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Aim: This study aimed to investigate the effects of LINC00240/miR-155/Nrf2 axis on trophoblast function and macrophage polarization in the pathogenesis of preeclampsia. Methods: Bindings between LINC00240, miR-155 and Nrf2 were validated by dual luciferase reporter assay or RNA-immunoprecipitation method. Cell proliferation, migration, invasion, and pyroptosis were detected by CCK-8, clone formation, wound healing, Transwell system and flow cytometry, respectively. Macrophage polarization was tested by flow cytometry. LINC00240, miR-155 and Nrf2 levels, and oxidative stress and pyroptosis related-protein levels in in vitro and in vivo preeclampsia model were analyzed by qPCR, western blot or ELISA assays. Blood pressure, urine protein level, liver and kidney damages, and trophoblast marker in placenta tissues were further studied in vivo. Results: Placenta tissues from preeclampsia patients and animals showed decreased LINC00240 and Nrf2 expressions and increased miR-155 expression. LINC00240 directly bound and inhibited expression of miR-155, which then inhibited oxidative stress-induced pyroptosis, promoting proliferation, migration and invasion abilities of trophoblasts, and M2 macrophage polarization. Inhibition of miR-155 led to the increased Nrf2 expression and similar changes as LINC00240 in trophoblast function and macrophages polarization. Overexpression of LINC00240 in an in vivo preeclampsia model decreased blood pressure, urine protein, liver and kidney damages, increased fetal weight and length, and also induced trophoblast function and M2 macrophage polarization. Conclusion: LINC00240 inhibited symptoms of preeclampsia through regulation on miR-155/Nrf2 axis, which suppressed oxidative stress-induced pyroptosis to improve trophoblast functions and polarization of M2 macrophages. LINC00240 could be a potential therapeutic target for preeclampsia. Funding Statement: This work was supported by A study on serum proteomics and clinical application of pregnancy induced hypertension based on iTRAQ technology（ SB201901087） and Relationship between fibronectin and hypertensive disorder complicating pregnancy and its clinical application (192102310335). Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: Written informed consent was collected from all participants before the procedure. The research protocol was approved by the Ethical Committee of the Henan Provincial People’s Hospital (Zhengzhou, Henan, China). All the animal experiment procedures were approved by the Animal Ethics Committee of Henan Provincial People’s Hospital (Zhengzhou, Henan, China).

This study aimed to investigate the roles of the lysine (K)-specific demethylase 5C (KDM5C)-bone morphogenetic protein-7 (BMP-7) signaling pathway in the pathogenesis of severe preeclampsia (sPE). A total of 180 pregnant patients were enrolled in the study and classified into three groups: an early-onset sPE group (EOsPE) (

Plasma fibronectin 1 (FN1) levels are elevated in individuals with pre-eclampsia (PE), which may be applied as a possible b marker for vascular endothelial injury during PE. In the present study, the possible role of FN1 in the pathogenesis of PE and regulation of apoptosis and autophagy in vascular endothelial cells was explored. Plasma FN1 levels in 80 patients with PE and 40 healthy pregnant individuals were measured using ELISA to verify its relationship with the severity of PE. pcDNA3.1-FN1 or FN1-small interfering (si) RNA was used to manipulate the expression of FN1 in human umbilical vein endothelial cells (HUVECs) to assess the effects of FN1 on cell apoptosis, autophagy, and the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) signaling pathway. It was found that upregulation of FN1 promoted apoptosis and autophagy, in addition to significantly inhibiting the activation of AKT and mTOR in HUVECs. By contrast, downregulation of FN1 expression inhibited cell apoptosis and autophagy, but increased AKT and mTOR phosphorylation in HUVECs that were cultured in serum samples obtained from patients with PE. Rescue experiments found that the PI3K/AKT inhibitor LY294002 reversed the effects of FN1-siRNA on apoptosis and autophagy in HUVECs cultured in serum from patients with PE. Therefore, data from the present study suggest that FN1 participates in the pathogenesis of PE by promoting apoptosis and autophagy in vascular endothelial cells, which is associated with the PI3K/AKT/mTOR signaling pathway.

Background Neuroblastoma (NB) displays the most heterogeneity in clinical manifestation. The insulin-like growth factor 1 receptor (IGF1R) has long been recognized for its role in tumourigenesis and growth. The IGF/IGF1R pathway is important in maintaining cell survival. It is reported that IGF1R participates in the occurrence of NB, but the mechanism is still unclear. Methods Human NB cell lines IMR-32 and SH-SY5Y were recruited in this study. IGF1R was knocked down by transfection with short hairpin RNA. Signal transducer and activator of transcription 3 (STAT3) expression was inhibited by Cryptotanshinone treatment. Cell proliferation, migration, and invasion were determined by MTT assay, wound healing assay, and cell invasion assay, respectively. The cancer stem cell properties were characterized by tumour sphere formation assay and colony formation assay. The mRNA and protein expression levels of related proteins were detected by RT-PCR and Western blot, respectively. Results The knockdown of IGF1R inhibits NB cell tumourigenesis and the epithelial-mesenchymal transition (EMT) of NB cells. Additionally, IGF1R was found to stimulate cancer stem cell-like properties in NPC cells. The knockdown of IGF1R significantly reduced the phosphorylation of AKT, and STAT3, indicating that the activation of the AKT and STAT3 pathways was inhibited by IGF1R knockdown. Furthermore, IGF1R was demonstrated to stimulate cancer stem cell-like properties in NB cells via the regulation of the STAT3/AKT axis. Conclusion IGF1R promotes cancer stem cell properties to facilitate EMT in neuroblastoma via the STAT3/AKT axis.

Cerous phosphate (CePO4) is attracting increasing attentions due to its potential sensing properties. But so far, the effect of morphology on its electrochemical sensing performance is scarcely reported. In this work, a bowknot-like CePO4 (B–CePO4) has been hydrothermally synthesized and characterized using XRD, BET, SEM, TEM, FT-IR spectroscopy and UV–Vis spectroscopy. It was shown that both the reaction time and the amount of urea had an important influence on the formation of CePO4 bowknots. The constructed B–CePO4 showed hierarchical structure and enhanced electron transfer ability. Then, it was utilized as an effective sensor for electrochemical sensing of ascorbic acid (AA) with wide linear range of 5.0–2150 ​μM, low detect limitation of 0.51 ​μM, high selectivity, good repeatability, and high stability. Furthermore, the B–CePO4 can also be used to detect AA in commercial vitamin tablets. In addition, due to its good fluorescent performance, B–CePO4 was used for fluorescence detecting of AA. This work provides an effective strategy for exploring new nanomaterials for sensing biomolecules.

Preeclampsia (PE) is a pregnancy-specific syndrome that substantially leads to maternal and fetal mortality. Multiple factors contribute to the disease, but the exact pathogenesis still remains elusive. Here we explored the roles of lncRNA MALAT1 and miR-206 in PE. qRT-PCR was applied to measure mRNA levels of MALAT1 and miR-206 in the placenta of PE patients. Scratch wound healing assay and transwell invasion assay were conducted to test the effects of MALAT1 and miR-206 on migration and invasion of trophoblast cells. In addition, we validated MALAT1/miR-206 and miR-206/IGF-1 interactions with dual luciferase reporter assay. Western bot was used to detect protein expressions of IGF-1, p-PI3K, PI3K, p-Akt and Akt. We found that MALAT1 was decreased but miR-206 was increased in the placenta of patients with PE. Inhibition of MALAT1, knockdown IGF-1, or miR-206 mimics suppressed the trophoblast cells migration and invasion, while overexpression of MALAT1, IGF-1 or miR-206 inhibitors exhibited opposite effects. Further, miR-206 was confirmed as a direct target of MALAT1. Besides, miR-206 inhibited IGF-1 expression by directly binding to the 3'UTR. Mechanistically, our study demonstrated that MALAT1 regulates IGF-1/PI3K/Akt signaling via miR-206. Together, these results suggest that MALAT1 and miR-206 play important roles in PE. MALAT1 regulates miR-206/IGF-1 axis, thereby modulating trophoblast cells migration and invasion through PI3K/Akt signal pathway. These results show light on the underlying mechanisms of PE and provide potential targets for PE therapy.Abbreviations: PE: Preeclampsia; lncRNA: Long-non-coding RNA; MALAT1: Metastasis-associated lung adenocarcinoma transcript 1; IGF-1: Insulin-like growth factor 1; PI3k: Phosphatidylinositol-4, 5-bisphosphate 3-kinase; Akt: Protein kinase B; GAPDH: Glyceraldehyde 3-phosphate dehydrogenase; qRT-PCR: Quantitative Reverse Transcription polymerase chain reaction; shRNA: Short hairpin RNA; siRNA: Small interfering RNA; EMT: Epithelial-mesenchymal transition.

Granule cells in the dentate gyrus regenerate constantly in adult hippocampus and then integrate into neural circuits in the hippocampus thereby providing the neural basis for learning and memory. Promoting the neurogenesis in the hippocampus facilitates learning and memory such as spatial learning, object identification, and extinction learning. The interaction between neuronal nitric oxide synthase (nNOS) and postsynaptic density protein-95 (PSD-95) is reported to negatively regulate neurogenesis in brain, so we hypothesized that disrupting this interaction might facilitate the neurogenesis in the dentate gyrus (DG) and thus enhance the extinction memory retrieval of fear learning. We found that uncoupling the nNOS-PSD-95 complex in remote contextual fear condition promoted both neuronal proliferation and survival in the DG, contributing to an enhanced retrieval of the extinction memory. Moreover, the nNOS-PSD-95 uncoupling-induced neurogenesis may be mediated by the extracellular signal-regulated kinase (ERK) as the phosphorylation level of ERK1/2 was increased after uncoupling. These findings suggest that the nNOS-PSD-95 complex may serve as a novel target for the treatment of post-traumatic stress disorder (PTSD).

Airway remodeling in asthma contributes to airway hyperreactivity, loss of lung function and persistent symptoms. Current therapies do not adequately treat the structural airway changes associated with asthma. Statin drugs have improved respiratory health and their therapeutic potential in asthma has been tested in clinical trials. However, the mechanism of action of statins in this context has remained elusive. The present study hypothesized that atorvastatin treatment of ovalbumin-exposed mice attenuates early features of airway remodeling via a mevalonate-dependent mechanism. BALB/c mice were sensitized with ovalbumin and atorvastatin was delivered via oral gavage prior to each ovalbumin exposure. Reverse transcription-semi-quantitative polymerase chain reaction (RT-semi-qPCR), ELISA and western blot analysis were used to assess the expression of a number of relevant genes, including tissue transglutaminase (tTG), triggering receptor expressed on myeloid cells (TREM)-1, nuclear factor erythroid 2-related factor (Nrf) 2, hypoxia-inducible factor (HIF)-1α, transforming growth factor (TGF)-β1, matrix metalloproteinase (MMP)-9 and tissue inhibitors of metalloproteinases (TIMP)-1 in lung tissue. α-Smooth muscle actin (α-SMA) activity was measured by immunohistochemistry. Airway hyperresponsiveness, lung collagen deposition, airway wall area, airway smooth muscle thickness and lung pathology were also assessed. Atorvastatin treatment led to downregulation of tTG and TREM-1 expression in lung tissue after ovalbumin sensitization, blocked the activity of MMP-9, vascular endothelial growth factor, nuclear factor-κB p65, α-SMA, HIF-α and TGF-β1 and up-regulated Nrf2 expression. Furthermore, the number of lymphocytes and eosinophils in the atorvastatin group was significantly lower than that in the control group. In addition, airway hyperresponsiveness, lung collagen deposition, airway wall area, airway smooth muscle thickness and pathological changes in the lung were significantly decreased in the atorvastatin group, and tumor necrosis factor-α, interleukin (IL)-8, IL-13 and IL-17 in serum were significantly decreased. Histological results demonstrated the attenuating effect of atorvastatin on ovalbumin-induced airway remodeling in asthma. In conclusion, the present study indicated that atorvastatin significantly alleviated ovalbumin-induced airway remodeling in asthma by downregulating tTG and TREM-1 expression. The marked protective effects of atorvastatin suggest its therapeutic potential in ovalbumin-induced airway remodeling in asthma treatment.

// Xiangchan Hong 1 , Qi Chen 2 , Lingyu Ding 3 , Ying Liang 1 , Ningning Zhou 1 ,Wenfeng Fang 1 , Xinru Chen 1 and Haiying Wu 1 1 Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangzhou, China 2 Department of Oncology, The First Affiliated Hospital of Clinical Medicine of Guangdong Pharmaceutical University, Guangzhou, China 3 Department of Medical Oncology, Hangzhou Cancer Hospital, Hangzhou, China Correspondence to: Haiying Wu, email: // Keywords : non-small-cell lung cancer, anaplastic lymphoma kinase, crizotinib, treatment beyond disease progression, progression-free survival Received : October 20, 2016 Accepted : February 22, 2017 Published : March 04, 2017 Abstract Purpose: Although most patients with ALK -positive non‒small-cell lung cancer (NSCLC) who benefit from treatment with crizotinib ultimately develop progressive disease (PD), continuing crizotinb beyond the initial PD (CBPD) in these patients may be beneficial. In this study, we investigated whether Chinese patients with advanced ALK -positive NSCLC benefit from CBPD, and whether any factors are predictive of a longer post-initial progression-free survival time (PFS2). Materials and Methods: Data on 33 patients with ALK-positive NSCLC who achieved disease control with crizotinib were analyzed retrospectively. The impact of continued crizotinib therapy on the patients’ PFS2 time was assessed after adjusting for potential confounding factors. Results: With initial crizotinib therapy, the objective response rate (ORR) and median PFS time (PFS1) in the 33 patients were 63.6% and 8.6 months, respectively. With continued crizotinib therapy after documentation of PD, the median PFS2 for all 33 patients was 16 weeks, and in those with CNS progression but systemic disease control it was 30 weeks. Patients who received local therapy after disease progression had a significantly longer PFS2 compared with those who did not ( P = 0.039). Multivariable Cox regression analysis showed that the PFS1 with initial crizotinib treatment and local therapy were independent predictors of PFS2. Discussion: This study provides further evidence of the benefit of continuing crizotinib therapy in Chinese patients with progressive ALK-positive NSCLC. Patients with a longer PFS1 and those who received local brain therapy would have a longer period of continuing crizotinib.

// Ling-yu Ding 1, 2, 3, 4 , Ke-jun Liu 5 , Zhe-long Jiang 6 , Hai-ying Wu 2, 3, 4 , Shi-xiu Wu 7 1 Department of Medical Oncology, Hangzhou Cancer Hospital, Hangzhou, China 2 Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China 3 State Key Laboratory of Oncology in South China, Guangzhou, China 4 Collaborative Innovation Center of Cancer Medicine, Guangzhou, China 5 Department of Medical Oncology, Dongguan People’s Hospital, Dongguan, China 6 Department of Emergency, Hangzhou First People’s Hospital, Nanjing Medical University, Hangzhou, China 7 Department of Radiation Oncology, Hangzhou Cancer Hospital, Hangzhou, China Correspondence to: Shi-xiu Wu, email: 827295917@qq.com Keywords: lung cancer, gastric metastasis, surgery, liver metastases, targeted therapy Received: March 10, 2016 Accepted: October 31, 2016 Published: November 04, 2016 ABSTRACT Gastric metastases from lung adenocarcinoma are rare and usually asymptomatic. A 61-year-old woman was referred to our department because of a right lower pulmonary mass found on a chest X-ray film in August 2012. Right lower lobectomy was performed for pulmonary adenocarcinoma. Four months later, she developed epigastric discomfort. A fluoro-deoxy-glucose positron emission tomography/computed tomography (FDG-PET/CT) scan showed a malignancy at the cardias of the stomach. A biopsy diagnosed poorly differentiated carcinoma and a gastric carcinoma was suspected. She underwent a subtotal gastrectomy and part of esophagectomy. The histologic diagnosis was metastasis from the pulmonary adenocarcinoma. She visited us again for her increasing level of carcinoembryonic antigen (CEA) after two months. FDG-PET/CT showed multiple malignant lesions in her liver, considering metastases from pulmonary origin. As she harbored activating epidermal growth factor receptor (EGFR) mutation, she received erlotinib from April, 2013. She survives 4 years after the lung resection and is still on erotinib treatment with complete response. Although gastric metastasis from lung cancer is considered a late stage of the disease, a radical resection might provide survival in solitary metastasis. Moreover, systemic therapy was emphasized after local treatment in some late stage cases.

Objective To summarize the clinical and MRI imaging features, treatment and prognosis of reversible splenial lesion syndrome (RESLES). Methods The clinical manifestation and MRI imaging appearances of 13 RESLES patients were retrospectively evaluated and the pertinent literatures of RESLES were reviewed. Results Of the 13 cases (11 males and 2 female, aged from 13 to 58 years), 1 was complicated with spontaneous intracranial hypotension syndrome, 1 with epidemic hemorrhagic fever, 1 with antiepileptic drug withdraw, 1 with pituitary crisis combining Sjogren syndrome, 1 with still disease, and 8 cases were complicated with viral encephalitis (meningoencephalitis). The first MRI imaging was performed from 2 to 39 days after onset. All the lesions were measured about 1-2cm, located in the central area and involved no other part of corpus callosum. They were characterized by high signal intensity on FLAIR and T2 sequences, with mild signal reduction on T1 sequence, and hyperintensity on DWI with low apparent diffusion coefficient (ADC) values. The lesions formed as ovoid and boomerang. Following intravenous injection of contrast medium in 3 cases, no enhancement was found in the splenial lesions. All the patients completely recovered or obviously improved after appropriate treatments. The splenial lesions disappeared or obviously weakened on the follow-up MRI imaging, ranging from 6 to 30 days after first MRI imaging. Conclusions RESLES is characterized by the MRI finding as a reversible lesion with transiently reduced diffusion in the splenium of corpus callosum. Symptoms of RESLES are various, the outcome is favorable in most cases, and the etiology and pathogenesis of RESLES are still unclear. DOI: 10.11855/j.issn.0577-7402.2016.10.09

Tree shrews are most closely related to the primates and so possess a number of advantages in experimental studies; they have been used as an animal model in bacterial and virus infection, cancer, endocrine system disease, and certain nervous system diseases. Their olfactory ensheathing cells (OECs) are able to release several cytokines to promote neuronal survival, regeneration and remyelination. The present study used western blot analysis to identify antibody specificity in protein extracts from whole tree shrew brains to identify the specificity of p75 nerve growth factor receptor (NGFR) derived from rabbits (75 kDa). OECs were cultured and isolated, then stained and identified using the antibodies for p75NGFR. To investigate the capacity of OECs to express cytokines and growth factors, microarray technology was used, and the analysis revealed that OECs were able to express 9,821 genes. Of these genes, 44 genes were from the neurotrophic factor family, which may indicate their potential in transplantation in vivo. The present study considered the function of OECs as revealed by other studies, and may contribute to future research.

Primary aldosteronism (PA) is mainly treated by mineralocorticoid receptor antagonists or laparoscopic adrenalectomy (LA), but the effectiveness of surgical versus medical treatment in patients with adrenal venous sampling (AVS)-proven unilateral PA is unclear. Fifty-one consecutive patients with AVS-proven PA were enrolled. We compared the therapeutic effects between the surgery group (n = 21) and medication group (n = 30) by evaluating the complete control rate (CCR) of hypertension, blood pressure (BP), and number of antihypertensive drugs after a long-term follow-up (12 months). The CCR of hypertension was assessed using a multivariate adjusted Cox proportional hazards regression model. After a mean follow-up of 21.18 ± 5.35 months, the CCR was significantly higher in the surgery than medication group (85.7% vs. 13.3%, respectively; p 0.001). Before adjustment for covariates, the CCR of hypertension in patients who underwent LA was 7.75 times higher than that in patients who underwent medical treatment (95% CI, 2.33-25.78; p = 0.001); significant results were also shown in the adjusted models. Systolic and diastolic BP were also lower in the surgery than medication group (120.3 ± 12.99 vs. 133.54 ± 16.60 and 79.00 ± 7.62 vs. 87.35 ± 12.36 mmHg, respectively; p = 0.01 for both), as was the number of antihypertensive drugs (0.19 ± 0.51 vs. 2.33 ± 0.78, respectively; p 0.001). The rate of hypokalemia was not significantly different between the two groups (0.0% vs. 13.3%, respectively; p = 0.13). In conclusion, AVS plays an essential role in the subtype diagnosis of PA, and surgical candidates with AVS-proven unilateral PA should be highly suggested to undergo LA.

Background Neuroblastoma (NB) displays the most heterogeneity in clinical manifestation. The insulin-like growth factor 1 receptor (IGF1R) has long been recognized for its role in tumourigenesis and growth. The IGF/IGF1R pathway is important in maintaining cell survival. It is reported that IGF1R participates in the occurrence of NB, but the mechanism is still unclear. Methods Human NB cell lines IMR-32 and SH-SY5Y were recruited in this study. IGF1R was knocked down by transfection with short hairpin RNA. Signal transducer and activator of transcription 3 (STAT3) expression was inhibited by Cryptotanshinone treatment. Cell proliferation, migration, and invasion were determined by MTT assay, wound healing assay, and cell invasion assay, respectively. The cancer stem cell properties were characterized by tumour sphere formation assay and colony formation assay. The mRNA and protein expression levels of related proteins were detected by RT-PCR and Western blot, respectively. Results The knockdown of IGF1R inhibits NB cell tumourigenesis and the epithelial-mesenchymal transition (EMT) of NB cells. Additionally, IGF1R was found to stimulate cancer stem cell-like properties in NPC cells. The knockdown of IGF1R significantly reduced the phosphorylation of AKT, and STAT3, indicating that the activation of the AKT and STAT3 pathways was inhibited by IGF1R knockdown. Furthermore, IGF1R was demonstrated to stimulate cancer stem cell-like properties in NB cells via the regulation of the STAT3/AKT axis. Conclusion IGF1R promotes cancer stem cell properties to facilitate EMT in neuroblastoma via the STAT3/AKT axis.

Background MYCN and LMO1 amplification are commonly observed in neuroblastoma (NB), which was often accompanied by genetic loss of let-7 microRNA (miRNA). Fibroblast growth factor (FGF) was found to regulate let-7 miRNA expression via FGF receptor substrate 2 (FRS2), which then activates transforming growth factor beta (TGF-β) signaling. Methods Expression of MYCN, LMO1, FRS2, let-7, and TGF-β receptor I (TGFβRI) was selectively knocked-down or enhanced in NB cells. Proliferation, invasion, migration, metastasis and tumorigenesis of NB, expression of downstream signaling factors and metastasis-associated protein were evaluated. Results Knock-down on either MYCN or LMO1 has led to inhibition on proliferation, invasion, migration, and metastasis of NB cells, and knock-down of FRS2 resulted in increases in MYCN and LMO1 expression and enhanced invasion, migration and metastasis of NB cells. Decreased expression of TGF-β1 or TGFβRI led to decrease expression in LMO1 and proliferation, invasion, migration and metastasis markers, except MYCN expression which appeared not to be regulated by TGF-β1 or TGFβRI. Furthermore, let-7 miRNA was shown to decrease the expression levels of TGF-βRI, LMO1 and MYCN. Conclusions FGF regulates MYCN and TGF-β1-induced LMO1 and metastasis of NB cells via let-7 miRNA.

In this work, a texture mapping scheme with massive data is proposed based on quadtree for multi-level scene modeling. A simplified LOD model is established for the multi-resolution texture data which enhance the fidelity of multilevel target simulation in scene. By predictable appreciation according to viewpoint displacement in real-time simulation, the correspongding nodes and level details of quadtree are confirmed when the dynamical scene is loading. This mean effectively decreases the schedule data in real-time simulation. A validation experiment has been performed to certificate the availabitity and improvement.

Building information modeling (Building Information Modeling, BIM) Was born of the new age effective, low-cost, life-information of unprecedented technological change, which contribute to modern information technology to a more humane, ecological, with the stride development of intelligent, but, in fact, BIM Century as far as promotion 2D CAD Technology in the global promotion of speed, the reason was BIM Technical implementation stage requires a lot of hardware resources and the service terminal configuration, contrary to BIM 'S original intention of low cost, high effectiveness, while if we can integrate cloud computing technology and BIM Practical implementation platform combines background consuming resources and configuration data to the cloud, update mobile devices are only used to improve the information, then the problem is solved.

// Qi Chen 1, 2, 3 , Qi Quan 1, 2, 3 , Lingyu Ding 1, 2, 3 , Xiangchan Hong 1, 2, 3 , Ningning Zhou 1, 2, 3 , Ying Liang 1, 2, 3 , Haiying Wu 1, 2, 3 1 State Key Laboratory of Oncology in South China, Guangzhou, China 2 Department of Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China 3 Collaborative Innovation Center of Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China Correspondence to: Haiying Wu, e-mail: chenqi4608@163.com Keywords: non-small-cell lung cancer, acquired resistance, continuation of epidermal growth factor receptor tyrosine kinase inhibitors, beyond PD, local treatment Received: April 21, 2015 Accepted: June 26, 2015 Published: July 09, 2015 ABSTRACT Objectives: Patients with non-small-cell lung cancer (NSCLC) develop acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) after tumor regression. No approved targeted therapies are currently available after initial EGFR TKI treatment. This study investigated the efficacy of continuing EGFR TKI therapy with local treatments for patients with NSCLC and local progression or minimal/slow progression on TKI therapy. Materials and Methods: Fifty-five patients with NSCLC treated with EGFR TKIs and developed acquired resistance to the drug were included. Initial response to target therapy, median progression free survival (PFS1), progression pattern, and first progression site were assessed. Median progression free survival to physician assessment progression (PFS2) and difference between PFS1 and PFS2 (PFS difference) were also recorded. Results and Conclusion: PFS1 was 11.2 months, PFS2 was 20.3 months, and PFS difference was 8.3 months. Nineteen patients (34.5%) who manifested progression received local therapy, and 16 (28.6%) underwent rebiopsy after progression with six positive EGFR T790M mutations detected. Cox proportional hazards regression model showed that only the first line of treatment was significantly correlated with PFS difference. NSCLC patients with acquired resistance to EGFR TKIs could benefit from the same TKI therapy through months to years of disease control.

Vascular endothelial growth factor (VEGF) plays a critical role in the pathogenesis of diabetic microvascular complications. Finasteride has been confirmed to decrease VEGF expression in prostate and prostatic suburethral tissue resulting in limiting hematuria from human benign prostatic hyperplasia. The purpose of this study was to evaluate the effects of finasteride on microvessel density (MVD), VEGF protein and mRNA expressions in the renal tissue of diabetic rats.Diabetic rats induced by streptozotocin were intragastrically given finasteride at 30 mg/kg body weight once a day for 4 weeks. Histomorphologic changes in kidney were observed under light microscope. Immunohistochemistry for CD34 and VEGF on kidney sections was performed to assess MVD and VEGF protein expression in glomeruli of rats, respectively. The VEGF mRNA expression in the renal tissue was examined using reverse transcription polymerase chain reaction analysis.The glomerular tuft area, glomerular volume, MVD, VEGF protein expression in glomeruli and VEGF mRNA expression in the renal cortex tissue were significantly increased in diabetic rats and finasteride-treated rats when compared with controls (P0.01, P0.05). When compared with diabetic rats, the glomerular tuft area, glomerular volume, MVD, VEGF protein expression in glomeruli and VEGF mRNA expression in the renal cortex tissue of finasteride-treated rats were significantly decreased (P0.05, P0.01).Finasteride reduces the VEGF expression and decreases the MVD in the renal tissue of diabetic rats, suggesting the therapeutic potential of finasteride on diabetic microvascular complications.

Replacing the saddle-point approximation extensively adopted in previous literature, an exact expression for the Fourier transformation of electric field distributions of reflected and refracted polarised Gaussian beams is derived to investigate the spin Hall effect of light. A general method based upon the partial differential of the light intensity distributions of the reflected and refracted propagating beams is presented to determine the beam shifts from the spin Hall effect of light. Compared with the previous integration method along one direction reported in the literature, our method not only is much more explicit, but also enables us simultaneously to obtain the transverse and longitude shifts of the reflected and refracted wave packets. Furthermore, at any propagation distance away from the interface between two optical media, the shifts of the propagating beams and their split ones can be analytically expressed by means of transverse- and longitude-deflected angles.

Non-small cell lung cancer (NSCLC) accounts for about 85% of all lung cancer cases. Patients with NSCLC often have an advanced disease at the time of diagnosis, with a 1-year survival rate about 10-15% under the best support treatment. As therapeutic methods for lung cancer developed rapidly in recent years, the prognosis of stage IIIB or IV NSCLC also improve to a large extend. Bevacizumab is a monoclonal antibody against VEGFR which inhibits abnormal vascular growth in malignant tumors. In October 2006, bevacizumab was approved by the U.S. Food and Drug Administration (FDA) for first-line use in advanced NSCLC. For patients with advanced NSCLC who failed in previously platinum-based chemotherapy, bevacizumab also showed enhancing efficacy to antitumor drugs recommended by the latest NCCN guideline. This review intends to present the recent progress and prospects of bevacizumab in second- or third-line treatment for patients with refractory NSCLC.

Introduction The aim of this study was to compare the efficacy and toxicity of dicycloplatin plus paclitaxel with those of carboplatin plus paclitaxel as first-line treatment for patients with advanced non-small-cell lung cancer (NSCLC). Material and methods In this study, 240 NSCLC patients with stage IIIB (with pleural effusion) and stage IV disease were randomly assigned (1: 1) to receive dicycloplatin 450 mg/m(2) or carboplatin AUC = 5, in combination with paclitaxel 175 mg/m(2) (D + P or C + P) every 3 weeks for up to 4 to 6 cycles. The primary endpoint was response rate. Secondary endpoints included progression-free survival (PFS), overall survival (OS) and adverse events. Results The response rates for the D + P and C + P arm were 36.44% and 30.51%, respectively (p = 0.33). The median PFS was 5.6 months in the D + P arm and 4.7 months in the C + P arm (p = 0.31). The median OS was 14.9 months for D + P and 12.9 months for C + P (p = 0.37). Adverse events in the two arms were well balanced. The most common grade 3/4 adverse event was hematologic toxicity. Conclusions Patients treated with D + P had similar response and survival rates to those treated with C + P, and toxicities of both treatments were generally tolerable.

In the paper , the combined aggregate concrete is regarded as a three-phase composite material based on the meso-scale level, it consists of lightweight aggregate, ordinary aggregate and mortar. According to Fuller’s grading curve, the number of aggregate with different size could be obtained. And the randomly aggregates model is generated base on the Monte Carlo method. APDL program is developed to generate finite element model of combined aggregate concrete, On the basis, the stress characteristics of combined aggregate concrete is studied.

Density functional theory (DFT) is used to calculate the C-NO2bond dissociation energies (BDEs) in nitrobenzene; 3-amino-nitrobenze; 4-amino-nitrobenze; 1,3-dinitrobenzene; 1,4-dinitrobenzene; 2-methyl-nitrobenzene; 4-methyl-nitrobenzene and 1,3,5-trinitrobenzene nitroaromatic molecular system. B3P86 and PBE0 methods in combination with 6-31G** and 6-311G** basis sets are employed. Comparison between the computational results and the experimental values reveals that the calculated C-NO2bond BDEs can be improved from B3P86 to PBE0 functional. Level of theory employing PBE0/6-311G** is found to be sufficiently reliable to compute BDEs of C-NO2bond for nitroaromatic molecules with an average absolute error of 0.98 kcal mol-1.

Haze, fog, and smoke are turbid medium in the atmosphere which usually degrade viewing condition of outdoor scenes. The resulted images lose contrast and color fidelity with serious degradation. Due to loss of large detailed information of measured scene, it will usually lead to invalid detection and measurement. The suspended particles in the atmosphere and the scene being measured give rise to polarization changes by their reflection. In the process of reflection, absorption and scattering, the object itself can be determined by its own polarization characteristics. Based on this point, we proposed an approach for target vision through haze. This approach is based on the polarization differences between the scene being measured and the scattering background to move the haze effects. It can realize a great visibility enhancement and enable the scene rendering even if imaged under restricted viewing conditions with low polarization. In this work, the detailed theoretical operation principle is presented. A validating imaging system is established and the corresponding experiment is carried out. We present the experimental results of haze-free image of scene with recovered high contrast. This method also can be used to effectively enhance the imaging performance of any other optical system.

The standard enthalpies of formation for 7 derivatives of 4,5-dinitroimidazole in gas at 298 K were determined using isodesmic reactions at B3LYP/6-311G** and B3P86/6-311G** levels. The results indicate that the substitution of nitro group can increase the enthalpies of formation. The more the number of nitro group, the higher the enthalpies of formation. The standard enthalpies of formation of –NO2 and –CH3 substitution compounds on N atom are larger than corresponding ones on C atom.

Background Chemotherapy-induced nausea and vomiting remain among the most feared adverse effects for cancer patients. Aim The aim of this study was to evaluate the efficacy and safety of a combination of aprepitant, palonosetron and dexamethasone as antiemetic prophylaxis in patients receiving multiple-day cisplatin-based chemotherapy. Methods Forty-one solid cancer patients received aprepitant, palonosetron and dexa- methasone during a 3-day cisplatin-based chemotherapy. Primary end-point was complete response in the overall phase (day 1 until 5 days after the end of chemotherapy). Results Aprepitant in combination with palonosetron and dexamethasone was safe, with hiccups (31.7%), fatigue (17.1%), headache (14.6%) and constipation (12.2%) the most common treatment-related adverse events, mostly mild. Complete response was seen in 58.5% of patients in the overall phase. In 23 patients receiving aprepitant in combination with palonosetron and dexamethasone more than one cycle (range: 2–5 cycles), the cumulative emetic protection rate after five cycles was 0.82. Conclusion This study shows aprepitant in combination with palonosetron and dex-amethasone is safe and effectively controls chemotherapy-induced nausea and vomiting in patients undergoing 3-day cisplatin-based chemotherapy, moreover, the efficacy is maintained during multiple cycles.

By the submicroscopic analysis, the combined aggregate concrete is regarded as a three-phase complex material, composed of light aggregate, common aggregate and mortar. APDL program is developed to generate two-dimension aggregate structure, the radius and position of aggregate distribute randomly. Using the Boolean operation, the light aggregate, common aggregate and mortar is meshed. On the basis, the loading process of combined aggregate concrete cube is studied. It would provide reference for mechanical property analysis of combined aggregate concrete.

To assess the prognostic value of pulse indicator continuous cardiac output (Picco) monitoring combined with plasma microRNA-150 detection in septic shock patients.Clinical data of 48 patients with septic shock admitted in General Intensive Care Unit (GICU), Shanghai First People's Hospital Songjiang Branch Affiliated to Shanghai Jiaotong University from August 2012 to August 2014 were analyzed retrospectively. The plasma levels of microRNA-150 in 48 patients at admission were assayed by qRT-PCR; and Picco monitoring was performed to record hemodynamic changes. The correlation of microRNA-150 or Picco parameters with prognosis of patients was assessed by univariate analysis and multivariate logistic analysis. Spearman correlation test showed the relationship between microRNA-150 and Picco parameters. Finally, the clinical value of combining microRNA-150 with Picco monitoring to predict the outcome of septic shock patients was analyzed by ROC curves.Twenty-three patients survived and 25 died in 28 d after admission in GICU. Compared with survival patients, microRNA-150 was significantly lower in fatal patients (t=-10.32, P0.05). Univariate analysis showed that low microRNA-150 level was a risk factor for poor prognosis(OR=2.176,95% CI:1.121-4.223, P0.05). Compared with fatal cases, the cardiac index of survival patients was higher, while EVLWI and PVPI were lower. MicroRNA-150 level was positively correlated with cardiac index (r=0.712, P0.05), negatively correlated with EVLWI and PVPI (r=-0.622 and-0.689, both P0.05). ROC curves showed a satisfactory diagnostic efficiency of combining microRNA-150 with Picco monitoring.Lower microRNA-150 may indicate a poor prognosis, and Picco monitoring combined with microRNA 150 detection may improve the prognostic efficiency in septic shock patients.

The hippocampal CA1 pyramid neuron has plenty of discharge actions. In the thesis, the dynamic characteristics of the hippocampal neuron model are analyzed and discussed by the neurodynamic theory and methods. Under a certain amplitude currents stimulation, the change of (the maximum conductance of the transient sodium channel) and (the maximum conductance of the delay rectification potassium channel) can cause different dynamic characteristics of the neuron model. The transient Na+current () caused by is indispensable in the discharges formation process of the model. The model can generate the discharge process only when reaches a certain threshold. In the discharge process of the neuron model,s changing affects little and the ISIs approximate to a straight line. The delay rectification K+current () caused by isnt indispensable in the discharges formation process of the model. Buts changing affects much in the discharge process of the neuron model. Withs changing, the neuron model undergoes different dynamic bifurcation process, and has plenty of discharge patterns such as the chaos, period, and so on. This investigation is helpful to know and investigate deeply the dynamic characteristics and the bifurcation mechanism of the hippocampal neuron; and it provides a certain theory assist to investigate the neural diseases such as the Alzheimer disease by neurodynamics.

Saracatinib, a highly selective, dual Src/Abl kinase inhibitor, is currently in a Phase II clinical trial for the treatment of ovarian cancer. In our study, we investigated the effect of saracatinib on the reversal of multidrug resistance (MDR) induced by ATP-binding cassette (ABC) transporters in vitro and in vivo. Our results showed that saracatinib significantly enhanced the cytotoxicity of ABCB1 substrate drugs in ABCB1 overexpressing HeLa/v200, MCF-7/adr and HEK293/ABCB1 cells, an effect that was stronger than that of gefitinib, whereas it had no effect on the cytotoxicity of the substrates in ABCC1 overexpressing HL-60/adr cells and its parental sensitive cells. Additionally, saracatinib significantly increased the doxorubicin (Dox) and Rho 123 accumulation in HeLa/v200 and MCF-7/adr cells, whereas it had no effect on HeLa and MCF-7 cells. Furthermore, saracatinib stimulated the ATPase activity and inhibited photolabeling of ABCB1 with [(125)I]-iodoarylazidoprazosin in a concentration-dependent manner. In addition, the homology modeling predicted the binding conformation of saracatinib within the large hydrophobic drug-binding cavity of human ABCB1. However, neither the expression level of ABCB1 nor the phosphorylation level of Akt was altered at the reversal concentrations of saracatinib. Importantly, saracatinib significantly enhanced the effect of paclitaxel against ABCB1-overexpressing HeLa/v200 cancer cell xenografts in nude mice. In conclusion, saracatinib reverses ABCB1-mediated MDR in vitro and in vivo by directly inhibiting ABCB1 transport function, without altering ABCB1 expression or AKT phosphorylation. These findings may be helpful to attenuate the effect of MDR by combining saracatinib with other chemotherapeutic drugs in the clinic.

The activation of 〈c + a〉 non-basal slip system can help to improving the mechanical properties of Magnesium alloys. The activation conditions of 〈c + a〉 non-basal slip system in Mg alloys are reviewed, such as the addition of lithium elements, increasing temperatures, and regions of stress concentration, and so on. Moreover, the article summarizes our results from the work on Mg alloys using equal channel angle pressing with back pressure, and points out that 〈c + a〉 non-basal slip systems also become active much easier under hydrostatic pressure, which will help to open new window to explore the basic physics of the activation of non-basal slip.