3 pathway, reduce inflammation in tumors, and consequently play a certain inhibitory effect on tumor.

Objective:To establish and validate a multimodal model based on radiomics and deep learning for predicting acute pancreatitis (AP) complicated with acute respiratory distress syndrome (ARDS).Methods:Patients diagnosed with AP from The First Affiliated Hospital of Soochow University, Donghai County People's Hospital and Jintan Affiliated Hospital of Jiangsu University between January 2017 and December 2023 were enrolled. Based on the diagnosis of ARDS within 1 week after admission, the patients were classified into the ARDS group and the non-ARDS group. Patients in the First Affiliated Hospital of Soochow University ( n=406) was used as the training set (non-ARDS group n=212 vs ARDS group n=194), while Donghai and Jintan hospitals served as the test set ( n=175; non-ARDS group n=104 vs ARDS group n=71). Clinical data, laboratory tests and the occurrence of systemic inflammatory response syndrome (SIRS) within 24 hours after admission were collected. Scoring systems such as bedside index for severity in acute pancreatitis (BISAP), Ranson score and modified CT severity index (MCTSI) were calculated. Radiomics features were extracted from three-dimensional CT images to develop a radiomics model based on XGBoost algorithm. At the same time, a deep learning model was constructed using deep convolutional networks to extract deep features. Finally, clinical features and the predictions from the aforementioned models were integrated to establish a multimodal model based on XGBoost algorithm. To enhance model visualization, variable importance ranking and local interpretable visualization were used. The receiver operating characteristic (ROC) curves of the three models and the three scores including BISAP, Ranson and MCTSI were plotted and the area under the curves (AUCs) were calculated to evaluate the prediction performance for ARDS in AP patients, as well as sensitivity and specificity. Results:In the multimodal model for predicting ARDS in AP patients, predictions of the deep learning model and the radiomics model were the most important variables, followed by SIRS, C-reactive protein, procalcitonin, albumin, glucose, creatinine, neutrophil, and Ca 2+. In the training set, the multimodal model achieved an AUC of 0.933 for predicting ARDS in AP patients, higher than the radiomics model (0.727), the deep learning model (0.877), MCTSI (0.870), Ranson (0.620) and BISAP (0.898). In the test set, the model's AUC was 0.916 for predicting ARDS in AP patients, higher than the radiomics model (0.660), the deep learning model (0.864), MCTSI (0.851), Ranson (0.609), and BISAP (0.860). Conclusions:Based on clinical structured data, radiomics and deep learning features, the multimodal model could predict the risk of ARDS in AP patients at an early stage, whose performance is better than the single-modal models and the traditional scoring systems.

Objective The study aimed to investigate whether montelukast sodium could alleviate airway inflammatory responses in asthmatic mice by affecting the PHD2/HIF-1α pathway.Methods An allergic asthma model was established by ovalbumin(OVA)induction,and 18 female BALB/c mice were randomly divided into a control group(Con group),an asthma group(OVA group),and an asthma group with montelukast sodium intervention(30 mg/kg montelukast sodium by oral administration 1 h before OVA challenge,Mon group).HE staining was used to analyze the pathological changes in the lungs of mice.Blood cell analyzer and kits were used to determine the number of inflammatory cells and the levels of cytokines,the content of lactic acid and pyruvic acid in the lungs,respectively.RT-PCR and Western blot were used to detect the mRNA and protein expression of HIF-1α,PHD2,E-cad and p120 in the lungs of mice.Results Compared with the Con group,there was a significant increase in the number of eosinophils,lymphocytes,neutrophils and monocytes,the levels of IL-5,IL-13,complement factor D(CFD)and contents of lactate and pyruvate in the lungs of mice in the OVA group.Lung HIF-1α,PHD2,p120 and E-cad mRNA levels were reduced,meanwhile HIF-1α and PHD2 protein expression were upregulated but E-cad and p120 protein expression were downregulated(all with P<0.05).After montelukast sodium intervention,the number of eosinophils and monocytes and CFD expression were significantly decreased in the lungs of Mon group,the contents of lactate and pyruvate were basically restored to normal,and the mRNA and protein expression of HIF-1α,PHD2,p120 and E-cad were effectively improved.Conclusion Montelukast sodium could alleviate the airway inflammatory responses in the lungs of asthmatic mice by regulating the PHD2/HIF-1α signaling pathway.

Objective:To establish and validate a multimodal model based on radiomics and deep learning for predicting acute pancreatitis (AP) complicated with acute respiratory distress syndrome (ARDS).Methods:Patients diagnosed with AP from The First Affiliated Hospital of Soochow University, Donghai County People's Hospital and Jintan Affiliated Hospital of Jiangsu University between January 2017 and December 2023 were enrolled. Based on the diagnosis of ARDS within 1 week after admission, the patients were classified into the ARDS group and the non-ARDS group. Patients in the First Affiliated Hospital of Soochow University ( n=406) was used as the training set (non-ARDS group n=212 vs ARDS group n=194), while Donghai and Jintan hospitals served as the test set ( n=175; non-ARDS group n=104 vs ARDS group n=71). Clinical data, laboratory tests and the occurrence of systemic inflammatory response syndrome (SIRS) within 24 hours after admission were collected. Scoring systems such as bedside index for severity in acute pancreatitis (BISAP), Ranson score and modified CT severity index (MCTSI) were calculated. Radiomics features were extracted from three-dimensional CT images to develop a radiomics model based on XGBoost algorithm. At the same time, a deep learning model was constructed using deep convolutional networks to extract deep features. Finally, clinical features and the predictions from the aforementioned models were integrated to establish a multimodal model based on XGBoost algorithm. To enhance model visualization, variable importance ranking and local interpretable visualization were used. The receiver operating characteristic (ROC) curves of the three models and the three scores including BISAP, Ranson and MCTSI were plotted and the area under the curves (AUCs) were calculated to evaluate the prediction performance for ARDS in AP patients, as well as sensitivity and specificity. Results:In the multimodal model for predicting ARDS in AP patients, predictions of the deep learning model and the radiomics model were the most important variables, followed by SIRS, C-reactive protein, procalcitonin, albumin, glucose, creatinine, neutrophil, and Ca 2+. In the training set, the multimodal model achieved an AUC of 0.933 for predicting ARDS in AP patients, higher than the radiomics model (0.727), the deep learning model (0.877), MCTSI (0.870), Ranson (0.620) and BISAP (0.898). In the test set, the model's AUC was 0.916 for predicting ARDS in AP patients, higher than the radiomics model (0.660), the deep learning model (0.864), MCTSI (0.851), Ranson (0.609), and BISAP (0.860). Conclusions:Based on clinical structured data, radiomics and deep learning features, the multimodal model could predict the risk of ARDS in AP patients at an early stage, whose performance is better than the single-modal models and the traditional scoring systems.

Objective:To investigate the inhibitory effect of Huqizhengxiao decoction (HQZXD) on subcutaneous tumor in H22 hepatoma-bearing mice and its potential mechanism.Methods:Twenty-five healthy male BALB/c inbred mice aged 4 to 6 weeks and weighing (20±2) g were taken. One of them was used for the amplification of H22 hepatoma cells. The amplified H22 hepatoma cells were inoculated subcutaneously at the left posterior axillary line of the remaining mice for modeling. After subcutaneous tumor formation, the mice were randomly divided into four groups: model group, HQZXD group, sorafenib group and combined (HQZXD+ sorafenib) group, with 6 mice in each group. Tumor inhibition rates, and serum levels of aspartate transaminase (AST) and alanine transaminase (ALT) were observed. The expression of interleukin (IL)-6, signal transducer and activator of transcription 3 (STAT3), phosphorylated STAT3 (p-STAT3), and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) in tumor tissues was detected using immunohistochemistry and Western blotting. Enzyme-linked immunosorbent assay was used to quantify the levels of IL-6, tumor necrosis factor-alpha (TNF-α), and IL-1β in tumor tissues. Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to assess the mRNA levels of IL-6, STAT3, and C-X-C motif chemokine ligand 1 (CXCL1) in tumor tissues.Results:The general condition of mice in all treatment groups improved compared to the model group. Notably, the tumor weight (0.50±0.22) g and tumor volume (0.37±0.18) cm 3 in the combined group were significantly lower than those in the model group [tumor weight: (1.63±0.26) g, tumor volume: (0.98±0.83) cm 3] with statistical significance (both P<0.05). The tumor inhibition rates for the sorafenib, HQZXD, and combination groups were 35.4%, 48.6%, and 69.7%, respectively. Compared to the model group, serum levels of AST and ALT were reduced in all treatment groups, with the combined group showing the most significant decrease [AST: (48.81±2.82) U/L vs. (188.12±6.51) U/L; ALT: (34.14±1.25) U/L vs. (116.62±4.72) U/L], and the differences were statistically significant (both P<0.05). The protein expression levels of IL-6, STAT3, p-STAT3, IL-1β, TNF-α, and NLRP3 in tumor tissues were reduced in all treatment groups compared to the model group, with the combined group showing the most marked reduction, and the differences were statistically significant (all P<0.05). Similarly, the mRNA levels of IL-6, STAT3, and CXCL1 in tumor tissues were lower in all treatment groups compared to the model group, with the combined group showing lower levels than the single treatment groups, and these differences were statistically significant (all P<0.05). Conclusion:HQZXD can inhibit the activation of IL-6/STAT3 pathway, reduce inflammation in tumors, and consequently play a certain inhibitory effect on tumor.

Objective:To investigate the effect of clinical practice of evidence-based medicine (EBM) in facilitating the essential competent capability of ultrasound medicine residents.Methods:A total of 39 residents undergoing standardized residency training in the Department of Ultrasound Medicine at the Second Affiliated Hospital of Zhejiang University School of Medicine from October 2021 to October 2024 were randomly assigned into two groups: control group (19 residents) and an evidence-based traceability group (20 residents). The two groups received same EBM theoretical teaching materials, however, the evidence-based traceability group was additionally required to complete a clinical practice component in ultrasound medicine as part of their EBM curriculum. A comparison was made between the two groups at the conclusion of the teaching cycle with respect to self-assessment (EBM attitude, skills, knowledge), objective test (case analysis, theoretical knowledge), and teaching satisfaction.Results:After the teaching period, the evidence-based traceability group exhibited significantly elevated self-assessment scores in both EBM theoretical knowledge and practice skills when compared to the control group with scores of (26.70±1.17)score vs (21.37±4.15)score and (22.40±1.39)score vs (17.79±3.15)score, respectively (both P<0.001). In the objective test (case analysis, theoretical knowledge), the evidence-based traceability group scored higher in case analysis relevant to clinical scenarios compared to the control group[(59.55±4.56) score vs (52.11±6.58) score, P<0.001], while no statistically significant difference was observed in theoretical knowledge[(29.00±3.08) score vs (27.89±4.19) score, P=0.357]. Both groups reported high teaching satisfaction, with no significant difference between groups ( P>0.05). Conclusions:The incorporation of clinical practice in EBM education for ultrasound medicine residents enhances their clinical practice abilities and improves their analytical and problem-solving skills in real clinical scenarios, contributing to the development of general competent capability among residents.

Objective:To investigate the effect of clinical practice of evidence-based medicine (EBM) in facilitating the essential competent capability of ultrasound medicine residents.Methods:A total of 39 residents undergoing standardized residency training in the Department of Ultrasound Medicine at the Second Affiliated Hospital of Zhejiang University School of Medicine from October 2021 to October 2024 were randomly assigned into two groups: control group (19 residents) and an evidence-based traceability group (20 residents). The two groups received same EBM theoretical teaching materials, however, the evidence-based traceability group was additionally required to complete a clinical practice component in ultrasound medicine as part of their EBM curriculum. A comparison was made between the two groups at the conclusion of the teaching cycle with respect to self-assessment (EBM attitude, skills, knowledge), objective test (case analysis, theoretical knowledge), and teaching satisfaction.Results:After the teaching period, the evidence-based traceability group exhibited significantly elevated self-assessment scores in both EBM theoretical knowledge and practice skills when compared to the control group with scores of (26.70±1.17)score vs (21.37±4.15)score and (22.40±1.39)score vs (17.79±3.15)score, respectively (both P<0.001). In the objective test (case analysis, theoretical knowledge), the evidence-based traceability group scored higher in case analysis relevant to clinical scenarios compared to the control group[(59.55±4.56) score vs (52.11±6.58) score, P<0.001], while no statistically significant difference was observed in theoretical knowledge[(29.00±3.08) score vs (27.89±4.19) score, P=0.357]. Both groups reported high teaching satisfaction, with no significant difference between groups ( P>0.05). Conclusions:The incorporation of clinical practice in EBM education for ultrasound medicine residents enhances their clinical practice abilities and improves their analytical and problem-solving skills in real clinical scenarios, contributing to the development of general competent capability among residents.

Objective To investigate the clinicopathological features of recurrent and de novo focal segmental glomerulosclerosis (FSGS) after kidney transplantation. Methods Thirty-four recipients pathologically diagnosed with FSGS by renal allograft biopsy were enrolled in this clinical trial. According to the detection of primary diseases of renal allografts and circulating permeability factors, 34 recipients were divided into the recurrent FSGS group (n=12) and de novo FSGS group (n=22). The differences of clinical indexes and the degree of pathological injury of renal allografts were compared between two groups. Results There was no significant difference in the mesangial hyperplasia score, glomerulosclerosis rate, renal tubular atrophy score, interstitial fibrosis score and podocyte proliferation rate between two groups (all P > 0.05). In the recurrent FSGS group, segmental glomerulosclerosis rate of the recipients was 0.10 (0.08, 0.27), lower than 0.19 (0.13, 0.33) in the de novo FSGS group (P < 0.05). No significant difference was found in the incidence of antibody-mediated rejection, drug-induced renal tubular injury and BK virus infection between two groups (all P > 0.05). The incidence of T cell-mediated rejection in the recurrent FSGS group was 17%, lower than 55% in the de novo FSGS group (P < 0.05). Immunohistochemical staining showed that the infiltrating inflammatory cells in the renal allografts were mainly T lymphocytes. The positive rates of C4d deposition in peripheral capillaries between the recurrent and de novo FSGS groups were 33% (4/12) and 32% (7/22), with no significant difference (P > 0.05). Immunofluorescence results revealed IgM deposition in the segmental glomerulosclerosis area of renal allografts in most cases. Electron microscopy showed extensive fusion or segmental distribution of podocytes in the glomerulus of renal allografts. Conclusions The degree of renal functional injury and the incidence of T cell-mediated rejection in the recurrent FSGS group are lower than those in the de novo FSGS group. Comprehensive analysis of preoperative and postoperative clinical manifestations, laboratory testing and pathological examination of kidney transplant recipients contribute to early diagnosis and treatment of recurrent and de novo FSGS.

Objective:To investigate the treatment efficacy of adjuvant anti-VEGF/VEGFR targeted therapy in patients with non-metastatic (cM 0) non-clear cell renal cell carcinoma and tumor thrombus (nccRCC-VTT). Methods:This retrospective study enrolled 26 patients who underwent radical nephrectomy combined with inferior vena cava tumor thrombectomy at Peking University Third Hospital from January 2014 to July 2021. Patients were divided into adjuvant therapy group (10 cases) and control group (16 cases)based on the use of postoperative targeted therapy. The distribution of baseline clinical characteristics in the adjuvant therapy group and the control group were as follows: gender (6 males and 4 females in the adjuvant therapy group, 12 males and 4 females in the control group, P=0.66), age (56.2±18.5 years old in the adjuvant therapy group; 54.6±14.5 years old in the control group; P=0.80), BMI(24.0±3.5 in the adjuvant therapy group; 24.3±3.3 in the control group; P=0.80), presence of clinical symptoms (8 cases in the adjuvant therapy group; 15 cases in the control group; P=0.54), tumor laterality(6 cases on the left and 4 cases on the right in the adjuvant therapy group; 6 cases on the left and 10 cases on the right in the control group; P=0.42), location of tumor thrombus (2 cases with renal vein tumor thrombus and 8 cases with inferior vena cava tumor thrombus in the adjuvant therapy group; 2 cases with renal vein tumor thrombus and 14 cases with inferior vena cava tumor thrombus in the control group; P=0.67), ASA classification (2 cases in ASA class 1 and 8 cases in ASA class 2 in the adjuvant therapy group; 2 cases in ASA class 1 and 14 cases in ASA class 2 in the control group; P=0.63), surgical approach (7 minimally invasive surgeries and 3 open surgeries in the adjuvant therapy group; 9 minimally invasive surgeries and 7 open surgeries in the control group; P=0.68), conversion to open surgery (2 cases in the adjuvant therapy group; 2 cases in the control group; P=0.63), operation time [287.5(222.2, 456.0) minutes in the adjuvant therapy group; 344.0(287.8, 482.5) minutes in the control group; P=0.34), blood loss [400.0(250.0, 600.0)ml in the adjuvant therapy group; 575.0(175.0, 800.0)ml in the control group; P=0.63), Clavien-Dindo classification of postoperative complications (8 cases with no postoperative complications, 2 cases with level 1-2 complications, and 0 cases with level ≥3 complications in the adjuvant therapy group; 10 cases with no postoperative complications, 4 cases with level 1-2 complications, and 2 cases with level ≥3 complications in the control group; P=0.68), postoperative hospital stay (8.5 [5.5, 11.5] days in the adjuvant therapy group; 7.5 [6.0, 13.0] days in the control group; P=1.00), maximum tumor diameter[ (9.2±2.7)cm in the adjuvant therapy group; (8.9±3.3)cm in the control group; P=0.81], sarcomatoid differentiation (0 cases in the adjuvant therapy group; 1 case in the control group; P=1.00), perinephric fat invasion (2 cases in the adjuvant therapy group; 7 cases in the control group; P=0.40), tumor necrosis (6 cases in the adjuvant therapy group; 5 cases in the control group; P=0.23), pathological subtype (1 case of PRCC type 1, 6 cases of PRCC type 2, and 3 cases of TFE3 rearrangement RCC in the adjuvant therapy group; 2 cases of PRCC type 1, 10 cases of PRCC type 2, and 1 case each of oncocytic PRCC, TFE3 rearrangement RCC, FH-deficient RCC, and unclassified RCC in the control group; P=0.72), WHO/ISUP nuclear grade (10 cases of grades 3-4 in the adjuvant therapy group; 4 cases of grades 1-2 and 12 cases of grades 3-4 in the control group; P=0.14), invasion of tumor thrombus into the vessel wall (5 cases in the adjuvant therapy group; 5 cases in the control group; P=0.43), T stage (1 case of T 3a, 3 cases of T 3b, 5 cases of T 3c, and 1 case of T 4 in the adjuvant therapy group; 1 case of T 3a, 4 cases of T 3b, 10 cases of T 3c, and 1 case of T 4 in the control group; P=1.00), and positive lymph nodes metastasis(3 cases in the adjuvant therapy group; 0 cases in the control group; P<0.05). The recommended doses for sunitinib, axitinib, and pazopanib are 50mg qd, 5mg q12h, and 800mg qd, respectively. The primary endpoint of this study was disease-free survival (DFS), and the secondary endpoint was overall survival (OS). Statistical analyses were performed using R v4.2.2. Confounding factors were adjusted using propensity score weighting. Results:The median follow-up time for DFS was 29 months in the adjuvant therapy group and not reached in the control group, while median follow-up time for OS was 28 and 26 months, respectively. In the univariate Cox regression analysis, there were no statistically significant difference in the impact of all baseline characteristics and exposure factors on DFS and OS between the two groups. In survival analysis, there were no significant difference between DFS and OS curves of patients in the adjuvant therapy group and the control group (DFS, P=0.62; OS, P=0.74). The median DFS of patients in the adjuvant therapy group and the control group were 17 and 19 months, respectively, while the median OS was 43 and 27 months. After adjusting for confounding factors, the median DFS of patients in the adjuvant therapy group and the control group were 26 and 12 months, respectively, and the median OS remained 43 and 27 months, with no significant difference (DFS, P=0.81; OS, P=0.40). Conclusion:There is currently a lack of definitive evidence for survival benefit from adjuvant anti-VEGF/VEGFR targeted therapy in patients with cM0 nccRCC-VTT after surgery.