ObjectiveThis paper aims to observe the role of Danlou tablet in treating coronary heart disease （CHD） with phlegm-stasis intermingling syndrome in minipigs by improving platelet function and explore the potential pharmacological mechanism of Danlou tablet in regulating platelet function by using proteomics technology. MethodsThirty Bama minipigs were randomly divided into a normal control group （6 pigs） and a high-fat diet group （24 pigs）. After 2 weeks of high-fat diet feeding， the high-fat diet group was randomly subdivided into a model group， an atorvastatin group （1 mg·kg^-1）， and Danlou tablet groups （0.6 g·kg^-1 and 0.3 g·kg^-1）. All groups continued to receive a high-fat diet for 8 weeks after the procedure. The normal control group was given a regular diet， underwent only coronary angiography， and did not receive an interventional injury procedure. The model group and each administration group were fed a high-fat diet. Two weeks later， they underwent a coronary angiography injury procedure. After the procedure， drugs were mixed into the feed every morning for 8 consecutive weeks， with the minipigs maintained on a continuous high-fat diet during this period. Quantitative proteomics technology was further used to study platelet proteins， and differential proteins were obtained by screening. Bioinformatics analysis was performed to analyze key regulatory proteins and biological pathways involved in the therapeutic effect of Danlou tablet on CHD with phlegm-stasis intermingling syndrome. ResultsCompared with the normal control group， the model group showed a significant increase in total cholesterol （TC）， triglyceride （TG）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C） of minipigs' serum （P<0.01）， a significant shortening in prothrombin time of （PT） （P<0.01）， a coagulation function index， and an increase in whole blood viscosity （P<0.01） and platelet aggregation rate （P<0.01）. Moreover， the platelet morphology was altered， and the contents of endothelin-1 （ET-1） and nitric oxide （NO） were significantly increased （P<0.01）. Hemodynamic parameters were obviously abnormal， including significantly decreased systolic blood pressure （SBP）， diastolic blood pressure （DBP）， mean arterial pressure （MAP）， left ventricular systolic pressure （LVSP）， and left ventricular maximal positive dp/dt （LV+dp/dt_max） （P<0.01）. Left ventricular maximal negative dp/dt （LV-dp/dt_max） was significantly increased （P<0.01）. Besides， there were myocardial cell hypertrophy， obvious edematous degeneration， massive interstitial inflammatory cell infiltration， high degree of fibrosis， and coronary endothelial atherosclerosis. TC and TG levels in minipigs' serum were significantly reduced in Danlou tablet groups with 0.6 g·kg^-1 and 0.3 g·kg^-1 （P<0.05， P<0.01）， compared with those in the model group. LDL-C was decreased in the Danlou tablet group with 0.6 g·kg^-1 （P<0.05）. The whole blood viscosity under low and high shear conditions was significantly reduced in the Danlou tablet group with 0.6 g·kg^-1 （P<0.05）. In groups with all doses of Danlou tablet， maximum aggregation rate （MAR） and average aggregation rate （AAR） were significantly decreased （P<0.05， P<0.01）， and platelets' morphological changes such as pseudopodia extension were reduced. ET-1 levels in the serum were significantly reduced. In the Danlou tablet group with 0.6 g·kg^-1， NO level in the serum was reduced （P<0.05）. In groups with all doses of Danlou tablet， DBP and MAP were significantly increased （P<0.05）. In the Danlou tablet group with 0.6 g·kg^-1， LVSP and LV+dp/dt_max were significantly increased （P<0.05， P<0.01）， and LV-dp/dt_max was significantly decreased （P<0.05）. In groups with all doses of Danlou tablet， edematous degeneration in myocardial tissue was milder， and coronary artery lesion degree was significantly alleviated. Compared with the normal control group， there were 94 differentially expressed proteins in the model group， including 81 up-regulated and 13 down-regulated proteins. Compared with the model group， the Danlou tablet group with 0.6 g·kg^-1 showed 174 differentially expressed proteins， including 100 up-regulated and 74 down-regulated proteins. A total of 30 proteins were reversed after Danlou tablet intervention. Bioinformatics analysis revealed that its pharmacological mechanism may exert anti-platelet activation， aggregation， and adhesion effects through biological pathways such as regulation of actin cytoskeleton， platelet activation pathway， Fcγ receptor-mediated phagocytosis， as well as proteins such as growth factor receptor-bound protein 2 （GRB2）， Ras-related C3 botulinum toxin substrate 2 （RAC2）， RAC1， and heat shock protein 90 alpha family class A member 1 （HSP90AA1）. ConclusionDanlou tablet can effectively reduce platelet activation and aggregation， exerting a good therapeutic effect on CHD with phlegm-stasis intermingling syndrome in minipigs. Its pharmacological mechanism may involve regulating biological pathways such as actin cytoskeleton and platelet activation pathway， as well as proteins like GRB2， RAC2， RAC1， and HSP90AA1， thereby exerting a pharmacological effect in anti-platelet activation， aggregation， and adhesion.

OBJECTIVE: To compare the effects of double-channel core decompression (CD) combined with medullary cavity irrigation with those of simple CD on progression of collapse and clinical outcomes in non-traumatic osteonecrosis of the femoral head (ONFH). METHODS: A retrospective analysis was conducted on the clinical data of 19 patients (30 hips) with non-traumatic ONFH who underwent double-channel CD combined with medullary cavity irrigation and admitted between January 2024 and October 2024 (CD+irrigation group). According to a 1: 2 ratio, 54 patients (60 hips) who underwent simple CD and were matched in terms of age, gender, and body mass index (BMI) were included as the control (CD group). There was no significant difference in baseline data such as age, gender, BMI, affected side, ONFH type, preoperative Association Research Circulation Osseous (ARCO) stage, bone marrow edema stage, visual analogue scale (VAS) score for pain, and Harris score between the two groups ( P>0.05). The postoperative discharge time and occurrence of complications were recorded for both groups. The VAS scores before operation and at discharge after operation were compared, and the differences between pre- and post-operation (change values) were calculated for intergroup comparison. The Harris scores before operation and at discharge and 3 months after operation were also compared. During follow-up, X-ray film, CT, and MRI were performed for reexamination. The ARCO stage and bone marrow edema stage were evaluated at 3 months after operation and compared with those before operation to determine whether there was radiological progression or relief. RESULTS: All incisions in both groups healed by first intention after operation, with no infection, femoral neck fracture, or other operation-related complications. All patients were followed up, and the follow-up time of the CD+irrigation group was (146.8±27.7) days, and that of the CD group was (164.3±48.2) days; there was no significant difference between the two groups ( t=1.840, P=0.069). There was no significant difference in the length of hospital stay between the two groups ( P>0.05). At discharge after operation, the VAS score of the CD+irrigation group was significantly lower than that of the CD group ( P<0.05), and the change value was significantly higher than that of the CD group ( P<0.05). The Harris scores at discharge and 3 months after operation in the CD+irrigation group were significantly higher than those in the CD group ( P<0.05). The Harris score gradually increased with time, and the differences between different time points were significant ( P<0.05). Radiological reexamination showed that there was no significant difference in the ARCO stage and the incidence of radiological progression between the two groups at 3 months after operation ( P>0.05); however, the bone marrow edema stage and the degree of bone marrow edema relief in the CD+irrigation group were better than those in the CD group, with significant differences ( P<0.05). CONCLUSION Double-channel CD combined with medullary cavity irrigation can significantly alleviate hip joint pain and improve joint function in patients with non-traumatic ONFH, reduce the degree of bone marrow edema in the femoral head, and delay the progression of ONFH.
Humans ; Femur Head Necrosis/therapy* ; Retrospective Studies ; Male ; Female ; Decompression, Surgical/methods* ; Therapeutic Irrigation/methods* ; Adult ; Treatment Outcome ; Middle Aged ; Femur Head/surgery*

OBJECTIVE: To observe the effect of electroacupuncture at "Sishencong" (EX-HN1) and "Fengchi" (GB20) on hippocampal neuronal ferritinophagy mediated by the nuclear receptor coactivator 4 (NCOA4)/ferritin heavy chain 1 (FTH1) signaling pathway in vascular dementia (VD) rats, and to explore the potential mechanisms of electroacupuncture for VD. METHODS: A total of 60 male rats of SPF grade were randomly divided into a blank group (12 rats), a sham surgery group (12 rats) and a modeling group (36 rats). In the modeling group, the modified 4-vessel occlusion method was used to establish the VD model. The 24 successfully modeled rats were randomly divided into a model group and an electroacupuncture group, with 12 rats in each group. In the electroacupuncture group, electroacupuncture was applied at left and right "Sishencong" (EX-HN1), and bilateral "Fengchi" (GB20), with continuous wave, in frequency of 2 Hz and current intensity of 1 mA, 30 min a time, once daily for 21 consecutive days. The learning and memory abilities were assessed using the Morris water maze test before modeling, after modeling and after intervention, as well as the novel object recognition test after intervention. After intervention, the neuronal morphology in the hippocampus was observed by Nissl staining; the iron deposition was observed by Prussian blue staining; the reactive oxygen species (ROS) level was detected by dihydroethidium (DHE) fluorescence staining; the levels of iron, malondialdehyde (MDA) and superoxide dismutase (SOD) in the hippocampal tissue were measured by the colorimetric assay, TBA method, and WST-1 method, respectively; the positive expression of NCOA4, FTH1 and glutathione peroxidase 4 (GPX4) was detected by immunohistochemistry; the protein expression of NCOA4, FTH1, GPX4, and the ratio of microtubule-associated protein 1 light chain 3B (LC3B) Ⅱ/Ⅰ in the hippocampus were detected by Western blot. RESULTS: Compared with the sham surgery group, in the model group, the escape latency was prolonged, and the number of platform crossings reduced (P<0.01), the recognition index (RI) was decreased (P<0.01); the hippocampal neurons displayed a blurred laminar structure, disorganized cellular arrangement, and the number of Nissl bodies was decreased (P<0.01); the percentage of iron deposition area in the hippocampus was increased (P<0.01); in the hippocampus, the levels of ROS, iron, MDA, and the protein expression of NCOA4, as well as the LC3B Ⅱ/Ⅰ ratio were increased (P<0.01), the SOD level, and the protein expression of FTH1 and GPX4 were decreased (P<0.01). Compared with the model group, in the electroacupuncture group, the escape latency was shortened and the number of platform crossings was increased (P<0.01), the RI was increased (P<0.01); the hippocampal neurons exhibited more regular morphology, better-organized cellular structure, and the number of Nissl bodies was increased (P<0.05); the percentage of iron deposition area in the hippocampus reduced (P<0.01); in the hippocampus, the levels of ROS, iron, MDA, and the protein expression of NCOA4, as well as the LC3B Ⅱ/Ⅰ ratio were decreased (P<0.01, P<0.05), the SOD level, and the protein expression of FTH1 and GPX4 were increased (P<0.01). CONCLUSION Electroacupuncture at "Sishencong" (EX-HN1) and "Fengchi" (GB20) can improve learning and memory abilities in VD rats, and its mechanism may be associated with the regulation of the hippocampal NCOA4/FTH1 signaling pathway, inhibition of ferritinophagy, and alleviation of oxidative stress damage.
Animals ; Electroacupuncture ; Dementia, Vascular/genetics* ; Male ; Rats ; Signal Transduction ; Humans ; Memory ; Rats, Sprague-Dawley ; Nuclear Receptor Coactivators/genetics* ; Ferritins/genetics* ; Learning ; Hippocampus/metabolism* ; Acupuncture Points

Objective : To explore the value of combined indicators of prognostic nutritional index ( PNI) ，nutri- tional risk screening 2002 scale ( NRS2002 ) ，body mass index ( BMI) ，monocyte / lymphocyte ratio ( MLR) ， platelet / lymphocyte ratio ( PLR) ，and neutrophil / lymphocyte ratio ( NLR) in evaluating the severity of pulmonary tuberculosis ( PTB) ． Methods : A total of 175 patients with pulmonary tuberculosis were selected as the study group，and 175 healthy subjects who underwent physical examination during the same period were selected as the control group．According to the range of lung lesions，the patients were divided into mild to moderate group ( ＜3 lung fields，n = 110) and severe group ( ≥3 lung fields，n = 65) ，PNI，NRS2002，BMI and peripheral blood MLR , PLR and NLR levels were compared between the two groups．Spearman rank correlation was used to analyze their correlation with the severity of the disease．A multivariate logistic regression model was established．A nomo- gram was drawn，and the efficiency of the model was evaluated by receiver operating characteristic ( ROC) curve， calibration curve，decision curve． Results: The PNI，BMI，peripheral blood lymphocyte and albumin levels in the study group were lower than those in the control group ( P＜0. 05) ，while the MLR , PLR and NLR levels were sig- nificantly higher than those in the control group ( P＜0. 05) ．The NRS2002，MLR , PLR and NLR levels in the se- vere group were higher than those in the mild and moderate group ( P＜0. 05) ，while the PNI and BMI levels were lower than those in the mild and moderate group ( P＜0. 05) ．NRS2002 and peripheral blood MLR , PLR and NLR levels in patients with pulmonary tuberculosis were positively correlated with the severity of the disease ( r = 0. 250， 0. 509，0. 431 and 0. 488) ．PNI and BMI were negatively correlated with the severity of the disease ( r = －0. 516， - 0. 231) ．Multivariate Logistic regression showed that NRS2002 and NLR were independent risk factors for severe disease，while PNI was a protective factor．The areas under the curve ( AUC) of NRS2002，NLR , PNI，and com- bined detection for evaluating the severity of pulmonary tuberculosis were 0. 692，0. 777，0. 786，and 0. 860，re- spectively，the sensitivity of the combined prediction was 81. 54% and the specificity was 76. 36%．The combined detection had better evaluation efficiency for severe pulmonary tuberculosis than the single indicator ( P ＜0. 05) ． Conclusion NRS2002 and NLR are independent risk factors for severe disease，while PNI is a protective factor． The combined detection model has a good fit，which can improve the evaluation efficiency and has potential for clin- ical application．

Objective:To analyze the current status of clinical trials of Chinese materia medica for the purpose of registration in China; To provide reference for the research and development of new TCM drugs.Methods:Clinical trials of Chinese materia medica/natural medicine registered in Drug Clinical Trial Registration and Information Disclosure Platform were retrieved from inception to December 31, 2024. Excel 2019 software was used to input and analyze the data such as the number of registered clinical trials, date of first publication, study status, field of indication, trial phases, sponsors, group leader, and design types.Results:A total of 1 137 Chinese materia medica clinical trials had been registered, accounting for 4.12% of the total number registered on the platform. Phase Ⅱ clinical trials accounted for the highest proportion (58.8%), and 99.7% of clinical trials conducted domestically. The sponsors were predominantly domestically pharmaceutical enterprises. These 1 137 clinical trials of Chinese materia medica clinical trials involved 752 drug categories, 28 dosage forms, and 796 varieties (the same class of drugs had different drug dosage forms), with capsules being the most common. The indications primarily focused on respiratory, digestive, cardio-cerebrovascular, neuropsychiatric, gynecological diseases. The group leader of clinical trials was distributed in 28 provinces, among which the First Teaching Hospital of Tianjin University of Traditional Chinese Medicine as the group leader, undertook the most clinical trials of TCM. 89.9% of the clinical trials adopted the randomized controlled trial design, and only 31.9% of the clinical trials purchased insurance for the subjects.Conclusion:The research and development of new TCM drugs has entered a phase of vigorous development. Further efforts are still needed in establishing systematic guidelines for Chinese materia medica clinical trials, accelerating the internationalization of TCM, exploring innovative dosage forms and indications, and strengthening the protection of participants' rights.

Non-small cell lung cancer(NSCLC)is the leading cause of cancer-related mortality worldwide,with approximately 30％of patients initially presenting at stage Ⅱ-Ⅲ and thus potentially eligible for surgical resection.However,surgery alone is insufficient to control postoperative recurrence and distant metastasis effectively.Therefore,neoadjuvant treatment has gradually become a critical approach to improving patient prognosis.Conventional neoadjuvant chemotherapy has historically shown limited pathological complete response(pCR)rates,while neoadjuvant targeted therapy,despite enhancing objective response rates(ORR),still results in relatively low pCR.Recently,neoadjuvant immunotherapy combined with chemotherapy has demonstrated groundbreaking progress.Several large-scale international and domestic clinical trials have reported that this combination strategy significantly increases pCR rates to between 17％and 41％and notably prolongs event-free survival.However,neoadjuvant immunotherapy also introduces new surgical challenges,including increased intraoperative difficulty due to tissue fibrosis,expanded surgical resections resulting from inadequate preoperative prediction,and emerging concerns surrounding the perioperative management of immune-related adverse events(irAEs).Recent advancements in artificial intelligence(AI)-assisted imaging models,multi-omics integration,and dynamic ctDNA monitoring offer novel perspectives and tools for accurately predicting pathological responses preoperatively.Furthermore,intensive studies on mechanisms underlying immunotherapy resistance,such as exosomal PD-L1 regulatory pathways and oxidative stress pathways,alongside emerging strategies involving bispecific antibodies and metabolic interventions,provide theoretical foundations for further optimizing therapeutic approaches.Looking forward,the development of precise preoperative efficacy prediction systems,deep integration of AI technology,and the expansion of multi-modal combination strategies will represent primary directions in the evolution of neoadjuvant immunotherapy for NSCLC.

Objective:To study the epidemic characteristics and clinical symptoms of patients with Hashimoto's thyroiditis (HT) in Shandong Province, and to provide a basis for further optimizing the clinical treatment strategies for HT.Methods:Data on HT patients admitted to Shandong Provincial Center for Disease Control and Prevention from January 2018 to December 2023 were collected. A retrospective analysis was conducted to analyze their epidemiological characteristics, clinical symptoms, and auxiliary examination results.Results:A total of 192 HT patients' data were included, comprising 42 males (21.87%) and 150 females (78.13%). The average age of patients was 40.38 years old, ranging from 9 to 74 years old. Most patients resided in urban areas (129 cases, 67.19%). HT cases occurred throughout the year in every mouth, with higher incidence in June (32 cases, 16.7%) and July (20 cases, 10.4%), lower incidence in March (8 cases, 4.2%) and April (10 cases, 5.2%), and sporadic cases in other months. Based on clinical manifestations, among all HT patients, there were 66 cases (34.38%) of Hashitoxicosis type, 11 cases (5.73%) of pseudothyrotoxicosis type, 7 cases (3.65%) of exophthalmic type, 5 cases (2.60%) of subacute thyroiditis-like type, 3 cases (1.56%) of juvenile type, 35 cases (18.23%) of fibrous type, 39 cases (20.31%) of thyroid adenoma or carcinoma type, and 26 cases (13.54%) of other autoimmune diseases type. Based on disease progression, among all HT patients, there were 61 cases (31.77%) in the hyperthyroid phase, 16 cases (8.33%) in the hyperthyroid-hypothyroid coexisting phase, and 115 cases (59.90%) in the hypothyroid phase. Based on clinical symptoms, among all HT patients,there were 78 cases(40.62%) of neck mass symptoms, 101 cases (52.60%) of digestive system symptoms, and 95 cases (49.48%) of low metabolic symptoms. Laboratory tests revealed that 144 cases had elevated levels of both thyroglobulin antibody and thyroid peroxidase antibody. Color ultrasound examination showed strip-like echoes in the thyroid in 99 cases (51.56%) and grid-like echoes in 43 cases (22.40%). After treatment with antithyroid drugs or appropriate thyroid hormone supplementation, all 192 HT patients experienced symptom relief.Conclusions:HT patients in Shandong Province were predominantly female and urban residents. Common clinical symptoms included anterior neck swelling, constipation, fever, and weight gain. Early detection, diagnosis, and treatment could delay disease progression.

Objective To investigate the influencing factors of ERCP stent implantation for patients with malignant obstructive jaundice.Methods 130 patients with malignant obstructive jaundice who received ERCP stent implantation in our hospital from January 2017 to January 2024 were retrospectively included,and grouped according to the jaundice control effect 4 weeks after surgery.Univariate and multivariate analysis of the efficacy of ERCP stent placement in malignant obstructive jaundice after 4 weeks.Construction of a predictive model for the efficacy of ERCP stent placement in malignant obstructive jaundice after 4 weeks and clinical efficacy analysis.Results There were 64 cases for jaundice resolved in 4 weeks after surgery among all 130 patients with the regression rate for 49.23％.The results of univariate analysis showed that the type of biliary obstruction,stent type,and preoperative Child Pugh grading may all be related to the efficacy of ERCP stent placement in malignant obstructive jaundice after 4 weeks(P＜0.05).The results of Logistic multivariate analysis showed that the type of biliary obstruction,stent type,and preoperative Child Pugh grade were all independent influencing factors on the efficacy of ERCP stent placement for malignant obstructive jaundice at 4 weeks(P＜0.05).Using the independent influencing factors and P-value prediction probability of Logistic regression model to predict the prognosis of patients,the ROC curve was used,with areas under the curve of 0.713,0.823,0.907,and 0.971,respectively.Conclusion The clinical effects of ERCP stent implantation in malignant obstructive jaundice was closely related to the type of biliary obstruction,stent type and preoperative Child-Pugh grade.The data model constructed using the above three factors has shown good performance in predicting the prognosis of patients.

Based on network pharmacology,molecular docking,and experimental validation,this study explored the mechanism by which Hypericum japonicum Thunb-Prunella vulgaris treat liver injury.Mice were randomly divided into four groups:a control group(CON),a model group(CCl4),a high-dose drug group(TXD-H),and a low-dose drug group(TXD-L).A mouse liver in-jury model was established using CCl4 induction.The pathological morphology of liver tissue was observed,and the serum levels of aspartate aminotransferase(AST)and alanine aminotransferase(ALT)were measured.Active ingredients of traditional Chinese medicine and targets related to these medicines and diseases were obtained from databases such as TCMSP,PubChem,Swiss Tar-get Prediction,GeneCards,and DisGeNET.The intersection of these targets was used to identify potential drug targets.A network diagram illustrating the relationships between"drug-active com-ponent-intersection target"was constructed using Cytoscape.Potential targets were analyzed using the STRING database for protein-protein interaction(PPI)analysis and the DAVID database for Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis.Molecular docking validation was performed using AutoDock Tools software.Subsequently,key target genes,including those related to the NLRP3 inflammasome and pyroptosis,were detected to validate the molecular docking results.Animal experimental results showed that compared to the CON group,serum AST and ALT activities in the CCl4 group mice were significantly increased(P＜0.01),while in the TXD-L group,serum AST and ALT activities were significantly decreased(P＜0.05)compared to the CCl4 group,and in the TXD-H group,AST and ALT activities were significantly decreased(P＜0.01).Through network pharmacology,135 potential targets were i-dentified,with key components found to be tetramethoxyluteolin,quercetin,kaempferol,luteolin and morin based on degree values,and key targets including TNF,SRC,AKT1,EGFR and ESR1.GO enrichment analysis yielded 304 entries,while KEGG enrichment analysis identified 91 biologi-cal pathways.Molecular docking results demonstrated strong binding between the main compo-nents of Hypericum japonicurn Thunb-Prunella vulgaris and key targets.qPCR results showed that compared to the CON group,the CCl4 group exhibited upregulated relative expression levels of SRC,EGFR,TNF-α,AKT1,and IL-18 mRNA,with significant increases in MyD88,NF-κB,IL-1β,NLRP3,Caspase-1,and ASC mRNA(P＜0.05),and significant upregulation of TLR4 and GS-DMD mRNA(P＜0.01).Compared to the CCl4 group,the TXD-H group displayed significant downregulation of EGFR,AKT1,TLR4,IL-1β,and GSDMD mRNA(P＜0.01),significant decrea-ses in TNF-α,MyD88,NF-κB,NLRP3,and ASC mRNA(P＜0.05),while SRC,IL-18,and Caspase-1 mRNA showed a downward trend.In conclusion,Hypericum japonicum Thunb-Prunel-la vulgaris exerts hepatoprotective effects through multiple components and pathways,among which inhibition of the NF-κB-NLRP3 pathway to reduce hepatocyte pyroptosis may be one of the important pathways for its protective effects.

Non-small cell lung cancer(NSCLC)is the leading cause of cancer-related mortality worldwide,with approximately 30％of patients initially presenting at stage Ⅱ-Ⅲ and thus potentially eligible for surgical resection.However,surgery alone is insufficient to control postoperative recurrence and distant metastasis effectively.Therefore,neoadjuvant treatment has gradually become a critical approach to improving patient prognosis.Conventional neoadjuvant chemotherapy has historically shown limited pathological complete response(pCR)rates,while neoadjuvant targeted therapy,despite enhancing objective response rates(ORR),still results in relatively low pCR.Recently,neoadjuvant immunotherapy combined with chemotherapy has demonstrated groundbreaking progress.Several large-scale international and domestic clinical trials have reported that this combination strategy significantly increases pCR rates to between 17％and 41％and notably prolongs event-free survival.However,neoadjuvant immunotherapy also introduces new surgical challenges,including increased intraoperative difficulty due to tissue fibrosis,expanded surgical resections resulting from inadequate preoperative prediction,and emerging concerns surrounding the perioperative management of immune-related adverse events(irAEs).Recent advancements in artificial intelligence(AI)-assisted imaging models,multi-omics integration,and dynamic ctDNA monitoring offer novel perspectives and tools for accurately predicting pathological responses preoperatively.Furthermore,intensive studies on mechanisms underlying immunotherapy resistance,such as exosomal PD-L1 regulatory pathways and oxidative stress pathways,alongside emerging strategies involving bispecific antibodies and metabolic interventions,provide theoretical foundations for further optimizing therapeutic approaches.Looking forward,the development of precise preoperative efficacy prediction systems,deep integration of AI technology,and the expansion of multi-modal combination strategies will represent primary directions in the evolution of neoadjuvant immunotherapy for NSCLC.