Atopic dermatitis （AD） is an atopic disease with a complex etiology and pathogenesis resulting from the interaction of multiple factors. The NOD-like receptor pyrin domain-containing 3 （NLRP3） inflammasome is an important component of innate immunity and is involved in the onset and progression of AD， encompassing multiple processes such as inflammation， pyroptosis， and autophagy. Traditional Chinese medicine （TCM） has shown significant clinical efficacy in the treatment of AD and also offers advantages including flexible compatibility， multi-target effects， and low drug resistance. A large number of studies have shown that single Chinese medicinal components and compound prescriptions can treat atopic diseases by modulating the NLRP3 inflammasome. This article elaborates on the activation of the NLRP3 inflammasome and its influence on the pathogenesis and progression of AD， and summarizes recent studies on the mechanisms by which active constituents， extracts， and compound formulations of Chinese medicine treat AD through regulation of the NLRP3 inflammasome and related signaling pathways， with the aim of providing a reference for the clinical treatment of AD and the development of TCM.

Periodontitis is a chronic inflammatory disease, and its occurrence and development are closely related to the imbalance of local innate immune responses. The caspase family plays a crucial role in regulating inflammatory responses and cell death pathways in periodontal innate immune cells (such as gingival epithelial cells, neutrophils, macrophages, dendritic cells, and natural killer cells). These proteases exhibit a dual regulatory effect on cellular functions. On one hand, apoptotic pathways mediated by caspase-3/7/9 enable the programmed clearance of senescent or damaged cells, while pyroptosis pathways mediated by caspase-1/4 contribute to immune defense and pathogen elimination, collectively helping to maintain tissue homeostasis. On the other hand, excessive activation of the caspase-1/gasdermin D pathway, as well as inflammatory amplification pathways involving caspase-4/6/8, promotes the release of inflammatory cytokines such as IL-1β and IL-18, leading to the disruption of the epithelial barrier and exacerbation of periodontal tissue damage. Caspase regulation exhibits both commonality and cell specificity. In gingival epithelial cells, caspase-1 mediates pyroptosis and inflammation activation, caspase-3 regulates apoptosis and proliferation signaling, and caspase-4 participates in differentiation regulation and pathogen-selective immune responses, collectively adapting to physiological and pathological changes. Neutrophils can utilize the caspase-1/gasdermin D signaling pathway to drive the release of neutrophil extracellular traps without triggering typical pyroptosis. In macrophages, caspase-1 and caspase-8 synergistically promote polarization toward the M1 phenotype, while caspase-3 acts as an apoptosis executor to facilitate macrophage transition to the M2 phenotype in specific microenvironments. This article reviews caspase’s specific mechanism of action in periodontal innate immune-related cells, aiming to provide a new theoretical basis for targeted regulation of caspase in the treatment of periodontitis.

ObjectiveTo explore effect of Xianlian Jiedu prescription on the recurrence of colorectal cancer （CRC） and investigate the related mechanisms. MethodsA postoperative recurrence model was established in 25 Balb/c mice by injecting CT26 cells subcutaneously into the armpit， followed by surgical removal of 99% of the subcutaneous tumor. The mice were randomly divided into model group， low-dose Xianlian Jiedu prescription （XLJDP-L） group （6.45 g·kg^-1·d^-1）， medium-dose Xianlian Jiedu prescription （XLJDP-M） group （12.9 g·kg^-1·d^-1）， high-dose Xianlian Jiedu prescription （XLJDP-H） group （25.8 g·kg^-1·d^-1）， and 5-fluorouracil （5-FU） group （1×10^-3 g·kg^-1·d^-1）. The mice were euthanized after 14 days of continuous intervention， and recurrent tumor tissue was harvested. Hematoxylin and eosin （HE） staining was used to observe pathological and morphological changes in the recurrent tumor tissue. Immunohistochemistry （IHC） was employed to assess the expression of proliferating cell nuclear antigen （Ki67）， vascular endothelial growth factor （VEGF）， and platelet-endothelial cell adhesion molecule （CD31） in recurrent tumor tissue. The Western blot was used to detect the protein expression levels of angiopoietin-2 （ANG-2）， VEGF， phosphorylated-protein kinase B （p-Akt）， protein kinase B （Akt）， phosphorylated-phosphatidylinositol 3-kinase （p-PI3K）， and phosphatidylinositol 3-kinase （PI3K） in recurrent tumor tissue. ResultsBefore treatment， there were no statistical differences in tumor volume， tumor weight， and body mass among the XLJDP-L， XLJDP-M， and XLJDP-H groups and the 5-FU group compared to the model group， indicating model stability. After treatment， compared with those in the model group， the tumor volume and tumor weight in the XLJDP-L， XLJDP-M， and XLJDP-H groups and the 5-FU group were significantly reduced （P<0.01）， showing dose dependency. Meanwhile， there were no significant differences in body weight among the XLJDP-L， XLJDP-M， and XLJDP-H groups and the 5-FU group compared to the model group. HE staining showed that compared with that in the model group， tumor tissue in the XLJDP-L， XLJDP-M， and XLJDP-H groups and the 5-FU group had loosely arranged cells， increased intercellular spaces， small and shriveled nuclei， light staining， fewer mitotic figures and atypical nuclei， and increased necrotic areas. IHC showed that compared with those of the model group， the positive rates of Ki67， VEGF， and CD31 in the recurrent tumor tissue of the XLJDP-L， XLJDP-M， and XLJDP-H groups and the 5-FU group were significantly reduced （P<0.01） in a dose-dependent manner. Western blot results showed that compared with those of the model group， the protein expression levels of ANG-2 and VEGF in the recurrent tumor tissue of the XLJDP-L， XLJDP-M， and XLJDP-H groups and the 5-FU group were significantly downregulated （P<0.05， P<0.01）， and the p-Akt/Akt and p-PI3K/PI3K ratios were significantly decreased in a dose-dependent manner （P<0.05， P<0.01）. ConclusionXianlian Jiedu prescription significantly inhibits the recurrence of CRC in mice after subcutaneous tumor surgery. The mechanism may involve regulating the PI3K/Akt pathway and downregulating key angiogenic proteins such as ANG-2， VEGF， and CD31.

Objective:To analyze the current situation and influencing factors of information need for cardiac rehabilitation of urban and rural patients with coronary heart disease, and explore the inequality of information need for cardiac rehabilitation among urban and rural patients with coronary heart disease and its influencing factors, so as to provide a scientific reference for formulating targeted cardiac rehabilitation programs.Methods:From June to July 2024, hospitalized patients with coronary heart disease from a Class A tertiary hospital in Suzhou City were selected by convenience sampling as the study subjects. A General Information Questionnaire, Information Need in Cardiac Rehabilitation Hospital Anxiety and Depression Scale, Health Literacy Management Scale, and Coronary Artery Disease Self-Management Scale were used to conduct a questionnaire survey. Multiple linear regression was used to analyze the influencing factors of the cardiac rehabilitation information needs and the oaxaca-blinder model was used to analyze the causes of unequal information needs in urban and rural patients.Results:A total of 254 hospitalized patients with coronary heart disease who met the inclusion and exclusion criteria were surveyed, included 127 males and 127 females, 182 of them were aged 60 years or older. The total cardiac rehabilitation information needs score of rural and urban patients with coronary heart disease were 168.00 (115.50, 255.00) and 213.00 (132.00, 255.00), respectively, the difference was significant ( U = 5 389.50, P<0.05). Multiple regression analysis showed that health literacy ( β = 0.871, P<0.05) was the influencing factor of cardiac rehabilitation information needs of rural coronary heart disease patients, and depression ( β = 0.719, P<0.05) and living status ( β = -0.186, P<0.05) was the influencing factor of cardiac rehabilitation information needs of urban coronary heart disease patients. Average monthly household income per capita (C = 14.50%) and health literacy (C = 88.30%) were the main causes of the difference in cardiac rehabilitation information needs between urban and rural patients with coronary heart disease. Conclusions:The information demand for cardiac rehabilitation of patients with coronary heart disease in rural area is lower than that in urban areas in Suzhou, mainly due to health literacy and monthly income. It is recommended to narrow the urban-rural gap by improving rural health literacy, optimizing medical insurance policies, and promoting a multi-level rehabilitation service network.

Objective To investigate the feasibility of simultaneous multi-slice(SMS)acquisition combined with single-shot echo-planar imaging(SSEPI)multi-model diffusion weighted imaging(DWI)for breast lesions.Methods Totally 108 cases of breast lesions were retrospectively enrolled and divided into malignant group(n=66)and benign group(n=42)based on pathology.3.0T MR scanner was used to acquire SSEPI and SMS-SSEPI multi-b values DWI,7 derived parameters were obtained through post-processing with mono-exponential,fractional-order calculus(FROC)and continuous-time random walk(CTRW)models.Then the imaging quality and derived parameters of SMS-SSEPI and SSEPI DWI were compared between groups.Spearman correlation analysis was performed to explore the relationships of corresponding parameters between SMS-SSEPI DWI and SSEPI DWI.Diagnostic performance of each parameter for distinguishing malignant and benign lesions was evaluated according to the area under the receiver operating characteristic curve(AUC).Results Background noise score of SMS-SSEPI DWI was lower than that of SSEPI DWI(P＜0.05),whereas no significant difference of overall imaging quality,normal anatomical structure depiction,lesion conspicuity,geometric distortion,signal-to-noise ratio(SNR)nor contrast-to-noise ratio(CNR)was found between SMS-SSEPI DWI and SSEPI DWI(all P＞0.05).Parameters derived from SMS-SSEPI DWI were all moderately to highly positively correlated with those from SSEPI DWI(rs=0.66-0.98).Malignant lesions exhibited significantly lower apparent diffusion coefficient(ADC),diffusion coefficient based on FROC(DFROC),fractional order derivative in space(βFROC),diffusion coefficient based on CTRW(DCTRW),temporal diffusion heterogeneity index(αCTRW)and spatial diffusion heterogeneity index(βCTRW)values,but higher spatial parameter(μFROC)value than benign lesions(all P＜0.05).AUC of SMS-SSEPI DWI derived parameters for differentiating malignant from benign lesions were 0.699-0.900,of those from SSEPI DWI were 0.654-0.887,while in both SMS-SSEPI DWI and SSEPI DWI,DFROC had the highest diagnostic efficacy(AUC=0.900,0.887).Conclusion SMS-SSEPI DWI could be used to effectively differentiate malignant and benign breast lesions.

Objective:To investigate the additional value of 99Tc m-hydrazinonicotinamide (HYNIC)-Tyr3-octreotide (TOC) SPECT/CT imaging in the diagnosis and treatment of gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Methods:A total of 54 patients (28 males and 26 females, age: (52.6±11.7) years) who underwent enhanced CT (MR) and 99Tc m-HYNIC-TOC SPECT/CT in People′s Hospital of Zhengzhou University between December 2017 and June 2023 were analyzed retrospectively. Surgical pathology or biopsy was the gold standard of patients′ diagnosis (primary tumors), and comprehensive evaluation based on pathology, imaging and follow-up results was used as the diagnostic criteria of lesions. McNemar χ2 test was used to compare the diagnostic efficacy of different imaging methods. Results:Pathological results showed that 43 of the 54 patients were with GEP-NETs and 11 were with non-neuroendocrine tumors (NETs). The sensitivities of enhanced CT and enhanced MR in the diagnosis of patients with GEP-NETs were 65.1%(28/43) and 60.0%(15/25) respectively, which increased to 93.0%(40/43) and 92.0%(23/25) with the addition of 99Tc m-HYNIC-TOC imaging ( χ2 values: 8.64, 4.90, P values: 0.002, 0.021). There were 22 and 15 patients showing atypical enhancement on enhanced CT and enhanced MR respectively. The sensitivities of these two methods for GEP-NETs in patients with atypical enhancement were 54.5%(12/22) and 8/15 respectively, which increased to 95.5%(21/22) and 14/15 with the addition of 99Tc m-HYNIC-TOC imaging ( χ2 values: 5.82, 4.17, P values: 0.012, 0.031). Compared with enhanced CT, the detection rates of liver and bone metastatic lesions were improved significantly from 90.8%(158/174) and 55.2%(32/58) to 96.6%(168/174) and 87.9%(51/58) with the addition of 99Tc m-HYNIC-TOC imaging ( χ2 values: 5.79, 9.82, P values: 0.013, 0.001). Compared with enhanced MR, the detection rate of bone metastases was improved significantly from 56.0%(14/25) to 88.0%(22/25) with the addition of 99Tc m-HYNIC-TOC imaging ( χ2=4.08, P=0.039). After 99Tc m-HYNIC-TOC imaging, stages were changed in 7.0%(3/43) of patients and a greater number or extent of metastases were detected in 11.6%(5/43) of patients. 99Tc m-HYNIC-TOC imaging detected additional recurrent or metastatic lesions in 40.0%(8/20) of patients during follow-up compared to enhanced CT. Conclusion:99Tc m-HYNIC-TOC imaging can provide an added value for diagnosing GEP-NETs with atypically enhanced CT(MR), and in the detection of liver metastasis and early bone metastasis, thus helping the optimization of clinical treatment strategies.

Objective:To analyze the clinical features and genetic sequencing results of a patient with Kallmann syndrome(KS) carrying digenic mutations who initially presented with osteoporosis, and to enhance awareness of this disease phenotype.Methods:Clinical data were collected, and peripheral blood DNA was extracted for whole-exome sequencing. Relevant literature was reviewed to summarize phenotypes associated with digenic/oligogenic variants involving CHD7.Results:The patient exhibited back pain, delayed development of secondary sexual characteristics, and hyposmia. Laboratory tests revealed reduced sex hormones and gonadotropin levels, while pituitary imaging was unremarkable. Bone mineral density imaging confirmed osteoporosis, and thoracolumbar X-rays showed multiple vertebral compression fractures. Genetic analysis identified a heterozygous splice-site mutation in CHD7(c.2698-1G>T) and a heterozygous missense mutation in WDR11(c.439G>A: p.D147N). According to ACMG criteria, the CHD7 mutation was classified as pathogenic, while the WDR11 variant was defined as a variant of uncertain significance(VUS). Literature review indicated that 40% of KS patients with digenic/oligogenic variants involving CHD7 presented with hearing or ocular abnormalities.Conclusion:This study reports a novel CHD7 mutation and a previously undescribed digenic combination of CHD7 and WDR11 variants in a KS patient. CHD7 variants may be implicated in auditory or ocular involvement in KS cases with digenic/oligogenic inheritances. KS patients may also manifest skeletal abnormalities in addition to hypogonadotropic hypogonadism. Tailored management of sex hormones and osteoporosis therapies across life stages is essential for optimizing bone health in KS.

Objective To develop a combined model integrating radiomics and 3D deep learning features for improving the predictive efficacy of overall survival in non-small cell lung cancer(NSCLC)patients undergoing radiotherapy,thereby providing a foundation for optimizing individualized radiotherapy strategies.Methods A retrospective analysis was conducted on 522 NSCLC patients from 3 centers.Radiomics features were extracted from the tumor region of interest on radiotherapy planning CT scans,and a 3D-SE-ResNet was constructed to extract deep learning features.Following feature extraction,features were selected via univariate Cox analysis and Lasso-Cox regression,and a combined model was established by fusing the two feature types through principal component analysis.The discriminative ability of the model was evaluated using the concordance index(C-index)and the area under the receiver operating characteristic curve(AUC),while the risk stratification efficacy was verified by Kaplan-Meier survival analysis.Results The predictive performance of deep learning features was significantly superior to that of radiomics features(C-index:0.73 vs 0.65).The combined model achieved the highest predictive performance in the training set,internal test set,and external test set(C-index:0.74,0.69,0.72 respectively),with higher AUC values for predicting 1-year,2-year,and 3-year OS than either single model.Kaplan-Meier analysis showed significant differences in survival between the high-and low-risk groups(Log-rank test,P<0.001),and calibration curves indicated good consistency between predicted and actual survival outcomes.Conclusion The combined model integrating radiomics and 3D deep learning features can accurately predict survival outcomes in NSCLC patients undergoing radiotherapy.The multi-center validation results support its potential application in prognosis stratification for individualized radiotherapy.

Objective To evaluate the diagnostic efficacy of sound touch viscoelastography(STVi)and shear wave elastography(SWE)in distinguishing between benign and malignant breast nodules.Methods A total of 104 breast nodules(52 benign and 52 malignant)from 102 patients scheduled for surgical treatment at Binzhou Medical University Hospital between October 2024 and February 2025 were prospectively enrolled.All nodules were pathologically confirmed through surgical excision or core needle biopsy.The viscosity coefficient and Young's modulus of both intranodular and perinodular tissues within a 2-mm range were measured using the Mindray Resona A20S ultrasound system.The diagnostic performance of each parameter,the correlation between elastic parameter values and the maximum nodule diameter,as well as the inter-correlation between the two parameters were systematically analyzed.Results The elasticity parameters were significantly higher in malignant nodules[maximum intranodular Viscosity coefficient(Vimax):5.93(4.33,8.47)Pa·s,maximum Young's modulus(Emax):81.18(58.31,120.33)kPa;maximum Viscosity coefficient of the surrounding 2-mm tissue(Vi2max):7.57(5.40,10.16)Pa·s,maximum Young's modulus(E2max):117.21(65.66,170.66)kPa]compared to benign nodules[Vimax:3.70(2.69,5.32)Pa·s,Emax:41.42(28.29,64.25)kPa;Vi2max:4.30(3.63,5.65)Pa·s,E2max:47.23(36.42,74.67)kPa](P<0.05).The diagnostic performance of the 2-mm perinodular tissue(Vi2max:0.78,E2max:0.81)surpassed that of intranodular tissue(Vimax:0.72,Emax:0.77)(P<0.05).The combined diagnostic model(Vi2+E2,Vi+E)achieved AUC values of 0.82 and 0.77,respectively,which outperformed STVi alone(P<0.05)and showed marginally better performance than SWE alone,although the difference was not statistically significant(P>0.05).The maximum nodule diameter showed a moderate correlation with the elasticity parameters,with E2max exhibiting the strongest correlation(r=0.510,P<0.05).Conclusions Both STVi and SWE show clinical value in distinguishing between benign and malignant breast nodules.Particularly,elasticity parameters obtained from the 2-mm perinodular tissue demonstrate better diagnostic performance than those measured within the nodule itself,and combining these parameters enhances the overall diagnostic accuracy of STVi.

Objective·To identify and evaluate novel and reliable non-invasive serological biomarkers for detecting pancreatic ductal adenocarcinoma(PDAC).Methods·Sixty-seven PDAC patients(Ruijin cohort Ⅰ)were recruited at Pancreatic Center,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,from May 2018 to December 2019.Global proteome profiling of 67 PDAC tumor tissues and 67 matched adjacent normal tissues was performed using mass spectrum.Bioinformatics analysis on the proteomics data was conducted to identify new biomarkers,and receiver operating characteristic(ROC)curves and the area under the curve(AUC)were used to evaluate their value of detecting PDAC.The proteomic and mRNA sequencing data were further downloaded and analysed from the Clinical Proteomic Tumor Analysis Consortium(CPTAC)cohort for validation.In addition,the Ruijin Cohort Ⅱ,consisting of 47 PDAC patients and 75 healthy individuals,was recruited for a case-control study from June 2021 to June 2022.Enzyme-linked immunosorbent assay(ELISA)was used to detect the expression level of new biomarkers in the serum of patients and healthy individuals to evaluate the serological diagnostic values of them.Results·Collagen type Ⅻ α1 chain(COL12A1)was identified as a candidate biomarker for PDAC diagnosis based on differential expression analysis on the proteomic data and was validated to be higher in tumor tissues than in adjacent normal tissues in the CPTAC cohort.In addition,COL12A1 protein levels were significantly higher in the sera of PDAC patients than in those of healthy controls,showing good diagnostic performance with an AUC of 0.82,a sensitivity of 81%,and a specificity of 83%.ROC analysis revealed that COL12A1 improved the performance of carbohydrate antigen 199(CA199)in distinguishing PDAC patients from healthy individuals(AUCCA199=0.91 vs AUCCA199+COL12A1=0.95,P<0.05).Furthermore,COL12A1 also showed excellent ability to distinguish early-stage PDAC patients(stage Ⅰ?Ⅱ)from healthy individuals(AUCCOL12A1=0.83),and significantly improved the AUC of CA199 in early-stage PDAC patients(AUCCA199=0.92 vs AUCCA199+COL12A1=0.97,P<0.05).Conclusion·COL12A1 is a potential serological diagnostic marker that complements CA199 in detecting early-stage PDAC.