The diagnostic potential role of thioredoxin reductase and TXNRD1 in early lung adenocarcinoma: A cohort study.

Background: Lung adenocarcinoma (LUAD) is the primary form of lung cancer, yet the reliable biomarkers for early diagnosis remain insufficient. Thioredoxin reductase (TrxR) is strongly linked to the occurrence, development, and drug resistance of lung cancer, making it a potential biomarker. However, further research is required to assess its diagnostic value in LUAD. Methods: A retrospective analysis was performed on patients who underwent pulmonary nodule resection at our center from 2018 to 2022. Clinical data, including preoperative TrxR levels, imaging, and laboratory characteristics, were identified as study variables. Two prediction models were constructed using multiple logistic regression, and their prediction performance was evaluated comprehensively. Besides, bioinformatics analyses of TrxR coding genes including differential expression, functional enrichment, immune infiltration, drug sensitivity, and single-cell landscape were performed based on TCGA database, which were subsequently validated by Human Protein Atlas. Results: A total of 506 eligible patients (72 benign lesions, 77 AISs, 185 MIAs and 172 IACs) were identified in the clinical cohort. Two TrxR-based models were developed, which were able to distinguish between benign and malignant pulmonary nodules, as well as pathological subtypes of LUAD, respectively. The models exhibited good predictive ability with all AUC values ranging from 0.7 to 0.9. Based on calibration curves and clinical decision analysis, the nomogram models showed high reliability. Functional analysis indicated that TXNRD1 primarily participated in cell cycle and lipid metabolism. Immune infiltration analysis showed that TXNRD1 has a strong association with immune cells and could impact immunotherapy. Then, we identified small molecular compounds that inhibit TXNRD1 and confirmed TXNRD1 expression by single-cell landscape and immunohistochemistry. Conclusion: This study validated the diagnostic value of TrxR and TXNRD1 in clinical cohorts and transcriptional data, respectively. TrxR and TXNRD1 could be used in the risk diagnosis of early LUAD and facilitate personalized treatment strategies.

Ultrafast Process Characterization of Laser-Induced Damage in Fused Silica Using Pump-Probe Shadow Imaging Techniques.

This study delves into the intricate dynamics of laser-induced damage in fused silica using a time-resolved pump-probe (TRPP) shadowgraph. Three typical ultra-fast processes, laser-induced plasma evolution, shockwave propagation and material fracture splashing, were quantitatively investigated. The results indicate that the diameter of plasma is proportional to the pulse laser energy and increases linearly during the pulse laser duration with an expansion rate of approximately 6 km/s. The maximum shockwave velocity on the air side is 9 km/s, occurring at the end of the pulse duration, and then rapidly decreases due to air resistance, reaching approximately 1 km/s around a 300 ns delay. After hundreds of nanoseconds, there is a distinct particle splashing phenomenon, with the splashing particle speed distribution ranging from 0.15 km/s to 2.0 km/s. The particle sizes of the splashing particles range from 4 µm to 15 µm. Additionally, the smaller the delay, the faster the speed of the splashing particles. Overall, TRPP technology provides crucial insights into the temporal evolution of laser-induced damage in fused silica, contributing to a comprehensive understanding essential for optimizing the performance and safety of laser systems.

High-Power Femtosecond Laser Processing of SiC Ceramics with Optimized Material Removal Rate.

Silicon carbide (SiC) ceramics are widely used as structural materials for various applications. However, the extraordinarily high hardness, brittleness, low material removal rate, and severe tool wear of these materials significantly impact the performance of conventional mechanical processing techniques. In this study, we investigated the influence of different parameters on the material removal rate, surface quality, and surface oxidation during the laser processing of SiC ceramic samples using a high-repetition-frequency femtosecond laser at a wavelength of 1030 nm. Additionally, an experimental investigation was conducted to analyze the effects of a burst mode on the material removal rate. Our results demonstrate that the surface oxidation, which significantly affects the material removal rate, can be effectively reduced by increasing the laser scanning speed and decreasing the laser scanning pitch. The material removal rate and surface quality are mainly affected by laser fluence. The optimal material removal rate is obtained with a laser fluence of 0.4 J/cm2 at a pulse width of 470 fs.

Formation mechanism of DKDP surface in single point diamond fly-cutting process and the resulting degradation of laser-induced damage performance.

Laser damage performance of DKDP (KD2xH2(1-x)PO4) crystal is largely determined by the surface microstructures generated in the manufacturing process, more specifically, single point diamond fly-cutting process. However, because of the lack of knowledge about the formation mechanism and damage performance of the microstructures, laser induced damage of DKDP crystal remains a key issue limiting the output energy of the high power laser systems. In this paper, the influence of fly-cutting parameters on the generation of DKDP surface and the underlying material deformation mechanism have been investigated. Except for cracks, two kinds of new microstructures, namely micro grains and ripples, have been found on the processed DKDP surfaces. GIXRD, nano-indentation and nano-scratch test results prove that the micro grains are generated by the slip motion of the crystal, while the simulation results show that the cracks are induced by the tensile stress formed behind the cutting edge. Moreover, the formation of micro grains can facilitate the plastic chip flow through the mechanism of grain boundary sliding, which will further lead to a periodic fluctuation of the chip separation point and the formation of micro ripples. Finally, laser damage test results demonstrate that cracks will degrade the damage performance of DKDP surface significantly, while the formation of micro grains and micro ripples has little impact. The results of this study can deepen the understanding of the formation mechanism of the DKDP surface during the cutting process and provide guidance to improve the laser-induced damage performance of the crystal.

Fully continuous spiral phase plate for ultraintense optical vortices.

Ultraintense optical vortices carrying orbital angular momentum have attracted much attention in strong-field laser physics due to their spiral phase and hollow intensity. This Letter introduces a fully continuous spiral phase plate (FC-SPP) that enables the generation of an ultraintense Laguerre-Gaussian beam. An optimization design method based on the spatial filter technique and chirp-z transform is proposed to match the polishing processing and the tightly focusing performance. To enable its use in high-power laser systems, a large-aperture (200 × 200 mm2) FC-SPP has been fabricated on a fused silica substrate through magnetorheological finishing without the use of mask techniques. The far-field phase pattern and intensity distribution based on vector diffraction calculation were compared with those of ideal spiral phase plate and fabricated FC-SPP, which confirmed the high quality of the output vortex beams and their feasibility for producing high-intensity vortices.

Evolution of the point defects involved under the action of mechanical forces on mechanically machined fused silica surfaces.

Point defects with different species are concentrated on most mechanically machined fused silica optical surfaces with surface defects, which would sharply decrease the laser damage resistance under intense laser irradiation. Various point defects have distinct roles in affecting the laser damage resistance. Especially, the proportions of various point defects have not been identified, posing the challenge in relating the intrinsic quantitative relationship among various point defects. To fully reveal the comprehensive effect of various point defects, it is necessary to systematically explore the origins, evolution laws and especially the quantitative relationship among point defects. Herein, seven types of point defects are determined. The unbonded electrons in point defects are found to tend to be ionized to induce laser damage and there is a definite quantitative relationship between the proportions of oxygen-deficient point defects and that of peroxide point defects. The conclusions are further verified based on the photoluminescence (PL) emission spectra and the properties (e.g., reaction rule and structural feature) of the point defects. On basis of the fitted Gaussian components and electronic-transition theory, the quantitative relationship between PL and the proportions of various point defects is constructed for the first time. E'-Center accounts for the highest proportion among them. This work is beneficial for fully revealing the comprehensive action mechanisms of various point defects and providing new insights in elucidating the defect-induced laser damage mechanisms of optical components under intense laser irradiation from the atomic scale.

lncRNA NORAD promotes lung cancer progression by competitively binding to miR-28-3p with E2F2.

Lung cancer (LC) is a prevailing primary tumor in the lung. lncRNA non-coding RNA activated by DNA damage (NORAD) is a popular target in human cancers. This experiment is designed to probe the mechanism of lncRNA in LC progression. NORAD expression in normal lung epithelial cells and LC cells was examined and then silenced to assess its effect on LC cell proliferation, invasion, and migration. Subcellular localization of NORAD was analyzed through online databases and then corroborated by fractionation of nuclear and cytoplasmic RNA assay. The target binding relations between NORAD and miR-28-3p and between miR-28-3p and E2F2 were verified. Eventually, LC cells with NORAD silencing were transfected with miR-28-3p inhibitor or pcDNA3.1-E2F2 to measure LC cell proliferation, invasion, and migration. NORAD was overexpressed in LC cells and NORAD knockout led to suppressed LC cell proliferation, invasion, and migration. Besides, NORAD targeted miR-28-3p and miR-28-3p targeted E2F2 transcription. Inhibiting miR-28-3p or overexpressing E2F2 could both annul the inhibitory role of si-NORAD in LC cell proliferation, invasion, and migration. Generally, our findings demonstrated that NORAD competitively bound to miR-28-3p with E2F2, to promote LC cell progression.

Erratum to "lncRNA NORAD promotes lung cancer progression by competitively binding to miR-28-3p with E2F2".

[This corrects the article DOI: 10.1515/med-2022-0538.].

Recurrent lung adenocarcinoma benefits from microwave ablation following multidisciplinary treatments: A case with long-term survival.

Lung cancer has become the leading cause of cancer death all over the world. Nowadays, there is a consensus that the treatment of non-small cell lung cancer (NSCLC) prefers a combination of multidisciplinary comprehensive treatment and individualized treatment, which can significantly improve the prognosis of patients. Here, we report a female patient with recurrence-prone NSCLC. She had a decade-long disease course, during which the lesion recurred twice and finally cured with Multi-Disciplinary Treatment (MDT). An elderly female patient was admitted to the hospital after diagnosis of lung cancer, and treated with surgery and postoperative adjuvant chemotherapy. Five years later, suspicious lesions were found by computed tomography (CT) reexamination, and then confirmed tumor recurrence by puncture biopsy. Based on the genetic test results, gefitinib was used for subsequent targeted therapy, and the lesion gradually shrunk to disappear. However, the lesion appeared again two years later, after consultation the microwave ablation was adopted and the curative effect was excellent. At last, regular reexamination showed no abnormality, the patient has survived so far. The case proves the great benefit of multidisciplinary comprehensive treatment, especially microwave ablation for patient with recurrence-prone NSCLC. And the effect of systemic anti-tumor immune response induced by microwave ablation on lung cancer also needs to be further explored.

Germline mutation analyses of malignant ground glass opacity nodules in non-smoking lung adenocarcinoma patients.

BACKGROUND: Germline mutations play an important role in the pathogenesis of lung cancer. Nonetheless, research on malignant ground glass opacity (GGO) nodules is limited. METHODS: A total of 13 participants with malignant GGO nodules were recruited in this study. Peripheral blood was used for exome sequencing, and germline mutations were analyzed using InterVar. The whole exome sequencing dataset was analyzed using a filtering strategy. KOBAS 3.0 was used to analyze KEGG pathway to further identify possible deleterious mutations. RESULTS: There were seven potentially deleterious germline mutations. NM_001184790:exon8: c.C1070T in PARD3, NM_001170721:exon4:c.C392T in BCAR1 and NM_001127221:exon46: c.G6587A in CACNA1A were present in three cases each; rs756875895 frameshift in MAX, NM_005732: exon13:c.2165_2166insT in RAD50 and NM_001142316:exon2:c.G203C in LMO2, were present in two cases each; one variant was present in NOTCH3. CONCLUSIONS: Our results expand the germline mutation spectrum in malignant GGO nodules. Importantly, these findings will potentially help screen the high-risk population, guide their health management, and contribute to their clinical treatment and determination of prognosis.

Influence of the arrangement of vacuum chuck holes on the transmittance wavefront of large-aperture KDP in single-point diamond turning.

Serious edge effects of potassium dihydrogen phosphate (${{\rm KH}_2}{{\rm PO}_4}$KH2PO4, KDP) manufactured using single-point diamond turning (SPDT) often result in disqualification of the transmittance wavefront for high-power laser systems. In this paper, based on the theoretical analysis of sucker hole configuration and the pressure distribution law under the vacuum chuck condition of crystal elements, the influence of sucker hole configuration on the transmittance wavefront root-mean-square gradient (GRMS) is verified through fly-cutting experiments. By adopting the newly designed vacuum chuck, the vacuum-chucking quality is effectively improved, and the edge effect is accordingly suppressed in the SPDT. Moreover, the accuracy of the transmittance wavefront GRMS has an improvement of about 25% under the same processing parameters.

Adjuvant Chemotherapy with Chinese Herbal Medicine Formulas Versus Placebo in Patients with Lung Adenocarcinoma after Radical Surgery: a Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: The toxicity and side effects caused by adjuvant chemotherapy (ACT) after radical surgery for lung adenocarcinoma (LAC) lead to early termination frequently. This study was conducted to provide an objective basis for the effect of Chinese herbal medicine formulas (CHMFs) combined with chemotherapy in reducing toxicity and enhancing efficacy of ACT. METHOD: From February 17th, 2012 to March 20th, 2015, 233 patients from 7 hospitals diagnosed with LAC in IB~IIIA stage were randomly assigned into ACT + CHMF group (116 patients) and ACT + placebo group (117 patients). CHMF was taken orally until the end of chemotherapy. Chemotherapy-related toxic, side effects were investigated as the primary outcome. Disease-free survival (DFS) and overall survival (OS) were used as the secondary outcome. RESULTS: At one week following chemotherapy, the incidence of dry mouth, diarrhea and thrombocytopenia significantly decreased in CHMF group (P = 0.017, P = 0.033, P = 0.019, respectively). At two weeks following chemotherapy, fatigue and diarrhea were more obvious in the placebo group (P = 0.028, P = 0.025, respectively). In addition, patients in the CHMF group showed an increase in median DFS from 37.1 to 51.5 months compared with placebo group although there was no statistical significance (P = 0.16). In the stage IB subgroup, the CHMF group had a significantly better DFS (HR (95% CI) = 0.53 (0.28-0.99), P = 0.046). There was no significant difference in OS between the groups (P = 0.72). CONCLUSION: For patients with LAC, ACT combined with CHMF after radical surgery can prolong the DFS time especially in the early stage, and reduces the chemotherapy-related toxic and side effects. TRIAL REGISTRATION: NCT01441752. Registered 14 July, 2011.

Simulation of the nanosecond-pulse laser damage of KDP surface by the smoothed particle hydrodynamics method.

We present a simulation method to reproduce the damage crater formation and particle ejection phenomena observed in the laser-induced surface damage process of potassium dihydrogen phosphate (KDP) crystals. Based on the smoothed particle hydrodynamics method, which is commonly used for solving shock and blast problems, equivalent explosion simulation models of the laser-induced damage process have been established. Moreover, laser damage experiments combined with time-resolved techniques are performed on KDP surfaces to investigate the impact of laser fluences on the shockwave propagation and the particle ejection speed. We find that the simulation models can predict the laser-induced damage behaviors of the KDP crystal, which verifies the validity of the proposed method.

Epidermal Growth Factor Receptor Mutations in Resectable Non-Small Cell Lung Cancer Patients and their Potential Role in the Immune Landscape.

BACKGROUND The epidermal growth factor receptor (EGFR) is a therapeutic target for non-small cell lung cancer (NSCLC), but knowledge on gene mutations that contribute to NSCLC development and persistence is lacking. In this study, we investigated genetic variations in EGFR and their association with the clinical and pathological factors of NSCLC. MATERIAL AND METHODS Clinical cases (331 patients) and The Cancer Genome Atlas (TCGA) cases (1040 patients) were selected and analyzed using the refractory mutation systems cBioPortal and the Tumor Immune Estimation Resource (TIMER). RESULTS EGFR mutation frequencies were 54.4% (180 of 331 patients) and 8.0% (83 of 1040 patients) in the clinical and TCGA cohorts, respectively. EGFR mutations were strongly associated with smoking and pathology (P≤0.05) in the clinical cohort, and with gender, smoking, and pathology (P=0.001, P<0.001, and P<0.001, respectively) in TCGA cohort. In cases of lung squamous carcinoma (LUSC), EGFR was overexpressed as a result of DNA amplification, but this amplified expression showed no association with the overall survival (OS) or progression-free survival of LUSC patients. EGFR gene alterations were, however, associated with worse OS in lung adenocarcinoma (LUAD) patients. Immune cell infiltrates from LUAD and LUSC tumors differed according to EGFR expression. EGFR mutations resulted in a decline of immune infiltration or a lack of infiltrating immune cells in the NSCLC microenvironment. CONCLUSIONS Mutational profiles of the EGFR in NSCLC patients provide useful information for the use of tyrosine kinase inhibitors for adjuvant or neoadjuvant therapy and immunotherapy.

Isolation and Retrieval of Extracellular Vesicles for Liquid Biopsy of Malignant Ground-Glass Opacity.

Extracellular vesicles (EVs) are cell-released vesicles of submicrometer size. EVs contain a tissue-specific signature wherein a variety of proteins and nucleic acids are selectively packaged. Recent studies validate that EVs can be used for cancer diagnostics, staging, and treatment monitoring. EV-related clinical translation requires effective EV isolation as a prerequisite. However, lengthy procedures, low yield, low throughput, and high levels of contaminants disqualify the existing isolation approaches for large-scale clinical use. Hence, new approaches for rapid, efficient, and low-cost isolation of EVs in high purity for flexible analyses of the diverse contents in real-world clinical settings are highly desired yet are currently unavailable. Here, we report the effective use of heparin/polymer-coated microspheres (HPM) for EV isolation and retrieval. Approximately 81% of EVs can be isolated from plasma in 1 h with depletion of ∼99.5% plasma protein and nucleic acid contaminants, and 72% of isolated EVs can be retrieved with saline in 5 min for various cargo analyses. This approach was further validated with clinical samples derived from patients with malignant ground-glass opacity (GGO). In eight patients, the mutation concordance between EV DNA and tissue DNA is 39.8%. The prevalence and mutation count of EGFR, TP53, and NF1 are higher than those of other oncogenes and antioncogenes that are intensely associated with lung adenocarcinoma. Moreover, different mutation prevalence and patterns between smokers and nonsmokers can be observed. Our findings suggest that the combination of HPM assay and targeted sequencing of EV DNA could be translated in the differential diagnosis of malignant GGO with short turnaround time.

Inflammation Promotes Progression of Pancreatic Cancer Through WNT/ß-Catenin Pathway-Dependent Manner.

OBJECTIVE: Identify the molecular mechanism of inflammatory stimuli induced pancreatic cancer progression. METHODS: RNA-seq, microarray assay and bioinformatics analyses were used to identify differentially expressed genes. Immunohistochemical staining was performed to evaluate CD68, CD163, ß-catenin, CD103, CCL3 markers. Quantitative real-time polymerase chain reaction (qRT-PCR), luciferase reporter assay, apoptosis assay, wound healing assay and immunofluorescence were performed to study the relationship of inflammatory stimuli and WNT/ß-catenin pathway. RESULTS: Differentially expressed genes of macrophage-conditioned medium-treated pancreatic cancer cells were related with WNT/ß-catenin pathway. Inflammatory stimuli could activate WNT/ß-catenin signaling pathway. In 106 pancreatic cancer patients, nuclear ß-catenin expression of CD68-high group was much higher than CD68-low group (P < 0.05), as same as CD163 (P < 0.05). Inflammatory stimuli downregulated the expression of CCL3 via WNT/ß-catenin pathway and inhibited the chemotaxis of CD103 dendritic cells. Six pancreatic cancer prognosis associating genes were upregulated by inflammatory stimuli via WNT/ß-catenin pathway. Transforming growth factor-ß promoted malignant biological behavior of pancreatic cancer cells through WNT/ß-catenin pathway-dependent mechanism. CONCLUSIONS: Our present study provided a novel mechanism involved in the inflammation-driven cancer progression through tumor immune escape and downstream gene regulation of WNT/ß-catenin pathway-dependent manner.

Investigation of the laser-induced surface damage of KDP crystal by explosion simulation.

Under nanosecond pulse irradiation, laser-induced damage of Potassium Dihydrogen Phosphate (KDP) crystal is a multi-physical coupling process which mainly includes energy absorption by precursor defects, temperature and pressure rise in the absorption center, and subsequent micro-explosion event. Till now, related research work mainly focuses on modeling the energy absorption stage and determining the temperature or pressure in the absorption center, but knowledge about the explosion stage is rather limited. In this paper, laser-induced damage of KDP crystal has been investigated through explosion simulation. According to the laser damage test results and morphologies of the damage craters, typical precursor defects inducing KDP surface damage have been determined. Based on the knowledge, equivalent explosion simulation models of the laser damage process have been established to reproduce damage crater formation and shockwave propagation. Finally, laser damage experiments, combined with time resolved techniques, have been utilized to investigate the variation of damage crater size and shockwave speed with laser fluences. Simulation results given by single core explosion models agree well with the experimental results at fluences lower than 60 J/cm2, while a multicore explosion model is needed to reliably simulate damage crater formation at higher fluences.

The PI3K inhibitor buparlisib suppresses osteoclast formation and tumour cell growth in bone metastasis of lung cancer, as evidenced by multimodality molecular imaging.

Non­small cell lung cancer (NSCLC) metastasis commonly occurs in bone, which often results in pathological fractures. Sustained phosphoinositide­3­kinase (PI3K) signalling promotes the growth of PI3K­dependent NSCLC and elevates osteoclastogenic potential. The present study investigated the effects of a PI3K inhibitor on NSCLC growth in bone and osteoclast formation, and aimed to determine whether it could control symptoms associated with bone metastasis. A bone metastasis xenograft model was established by implanting NCI­H460­luc2 lung cancer cells, which contain a phosphatidylinositol­â€‹4,5­bisphosphate 3­kinase catalytic subunit α mutation, into the right tibiae of mice. After 1 week, the tumours were challenged with a PI3K inhibitor (buparlisib) or blank control for 3 weeks. Tumour growth and burden were longitudinally assessed in vivo via reporter gene bioluminescence imaging (BLI), small animal positron emission tomography/computed tomography (CT) [18F­fluorodeoxyglucose (18F­FDG)] and single­photon emission computed tomography/CT [99mTc­methylene diphosphonate (99mTc­MDP)] imaging. Tibia sections of intraosseous NCI­H460 tumours were analysed by immunohistochemistry (IHC), western blotting and flow cytometry. Dynamic weight bearing (DWB) tests were further performed to examine the improvement of symptoms associated with bone metastasis during the entire study. Administration of buparlisib significantly inhibited the progression of bone metastasis of NSCLC, as evidenced by significantly reduced uptake of 18F­FDG, 99mTc­MDP and BLI signals in the treated lesions. In addition, buparlisib appeared to inhibit the expression of tartrate­resistant acid phosphatase and receptor activator of nuclear factor­κB ligand, as determined by IHC. Buparlisib also resulted in increased cell apoptosis, as determined by a higher percentage of Annexin V staining and increased caspase 3 expression. Furthermore, buparlisib significantly increased weight­bearing capacity, as revealed by DWB tests. The PI3K inhibitor, buparlisib, suppressed osteoclast formation in vivo, and exhibited antitumour activity, thus leading to increased weight­bearing ability in mice with bone metastasis of lung cancer. Therefore, targeting the PI3K pathway may be a potential therapeutic strategy that prevents the structural skeletal damage associated with bone metastasis of lung cancer.

Preoperative brain MRI for clinical stage IA lung cancer: is routine scanning rational?

PURPOSE: Early detection and control of lung cancer brain metastases (BMs) are important. However, several guideline recommendations are inconsistent with regard to routine preoperative brain MRI, especially in patients with clinical stage IA lung cancer. Our study evaluated the value of preoperative brain MRI in patients with clinical stage IA lung cancer. METHODS: A retrospective analysis of patients with lung cancer was performed using a prospectively collected database. Clinical data and the results of brain MRI were collected and analyzed. RESULTS: Patients with pathologically proved primary lung cancer who underwent an MRI at initial diagnosis were identified (3392 patients). In total, 170 patients (5.0%) were diagnosed with BMs. The increased frequency of BMs was significantly associated with advanced clinical stage (P = 0.000) and pathological type (P = 0.011). BMs were detected in 11 out of 1595 patients with clinical stage IA lung cancer (0.7%). BMs were more common in patients with clinical stage cT1c lung cancer (1.9%) than those with clinical stage cT1a or cT1b (0.1%, odds ratio = 21.30, 95% confidence interval: 2.7-166.9, P = 0.000). All patients with stage IA lung cancer and BMs had solid lung lesions (P = 0.002). CONCLUSIONS: Preoperative brain MRI might help identify BMs in patients with lung cancer that has progressed beyond stage IA. In patients with clinical stage IA lung cancer, we do not recommend preoperative brain MRI, but it may potentially be beneficial in those with solid T1c cancers.