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Video‐assisted thoracoscopic surgery (VATS) subsegmentectomy has been widely used to resect small‐sized lung lesions in clinical practice. Precise identification of the subsegmental bronchus is one of the essential steps in performing thoracoscopic anatomic subsegmentectomy. Here, we report a thoracoscopic right S2a segmentectomy with preoperative electromagnetic navigational bronchoscopy (ENB)‐guided injection of methylene blue to identify the subsegmental bronchus in a 51‐year‐old male. We successfully performed complicated surgery using this method. This ENB‐guided dye marking method may accurately distinguish the subsegmental bronchus to effectively guide surgery., We successfully performed a thoracoscopic right S2a segmentectomy with preoperative electromagnetic navigational bronchoscopy (ENB)‐guided injection of methylene blue to identify the subsegmental bronchus. This ENB‐guided dye marking method may accurately distinguish the subsegmental bronchus to effectively guide surgery. more...

Gefitinib, the first-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), has become the standard of care for the first-line of therapy for advanced non-small cell lung cancer (NSCLC) with common EGFR mutation. However, the efficacy of preoperative gefitinib therapy in patients with common EGFR mutations remains poorly defined. We describe a NSCLC patient with bilateral synchronous lesions who had a significantly positive response to gefitinib before radical surgical resection. At the time of initial diagnosis, we were unable to confirm whether the two lesions were metastatic or synchronous primary lesions. Accordingly, we performed CT-guided percutaneous left lung biopsy resulting in a diagnosis of lung adenocarcinoma with exon 21 L858R point mutation of EGFR, This diagnosis was followed by preoperative gefitinib therapy for 8 weeks leading to a significant reduction in the lesion in the left lower lobe. Then the left lower lobectomy and mediastinal lymphadenectomy were performed. In addition, 3 months following resection of the left lower lobe tumor the patient underwent a right lower lobe wedge resection. This report indicates that NSCLC patient harboring common EGFR mutation accepting the first-generation EGFR-TKI gefitinib as a neoadjuvant targeted therapy option is safe, feasible, and well-tolerated. more...

Background Circular RNA has been revealed as a potential biomarker in multiple malignancies. However, few studies have focused on its potential to be prognostic markers in lung squamous cell carcinoma (LSCC). In this work, we aimed to build a prognostic model of resected LSCC based on circular RNA pyruvate dehydrogenase kinase 1 (circPDK1) and other clinicopathological factors. Methods circPDK1 was identified via next-generation sequencing. Three hundred two cases of LSCC tissue and their adjacent normal lung tissues were obtained from multiple medical centers and divided into study cohort (n=232) and validation cohort (n=70). The expression of circPDK1 was detected for analyzing its potential prognostic value for recurrence-free survival (RFS) and overall survival (OS) in LSCC. Finally, combined with circPDK1, T staging, lymph nodes (LN) metastasis status, age, and serum squamous cell Carcinoma Antigen (SCCAg), we built a prognostic model by nomograms method and confirmed it in the validation cohort. Results CircPDK1 was identified to be overexpressed (P more...

Calcific aortic valve disease (CAVD) is a complex heart valve disease involving a wide range of pathological changes. Emerging evidence indicates that osteogenic differentiation of human aortic valve interstitial cells (hAVICs) plays a key role in valve calcification. In this study, we aimed to investigate the function of miR‐638 in hAVICs osteogenesis. Both miRNA microarray assay and qRT‐PCR results demonstrating miR‐638 was obviously up‐regulated in calcific aortic valves compared with non‐calcific valves. We also proved that miR‐638 was significantly up‐regulated during hAVICs osteogenic differentiation. Overexpression of miR‐638 suppressed osteogenic differentiation of hAVICs in vitro, whereas down‐regulation of miR‐638 enhance the process. Target prediction analysis and dual‐luciferase reporter assay confirmed that Sp7 transcription factor (Sp7) was a direct target of miR‐638. Furthermore, knockdown of Sp7 inhibited osteogenic differentiation of hAVICs, which is similar to the results observed in up‐regulation miR‐638. Our data indicated that miR‐638 plays an inhibitory role in hAVICs osteogenic differentiation, which may act by targeting Sp7. MiR‐638 may be a potential therapeutic target for CAVD. more...

Background Clinical options for lung squamous carcinoma (LUSC) are still quite limited. Carcinogenesis is an exceedingly complicated process involving multi-level dysregulations. Therefore, only looking into one layer of genomic dysregulation is far from sufficient. Methods We identified differentially expressed genes with consistent upstream genetic or epigenetic dysregulations in LUSC. Random walk was adopted to identify genes significantly affected by upstream abnormalities. Expression differentiation and survival analysis were conducted for these significant genes, respectively. Prognostic power of selected gene was also tested in 102 male LUSC samples through immunohistochemistry assay. Results Twelve genes were successfully retrieved from biological network, including ERα (ESRS1), EGFR, AR, ATXN1, MAPK3, PRKACA, PRKCA, SMAD4, TP53, TRAF2, UBQLN4 and YWHAG, which were closely related to sex hormone signaling pathway. Survival analysis in public datasets indicated ERα was significantly associated with a poor overall survival (OS) in male LUSC. The result of our immunohistochemistry assay also demonstrated this correlation using R0 resected tumors (n = 102, HR: 2.152, 95% CI: 1.089–4.255, p = 0.024). Although disease-free survival (DFS) difference was non-significant (n = 102, p = 0.12), the tendency of distinction was straight-forward. Cox analysis indicated ERα was the only independent prognostic factor for male patients’ OS after R0 resection (HR = 2.152, p = 0.037). Conclusion ERα was significantly related to a poor prognosis in LUSC, especially for male patients after radical surgery, confirmed by our immunohistochemistry data. more...

Background Circular RNAs (circRNAs) belong to a new type of endogenous non-coding RNA and plays a key role in carcinogenesis. Circ-ZKSCAN1 (hsa_circ_0001727) has been proven to be a tumor-dependent circRNA. However, its role in non-small cell lung cancer (NSCLC) has been underreported. Methods The expression patterns of circ-ZKSCAN1 were determined using qRT-PCR in NSCLC samples and cell lines. Cell proliferation was examined utilizing the CCK-8 assay. Cell migration and invasion were evaluated using the Transwell assay. The combination of circ-ZKSCAN1 and miR-330-5p in NSCLC cells was analyzed by RNA pull-down and luciferase reporter assay. We used the bioinformatics software circbank, CircInteractome, TargetScan and Miranda to predict circRNA-miRNA and miRNA-mRNA interactions. Results Our results showed that circ-ZKSCAN1 was significantly up-regulated in NSCLC, closely related to malignant characteristics and poor prognosis, and clinically related to tumor size and clinical stage. Subsequent experiments showed that circ-ZKSCAN1 could inhibit the growth of NSCLC cells in vitro and in vivo. Importantly, circ-ZKSCAN1 can act as a sponge of carcinogenic miR-330-5p to increase the expression of FAM83A, resulting in the inhibition of MAPK signal transduction pathway, thus promoting the progress of NSCLC. Interestingly, the increase in FAM83A expression caused by circ-ZKSCAN1 overexpression could in turn promote the expression of circ-ZKSCAN1. Conclusions Circ-ZKSCAN1 is a key positive regulator of NSCLC, and clarifies the potential molecular mechanism of the new circ-ZKSCAN1/miR-330-5p/FAM83A feedback loop in promoting the progress of NSCLC. more...

Background: Post-stroke cognitive impairment (PSCI) is commonest clinical disorder in which peripheral cholinergic activity is important. Oleuropein (OLP) is polyphenol is present in olive oil. Here we evaluated the effect of OLP in cognitive dysfunction rats in post cerebral stroke model. Methods: The post cerebral stroke cognitive dysfunction PSD rat model was created by occlusion of transient middle cerebral artery. The rats were divided into 6 groups named, Sham + Vehicle, Sham + OLP (50 mg/kg), PSD rats + Vehicle, PSD rats + OLP (20, 50 or 100 mg/kg). The spatial learning was assessed by Morris water maze (MWM). The expression of choline acetyltransferase (ChAT), acetylcholine (ACH), extent of histone acetylation and phosphorylation of cAMP response element-binding protein (CREB) were evaluated by Western blot assay and immunofluorescence staining. Results: Treatment of OLP at various doses showed higher number of spontaneous and rewarded alterations and lesser percentage bias compared to vehicle treated PSD rats. OLP resulted in decreased levels of ChAT and ACH, whereas the degree of histone acetylation and phosphorylation of CREB improved in dose dependent pattern. Conclusion: treatment of OLP improved PSCI via increasing the phosphorylation of CREB and histone acetylation, thus attenuating cholinergic activity. more...

The purpose of this study was to explore the potential relationship between intravenous leiomyomatosis (IVL) and uterine myoma (UM) at the molecular level. RNA-sequencing was performed on IVL tumours, UM tumours, and adjacent normal uterine muscle. We compared the gene expression levels between IVL and normal uterine muscle, UM and normal uterine muscle, to identify differentially expressed genes (DEGs). Then we used Gene Ontology Enrichment Analysis to determine the functions of the DEGs and performed specimen cluster analysis. We obtained 98 DEGs between IVL and adjacent normal uterine muscle, and 61 DEGs between UM and adjacent normal uterine muscle. Functional enrichment of both IVL and UM DEGs showed that they are associated with hormone stimulus, extracellular matrix, and cell adhesion. Unsupervised clustering analysis showed that IVL and UM could not be separated completely. Among these dysregulated genes, we found that HOXA13 showed a distinct dysregulated status between IVL and UM. HOXA13 may therefore serves as a biomarker to distinguish IVL and UM. Our results showed that IVL and UM may have similar dysregulated gene networks. They may be closely related, and HOXA13 may serves as a biomarker to distinguish between IVL and UM. more...

Calcific aortic valve disease (CAVD) is the most common heart valve disorder, yet its mechanism remains poorly understood. Valve interstitial cells (VICs) are the prevalent cells in aortic valve and their osteogenic differentiation may be responsible for calcific nodule formation in CAVD pathogenesis. Emerging evidence shows microRNA (miRNA, or miR) can function as important regulators of many pathological processes, including osteogenic differentiation. Here, we aimed to explore the function of miR-449c-5p in CAVD pathogenesis. In this study, we demonstrated the role of miR-449c-5p in VICs osteogenesis. MiRNA microarray assay and qRT-PCR results revealed miR-449c-5p was significantly down-regulated in calcified aortic valves compared with non-calcified valves. MiR-449c-5p overexpression inhibited VICs osteogenic differentiation in vitro, whereas down-regulation of miR-449c-5p enhanced the process. Target prediction analysis and dual-luciferase reporter assay confirmed Smad4 was a direct target of miR-449c-5p. Furthermore, knockdown of Smad4 inhibited VICs osteogenic differentiation, similar to the effect observed in up-regulation miR-449c-5p. In addition, animal experiments proved indirectly miR-449c-5p could alleviate aortic valve calcification. Our data suggested miR-449c-5p could function as a new inhibitory regulator of VICs osteogenic differentiation, which may act by targeting Smad4. MiR-449c-5p may be a potential therapeutic target for CAVD. more...

The present study aimed to investigate the effect of laser therapy on the expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in the plasma of infants diagnosed with cutaneous hemangioma, in order to identify biomarkers for assessing the clinical efficacy of laser therapy. In total, 109 infants with superficial abdominal hemangioma received laser treatment, of which 74 were diagnosed in the proliferation phase, 20 in the regression phase and 15 in the involution phase. In addition, 10 infants without cutaneous hemangioma were recruited as normal controls. The concentrations of VEGF and bFGF in peripheral plasma samples were measured using ELISAs. Dynamic changes in the VEGF and bFGF concentrations of 23 infants diagnosed in the proliferation phase were compared before and after laser therapy. The plasma concentration of VEGF in the proliferation phase group was significantly higher compared with that in the regression phase, involution phase and normal control groups (all P0.05). The plasma concentration of bFGF in the proliferation phase group was significantly higher compared with that in the regression phase, involution phase and normal control groups (all P0.05). Following laser therapy, the plasma concentrations of VEGF and bFGF in infants with cutaneous hemangioma were significantly decreased (both P more...

Intravenous leiomyomatosis (IVL) is a rare neoplastic disorder. It may extend into the right cardiac chambers, which are named after intracardiac leiomyomatosis (ICL). We describe a case of IVL extending into the right heart and pulmonary artery in a 46-year-old woman. The patient successfully underwent a one-stage operation under cardiopulmonary bypass (CPB) with deep hypothermic circulatory arrest. The patient fully recovered without major complications and did not exhibit any recurrence at the 9-month follow-up. The unique feature of this case is its involvement with the pulmonary artery, which is uncommon but potentially lethal. more...