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Background: Early postoperative small bowel obstruction (EPSBO) is a common complication following colon cancer surgery. EPSBO is associated with increased hospital stays, mortality rates, and healthcare costs. The purpose of this study was to identify risk factors for EPSBO following elective colon cancer surgery., Study Design: We retrospectively reviewed the clinicopathological variables of 1,244 patients with colon cancer who underwent partial colectomy from January 2000 to December 2014. A multivariable logistic regression model was used to identify risk factors for EPSBO., Results: The EPSBO rate was 3.5%. In multivariate analysis, preoperative bowel obstruction (OR 2.378; 95% CI 0.986-5.735, p = 0.054), weight loss >10% of body weight (OR 3.029; 95% CI 1.000-9.178, p = 0.05), albumin level (in g/L; OR 0.966; 95% CI 0.937-0.996, p = 0.024), and surgical duration (in min; OR 1.008; 95% CI 1.003-1.012, p = 0.003) were significant predictors of EPSBO., Conclusion: EPSBO is more likely to develop in the presence of poor systemic conditions (e.g., weight loss >10% of body weight, hypoalbuminemia, and preoperative bowel obstruction) and following operations of longer duration. These predictors may facilitate the stratification of patients at risk for EPSBO following surgery for elective colon cancer., (© 2017 S. Karger AG, Basel.)

Rationale: The mechanism of the first-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) acquired resistance included T790M mutation, cellular-mesenchymal to epithelial transition factor (MET) or EGFR amplification, PIK3CA mutation, and transformation to small cell lung cancer. MET amplification accounted for only about 5% of the resistance cases., Patients Concerns: Few report detected MET amplification in pleural effusion. Here, we reported 2 lung adenocarcinoma cases with MET amplification in pleural effusion rapidly responded to crizotinib after EGFR-TKIs acquired resistance., Diagnoses: Biopsy via bronchoscopy, next-generation sequencing (NGS) in pleural effusion., Interventions: EGFR-TKIs (Icotinib), MET inhibitor crizotinib., Outcomes: After a progression-free survival of 9 months and 23months, respectively, both cases progressed accompanying with pleural effusion. Results of NGS in pleural effusion showed MET amplification (2-3 times) in both cases. The 2 patients were treated with a MET inhibitor crizotinib and rapidly responded., Conclusion: MET amplification in pleural effusion could predict a perfect response to crizotinib after EGFR-TKIs acquired resistance, even only a low times gene amplification., (Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background and Objective: Apolipoprotein E (APOE) plays important roles in lipoprotein metabolism and cardiovascular disease. Evidence suggests the APOE gene epsilon2/epsilon3/epsilon4 (ε2/ε3/ε4) polymorphisms might be associated with the susceptibility of coronary artery disease (CAD) in patients with type 2 diabetes mellitus (T2DM). However, no clear consensus has yet been established. Therefore, the aim of this meta-analysis is to provide a precise conclusion on the potential association between APOE ε2/ε3/ε4 polymorphisms and the risk of CAD in patients with T2DM based on case-control studies. Methods: Pubmed, Embase, Chinese National Knowledge Infrastructure (CNKI), and Wanfang databases were searched for all relevant studies prior to August 2017 in English and Chinese language. The pooled odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were used to assess the strength of the relationships. The between-study heterogeneity was evaluated by Cochran's Q-test and the I 2 index to adopt fixed- or random- effect models. Results: A total of 13 studies were eligible for inclusion. There was evidence for significant associations between APOE ε4 mutation and the risk of CAD in patients with T2DM (for ε3/ε4 vs. ε3/ε3: OR = 1.69, 95% CI = 1.38-2.08, P < 0.001; for ε4/ε4 vs. ε3/ε3: OR = 2.72, 95% CI = 1.61-4.60, P < 0.001; for ε4/ε4+ε3/ε4 vs. ε3/ε3: OR = 1.83, 95% CI = 1.52-2.22, P < 0.001; for ε4 allele vs. ε3 allele: OR = 1.64, 95% CI = 1.40-1.94, P < 0.001). In contrast, no significant associations were found in genetic model of APOE ε2 mutation (for ε2/ε2 vs. ε3/ε3: OR = 1.67, 95% CI = 0.90-3.09, P = 0.104; for ε2/ε3 vs. ε3/ε3: OR = 1.18, 95% CI = 0.93-1.51, P = 0.175; for ε2/ε2+ε2/ε3 vs. ε3/ε3: OR = 1.26, 95% CI = 0.88-1.82, P = 0.212; for ε2 allele vs. ε3 allele: OR = 1.34, 95% CI = 0.98-1.84, P = 0.07). Conclusions: The APOE gene ε4 mutation is associated with an increased risk of CAD in patients with T2DM, while the ε2 variation has null association with this disease.

Berberine hydrochloride (BBH) has a variety of pharmacological activities such as antitumor, antimicrobial, anti-inflammation, and reduce irritable bowel syndrome. However, poor stability and low oral bioavailability limited its usage. Herein, an oil-in-water nanoemulsion system of BBH was developed to improve its stability and oral bioavailability. The pseudoternary phase diagrams were constructed for the determination of composition of various nanoemulsions. The nanoemulsions of BBH composed of Labrafil M 1944 CS (oil phase), RH-40 (surfactant), glycerin (co-surfactant), and water (aqueous phase). The O/W nanoemulsion of BBH showed a relative bioavailability of 440.40% compared with unencapsulated BBH and was stable in our 6-month stability study. Further, there was a significant increase in intestinal permeability of BBH as assessed by Caco-2 cell monolayers and a significant reduction in efflux of BBH by the multidrug efflux pump P-glycoprotein. This study confirmed that the nanoemulsion formulation could be used as an alternative oral formulation of BBH to improve its stability, oral bioavailability and permeability.

Background: Interleukin-17 (IL-17) plays an important role in cancer progression. Previous studies remained controversial regarding the correlation between IL-17 expression and lung cancer (LC) prognosis. To comprehensively and quantitatively summarize the prognostic value of IL-17 expression in LC patients, a systematic review and meta-analysis were performed., Methods: We identified the relevant literatures by searching the PubMed, EMBASE, Cochrane Library, SinoMed, China National Knowledge Infrastructure (CNKI) and Wanfang Data databases, up until April 1, 2017. Overall survival (OS), disease free survival (DFS) and clinicopathological characteristics were collected from relevant studies. Pooled hazard ratios (HR) and corresponding 95% confidence intervals (CI) were calculated to estimate the effective value of IL-17 expression on clinical outcomes., Results: Six studies containing 479 Chinese LC patients were involved in this meta-analysis. The results indicated high IL-17 expression was independently correlated with poorer OS (HR = 1.82, 95% CI 1.44-2.29, P < 0.00001) and shorter DFS (HR = 2.41, 95% CI 1.42-4.08, P = 0.001) in LC patients. Further, when stratified by LC histological type (non-small cell lung cancer and small cell lung cancer), tumor stage (Ⅰ-Ⅲ,Ⅰ-Ⅳ and Ⅳ), detection specimen (serum, intratumoral tissue and pleural effusion), test method (immunological histological chemistry and enzyme linked immunosorbent assay), and HR estimated method (reported and estimated), all of the results were statistically significant. These data indicated that elevated IL-17 expression is correlated with poor clinical outcomes in LC. The meta-analysis did not show heterogeneity or publication bias., Conclusions: The present meta-analysis revealed that high IL-17 expression was an indicator of poor prognosis for Chinese patients with LC. It could potentially help to assess patients' prognosis and estimate treatment efficacy in therapeutic interventions.

Oleaginous microalgae hold great promises for biofuel production. However, commercialization of microalgal biofuels remains impracticable due to the lack of suitable industrial strains with high growth rate and lipid productivity. Engineering of metabolic pathways is a potential strategy for the improvement of microalgal strains for the production of lipids and also value-added products in microalgae. Malonyl CoA-acyl carrier protein transacylase (MCAT) has been reported to be involved in fatty acid biosynthesis. Here, we identified a putative MCAT in the oleaginous marine microalga Nannochloropsis oceanica. NoMCAT overexpressing N. oceanica showed a higher growth rate and photosynthetic efficiency. The neutral lipid content of engineered lines showed a significant increase by up to 31% compared to wild type. Gas chromatography-mass spectrometry analysis revealed that NoMCAT overexpression significantly altered the fatty acid composition. The composition of eicosapentaenoic acid (C20:5), which is a polyunsaturated fatty acid necessary for animal nutrition, increased by 8%. These results demonstrate the role of MCAT in enhancing fatty acid biosynthesis and growth in microalgae, and also provide an insight into metabolic engineering of microalgae with high industrial potential., (© 2016 International Union of Biochemistry and Molecular Biology, Inc.)

Elevated homocysteine levels are known to be a risk factor for congenital cardiac septal defects (CCSDs), but the mechanism underlying this effect is unknown. The genetic variants that were significantly associated with circulating homocysteine concentrations have been systematically identified through the genome-wide association studies of one-carbon core metabolites. To examine the role of the genome-wide significant homocysteine related variants in the occurrence of CCSDs, we investigated the association between these variants and CCSDs in Han Chinese populations. Five variants of the genome-wide significant homocysteine-related genes were selected for analysis in two stages of case-controlled studies with a total of 904 CCSD patients and 997 controls. SYT9 expression was detected in human cardiovascular tissue using qRT-PCR. The intronic variant rs11041321 of the SYT9 gene was associated with an increased risk of developing CCSDs in both the separate and combined case-controlled studies. Combined samples from the two stage cohorts had a significant elevation in CCSD risk for the T allele (OR = 1.43, P = 2.6 × 10 -6 ), CT genotype and TT genotype (CT: OR = 1.30, TT: OR = 2.21; P = 1 × 10 -4 ) compared with the wild-type C allele and CC genotype, respectively. The risky T allele carriers exhibited decreased SYT9 mRNA expression, compared with wild-type C allele carriers. The intronic SYT9 variant rs11041321, which exhibits a significant genome-wide association with circulating homocysteine, was associated with the occurrence of CCSDs. This finding helps to characterize the unexpected role of SYT9 in homocysteine metabolism and the development of CCSDs, which further highlighted the interplay of diet, genetics, and human birth defects. © 2017 IUBMB Life, 69(9):700-705, 2017., (© 2017 International Union of Biochemistry and Molecular Biology.)

Activating KRAS mutations in lung adenocarcinoma are characterized with treatment resistance and poor prognosis. As a small molecule inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase, apatinib has been proven successful in advanced gastric cancer and breast cancer. In this study, we show the result of apatinib as salvage treatment in lung adenocarcinoma patients with KRAS mutation. Four advanced lung adenocarcinoma patients with KRAS mutation were orally administered apatinib (250 mg/d) after second-line treatment. One patient showed progressive disease, while 3 patients showed stable disease response to apatinib, with a median progression-free survival (PFS) of 3.8 months (1.5-5.5 months). The main toxicities were hoarseness and hemoptysis, which were manageable. Therefore, apatinib might be an optional choice for advanced lung adenocarcinoma patients with KRAS mutation in post second-line treatment., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Autism spectrum disorders (ASDs) are a class of severe and chronic conditions and core symptoms are deficits in social interaction, language communication impairments, and repetitive/stereotyped behavior. Given the limitations of available treatments and substantially increased prevalence of the disease, additional interventions are needed. Since the use of dietary supplements for ASD is of high prevalence, up-to-date information about those supplements are required for both parents and clinicians. Relevant articles were identified through a systematic search of PubMed, EMBASE, Cochrane library, and PsychINFO databases (through May 2017). Current best evidences of 22 randomized controlled trials on 8 different dietary supplements for core symptoms of ASD were reviewed. For each supplement, this report focuses on the definition and potential therapeutic mechanisms, the latest advances, and discussion of study limitations and future directions. Most studies were small and short term, and there is little evidence to support effectiveness of dietary supplements for children with ASD.

Chemotherapy is the standard treatment of in advanced lung adenocarcinoma patients without driver mutation. However, few drugs could be selected when diseases progressed after second-line treatment. As a small molecule inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-2), apatinib was suggested mainly using in advanced gastric cancer. In this study, we showed the results of apatinib as second-line to fourth-line treatment in EGFR wild-type advanced lung adenocarcinoma patients. 16 EGFR wild-type advanced lung adenocarcinoma patients were administrated apatinib (250-500 mg/d) orally. 3 patients showed partial response and 8 patients showed stable diseases response to apatinib, with a medium progression-free survival (PFS) of 4.4 month (2-10 months). The objective remission rate (ORR) was 18.75%(3/16). The total disease control rate (DCR) was 68.75% (11/16). The main toxicities were hypertension, hand-foot syndrome, proteinuria and thrombocytopenia which were tolerable and manageable. So, apatinib might be an optional choice for post-first-line treatment of EGFR wild-type advanced lung adenocarcinoma patients., Competing Interests: CONFLICTS OF INTEREST The authors declared no conflicts of interest.

Background: Invasive fungal infection (IFI) is one of the leading causes of early death after renal transplantation. Voriconazole (VRC) is the first-line drug of IFI. Because of the large inter- and intraindividual variability in VRC plasma concentrations and the narrow therapeutic window for treating patients with IFIs, it is crucial to study the factors which could influence pharmacokinetic variability. We performed a population pharmacokinetics (PPK) study of VRC for personalized medicine., Methods: A total of 125 trough concentrations (Cmin) from 56 patients were evaluated, retrospectively. Nonlinear mixed effect model was used to describe a PPK model that was internally validated by bootstrap method. Potential covariates included demographic characteristics, physiological and pathological data, concomitant medications, and CYP2C19 genotype., Results: A 1-compartment model with first-order absorption and elimination was fit to characterize the VRC pharmacokinetics in renal transplant recipients (RTRs). Aspartate aminotransferase (AST) had a significant influence on clearance (CL) while CYP2C19 genotype had a major impact on the volume of distribution (V). The parameters of CL and V were 4.76 L/h and 22.47 L, respectively. The final model was V (L) = 22.47 × [1 + 2.21 × (EM = 1)] × [1 + 4.67 × (IM = 1)] × [1 + 3.30 × (PM = 1)] × exp (0.96); CL (L/h) = 4.76 × (AST/33)^(-0.23) × exp (0.14). VRC Cmin in intermediate metabolizers was significantly higher than in extensive metabolizers., Conclusions: Liver function and CYP2C19 polymorphism are major determinants of VRC pharmacokinetic variability in RTRs. Genotypes and clinical biomarkers can determine the initial scheme. Subsequently, therapeutic drug monitoring can optimize clinical efficacy and minimize toxicity. Hence, this is a feasible way to facilitate personalized medicine in RTRs. In addition, it is the first report about PPK of VRC in RTRs.

Objective: To observe the effect of S100A4 gene silencing mediated by small interfering RNA (siRNA) on the proliferation of bladder cancer stem cells (CSCs) and their capacity of xenograft tumor formation., Methods: MB49 bladder cancer stem cells (MCSCs) were isolated and identified. The differentially expressed protein S100A4 was identified in MCSCs using isobaric tags for relative and absolute quantitation technology (iTRAQ). A siRNA targeting S100A4 was constructed and transfected into MCSCs, and its inhibitory effects on S100A4 expression in MCSCs were assessed with Western blotting and qPCR. The effects of siRNA-mediated S100A4 silencing on the proliferation and xenograft tumor formation ability of MCSCs were observed., Results: Among the 65 differentially expressed proteins identified by iTRAQ combined with LC/MS/MS, S100A4 protein showed the most distinct differential expression in MCSCs. Transfection of MCSCs with S100A siRNA significantly inhibited the expressions of S100A4 at both mRNA and protein levels, caused obvious suppression of the cell proliferation, and attenuated the xenograft tumor formation ability of the cells in nude mice., Conclusion: S100A4 in MCSCs is associated with the recurrence and metastasis of bladder cancer. S100A4 may serve as a potential therapeutic target for eliminating bladder CSCs.

Potassium channels are the targets of antiepileptic drugs (AEDs), which play important roles in the etiology of epilepsy. KCNA1 and KCNA2 encode mammalian Kv1.1 and Kv1.2 channels, which are essential roles in the initiation and shaping of action potentials. KCNV2 encodes Kv8.2, which is a regional overlap with Kv2 subunits as functional heterotetramers. In our study, we aim to investigate whether variants of KCNA1, KCNA2, and KCNV2 genes influence susceptibility to genetic generalized epilepsies (GGEs) and the efficacy of AEDs. Seven hundred sixty-seven subjects (284 healthy controls, 279 drug-responsive, and 204 drug-resistant GGE patients) were enrolled in our study. Eight variants of KCNA1, KCNA2, and KCNV2 were assessed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry method. Results showed that there were no statistically significant correlations between the 8 variants of KCNA1, KCNA2, and KCNV2 and the risk/drug resistance of GGEs. In conclusion, our study suggests that KCNA1, KCNA2, and KCNV2 variants may not be involved in the risk/drug resistance of GGEs. Further multicenter, multiethnic, and large sample size pharmacogenetic and case-control studies are warranted to confirm our negative results.

Icotinib is a novel and the third listed epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), which exerts a good anti-tumor efficacy on non-small cell lung cancer (NSCLC). The efficacy of EGFR-TKIs has been shown to be associated with the EGFR mutation status, especially exon 19 deletion (19Del) and exon 21 L858R mutation. Therefore, a meta-analysis was performed to assess the efficacy of icotinib in NSCLC patients harboring EGFR mutations (19Del or L858R) and wild type (19Del and L858R loci wild type). A total of 24 studies were included for comparing the objective response rate (ORR) in the EGFR wild type and mutant patients treated with icotinib. The ORRs of EGFR mutant patients (19Del or L858R) are better than those of EGFR wild type patients (OR = 7.03(5.09-9.71), P < 0.00001). The pooling ORs from 21 studies on the disease control rate (DCR) in EGFR mutant patients are better than those of EGFR wild type patients (OR = 10.54(5.72-19.43), P < 0.00001). Moreover, the ORRs of EGFR 19Del patients are better than those of EGFR L858R patients after pooling ORs of 12 studies (OR = 2.04(1.12-3.73), P = 0.019). However, there was no significant difference on DCRs of EGFR 19Del patients and those of EGFR L858R patients (OR = 2.01(0.94-4.32), P = 0.072). Our findings indicated that compared with EGFR wild type patients, EGFR mutant patients have better ORRs and DCRs after icotinib treatment; EGFR 19Del patients treated with icotinib have better ORRs than EGFR L858R patients. EGFR mutation status is a useful biomarker for the evaluation of icotinib efficacy in NSCLC patients.

Optical manipulation and label-free characterization of nanoscale structures open up new possibilities for assembly and control of nanodevices and biomolecules. Optical tweezers integrated with Raman spectroscopy allows analyzing a single trapped particle, but is generally less effective for individual nanoparticles. The main challenge is the weak gradient force on nanoparticles that is insufficient to overcome the destabilizing effect of scattering force and Brownian motion. Here, we present standing-wave Raman tweezers for stable trapping and sensitive characterization of single isolated nanostructures with a low laser power by combining a standing-wave optical trap with confocal Raman spectroscopy. This scheme has stronger intensity gradients and balanced scattering forces, and thus can be used to analyze many nanoparticles that cannot be measured with single-beam Raman tweezers, including individual single-walled carbon nanotubes (SWCNT), graphene flakes, biological particles, SERS-active metal nanoparticles, and high-refractive semiconductor nanoparticles. This would enable sorting and characterization of specific SWCNTs and other nanoparticles based on their increased Raman fingerprints.

The antibacterial agent helvolic acid, which was isolated from the active antitumor fraction of Cordyceps taii, showed potent cytotoxicity against different human cancer cells. In the present study, the in vivo antitumor effect of helvolic acid was investigated in murine sarcoma S180 tumor-bearing mice. Doses of 10 and 20 mg/kg/day helvolic acid did not exert significant antitumor activity. Interestingly, co-administration of 10 mg/kg/day helvolic acid and 20 mg/kg/day cyclophosphamide (CTX) - a well-known chemotherapy drug - showed promising antitumor activity with a growth inhibitory rate of 70.90%, which was much higher than that of CTX alone (19.5%). Furthermore, the combination markedly prolonged the survival of tumor-bearing mice. In addition, helvolic acid enhanced the immune organ index. The protein expression levels of β-catenin, cyclin D1, and proliferating cell nuclear antigen were significantly suppressed in mice treated with 20 mg/kg/day helvolic acid and in those receiving combination therapy. Taken together, these results indicated that helvolic acid in combination with CTX showed potent in vivo synergistic antitumor efficacy, and its mechanism of action may involve the Wnt/ β-catenin signaling pathway.

To investigate the potential role of nuclear factor erythroid 2-related factor 2 (Nrf2) in licorice ethanol extract (LEE) against triptolide- (TP-) induced hepatotoxicity, HepG2 cells were exposed to LEE (30, 60, and 90 mg·L -1 ) for 12 h and then treated with TP (50 nM) for 24 h. Besides, an acute liver injury model was established in ICR mice by a single dose of TP (1.0 mg·kg -1 , i.p.). Relevant oxidant and antioxidant mediators were analyzed. TP led to an obvious oxidative stress as evidenced by increasing levels of ROS and decreasing GSH contents in HepG2 cells. In vitro results were likely to hold true in in vivo experiments. LEE protected against TP-induced oxidative stress in both in vitro and in vivo conditions. Furthermore, the decreased level of Nrf2 in the TP-treated group was observed. The mRNA levels of downstream genes decreased as well in ICR mice liver, whereas they increased in HepG2 cells. In contrast, LEE pretreatment significantly increased the level of Nrf2 and its downstream genes. LEE protects against TP-induced oxidative stress partly via the activation of Nrf2 pathway.

Local excision is an alternative to radical surgery that is indicated in patients with locally advanced rectal cancer (LARC) who have a good response to chemoradiotherapy (CRT). Regional lymph node status is a major uncertainty during local excision of LARC following CRT. We retrospectively reviewed clinicopathologic variables for 244 patients with LARC who were treated at our institute between December 2000 and December 2013 in order to identify independent predictors of regional lymph node metastasis. Multivariate analysis of the training sample demonstrated that histopathologic type, tumor size, and the presence of lymphovascular invasion were significant predictors of regional nodal metastasis. These variables were then incorporated into a scoring system in which the total scores were calculated based on the points assigned for each parameter. The area under the curve in the receiver operating characteristic analysis was 0.750, and the cutoff value for the total score to predict regional nodal metastasis was 7.5. The sensitivity of our system was 73.2% and the specificity was 69.4%. The sensitivity was 77.8% and the specificity was 51.2% when the scoring system was applied to the testing sample. Using this system, we could accurately predict regional nodal metastases in LARC patients following CRT, which may be useful for stratifying patients in clinical trials and selecting potential candidates for organ-sparing surgery following CRT for LARC.

This study investigated the pro-proliferative effect of hyaluronic acid (HA) on human amniotic mesenchymal stem cells (hAMSCs) and the underlying mechanisms. Treatment with HA increased cell population growth in a dose- and time-dependent manner. Analyses by flow cytometry and immunocytochemistry revealed that HA did not change the cytophenotypes of hAMSCs. Additionally, the osteogenic, chondrogenic, and adipogenic differentiation capabilities of these hAMSCs were retained after HA treatment. Moreover, HA increased the mRNA expressions of wnt1, wnt3a, wnt8a, cyclin D1, Ki-67, and β-catenin as well as the protein level of β-catenin and cyclin D1 in hAMSCs; and the nuclear localization of β-catenin was also enhanced. Furthermore, the pro-proliferative effect of HA and up-regulated expression of Wnt/β-catenin pathway-associated proteins - wnt3a, β-catenin and cyclin D1 in hAMSCs were significantly inhibited upon pre-treatment with Wnt-C59, an inhibitor of the Wnt/β-catenin pathway. These results suggest that HA may positively regulate hAMSCs proliferation through regulation of the Wnt/β-catenin signaling pathway., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Isoliquiritigenin, a flavonoid found in licorice, has been considered as an antioxidive and hepato-protective agent. Recent studies have shown that a possible mechanism for triptolide-induced hepatotoxicity is related to oxidative damage induced by reactive oxygen species. This study was done to investigate the protection effect of isoliquiritigenin against triptolide-induced hepatotoxicity and the mechanism involved. An acute liver injury model was established by intraperitoneal injection of triptolide (1.0 mg · kg-1) in mice. Different doses of isoliquiritigenin (12.5, 25 and 50 mg · kg-1) were employed as protection. The activities of AST, ALT, ALP and LDH in serum and levels of GSH, GPx, SOD, CAT and MDA in liver tissue were detected. The histopathological changes of liver tissues were observed after HE staining. The protein expression of Nrf2 was detected by western blot. Pretreatment with isoliquiritigenin significantly prevented the triptolide-induced hepatotoxicity indicated by reduced activities of AST, ALT, ALP and LDH. Moreover, isoliquiritigenin pretreatment also prevented from triptolide-induced hepatotoxicity by inhibiting MDA and restoring the levels of GSH, GPx, SOD and CAT. In addition, isoliquiritigenin could attenuate histopathological changes induced by triptolide. Furthermore, the results indicated that isoliquiritigenin pretreatment caused an increase in the protein expression of Nrf2. These results indicated that isoliquiritigenin could protect against triptolide-induced hepatotoxicity via activation of the Nrf2 pathway.

Non-small cell lung cancer (NSCLC) patients with activating epidermal growth factor receptor (EGFR) mutations initially respond well to the EGFR tyrosine kinase inhibitors (TKIs) erlotinib and gefitinib. However, clinical efficacy is limited by the development of resistance. In most cases, this resistance is in the form of the T790M mutation. Here, we report the design, synthesis and biochemical evaluation of a novel series of irreversible EGFR tyrosine kinase inhibitors (EGFR-TKIs) that are derived from the anilinoquinazoline scaffold. Guided by molecular modeling, this series of analogs was evolved to target a cysteine residue in the ATP binding site via covalent bond formation and to achieve high levels of anti-tumor activity in cell cultures and in xenografts. The most promising compound 13c ((E) -N - (4 - (4 - (3-fluorobenzyloxy) -3- chlorophenylamino) -7-ethoxyquinazolin-6-yl) -3- ((S) -pyrrolidin-2-yl)acrylamide, which we named Transtinib) displayed strong anti-proliferative activity against the H1975 and A431 cell lines with IC50 values of 34 nM and 62 nM, respectively. In xenograft models, Transtinib significantly decreases tumor size for a prolonged period of time. These results suggest that Transtinib is a potential cancer therapeutic drug lead for the inhibition of mutant EGFR to overcome the development of resistance., Competing Interests: The authors declare no conflicts of interest.

A strategic selection of tree species will shift the type and quality of litter input, and subsequently magnitude and composition of the soil organic carbon (SOC) through soil microbial community. We conducted a manipulative experiment in randomized block design with leaf litter inputs of four native subtropical tree species in a Pinus massoniana plantation in southern China and found that the chemical composition of SOC did not differ significantly among treatments until after 28 months of the experiment. Contrasting leaf litter inputs had significant impacts on the amounts of total microbial, Gram-positive bacterial, and actinomycic PLFAs, but not on the amounts of total bacterial, Gram-negative bacterial, and fungal PLFAs. There were significant differences in alkyl/O-alkyl C in soils among the leaf litter input treatments, but no apparent differences in the proportions of chemical compositions (alkyl, O-alkyl, aromatic, and carbonyl C) in SOC. Soil alkyl/O-alkyl C was significantly related to the amounts of total microbial, and Gram-positive bacterial PLFAs, but not to the chemical compositions of leaf litter. Our findings suggest that changes in forest leaf litter inputs could result in changes in chemical stability of SOC through the altered microbial community composition.

The purpose of this study was to prepare Brucea javanica oil cationic nanoemulsions (BJO-CN) with BJO as drug as well as oil phase and chitosan as cationic inducer, to explore the practical suitability of using cationic nanoemulsions for oral delivery of mixed oil, and to test its bioavailability and antitumor effect. BJO-CN was prepared by chitosan solution stirring method and then characterized physicochemically. The obtained BJO-CN had a spherical morphology with a positive zeta potential of 18.9 mV and an average particle size of 42.36 nm, showing high colloidal stability. The drug loading of BJO-CN was 91.83 mg·mL(-1), determined by high-performance liquid chromatography with precolumn derivatization. Pharmacokinetic studies revealed that, compared with BJO emulsion (BJO-E) (the dosage of BJO-CN and BJO-E was equal to 505 mg·kg(-1), calculated by oleic acid), BJO-CN exhibited a significant increase in the area under the plasma drug concentration-time curve over the period of 24 hours and relative bioavailability was 1.6-fold. Furthermore, the antitumor effect of BJO-CN in the orthotopic mouse model of lung cancer was evaluated by recording the median survival time and the weight of lung tissue with tumor, hematoxylin and eosin staining, and immunohistochemical technique. Results of anticancer experiments illustrated that, even though the administrated dosage in the BJO-CN group was half of that in the BJO-E group, BJO-CN exhibited similar antitumor effect to BJO-E. Moreover, BJO-CN had good synergistic effect in combination therapy with vinorelbine. These results suggested that cationic nanoemulsions are an effective and promising delivery system to enhance the oral bioavailability and anticancer effect of BJO.

MicroRNAs are highly conserved non-coding RNAs that regulate gene expression at the post-transcriptional level, and play pivotal roles in cancer development and progression. miR-100 has been reported to be significantly downregulated in a variety of cancers, including esophageal cancer. However, the role of miR-100 in human esophageal cancer has not been fully elucidated. We demonstrated that overexpression of miR-100 in esophageal cancer cells markedly inhibited cell proliferation, migration and invasion as well as tumor growth. We subsequently showed that CXCR7 is a direct target gene of miR-100. Our results indicated that miR-100 plays a tumor-suppressor role in esophageal cancer and suggest its potential application for esophageal cancer treatment.

Spontaneous axonal regeneration of neurons does not occur after spinal cord injury because of inhibition by myelin and other inhibitory factors. Studies have demonstrated that blocking the Rho/Rho-kinase (ROCK) pathway can promote neurite outgrowth in spinal cord injury models. In the present study, we investigated neurite outgrowth and neuronal differentiation in neural stem cells from the mouse subventricular zone after inhibition of ROCK in vitro. Inhibition of ROCK with Y-27632 increased neurite length, enhanced neuronal differentiation, and upregulated the expression of two major signaling pathway effectors, phospho-Akt and phospho-mitogen-activated protein kinase, and the Hippo pathway effector YAP. These results suggest that inhibition of ROCK mediates neurite outgrowth in neural stem cells by activating the Hippo signaling pathway.

A field experiment was conducted on fluvo-aquic soil in the North China Plain to study the effects of nitrogen application rate on soil nitrogen contents and enzyme activities in rhizosphere and non-rhizosphere of summer maize. The results showed that the soil enzyme activities under different nitrogen application rates showed similar seasonal patterns. In comparison to no nitrogen ferti-lizer treatment, all nitrogen application treatments significantly increased NO 3 - -N contents in rhizosphere and non-rhizosphere soils, NH 4 + -N content in rhizosphere soil and the activities of β-N-acetylglucosaminidase, β-glucosidase, β-xylosidase and Cellobiohyrolase. During the whole summer maize growing season, the NO 3 - -N content in non-rhizosphere soil was significantly higher than that in rhizosphere soil. The NH 4 + -N content in non-rhizosphere soil was also significantly higher than that in rhizosphere soil at filling stage but significantly lower at seedling and maturity stages. Furthermore, soil enzyme activities in rhizosphere soil were significantly higher than those in non-rhizosphere soil. Effect of nitrogen application on soil organic carbon content was not significant. Soil total nitrogen content increased significantly when the nitrogen application rate was 0-180 kg·hm -2 but decreased significantly when the rate was higher than 180 kg·hm -2 . Generally, a proper rate of nitrogen fertilizer application could significantly increase soil enzyme activities and total nitrogen content, and then improve soil biochemistry properties.

Background: The marine diatom, Phaeodactylum tricornutum, has become a model for studying lipid metabolism and its triacylglycerol (TAG) synthesis pathway makes it an ideal target for metabolic engineering to improve lipid productivity. However, the genetic background and metabolic networks of fatty acid biosynthesis in diatoms are not well understood. Glycerol-3-phosphate acyltransferase (GPAT) is the critical enzyme that catalyzes the first step of TAG formation. So far, characterization of GPAT in marine microalgae has not been reported, especially at the level of comprehensive sequence-structure and functional analysis., Results: A GPAT was cloned from P. tricornutum and overexpressed in P. tricornutum. Volumes of oil bodies were produced and the neutral lipid content was increased by twofold determined by Nile red fluorescence staining. Fatty acid composition was analyzed by GC-MS, which showed significantly higher proportion of unsaturated fatty acids compared to wild type., Conclusion: These results suggested that the identified GPAT could upregulate TAG biosynthesis in P. tricornutum. Moreover, this study offers insight into the lipid metabolism of diatoms and supports the role of microalgal strains for biofuels production.

Objective: This study aimed to evaluate fluorine-18 fludeoxyglucose positron emission tomography-CT ((18)F-FDG PET-CT) for the diagnosis, targeted biopsy and therapy of relapsing polychondritis (RP)., Methods: The literature pertaining to the use of (18)F-FDG PET-CT in patients with RP was retrieved from the Cochrane Library, PubMed, Excerpta Medica Database (EMBASE), China National Knowledge Infrastructure (CNKI) and Wanfang databases until July 2015. Clinical characteristics, auxiliary examination results, chest CT findings, tracheoscopy and biopsy findings, high metabolic activity lesions, maximum standardized uptake values, (18)F-FDG PET-CT-guided biopsy site, pathologic results of biopsy samples and alteration in high (18)F-FDG-uptake lesions after treatment were retrospectively analysed., Results: 18 publications with 26 cases were enrolled. The five most common symptoms of patients with RP diagnosed with (18)F-FDG PET-CT were cough, fever, chest tightness, sore throat and arthralgia. Of the 26 patients, 23 patients had multiple and symmetric cartilage lesions with high metabolic activity, revealed by (18)F-FDG PET-CT. The disease mainly affected organs such as the bronchus, trachea, throat, costicartilage and auricle. The maximum standardized uptake values ranged from 1.93 to 13.03 (mean, 4.94). (18)F-FDG PET-CT revealed that patients with RP with tracheal and bronchial involvement had a close correlation with cough (χ(2) = 6.80, p = 0.006). (18)F-FDG PET-CT showed a significantly higher positive biopsy rate compared with bronchoscopy (χ(2) = 12.91, p < 0.001) for targeted lesions with high metabolic activity. Post-treatment re-examinations with (18)F-FDG PET-CT showed obvious subsidence or complete disappearance of high (18)F-FDG-uptake lesions in 13 cases, showing highly consistent symptom improvements., Conclusion: (18)F-FDG PET-CT is likely to become a valuable imaging tool in the diagnosis and treatment of RP., Advances in Knowledge: The presence of symmetrically distributed high FDG-uptake lesions may be a criterion for the diagnosis of RP. (18)F-FDG PET-CT is useful for targeting biopsy sites, which remarkably increase the positive biopsy rate. Therefore, (18)F-FDG PET-CT may be of great value in the diagnosis and treatment of RP.

Aims: As a transcription factor of the nuclear receptor superfamily, neuron-derived orphan receptor 1 (NOR1) is induced rapidly in response to various extracellular stimuli. But, it is still unclear its role in pulmonary artery smooth muscle cells proliferation., Materials and Methods: Human PASMCs were cultured in vitro and stimulated by serum. The special antisense oligodeoxynucleotides (AS-ODNs) were used to knockdown human NOR1 gene expression. Real-time PCR and Western-blot were used to evaluate the gene expression and protein levels., Results: Fetal bovine serum (FBS) induced human PASMCs proliferation in a dose dependent manner. Furthermore, FBS promoted NOR1 gene expression in a dose dependent manner and a time dependent manner. 10% FBS induced a maximal NOR1 mRNA levels at 2 h. FBS also induced a significant higher NOR1 protein levels as compared with control. The NOR1 over-expressed plasmid significantly promoted DNA synthesis and cells proliferation. Moreover, the special AS-ODNs against human NOR1 not only prevented NOR1 expression but also inhibited DNA synthesis and cells proliferation significantly. The NOR1 over-expression plasmid could up-regulate cyclin D1 expression markedly, but the AS-ODNs inhibited cyclin D1 expression significantly., Conclusion: So, we concluded that NOR1 could promote human PASMCs proliferation. Cyclin D1 might be involved in this process.

9,10-Distyrylanthracene has been introduced to bridge two pillarenes to form a dimeric host, which can assemble into a linear supramolecular polymer upon cooperatively binding to a neutral guest linker, exhibiting yellow fluorescence emission in solution and solid states.

Background: Traditionally, conventional intersphincteric resection requires a combined abdominal and perineal approach and a handsewn coloanal anastomosis procedure, which is difficult to accomplish via the perineal approach. A completely abdominal approach partial intersphincteric resection (APISR) with laparoscopy can simplify the anastomosis procedure. This study evaluated the intermediate-term oncological and functional results of laparoscopic versus open APISR for low rectal cancer., Methods: A total of 137 consecutive patients with low rectal cancer who underwent APISR from January 2006 to August 2013 were retrospectively evaluated. Patient groups were classified into as open surgery (OP, n = 48) group and laparoscopy (LAP, n = 89). The primary endpoint was 3-year disease-free survival and the Wexner score for anal function., Results: The LAP group had longer operating time, less intraoperative blood loss, and shorter hospital stay after surgery compared with the OP group. Median follow-up was 32.3 months. The local recurrence rates were similar in the two groups (LAP 3.2% vs. OP 6.1%; P = 0.652). The combined 3-year disease-free survival rate was 83.2% in the LAP group and 83.8% in the OP group (P = 0.857). Wexner scores were similar in the two groups (LAP 2.9 ± 4.5 vs. OP 3.1 ± 5.0). In the LAP group, 89.7% of patients had good continence compared with 91.4% in the OP group (P = 0.311)., Conclusions: Laparoscopic APISR can be performed safely and offers similar intermediate-term oncological and functional outcome compared with the open procedure. The oncological adequacy requires long-term follow-up data.

Spurred on by recent advances in materials chemistry and drug delivery, a new stimuli-responsive theranostic hybrid platform, based on mechanized monodisperse nano metal-organic frameworks (NMOFs) gated by carboxylatopillar[5]arene (CP5) switches with bio-friendly pH-triggered cargo release capabilities, has been constructed for the first time. This nanoscale smart cargo delivery system showed pH- and/or competitive binding agent-triggered controlled cargo release with negligible premature release, large pore sizes for drug encapsulation, low cytotoxicity, good biodegradability and biocompatibility, and potential application in cell imaging, which offers a new tool in targeted drug delivery and the controlled release of therapeutic agents.

Cigarette smoking contributes to the development of pulmonary hypertension (PH) complicated with chronic obstructive pulmonary disease (COPD), and the pulmonary vascular remodeling, the structural basis of PH, could be attributed to abnormal proliferation of pulmonary artery smooth muscle cells (PASMCs).In this study, morphometrical analysis showed that the pulmonary vessel wall thickness in smoker group and COPD group was significantly greater than in nonsmokers. In addition, we determined the expression patterns of connective tissue growth factor (CTGF) and cyclin D1 in PASMCs harvested from smokers with normal lung function or mild to moderate COPD, finding that the expression levels of CTGF and cyclin D1 were significantly increased in smoker group and COPD group. In vitro experiment showed that the expression of CTGF, cyclin D1 and E2F were significantly increased in human PASMCs (HPASMCs) treated with 2% cigarette smoke extract (CSE), and two CTGF siRNAs with different mRNA hits successfully attenuated the upregulated cyclin D1 and E2F, and significantly restored the CSE-induced proliferation of HPASMCs by causing cell cycle arrest in G0. These findings suggest that CTGF may contribute to the pathogenesis of abnormal proliferation of HPASMCs by promoting the expression of its downstream effectors in smokers with or without COPD.

A laser induced breakdown spectroscopy experiment was carried out using Nd:YAG laser in air, and time-resolved spectra were measured. Based on local thermodynamic equilibrium assumption, a method used to simulate LIBS spectra is proposed. A LIBS spectrum of air in the wavelength range of 700~900 nm was simulated using this method. A good agreement between experiment and simulation was obtained, and moreover, the relative concentrations of the N, O and Ar in air were obtained.

Objective: To retrospectively analyze the epidemiological characteristics of pediatric bedside stove burns (PBSB) in China and to explore prevention and control measures., Methods: Data on pediatric burns from three hospitals located in the epidemic area were collected from January 1996 to December 2010 and were divided into the PBSB group and the control group. The epidemiological characteristics and related information for each patient were analyzed., Results: A total of 16,595 pediatric burns were found, including 5089 PBSB and 11,506 other types of burns. The two groups differed significantly in terms of age, gender, body parts burned, degree of burn, delay of hospitalization, and treatment measures (Ps all<0.05). Risk factors for PBSB included being younger than 3 years old, living in a rural area, low literacy level of guardians, not receiving health education, and lack of a protective fence protection (Ps all<0.05). Furthermore, meal time and winter and spring seasons were high risk periods for PBSB., Conclusion: The risk factors for PBSB include age, region, time of occurrence, and literacy level of guardians. Health education and installation of a protective fence between the stove and the bed could reduce the incidence of PBSB., (Copyright © 2014 Elsevier Ltd and ISBI. All rights reserved.)

Objective: To explore the value of (18)F-fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) combined with transbronchial needle aspiration (TBNA) in diagnosing atypical relapsing polychondritis (RP)., Methods: Data from two patients with atypical RP, which had been diagnosed in our hospital using FDG PET-CT combined with TBNA, were retrospectively analyzed. A review of the relevant literature was also performed., Results: Consistent with the previously reported 20 cases of RP that had been diagnosed using FDG PET-CT, the two patients in the present study showed the involvement of multiple organs, including the nose, throat, trachea, bronchi, costicartilage and joint cartilages, and increased FDG uptake was found in these areas. The mean value of SUVmax was 5.14. PET-CT revealed that 86.4% of the patients with RP had airway involvement. TBNA technique was used for biopsy of the hypermetabolic lesions, and pathologic examinations confirmed the diagnosis of RP. The time to diagnosis in these two patients and the 20 cases reported previously was about 6.9 months, significantly shorter than the average diagnosis time (20 months)., Conclusions: FDG PET-CT has several advantages for diagnosing RP, especially atypical RP. TBNA is a minimally invasive and safe technique for obtaining airway cartilage. Combining PET-CT with TBNA may play an important role in shortening the time to diagnosis in patients with RP involvement of airway.

A tetraphenylethene-bridged pillarene tetramer with aggregation-induced emission properties forms an A4/B2-type supramolecular polymer and a gel with a symmetric neutral guest linker, showing a remarkable fluorescence emission enhancement in solution and the solid state and a good responsiveness to temperature and solvent composition.

Background: The purpose of this study was to explore the effectiveness and safety of three-dimensional (3D) digitalized planning for the sural neurovascular island flap in repair of soft tissue defects in the ankle and foot., Methods: This study included 40 patients with soft tissue defects of the ankle and foot who underwent soft tissue reconstruction between October 2008 and June 2012. The patients were randomly assigned into two groups: 3D-reconstruction group (Group A, n=20) and control group (Group B, n=20). Three-dimensional, digitalized virtual planning was performed in the patients in Group A, who underwent computed topographic angiography. The survival rate, operation time, and surgical accuracy were compared between the two groups., Results: All flaps in Group A survived and the recipient site primarily healed, but 4 flaps in Group B had marginal necrosis after the operation. During the 6-12 month follow-up period, all flaps in Group A had good skin quality. In Group B, hard scarring and mild contracture occurred in 4 cases, and the patients experienced pain when walking. The survival rate of the flap in Group A (100%) was significantly higher than in Group B (70%). The operation time in Group A was significantly less than in Group B. The surgical accuracy in Group A was significantly better than in Group B., Conclusion: The preoperative use of 3D digitalized virtual planning for the sural neurovascular island flap improves the surgical accuracy, decreases the operation time, and increases the survival rate of the flap., Clinical Question/level of Evidence: Therapeutic III., (Copyright © 2013 Elsevier Ltd and ISBI. All rights reserved.)

To make a thorough investigation of the common She's nationality wild medicinal plants resources in our country, including the species, the distribution, the folk application and the endemic medicinal plant species, Field surveyed was conducted with 25 She people mainly lived area (county, district or city) throughout the country, the folk prescription and treatment cases provided by She's medical personnel, the drug usage and dosage, the commonly used traditional She's medicine and drug samples were collected. And the distribution, growing environment of these plants were investigated, their characteristics, photographs, GPS data and track were record , and the fresh wax leaf or plants specimens were collected. In total 1 600 varieties of folk medicine of She's nationality, 450 disease names and 1 016 prescriptions were collected. 520 kinds of these medicinal plants were commonly used, growing mainly distributed in the southeastern China, about 200 meters above sea level to 1 500 meters. There are 5 First-Grade State protection wild plants (medicinal), 15 second-Grade State protection wild plants (medicinal), and 11 She characteristic medicinal plants in our study, they belong to 144 families, 312 genera 494 species, 2 subspecies, 17 varieties, 3 forms and 1 cultivated varieties of She's nationality. Folk medicine usage is different from the traditional Chinese medicine and ethnic medicine. This survey finds out the common She's nationality wild medicinal plants resources in China, including the species, the distribution, the folk application and commonly used drugs, and found the rare and endangered medicinal plants and the She's nationality endemic medicinal plants, which provides a basis for further development and use the traditional She's medicine resources.

Soil aggregate stability and microbial diversity play important roles in nutrient recycling in soil-crop systems. This study investigated the impacts of different soil tillage systems on soil aggregation and soil microbial diversity based on a 15-year long-term experiment on loess soil in Henan Province of China. Treatments included reduced tillage (RT), no-tillage (NT), sub-soiling with mulch (SM), wheat-peanut two crops (TC), and conventional tillage (CT). Soil aggregates were separated by wet sieving method, and soil microbial (bacterial, archaeal and fungal) diversity was examined by using the techniques of denaturing gradient gel electrophoresis (PCR-DGGE) analysis. The results showed that water-stable macroaggregates concent (R0.25) and the mean mass diameter (MWD) in the surface soil significantly increased under NT, SM and TC, R0.25 increased by 21.5%, 29.5% and 69.2%, and MWD increased by 18.0%, 12.2% and 50.4%, respectively, as compared with CT. Tillage practices caused changes in bacterial, archaeal and fungal community compositions. With NT, SM and TC, the bacterial, archaeal and fungal Shannon indices increased by 0.3%, 0.3%, and 0.6%, and 20.2%, 40.5%, and 49.1%, and 23.7%, 19.5%, and 25.8%, respectively, as compared with CT. Both bacterial and archaeal Shannon indices were significantly correlated with the indices of R0.25 and MWD, while the fungal Shannon index was not significantly correlated with these two indices. In conclusion, conservation tillage, including NT and SM, and crop rotation, including TC, improved soil aggregation and soil microbial diversity.

Objective: To investigate whether the expression of OX40/OX40 ligand (OX40L) was upregulated in a murine model of asthma and their significance in the pathogenesis of asthma., Methods: After an ovalbumin-sensitized/challenged murine model of asthma was established, the expressions of OX40, OX40L in peripheral blood mononuclear cells (PBMCs) and bronchoalveolar lavage fluid (BALF) cell pellets were measured. Then T cell proliferation was analyzed by cell counting kit-8 (CCK8), and the protein levels of OX40 and OX40L in the lungs were determined by immunohistochemistry. The concentrations of IL-4 and IFN-γ in BALF and T cell culture supernatant were evaluated by ELISA., Results: The percentages of CD4(+)OX40(+), CD19(+)OX40L(+), F4/80(+)OX40L(+) in PBMCs and BALF cell pellets were higher in asthma group than in control group (all P<0.01). The proliferation capacity of T cells in asthma group was higher than that in control group (P<0.05). In asthma group, stimulation of OX40 by anti-OX40 mAb obviously promoted T cell proliferation and secretion of IL-4 and IFN-γ. Immunohistochemistry assay showed that OX40 and OX40L protein levels were higher in asthma group than those in control group (all P<0.05)., Conclusions: The expressions of OX40 and OX40L were upregulated in the murine asthmatic model. The upregulation of OX40/OX40L signals could induce the proliferation and cytokines secretion of T cells in asthmatic mice, indicating that OX40/OX40L signal was involved in the pathogenesis of asthma.

Objective: To investigate the effect of the spinal cord extracts (SCE) after spinal cord injuries (SCIs) on the proliferation of rat embryonic neural stem cells (NSCs) and the expressions of mRNA of Notch1 as well as of Hes1 in this process in vitro., Methods: The experiment was conducted in 4 different mediums: NSCs+PBS (Group A-blank control group), NSCs+SCE with healthy SD rats (Group B-normal control group), NSCs+SCE with SD rats receiving sham-operation treatment (Group C-sham-operation group) and NSCs+ SCE with SCIs rats (Group D-paraplegic group). Proliferative abilities of 4 different groups were analyzed by MTT chromatometry after co-culture for 1, 2, 3, 4 and 5 d, respectively. The expressions of Notch1 and Hes1 mRNA were also detected with RT-PCR after co-culture for 24 and 48 h, respectively., Results: After co-culture for 1, 2, 3, 4 and 5 d respectively, the MTT values of group D were significantly higher than those of group A, group B and group C (P<0.05). However, there were no significantly differences regarding MTT values between group A, group B and group C after co-culture for 1, 2, 3, 4 and 5 d, respectively (P>0.05). Both the expressions of Notch1 and Hes1 mRNA of group D were significantly higher than those of other 3 groups after co-culture for 24 h and 48 h as well (P<0.05). But there was no difference oin expressions of Notch1 and Hes1 mRNA among group A, group B and group C after co-culture for 24 h and 48 h (P>0.05). There was no difference in expressions of Notch1 and Hes1 mRNA between 24 h and 48 h treatment in group D., Conclusions: SCE could promote the proliferation of NSCs. It is demonstrated that the microenvironment of SCI may promote the proliferation of NSCs. Besides, SCE could increase the expression of Notch1 and Hes1 mRNA of NSC. It can be concluded that the Notch signaling pathway activation is one of the mechanisms that locally injured microenvironment contributes to the proliferation of ENSC after SCIs. This process may be performed by up-regulating the expressions of Notch1 and Hes1 gene., (Copyright © 2014 Hainan Medical College. Published by Elsevier B.V. All rights reserved.)

Carbon storage and its allocation of 7-, 29- and 32-year-old Erythrophleum fordii plantation ecosystems in Guangxi were studied on the basis of biomass survey. The results showed that the carbon contents in different organs of E. fordii, ranging from 509.0 to 572.4 g x kg(-1), were in the order of stem > branch > root > bark > leaf. No significant differences in carbon content were observed among the shrub, herb and litter layers of the E. fordii plantations with different ages. Carbon content in the soil layer (0-100 cm) decreased with increasing the soil depth, but increased with increasing the stand age. The carbon storage of the arbor layer was 21.8, 100.0 and 121.6 t x hm(-2) for 7-, 29- and 32-year-old stands, respectively, and the order of carbon storage allocation in different organs was same as the order of carbon content. The 7-, 29- and 32-year-old E. fordii plantation ecosystems stored carbon at 132.6, 220.2 and 242.6 t x hm(-2), respectively. The arbor layer and soil layer were the main carbon pools, accounting for more than 97% of carbon storage in the ecosystem. Carbon storage allocation increased in arbor layer but decreased in soil layer with increasing the stand age. The influence of stand age on carbon storage allocation in shrub, herb and litter layers did not show a obvious regular pattern.

Several studies demonstrate that estradiol can prevent arterial calcification. However, little is known regarding the effect of puerarin, a phytoestrogen extracted from Radix Puerariae, on arterial calcification. The aim of the present study was to determine whether puerarin reduced osteoblastic differentiation of calcifying vascular smooth muscle cells (CVSMCs). The CVSMCs were isolated from mice aorta and treated with different concentrations of puerarin. The alkaline phosphatase (ALP) activity, osteocalcin secretion and Runx2 expression were determined. To examine whether estrogen receptors (ERs) PI3K and Akt play a role in this effect, ICI182789, phosphoinositide 3-kinase (PI3K) inhibitor, LY294002, or the Akt inhibitor, 1L-6-hydroxymethyl-chiro-inositol 2-(R)-2-O-methyl-3-O-octadecylcarbonate (HIMO) was used. Our results showed puerarin could inhibit ALP activity, osteocalcin secretion and Runx2 expression in CVSMCs. Puerarin could induce the activation of Akt. Furthermore, pretreatment of ICI182780, LY294002, HIMO could abolish the effect of puerarin on ALP activity in CVSMCs. Our experiment demonstrated that puerain could attenuate the osteoblastic differentiation of VSMCs through the ER/PI3K-Akt signal pathway.

Our previous study has demonstrated that a plasmid-based short hairpin RNA (shRNA) against cyclin D1 could attenuate the pulmonary artery smooth muscle cell (PASMC) proliferation and pulmonary vascular remodeling in smoking rats. In this report, we examined the efficiency of this shRNA plasmid in monocrotaline-induced pulmonary vascular remodeling. A single injection of monocrotaline induced pulmonary vascular remodeling and cyclin D1 over-expression in pulmonary vascular smooth muscle. The shRNA successfully suppressed the up-regulation of cyclin D1 in pulmonary vessels of monocrotaline-treated rats. Moreover, this shRNA decreased the percentage of muscularized vessels and the wall thickness of pulmonary vessels. So, we concluded that plasmid-based shRNA against cyclin D1 ameliorated pulmonary vascular remodeling in monocrotaline-treated rats. Cyclin D1 might be a potential target for the therapy of pulmonary vascular remodeling and pulmonary hypertension., (© 2013.)