Summary of the best evidence for the prevention and management of myasthenic crisis after thymectomy.

Background: Myasthenic crisis (MC) may occur after thymectomy in patients with myasthenia gravis (MG), but effective preventive interventions can reduce the occurrence of this complication. Previous research on MC focused on risk factors, emergency treatment, etc., which was relatively scattered and did not form a comprehensive management framework. This study sought to retrieve and summarize the relevant evidence on the prevention and management of postoperative MC to provide a theoretical reference for clinical medical staff. Methods: According to the evidence pyramid model, relevant articles were retrieved from UpToDate, British Medical Journal (BMJ) Best Practice, World Health Organization (WHO), Scottish Intercollegiate Guidelines Network (SIGN), Guidelines International Network (GIN), Australian Joanna Briggs Institute (JBI) Healthcare Database, Medlive, PubMed, Cochrane Library, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang. The types of evidence included clinical guidelines, expert consensus articles, clinical decisions, systematic reviews, and randomized controlled trials (RCTs). The quality evaluations were conducted using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) evaluation tool for guidelines, the Australian JBI Evidence-Based Healthcare Center evaluation tool for expert consensus articles, the Critical Appraisal for Summaries of Evidence (CASE) evaluation tool for clinical decisions, the Assessment of Multiple Systematic Reviews (AMSTAR) evaluation tool for systematic reviews, and the Cochrane risk-of-bias tool for RCTs. Results: A total of 12 articles were included in this study, including three clinical guidelines, three expert consensus articles, three clinical decisions, two systematic reviews, and one RCT. From these articles, we summarized 39 pieces of evidence on the prevention and management of postoperative MC. Conclusions: This study summarized the best evidence on the prevention and management of postoperative MC and provided to clinical staffs evidence-based clinical approaches to help reduce the incidence of this complication.

Study protocol of an open-label prospective phase II umbrella study of precise neoadjuvant therapy for patients with stage II-IIIB resectable non-small cell lung cancer (PURPOSE).

Background: The outcomes of locally advanced non-small cell lung cancer (LA-NSCLC) are unfavorable mainly due to a high risk of cancer recurrence. Only around 5% of patients can benefit from perioperative chemotherapy which is the current standard treatment. Recently, promising results with neoadjuvant targeted and immune-therapy therapy have been seen. However, most clinical trials are looking for patients eligible for certain drugs, instead of seeking suitable treatments for certain patients. Therefore, it is necessary to look for more efficient perioperative therapies to increase resectability, reduce recurrence and improve prognosis. Methods/Design: The study is an open-label, prospective, phase II, umbrella trial, enrolling patients diagnosed with treatment-naïve potentially resectable Stage II-IIIB NSCLC. Next-generation sequencing (NGS) using a 68-gene panel is performed for biopsies of tumor tissues from eligible patients. Enrolled patients are then stratified into six independent cohorts based on the status of gene mutations and PD-L1 status in tumor tissues, that is, ①EGFR 19del group, ②EGFR 21 L858R group, ③EGFR rare mutation group, ④Other driver mutation group, ⑤Drive mutation-negative group with PD-L1≥1%, ⑥Drive mutation-negative group with PD-L1<1%. A Simon's two-stage design is performed in each cohort independently and patients receive corresponding standard therapies accordingly. We aim to enroll 26 patients in each cohort and totally 156 patients will be enrolled. The primary endpoint is objective response rate (ORR). Secondary endpoints include oncological prognosis and perioperative outcomes. Exploratory endpoint is to investigate patient-specific minimal residual disease (MRD) in predicting treatment efficacy and oncological prognosis. Discussions: This is the first umbrella trial focusing on the safety and efficacy of precise neoadjuvant therapy for patients diagnosed with potentially resectable LA-NSCLC based on NGS results. The results of this trial would help improve overall treatment results in LA-NSCLC patients. Trial registration: Chinese Clinical Trial Registry. Trial registration number: ChiCTR2100053021. Advantages and limitations of this study: There is no neoadjuvant umbrella trial focusing on LA-NSCLCs. This is the first neoadjuvant umbrella trial, using a precise individualized approach and seeking suitable drugs for LA-NSCLC patients, with the aim to improve overall treatment outcomes. Clinical trial registration: https://www.chictr.org.cn/, identifier ChiCTR2100053021.

An N6-methyladenosine and target genes-based study on subtypes and prognosis of lung adenocarcinoma.

Purpose: Lung adenocarcinoma (LUAD) is a highly lethal subtype of primary lung cancer with a poor prognosis. N6-methyladenosine (m6A), the most predominant form of RNA modification, regulates biological processes and has critical prognostic implications for LUAD. Our study aimed to mine potential target genes of m6A regulators to explore their biological significance in subtyping LUAD and predicting survival. Methods: Using gene expression data from TCGA database, candidate target genes of m6A were predicted from differentially expressed genes (DEGs) in tumor based on M6A2 Target database. The survival-related target DEGs identified by Cox-regression analysis was used for consensus clustering analysis to subtype LUAD. Uni-and multi-variable Cox regression analysis and LASSO Cox-PH regression analysis were used to select the optimal prognostic genes for constructing prognostic score (PS) model. Nomogram encompassing PS score and independent prognostic factors was built to predict 3-year and 5-year survival probability. Results: We obtained 2429 DEGs in tumor tissue, within which, 1267 were predicted to m6A target genes. A prognostic m6A-DEGs network of 224 survival-related target DEGs was established. We classified LUAD into 2 subtypes, which were significantly different in OS time, clinicopathological characteristics, and fractions of 12 immune cell types. A PS model of five genes (C1QTNF6, THSD1, GRIK2, E2F7 and SLCO1B3) successfully split the training set or an independent GEO dataset into two subgroups with significantly different OS time (p < 0.001, AUC = 0.723; p = 0.017, AUC = 0.705).A nomogram model combining PS status, pathologic stage, and recurrence was built, showing good performance in predicting 3-year and 5-year survival probability (C-index = 0.708, 0.723, p-value = 0). Conclusion: Using candidate m6A target genes, we obtained two molecular subtypes and designed a reliable five-gene PS score model for survival prediction in LUAD.

Learning curve for two-port video-assisted thoracoscopic surgery lung segmentectomy.

OBJECTIVES: When lung cancer evolves from a large, centrally located mass to small, peripherally located pulmonary nodules, such as ground glass nodules, segmentectomy offers a reasonable method by which to save lung parenchyma without eliciting compromising oncological effects. To master these techniques, it is important to analyse the learning curve of surgeons. Therefore, the aim of the present study was to analyse the learning curve for two-port video-assisted thoracoscopic surgery (VATS) segmentectomy in our institution. METHODS: We retrospectively collected data from 86 consecutive patients who underwent two-port VATS segmentectomy between June 2019 and November 2019. The operative time (OT) and estimated blood loss and other complications were analysed. The learning curve was evaluated using the OT and the cumulative sum (CUSUM) value of OTs across all cases. RESULTS: We generated a graph of the CUSUM of OTs and found that the learning curve could be differentiated into 3 phases: phase 1, the initial learning phase (1st to 27th operation); phase 2, the increased competence phase (28th to 54th operation); and phase 3, the experienced phase (55th to 86th operation). The CUSUM value inflected at patient number 47. There were significant reductions in the OT and bleeding in phase 3 relative to phases 1 and 2. There were also significant differences in OT and estimated blood loss between the simple and complex segmentectomy procedures. CONCLUSIONS: In conclusion, the 3 phases identified using CUSUM analysis of the OT represented characteristic stages of the learning curve for two-port VATS segmentectomy. The data indicate that, in our institution, the inflection point for the learning curve was achieved after operating on 47 cases.

Electromagnetic bronchoscopy guided microwave ablation for early stage lung cancer presenting as ground glass nodule.

BACKGROUND: Patients with early-stage lung cancer are sometimes medically inoperable, and for patients with multiple primary lung cancers, surgical resection alone sometimes proves to be impractical. Local treatments like microwave ablation (MWA) are investigational alternatives for these patients. Most reported MWA procedures for lung cancers are performed percutaneously under CT guidance. MWA navigated by electromagnetic bronchoscopy (ENB) has been limitedly studied. In this study, we aimed to evaluate the safety and feasibility of MWA under ENB guidance in patients with inoperable early-stage lung cancers or multiple primary lung cancers which cannot be completely resected. METHODS: From June 2019 to December 2020, preliminary attempts of ENB-guided MWA were made in five medically inoperable patients with a single early-stage lung cancer and ten patients with multiple primary lung cancers which were difficult to resect at the same time. For patients with concomitant pulmonary nodules which needed surgical resection, thoracoscopic resections were performed following ENB-guided MWA. The safety, feasibility, and technique effectiveness of treatments were evaluated. RESULTS: ENB-guided MWA for 15 ground glass nodules (GGNs) in 15 patients was completed in accordance with the planned protocol. Biopsy of 13 GGNs showed malignancy. Five patients received simple ENB-guided MWA without simultaneous surgical resection and ten patients received simultaneous surgical resection for 13 concomitant pulmonary nodules. CT scan by the first postoperative week showed technique effectiveness of ablation for 11 nodules indicated for MWA. Four patients had mild complications after the procedure and recovered shortly after treatment. CONCLUSIONS: For medically inoperable patients with a single GGN manifesting early-stage lung cancer and patients with multiple primary early-stage lung cancers which cannot be resected at the same time, ENB-guided MWA might be a safe and feasible alternative local treatment, whether combined with surgical resection or not. However, large, prospective, randomized, multicenter studies are needed to confirm its role in the treatment of early-stage lung cancer.

Surgical resection of superior pulmonary sulcus tumor after neoadjuvant chemoradiation via the anterior transmanubrial approach: a case report.

Superior pulmonary sulcus tumor is a cancer arising in the apex of the lung that with potential invasion of the brachial plexus, upper ribs, vertebrae, subclavian vessels, and stellate ganglion. Induction concurrent chemoradiotherapy followed by radical surgical resection with lobectomy combined with any structures in the thoracic inlet invaded by tumor and thorough mediastinal lymph node dissection is the preferred treatment. Both anterior and posterior approaches are applied for resection. Here, we report a 61-year-old man with an 8.6 cm × 5.1 cm mass arising from the right upper lobe invading the apex of the chest wall. Brachial plexus magnetic resonance imaging suggested tumor invasion of the inferior trunk of the brachial plexus, anterior portion of the first 2 ribs, and suspicious involvement of the subclavian artery. Biopsy of the mass showed stage cT4N2M0, IIIB, poorly differentiated adenocarcinoma. The patient was treated by induction concurrent chemoradiotherapy, which was followed by surgical resection of the right upper lobe and the affected chest wall via the transmanubrial approach. The patient suffered prolonged postoperative air leak and empyema. After continuous chest tube drainage and intrapleural fibrinolytic therapy, he recovered well and was discharged safely. Final pathology showed no viable residue tumor, pathologic complete response of the tumor to induction treatment, a tumor size of 4.1 cm, and no lymph nodes; therefore, the final stage was ypT0N0M0. The transmanubrial approach is feasible for resection of tumor invading the branches of the subclavian artery; however, postoperative empyema which might have resulted from prolonged air leak should be carefully treated by meticulous air leak management.

The Feasibility and Safety of Routine Thoracic Surgeries in the Low-Risk Areas During the Coronavirus Disease 2019 Pandemic.

Coronavirus disease 2019 (COVID-19) has been under good control, and work resumption has been gradually carried out in most parts of the People's Republic of China including Shanghai after March 2020. However, intense focus and resources have been diverted to patients with COVID-19, leaving patients with diseases other than COVID-19 somehow neglected owing to limited access to routine health care. Furthermore, whether routine thoracic surgery service is safe in low-risk areas of COVID-19 infection is still unknown. We hereby retrospectively analyzed the quantity and quality of thoracic surgeries performed by a single team from the Shanghai Chest Hospital between January and May 2020, compared with the corresponding period in the past year. Results suggested that comparable qualities of diagnosis, surgical treatment, and perioperative outcomes were safely and successfully achieved. The total number of surgical procedures gradually increased and surpassed with that of the corresponding period in the past year when the situation of COVID-19 has been in good control in Shanghai by April. Importantly, neither medical staffs nor patients were diagnosed of having COVID-19 infection. In conclusion, although COVID-19 has made considerable impact on elective surgery for thoracic diseases, it is safe and feasible to carry out routine thoracic surgery services in low-risk areas, provided that careful screening of COVID-19 and thorough protection of medical staffs and patients are taken. It is hoped that these findings would serve as a useful reference for thoracic departments all over the world during the COVID-19 pandemic, especially after work resumption.

[Predictors for the Bronchiolitis Obliterans Syndrome in Lung Transplant Patient].

Lung transplantation is the ultimate treatment of end-stage lung disease. After transplantation, the 1-year survival rate is 80%, while the 5-year survival rates remaines at around 50% mainly due to bronchiolitis obliterans syndrome (BOS). BOS is regarded as a fibrosing process in the small airways leading to irreversible airway obstruction. A lot of factors are involved in the development of BOS, such as Ischemia/reperfusion injury, infections, oxidative stress, and acute rejection, etc. Studies have shown that early diagnosis of BOS may improve outcome. It is valuable for the long-term survival of lung transplantation to find out several predictors for the BOS. This article reviews the current state of knowledge on predictors for BOS.

Safety of early discharge with a chest tube after pulmonary segmentectomy.

OBJECTIVES: Early removal of chest tube is an important step in enhanced recovery after surgery protocols. However, after pulmonary resection with a wide dissection plane, such as pulmonary segmentectomy, prolonged air leak, a large volume of pleural drainage and the risk of developing empyema in patients can delay chest tube removal and result in a low rate of completion of the enhanced recovery after surgery protocol. In this study, we aimed to assess the safety of discharging patients with a chest tube after pulmonary segmentectomy. METHODS: We retrospectively reviewed a single surgeon's experience of pulmonary segmentectomy from May 2019 to September 2019. Patients who fulfilled the criteria for discharging with a chest tube were discharged and provided written instructions. They returned for chest tube removal after satisfactory resolution of air leak or fluid drainage. RESULTS: In total, 126 patients underwent pulmonary segmentectomy. Ninety-five (75%) patients were discharged with a chest tube postoperatively. The mean time to chest tube removal after discharge was 5.6 (range 2-32) days, potentially saving 532 inpatient hospital days. Overall, 90 (95%) patients experienced uneventful and successful outpatient chest tube management. No life-threatening complications were observed. No patient experienced complications resulting from chest tube malfunction. Five (5%) patients experienced minor complications. Overall, all patients reported good-to-excellent mobility with a chest tube. CONCLUSIONS: Successful postoperative outpatient chest tube management after pulmonary segmentectomy can be accomplished in selected patients without a major increase in morbidity or mortality.

Metformin reverses chemoresistance in non-small cell lung cancer via accelerating ubiquitination-mediated degradation of Nrf2.

BACKGROUND: The therapeutic efficacy of cisplatin-based chemotherapy for non-small cell lung cancer (NSCLC) is limited by drug resistance. In NSCLC, hyperactivation of nuclear factor erythroid 2-related factor 2 (Nrf2) counteracts oxidative stress to promote chemoresistance. Metformin-mediated downregulation of Nrf2 plays a pivotal role in overcoming drug resistance in NSCLC cells. Therefore, a deeper understanding of the molecular mechanisms of combination therapy and the role of Nrf2 in chemotherapeutic response is critical to clinical translation. METHODS: The effects of combination therapy with metformin and cisplatin on cell proliferation and apoptosis, intracellular reactive oxygen species (ROS) levels, and xenograft tumor formation were analyzed in NSCLC cells. Co-immunoprecipitation (co-IP) and Phos-tag assays were used to explore the mechanism of metformin-mediated Nrf2 suppression. Immunohistochemical (IHC) staining was performed to detect Nrf2 expression in matched tumor samples before and after neoadjuvant chemotherapy. RESULTS: Metformin was observed to synergistically augment cisplatin-induced cytotoxicity by strongly inhibiting the level of Nrf2, thereby weakening the antioxidant system and detoxification ability of Nrf2 and enhancing ROS-mediated apoptosis in NSCLC. The synergistic antitumor effect of combination therapy is blocked by treatment with the ROS scavenger N-acetyl cysteine (NAC) as well as overexpression of Nrf2 and its downstream antioxidant protein. Mechanistically, metformin extensively dephosphorylates Nrf2 by attenuating the interaction between Nrf2 and extracellular signal-regulated kinases 1/2 (ERK1/2), which then restores its polyubiquitination and accelerates its proteasomal degradation. Moreover, for the first time, an association of non-decreased Nrf2 expression in patients after neoadjuvant chemotherapy with poor survival and chemoresistance in NSCLC was revealed. CONCLUSIONS: Our findings illustrate the mechanism of metformin-mediated Nrf2 degradation through posttranslational modifications (PTMs), which weakens the ROS defense system in NSCLC. Fluctuations in Nrf2 expression have a strong predictive ability for chemotherapeutic response in neoadjuvant NSCLC patients. Targeting of the Nrf2 pathway could be a therapeutic strategy for overcoming chemoresistance, with metformin as the first choice for this strategy.

Downregulation of HSPA2 inhibits proliferation via ERK1/2 pathway and endoplasmic reticular stress in lung adenocarcinoma.

BACKGROUND: To explore the mechanisms of HSPA2 downregulation in inhibiting the proliferation of lung adenocarcinoma. METHODS: We obtained 85 specimens of human lung adenocarcinoma and specimens of adjacent nontumor tissues from the First Affiliated Hospital, School of Medicine, Zhejiang University. We then analyzed the expression of HSPA2 in these tissues and in lung adenocarcinoma and normal lung cell lines. Human lung adenocarcinoma cell lines were transfected with siRNA silencing HSPA2 and subjected to colony forming, Thiazolyl blue tetrazolium bromide (MTT), propidium iodide flow cytometry, immunofluorescence assay and western blotting to explore the causes of the reduction in the proliferation of lung adenocarcinoma cells and the endoplasmic reticulum stress induced by HSPA2 downregulation. Finally, we confirmed these mechanisms via rescue assay. RESULTS: Greater HSPA2 expression was found in the lung adenocarcinoma specimens than in the specimens of adjacent nontumor tissues, and greater expression was found in lung adenocarcinoma cell lines than in normal cell lines. HSPA2 knockdown via siRNA reduced proliferation and led to G1/S phase cell cycle arrest in the lung adenocarcinoma cell lines. G1/S phase cell cycle arrest triggered by HSPA2 downregulation could be attributed, at least in part, to phosphorylation and activation of the Erk1/2 pathway and probably to activation of IRE1α/PERK-mediated endoplasmic reticulum stress. CONCLUSIONS: HSPA2 plays an important role in the origin and development of lung adenocarcinoma. It is thus deserving of further study as a promising clinical therapeutic target.

Discriminating association of a common telomerase reverse transcriptase promoter polymorphism with telomere parameters in non-small cell lung cancer with or without epidermal growth factor receptor mutation.

BACKGROUND: The role of epidermal growth factor receptor (EGFR) pathways in regulating telomerase is increasingly being recognised. We analysed the impact of rs2853669 single nucleotide polymorphism (SNP) on telomere parameters and its prognostic value for non-small cell lung cancer (NSCLC) with or without EGFR mutation. METHODS: The association of rs2853669 with telomerase reverse transcriptase (TERT) mRNA level and relative telomere length (RTL) was analysed using resected tumour samples from 250 NSCLC patients. We also investigated the patients' clinical outcomes with a median follow-up of 57 months (2-99 months). RESULTS: The rs2853669 T/C allele was significantly associated with lower TERT mRNA expression (versus C/C and versus T/T; p < 0.001 for both) and shorter RTL (versus C/C and versus T/T; p = 0.039 and 0.023) in patients without EGFR mutation. Such difference was not observed in their counterparts harbouring EGFR mutation. When considering the cohort as a whole, T/C allele was significantly associated with shortest overall survival compared with T/T or C/C allele (mean: 61.8, 80.9 and 88.7 months, plog-rank < 0.001) and disease-free survival (mean: 78.3, 87.9 and 91.5 months, plog-rank = 0.019). Stratification analyses showed that the negative prognostic effect of T/C on OS was constrained in patients without EGFR mutation. CONCLUSION: Our study revealed significant associations of a common SNP within TERT promoter region on telomere parameters and survival in NSCLC patients without EGFR mutation. The result may help providing instruction for therapeutic interventions targeting telomerase and evidence for investigation of TERT-EGFR interacting mechanism in telomere biology.

Clinical outcomes of harmonic scalpel in esophageal cancer surgery / 中国胸心血管外科临床杂志

@#Objective    To assess the outcome of harmonic scalpel (HS) in esophageal cancer surgery and to provide evidence for the role of HS in the enhanced recovery after surgery (ERAS) and short-term prognosis after esophageal cancer surgery. Methods    We collected the clinical data of 81 esophageal cancer patients receiving surgery by HS between January 1 and December 31, 2016 and successfully followed up in our department. There were 67 males and 14 females with an average age of 64.07±7.52 years. Sweet approach was adopted in 16 patients, Ivor-Lewis approach in 23 and McKeown approach in 40. Intrathoracic anastomosis was completed in 41 patients and cervical anastomosis in 40. The length of total hospital stay and postoperative hospital stay, operation time, intraoperative blood loss, duration and volume of thoracic drainage and perioperative complications were recorded and compared in patients with different surgical approaches and anastomosis sites. Results    For these 81 patients, the operation time was 276.7±70.4 min, and the intraoperative blood loss was 115.9±69.7 ml. The postoperative duration of thoracic drainage, postoperative complication rate and the drainage volume were 12.3±5.3 d, 35.80% and 1 411.9±1 199.5 ml, respectively. During the follow-up, 15 patients died and the cumulative survival rate was 81.48%. There was no obvious HS-related complication. The operation time of Sweet approach was shorter than that of Ivor-Lewis or McKeown approach (P=0.012) and the dissected lymph nodes were less in Sweet approach (P=0.035). There was no significant difference in perioperative indexes and postoperative short-term prognosis between intrathoracic anastomosis and cervical anastomosis. Conclusion    HS is widely used in the surgery for esophageal cancer with safety and effectiveness, which is worthy of clinical application.

Sublobar Resection for Pulmonary Aspergilloma: A Safe Alternative to Lobectomy.

BACKGROUND: This study was performed to evaluate the effectiveness of sublobar resection for the treatment of pulmonary aspergilloma compared with lobectomy. METHODS: Patients with pulmonary aspergilloma who underwent lobectomy or sublobar resection in our department between March 2007 and December 2015 were retrospectively reviewed. Data were collected for patient demographic characteristics, medical history, preoperative investigations, perioperative findings, postoperative conditions, and recurrence status. Propensity-matched comparative analyses were performed to adjust for potential differences of patients' baseline characteristics between the groups. RESULTS: A total of 96 patients underwent lobectomy, 46 patients underwent attempted sublobar resection. The median follow-up time is 53 months. No recurrence was found in either group. Three patients (3.1%) in the lobectomy group required reoperation for bleeding. The patients who underwent sublobar resection had less underlying lung disease (p = 0.031), smaller lesions (p = 0.033), and were more likely to have been treated with video-assisted thoracic surgery (p < 0.001). These differences were eliminated by propensity score matching (46 pairs were successfully matched). Comparative analyses in matched groups demonstrate that there was no marked difference in the volume and duration of chest drainage or the length of postoperative hospital stay. However, the patients with sublobar resection had shorter operation time (p = 0.004), less blood loss (p = 0.042), and less postoperative complication (p = 0.048). CONCLUSIONS: Sublobar resection performed for small simple pulmonary aspergilloma and selected complex pulmonary aspergilloma has a low recurrence rate and confers perioperative advantages compared with lobectomy.

Clinical, cellular, and bioinformatic analyses reveal involvement of WRAP53 overexpression in carcinogenesis of lung adenocarcinoma.

Lung cancer, of which non-small cell lung cancer accounts for 80%, remains a leading cause of cancer-related mortality and morbidity worldwide. Our study revealed that the expression of WD repeat containing antisense to P53 (WRAP53) is higher in lung-adenocarcinoma specimens than in specimens from adjacent non-tumor tissues. The prevalence of WRAP53 overexpression was significantly higher in patients with tumor larger than 3.0 cm than in patients with tumor smaller than 3.0 cm. The depletion of WRAP53 inhibits the proliferation of lung-adenocarcinoma A549 and SPC-A-1 cells via G1/S cell-cycle arrest. Several proteins interacting with WRAP53 were identified through co-immunoprecipitation and liquid chromatography/mass spectrometry. These key proteins indicated previously undiscovered functions of WRAP53. These observations strongly suggested that WRAP53 should be considered a promising target in the prevention or treatment of lung adenocarcinoma.

Downregulation of RUVBL1 inhibits proliferation of lung adenocarcinoma cells by G1/S phase cell cycle arrest via multiple mechanisms.

Lung cancer remains a leading cause of cancer-related mortality and morbidity worldwide, of which non-small cell lung cancer (NSCLC) accounts for 80 %. RUVBL1 is a highly conserved eukaryotic AAA+ adenosine 5'-triphosphatase (ATPase) that has many functions highly relevant to cancer. We therefore attempted to determine the potential role of RUVBL1 in the biogenesis of lung adenocarcinoma and obtained some interesting results. Our study revealed that RUVBL1 expression was higher in lung adenocarcinoma specimens than in those of adjacent non-tumor tissues and in lung cancer cell lines than in normal lung cell lines. RUVBL1 knockdown via siRNA reduced proliferation and caused G1/S phase cell cycle arrest in lung adenocarcinoma cell lines. The G1/S phase cell cycle arrest triggered by RUVBL1 downregulation could be attributed, at least in part, to repression of the AKT/GSK-3ß/cyclin D1 pathway and probably to the activation of IRE1α-mediated endoplasmic reticulum (ER) stress. We thus demonstrated for the first time that a knockdown of RUVBL1 could effectively inhibit the proliferation of lung adenocarcinoma A549 and H292 cells through the induction of G1/S phase cell cycle arrest via multiple mechanisms. These observations strongly suggested that RUVBL1 should be considered a promising target for the prevention or therapy of lung adenocarcinoma.

Comparison of robotic and video-assisted thoracic surgery for lung cancer: a propensity-matched analysis.

BACKGROUND: Reports of comparison between robotic and thoracoscopic surgery for lung cancer are limited, we aimed to compare the perioperative outcomes of robotic and thoracoscopic anatomic pulmonary resection for lung cancer. METHODS: A total of 184 patients with lung cancer underwent anatomic pulmonary resection by robotics or thoracoscopy. A propensity-matched analysis with incorporated preoperative variables was used to compare the perioperative outcomes between the two procedures. RESULTS: Overall, 71 patients underwent robotic pulmonary resection, including 64 lobectomies and 7 segmentectomies, while 113 patients underwent thoracoscopic lobectomy and segmentectomy. Propensity match produced 69 pairs. The mean length of postoperative stay (7.6±4.6 vs. 6.4±2.6 d, P=0.078), chest tube duration (5.3±3.7 vs. 4.4±1.7 d, P=0.056), number of lymph nodes retrieved (17.9±6.9 vs. 17.4±7.0, P=0.660), stations of lymph nodes resected (7.4±1.6 vs. 7.6±1.7, P=0.563), operative blood loss (53.9±29.3 vs. 50.3±37.9 mL, P=0.531), morbidity rates (42.0% vs. 30.4%, P=0.157) were similar between the robotics and thoracoscopy. However, robotics was associated with higher cost ($12,067±1,610 vs. $8,328±1,004, P<0.001), and longer operative time (136±40 vs. 111±28 min, P<0.001). CONCLUSIONS: Robotics seems to have higher hospital costs and longer operative time, without superior advantages in morbidity rates and oncologic efficiency. Further prospective randomized clinical trials were needed to validate both of its short- and long-term oncologic efficiency.

Quantitative chemical proteomics profiling of de novo protein synthesis during starvation-mediated autophagy.

Autophagy is an intracellular degradation mechanism in response to nutrient starvation. Via autophagy, some nonessential cellular constituents are degraded in a lysosome-dependent manner to generate biomolecules that can be utilized for maintaining the metabolic homeostasis. Although it is known that under starvation the global protein synthesis is significantly reduced mainly due to suppression of MTOR (mechanistic target of rapamycin serine/threonine kinase), emerging evidence demonstrates that de novo protein synthesis is involved in the autophagic process. However, characterizing these de novo proteins has been an issue with current techniques. Here, we developed a novel method to identify newly synthesized proteins during starvation-mediated autophagy by combining bio-orthogonal noncanonical amino acid tagging (BONCAT) and isobaric tags for relative and absolute quantitation (iTRAQTM). Using bio-orthogonal metabolic tagging, L-azidohomoalanine (AHA) was incorporated into newly synthesized proteins which were then enriched with avidin beads after a click reaction between alkyne-bearing biotin and AHA's bio-orthogonal azide moiety. The enriched proteins were subjected to iTRAQ labeling for protein identification and quantification using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Via the above approach, we identified and quantified a total of 1176 proteins and among them 711 proteins were found to meet our defined criteria as de novo synthesized proteins during starvation-mediated autophagy. The characterized functional profiles of the 711 newly synthesized proteins by bioinformatics analysis suggest their roles in ensuring the prosurvival outcome of autophagy. Finally, we performed validation assays for some selected proteins and found that knockdown of some genes has a significant impact on starvation-induced autophagy. Thus, we think that the BONCAT-iTRAQ approach is effective in the identification of newly synthesized proteins and provides useful insights to the molecular mechanisms and biological functions of autophagy.