Compared to other conventional scaffold fabrication techniques, three-dimensional (3D) printing is advantageous in producing bone tissue engineering scaffolds with customized shape, tailored pore size/porosity, required mechanical properties and even desirable biomolecule delivery capability. However, for scaffolds with a large volume, it is highly difficult to get seeded cells to migrate to the central region of the scaffolds, resulting in an inhomogeneous cell distribution and therefore lowering the bone forming ability. To overcome this major obstacle, in this study, cell-laden bone tissue engineering scaffolds consisting of osteogenic peptide (OP) loaded β -tricalcium phosphate (TCP)/poly(lactic- co -glycolic acid) (PLGA) (OP/TCP/PLGA, designated as OTP) nanocomposite struts and rat bone marrow derived mesenchymal stem cell (rBMSC)-laden gelatin/GelMA hydrogel rods were produced through ‘dual-nozzle’ low temperature hybrid 3D printing. The cell-laden scaffolds exhibited a bi-phasic structure and had a mechanical modulus of about 19.6 MPa, which was similar to that of human cancellous bone. OP can be released from the hybrid scaffolds in a sustained manner and achieved a cumulative release level of about 78% after 24 d. rBMSCs encapsulated in the hydrogel rods exhibited a cell viability of about 87.4% right after low temperature hybrid 3D printing and could be released from the hydrogel rods to achieve cell anchorage on the surface of adjacent OTP struts. The OP released from OTP struts enhanced rBMSCs proliferation. Compared to rBMSC-laden hybrid scaffolds without OP incorporation, the rBMSC-laden hybrid scaffolds incorporated with OP significantly up-regulated osteogenic differentiation of rBMSCs by showing a higher level of alkaline phosphatase expression and calcium deposition. This ‘proof-of-concept’ study has provided a facile method to form cell-laden bone tissue engineering scaffolds with not only required mechanical strength, biomimetic structure and sustained biomolecule release profile but also excellent cell delivery capability with uniform cell distribution, which can improve the bone forming ability in the body.

Variants of cancer susceptibility genes other than BRCA1/2 have been proved to be associated with increased risks of breast cancer. This study was performed to investigate the spectrum and prevalence of mutations in 10 cancer susceptibility genes in paired tumor/normal tissues of 292 unselected Chinese breast cancer patients. We performed an analysis of germline and somatic variants in ATM, CDH1, CHEK2, ESR1, GATA3, MAP3K1, MSH2, PALB2, RB1 and STK11 genes by integrating microfluidic PCR‐based target enrichment and next‐generation sequencing technologies. In total, 3 germline and 25 somatic deleterious mutations were found among 27 patients (9.25%), and 17 of them were novel mutations. Most deleterious mutations were prevalent in luminal A invasive breast cancer (P = .014). We also observed 83 variants of uncertain significance (VUS) in 100 patients (34.25%), 23 of which were predicted to be deleterious by in silico prediction programs (MetaSVM and MetaLR). VUS carriers had higher positive rate of lymph node metastasis than non‐carriers (P = .008) and were predominantly present in ER+ tumors (P = .018). Our findings would enhance the understanding of the molecular mechanisms of breast cancer in Chinese population.

Esophageal liposarcoma is a rare malignant tumor and an esophageal dedifferentiated liposarcoma (DDL) is extremely rare. There are no reports on the treatment of DDL by thoracoscopic surgery. A 38-year-old woman presented with dysphagia and dyspnea. Imaging examination showed a large mass in the posterior mediastinum. The patient also developed respiratory failure and it was unclear whether this was caused by a mass from inside or outside the esophagus. We decided to perform thoracoscopic exploration to relieve the obstruction caused by tracheal compression. The upper segment of the esophagus was split longitudinally, and most of the mass could be removed from the esophageal lumen to the thoracic cavity. The pedicle was excised by linear cutting closers under mirrors. Little residual mass was visualized by gastroscopy. The mucous and muscular layers were closed by interrupted sutures. Pathological examination showed that the mass was a DDL. The patient did not have any dysphagia or dyspnea 2 wk postoperatively and refused any further treatment. Computed tomography and esophagoscopy did not find any recurrence at up to 20 mo postoperatively. Thoracoscopy can be used to treat large esophageal masses.

Background: Non-small cell lung cancer (NSCLC) is one of the most lethal malignancies worldwide. Deepening understanding of the pathogenesis of NSCLC is quite important for its treatment. Circular (circ) RNA_0015278 has been found to be downregulated in NSCLC, but its role in NSCLC and the underlying regulatory mechanism is unknown. Methods: Circ_0015278, microRNA (miR)-1278 and SOCS6 were analyzed with real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) or western blot. Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) staining were used to evaluate cell proliferation. The colony forming capacity and invasion of NSCLC cells were assessed with colony formation and transwell assays, respectively. The interaction among circ_0015278, miR-1278, and SOCS6 was evaluated using luciferase, receptor interacting protein (RIP), and RNA-pull down assays. Cell apoptosis was analyzed using flow cytometry. A subcutaneous NSCLC xenograft mouse model was established for evaluating circ_0015278-mediated effects on the growth of NSCLC in vivo. Results: Circ_0015278 was downregulated in NSCLC tissues and cells, and its reduced expression indicated poor prognosis. Overexpression of circ_0015278 restrained the proliferation, colony formation, invasion, and epithelial-mesenchymal transition (EMT) of NSCLC cells and induced NSCLC cell apoptosis. Moreover, overexpression of circ_0015278 inhibited the growth of NSCLC in vivo. Mechanically, circ_0015278 acted as an miR-1278 sponge to reduce its quantity, and miR-1278 targeted SOCS6 to inhibit its expression in NSCLC cells. Circ_0015278 promoted SOCS6 expression by sponging miR-1,278 in NSCLC cells. Overexpression of circ_0015278 attenuated the malignant phenotypes of NSCLC through sponging miR-1278 and consequently promoting SOCS6 expression. Conclusions: We demonstrated for the first time that circ_0015278 attenuated the progression of NSCLC via targeting the miR-1278/SOCS6 axis, which provides potential diagnostic biomarkers and therapeutic targets.

Objective We aimed to construct a novel prognostic model based on N6-methyladenosine (m6A)-related autophagy genes for predicting the prognosis of lung squamous cell carcinoma (LUSC). Methods Gene expression profiles and clinical information of Patients with LUSC were downloaded from The Cancer Genome Atlas (TCGA) database. In addition, m6A- and autophagy-related gene profiles were obtained from TCGA and Human Autophagy Database, respectively. Pearson correlation analysis was performed to identify the m6A-related autophagy genes, and univariate Cox regression analysis was conducted to screen for genes associated with prognosis. Based on these genes, LASSO Cox regression analysis was used to construct a prognostic model. The corresponding prognostic score (PS) was calculated, and patients with LUSC were assigned to low- and high-risk groups according to the median PS value. An independent dataset (GSE37745) was used to validate the prognostic ability of the model. CIBERSORT was used to calculate the differences in immune cell infiltration between the high- and low-risk groups. Results Seven m6A-related autophagy genes were screened to construct a prognostic model: CASP4, CDKN1A, DLC1, ITGB1, PINK1, TP63, and EIF4EBP1. In the training and validation sets, patients in the high-risk group had worse survival times than those in the low-risk group; the areas under the receiver operating characteristic curves were 0.958 and 0.759, respectively. There were differences in m6A levels and immune cell infiltration between the high- and low-risk groups. Conclusions Our prognostic model of the seven m6A-related autophagy genes had significant predictive value for LUSC; thus, these genes may serve as autophagy-related therapeutic targets in clinical practice.

Pulmonary sequestration (PS) is an uncommon lung disease. Carcinoid tumorlets in pulmonary sequestration are extremely rare. This case report presents a rare clinical case of carcinoid tumorlet in pulmonary sequestration with bronchiectasis after breast cancer. A 64-year-old female was diagnosed with infiltrating ductal carcinoma of the left breast in February 2009. Chest computer tomography (CT) revealed a cystic low-density mass of ~2.5x4.7 cm in the right lower lung field, as well as cystic bronchiectasis in the right lower lobe. A right lower lobectomy was performed. In the surgery, abnormal vessel growth from the mass was found. Therefore, intralobar PS was diagnosed and pathological examination supported the diagnosis. Subsequently, pathological examination identified a carcinoid tumorlet in the PS. This report presents a rare clinical case of PS and bronchiectasis as well as carcinoid tumorlet in PS following diagnosis of breast cancer three years earlier. When a mass is found in the lung of patents with bronchiectasis with a history of breast cancer, aggressive therapy should be considered, since the mass may be a tumor or precancerous lesion.