Is the Glasses-Free 3-Dimensional Display System More Effective for Complex Video-Assisted Thoracic Surgery? A Self-Controlled Study Ex Vivo.

Objective. Considering the demerits of a high-definition 2-dimensional (HD-2D) system, with its lack of stereopsis, and a conventional 3-dimensional (C-3D) system, which results in a dimmed image, we have recently developed a glasses-free 3-dimensional (GF-3D) display system for reconstruction surgeries such as video-assisted thoracic surgery (VATS) for tracheal reconstruction. Methods. Thoracic surgeons were invited to complete thoracoscopic continuous suture of a transected porcine trachea using the HD-2D, C-3D, and GF-3D systems on separate mornings in randomized order. The duration, numbers of stitches, and distance between every 2 stitches were recorded for every procedure. The surgeons' spontaneous eye blink rate was recorded for 5 minutes before the procedure and the last 5 minutes of the procedure. Results. Fifteen volunteers successfully completed the tracheal reconstruction procedures in this study. Both C-3D (0.403 ± 0.064 stitch/min, P < .001) and GF-3D (0.427 ± 0.079 stitch/min, P < .001) showed significant advantages in speed compared with HD-2D (0.289 ± 0.065 stitch/min). Both C-3D (2.536 ± 2.223 mm, P < .001) and GF-3D (2.603 ± 2.159 mm, P < .001) showed significant advantages in accuracy compared with HD-2D (3.473 ± 3.403 mm). Both HD-2D (1.240 ± 0.642, P < .001) and GF-3D (1.307 ± 0.894, P < .001) showed significant advantages in eye fatigue compared with C-3D (3.333 ± 1.44). Conclusions. All 3 available display systems are efficient for complex VATS. With the help of stereopsis, surgeons can achieve faster operation using C-3D and GF-3D systems in a thoracoscopic simulated setting. GF-3D may be a more effective display system for VATS reconstruction in terms of speed, accuracy, and eye fatigue during operations.

Metastatic EML4-ALK fusion detected by circulating DNA genotyping in an EGFR-mutated NSCLC patient and successful management by adding ALK inhibitors: a case report.

BACKGROUND: Rebiopsy is highly recommended to identify the mechanism of acquired resistance to EGFR-TKIs in advanced lung cancer. Recent advances in multiplex genotyping based on circulating tumor DNA (ctDNA) provide a strong and non-invasive alternative for detection of the resistance mechanism. CASE PRESENTATION: Here we report a multiple metastatic NSCLC patient who was detected to have pure EGFR 19 exon deletion (negative for EML4-ALK and ROS1 in both IHC-based and sequencing assay) in the primary lesion and responded to first-line and second-line EGFR-TKI treatments (erlotinib then HY-15772). At 8 months, most lesions remained well controlled except for the liver metastases which presented dramatic progression. Considering the high risk of bleeding in rebiopsy of hepatic lesions, we conducted a multiplex genomic profiling with ctDNA. Results reported coexistence of EGFR mutation and EML4-ALK gene translocation in plasma which heavily indicated that ALK was the primary reason for progression of the liver lesions. This deduction was supported by the repeated response to ALK inhibitors (crizotinib then AP26113) of the hepatic metastases. CONCLUSIONS: This is the first report of the existence of ALK rearrangement in metastatic lesions in an EGFR mutated patient. It highlighted the feasibility and advantages of using ctDNA multiplex genotyping in identifying the heterogeneity across lesions and the resistance mechanism of targeted treatments.

Pulmonary artery anastomosis during lung transplantation: a novel technique.

Pulmonary artery anastomosis (PAA) is a critical step in lung transplantation. The conventional approach involves end-to-end anastomosis, which can lead to arterial tortuosity, oozing, stenosis, and thrombosis. Here, we present a modified PAA technique for lung transplantation. The anesthesia protocol and the incision for lung transplantation adhere to standard lung transplantation protocols. The primary innovation is the enhanced pulmonary anastomosis technique. The donor and recipient artery stumps are adjusted to restore their natural anatomical alignment. The donor-recipient stump is everted, ensuring precise alignment of the intima of the donor and recipient arteries. Both ends of the anastomosis are secured using 5-0 Prolene sutures to ensure stability and traction, followed by continuous suturing. In this study, seven patients underwent PAA using this novel technique. Notably, no bleeding was observed upon unveiling and deaerating the anastomosis, eliminating the need for additional sutures. Furthermore, no pulmonary artery torsion or significant prolongation of the anastomotic procedure was observed. Postoperative computed tomography of the chest revealed no anastomotic stenosis or mural thrombosis. This novel cuff anastomosis technique can reduce the risk of thrombosis and prevent torsion and stenosis in the reconstructed artery.

A risk score for predicting extracorporeal membrane oxygenation support before lung transplantation.

Background: Extracorporeal membrane oxygenation (ECMO) has been increasingly used as life support for lung transplantation. However, there are no clinical risk models to predict whether ECMO support is required for lung transplantation. This study developed a simple risk score to predict the need for intraoperative ECMO in patients undergoing lung transplantation, identify high-risk patients who need ECMO support, and guide clinical interventions. Methods: Patients, who underwent lung transplantation between January 1, 2016 and July 31, 2021, were systematically reviewed. All enrolled patients were divided in a ratio of 7:3 to establish the development and validation datasets. A risk score model was established using stepwise logistic regression and verified using bootstrapping and the split-sample method. Results: A total of 248 patients who underwent lung transplants were enrolled. Multivariate analysis showed that the primary disease diagnosis, pulmonary artery systolic pressure, sex, surgical type, creatine kinase isoenzyme-MB, and pro-B-type natriuretic peptide were risk factors for intraoperative ECMO during lung transplantation. The risk score was established and calibrated according to these six factors, ranging from 0 to 41, with the associated prediction of intraoperative use of ECMO ranging from 1.5% to 99.7% (Hosmer-Lemeshow χ2=5.624; P=0.689). Good discrimination was verified by developing and validating the datasets (C-statistics =0.850 and 0.842, respectively). Based on the distribution of the scores, the three levels were classified as low-risk (0-10], moderate-risk (10-20], and high-risk (20-41]. Conclusions: This simple risk score model effectively predicts the need for intraoperative ECMO and stratifies high-risk patients who require ECMO support.

Lobar lung transplantation in the mouse.

Background: As an important supplementary approach to clinical in orthotopic lung transplantation (LTx), lobar LTx currently lacks a stable animal model and in the orthotopic left LTx model, the right lung of the donor mouse is completely removed and discarded. We introduce a novel mouse lobar LTx model that potentially provides a mouse model for clinical lobar LTx and increase the utilization rate of the experimental donor. Methods: Lobar and orthotopic left LTx were performed in syngeneic strain combinations. We performed micro-computed tomography and tested arterial blood gases to assess the graft function 28 days after transplantation. Hematoxylin-eosin and Masson's trichrome staining were used to evaluate pathological changes. Results: We performed ten lobar LTx with an operation success rate of 90%, accompanied by ten orthotopic left LTx from the same donors with an operation success rate of 100%. The graft preparation for lobar LTx was longer than that of the orthotopic left LTx (42.11±3.79 vs. 30.10±3.14 minutes, P<0.001). The recipient procedure for lobar LTx was nearly equivalent to the orthotopic left LTx. The graft function and histopathological changes for lobar LTx were comparable to those of orthotopic left LTx 28 days after transplantation. Conclusions: We describe a lobar LTx model in the mouse, which potentially provides a model for clinical lobar LTx and effectively addresses the issue of resource wastage in the orthotopic left LTx model.

Heparin-free veno-arterial extracorporeal membrane oxygenation in lung transplantation: a retrospective cohort study.

BACKGROUND: In lung transplantation (LTx) surgery, veno-arterial extracorporeal membrane oxygenation (VA-ECMO) can provide mechanical circulatory support to patients with cardiopulmonary failure. However, the use of heparin in the administration of ECMO can increase blood loss during LTx. This study aimed to evaluate the safety of heparin-free V-A ECMO strategies. METHODS: From September 2019 to April 2022, patients who underwent lung transplantation at the First Affiliated Hospital of Guangzhou Medical University were retrospectively reviewed. A total of 229 patients were included, including 117 patients in the ECMO group and 112 in the non-ECMO group. RESULT: There was no significant difference in the incidence of thrombus events and bleeding requiring reoperation between the two groups. The in-hospital survival rate after single lung transplantation (SLTx) was 81.08%in the ECMO group and 85.14% in the Non-ECMO group, (P = 0.585). The in-hospital survival rate after double lung transplantation (DLTx) was 80.00% in the ECMO group and 92.11% in the Non-ECMO groups (P = 0.095). CONCLUSIONS: In conclusion, the findings of this study suggest that the heparin-free V-A ECMO strategy in lung transplantation is a safe approach that does not increase the incidence of perioperative thrombotic events or bleeding requiring reoperation.

Zeaxanthin Combined with Tocopherol to Improve the Oxidative Stability of Chicken Oil.

Chicken oil is prone to oxidation due to the high content of unsaturated fatty acids. The interaction of antioxidants was affected by their concentration, ratio, and reaction system. In this article, mixtures of zeaxanthin and tocopherols (α-tocopherol and γ-tocopherol) were chosen to enhance the oxidative stability of chicken oil. The antioxidation of zeaxanthin with tocopherols was analyzed using the Rancimat test, the free radical scavenging capacity and the Schaal oven test (the variation of antioxidant content, PV and shelf life prediction). The optimal concentration of zeaxanthin determined by Rancimat in chicken oil was 20 mg/kg. The binary mixtures have a strong synergistic effect in the ABTS experiment, and the clearance rate was up to 99%, but antagonistic effect in ORAC. The degree of synergism between zeaxanthin and tocopherols was determined by ratio. The interaction between zeaxanthin and α-tocopherol was synergistic, while the types of interaction between zeaxanthin and γ-tocopherol were affected by concentration. The main synergistic interaction mechanism was the regeneration of tocopherol by zeaxanthin. Synergistic combinations of zeaxanthin with α-tocopherol and γ-tocopherol played a key role in the primary oxidation stage of the lipid. The best synergistic combination was A3 (zeaxanthin+α-tocopherol: 15+50 23 mg/kg), which could extend the shelf life of chicken oil (92.46 d) to 146.93 days. This work provides a reference for zeaxanthin and tocopherol to improve the oxidative stability of animal fat.

The outcome of lung transplantation for end-stage pulmonary diseases with pulmonary hypertension: a single-center experience.

Background: Lung transplantation is a treatment for end-stage lung disease. The optimal transplant strategy for patients with end-stage lung disease complicated by pulmonary hypertension (PH) is controversial. The aim of this study is to review this experience and analyze the outcomes of lung transplantation for PH. Methods: This retrospective study collected data on patients with PH undergoing lung transplantation between March 2016 and December 2019 at a single center in China. The perioperative features and short- and medium-term outcomes between single-lung transplantation (SLT) and double-lung transplantation (DLT) were compared. Kaplan-Meier methods were used to analyze overall survival across a variety of transplantation procedures, age, mean pulmonary artery pressure (mPAP), body mass index (BMI), and indications of transplantation. Results: A total of 63 patients with PH were finally included in the analysis. The mean age, mean BMI, and mPAP were 56.37 years, 19.56 kg/m2, and 35.4 mmHg respectively. The overall 1-, 2-, and 3-year survival was 70%, 63%, and 60%, respectively. Five (7.94%) patients died within 30 days after surgery and nine patients (14.3%) died from infection during the followed-up period. There were no significant differences in the short- and medium-term survival outcomes of SLT and DLT, but postoperative pulmonary function was better in DLT. Patients older than 60 years of age had worse survival (P=0.01). Conclusions: The short- and medium-term survival outcomes between SLT and DLT are similar in selected patients with PH. DLT provides better pulmonary function. Patients older than 60 years are associated with worse survival.

Impact of prior cancer history on outcomes in thymoma: a propensity score, population-based study.

BACKGROUND: Prior cancer history is a common exclusion in thymoma trials. However, whether prior cancer impacts the survival of thymoma patients and the outcomes of clinical trials remains uncertain. The aim of this study is to identify the impact of prior cancer on outcomes in thymoma. METHODS: Patients with thymoma diagnosed between 1975 to 2017 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Age, histologic types, and thymoma size were stratified to analyze. Propensity score matching (PSM), Kaplan-Meier methods and Cox proportional hazard models were used to analyze the prognostic effect of prior cancer on overall survival (OS). RESULTS: A total of 3,827 thymoma patients were enrolled, of whom 13.22% had a prior cancer history. The Kaplan-Meier curves showed statistically significantly different survival before (P<0.001) and after PSM (P=0.0003). Subgroup analyses stratified by histologic types and thymoma size showed that thymoma patients with prior cancer had inferior survival. But thymoma patients with prior cancer displayed similar OS among patients older than 65 years (P=0.693). In multivariate analyses, patients with prior cancer displayed inferior OS [hazard ratio (HR) =1.39, 95% confidence interval (CI), 1.18 to 1.63]. CONCLUSIONS: Prior cancer conveys an inferior OS among patients with thymoma. But it does not affect the survival adversely in older patients thus broader inclusion trial criteria may be adopted in thymoma patients with a prior cancer history.

Tubeless video-assisted thoracoscopic surgery in mediastinal tumor resection.

BACKGROUND: It has been reported that tubeless video-assisted thoracoscopic surgery (tubeless-VATS) is feasible and safe for thoracic diseases. Herein, we compared the early outcomes of mediastinal lesion resection between the tubeless and traditional VATS. METHODS: Clinical data of all patients who underwent thoracoscopic mediastinal tumor resection were retrospectively collected. The study involved two groups: tubeless and traditional VATS group. Propensity score matching (PSM) was applied to eliminate the population bias. Intraoperative and postoperative variables were compared among matched cohorts. RESULTS: In total, 43 patients in the tubeless group and 231 patients in the traditional VATS group were included. After 1:1 PSM, baseline characteristics were comparable. Anesthesia time (177.63 vs. 202.53 min; P=0.004) was shorter in tubeless group, while operation time (90.95 vs. 101.47 min; P=0.109) was similar. Overall, the total postoperative morbidity rate was similar in the two groups (15% vs. 12.5%; P=0.556). Specially, 4/43 patients in tubeless VATS group need to be re-put chest tubes postoperatively. A significant lower similar level of visual analogue scale score was observed in tubeless VATS group (1.73±0.48 vs. 3.41±0.87, P<0.001) in postoperative day 1. Meanwhile, the number of patients using postoperative opioid analgesia was also lower in tubeless VATS group (22.88% vs. 48.38%, P=0.016). Furthermore, hospital duration after surgery (2.58 vs. 5.47 days; P=0.002) was shorter in tubeless group. CONCLUSIONS: Compared with traditional VATS, tubeless VATS for mediastinal tumor may shorten the anesthesia time, decrease postoperative pain and fasten postoperative recovery in carefully selected patients.

Pulmonary fibrosis combined with lung cancer following lung transplantation: should we do more?

Currently, lung transplantation is the standard of care for patients with end-stage lung disease, with interstitial lung disease (ILD) being the most common reason in the recent years In the other hand, in cases where stage II and III lung cancer have been identified following lung transplantation, long-term survival outcomes are poor when compared to lung cancer patients that have not received a lung transplant because the use of immunosuppressant and the problem of rejection and infection and the treatment of recurrence and so on. However, there is no statistical difference observed in stage I (pT1N0M0) patients. In this paper we report about a patient with ILD receiving left lung transplantation in the early time. A lesion of the right lung which was considered the normal ILD tissue and without enough attention. Post-transplant it showed progress and finally the whole right lung (native lung) was occupied by the tumor. Some ground glass changes could also be found in the transplanted lung several months later. A secondary lung transplant was performed for this patient, and there has been no postoperative recurrence thus far. For lung transplant patients with high-risk factors, effective surveillance methods are required for the early detection of lung cancer.

Andrographolide alleviates bleomycin-induced NLRP3 inflammasome activation and epithelial-mesenchymal transition in lung epithelial cells by suppressing AKT/mTOR signaling pathway.

BACKGROUND: Andrographolide (Andro), a diterpenoid extracted from Andrographis paniculata, has been shown to attenuate pulmonary fibrosis in rodents; however, the potential mechanisms remain largely unclear. This study investigated whether and how Andro alleviates bleomycin (BLM)-induced NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activation and epithelial-mesenchymal transition (EMT) in the lung epithelial cells. METHODS: The in vivo effects of Andro were evaluated in a rat model of BLM-induced pulmonary fibrosis. The roles of Andro in BLM-induced NLRP3 inflammasome activation, EMT and AKT/mTOR signaling were investigated using human alveolar epithelial A549 cells. RESULTS: We found that Andro significantly alleviated pulmonary edema and histopathological changes, decreased weight loss, and reduced collagen deposition. Andro downregulated the levels of NLRP3, the adaptor molecule apoptosis-associated speck-like protein containing a CARD (ASC), and Caspase-1 in the lungs of BLM-treated rats, suggesting the inhibitory effect of Andro on NLRP3 inflammasome activation in vivo. Additionally, the symptoms of BLM-mediated EMT phenotype in the lung were also attenuated after Andro administration. In vitro, Andro also markedly inhibited BLM-induced NLRP3 inflammasome activation and EMT in A549 cells. Moreover, Andro inhibited BLM-induced phosphorylation of AKT and mTOR in A549 cells, suggesting that AKT/mTOR inactivation mediates Andro-induced effects on BLM-induced NLRP3 inflammasome activation and EMT. CONCLUSIONS: These data indicate that Andro can reduce BLM-induced pulmonary fibrosis through suppressing NLRP3 inflammasome activation and EMT in lung epithelial cells via AKT/mTOR signaling pathway.

Non-In Situ Technique of Heart-Lung Transplantation: Case Series and Technique Description.

PURPOSE: Heart-lung transplantation (HLTx) is a life-saving treatment option for patients with advanced cardiopulmonary failure. However, posterior mediastinal bleeding and phrenic nerve damage are still intraoperative challenges for the traditional surgical method. This study reports an innovative non-in situ HLTx performed in our center, preventing posterior mediastinal bleeding and phrenic nerve damage effectively. DESCRIPTION: Between September 2015 and September 2020, 12 patients without previous heart surgery underwent a traditional HLTx and were deemed a control group, and 3 patients underwent an innovative non-in situ HLTx. The operative time, cold ischemic time, intraoperative bleeding, intraoperative transfusion, and the intensive care unit and hospital lengths of stay were assessed between traditional HLTx and non-in situ HLTx. EVALUATION: The innovative non-in situ HLTx was successfully performed in the 3 patients. We found that the intensive care unit and hospital lengths of stay, total surgical time, cold ischemic time, intraoperative bleeding, and intraoperative transfusion were decreased in the 3 patients compared with the traditional surgical method. CONCLUSION: Non-in situ HLTx may decrease posterior mediastinal bleeding and phrenic nerve damage effectively.

The Application of Transbronchial Lung Cryobiopsy and Uniportal and Tubeless Video-Assisted Thoracic Surgery in the Multidisciplinary Diagnosis of Interstitial Lung disease-A Real-World Prospective Study.

The application of transbronchial lung cryobiopsy (TBLC) and uniportal and tubeless video-assisted thoracic surgery (UT-VATS) in the multidisciplinary diagnosis of interstitial lung disease (ILD) has not been demonstrated in real-world clinical practice. This prospective study included 137 patients with no definitive diagnosis who were the subject of two multidisciplinary discussion (MDD) sessions. As indicated in the first MDD, 67 patients underwent UT-VATS and 70 underwent TBLC. The specificity of biopsy information and its contribution to final MDD diagnosis were evaluated in the second MDD. The post-operative complications and hospitalization costs associated with the two biopsy methods were compared. UT-VATS was favored for patients initially diagnosed with idiopathic pulmonary fibrosis (IPF), bronchiolitis-associated interstitial lung disease (RB-ILD)/desquamative interstitial pneumonia (DIP) and undefined idiopathic interstitial pneumonia (UIIP), while TBLC was preferred for pulmonary lymphangioleiomyomatosis (PLAM) and pulmonary alveolar proteinosis (PAP). The spirometry parameters were better in patients who underwent UT-VATS than those who underwent TBLC. UT-VATS provided more specific pathological results than TBLC (85.7 vs 73.7%, p = 0.06). In patients initially diagnosed with UIIP, pathological information from UT-VATS was more clinically useful than that obtained from TBLC, although both tests contributed similarly to cases initially diagnosed as interstitial pneumonia with auto-immune features (IPAF)/connective tissue disease-related ILD (CTD-ILD). The safety of UT-VATS was comparable with TBLC although TBLC was cheaper during hospitalization (US$4,855.7 vs US$3,590.9, p < 0.001). multidisciplinary discussion decisions about biopsies were driven by current knowledge of sampling and diagnosis capacity as well as potential risks of different biopsy methods. The current MDD considered UT-VATS more informative than TBLC in cases initially diagnosed as UIIP although they were equally valuable in patients initially diagnosed with IPAF/CTD-ILD.

Early extubation in operating room after single-lung transplantation: a single institutional experience.

BACKGROUND: Early endotracheal extubation in operating room (E-OR) after lung transplantation is rarely reported worldwide. Herein, we aim to explore the feasibility and safety of E-OR after lung transplantation and demonstrate its potential benefits. METHODS: This study is a single-center retrospective database analysis of 18 patients. All lung transplantation patients with E-OR attempted between June 2018 and September 2019 were included retrospectively. Perioperative variables, including ischemia time, total blood loss, blood lactic acid, the partial pressure of oxygen, partial pressure of oxygen/fraction of inspiration oxygen ratio, time of semi-open pulmonary artery occlusion clamp, extubation rate, and complications after E-OR, were analyzed. Data were compared using non-parametric tests and expressed as the median or number (percentage). RESULTS: Clinical data of 18 patients with E-OR attempted were collected. Overall, 15/18 (83.33%) patients successfully underwent E-OR without reintubation. Reintubation occurred in 3/18 (16.67%) patients; one patient presented with decreased blood oxygen saturation and unconsciousness, while two patients developed hypoxemia and respiratory failure after E-OR. Extracorporeal membrane oxygenation (ECMO) was not used postoperatively. No grade 3 primary graft dysfunction was observed and all eighteen patients were alive 1 year after the transplant. No postoperative hemodialysis and tracheotomy occurred. The median length of stay in the intensive care unit (ICU) for E-OR patients was 120 hours, the median length of postoperative hospital stay was 19 days, and the median hospitalization cost was 35,577 USD. CONCLUSIONS: Early endotracheal extubation in operating room was feasible and did not delay postoperative recovery in these 18 lung transplantation recipients.

Novel Lung Biopsy Surgical Technique for Definitive Diagnosis of Pulmonary Capillary Hemangiomatosis.

PURPOSE: The 2015 European Society of Cardiology/European Respiratory Society Guidelines for the Diagnosis and Treatment of Pulmonary Hypertension state that lung biopsy is still the gold standard for confirming pulmonary capillary hemangiomatosis; however, the surgical lung biopsy is no longer recommended in most cases for its inherent risks. Nonintubated and uniportal video-assisted thoracoscopic surgery are the new developments in video-assisted thoracoscopic surgery technology. We combined these 2 technologies to create a novel approach for pulmonary capillary hemangiomatosis lung biopsy. DESCRIPTION: A incision is made in chest wall. Sponge forceps are used to pull the lung out of the pleural space, and to resect target lung tissue. The incised margin is sutured with 3-0 Prolene (Ethicon, Somerville, NJ), and a negative pressure suction tube is used to fully expand the lung. EVALUATION: Three patients were definitively diagnosed with pulmonary capillary hemangiomatosis by this technology. One patient developed a postoperative fever, with no other complications. CONCLUSIONS: The tubeless and uniportal video-assisted thoracoscopic surgery lung biopsy is a safe, effective, and feasible technology for definitively diagnosing patients with pulmonary capillary hemangiomatosis.

Downregulation of Hsa_circ_0000735 Inhibits the Proliferation, Migration, Invasion, and Glycolysis in Non-small-cell Lung Cancer by Targeting miR-940/BMPER Axis.

BACKGROUND: Lung cancer is the most commonly diagnosed cancer and the major cause of cancer-related deaths worldwide. The increasing studies have demonstrated that circular RNA (circRNA) was involved in the progression of various cancers, including non-small-cell lung cancer (NSCLC). This study was designed to assess the expression, roles and functional mechanisms of circ_0000735 in NSCLC. MATERIALS AND METHODS: The expression levels of circ_0000735, miR-940 and bone morphogenetic protein binding endothelial cell precursor-derived regulator (BMPER) were estimated by the real-time quantitative polymerase chain reaction (RT-qPCR). The biological behaviors of NSCLC cells such as proliferation, migration and invasion were analyzed by cell counting kit-8 (CCK-8), colony-forming assays and transwell assay, respectively. Furthermore, extracellular acid ratio and lactate production were tested to assess glycolysis levels of NSCLC cells. The interaction relationship among circ_0000735, BMPER and miR-940 was analyzed by bioinformatics database and dual-luciferase reporter assay. The protein expression level of BMPER was assessed by Western blot assay. Tumorigenesis assay was established to clarify the functional roles of circ_0000735 in vivo. RESULTS: Circ_0000735 was upregulated and significantly correlated with overall survival in patients with NSCLC. In addition, the loss-of-functional experiments revealed that knockdown of circ_0000735 repressed proliferation, migration, invasion and glycolysis of NSCLC cells and tumor growth in vivo, which was overturned by overexpression of BMPER. Similarly, overexpression of circ_0000735 enhanced proliferation, migration, invasion, and glycolysis of NSCLC cells. In addition, we also confirmed that overexpression of miR-940 impeded proliferation, migration, invasion, and glycolysis of NSCLC cells. Furthermore, overexpression of BMPER abolished si-circ_0000735 induced effects on NSCLC cells. CONCLUSION: Circ_0000735 regulated proliferation, migration, invasion, and glycolysis in NSCLC cells by targeting miR-940/BMPER axis.

Andrographolide ameliorates bleomycin-induced pulmonary fibrosis by suppressing cell proliferation and myofibroblast differentiation of fibroblasts via the TGF-ß1-mediated Smad-dependent and -independent pathways.

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with no effective medication. Andrographolide (Andro), extracted from Chinese herbal Andrographis paniculata, could attenuate bleomycin (BLM)-induced pulmonary fibrosis via inhibition of inflammation and oxidative stress, however, the anti-fibrotic mechanisms have not been clarified. Myofibroblasts are the primary cell types responsible for the accumulation of extracellular matrix (ECM) in fibrotic diseases, and targeting fibroblast proliferation and differentiation is an important therapeutic strategy for the treatment of IPF. Hence, this study aimed to investigate the effects of Andro on the fibroblast proliferation and differentiation in the in vivo and in vitro models. The results showed that Andro improved pulmonary function and inhibited BLM-induced fibroblast proliferation and differentiation and ECM deposition in the lungs. In vitro, Andro inhibited proliferation and induced apoptosis of TGF-ß1-stimulated NIH 3T3 fibroblasts and primary lung fibroblasts (PLFs). Andro also inhibited TGF-ß1-induced myofibroblast differentiation and ECM deposition in both cells. We also found that Andro suppressed TGF-ß1-induced Smad2/3 and Erk1/2 activation, suggesting that Smad2/3 and Erk1/2 inactivation mediates Andro-induced effects on TGF-ß1-induced fibroblast proliferation and differentiation. These results indicated that Andro has novel and potent anti-fibrotic effects in lung fibroblasts via inhibition of the proliferation and myofibroblast differentiation of fibroblasts and subsequent ECM deposition, which are modulated by TGF-ß1-mediated Smad-dependent and -independent pathways.

Preoperative risk factors for successful extubation or not after lung transplantation.

BACKGROUND: The purpose of this study was to uncover preoperative risk factors for extubation failure or re-intubation for patients undergoing lung transplant (LTx). METHODS: We performed a retrospective case-control study of LTx from our center between January 2017 and March 2019. Demographic and preoperative characteristics were collected for all included patients. Univariable analysis and multivariable logistic regression were used to analyze risk factors of postoperative unsuccessful extubation following LTx. RESULTS: Among 107 patients undergoing first LTx investigated, 74 (69.16%) patients who were successfully liberated from mechanical ventilation (MV), and 33 (30.84%) patients who were unsuccessful extubation, which 18 (16.82%) patients suffered from reintubation. associated preoperative factors for unsuccessful extubation following LTx included preoperative extracorporeal membrane oxygenation (ECMO) support [OR =4.631, 95% confidence interval (CI): 1.403-15.286, P=0.012], the preoperative ability of independent expectoration (OR =4.517, 95% CI: 1.498-13.625, P=0.007), the age older than 65-year-old (OR =4.039, 95% CI: 1.154-14.139, P=0.029), and receiving the double lung and heart-LTx (OR =3.390, 95% CI: 0.873-13.162, P=0.078; and OR =16.579, 95% CI: 2.586-106.287, P=0.012, respectively). Further, we investigated the preoperative predicted factors for reintubation. Only the preoperative ECMO remained a significant predictor of re-intubation (OR =4.69, 95% CI: 1.56-15.286, P=0.012). CONCLUSIONS: Preoperative independent sputum clearance, preoperative ECMO, older than 65-year-old, and double lung or heart-LTx were four independent risk factors for unsuccessful extubation. Moreover, preoperative ECMO was the only independent risk factor for reintubation.

Cancer Risks in Solid Organ Transplant Recipients: Results from a Comprehensive Analysis of 72 Cohort Studies.

Understanding the cancer risks in different transplant recipients helps early detection, evaluation, and treatment of post-transplant malignancies. Therefore, we performed a meta-analysis to determine the cancer risks at multiple sites for solid organ transplant recipients and their associations with tumor mutation burden (TMB), which reflects the immunogenicity. A comprehensive search of PubMed, Web of Science, EMBASE, Medline, and Cochrane Library was conducted. Random effects models were used to calculate the standardized incidence ratios (SIRs) versus the general population and determine the risks of different cancers. Linear regression (LR) was used to analyze the association between the SIRs and TMBs. Finally, seventy-two articles met our criteria, involving 2,105,122 solid organ transplant recipients. Compared with the general population, solid organ transplant recipients displayed a 2.68-fold cancer risk (SIR 2.68; 2.48-2.89; P <.001), renal transplant recipients displayed a 2.56-fold cancer risk (SIR 2.56; 2.31-2.84; P <.001), liver transplant recipients displayed a 2.45-fold cancer risk (SIR 2.45; 2.22-2.70; P <.001), heart and/or lung transplant recipients displayed a 3.72-fold cancer risk (SIR 3.72; 3.04-4.54; P <.001). The correlation coefficients between SIRs and TMBs were 0.68, 0.64, 0.59, 0.79 in solid organ recipients, renal recipients, liver recipients, heart and/or lung recipients, respectively. In conclusion, our study demonstrated that solid organ transplant recipients displayed a higher risk of some site-specific cancers, providing individualized guidance for clinicians to early detect, evaluate, and treat cancer among solid organ transplantation recipients. In addition, the increased cancer risk of solid organ transplant recipients is associated with TMB, suggesting that iatrogenic immunosuppression may contribute to the increased cancer risk in transplant recipients. (PROSPERO ID CRD42020160409).