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Targeted therapy for lung cancer research has advanced quickly in recent years, particularly EGFR-TKIs in the grouping of EGFR-mutant lung cancer, however clinical treatment has encountered difficulties with acquired drug resistance. Due to their great specificity, few adverse reactions, and prolonged tumor control duration, immune checkpoint inhibitors PD-1 and PD-L1 antibodies have emerged as a new therapy approach for NSCLC with the advancement of tumor biology. AXL, a gene that codes for receptor tyrosine kinases, has been linked to the growth, treatment resistance, and immunological imbalance of cancer cells. Its protein has been found to be abnormally expressed in NSCLC cancer tissues. Our study shows a positive regulatory link between AXL and PD-L1 expression, and AXL can upregulate PD-L1 to facilitate the development of acquired drug resistance in EGFR-mutant lung cancer treated with gefitinib. We offer additional understandings for AXL to overcome the gefitinib resistance mechanism in NSCLC, while also providing ideas for addressing targeted therapy resistance.

Aims: The serratus anterior plane block (SAPB) has commonly been utilized as a regional anesthesia technique for pain management in various upper chest surgical procedures. The purpose of this study was to investigate the analgesic effect and pharmacokinetics of ropivacaine in continuous SAPB undergoing VATS. Methods: This prospective randomized study included patients scheduled for elective VATS. Patients first received a bolus of 20 ml of 0.2% (Group L) or 0.375% (Group H) ropivacaine that was administered beneath the serratus anterior muscle. The pump was connected to the catheter for continuous administration within 48 hours postoperatively, in which a background infusion at a rate of 7 ml·h−1 of low-dose at 0.2% (Group L) or high-dose at 0.375% (Group H) of ropivacaine was administered. The main results were to compare the analgesic effects and analyze the pharmacokinetics of different concentrations of ropivacaine. Results: Eighty-eight patients agreed to participate in the trial and were recruited. The VAS scores in Group H at 12, 24, and 48 hours postoperatively at rest and on coughing were significantly lower than those in Group L. The peak values of total ropivacaine plasma concentrations were observed at 48 hours (2.01 μg·mL−1 for Group L and 2.93 μg·mL−1 for Group H), which were far below the theoretical toxicity threshold. Postoperative rescue analgesia, complications, and other outcomes did not differ significantly. Conclusions: In VATS patients, the analgesic effect of 0.2% ropivacaine for continuous SAPB was not inferior to that of 0.375% ropivacaine, and the blood concentration of 0.2% ropivacaine was

The fifth-generation (5G) wireless communication has an urgent need for target tracking. Digital programmable metasurface (DPM) may offer an intelligent and efficient solution owing to its powerful and flexible controls of electromagnetic waves and advantages of lower cost, less complexity and smaller size than the traditional antenna array. Here, we report an intelligent metasurface system to perform target tracking and wireless communications, in which computer vision integrated with a convolutional neural network (CNN) is used to automatically detect the locations of moving targets, and the dual-polarized DPM integrated with a pre-trained artificial neural network (ANN) serves to realize smart beam tracking and wireless communications. Three groups of experiments are conducted for demonstrating the intelligent system: detection of moving targets, detection of radio-frequency signals, and real-time wireless communications. The proposed method sets the stage for an integrated implementation of target identification, radio environment tracking, and wireless communications. This strategy opens up a new avenue for intelligent wireless networks and self-adaptive systems.

Significance As a master transcription factor, the tumor suppressor p53 regulates a variety of cellular processes by modulating target gene expression. Although well known as a transcriptional activator, p53 is also able to repress expression of a number of protein-coding genes. However, it remains largely unknown whether long noncoding RNA (lncRNA) gene repression is involved in the regulation of p53 function. Here, we show that p53 can transcriptionally repress expression of the lncRNA E2F1 messenger RNA (mRNA) stabilizing factor (EMS) and vice versa and that EMS can suppress p53 translation and negatively regulate p53 function. Our study reveals an important double-negative feedback loop that controls p53 activity and provides insights into the mechanisms whereby EMS promotes tumorigenesis., p53 plays a central role in tumor suppression. Emerging evidence suggests long noncoding RNA (lncRNA) as an important class of regulatory molecules that control the p53 signaling. Here, we report that the oncogenic lncRNA E2F1 messenger RNA (mRNA) stabilizing factor (EMS) and p53 mutually repress each other’s expression. EMS is negatively regulated by p53. As a direct transcriptional repression target of p53, EMS is surprisingly shown to inhibit p53 expression. EMS associates with cytoplasmic polyadenylation element-binding protein 2 (CPEB2) and thus, disrupts the CPEB2–p53 mRNA interaction. This disassociation attenuates CPEB2-mediated p53 mRNA polyadenylation and suppresses p53 translation. Functionally, EMS is able to exert its oncogenic activities, at least partially, via the CPEB2–p53 axis. Together, these findings reveal a double-negative feedback loop between p53 and EMS, through which p53 is finely controlled. Our study also demonstrates a critical role for EMS in promoting tumorigenesis via the negative regulation of p53.

BackgroundLung adenocarcinoma (LUAD) is a fatal malignancy in the world. Growing evidence demonstrated that autophagy-related genes regulated the immune cell infiltration and correlated with the prognosis of LUAD. However, the autophagy-based signature that can predict the prognosis and the efficiency of checkpoint immunotherapy in LUAD patients is yet to be discovered.MethodsWe used conventional autophagy-related genes to screen candidates for signature construction in TCGA cohort and 9 GEO datasets (tumor samples, n=2181; normal samples, n=419). An autophagy-based signature was constructed, its correlation with the prognosis and the immune infiltration of LUAD patients was explored. The prognostic value of the autophagy-based signature was validated in an independent cohort with 70 LUAD patients. Single-cell sequencing data was used to further characterize the various immunological patterns in tumors with different signature levels. Moreover, the predictive value of autophagy-based signature in PD-1 immunotherapy was explored in the IMvigor210 dataset. At last, the protective role of DRAM1 in LUAD was validated by in vitro experiments.ResultsAfter screening autophagy-related gene candidates, a signature composed by CCR2, ITGB1, and DRAM1 was established with the ATscore in each sample. Further analyses showed that the ATscore was significantly associated with immune cell infiltration and low ATscore indicated poor prognosis. Meanwhile, the prognostic value of ATscore was validated in our independent LUAD cohort. GSEA analyses and single-cell sequencing analyses revealed that ATscore was associated with the immunological status of LUAD tumors, and ATscore could predict the efficacy of PD-1 immunotherapy. Moreover, in vitro experiments demonstrated that the inhibition of DRAM1 suppressed the proliferation and migration capacity of LUAD cells.ConclusionOur study identified a new autophagy-based signature that can predict the prognosis of LUAD patients, and this ATscore has potential applicative value in the checkpoint therapy efficiency prediction.

IntroductionSegmentectomy is widely used for early-stage lung cancer presenting as single or multiple ground-glass opacities (GGOs). Precise segmentectomy is the recommended procedure in China. However, clinically, most routine segmentectomies are performed using only high-resolution computed tomography (CT). The aim of this study was to evaluate the effect of two segmentectomy approaches for GGOs in the lung.MethodsFrom January 2020 to September 2020, 55 precise segmentectomies performed with real-time guidance using 3D reconstruction and 343 routine segmentectomies for patients with single or multiple GGOs were performed as uniportal procedures. To reduce bias related to outcomes, preoperative clinical factors were used for propensity score matching (1:1); 55 precision and 55 routine segmentectomies were selected and further analyzed. Perioperative outcomes, namely operation time, blood loss, resection margins, number of removed lymph nodes, postoperative pulmonary function (1 month after surgery), length of postoperative stay, and postoperative complications were compared between the two groups.ResultsPatients constituted 43 men and 67 women, with an age range of 25–68 years (median: 53 years). No significant differences were seen between the groups regarding blood loss, complications, histological type, and postoperative pulmonary function, and there were no 30-day postoperative deaths in either group. The median operation time for the Precision group (74 min) was longer than in the Routine group (55 min) (p <0.01), and the number of removed lymph nodes in the Precision group (5 ± 1.1) was higher than in the Routine group (3 ± 0.8) (p <0.01). Chest tube duration days and postoperative stay days were similar in both groups; however, the rate of air leakage on postoperative day 1 was higher in the Precision group (p = 0.020). All patients in the Precision group had adequate resection margins. Four patients (7.3%) undergoing complex segmentectomy in the Routine group had inadequate resection margins and required resection of additional lung tissue.ConclusionRoutine segmentectomy can significantly shorten the operation time and might prevent postoperative air leakage in uniportal segmentectomy for lung GGOs. However, precision segmentectomy may be more precise for complex cases, ensuring adequate resection margins and lymph node dissection.

ObjectiveThis study aimed to analyze the relationship between the number of examined lymph nodes (ELNs) at the N1 station and the postoperative clinicopathological features and prognosis of patients with pT1-3N0M0 non-small cell lung cancer (NSCLC).MethodsThe cut-off value of the number of ELNs at the N1 station was obtained using X-tile software analysis. Kaplan-Meier survival curve analysis and the Cox proportional hazard model were used to study the impact of the number of ELNs at the N1 station on the prognosis of postoperative patients with pT1-3N0M0 NSCLC.ResultsThe median survival time and 1-, 3- and 5-year survival rates of 0 ELNs at the N1 station were 28.0 months and 74.8%, 45.4%, and 21.2%, respectively. The median survival time and 1-, 3-, and 5-year survival rates of 1–4 ELNs at the N1 station were 45.0 months and 85.5%, 55.4%, and 39.1%, respectively. In the group with ≥ 5 ELNs at the N1 station, the median survival time and the 1-, 3- and 5-year survival rates were 59.0 months and 94.0%, 62.7%, and 48.2%, respectively. Both univariate and multivariate Cox regression analyses showed that the number of ELNs at the N1 station, T stage and operation type were independent factors affecting the prognosis of patients with pT1-3N0M0 NSCLC.ConclusionIncreasing the number of ELNs at the N1 station is positively correlated with the long-term survival rate of patients with T1-3N0M0 NSCLC. At least 5 LNs at the N1 station should be examined in pathological examination.

IntroductionCancer progression is determined not only by the malignant behavior of tumors but also by the immune microenvironment. The tumor immune microenvironment also plays a pivotal role in determining the clinical response of non-small-cell lung cancer (NSCLC) to immunotherapies. To understand the possible mechanisms and explore new targets in lung cancer immunotherapy, we characterized the immune profiles in NSCLC patients.MethodsSeventy-one NSCLC patients who underwent radical resection were selected. The immune cell composition in paired tumor and adjacent normal lung tissues was tested by flow cytometry. The associations of tumor immune microenvironment characteristics with clinicopathological factors and overall survival were analyzed. Kaplan–Meier curves and Cox proportional hazards models were used to determine differences in survival.ResultsCompared with adjacent normal lung tissues, an increased proportion of CD45+ hematopoietic-derived cells, CD4+ T cell subtypes, Tregs and B cells was observed in tumor samples with a reduced frequency of myeloid cell populations. There was no significant increase in total CD8+ T cells, but both PD1+ and CD38+ CD8+ T cells were significantly enriched in tumor samples and statistically significantly associated with tumor size. In addition, positive CD38 expression was highly correlated with PD1 positivity. A high proportion of CD8+ T cells and a low percentage of PD1+ CD8+ T cells were statistically significantly associated with better survival in stage II and III patients, whereas a low frequency of CD38+ CD8+ T cells was statistically significantly associated with better survival in all patients and identified as an independent prognostic factor (p=0.049).ConclusionWe profiled the immune cells in the tumor tissues of NSCLC patients using flow cytometry. The results revealed significant enrichment of infiltrating immune cells. A strong correlation was identified between CD38 and PD-1 expression on CD8+ T cells in tumors. CD8+ T cells and their subtypes play a critical role in the prediction of prognosis.

Accumulating evidence suggests that p53 plays a suppressive role in cancer metastasis, yet the underlying mechanism remains largely unclear. Regulation of actin dynamics is essential for the control of cell migration, which is an important step in metastasis. The Arp2/3 complex is a major nucleation factor to initiate branched actin polymerization that drives cell migration. However, it is unknown whether p53 could suppress metastasis through modulating Arp2/3 function. Here, we report that WDR63 is transcriptionally upregulated by p53. We show with migration assays and mouse xenograft models that WDR63 negatively regulates cell migration, invasion, and metastasis downstream of p53. Mechanistically, WDR63 interacts with the Arp2/3 complex and inhibits Arp2/3‐mediated actin polymerization. Furthermore, WDR63 overexpression is sufficient to dampen the increase in cell migration, invasion, and metastasis induced by p53 depletion. Together, these findings suggest that WDR63 is an important player in the regulation of Arp2/3 function and also implicate WDR63 as a critical mediator of p53 in suppressing metastasis.

Major lung resection combined with mediastinal lymph node dissection is the standard operation for early-stage non-small cell lung cancer (NSCLC), and lymph node staging is the main predictor of long-term survival. This study aims to identify the prognostic significance of the number of removed lymph nodes in patients with pathologic node-negative (pN0) non-small cell lung cancer (NSCLC). Five hundred thirty-six stage pN0 NSCLC patients, received curative resection between January 2004 and July 2011, were enrolled in this retrospective study. The prognostic factors including the number of removed lymph nodes and clinicopathological characteristics were analyzed. Increasing number of removed lymph nodes was associated with better overall survival (OS) (p = 0.009) of stage pN0 NSCLC patients. The number (p

Deregulated expression of c-Myc is an important molecular hallmark of cancer. The oncogenic function of c-Myc has been largely attributed to its intrinsic nature as a master transcription factor. Here, we report the long noncoding RNA (lncRNA) E2F1 messenger RNA (mRNA) stabilizing factor (EMS) as a direct c-Myc transcriptional target. EMS functions as an oncogenic molecule by promoting G1/S cell cycle progression. Mechanistically, EMS cooperates with the RNA binding protein RALY to stabilize E2F1 mRNA, and thereby increases E2F1 expression. Furthermore, EMS is able to connect c-Myc to cell cycle control and tumorigenesis via modulating E2F1 mRNA stability. Together, these findings reveal a previously unappreciated mechanism through which c-Myc induces E2F1 expression and also implicate EMS as an important player in the regulation of c-Myc function.

To discuss the safety and feasibility of gastric tube in construction technique in total thoracoscopic and laparoscopic Ivor-Lewis esophagectomy.Clinical data of 358 patients with esophageal cancer who underwent the Ivor-Lewis procedure by the same surgical team in our department from June 2015 to June 2016 were retrospectively analyzed. Patients were divided into two groups: group MI (mini-incision): 92 patients undergoing extracorporeally gastric tube through a 4-cm abdominal mini-incision after gastric mobilization; group TL (total laparoscopy): 266 patients undergoing gastric tube made by total laparoscopy and jejunostomy. Intra-operative and postoperative data were compared between two groups.Of 358 patients, 290 were male and 68 were female. The average age was (62.3±15.6) years. The tumor location ratio of group TL and group MI was 27.1%(72/266) and 25.0%(23/92) in middle thoracic esophageal cancer, 35.3%(94/266) and 34.8%(32/92) in mid-lower thoracic esophageal cancer, and 37.6%(100/266) and 40.2%(37/92) in lower thoracic esophageal cancer, respectively. In group TL and group MI, 42.1% (112/266) and 46.7%(43/92) patients were stage I( to II(a; 57.9%(154/266) and 53.3%(49/92) patients were stage II(b to III(a, respectively. All the patients from two groups received successful Ivor-Lewis esophagectomy. There were no significant differences between group TL and MI in operative time [abdominal operative time: (65.6±25.8) min vs. (62.3±25.6) min; thoracic operative time: (180.3±37.4) min vs. (178.1±39.2) min; time of making gastric tube:(16.1±3.2) min vs.(15.7±3.5) min], blood loss [abdominal: (60.5±19.8) ml vs. (62.3±20.9) ml; thoracic: (228.7±47.3) ml vs. (231.6±46.8) ml], and the number of lymph nodes dissection (abdominal: 8.9±1.8 vs. 8.7±1.6; mediastinal: 21.2±3.6 vs. 20.8±3.8)(all P0.05). And there were no significant differences in occurrence of postoperative anastomotic leakage [4.5%(12/266) vs. 4.3%(4/92), χDuring minimally invasive Ivor-Lewis esophagectomy, gastric tube by total laparoscopy is safe and reliable.

Hepcidin is a low-molecular-weight hepatic peptide that regulates iron homeostasis, and acts by causing the degradation of its receptor, the cellular iron exporter ferroportin. On the basis of the major role of the hepcidin-ferroportin axis in iron regulation, recently several studies have discussed its expression and influence on the development and prognosis of cancer. Iron plays a pivotal role in homeostasis. However, insights into the mechanisms of normal iron regulation have provided a new perspective on the basic mechanisms, biological rationale, and pathophysiologic implications of changes in iron metabolism in cancer. Besides being a crucial stimulus for cancer, iron dysfunction also causes cancer-related anemia. In this review, we discuss aspects of the hepcidin-ferroportin axis and iron regulation, as well as the inherent connections between them in cancer. We also attempt to consider the possibility in theory of novel targets for further individualized therapy. However, many molecular mechanisms and functions of these regulators remain unclear.

Background Hepcidin is a small secreted peptide that plays a key role in iron metabolism. A high level of hepcidin expression may be implicated in colorectal cancer; however, the relationship between hepcidin and lung cancer has not yet been studied. Methods Serum hepcidin-25, bone morphogenetic protein (BMP)-2, and interleukin (IL)-6 concentration in 53 patients and 16 non-cancerous individuals was measured by enzyme-linked immune sorbent assay. Reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) was utilized to study the expression of hepcidin mRNA in paired tumor and non-tumor lung tissues in surgical specimens from 65 patients with non small cell lung cancer (NSCLC), as well as in six types of lung cancer cell lines and human bronchial epithelial (HBE) cells. Hepcidin protein expression and cellular localization in NSCLC was determined by immunohistochemistry. Results The serum hepcidin-25 concentration was higher in patients with NSCLC than in non-cancerous individuals, and was positively correlated with serum BMP2 concentration, but negatively with serum IL-6 levels. Serum hepcidin was also correlated with lymph node metastasis and clinical stage. Hepcidin mRNA expression was higher in cancerous tissues of NSCLC than in normal pulmonary tissues (P = 0.001). Hepcidin mRNA levels in four lung carcinoma cell lines were higher than in HBE cells. Immunohistochemistry showed that hepcidin protein was increased in cancerous tissues of NSCLC. Conclusions The level of hepcidin expression increased in NSCLC tissue and serum. Serum hepcidin-25 level was associated with lymph node metastasis and tumor clinical stage in patients with NSCLC.

We present a case of a 58-year-old female with a rare vascular tumor of intermediate malignancy. The initial manifestation was a pseudoaneurysm caused by the rupture of the right pulmonary artery after tumor invasion. The diagnosis of epithelioid hemangioendothelioma was confirmed by the morphologic and immunocytochemical features after surgery. The patient recovered smoothly and there has been no evidence of local recurrence or metastasis during the 2 years of follow-up.

Hepcidin is a small secreted peptide that plays a key role in iron metabolism. A high level of hepcidin expression may be implicated in colorectal cancer; however, the relationship between hepcidin and lung cancer has not yet been studied.Serum hepcidin-25, bone morphogenetic protein (BMP)-2, and interleukin (IL)-6 concentration in 53 patients and 16 non-cancerous individuals was measured by enzyme-linked immune sorbent assay. Reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) was utilized to study the expression of hepcidin mRNA in paired tumor and non-tumor lung tissues in surgical specimens from 65 patients with non small cell lung cancer (NSCLC), as well as in six types of lung cancer cell lines and human bronchial epithelial (HBE) cells. Hepcidin protein expression and cellular localization in NSCLC was determined by immunohistochemistry.The serum hepcidin-25 concentration was higher in patients with NSCLC than in non-cancerous individuals, and was positively correlated with serum BMP2 concentration, but negatively with serum IL-6 levels. Serum hepcidin was also correlated with lymph node metastasis and clinical stage. Hepcidin mRNA expression was higher in cancerous tissues of NSCLC than in normal pulmonary tissues (P = 0.001). Hepcidin mRNA levels in four lung carcinoma cell lines were higher than in HBE cells. Immunohistochemistry showed that hepcidin protein was increased in cancerous tissues of NSCLC.The level of hepcidin expression increased in NSCLC tissue and serum. Serum hepcidin-25 level was associated with lymph node metastasis and tumor clinical stage in patients with NSCLC.

To study the reconstruction method and effectiveness of titanium plate and Teflon patch for the chest wall after resection of sternal tumors.Between October 2006 and November 2009, 4 patients with sternal tumors were treated and the thoracic cages were reconstructed. There were 2 males and 2 females, aged 30-55 years. The patients were admitted because of chest lump or pain. The sizes of palpable lump ranged from 4 cm x 3 cm to 10 cm x 8 cm. CT examination showed bone destruction. After sternal tumor resection, defect size ranged from 10 cm x 8 cm to 18 cm x 14 cm, and titanium plate and Teflon patch were used to repair and reconstruct the chest wall defect.The operations of the tumor resection and reconstruction of chest wall defect were successfully performed in 4 cases. Incisions healed by first intention with no abnormal breath, subcutaneous emphysema, pneumothorax, and infection. One case failed to be followed up after 6 months; 1 case died of intracranial hemorrhage; and 2 cases were followed up 1 and 4 years respectively without tumor recurrence. The chest wall had good remodeling. No loosening and exposure of titanium plate, difficulty in breathing, chest distress, and chest pain were observed during follow-up.Surgical resection of sternal tumors will cause large chest wall defect which can be repaired by titanium plate and Teflon patch because it had the advantages of easy operation, satisfactory remodeling, and less complication.

To observe the clinical results of laminated anastomosis using absorbable suture in cervical esophagogastrostomy, and to reduce the incidence of cervical esophagogastric anastomotic stricture.A retrospective analysis was carried out on 210 patients who underwent cervical esophagogastrostomy after subtotal esophagectomy from January 2008 to June 2010. Among them, 96 cases were treated with traditional full layer interrupted varus suture (varus group) and the remaining 114 cases were treated with seromuscular layer and mucosal layer laminated anastomosis with absorbable suture (laminated group). Esophageal angiography was performed in 1 week, 1 month, and 3 months after the operation. The diameter of anastomatic stoma was measured on the anteroposterior and lateral angiography image respectively. The area of anastomatic stoma was calculated. The degree of stenosis was assessed according to the patients' dysphagia symptom.There was no operative deaths, no serious pulmonary complications and chylothorax, no sever esophageal reflux in all patients. The ratio of cervical esophagogastric anastomotic leakage was 2.1% (2/96) in the varus group. No anastomotic leakage in the laminated group. Compared with the varus group, the area of the anastomatic stoma in the laminated group was significantly increased in all measured time points (P0.01). The incidence of obstruction in the laminated group was decreased significantly (P0.01) in 1 month or in 3 months after operation compared with the varus group.Application of the laminated anastomosis with absorbable suture in cervical esophagogastrostomy can significantly reduce the incidence of anastomotic stenosis.