Fangbao Ding

miR-342-3p targets RAP2B to suppress proliferation and invasion of non-small cell lung cancer cells.

MicroRNAs (miRNAs) play critical roles in cancer development and progression. In this study, we examined the roles and molecular mechanisms of miR-342-3p in human non-small cell lung cancer (NSCLC). The results showed that miR-342-3p is downregulated in NSCLC cell lines and tissues, and its overexpression induces significant inhibition of NSCLC cell proliferation, invasion, and tumor growth in nude mice. In addition, miR-342-3p repressed RAP2B expression through interactions with its 3′-UTR region. Restoration of RAP2B expression reversed miR-342-3p-mediated inhibitory activity in NSCLC cells. Finally, analyses of miR-342-3p and RAP2B levels in NSCLCs revealed that miR-342-3p inversely correlated with RAP2B mRNA expression. Our collective findings provide preliminary evidence that miR-342-3p acts as a tumor suppressor in NSCLC through repression of RAP2B.

USP22 promotes NSCLC tumorigenesis via MDMX up-regulation and subsequent p53 inhibition.

Increasing evidence suggests that ubiquitin-specific protease 22 (USP22) has great clinicopathologic significance in oncology. In this study, we investigated the role of USP22 in human NSCLC tumorigenesis along with the underlying mechanisms of action. First, we determined the expression of USP22 in human NSCLC, as well as normal tissues and cell lines. We then studied the effects of USP22 silencing by shRNA on NSCLC cell growth in vitro and tumorigenesis in vivo, along with the effect on the p53 pathway. We found that USP22 is overexpressed in human NSCLC tissues and cell lines. USP22 silencing by shRNA inhibits proliferation, induces apoptosis and arrests cells at the G0/G1 phases in NSCLC cells and curbs human NSCLC tumor growth in a mouse xenograft model. Additionally, USP22 silencing downregulates MDMX protein expression and activates the p53 pathway. Our co-immunoprecipitation analysis shows that USP22 interacts with MDMX in NSCLC cells. Furthermore, MDMX silencing leads to growth arrest and apoptosis in NSCLC cells, and over-expression of MDMX reverses the USP22 silencing-induced effects. Taken together, our results suggest that USP22 promotes NSCLC tumorigenesis in vitro and in vivo through MDMX upregulation and subsequent p53 inhibition. USP22 may represent a novel target for NSCLC treatment.

The involvement of AQP1 in heart oedema induced by global myocardial ischemia

Aquaporin‐1 (AQP1) is a member of aquaporin family that was previously proven to be involved in myocardial dysfunction; however, the role of AQP1 in myocardial stunning is less clear. To determine the change of AQP1 expression level in the heart and its effect on oedema after global myocardial ischemia, 40 adult goats underwent cardiopulmonary bypass (CPB) with an aortic cross‐clamp time of 2 h and total bypass time of 6, 12, 24, 48 and 72 h followed by subsequent reperfusion. AQP1 function of eight goats was inhibited by HgCl2 during the 24 h on CPB. All groups were compared with eight sham bypass control goats. Myocardial water content was measured, and the APQ1 mRNA and protein levels were detected by RT‐PCR and immunoblotting, respectively. The results showed that the degree of myocardial oedema increased significantly at 6, 12, 24 and 48 h of reperfusion after CPB as compared with the control and recovered at 72 h of subsequent reperfusion. Expression levels of AQP1 mRNA and protein began to increase at 12 h and peaked at 24 h of CPB following reperfusion. Furthermore, myocardial oedema was reduced in the HgCl2 group compared with the time‐matched CPB and control groups. These data suggested that AQP1 expression increases in CPB and AQP1 plays an important role in myocardial oedema during CPB. Copyright

USP22 acts as an oncogene by regulating the stability of cyclooxygenase-2 in non-small cell lung cancer.

The histone ubiquitin hydrolase ubiquitin-specific protease 22 (USP22) is an epigenetic modifier and an oncogene that is upregulated in many types of cancer. In non-small cell lung cancer (NSCLC), aberrant expression of USP22 is a predictor of poor survival, as is high expression of cyclooxygenase-2 (COX-2). Despite its oncogenic role, few substrates of USP22 have been identified and its mechanism of action in cancer remains unclear. Here, we identified COX-2 as a direct substrate of USP22 and showed that its levels are modulated by USP22 mediated deubiquitination. Silencing of USP22 downregulated COX-2, decreased its half-life, and inhibited lung carcinoma cell proliferation by directly interacting with and modulating the stability and activity of COX-2 through the regulation of its ubiquitination status. The findings of the present study suggest a potential mechanism underlying the oncogenic role of USP22 mediated by the modulation of the stability and activity of COX-2.

Application of endovascular occlusion of both caval veins in minimally invasive isolated redo tricuspid surgery through right thoracotomy.

OBJECTIVE To summarise the experiences of applying vena cava endovascular occlusion technique in minimally invasive isolated redo tricuspid surgery. METHODS Forty-six consecutive patients received minimally invasive redo tricuspid surgery through right thoracotomy at our institute. All the patients had isolated significant tricuspid regurgitation after previous cardiac surgeries. Preoperative chest computed tomography showed high risk of conventional median sternotomy and vena cava exposure. A right anterolateral thoracotomy incision was made from the fourth intercostal space. The arterial cannula was placed in femoral artery, and balloon cannulas were used for bicaval cannulation. The venous cannulation was guided by transoesophageal echocardiography. Tricuspid valve operation was performed with heart beating after both venous cannulas were endovascularly occluded by inflating the balloons. RESULTS There were no complications related to this cannulation technique. Two patients needed position adjustment or re-inflation of the balloon to obtain complete occlusion. The average time of cardiopulmonary bypass establishment was 55 ± 15 min and pump time was 58 ± 23 min. The length of stay was 8 ± 7 days. There was no early death in hospital. CONCLUSION Endovascular occlusion of both vena cava in isolated redo tricuspid surgery was safe, effective and reliable. This approach significantly simplified the complexity of the surgery.

Congenital quadricuspid aortic valve associated with aortic insufficiency and mitral regurgitation

Congenital quadricuspid aortic valve is a rare cardiac anomaly. More than half of the patients with this abnormality will develop aortic insufficiency in adulthood. It is vital that patients with quadricuspid aortic valve who present with progressive aortic regurgitation undergo valve replacement or repair at appropriate time. Here, we present two cases of quadricuspid aortic valve. We first describe a 58-year-old man who had mitral regurgitation and ascending aorta dilatation with quadricuspid aortic valve. He underwent aortic valve replacement and mitral valve plasty and recovered well. The second patient is a 20-year-old asymptomatic boy who has been closely followed up and has not received any surgical treatment.

Phosphorylation of eIF2α suppresses cisplatin-induced A549 cell apoptosis via p38 inhibition.

Cisplatin-based chemotherapy is considered a golden standard for treatment of advanced non-small cell lung cancer (NSCLC). However, drug resistance is one of the major problems in NSCLC chemotherapy. The mechanisms and related biological pathways that contribute to chemoresistance are relatively poorly understood. Here, we demonstrated that the phosphorylation of eukaryotic translation initiation factor 2α (eIF2α) suppresses cisplatin-induced A549 cell apoptosis. Cisplatin induced eIF2α phosphorylation through protein kinase RNA. Importantly, phospho-eIF2α inhibited cisplatin-induced A549 cells apoptosis, at least in part, by suppressing the p38 pathway. Moreover, analysis of tissue microarrays information demonstrated that phospho-eIF2α predicted a poor prognosis in patients with NSCLC. Taken together, these results provide a potential mechanism that is used for explaining how eIF2α promotes cisplatin resistance in A549 cells. Therefore, the regulation of eIF2α may improve treatment outcomes of cisplatin-based chemotherapy for patients with NSCLC.

Interventricular Septal Hematoma After Congenital Cardiac Surgery

Interventricular septal hematoma is a very rare complication after congenital heart surgery. We report our experience with 2 cases; 1 unsuccessful attempt in a child with a ventricular septal defect and 1 successful palliation in a child with tetralogy of Fallot. On comparison with previously reported results, children seem to have better outcomes than adults. While the first choice for a hemodynamically unstable patient is surgical revision, individualized therapy should also be considered.

Continuous vagal nerve stimulation affects atrial neural remodeling and reduces atrial fibrillation inducibility in rabbits

BACKGROUND The effects of continuous vagal nerve stimulation (VNS) on atrial neural remodeling during atrial fibrillation (AF) remain unclear. OBJECTIVE To test the hypothesis that VNS affects atrial neural remodeling and reduces AF inducibility. METHODS Twenty rabbits were randomly divided into two groups: rapid atrial pacing (RAP) group and RAP with VNS group. AF inducibility studies and atrial histologic analyses were performed after 4 weeks. RESULTS Five rabbits of RAP group (5/10) in the RAP group developed sustained AF. None of rabbits in RAP with VNS group had developed AF. The incidence of sustained AF in VNS group was significant lower than that in rapid pacing group (P<.01). Treatment with VNS resulted in a significant reduction in atrial neural remodeling and AF duration (P<.01). CONCLUSIONS Atrial neural remodeling plays an important role in the initiation and maintenance of AF. Modulating autonomic nerve function with VNS can contribute to AF control.

MiR-196a2 rs11614913 T>C Polymorphism is Associated with an Increased Risk of Tetralogy of Fallot in a Chinese Population

BACKGROUND MicroRNAs (miRNAs) are a family of endogenous, small, noncoding single-stranded RNAs that act as post-transcriptional gene regulatory elements. MiRNA polymorphisms may be associated with susceptibility to congenital heart disease (CHD). The aim of this study was to evaluate the impact of miRNA single nucleotide polymorphisms (SNPs) on CHD susceptibility. METHODS We genotyped two functional SNPs, miR-196a2 rs11614913 and miR-146a rs2910164, in a case-control cohort of 173 Chinese patients with tetralogy of Fallot (TOF) and 207 non-CHD controls. RESULTS When the miR-196a2 rs11614913 TT homozygote genotype was used as the reference group, the TC genotype was not associated with an increased risk of TOF. The CC genotype was associated with a borderline significantly increased risk for TOF. In the recessive model, when the miR-196a2 rs11614913 TT/TC genotypes were used as the reference group, the CC homozygote genotype was associated with a significantly increased risk of TOF (OR = 1.96, 95% CI = 1.18-3.25, p = 0.01). The miR-146a rs2910164 C>G polymorphism was not associated with developing TOF. CONCLUSIONS Our findings suggested that the miR-196a2 rs11614913 T>C polymorphism may play a role in the development of TOF. Future larger studies that include populations of other ethnicities are required to confirm these findings. KEY WORDS Congenital heart disease; MiRNA; Molecular epidemiology; Polymorphisms; Tetralogy of Fallot.