Efficacy and safety of novel immune checkpoint inhibitor-based combinations versus chemotherapy as first-line treatment for patients with extensive-stage small cell lung cancer: A network meta-analysis.

BACKGROUND: Patients with extensive-stage small cell lung cancer (ES-SCLC) have an exceptionally poor prognosis and immune checkpoint inhibitors (ICIs) combined with etoposide-platinum is recommended as standard first-line therapy. However, which combination pattern is the best still remains unknown. This network meta-analysis was performed to compare the efficacy and safety of currently available patterns including an antiangiogenic agent containing regimen and probed into the most appropriate therapy for patients. METHODS: Hazard ratios (HRs) and odds ratios (ORs) were generated using R software. The outcomes of overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events of grade 3 or higher (grade ≥ 3 adverse events [AEs]) were analyzed. RESULTS: A total of 10 randomized controlled trials (RCTs) involving 5544 patients were included for analysis. Drug combination patterns included adebrelimab, atezolizumab, durvalumab, durvalumab plus tremelimumab, ipilimumab, pembrolizumab, serplulimab, benmelstobart plus anlotinib, tislelizumab, tiragolumab plus atezolizumab and toripalimab in combination with chemotherapy. The novel antiangiogenic agent containing regimen benmelstobart + anlotinib + chemotherapy showed the highest possibility to present the best PFS and OS versus chemotherapy. Compared with ICI plus chemotherapy, it also achieved significantly better PFS and presented a tendency of OS benefit. As for safety and toxicity, patients treated with benmelstobart + anlotinib + chemotherapy and durvalumab + tremelimumab + chemotherapy suffered a higher likelihood of more grade ≥ 3 AEs without unexpected AEs. CONCLUSION: PD-1/PD-L1 inhibitors-based combinations are associated with significant improvement in both PFS and OS for treatment-naïve ES-SCLC patients. Benmelstobart plus anlotinib with chemotherapy (CT) yielded better survival benefit versus CT alone or other ICIs + CT with caution for more adverse effects along with the addition of an antiangiogenic agent.

Involvement of the Keap1-Nrf2-ARE pathway in the antioxidant activity of sinomenine.

Sinomenine is a pure alkaloid isolated from Sinomenium acutum. This study is aimed to investigate the critical role of the nuclear factor erythroid 2-related factor 2 (Nrf2)-kelch-like ECH-associated protein-1(Keap1)-antioxidant response element (ARE) antioxidative signaling pathway in protecting sinomenine against H2O2-induced oxidative injury. Cytotoxicity and antioxidant experiments to initially determine the protective effects of sinomenine show that sinomenine has no effect on the decreased cell viability and presents similar potency in scavenging all three free radicals. The binding affinity between sinomenine and Keap1 was determined via fluorescence polarization assay, with IC50 of 13.52 µM. Quantum chemical calculation and theoretical simulation illustrated that sinomenine located into the Nrf2-binding site of Keap1 via hydrophobic and hydrogen interactions, showing high stability and binding affinity. On the basis of the stable binding of sinomenine with Keap1, sinomenine efficiently induced nuclear translocation of Nrf2, and increased in ARE activity in a concentration-dependent manner. Quantitative polymerase chain reaction provided further evidences that sinomenine-induced protection upregulated ARE-dependent genes, such as NAD(P)H quinone oxidoreductase 1, hemeoxygenase-1, and glutamate-cysteine ligase modifier subunit. Western blot confirmed that sinomenine increased the expressions of these antioxidative enzymes. Taken together, in vitro and in silico evaluations demonstrate that sinomenine inhibits the binding of Keap1 to Nrf2, promotes the nuclear accumulation of Nrf2 and thus leads to the upregulated expressions of Nrf2-dependent antioxidative genes. Our findings also highlight the use of sinomenine for pharmacological or therapeutic regulation of the Nrf2-Keap1-ARE system, which is a novel strategy to prevent the progression of oxidative injury.

Computational modeling of the cephalic arch with jugulocephalic vein variant predicts hemodynamic profiles in patients with brachiocephalic fistula.

BACKGROUND: The cephalic vein is often used in for arteriovenous fistula creation; however, the cephalic vein variation is common. This study will propose new theoretical explanations for a new discovered variation of cephalic vein draining into external jugular vein with "T-junction" shape by means of 3D computational hemodynamic modeling, which may provide reference for clinical practice. METHODS: The precise measurements were conducted for the variant right cephalic vein draining into external jugular vein and for a normal right cephalic vein as a control. After processing the anatomical data, 3D geometrical model was reconstructed. Then, the influent field inside the variant jugulocephalic vein was mathematically modeled to get a detailed description of hemodynamic environment. RESULTS: The anatomical parameters of the "T-junction" jugulocephalic vein variant were much more different from the normal right cephalic vein. The wall shear stress of variant cephalic vein at the corresponding position was higher and changed more rapidly than that of normal cephalic vein. The shear rate contour lines are disordered in several areas of the variant cephalic vein, indicating that the hemodynamic parameters in these areas are unstable. The hemodynamic characteristics at the confluence of the variant cephalic vein are more complex, with more areas where hemodynamic parameters are disrupted. CONCLUSIONS: The variation of cephalic arch in a "T-junction" with external jugular vein largely altered the fluid dynamics, especially in hemodialysis patients with brachiocephalic fistula in terms of the simulating flow in 3D computational model. This computational model provides hemodynamic profiles for stabilizing or modulating fluid dynamics in patients with jugulocephalic vein variant after brachiocephalic fistula.

A nomogram combining thoracic CT and tumor markers to predict the malignant grade of pulmonary nodules ≤3 cm in diameter.

Background: With the popularity of computed tomography (CT) of the thorax, the rate of diagnosis for patients with early-stage lung cancer has increased. However, distinguishing high-risk pulmonary nodules (HRPNs) from low-risk pulmonary nodules (LRPNs) before surgery remains challenging. Methods: A retrospective analysis was performed on 1064 patients with pulmonary nodules (PNs) admitted to the Qilu Hospital of Shandong University from April to December 2021. Randomization of all eligible patients to either the training or validation cohort was performed in a 3:1 ratio. Eighty-three PNs patients who visited Qianfoshan Hospital in the Shandong Province from January through April of 2022 were included as an external validation. Univariable and multivariable logistic regression (forward stepwise regression) were used to identify independent risk factors, and a predictive model and dynamic web nomogram were constructed by integrating these risk factors. Results: A total of 895 patients were included, with an incidence of HRPNs of 47.3% (423/895). Logistic regression analysis identified four independent risk factors: the size, consolidation tumor ratio, CT value of PNs, and carcinoembryonic antigen levels in blood. The area under the ROC curves was 0.895, 0.936, and 0.812 for the training, internal validation, and external validation cohorts, respectively. The Hosmer-Lemeshow test demonstrated excellent calibration capability, and the fit of the calibration curve was good. DCA has shown the nomogram to be clinically useful. Conclusion: The nomogram performed well in predicting the likelihood of HRPNs. In addition, it identified HRPNs in patients with PNs, achieved accurate treatment with HRPNs, and is expected to promote their rapid recovery.

Effects of Neoadjuvant Radiotherapy on Survival in Patients with Stage IIIA-N2 Non-Small-Cell Lung Cancer Following Pneumonectomy.

Background: Pneumonectomy is a drastic but sometimes inevitable treatment option for patients with non-small-cell lung cancer (NSCLC) to improve their chances for long-term survival. However, the optimal adjuvant radiotherapy used for patients with N2 NSCLC following pneumonectomy remains unclear in the literature. Methods: T1-4N0-2M0 NSCLC patients registered in the Surveillance, Epidemiology, and End Results database were retrospectively analyzed. Propensity score matching was applied to balance the assignment of patients. Cox proportional hazards models and Kaplan−Meier analyses were used to identify the factors related to overall survival rates. Restricted cubic splines were used to detect the possible nonlinear dependency of the relationship between the risk of survival and age. Results: A total of 4308 NSCLC patients were enrolled in this study. In N2 patients, the long-term outcome of the chemotherapy and postoperative radiotherapy groups was the worst (p = 0.014). Subgroup analyses showed that the influence of age on survival outcome was confined to patients who received chemotherapy and neoadjuvant radiotherapy (p = 0.004). Meanwhile, patients >65 years of age who received chemotherapy and neoadjuvant radiotherapy had significantly worse prognoses than those in the chemotherapy group (p = 0.005). Conclusions: Our results show that neoadjuvant radiotherapy may have potential benefits in patients aged ≤ 65 years who are scheduled for pneumonectomy, but not in elderly patients.

V7 ENB-guided thoracoscopic sublobectomy for stage IA synchronous multiple primary lung cancer.

BACKGROUND: An increasing number of patients are being diagnosed with synchronous multiple primary lung cancer (SMPLC) with the popularization of lung cancer screening programs. However, a strategy for accurate location and suitable surgery therapy is still lacking. The present study aimed to explore the accuracy and feasibility of electromagnetic navigation bronchoscopy (ENB)-guided thoracoscopic sublobectomy for stage IA SMPLC. METHODS: Patients with SMPLC who underwent ENB-guided sublobectomy from January 2020 to June 2022 were enrolled in this study. The analysis of localization accuracy of ENB and surgical outcome was conducted. RESULTS: Overall, 138 patients with 353 malignant nodules were enrolled. The tumor size was 0.7 cm (range from 0.5 to 1.1 cm). ENB localization was performed on 162 nodules, and a customized scoring system was developed to evaluate localization accuracy. The success rate of localization was 98.3% (178/181). Notably, localization accuracy was positively correlated with bronchial signs (p < 0.01) and negatively correlated with the distance from the nodule to the pleura (p = 0.02). All nodules were completely resected. Operation time, drainage volume on the third postoperative day, and catheter time were significantly correlated with the resected lesion numbers (p = 0.009, p = 0.004, and p = 0.01, respectively). CONCLUSIONS: ENB-guided uniportal video-assisted thoracoscopic sublobectomy provides accurate preoperative localization and avoids unnecessary lung resection of patients with stage IA SMPLC. However, complete resection of multilocation nodules (more than four lesions) increases the risk of postoperative complications. A new combined treatment strategy for SMPLC should be explored.

EPHA5 mutation was associated with adverse outcome of atezolizumab treatment in late-stage non-small cell lung cancers.

BACKGROUND: The aim of the study was to investigate predictive value of gene mutation for atezolizumab treatment response from OAK and POPLAR cohorts. METHODS: Several public databases were used for analyzing gene mutation type of EPHA5 and association with alterations of other genes. Survival analysis was performed for patients receiving atezolizumab from OAK and POPLAR cohorts. RESULTS: EPHA5 mutation have high frequency to harbor TP53 and KEAP1 mutations. The bTMB value has significant difference between EPHA5 mutant and wild-type cases. Patients with EPHA5 mutation got worse survival compared to those without gene mutations receiving atezolizumab (P = 0.0186). CONCLUSIONS: EPHA5 mutant NSCLC may represent a subpopulation which showed worse response after treatment of atezolizumab compared to wild-type ones.

Comparison of perioperative outcomes between robotic-assisted and video-assisted thoracoscopic surgery for mediastinal masses in patients with different body mass index ranges: A population-based study.

Background: The effectiveness of robotic-assisted thoracoscopic surgery (RATS) for mediastinal masses has not been fully evaluated. This study aimed to compare the perioperative outcomes between RATS and video-assisted thoracoscopic surgery (VATS) for mediastinal masses, and then explore which group of people would benefit more from RATS. Methods: This retrospective study compared the perioperative outcomes of patients with mediastinal masses who underwent RATS and VATS from September 2018 to December 2021. Subgroup analysis were performed according to body mass index (BMI) ranges. Results: A total of 212 patients with mediastinal masses (106 RATS cases and 106 VATS cases) were included. Compared with the VATS group, the RATS group had a significantly reduced incidence of overall postoperative complications (5.7% vs. 14.2%, p = 0.039), complications of grade II or less (3.8% vs. 12.3%, p = 0.023), and pneumonia (2.8% vs. 9.4%, p = 0.045). Hospitalization costs were significantly higher in the RATS group (¥ 49350.0 vs. ¥ 32551.9, p < 0.001). There was no significant difference in operation duration, intraoperative estimated blood loss, postoperative chest tube drainage volume, NRS pain score, day of chest tube removal, complications of grade III or more, or in-hospital mortality rate (p > 0.05). Subgroup analysis indicated that the incidence of overall postoperative complications (3.1% vs. 15.2%, p = 0.017), complications of grade II or less (1.5% vs. 12.1%, p = 0.033) and postoperative length of stay (4 days vs. 4.5 days, p = 0.046) were significantly reduced in the RATS group for overweight and obese patients (BMI ≥ 24 kg/m2), while these differences became insignificant in the BMI < 24 kg/m2 subgroup. Conclusion: RATS could reduce the incidence of postoperative complications, shorten the postoperative length of stay and might be a more cost-effective surgical treatment for overweight and obese patients with mediastinal masses.

Genomics Analysis and Nomogram Risk Prediction of Occult Lymph Node Metastasis in Non-Predominant Micropapillary Component of Lung Adenocarcinoma Measuring ≤ 3 cm.

Background: The efficacy of sublobar resection and selective lymph node dissection is gradually being accepted by thoracic surgeons for patients within early-stage non-small cell lung cancer (NSCLC). Nevertheless, there are still some NSCLC patients develop lymphatic metastasis at clinical T1 stage. Lung adenocarcinoma with a micropapillary (MP) component poses a higher risk of lymph node metastasis and recurrence even when the MP component is not predominant. Our study aimed to explore the genetic features and occult lymph node metastasis (OLNM) risk factors in patients with a non-predominant micropapillary component (NP-MPC) in a large of patient's cohort with surgically resected lung adenocarcinoma. Methods: Between January 2019 and December 2021, 6418 patients who underwent complete resection for primary lung adenocarcinoma at the Qilu Hospital of Shandong University. In our study, 442 patients diagnosed with lung adenocarcinoma with NP-MPC with a tumor size ≤3 cm were included. Genetic alterations were analyzed using amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). Abnormal protein expression of gene mutations was validated using immunohistochemistry. A nomogram risk model based on clinicopathological parameters was developed to predict OLNM. This model was invalidated using the calibration plot and concordance index. Results: In our retrospective cohort, the incidence rate of the micropapillary component was 11.17%, and OLNM was observed in 20.13% of the patients in our study. ARMS-PCR suggested that EGFR exon 19 del was the most frequent alteration in NP-MCP patients compared with other gene mutations (frequency: 21.2%, P<0.001). Patients harboring exon 19 del showed significantly higher risk of OLNM (P< 0.001). A nomogram was developed based on five risk parameters, which showed good calibration and reliable discrimination ability (C-index = 0.84) for evaluating OLNM risk. Conclusions: Intense expression of EGFR exon 19 del characterizes lung adenocarcinoma in patients with NP-MCP and it's a potential risk factor for OLNM. We firstly established a nomogram based on age, CYFRA21-1 level, tumor size, micropapillary and solid composition, that was effective in predicting OLNM among NP-MCP of lung adenocarcinoma measuring ≤ 3 cm.

Construction and validation of a nomogram for predicting prolonged air leak after minimally invasive pulmonary resection.

BACKGROUND: Prolonged air leak (PAL) remains one of the most frequent postoperative complications after pulmonary resection. This study aimed to develop a predictive nomogram to estimate the risk of PAL for individual patients after minimally invasive pulmonary resection. METHODS: Patients who underwent minimally invasive pulmonary resection for either benign or malignant lung tumors between January 2020 and December 2021 were included. All eligible patients were randomly assigned to the training cohort or validation cohort at a 3:1 ratio. Univariate and multivariate logistic regression were performed to identify independent risk factors. All independent risk factors were incorporated to establish a predictive model and nomogram, and a web-based dynamic nomogram was then built based on the logistic regression model. Nomogram discrimination was assessed using the receiver operating characteristic (ROC) curve. The calibration power was evaluated using the Hosmer-Lemeshow test and calibration curves. The nomogram was also evaluated for clinical utility by the decision curve analysis (DCA). RESULTS: A total of 2213 patients were finally enrolled in this study, among whom, 341 cases (15.4%) were confirmed to have PAL. The following eight independent risk factors were identified through logistic regression: age, body mass index (BMI), smoking history, percentage of the predicted value for forced expiratory volume in 1 second (FEV1% predicted), surgical procedure, surgical range, operation side, operation duration. The area under the ROC curve (AUC) was 0.7315 [95% confidence interval (CI): 0.6979-0.7651] for the training cohort and 0.7325 (95% CI: 0.6743-0.7906) for the validation cohort. The P values of the Hosmer-Lemeshow test were 0.388 and 0.577 for the training and validation cohorts, respectively, with well-fitted calibration curves. The DCA demonstrated that the nomogram was clinically useful. An operation interface on a web page ( https://lirongyangql.shinyapps.io/PAL_DynNom/ ) was built to improve the clinical utility of the nomogram. CONCLUSION: The nomogram achieved good predictive performance for PAL after minimally invasive pulmonary resection. Patients at high risk of PAL could be identified using this nomogram, and thus some preventive measures could be adopted in advance.

Comparison of perioperative outcomes with or without routine chest tube drainage after video-assisted thoracoscopic pulmonary resection: A systematic review and meta-analysis.

Background: In recent years, an increasing number of thoracic surgeons have attempted to apply no routine chest tube drainage (NT) strategy after thoracoscopic lung resection. However, the safety and feasibility of not routinely placing a chest tube after lung resection remain controversial. This study aimed to investigate the effect of NT strategy after thoracoscopic pulmonary resection on perioperative outcomes. Methods: A comprehensive literature search of PubMed, Embase, and the Cochrane Library databases until 3 January 2022 was performed to identify the studies that implemented NT strategy after thoracoscopic pulmonary resection. Perioperative outcomes were extracted by 2 reviewers independently and then synthesized using a random-effects model. Risk ratio (RR) and standardized mean difference (SMD) with 95% confidence interval (CI) served as the summary statistics for meta-analysis. Subgroup analysis and sensitivity analysis were subsequently performed. Results: A total of 12 studies with 1,381 patients were included. The meta-analysis indicated that patients in the NT group had a significantly reduced postoperative length of stay (LOS) (SMD = -0.91; 95% CI: -1.20 to -0.61; P < 0.001) and pain score on postoperative day (POD) 1 (SMD = -0.95; 95% CI: -1.54 to -0.36; P = 0.002), POD 2 (SMD = -0.37; 95% CI: -0.63 to -0.11; P = 0.005), and POD 3 (SMD = -0.39; 95% CI: -0.71 to -0.06; P = 0.02). Further subgroup analysis showed that the difference of postoperative LOS became statistically insignificant in the lobectomy or segmentectomy subgroup (SMD = -0.30; 95% CI: -0.91 to 0.32; P = 0.34). Although the risk of pneumothorax was significantly higher in the NT group (RR = 1.75; 95% CI: 1.14-2.68; P = 0.01), the reintervention rates were comparable between groups (RR = 1.04; 95% CI: 0.48-2.25; P = 0.92). No significant difference was found in pleural effusion, subcutaneous emphysema, operation time, pain score on POD 7, and wound healing satisfactory (all P > 0.05). The sensitivity analysis suggested that the results of the meta-analysis were stabilized. Conclusions: This meta-analysis suggested that NT strategy is safe and feasible for selected patients scheduled for video-assisted thoracoscopic pulmonary resection. Systematic Review Registration: https://inplasy.com/inplasy-2022-4-0026, identifier INPLASY202240026.

Robotic-assisted thoracoscopic surgery improves perioperative outcomes in overweight and obese patients with non-small-cell lung cancer undergoing lobectomy: A propensity score matching analysis.

BACKGROUND: The effectiveness of robotic-assisted lobectomy (RAL) for patients with non-small-cell lung cancer (NSCLC) has not been fully evaluated. METHODS: This retrospective study compared the perioperative outcomes of NSCLC patients who underwent RAL and video-assisted lobectomy (VAL) using propensity score matching (PSM) analysis. Subgroup analyses were then performed. RESULTS: A total of 822 NSCLC patients (359 RAL cases and 463 VAL cases) were included, and there were 292 patients in each group after PSM. Compared with the VAL group, the RAL group had a significantly higher number of lymph nodes (LNs) harvested (10 vs. 8, p < 0.001) and more LN stations examined (6 vs. 5, p < 0.001). The operative duration (95 minutes vs. 115 minutes, p < 0.001) and intraoperative estimated blood loss (65 mL vs. 80 mL, p < 0.001) were significantly reduced, and the drainage volume on postoperative day (POD) 1 (240 mL vs. 200 mL, p < 0.001) and hospitalization costs (¥81084.96 vs. ¥66142.55, p < 0.001) were significantly higher in the RAL group. Subgroup analysis indicated that the incidence of postoperative complications (17.9% vs. 26.7%, p = 0.042) was significantly reduced in the RAL group for overweight and obese patients (body mass index [BMI] ≥24 kg/m2 ), which became insignificant in the BMI < 24 kg/m2 subgroup (31.0% vs. 24.8%, p = 0.307). CONCLUSION: RAL might have potential advantages in terms of lymph node assessment, reducing intraoperative blood loss, and shortening operation duration. Overweight and obese patients could benefit more from RAL because of reduced risk of postoperative complications.

Comparison of the perioperative outcomes between robotic-assisted thoracic surgery and video-assisted thoracic surgery in non-small cell lung cancer patients with different body mass index ranges.

Background: Non-small cell lung cancer (NSCLC) is the most common malignancy and one of the most common causes of cancer-related death worldwide. Robotic-assisted thoracic surgery (RATS) has gradually become a prevalent surgical method for patients with NSCLC. Previous studies have found that body mass index (BMI) is associated with postoperative outcomes. This study aimed to investigate the effectiveness of RATS compared to video-assisted thoracic surgery (VATS) in the treatment of NSCLC with different BMI, in terms of perioperative outcomes. Methods: The baseline and perioperative data, including BMI, of 849 NSCLC patients who underwent minimally invasive anatomic lung resections from August 2020 to April 2021 were retrospectively collected and analyzed. Propensity score matching analysis was applied to minimize potential bias between the two groups (VATS and RATS), and the perioperative outcomes were compared. Subgroup analysis was subsequently performed. Results: Compared to VATS, RATS had more lymph nodes dissected {9 [inter-quartile range (IQR), 6-12] vs. 7 (IQR, 6-10), P<0.001}, a lower estimated bleeding volume [40 (IQR, 30-50) vs. 50 (IQR, 40-60) mL, P<0.001], and other better postoperative outcomes, but a higher cost of hospitalization [¥83,626 (IQR, 77,211-92,686) vs. ¥75,804 (IQR, 66,184-83,693), P<0.001]. Multivariable logistic regression analysis indicated that RATS (P=0.027) and increasing BMI (P=0.030) were associated with a statistically significant reduction in the risk of postoperative complications. Subgroup analysis indicated that the advantages of RATS may be more obvious in patients with a BMI of 24-28 kg/m2, in which the RATS group had more lymph nodes dissected [9 (IQR, 6-12) vs. 7 (IQR, 5-10), P<0.001] and a decreased risk of total postoperative complications [odds ratio (OR), 0.443; 95% confidence interval (CI), 0.212-0.924; P=0.030] compared to the VATS group. Conclusions: Both, RATS and VATS can be safely applied for patients with NSCLC. Perioperative outcome parameters indicate advantages for RATS, however at a higher cost of hospitalization. The advantages of RATS might be more obvious in patients with a BMI of 24-28 kg/m2.

Prognostic Significance and Therapeutic Target of CXC Chemokines in the Microenvironment of Lung Adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) is one of the most important subtypes of lung cancer and has a high morbidity and mortality. Inflammatory CXC chemokines in tumor microenvironment can stimulate tumor growth, invasion, and metastasis, affecting the prognosis of patients. However, the differential expression profiles, prognostic values, and specific mechanisms of the CXC chemokine family in LUAD have not been clarified. METHODS: Transcriptome expression profile data were extracted from TIMER and TCGA. GEPIA was used to compare the relationship between CXC chemokines and clinicopathologic parameters. The prognostic analysis was performed using a Kaplan-Meier curve in GEPIA. LinkedOmics and TRRUST were applied to conduct the enrichment analysis of the regulatory networks containing the kinase targets, miRNA targets, and transcriptional factor targets. The characteristics of immune infiltration and immune-related clinical outcomes were evaluated with TIMER algorithms. Single-cell RNA sequencing localization analysis of genes as prognostic biomarkers were performed by PanglaoDB. RESULTS: Nine differentially expressed genes were identified in LUAD compared to normal tissues. Aberrant expression of CXCL2 (P =0.0017), CXCL13 (P= 0.0271), CXCL16 (P= 0.016), and CXCL17 (P= 2.14e-5) was significantly correlated with clinical cancer stage. Furthermore, patients with low gene transcription of CXCL 7 (P = 0.017) and high expression of CXCL 17 (P = 0.00045) had a better prognosis in LUAD. We also found that immune cell infiltration was significantly correlated with LUAD microenvironment mediated by CXC chemokines. Cox proportional hazard model test was conducted and indicated that B cell infiltration could prolong the survival of the LUAD patients. CXCL17 exerted anti-tumors effect through pulmonary alveolar type II cells according to single-cell analysis. CONCLUSION: Our research identified the aberrant expression profiles and prognostic biomarkers of CXC chemokines in LUAD. This detailed analysis of the regulatory factor networks for CXC chemokine gene expression may provide novel insights for selecting potential immunotherapeutic targets.

The effect of the enhanced recovery after surgery program on lung cancer surgery: a systematic review and meta-analysis.

BACKGROUND: Lung cancer is one of the most common causes of cancer-related death worldwide. The enhanced recovery after surgery (ERAS) program is an effective evidence-based multidisciplinary protocol of perioperative care. However, the roles of ERAS in lung cancer surgery remain unclear. This systematic review and meta-analysis aimed to investigate the short-term impact of the ERAS program on lung resection surgery, especially in relation to postoperative complications. METHODS: A systematic literature search of PubMed, EMBASE, and the Cochrane Library databases until October 2020 was performed to identify the studies that implemented an ERAS program in lung cancer surgery. The studies were selected and subjected to data extraction by 2 reviewers independently, which was followed by quality assessment. A random effects model was used to calculate overall effect sizes. Risk ratio (RR), risk difference (RD), and standardized mean difference (SMD) with 95% confidence interval (CI) served as the summary statistics for meta-analysis. Subgroup analysis and sensitivity analysis were subsequently performed. RESULTS: A total of 21 studies with 6,480 patients were included. The meta-analysis indicated that patients in the ERAS group had a significantly reduced risk of postoperative complications (RR =0.64; 95% CI: 0.52 to 0.78) and shortened postoperative length of stay (SMD=-1.58; 95% CI: -2.38 to -0.79) with a significant heterogeneity. Subgroup analysis showed that the risks of pulmonary (RR =0.58; 95% CI: 0.45 to 0.75), cardiovascular (RR =0.73; 95% CI: 0.59 to 0.89), urinary (RR =0.53; 95% CI: 0.32 to 0.88), and surgical complications (RR =0.64; 95% CI: 0.42 to 0.97) were significantly lower in the ERAS group. No significant reduction was found in the in-hospital mortality (RD =0.00; 95% CI: -0.01 to 0.00) and readmission rate (RR =1.00; 95% CI: 0.76 to 1.32). In the qualitative review, most of the evidence reported significantly decreased hospitalization costs in the ERAS group. CONCLUSIONS: The implementation of an ERAS program for surgery of lung cancer can effectively reduce risks of postoperative complications, length of stay, and costs of patients who have undergone lung cancer surgery without compromising their safety.

Circular RNA hsa-circ-000881 suppresses the progression of lung adenocarcinoma in vitro via a miR-665/PRICKLE2 axis.

BACKGROUND: Circular RNA (circRNA) has become a new focus in the field of tumor biology research in recent years. Many circRNAs have been showed to play an important role in the progression of lung adenocarcinoma (LUAD). In this work, we studied the oncological role of hsa-circ-000881 in LUAD and attempted to explore the related mechanism. METHODS: The relative expressions of hsa-circ-000881, miR-665, and PRICKLE2 were detected by RT-qPCR or western blot. Functional assays were conducted to analyze the role of hsa-circ-000881 in the proliferation, migration, and invasion of LUAD cells. A luciferase reporter assay was performed to verify whether hsa-circ-000881, miR-665, and PRICKLE2 interact with each other. RESULTS: Circ-000881 was remarkably downregulated in LUAD. Overexpression of circ-000881 attenuated cell growth, migration, and invasion, whereas its knockdown enhanced the malignancy of LUAD cells. The results of luciferase reporter assay and bioinformatics analysis confirmed that circ-000881 served as a sponge for miR-665, and PRICKLE2 was a direct target of miR-665.Overexpression of miR-665 or silencing of PRICKLE2 abolished circ-000881-mediated inhibition of malignant tumor behavior in LUAD cells. CONCLUSIONS: Circ-000881 has inhibitory effects on LUAD via a miR-665/PRICKLE2 axis, suggesting that circ-000881 may be an underlying therapeutic target for LUAD.

Comparison of computed tomographic imaging-guided hook wire localization and electromagnetic navigation bronchoscope localization in the resection of pulmonary nodules: a retrospective cohort study.

The resection of nodules by thoracoscopic surgery is difficult because the nodules may be hard to identify. Preoperative localization of pulmonary nodules is widely used in the clinic. In this study, we retrospectively compared CT-guided hook wire localization and electromagnetic navigation bronchoscopy (ENB) localization of small pulmonary nodules before resection. Patients who underwent localization with CT-guided hook wire or ENB followed by video-assisted thoracoscopic surgery (VATS) at Qilu Hospital of Shandong University between January 2016 and December 2019 were retrospectively included. Clinical parameters, complication and failure rate, and localization time were compared between two groups. A total of 157 patients underwent the localization procedure successfully. Pulmonary nodules were localized by CT-guided hook wire in 105 patients and by ENB in 52 patients. The nodule size in ENB group was smaller than that in CT-guided localization group (P < 0.001). Both CT-guided localization and ENB localization were well tolerated in all patients, while ENB localization leaded to less complications (P = 0.0058). In CT-guided localization group, 6 patients failed to be located while none failed in ENB group (P = 0.079). The procedure time was 15.15 ± 3.70 min for CT-guided localization and 21.29 ± 4.00 min for ENB localization (P < 0.001). CT-guided localization is simple and feasible for uncertain pulmonary nodules before surgery. ENB localization could identify small lung nodules with high accuracy and achieve lower incidence of complications.

Expression of MiR-608 in Nonsmall Cell Lung Cancer and Molecular Mechanism of Apoptosis and Migration of A549 Cells.

OBJECTIVE: This Work is aimed at exploring the effect of microRNA (MiR)-608 on the function of nonsmall cell lung cancer (NSCLC) A549 cells and related mechanisms. METHODS: Blood samples of 106 NSCLC patients (experimental group) as well as 124 normal people (control group) were selected for relevant investigation. Polymerase chain reaction (PCR) as well as DNA sequencing was used to determine the genotyping of the MiR-608 rs4919510 polymorphism. MiR-608 expression in cells was detected by real-time PCR technology. Western blotting was used to detect changes in protein levels. NSCLC tissues as well as adjacent tissues were explored in 33 patients undergoing surgery. RESULTS: MiR-608 rs4919510 does not influence the incidence of NSCLC patients. In addition, MiR-608 expression was downregulated in the tumor tissue of NSCLC patients, while the transcription factor activating enhancer-binding protein 4 (TFAP4) expression was upregulated. MiR-608 promotes DOX- (Doxorubicin-) induced apoptosis by negatively regulating TFAP4 expression in NSCLC tissue. TFAP4 can significantly inhibit the migration of A549 cells. CONCLUSION: The findings in this investigation can contribute to the effective treatment of NSCLC patients. Also, the investigation can provide some theoretical support for the application of new targets for NSCLC treatment.

ZHX2 inhibits proliferation and promotes apoptosis of human lung cancer cells through targeting p38MAPK pathway.

OBJECTIVE: To investigate the effect of ZHX2 on lung cancer cells proliferation and apoptosis. MATERIALS AND METHODS: The mRNA and protein expression of ZHX2 were detected by qRT-PCR and western blot, respectively. The human lung cancer cells were divided into Control, NC, ZHX2, SB, and ZHX2 + Ani groups. The cell proliferation was detected by CCK-8 assay and the cell migration and invasion were detected by Transwell assay. Cell apoptosis was detected by flow cytometry. Apoptosis and p38MAPK signaling pathway related proteins were detected by western blot. The nude mice model of lung cancer xenograft was constructed. The tumor volume and tumor weight were measured. The expression of PCNA protein in tumor tissues was detected by immunohistochemistry. The apoptosis of tumor cells was detected by TUNEL staining. The ZHX2 and p38MAPK signaling pathway related proteins in tumor tissues were detected by western blot. RESULTS: The expression of ZHX2 gene and protein in the cancer cell lines were significantly decreased. Compared with control and NC groups, the cells proliferation, migration and invasion were inhibited in ZHX2 and SB groups, while the apoptosis and apoptosis related proteins were increased (p< 0.05). Meanwhile, compared with ZHX2 group, the tumor growth rate, volume, weight, the percentage of PCNA-positive cells, and p-P38 MAPK/P38 MAPK were increased significantly in ZHX2 + Ani group, while the apoptotic index and the expression of MMP-9 protein were significantly decreased (p< 0.05). CONCLUSION: ZHX2 could inhibit proliferation and promote apoptosis of lung cancer cells by inhibiting p38MAPK signaling pathway.

Potential use of microRNA-200c as a prognostic marker in non-small cell lung cancer.

MicroRNAs (miRNAs/miRs) are a class of small, highly conserved non-coding RNAs that can serve either oncogenic or tumor-suppressive roles in a wide variety of tumors. miR-200c is a member of the miR-200 family whose specific role in non-small cell lung cancer (NSCLC) has not yet been elucidated. The purpose of the present study was to detect the expression level of miR-200c in NSCLC, and to analyze its association with clinicopathological factors and patient prognosis. The present study determined the expression levels of miR-200c in 110 tumor samples collected from patients diagnosed with NSCLC who underwent complete tumor resection with regional lymph node dissection, as assessed by reverse transcription-quantitative polymerase chain reaction. The association between the expression level of miR-200c and clinicopathological features and patient prognosis was also analyzed. The results showed that miR-200c overexpression was detected in 66 of the 110 cases and was significantly associated with positive lymph node metastasis (P<0.001). Univariate survival analysis demonstrated that high miR-200c expression, positive lymph node metastasis and advanced Tumor-Node-Metastasis (TNM) classification stage significantly predicted decreased 5-year disease-free survival rates (all P<0.05) and poor 5-year overall survival rates (all P<0.01), respectively. The results of multivariate Cox regression analysis showed that TNM stage and miR-200c expression retained its significance as an independent prognostic factor for unfavorable 5-year disease-free survival rates (P<0.05) and poor 5-year overall survival rates (P<0.01). The present findings suggest that miR-200c overexpression is significantly associated with poor survival rates in NSCLC and that miR-200c could play an oncogenic role. miR-200c may have clinical potential as a promising prognostic predictor for patients with NSCLC.