Hsa_circ_0008133 contributes to lung cancer progression by promoting glycolysis metabolism through the miR-760/MEX3A axis.

BACKGROUND: Lung cancer is a very common cancer with poor prognosis and high mortality. Circular RNAs (circRNAs) have been confirmed to be related to the occurrence of lung cancer, and circ_0008133 has been found to be possibly related to lung cancer. METHODS: Expression of circ_0008133, miR-760, and mex-3 RNA binding family member A (MEX3A) messenger RNA (mRNA) was detected using quantitative real-time polymerase chain reaction (qRT-PCR). Cell viability, colony number, migration, and invasion were assessed using cell counting kit-8 (CCK8), colony formation, wound healing, and transwell assays. Glucose consumption and lactate production were detected using commercial kits. Protein expression was measured using western blot. Dual-luciferase reporter assay and RNA pull-down assay were used to analyze the relationships between miR-760 and circ_0008133 or MEX3A. The effects of circ_0008133 knockdown on tumor growth in vivo were examined by the nude mice expriment. Immunohistochemistry (IHC) assay analyzed Ki-67 expression. RESULTS: Circ_0008133 and MEX3A were markedly boosted in lung cancer tissues and cells. Circ_0008133 knockdown decreased lung cancer cell viability, glucose consumption, lactate production, colony formation, migration, and invasion. In mechanism, circ_0008133 might positively regulate MEX3A expression by sponging miR-760. Additionally, knockdown of circ_0008133 inhibited tumor growth in vivo. CONCLUSION: Circ_0008133 accelerated the progression of lung cancer by promoting glycolysis metabolism through the miR-760/MEX3A axis.

PLGA-PTMC-Cultured Bone Mesenchymal Stem Cell Scaffold Enhances Cartilage Regeneration in Tissue-Engineered Tracheal Transplantation.

The treatment of long-segment tracheal defect requires the transplantation of effective tracheal substitute, and the tissue-engineered trachea (TET) has been proposed as an ideal tracheal substitute. The major cause of the failure of segmental tracheal defect reconstruction by TET is airway collapse caused by the chondromalacia of TET cartilage. The key to maintain the TET structure is the regeneration of chondrocytes in cartilage, which can secrete plenty of cartilage matrices. To address the problem of the chondromalacia of TET cartilage, this study proposed an improved strategy. We designed a new cell sheet scaffold using the poly(lactic-co-glycolic acid) (PLGA) and poly(trimethylene carbonate) (PTMC) to make a porous membrane for seeding cells, and used the PLGA-PTMC cell-scaffold to pack the decellularized allogeneic trachea to construct a new type of TET. The TET was then implanted in the subcutaneous tissue for vascularization for 2 weeks. Orthotopic transplantation was then performed after implantation. The efficiency of the TET we designed was analyzed by histological examination and biomechanical analyses 4 weeks after surgery. Four weeks after surgery, both the number of chondrocytes and the amount of cartilage matrix were significantly higher than those contained in the traditional stem-cell-based TET. Besides, the coefficient of stiffness of TET was significantly larger than the traditional TET. This study provided a promising approach for the long-term functional reconstruction of long-segment tracheal defect, and the TET we designed had potential application prospects in the field of TET reconstruction.

Melatonin attenuates intestinal ischemia--reperfusion-induced lung injury in rats by upregulating N-myc downstream-regulated gene 2.

BACKGROUND: Successful drug treatment for ischemia--reperfusion-induced lung injury remains a major clinical problem. Melatonin (MT) is a hormone that is principally synthesized in the pineal gland. It has been shown to exhibit a variety of functions including anti-inflammatory and antioxidant effects. Previous reports on N-myc downstream-regulated gene (NDRG)2 have suggested that it is involved in cellular differentiation, development, antiapoptosis, anti-inflammatory cytokine, and antioxidant. The objective of this study was to test whether MT, a novel NDRG2 activator, can protect against intestinal ischemia-reperfusion-induced lung injury (IIRI). MATERIALS AND METHODS: IIRI was induced in rats by occlusion of the superior mesenteric artery for 60 min, and the occlusion was then released for reperfusion. Rats were randomly divided into six groups as follows: control group; MT group; IIRI group; IIRI+5 mg/kg MT group; IIRI+15 mg/kg MT group; and IIRI+25 mg/kg MT group. The effects of MT on intestinal ischemia-reperfusion-induced lung pathologic changes, inflammatory cytokines release, myeloperoxidase and superoxide dismutase activities, and malondialdehyde level were examined. In addition, the NDRG2 activation in lung tissues was detected by Western blot analysis. RESULTS: MT pretreatment attenuated edema and the pathologic changes in the lung. MT also decreased the levels of tumor necrosis factor-α, interleukin-1ß, and interleukin-8 in bronchoalveolar lavage fluid. In addition, MT markedly prevented IIRI-induced elevation of malondialdehyde and myeloperoxidase levels, as well as reduction of superoxide dismutase activity. Furthermore, the expression of NDRG2 was activated by MT pretreatment in lung tissues. CONCLUSIONS: The present study demonstrates that MT exerted protection against IIRI-induced oxidative stress. The potential mechanism of this action may attribute partly to the activation of NDRG2 expression.

Bronchiolitis obliterans complicating a pneumothorax after Stevens-Johnson syndrome induced by lamotrigine.

Bronchiolitis obliterans (BO) was defined as a nonreversible obstructive lung disease in which the bronchioles are always compressed and narrowed by fibrosis or inflammation. In the severe event of lung collapse after BO, surgical intervention is often recommended, and conservative therapy is thought to be ineffective. Here, we report the case of a 9-year old girl clinically diagnosed as having bronchiolitis obliterans with abrupt occlusion of the right B4b bronchus. After a lamotrigine-induced Stevens-Johnson syndrome (SJS) occurred, she presented with total collapse of the right lung on admission, which was subsequently complicated by a pneumothorax during conservative treatment, but with the re-expansion of the right upper lobe after intervention. The case indicates the possibility of reversing pulmonary atelectasis in BO. Thus, surgery may not be necessary.

Evaluation of Raman spectroscopy for diagnosing EGFR mutation status in lung adenocarcinoma.

Somatic mutations in the epidermal growth factor receptor (EGFR) gene were associated with sensitivity to small molecule tyrosine kinase inhibitors for patients with lung adenocarcinomas. In this research, EGFR mutation status was analyzed by DNA sequencing in 153 lung adenocarcinoma tissues. Of these, 75 samples carried EGFR mutations, including 29 with E19del mutation, 33 with L858R mutation, 7 with T790M mutation, and 6 with multiple mutations. Then, 30 samples including 10 with wild type (wt)-EGFR, 10 with L858R and 10 with E19del mutations were selected for Raman and immunohistochemistry (IHC) analyses. After removing the spectra from normal and non-mutated regions, 441 spectra were found appropriate for Raman analysis: 149 from wt-EGFR, 135 from L858R and 157 from E19del mutations. The Raman peaks at 675, 1107, 1127 and 1582 cm(-1) were significantly increased in wt-EGFR tissues which can be attributed to specific amino acids and DNA. The Raman peaks at 1085, 1175 and 1632 cm(-1) assigned to arginine were slightly increased in L858R tissues. The overall intensity of E19del tissues was weaker than others due to exon 19 deletion that removes residues 746-750 of the expressed protein. Principal component analysis (PCA) and support vector machine (SVM) were applied for final prediction. The PCA/SVM algorithm yielded an overall accuracy of 87.8% for diagnosing L858R or E19del from wt-EGFR tissues. Finally, RS provides a simple, rapid and low-cost procedure based upon the molecular signatures for predicting EGFR mutation status.

Early postoperative endoscopy for predicting anastomotic leakage after minimally invasive esophagectomy: A large-volume retrospective study.

BACKGROUND: Anastomotic leakage is one of the most severe adverse events of minimally invasive esophagectomy for esophageal cancer. Early postoperative endoscopy is considered to be the most objective means to diagnose anastomotic leakage, but its safety is questioned by clinicians. This study aimed to evaluate the safety and effectiveness of early postoperative endoscopy in predicting anastomotic leakage. METHODS: Patients who underwent minimally invasive esophagectomy (from January 2017 to June 2021) in our center were identified and divided into early postoperative endoscopy and control groups according to whether they underwent early postoperative endoscopy within 72 hours after surgery. Propensity score matching was used to balance baseline characteristics. The incidence of postoperative adverse events was compared between the 2 groups, risk variables for anastomotic leakage were identified using logistic regression, and abnormal endoscopic findings related to anastomotic leakage occurrence were explored. RESULTS: A total of 436 patients were enrolled, of whom 134 underwent early postoperative endoscopy. One hundred and thirty-two pairs were matched by propensity score matching, and baseline characteristics were well-balanced. Both before and after propensity score matching, early postoperative endoscopy did not increase the incidence of postoperative adverse events (chyle leak, hypoproteinemia, pneumonia, etc) and in-hospital mortality. Notably, the incidence of anastomotic leakage (9.8% vs 22.7%) and the length of mean postoperative hospital stay (17.6 vs 20.9 days) was significantly decreased in the early postoperative endoscopy group. Finally, based on the findings under early postoperative endoscopy, we found that gastric graft ischemia is related to a higher incidence of anastomotic leakage (P = .023). CONCLUSION: Early postoperative endoscopy does not increase postoperative adverse events after minimally invasive esophagectomy and may guide early prediction and intervention strategies for anastomotic leakage in patients undergoing minimally invasive esophagectomy.

Construction of a nomogram model based on biomarkers for liver metastasis in non-small cell lung cancer.

BACKGROUND: Patients with non-small cell lung cancer (NSCLC) with liver metastasis have a poor prognosis, and there are no reliable biomarkers for predicting disease progression. Currently, no recognized and reliable prediction model exists to anticipate liver metastasis in NSCLC, nor have the risk factors influencing its onset time been thoroughly explored. METHODS: This study conducted a retrospective analysis of 434 NSCLC patients from two hospitals to assess the association between the risk and timing of liver metastasis, as well as several variables. RESULTS: The patients were divided into two groups: those without liver metastasis and those with liver metastasis. We constructed a nomogram model for predicting liver metastasis in NSCLC, incorporating elements such as T stage, N stage, M stage, lack of past radical lung cancer surgery, and programmed death ligand 1 (PD-L1) levels. Furthermore, NSCLC patients with wild-type EGFR, no prior therapy with tyrosine kinase inhibitors (TKIs), and no prior radical lung cancer surgery showed an elevated risk of early liver metastasis. CONCLUSION: In conclusion, the nomogram model developed in this study has the potential to become a simple, intuitive, and customizable clinical tool for assessing the risk of liver metastasis in NSCLC patients following validation. Furthermore, it provides a framework for investigating the timing of metachronous liver metastasis.

Neoadjuvant chemotherapy with or without camrelizumab in resectable esophageal squamous cell carcinoma: the randomized phase 3 ESCORT-NEO/NCCES01 trial.

Recent single-arm studies involving neoadjuvant camrelizumab, a PD-1 inhibitor, plus chemotherapy for resectable locally advanced esophageal squamous cell carcinoma (LA-ESCC) have shown promising results. This multicenter, randomized, open-label phase 3 trial aimed to further assess the efficacy and safety of neoadjuvant camrelizumab plus chemotherapy followed by adjuvant camrelizumab, compared to neoadjuvant chemotherapy alone. A total of 391 patients with resectable thoracic LA-ESCC (T1b-3N1-3M0 or T3N0M0) were stratified by clinical stage (I/II, III or IVA) and randomized in a 1:1:1 ratio to undergo two cycles of neoadjuvant therapy. Treatments included camrelizumab, albumin-bound paclitaxel and cisplatin (Cam+nab-TP group; n = 132); camrelizumab, paclitaxel and cisplatin (Cam+TP group; n = 130); and paclitaxel with cisplatin (TP group; n = 129), followed by surgical resection. Both the Cam+nab-TP and Cam+TP groups also received adjuvant camrelizumab. The dual primary endpoints were the rate of pathological complete response (pCR), as evaluated by a blind independent review committee, and event-free survival (EFS), as assessed by investigators. This study reports the final analysis of pCR rates. In the intention-to-treat population, the Cam+nab-TP and Cam+TP groups exhibited significantly higher pCR rates of 28.0% and 15.4%, respectively, compared to 4.7% in the TP group (Cam+nab-TP versus TP: difference 23.5%, 95% confidence interval (CI) 15.1-32.0, P < 0.0001; Cam+TP versus TP: difference 10.9%, 95% CI 3.7-18.1, P = 0.0034). The study met its primary endpoint of pCR; however, EFS is not yet mature. The incidence of grade ≥3 treatment-related adverse events during neoadjuvant treatment was 34.1% for the Cam+nab-TP group, 29.2% for the Cam+TP group and 28.8% for the TP group; the postoperative complication rates were 34.2%, 38.8% and 32.0%, respectively. Neoadjuvant camrelizumab plus chemotherapy demonstrated superior pCR rates compared to chemotherapy alone for LA-ESCC, with a tolerable safety profile. Chinese Clinical Trial Registry identifier: ChiCTR2000040034 .

Shikonin attenuates lipopolysaccharide-induced acute lung injury in mice.

BACKGROUND: Shikonin, a natural naphthoquinone pigment extracted from the root of Lithospermum erythrorhizon, has shown a variety of pharmacologic properties including anti-inflammatory effect. In the present study, we analyzed the role of shikonin in acute lung injury induced by lipopolysaccharide (LPS) in mice. MATERIALS AND METHODS: Sixty male BALB/C mice were randomly allocated into six groups (n = 10, each): control group, shikonin group (50 mg/kg), LPS group, and three different doses (12.5, 25, and 50 mg/kg) for shikonin-treated groups. Shikonin or vehicle was given with an intragastric administration 1 h before an intratracheal instillation of LPS (5 mg/kg). The severity of pulmonary injury was evaluated 6 h after LPS challenge. RESULTS: Shikonin pretreatment significantly attenuated LPS-induced pulmonary histopathologic changes, alveolar hemorrhage, and neutrophil infiltration. The lung wet-to-dry weight ratios, as the index of pulmonary edema, were markedly decreased by shikonin pretreatment. Moreover, shikonin decreased the productions of the proinflammatory cytokines including tumor necrosis factor alpha and interleukin 1ß and the concentration of total proteins in the bronchoalveolar lavage fluid. Shikonin pretreatment also reduced the concentrations of myeloperoxidase and nitric oxide in lung tissues. In addition, shikonin pretreatment significantly suppressed LPS-induced activation of cyclooxygenase 2 and inducible nitric oxide synthase and the nuclear factor κB DNA-binding activity in lung tissues. CONCLUSIONS: This study indicates that shikonin may have a protective effect against LPS-induced acute lung injury, and the potential mechanism of this action may attribute partly to the inhibition of inducible nitric oxide synthase and cyclooxygenase 2 expression by downregulating nuclear factor κB activation.

Systematic review of the perioperative immunotherapy in patients with non-small cell lung cancer: evidence mapping and synthesis.

Objectives: This study aimed to use evidence mapping to provide an overview of immune checkpoint inhibitors (ICIs) as perioperative treatments for non-small cell lung cancer (NSCLC) and to identify areas of this field where future research is most urgently needed. Methods: Multiple databases (PubMed, EMBASE, Cochrane Library, and Web of Science) were searched to identify clinical trials published up to November 2021 that examined the effect of perioperative ICIs for perioperative treatment of NSCLC. Study design, sample size, patient characteristics, therapeutic regimens, clinical stages, short-term and long-term therapeutic outcomes, surgery associated parameters, and therapeutic safety were examined. Results: We included 66 trials (3564 patients) and used evidence mapping to characterize the available data. For surgery associated outcomes, sixty-two studies (2480 patients) provided complete information regarding the use of surgery after neoadjuvant immunotherapy and data on R0 resection were available in 42 studies (1680 patients); for short-term clinical outcomes, 57 studies (1842 patients) evaluated pathologic complete response (pCR) after neoadjuvant immunotherapy and most of included studies achieved pCR in the range of 30 to 40%; for long-term clinical outcomes, 15 studies (1932 patients) reported DFS, with a median range of 17.9-53.6 months; and only a few studies reported the safety profiles of perioperative immunotherapies. Conclusion: Our evidence mapping systematically summarized the results of all clinical trials and studies that examined ICIs as perioperative treatments for NSCLC. The results indicated more studies that evaluate long-term patient outcomes are needed to provide a stronger foundation for the use of these treatments.

Mediastinal lymph node dissection versus spared mediastinal lymph node dissection in stage IA non-small cell lung cancer presented as ground glass nodules: study protocol of a phase III, randomised, multicentre trial (MELDSIG) in China.

INTRODUCTION: Radical surgery including mediastinal lymph node dissection is the standard treatment for early-stage non-small cell lung cancer (NSCLC). About 50% lung nodules are pure ground glass or part-solid nodules, which are predominantly clinical stage IA NSCLC. Non-solid nodules rarely develop mediastinal lymph node metastasis. METHOD AND ANALYSIS: A phase III study was started in China to evaluate the non-inferiority in overall survival of spared mediastinal lymph node dissection compared with mediastinal lymph node dissection in stage IA NSCLC. A total of 1362 patients will be enrolled from 4 institutions in 2-3 years. The second endpoints are relapse-free survival and perioperative data, including duration of hospitalisation, duration of chest tube placement, operation time, blood loss. ETHICS AND DISSEMINATION: This protocol has been reviewed and approved by the Clinical Research Review Board of Tianjin Medical University Cancer Institute and Hospital. The findings will be disseminated in peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT04631770.

Regulation of CD18 stability by SIGIRR-modulated ubiquitination: new insights into the relationship between innate immune response and acute lung injury.

Inappropriate accumulation of alveolar macrophages (AMs) and subsequent excessive production of immune responses play critical roles in the pathogenesis of acute lung injury (ALI), but the core negative regulators governing innate signalling in AMs are ill defined. We have previously shown that single immunoglobin IL-1 receptor-related protein (SIGIRR), a negative regulator of IL-1 receptor and Toll-like receptor signalling, inhibits lipopolysaccharide (LPS)-induced inflammatory responses in AMs. To address the biological relevance of SIGIRR in vivo, we generated a murine ALI model via intratracheal instillation of LPS. Intriguingly, SIGIRR expression was observed to be decreased in resident and recruited macrophages during ALI. This decrease was associated with parallel induction in CD18 protein levels in LPS-challenged lung tissues. Through intranasal injection of SIGIRR lentiviral particles studies, we showed that the overexpression of SIGIRR attenuated recruitment of macrophages and neutrophils, decreased production of inflammatory cytokines and ameliorated pathological changes in lungs. Whilst exploring the basis for this phenotype, SIGIRR was found to be coexpressed with CD18 in AMs, and SIGIRR potentiated the instability of CD18 protein via enhancement of its ubiquitination and proteasome degradation. Conversely, by using CD18-/- mice, we further observed that CD18 deletion completely abolished the therapeutic effects of overexpression of SIGIRR on LPS-induced ALI. Mover, overexpression of CD18 in AMs promoted adhesion to ECM components, enhanced TLR4-mediated inflammasome activation and thereby potentiated IL-1ß production. These data collectively identify SIGIRR/CD18 as a key negative regulatory circuit maintaining innate immune homeostasis in AMs along the pathogenesis of ALI.

CXCL12-CXCR4/CXCR7 Axis in Cancer: from Mechanisms to Clinical Applications.

Cancer is a multi-step disease caused by the accumulation of genetic mutations and/or epigenetic changes, and is the biggest challenge around the world. Cytokines, including chemokines, exhibit expression changes and disorders in all human cancers. These cytokine abnormalities can disrupt homeostasis and immune function, and make outstanding contributions to various stages of cancer development such as invasion, metastasis, and angiogenesis. Chemokines are a superfamily of small molecule chemoattractive cytokines that mediate a variety of cellular functions. Importantly, the interactions of chemokine members CXCL12 and its receptors CXCR4 and CXCR7 have a broad impact on tumor cell proliferation, survival, angiogenesis, metastasis, and tumor microenvironment, and thus participate in the onset and development of many cancers including leukemia, breast cancer, lung cancer, prostate cancer and multiple myeloma. Therefore, this review aims to summarize the latest research progress and future challenges regarding the role of CXCL12-CXCR4/CXCR7 signaling axis in cancer, and highlights the potential of CXCL12-CXCR4/CXCR7 as a biomarker or therapeutic target for cancer, providing essential strategies for the development of novel targeted cancer therapies.

A multicenter, single-arm, open study of neoadjuvant or conversion atezolizumab in combination with chemotherapy in resectable small cell lung cancer (Cohort Study).

BACKGROUND: This study aimed to investigate the prospects of using chemotherapy in combination with atezolizumab in the neoadjuvant or conversion treatment of small cell lung cancer (SCLC). METHODS: Prior to surgery, untreated patients with limited-stage SCLC received three cycles of neoadjuvant or conversion atezolizumab combined with chemotherapy of etoposide and platinum. The primary endpoint of the trial was pathological complete response (pCR) in the per-protocol (PP) cohort. In addition, safety was assessed based on treatment-related adverse events (AEs) and postoperative complications. RESULTS: Overall, 13 of 17 patients (including 14 males and 3 females) underwent surgery. In the PP cohort, pCR and major pathological response were observed in 8 (8/13, 61.5%) and 12 (12/13, 92.3%) patients, respectively. According to the intention-to-treat (ITT) analysis, the pCR and major pathological response in the ITT cohort were 47.1% (8/17) and 70.6% (12/17), respectively. In addition, an overall response rate of 100% was recorded in the PP cohort. Moreover, 15 (15/17, 88.2%) patients and 1 (1/17, 5.9%) in the ITT cohort attained partial remission (PR), and complete remission, respectively, with an overall response rate of 94.1%. The median overall survival of the patients of pCR and the median event-free survival of the patients on surgery had not achieved. However, the median overall survival of the patients of non-pCR was 18.2 months and the median event-free survival of the nonsurgical patients was 9.5 months. During the neoadjuvant treatment, the incidence of grade 3 or higher AEs was 58.8% (10/17). Additionally, three patients (17.6%) developed immune-related adverse event (grades 1-2). CONCLUSION: In patients with SCLC, neoadjuvant or conversion atezolizumab combined with chemotherapy significantly improved pCR with manageable AEs. Therefore, this regimen may be considered a safe and effective treatment for SCLC.

Neoadjuvant Camrelizumab Plus Platinum-Based Chemotherapy vs Chemotherapy Alone for Chinese Patients With Resectable Stage IIIA or IIIB (T3N2) Non-Small Cell Lung Cancer: The TD-FOREKNOW Randomized Clinical Trial.

Importance: The benefit of neoadjuvant camrelizumab plus chemotherapy for resectable stage IIIA or IIIB non-small cell lung cancer (NSCLC) remains unknown. Objective: To assess the efficacy and safety of neoadjuvant camrelizumab plus chemotherapy vs chemotherapy alone for patients with resectable stage IIIA or IIIB NSCLC. Design, Setting, and Participants: In this randomized phase 2 clinical trial conducted at 2 hospitals in China, patients aged 18 to 70 years with resectable stage IIIA or IIIB (T3N2) NSCLC were enrolled between April 7, 2020, and January 12, 2022. Interventions: Patients were randomly assigned to receive 3 cycles of camrelizumab (200 mg) plus chemotherapy (nab-paclitaxel, 130 mg/m2, and platinum [cisplatin, 75 mg/m2; carboplatin, area under the curve, 5; or nedaplatin, 100 mg/m2]) or chemotherapy alone, followed by surgery after 4 to 6 weeks. Main Outcomes and Measures: The primary end point was the pathologic complete response (pCR) rate. Secondary end points included the major pathologic response (MPR) rate, objective response rate (ORR), event-free survival (EFS), and safety. Disease-free survival (DFS, defined as the time from surgery to disease recurrence or death from any cause) was analyzed post hoc. Efficacy was assessed on a modified intention-to-treat basis. Results: Ninety-four Chinese patients were randomized, and 88 (93.6%; median age, 61 years [IQR, 54-65 years]; 74 men [84.1%]) received allocated neoadjuvant treatment (43 received camrelizumab plus chemotherapy, and 45 received chemotherapy alone). Among these 88 patients, the pCR rate was 32.6% (14 of 43; 95% CI, 19.1%-48.5%) with camrelizumab plus chemotherapy vs 8.9% (4 of 45; 95% CI, 2.5%-21.2%) with chemotherapy alone (odds ratio, 4.95; 95% CI, 1.35-22.37; P = .008). The MPR rates were 65.1% (95% CI, 49.1%-79.0%) with camrelizumab plus chemotherapy and 15.6% (95% CI, 6.5%-29.5%) with chemotherapy alone. The radiographic ORRs were 72.1% (95% CI, 56.3%-84.7%) with camrelizumab plus chemotherapy and 53.3% (95% CI, 37.9%-68.3%) with chemotherapy alone. With a median follow-up of 14.1 months (IQR, 9.2-20.9 months), the median EFS and DFS were not reached in either group. The most common neoadjuvant treatment-related adverse events of grade 3 or higher were decreased white blood cell count (6 of 43 [14.0%] in the camrelizumab plus chemotherapy group vs 2 of 45 [4.4%] in the chemotherapy group) and decreased neutrophil count (3 of 43 [7.0%] in the camrelizumab plus chemotherapy group vs 5 of 45 [11.1%] in the chemotherapy group). No treatment-related deaths were reported. Conclusions and Relevance: This randomized clinical trial found that among patients with resectable stage IIIA or IIIB (T3N2) NSCLC, camrelizumab plus chemotherapy, compared with chemotherapy alone, significantly improved the pCR rate with manageable toxic effects. Trial Registration: ClinicalTrials.gov Identifier: NCT04338620.

Isolated Crohn's disease of the esophagus with esophago-mediastinal fistula formation.

Isolated Crohn's disease of the esophagus is rare, and accurate diagnosis and treatment in its early course are difficult. Most cases are often found very late, when severe strictures or other complications have occurred. We report the case of a male 60-year-old patient with complaints of progressive dysphagia for more than two months and the sudden appearance of heartburn for seven consecutive days. Clinical examination revealed severe esophageal stricture with a suspected fistula and mediastinitis. The patient received a successful esophagectomy. The resected specimen and pathological results confirmed a deep linear ulcer, chronic and noncaseating granulomatous inflammation, as well as a circular stricture of the esophagus with fistula into the mediastinum due to isolated esophageal Crohn's disease.

CircRIP2 promotes NSCLC progression by sponging for miR-671-5p to regulate FOXM1 expression.

Lot of attention had been paid to the role of circular RNAs (circRNAs) in carcinogenesis recently. However, knowledge about circRNAs in NSCLC development is far from satisfactory. In this study, we aimed to provide a novel insight into the circRIP2 in NSCLC development. We used NSCLC tissues, as well as cell lines to elucidate the expression and location of circRIP2 in NSCLC. We also established the circRIP2 overexpression cells A549-circRIP2 and repression cells HCC827-shcircRIP2 for further functional and mechanism studies. The pro-tumorigenic role of circRIP2 was tested by using CCK-8, BrdU and transwell assays. The interaction between circRIP2 and miR-671-5p were validated by luciferase reporter assay, RIP assay, as well as RNA pull down assay. We showed circRIP2 is differentially expressed NSCLC, and acted as a predictor for overall survival (OS) and disease-free survival (DFS). CircRIP2 promoted NSCLC progression by acting as a miRNA sponge for miR-671-5p, thus facilitating its target gene FOXM1 expression. Targeting circRIP2 could be potentially beneficial for NSCLC patients in the future.

QKI-6 Suppresses Cell Proliferation, Migration, and EMT in Non-Small Cell Lung Cancer.

The RNA-binding protein quaking homolog 6 (QKI-6) is a tumor-suppressor gene in several cancers. However, its role in non-small cell lung cancer (NSCLC) is unclear. In this study, we aimed to determine the association between QKI-6 expression and survival and clinicopathological features in patients with NSCLC and identify the related mechanisms. Western blot and immunohistochemistry (IHC) were used to detect QKI-6 expression in NSCLC. The effect of QKI-6 on NSCLC cells was determined by overexpression and knockdown assays, and label-free quantitative proteomics and Western blot were used to identify the underlying mechanisms. Low QKI-6 expression level was positively correlated with poor overall survival in patients with NSCLC. Furthermore, QKI-6 overexpression inhibited NSCLC cell proliferation and migration and induced a block in the G0/G1 phase, and QKI-6 downregulation increased proliferation and migration. QKI-6 inhibited EMT processes via EGFR/SRC/STAT3 signaling by upregulating AGR2. In conclusion, QKI-6 could be used to develop novel strategies for the treatment of NSCLC.

Surgical treatment of primary tracheobronchial tumors: 16-year experience in a single center.

Background: Primary tracheobronchial tumor (TBT) is a rare disease, and the prognostic factors of surgical treatment have not been well identified. Methods: Patients with primary TBT and accepted surgical treatment between January 2004 and January 2020 at our institution were retrospectively analyzed. The univariate analysis and multivariate analysis were conducted on the malignant cases. The overall survival (OS) was analyzed using Kaplan-Meier method, and potential prognostic factors were analyzed using Cox regression analysis. Results: A total of 69 patients (29 males and 40 females) were included. The median follow-up duration was 75.7 months (1.2-177.4 months). The most common histology was adenoid cystic carcinoma (ACC) (37.7%) followed by squamous cell carcinoma (SCC) (23.2%). For patients with malignant tumors, the estimated 5-year OS of the overall population was 77.2% and the estimated 5-year OS of SCC patients was 73.8% especially. The univariate Cox regression analysis identified that age and tumor size had significant effects on OS. The multivariate analysis showed that age (≤50 or >50 years) was independent prognostic factor for OS (P<0.05). Conclusions: Age is independent factor affecting the OS of primary TBT treated by surgery. And patients of TBT with younger age should be much more referred for surgery.

Predicting checkpoint inhibitors pneumonitis in non-small cell lung cancer using a dynamic online hypertension nomogram.

OBJECTIVES: Checkpoint inhibitors pneumonitis (CIP) is one of the most lethal adverse events in non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs). Currently, there is no recognized and effective predictive model to predict CIP in NSCLC. MATERIALS AND METHODS: This study retrospectively analyzed 460 NSCLC patients who were first treated with ICIs. Patients were divided into three cohorts based on the occurrence of CIP: any grade CIP cohort, grade ≥ 2 CIP cohort and grade ≥ 3 CIP cohort. RESULTS: A dynamic hypertension nomogram was constructed with elements including hypertension, interstitial lung disease (ILD), emphysema at baseline, and higher baseline platelet/lymphocyte ratio (PLR). The C indices of the training cohort and the internal and external validation cohort in any grade CIP cohort were 0.872, 0.833 and 0.840, respectively. The constructed hypertension nomogram was applied to grade ≥ 2 cohort and grade ≥ 3 cohort, and their C indices were 0.844 and 0.866, respectively. Compared with the non-hypertension nomogram, the hypertension nomogram presented better predictive power. CONCLUSIONS: After validated by internal and external validation cohorts, the dynamic online hypertension has the potential to become a convenient, intuitive, and personalized clinical tool for assessing the risk of CIP in NSCLC patients.