Objective To understand the driver gene mutation status in patients with non-small cell lung cancer (NSCLC) in Xi'an City, and to analyze the association with environmental exposure factors. Methods A total of 305 NSCLC patients admitted to the First Affiliated Hospital of the Air Force Medical University from January 2019 to December 2023 were included. The driver gene mutation status was observed, and the relationship with environmental exposure factors was analyzed. Results The driver gene mutation rate of 305 patients was 46.89%, with EGFR gene mutation accounting for the highest proportion, and 4 cases of gene co-mutations were detected. There was a difference in gender among patients with different single drive gene mutations (P<0.05), and the proportion of EGFR in women was significantly higher (P<0.05). Univariate analysis showed that there were statistical differences in family history, smoking history, long-term cooking history, and fried smoked food intake between patients with driver gene mutation and patients without driver gene mutation (P<0.05). Logistic regression analysis suggested that long-term cooking history (OR=2.392), and fried smoked food intake (OR=2.849) were the environmental exposure factors affecting EGFR gene mutation (P<0.05), and smoking history (OR=1.377) was an environmental exposure factor of KRAS gene mutation (P<0.05). Conclusion EGFR gene mutation accounts for the highest proportion of NSCLC patients in Xi'an City, and is mainly female. Long-term cooking history, and fried smoked food intake are related to EGFR gene mutation. There is a certain association between smoking history and KRAS gene mutation.

Objective:To systematically evaluate the safety and efficacy of the novel fibroblast activation protein (FAP)-targeted tracer 64Cu-FAP inhibitor (FAPI)-XT117 in patients with malignant solid tumors, and to compare with 18F-FDG. Methods:This self-controlled study was conducted on fifteen patients (8 males, 7 females; age (60 ±9) years) with malignant solid tumors from the First Affiliated Hospital of Guangzhou Medical University between July 2023 and December 2023. Each subject underwent 64Cu-FAPI-XT117 PET/CT at 30, 60, and 120min post-injection and was assigned to three dose cohorts (111MBq, 148MBq, and 185MBq; 5 patients in each cohort), and safety assessments were conducted within 24h after injection. In addition, all patients underwent 18F-FDG PET/CT at 60min post-injection. Time-activity curves were generated for 64Cu-FAPI-XT117, and the dosimetry was calculated. Image quality was evaluated using a 5-point Likert scale, and the optimal injected activity and imaging time point were determined. The paired t test was used to compare differences of the lesion detection count and SUV max between 64Cu-FAPI-XT117 and 18F-FDG PET/CT. Results:64Cu-FAPI-XT117 was well tolerated, with no adverse events reported. Time-activity curves of 68Ga-FAPI-XT117 revealed prominent uptake in the uterus, while the background activity in other organs remained low, with the whole-body effective dose of (0.0084±0.0021)mSv/MBq. The optimal imaging time point for 64Cu-FAPI-XT117 PET/CT was 60min post-injection, with an optimal administered activity of 111MBq. Compared with 18F-FDG, 64Cu-FAPI-XT117 demonstrated significantly higher uptake and more lesions in lymph-node metastases (SUV max: 8.6±3.8 vs 15.3±6.8, t=2.33, P=0.048; number of lesions: 8.3±5.4 vs 15.0±6.4; t=4.21, P=0.003) and distant metastases (SUV max: 11.8±3.7 vs 20.9±7.2, t=3.66, P=0.022; number of lesions: 7.0±3.2 vs 12.4±3.7, t=2.86, P=0.046). Conclusions:64Cu-FAPI-XT117 PET/CT is well tolerated in patients with solid tumors, with a controllable radiation risk. Moreover, it outperforms 18F-FDG PET/CT in the assessment of metastases.

OBJECTIVE: To develop an artificial intelligence-assisted system for the automatic detection of the features of common 21 auricular points based on the YOLOv8 neural network. METHODS: A total of 660 human auricular images from three research centers were collected from June 2019 to February 2024. The rectangle boxes and features of images were annotated using the LabelMe5.3.1 tool and converted them into a format compatible with the YOLO model. Using these data, transfer learning and fine-tuning training were conducted on different scales of pretrained YOLO neural network models. The model's performance was evaluated on validation and test sets, including the mean average precision (mAP) at various thresholds, recall rate (recall), frames per second (FPS) and confusion matrices. Finally, the model was deployed on a local computer, and the real-time detection of human auricular images was conducted using a camera. RESULTS: Five different versions of the YOLOv8 key-point detection model were developed, including YOLOv8n, YOLOv8s, YOLOv8m, YOLOv8l, and YOLOv8x. On the validation set, YOLOv8n showed the best performance in terms of speed (225.736 frames per second) and precision (0.998). On the external test set, YOLOv8n achieved the accuracy of 0.991, the sensitivity of 1.0, and the F1 score of 0.995. The localization performance of auricular point features showed the average accuracy of 0.990, the precision of 0.995, and the recall of 0.997 under 50% intersection ration (mAP⁵⁰). CONCLUSION The key-point detection model of 21 common auricular points based on YOLOv8n exhibits the excellent predictive performance, which is capable of rapidly and automatically locating and classifying auricular points.
Humans ; Neural Networks, Computer ; Artificial Intelligence ; Acupuncture Points

To evaluate the clinical application value of magnetic bead sorting technology (MBS) using the T-cell select kit combined with an automatic cell sorter for isolating peripheral blood mononuclear cells (PBMCs) to realize automated specimen pre-processing and process optimization in T-SPOT.TB assay. A cross-sectional study was conducted involving 300 patients recruited from the first affiliated hospital of Air Force Medical University from March 2023 to July 2024. Among them, there were 167 males and 133 females. The age range of the patients was 18 to 65 years, with a median age of 49.0 (33.3, 59.0) years and a mean age of (46.4±13.9) years. 4 ml of anticoagulated whole blood samples in duplicate were collected from each patient. One fresh sample (0-4 h) was processed immediately using density gradient centrifugation (DGC) for PBMC isolation, while the other was processed using MBS method at either 0-4 h or 34-54 h post-collection. The cycles for cell enrichment step of the automatic cell sorter were adjusted from the conventional 4 cycles to 2 cycles. Statistical analysis was performed using Cohen′s Kappa test to evaluate the concordance of T-SPOT.TB results across all processing groups. The results showed that for fresh samples (0-4 h), the T-SPOT.TB results for samples processed with 4-cycle and 2-cycle MBS enrichment steps demonstrated positive concordance rates of 91.7% and 93.1%, negative concordance rates of 100% for both, overall concordance rates of 98.0% and 97.9%, and Kappa values of 0.94 and 0.95, respectively, compared with the reference results for paired samples processed using DGC. Correspondingly, the results for samples processed with the 4-cycle and 2-cycle MBS methods at 34-54 h post-collection yielded positive concordance rates of 90.0% and 81.3%, negative concordance rates of 95.1% and 100%, overall concordance rates of 93.0% and 82.9%, and Kappa values of 0.86 and 0.43, respectively, compared with the reference results for fresh samples processed using DGC. In conclusion,for 0-4 h samples, the T-SPOT.TB results from both 4-cycle and 2-cycle MBS enrichment protocols were highly consistent with the reference results from conventional DGC methods. However, for 34-54 h stored samples, results from the 4-cycle MBS method rather than the 2-cycle protocol exhibited significantly superior concordance with the reference results. The MBS method using T-Cell Select kit achieves automated sample pre-processing for T-SPOT.TB assay, reduces hands-on time, and provides a viable alternative with reliable results for long-stored specimens.

Objective:To systematically evaluate the safety and efficacy of the novel fibroblast activation protein (FAP)-targeted tracer 64Cu-FAP inhibitor (FAPI)-XT117 in patients with malignant solid tumors, and to compare with 18F-FDG. Methods:This self-controlled study was conducted on fifteen patients (8 males, 7 females; age (60 ±9) years) with malignant solid tumors from the First Affiliated Hospital of Guangzhou Medical University between July 2023 and December 2023. Each subject underwent 64Cu-FAPI-XT117 PET/CT at 30, 60, and 120min post-injection and was assigned to three dose cohorts (111MBq, 148MBq, and 185MBq; 5 patients in each cohort), and safety assessments were conducted within 24h after injection. In addition, all patients underwent 18F-FDG PET/CT at 60min post-injection. Time-activity curves were generated for 64Cu-FAPI-XT117, and the dosimetry was calculated. Image quality was evaluated using a 5-point Likert scale, and the optimal injected activity and imaging time point were determined. The paired t test was used to compare differences of the lesion detection count and SUV max between 64Cu-FAPI-XT117 and 18F-FDG PET/CT. Results:64Cu-FAPI-XT117 was well tolerated, with no adverse events reported. Time-activity curves of 68Ga-FAPI-XT117 revealed prominent uptake in the uterus, while the background activity in other organs remained low, with the whole-body effective dose of (0.0084±0.0021)mSv/MBq. The optimal imaging time point for 64Cu-FAPI-XT117 PET/CT was 60min post-injection, with an optimal administered activity of 111MBq. Compared with 18F-FDG, 64Cu-FAPI-XT117 demonstrated significantly higher uptake and more lesions in lymph-node metastases (SUV max: 8.6±3.8 vs 15.3±6.8, t=2.33, P=0.048; number of lesions: 8.3±5.4 vs 15.0±6.4; t=4.21, P=0.003) and distant metastases (SUV max: 11.8±3.7 vs 20.9±7.2, t=3.66, P=0.022; number of lesions: 7.0±3.2 vs 12.4±3.7, t=2.86, P=0.046). Conclusions:64Cu-FAPI-XT117 PET/CT is well tolerated in patients with solid tumors, with a controllable radiation risk. Moreover, it outperforms 18F-FDG PET/CT in the assessment of metastases.

To evaluate the clinical application value of magnetic bead sorting technology (MBS) using the T-cell select kit combined with an automatic cell sorter for isolating peripheral blood mononuclear cells (PBMCs) to realize automated specimen pre-processing and process optimization in T-SPOT.TB assay. A cross-sectional study was conducted involving 300 patients recruited from the first affiliated hospital of Air Force Medical University from March 2023 to July 2024. Among them, there were 167 males and 133 females. The age range of the patients was 18 to 65 years, with a median age of 49.0 (33.3, 59.0) years and a mean age of (46.4±13.9) years. 4 ml of anticoagulated whole blood samples in duplicate were collected from each patient. One fresh sample (0-4 h) was processed immediately using density gradient centrifugation (DGC) for PBMC isolation, while the other was processed using MBS method at either 0-4 h or 34-54 h post-collection. The cycles for cell enrichment step of the automatic cell sorter were adjusted from the conventional 4 cycles to 2 cycles. Statistical analysis was performed using Cohen′s Kappa test to evaluate the concordance of T-SPOT.TB results across all processing groups. The results showed that for fresh samples (0-4 h), the T-SPOT.TB results for samples processed with 4-cycle and 2-cycle MBS enrichment steps demonstrated positive concordance rates of 91.7% and 93.1%, negative concordance rates of 100% for both, overall concordance rates of 98.0% and 97.9%, and Kappa values of 0.94 and 0.95, respectively, compared with the reference results for paired samples processed using DGC. Correspondingly, the results for samples processed with the 4-cycle and 2-cycle MBS methods at 34-54 h post-collection yielded positive concordance rates of 90.0% and 81.3%, negative concordance rates of 95.1% and 100%, overall concordance rates of 93.0% and 82.9%, and Kappa values of 0.86 and 0.43, respectively, compared with the reference results for fresh samples processed using DGC. In conclusion,for 0-4 h samples, the T-SPOT.TB results from both 4-cycle and 2-cycle MBS enrichment protocols were highly consistent with the reference results from conventional DGC methods. However, for 34-54 h stored samples, results from the 4-cycle MBS method rather than the 2-cycle protocol exhibited significantly superior concordance with the reference results. The MBS method using T-Cell Select kit achieves automated sample pre-processing for T-SPOT.TB assay, reduces hands-on time, and provides a viable alternative with reliable results for long-stored specimens.

Objective Given the extensive application of machine learning(ML)in medical models and its remarkable learning and generalization capabilities,this study employed automated ML(AutoML)combined with patient demographics and clinical conditions to early assess the risk of failure in bowel preparation prior to colonoscopy.Methods A retrospective analysis was conducted on patients who underwent colonoscopy examinations in Hospital 1 and Hospital 2 from January 2022 to January 2023,and their general and clinical information was collected.According to the Boston bowel preparation scale(BBPS),a BBPS of≤5 was defined as a failure in bowel preparation,>5 was deemed satisfactory.From the data of the two hospitals,we randomly divided the dataset into a training set(n=303)and a validation set(n=76)at an 8∶2 ratio.Least absolute shrinkage and selection operator(LASSO)logistic regression(LR)model was used for feature selection,a nomogram scoring system was constructed,and models were established using AutoML based on five algorithms.Model performance was evaluated through receiver operator characteristic curve(ROC curve),calibration curves,LR-based decision curve analysis(DCA),SHAP plots,and force plots.Results Among the 379 patients,105 cases(27.7%)experienced bowel preparation failure(BBPS≤5).21 study variables were narrowed down to 10 through LASSO with 5-fold cross-validation,resulting in the development of a Nomogram chart with demonstrated reliability via calibration curves.Using the H2O platform and five algorithms[gradient boosting machine(GBM),deep learning(DL),generalized linear model(GLM),Stacked Ensemble and distributed random forest(DRF)],67 models were developed.Stacked Ensemble outperformed the others with an area under the curve(AUC)of 0.871,LogLoss of 0.403,and RMSE of 0.354,surpassing traditional LR model and other models.Variable importance contribution plots indicated significant predictive influences from factors such as the interval between laxative ingestion and examination,history of constipation,completion of laxative regimen,age,and presence of a companion during the procedure.Finally,SHAP plots and force plots revealed variable distribution patterns in binary classification predictions and the impact of variables on predictive outcomes.Conclusion The AutoML model based on the Stacked Ensemble algorithm exhibits clear clinical utility in early prediction of bowel preparation failure risk.Moreover,a clinically applicable column chart scoring tool is constructed.

AIM: To analyze the chemical ingredients of Qingxin-zishen prescription decoction (QZPD) and predict its main pharmacodynamic substances and mechanism in the prevention and treatment of menopause syndrome (MPS) with the help of high performance liquid chromatography-quadrupole-time of flight mass spectrometry (HPLC-Q-TOF/MS) combined with network pharmacology. METHODS: The chemical ingredients of QZPD were identified after analyzing the retention time, exact mass, secondary mass spectrometry fragmentation and other information obtained from HPLC-Q-TOF/MS and comparing them with the established chemical ingredients database and the literatures. The targets of ingredients in QZPD were predicted by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and SwissTargetPrediction database. The disease targets of MPS were obtained through Online Mendelian Inheritance in Man (OMIM) and GeneCards Database. Gene ontology (GO) function enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of potential targets were analyzed with the Metascape database. Cytoscape 3.7.2 software was used to construct the network of active components-key targets-pathways. AutoDockTools 4.2.5 software was applied in the molecular docking verification between the key active components and key targets. RESULTS: A total of 83 components were identified in QZPD and 847 drug targets were predicted. After intersection them with 3 050 disease targets, 395 common targets were obtained. After network topology analysis, 74 key targets were obtained, involving mitogen-activated protein kinase (MAPK), phosphatidylinositol-3 kinase/protein kinase B (PI3K/Akt), transforming growth factor-β (TGF-β) and other signaling pathways. Molecular docking analysis results indicated that 23 key active components, such as berberine, epiberberine, coptisine, geissoschizine methyl ether, liensinine, norcoclaurine, palmatine, quercetin, and luteolin, had good binding activity with several of the key targets. CONCLUSION: This study preliminarily identifies the potential effective chemical ingredients of QZPD, predicts its targets in the prevention and treatment of MPS, which provides supporting information for the further study of the pharmacodynamic substances and mechanisms of QZPD.

Anaplastic lymphoma kinase (ALK) fusion gene, as a tumor driver gene, was crucial for the occurrence and development of non-small cell lung cancer (NSCLC). Recently, targeted ALK fusion gene has become the main treatment method for ALK-positive NSCLC. The first and second generation ALK inhibitors (ALKi), such as crizotinib, ceritinib, alectinib and ensartinib have been approved in China. However, there was no guidance for the management of ALKi adverse reactions. Therefore, this "Recommendations from experts in the management of adverse reactions to ALK inhibitors (2021 version)" has been summarized, led by Lung Cancer Professional Committee of Sichuan Cancer Society and Sichuan Medical Quality Control Center for Tumor Diseases, to provide practical and feasible strategies for clinical ALKi management specification of adverse reactions.
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Carcinoma, Non-Small-Cell Lung ; Crizotinib ; Humans ; Lung Neoplasms/genetics* ; Protein Kinase Inhibitors/adverse effects* ; Receptor Protein-Tyrosine Kinases/antagonists & inhibitors*

BACKGROUND: Anaplastic lymphoma kinase (ALK) rearrangement is a common driver gene of non-small cell lung cancer (NSCLC). Ceritinib is a second-generation ALK inhibitor, which can bring survival benefits to ALK-positive metastatic NSCLC. However, few studies focus on the safety and efficacy of ceritinib in China. Therefore, this study intends to investigate the safety and preliminary efficacy of ceritinib 450 mg with meals in Chinese patients with ALK-positive NSCLC through a real world study. METHODS: From October 2018 to December 2019, patients with ALK-positive NSCLC from 8 medical centers in Sichuan province were recruited in this study. All of these participants received ceritinib 450 mg/d with food. The basic characteristics, adverse effects (AEs) and responses were collected and analyzed in order to evaluate the safety and efficacy of ceritinib. RESULTS: A total of 109 patients were included in this study. Data cutoff was January 23, 2020. The median duration of treatment exposure was 5.87 mon (range: 0.4 mon-15.7 mon). Total AEs were reported in 98 (89.9%) of 109 patients and grade 3 or 4 AEs were reported in 22.9% of patients. Most common AEs (mainly grade 1 or 2) were diarrhea (60.6%), elevated alanine aminotransferase (ALT)(38.5%) and aspartate aminotransferase (AST)(37.6%). As of data cutoff, 45 patients discontinued ceritinib. The overall response rate (ORR) was 37.6% (95%CI: 28.5%-47.4%) and disease control rate (DCR) was 86.2% (95%CI: 78.3%-92.1%). CONCLUSIONS The treatment of ceritinib 450 mg with food for Chinese ALK-positive NSCLC patients had a good safety profile and favorable DCR in real-world setting. However, this conclusion needs to be further verified by large sample, prospective trials.