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.

Germplasm degeneration occurs during the long-term cultivation of root-and rhizome-derived traditional Chinese medicine(RR-TCM), which seriously restricts the high-quality development of their industry. Therefore, it is urgent to solve the problem of germplasm degeneration through variety breeding. In this paper, based on previously published research articles, monographs, and news reports, the research progresses on the number and origins, breeding methods, and selection of new varieties of RR-TCM listed in the Chinese Pharmacopoeia(Edition 2020) were summarized and analyzed. The results show that there are 169 kinds of RR-TCM listed in the Chinese Pharmacopoeia(Edition 2020), originated from 223 origins with three breeding methods(i.e., seed propagation, vegetative reproduction, and tissue culture), and there are 215 species derived from seed propagation, 177 species derived from vegetative reproduction, and 164 species derived from tissue culture. To date, there are 62 origins breeding new varieties through conventional breeding, cross breeding, mutation breeding, ploidy breeding, or modern biotechnology breeding methods, including 57 origins breeding 145 new varieties through conventional breeding, 10 origins breeding 43 new varieties through mutation breeding, and seven origins breeding 12 new varieties through cross breeding method. They are used mainly to improve yield, disease resistance, and active ingredient content, but only a few new varieties have been widely used. This review will provide useful references in variety breeding, quality breeding, and standardized planting of RR-TCM.
Plant Breeding/methods* ; Plant Roots/growth & development* ; Rhizome/growth & development* ; Drugs, Chinese Herbal ; Plants, Medicinal/classification* ; Medicine, Chinese Traditional

Non-functioning pituitary adenomas(NFPAs)are relatively common.Apart from hyperprolactinemia caused by pituitary compression,they typically lack overt hormonal hypersecretion and usually present with clinical symptoms due to mass effects.Previously considered a uniform entity,NFPAs are actually a highly heterogeneous group of tumors,including aggressive subtypes like silent corticotroph adenomas(SCA)and null cell adenomas.The 2022 WHO new classification of pituitary tumors employs transcription factors[e.g.,pituitary-specific transcription factor 1(PIT-1),T-box transcription factor 19(TBX19,also known as TPIT),steroidogenic factor 1(SF-1)]for detailed categorization,allowing precise subclassification of NFPAs into multiple subtypes derived from distinct cell lineages,including silent gonadotroph adenomas,SCA,and plurihormonal PIT-1-positive adenomas.This helps identify highly invasive subtypes with high recurrence risk,guiding clinical diagnosis and treatment,prognostic assessment,and individualized management.The new classification also provides a theoretical basis for targeted therapies of NFPAs(e.g.,somatostatin analogs and temozolomide).This review comprehensively discusses the latest pathological classification of NFPAs and its clinical implications,aiming to enhance understanding of this disease and offer valuable insights for precise diagnosis,treatment,and prognostic assessment.

BACKGROUND: Disease-modifying therapies have been approved for the treatment of relapsing multiple sclerosis (RMS). The present study aims to examine the safety of teriflunomide in Chinese patients with RMS. METHODS: This non-randomized, multi-center, 24-week, prospective study enrolled RMS patients with variant (c.421C>A) or wild type ABCG2 who received once-daily oral teriflunomide 14 mg. The primary endpoint was the relationship between ABCG2 polymorphisms and teriflunomide exposure over 24 weeks. Safety was assessed over the 24-week treatment with teriflunomide. RESULTS: Eighty-two patients were assigned to variant ( n  = 42) and wild type groups ( n  = 40), respectively. Geometric mean and geometric standard deviation (SD) of pre-dose concentration (variant, 54.9 [38.0] μg/mL; wild type, 49.1 [32.0] μg/mL) and area under plasma concentration-time curve over a dosing interval (AUC tau ) (variant, 1731.3 [769.0] μg∙h/mL; wild type, 1564.5 [1053.0] μg∙h/mL) values at steady state were approximately similar between the two groups. Safety profile was similar and well tolerated across variant and wild type groups in terms of rates of treatment emergent adverse events (TEAE), treatment-related TEAE, grade ≥3 TEAE, and serious adverse events (AEs). No new specific safety concerns or deaths were reported in the study. CONCLUSION: ABCG2 polymorphisms did not affect the steady-state exposure of teriflunomide, suggesting a similar efficacy and safety profile between variant and wild type RMS patients. REGISTRATION NCT04410965, https://clinicaltrials.gov .
Humans ; Crotonates/adverse effects* ; Toluidines/adverse effects* ; Nitriles ; Hydroxybutyrates ; Female ; Male ; Adult ; ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics* ; Middle Aged ; Multiple Sclerosis, Relapsing-Remitting/genetics* ; Prospective Studies ; Young Adult ; Neoplasm Proteins/genetics* ; East Asian People

OBJECTIVE: Varied acupoint selections represent a potential cause of the uncertainty surrounding the efficacy of acupuncture for knee osteoarthritis (OA). Skin temperature, a guiding factor for acupoint selection, may help to address this issue. This study explored thermal sensitization of acupoints used for the treatment of knee OA. METHODS: This cross-sectional case-control study enrolled cases aged 45-75 years with symptomatic knee OA and age- and gender-matched non-knee OA controls in a 1:1 ratio. All participants underwent infrared thermographic imaging. The primary outcome was the relative skin temperature of acupoint (STA), and the secondary outcome was the absolute STA of 11 acupoints. The Z test was used to compare the relative and absolute STAs between the groups. Principal component analysis was used to extract the common factors (CFs, acupoint cluster) in the STAs. A general linear model was used to identify factors affecting the STA in the knee OA cases. For the group comparisons of relative STA, P < 0.0045 (adjusted for 11 acupoints through Bonferroni correction) was considered to indicate statistical significance. For other analyses, P < 0.05 was used as the threshold for statistical significance. RESULTS: The analysis included 308 participants, consisting of 151 cases (mean age: [64.58 ± 6.67] years; male: 25.83%; mean body mass index: [25.70 ± 3.16] kg/m²) and 157 controls (mean age: [63.37 ± 5.96] years; male: 26.11%; mean body mass index: [24.47 ± 2.84] kg/m²). The relative STAs of ST34 (P = 0.0001), EX-LE2 (P < 0.0001), EX-LE5 (P = 0.0006), SP10 (P < 0.0001), BL40 (P = 0.0012) and GB39 (P = 0.0037) were higher in the knee OA group. No difference was found in the STAs of ST35, ST36, SP9, GB33 and GB34. Four CFs were identified for relative STA in both groups. The acupoints within each CF were consistent between the groups. The mean values of the relative STAs across each CF were higher in the knee OA group. In the knee OA cases, no factors were observed to affect the relative STA, while age and gender were found to affect the absolute STA. CONCLUSION Among patients with knee OA, thermal sensitization occurs in the acupoints of the lower extremity, exhibiting localized and regional thermal consistencies. The thermally sensitized acupoints that we identified in this study, ST34, SP10, EX-LE2, EX-LE5, GB39 and BL40, may be good choices for the acupuncture treatment of knee OA. Please cite this article as: Tu JF, Wang XZ, Yan SY, Wang YR, Yang JW, Shi GX, Zhang WZ, Jing LN, Yang LS, Liu DH, Wang LQ, Mi BH. Thermal sensitization of acupoints in patients with knee osteoarthritis: A cross-sectional case-control study. J Integr Med. 2025; 23(3): 289-296.
Humans ; Osteoarthritis, Knee/physiopathology* ; Male ; Cross-Sectional Studies ; Middle Aged ; Female ; Acupuncture Points ; Case-Control Studies ; Aged ; Skin Temperature ; Acupuncture Therapy

OBJECTIVE: To investigate the association between long-term glycemic control and cerebral infarction risk in patients with diabetes through a large-scale cohort study. METHODS: This prospective, community-based cohort study included 12,054 patients with diabetes. From 2006 to 2012, 38,272 fasting blood glucose (FBG) measurements were obtained from these participants. FBG trajectory patterns were generated using latent mixture modelling. Cox proportional hazards models were applied to assess the subsequent risk of cerebral infarction associated with different FBG trajectory patterns. RESULTS: At baseline, the mean age of the participants was 55.2 years. Four distinct FBG trajectories were identified based on FBG concentrations and their changes over the 6-year follow-up period. After a median follow-up of 6.9 years, 786 cerebral infarction events were recorded. Different trajectory patterns were associated with significantly varied outcome risks (Log-Rank P < 0.001). Compared with the low-stability group, Hazard Ratio ( HR) adjusted for potential confounders were 1.37 for the moderate-increasing group, 1.23 for the elevated-decreasing group, and 2.08 for the elevated-stable group. CONCLUSION Sustained high FBG levels were found to play a critical role in the development of ischemic stroke among patients with diabetes. Controlling FBG levels may reduce the risk of cerebral infarction.
Humans ; Cerebral Infarction/blood* ; Middle Aged ; Male ; Female ; Blood Glucose/analysis* ; Fasting/blood* ; Aged ; Prospective Studies ; Risk Factors ; Diabetes Mellitus/blood* ; Adult ; Proportional Hazards Models

Listeria brainstem encephalitis with myelitis is extremely rare in clinical practice.Since the clinical manifestations are non-specific,MRI is helpful for diagnosis.Positive cerebrospinal fluid culture is considered the gold standard for diagnosis.This article reports a case of an immunocompetent individual with listeria brainstem encephalitis with myelitis,aiming to enhance the awareness of this condition.
Humans ; Brain Stem/pathology* ; Diagnostic Errors ; Encephalitis/complications* ; Encephalomyelitis, Acute Disseminated/diagnosis* ; Listeriosis/complications* ; Myelitis/complications*

Objectives:To investigate the prognostic value of the CHA2DS2-VASc and R2CHA2DS2-VASc scores in patients with atrial fibrillation(AF)and heart failure(HF).Methods:Patients with AF and HF from hospitals diagnosed by the Heart Failure Center in Guangdong Province between January 2017 and December 2021 were selected.Major adverse cardiovascular events(MACE)were used as the follow-up endpoint.Statistical methods such as the area under the receiver operating characteristic(ROC)curve(AUC),net reclassification index(NRI),and integrated discrimination improvement(IDI)were applied to evaluate the predictive value of the CHA2DS2-VASc and R2CHA2DS2-VASc scores in patients with AF and HF.Results:A total of 1 839 patients were enrolled in this study,comprising 703 patients in the MACE group and 1 136 patients in the non-MACE group.Compared with the non-MACE group,the MACE group exhibited significantly advanced age,higher prevalence of New York Heart Association class Ⅳ and coronary artery disease,lower diastolic blood pressure and estimated glomerular filtration rate levels,and elevated serum N-terminal pro-B-type natriuretic peptide concentrations(all P<0.05).Additionally,significantly lower proportions of patients in the MACE group received angiotensin-converting enzyme inhibitors/angiotensin receptor blockers/angiotensin receptor-neprilysin inhibitors,beta-blockers,mineralocorticoid receptor antagonists,or anticoagulant therapy(all P<0.05).Multivariable logistic regression analysis revealed that each 1-point increment in both CHA2DS2-VASc and R2CHA2DS2-VASc scores was associated with approximately 10%increased risk of MACE.ROC curve analysis demonstrated that the AUC values for predicting MACE in AF patients with HF were 0.555(95%CI:0.528-0.582,P<0.001)for CHA2DS2-VASc and 0.576(95%CI:0.549-0.608,P<0.001)for R2CHA2DS2-VASc,indicating marginally superior discriminatory capacity of the R2CHA2DS2-VASc score.Delong's test confirmed statistically significant differences between the two scoring systems(P=0.001).The R2CHA2DS2-VASc score demonstrated a NRI of 0.259(95%CI:0.166-0.352,P<0.001)and an IDI of 0.007(95%CI:0.005-0.010,P<0.001)compared with the conventional CHA2DS2-VASc score.Although the R2CHA2DS2-VASc score exhibited slightly better predictive accuracy and outcome discrimination capacity than the original scoring system,both scores demonstrated suboptimal clinical predictive performance.Conclusions:Both the R2CHA2DS2-VASc and CHA2DS2-VASc scores show suboptimal performance for predicting the risk of MACE in patients with AF and HF,and the predicting performance of R2CHA2DS2-VASc score is marginally superior to CHA2DS2-VASc score in this patient cohort.

Objective To summarize the changing prevalence of carbapenem resistance in Enterobacterales based on the data of CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021 for improving antimicrobial treatment in clinical practice.Methods Antimicrobial susceptibility testing was performed using a commercial automated susceptibility testing system according to the unified CHINET protocol.The results were interpreted according to the breakpoints of the Clinical & Laboratory Standards Institute(CLSI)M100 31st ed in 2021.Results Over the seven-year period(2015-2021),the overall prevalence of carbapenem-resistant Enterobacterales(CRE)was 9.43％(62 342/661 235).The prevalence of CRE strains in Klebsiella pneumoniae,Citrobacter freundii,and Enterobacter cloacae was 22.38％,9.73％,and 8.47％,respectively.The prevalence of CRE strains in Escherichia coli was 1.99％.A few CRE strains were also identified in Salmonella and Shigella.The CRE strains were mainly isolated from respiratory specimens(44.23±2.80)％,followed by blood(20.88±3.40)％and urine(18.40±3.45)％.Intensive care units(ICUs)were the major source of the CRE strains(27.43±5.20)％.CRE strains were resistant to all the β-lactam antibiotics tested and most non-β-lactam antimicrobial agents.The CRE strains were relatively susceptible to tigecycline and polymyxins with low resistance rates.Conclusions The prevalence of CRE strains was increasing from 2015 to 2021.CRE strains were highly resistant to most of the antibacterial drugs used in clinical practice.Clinicians should prescribe antimicrobial agents rationally.Hospitals should strengthen antibiotic stewardship in key clinical settings such as ICUs,and take effective infection control measures to curb CRE outbreak and epidemic in hospitals.