Objective To explore the recognition capabilities of electronic nose combined with machine learning in identifying the breath odor map of benign and malignant pulmonary nodules and Traditional Chinese Medicine (TCM) syndrome elements. Methods The study design was a single-center observational study. General data and four diagnostic information were collected from 108 patients with pulmonary nodules admitted to the Department of Cardiothoracic Surgery of Hospital of Chengdu University of TCM from April 2023 to March 2024. The patients' TCM disease location and nature distribution characteristics were analyzed using the syndrome differentiation method. The Cyranose 320 electronic nose was used to collect the odor profiles of oral exhalation, and five machine learning algorithms including random forest (RF), K-nearest neighbor (KNN), logistic regression (LR), support vector machine (SVM), and eXtreme gradient boosting (XGBoost) were employed to identify the exhaled breath profiles of benign and malignant pulmonary nodules and different TCM syndromes. Results (1) The common disease locations in pulmonary nodules were ranked in descending order as liver, lung, and kidney; the common disease natures were ranked in descending order as Yin deficiency, phlegm, dampness, Qi stagnation, and blood deficiency. (2) The electronic nose combined with the RF algorithm had the best efficacy in identifying the exhaled breath profiles of benign and malignant pulmonary nodules, with an AUC of 0.91, accuracy of 86.36%, specificity of 75.00%, and sensitivity of 92.85%. (3) The electronic nose combined with RF, LR, or XGBoost algorithms could effectively identify the different TCM disease locations and natures of pulmonary nodules, with classification accuracy, specificity, and sensitivity generally exceeding 80.00%.Conclusion Electronic nose combined with machine learning not only has the potential capabilities to differentiate the benign and malignant pulmonary nodules, but also provides new technologies and methods for the objective diagnosis of TCM syndromes in pulmonary nodules.

BACKGROUND:Various proteins,signaling pathways,and inflammatory mediators are involved in the pathophysiological process of osteoarthritis.The development of small molecule drugs targeting these proteins,signaling pathways,and inflammatory mediators can effectively delay the progression of osteoarthritis and ameliorate its clinical manifestations. OBJECTIVE:To review the research progress of small molecule drugs in the treatment of osteoarthritis based on the pathogenesis of osteoarthritis. METHODS:PubMed,CNKI,and WanFang databases were searched with English search terms"osteoarthritis,arthritis,osteoarthrosis,degenerative,arthritides,deformans,small molecule drugs,small molecule inhibitors,small molecule agents"and Chinese search terms"osteoarthritis,small molecule drugs,small molecule inhibitors."A total of 68 articles were included for review according to the inclusion and exclusion criteria. RESULTS AND CONCLUSION:(1)Currently,studies concerning the pathogenesis of osteoarthritis remain unclear.The occurrence and development of osteoarthritis are strongly associated with proteins,cytokines,and signal transduction pathways,so its therapeutic mechanism is relatively complex.Currently,targeting proteins,cytokines,and signal transduction pathways related to osteoarthritis with small molecule drugs has become a major research focus.(2)Small molecule drugs frequently possess visible intracellular or extracellular targets and efficacy,containing enhancing cartilage repair,resisting joint degradation,attenuating inflammation,and relieving pain.Other anti-osteoarthritis small molecule drugs have shown promise in promoting stem cell chondrogenic differentiation and cartilage matrix reconstruction.(3)At present,small molecule drugs targeting the pathophysiological process of osteoarthritis to delay the progression of osteoarthritis are still in the experimental stage,but most of these small molecule drugs have shown the expected results in the experimental process,and there are no relevant studies to illustrate the efficacy of small molecule drugs in the treatment of osteoarthritis.(4)Small molecule drugs for the treatment of osteoarthritis have reached the expected experimental results in the basic experimental stage.Numerous studies have exhibited that small molecule drugs can target the suppression of specific proteins,cytokines,and signal transduction pathways that cause osteoarthritis,so as to treat osteoarthritis.Nevertheless,its safety and effectiveness still need to be identified by further basic and clinical studies.This process needs to be investigated and studied by more scholars.(5)At present,many scholars in and outside China have made contributions to the treatment of osteoarthritis.Compared with traditional treatment methods,small molecule drugs reveal better efficacy and safety in the basic experimental stage,and it is expected to become an emerging method for the treatment of osteoarthritis in the future to rid patients of pain.

Objective To construct a "disease-syndrome combination" mathematical representation model for pulmonary nodules based on oral microbiome data, utilizing a multimodal data algorithm framework centered on dynamic systems theory. Furthermore, to compare predictive models under various algorithmic frameworks and validate the efficacy of the optimal model in predicting the presence of pulmonary nodules. Methods A total of 213 subjects were prospectively enrolled from July 2022 to March 2023 at the Hospital of Chengdu University of Traditional Chinese Medicine, Sichuan Cancer Hospital, and the Chengdu Integrated Traditional Chinese and Western Medicine Hospital. This cohort included 173 patients with pulmonary nodules and 40 healthy subjects. A novel multimodal data algorithm framework centered on dynamic systems theory, termed VAEGANTF (Variational Auto Encoder-Generative Adversarial Network-Transformer), was proposed. Subsequently, based on a multi-dimensional integrated dataset of “clinical features-syndrome elements-microorganisms”, all subjects were divided into training (70%) and testing (30%) sets for model construction and efficacy testing, respectively. Using pulmonary nodules as dependent variables, and combining candidate markers such as clinical features, lesion location, disease nature, and microbial genera, the independent variables were screened based on variable importance ranking after identifying and addressing multicollinearity. Missing values were then imputed, and data were standardized. Eight machine learning algorithms were then employed to construct pulmonary nodule risk prediction models: random forest, least absolute shrinkage and selection operator (LASSO) regression, support vector machine, multilayer perceptron, eXtreme Gradient Boosting (XGBoost), VAE-ViT (Vision Transformer), GAN-ViT, and VAEGANTF. K-fold cross-validation was used for model parameter tuning and optimization. The efficacy of the eight predictive models was evaluated using confusion matrices and receiver operating characteristic (ROC) curves, and the optimal model was selected. Finally, goodness-of-fit testing and decision curve analysis (DCA) were performed to evaluate the optimal model. Results There were no statistically significant differences between the two groups in demographic characteristics such as age and sex. The 213 subjects were randomly divided into training and testing sets (7 : 3), and prediction models were constructed using the eight machine learning algorithms. After excluding potential problems such as multicollinearity, a total of 301 clinical feature information, syndrome elements, and microbial genera markers were included for model construction. The area under the curve (AUC) values of the random forest, LASSO regression, support vector machine, multilayer perceptron, and VAE-ViT models did not reach 0.85, indicating poor efficacy. The AUC values of the XGBoost, GAN-ViT, and VAEGANTF models all reached above 0.85, with the VAEGANTF model exhibiting the highest AUC value (AUC=0.923). Goodness-of-fit testing indicated good calibration ability of the VAEGANTF model, and decision curve analysis showed a high degree of clinical benefit. The nomogram results showed that age, sex, heart, lung, Qixu, blood stasis, dampness, Porphyromonas genus, Granulicatella genus, Neisseria genus, Haemophilus genus, and Actinobacillus genus could be used as predictors. Conclusion The “disease-syndrome combination” risk prediction model for pulmonary nodules based on the VAEGANTF algorithm framework, which incorporates multi-dimensional data features of “clinical features-syndrome elements-microorganisms”, demonstrates better performance compared to other machine learning algorithms and has certain reference value for early non-invasive diagnosis of pulmonary nodules.

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

OBJECTIVES: To identify immunosuppressive neutrophil subsets in patients with prostate cancer (PCa) and construct a risk prediction model for prognosis and immunotherapy response of the patients based on these neutrophil subsets. METHODS: Single-cell and transcriptome data from PCa patients were collected from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). Neutrophil subsets in PCa were identified through unsupervised clustering, and their biological functions and effects on immune regulation were analyzed by functional enrichment, cell interaction, and pseudo-time series analyses. Lasso-Cox regression was utilized to construct a prognostic risk model based on the immunosuppressive neutrophil subsets, and survival analysis and ROC curve analysis were used to compare the prognosis of PCa patients with high and low risks stratified using this model. The relationship of the prognostic risk model with PCa immune infiltration and immune response was evaluated using CIBERSORT and TIDE scores. RESULTS: PCa tissues showed a significantly greater proportion of infiltrating neutrophils than the adjacent normal tissues (P<0.05). PCa-associated neutrophils could be clustered into two independent cell subsets: Neu_1 and Neu_2. Neu_2 cells exhibited highly enriched immunoregulatory functions and were highly differentiated and mature, with upregulated immunosuppressive cytokines such as TGFB1, ITGB2, and LGALS3. Based on the genetic characteristics of Neu_2 cell subsets, the prognostic risk model was constructed. The patients in the high-risk group identified by the model had a shorter biochemical recurrence time (P<0.05) and a higher proportion of Tregs and M2-TAMs cell infiltration (P<0.05) with a higher risk of immune rejection and poorer immune response scores. CONCLUSIONS PCa-associated neutrophils are highly heterogeneous. The prognostic risk model constructed based on the immunosuppressive neutrophil Neu_2 subset can effectively predict both the survival outcomes and immune response of PCa patients.
Humans ; Male ; Prostatic Neoplasms/diagnosis* ; Prognosis ; Neutrophils/immunology* ; Immunotherapy

AIM:The paper is to explore a rapid and simple method for the culture of mouse primary thyroid cells.METHODS:Mouse thyroid cells were isolated by enzyme digestion and cultured with improved medium,and their morphology,characteristics and secretory function were observed within 14 d.RESULTS:In the cultures,the active pri-mary cells were obtained from the thyroid tissue after digestion for 25 min;adherent growth was observed on the 2nd day.And secondary follicles appeared from the 5th to 7th day.Over 95%cells were detected with thyroglobulin.The secretion of total triiodothyronine and total thyroxine maintains over 60%in 7 d.The expression levels of specific genes can still maintain more than 50%in 10 d.CONCLUSION:Mouse thyroid primary cells can be rapidly cultured by this method,and the cells can be used for studying thyroid endocrine secretion within 7 d and studying thyroid genes within 10 d.

Objective:To establish the reference value of the angle between the left ventricular inflow and outflow tract (LIOA) in normal fetuses in the second and third trimesters, and observe the correlation between fetal LIOA and gestational age, cardiac axis, cardiac size, and estimated fetal weigh (EFW).Methods:Fetal LIOA in normal fetuses with gestational age from 16 weeks to 39 + 6 weeks were obtained prospectively by two-dimensional ultrasound in the Second Xiangya Hospital from November 2022 to April 2023. Pearson′s correlation coefficient was used to analyze the correlation between fetal LIOA and gestational age, cardiac axis, cardiovascural size and EFW. Results:The LIOA range of 651 normal fetuses was (44.39±7.67)°, and it was found that LIOA was not related to gestational age. LIOA mildly positively correlated with the cardiac axis ( r=0.22, P<0.05) while not correlated with gestational age, cardiovascural size or EFW (all P>0.05). Conclusions:The range of LIOA in normal fetuses were established. Fetal LIOA is constant in the second and third trimesters and it is mildly positively correlated with the cardiac axis. Evaluating fetal LIOA may also provide information for future research on the fetal aortic hemodynamic development.

Objective:To explore the effect of health education based on outcome-based concept on self-management ability and glycemic control in hospitalized patients with type 2 diabetes melittus (T2DM).Methods:A total of 103 T2DM patients admitted in the Endocrinology Department of 903 Hospital of PLA from March 2022 to September 2022 were recruited and randomly divided into study group ( n=52) and control group ( n=51). Routine health education was given to all patients, while additional outcome-based health education was provided by diabetes specialist nurses for the study group during hospitalization. At 12 weeks after discharge, the self-management ability and glycemic control were compared between the two groups. Results:At 12 weeks after discharge, patients in the study group had significantly better self-management ability (dietary control: (4.06±0.75) vs. (3.70±0.88), t=2.50, regular exercise: (3.88±0.62) vs. (3.52±0.94), t=2.30, medical compliance: (4.47±0.51) vs. (4.12±0.64), t=3.14, self blood glucose monitoring: (3.43±0.87) vs. (2.94±0.95), t=2.71, foot care: (3.56±0.57) vs. (2.77±0.87), t=5.42, and management of hyper or hypoglycemia:(3.65±0.72) vs. (3.24±0.96), t=2.48); glycemic control (fasting blood glucose: (6.31±0.90) vs. (6.88±1.37)mmol/L, t=-2.46, 2-h postprandial blood glucose: (8.39±1.64) vs. (9.27±2.50)mmol/L, t=-2.11, HbA1c: (6.76±0.98)% vs. (7.17±0.93)%, t=-2.22). The control rate of HbA1c in the study group was significantly higher and the incidence of hypoglycemia was significantly lower than those in the control group (78.8%(41/52) vs. 58.8%(30/51), χ 2=4.82 and 11.5%(6/52) vs. 29.4%(15/51), χ 2=5.07, respectively). Conclusions:The outcome-based health education can effectively enhance self-management ability and glycemic control in hospitalized type 2 diabetic patients.

Objective To prepare paclitaxel-natural borneol complex,and to explore the prescription and preparation process of paclitaxel-natural borneol complex drug-loaded submicroemulsion,and its in vitro anti-tumor effect.Methods The Paclitaxel-natural borneol complex was prepared by grinding method and identified by Fourier Transform infrared spectroscopy(FT-IR)and differential scanning calorimetry(DSC).The compound drug-loaded submicroemulsion was prepared using a two-step high-pressure emulsification method.The single-factor investigation and the orthogonal experimental design were applied to optimize the formulation and preparation process.MTT assay,cell cloning assay,and cell scratch assay were used to evaluate the effect of this preparation on HCT-116 cells.Results The infrared spectral absorption peaks of taxol-natural borneol complex at 3 312.76 cm-1 and 3 513.92 cm-1 disappeared,and DSC analysis showed that a new absorption peak of taxol-natural borneol complex appeared at 154.56 ℃,indicating that taxol be coupled with natural borneol to form a new complex.The optimal prescription was 0.44％active pharmaceutical ingredient[paclitaxel-natural borneol(1∶3)],10％medium chain triglyceride,3％emulsifier[egg yolk lecithin-Poloxam 188(1∶2)],2％glycerol,0.3％oleate.The optimal process was emulsification at 80 ℃,60 MPa high pressure homogenization 10 times.The half inhibitory concentration(IC50)was 0.75 μg·mL-1 by MTT asssy in cell.In the cell cloning assay,the scratch healing area of blank control group,paclitaxel raw material and paclitaxel/natural borneol submicroemulsion were(36.44±3.35)％,(13.59±9.28)％,(8.30±4.09)％,respectively.The results were statistically significant(P＜0.05).In the plate cloning experiment,the cell cloning rates of blank control group,paclitaxel bulk drug group and submicroemulsion group were(37.92±0.729)％,(9.16±1.335)％and(3.36±1.065)％,respectively,the differents were statistically significant(P＜0.05).Conclusion This submicroemulsion has reasonable prescription,feasible process and good stability.Cell experiments showed that the submicronemulision effectively inhibits the proliferation and migration of HCT-116 cells,suggesting its potential as a promising antitumor agent.

Objective To summarize the clinical characteristics of children with drug-induced hypersensitivity syndrome(DIHS)complicated with herpesvirus reactivation,and to promote the early and accurate identification,diagnosis,and treatment of DIHS in children.Methods The medication history,clinical manifestations,treatment,and prognosis of 12 children confirmed DIHS complicated with herpesvirus reactivation in Guangzhou Women and Children's Medical Center between January 2018 and March 2023 were retrospectively analyzed.The changes in hematological parameters,inflammatory indexes,and hepatic and renal function within 5 d before the eruption,5 d,and 6-10 d after eruption were compared.Results Of the 12 patients,the male-to-female ratio was 5∶1,with a median age of 27(interquartile range 20.50-34.75)months.Two or more antibiotics were used at least two to six weeks before onset,with a combination of 3 or more antibiotics in 7 children,and a combined or sequential application of 2 antibiotics in 5 children.The antibiotics included cephalosporins(n=12),semisynthetic penicillins(n=5),vancomycin(n=4)and azithromycins(n=7).All 12 patients presented fever,rashes,and multiple organ involvement.The rashes were red maculopapules in the early stage and then gradually developed into massive fusion exceeding 50%of the whole body.Among them,seven children were accompanied by facial edema,and two had purplish-red facial rashes.11 children suffered from exfoliative dermatitis in the later stage.12 children presented obviously enlarged lymph nodes.Liver involvement was the most common(100%,simple increase of transaminase in four children,cholestasis in six children,and hepatic failure in two children),and lung involvement was found in nine children.Laboratory examination showed no significant increase in leukocytes or eosinophils within 5 d before the eruption,but low levels of atypical lymphocytes.After the eruption,leukocytes,eosinophils,and atypical lymphocytes increased progressively.Inflammatory indexes of hypersensitive C-reactive protein(CRP),procalcitonin(PCT)increased dramatically before and after the eruption.All the children received intravenous immunoglobulin(IVIG)and methylprednisolone,two children were given antiviral therapy,and nine children were treated with multiple plasma exchanges.After treatment,nine children were cured,one developed immune reconstitution syndrome,and two died of hepatic failure.Conclusions Antibiotics are common allergenic drugs for DIHS in children.Its clinical manifestations include fever and rashes,accompanied by multiple organ involvement,such as the liver and lung.When leukocytes,eosinophils,and atypical lymphocytes are progressively elevated after the eruption,DIHS should be highly suspected,herpesvirus activation should be monitored,medication history should be traced,and early active immunotherapy and antiviral therapy should be conducted if necessary.