Case Report: ECMO-assisted tracheal reconstruction in a 30-week-gestation preterm infant with tracheal stenosis.

Tracheal stenosis is a rare but life-threatening disease in preterm infants. Misdiagnosis as congenital tracheal stenosis is common, making surgical management challenging. This report presents a case of a preterm infant with tracheal stenosis and congenital heart malformation treated with ECMO-assisted tracheal resection and end-to-end anastomosis. A male infant was born at 30 weeks of gestation with severe asphyxia, cardiac insufficiency, and pneumonia. Following failed medical treatment, fiberoptic bronchoscopy confirmed mid-tracheal to carinal stenosis. After a 2-week treatment course, ECMO-assisted tracheal resection and end-to-end anastomosis were performed successfully. This case confirms the feasibility of tracheal resection and end-to-end anastomosis in low-weight, preterm infants with tracheal stenosis born at 30 weeks gestation. The utilization of ECMO for oxygenation during surgery provides a clear surgical field and shorter operating time. Surgical intervention may be necessary for neonatal tracheal stenosis depending on the clinical presentation.

SLCO4A1, as a novel prognostic biomarker of non­small cell lung cancer, promotes cell proliferation and migration.

Solute carrier organic anion transporter family member 4A1 (SLCO4A1) is a membrane transporter protein. The role of this molecule in non­small cell lung cancer (NSCLC) remains unclear. Bulk sequencing was carried out using early­stage NSCLC tissues with lymph node metastasis to identify SLCO4A1 that influences NSCLC cell proliferation, metastasis and prognosis. The in vitro functional assays carried out included the following: Cell Counting Kit­8, plate colony formation, Transwell and wound healing assays. The molecular techniques used included reverse transcription­quantitative PCR, western blotting and immunohistochemistry. The present study revealed the role of SLCO4A in NSCLC. SLCO4A1 was found to be expressed at high levels in NSCLC tissues and cells, and promotes cell proliferation, migration and invasion. Kaplan­Meier survival analysis indicated that patients with NSCLC and high expression of SLCO4A1 had a poor prognosis. SLCO4A was revealed to regulate the expression of the proliferation­related proteins Ki­67 and PCNA, and that of the extracellular matrix proteins vimentin and E­cadherin. Mechanistically, SLCO4A1 may affect the MAPK signaling pathway to promote NSCLC cell proliferation, migration and invasion. In addition, bioinformatics analysis demonstrated a strong association between SLCO4A1 and tumor infiltrating immune cells, highlighting its critical role in immune therapies such as immune checkpoint inhibitor treatment of patients with NSCLC.

Case report: Uniportal video-assisted thoracoscopic sleeve lobectomy in a 6-year-old patient with inflammatory myofibroblastic tumor (IMT).

Inflammatory myofibroblastic tumor (IMT) is a rare neoplasm that can occur in various organs, including the lung. Surgical resection is usually the preferred treatment for localized IMT.A 6-year-old female was admitted to our hospital with complaints of "coughing and vomiting for 6 days". A chest CT scan revealed occlusion of the left main bronchus, segmental atelectasis of the left lower lung, and cystic low-density shadows along the bronchial pathway. Subsequent fiberoptic bronchoscopy confirmed the diagnosis of IMT through pathological biopsy. After excluding surgical contraindications, the patient underwent uniportal video-assisted thoracoscopic sleeve lobectomy for treatment. The patient had an uneventful postoperative course and was discharged four days after surgery. After one month, the patient received a follow-up examination and reported no significant discomfort. A chest CT scan revealed no postoperative complications.Our experience suggests that uniportal video-assisted thoracoscopic surgery may be a safe and effective approach for the treatment of pediatric patients with IMT requiring complex surgical procedures such as sleeve lobectomy and tracheoplasty.

A pan-cancer analysis of the oncogenic role of secreted phosphoprotein 1 (SPP1) in human cancers.

Background: Emerging evidence suggests that secreted phosphoprotein 1 (SPP1) is involved in tumor cell progression in multiple cancer types. However, the role of SPP1 in different cancers is still not clear. Methods: We used data from The Cancer Genome Atlas (TCGA) to analyze the multiomic roles of SPP1, including RNA expression, DNA methylation, protein phosphorylation, immune infiltration, and overall survival (OS) in 33 tumor types. Results: SPP1 is highly expressed in most cancer types, and its methylation variability and mRNA expression level are both correlated with prognosis in multiple cancer types. A higher S234 phosphorylation level was observed in 4 types of tumors, including colon adenocarcinoma (COAD) and lung adenocarcinoma (LUAD). SPP1 expression level was positively associated with the infiltration level of dendritic cells, neutrophils, and macrophages in multiple cancer types. It was also significantly positively correlated with hepatitis A virus cellular receptor 2 (HAVCR2), which was observed in most tumor types, including brain lower grade glioma (LGG) and ovarian serous cystadenocarcinoma (OV). Moreover, myeloid cell differentiation and leukocyte migration were observed in the enrichment analysis, suggesting that SPP1 might induce immune escape. Conclusions: Pan-cancer analysis using a multiomic approach offered a comprehensive overview of SPP1. This protein plays an important role in most of the analyzed tumor types and could be a valuable prognostic marker across different types of cancer.

Case Report: ECMO-Assisted Uniportal Thoracoscopic Tracheal Tumor Resection and Tracheoplasty: A New Breakthrough Method.

Primary tracheal tumors are seldom seen, and most of them are malignant. At present, the main treatment is surgical resection. It is rare to accomplish tracheal tumor resection and tracheoplasty via uniportalal thoracoscopy. In order both to maintain the patient's oxygen supply during surgery and to reduce the size of the surgical incision, we have innovatively integrated the ECMO-assisted and uniportal thoracoscopic techniques for the first time, perfectly achieving tracheal tumor resection and tracheoplasty. The intraoperative manipulation was only 180 min in duration. The patient returned to the intensive care unit and recovered smoothly after the surgery. The patient was discharged from the hospital 17 days after the operation. ECMO-assisted uniportal thoracoscopic tracheal resection and tracheoplasty provides a new idea and method for colleagues.

PRDM5 suppresses oesophageal squamous carcinoma cells and modulates 14-3-3zeta/Akt signalling pathway.

Dysregulation of PR (PRDI-BF1 and RIZ) domain protein 5 (PRDM5) expression has been shown to be associated with the progression of many malignancies. Nevertheless, the role and underlying mechanism of PRDM5 in oesophageal squamous cell carcinoma (ESCC) remain elusive. qRT-PCR was performed to analyze PRDM5 mRNA expression, and western blot was used to determine protein expression of PRDM5, MMP-2, MMP-9, 14-3-3zeta, pan-Akt and phosphorylated Akt expression. CCK-8 staining was employed to evaluate cell proliferation, while wound scratch assay and Transwell assay were carried out to detect cell migration. A tumour xenograft model of ESCC was also established to validate the effect of PRDM5. PRDM5 expression was downregulated in ESCC tissues and positively correlated with the overall survival of ESCC patients. Silencing PRDM5 expression promoted cell proliferation in ESCC cells, while overexpressing PRDM5 inhibited cell proliferation. Moreover, the migratory abilities of ESCC cells were promoted by PRDM5 knockdown but were attenuated by PRDM5 overexpression. Importantly, 14-3-3zeta expression, along with the phosphorylation of Akt, was suppressed by PRDM5 in ESCC cells. In the established tumour xenograft model, PRDM5 regulated ESCC tumour growth as well as the expression of 14-3-3zeta and phosphorylation of Akt protein. In conclusion, PRDM5 suppresses ESCC cell proliferation and migration and negatively regulates 14-3-3zeta/Akt signalling pathway in vitro and in vivo.

Correlation of m6A methylation with immune infiltrates and poor prognosis in non-small cell lung cancer via a comprehensive analysis of RNA expression profiles.

BACKGROUND: Non-small cell lung cancer (NSCLC) is a common type of lung cancer with a poor prognosis. N6-methyladenosine (m6A) methylation, which is a reversible ribonucleic acid (RNA) modification, plays an important role in the occurrence and development of NSCLC. However, the potential effect of m6A methylation on immune infiltrates and prognosis remains unclear. METHODS: In this study, a weighted gene co-expression network analysis was used to screen out messenger RNAs (mRNAs) and non-coding RNAs (ncRNAs) that were co-expressed with m6A regulators. Additionally, 2 molecular subtypes (Clusters 1 and 2) were determined via consensus clustering. Subsequently, a prognostic risk model was constructed using both co-expressed mRNAs and ncRNAs. Based on the risk scores calculated by the prognostic model, the patients were divided into the high-risk group or low-risk group. Finally, the altered patterns of the tumor immune microenvironments (TIMEs) between the 2 stratification methods were thoroughly investigated, and a gene set enrichment analysis was conducted to further examine the potential mechanism. RESULTS: Patients in Cluster 1 had lower immunoscores, higher programmed death-ligand 1 (PD-L1) expression, and shorter overall survival (OS) compared to patients in Cluster 2. A further investigation based on the prognostic model revealed that the PD-L1 expression levels of patients in the high-risk group were significantly upregulated, and the immunoscores were lower than those in the low-risk group. The immune cells with a high infiltration in Cluster 1 showed a significant positive correlation with the risk score; those with low infiltration showed a significant negative correlation. The hallmarks of the Myelocytomatosis viral oncogene (MYC) targets, the second Gap/Mitosis (G2/M) checkpoint, E2 transcription Factor (E2F) targets, glycolysis, deoxyribonucleic acid (DNA) repair, and unfolded protein response were significantly enriched in Cluster 1, the low-immunoscore group, and the high-risk group. CONCLUSIONS: This study revealed that m6A methylation is closely related to the poor prognosis of NSCLC patients via interference with the TIME, which suggests that m6A may play a role in optimizing individualized immunotherapy management and improving prognosis.

miRNA-218/FANCI is associated with metastasis and poor prognosis in lung adenocarcinoma: a bioinformatics analysis.

BACKGROUND: In this study, tumor microarray analysis was used to screen the key messenger RNAs (mRNAs) and microRNAs related to the progression of lung adenocarcinoma (LUAD), in order to provide a theoretical basis for early diagnosis, therapeutic targets, and prognosis evaluation of patients with LUAD. METHODS: The mRNA and miRNA expression datasets came from the Gene Expression Omnibus (GEO) project database. Differentially expressed genes (DEGs) and microRNAs (DEMs) between LUAD tissues and adjacent lung tissue were obtained using GEO2R. The Search Tool for the Retrieval of Interacting Genes website was also employed to construct and visualize the interactions of overlapped DEGs. The overall survival of DEMs was investigated using the Kaplan-Meier plotter. The TargetScan website (http://www.targetscan.org/) was used to verify the relationship between FA Complementation Group I (FANCI) and the expression of miRNA-218 (miR-218). The expression of FANCI was verified using the GEO and Human Protein Atlas databases, as well as Real Time Quantitative PCR using our own samples. Next, we analyzed the relationship between the expression of FANCI and the clinicopathological characteristics as well as the prognosis of patients with LUAD. We also explored whether the FANCI was related to immune cell infiltration in LUAD. RESULTS: FANCI was identified as a hub gene and associated with poor OS. We found that miR-218 negatively regulates FANCI mRNA expression. At the mRNA expression and protein level, FANCI was more highly expressed in LUAD tissues. The expression of FANCI in LUAD was related to tumor size (χ2=13.96, P<0.001), lymphatic metastasis (χ2=3.88, P<0.05), distant metastasis (χ2=45.39, P<0.001), and stage (χ2=11.03, P<0.05). In addition, the Cox regression model found that FANCI mRNA expression was an independent predictive factor of patient survival (P<0.05). FANCI expression was both weakly related to B cells and neutrophil infiltration in LUAD. CONCLUSIONS: miR-218 may negatively regulate FANCI, and FANCI could promote metastasis via extracellular matrix (ECM) receptor interaction, leading to poor prognosis of LUAD. FANCI may be a key gene to the determine metastasis and poor prognosis in patients with LUAD. Changes in the immune microenvironment may be the mechanism through which FANCI leads to poor prognosis of LUAD.

Catamenial pneumothorax with bubbling up on the diaphragmatic defects: a case report.

BACKGROUND: Catamenial pneumothorax is characterized by spontaneous recurring pneumothorax during menstruation, which is a common clinical manifestation of thoracic endometriosis syndrome. There are still controversies about its pathogenesis. CASE PRESENTATION: A 43-year-old woman with a history of endometriosis came to our hospital due to recurring pneumothorax during menstruation. Uniportal Video-assisted Thoracoscopic Surgery (VATS) exploration was performed on the eve of menstruating. We thoroughly explored the diaphragm, visceral and parietal pleura: The lung surface was scattered with yellowish-brown implants; no bullae were found; multiple diaphragmatic defects were found on the dome. And surprisingly, we caught a fascinating phenomenon: Bubbles were slipping into pleural cavity through diaphragmatic defects. We excised the diaphragmatic lesions and wedge resected the right upper lung lesion; cleared the deposits and flushed the thoracic cavity with pure iodophor. Diaphragmatic lesions confirmed the presence of endometriosis, and interestingly enough, microscopically, endometrial cells were shedding with impending menses. After a series of intraoperative operations and postoperative endocrine therapy, the disease did not recur after a period of follow-up. CONCLUSION: We have witnessed the typical signs of catamenial pneumothorax at the accurate timing: Not only observed the process of gas migration macroscopically, but also obtained pathological evidence of diaphragmatic periodic perforation microscopically, which is especially precious and confirms the existing theory that retrograde menstruation leads to diaphragmatic endometriosis, and the diaphragmatic fenestration is obtained due to the periodic activities of ectopic endometrium.

Key microRNAs and hub genes associated with poor prognosis in lung adenocarcinoma.

In the study, we obtained 36 pairs of lung adenocarcinoma (LUAD) tissues and adjacent non-tumorous tissues. Then, we chose a specific hub-target gene of miRNA and used qRT-PCR to evaluate the expression of PECAM1. We found that the expression level of PECAM1 mRNA in LUAD was significantly lower than that in adjacent nontumor tissues (P<0.0001). Univariate and multivariate analyses were conducted on 481 LUAD patients from The Cancer Genome Atlas (TCGA) according to the Cox proportional hazard regression model to evaluate the impact of PECAM1 expression and other clinicopathological factors on survival. The results showed that the low expression of PECAM1 was an important independent predictor of poor overall survival (HR, 0.704; 95% CI, 0.518-0.957; P = 0.025). Based on the Tumor Immune Estimation Resource (TIMER) database, the relationship between PECAM1 expression and B cell, CD8+ T cell, CD4+ T cell, macrophage, neutrophil, and dendritic cell infiltration was weak in LUAD (P<0.01). In particular, a more significant positive correlation between PECAM1 expression and HLA-complex members, CD1C, NRP1, and ITGAX expression in dendritic cell was detected in LUAD. The mechanism which PECAM1 involved in the development of LUAD may be closely related to changes in the immune microenvironment.

Single-cell transcriptome analysis demonstrates inter-patient and intra-tumor heterogeneity in primary and metastatic lung adenocarcinoma.

In this study, we performed single-cell transcriptome data analysis of fifty primary and metastatic lung adenocarcinoma (LUAD) samples from the GSE123902 and GSE131907 datasets to determine the landscape of inter-patient and intra-tumoral heterogeneity. The gene expression profiles and copy number variations (CNV) showed significant heterogeneity in the primary and metastatic LUAD samples. We observed upregulation of pathways related to translational initiation, endoplasmic reticulum stress, exosomes, and unfolded protein response in the brain metastasis samples as compared to the primary tumor samples. Pathways related to exosomes, cell adhesion and metabolism were upregulated and the epithelial-to-mesenchymal-transition (EMT) pathway was downregulated in brain metastasis samples from chemotherapy-treated LUAD patients as compared to those from the untreated LUAD patients. Tumor cell subgroups in the brain metastasis samples showed differential expression of genes related to type II alveolar cells, chemoresistance, glycolysis and oxidative phosphorylation (metabolic reprogramming), and EMT. Thus, single-cell transcriptome analysis demonstrated intra-patient and intra-tumor heterogeneity in the regulation of pathways related to tumor progression, chemoresistance and metabolism in the primary and metastatic LUAD tissues. Moreover, our study demonstrates that single cell transcriptome analysis is a potentially useful tool for accurate diagnosis and personalized targeted treatment of LUAD patients.

A new technology for reducing anastomotic fistula in the neck after esophageal cancer surgery.

BACKGROUND: To explore the risk factors and prevention methods of cervical mechanical anastomotic fistula and stenosis after the radical resection of esophageal cancer. METHODS: From March 2018 to November 2018, 128 patients undergoing mechanical anastomosis of esophageal cancer were selected from the Department of Thoracic Surgery of The First Affiliated Hospital of Zhengzhou University. All the enrolled patients were operated on using the Mckeown method, and a retrospective study was conducted. Data for preoperative and postoperative test indices, intraoperative embedding materials, postoperative complications, and preoperative and postoperative treatment were collected, and the relationship between various factors and the incidence of cervical anastomotic fistula and stenosis was analysed. Univariate analysis was conducted using t tests or Fisher's exact probability method, and multivariate analysis was conducted using logistic regression models. RESULTS: All 128 patients successfully underwent surgery without dying. The enrolled patients were evaluated using the Stooler classification, with 28 patients having grade 0, 41 patients having grade 1, 34 patients having grade 2, 21 patients having grade 3, and 4 patients having grade 4 stenosis. Patients with stenosis of grade 3 or above had obvious choking sensation, which could only be relieved by balloon dilation. Symptoms in all patients with stenosis were relieved by balloon dilation. There were no significant differences between the two groups regarding embedding materials, preoperative choking history, history of alcohol consumption, history of hypertension, history of coronary heart disease, history of diabetes, postoperative calcium concentration, average albumin concentration, average platelet concentration, body mass index, anastomotic fistula, preoperative chemotherapy, postoperative chemotherapy, or postoperative cough (P>0.05). There were significant differences in postoperative reflux (χ2=11.338, P<0.05) and scar constitution (χ2=12.497, P<0.05). The effects of embedding materials in patients with anastomotic fistula were significantly different (χ2=4.372, P<0.05). CONCLUSIONS: Postoperative reflux and scar constitution may be risk factors for postoperative anastomotic stenosis after resection of esophageal cancer. There was almost no difference in the effects on esophageal anastomotic stenosis between embedding materials and the omentum majus, but Neoveil® may have certain advantages in preventing cervical anastomotic fistula, and thus may have certain clinical application value.

A novel pathway in NSCLC cells: miR­191, targeting NFIA, is induced by chronic hypoxia, and promotes cell proliferation and migration.

MicroRNAs (miRs) have emerged as being important in cancer biology. miR­191 is a conserved miRNA, which has been investigated in detail and is reported to be induced by hypoxia-inducible factor (HIF)­1α and has an contributory action in the progression of breast, hepatic and pancreatic cancer. However, the effects of miR­191 in the progression of lung cancer are a subject of debate. In the present study, it was found that the expression of miR-191 was significantly upregulated in non­small cell lung cancer (NSCLC) cells in patients in vivo. However, the levels of miR­191 remained unchanged in SK­MES­1, A549 and NCI­H460 NSCLC cell lines, compared with the level in the normal HBE lung cell line, however, the levels were markedly upregulated in these NSCLC cell lines under conditions of chronic hypoxia. Subsequently, an miR­191 mimic was transfected into the NSCLC cell lines to examine its effect on the progression of the NSCLC cells in vitro. The data obtained using MTT and Cell counting kit­8 assays revealed that miR­191 had no effect on the proliferation of the cells under normal condition, however, their proliferation was promoted under mild hypoxic conditions. In addition, the results of a Transwell migration assay showed that miR­191 had a promoting effect on NSCLC cell migration under the conditions of chronic hypoxia. Furthermore, the TargetScan bioinformatics server and 3'-untranslated region luciferase reporter assay indicated that the transcription factor, nuclear factor 1α (NFIA) was a target of miR­191. Subsequent western blot analysis showed that, in chronic­hypoxia, the protein levels of NFIA and the tumor suppressor, CCAAT-enhancer-binding protein α, were sharply reduced in A549 cells. In conclusion, miR­191 was induced by chronic hypoxia and promoted the proliferation and migration of NSCLC cells under chronic hypoxic conditions. This promotion may be associated with its targeting of NFIA. The present findings may provide a potential molecular target for the therapeutic treatment of NSCLC.