OBJECTIVES: Non-small cell lung cancer (NSCLC) is associated with poor prognosis, with 30% of patients diagnosed at an advanced stage. Mutations in the EGFR and KRAS genes are important prognostic factors for NSCLC, and targeted therapies can significantly improve survival in these patients. Although tissue biopsy remains the gold standard for detecting gene mutations, it has limitations, including invasiveness, sampling errors due to tumor heterogeneity, and poor reproducibility. This study aims to develop machine learning models based on radiomic features to predict EGFR and KRAS gene mutation status in NSCLC patients, thereby providing a reference for precision oncology. METHODS: Imaging and mutation data from eligible NSCLC patients were obtained from the publicly available Lung-PET-CT-Dx dataset in The Cancer Imaging Archive (TCIA). A three-dimensional-convolutional neural network (3D-CNN) was used to extract imaging features from the regions of interest (ROI). The LightGBM algorithm was employed to build classification models for predicting EGFR and KRAS gene mutation status. Model performance was evaluated using 5-fold cross-validation, with receiver operator characteristic (ROC) curves, area under the curve (AUC), accuracy, sensitivity, and specificity used for validation. RESULTS: The models effectively predicted EGFR and KRAS mutations in NSCLC patients, achieving an AUC of 0.95 for EGFR mutations and 0.90 for KRAS. The models also demonstrated high accuracy (EGFR 89.66%; KRAS 87.10%), sensitivity (EGFR 93.33%; KRAS 87.50%), and specificity (EGFR 85.71%; KRAS 86.67%). CONCLUSIONS A radiogenomics-machine learning predictive model can serve as a non-invasive tool for anticipating EGFR and KRAS gene mutation status in NSCLC patients.
Humans ; Carcinoma, Non-Small-Cell Lung/diagnostic imaging* ; Lung Neoplasms/diagnostic imaging* ; Mutation ; Proto-Oncogene Proteins p21(ras)/genetics* ; ErbB Receptors/genetics* ; Machine Learning ; Positron Emission Tomography Computed Tomography ; Female ; Male ; Neural Networks, Computer ; Middle Aged ; Aged

Tongue squamous cell carcinoma (TSCC) is a prevalent malignancy that afflicts the head and neck area and presents a high incidence of metastasis and invasion. Accurate diagnosis and effective treatment are essential for enhancing the quality of life and the survival rates of TSCC patients. The current treatment modalities for TSCC frequently suffer from a lack of specificity and efficacy. Nanoparticles with diagnostic and photothermal therapeutic properties may offer a new approach for the targeted therapy of TSCC. However, inadequate accumulation of photosensitizers at the tumor site diminishes the efficacy of photothermal therapy (PTT). This study modified gold nanodots (AuNDs) with the TSCC-targeting peptide HN-1 to improve the selectivity and therapeutic effects of PTT. The Au-HN-1 nanosystem effectively targeted the TSCC cells and was rapidly delivered to the tumor tissues compared to the AuNDs. The enhanced accumulation of photosensitizing agents at tumor sites achieved significant PTT effects in a mouse model of TSCC. Moreover, owing to its stable long-term fluorescence and high X-ray attenuation coefficient, the Au-HN-1 nanosystem can be used for fluorescence and computed tomography imaging of TSCC, rendering it useful for early tumor detection and accurate delineation of surgical margins. In conclusion, Au-HN-1 represents a promising nanomedicine for imaging-based diagnosis and targeted PTT of TSCC.
Tongue Neoplasms/diagnostic imaging* ; Carcinoma, Squamous Cell/diagnostic imaging* ; Animals ; Gold/chemistry* ; Mice ; Photothermal Therapy/methods* ; Tomography, X-Ray Computed ; Photosensitizing Agents ; Metal Nanoparticles ; Humans ; Cell Line, Tumor

Periodontal bone defects, primarily caused by periodontitis, are highly prevalent in clinical settings and manifest as bone fenestration, dehiscence, or attachment loss, presenting a significant challenge to oral health. In regenerative medicine, harnessing developmental principles for tissue repair offers promising therapeutic potential. Of particular interest is the condensation of progenitor cells, an essential event in organogenesis that has inspired clinically effective cell aggregation approaches in dental regeneration. However, the precise cellular coordination mechanisms during condensation and regeneration remain elusive. Here, taking the tooth as a model organ, we employed single-cell RNA sequencing to dissect the cellular composition and heterogeneity of human dental follicle and dental papilla, revealing a distinct Platelet-derived growth factor receptor alpha (PDGFRA) mesenchymal stem/stromal cell (MSC) population with remarkable odontogenic potential. Interestingly, a reciprocal paracrine interaction between PDGFRA⁺ dental follicle stem cells (DFSCs) and CD31⁺ Endomucin⁺ endothelial cells (ECs) was mediated by Vascular endothelial growth factor A (VEGFA) and Platelet-derived growth factor subunit BB (PDGFBB). This crosstalk not only maintains the functionality of PDGFRA⁺ DFSCs but also drives specialized angiogenesis. In vivo periodontal bone regeneration experiments further reveal that communication between PDGFRA⁺ DFSC aggregates and recipient ECs is essential for effective angiogenic-osteogenic coupling and rapid tissue repair. Collectively, our results unravel the importance of MSC-EC crosstalk mediated by the VEGFA and PDGFBB-PDGFRA reciprocal signaling in orchestrating angiogenesis and osteogenesis. These findings not only establish a framework for deciphering and promoting periodontal bone regeneration in potential clinical applications but also offer insights for future therapeutic strategies in dental or broader regenerative medicine.
Receptor, Platelet-Derived Growth Factor alpha/metabolism* ; Humans ; Neovascularization, Physiologic/physiology* ; Dental Sac/cytology* ; Single-Cell Analysis ; Transcriptome ; Mesenchymal Stem Cells/metabolism* ; Bone Regeneration ; Animals ; Dental Papilla/cytology* ; Periodontium/physiology* ; Stem Cells/metabolism* ; Regeneration ; Angiogenesis

A 70-year-old female patient presented with fatigue and edema for 3 months and was found to have elevated serum creatinine for 3 weeks. During the course of the disease, she had fever and cough. Examinations revealed multiple ground-glass opacities in both lungs and positivity for myeloperoxidase-anti-neutrophil cytoplasmic antibodies (ANCA), leading to a diagnosis of ANCA-associated vasculitis. The patient′s condition initially improved after pulse glucocorticoid therapy combined with cyclophosphamide. During treatment, however, the patient developed hematochezia, and colonoscopy revealed multiple colonic ulcers. Immunohistochemistry of colonic mucosal biopsy confirmed cytomegalovirus (CMV) positivity, establishing a diagnosis of CMV colitis. The patient was found to have concurrent Clostridioidesdifficile and pulmonary infections. During the disease course, the patient also developed deep vein thrombosis and roxadustat-associated central hypothyroidism. Given the presence of multiple comorbidities, rituximab was subsequently used for vasculitis treatment, resulting in sustained remission. This case highlights the importance of highly individualized treatment strategies for older patients with vasculitis, requiring adjustment of immunosuppressive therapy intensity based on disease progression.

Objective: To investigate the effect of different volumes of isotonic washing solution (0.9% NaCl) on the quality of intraoperative autologous blood salvage in craniocerebral surgery. Methods: Thirty patients who underwent neurosurgical procedures with intraoperative salvaged blood volumes exceeding 800 mL between August 2022 and July 2024 were enrolled as study subjects. The salvaged blood was divided into four groups: group A, group B, group C, and group D. Group A was washed with 500 mL of isotonic solution (blood-to-washing solution ratio of 1∶2), group B with 1000 mL (ratio of 1∶4), and group C with 1 500 mL (ratio of 1∶6). After centrifugation, the washed blood was stored in designated blood bags (A, B, and C, respectively). Blood gas analysis was performed on 5 mL samples obtained from the centrifuged blood in groups A, B, and C, and from the unwashed blood in the reservoir of the control group (group D). Parameters including red blood cell (RBC) count, pH, hemoglobin (Hb), hematocrit (HCT), potassium ion (K ), sodium ion (Na ), and lactate levels were also measured using these samples. Additionally, blood samples from each group were examined microscopically to assess red blood cell morphology. Results: No significant differences were observed among groups A, B, and C in terms of RBC recovery rate, HCT, Na concentration, or lactate clearance rate (P>0.05). All three groups exhibited a reduction in pH, with group C showing a more pronounced decrease compared to groups A and B. Similarly, K clearance was achieved in all groups, with group C demonstrating superior efficiency. Microscopic analysis revealed a reduction in spiculated red blood cells across all groups, with group C achieving the highest clearance rate. Conclusion: Group C (washed with 1 500 mL solution) demonstrated optimal performance in reducing pH levels, clearing K , and removing spherocytes, while maintaining red blood cell recovery rate. Additionally, it did not significantly increase the risk of hypernatremia in critically ill neurosurgical patients, making it more suitable for craniocerebral surgeries.

Objective:To analyze the real-world practices of resecting sessile colorectal polyps of varying long diameters using cold forcep polypectomy (CFP), cold snare polypectomy (CSP), or endoscopic mucosal resection (EMR).Methods:A total of 12 290 nonpedunculated colorectal polyps of long diameter ≤19 mm (from 10 295 patients) were retrospectively enrolled from January 2022 to December 2023. Polypectomy was conducted by 30 endoscopists. The polyps were categorized into three groups based on long diameter: 1-5 mm, >5-10 mm and >10-19 mm, and the differences of polypectomy methods were compared in three groups. The usage of hemostatic clips in CSP among >5-10 mm polyps and the changes in resection methods between 2022 and 2023 were analyzed.Results:CFP (6 769 polyps, 81.7%) was the predominant method for resecting 1-5 mm sessile polyps (8 289 polyps). For sessile polyps sized >5-10 mm (2 455 polyps), CSP was used most (1 372, 55.9%), although its utilization varied significantly among physicians with the median usage rate of 52.9% (40.3%, 60.0%). EMR (1 349 poolyps, 87.3%) was the main method for >10-19 mm sessile polyps. The usage rate of CSP in sessile polypectomy for polyps >5-10 mm significantly increased from 45.7% (503/1 101) in 2022 to 64.2% (869/1 354) in 2023. The overall frequency of using clip in CSP for >5-10 mm sessile polyps was 40.1% (550/1 372), demonstrating notable variability among different endoscopists with median usage rate of 48.3% (29.8%, 67.9%).Conclusion:Varied resection methods are observed among endoscopists for sessile polyps measuring ≤19 mm. CFP is primarily utilized for polyps of 1-5 mm, while CSP is favored for polyps >5-10 mm, with an increasing annual usage rate. EMR is the main approach for the polyps >10-19 mm. Additionally, notable variations in the use of metal clips during CSP are observed among different physicians.

Bladder paraganglioma is a rare neuroendocrine tumor, accounting for only 0.05% of all bladder tumors. This article reports the diagnosis and treatment of a 16-year-old male patient with acute hemorrhage secondary to a giant bladder paraganglioma(approximately 10 cm in maximum diameter). Preoperative imaging evaluation suggested locally advanced disease, and the patient subsequently received three cycles of neoadjuvant chemotherapy with temozolomide. He patient's blood tests revealed hemorrhagic shock. During the waiting period of surgery, hemostasis was successfully achieved through emergency transarterial embolization. Subsequently, the patient underwent emergency radical cystectomy combined with orthotopic ileal neobladder reconstruction under general anesthesia and recovered well after surgery. Postoperative pathological examination confirmed the diagnosis of bladder paraganglioma, with positive immunohistochemical staining for succinate dehydrogenase subunit B and a Ki-67 proliferation index of 3%. At the 6-week follow-up, the patient's blood pressure and endocrine parameters had returned to normal, with a satisfactory quality of life. This case demonstrates that a multidisciplinary team approach can effectively integrate expertise from various specialties to formulate comprehensive and systematic treatment plans, which is crucial for ensuring successful management of such complex cases.

Objective:To analyze the real-world practices of resecting sessile colorectal polyps of varying long diameters using cold forcep polypectomy (CFP), cold snare polypectomy (CSP), or endoscopic mucosal resection (EMR).Methods:A total of 12 290 nonpedunculated colorectal polyps of long diameter ≤19 mm (from 10 295 patients) were retrospectively enrolled from January 2022 to December 2023. Polypectomy was conducted by 30 endoscopists. The polyps were categorized into three groups based on long diameter: 1-5 mm, >5-10 mm and >10-19 mm, and the differences of polypectomy methods were compared in three groups. The usage of hemostatic clips in CSP among >5-10 mm polyps and the changes in resection methods between 2022 and 2023 were analyzed.Results:CFP (6 769 polyps, 81.7%) was the predominant method for resecting 1-5 mm sessile polyps (8 289 polyps). For sessile polyps sized >5-10 mm (2 455 polyps), CSP was used most (1 372, 55.9%), although its utilization varied significantly among physicians with the median usage rate of 52.9% (40.3%, 60.0%). EMR (1 349 poolyps, 87.3%) was the main method for >10-19 mm sessile polyps. The usage rate of CSP in sessile polypectomy for polyps >5-10 mm significantly increased from 45.7% (503/1 101) in 2022 to 64.2% (869/1 354) in 2023. The overall frequency of using clip in CSP for >5-10 mm sessile polyps was 40.1% (550/1 372), demonstrating notable variability among different endoscopists with median usage rate of 48.3% (29.8%, 67.9%).Conclusion:Varied resection methods are observed among endoscopists for sessile polyps measuring ≤19 mm. CFP is primarily utilized for polyps of 1-5 mm, while CSP is favored for polyps >5-10 mm, with an increasing annual usage rate. EMR is the main approach for the polyps >10-19 mm. Additionally, notable variations in the use of metal clips during CSP are observed among different physicians.

A 70-year-old female patient presented with fatigue and edema for 3 months and was found to have elevated serum creatinine for 3 weeks. During the course of the disease, she had fever and cough. Examinations revealed multiple ground-glass opacities in both lungs and positivity for myeloperoxidase-anti-neutrophil cytoplasmic antibodies (ANCA), leading to a diagnosis of ANCA-associated vasculitis. The patient′s condition initially improved after pulse glucocorticoid therapy combined with cyclophosphamide. During treatment, however, the patient developed hematochezia, and colonoscopy revealed multiple colonic ulcers. Immunohistochemistry of colonic mucosal biopsy confirmed cytomegalovirus (CMV) positivity, establishing a diagnosis of CMV colitis. The patient was found to have concurrent Clostridioidesdifficile and pulmonary infections. During the disease course, the patient also developed deep vein thrombosis and roxadustat-associated central hypothyroidism. Given the presence of multiple comorbidities, rituximab was subsequently used for vasculitis treatment, resulting in sustained remission. This case highlights the importance of highly individualized treatment strategies for older patients with vasculitis, requiring adjustment of immunosuppressive therapy intensity based on disease progression.

Vaccination is the most effective measure for reducing and preventing influenza and related complications. In this study, we analyzed the mutation trend and the antigen dominant site changes of the amino acid sequence of hemagglutinin subunit 1 (HA1) of human influenza A virus (IAV) in the northern hemisphere from 2012 to 2022. According to the HA1 sequences of A/Darwin/6/2021 (H3N2) and A/Wisconsin/588/2019 (H1N1) recommended by the World Health Organization in the 2022 influenza season in northern hemisphere, we employed the mosaic algorithm to design three Mosaic-HA1 antigens through stepwise substitution. Mosaic-HA1 was expressed and purified in 293F cells and then mixed with the alum adjuvant at a volume ratio of 1:1. The mixture was used to immunize BALB/c mice, and the immunogenicity was evaluated. Enzyme-linked immunosorbent assay showed that Mosaic-HA1 induced the production of IgG targeting two types of HA1, the specific IgG titers for binding to H3 protein and H1 protein reached 10⁵ and 10³ respectively. The challenge test showed that Mosaic-HA1 protected mice from H3N2 or H1N1. This study designs the vaccines by recombination of major antigenic sites in different subtypes of IAV, giving new insights into the development of multivalent subunit vaccines against influenza.
Animals ; Influenza A Virus, H1N1 Subtype/genetics* ; Influenza A Virus, H3N2 Subtype/genetics* ; Mice, Inbred BALB C ; Mice ; Influenza Vaccines/genetics* ; Hemagglutinin Glycoproteins, Influenza Virus/genetics* ; Humans ; Antibodies, Viral/blood* ; Antigens, Viral/genetics* ; Immunoglobulin G/immunology* ; Female ; Orthomyxoviridae Infections/prevention & control* ; HEK293 Cells