Objective To construct and validate an interpretable machine learning model integrating contrast-enhanced venous phase CT radiomics and clinical features for preoperative prediction of central lymph node metastasis(CLNM)of papillary thyroid carcinoma(PTC).Methods A case-control study was conducted on 243 histologically confirmed PTC patients.Among them,196 patients from the First Affiliated Hospital of Army Medical University were randomly allocated into a training set(n=137)and an internal validation set(n=59)at a 7:3 ratio,while the left 47 patients from No.958 Hospital of PLA Army were assigned into an external validation set.All participants completed standardized preoperative contrast-enhanced neck CT scanning.Quantitative radiomic features were systematically extracted from venous phase CT images through an open-source big data AI platform.Six machine learning classifiers,eXtreme Gradient Boosting(XGBoost),Support Vector Machine(SVM),Random Forest(RF),Logistic Regression(LR),k-Nearest Neighbors(KNN),and Decision Tree(DT)were implemented to construct clinical-radiomics integration models.The predictive performance was quantitatively assessed through receiver operating characteristic(ROC)curve analysis,with area under the curve(AUC)values calculated for training,internal validation,and external validation sets.Model interpretability was achieved using Shapley additive explanations(SHAP)framework,with particular focus on elucidating feature contributions in the best-performing model.Results The XGBoost model had an AUC value of 0.936(95%CI:0.895～0.976),0.832(95%CI:0.724～0.941),and 0.772(95%CI:0.632～0.912)in training,internal and external validation sets,respectively.SHAP analysis revealed age as the most influential clinical predictor,with younger patients showing higher CLNM risk(OR=0.968,P=0.042).Conclusion Our machine learning-based clinic-radiomic prediction model demonstrates satisfactory performance in predicting CLNM of PTC,providing valuable references for clinical decision-making.

Objective To investigate the predictive value of a nomogram for central lymph node metastasis(CLNM)in patients with papillary thyroid microcarcinoma(PTMC)based on CT features combined with clinical factors.Methods A case-control study was conducted on 256 pathologically confirmed PTMC patients from 2 tertiary hospitals from January 2022 to November 2024.All participants underwent contrast-enhanced neck CT scanning within 2 weeks before surgery and received central lymph node dissection.The 201 patients from the First Affiliated Hospital of Army Medical University were randomized into a training set(n=140)and an internal validation set(n=61)in a 7∶3 ratio.The 55 patients from the Second Affiliated Hospital of Chongqing Medical University were all assigned into an external validation set.Their clinical data and CT features were collected.Univariate and multivariate logistic regression analyses were employed to identify independent predictive factors for CLNM,and then a nomogram model was constructed.Receiver operating characteristic(ROC)curve analysis(area under the curve,AUC),calibration curve,and decision curve analysis(DCA)were performed to evaluate the model performance,discrimination and clinical utility.Results Multivariate logistic regression analysis identified 4 independent CLNM predictors(P<0.05),that is,male(OR=5.991,95%CI:2.209～18.350),tumor size≥0.82 cm(OR=18.880,95%CI:1.803～229.500),capsular involvement(OR=9.805,95%CI:4.015～26.340),and CT-diagnosed lymph node positivity(OR=2.872;95%CI:1.176～7.232).The nomogram achieved an AUC value of 0.859(95%CI:0.796～0.922),0.786(95%CI:0.671～0.901),and 0.783(95%CI:0.648～0.917)in the training and internal and external validation sets,respectively.Calibration curves demonstrated high consistency between predicted and observed probabilities(Hosmer-Lemeshow P>0.05).DCA confirmed net clinical benefits for CLNM before surgical treatment with a threshold probability range of 0.18～0.80.Conclusion Based on sex,tumor size,capsular involvement,and CT-diagnosed lymph node metastasis,our nomogram model effectively predicts CLNM risk in PTMC patients.It can be used as a quantitative tool for personalized surgical planning and shows high clinical applicability.

Objective To explore the medication rules and therapeutic principles of Zhang Jingyue's miscarriage prevention therapies based on data mining technique and literature analysis.Methods The prescription data recorded in the chapter about pregnancy and fetal development from the volume of Women's Diseases in Jing Yue Quan Shu(Jingyue's Complete Works)were collected to establish a database.Frequency analysis,association analysis,and cluster analysis of the herbal medicines from the prescriptions for preventing miscarriage were performed using SPSS Modeler 18.0 and SPSS Statistics 26.0 to investigate Zhang's medication rules.Additionally,discussions on miscarriage prevention in the chapter about pregnancy and fetal development were systematically reviewed to summarize his therapeutic principles.Results A total of 76 miscarriage-prevention prescriptions involving 102 herbal medicinals were analyzed.Among them,26 high-frequency herbal medicinals(used≥5 times)were identified,and primarily belonged to the tonifying deficiency category(11 medicinals).Association analysis revealed 10 association rules with high support,such as"Atractylodis Macrocephalae Rhizoma→Ginseng Radix et Rhizoma"and"Glycyrrhizae Radix et Rhizoma Praeparata cum Melle→Ginseng Radix et Rhizoma,Atractylodis Macrocephalae Rhizoma".The network graph of drug association presented high-correlation herbs including Glycyrrhizae Radix et Rhizoma Praeparata cum Melle,Atractylodis Macrocephalae Rhizoma,Poria,Ginseng Radix et Rhizoma,and Angelicae Sinensis Radix.Cluster analysis yielded four core prescription groups:(1)Ziziphi Spinosae Semen,Polygalae Radix,Dioscoreae Rhizoma,and Corni Fructus;(2)Paeoniae Radix Alba,Chuanxiong Rhizoma,Rehmanniae Radix Praeparata,Atractylodis Macrocephalae Rhizoma,Ginseng Radix et Rhizoma,Glycyrrhizae Radix et Rhizoma Praeparata cum Melle,Angelicae Sinensis Radix,Poria,and Citri Reticulatae Pericarpium;(3)Rehmanniae Radix,Glycyrrhizae Radix et Rhizoma,and Scutellariae Radix;(4)Pinelliae Rhizoma,Magnoliae Officinalis Cortex,Zingiberis Rhizoma Recens,and Jujubae Fructus.Zhang's therapeutic principles for preventing miscarriage were as follows:(1)treating primary diseases together by preventing miscarriage;(2)monthly-specific cultivation of the fetus to preemptively address deficiencies;(3)emphasis on maternal health to consolidate fetal vitality;(4)strict adherence to medication and dietary contraindications and lifestyle management during pregnancy.Conclusion Zhang Jingyue's miscarriage-prevention principles emphasize etiological diagnosis with dual focus on treating primary diseases and preventing miscarriage.His therapies prioritize replenishing qi and blood,skillfully regulating spleen-stomach function and qi movement by employing special and mild herbs and prescribing simplified and flexible formulas.These medication rules and therapeutic principles may provide valuable references for modern miscarriage-prevention strategies.

Objective To explore the effects of sumatriptan on the modulation of calcitonin generelated peptide(CGRP) expression and its involving intracellular signaling transduction mechanisms in rat trigeminal ganglion(TG) after organ culture.Methods Using organ culture in vitro model,54 isolated TGs of SD rats were randomly divided into fresh group ( n =6 ),control group ( n =6 ) and experimental group (n =42,6 TGs for each subgroup).Experimental group included seven subgroups,which were respectively pretreated with four different concentrations of sumatriptan,specific inhibitors of extracellular signalregulated kinases 1/2 (ERK1/2) pathway (U0126 and PD98059 ),and the inhibitor of c-Jun N-terminal kinase (JNK) (SP600125).After co-cultured with above intervention agents for 24 h,CGRP-immunoreactivity (CGRP-ir) positive neurons and CGRP-mRNA expression levels were quantified by immunohistoehemistry stain and real-time polymerase chain reaction,respectively.Phosphorylated ERK1/2 (pERK1/2) and JNK (pJNK) proteins levels were determined by Western-blotting method.Results The CGRP-ir ( + ) neurons expression levels were significantly increased after 24 h organ culture.However,0.10 and 0.50 mg/ml concentrations of sumatriptan remarkably decreased the CGRP-ir ( + ) neurons expression levels.The positive cell percentage,positive optic area,integrated optical density,mean optical density and CGRP-mRNA expression level in TG were significantly reduced than control groups (tPCP =8.652,26.382; tarea =6.220,13.917; tIA =5.606,15.904; tM14 =2.661,21.748; tmRNA =8.032,15.675.P ＜ 0.05 ).The CGRP-mRNA expressions were significantly down-regulated after co-incubation with concentration of 0.50 mg/ml sumatriptan for 24 h in TG of SD rat ( P ＜0.05 ).The levels of pERK1/2 and pJNK protein kinase detected by Western-blotting were significantly reduced by 0.50 mg/ml concentration of sumatriptan,the degrees of which were closed to the ERK1/2 and JNK pathway specific blockers.Conclusion It suggests that the optimal concentration of sumatriptan significantly down-regulates CGRP over-expression via intracellular ERK1/2 and JNK signaling transduction pathways in TG after organ culture.

The Chinese herbal medicine Tianma (Gastrodia elata) has been used for treating and preventing primary headache over thousands of years, but the exact pharmacological mechanism of the main bioactive ingredient gastrodin remains unclear. In present study, the effects of gastrodin on calcitonin gene-related peptide (CGRP) and phosphorylated extracellular signal-regulated kinase1/2 (pERK1/2) expression were observed in rat trigeminal ganglion (TG) after in vitro organ culture to explore the underlying intracellular mechanism of gastrodin on primary vascular-associated headache. CGRP-immunoreactivity (CGRP-ir) positive neurons count, positive area, mean optical density and integrated optical density by means of immunohistochemistry stain were compared at different concentrations of gastrodin, which was separately co-incubated with DMEM in SD rat TG for 24 hours. Only at 5 or 10 mmol L(-1) concentration, gastrodin demonstrated significantly concentration-dependent reduction of CGRP-ir (+) expression and its action closed to 1.2 mmol L(-1) sumatriptan succinate. While at 2.5, 20, and 40 mmol L(-1) concentration, gastrodin did not show remarkable effects on CGRP-ir (+) expression. The optimal concentration of gastrodin (5 and 10 mmol L(-1)) similarly inhibited CGRP-mRNA expression level separately compared with 1.2 mmol L(-1) sumatriptan succinate and 10 micromol L(-1) flunarizine hydrochloride, which was quantitatively analyzed by real-time PCR (RT-PCR). pERK1/2 level was examined by Western blotting after co-cultured with optimal concentration of gastrodin and effective specific ERK1/2 pathway inhibitors PD98059, U0126. The result indicated that gastrodin significantly reduced pERK1/2 protein actions similarly to ERK1/2 pathway specific blockade. It suggests ERK1/2 signaling transduction pathway may be involved in gastrodin intracellular mechanism. This study indicates gastrodin (5 and 10 mmol L(-1)) can remarkably reduce CGRP-ir (+) neuron, CGRP-mRNA and pERK1/2 expression level in cultured rat TG, with its actions similar to the effective concentration of sumatriptan succinate, flunarizine hydrochloride and specific ERK1/2 pathway blocker. The intracellular signaling transduction ERK1/2 pathway may be involved in the gastrodin reducing CGRP up-regulation in rat TG after organ culture.