Delayed subcutaneous emphysema, mediastinal emphysema and pneumothorax after tracheal intubation in a child: a case report.

Background: Subcutaneous emphysema and mediastinal emphysema and/or pneumothorax after mechanical ventilation through endotracheal intubation is not uncommon. However, cases of delayed mediastinal emphysema and subcutaneous emphysema after extubation and their further development into pneumothorax have rarely been reported, especially in children. Given this, we provide such a case for the reference of clinicians. Case Description: We report a case of a 2-year-old girl with no abnormalities at the preoperative examination, who developed subcutaneous emphysema and mediastinal emphysema 4 hours after recovery from general anesthesia due to ophthalmic arterial infusion chemotherapy for retinoblastoma, and bilateral pneumothorax 12 hours later. The patient recovered and was discharged following aggressive treatment of subcutaneous exhaust and thoracic closed drainage. Due to fiberoptic bronchoscopy was refused by the guardian to determine the cause, we hypothesized tracheal intubation injury occurs, air enter the trachea or bronchial mucosa, extend up to the neck, head and face along the blood vessels, larynx and deep cervical fascia spaces, causing subcutaneous emphysema, and then gradually spread to the mediastinum, resulting in mediastinal emphysema and pneumothorax. However, the etiology and preventive measures warrant further study. Conclusions: Strengthen the etiological study of subcutaneous and/or mediastinal emphysema and pneumothorax due to endotracheal intubation, perioperative observation and postoperative follow-up are important measures for the effective prevention, early diagnosis, and timely treatment of subcutaneous and/or mediastinal emphysema and pneumothorax, and are also conducive to ensuring the safety of patients.

CircTP63 promotes cell proliferation and invasion by regulating EZH2 via sponging miR-217 in gallbladder cancer.

BACKGROUND: Gallbladder cancer (GBC) is the most common biliary tract malignancy and has a poor prognosis in patients with GBC. CircRNA TP63 (circTP63) has been implicated in cell proliferation and invasion in some tumor progress. The study aims to investigate the clinical significance and functional role of circTP63 expression in GBC. METHODS: The expression of circTP63 in GBC tissues or cells was detected by qRT-PCR and the association between circTP63 expression and prognosis of GBC patients was analyzed. CCK8 assay, flow cytometry analysis, transwell assay and in vivo studies were used to evaluate the cell proliferation and invasion abilities after circTP63 knockdown in GBC cells. Luciferase reporter assays and RNA pull-down assay were used to determine the correlation between circTP63 and miR-217 expression. Besides, western blot analysis was also performed. RESULTS: In the present study, we showed that circTP63 expression was upregulated in GBC tissues and cells. Higher circTP63 expression was associated with lymph node metastasis and short overall survival (OS) in patients with GBC. In vitro, knockdown of circTP63 significantly inhibited cell proliferation, cell cycle progression, migration and invasion abilities in GBC. Besides, we demonstrated that knockdown of circTP63 inhibited GBC cells Epithelial-Mesenchymal Transition (EMT) process. In vivo, knockdown of circTP63 inhibited tumor growth in GBC. Mechanistically, we demonstrated that circTP63 competitively bind to miR-217 and promoted EZH2 expression and finally facilitated tumor progression. CONCLUSIONS: Our findings demonstrated that circTP63 sponged to miR-217 and regulated EZH2 expression and finally facilitated tumor progression in GBC. Thus, targeting circTP63 may be a therapeutic strategy for the treatment of GBC.

Circß-catenin promotes tumor growth and Warburg effect of gallbladder cancer by regulating STMN1 expression.

Gallbladder cancer (GBC) is the most malignant cancer of the biliary tract cancer and presents poor prognosis. CircRNAs have been identified as critical regulators of multiple stages in tumor progression. In the study, we first demonstrated that circular RNA circß-catenin expression was upregulated in GBC tissues when compared to adjacent normal tissues and associated with advanced clinical stage and poor prognosis in GBC patients. Silencing of circß-catenin obviously suppressed GBC cell proliferation and cell cycle progression in vitro, but circß-catenin overexpression had the opposite effects. In vivo, silencing of circß-catenin inhibited tumor growth. Furthermore, we also found that circß-catenin promoted GBC cell lactate production, pyruvate production, ATP quantity, and extracellular acidification rate (ECAR), which suggested that circß-catenin regulated Warburg effect in GBC. Mechanistic analysis further highlighted that circß-catenin promoted Stathmin 1 (STMN1) expression through sponging miR-223 in GBC progression. In addition, knockdown of STMN1 inhibited cell growth and Warburg effect in GBC. In summary, our findings indicated that circß-catenin/miR-223/STMN1 axis could regulate cell growth and Warburg effect in GBC. Targeting circß-catenin might be a potential therapeutic strategy for GBC.

CircPVT1 promotes gallbladder cancer growth by sponging miR-339-3p and regulates MCL-1 expression.

Circular RNAs (circRNAs) have been implicated in modulating biological processes in some tumors. However, the contributions and molecular mechanisms of circRNAs to gallbladder cancer (GBC) remain largely unknown. In the present study, our results showed circPVT1 expression was significantly upregulated in GBC tissues and cells. Higher circPVT1 expression was correlated with lymph node metastasis, advanced TNM stage, and poor overall survival (OS) in patients with GBC. Subsequently, knockdown of circPVT1 significantly impeded GBC cell proliferation, migration, invasion, while induced cell apoptosis in vitro. However, upregulated circPVT1 had the opposite effects. In vivo, we also demonstrated that knockdown of circPVT1 inhibited tumor growth. Furthermore, we confirmed that circPVT1 could regulate Myeloid cell leukemia-1 (MCL-1) expression by sponging to miR-339-3p, which affected tumor progression in GBC cells. In summary, our findings indicated that circPVT1 may serve as a promising prognostic marker and therapeutic target for GBC.

Long Non-coding RNA FIRRE Acts as a miR-520a-3p Sponge to Promote Gallbladder Cancer Progression via Mediating YOD1 Expression.

OBJECTIVES: The role of lncRNAs in gallbladder cancer (GBC) remains poorly understood. In this study, we explored the function of functional intergenic repeating RNA element (FIRRE) in GBC. MATERIALS AND METHODS: Whole transcriptome resequencing was performed in three pairs of GBC tissues and adjacent non-tumor tissues. lncRNA FIRRE expression was verified by real-time PCR. The function of FIRRE in GBC was evaluated by experiments in vitro and in vivo. The mechanism of FIRRE was investigated via fluorescent in situ hybridization, RNA pull-down, dual luciferase reporter assays, and RNA immunoprecipitation. RESULTS: FIRRE level was dramatically increased in GBC tissues compared to that in the adjacent non-tumor tissues. High expression of FIRRE was closely related to clinical stage and poor prognosis in GBC patients. Moreover, FIRRE remarkably enhanced proliferation and migration, and inhibited apoptosis of GBC cells. Mechanistically, FIRRE modulated YOD1 expression by sponging miR-520a-3p, thus contributing to the development of GBC. CONCLUSION: Our data revealed that FIRRE might act as a novel mediator in GBC progression by sponging miR-520a-3p and regulating YOD1. FIRRE might be regarded as a potential diagnostic marker or target for GBC treatment.

Long noncoding RNA PVT1 promoted gallbladder cancer proliferation by epigenetically suppressing miR-18b-5p via DNA methylation.

Gallbladder cancer (GBC) accounts for 85-90% malignancies of the biliary tree worldwide. Considerable evidence has demonstrated that dysregulation of lncRNAs is involved in the progression of cancer. LncRNA PVT1 has been reported to play important roles in various cancers, but its role in gallbladder cancer remains unknown. In the present study, we found that PVT1 was upregulated in GBC tissues and cells, and its upregulation was related with poor prognosis in GBC patients. PVT1 promoted GBC cells proliferation in vitro and in vivo. Mechanistically, PVT1 recruited DNMT1 via EZH2 to the miR-18b-5p DNA promoter and suppressed the transcription of miR-18b-5p through DNA methylation. Moreover, HIF1A was proved to be the downstream target gene of miR-18b-5p and PVT1 regulated GBC cells proliferation via HIF1A. In conclusion, our studies clarified the PVT1/miR-18b-5p/HIF1A regulation axis and indicated that PVT1 could be a potential therapeutic target for GBC.

Trends of gallbladder cancer incidence, mortality, and diagnostic approach in urban Shanghai between 1973 and 2009.

PURPOSE: To describe and interpret secular time trends in gallbladder cancer (GBC) incidence, mortality, and diagnostic approach using 37 years of cancer registry data in urban Shanghai. METHODS: Data on registration of GBC in urban Shanghai during 1973 and 2009 were collected by the Shanghai Cancer Registry. To describe time trends and to identify specific time points when significant changes occurred, we used joinpoint regression analysis. RESULTS: The age-standardized rates (ASRs) of incidence increased from 1.1/100,000 (1973-1975) to 2.9/100,000 (2006-2009) in men and from 1.7/100,000 (1973-1975) to 3.9/100,000 (2006-2009) in women. ASRs of incidence increased significantly with estimated annual percent changes (EAPCs) of 2.8% in men and 2.5% in women. The mortality trends increased significantly, with EAPCs of 2.8% in men and 2.5% in women. The increasing incidence and mortality rates were primarily observed in men ⩾60 years of age and in women ⩾70 years of age. Notable downward trends in incidence and mortality were identified among women age 60-69 years over the last decade. The percentage of GBC diagnosed by pathology increased steadily over the years while the percentage of GBC diagnosed by imaging, surgery, and biochemistry sharply increased from 1987 onwards. CONCLUSIONS: Thirty-seven years of cancer registry data document a tremendous increase in incidence/mortality and a slight decline in incidence/mortality over the last decades for GBC, especially among women, in Shanghai. The development of diagnostic approaches and aging population may play important roles.

Circular RNA FOXP1 promotes tumor progression and Warburg effect in gallbladder cancer by regulating PKLR expression.

BACKGROUND: Circular RNAs (circRNAs) have recently been identified as potential functional modulators of the cellular physiology processes. The study aims to uncover the potential clinical value and driving molecular mechanisms of circRNAs in gallbladder cancer (GBC). PATIENTS AND METHODS: We performed RNA sequencing from four GBC and paired adjacent normal tissues to analyze the circRNA candidates. Quantitative real-time polymerase chain reaction (QRT-PCR) was used to measure the circFOXP1 expression from 40 patient tissue samples. Short hairpin RNA mediated knockdown or exogenous expression of circFOXP1 combined with in vitro and in vivo assays were performed to prove the functional significance of circFOXP1. Double luciferase reporter, RNA immunoprecipitation (RIP) and RNA pull-down assays were also performed. RESULTS: By performing RNA sequencing from GBC and paired adjacent normal tissues to analyze the circRNA candidates, we identified that circFOXP1 (hsa_circ_0008234) expression was significantly upregulated in GBC tissues and positively associated with lymph node metastasis, advanced TNM stage and poor prognosis in patients. Short hairpin RNA mediated knockdown or exogenous expression of circFOXP1 combined with in vitro assays demonstrated that circFOXP1 has pleiotropic effects, including promotion of cell proliferation, migration, invasion, and inhibition of cell apoptosis in GBC. In vivo, circFOXP1 promoted tumor growth. Mechanistically, double luciferase reporter, RNA immunoprecipitation (RIP) and biotin-labeled RNA pull-down assays clarified that circFOXP1 interacted with PTBP1 that could bind to the 3'UTR region and coding region (CDS) of enzyme pyruvate kinase, liver and RBC (PKLR) mRNA (UCUU binding bites) to protect PKLR mRNA from decay. Additionally, circFOXP1 acted as the sponge of miR-370 to regulate PKLR, resulting in promoting Warburg effect in GBC progression. CONCLUSIONS: These results demonstrated that circFOXP1 serve as a prognostic biomarker and critical regulator in GBC progression and Warburg effect, suggesting a potential target for GBC treatment.

Regional lymphadenectomy vs. extended lymphadenectomy for hilar cholangiocarcinoma (Relay-HC trial): study protocol for a prospective, multicenter, randomized controlled trial.

BACKGROUND: The prognostic benefits and safety of extended lymphadenectomy for hilar cholangiocarcinoma remain uncertain. The available evidence is still insufficient concerning its retrospective aspect. The aim of this study is to explore the clinical effect and safety of extended lymphadenectomy compared to regional lymphadenectomy in patients with hilar cholangiocarcinoma. METHODS: The Relay-HC trial is a prospective, multicenter, and randomized controlled trial. Seven hundred and thirty-four eligible patients with resectable perihilar cholangiocarcinoma across 15 tertiary hospitals in China will be randomly assigned (1:1) to receive either regional lymphadenectomy or extended lymphadenectomy. The primary objective is to determine the overall survival after the two approaches. Secondary objectives of the study include the evaluation of perioperative mortality, postoperative complication, and disease-free survival. This study has been approved by the ethics committee of each participating hospital. DISCUSSION: The Relay-HC trial is designed to investigate the prognostic benefits and safety of expanded lymphadenectomy for hilar cholangiocarcinoma. Currently, it has never been investigated in a prospective randomized controlled clinical trial. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR), ChiCTR1800015688 . Registered on 15 April 2018.

Long non-coding RNA GBCDRlnc1 induces chemoresistance of gallbladder cancer cells by activating autophagy.

BACKGROUND: Gallbladder cancer is the most common biliary tract malignancy and not sensitive to chemotherapy. Autophagy is an important factor prolonging the survival of cancer cells under chemotherapeutic stress. We aimed to investigate the role of long non-coding RNAs (lncRNAs) in autophagy and chemoresistance of gallbladder cancer cells. METHODS: We established doxorubicin (Dox)-resistant gallbladder cancer cells and used microarray analysis to compare the expression profiles of lncRNAs in Dox-resistant gallbladder cancer cells and their parental cells. Knockdown or exogenous expression of lncRNA combined with in vitro and in vivo assays were performed to prove the functional significance of lncRNA. The effects of lncRNA on autophagy were assessed by stubRFP-sensGFP-LC3 and western blot. We used RNA pull-down and mass spectrometry analysis to identify the target proteins of lncRNA. RESULTS: The drug-resistant property of gallbladder cancer cells is related to their enhanced autophagic activity. And we found a lncRNA ENST00000425894 termed gallbladder cancer drug resistance-associated lncRNA1 (GBCDRlnc1) that serves as a critical regulator in gallbladder cancer chemoresistance. Furthermore, we discovered that GBCDRlnc1 is upregulated in gallbladder cancer tissues. Knockdown of GBCDRlnc1, via inhibiting autophagy at initial stage, enhanced the sensitivity of Dox-resistant gallbladder cancer cells to Dox in vitro and in vivo. Mechanically, we identified that GBCDRlnc1 interacts with phosphoglycerate kinase 1 and inhibits its ubiquitination in Dox-resistant gallbladder cancer cells, which leads to the down-regulation of autophagy initiator ATG5-ATG12 conjugate. CONCLUSIONS: Our findings established that the chemoresistant driver GBCDRlnc1 might be a candidate therapeutic target for the treatment of advanced gallbladder cancer.

Improvement in the diagnosis and treatment of T2 gallbladder carcinoma is pivotal to improvement in the overall prognosis for this disease.

Since the American Joint Committee on Cancer (AJCC) subdivided the T2 stage of gallbladder carcinoma (GBC) into T2a and T2b, the diagnosis and treatment of those stages have been a subject of heated discussion and controversy. T2 is a stage of GBC that might be treatable. Based on the extent of lymph node metastasis and distant metastasis, T2 GBC can be classified into various pathological stages such as IIA, IIB, IIIB, and IVB, leading to controversy in clinical settings. This review aims to discuss the effectiveness of and controversies concerning S4b+5 resection, the acceptable extent of lymph node dissection, the timing for treatment of incidental gallbladder cancer, and adjuvant therapy. This review also aims to suggest directions for and recommendations regarding clinical research in the future.

Long noncoding RNA MEG3 regulates LATS2 by promoting the ubiquitination of EZH2 and inhibits proliferation and invasion in gallbladder cancer.

Gallbladder cancer (GBC) is the most common type of biliary tract cancer worldwide. Long noncoding RNAs (lncRNAs) play essential roles in physiological and pathological development. LncRNA MEG3, a tumor suppressor, has been reported to play important roles in some cancers, but the role of MEG3 in GBC remains largely unknown. The purpose of the present study was to explore the role of MEG3 in proliferation and invasion and the potential molecular mechanism in GBC. We found that MEG3 was downregulated in GBC tissues and cells, and low expression of MEG3 was correlated with poor prognostic outcomes in patients. Overexpression of MEG3 inhibited GBC cell proliferation and invasion, induced cell apoptosis and decreased tumorigenicity in nude mice. Moreover, we found that MEG3 was associated with EZH2 and attenuated EZH2 by promoting its ubiquitination. Furthermore, MEG3 executed its functions via EZH2 to regulate the downstream target gene LATS2. Taken together, these findings suggest that MEG3 is an effective target for GBC therapy and may facilitate the development of lncRNA-directed diagnostics and therapeutics against GBC.

MicroRNA­424 suppresses the proliferation of hemangioma­derived endothelial cells by targeting VEGFR­2.

Hemangioma (HA) is a type of benign tumor common in infancy. The main feature of HA is the abnormal proliferation of vascular endothelial cells. To date, the pathogenesis of HA remains unclear. Fully understanding the process of HA tumorigenesis is essential for developing novel treatment for HAs. Dysregulation of microRNAs (miRNAs/miR) has been reported to be involved in the development of various diseases, including HA. In the present study, the expression of miR­424 decreased in HA­derived endothelial cells (HemECs). To elucidate the role of miR­424 in HAs development, the present study overexpressed or inhibited miR­424 in HemECs, revealing that miR­424 overexpression significantly inhibited HemEC growth and promoted apoptosis, while the downregulation of miR­424 promoted cell growth and inhibited cell apoptosis. To elucidate the underlying mechanism, bioinformatic analyses were performed, the result of which demonstrated that the 3'­untranslated region of vascular endothelial growth factor receptor 2 (VEGFR­2) may be a target of miR­424. The result of a dual luciferase reporter assay confirmed that the expression of VEGFR­2 was inhibited by miR­424. In addition, it was revealed that the hyper­phosphorylation of protein kinase B (AKT) and extracellular signal­regulated kinase (ERK) in HemECs, and the restoration of miR­424 markedly inhibited the activation of AKT and ERK. In conclusion, these results indicated that miR­424 may target VEGFR­2 and inhibit HemECs growth, and that low expression of miR­424 in HemECs may lead to an increase in cell growth and a decrease in cell apoptosis. Thus, it was proposed that miR­424 may serve as a tumor suppressor in HemECs, and that VEGFR­2 may be a potential tumor suppressive target in HemECs and for the treatment of HA.

Current status of malignant mesothelioma with liver involvement in China: A brief report and review of the literature.

Primary and secondary intrahepatic malignant mesothelioma (PIHMM & SIHMM) caused by Peritoneal mesothelioma (PM) are extremely rare tumors and their clinicopathological characteristics remain unclear. The current study presented a case of a 63-year-old female with PIHMM and a literature review of Chinese case reports of SIHMM and PIHMM was performed. The patient received curative left hemihepatectomy because of a 5.5 × 5.0 × 4.0 cm mass occupying the II, III and the lateral portion of the IV segments and meanwhile tightly infiltrating the diaphragm (yellow arrow) was also observed. The pathological diagnosis was epithelial type PIHMM. Immunohistochemistry revealed that the tumor was positive for Calretinin, CK5/6, WT-1 and D2-40(N). The literature review included 11 studies and 6 case reports with a total of 293 PM patients accompanied with 31 SIHMM cases and then 3 case reports of PIHMM. SIHMM and PIHMM are extremely rare, easy to misdiagnose malignant tumors. Immunohistochemistry should be performed strictly in accordance with guidelines, which is crucial for pathological diagnosis. Comprehensive treatment of surgery combined with chemotherapy are mainstream methods for SIHMM and PIHMM. Also, exact survival data should be carefully explored so that objective evaluation of the efficacy of the treatment could be achieved.