ALDH1+ tumor stem cells promote the progression of malignant fibrous tissue sarcoma by inhibiting SYNPO2 through hsa-mir-206.

This research aims to explore the mechanism by which microRNAs may regulate the biological behavior of tumor cells in ALDH1+ fibrosarcoma. We identified differentially expressed miRNAs in ALDH + NMFH-1 cells, screened genes related to sarcoma metastasis in the TCGA database, and finally obtained key genes regulated by miRNAs that are involved in metastasis. The function and mechanism of these key genes were then validated at the cellular level. Using the ULCAN database, a significant correlation was found between hsa-mir-206 and mortality in sarcoma patients. WGCNA analysis identified 352 genes related to tumor metastasis. Through Venn diagrams, we obtained 15 metastasis-related genes regulated by hsa-mir-206. Survival analysis showed that SYNPO2 expression is significantly correlated with survival rate and is significantly underexpressed in multiple tumors. SYNPO2 showed a negative correlation with macrophages and a positive correlation with CD8+ T cells. After inhibiting the expression of hsa-mir-206 with siRNA plasmids, the mRNA expression of SYNPO2 was significantly upregulated. The results of CCK8 assay, scratch assay, and transwell assay showed that the proliferation and migration ability of NFMH-1 cells were promoted after SYNPO2 was inhibited. ALDH1+ tumor stem cells promote the proliferation and invasion of malignant fibrous histiocytoma cells by inhibiting SYNPO2 through hsa-mir-206.

Facile fabrication of nano-bioactive glass functionalized blended hydrogel with nucleus pulposus-derived MSCs to improve regeneration potential in treatment of disc degeneration by in vivo rat model.

Orthopaedic medicine often treats intervertebral disc degeneration (IVDD), which is caused by nucleus pulposus (NP) tissue damage and mechanical stress. Bioactive glasses (BGs), widely used for bone regeneration, can incorporate therapeutic ions into their network. Manganese (Mn) activates human osteoblast integrins, proliferation, and spreading. The CMnBGNPs-NPMSCs are carboxymethyl cellulose hydrogels functionalized with MnBGsNPs and NP-derived mesenchymal stem cells to treat IVDD. To ensure stability and biocompatibility of CMnBGNPs-NPMSCs were characterized for rheological properties like gelation time and swelling ratio. Gene expression analysis of PAX1, FOXF1, CA12, HBB, and OVOS2 via qRT-PCR further assessed the hydrogel's characteristics. Rat models with induced IVDD had hydrogel-MSC composite injected into their intervertebral discs for in vivo studies. Histological examination, immunohistochemical staining for inflammation and disc regeneration markers, and disc height assessments assessed therapeutic efficacy. CMnBGNPs-NPMSCs show promising results for IVDD treatment, offering a novel therapeutic strategy with clinical implications for degenerative disc diseases.

Injectable smart-blended hydrogel cross-linked with Vanillin to accelerate differentiation of intervertebral disc-derived stem cells (IVDSCs) for promoting degenerative nucleolus pulposus in a rat model.

BACKGROUND: The nucleus pulposus (NP) degradation is a primary factor in intervertebral disk degeneration (IVD) and a major contributor to low back pain. Intervertebral disk-derived stem cell (IVDSC) therapy presents a promising solution, yet identifying suitable cell carriers for NP transplantation remains challenging. The present study investigates this issue by developing smart injectable hydrogels incorporating vanillin (V) and hyaluronic acid (HA) encapsulated with IVDSCs to facilitate IVD regeneration. MATERIALS AND METHODS: The hydrogel was cross linked by carbodiimide-succinimide (EDC-NHS) method. Enhanced mechanical properties were achieved by integrating collagen and HA into the hydrogel. The rheological analysis revealed the pre-gel viscoelastic and shear-thinning characteristics. RESULTS: In vitro, cell viability was maintained up to 500 µg/mL, with a high proliferation rate observed over 14 days. The hydrogels supported multilineage differentiation, as confirmed by osteogenic and adipogenic induction. Anti-inflammatory effects were demonstrated by reduced cytokine release (TNF-α, IL-6, IL-1ß) after 24 h of treatment. Gene expression studies indicated elevated levels of chondrocyte markers (Acan, Sox9, Col2). In vivo, hydrogel injection into the NP was monitored via X-ray imaging, showing a significant increase in disk height index (DHI%) after 8 weeks, alongside improved histologic scores. Biomechanical testing revealed that the hydrogel effectively mimicked NP properties, enhancing compressive stiffness and reducing neutral zone stiffness post-denucleation. CONCLUSION: The results suggest that the synthesized VCHA-NP hydrogel can be used as an alternative to NPs, offering a promising path for IVD regeneration.

Highly Safe Electrolyte Enabled via Controllable Polysulfide Release and Efficient Conversion for Advanced Lithium-Sulfur Batteries.

Conventional lithium-sulfur batteries often suffer from fatal problems such as high flammability, polysulfide shuttling, and lithium dendrites growth. Here, highly-safe lithium-sulfur batteries based on flame-retardant electrolyte (dimethoxyether/1,1,2,2-tetrafluoroethyl 2,2,3,3-tetrafluoropropyl ether) coupled with functional separator (nanoconductive carbon-coated cellulose nonwoven) to resolve aforementioned bottle-neck issues are demonstrated. It is found that this flame-retardant electrolyte exhibits excellent flame retardancy and low solubility of polysulfide. In addition, Li/Li symmetrical cells using such flame-retardant electrolyte deliver extraordinary long-term cycling stability (less than 10 mV overpotential) for over 2500 h at 1.0 mA cm-2 and 1.0 mAh cm-2 . Moreover, bare sulfur cathode-based lithium-sulfur batteries using this flame retardant electrolyte coupled with nanoconductive carbon-coated cellulose separator can retain 83.6% discharge capacity after 200 cycles at 0.5 C. Under high charge/discharge rate (4 C), lithium-sulfur cells still show high charge/discharge capacity of ≈350 mAh g-1 . Even at an elevated temperature of 60 °C, discharge capacity of 870 mAh g-1 can be retained. More importantly, high-loading bare sulfur cathode (4 mg cm-2 )-based lithium-sulfur batteries can also deliver high charge/discharge capacity over 806 mAh g-1 after 56 cycles. Undoubtedly, the strategy of flame retardant electrolyte coupled with carbon-coated separator enlightens highly safe lithium-sulfur batteries at a wide range of temperature.

Highly Reversible Cuprous Mediated Cathode Chemistry for Magnesium Batteries.

Sluggish kinetics and poor reversibility of cathode chemistry is the major challenge for magnesium batteries to achieve high volumetric capacity. Introduction of the cuprous ion (Cu+ ) as a charge carrier can decouple the magnesiation related energy storage from the cathode electrochemistry. Cu+ is generated from a fast equilibrium between copper selenide electrode and Mg electrolyte during standing time, rather than in the electrochemical process. A reversible chemical magnesiation/de-magnesiation can be driven by this solid/liquid equilibrium. During a typical discharge process, Cu+ is reduced to Cu and drives the equilibrium to promote the magnesiation process. The reversible Cu to Cu+ redox promotes the recharge process. This novel Cu+ mediated cathode chemistry of Mg battery leads to a high reversible areal capacity of 12.5 mAh cm-2 with high mass loading (49.1 mg cm-2 ) of the electrode. 80 % capacity retention can be achieved for 200 cycles after a conditioning process.

Fluorescence Probing of Active Lithium Distribution in Lithium Metal Anodes.

The uncontrollable growth of Li dendrites and the accumulation of byproducts are two severe concerns for lithium metal batteries, which leads to safety hazards and a low Coulombic efficiency. To investigate the deterioration of the cell, it is important to figure out the distribution of active Li species on the anode surface and distinguish Li dendrites from byproducts. However, it is still challenging to identify these issues by conventional visual observation methods. In this work, we introduce a novel fluorescent probing strategy using 9,10-dimethylanthracene (DMA). By marking the cycled Li-anode surface, the active Li distribution can be visualized by the fluorescence quenching of DMA reacting with active Li. The method demonstrates validity for electrolyte selection and predictive detection of uneven Li deposition on Li metal anodes. Furthermore, the location of dendrites can be clearly identified after destructive utilization of the anode, which will contribute to the development of failure-analysis technology for Li metal batteries.

[An epidemiological investigation of chronic kidney disease in children with hearing disorder in Hunan province, China].

OBJECTIVE: To investigate the prevalence of chronic kidney disease (CKD) among the children with hearing disorder in Hunan province, China. METHODS: In this cross-sectional study, the multi-stage cluster sampling method was used to select 1 500 children as subjects. Questionnaire surveys, physical examinations, and laboratory examinations were performed on the spot. RESULTS: Among the 1 500 children, 1 459 with complete data were included in analysis. Among the 1 459 children, 43 had CKD, with a prevalence rate of 2.95%. The <7 years group had a significantly higher prevalence rate than the 7-14 years group [5.8% (35/604) vs 0.9% (8/855); P<0.05]. Among the 43 children with CKD, 31 (72%) had proteinuria, 27 (63%) had hematuria, and 11 (26%) had a decreased glomerular filtration rate. Among the 43 children with CKD, stage 1, 2, 3a, 3b, 4, and 5 CKD accounted for 30% (13 cases), 44% (19 cases), 12% (5 cases), 7% (3 cases), 7% (3 cases), and 0% (0 case) respectively. The prevalence rate of CKD increased with the severity of hearing disorder (P<0.01). CONCLUSIONS: The prevalence rate of CKD is higher among the children with hearing disorder in Hunan province. Most children have early-stage CKD. CKD is commonly seen in preschool children. Severity of hearing disorder is associated with the prevalence of CKD.

A Retrospective Study of 91 Patients Treated with Percutaneous Kyphoplasty for Mild Osteoporotic Vertebral Compression Fractures and a New Evaluation Scale of Shape and Filling Effect of Cement.

BACKGROUND: Percutaneous kyphoplasty (PKP) is commonly used to treat severe osteoporotic vertebral compression fractures (OVCFs) by restoring vertebral height. However, its application in mild cases is not frequently discussed. METHODS: The study retrospectively included 100 treated vertebral bodies of the 91 patients mentioned before, and efficacy was evaluated using visual analog scale (VAS) and Oswestry Disability Index (ODI) scores preoperatively, 2 days postoperatively, and at 1 and 6 months after treatment, as well as mean variation in vertebral body height. The study also examined complications such as pain recurrence, delayed vertebral fracture, and loss of vertebral height, and developed a scale to assess the shape and filling effect of cement (SFEC) and its impact on complications. RESULTS: The results showed significant reductions in mean VAS and ODI scores from pre-to post-surgery and an increase in vertebral body height. However, complications occurred in 10 patients who received treatment for 11 vertebral bodies, including pain recurrence, fractures, and loss of vertebral height. Among the 10 patients with complications, 7 (63.6%) vertebral bodies had dissatisfied SFEC scores, compared with 22 (24.7%) vertebral bodies with dissatisfied SFEC scores in 81 patients without complications (89 vertebral bodies). CONCLUSIONS: PKP is a safe and effective method for treating mild OVCFs, but attention should be paid to the shape and filling effects of cement during surgery to prevent later complications. The developed SFEC scale provides a specific and quantitative standards for evaluating the recovery status after PKP, which need further validations.

Succession of microbiota and its influence on the dynamics of volatile compounds in the semi-artificial inoculation fermentation of mulberry wine.

To improve the delightful flavor of mulberry wine through semi-artificial inoculation fermentation with Saccharomyces cerevisiae, we studied the dynamics change of microbiota, along with the physicochemical properties and metabolite profiles and their interaction relationship during the fermentation process. The abundance of lactic acid bacteria (Weissella, Lactobacillus, Fructobacillus, and Pediococcus) increased significantly during fermentation, while yeasts gradually established dominance. The inter-kingdom network of the dominant genera analysis further identified the following as core microbiota: Alternaria, Botrytis, Kazachstania, Acremonium, Mycosphaerella, Pediococcus, Gardnerella, and Schizothecium. Additionally, pH, alcohol, and total acid were significantly affected by microbiota variation. Fourteen of all identified volatile compounds with key different aromas were screened using PCA, OPLS-DA, and rOAV. The network of interconnected core microbiota with key different aromas revealed that Kazachstania and Pediococcus had stronger correlations with 1-butanol, 3-methyl-, propanoic acid, and 2-methyl-ethyl ester.

Capnographic monitoring reduces hypoxia incidence in older patients undergoing gastrointestinal endoscopy under propofol sedation: study protocol for a multicenter randomized controlled trial.

BACKGROUND: Hypoxia is a very common adverse event that occurs during gastrointestinal endoscopy under sedation, especially in older patients, owing to limited reservation of heart, brain, lung, and other organs. Prolonged or severe hypoxia can cause ischemia of the coronary artery and permanent nervous system damage, and even result in death. Hence, it is imperative to reduce or prevent hypoxia during gastrointestinal endoscopy under sedation in older patients. Although several oxygen delivery methods would reduce hypoxia during this procedure, early detection of respiratory depression and early administration of intervention would be the best method to reduce or even confirm the hypoxia. Capnographic monitoring is reportedly more sensitive for detecting respiratory depression before the onset of hypoxia than the current clinical routine monitoring of pulse oxygen saturation; however, its effect is controversial. Therefore, in this study, we aimed to improve the safety of gastrointestinal endoscopy under sedation in older patients. METHODS: A multicenter, randomized, single-blind, two-arm parallel-group, controlled with an active comparator, interventional superiority clinical trial will be conducted to evaluate the impact of an additional capnographic monitoring-based intervention on the incidence of hypoxia in older patients. Patients (n = 1800) scheduled for gastrointestinal endoscopy with propofol sedation will be randomly assigned to either a control or interventional arm, wherein standard or capnographic monitoring is implemented, respectively. DISCUSSION: This study primarily aims to examine whether an additional capnographic monitoring-based intervention can reduce the incidence of hypoxia in older patients during gastrointestinal endoscopy under propofol and sufentanil sedation. The results of this study may extensively impact gastrointestinal endoscopy under sedation and the development of associated guidelines. TRIAL REGISTRATION: ClinicalTrials.gov NCT05030870. Registered on September 1, 2021.

Exosome miR-4738-3p-mediated regulation of COL1A2 through the NF-κB and inflammation signaling pathway alleviates osteoarthritis low-grade inflammation symptoms.

This study aimed to elucidate the roles of microRNA (miR)-4738-3p and the collagen type I alpha 2 chain (COL1A2) gene in the pathogenesis of osteoarthritis (OA) through bioinformatics analysis and cellular assays. The GSE55235 dataset was analyzed using the weighted gene co-expression network analysis (WGCNA) method to identify gene modules associated with OA. Key overlapping genes were identified from these modules and the GSE55235-differential expressed genes (DEGs). The expression levels of selected genes were determined in C28/I2 cells using the quantitative real-time polymerase chain reaction (qRT-PCR). The interaction between miR-4738-3p and COL1A2 was examined in the context of interleukin 1 beta (IL-1ß) induction. Exosome characterization was achieved through transmission electron microscopy (TEM), western blotting (WB), and other analyses. The study also investigated the functional relevance of miR-4738-3p in OA pathology through various molecular and cellular assays. Our findings revealed that the green module exhibited a strong correlation with the OA phenotype in the GSE55235 dataset, with COL1A2 emerging as a hub gene and miR-4738-3p as its key downstream target. IL-1ß induction suggested that COL1A2 is involved in inflammation and apoptosis, while miR-4738-3p appeared to play an antagonistic role. The analysis of exosomes underscored the significance of miR-4738-3p in cellular communication, with an enhanced level of exo-miR-4738-3p antagonizing IL-1ß-induced inflammation and promoting cell survival. Conversely, a reduction in exo-miR-4738-3p led to increased cell damage. This study established a clear regulatory relationship between miR-4738-3p and COL1A2, with the nuclear factor kappa B (NF-κB) signaling pathway playing a central role in this regulation. The miR-4738-3p significantly influences the OA-associated inflammation, primarily through modulation of COL1A2 and the NF-κB pathway. Therefore, targeting miR-4738-3p offers a potential therapeutic approach for OA, with exosome miR-4738-3p presenting a promising strategy.

[Value of endobronchial ultrasound-transbronchial needle aspiration biopsy for diagnosis of PET-CT positive mediastinal lymph nodes].

OBJECTIVE: To evaluate the clinical value of endobronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA) biopsy for diagnosis of PET-CT positive mediastinal lymph nodes. METHODS: One hundred and twenty-six patients with lung cancer undergoing both PET-CT scanning and EBUS-TBNA biopsy in the First Affiliated Hospital of Guanzhou Medical College from July 2008 to August 2010 were included in this study. There were 89 male and 37 female patients with a mean age of 56.3 years (range 34 to 81 years). (18)FDG-PET was considered positive in mediastinal nodes if the PET-CT reported hypermetabolic activity consistent with malignant disease (standardized uptake value > 2.5). All of the patients were clinically followed up. RESULTS: Among the 126 patients, 185 stations of lymph nodes were punctured. The mean diameter of the nodes was 13.6 mm and the range was 6 - 23 mm. There were no procedural complications. The diagnostic accuracy, sensitivity, and specificity of EBUS-TBNA were 95.7%, 95.7%, and 100%, respectively. CONCLUSIONS: EBUS-TBNA is a minimally invasive, highly effective and accurate, practical and safe procedure for diagnosis of PET-CT positive mediastinal lymph nodes.

How Does Employee Green Behavior Impact Employee Well-Being? An Empirical Analysis.

The issue of environmental protection and sustainable development is a key research focus across multiple fields. Employee green behavior is considered to be an important micro-activity to address this. Researchers in the field of organizational behavior and sustainable development have been focusing on the influencing factors of employee green behavior. However, few have explored the beneficial effects of employee green behavior on behavioral implementers. The objective of this study is to investigate the relationships among employee green behavior, self-esteem, perceived organizational support for employee environmental efforts, and employee well-being, and to explore a new dimension of employee green behavior. We empirically examined the underlying framework by conducting two surveys to collect data from 900 employees working in manufacturing, construction, and the service industry in China. We performed multilevel path analysis using SPSS and AMOS software, and confirmed that employee green behavior includes four dimensions: green learning, individual practice, influencing others, and organizational voices. Further, employee green behavior has a significant positive impact on self-esteem, which in turn is converted into employee well-being. Finally, perceived organizational support for employee environmental efforts not only positively moderated the relationship between employee green behavior and self-esteem, but was also confirmed as a moderated mediation model. This study enriches the current literature on the measurement framework and variables of employee green behavior.

Case Report: Complete Response to Nivolumab in a Patient With Programmed Cell Death 1 Ligand 1-Positive and Multiple Gene-Driven Anaplastic Lymphoma Kinase Tyrosine Kinase Inhibitor-Resistant Lung Adenocarcinoma.

Multiple gene-driven programmed cell death 1 ligand 1 (PD-L1)-expressing non-small-cell lung cancer (NSCLC) is very rare. Previous studies have shown that patients with NSCLC with anaplastic lymphoma kinase (ALK) gene rearrangement rarely benefit from PD-L1 inhibitors. Besides the secondary mutations in ALK gene, other mechanisms might contribute to tumor resistance to ALK tyrosine kinase inhibitors (ALK-TKIs). Herein, we present a case of PD-L1-overexpressing lung adenocarcinoma that harbors both EML4-ALK gene rearrangement and BRAF mutation. In particular, a second molecular analysis after resistance to first- and second-generation ALK-TKIs revealed a high PD-L1 expression and tumor mutation burden. Therefore, treatment with nivolumab monotherapy, an anti-PD-1 inhibitor, was started and the patient achieved complete remission. This case report suggested that PD-1 inhibitors might be an effective treatment option for patients with multiple gene-driven PD-L1-expressing NSCLC harboring ALK gene rearrangement.

MicroRNA-590-3p relieves hypoxia/reoxygenation induced cardiomyocytes apoptosis and autophagy by targeting HIF-1α.

Autophagy and apoptosis are key factors in myocardial ischemia/reperfusion (I/R) injury. MicroRNAs (miRNAs or miRs) participate in occurrence and development of myocardial I/R injury by regulating autophagy and apoptosis. The purpose of the present study was to investigate the role of miR-590-3p in the regulation of autophagy and apoptosis in hypoxia/reoxygenation (H/R)-treated cardiomyocytes. Following 6 h hypoxia and 6 h reoxygenation in primary rat cardiomyocytes, miR-590-3p was downregulated. Transfection of miR-590-3p mimic inhibited the increased autophagy and apoptosis following H/R treatment. Subsequent experiments demonstrated that miR-590-3p regulated induction of autophagy and apoptosis by targeting hypoxia inducible factor (HIF)-1α. Forced expression of HIF-1α rescued the protective effect of miR-590-3p on H/R-induced cardiomyocytes. In summary, the present study showed that miR-590-3p exhibited a protective effect on H/R-induced cardiomyocyte injury and may be a novel target for the treatment of myocardial ischemia disease.

Investigation of PALB2 Mutation and Correlation With Immunotherapy Biomarker in Chinese Non-Small Cell Lung Cancer Patients.

BACKGROUND: PALB2, a gene in the homologous recombination repair (HRR) pathway of the DNA damage response (DDR), is associated with the efficacy of platinum-based chemotherapy, immunotherapy, and PARP inhibitor therapy in several tumors. However, the PALB2 characteristics, its correlation with immunotherapy biomarker, and the prognostic effect of immunotherapy in non-small cell lung cancer (NSCLC) were unknown. METHODS: Tumor tissue samples from advanced Chinese NSCLC patients were analyzed by next-generation sequencing (NGS) (panel on 381/733-gene). Tumor mutation burden (TMB) is defined as the total number of somatic non-synonymous mutations in the coding region. Microsatellite instability (MSI) was evaluated by NGS of 500 known MSI loci. Programmed Cell Death-Ligand 1 (PD-L1) expression was evaluated using immunohistochemistry (Dako 22C3 or SP263). One independent cohort (Rizvi2018.NSCLC.240.NGS cohort) containing genomic and clinical data from 240 patients with advanced NSCLC and two cohorts (the OAK and POPLAR study cohort) containing genomic and clinical data from 429 patients with advanced NSCLC were used to analyze the prognostic effect of PALB2 on immunotherapy. RESULTS: Genetic mutation of 5,227 NSCLC patients were analyzed using NGS, of which 162 (3.1%) harbored germline PALB2 mutation (PALB2gmut ) and 87 (1.66%) harbored somatic PALB2 mutation (PALB2 smut). In NSCLC patients with PALB2gmut and PALB2smut , the most frequently mutated gene was TP53 (65%, 64%). PALB2smut (14.52 Muts/Mb) was associated with higher TMB (p < 0.001) than PALB wild-type (PALB2wt ) (6.15 Muts/Mb). However, there was no significant difference in TMB between PALB2gmut (6.45 Muts/Mb) and PALB2 wt (6.15 Muts/Mb) (p = 0.64). There was no difference in PD-L1 expression among PALB2gmut , PALB2smut , and PALB2wt . In the Rizvi2018.NSCLC.240.NGS cohort, there was no difference in progression-free survival (PFS) (HR =1.06, p = 0.93) between PALB2 mutation (3.15 months) and PALB2wt (3.17 months). The OAK and POPLAR study cohort of NSCLC patients showed that there was no difference in overall survival (OS) (HR =1.1, p = 0.75) between PALB2 mutation (10.38 months) and PALB2wt (11.07 months). CONCLUSIONS: These findings suggest that PALB2 may not be used as a biomarker for determining prognosis on immunotherapy in NSCLC.

Circular RNA circFAT1(e2) Promotes Osteosarcoma Progression and Metastasis by Sponging miR-181b and Regulating HK2 Expression.

As a subclass of noncoding RNAs, circular RNAs (circRNAs) have been demonstrated to play a critical role in regulating gene expression in eukaryotes. Recent studies have revealed the pivotal functions of circRNAs in cancer progression. Nevertheless, how circRNAs participate in osteosarcoma (OS) development and progression are not well understood. In the present study, we identified a circRNA circFAT1(e2) with an upregulated expression level in OS tissues. By functional experiments, we found that circFAT1(e2) depletion significantly suppressed the proliferation and reduced migration in OS. In terms of mechanism, we found that circFAT1(e2) inhibited miR-181b, while miR-181b targeted HK2. By releasing the inhibition of miR-181b on HK2 expression, leading to attenuated OS progression. Mechanistic investigations suggested that circFAT1(e2) served as a competing endogenous RNA (ceRNA) of miR-181b to enhance HK2 expression. On the whole, our study indicated that circFAT1(e2) exerted oncogenic roles in OS and suggested the circFAT1(e2)/miR-181b/HK2 axis might be a potential therapeutic target.

Next Generation Sequencing Reveals a Synchronous Trilateral Lung Adenocarcinoma Case with Distinct Driver Alterations of EGFR 19 Deletion or EGFR 20 Insertion or EZR-ROS1 Fusion.

OBJECTIVE: Synchronous multiple primary lung cancer (SMPLC) has a reported occurrence from 0.5% to 2% in lung cancer, and the surgical treatment and prognosis were quite diverse. With the discovery of driver mutations in lung adenocarcinoma (ADC), next-generation sequencing (NGS) would provide an explicit answer to the key question, whether individual tumors represent intrapulmonary metastases or independent tumors. Here, we reported a 64-year-old female diagnosed with a synchronous trilateral early-stage ADC with distinct driver alterations. MATERIALS AND METHODS: NGS test targeting 31 cancer-relevant genes and amplification RNA sequencing (if gene fusion was found on DNA level) were performed on the surgical tumor tissue. RESULTS: A 64-year-old Chinese female never smoker was found with one nodule in the right upper lobe and two nodules in the right middle lobe through chest computed tomography. The lesions were resected through video-assisted thoracic surgery and diagnosed with stage IA ADC, T1N0M0, in the postoperative pathology. NGS detected three independent driver mutations in three primary sites, respectively, EGFR 19del, EGFR 20ins and ROS1 fusion. CONCLUSION: This is the first report of a synchronous trilateral early-stage ADC with distinct driver alterations. All individual tumors were independent identified by NGS methodology, which had provided a clear answer to the key question of SMPLC in this case and should be used as a routine genetic test to explore fully pathological diagnosis and more comprehensive oncogenesis information in the early-stage ADC clinical prevention.

Spectrum of Pathogenic Germline Mutations in Chinese Lung Cancer Patients through Next-Generation Sequencing.

Lung cancer is currently a leading cause of cancer-associated mortality worldwide. Despite the increasing evidences of variants that were associated with lung cancer risk, investigations of genetic factors and their roles in genetic susceptibility to lung cancer were limited. Here we systematically investigated the spectrum of pathogenic germline mutations in Chinese population with lung cancer. Genomic profiling of DNA was performed through next-generation sequencing (NGS) on tissue biopsy from 1764 Chinese lung cancer patients with a 381 cancer gene panel between January 01, 2017 and May 07, 2019. Patients with germline mutations were identified, and their clinical information were collected. Of 1764 patients with lung cancer, 67 (3.8%) patients were identified to carry pathogenic or likely pathogenic germline mutations in 25 cancer predisposition genes, with a frequency of 3.6% in lung adenocarcinoma (49/1349), 4.3% in squamous cell lung cancer (14/322), 5.6% in small cell lung cancer (4/72), and none in lung adenosquamous carcinoma (0/21), respectively. The highest pathogenic germline mutational prevalence were found in BRCA2 (0.79%), CHEK2 (0.40%), BRCA1 (0.34%), and TP53 (0.34%). Two splice mutations were reported for the first time in this study. Notably, a majority (85.5%) of the detected germline mutations fell in DNA damage repair pathways.

Circular RNA circHIPK3 Promotes Cell Metastasis through miR-637/STAT3 Axis in Osteosarcoma.

Recent studies have suggested that circular RNAs play an important role in the progression of various cancers. However, few studies have revealed the great value of circRNAs in the diagnosis and prognosis prediction of osteosarcoma (OS). In this study, we performed experiments with the human OS cell lines and the results showed that the expression of circHIPK3 in OS cell lines was significantly upregulated compared to that in the normal cell line. In addition, the results showed that circHIPK3 could promote the migration, invasion, and growth of OS cells. Furthermore, miR-637 was identified as a target of circHIPK3, while STAT3 was targeted by miR-637. circHIPK3 could promote STAT3 expression via interacting with miR-637 in OS cells. In conclusion, our research uncovered an important role of the circHIPK3/miR-637/STAT3 pathway in the migration and invasion of OS cells and suggested that circHIPK3 may be a prognostic marker and a promising therapeutic target for OS.