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.

Intraoperative cell salvage (IOCS) has been widely applied as an important blood conservation measure in surgical operations. However, there is currently a lack of clinical practice guidelines for the implementation of IOCS in patients with malignant tumors. This report aims to provide clinicians with recommendations on the use of IOCS in patients with malignant tumors based on the review and assessment of the existed evidence. Data were derived from databases such as PubMed, Embase, the Cochrane Library and Wanfang. The guideline development team formulated recommendations based on the quality of evidence, balance of benefits and harms, patient preferences, and health economic assessments. This study constructed seven major clinical questions. The main conclusions of this guideline are as follows: 1) Compared with no perioperative allogeneic blood transfusion (NPABT), perioperative allogeneic blood transfusion (PABT) leads to a more unfavorable prognosis in cancer patients (Recommended); 2) Compared with the transfusion of allogeneic blood or no transfusion, IOCS does not lead to a more unfavorable prognosis in cancer patients (Recommended); 3) The implementation of IOCS in cancer patients is economically feasible (Recommended); 4) Leukocyte depletion filters (LDF) should be used when implementing IOCS in cancer patients (Strongly Recommended); 5) Irradiation treatment of autologous blood to be reinfused can be used when implementing IOCS in cancer patients (Recommended); 6) A careful assessment of the condition of cancer patients (meeting indications and excluding contraindications) should be conducted before implementing IOCS (Strongly Recommended); 7) Informed consent from cancer patients should be obtained when implementing IOCS, with a thorough pre-assessment of the patient's condition and the likelihood of blood loss, adherence to standardized internally audited management procedures, meeting corresponding conditions, and obtaining corresponding qualifications (Recommended). In brief, current evidence indicates that IOCS can be implemented for some malignant tumor patients who need allogeneic blood transfusion after physician full evaluation, and LDF or irradiation should be used during the implementation process.

ObjectiveMagnetoencephalography (MEG), a non-invasive neuroimaging technique, meticulously captures the magnetic fields emanating from brain electrical activity. Compared with MEG based on superconducting quantum interference devices (SQUID), MEG based on optically pump magnetometer (OPM) has the advantages of higher sensitivity, better spatial resolution and lower cost. However, most of the current studies are clinical studies, and there is a lack of animal studies on MEG based on OPM technology. Pain, a multifaceted sensory and emotional phenomenon, induces intricate alterations in brain activity, exhibiting notable sex differences. Despite clinical revelations of pain-related neuronal activity through MEG, specific properties remain elusive, and comprehensive laboratory studies on pain-associated brain activity alterations are lacking. The aim of this study was to investigate the effects of inflammatory pain (induced by Complete Freund’s Adjuvant (CFA)) on brain activity in a rat model using the MEG technique, to analysis changes in brain activity during pain perception, and to explore sex differences in pain-related MEG signaling. MethodsThis study utilized adult male and female Sprague-Dawley rats. Inflammatory pain was induced via intraplantar injection of CFA (100 μl, 50% in saline) in the left hind paw, with control groups receiving saline. Pain behavior was assessed using von Frey filaments at baseline and 1 h post-injection. For MEG recording, anesthetized rats had an OPM positioned on their head within a magnetic shield, undergoing two 15-minute sessions: a 5-minute baseline followed by a 10-minute mechanical stimulation phase. Data analysis included artifact removal and time-frequency analysis of spontaneous brain activity using accumulated spectrograms, generating spectrograms focused on the 4-30 Hz frequency range. ResultsMEG recordings in anesthetized rats during resting states and hind paw mechanical stimulation were compared, before and after saline/CFA injections. Mechanical stimulation elevated alpha activity in both male and female rats pre- and post-saline/CFA injections. Saline/CFA injections augmented average power in both sexes compared to pre-injection states. Remarkably, female rats exhibited higher average spectral power 1 h after CFA injection than after saline injection during resting states. Furthermore, despite comparable pain thresholds measured by classical pain behavioral tests post-CFA treatment, female rats displayed higher average power than males in the resting state after CFA injection. ConclusionThese results imply an enhanced perception of inflammatory pain in female rats compared to their male counterparts. Our study exhibits sex differences in alpha activities following CFA injection, highlighting heightened brain alpha activity in female rats during acute inflammatory pain in the resting state. Our study provides a method for OPM-based MEG recordings to be used to study brain activity in anaesthetized animals. In addition, the findings of this study contribute to a deeper understanding of pain-related neural activity and pain sex differences.

BACKGROUND:Primary osteoporosis has a high incidence,but the pathogenesis is not fully understood.Currently,there is a lack of effective early screening indicators and treatment programs. OBJECTIVE:To further explore the mechanism of primary osteoporosis through comprehensive bioinformatics analysis. METHODS:The primary osteoporosis data were obtained from the gene expression omnibus(GEO)database,and the differentially expressed genes were screened for Gene Ontology(GO)function and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis.In addition,the differentially expressed genes were subjected to protein-protein interaction network to determine the core genes related to primary osteoporosis,and the least absolute shrinkage and selection operator algorithm was used to identify and verify the primary osteoporosis-related biomarkers.Immune cell correlation analysis,gene enrichment analysis and drug target network analysis were performed.Finally,the biomarkers were validated using qPCR assay. RESULTS AND CONCLUSION:A total of 126 differentially expressed genes and 5 biomarkers including prostaglandins,epidermal growth factor receptor,mitogen-activated protein kinase 3,transforming growth factor B1,and retinoblastoma gene 1 were obtained in this study.GO analysis showed that differentially expressed genes were mainly concentrated in the cellular response to oxidative stress and the regulation of autophagy.KEGG analysis showed that autophagy and senescence pathways were mainly involved.Immunoassay of biomarkers showed that prostaglandins,retinoblastoma gene 1,and mitogen-activated protein kinase 3 were closely related to immune cells.Gene enrichment analysis showed that biomarkers were associated with immune-related pathways.Drug target network analysis showed that the five biomarkers were associated with primary osteoporosis drugs.The results of qPCR showed that the expression of prostaglandins,epidermal growth factor receptor,mitogen-activated protein kinase 3,and transforming growth factor B1 in the primary osteoporosis sample was significantly increased compared with the control sample(P<0.001),while the expression of retinoblastoma gene 1 in the primary osteoporosis sample was significantly decreased compared with the control sample(P<0.001).Overall,the study screened and validated five potential biomarkers of primary osteoporosis,providing a reference basis for further in-depth investigation of the pathogenesis,early screening and diagnosis,and targeted treatment of primary osteoporosis.

The study aims to explore the herb-drug interaction between Xuefu Zhuyu Decoction(XFZY) and atorvastatin(AT). Reverse transcription polymerase chain reaction(RT-PCR) was used to analyze the transcription levels of proteins related to drug metabolism and transport in LS174T cells, detect the intracellular drug uptake under various substrate concentrations and incubation time, and optimize the model reaction conditions of transporter multidrug resistance protein 1(MDR1)-specific probe Rhodamine 123 and AT to establish a cell model for investigating the human intestinal drug interaction. The cell counting kit-8(CCK-8) method was adopted to evaluate the cytotoxicity of XFZY on LS174T cells. After a single and continuous 48 h culture with XFZY, AT or Rhodamine 123 was added for co-incubation. The effect and mechanism of XFZY on human intestinal absorption of AT were analyzed by measuring the intracellular drug concentrations and transcription levels of related transporters and metabolic enzymes. The results of in vitro experiments show that a single co-culture with a high concentration of XFZY significantly increases the intracellular concentrations of Rhodamine 123 and AT. A high concentration of XFZY co-culture for 48 h increases the AT uptake level, significantly induces the CYP3A4 and UGT1A1 gene expression levels, and inhibits the OATP2B1 gene expression level. To compare with the evaluation results of the in vitro human cell model, the pharmacokinetic experiment of XFZY combined with AT was carried out in rats. Sprague-Dawley(SD) rats were randomly divided into a blank control group and an XFZY group. After 14 days of continuous intragastric administration, AT was given in combination. The liquid chromatography-mass spectrometry(LC-MS)/MS method was used to detect the concentrations of AT and metabolites 2-hydroxyatorvastatin acid(2-HAT), 4-hydroxyatorvastatin acid(4-HAT), atorvastatin lactone(ATL), 2-hydroxyatorvastatin lactone(2-HATL), and 4-hydroxyatorvastatin lactone(4-HATL) in plasma samples, and the pharmacokinetic parameters were calculated. Pharmacokinetic analysis in rats shows that continuous administration of XFZY does not significantly change the pharmacokinetic characteristics of AT in rats, but the AUC_(0-6 h) values of AT and metabolites 2-HAT, 4-HAT, and 2-HATL increase by 21.37%, 14.94%, 12.42%, and 6.68%, respectively. The metabolic rate of the main metabolites shows a downward trend. The study indicates that administration combined with XFZY can significantly increase the uptake level of AT in human intestinal cells and increase the exposure level of AT and main metabolites in rats to varying degrees. The mechanism may be mainly due to the inhibition of intestinal MDR1 transport activity.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Atorvastatin/administration & dosage* ; Humans ; Rats ; Rats, Sprague-Dawley ; Male ; Intestines/cytology* ; Intestinal Mucosa/metabolism* ; Herb-Drug Interactions ; Cytochrome P-450 CYP3A/metabolism* ; Intestinal Absorption/drug effects*

Transarterial radioembolization (TARE) is a widely utilized therapeutic approach for hepatocellular carcinoma (HCC), however, the clinical implementation is constrained by the stringent preparation conditions of radioembolization agents. Herein, we incorporated the superstable homogeneous iodinated formulation technology (SHIFT), simultaneously utilizing an enhanced solvent form in a carbon dioxide supercritical fluid environment, to encapsulate radionuclides (such as ¹³¹I,¹⁷⁷Lu, or ¹⁸F) with lipiodol for the preparation of radiolipiodol. The resulting radiolipiodol exhibited exceptional stability and ultra-high labeling efficiency (≥99%) and displayed notable intratumoral radionuclide retention and in vivo stability more than 2 weeks following locoregional injection in subcutaneous tumors in mice and orthotopic liver tumors in rats and rabbits. Given these encouraging findings, ¹⁸F was authorized as a radiotracer in radiolipiodol for clinical trials in HCC patients, and showed a favorable tumor accumulation, with a tumor-to-liver uptake ratio of ≥50 and minimal radionuclide leakage, confirming the feasibility of SHIFT for TARE applications. In the context of transforming from preclinical to clinical screening, the preparation of radiolipiodol by SHIFT represents an innovative physical strategy for radionuclide encapsulation. Hence, this work offers a reliable and efficient approach for TARE in HCC, showing considerable promise for clinical application (ChiCTR2400087731).

ObjectiveTo investigate the role of 4-week high-intensity interval training (HIIT) in modulating the metabolic homeostasis of the pyruvate-lactate axis in the hippocampus of rats with chronic unpredictable mild stress (CUMS) to improve their depressive-like behavior. MethodsForty-eight SPF-grade 8-week-old male SD rats were randomly divided into 4 groups: the normal quiet group (C), the CUMS quiet group (M), the normal exercise group (HC), and the CUMS exercise group (HM). The M and HM groups received 8 weeks of CUMS modeling, while the HC and HM groups were exposed to 4 weeks of HIIT starting from the 5th week (3 min (85%-90%) S_max+1 min (50%-55%) S_max, 3-5 cycles, S_max is the maximum movement speed). A lactate analyzer was used to detect the blood lactate concentration in the quiet state of rats in the HC and HM groups at week 4 and in the 0, 2, 4, 8, 12, and 24 h after exercise, as well as in the quiet state of rats in each group at week 8. Behavioral indexes such as sucrose preference rate, number of times of uprightness and number of traversing frames in the absenteeism experiment, and other behavioral indexes were used to assess the depressive-like behavior of the rats at week 4 and week 8. The rats were anesthetized on the next day after the behavioral test in week 8, and hippocampal tissues were taken for assay. LC-MS non-targeted metabolomics, target quantification, ELISA and Western blot were used to detect the changes in metabolite content, lactate and pyruvate concentration, the content of key metabolic enzymes in the pyruvate-lactate axis, and the protein expression levels of monocarboxylate transporters (MCTs). Results4-week HIIT intervention significantly increased the sucrose preference rate, the number of uprights and the number of traversed frames in the absent field experiment in CUMS rats; non-targeted metabolomics assay found that 21 metabolites were significantly changed in group M compared to group C, and 14 and 11 differential metabolites were significantly dialed back in the HC and HM groups, respectively, after the 4-week HIIT intervention; the quantitative results of the targeting showed that, compared to group C, lactate concentration in the hippocampal tissues of M group, compared with group C, lactate concentration in hippocampal tissue was significantly reduced and pyruvate concentration was significantly increased, and 4-week HIIT intervention significantly increased the concentration of lactate and pyruvate in hippocampal tissue of HM group; the trend of changes in blood lactate concentration was consistent with the change in lactate concentration in hippocampal tissue; compared with group C, the LDHB content of group M was significantly increased, the content of PKM2 and PDH, as well as the protein expression level of MCT2 and MCT4 were significantly reduced. The 4-week HIIT intervention upregulated the PKM2 and PDH content as well as the protein expression levels of MCT2 and MCT4 in the HM group. ConclusionThe 4-week HIIT intervention upregulated blood lactate concentration and PKM2 and PDH metabolizing enzymes in hippocampal tissues of CUMS rats, and upregulated the expression of MCT2 and MCT4 transport carrier proteins to promote central lactate uptake and utilization, which regulated metabolic homeostasis of the pyruvate-lactate axis and improved depressive-like behaviors.

ObjectiveThis study aimed to investigate the effects of 4-week high-intensity interval training (HIIT) on synaptic plasticity in the prefrontal cortex (PFC) of rats exposed to chronic unpredictable mild stress (CUMS), and to explore its potential mechanisms. MethodsA total of 48 male Sprague-Dawley rats were randomly divided into 4 groups: control (C), model (M), control plus HIIT (HC), and model plus HIIT (HM). Rats in groups M and HM underwent 8 weeks of CUMS to establish depression-like behaviors, while groups HC and HM received HIIT intervention beginning from the 5th week for 4 consecutive weeks. The HIIT protocol consisted of repeated intervals of 3 min at high speed (85%-90% maximal training speed, S_max) alternated with one minute at low speed (50%-55% S_max), with 3 to 5 sets per session, conducted 5 d per week. Behavioral assessments and tail-vein blood lactate levels were measured at the end of the 4th and 8th weeks. After the intervention, rat PFC tissues were collected for Golgi staining to analyze synaptic morphology. Enzyme-linked immunosorbent assays (ELISA) were employed to detect brain-derived neurotrophic factor (BDNF), monocarboxylate transporter 1 (MCT1), lactate, and glutamate levels in the PFC, as well as serotonin (5-HT) levels in serum. Additionally, Western blot analysis was conducted to quantify the expression of synaptic plasticity-related proteins, including c-Fos, activity-regulated cytoskeleton-associated protein (Arc), and N-methyl-D-aspartate receptor 1 (NMDAR1). ResultsCompared to the control group (C), the CUMS-exposed rats (group M) exhibited significant reductions in sucrose preference rates, number of grid crossings, frequency of upright postures, and entries into and duration spent in open arms of the elevated plus maze, indicating marked depressive-like behaviors. Additionally, the group M showed significantly reduced dendritic spine density in the PFC, along with elevated levels of c-Fos, Arc, NMDAR1 protein expression, and increased concentrations of lactate and glutamate. Conversely, BDNF and MCT1 contents in the PFC and 5-HT levels in serum were significantly decreased. Following HIIT intervention, rats in the group HM displayed considerable improvement in behavioral indicators compared with the group M, accompanied by significant elevations in PFC MCT1 and lactate concentrations. Furthermore, HIIT notably normalized the expression levels of c-Fos, Arc, NMDAR1, as well as glutamate and BDNF contents in the PFC. Synaptic spine density also exhibited significant recovery. ConclusionFour weeks of HIIT intervention may alleviate depressive-like behaviors in CUMS rats by increasing lactate levels and reducing glutamate concentration in the PFC, thereby downregulating the overexpression of NMDAR, attenuating excitotoxicity, and enhancing synaptic plasticity.

Objective To explore the occurrence risk of enteral nutrition intolerance and analyze its influencing factors in 302 elderly critically ill patients. Methods The clinical case data of elderly critically ill patients in department of elderly cadres of the hospital were retrospectively analyzed from January 2019 to January 2024. According to the occurrence of enteral nutrition intolerance or not, they were divided into occurrence group (n=156) and non-occurrence group (n=146). The risk of nutritional intolerance in elderly critically ill patients was evaluated by feeding intolerance risk assessment form, and the influencing factors of enteral nutrition intolerance were analyzed by multivariate logistic regression analysis. Results Among the 302 elderly patients with critical illness, 53.31% (161/302) had high risk of enteral nutrition intolerance, and 51.66% (156/302) had enteral nutrition intolerance. Multivariate logistic analysis revealed that CRP level>10mg/L, APACHE-II score≥20 points, Lac≥3mmol/L and hypoalbuminemia were risk factors in elderly critically ill patients (OR=1.806, 2.977, 8.232, 3.031, P=0.011, 0.001, 0.041, 0.047), and addition of dietary fiber was a protective factor for enteral nutrition intolerance (OR=1.652, P=0.037). Conclusion The risk of enteral nutrition intolerance is high in elderly critically ill patients. Lac level, CRP level, hypoalbuminemia, and APACHE-II score of patients are independent risk factors for enteral nutrition intolerance, and addition of dietary fiber is a protective factor. It is necessary to take targeted interventions for patients according to the above factors to minimize the occurrence of enteral nutrition intolerance.

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.