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.

Objective To analyze the differences in distribution of traditional Chinese medicine (TCM) syndrome elements and salivary microbiota between the individuals with pulmonary nodules and those without, and to explore the potential correlation between the distribution of TCM syndrome elements and salivary microbiota in patients with pulmonary nodules. Methods We retrospectively recruited 173 patients with pulmonary nodules (PN) and 40 healthy controls (HC). The four diagnostic information was collected from all participants, and syndrome differentiation method was used to analyze the distribution of TCM syndrome elements in both groups. Saliva samples were obtained from the subjects for 16S rRNA high-throughput sequencing to obtain differential microbiota and to explore the correlation between TCM syndrome elements and salivary microbiota in the evolution of the pulmonary nodule disease. Results The study found that in the PN group, the primary TCM syndrome elements related to disease location were the lung and liver, and the primary TCM syndrome elements related to disease nature were yin deficiency and phlegm. In the HC group, the primary TCM syndrome elements related to disease location were the lung and spleen, and the primary TCM syndrome elements related to disease nature were dampness and qi deficiency. There were differences between the two groups in the distribution of TCM syndrome elements related to disease location (lung, liver, kidney, exterior, heart) and disease nature (yin deficiency, phlegm, qi stagnation, qi deficiency, dampness, blood deficiency, heat, blood stasis) (P<0.05). The species abundance of the salivary microbiota was higher in the PN group than that in the HC group (P<0.05), and there was significant difference in community composition between the two groups (P<0.05). Correlation analysis using multiple methods, including Mantel test network heatmap analysis and Spearman correlation analysis and so on, the results showed that in the PN group, Prevotella and Porphyromonas were positively correlated with disease location in the lung, and Porphyromonas and Granulicatella were positively correlated with disease nature in yin deficiency (P<0.05). Conclusion The study concludes that there are notable differences in the distribution of TCM syndrome elements and the species abundance and composition of salivary microbiota between the patients with pulmonary nodules and the healthy individuals. The distinct external syndrome manifestations in patients with pulmonary nodules, compared to healthy individuals, may be a cascade event triggered by changes in the salivary microbiota. The dual correlation of Porphyromonas with both disease location and nature suggests that changes in its abundance may serve as an objective indicator for the improvement of symptoms in patients with yin deficiency-type pulmonary nodules.

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.

Objective To analyze the trend of global cellulitis disease burden from 1990 to 2019, and to provide a theoretical basis for the prevention and control of cellulitis disease. Methods The Global Burden of Disease 2021 (GBD2021) data were collected, and data on the incidence, mortality, and disability-adjusted life year (DALY) of cellulitis were analyzed for each country worldwide. The estimated annual percentage change (EAPC) and age-standardized rate (ASR) were used to estimate the trend change of cellulitis from 1990 to 2021. Results The global burden of cellulitis increased significantly in 2021, with 55.96 million cases, 28.9 million deaths and 876.1 million DALYs, respectively. Incidence and mortality rates were generally higher in males than in females. The incidence and DALYs were higher in high SDI regions, with the highest burden observed in South Asia. In contrast, East Asia exhibited the lowest burden and demonstrated a declining trend. There were significant differences between countries, with India having the highest prevalence, the United States having the highest incidence, and Bahrain having the fastest growing rate.In 2021, China had the lowest age-standardised incidence of cellulitis in the world and the fastest declining age-standardised incidence and age-standardised DALYs. Conclusion The global disease burden of cellulitis is increasing from 1990-2021, and cellulitis remains an an important global public health problem. Targeted preventive meausres should be taken in areas with different economical levels. Men, middle-aged and elderly people, and newborns are the key groups in need of attention and health education.

Objective:To observe any effect of exercise preconditioning on the levels of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) in the brain tissue of rats after induced cerebral ischemia and reperfusion, and how it might promote angiogenesis.Methods:Thirty-six male Sprague-Dawley rats were randomly divided into a sham-operation group, a model group and an exercise preconditioning group, each of 12. After adaptive running training for 3 days, the exercise preconditioning group ran daily for 30 minutes at 15m/min for 14 days, while the other two groups did not exercise. Middle cerebral artery occlusion and reperfusion were then induced in the model and exercise preconditioning groups using the modified Zea-Longa suture method. Rats in the sham-operation group were only cut open to expose the right carotid artery. Right after the modeling, and again 24 hours later neurological deficit was evaluated using the Zea-Longa score and modified neurological severity scoring (mNSS). Infarct sizes were measured using 2, 3, 5-triphenyl tetrazolium chloride staining. Any morphological changes were noted using hematoxylin and eosin (HE) staining, and the expression of CD31 protein, hypoxia-inducible factor-1α and vascular endothelial growth factor in the ischemic cerebral cortex were quantified immunohistochemically.Results:Right after the modelling, compared with the sham-operation group, the average Zea-Longa scores of the model and exercise groups had increased significantly, but were not significantly different from each other. Twenty-four hours later the average Zea-Longa score, mNSS score and relative cerebral infarction area of the model group had increased significantly compared with the sham-operation group, while the exercise preconditioning group′s averages had decreased significantly. The HE staining showed that compared with the sham-operation group, pathological changes such as loose tissue, reduced number of nerve cells, nucleolysis, and vacuolization of the cerebral cortex on the ischemic side were found in the model group. Compared with the model group, the pathological changes in the exercise preconditioning group were less serious. The levels of CD31 protein, HIF-1α and VEGF in the ischemic cerebral cortexes of the model group had by then increased significantly. But compared with the model group, those levels had increased more in the exercise preconditioning group.Conclusion:Exercise preconditioning can effectively promote angiogenesis after cerebral ischemia and reduce chronic injury. That may be related to the activation of the HIF-1α and/or VEGF signaling pathways.

ObjectiveTo study the anti-inflammatory effects of Blumea balsamifera （L.） DC oil （BBO） based on nuclear factor kappa-B （NF-κB） nonclassical and arachidonic acid （AA） pathway. MethodsEffects of BBO on the production of slow reacting substance of anaphylaxis （SRS-A） were detected by the ileal smooth muscle method. The contents of prostaglandin E₂ （PGE₂） and leukotriene B₄ （LTB₄） in lipopolysaccharides （LPS） -induced macrophages were detected by ELISA kit. The expression of COX-2， 5-LOX， FLAP and RelB were detected by qRT-PCR. Western blot was performed to detect the effects of BBO on the level of NF-κB nonclassical pathway proteins TNF receptor associated factor 3 （TRAF3）， TNF receptor associated factor 2 （TRAF2）， NF-κB-inducing kinase （NIK）， p100 and RelB. ResultsThe contractile tension of guinea pig ileum was reduced （P<0.001）， and the SRS-A production inhibition rate reached 65.34% at 1mg·mL^-1 BBO concentration. Compared with LPS group， BBO reduced the concentrations of PGE₂ （P<0.05） and LTB₄ （P<0.05）_， and decreased the expressions of COX-2 （P<0.05）， 5-LOX （P<0.05） and FLAP （P<0.05） in AA pathway at concentrations of 40-80 μg·mL^-1. Moreover， 40-80 μg·mL^-1 BBO decreased the concentrations of TRAF3 （P<0.05）， TRAF2 （P<0.05）， and NIK （P<0.05）， and further inhibited the phosphorylation of p100 （P<0.05）， as well as the level of the transcription factor RelB in genes （P<0.05） and proteins （P<0.05） in nonclassical NF-κB pathway， whereas BBO did not cause such changes. ConclusionBBO may potentially exert its anti-inflammatory effects by suppressing the regulatory proteins TRAF3 and TRAF2 and the transcription factor RelB in NF-κB nonclassical pathway. The inhibitory action extending to the induction kinase function of NIK， further hindering the phosphorylation of p100 and its binding with the transcription factor RelB. Consequently， downstream elements in the AA pathway， including the pivotal rate-limiting enzymes COX-2， 5-LOX and FLAP， were altered. This modulation influences the levels of inflammatory mediators such as PGE₂ and LTB₄.

This study investigates whether compounds in Salvia miltiorrhiza Bunge can bind to the Toll like receptor 4/myeloid differentiation protein 2 (TLR4/MD2) protein complex and exhibit anti-inflammatory activity. Virtual screening of reported chemical components of Salvia miltiorrhiza Bunge against TLR4/MD2 was conducted in this study. The selected compound, neoprzewaquinone A (Neo A), was tested for its impact on the binding of lipopolysaccharide (LPS) to receptors on the cell membrane, its affinity for the protein, its influence on the dimerization of TLR4 and MD2 in LPS-induced cells, and its effects on the phosphorylation of nuclear factor-κB (NF-κB) p65 protein and the secretion of inflammatory cytokines in cells. Results indicate that Neo A in Salvia miltiorrhiza Bunge exhibited the highest virtual binding affinity with TLR4/MD2, with a value of -12.8 kcal·mol^-1. Neo A significantly inhibited the binding of LPS to receptors on the cell membrane (P < 0.01). Moreover, Neo A demonstrated affinity for rhTLR4/MD2, rhTLR4, and rhMD2, with K_D values of 267, 534, and 228 nmol·L^-1, respectively. Amino acid residues like TYR131 and PHE121 in TLR4/MD2 might play a role in the alkyl and π-alkyl hydrophobic interactions with Neo A. Neo A also significantly inhibited the dimerization of TLR4 and MD2 in LPS-mediated cells (P < 0.01) and markedly suppressed the phosphorylation of NF-κBp65 protein (P < 0.05). Furthermore, Neo A significantly or markedly inhibited the secretion of nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) in LPS-induced cells (P < 0.05, P < 0.01). In conclusion, Neo A exerts its anti-inflammatory effects by binding TLR4/MD2 then disrupting the binding of LPS to TLR4/MD2. It may serve as a TLR4/MD2 inhibitor with the potential to treat inflammation-related diseases targeting TLR4/MD2.

Objective To observe the clinical efficacy and safety of Sangxing Zhike Prescription in treating postinfectious cough(PIC)of warm dryness invading the lung type.Methods A total of 66 PIC patients with warm dryness invading the lung type who were admitted to the First Affiliated Hospital of Guangzhou University of Chinese Medicine from January 2020 to June 2022 were randomly divided into a treatment group and a control group,with 33 patients in each group.The treatment group was given Sangxing Zhike Prescription combined with Compound Methoxyphenamine Capsules,and the control group was given Compound Methoxyphenamine Capsules combined with Chinese medicine placebo.The course of treatment covered 7 days.The changes in the Visual Analogue Scale(VAS)scores of the severity of cough,the scores of cough symptom,and the scores of traditional Chinese medicine(TCM)syndrome in the two groups were observed before and after the treatment.After treatment,the clinical efficacy and safety in the two groups were evaluated.Results(1)During the trial,one case fell off from the treatment group and 4 cases fell off from the control group,and eventually 61 cases completed the observation,of which 32 cases were in the treatment group and 29 cases were in the control group.(2)After 7 days of treatment,the total effective rate of the treatment group was 84.38%(27/32)and that of the control group was 58.62%(17/29),and the intergroup comparison(tested by chi-square test)showed that the therapeutic efficacy of the treatment group was significantly superior to that of the control group(P＜0.05).(3)After treatment,the VAS scores of the severity of cough,and the scores of daytime cough,nighttime cough of the Cough Symptom Score Scale as well as the overall cough scores in the two groups were significantly lower than those before treatment(P＜0.05 or P＜0.01),and the reduction of the VAS scores and the overall cough symptom scores in the treatment group was significantly superior to that in the control group(P＜0.05).(4)After treatment,obvious improvement was presented in the scores of TCM symptoms of cough,throat itching,dry throat,foreign body sensation in the throat,sore throat and pharyngeal signs as well as total TCM syndrome scores in the treatment group when compared with the pre-treatment period(P＜0.01),whereas in the control group,only the scores of cough,throat itching,dry throat,and sore throat and the total TCM syndrome scores were improved compared with the pre-treatment period(P＜0.05 or P＜0.01).The post-treatment intergroup comparison showed that the treatment group was significantly superior to the control group in improving the scores of throat itching,foreign body sensation in the throat,and pharyngeal signs as well as total TCM syndrome scores(P＜0.05 or P＜0.01).(5)During the treatment process,no significant adverse reactions occurred in both groups,or no abnormal changes were shown in the safety indexes such as blood routine test,liver and kidney functions of the patients.Conclusion Sangxing Zhike Prescription combined with Compound Methoxyphenamine Capsules exerts certain effect in treating patients with PIC of warm dryness invading the lung type,and its efficacy is significantly superior to that of Compound Methoxyphenamine Capsules treatment alone with relatively high safety profile.

Objective:To observe the effects of electroacupuncture(EA)on gut microbiota and serum inflammatory factors interleukin(IL)-1β and tumor necrosis factor(TNF)-α in Crohn disease(CD)model rats. Methods:Thirty-six Sprague-Dawley rats were randomly divided into a normal control(NC)group with 10 rats and a modeling group with 26 rats.In the modeling group,the CD rat model was prepared with 2,4,6-trinitrobenzene sulfonic acid(TNBS)enema.After successful modeling,the rats were randomly divided into a CD model(CD)group,an EA group,and a Western medicine(WM)group.The NC and CD groups received no treatment;the EA group was treated with EA for 20 min each time,with 7 consecutive days'intervention;the WM group received mesalazine enteric-coated tablet solution by gavage once a day for 7 d.The changes in body mass and disease activity index(DAI)were observed.Serum IL-1β and TNF-α were determined by enzyme-linked immunosorbent assay.Hematoxylin-eosin staining was used to observe the pathological changes of colon tissues,and 16S rDNA sequencing was used to analyze the structural changes of gut microbiota. Results:Compared with the NC group,the body mass of rats in the CD group decreased(P<0.01),and the DAI score increased(P<0.01);the colon tissue structure was disordered,and many inflammatory cells were present;also,IL-1β and TNF-α increased significantly(P<0.01).As a result,the diversity of gut microbiota decreased,and the abundance of some conditional pathogenic bacteria(such as Prevotella)increased,while the abundance of beneficial bacteria(such as Lactobacillus,Rochella,and Spirillum)decreased.After the intervention,compared with the CD group,the body mass of rats in the EA group and WM group increased(P<0.01);the DAI score decreased(P<0.01),the colon tissue structure improved,and the IL-1β and TNF-α levels decreased(P<0.01);the diversity of gut microbiota increased(P<0.05),and the abundance of some conditional pathogenic bacteria decreased while the abundance of beneficial bacteria increased in the EA group;whereas the diversity of gut microbiota in the WM group was not statistically different(P>0.05). Conclusion:EA can reduce the damage of colon mucosa,regulate the imbalance of gut microbiota,and inhibit the serum inflammatory factor IL-1β and TNF-α expression in CD rats.

Obiective Alzheimer’s disease (AD) is a degenerative disease of the central nervous system (CNS) caused by a variety of risk factors. There are various pathological changes, but apoptosis of the neurological meridian cells is one of the most important pathological bases. Hyperlipidemia is a high-risk factor for the development of AD, which can lead to increased levels of oxidized low-density lipoprotein (ox-LDL) in brain tissues. PCSK9 is a protease closely related to lipid metabolism, but studies have shown that it may be related to the development of AD. LRP1 is abundantly expressed in neuronal cells, and it is an important transporter for the clearance of Aβ. There is now a large amount of literature confirming that PCSK9 can induce the degradation of LRP1. PI3K/AKT is an important signaling pathway in vivo, which plays an important role in apoptosis, and there is now a large amount of literature confirming that LRP1 activates the PI3K/AKT pathway, which has an anti-apoptotic effect. So can PCSK9 affect the PI3K/AKT pathway through LRP1 and thus regulate neuronal apoptosis? This deserves further investigation.The aim of this study was to explore the role of PCSK9 in mediating ox-LDL pro-apoptotic neuronal cell death and its mechanism, and then further elaborate the mechanism of hyperlipidemia leading to neurodegenerative diseases such as AD. MethodsFirstly, PC12 cells were treated with different concentrations of ox-LDL (0, 25, 50, 75 and 100 mg/L) for 24 h. Oil red O staining was used to detect lipid accumulation in PC12 cells, Hoechst33258 staining and flow cytometry to detect apoptosis in PC12 cells, ELISA to detect the content of Aβ secreted by PC12, Western blot to detect expression of SREBP2, PCSK9 and LRP1. Then PC12 cells were treated with 75 mg/L ox-LDL for different times (0, 6, 12, 24, 48 h), and Western blot were performed to detect the expression of SREBP2, PCSK9 and LRP1. Finally, after transfecting 100 nmol/L PCSK9 siRNA into PC12 cells for 48 h, PC12 cells were treated with 75 mg/L ox-LDL for 24 h, Hoechst33258 staining and flow cytometry to detect apoptosis rate of PC12 cells, and Western blot to detect PCSK9, LRP1, PI3K, AKT, P-PI3K , P-AKT, NF-κB, Bcl-2, Bax, Caspase-9 and Caspase-3 expression, and ELISA detected Aβ content secreted by PC12 cells. Resultsox-LDL increased lipid accumulation and promoted apoptosis and Aβ secretion in PC12 cells, as well as increasing the expression of SREBP2 and PCSK9 and decreasing the expression of LRP1 in PC12 cells. pCsk9 siRNA could be inhibited through the PI3K/AKT pathway and the NF-κB-Bcl-2/Bax-Caspase-9/3 pathway to inhibit ox-LDL-induced apoptosis in PC12 cells while increasing Aβ secretion in PC12 cells. Conclusionox-LDL plays a bidirectional regulatory role in ox-LDL-induced apoptosis of PC12 cells by inducing an increase in PCSK9 expression and a decrease in LRP1 expression in PC12 cells, which in turn affects different signaling pathways downstream.