ObjectiveTo explore the role of cuproptosis and identify cuproptosis-related genes in Wilson disease （WD） through bioinformatics analysis and clinical validation，providing implications and directions for the diagnosis and treatment of WD. Methods（1） Screening of target genes： The differentially expressed genes （DEGs） between WD and healthy control were obtained from GeneCards，and the cuproptosis-related genes were obtained from Gene Expression Omnibus （GEO） and published literature.The cuproptosis-related genes in WD were obtained by intersection.Through gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analyses，the specific biological process，functions or metabolic pathways of cuproptosis-related genes in WD were predicted.Molecular docking and PyMOL visualization were then performed to analyze and verify the potential regulatory mechanism of Gandou Fumu Decoction for cuproptosis.（2）Validation of target genes： The blood samples of 15 WD patients treated in the department of encephalopathy and 15 healthy volunteers undergoing physical examinations in the health management center were randomly collected from the First Affiliated Hospital of Anhui University of Chinese Medicine.The expression levels of target genes were determined by Western blot and real-time PCR. Results（1） A total of 3 607 DEGs in WD were obtained from GSE107323 in GEO，and 68 cuproptosis-related genes were obtained from GeneCards and published literature.Twelve common target genes were obtained by intersection，including three up-related genes（SQSTM1，MIF1，and TAX1BP1） and nine down-regulated genes（CP，SERPINE1，AOC3，GPX4，SLC27A5，VEGF-A，PDHB，PDK1，and ATP7B）.The common target genes were mainly enriched in monocarboxylic acid metabolism，oxidoreductase activity，negative regulation of molecular functions，which mainly involved HIF-1，ferroptosis and other signaling pathways.Molecular docking and PyMOL visualization results showed Gandou Fumu Decoction had good binding ability with the cuproptosis-related genes PDK1，SERPINE1，VEGFA，and AOC3 in WD.（2）A total of 30 blood samples were collected，including 15 WD patients and 15 health volunteers.Western blot results showed that expression levels of target genes were consistent with the results obtained by bioinformatics analysis.RT-qPCR results showed that compared with healthy volunteers，WD patients had down-regulated mRNA levels of SERPINE1，GPX4，SLC27A5，and VEGF-A and up-regulated mRNA levels of SQSTM1 and MIF1（P<0.05）. ConclusionThe expression levels of cuproptosis-related genes in WD patients are consistent with the results predicted by bioinformatics analysis.The characteristic preparation Gandou Fumu Decoction of Xin'an Medicine showed good binding abilities with the cuproptosis-related genes in WD.Cuproptosis may play a key role in the pathophysiological mechanism of WD，which can provide a new target for the diagnosis and treatment of WD.

The 2025 European Lung Cancer Congress (ELCC) convened in Paris, France, centering on the optimization and innovation of immunotherapy for non-small cell lung cancer (NSCLC). Key topics at the congress included the application strategies for perioperative immunotherapy, breakthroughs in combination therapy models for advanced NSCLC, and the emerging roles of biomarkers in predicting diverse treatment outcomes. This paper integrates data from several key pivotal studies to systematically analyze the clinical value of neoadjuvant therapy within the perioperative setting, the potential of targeted combination regimens, and the challenges of managing drug resistance, thus offering new directions for clinical practice.

Yigongsan is derived from Xiaoer Yaozheng Zhijue written by QIAN Yi in the Northern Song dynasty， which is the No. 3 formula in the Catalogue of Ancient Famous Classical Formulas（The Second Batch of Pediatrics） released by the National Administration of Traditional Chinese Medicine（TCM） in September 2022， and it can be developed as a class 3.1 new TCM drug. By referring to ancient medical books and modern literature， this study conducted herbal textual research on Yigongsan from five aspects， including historical evolution， origin and processing， dosage conversion， usage and preparation methods， and functional application， then formed the key information table of this formula， in order to provide reference for the development of reference samples and preparations of Yigongsan. Based on the results of the study， it is recommended that Panax ginseng should be removed the basal part of stem（rhizoma）， Poria cocos should be removed the peel， Citrus reticulata should be cut into shreds and Glycyrrhiza uralensis should be used. According to 4.13 g/Qian（钱）， 1 g/slice for ginger， 3 g for each jujube and 300 mL/Zhan（盏）， the doses of Ginseng Radix， Poria， Atractylodis Macrocephalae Rhizoma， Glycyrrhizae Radix et Rhizoma， Citri Reticulatae Pericarpium， Zingiberis Rhizoma Recens， Jujubae Fructus were 1.652， 1.652， 1.652， 1.652， 1.652， 5， 6 g， and the total amount was 19.26 g. The decocting method was to crush the medicinal materials into fine powder with 50-80 mesh， add 300 mL of water and decoct to 210 mL for each dose， then remove the dregs and take it warmly. This formula was recorded in ancient books as the main treatment for the cold-deficiency of spleen and stomach， and Qi stagnation in children with vomiting and diarrhea and lack of appetite. It has been flexibly applied by later generations of physicians， and is often used to treat anorexia， inflammation of the digestive tract， diarrhea and other diseases in children.

Objective To evaluate the potential clinical value of T2 mapping and mDixon Quant in the diagnosis of early interver-tebral disc degeneration.Methods A total of 79 volunteers who underwent lumbar MRI examination were enrolled.All subjects were examined for 3.0T MR with T2WI,T2 mapping,and mDixon Quant while recording the condition of low back pain.The differ-ences between T2 mapping(map)value and fat fraction(FF)values of the vertebral(V)and nucleus pulposus(NP)within the Pfir-rmann Ⅰ and Pfirrmann Ⅱ intervertebral disc(grade Ⅰ 76,grade Ⅱ 87)were statistically analyzed.Receiver operating characteristic(ROC)curve analyses were performed for meaningful parameters.Results V-FF showed a mild positive correlation with degenera-tive intervertebral disc lesions,and NP-FF and NP-map values showed a mild negative correlation with lesions.There were statistically significant differences between the two groups in V-FF(P＜0.001),NP-FF(P=0.005),and NP-map(P＜0.001).Some measure-ments had statistically significant differences when different intervertebral disc segments were compared.Conclusion V-FF,NP-FF,and NP-map are associated with intervertebral disc degeneration.T2 mapping and mDixon Quant are potentially valuable as diagnostic tools to quantitatively assess early intervertebral disc degeneration and help diagnose.

BACKGROUND:Intervertebral disk degeneration is a pathological change caused by a series of complex molecular mechanisms that result in the aging and damage of intervertebral discs,ultimately leading to severe clinical symptoms.Traditional Chinese medicine has unique advantages in the treatment of intervertebral disk degeneration due to its low cost,non-addictive nature,multi-target effects,minimally toxic and side effects,and high patient acceptance. OBJECTIVE:To review the latest research results of traditional Chinese medicine monomer intervention-related signaling pathways in the treatment of intervertebral disk degeneration,describe and analyze the action mechanism of traditional Chinese medicine monomer on intervertebral disk degeneration,and provide a new approach and theoretical basis for future basic research and clinical treatment. METHODS:The first author searched for relevant literature from January 2018 to February 2023 in CNKI,PubMed,VIP,and WanFang using the search terms"intervertebral disc,signal pathway".The articles that did not meet the criteria were excluded after preliminary screening of the titles and abstracts.Finally,72 articles were selected for review and analysis. RESULTS AND CONCLUSION:Traditional Chinese medicine monomers can regulate multiple classical signaling pathways such as Wnt/β-catenin,PI3K/Akt,mTOR,NF-κB,and MAPK.They achieve this by regulating oxidative stress,adjusting the expression of pro/anti-apoptotic proteins in cells,stimulating cellular autophagy function,reducing stimulation of cell inflammatory factors,increasing the expression of extracellular matrix markers,reducing the production of matrix-degrading enzymes,maintaining the synthesis and stability of extracellular matrix,inducing differentiation of mesenchymal stem cells in the nucleus pulposus into nucleus pulposus cells,promoting endogenous repair and reconstruction,controlling apoptosis and aging of nucleus pulposus cells,and increasing the activity of nucleus pulposus cells.These actions improve the microenvironment within the intervertebral disc,maintain the normal physiological function of the intervertebral disc,and delay intervertebral disc degeneration.

Background and purpose:The standard therapy for locally advanced rectal cancer(LARC)is neoadjuvant chemoradiotherapy(nCRT)followed by surgery.NCRT can make the tumor regress and downstage,and increase the R0 resection rate.However,individual differences in rectal cancer are large,and some patients respond poorly to nCRT and cannot benefit from nCRT.Therefore,it is necessary to establish effective screening measures to identify patients with poor response to nCRT.This study aimed to analyze the influencing factors of nCRT for LARC and construct the tumor regression prediction model.Methods:Data of 158 LARC patients who underwent total mesenteric resection after receiving nCRT at the First Hospital Affiliated to Air Force Medical University from January 2016 to December 2020 were collected.Baseline clinical indicators before nCRT were collected,including laboratory examination,tumor markers and magnetic resonance imaging(MRI).According to the tumor size reported by MRI before and after nCRT,Response Evaluation Criteria in Solid Tumors(RECIST)was used to evaluate the extent of tumor regression after nCRT.After receiver operating characteristic(ROC)curve was used to standardize the clinical baseline indicators,logistic regression analysis was carried out to screen the factors affecting the tumor regression.The tumor regression prediction model was constructed by logistic regression,and the performance of the model was evaluated based on decision curve analysis(DCA)and the calibration curve.The accuracy of the model was tested by 10-fold cross-validation.Results:This retrospective cohort study enrolled 158 patients,in which,98 patients achieved complete response(CR)or partial response(PR).The objective response rate was 62%.Sixty patients had poor response to nCRT,either stable disease(SD)or progressive disease(PD).Multivariate logistic regression analysis showed that tumor diameter before treatment(P＜0.001),time to surgery after nCRT(P = 0.006),D-dimer(P = 0.010),prognostic nutrition index(PNI)(P = 0.035),carcinoembryonic antigen(CEA)(P = 0.004)and extramural vascular invasion(EMVI)(P = 0.026)were significantly related to tumor regression after nCRT.The area under ROC curve(AUC)of tumor regression after nCRT prediction model for LARC was 0.84(95%CI:0.780-0.899),sensitivity was 85.0%,and specificity was 72.4%.In the calibration curve,the predicted results were in good agreement with the actual results,and the prediction accuracy was good.The DCA showed that the tumor regression prediction model could bring clinical net benefit to diagnosis.Conclusion:Tumor diameter before treatment,time to surgery after nCRT,D-dimer,PNI,CEA and EMVI are independent risk factors for the tumor regression after nCRT in LARC patients.The tumor regression prediction model based on the above factors has good predictive efficacy for the tumor regression after nCRT in LARC patients.

OBJECTIVE To predict the in vivo bioequivalence of lenvatinib mesilate capsules and reference preparation by using the parallel artificial membrane permeability analysis. METHODS Based on the biopharmaceutics classification system classification of lenvatinib mesilate and the parallel artificial membrane permeation model, the in vitro dissolution permeation rate test model of lenvatinib mesilate capsules was established, through real-time monitoring of the dissolution and penetration of lenvartinib mesylate capsules and reference preparations in fasting gastric juice, intestinal fluid and postprandial intestinal fluid, the flux and total penetration of drugs through the membrane were calculated. RESULTS In fasting state and fed state, the 90% confidence interval of geometric mean ratio of two key quality parameters (permeation flux and permeation amount) of the preparation A all were in the range of 80.00%−125.00%, the preparation B did not fall into this interval. CONCLUSION This research method can predict the bioequivalence of renvartinib mesylate capsule and reference preparation, and has a certain correlation in vivo and in vitro.

ObjectiveTo establish the fingerprint of seven commercially available Yangyin Qingfei preparations， to quantitatively analyze the index components， to evaluate their quality uniformity with multivariate statistical analysis， and to explore the quality differences among different dosage forms. MethodA total of 33 batches of commercially available 7 kinds of Yangyin Qingfei preparations were analyzed by high performance liquid chromatography（HPLC）， the fingerprints were established and the common peaks were identified. Paeoniflorin， verbascoside， harpagoside， glycyrrhizic acid and paeonol were selected as the indicators of quality attributes to quantitatively analyze 33 batches of preparations. Based on the administration methods of Yangyin Qingfei preparations， the daily intake was calculated and the radar charts were poltted， and cluster analysis and principal component analysis were used to explore the quality differences of 7 kinds of Yangyin Qingfei preparations and the quality uniformity among different batches of the same dosage form. ResultThe similarity of fingerprints of 7 dosage forms was 0.248-0.956， suggesting that there were significant differences among different dosage forms of Yangyin Qingfei preparations， and a total of 15 common peaks were calibrated， of which peak 7， peak 8， peak 11， peak 13 and peak 15 were paeoniflorin， verbascoside， harpagoside， glycyrrhizic acid and paeonol， respectively. The radar plots showed that the average total daily intake of large honeyed pills and water honeyed pills was the highest， and the uniformity of pill components was better. The quality of 33 batches of samples was divided into poor quality and high quality by cluster analysis. Principal component analysis showed that the uniformity and dosage form of different dosage forms were significantly different， the oral liquid had the best quality homogeneity with the minimum dispersion. And the content of paeonol in different dosage forms was significantly different， which was the key component of quality control of Yangyin Qingfei preparations. ConclusionYangyin Qingfei large honeyed pills and water honeyed pills show high content and good uniformity， which are relatively preferred dosage forms. Different preparation processes have a great influence on the content of paeonol， and its quality control should be emphasized during production. This study provides a scientific method for the comparison of product quality of different dosage forms of traditional Chinese medicine prescriptions， which is helpful for the development of preferred dosage forms of different prescriptions， and provides a reference for efficient use of medication in the clinical practice.

Objective:To explore the clinical value of semi-ex vivo intestinal autotrans-plantation (IATx) for patients with mesenteric root regional tumors accompanied by vascular invasion.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 6 patients who underwent semi-ex vivo IATx in the Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital from September 2021 to December 2022 were collected. There were 4 males and 2 females, aged (47±21)years. Observation indicators: (1) surgical conditions; (2) postoperative conditions; (3) follow-up. Measurement data with normal distribution were represented by Mean± SD. Count data were represented by absolute numbers. Results:(1) Surgical conditions. All 6 patients completed semi-ex vivo IATx successfully. The operation time, warm ischemia time, cold ischemia time, volume of intraoperative blood transfusion were (10.2±2.1)hours, (2.3±1.6)minutes, (49.2±15.6)minutes, (707±263)mL. Of the 6 patients, 3 patients were intraoperatively perfused with cold UW solution, while the other 3 were not. (2) Postoperative conditions. Results of postoperative pathological examination of the 6 patients showed 4 cases of pancreatic ductal adenocarcinoma, 1 case of cholangiocarcinoma, and 1 case of mesenteric fibromatosis. All 6 cases had nega-tive surgical margins and the duration of postoperative hospital stay was (19±4)days. None of the patient had gastrointestinal bleeding or anastomotic leakage postoperatively, and the autotransplanted intestine functioned well. There was no perioperative death, and intravenous rehydration was not required after discharge. (3) Follow-up. All 6 patients were followed up for (12±5)months. Only 1 patient with mesenteric fibromatosis had recurrence in the 7th month postoperatively, while the remaining 5 patients showed no sign of recurrence or metastasis. There were 4 of 6 patients with chronic diarrhea. They were improved after oral loperamide, bifidobacterium and pancreatin capsules. All 6 patients survived.Conclusion:Semi-ex vivo IATx for the treatment of patients with mesenteric root regional tumors accompanied by vascular invasion is safe and feasible, which can achieve good short-term efficacy.

The development of famous classical formula compound preparations has been a research hotspot in recent years， carrying great expectations from the government， academia and industry. During the process of its research and development， it reflects many problems related to traditional Chinese medicine （TCM） industry and deserves deep consideration by the academic community. Based on the current status of development of famous classical formulas， this paper summarizes the key problems and made an in-depth analysis. The results show that three key issues should be paid attention. The first is the weakness of basic research in TCM， which affect the healthy development of TCM. The second is the understanding of development of famous classical formula compound preparations is not in-depth， and the formulation of relevant policies needs to be more reasonable. Thirdly， the expectation for the development of famous classical formula compound preparations is too high， which affects the research and development process of the compound preparations. It is hoped that the TCM industry can take this opportunity to face the problems， propose solutions， and form new breakthroughs to promote the development and progress of TCM.