LncRNA-599554 sponges miR-15a-5p to contribute inductive ability of dermal papilla cells through positive regulation of the expression of Wnt3a in cashmere goat

BACKGROUND: Long non-coding RNAs (lncRNAs), as post-transcriptional regulators, were thought to function in the inductive property of dermal papilla cells (DPCs) in cashmere goat. Previously, lncRNA-599554 was identified in secondary hair follicle (SHF) of cashmere goat, but its functional significance is unknown. RESULTS: In the present investigation, we verified that lncRNA-599554 had significantly higher expression at the anagen dermal papilla of cashmere goat SHF than that at telogen. Based on overexpression and knockdown techniques, we found that lncRNA-599554 contributes the inductive property of DPCs of cashmere goat, which was assessed by detecting the changes in the expression of several typical indictor genes in DPCs including ET-1, SCF, Versican, ALP, Lef1 and Ptc-1. Based on RNA pull-down assay, we verified that lncRNA-599554 directly interacted with chi-miR-15a-5p. Also, we showed that lncRNA-599554 positively regulated the Wnt3a expression in DPCs but which did not appear to involve its modulating of promoter methylation. Based on the use of Dual-luciferase reporter assays, our data indicated that lncRNA-599554 regulated the Wnt3a expression through chi-miR-15a-5p-mediated post-transcriptional level. CONCLUSIONS: We showed that lncRNA-599554 contributes the inductive property of DPCs in cashmere goat which might be achieved through sponging chi-miR-15b-5p to promote the Wnt3a expression. The results from the present investigation provided a novel insight into the functional mechanism of lncRNA-599554 in the SHF regeneration of cashmere goat along with the formation and growth of cashmere fiber.

Trends and Predictors of Clostridium difficile Infection among Children: A Canadian Population-Based Study.

OBJECTIVE: To assess time trends in Clostridium difficile infection (CDI) rates, and predictors of CDIs, including recurrent CDIs, in children. STUDY DESIGN: Data were extracted from Manitoba Health Provider Claims, and other population registry datasets from 2005 to 2015. CDI was identified from the Manitoba Health Public Health Branch Epidemiology and Surveillance population-based laboratory-confirmed CDI dataset. Children aged 2-17 years with CDI were matched by age, sex, area of residence, and duration of residence in Manitoba with children without CDI. The rates and time trends of CDIs using previously recommended definitions were determined. Predictors of CDI subtypes were determined using multivariable logistic regression models. Cox regression analysis was used to assess for the potential predictors of recurrent CDI. RESULTS: Children with and without CDI were followed for 828 and 2753 persons-years, respectively. The overall CDI rate during the study period was 7.8 per 100 000 person-years. There was no significant change in CDI rates over the observation period. Comorbid conditions, more prevalent among children with CDI than matched controls, included Hirschsprung disease (P < .001) and inflammatory bowel disease (P < .0001). Recurrent CDIs (>2 occurrences) were responsible for 10% of CDI episodes (range, 2-6 infections). Predictors of recurrence included malignancy (hazard ratio, 3.0, 95% CI, 1.1-8.8), diabetes (hazard ratio, 4.8; 95% CI, 1.1-21.4), and neurodegenerative diseases (hazard ratio, 8.4; 95% CI, 1.9-37.5). CONCLUSIONS: The incidence of CDI is stable among children in Manitoba. Children with Hirschsprung disease and inflammatory bowel disease are more susceptible to CDI, and those with malignancy, diabetes. and neurodegenerative disorders are more likely to develop recurrent CDI.

CXCL12 gene silencing down-regulates metastatic potential via blockage of MAPK/PI3K/AP-1 signaling pathway in colon cancer.

BACKGROUND: To investigate the effect of CXCL12 gene silencing on proliferation,invasion, angiogenesis and the relationship of MAPK/PI3K/AP-1 signaling pathway in colon cancer cells. METHODS: RT-PCR and Western-blot were used to detect the expression of CXCL12 mRNA and protein in four colon cancer cell lines. Human colon cancer cells were transfected with CXCL12 siRNA carrying by Lipofectamine 2000. The expression of CXCL12 protein was confirmed by immunoblotting. WST-1, invasion and angiogenesis assay were used to examine the effect on proliferation, invasion and angiogenesis in colon cancer cells after CXCL12 siRNA silence, respectively. The phosphorylation of MAPK/PI3K/AP-1 protein levels was detected by Western blotting in CXCL12 siRNA suppression DLD-1 cell. RESULTS: CXCL12 mRNA and proteins were only expressed in DLD-1 colon cancer cell lines. CXCL12 siRNA were transfected into DLD-1 cells, the expression CXCL12 proteins was significantly inhibited (P < 0.01), and the proliferation, invasion and angiogenesis of DLD-1 cells were inhibited significantly (P < 0.01). CXCL12 gene silencing resulted in blockage of MAPK, PI3K and AP-1 phosphorylation by CXCL12-induced in DLD-1 colon cancer cell. CONCLUSION: The silencing CXCL12 gene significantly inhibits the proliferation, invasion and angiogenesis ability of some types colon carcinoma cells through down-regulation of MAPK/PI3K/AP-1 signaling pathway.

Bevacizumab and gefitinib enhanced whole-brain radiation therapy for brain metastases due to non-small-cell lung cancer

Non-small-cell lung cancer (NSCLC) patients who experience brain metastases are usually associated with poor prognostic outcomes. This retrospective study proposed to assess whether bevacizumab or gefitinib can be used to improve the effectiveness of whole brain radiotherapy (WBRT) in managing patients with brain metastases. A total of 218 NSCLC patients with multiple brain metastases were retrospectively included in this study and were randomly allocated to bevacizumab-gefitinib-WBRT group (n=76), gefitinib-WBRT group (n=77) and WBRT group (n=75). Then, tumor responses were evaluated every 2 months based on Response Evaluation Criteria in Solid Tumors version 1.0. Karnofsky performance status and neurologic examination were documented every 6 months after the treatment. Compared to the standard WBRT, bevacizumab and gefitinib could significantly enhance response rate (RR) and disease control rate (DCR) of WBRT (P<0.001). At the same time, RR and DCR of patients who received bevacizumab-gefitinib-WBRT were higher than those who received gefitinib-WBRT. The overall survival (OS) rates and progression-free survival (PFS) rates also differed significantly among the bevacizumab-gefitinib-WBRT (48.6 and 29.8%), gefitinib-WBRT (36.7 and 29.6%) and WBRT (9.8 and 14.6%) groups (P<0.05). Although bevacizumab-gefitinib-WBRT was slightly more toxic than gefitinib-WBRT, the toxicity was tolerable. As suggested by prolonged PFS and OS status, bevacizumab substantially improved the overall efficacy of WBRT in the management of patients with NSCLC.

Improving Nutrition Utilization and Meat Quality of Broiler Chickens Through Solid-State Fermentation of Agricultural By-Products by Aureobasidium Pullulans

A 35 d trial was conducted to evaluate the effects of dietary supplementation of co-fermented agricultural by-products, soybean hulls and Pleurotus eryngii stalk residue (PESR), with Aureobasidium pullulans on nutrients digestibility and meat quality in broilers fed on conventional corn-soybean meal basal diet. A total of 400 1-d-old Ross broilers were allotted to 4 dietary treatments with 4 replicate pens (25 birds per pen). Birds were fed the corn-soybean meal diets supplemented with 0% (CON), 0.5% fermented soybean hulls (0.5% FSBH), 0.5% fermented soybean hulls partially replaced with PESR (0.5% FSHP) and 1.0% FSHP. The broilers fed on the diet that contained fermented products had higher total tract apparent digestibility for hemicellulose than those on CON (p 0.05). Meanwhile, the birds fed on 0.5% FSHP also showed the lightest duodenum and jejunum weight among all groups. Compared with the CON, the inclusion of 1.0% FSHP in the diet significantly decreased ammonia N concentration in cecum followed by 0.5% FSHP and subsequent 0.5% FSBH group. Dietary supplementation of fermented products significantly improved WHC and increased protein content in meat as compared with the CON. Moreover, the fat content in meat decreased in the broilers that received 0.5% FSBH and 1.0% FSHP. In conclusion, dietary supplementation of co-fermented agricultural by-products, PESR and soybean meal, could improve the digestibility of hemicellulose and decrease the cecal ammonia N concentration; moreover, the increased WHC and protein level as well as decreased fat content in meat suggested the promising utilization of these low-cost materials as broiler feed additives.

Improving Nutrition Utilization and Meat Quality of Broiler Chickens Through Solid-State Fermentation of Agricultural By-Products by Aureobasidium Pullulans

A 35 d trial was conducted to evaluate the effects of dietary supplementation of co-fermented agricultural by-products, soybean hulls and Pleurotus eryngii stalk residue (PESR), with Aureobasidium pullulans on nutrients digestibility and meat quality in broilers fed on conventional corn-soybean meal basal diet. A total of 400 1-d-old Ross broilers were allotted to 4 dietary treatments with 4 replicate pens (25 birds per pen). Birds were fed the corn-soybean meal diets supplemented with 0% (CON), 0.5% fermented soybean hulls (0.5% FSBH), 0.5% fermented soybean hulls partially replaced with PESR (0.5% FSHP) and 1.0% FSHP. The broilers fed on the diet that contained fermented products had higher total tract apparent digestibility for hemicellulose than those on CON (p 0.05). Meanwhile, the birds fed on 0.5% FSHP also showed the lightest duodenum and jejunum weight among all groups. Compared with the CON, the inclusion of 1.0% FSHP in the diet significantly decreased ammonia N concentration in cecum followed by 0.5% FSHP and subsequent 0.5% FSBH group. Dietary supplementation of fermented products significantly improved WHC and increased protein content in meat as compared with the CON. Moreover, the fat content in meat decreased in the broilers that received 0.5% FSBH and 1.0% FSHP. In conclusion, dietary supplementation of co-fermented agricultural by-products, PESR and soybean meal, could improve the digestibility of hemicellulose and decrease the cecal ammonia N concentration; moreover, the increased WHC and protein level as well as decreased fat content in meat suggested the promising utilization of these low-cost materials as broiler feed additives.(AU)

Bevacizumab and gefitinib enhanced whole-brain radiation therapy for brain metastases due to non-small-cell lung cancer.

Non-small-cell lung cancer (NSCLC) patients who experience brain metastases are usually associated with poor prognostic outcomes. This retrospective study proposed to assess whether bevacizumab or gefitinib can be used to improve the effectiveness of whole brain radiotherapy (WBRT) in managing patients with brain metastases. A total of 218 NSCLC patients with multiple brain metastases were retrospectively included in this study and were randomly allocated to bevacizumab-gefitinib-WBRT group (n=76), gefitinib-WBRT group (n=77) and WBRT group (n=75). Then, tumor responses were evaluated every 2 months based on Response Evaluation Criteria in Solid Tumors version 1.0. Karnofsky performance status and neurologic examination were documented every 6 months after the treatment. Compared to the standard WBRT, bevacizumab and gefitinib could significantly enhance response rate (RR) and disease control rate (DCR) of WBRT (P<0.001). At the same time, RR and DCR of patients who received bevacizumab-gefitinib-WBRT were higher than those who received gefitinib-WBRT. The overall survival (OS) rates and progression-free survival (PFS) rates also differed significantly among the bevacizumab-gefitinib-WBRT (48.6 and 29.8%), gefitinib-WBRT (36.7 and 29.6%) and WBRT (9.8 and 14.6%) groups (P<0.05). Although bevacizumab-gefitinib-WBRT was slightly more toxic than gefitinib-WBRT, the toxicity was tolerable. As suggested by prolonged PFS and OS status, bevacizumab substantially improved the overall efficacy of WBRT in the management of patients with NSCLC.

microRNA-142-3p inhibits apoptosis and inflammation induced by bleomycin through down-regulation of Cox-2 in MLE-12 cells.

microRNA (miR)-142-3p is implicated in malignancy and has been identified as a biomarker for aggressive and recurrent lung adenocarcinomas. This study aimed to evaluate the inhibitory effect of miR-142-3p on apoptosis and inflammation induced by bleomycin in MLE-12 cells. MLE-12 cells were first transfected either with miR-142-3p mimic or miR-142-3p inhibitor and then the cells were exposed to 50 µg/mL of bleomycin. Thereafter, cell viability, apoptosis and the expression of pro-inflammatory cytokines were assessed using CCK-8, flow cytometry, RT-PCR and western blot analyses. Cox-2, PI3K, AKT and mTOR expressions were detected by western blotting after bleomycin was administered together with NS-398 (an inhibitor of Cox-2). As a result, cell viability was significantly decreased, as well as apoptosis and the expression of IL-1 and TNF-α were remarkably increased after 50 and 100 µg/mL of bleomycin administration. miR-142-3p overexpression alleviated bleomycin-induced apoptosis and overproduction of these two pro-inflammatory cytokines, while miR-142-3p suppression exhibited completely opposite results. Up-regulation of Cox-2 and inactivation of PI3K/AKT/mTOR were found in bleomycin-pretreated cells, while these abnormal regulations were partially abolished by miR-142-3p overexpression and NS-398. In conclusion, this study demonstrated that miR-142-3p overexpression protected bleomycin-induced injury in lung epithelial MLE-12 cells, possibly via regulating Cox-2 expression and PI3K/AKT/mTOR signaling pathway. These findings provide evidence that miR-142-3p may be a therapeutic strategy for idiopathic pulmonary fibrosis (IPF) treatment.

microRNA-142-3p inhibits apoptosis and inflammation induced by bleomycin through down-regulation of Cox-2 in MLE-12 cells

microRNA (miR)-142-3p is implicated in malignancy and has been identified as a biomarker for aggressive and recurrent lung adenocarcinomas. This study aimed to evaluate the inhibitory effect of miR-142-3p on apoptosis and inflammation induced by bleomycin in MLE-12 cells. MLE-12 cells were first transfected either with miR-142-3p mimic or miR-142-3p inhibitor and then the cells were exposed to 50 μg/mL of bleomycin. Thereafter, cell viability, apoptosis and the expression of pro-inflammatory cytokines were assessed using CCK-8, flow cytometry, RT-PCR and western blot analyses. Cox-2, PI3K, AKT and mTOR expressions were detected by western blotting after bleomycin was administered together with NS-398 (an inhibitor of Cox-2). As a result, cell viability was significantly decreased, as well as apoptosis and the expression of IL-1 and TNF-α were remarkably increased after 50 and 100 μg/mL of bleomycin administration. miR-142-3p overexpression alleviated bleomycin-induced apoptosis and overproduction of these two pro-inflammatory cytokines, while miR-142-3p suppression exhibited completely opposite results. Up-regulation of Cox-2 and inactivation of PI3K/AKT/mTOR were found in bleomycin-pretreated cells, while these abnormal regulations were partially abolished by miR-142-3p overexpression and NS-398. In conclusion, this study demonstrated that miR-142-3p overexpression protected bleomycin-induced injury in lung epithelial MLE-12 cells, possibly via regulating Cox-2 expression and PI3K/AKT/mTOR signaling pathway. These findings provide evidence that miR-142-3p may be a therapeutic strategy for idiopathic pulmonary fibrosis (IPF) treatment.

Daidzein promotes osteoblast proliferation and differentiation in OCT1 cells through stimulating the activation of BMP-2/Smads pathway.

Daidzein, the most widely studied soy phytoestrogen, is not only a potential antiosteoporosis agent owing to its possible osteogenic activity, but also shows anticancer activity. However, the mechanisms through which daidzein affects osteoblast function have not been investigated thoroughly. Here, we show that daidzein stimulated cell proliferation and differentiation of osteoblasts, demonstrated by upregulation of XTT activity, enhancement of alkaline phosphatase (ALP) activity, and upregulation of osteoblast-specific marker genes, including Runt-related transcription factor 2 (Runx2) and Smad1, as well as upregulation of Runx2 and Smad1 protein expression. To determine the mechanisms underlying daidzein's effects on osteoblast differentiation, we first tested the role of daidzein in bone morphogenetic protein (BMP)-2 gene expression in OCT1 cells, and found that it significantly upregulated the expression of BMP-2. Furthermore, it significantly enhanced the phosphorylated protein level of Smad1/5/8 and the protein level of Osterix and increased the activity of 12xSBE-OC-Luc. Finally, we demonstrated that daidzein stimulated Col I, Runx2, and ALP expression, while these effects were significantly blocked by the BMP signaling inhibitor noggin. Together, our data indicate that daidzein acts through stimulating the activation of BMP-2/Smads pathway to promote osteoblast proliferation and differentiation.

ERCC1 C118T polymorphism has predictive value for platinum-based chemotherapy in patients with late-stage bladder cancer.

This study aims to investigate the association between ERCC1 codon C118T polymorphism and the response rate of platinum-based chemotherapy in patients with late-stage bladder cancer. A total of 41 eligible patients histologically confirmed as having stage IV muscle-invasive transitional cell carcinoma of the bladder were treated with platinum-based chemotherapy for 2-6 cycles. The genotypes of patients were determined by PCR amplification of genomic DNA followed by restriction enzyme digestion. Positive responses were categorized as complete and partial responses. In addition, progression-free survival (PFS) and overall survival (OS) were also determined as indicators of long-term outcomes. The genotype frequencies of C/C, C/T and T/T genotypes were 56.1, 34.1, and 9.8%, respectively. Positive response was observed in 14 patients (34.1%), while 27 patients (65.9%) were negative responders. As compared with individuals carrying the C/T and T/T genotypes, those with the C/C genotype had significantly improved short-term treatment responses (P = 0.018). The median PFS of patients carrying the C/C genotype was 6.3 months, while that of patients with C/T and T/T genotypes was 4.2 months (P = 0.023). Moreover, the median OS for patients carrying the C/C genotype was also longer as compared with that of patients carrying C/T and T/T (11.7 months vs 8.5 months, P = 0.040). Our results indicated that the ERCC1 codon 118 polymorphism may have predictive potential for chemotherapy treatment responses in late-stage bladder cancer patients.

Clinical significance of CD44 expression in children with hepatoblastoma.

The aim of this study was to investigate the expression of CD44 and its clinical significance in children suffering from hepatoblastoma (HB). CD44 expression was detected with immunohistochemistry staining in 30 samples from hepatoblastoma children and 10 normal liver tissue samples from normal children. The data obtained was statistically analyzed using the chi-square test, using the SPSS (v.11.0) software. The rate of CD44 expression was significantly higher (66.7%) in hepatoblastoma tissues than in normal liver tissues (χ(2) = 4.848, P < 0.05). The rate of CD44 expression was significantly higher in children with stage III or IV hepatoblastoma (83.3%) than that in children with stage I and II hepatoblastoma (χ(2) ＝ 5.625, P < 0.05) (41.7%). Therefore, CD44 expression might play an important role in the pathogenesis, progression, and prognosis of HB in children.

Repairing rabbit radial defects by combining bone marrow stroma stem cells with bone scaffold material comprising a core-cladding structure.

We prepared a bone scaffold material comprising a PLGA/ß-TCP core and a Type I collagen cladding, and recombined it with bone marrow stroma stem cells (BMSCs) to evaluate its potential for use in bone tissue engineering by in vivo and in vitro experiments. PLGA/ß-TCP without a cladding was used for comparison. The adherence rate of the BMSCs to the scaffold was determined by cell counting. Cell proliferation rate was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. The osteogenic capability was evaluated by alkaline phosphatase activity. The scaffold materials were recombined with the BMSCs and implanted into a large segmental rabbit radial defect model to evaluate defect repair. Osteogenesis was assessed in the scaffold materials by histological and double immunofluorescence labeling, etc. The adherence number, proliferation number, and alkaline phosphatase expression of the cells on the bone scaffold material with core-cladding structure were significantly higher than the corresponding values in the PLGA/ß-TCP composite scaffold material (P < 0.05). An in vivo test indicated that the bone scaffold material with core-cladding structure completely degraded at the bone defect site and bone formation was completed. The rabbit large sentimental radial defect was successfully repaired. The degradation and osteogenesis rates matched well. The bone scaffold with core-cladding structure exhibited better osteogenic activity and capacity to repair a large segmental bone defect compared to the PLGA/ß-TCP composite scaffold. The bone scaffold with core-cladding structure has excellent physical properties and biocompatibility. It is an ideal scaffold material for bone tissue engineering.

Association between ERCC1 and ERCC2 gene polymorphisms and chemotherapy response and overall survival in osteosarcoma.

We aimed to evaluate the influence of four SNPs in ERCC1 and ERCC2 on the response to cisplatin-based treatment and on clinical outcome in patients with osteosarcoma. We identified 186 patients with osteosarcoma diagnosed between April 2009 and April 2011 who were eligible for inclusion in our study. Genotyping of ERCC1 rs11615, rs3212986, and rs2298881; and ERCC2 rs1799793 and rs13181 was conducted by a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. By conditional logistic regression analysis, patients carrying the CC genotypes of ERCC1 rs11615 and rs2298881 were shown to be more likely to have good response to chemotherapy when compared with patients carrying wild-type genotypes; the ORs (95%CIs) were 2.56 (1.02-7.35) and 3.01 (1.07-9.71), respectively. By Cox regression analysis, individuals carrying the CC genotype of ERCC1 rs11615 were associated with longer overall survival time and decreased risk of death from osteosarcoma; the hazards ratio (95%CI) was 0.32 (0.07-0.98). In summary, our results suggested that the ERCC1 rs11615 and rs2298881 polymorphisms play important roles in the response to chemotherapy mediated by the DNA repair pathway and in the clinical outcome of osteosarcoma.

Genetic polymorphism at the KIR gene locus: determination of gene, genotype, and haplotype frequencies in the Xinjiang Han population.

The aim of this study was to explore the genetic polymorphism, genotype, and haplotype characteristics of the KIR locus in the Xinjiang Han population in order to establish a foundation for future analysis of the relationship between KIR genes and disease. KIR genes were detected by sequence-specific primer-polymerase chain reaction in 184 randomly selected, healthy individuals from the Han population in Xinjiang, China. Standard genotype and haplotype analyses were conducted using Hsu's standards classified for analysis. Sixteen KIR genes were detected: 3DL3, 2DL4, 3DL2, and 3DL2 (100%); 2DL1 and 2DP1 (99.46%); 2DL3 (98.91%); and so on. The 2DS2 gene frequency was the lowest at 21.74%. Twenty-one genotypes were detected: AJ (2, 2) was relatively common (42.39%), followed by AH (5, 2), AE (2, 8) and H (2, 4), with frequencies of 17.39, 11.96, and 8.15%, respectively. In addition, six novel genotypes were identified in 11 Han individuals as well as in other populations in China, which could not be classified for analysis. These results indicated that the Xinjiang Han population shares KIR gene, genotype, and haplotype frequency distributions with the Chinese Han population, but also has unique genotypes and haplotypes.

Adult male circumcision with a circular stapler versus conventional circumcision: A prospective randomized clinical trial

Male circumcision is the most frequently performed procedure by urologists. Safety and efficacy of the circumcision procedure requires continual improvement. In the present study, we investigated the safety and efficacy of a new male circumcision technique involving the use of a circular stapler. In total, 879 consecutive adult male patients were randomly divided into 2 groups: 441 underwent stapler circumcision, and 438 underwent conventional circumcision. The operative time, pain score, blood loss volume, healing time, treatment costs, and postoperative complications were compared between the two groups. The operative time and blood loss volume were significantly lower in the stapler group than in the conventional group (6.8 ± 3.1 vs 24.2 ± 3.2 min and 1.8 ± 1.8 vs 9.4 ± 1.5 mL, respectively; P<0.01 for both). The intraoperative and postoperative pain scores were significantly lower in the stapler group than in the conventional group (0.8 ± 0.5 vs 2.4 ± 0.8 and 4.0 ±0.9 vs 5.8 ± 1.0, respectively; P<0.01 for both). Additionally, the stapler group had significantly fewer complications than the conventional group (2.7% vs 7.8%, respectively; P<0.01). However, the treatment costs in the stapler group were much higher than those in the conventional group (US$356.60 ± 8.20 vs US$126.50 ± 7.00, respectively; P<0.01). Most patients (388/441, 88.0%) who underwent stapler circumcision required removal of residual staple nails. Overall, the present study has shown that stapler circumcision is a time-efficient and safe male circumcision technique, although it requires further improvement.

Transthoracic closure of atrial septal defect and ventricular septal defect without cardiopulmonary bypass.

The minimally invasive surgical transthoracic occlusion of an atrial septal defect (ASD) or a ventricular septal defect (VSD) is an increasingly widespread alternative treatment for congenital heart disease. The aim of this study is to summarize our clinical experience with minimally invasive surgical transthoracic occlusion of ASD and VSD without cardiopulmonary bypass (CPB). Between April 2011 and October 2012, 27 patients with ASD and 95 patients with VSD (78 men and 44 women) were considered for minimally invasive surgical transthoracic occlusion without CPB. A small infrasternal incision (2.0-4.0 cm) was made under general anesthesia, under transesophageal echocardiography (TEE) guidance; the ASD and VSD were closed by using an appropriate occluder; and TEE was performed simultaneously to demonstrate the position of the device, any residual shunting, or encroachment on the atrioventricular valve, coronary sinus, or aortic valve. Successful transthoracic occlusion was performed in all 122 patients without complications. No complications such as third-degree atrioventricular block and residual shunting occurred after the procedures. The ventilation time was 2.2 ± 1.2 h, and the average length of hospital stay was 4.7 ± 1.7 days. All patients received aspirin at 3 mg·kg(-1)·day(-1) (maximum 100 mg/day) 24 h after the procedure. Minimally invasive surgical transthoracic occlusion without CPB is a new treatment that has many advantages such as causing little trauma, promoting quick recovery, having less complications, and avoiding radiation damage. However, the appropriate selection of patients is still key to improving the success rate of the operation.

Adult male circumcision with a circular stapler versus conventional circumcision: A prospective randomized clinical trial.

Male circumcision is the most frequently performed procedure by urologists. Safety and efficacy of the circumcision procedure requires continual improvement. In the present study, we investigated the safety and efficacy of a new male circumcision technique involving the use of a circular stapler. In total, 879 consecutive adult male patients were randomly divided into 2 groups: 441 underwent stapler circumcision, and 438 underwent conventional circumcision. The operative time, pain score, blood loss volume, healing time, treatment costs, and postoperative complications were compared between the two groups. The operative time and blood loss volume were significantly lower in the stapler group than in the conventional group (6.8 ± 3.1 vs 24.2 ± 3.2 min and 1.8 ± 1.8 vs 9.4 ± 1.5 mL, respectively; P<0.01 for both). The intraoperative and postoperative pain scores were significantly lower in the stapler group than in the conventional group (0.8 ± 0.5 vs 2.4 ± 0.8 and 4.0 ±0.9 vs 5.8 ± 1.0, respectively; P<0.01 for both). Additionally, the stapler group had significantly fewer complications than the conventional group (2.7% vs 7.8%, respectively; P<0.01). However, the treatment costs in the stapler group were much higher than those in the conventional group (US$356.60 ± 8.20 vs US$126.50 ± 7.00, respectively; P<0.01). Most patients (388/441, 88.0%) who underwent stapler circumcision required removal of residual staple nails. Overall, the present study has shown that stapler circumcision is a time-efficient and safe male circumcision technique, although it requires further improvement.

Association between the CYP1A1 polymorphisms and hepatocellular carcinoma: a meta-analysis.

Numerous studies have evaluated the association between CYP1A1 gene polymorphisms and hepatocellular carcinoma (HCC) risk. However, the specific association is still controversial. The aim of our study was to clarify the effects of CYP1A1 gene polymorphisms (3801 T＞C and A2455G) on HCC risk by conducting a meta-analysis. We conducted searches of the literature published in PubMed and EMBASE databases up to April 2014. We estimated the pooled odds ratio with its 95% confidence interval to assess the association using a fixed or random-effects model. Publication bias was investigated by the Begg funnel plot. Meta-analysis was performed using the STATA package version 12.0. Meta-analysis results showed no significant association between the CYP1A1 3801 T＞C polymorphism and HCC risk. In a subgroup analysis by nationality, we found a significant association between 3801 T＞C polymorphism and HCC risk in Asians (TT vs TC: OR = 0.77, 95%CI = 0.60-0.99). As for A2455G, the meta-analysis indicated no significant association between the CYP1A1 A2455G polymorphism and HCC risk. In conclusion, the 3801 T＞C polymorphism in the CYP1A1 gene may be related to increased risk of HCC in Asians. Conclusive evidence on the effects of the variants in HCC should be addressed in further studies.

BMP-2 and titanium particles synergistically activate osteoclast formation

A previous study showed that BMP-2 (bone morphogenetic protein-2) and wear debris can separately support osteoclast formation induced by the receptor activator of NF-κB ligand (RANKL). However, the effect of BMP-2 on wear debris-induced osteoclast formation is unclear. In this study, we show that neither titanium particles nor BMP-2 can induce osteoclast formation in RAW 264.7 mouse leukemic monocyte macrophage cells but that BMP-2 synergizes with titanium particles to enhance osteoclast formation in the presence of RANKL, and that at a low concentration, BMP-2 has an optimal effect to stimulate the size and number of multinuclear osteoclasts, expression of osteoclast genes, and resorption area. Our data also clarify that the effects caused by the increase in BMP-2 on phosphorylated SMAD levels such as c-Fos expression increased throughout the early stages of osteoclastogenesis. BMP-2 and titanium particles stimulate the expression of p-JNK, p-P38, p-IkB, and P50 compared with the titanium group. These data suggested that BMP-2 may be a crucial factor in titanium particle-mediated osteoclast formation.