Efficacy of Near-Infrared Fluorescence Video-Assisted Thoracoscopic Surgery for Small Pulmonary Nodule Resection with Indocyanine Green Inhalation: A Randomized Clinical Trial.

BACKGROUND: Small pulmonary nodules (<3 cm) can sometimes be unrecognizable and nonpalpable in video-assisted thoracoscopic surgery (VATS). Near-infrared fluorescence (NIF) VATS after indocyanine green (ICG) inhalation may effectively guide surgeons to locate the nodules. OBJECTIVE: This study aimed to investigate the safety, feasibility, and efficacy of ICG inhalation-based NIF imaging for guiding small pulmonary nodule resections. METHODS: Between February and May 2021, the first-stage, non-randomized trial enrolled 21 patients with different nodule depth, ICG inhalation doses, post-inhalation surgery times, and nodule types at a tertiary referral hospital. Between May 2021 and May 2022, the second-stage randomized trial enrolled 56 patients, who were randomly assigned to the fluorescence VATS (FLVATS) or the white-light VATS (WLVATS) group. The ratio of effective guidance and the time consumption for nodule localization were compared. RESULTS: The first-stage trial proved this new method is safe and feasible, and established a standardized protocol with optimized nodule depth (≤1 cm), ICG dose (0.20-0.25 mg/kg), and surgery window (50-90 min after ICG inhalation). In the second-stage trial, the FLVATS achieved 87.1% helpful nodule localization guidance, which was significantly higher than the WLVATS (59.1%, p < 0.05). The mean nodule locating time (standard deviation) was 1.8 [0.9] and 3.3 [2.3] min, respectively. Surgeons adopting FLVATS were significantly faster (p < 0.01), especially when locating small ground-glass opacities (1.3 [0.6] min vs. 7.0 [3.5] min, p < 0.05). Five of 31 nodules (16.1%) were only detectable by FLVATS, whereas both white light and palpation failed. CONCLUSIONS: This new method is safe and feasible for small pulmonary nodule resection. It significantly improves nodule localization rates with less time consumption, and hence is highly worthy for clinical promotion. Clinical Trial Registration Chinese Clinical Trial Registry Identifier: ChiCTR2100047326.

CircDENND2D Inhibits PD-L1-Mediated Non-Small Cell Lung Cancer Metastasis and Immune Escape by Regulating miR-130b-3p/STK11 Axis.

Local recurrence and distant metastasis of non-small cell lung cancer (NSCLC) caused by immune escape is one of the root causes of treatment difficulties. We aim to investigate the mechanism of immune escape in NSCLC. NSCLC tissues were collected. Cell proliferation was detected by CCK-8 assay. Cell migration and invasion ability was measured by Transwell assay. The expressions of E-cadherin, N-cadherin and PD-L1 were detected by Western blot. NSCLC cells were co-cultured with CD8+ T cells to simulate tumor microenvironment in vitro. The proportion of CD8+ T cells and apoptosis were detected by flow cytometry. Dual-luciferase reporter gene assay confirmed the targeting relationship of circDENND2D and STK11. The expressions of circDENND2D and STK1 were down-regulated, while miR-130b-3p expression was up-regulated in NSCLC tissues. Overexpression of circDENND2D or STK11 inhibited NSCLC cells proliferation, migration and invasion, and attenuated the immune escape of NSCLC cells. CircDENND2D targeted miR-130b-3p to competitively promote STK11 expression. STK11 knockdown or miR-130b-3p overexpression attenuated the function of circDENND2D overexpression on NSCLC cells. CircDENND2D inhibited metastasis and immune escape of NSCLC by regulating miR-130b-3p/STK11 axis.

Intraoperative Fluorescence Visualization in Thoracoscopic Surgery.

We report a clinical case of using indocyanine green inhalation to achieve intraoperative near-infrared fluorescence visualization of pulmonary ground-glass opacity in thoracoscopic wedge resection. The patient underwent thoracoscopic wedge resection under the real-time navigation of a near-infrared fluorescence imaging system with the indocyanine green inhalation performed 85 minutes before the surgery. The nebulized inhalation of indocyanine green (dose of 0.25 mg/kg) successfully guided surgeons to localize the small ground-glass opacity due to a filling defect of the fluorescence. The thoracoscopic near-infrared fluorescence navigation system delineated the tumor margin with high contrast and helped to minimize the damage to lung function.

A Novel N-Gram-Based Image Classification Model and Its Applications in Diagnosing Thyroid Nodule and Retinal OCT Images.

Imbalanced classes and dimensional disasters are critical challenges in medical image classification. As a classical machine learning model, the n-gram model has shown excellent performance in addressing this issue in text classification. In this study, we proposed an algorithm to classify medical images by extracting their n-gram semantic features. This algorithm first converts an image classification problem to a text classification problem by building an n-gram corpus for an image. After that, the algorithm was based on the n-gram model to classify images. The algorithm was evaluated by two independent public datasets. The first experiment is to diagnose benign and malignant thyroid nodules. The best area under the curve (AUC) is 0.989. The second experiment is to diagnose the type of fundus lesion. The best result is that it correctly identified 86.667% of patients with dry age-related macular degeneration (AMD), 93.333% of patients with diabetic macular edema (DME), and 93.333% of normal individuals.

Concordance Study of a 520-Gene Next-Generation Sequencing-Based Genomic Profiling Assay of Tissue and Plasma Samples.

INTRODUCTION: Next-generation sequencing (NGS) enables simultaneous detection of actionable somatic variants and estimation of genomic signatures such as tumor mutational burden (TMB) or microsatellite instability (MSI) status, which empowers therapeutic decisions in clinical oncology. OBJECTIVE: Our retrospective study investigated the clinical performance of somatic variant detection in paired tissue and blood samples using a large targeted gene panel, the OncoScreen Plus, which interrogates 520 cancer-related genes. METHODS: We analyzed sequencing data derived from paired tissue and blood samples of 3005 patients spanning 20 solid tumor types, including lung (n = 1971), gastrointestinal (n = 625), breast (n = 120) and gynecological (n = 110), genitourinary (n = 38), and other cancers (n = 141). RESULTS: Across tumor types, the OncoScreen Plus panel achieved a high tissue detection rate, with an average of 97.9%. The average plasma detection rate was 72.2%, with an average tissue concordance rate of 36.6%. Considering all variant types, the plasma assay yielded an average sensitivity/true positive rate of 45.7%, with a positive predictive value of 64.7% relative to tissue assay. Pearson correlation analysis revealed a strong correlation in TMB estimated from blood and tissue samples (correlation coefficient 0.845, R2 = 0.756). MSI-high status was identified in five tumor types, including endometrial cancer (28.6%), colorectal cancer (2.5%), ovarian cancer (2.0%), gastric cancer (1.5%), and lung adenocarcinoma (0.2%). CONCLUSION: Paired tumor and blood samples from a large cohort of patients spanning 20 tumor types demonstrated that the OncoScreen Plus is a reliable pan-cancer panel for the accurate detection of somatic variants and genomic signatures that could guide individualized treatment strategies to improve the care of patients with advanced cancer.

lncRNA SLC9A3-AS1 Promotes Oncogenesis of NSCLC via Sponging microRNA-760 and May Serve as a Prognosis Predictor of NSCLC Patients.

Background: Non-small cell lung cancer (NSCLC) is a prevalent type of lung cancer worldwide. Long noncoding RNA (lncRNA) SLC9A3-AS1 is reported to play a carcinogenic role in nasopharyngeal carcinoma, but its full-scale role in NSCLC remains elusive. Methods: SLC9A3-AS1 expression was detected in serum and tissue of NSLCC patients and NSCLC cell lines. The effects of SLC9A3-AS1 on NSCLC proliferation, migration and invasion were evaluated using CCK-8 and transwell assays. In addition, the potential downstream molecules of SLC9A3-AS1 were searched and explored by bioinformatics analysis, RT-qPCR, dual-luciferase reporter, and rescue experiments. Results: SLC9A3-AS1 was upregulated in NSCLC tissues and cell lines. SLC9A3-AS1 possessed a favorable ability in diagnosing NSCLC. A high level of SLC9A3-AS1 was associated with poor prognosis in NSCLC patients. Functionally, SLC9A3-AS1 knockdown inhibited cell proliferation, migration, and invasion of NSCLC cells. Mechanistically, SLC9A3-AS1 acted as competing endogenous RNA for miR-760 to regulate NSCLC progression. In addition, rescue assay showed that downregulation of miR-760 could reverse the modulatory activity of SLC9A3-AS1 knockdown on NSCLC cells. Conclusion: SLC9A3-AS1 was upregulated in NSCLC, and SLC9A3-AS1 knockdown hindered NSCLC progression through targeting miR-760, suggesting that it may prove to be a novel biomarker and therapeutic target for NSCLC.

A comprehensive pan-cancer study of fibroblast growth factor receptor aberrations in Chinese cancer patients.

BACKGROUND: The prevalence and types of fibroblast growth factor receptor (FGFR) mutations vary significantly among different ethnic groups. The optimal application of FGFR inhibitors depends on these variations being comprehensively understood. However, such an analysis has yet to be conducted in Chinese patients. METHODS: We retrospectively screened the genomic profiling results of 10,582 Chinese cancer patients across 16 cancer types to investigate the frequency and distribution of FGFR aberrations. RESULTS: FGFR aberrations were identified in 745 patients, equating to an overall prevalence of 7.0%. A majority of the aberrations occurred on FGFR1 (56.8%), which was followed by FGFR3 (17.7%), FGFR2 (14.4%), and FGFR4 (2.8%). Further, 8.5% of patients had aberrations of more than 1 FGFR gene. The most common types of aberrations were amplification (53.7%), other mutations (38.8%), and fusions (5.6%). FGFR fusion and amplification occurred concurrently in 1.9% of the patients. FGFR aberrations were detected in 12 of the 16 cancers, with the highest prevalence belonging to colorectal cancer (CRC) (31%). Other FGFR-aberrant cancer types included stomach (16.8%), breast (14.3%), and esophageal (12.7%) cancer. Breast tumors were also more likely than other cancer types to have concurrent FGFR rearrangements and amplifications (P<0.001). In comparison with the public dataset, our cohort had a significantly higher number of FGFR aberrations in colorectal (P<0.001) and breast cancer (P=0.05). CONCLUSIONS: Among the Chinese cancer patients in our study, the overall prevalence of FGFR aberrations was 7.0%. FGFR1 amplification was the most common genetic alteration in CRC, breast cancer, and lung cancer; while FGFR2 amplification was more commonly observed in gastric cancer than in other cancers in our cohort. Our study advances the understanding of the distribution of FGFR aberrations in various cancer types in the Chinese population, which will facilitate the further development of FGFR inhibitors.

Serotonin transporter-linked polymorphic region genotypes in relation to stress conditions among patients with papillary thyroid carcinoma.

The serotonin-transporter-linked polymorphic region (5-HTTLPR) gene has been reported to predispose individuals experiencing trauma to affective disorders such as anxiety and depression. We hypothesized that SS genotype of 5-HTTLPR gene would induce stress conditions and poor prognosis of papillary thyroid carcinoma (PTC). The study enrolled 287 patients with or without post-traumatic stress disorder (PTSD) following surgical treatment of PTC with their baseline characteristics collected. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was conducted to detect genotype frequency. Five self-rating scales, including Impact of Event Scale-Revised Edition (IES-R), MedicaI Coping Modes Questionnaire (MCMO), Hamilton Depression Scale (HAMD), Social Support Rating Scale (SSRS) and Stressful Life Events (SLEs), were used for depressive state assessment. Survival situations were observed through 15-year follow-up visits one time every six months. Survival rate was calculated using Life Table. Logistic regression analysis was used to analyze factors related to prognosis of PTC. Increased SS genotype and decreased LL genotypes were found in patients with PTSD. PTSD is associated with high stress, and inter-group analysis revealed that patients carrying SS genotype exhibited a high stress condition. PTSD and SS genotype correlated to large tumor size, advanced clinical stage, lymph node metastasis, and decreased 10-year and 15-year survival rate. As for patients carrying the same genotype, those suffering from PTSD showed poorer survival. Also, 5-HTTPRL, MCMQ score (confrontation/avoidance/surrender), HAMD score, SSRS total score, SLEs score, tumor size, clinical stage, and lymph node metastasis were relevant factors for prognosis of PTC. The results demonstrate SS genotype of the 5-HTTPRL gene as a contributor of high stress among patients with PTC. Thus, 5-HTTPRL and stress conditions represent potential investigative focus targets for prognosis of PTC.

CpG methylation of brain-derived the neurotrophic factor gene promoter as a potent diagnostic and prognostic biomarker for post-traumatic stress disorder.

Posttraumatic stress disorder (PTSD) is a common response to traumatic events. Many PTSD patients recover in the next few months, but in a significant subgroup, the symptoms persist, often for years. The present study shows that brain-derived neurotrophic factor (BDNF) gene is related to the pathological mechanism of a variety of mental diseases. Here we investigate the effect of methylation of BDNF gene and different loci on the occurrence and development of PTSD. Initially, using case-control method, 322 PTSD patients as well as 215 normal controls were selected as the subjects. Following peripheral venous blood being collected from the subjects, genomic DNA was extracted. Methylation of the cytosine-guanine dinucleotide (CpG) island in BDNF gene promoter was then modified by bisulfite and detected through direct sequencing. Methylation of CpG in BDNF gene promoter was closely related to PTSD, and the methylation level of CpG in BDNF gene promoter may serve as a biomarker for PTSD diagnosis. Types of trauma of PTSD patients may have a certain effect on the methylation level of BDNF gene promoter. Methylation level of the BDNF promoter, depressive degree score, poor sleep quality score, early trauma score, mental stress score, and trauma type were closely related to the occurrence and development of PTSD. Taken together, our data support the notion that stressful life events may directly cause CpG methylation in the BDNF promoter of PTSD patients. Stress types may be associated with methylation levels of CpG1, CpG7, and CpG18 in the BDNF promoter of PTSD patients. These findings provide a new way for the diagnosis and treatment of PTSD.

Complete video-assisted thoracoscopic lobectomy of the left lower lobe and lung lymph node dissection.

We describe herein a case of complete video-assisted thoracoscopic lobectomy of the left lower lobe and lung lymph node dissection. The patient was a 67-year-old man. A physical examination revealed a nodule in the left lower lobe that had been present for 7 years. According to the chest computed tomography (CT) report recently, a diagnosis of lung cancer was not excluded. Due to the surgical indications, he was underwent complete video-assisted thoracoscopic lobectomy of the left lower lobe and lung lymph node dissection. The frozen pathology report was consistent with adenocarcinoma. He recovered smoothly, without any perioperative complications.

[Effects of artesunate on the invasion of lung adenocarcinoma A549 cells and expression of ICAM-1 and MMP-9].

BACKGROUND AND OBJECTIVE: Artesunate, an anti-malarial drug, elicits an inhibitory effect on pulmonary carcinoma. However, the mechanisms of artesunate activity on pulmonary carcinoma have not been completely elucidated. The aim of this study is to investigate the effect of artesunate on the invasion of human lung adenocarcinoma A549 cells. METHODS: The inhibitory effect of artesunate on the proliferation and invasion of A549 cells was determined in vitro by MTT assay and transwell chamber invasion assay, respectively. A nude mouse model of human lung A549 cell xenograft tumor was established. The inhibitory effect of artesunate on the tumor of the mouse model as well as ICAM-1 and MMP-9 protein expressions were determined by Western blot. RESULTS: A low dose of artesunate ranging between 1.25 µg/L and 5 µg/L did not significantly inhibit the proliferation of A549 cells in vitro. By contrast, 1.25 µg/L artesunate inhibited the invasion of A549 cells in vitro as determined by transwell chamber invasion assay (96.33 ± 6.41 vs 75.43 ± 4.37, P<0.05). Although 10 mg/kg artesunate did not significantly inhibit A549 xenograft tumor proliferation (P>0.05), artesunate decreased the ICAM-1 and MMP-9 protein levels in the mouse model (P<0.05). CONCLUSIONS: Artesunate could inhibit the invasion of human lung adenocarcinoma A549 cells by possibly downregulating ICAM-1 and MMP-9 expressions.