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简介：AbstractBackground:Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. It has been demonstrated that microRNA-145 (miR-145) is correlated with the progression of various cancers by regulating the expression of multiple target genes, especially a number of genes that regulate angiogenesis and proliferation. However, the underlying mechanisms of miR-145 in tumor angiogenesis of UM are still not well illustrated. Thus, we aimed to explore the potential target genes or pathways regulated by miR-145 in UM and the effect of miR-145 on invasion and angiogenesis.Methods:Totally, 24 choroid samples were collected in our study, including 12 UM samples and 12 normal uveal tissues. The expression of neuroblastoma RAS viral oncogene homolog (N-RAS), phosphorylated protein kinase B (p-AKT), and vascular endothelial growth factor (VEGF) in UM tissues and normal uveal tissues was analyzed using Western blotting analysis. Lentivirus expression system was used to construct MUM-2B and OCM-1 cell lines with stable overexpression of miR-145. Transwell and endothelial cell tube formation assay were used to measure the effects of miR-145 on the invasion and angiogenesis of UM in vitro. The downstream target genes of miR-145 were predicted by bioinformatics and confirmed using a luciferase assay. BALB/c nude mice models were established to investigate the mechanisms of miR-145 on tumor growth and angiogenesis in vivo. Group data comparisons were performed using analysis of Student’s t test. A two-tailed P < 0.05 was considered as statistically significant.Results:The results of Western blotting analysis indicated that the expressions of N-RAS (1.10 ± 0.35 vs. 0.41 ± 0.36, t = 3.997, P = 0.012), p-AKT (1.16 ± 0.22 vs. 0.57 ± 0.03, t = 7.05, P = 0.001), and VEGF (0.97 ± 0.32 vs. 0.45 ± 0.21, t = 3.314, P = 0.008) in UM tumor tissues were significantly higher than those in normal uveal tissue. Luciferase assay demonstrated N-RAS and VEGF as downstream targets of miR-145. Moreover, tube formation assay revealed that miR-145-transfected human microvascular endothelial cell line formed shorter tube length (36.10 ± 1.51 mm vs. 42.91 ± 0.94 mm, t = 6.603, P = 0.003) and less branch points (350.00 ± 19.97 vs. 406.67 ± 17.62, t = 3.685, P = 0.021) as compared with controls. In addition, the numbers of invaded MUM-2B and OCM-1 cells with miR-145 overexpression were significantly lower than the controls (35.7 ± 3.3 vs. 279.1 ± 4.9, t = 273.75, P < 0.001 and 69.5 ± 4.4 vs. 95.6 ± 4.7, t = 21.27, P < 0.001, respectively). In vivo, xenografts expressing miR-145 had smaller sizes (miR-145 vs. miR-scr, 717.41 ± 502.62 mm3vs. 1694.80 ± 904.33 mm3, t = 2.314, P = 0.045) and lower weights (miR-145 vs. miR-scr, 0.74 ± 0.46 g vs. 1.65 ± 0.85 g, t = 2.295, P = 0.045).Conclusion:Our results indicated that miR-145 is an important tumor suppressor and the inhibitory strategies against N-RAS/VEGF signaling pathway might be potential therapeutic applications for UM in the future.

简介：摘要ObjectiveTo establish the local data on the growth of ear in Hong Kong children and provide a reference for the timing of reconstruction in unilateral microtia.MethodsWe reviewed case notes of paediatric patients up to 18 years of age who had attended our Ear, Nose and Throat Out-patient Clinic from March to November 2017. We recorded the pinna length of these patients and that of their parents, compared the patients’ ear length against that of their parents, and investigated any discrepancy of pinna.ResultsWe recruited 226 local individuals (139 males and 87 females). The patients were divided into different age groups. The means of ear length of patients were compared with the mean length of pinna of their parents. Data of boys and girls are analyzed separately. Boys at 7－8 years old achieved 87.33% and 93.54% of their fathers’ and mothers’ ear length respectively. Girls at 7－8 years old achieved 83.00% and 90.80% of their fathers’ and mothers’ ear length respectively. Moreover, the average ratio of the length of left and right ear ratio is 97.3% in all groups of children.ConclusionsIn Hong Kong children, at the age of 7－8 the ear approaches the size of normal adult ear and is the feasible age with less asymmetry after reconstruction of the microtia.

简介：AbstractObjective:To explore the levels of fibroblast growth factor 23 (FGF23) during pregnancy and its relationship with intrauterine growth restriction (IUGR).Methods:Pregnant rats were classified into an ad libitum rat chow group (ad libitum rat chow, AD group, n = 25) and an undernutrition group (50% of their daily food requirement, UN group, n= 25). The levels of maternal serum FGF23, tissue homogenate FGF23, and bone gla protein in fetal rats, and placental FGF23 mRNA and protein expression were examined by enzyme-linked immunosorbent assay, real-time qPCR analysis respectively. Finally, the effect of recombinant FGF23 on the viability of MG-63 cells was determined by cell proliferation assay. Data were analyzed with independent two-tailed t test and one-way analysis of variance. Spearman rank-order correlation coefficients (continuous variables) was performed to determine the relationship of results.Results:The diet restriction induced IUGR in rat offsprings, and the UN group exhibited a significantly lower FGF23 level (P < 0.05, n= 5). The FGF23 level was increased and peaked in maternal serum on gestation day (GD) 15, but peaked in fetal and placenta on GD20. Moreover, the tissue homogenate levels of FGF23 and bone gla protein in fetal rats in both groups were positively correlated (r= 0.923, P < 0.05; r= 0.925, P < 0.05, respectively, n = 15), FGF23 was localized to both decidual and labyrinth zones, with remarkably higher expression on GD20, P < 0.05, n= 5. In vitro, recombinant human FGF23 enhanced MG-63 cell viability, P < 0.05, n= 5.Conclusion:Prenatal undernutrition could decrease the FGF23 expression in fetal rats caused by the mother through the placenta, and induced the IUGR and hindered the ossification. And the FGF23 levels are peaked on GD15 mother but peaked on GD20 placenta and fetuses, these might be associated with the over compensation of maternal placenta on GD20.

简介：AbstractBackground:In consideration of the difficulty in diagnosing high heterogeneous glioma, valuable prognostic markers are urgent to be investigated. This study aimed to verify that connective tissue growth factor (CTGF) is associated with the clinical prognosis of glioma, also to analyze the effect of CTGF on the biological function.Methods:In this study, glioma and non-tumor tissue samples were obtained in 2012 to 2014 from the Department of Neurosurgery of Nanfang Hospital of Southern Medical University, Guangzhou, China. Based on messenger RNA (mRNA) data from the Cancer Genome Atlas (TCGA) and CCGA dataset, combined with related clinical information, we detected the expression of CTGF mRNA in glioma and assessed its effect on the prognosis of glioma patients. High expression of CTGF mRNA and protein in glioma were verified by reverse transcription-polymerase chain reaction, immunohistochemistry, and Western blotting. The role of CTGF in the proliferation, migration, and invasion of gliomas were respectively identified by methylthiazoletetrazolium assay, Transwell and Boyden assay in vitro. The effect on glioma cell circle was assessed by flow cytometry. For higher expression of CTGF in glioblastoma (GBM), the biological function of CTGF in GBM was investigated by gene ontology (GO) analysis.Results:In depth analysis of TCGA data revealed that CTGF mRNA was highly expressed in glioma (GBM, n= 163; lowly proliferative glioma [LGG], n = 518; non-tumor brain tissue, n = 207; LGG, t = 2.410, GBM, t = 2.364, P < 0.05). CTGF mRNA and protein expression in glioma (86%) was significantly higher than that in non-tumor tissues (18%) verified by collected samples. Glioma patients with higher expression of CTGF showed an obviously poorer overall survival (35.4 and 27.0 months compared to 63.3 and 55.1 months in TCGA and Chinese Glioma Genome Atlas (CGGA) databases separately, CGGA: χ2 = 7.596, P = 0.0059; TCGA: χ2 = 10.46, P = 0.0012). Inhibiting CTGF expression could significantly suppress the proliferation, migration, and invasion of gliomas. CTGF higher expression had been observed in GBM, and GO analysis demonstrated that the function of CTGF in GBM was mainly associated with metabolism and energy pathways (P < 0.001).Conclusions:CTGF is highly expressed in glioma, especially GBM, as an unfavorable and independent prognostic marker for glioma patients and facilitates the progress of glioma.

简介：AbstractObjective:To assess the clinical features of fetal growth restriction (FGR) in women with hypertensive disorders of pregnancy in China.Methods:This is a retrospective cohort study. The clinical data of 4 451 women with hypertensive disorders of pregnancy were retrospectively collected from 11 tertiary hospitals across ten provinces in China during January 2015 to December 2015. The mean maternal age was (31.0±5.4) years old. Participants were divided into FGR group (n= 670) and non-FGR group (n= 3 781). The incidence and clinical features of FGR, and its correlation with gestational age, previous FGR history, 24-hour urinary protein excretion, and hemolysis, elevated liver enzyme and low platelet count (HELLP) syndrome were analyzed. Student’s t-test and Chi-square test were used when comparing clinical features between FGR and non-FGR groups.Results:The overall incidence of FGR was 15.1% (670/4 451). The FGR incidence was 22.4% (433/1 937) in women with severe preeclampsia and 18.6% (68/365) in women with chronic hypertension with superimposed preeclampsia, respectively. FGR was more prevalent in women who had preterm births than those who had term births (22.8% (432/1 898) vs. 9.3% (238/2 553), P < 0.001). It was also more prevalent in women with early-onset preeclampsia than those with late-onset preeclampsia (18.4% (189/1 025) vs. 14.0% (481/3 426), P= 0.001). Women with a previous FGR history had a significantly higher FGR incidence than those without an FGR history (66.7% (4/6) vs. 15.7% (250/1 596), P= 0.007). The presence of abnormal results of the umbilical artery Doppler (13% (87/670) vs. 2.4% (89/3 781), P < 0.001) and the middle cerebral artery Doppler (3.3% (22/670) vs. 0.4% (15/3 781), P < 0.001) was higher in the FGR group compared with the non-FGR group, while the presence of increased uterine artery resistance was not statistically different (1.5% (10/670) vs. 0.8% (29/3 781), P= 0.072). The FGR group delivered earlier than the non-FGR group ((35.3±3.0) weeks vs. (36.4±4.3) weeks, P < 0.001) with lower birth weight (1 731.0±574.5) g vs. (2 753.9±902.1) g, P < 0.001, higher fetal or neonatal death (9.4% (63/670) vs. 4.2% (157/3 781), P < 0.001), and higher cesarean section rate (82.5% (553/670) vs. 70.2% (2 656/3 781), P < 0.001). In the FGR group, more neonates had 5-minute Apgar score ≤7 (7.9% (53/670) vs. 3.9% (149/3 780), P < 0.001), with higher neonatal intensive care unit admission rate (48.1 % (322/670) vs. 23.3% (881/3 781), P < 0.001). More cases of HELLP syndrome occurred in the FGR group (6.9% (46/670) vs. 3.2% (122/3 781), P < 0.001). Women with FGR had heavier 24-hour urinary protein excretion than those without FGR ((3.9±3.7) g vs. (3.1±4.2) g, P= 0.005).Conclusion:In pregnancies with hypertensive disorders, increased risks of FGR are associated with preterm birth, birth before 34 weeks, and a previous FGR history. FGR is related to higher occurrence of abnormal uterine artery Doppler and umbilical artery Doppler. When hypertensive disorders is complicated by FGR, there appears to be higher maternal morbidity including higher rate of HELLP syndrome, cesarean section, and heavier proteinuria, as well as worse neonatal outcomes.

简介：摘要：农村电商的规模逐年增长，不过因为交通和信息的缺陷成本依然较高，尤其影响农村电商上行成本。本文研究了一种基于 FP-Growth关联规则的农村电商推荐算法，算法以皮尔逊相关系数为基础对商品进行 K-means聚类，挖掘了潜在的连续购买关系，并据此推荐处于同区域内的若干相关商品。经离线评估，算法改进了订单撮合方法，提升上行订单的时间和空间集中度，降低了农村电商上行成本。

简介：摘要：由于协同过滤算法的推荐准确度较高，越来越多的智能推荐应用开始使用协同过滤算法来对用户进行推荐。而受限于评分矩阵的缺失，在论文推荐的领域中，多为基于内容的论文推荐，较少看到协同过滤算法的应用。本文利用 FP-growth算法挖掘论文关键词的频繁项集，根据相关参数设置了虚拟评分矩阵，实现了使用协同过滤算法对论文的智能推荐。

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简介：AbstractNearly 70% of breast cancer (BC) is hormone-receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, and endocrine therapy is the mainstay of treatment for this subtype. However, intrinsic or acquired endocrine resistance can occur during the endocrine treatment. Based on insights of endocrine resistance mechanisms, a number of targeted therapies have been and continue to be developed. With regard to HR-positive, HER2-negative advanced BC, aromatase inhibitor (AI) is superior to tamoxifen, and fulvestrant is a better option for patients previously exposed to endocrine therapy. Targeted drugs, such as cyclindependent kinases (CDK) 4/6 inhibitors, mammalian target of rapamycin (mTOR) inhibitors, phosphoinositide-3-kinase (PI3K) inhibitors, and histone deacetylase (HDAC) inhibitors, play a significant role in the present and show a promising future. With the application of CDK4/6 inhibitors becoming common, mechanisms of acquired resistance to them should also be taken into consideration.

简介：AbstractBackground:Proliferative diabetic retinopathy (PDR) is a progressive stage of diabetic retinopathy featured by the formation of neovascular and proliferative membrane. Vascular endothelial growth factor (VEGF) acts as a pivot factor in the development of neovascularization. This study was to investigate the changes of intravitreal VEGF concentrations of severe PDR after intravitreal injection of conbercept (IVC) and its potential advantages to the following vitrectomy.Methods:This was a prospective, interventional, randomized controlled study. Sixty eyes (60 patients) with severe PDR and 20 eyes from 20 patients with rhegmatogenous retinal detachment complicated with proliferative vitreoretinopathy were enrolled in this study. PDR eyes were randomly assigned to three groups by sortation randomization method with 20 eyes in each based on the interval of preoperative IVC (group A: 7 days, group B: 14 days, group C: non-IVC). Another 20 eyes without diabetes were enrolled as the non-diabetic control group (group D), receiving PPV directly. Vitreous specimens of all 80 patients were collected and evaluated afterwards. The intravitreal VEGF concentration of the four groups, and the total surgical time and the intraoperative bleeding rate of the PDR groups were recorded.Results:The mean intravitreal VEGF concentrations of groups A-D were 66.6 ± 43.3, 93.1 ± 52.3, 161.4 ± 106.1 and 1.8 ± 1.2 pg/mL, respectively. It increased significantly in PDR patients (groups A, B and C) (P = 0.002, <0.001, and <0.001, respectively). PDR patients with preoperative IVC (groups A and B) presented significantly lower VEGF concentrations (P < 0.001 and 0.001), intraoperative bleeding rates (P= 0.004) and total surgical time (P < 0.001, P= 0.003) compared with group C. No statistical differences were presented between groups A and B on the three parameters.Conclusion:Seven days and 14 days of preoperative IVC are equally efficient and safe for the vitrectomy of severe PDR patients through decreasing vitreous VEGF concentrations, intraoperative bleeding rate and total surgical times.

简介：AbstractBackground:Both bone marrow mesenchymal stem cell (BM-MSC) and transforming growth factor-β1 (TGF-β1) have a strong anti-inflammatory capacity in stroke. But their relationship has not been well addressed. In this study, we investigated how intravenous BM-MSC transplantation in rats effected the expression of TGF-β1 48 h post cerebral ischemia, and we analyzed the main cells that produce TGF-β1.Methods:We used a distal middle cerebral artery occlusion (dMCAO) model in twenty Sprague-Dawley (SD) rats. The rats were randomly divided into two groups: the ischemic control group and the postischemic BM-MSC transplantation group. One hour after the dMCAO model was established, the rats were injected in the tail vein with either 1 ml saline or 1 × 106 BM-MSCs suspended in 1 ml saline. ELISAs were used to detect TGF-β1 content in the brain infarct core area, striatum and the plasma at 48 h after cerebral infarction. Immunofluorescent staining of brain tissue sections for TGF-β1, Iba-1, CD68 and NeuN was performed to determine the number and the proportion of double stained cells and to detect possible TGF-β1 producing cells in the brain tissue.Results:Forty-eight hours after ischemia, the TGF-β1 content in the infarcted area of the BM-MSC transplantation group (23.94 ± 4.48 pg/ml) was significantly lower than it was in the ischemic control group (34.18 ± 4.32 pg/ml) (F = 13.534, P = 0.006). The TGF-β1 content in the rat plasma in the BM-MSC transplantation group (75.91 ± 12.53 pg/ml) was significantly lower than it was in the ischemic control group (131.18 ± 16.07 pg/ml) (F = 36.779, P = 0.0002), suggesting that after transplantation of BM-MSCs, TGF-β1 levels in the plasma decreased, but there was no significant change in the striatum area. Immunofluorescence staining showed that the total number of nucleated cells (1037.67 ± 222.16 cells/mm2) in the infarcted area after transplantation was significantly higher than that in the ischemic control group (391.67 ± 69.50 cells/mm2) (F = 92.421, P < 0.01); the number of TGF-β1+ cells after transplantation (35.00 ± 13.66 cells/mm2) was significantly reduced in comparison to that in the ischemic control group (72.33 ± 32.08 cells/mm2) (F = 37.680, P < 0.01). The number of TGF-β1+/Iba-1+ microglia cells in the transplantation group (3.67 ± 3.17 cells/mm2) was significantly reduced in comparison to that of the ischemic control group (13.67 ± 5.52 cells/mm2) (F = 29.641, P < 0.01). The proportion of TGF-β1+/Iba-1+ microglia cells out of all Iba-1+ microglia cells after transplantation (4.38 ± 3.18%) was significantly decreased compared with that in the ischemic control group (12.81 ± 4.86%) (F = 28.125, P < 0.01).Conclusions:Iba-1+ microglia is one of the main cell types that express TGF-β1. Intravenous transplantation of BM-MSCs does not cooperate with TGF-β1+ cells in immune-regulation, but reduces the TGF-β1 content in the infarcted area and in the plasma at 48 h after cerebral infarction.

简介：AbstractBackground:The transforming growth factor β1 (TGF-β1)-induced epithelial-mesenchymal transition (EMT) has been proven associated with the pathogenesis of asthmatic airway remodeling, in which the Wnt/β-catenin pathway plays an important role, notably with regard to TGF-β1. Recent studies have shown that 1α, 25-dihydroxyvitamin D3(1α, 25(OH)2D3) inhibits TGF-β1-induced EMT, although the underlying mechanism have not yet been fully elucidated.Methods:Alveolar epithelial cells were exposed to 1α, 25(OH)2D3, ICG-001, or a combination of both, followed by stimulation with TGF-β1. The protein expression of E-cadherin, α-smooth muscle actin, fibronectin, and β-catenin was analyzed by western blotting and immunofluorescence analysis. The mRNA transcript of Snail was analyzed using RT-qPCR, and matrix metalloproteinase 9 (MMP-9) activity was analyzed by gelatin zymogram. The activity of the Wnt/β-catenin signaling pathway was analyzed using the Top/Fop flash reporters.Results:Both 1α, 25(OH)2D3 and ICG-001 blocked TGF-β1-induced EMT in alveolar epithelial cells. In addition, the Top/Fop Flash reporters showed that 1α, 25(OH)2D3 suppressed the activity of the Wnt/β-catenin pathway and reduced the expression of target genes, including MMP-9 and Snail, in synergy with ICG-001.Conclusion:1α, 25(OH)2D3 synergizes with ICG-001 and inhibits TGF-β1-induced EMT in alveolar epithelial cells by negatively regulating the Wnt/β-catenin signaling pathway.

简介：AbstractPurpose:Severe damage to the femoral head in patients with osteonecrosis has a high impact on morbidity. Despite early diagnosis, the treatment outcome is still unsatisfactory. This study aimed to explore the expression of vascular endothelial growth factor (VEGF) and cyclic guanine monophosphate (cGMP) serum level as the risk factors of femoral head osteonecrosis in alcohol-exposed Wistar rats.Methods:This was an experimental study using randomized post-test only control group design, with samples using 10-14 weeks Wistar male rats. Rats were then divided into 6 groups: 3 groups without intervention, and 3 groups with intervention using 40% alcohol given perorally. Each one group from intervention and control group was euthanized by the end of the week for 3 consecutive weeks. Proximal femurs were examined under microscope for osteonecrosis, immunohistochemically for VEGF, and blood serum for cGMP levels.Results:VEGF expression in the femoral head of alcohol-exposed Wistar rats was lower than those not exposed to alcohol (p < 0.005). Blood serum cGMP levels of alcohol-exposed Wistar rats were higher than those not exposed to alcohol (p < 0.005). The number of necrotic osteocytes in the femoral head of Wistar rats exposed to alcohol was greater than those not exposed to alcohol (p < 0.005). There are significant differences between VEGF, cGMP levels, and number of necrotic osteocytes in the control group and treatment at 1st, 2nd, and 3rd week (p < 0.005).Conclusions:Based on the result of this study, VEGF and cGMP may be considered as diagnostic biomarkers for alcohol-induced femoral head osteonecrosis.

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简介：AbstractBackground:The use of microRNAs in the therapy of kidney disease is hampered by the difficulties in their effective delivery. Microvesicles (MVs) are known as natural carriers of small RNAs. Our prior research has demonstrated that MVs isolated from mesenchymal stem cells (MSCs) are capable of attenuating kidney injuries induced by unilateral ureteral obstruction and 5/6 sub-total nephrectomy in mice. The present study aimed to evaluate the effects of miR-34a-5p (miR-34a)-modified MSC-MVs on transforming growth factor (TGF)-β1-induced fibrosis and apoptosis in vitro.Methods:Bone marrow MSCs were modified by lentiviruses over-expressing miR-34a, from which MVs were collected for the treatment of human Kidney-2 (HK-2) renal tubular cells exposed to TGF-β1 (6 ng/mL). The survival of HK-2 cells was determined using 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) and Annexin V-Light 650/propidium iodide (PI) assays. The expression levels of epithelial markers (tight junction protein 1 [TJP1] and E-cadherin) and mesenchymal markers (smooth muscle actin alpha (α-SMA) and fibronectin) in HK-2 cells were measured using Western blot analysis and an immunofluorescence assay. In addition, changes in Notch-1/Jagged-1 signaling were analyzed using Western blotting. Data were analyzed using a Student’s t test or one-way analysis of variance.Results:MiR-34a expression increased three-fold in MVs generated by miR-34a-modified MSCs compared with that expressed in control MVs (P < 0.01, t= 16.55). In HK-2 cells, TJP1 and E-cadherin levels decreased to 31% and 37% after treatment with TGF-β1, respectively, and were restored to 62% and 70% by miR-34a-enriched MSC-MVs, respectively. The expression of α-SMA and fibronectin increased by 3.9- and 5.0-fold following TGF-β1 treatment, and decreased to 2.0- and 1.7-fold after treatment of HK-2 cells with miR-34a-enriched MSC-MVs. The effects of miR-34a-enriched MSC-MVs on epithelial-mesenchymal transition (EMT) markers were stronger than control MSC-MVs. The effects of miR-34a-enriched MSC-MVs on these EMT markers were stronger than control MSC-MVs. Notch-1 receptor and Jagged-1 ligand, two major molecules of Notch signaling pathway, are predicted targets of miR-34a. It was further observed that elevation of Notch-1 and Jagged-1 induced by TGF-β1 was inhibited by miR-34a-enriched MSC-MVs. In addition, TGF-β1 exposure also induced apoptosis in HK-2 cells. Although miR-34a-mofidied MSC-MVs were able to inhibit TGF-β1-triggered apoptosis in HK-2 cells, the effects were less significant than control MSC-MVs (control:TGF-β1 :miR-nc-MV:miR-34a-MV = 1.3:0.6:1.1:0.9 for MTT assay, 1.8%:23.3%:9.4%:17.4% for apoptosis assay). This phenomenon may be the result of the pro-apoptotic effects of miR-34a.Conclusions:The present study demonstrated that miR-34a-over-expressing MSC-MVs inhibit EMT induced by pro-fibrotic TGF-β1 in renal tubular epithelial cells, possibly through inhibition of the Jagged-1/Notch-1 pathway. Genetic modification of MSC-MVs with an anti-fibrotic molecule may represent a novel strategy for the treatment of renal injuries.