Purpose: Our previous study showed that circulating tumor cell (CTC) count combined with gene mutation detection might help differentiate benign and malignant pulmonary nodules (PNs). Herein, we aimed to expand the study cohort and conduct further sequencing analysis. Materials and Methods: Patients with PNs were included, and CTCs were identified before operation. Low-coverage whole-genome sequencing (LC-WGS) and lung cancer-related targeted gene sequencing were performed on CTCs. The diagnostic efficacy was evaluated by receiver operating characteristic (ROC) curve. The differences in CTC counts among subgroups classified by demographic–clinical characteristics were analyzed. LC-WGS–based copy number variation (CNV) analysis and targeted gene mutation analysis were conducted. Results: A total of 172 patients were included. CTC count of 2.5 was identified by the ROC curves as the optimal diagnostic cutoff. The sensitivity and specificity of CTC count for differentiating benign and malignant PNs were 54.2% and 78.6%, respectively. The diagnostic sensitivity and specificity of combined CTC count, radiological nodule type, and any malignant imaging features were 84.7% and 71.4%, respectively. The CTC counts were significantly greater in patients with aggressive tumors, later stage, and spread through air spaces. CTCs from malignant cases had more CNVs than those from benign cases. Conclusion CTC count can be used in identifying malignant PNs. The diagnostic efficacy can be improved if combined with computed tomography imaging characteristics. Further CNV analysis might help differential diagnosis. Greater CTC count might suggest more aggressive tumors. CTC detection can provide important information and guidance for subsequent management of PNs.

Objective:To establish a detailed teaching syllabus for the standardized training of radiation oncology residents, apply it in clinical teaching practice, and evaluate its practical teaching value.Methods:Based on the radiation oncology teaching syllabus and clinical competency assessment content, a detailed teaching syllabus, scoring criteria, and a refined assessment scoring table were developed. From June 2022 to March 2023, 36 resident physicians rotating through the radiation oncology training base at the Cancer Hospital Chinese Academy of Medical Sciences were randomly divided into two groups using a random number table: the original syllabus group ( n=19) was trained according to the original teaching syllabus, while the detailed syllabus group ( n=17) was trained according to the refined teaching syllabus. The refined assessment scoring table was completed based on the scoring criteria, and the assessment results of the two groups were compared using independent sample t-tests. Results:A detailed teaching syllabus covering 25 tumors types across 4 categories (head and neck, thoracic, abdominopelvic, and gynecological) was established. The syllabus included 16 items: applied anatomy, clinical symptoms, physical examination, pathological characteristics, staging examinations / imaging, clinical / pathological staging, other diagnostic / therapeutic factors, general treatment principles, radiotherapy indications, localization methods, radiotherapy target areas / doses, special treatment fields, dose-limiting requirements, treatment-related adverse effects and management, prognosis, and essential reading literature. Corresponding scoring criteria and a refined scoring table were developed, encompassing key points and skills for medical history collection, specialized physical examination, and clinical reasoning. Assessment results showed that the overall score of the detailed syllabus group was 90.85±1.97, significantly higher than that of the original syllabus group (70.81±4.21), with a statistically significant difference ( t=17.94, P<0.001). In all 10 assessment items, the detailed syllabus group outperformed the original syllabus group (all P<0.01). Conclusion:Quantitative evaluation demonstrated that the detailed teaching syllabus for standardized training of radiation oncology residents significantly improved the clinical competency of resident physicians in teaching practice.

Objective:To establish a detailed teaching syllabus for the standardized training of radiation oncology residents, apply it in clinical teaching practice, and evaluate its practical teaching value.Methods:Based on the radiation oncology teaching syllabus and clinical competency assessment content, a detailed teaching syllabus, scoring criteria, and a refined assessment scoring table were developed. From June 2022 to March 2023, 36 resident physicians rotating through the radiation oncology training base at the Cancer Hospital Chinese Academy of Medical Sciences were randomly divided into two groups using a random number table: the original syllabus group ( n=19) was trained according to the original teaching syllabus, while the detailed syllabus group ( n=17) was trained according to the refined teaching syllabus. The refined assessment scoring table was completed based on the scoring criteria, and the assessment results of the two groups were compared using independent sample t-tests. Results:A detailed teaching syllabus covering 25 tumors types across 4 categories (head and neck, thoracic, abdominopelvic, and gynecological) was established. The syllabus included 16 items: applied anatomy, clinical symptoms, physical examination, pathological characteristics, staging examinations / imaging, clinical / pathological staging, other diagnostic / therapeutic factors, general treatment principles, radiotherapy indications, localization methods, radiotherapy target areas / doses, special treatment fields, dose-limiting requirements, treatment-related adverse effects and management, prognosis, and essential reading literature. Corresponding scoring criteria and a refined scoring table were developed, encompassing key points and skills for medical history collection, specialized physical examination, and clinical reasoning. Assessment results showed that the overall score of the detailed syllabus group was 90.85±1.97, significantly higher than that of the original syllabus group (70.81±4.21), with a statistically significant difference ( t=17.94, P<0.001). In all 10 assessment items, the detailed syllabus group outperformed the original syllabus group (all P<0.01). Conclusion:Quantitative evaluation demonstrated that the detailed teaching syllabus for standardized training of radiation oncology residents significantly improved the clinical competency of resident physicians in teaching practice.

Background and objective Radiation therapy is one of the most common treatments for non-small cell lung cancer(NSCLC).However,the insensitivity of some tumor cells to radiation is one of the major reasons for the poor efficacy of radiotherapy and the poor prognosis of patients,and exploring the underlying mechanisms behind radioresistance is the key to solving this clinical challenge.This study aimed to identify the molecules associated with radioresistance in lung ad-enocarcinoma(LUAD),identified thyroid hormone receptor interactor 13(TRIP13)as the main target initially,and explored whether TRIP 13 is related to radioresistance in LUAD and the specific mechanism,with the aim of providing theoretical basis and potential targets for the combination therapy of LUAD patients receiving radiotherapy in the clinic.Methods Three data-sets,GSE18842,GSE19188 and GSE33532,were selected from the Gene Expression Omnibus(GEO)database and screened for differentially expressed genes(|log FC|＞1.5,P＜0.05)in each of the three datasets using the R 4.1.3 software,and then Venn diagram was used to find out the differentially expressed genes common to the three datasets.The screened differential genes were then subjected to protein-protein interaction(PPI)analysis and module analysis with the help of STRING online tool and Cytoscape software,and survival prognosis analysis was performed for each gene with the help of Kaplan-Meier Plotter database,and the TRIP13 gene was identified as the main molecule for subsequent studies.Subsequently,the human LUAD cell line H292 was irradiated with multiple X-rays using a sub-lethal dose irradiation method to construct a radioresistant cell line,H292DR.The radioresistance of H292DR cells was verified using cell counting kit-8(CCK-8)assay and clone formation assay.The expression levels of TRIP 13 in H292 and H292DR cells were measured by Western blot.Small interfering RNA(siRNA)was used to silence the expression of TRIP 13 in H292DR cells and Western blot assay was performed.The clone formation ability and migration ability of H292DR cells were observed after TRIP13 silencing,followed by the detection of changes in the expression levels of proteins closely related to homologous recombination,such as ataxia telangiectasia mutated(ATM)protein.Results Screening of multiple GEO datasets,validation of external datasets and survival analysis revealed that TRIP 13 was highly expressed in LUAD and was associated with poor prognosis in LUAD patients who had received radiation therapy.And the results of gene set enrichment analysis(GSEA)of TRIP13 suggested that TRIP13 might be closely associated with LUAD radioresistance by promoting homologous recombination repair after radiation therapy.Experimentally,TRIP13 expression was found to be upregulated in H292DR,and silencing of TRIP13 was able to increase the sensitivity of H292DR cells to radiation.Conclusion TRIP13 is associated with poor prognosis in LUAD patients treated with radiation,possibly by promoting a homologous recombination repair pathway to mediate resistance of LUAD cells to radiation.

BACKGROUND: Low-density computed tomography (LDCT) improved early lung cancer diagnosis but introduces an excess of false-positive pulmonary nodules data. Hence, accurate diagnosis of early-stage lung cancer remains challenging. The purpose of the study was to assess the feasibility of using circulating tumour cells (CTCs) to differentiate malignant from benign pulmonary nodules. METHODS: 122 patients with suspected malignant pulmonary nodules detected on chest CT in preparation for surgery were prospectively recruited. Peripheral blood samples were collected before surgery, and CTCs were identified upon isolation by size of epithelial tumour cells and morphological analysis. Laser capture microdissection, MALBAC amplification, and whole-exome sequencing were performed on 8 samples. The diagnostic efficacy of CTCs counting, and the genomic variation profile of benign and malignant CTCs samples were analysed. RESULTS: Using 2.5 cells/5 mL as the cut-off value, the area under the receiver operating characteristic curve was of 0.651 (95% confidence interval: 0.538-0.764), with a sensitivity and specificity of 0.526 and 0.800, respectively, and positive and negative predictive values of 91.1% and 30.3%, respectively. Distinct sequence variations differences in DNA damage repair-related and driver genes were observed in benign and malignant samples. TP53 mutations were identified in CTCs of four malignant cases; in particular, g.7578115T>C, g.7578645C>T, and g.7579472G>C were exclusively detected in all four malignant samples. CONCLUSIONS CTCs play an ancillary role in the diagnosis of pulmonary nodules. TP53 mutations in CTCs might be used to identify benign and malignant pulmonary nodules.
Humans ; Lung Neoplasms ; Exome Sequencing ; Multiple Pulmonary Nodules ; Carcinoma ; DNA Repair

The feasibility and safety of intracardiac echocardiography (ICE)-guided catheter ablation for atrial fibrillation (AF) using a minimal/zero-fluoroscopy approach have recently been reported. This approach helps to reduce ionizing radiation exposure and orthopedic complications resulting from using lead aprons. The objectives of this planned prospective, multicenter randomized controlled trial (RCT) (paroxysmal AF (PAF)-ICE trial; ChiCTR2000033624) are to evaluate the efficacy and safety of ICE-guided minimal-fluoroscopy ablation in patients with PAF and the impact on occupational hazards among lab staff.Patients will be randomized in a 1:1 ratio to 2 groups: minimal fluoroscopy group ( n = 216) and traditional approach group ( n = 216). In the minimal fluoroscopy group, an ICE catheter will be used for geometry/anatomic construction, transseptal puncture, catheter tracking, and effusion monitoring. Pulmonary vein isolation (PVI) will be performed using an open-irrigated radiofrequency SmartTouch Surround Flow or SmartTouch catheter (Biosense Webster, Diamond Bar, California, USA), and confirmed by a multipolar Lasso or PentaRay catheter (Biosense Webster). In the traditional approach group, an ICE catheter will not be used. Transseptal puncture will be performed under fluoroscopic guidance, with all geometries constructed by mapping the catheters. The primary efficacy endpoint is freedom from AF recurrence (without antiarrhythmic medications) at 12 months after ablation. Other endpoints include duration of lead apron use, measures of intra-procedural efficiency, and peri-procedural complications. This RCT will evaluate the efficacy and safety of ICE-guided minimal-fluoroscopy ablation in patients with PAF, also evaluate the benefits to lab staff (regarding reducing occupational hazards) related to this "minimal/zero-fluoroscopy" and "leadless" mode.

The feasibility and safety of intracardiac echocardiography (ICE)-guided catheter ablation for atrial fibrillation (AF) using a minimal/zero-fluoroscopy approach have recently been reported. This approach helps to reduce ionizing radiation exposure and orthopedic complications resulting from using lead aprons. The objectives of this planned prospective, multicenter randomized controlled trial (RCT) (paroxysmal AF (PAF)-ICE trial; ChiCTR2000033624) are to evaluate the efficacy and safety of ICE-guided minimal-fluoroscopy ablation in patients with PAF and the impact on occupational hazards among lab staff.Patients will be randomized in a 1:1 ratio to 2 groups: minimal fluoroscopy group ( n = 216) and traditional approach group ( n = 216). In the minimal fluoroscopy group, an ICE catheter will be used for geometry/anatomic construction, transseptal puncture, catheter tracking, and effusion monitoring. Pulmonary vein isolation (PVI) will be performed using an open-irrigated radiofrequency SmartTouch Surround Flow or SmartTouch catheter (Biosense Webster, Diamond Bar, California, USA), and confirmed by a multipolar Lasso or PentaRay catheter (Biosense Webster). In the traditional approach group, an ICE catheter will not be used. Transseptal puncture will be performed under fluoroscopic guidance, with all geometries constructed by mapping the catheters. The primary efficacy endpoint is freedom from AF recurrence (without antiarrhythmic medications) at 12 months after ablation. Other endpoints include duration of lead apron use, measures of intra-procedural efficiency, and peri-procedural complications. This RCT will evaluate the efficacy and safety of ICE-guided minimal-fluoroscopy ablation in patients with PAF, also evaluate the benefits to lab staff (regarding reducing occupational hazards) related to this "minimal/zero-fluoroscopy" and "leadless" mode.

Objective:To evaluate the effect of Salvianolic acid B on the radiosensitivity of human non-small cell lung cancer cells and investigate its possible mechanism.Methods:Non-small cell lung cancer cells A549 and H1299 were cultured in vitro. The toxicity of Salvianolic acid B on non-small cell lung cancer cells was detected by MTT assay. The effect of Salvianolic acid B on the radiosensitivity was assessed by clone formation assay. Transwell chamber assay was used to evaluate the effect of Salvianolic acid B on the migration of tumor cells. Western blot was employed to detect the expression levels of OTUD7B, MMP-2, MMP-9, E-cadherin, Akt and p-Akt regulated by Salvianolic acid B. Results:Salvianolic acid B (5 μmol/L) could inhibit the proliferation of A549 and H1299 cells. Clone formation assay showed that Salvianolic acid B increased the radiosensitivity of A549 and H1299 cells, with a radiosensitization ratio of 1.45 and 1.38, respectively. Transwell chamber assay indicated that the ability of cell migration was significantly inhibited by Salvianolic acid B ( P<0.05). Western blot revealed that the expression levels of OTUD7B in A549 and H1299 cells were induced by irradiation in a time-dependent manner. Salvianolic acid B could down-regulate the expression levels of MMP-2, MMP-9 and p-Akt, whereas up-regulate the expression level of E-cadherin by down-regulating the expression level of OTUD7B. Conclusions:Salvianolic acid B can enhance the radiosensitivity of A549 and H1299 cells. The possible mechanism is that Salvianolic acid B down-regulates the expression level of OTUD7B induced by irradiation and inhibits the epithelial-mesenchymal transition process of tumor cells.

Objective:To explore the effect of applying individualized progressive nutrition guide sheet in postoperative enteral nutrition (EN) for patients with oral cancer.Methods:Using convenient sampling method, 40 oral cancer patients admitted to Sichuan Cancer Hospital from November 2017 to October 2018 were selected as the control group, and 46 from November 2018 to October 2019 were selected as the observation group. Both groups received EN support but the observation group were applied with progressive nutrition guide sheet. The pre- and post-operative body weight, nutrition related indicators, gastrointestinal symptoms, proportion of patients achieving daily target energy intake, patient/family satisfaction and other indicators were compared between the two groups.Results:There were significant differences in preoperative potassium, total protein and albumin at 7 days after operation, prealbumin at 3 and 7 days after operation, potassium at 3 days after operation and sodium at 3 days after operation between the two groups( Z=4.963, P<0.01; Z=5.094, P<0.01; Z=-2.022, P<0.05; Z=4.048, P<0.01; Z=2.14, P<0.05, Z=-6.04, P<0.01, Z=-7.13, P<0.01). The dynamic changes of potassium and sodium in the two groups were compared before operation, 3 days after operation and 7 days after operation ( F=30.20, F= 118.51, all P<0.01). There were significant differences in incidence of abdominal pain, abdominal distension and diarrhea between the two groups ( χ2=6.91, P=0.009, χ2=10.36, P=0.001, χ2=4.71, P=0.03). There were also significant differences in the proportion of patients achieving daily target energy intake at 1 day, 2 days, 3 days, 4 days, 5 days, and 6 days after operation between the two groups ( χ2=41.77, χ2=45.09, χ2=45.71, χ2=40.53, χ2=29.97, χ2=6.11, all P<0.01). Conclusion:The application of progressive nutrition guidelines in early postoperative EN support for patients with oral cancer can help to improve postoperative nutritional status, avoid potassium, sodium and electrolyte disturbance, alleviate postoperative gastrointestinal symptoms, improve the achievement of daily target energy intake and patient/family satisfaction, and promote disease recovery.

BACKGROUND: It was believed that immunoglobulin G (IgG) was synthesized only by B cells. However, in recent years, researchers have found that a variety of cancer cells can also synthesize IgG (cancer-IgG) which promote the development of tumors. This study analyzed the expression and clinical significance of cancer-IgG in non-small cell lung cancer (NSCLC), and initially explored its mechanism. METHODS: The expression of IgG1 heavy chain gamma 1 (IGHG1) and cancer-IgG were detected by bioinformatics and immunohistochemistry in NSCLC; The gene set enrichment analysis (GSEA) method was used to explore the signaling pathways involved in IGHG1 regulation. RESULTS: The expression level of cancer-IgG in NSCLC was significantly higher than that in normal tissues. The high expression group had a poor prognosis and was associated with clinical stage (P=0.042), T stage (P=0.044) and metastasis (P=0.007). GSEA analysis showed that IGHG1 was associated with cell adhesion, cytokine interaction and chemokine signaling pathway. CONCLUSIONS High expression of cancer-IgG in NSCLC is a poor prognosis factor, which may be related to the promotion of tumor invasion and metastasis.
Adult ; Aged ; Biomarkers, Tumor ; metabolism ; Carcinoma, Non-Small-Cell Lung ; genetics ; metabolism ; pathology ; Carrier Proteins ; genetics ; metabolism ; Computational Biology ; Female ; Humans ; Immunoglobulin G ; genetics ; metabolism ; Immunohistochemistry ; Lung Neoplasms ; genetics ; metabolism ; pathology ; Male ; Middle Aged ; Neoplasm Staging ; Young Adult