SNHG9 promotes Hepatoblastoma Tumorigenesis via miR-23a-5p/Wnt3a Axis.

Background: Hepatoblastoma is a common hepatic tumor occurring in children between 0-5 years. Accumulating studies have shown lncRNA's potential role in distinct cancer progression and development, including hepatoblastoma. SnoRNA host gene 9 (SNHG9) is associated with the progression of distinct human cancers, but, its specific molecular mechanisms in hepatoblastoma is not unknown. Methods: In this study, we estimated SNHG9 expression in hepatoblastoma tissue and cell lines by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). Next, we downregulated and upregulated SNHG9 expression in hepatoblastoma cell lines and then determined cell proliferation (CCK-8), colony formation, and cellular apoptosis activity. The dual luciferase reporter activity, RNA immunoprecipitation (RIP), biotin RNA pull down and Spemann's Pearson correlation coefficient assay were performed to establish the interaction between SNHG9, WNt3a and miR- 23a-5p. A xenograft in-vivo tumorgenicity test was performed to elucidate the role of SNHG9 hepatoblastoma in tumorigenesis. SNHG9 role in Cisplatin drug resistance in hepatoblastoma was also determined. Results: SNHG9 was significantly upregulated in hepatoblastoma tissue and cell lines. SNHG9 overexpression on HUH6 & HepG2 resulted in a significant increase in cell proliferation and clonogenic activity while SNHG9 knock down resulted in a sustained inhibition of cell proliferation and clonogenic activity. Dual luciferase activity, RNA immunoprecipitation and biotin pull down confirmed the direct interaction of miR-23a-5p with SNHG9. The xenograft tumorgenicity test showed SNHG9 downregulation significantly inhibited the tumor growth in BALB/c mice. ROC and Kaplan-Meier analysis showed potential prognostic and diagnostic importance of SNHG9 in hepatoblastoma. Conclusion: We concluded that SNHG9/miR-23a-5p/Wnt3a axis promotes the progression hepatoblastoma tumor.

Transfemoral and perventricular device occlusions and surgical repair for doubly committed subarterial ventricular septal defects.

BACKGROUND: Transfemoral and perventricular device occlusions are performed for doubly committed subarterial ventricular septal defect (dcVSD) to reduce the invasiveness of the conventional surgical repair through a median sternotomy. Few comparative studies have been conducted of these three procedures. METHODS: Inpatients with isolated dcVSD who had undergone transfemoral and perventricular device occlusions or conventional surgical repair from January 2009 to June 2013 were reviewed to compare the three procedures. RESULTS: Procedure success was achieved in 33 transfemoral (66%), in 74 perventricular (94.9%), and in 205 repair (97.6%) procedures. The transfemoral group had the lowest success rate (p < 0.001), whereas the perventricular and repair groups had similar success rates (p = 0.418). Transfemoral patients were the oldest (p < 0.001) and had a dcVSD size similar to that of patients in other two groups (p = 0.518). The repair group required the longest hospitalization and longest stays in the intensive care unit (p < 0.001), required the longest operating room and mechanical ventilation times (p < 0.001), and had the highest rate of transfusion (p < 0.001). Major adverse events occurred in one transfemoral (3%), in two perventricular (2.7%), and in three repair (1.4%) procedures. Minor adverse events were absent in transfemoral (0%) and occurred in three perventricular (4%) and 14 repair (6.7%) procedures. No significant difference was noted in the rates of adverse events the three groups (p = 0.569). No grade 3 valvular regurgitation or complete atrioventricular block was observed in the studied patients. CONCLUSIONS: Device occlusion may be an alternative to surgical repair in selected patients with dcVSD. Perventricular occlusion was the preferred approach because it showed a higher success rate than transfemoral occlusion.

[Genomic characteristics of coxsackievirus B5 A210/KM/09 strain isolated in Yunnan, China].

OBJECTIVE: To characterize the complete genome sequence of coxsackievirus B5 (CVB5)A210/KM/09 strain which was isolated from Yunnan, China, 2009. METHODS: Eight overlapping clones covering the whole viral genome (excluding the poly-A tail)were obtained by RT-PCR and sequenced, with their nucleotide and amino acid sequences compared with other known CVB5 strains. RESULTS: The genome of the CVB5 A210/KM/09 strain had 7 372 nucleotides in length, and containing a 742-nt non-translated region (NTR) at the 5' end and a 98-nt NTR at the 3' end. The entire open reading frame contained 6 555 nt, encoding a 2 185-aa polyprotein. In the coding region, there appeared no nucleotide deletion or insertion, but some changes of amino acid seemed unique. Based on the complete genome sequence alignments, CVB5 isolate A210/KM/09 strain showed the highest nucleotide (92.5%) and amino acid (97.3%) identities to the CVB5/CC10/10. It also shared nucleotide (80.1%-92.5%) and amino acid (95.0%-97.3%) homology with other CVB5 strains: 17Y, 19CSF, 20CSF, 1954/85/US, 2000/CSF/KOR, 03001N, CoxB5/Henan/2010, VB5/SD/09 and Faulkner. Blast between genome fragments, A210/KM/09 showed similarity on nucleotide (80.1%-92.5%) and amino acid (95.0%-97.3%) identities with other CVB5 strains. The phylogenetic tree, constructed on the complete VP1 regions, indicated that CVB5 could be divided into genotype A, B, C and D. while Genotype C and D could be further divided into C1-C4 and D1-D4 subgenotypes. CONCLUSION: A210/KM/09 and other CVB5 predominant strains isolated in China belonged to CVB5 subgenotype C4.

[Therapeutic efficacy of three-dimensional conformal radiation therapy for patients with locally advanced non-small cell lung cancer].

OBJECTIVE: To compare the treatment results of three-dimensional conformal radiotherapy (3D-CRT) and conventional radiotherapy (2D) for patients with locally advanced non-small-cell lung cancer (NSCLC). METHODS: Five hundred and twenty seven patients with stage III NSCLC treated between Jan 2000 and Dec 2006 were included in this study. Among them, 253 cases were treated with 3D-CRT, and 274 with conventional radiotherapy. In the 3D group, 159 (62.8%) patients received chemoradiotherapy, 77 with total radiotherapy dose of > 60 Gy, 49 with 50 - 60 Gy. In the 2D group, 127 (46.4%) patients received chemoradiotherapy, 48 with total radiotherapy dose of > 60 Gy, 75 with 50 - 60 Gy. RESULTS: The 1-, 3-, 5-year overall survival rates (OS) and median survival time for patients treated with 3D-CRT were 73.3%, 26.1%, 14.4% and 20.1 months, respectively, and that of patients treated with 2D radiotherapy were 61.0%, 13.8%, 8.0% and 15.6 months, respectively (P = 0.002). The 1-, 3-, 5-year cause-specific survival rates (CSS) were 79.0%, 33.3%, and 20.8% for the 3D group and 65.1%, 16.7%, 11.2%, respectively, for the 2D group (P = 0.000). The 1-, 3-, and 5-year locoregional control rates were 71.6%, 34.3% and 31.0% for patients treated with 3D radiotherapy and 57.3%, 22.1% and 19.2%, respectively, for patients treated with 2D treatment (P = 0.002). The results of multivariate analysis showed that 3D-CRT, KPS, clinical tumor response and pretreatment hemoglobin level were independently associated with increased OS and CSS. No statistically significant differences were found between the radiation complications in the two groups. CONCLUSIONS: The results of our study demonstrate that 3D-conformal radiotherapy improves the survival rate in patients with stage III NSCLC compared with that of 2D radiation therapy.

Host cell protein C9orf69 promotes viral proliferation via interaction with HSV-1 UL25 protein.

In light of the scarcity of reports on the interaction between HSV-1 nucleocapsid protein UL25 and its host cell proteins, the purpose of this study is to use yeast two-hybrid screening to search for cellular proteins that can interact with the UL25 protein. C9orf69, a protein of unknown function was identified. The interaction between the two proteins under physiological conditions was also confirmed by biological experiments including co-localization by fluorescence and immunoprecipitation. A preliminary study of the function of C9orf69 showed that it promotes viral proliferation. Further studies showed that C9orf69 did not influence viral multiplication efficiency by transcriptional regulation of viral genes, but indirectly promoted proliferation via interaction with UL25.

Coagulation factor XIII-A Val34Leu polymorphism and the risk of coronary artery disease and myocardial infarction in a Chinese Han population.

There are controversial data regarding the impact of coagulation factor XIII A subunit (FXIII-A) Val34Leu polymorphism in the pathogeneric of coronary artery disease (CAD) and myocardial infarction (MI). Assuming this genetic factor is associated with the thrombotic process, we explored the role of FXIII-A Val34Leu in CAD and MI in a Chinese Han population. We recruited 195 consecutive patients with CAD confirmed by coronary angiography as well as a group of 203 controls. Factor XIII A Val34Leu polymorphism was determined through polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) analysis. We did not find the Leu/Leu genotype in patients with CAD or controls. No significant difference in Val34Leu gene polymorphism distribution was found between patients with CAD and the controls (P = .923). Subgroup analysis according to the history of MI showed the heterozygote Val/Leu genotype was associated with a significantly decreased risk of MI (P = .005; adjusted odds ratio [OR] = 1.75; 95% confidence interval [CI] = 1.28-2.25). Furthermore, our study displayed that the frequency of the Leu34 allele in a Chinese Han population was lower than that in Caucasian populations (2.5 vs 20.4%-28.3%). Our preliminary data indicate that the FXIII-A Leu34 allele may contribute to a protective effect against the development of MI. There is a low prevalence of the Leu34 allele in Han Chinese compared to Caucasians.

[Clinical analysis of 126 patients with primary small cell carcinoma of the esophagus].

OBJECTIVE: To investigate the prognostic factors and the principles of treatment of primary esophageal small cell carcinoma (SCEC) retrospectively. METHODS: The data of 126 patients with histologically confirmed SCEC treated in our department between May 1985 and June 2005 were retrospectively analyzed. 85 patients were in limited disease stage (LD) and 41 patients as extensive disease stage (ED) according to the Veterans Administration Lung Study Group staging system. Among the 84 patients treated with esophagectomy, 8 cases were in stage I, 16 in stage IIa, 10 in stage IIb, 40 in stage III, 4 in stage IVa and 6 in stage IVb, according to the TNM system (6(th) edition, AJCC). Cox's hazard regression model was used to identify the prognostic factors, and Chi-square test to detect the difference of frequencies among different groups. Kaplan-Meier and log-rank methods were used to estimate and compare the survival rates. RESULTS: The median follow-up duration of this series was 13 months. One hundred and eight patients died of the disease during the follow-up, 10 were still alive and 8 were lost to follow-up. The 1-, 3-, and 5-year overall survival rates (OS) were 52.2%, 15.9%, and 12.2%, respectively, with a median survival time (MST) of 12.5 months. The 1-, 2-, and 3-year OS were 62.1%, 30.8%, and 22.4% with a MST of 14.0 months for LD, and 29.3%, 13.6% and 2.7% with a MST of 7.0 months for ED, respectively. There was a statistically significant difference in OS between LD and ED (P = 0.0001). The MST of the patients treated with chemotherapy was 14.5 months, significantly longer than the 5.2 months of the patients without (P = 0.0001). Multivariate analysis showed that stage (HR 1.91, 95% CI 1.26 approximately 2.91, P = 0.002), length of the primary lesion (HR 1.75, 95% CI 1.17 approximately 2.63, P = 0.007), and chemotherapy (HR 0.42, 95% CI 0.28 approximately 0.65, P = 0.000) were independent prognostic factors. CONCLUSION: Esophageal small cell carcinoma is a systemic disease. The tumor stage (LD or ED), length of the primary lesion and chemotherapy are independent prognostic factors. Therefore, a systemic therapy based on chemotherapy should be recommended.

[Effect of different chemotherapy regimens for concurrent chemoradiotherapy on locally advanced non-small cell lung cancer].

OBJECTIVE: To retrospectively analyze the effects of different chemotherapy regimens for concurrent chemoradiation on locally advanced non-small cell lung cancer (NSCLC). METHODS: The data from 106 patients diagnosed as locally advanced NSCLC (IIIa: 29, IIIb: 77), who received various chemotherapy regimens for concurrent chemoradiotherapy, were retrospectively analyzed. Paclitaxel-based chemotherapy regimen was administered in 55 patients, topotecan regimen in 21 patients, PE (cisplatin and etopside) regimen in 26 patients, and other regimens in the remaining 4 patients. The effect of different chemotherapy regimens on overall survival and toxicity was analyzed. RESULTS: The median survival time was 18.6 months, and the overall 1- and 3-year survival rates were 72.2% and 27.5%, respectively. The median survival time of 102 patients treated with paclitaxel-containing, topotecan-containing or PE regimens was 16.3, 27.3 and 29.1 months, respectively. The overall survival times of topotecan and PE groups were superior to that of paclitaxol-based group, but not significantly different (P = 0.32). Both univariate and multivariate analysis showed that paclitaxol-based chemotherapy regimen was significantly associated with a poorer survival (P < 0.05). N stage was another significant prognostic factor determined by COX multivariate regression model. Compared with the other regimens (10.6%), paclitaxel-based regimen (27.3%) had more acute radiation pneumonitis (grade >or= 2, P = 0.03), but no significant differences were observed in blood toxicity and esophagitis. CONCLUSION: There is a correlation between different chemotherapy regimens for concurrent chemoradiotherapy and the overall survival and acute radiation pneumonitis in patients with locally advanced NSCLC.

[Postoperative three-dimensional conformal radiotherapy for resected non-small cell lung cancer].

OBJECTIVE: To investigate the association between survival and postoperative three-dimensional conformal radiotherapy (3DCRT) in patients with resected non-small cell lung cancer (NSCLC). METHODS: Eighty-four patients were treated with surgery and postoperative 3DCRT for NSCLC. Sixty-five (77.4%) patients received lobectomy, and 19 (22.6%) received pneumonectomy. Fifty-four (64.3%) patients achieved R0 resection and 30 cases (35.8%) received R1/R2 resection. Fifty-two patients were of stage IIIA and 24 patients were of stage IIIB. Photon energy of 6 MV was used for all the patients. The median 3DCRT dose was 60 Gy (40 - 70 Gy) with a fraction size of 2 Gy. Thirty-seven patients received median 3 cycles of adjuvant chemotherapy. The median follow-up was 35.5 months for survivors. RESULTS: The overall 3-year survival rate was 58.6%, and the 4-year overall survival rate was 43.9%. Of the 43 patients who had treatment failure, only 8 (9.9%) patients showed intrathoracic recurrence, but 38 (46.9%) patients had distant metastasis. The univariate analysis for all patients showed that sex, age, weight loss, tumor size, pathology and stage were not correlated with prognosis. R1/R2 resection was associated with a significantly worse survival. Toxicities were acceptable, with 9 (11.1%) patients appeared higher than NCI CTC grade 2 radiation pneumonitis. CONCLUSION: In a population-based cohort, postoperative 3DCRT for NSCLC provides a good prognosis, and the radiation-related pneumonitis is acceptable.

[Three-dimensional conformal radiotherapy for locoregionally recurrent non-small cell lung cancer after initial radiotherapy].

OBJECTIVE: To evaluate the feasibility, therapeutic effects and normal tissue complications of three-dimensional conformal radiotherapy (3DCRT) for locoregionally recurrent non-small cell lung cancer after initial radiotherapy. METHODS: Between August 1999 and August 2003, 27 such patients were treated with 3DCRT after initial radiotherapy. This series consisted of 25 men and 2 women with a median age of 64 years. Radiotherapy was delivered at 2 Gy per fraction, 5 fractions per week, to a median dose of 50 Gy. Treatment results and normal tissue complications were assessed with WHO and RTOG/EORTC criteria. RESULTS: Based upon a median follow-up time of 20.6 months, 25 patients (92.6%) completed the planned 3DCRT treatment. Their clinical symptom relief rate was 79.1%, and the response rate was 59.3% with a complete remission rate of 14.8% (4/27), partial remission rate of 44.4% (12/27). The overall 1- and 2-year survival (OS) rates were 73.8% and 25.4% with a median survival time (MST) of 20 months. The 1- and 2-year local progression free survival (LPFS) rates were both 88.8%. Grade 2 and grade 3 acute radiation pneumonitis developed in 7.4% (2/27) and 11.1% (3/27). Grade 2 late radiation pneumonitis developed in 11.1% (3/27). CONCLUSION: 3DCRT is feasible and advisable for locoregionally recurrent non-small-cell lung cancer, giving a good immediate tumor response and acceptable normal tissue complications.