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•Cartilage decellularized matrix (CDM) is processed into inks for 3D printing.•CDM-based scaffolds with controlled 3D shape and pore structure are obtained.•Fibers can improve the ...mechanical property of 3D-printed CDM scaffolds.•3D-printed fiber-reinforced CDM scaffolds exhibit elasticity in wet condition.•Fiber-reinforced CDM scaffolds can repair articular cartilage defects in rabbits.
Cartilage decellularized matrix (CDM) is considered a promising biomaterial for fabricating cartilage tissue engineering scaffolds. An ideal CDM-based scaffold should possess customizable 3D shape for complex tissue regeneration and proper pore size for cell infiltration, as well as provide mechanical support for cell growth. 3D printing is an efficiently technique for preparing customizable 3D scaffolds, however, fabricating CDM-based 3D-printed scaffolds with customizable shapes, proper pore structure and satisfactory mechanical properties remains a challenge. In the current study, to achieve customizable CDM-based 3D scaffolds, CDM was successfully processed into inks suitable for 3D printing. Further, the poor mechanics of CDM-based scaffolds were significantly improved by adding electrospinning fiber into the CDM-based inks for 3D printing. Importantly, the 3D-printed electrospinning fiber-reinforced CDM-based scaffold presented good biocompatibility and can enhance repair articular cartilage defects in rabbits. The current study provides a novel strategy for printing electrospinning fiber-reinforced CDM-based scaffolds for tissue regeneration.
Safety and short-term efficacy of video-assisted thoracoscopic surgery (VATS) for early-stage non-small lung cancer (NSCLC) has been demonstrated by observational studies previously. However, these ...outcomes have never been verified by a large randomized controlled trial (RCT). The aim of our RCT was to confirm that VATS is not inferior or even superior to open operation for early-stage NSCLC in terms of short-term and oncologic efficacy.
The trial was undertaken at five tertiary hospitals. Patients aged between 18 and 75 years with clinically early-stage NSCLC were randomly assigned to the VATS and axillary thoracotomy groups. Lobectomy plus mediastinal lymph node dissection was standard surgical intervention. Because patients continue to be followed up for oncologic outcome, the short-term perioperative outcomes would be reported here.
Between 2008 and 2014, 508 patients were recruited and 425 were eligible for analyses (215 VATS and 210 axillary thoracotomy). Eight VATS procedures were converted to open operation intraoperatively (3.72%). Median operation time with VATS was significantly less than axillary thoracotomy (150 versus 166 minutes, p = 0.009). In addition, VATS was associated with less intraoperative blood loss (p = 0.001). There was no difference for postoperative pleural drainage, length of hospitalization, and rates of morbidity and mortality. Cancer residual margins were found in 1 patient with VATS and 5 with axillary thoracotomy (p = 0.128). The yield of lymph nodes from either surgical approach was similar (p = 0.389).
Our study demonstrates that VATS lobectomy is safe and reliable to treat NSCLCs, and it may be superior to axillary thoracotomy for operation time and intraoperative blood loss. ClinicalTrials.gov identifier: NCT01102517.
The fabrication of three-dimensional (3D) electrospun fibrous scaffolds with customizable shapes and large pores is a challenging task. In this study, for the first time, one-dimensional (1D) ...gelatin/poly (lactic-co-glycolic acid) (PLGA) electrospun fibers were processed into inks suitable for 3D printing. By combining 3D printing and freeze drying, electrospun fiber-based inks were successfully fabricated into 3D-printed scaffolds (3DP) with precisely controlled shapes and large pores, in addition to fibrous surface morphologies similar to that of a native extracellular matrix (ECM). The 3DP exhibited good elasticity and water-induced shape memory, and was found to be superior to 3D-printed scaffolds fabricated using pure gelatin fibers and freeze-shaped scaffolds fabricated using non-fibrous gelatin/PLGA powder. Moreover, 3DP combined with chondrocytes achieved satisfactory cartilage regeneration in vivo. The novel strategy of 3D printing electrospun fibers established in this study provides a research model for the design and fabrication of multiple scaffolds for various tissue regeneration applications.
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•Electrospun fibers were processed into three-dimensional inks for the first time.•Fiber scaffolds with controlled shapes and large pores were successfully fabricated.•Three-dimensional printed fiber scaffolds exhibited elastic property in the wet condition.•Three-dimensional fiber scaffolds combined with chondrocytes achieved satisfactory cartilage regeneration in vivo.
Abstract
Background
Malignant transformation and progression of cancer are driven by the co-evolution of cancer cells and their dysregulated tumor microenvironment (TME). Recent studies on ...immunotherapy demonstrate the efficacy in reverting the anti-tumoral function of T cells, highlighting the therapeutic potential in targeting certain cell types in TME. However, the functions of other immune cell types remain largely unexplored.
Results
We conduct a single-cell RNA-seq analysis of cells isolated from tumor tissue samples of non-small cell lung cancer (NSCLC) patients, and identify subtypes of tumor-infiltrated B cells and their diverse functions in the progression of NSCLC. Flow cytometry and immunohistochemistry experiments on two independent cohorts confirm the co-existence of the two major subtypes of B cells, namely the naïve-like and plasma-like B cells. The naïve-like B cells are decreased in advanced NSCLC, and their lower level is associated with poor prognosis. Co-culture of isolated naïve-like B cells from NSCLC patients with two lung cancer cell lines demonstrate that the naïve-like B cells suppress the growth of lung cancer cells by secreting four factors negatively regulating the cell growth. We also demonstrate that the plasma-like B cells inhibit cancer cell growth in the early stage of NSCLC, but promote cell growth in the advanced stage of NSCLC. The roles of the plasma-like B cell produced immunoglobulins, and their interacting proteins in the progression of NSCLC are further validated by proteomics data.
Conclusion
Our analysis reveals versatile functions of tumor-infiltrating B cells and their potential clinical implications in NSCLC.
Chronic obstructive pulmonary disease (COPD) and lung cancer are devastating pulmonary diseases that commonly coexist and present a number of clinical challenges. COPD confers a higher risk for lung ...cancer development, but available chemopreventive measures remain rudimentary. Current studies have shown a marked benefit of cancer screening in the COPD population, although challenges remain, including the common underdiagnosis of COPD. COPD-associated lung cancer presents distinct clinical features. Treatment for lung cancer coexisting with COPD is challenging as COPD may increase postoperative morbidities and decrease survival. In this review, we outline current progress in the understanding of the clinical association between COPD and lung cancer, and suggest possible cancer prevention strategies in this patient population.
In response to infection, polymorphonuclear neutrophils (PMN) are recruited in the infectious sites, and employ three major strategies to fight against the microbes including phagocytosis, ...degranulation, and neutrophil extracellular traps (NETs). NETs are a meshwork of chromatin fibers mixed with granule-derived antimicrobial peptides and enzymes, which trap and kill the bacteria extracellularly. In this study, by using a mouse sepsis model, we identified a novel mechanism by which NETs induce macrophage (Mϕ) pyroptosis, a caspase-1-dependent regulated cell death. We show that NET-derived HMGB1, acting through RAGE and dynamin-dependent signaling, triggers an intra-Mϕ cascade of molecular events including cathepsin B (CatB) release from the ruptured lysosomes, followed by pyroptosome formation and caspase-1 activation, and subsequent Mϕ pyroptosis. The study further demonstrates that Mϕ pyroptosis augments inflammatory responses following sepsis. These findings shed light on the proinflammatory role of NETs in mediating PMN-Mϕ interaction, which therefore influences the progress of inflammation following infection.
Predictors of survival in lung torsion: A systematic review and pooled analysis Dai, Jie, PhD; Xie, Dong, MD; Wang, Haifeng, MD ...
Journal of thoracic and cardiovascular surgery/The Journal of thoracic and cardiovascular surgery/The journal of thoracic and cardiovascular surgery,
09/2016, Letnik:
152, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Abstract Objective Lung torsion (LT) is a rare but life-threatening event. The objective of this study was to systematically review the natural history and clinical outcome of LT in published ...studies. Methods A review of publications on LT from January 1950 to December 2014 was performed using 3 databases (PubMed, EMBASE, and Web of Science). The primary efficacy outcome was LT-related mortality. Intervention was classified as direct resection (resection without detorsion), indirect resection (resection after detorsion), and reposition. Univariate comparisons of survival were performed using a logistic regression model. Results There were 109 patients from 91 studies identified in this analysis. LT was frequently reported after upper lobectomy (74.4%) and the middle lobe was the most vulnerable lesion (29.4%). The main clinical presentations were dyspnea (38.4%), fever (23.3%), and chest pain (17.4%). Radiologic findings suggestive of LT included worsening consolidation and abrupt truncation/tapering of the pulmonary artery. The overall mortality was 8.3%. Univariate analysis showed that the extent of torsion (whole LT vs lobar torsion) was significantly associated with survival (odds ratio, 5.867; P = .017). No significant difference was found between patients receiving direct resection and those receiving reposition; a trend was observed for worsening outcomes in patients treated with indirect resection (odds ratio, 5.300; P = .060). Conclusions The systematic review reveals the prevalence, key diagnostic tests, and optimal treatment methods for lung torsion. Whole LT is associated with higher mortality rates than lobar torsion. If the tortuous part is viable, reposition and direct resection have similar survival rates; otherwise, direct resection should be performed.
Performing sublobar resection for early stage non-small cell lung carcinoma is becoming increasingly popular, with studies suggesting equivalent outcomes to lobectomy when sufficient lymph node ...sampling is performed. Furthermore, there has been a move to minimally invasive thoracic surgery facilitating enhanced recovery and reduced postoperative morbidity. The subxiphoid video-assisted thoracic surgery (SVATS) approach is a novel technique that is becoming increasingly popular, with evidence of reduced postoperative pain. Here, we report experience and the technique of performing segmentectomy by the uniportal SVATS approach.
The uniportal SVATS approach was used to perform all possible segmentectomies. Specific instruments were designed to facilitate performing surgery through this approach, and the operative technique is described and demonstrated with videos.
Between September 2014 and April 2017, 242 segmentectomies were performed by uniportal SVATS. Twenty-nine of the patients underwent bilateral procedures. The mean duration of surgery was 2.14 ± 0.78 hours. Lymph node stations were accessible, and a mean of 4.00 ± 1.00 lymph node stations and 10.64 ± 3.38 lymph nodes were sampled. The mean postoperative hospital length of stay was 4.67 ± 9.54 days. Only 4 cases required conversion to thoracotomy, and 3 required conversion to full lobectomy. There were no perioperative deaths, with 30-day survival of 100%.
This report demonstrates that the uniportal SVATS approach can be safely and effectively utilized to perform pulmonary segmentectomies. Our series demonstrates that it is possible to access and resect all segments by this novel approach to VATS.
Hemorrhagic shock (HS) often renders patients more susceptible to lung injury by priming for an exaggerated response to a second infectious stimulus. Acute lung injury (ALI) is a major component of ...multiple organ dysfunction syndrome following HS and regularly serves as a major cause of patient mortality. The lung vascular endothelium is an active organ that has a central role in the development of ALI through synthesizing and releasing of a number of inflammatory mediators. Cell pyroptosis is a caspase-1-dependent regulated cell death, which features rapid plasma membrane rupture and release of proinflammatory intracellular contents. In this study, we demonstrated an important role of HS in priming for LPS-induced lung endothelial cell (EC) pyroptosis. We showed that LPS through TLR4 activates Nlrp3 (NACHT, LRR, and PYD domains containing protein 3) inflammasome in mouse lung vascular EC, and subsequently induces caspase-1 activation. However, HS induced release of high-mobility group box 1 (HMGB1), which acting through the receptor for advanced glycation end products initiates EC endocytosis of HMGB1, and subsequently triggers a cascade of molecular events, including cathepsin B release from ruptured lysosomes followed by pyroptosome formation and caspase-1 activation. These HS-induced events enhance LPS-induced EC pyroptosis. We further showed that lung vascular EC pyroptosis significantly exaggerates lung inflammation and injury. The present study explores a novel mechanism underlying HS-primed ALI and thus presents a potential therapeutic target for post-HS ALI.
Our aim was to validate and analyze the prognostic impact of the novel International Association for the Study of Lung Cancer (IASLC) Pathology Committee grading system for invasive pulmonary ...adenocarcinomas (IPAs) in Chinese patients and to evaluate its utility in predicting a survival benefit from adjuvant chemotherapy (ACT). In this multicenter, retrospective, cohort study, we included 926 Chinese patients with completely resected stage I IPAs and classified them into three groups (Grade 1, n = 119; Grade 2, n = 431; Grade 3, n = 376) according to the new grading system proposed by the IASLC. Recurrence-free survival (RFS) and overall survival (OS) were estimated by the Kaplan-Meier method, and prognostic factors were assessed using univariable and multivariable Cox proportional hazards models. All included cohorts were well stratified in terms of RFS and OS by the novel grading system. Furthermore, the proposed grading system was found to be independently associated with recurrence and death in the multivariable analysis. Among patients with stage IB IPA (N = 490), the proposed grading system identified patients who could benefit from ACT but who were undergraded by the adenocarcinoma (ADC) classification. The novel grading system not only demonstrated prognostic significance in stage I IPA in a multicenter Chinese cohort but also offered clinical value for directing therapeutic decisions regarding adjuvant chemotherapy.
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