CircPLK1 Acts as a Carcinogenic Driver to Promote the Development of Malignant Pleural Mesothelioma by Governing the miR-1294/HMGA1 Pathway.

The deregulation of circular RNAs (circRNAs) is involved in cancer development. CircRNA polo-like kinase 1 (circPLK1) was reported to promote breast cancer development. However, the role of circPLK1 in malignant pleural mesothelioma (MPM) is unclear. The expression of circPLK1, miR-1294, and high mobility group AT-hook 1 (HMGA1) mRNA was measured by quantitative real-time PCR (qPCR). Cell viability was detected by CCK-8 assay. Colony formation ability was monitored by colony formation assay. Cell proliferation was detected by EdU assay. Cell migration and cell invasion were monitored by transwell assay. Cancer cell stemness was investigated by sphere formation assay. The protein levels of marker proteins and HMGA1 expression were measured by western blot analysis. The binding relationship between miR-1294 and circPLK1 or HMGA1 was validated by pull-down assay, dual-luciferase reporter assay or RIP assy. Animal study was performed to disclose the role of circPLK1 in vivo. Exosomes were identified by transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). CircPLK1 was upregulated in MPM tumor tissues and cell lines. CircPLK1 knockdown suppressed the proliferation, migration, invasion and stemness of MPM cells. CircPLK1 contained a binding site for miR-1294 and thus bound to miR-1294 to sequester its expression. Inhibition of miR-1294 reversed the effects of circPLK1 knockdown. HMGA1 was a target of miR-1294, and circPLK1 bound to miR-1294 to increase the expression of HMGA1. MiR-1294 restoration also suppressed the proliferation, migration, invasion and stemness of MPM cells, while these effects were abolished by HMGA1 overexpression. In addition, circPLK1 knockdown inhibited tumor growth in vivo. CircPLK1 was overexpressed in exosomes derived from serum of MPM patients. CircPLK1 knockdown inhibited MPM cell proliferation, migration, invasion and stemness by targeting the miR-1294/HMGA1 pathway.

Perioperative Clinical Results of Transcervical and Transhiatal Esophagectomy versus Thoracoscopic Esophagectomy in Patients with Esophageal Carcinoma: A Prospective, Randomized, Controlled Study.

Background: This study assessed the efficacy of transcervical and transhiatal esophagectomy versus thoracoscopic esophagectomy in patients with esophageal carcinoma (EC). Methods: A total of 80 patients with EC were enrolled in this study, including 40 cases in the observation group that received transcervical combine transhiatal esophagectomy and the rest 40 cases of the group that underwent thoracoscopic esophagectomy. The preoperative, intraoperative, and postoperative data were analyzed between the two surgeries, regarding perioperative bleeding, the total number of dissected mediastinal lymph nodes, operative time, number of lymph nodes in the left para-recurrent laryngeal nerve (para-RLN) or the right para-RLN, time in the intensive care unit (ICU), postoperative pain score, the length of postoperative stay (LOPS), PO2/fraction of inspired oxygen (PO2/FiO2), pulmonary infection, and lymphatic metastasis. Results: The operations were successfully performed in all 80 patients. The results showed that patients who underwent transcervical and transhiatal esophagectomy had shorter operations than those with transthoracic esophagectomy (200 minutes vs 235 minutes, Kruskal-Wallis test [Z] = -3.700, P < 0.001). The number of dissected mediastinal lymph nodes in the left para-RLN in the observation group was higher than in the control group (25.0% vs 2.5%, Z = 2.568, P = 0.010). The postoperative pain score day 1 (0.0% vs 17.5%, Z = -4.292, P < 0.001), postoperative pain score day 3 (12.5% vs 37.5%, Z = -3.363, P < 0.001) and 48-h PO2/FiO2 (290 minutes vs 255 minutes, Z = 3.747, P < 0.001) were significant between the two groups. The LOPS of patients with EC in the observation group was shorter than the control group (7 vs 8, Z = -2.119, P = 0.034). The number of patients receiving transcervical and transhiatal esophagectomy that developed postoperative pulmonary infections was less than the controls (chi-square [χ 2] = 4.114, P = 0.043). Moreover, the transcervical and transhiatal esophagectomy was an independent protect factor for postoperative pulmonary infection (odds ratio [OR] =7.801, P = 0.037). Conclusion: The transcervical and transhiatal esophagectomy is a good operation for treating patients with EC, which may offer an opportunity to treat cases who cannot have thoracotomy.

Application of Simultaneous Localization of Multiple Pulmonary Nodules in a Hybrid Operating Room for Uniportal Video-Assisted Thoracic Surgery.

OBJECTIVE: This study explores the value of the application of simultaneous localization of multiple pulmonary nodules in a hybrid operating room for uniportal video-assisted thoracic surgery (VATS). METHODS: This study performed a retrospective analysis of 60 patients with multiple pulmonary nodules (the number of nodules in every patient was ≥2, 131 in total) admitted to our hospital from September 2020 to September 2021. After computerized tomography (CT) scanning in a hybrid operating room, a multi-hook locating needle was used for simultaneous localization. The localization success, surgical resection, and locating needle unhooking rates of multiple pulmonary nodules were analyzed. The complication incidence, localization time, operation time, anesthesia time, post-isolation nodule search time, and postoperative hospital stay length were analyzed. In addition, the patients' anxieties about the puncture localization were evaluated. RESULTS: The intraoperative CT scans successfully showed all pulmonary nodules. The localization success, unhooking, and nodule resection rates were 98.5% (129/131), 1.5% (2/131), and 100% (131/131), respectively. The median times of the localization, operation, anesthesia, post-isolation pulmonary nodule search, and hospital stay were 19 min [interquartile range (IQR): 15-30 min], 98 min (IQR: 80-110 min), 149.5 min (IQR: 126-171 min), 3.5 min (IQR: 1-5 min), and 6 d (IQR: 4-9 d), respectively. The incidences of pneumothorax and pulmonary hemorrhage were 20.0% (12/60) and 13.3% (8/60), respectively. The self-rating anxiety scale score of the patients was 53.6 ± 6.1. CONCLUSION: The hybrid operating room could be beneficial in accurately localizing multiple pulmonary nodules with reasonable safety and patient tolerance, and it is applicable to uniportal VATS.

The application value of computed tomography in combination with intraoperative noninvasive percutaneous ultrasonic localisation of subpleural pulmonary nodules/ground-glass opacity in uniportal video-assisted thoracoscopy.

INTRODUCTION: This study investigates the application value of preoperative noninvasive computed tomography (CT) localisation, combined with intraoperative percutaneous ultrasonic localisation, in the precise positioning and excision of subpleural pulmonary nodules/ground-glass opacity in uniportal video-assisted thoracoscopic surgery (U-VATS). AIM: To derive the precise positioning and excision of subpleural pulmonary nodules by CT combined with intraoperative percutaneous ultrasonic localisation and to avoid the complications caused by preoperative CT-guided puncture localisation, reduce physiological and psychological stress such as anxiety, CT radiation dose, and treatment cost, and to improve the treatment satisfaction of patients. MATERIAL AND METHODS: A total of 54 patients with subpleural pulmonary nodules/ground-glass opacity (SPN/GGO), who were treated in our hospital from June 2017 to January 2020, were enrolled in this study. The patients were randomly divided into a treatment group (n = 23), and the nodules were scanned by high-resolution CT and marked at the shortest distance on the surface of the body prior to surgery. These pulmonary nodules were relocated by ultrasound at the original CT positioning points in the same body position following the administration of general anaesthesia. Then, the hookwire puncture location was performed under real-time guidance. For the control group (n = 31), the subpleural pulmonary nodules were located by CT-guided puncture and embedding a hookwire prior to surgery. Pulmonary wedge resection was performed by U-VATS in each group. The subpleural nodules were confirmed by the naked eye and rapid pathological diagnosis after surgery. The difference in positioning success rate, positioning time, the incidence of complications, and patient anxiety scores for subpleural pulmonary nodules were compared and analysed between the two groups. RESULTS: A total of 22 cases of subpleural nodules were successfully located in the treatment group at a success rate of 95.6% (22/23). The average positioning time for CT in combination with ultrasound was 22.0 ±5.9 min. In the control group, 31 cases of subpleural pulmonary nodules were satisfactorily located at a success rate of 100% (31/31). The average positioning time of CT was 24.2 ±5.4 min. The difference in positioning success rate and positioning time was not statistically significant (p = 0.24; p = 0.15) between the two groups. The incidence of complications and SAS anxiety scores in the treatment group were lower compared with the control group. The difference was statistically significant (p = 0.002; p < 0.001). CONCLUSIONS: Preoperative CT combined with intraoperative percutaneous real-time noninvasive ultrasonic localisation can accurately locate subpleural pulmonary nodules, with a high degree of safety and good tolerance in patients who are suitable for U-VATS.

Pseudolaric Acid B Inhibits Proliferation, Invasion, and Angiogenesis in Esophageal Squamous Cell Carcinoma Through Regulating CD147.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a common malignant tumor of the digestive system. Studies have shown that pseudolaric acid B (PAB) has several pharmacological effects like anti-microtubule, anti-angiogenesis, and antitumor functions, while the effect and mechanism of PAB on esophageal cancer are still unclear. This study was designed to investigate the effects of PAB on ESCC. METHODS: To study the effects of PAB on the biological function through a series of in vitro and in vivo experiments. RESULTS: The results revealed that PAB inhibited the proliferation, invasion, and migration, but promoted the apoptosis of ESCC. Moreover, PAB restrained the growth of cancer cells in vivo and inhibited the angiogenesis of HUVEC in mice with ESCC. CD147 expression was increased in the esophageal squamous cell lines, and interference with CD147 hindered the proliferation, invasion, and migration of ESCC cells, and inhibited the growth and angiogenesis of the esophageal squamous cell line. PAB reduced the expression of CD147 in vivo and in vitro. The expression of MMP2, 3, and 9 was increased after overexpression of CD147, which provided the opportunity to reverse the role of PAB in inhibiting proliferation, invasion, migration, and angiogenesis of ESCC. DISCUSSION: The results revealed that PAB inhibited the proliferation, invasion, migration, and angiogenesis of ESCC in vitro and in vivo by CD147. PAB is a promising monomer for therapy of ESCC, providing references for future research on ESCC treatment.

Prognostic and Clinicopathological Value of Programmed Cell Death Ligand1 Expression in Patients With Small Cell Lung Cancer: A Meta-Analysis.

Background: Programmed death-ligand 1 (PD-L1) is an immune checkpoint molecule expressed by cancer cells. Previous studies have demonstrated the prognostic role of PD-L1 expression in patients with small cell lung cancer (SCLC), where the results were inconsistent. Therefore, we conducted a meta-analysis to identify the prognostic impact of PD-L1 on SCLC. Methods: We searched the PubMed, Embase, ISI Web of Science, and Cochrane Library databases for articles published before and on March 2nd, 2020. Data of PD-L1 expression in tumor cells detected using immunohistochemistry methods were extracted for analysis. Pooled hazard ratios (HRs) with confidence intervals (CIs) and odds ratios (ORs) with 95% CIs were calculated to assess the correlations among PD-L1, overall survival (OS), and clinicopathological factors. Results: Nine studies of 921 patients published between 2015 and 2019 were included in this meta-analysis. The pooled data (HR = 0.91, 95% CI = 0.46-1.80, p = 0.787) indicated that PD-L1 expression is not a significant predictor of poor OS. Moreover, the results also revealed that PD-L1 expression is not significantly associated with gender (OR = 1.12, 95% CI = 0.73-1.74, p = 0.601), age (OR = 1.15, 95% CI = 0.58-2.30, p = 0.683), pN stage (OR = 0.65, 95% CI = 0.24-1.72, p = 0.381), pT stage (OR = 1.16, 95% CI = 0.26-5.23, p = 0.847), serum lactate dehydrogenase level (OR = 1.06, 95% CI = 0.13-8.43, p = 0.958), or performance status (OR = 0.69, 95% CI = 0.24-1.95, p = 0.479). No significant publication bias was detected in this meta-analysis. Conclusions: This meta-analysis suggests that PD-L1 expression is not a significant prognostic factor of poor survival in SCLC. Because of significant variations, high-quality studies are needed to validate our results.

A novel technique for cervical gastro-oesophageal anastomosis during minimally invasive oesophagectomy.

BACKGROUND: Anastomotic leakage, fibrous stricture and gastro-oesophageal reflux are three major complications of gastro-oesophageal anastomosis, particularly in cervical anastomosis. Our aim was to evaluate the safety and efficacy of a novel cervical anastomosis technique (NA) by comparing it to traditional side-to-side anastomosis (SS) and end-to-side anastomosis using a circular stapler (CS) in terms of postoperative leakage, stricture and reflux. METHODS: A total of 390 patients with thoracic oesophageal cancer underwent minimally invasive oesophagectomy with cervical anastomosis (192 with NA, 34 with SS and 164 with CS) in our institute from January 2013 and May 2016. A detailed description of the surgical procedure is provided, and the major postoperative complications, including postoperative leakage, stricture and reflux, were compared using a three-armed controlled study. RESULTS: The anastomotic method was an independent risk factor for anastomotic leakage, as well as stricture and reflux. The rate of anastomotic leakage of the NA group (1.0%) was significantly lower than that in the SS group (8.8%, P = 0.025) and in the CS group (8.5%, P = 0.001). The rate of anastomotic stricture in the NA group was not significantly different than that in the SS group (1.5% vs. 2.9%, P = 0.368) but was significantly lower than that in the CS group (1.5% vs. 18.9%, P < 0.001). The incidence of gastro-oesophageal reflux in the NA group was significantly lower than that in the SS group and the CS group (5.7% vs. 23.5% and 18.3%, P = 0.003 and 0.001, respectively). CONCLUSION: Jiang's anastomosis technique remarkably reduces the incidence of gastro-oesophageal anastomotic leakage, stricture and reflux, and it is a safe and effective technique for minimally invasive oesophagectomy.

Killing effect of TNF-mediated by conditionally replicating adenovirus on esophageal cancer and lung cancer cell lines.

OBJECTIVE: The killing effect of TNF mediated by conditionally replicating adenovirus SG502 on human cancer cell lines was assessed by in vivo and in vitro experiments. METHODS: The recombinant adenovirus SG502-TNF was used to infect human lung cancer cell line A549 and human esophageal cancer cell line TE-1. The expression of the exogenous gene and its inhibitory effect on the tumor cell lines were thus detected. Tumor transplantation experiment was performed in mice with the purpose of assessing the inhibitory effect of the adenovirus on tumor cells and tumor formation. The targeting of the adenovirus and the mechanism of tumor inhibition were discussed by in vivo imaging technology, HE staining and TUNEL assay. RESULTS: Recombinant adenovirus SG502-TNF targeted the tumor cells specifically with stable expression of TNF, which produced a killing effect on tumor cells by regulating the apoptotic signaling pathway. CONCLUSION: Recombinant adenovirus SG502-TNF possessed significant killing effect on TE-1 cells either in vivo or in vitro. This finding demonstrated the potential clinical application of adenovirus SG502.