OBJECTIVE To analyze the influencing factors for achieving target plasma drug concentration （trough） （abbreviated as “PDC”） of vancomycin in patients from high-altitude regions and establish a predictive model for PDC using single- center data， providing references for rational clinical drug use. METHODS Inpatients with vancomycin （1 g， q12 h） administered intravenously in our hospital from January 2021 to June 2024 were retrospectively included. Demographic data， liver and kidney function and hematological indexes were collected. Spearman correlation analysis was used to evaluate the correlation between vancomycin PDC and each detection index. Univariate analysis was used to evaluate the differences of each index in patients with different PDC， and the effects of different gender， body mass index， age and underlying diseases （hypertension/diabetes） on vancomycin PDC. Based on the results of correlation analysis and univariate analysis， multiple linear stepwise regression analysis was used to obtain the independent predictors of vancomycin PDC and construct the prediction model. RESULTS A total of 141 patients were included， with an overall attainment rate of 46.81% for the target PDC of vancomycin. Correlation analysis showed that the vancomycin PDC was positively correlated with age， blood urea nitrogen， uric acid （UA）， serum creatinine （CRE） and β2- microglobulin （β2-MG）， and negatively correlated with height， weight， creatinine clearance rate （CCR）， glomerular filtration rate （GFR）， alanine transaminase （ALT）， hemoglobin （HGB）， white blood cell count and neutrophils （P＜0.05）. There were significant differences in age， CRE and other 14 indexes among different PDC groups （P＜0.05 or P＜0.01）. Age and underlying diseases had significant effects on vancomycin PDC （P＜0.05 or P＜0.01）. CCR， direct bilirubin （DBil）， β2-MG， UA， HGB and height （standardized coefficients were －0.371， 0.367， 0.169， 0.232， －0.140， －0.132； P＜0.05） were independent predictors of vancomycin PDC. The F value of the regression equation was 34.858 （P＜0.05）， the R2 was 0.610， and the adjusted R2 was 0.592. CONCLUSIONS The vancomycin PDC of patients in high-altitude regions is affected by multiple factors such as renal function， liver function and hematological indexes. CCR， HGB and height could be used to predict vancomycin PDC negatively， while DBil， β2-MG and UA could be used to predict vancomycin PDC positively. The variables of the established prediction model could explain 59.2% of the variation of vancomycin PDC.

ObjectiveTo explore the clinical and phenomics characteristics of patients with phlegm-stasis binding syndrome and its accompanied patterns in stable angina pectoris （SAP） of coronary heart disease （CHD）. MethodsA multicenter cross-sectional study design was adopted. A total of 300 patients with SAP of CHD were enrolled and classified into 120 cases of phlegm-stasis binding syndrome， 125 cases of qi deficiency-accompanied syndrome， 38 cases of qi stagnation-accompanied syndrome， and 17 cases of toxin accumulation-accompanied syndrome according to traditional Chinese medicine （TCM） patterns. Data of patients with different TCM patterns were collected， including general condition， TCM symptoms， blood lipids， coagulation function， immune indicators， and serum metabolomics. Metabolic pathway enrichment analysis was used to compare differences in phenomics characteristics among groups. Metabolites with variable importance in projection （VIP） ≥1 and fold change （FC） ≥2 were considered as representative differential metabolites. ResultsPatients in each TCM pattern type were most commonly in the 60-75 years age group， with a relatively high proportion of males. Regarding TCM symptoms， patients with phlegm-stasis binding syndrome most commonly presented with wiry-choppy or wiry-slippery pulse， chest pain， and chest tightness； in patients with qi deficiency-accompanied syndrome， fatigue， chest pain， and weak pulse were most common； in patients with qi stagnation-accompanied sydnrome， wiry-choppy or wiry-slippery pulse， chest pain， and symptoms that increase or decrease with emotional changes， belching， or flatulence were most common； in patients with toxin accumulation-accompanied syndrome， bitter taste in the mouth， chest tightness， irritability， restlessness or manic delirium， and dry and hard stools or foul-smelling diarrhea were most common. Comparisons among the different TCM patterns showed statistically significant differences in coagulation parameters （P＜0.05）， whereas no statistically significant difference was found in blood lipid levels and immune indicators （P＞0.05）.Metabolomics analysis suggested that disorders of glycerophosphate metabolism and valine， leucine， and isoleucine metabolism are characteristic features of phlegm-stasis binding syndrome and its accompanied patterns. The representative differential metabolites between phlegm-stasis binding syndrome and qi deficiency-accompanied syndrome were 7,8-dihydrobiopterin （FC = 3.58） and oxypurinol （FC = 124.50）. Those between phlegm-stasis binding syndrome and qi stagnation-accompanied syndrome were cytidine 5′-diphosphocholine （FC = 2.62） and D-mannosamine （FC = 2.99）. Those between phlegm-stasis binding syndrome and toxin accumulation-accompanied syndrome were anserine （FC = 7.83） and canrenone （FC = 8.94）. ConclusionThere are certain differences in the clinical characteristics and phenomics characteristics among patients with SAP due to CHD exhibiting phlegm-stasis binding syndrome and its accompanied patterns. The phenomics characteristics mainly involve biological alterations such as lipid metabolism disorders， amino acid metabolism abnormalities， and multiple immune indicators activation， which may provide a reference for precise differentiation and treatment of SAP of CHD in TCM clinical practice.

ObjectiveTo explore the clinical and phenomics characteristics of patients with phlegm-stasis binding syndrome and its accompanied patterns in stable angina pectoris （SAP） of coronary heart disease （CHD）. MethodsA multicenter cross-sectional study design was adopted. A total of 300 patients with SAP of CHD were enrolled and classified into 120 cases of phlegm-stasis binding syndrome， 125 cases of qi deficiency-accompanied syndrome， 38 cases of qi stagnation-accompanied syndrome， and 17 cases of toxin accumulation-accompanied syndrome according to traditional Chinese medicine （TCM） patterns. Data of patients with different TCM patterns were collected， including general condition， TCM symptoms， blood lipids， coagulation function， immune indicators， and serum metabolomics. Metabolic pathway enrichment analysis was used to compare differences in phenomics characteristics among groups. Metabolites with variable importance in projection （VIP） ≥1 and fold change （FC） ≥2 were considered as representative differential metabolites. ResultsPatients in each TCM pattern type were most commonly in the 60-75 years age group， with a relatively high proportion of males. Regarding TCM symptoms， patients with phlegm-stasis binding syndrome most commonly presented with wiry-choppy or wiry-slippery pulse， chest pain， and chest tightness； in patients with qi deficiency-accompanied syndrome， fatigue， chest pain， and weak pulse were most common； in patients with qi stagnation-accompanied sydnrome， wiry-choppy or wiry-slippery pulse， chest pain， and symptoms that increase or decrease with emotional changes， belching， or flatulence were most common； in patients with toxin accumulation-accompanied syndrome， bitter taste in the mouth， chest tightness， irritability， restlessness or manic delirium， and dry and hard stools or foul-smelling diarrhea were most common. Comparisons among the different TCM patterns showed statistically significant differences in coagulation parameters （P＜0.05）， whereas no statistically significant difference was found in blood lipid levels and immune indicators （P＞0.05）.Metabolomics analysis suggested that disorders of glycerophosphate metabolism and valine， leucine， and isoleucine metabolism are characteristic features of phlegm-stasis binding syndrome and its accompanied patterns. The representative differential metabolites between phlegm-stasis binding syndrome and qi deficiency-accompanied syndrome were 7,8-dihydrobiopterin （FC = 3.58） and oxypurinol （FC = 124.50）. Those between phlegm-stasis binding syndrome and qi stagnation-accompanied syndrome were cytidine 5′-diphosphocholine （FC = 2.62） and D-mannosamine （FC = 2.99）. Those between phlegm-stasis binding syndrome and toxin accumulation-accompanied syndrome were anserine （FC = 7.83） and canrenone （FC = 8.94）. ConclusionThere are certain differences in the clinical characteristics and phenomics characteristics among patients with SAP due to CHD exhibiting phlegm-stasis binding syndrome and its accompanied patterns. The phenomics characteristics mainly involve biological alterations such as lipid metabolism disorders， amino acid metabolism abnormalities， and multiple immune indicators activation， which may provide a reference for precise differentiation and treatment of SAP of CHD in TCM clinical practice.

ObjectiveTo compare the performance of different automatic evaluation methods for detecting pattern hallucinations generated by large language models （LLMs） in traditional Chinese medicine （TCM） syndrome differentiation and to identify a strategy with higher overall discriminative performance against expert manual judgment. MethodsA standardized TCM syndrome-differentiation dataset containing 598 cases was constructed from case reports published in Chinese core journals indexed by Peking University Core Journals or Chinese Science Citation Database. Each of the 598 cases was submitted to five Chinese LLMs， with each model generating one syndrome-pattern output per case， yielding 2990 outputs in total. The 598 outputs generated by Qwen3-Next-80B-A3B-Thinking were independently annotated for syndrome-pattern hallucinations by two licensed TCM physicians with intermediate or higher professional titles. Disagreements were adjudicated by a third licensed TCM physician with a senior associate professional title and more than 10 years of clinical experience. The resulting consensus annotations served as the reference labels for training and validating the automated evaluation method. Based on these reference labels， three categories of automated evaluation methods were developed and compared following a progressive strategy from text-level semantic similarity， to syndrome-element structural consistency， and finally multi-feature fusion. Method A employed sentence-embedding models based on semantic similarity between pattern texts. Method B adopted a rule-based threshold method using weighted Jaccard coefficients of disease-location and disease-nature syndrome elements. Method C utilized a machine-learning classifier integrating syndrome-element matching scores， missing and redundant syndrome-element counts， and multiple semantic-similarity features. Five-fold cross-validation was used to evaluate the discriminative performance of each method against manual judgment. The optimal method was then applied to uniformly assess the pattern hallucination rates of five LLMs. ResultsIn method A， text2vec-large-chinese showed best overall performance， with an area under the receiver operating characteristic curve （AUROC）， area under the precision-recall curve （PR-AUC）， F1-score， sensitivity， and specificity of 0.849， 0.884， 0.794， 0.801， and 0.691， respectively. In method B， the corresponding metrics of the rule-based syndrome-element Jaccard threshold method were 0.848， 0.851， 0.817， 0.845， and 0.684， respectively； those of the LLM-based syndrome-element Jaccard method were 0.872， 0.906， 0.795， 0.764， and 0.780， respectively. In method C， the multilayer perceptron （MLP） classifier showed the best overall performance， with AUROC， PR-AUC， F1-score， sensitivity， and specificity of 0.933， 0.951， 0.871， 0.857， and 0.846， respectively. Under the unified evaluation framework combining DeepSeek-R1 syndrome-element extraction and MLP classifier， the estimated pattern hallucination rates of the five LLMs ranged from 56.0% to 77.4%. ConclusionAmong the three automatic evaluation methods， Method C integrating syndrome-element discrepancy features and text semantic features using an MLP classifier showed the highest overall discriminative performance against manual judgment， and is more suitable for evaluating syndrome hallucinations in LLM-based TCM syndrome differentiation tasks.

Objective To analyze the gene expression characteristics of chronic rhinosinusitis with nasal polyps(CRSwNP)using bioinformatics methods,aim to investigate the potential biomarkers and their diagnostic value of CRSwNP.Methods(1)The CRSwNP Gene expression data set was downloaded from the American Gene Expression Omnibus(GEO)database.The differentially expressed genes(DEGs)between CRSwNP patients and healthy controls were screened through data analysis.Gene Ontology(GO)functional enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis were performed on the identified DEGs.Protein-protein interaction(PPI)networks were constructed utilizing the STRING database,and the key genes were identified by using the cytoHubba plugin.The"Cibersort"package was used to analyze the influence of key genes on common immune cells.(2)Thirty-two patients diagnosed with CRSwNP in the First Affiliated Hospital of Hebei North University from June 2022 to June 2023 were selected as the CRSwNP group,and 21 patients with simple deviation of nasal septum without a history of sinusitis during the same period were selected as control group.The pathological characteristics of specimens in the two groups were examined using hematoxylin-eosin(HE)staining.Immunohistochemistry and Western blotting were used to detect the expression levels of key genes in CRSwNP.The levels of key proteins in plasma were detected using ELISA,and ROC curve was used to analyze its efficacy in diagnosing CRSwNP.Results(1)Analysis of three gene expression database sets(GSE36830,GSE23552,and GSE194282)showed that there were 156 DEGs in CRSwNP.GO functional enrichment and KEGG pathway analysis indicated that the functions of the above DEGs were mostly related to immune functions.Key genes such as cytochrome b-245 β chain(CYBB)and colony-stimulating factor 1 receptor(CSF1R)were identified.(2)The results of HE staining revealed that the epithelial of CRSwNP tissue was metaplastic into stratified squamous epithelium with interstitial edema.Both immunohistochemistry and Western blotting analyses indicated that the expression levels of CYBB and CSF1R in the CRSwNP group were significantly increased compared to control group(P＜0.05).ELISA results demonstrated that CYBB[(21.20±3.00)μg/ml vs.(17.66±1.66)μg/ml,P＜0.05]and CSF1[(477.37±86.63)pg/ml vs.(370.71±66.24)pg/ml,P＜0.05]in CRSwNP group were significantly increased compare to control group.ROC curve analysis showed that plasma concentrations of CYBB and CSF1 had AUCs of 0.888(95%CI 0.802-0.974)and 0.821(95%CI 0.711-0.931)for diagnosing of CRSwNP,respectively;their combined AUC was 0.927(95%CI 0.851-1.000).Conclusions CYBB and CSF1R may be involved in the occurrence and development of CRSwNP.Plasma CYBB and CSF1 have high diagnostic value for CRSwNP.

Objective The study aims to investigate the impact of microRNA-874-3p(miR-874-3p)regulation of plakophilin 3(PKP3)on the malignant biological behavior of lung adenocarcinoma cells and its underlying mechanism.Methods Immunohistochemistry and immunocytochemistry were used to detect the expression of PKP3 in lung adenocarcinoma tissue microarray and lung adenocarcinoma cell line A549 cells respectively,and the relationship between PKP3 and clinicopathological features of lung adenocarcinoma patients was analyzed.Select lung adenocarcinoma cell line A549,the experiment was divided into A549 cell group(blank control group),miR-NC group(transfected with miR-NC)and miR-mimics group(transfected with miR-874-3p mimics),sh-NC group(control group transfected with PKP3 silencing plasmid),sh-PKP3 group(transfected with PKP3 silencing plasmid),miR+pcDNA-PKP3 group(transfected with miR-874-3P mimics+pcDNA-PKP3,rescue group)and miR+pcDNA-NC group(transfected with miR-874-3p mimics+pcDNA-NC).The proliferation,invasion,migration and apoptosis of cells in each group were detected.ENCORI database was used to predict the upstream gene of PKP3,and dual luciferase assay was used to detect the targeting relationship between miR-874-3p and PKP3.MAPK/mTOR pathway-related proteins were detected by Western blotting.Results The expression of PKP3 in lung adenocarcinoma tissue was significantly higher than that in adjacent tissues.The high expression of PKP3 was related to clinical stage,tumor size,and lymph node metastasis(P＜0.05).Compared with the human normal lung epithelial cells(BEAS-2B),the expression of PKP3 in A549 cells increased significantly,and the expression of miR-874-3p decreased(P＜0.05).Overexpression of miR-874-3p decreased the PKP3 expression level(P＜0.05).Compared with the control group,both overexpression of miR-874-3p and silenced PKP3 inhibited the cloning and invasion ability of A549 cells,caused cell cycle arrest,and decreased the expression levels of cyclin dependent kinase 4(CDK4),cyclin D1,cyclin E1 proteins in A549 cells(P＜0.05).The expressions of Bax protein and Caspase-3 protein were up-regulated(P＜0.05),and apoptosis increased.Overexpression of PKP3 could reverse the biological behavior of overexpression of miR-874-3p.Overexpression of miR-874-3p and silencing of PKP3 significantly decreased the expressions of P38 MAPK and mTOR phosphorylated proteins.Conclusion MiR-874-3p can negatively regulate PKP3 expression and inhibit the malignant biological behavior of A549 cells through MAPK/mTOR pathway.

Objective:To establish a prognostic model based on endoplasmic reticulum stress-related genes for evaluating the prognosis of patients with renal cell carcinoma.Methods:This study utilized Non-negative Matrix Factorization to identify molecular subgroups based on endoplasmic reticulum stress-related genes and employed Weighted Correlation Network Analysis to determine co-expressed genes associ-ated with these subgroups.A risk prognostic model was constructed using univariate Cox regression analysis and Lasso regression analysis.Preliminary experimental validations were conducted to elucidate the biological functions of model genes in renal cell carcinoma.Results:Two molecular subgroups with distinct survival prognoses were identified,and an intersection of related genes was used to construct a nov-el endoplasmic reticulum stress-related prognostic model.Patients in the high-risk group exhibited significantly poorer overall survival in both the training and validation cohorts.In vivo experiments demonstrated that PCK1,a model gene,could inhibit the proliferation,migra-tion,and invasion of renal cell carcinoma cells.Conclusions:The risk scoring model developed in this study effectively predicts the survival probability of renal cell carcinoma patients and can serve as an independent prognostic indicator.This model offers a new direction for per-sonalized treatment strategies in renal cell carcinoma patients.

Arthroscopic surgery currently faces challenges such as limited intraoperative visibility and high technical demands, resulting in a particularly steep learning curve. However, traditional teaching methods at present also present problems including significant operational risks, high learning costs, and ethical dilemmas associated. This has created an urgent need among surgeons for a more efficient and economical training approach. Recent advancements in virtual reality technology have created high-fidelity virtual environments which allow surgeon users to undergo immersive surgical training within simulated settings, offering novel perspectives for standardised arthroscopic skills training. This review systematically summarises the current application progress, technical challenges, and potential future directions of virtual reality arthroscopy simulators, focusing on their technical architecture, characteristics, and advantages. We aim to provide a theoretical basis for the technical standardisation and clinical translation of virtual reality technology in the field of arthroscopic surgical training.

AIM To explore the clinical effects of Jinfukang Oral Liquid combined with thymosin α1 on patients with non-small cell lung cancer due to Dual Deficiency of Qi and Yin.METHODS Seventy-five patients were randomly assigned into thymosin α1 group(15 cases)for 4-week administration,Jinfukang Oral Liquid group(30 cases)for 4-week administration,and combination group(30 cases)for 4-week administration.The changes in TCM clinical syndrome effects,immunity indices(CD3+T,Th,CTL,total NK,CD56dim CD16+NK,NKT,Treg,MDSC),lethality/inhibition ratios(CTL/Treg,total NK/Treg,NKT/Treg,CTL/MDSC,total NK/MDSC,NKT/MDSC)and FACT-L scores were detected.RESULTS The Jinfukang Oral Liquid group and combination group demonstrated higher total effective rates than the thymosin α1 group(P＜0.05).After the treatment,the Jinfukang Oral Liquid group and combination group displayed increased NKT(P＜0.05)and decreased MDSC(P＜0.05),which were more obvious than those in the thymosin α1 group(P＜0.05),and higher NKT was observable in the Jinfukang Oral Liquid group(P＜0.05);the Jinfukang Oral Liquid group and combination group displayed increased lethality/inhibition ratios(P＜0.05),among which NKT/Treg,CTL/MDSC,total NK/MDSC,NKT/MDSC were higher than those in the thymosin α1 group(P＜0.05),and higher CTL/MDSC,NKT/MDSC were observable in the Jinfukang Oral Liquid group(P＜0.05);the Jinfukang Oral Liquid group(except for physiological status,society and family status)and combination group(except for society and family status)displayed increased FACT-L scores(P＜0.05).CONCLUSION For the patients with non-small cell lung cancer due to Dual Deficiency of Qi and Yin,Jinfukang Oral Liquid single use or combined with thymosin α1 can enhance peripheral blood immune surveillance,inhibit immune escape,restore the balanced state of tumor immune responses,and improve TCM syndromes and life quality.