Clinical responses to vemurafenib in postoperative recurrence of papillary thyroid carcinoma with esophageal fistula: A case report.

BACKGROUND: While papillary thyroid carcinoma (PTC) generally exhibits a favorable prognosis post-surgery, the poorly differentiated subtype presents elevated rates of postoperative recurrence. Certain aggressive cases demonstrate invasive behavior, compromising adjacent structures and leading to a poor prognosis. This study delineates a unique case of postoperative PTC recurrence, complicated by esophageal fistula, that showed favorable outcomes following brief Vemurafenib treatment. PATIENT DESCRIPTION: A 64-year-old female patient underwent surgical resection for PTC, subsequently experiencing rapid tumor recurrence and development of an esophageal fistula. DIAGNOSIS: The patient was confirmed to have locally advanced PTC through intraoperative cytopathology. The cancer recurred postoperatively, culminating in the formation of an esophageal fistula. METHODS: The patient was administered Vemurafenib at a dosage of 960 mg twice daily following tumor recurrence. RESULTS: A 12-month regimen of targeted Vemurafenib therapy led to a substantial reduction in tumor size. Concurrently, the esophageal fistula underwent complete healing, facilitating successful removal of the gastrostomy tube. The tumor response was classified as stable disease. CONCLUSION SUBSECTIONS: Vemurafenib demonstrates potential as a targeted therapeutic strategy for recurrent PTC harboring the BRAFV600E mutation. This approach may effectively mitigate tumor dimensions and the associated risk of esophageal and tracheal fistulas.

PDPOB Exerts Multiaspect Anti-Ischemic Effects Associated with the Regulation of PI3K/AKT and MAPK Signaling Pathways.

The discovery of new therapeutic agents for ischemic stroke remains an urgent need. Here, we identified a novel phenyl carboxylic acid derivative, n-pentyl 4-(3,4-dihydroxyphenyl)-4-oxobutanoate (PDPOB), with anti-ischemic activities. The in vitro anti-ischemic neuroprotective and anti-inflammatory capacities of PDPOB were investigated using neuronal cells suffering from oxygen-glucose deprivation/reperfusion (OGD/R) and microglial cells stimulated by lipopolysaccharide (LPS). PDPOB attenuated the OGD/R-evoked cellular damage of SH-SY5Y cells and primary cortical neurons in a concentration-dependent manner. Likewise, PDPOB displayed protective roles against OGD/R-evoked multiaspect neuronal deterioration in SH-SY5Y cells, as evidenced by alleviated mitochondrial dysfunction, oxidative stress, and apoptosis. A further study unveiled the accelerated phosphorylation of protein kinase B (AKT) by PDPOB treatment, while blockade of phosphoinositide 3-kinase (PI3K)/AKT signaling substantially diminished the neuroprotective capacities of PDPOB. Additionally, the PDPOB pretreatment dampened the LPS-evoked neuroinflammation in BV2 cells, characterized by the suppressed secretion of nitric oxide (NO) and proinflammatory cytokines, as well as normalized expression of nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Western blotting further revealed that PDPOB abated the overabundant phosphorylation of the extracellular signal-regulated kinase (ERK), c-Jun-N-terminal kinase (JNK), and p38 in LPS-exposed BV2 cells. The intravenous application of PDPOB (30 mg/kg, single dose) attenuated ipsilateral cerebral infarction in middle cerebral artery occlusion (MCAO) rats, accompanied by recovered neurological behaviors. Collectively, the above observations provided substantial evidence for the favorable properties and mechanistic explanations of PDPOB in the regulation of ischemia-associated neuronal injury and microglial inflammation, which may furnish ideas for the discovery of new therapeutic strategies against cerebral ischemia.

An optically active isochroman-2H-chromene conjugate potently suppresses neuronal oxidative injuries associated with the PI3K/Akt and MAPK signaling pathways.

Increasing evidence suggests that the use of potent neuroprotective agents featured with novel pharmacological mechanism would offer a promising strategy to delay or prevent the progression of neurodegeneration. Here, we provide the first demonstration that the chiral nonracemic isochroman-2H-chromene conjugate JE-133, a novel synthetic 1,3-disubstituted isochroman derivative, possesses superior neuroprotective effect against oxidative injuries. Pretreatment with JE-133 (1-10 µM) concentration-dependently prevented H2O2-induced cell death in SH-SY5Y neuroblastoma cells and rat primary cortical neurons. Pretreatment with JE-133 significantly alleviated H2O2-induced apoptotic changes. These protective effects could not be simply attributed to the direct free radical scavenging as JE-133 had moderate activity in reducing DPPH free radical. Further study revealed that pretreatment with JE-133 (10 µM) significantly decreased the phosphorylation of MAPK pathway proteins, especially ERK and P38, in the neuronal cells. In addition, blocking PI3K/Akt pathway using LY294002 partially counteracted the cell viability-enhancing effect of JE-133. We conclude that JE-133 exerts neuroprotection associated with dual regulative mechanisms and consequently activating cell survival and inhibiting apoptotic changes, which may provide important clues for the development of effective neuroprotective drug lead/candidate.

Akt1 and dCIZ1 promote cell survival from apoptotic caspase activation during regeneration and oncogenic overgrowth.

Apoptosis is an ancient and evolutionarily conserved cell suicide program. During apoptosis, executioner caspase enzyme activation has been considered a point of no return. However, emerging evidence suggests that some cells can survive caspase activation following exposure to apoptosis-inducing stresses, raising questions as to the physiological significance and underlying molecular mechanisms of this unexpected phenomenon. Here, we show that, following severe tissue injury, Drosophila wing disc cells that survive executioner caspase activation contribute to tissue regeneration. Through RNAi screening, we identify akt1 and a previously uncharacterized Drosophila gene CG8108, which is homologous to the human gene CIZ1, as essential for survival from the executioner caspase activation. We also show that cells expressing activated oncogenes experience apoptotic caspase activation, and that Akt1 and dCIZ1 are required for their survival and overgrowth. Thus, survival following executioner caspase activation is a normal tissue repair mechanism usurped to promote oncogene-driven overgrowth.

Transcatheter Intra-Arterial Infusion Combined with Interventional Photothermal Therapy for the Treatment of Hepatocellular Carcinoma.

BACKGROUND: Photothermal therapy (PTT) has great potential application in the treatment of tumors. However, due to the low penetration of near-infrared light (NIR) and the low concentration of nanomaterials in the tumor site, the application of PTT has been limited. PURPOSE: The objective of this study was to investigate the therapeutic effect of transcatheter intra-arterial infusion of lecithin-modified Bi nanoparticles (Bi-Ln NPs) combined with interventional PTT (IPTT) on hepatocellular carcinoma. METHODS: Bi-Ln NPs were prepared by emulsifying the hydrophobic Bi nanoparticles and lecithin, and the photothermal conversion and cytotoxicity of Bi-Ln NPs were then measured by infrared imaging and MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, respectively. Twenty-four VX2 hepatic carcinoma rabbits were randomly divided into four groups. Rabbits in group A received Bi-Ln NPs by intra-arterial infusion and NIR laser treatment (IA Bi-Ln NPs + Laser), group B received Bi-Ln NPs by intravenous infusion and NIR laser treatment (IV Bi-Ln NPs + Laser), group C received PBS (phosphate buffer saline) via intra-arterial infusion with NIR laser treatment (IA PBS + Laser), group D received PBS via intra-arterial infusion (IA PBS). Transcatheter intra-arterial infusion was conducted by superselective intubation under digital subtraction angiography (DSA) guidance. IPTT was performed by introducing an NIR optical fiber access to the rabbit VX2 hepatic carcinoma under real-time ultrasound guidance. Magnetic resonance imaging (MRI) was performed to evaluate the tumor size. Hematoxylin and eosin (H&E) stain and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) were conducted 7 days after treatment to evaluate the necrosis rate and viability of tumor, respectively. RESULTS: The Bi-Ln NPs have the advantages of good biological compatibility and high photothermal conversion efficiency. Minimally invasive transcatheter intra-arterial infusion can markedly increase the concentration of Bi-Ln NPs in tumor tissues. IPTT can contribute to the significant improvement in the photothermal efficiency of Bi-Ln NPs. Compared to other groups, the group of IA Bi-Ln NPs + Laser showed a significantly higher tumor inhibition rate (TIR) of 93.38 ± 19.57%, a higher tumor necrosis rate of 83.12 ± 8.02%, and a higher apoptosis rate of (43.26 ± 10.65%) after treatment. CONCLUSION: Transcatheter intra-arterial infusion combined with interventional PTT (IPTT) is safe and effective in eradicating tumor cells and inhibiting tumor growth and may provide a novel and valuable choice for the treatment of hepatocellular carcinoma in the future.

Development of Novel N-hydroxypyridone Derivatives as Potential Anti-Ischemic Stroke Agents.

Our previous study had identified ciclopirox (CPX) as a promising lead compound for treatment of ischemic stroke. To find better neuroprotective agents, a series of N-hydroxypyridone derivatives based on CPX were designed, synthesized, and evaluated in this study. Among these derivatives, compound 11 exhibits significant neuroprotection against oxygen glucose deprivation and oxidative stress-induced injuries in neuronal cells. Moreover, compound 11 possesses good blood-brain barrier permeability and superior antioxidant capability. In addition, a complex of compound 11 with olamine-11·Ola possesses good water solubility, negligible hERG inhibition, and superior metabolic stability. The in vivo experiment demonstrates that 11·Ola significantly reduces brain infarction and alleviates neurological deficits in middle cerebral artery occlusion rats. Hence, compound 11·Ola is identified in our research as a prospective prototype in the innovation of stroke treatment.

Support effects on adsorption and catalytic activation of O2 in single atom iron catalysts with graphene-based substrates.

The adsorption and catalytic activation of O2 on single atom iron catalysts with graphene-based substrates were investigated systematically by density functional theory calculation. It is found that the support effects of graphene-based substrates have a significant influence on the stability of the single atom catalysts, the adsorption configuration, the electron transfer mechanism, the adsorption energy and the energy barrier. The differences in the stable adsorption configuration of O2 on single atom iron catalysts with different graphene-based substrates can be well understood by the symmetrical matching principle based on frontier molecular orbital analysis. There are two different mechanisms of electron transfer, in which the Fe atom acts as the electron donor in single vacancy graphene-based substrates while the Fe atom mainly acts as the bridge for electron transfer in double vacancy graphene-based substrates. The Fermi softness and work function are good descriptors of the adsorption energy and they can well reveal the relationship between electronic structure and adsorption energy. This single atom iron catalyst with single vacancy graphene modified by three nitrogen atoms is a promising non-noble metal single atom catalyst in the adsorption and catalytic oxidation of O2. Furthermore, the findings can lay the foundation for the further study of graphene-based support effects and provide a guideline for the development and design of new non-noble-metal single atom catalysts.

[Effect of overexpression of transcription factor Runx2 and Osterix on osteogenic differentiation of endothelial cells].

PURPOSE: To explore the effect of overexpression of Runx2 and Osterix (OSX) genes on osteogenic differentiation of human umbilical vein endothelial cells (HUVECs). METHODS: Overexpressed Runx2 and OSX lentiviral vectors were transfected into HUVECs respectively. The osteogenic potential of transfected cells was identified by alkaline phosphatase (ALP) staining and ALP activity. Furthermore, real time-PCR, Western blot and immunofluorescence staining were performed to detect the expression of osteogenic genes and proteins in HUVECs. GraphPad Prism 6.01 software was used for statistical analysis. RESULTS: Overexpression of Runx2 gene was beneficial for osteogenic differentiation of HUVECs, while overexpression of osterix gene did not show osteogenic differential potential. Moreover, overexpression of Runx2 gene in HUVECs up-regulated the gene expression level of Runx2, OSX, ALP, bone sialoprotein (BSP), osteopontin (OPN), and osteocalcin (OCN), and up-regulated protein level of OPN and OCN. CONCLUTIONS: Overexpression of Runx2 could promote osteogenic differentiation of HUVECs.

Effects of Sr-HT-Gahnite on osteogenesis and angiogenesis by adipose derived stem cells for critical-sized calvarial defect repair.

Tissue engineering strategies to construct vascularized bone grafts are now attracting much attention. Strontium-hardystonite-Gahnite (Sr-HT-Gahnite) is a strong, highly porous, and biocompatible calcium silicate based bio-ceramic that contains strontium and zinc ions. Adipose derived stem cells (ASCs) have been demonstrated to have the ability in promoting osteogenesis and angiogenesis. In this study, the effects of Sr-HT-Gahnite on cell morphology, cell proliferation, and osteogenic differentiation of ASCs were systematically investigated. The cell proliferation, migration and angiogenic differentiation of human umbilical vein endothelial cell (HUVECs) were studied. Beta-tricalcium phosphate/hydroxyapatite (TCP/HA) bioceramic scaffolds were set as the control biomaterial. Both bio-ceramics exhibited no adverse influence on cell viability. The Sr-HT-Gahnite scaffolds promoted cell attachment and alkaline phosphatase (ALP) activity of ASCs. The Sr-HT-Gahnite dissolution products enhanced ALP activity, matrix mineralization, and angiogenic differentiation of ASCs. They could also improve cell proliferation, migration, and angiogenic differentiation of HUVECs. Levels of in vivo bone formation with Sr-HT Gahnite were significantly higher than that for TCP/HA. The combination of Sr-HT-Gahnite and ASCs promoted both osteogenesis and angiogenesis in vivo study, compared to Sr-HT-Gahnite and TCP/HA bio-ceramics when administered alone, suggesting Sr-HT-Gahnite can act as a carrier for ASCs for construction of vascularized tissue-engineered bone.

Surface thermal oxidation on titanium implants to enhance osteogenic activity and in vivo osseointegration.

Thermal oxidation, which serves as a low-cost, effective and relatively simple/facile method, was used to modify a micro-structured titanium surface in ambient atmosphere at 450 °C for different time periods to improve in vitro and in vivo bioactivity. The surface morphology, crystallinity of the surface layers, chemical composition and chemical states were evaluated by field-emission scanning electron microscopy (FESEM), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS). Cell behaviours including cell adhesion, attachment, proliferation, and osteogenic differentiation were observed in vitro study. The ability of the titanium surface to promote osseointegration was evaluated in an in vivo animal model. Surface thermal oxidation on titanium implants maintained the microstructure and, thus, both slightly changed the nanoscale structure of titanium and enhanced the crystallinity of the titanium surface layer. Cells cultured on the three oxidized titanium surfaces grew well and exhibited better osteogenic activity than did the control samples. The in vivo bone-implant contact also showed enhanced osseointegration after several hours of oxidization. This heat-treated titanium enhanced the osteogenic differentiation activity of rBMMSCs and improved osseointegration in vivo, suggesting that surface thermal oxidation could potentially be used in clinical applications to improve bone-implant integration.

Effect of early goal directed therapy in the treatment of severe sepsis and/or septic shock.

BACKGROUND: Many investigators have reproduced the mortality reduction shown in the original trial of early goal directed therapy (EGDT) in patients with severe sepsis and/or septic shock. Three large randomized controlled trials (RCTs) found neutral results when compared to usual care and a modified form of EGDT. Some have interpreted these studies as a reason to question the efficacy of EGDT. OBJECTIVES: The purpose of this study was to comprehensively examine the effect of EGDT in the treatment of severe sepsis and/or septic shock in the literature. METHODS: A systematic review and meta-analysis of RCTs and prospective studies were performed, which extracted studies from PubMed, Elsevier ScienceDirect, Cochrane, Clinicaltrials.gov, Google Scholar, China Knowledge Resource Integrated Database, and Wanfang Database. The mortality trend in the control group from included studies was analyzed. RESULTS: Seven RCTs and twelve prospective studies enrolling 3502 EGDT and 3791 usual care participants were included in the analysis. EGDT was found to reduce overall mortality compared to usual care groups. This reduction in mortality was apparent in prospective and randomized control trials conducted before 2010. Over this time period there was a reduction in mortality in patients receiving usual care. LIMITATIONS: This conclusion was limited by the small size of some selected studies and complicated by the long range of time during the conduction of these studies. These studies were further biased because of the lack of blinding and the crossover of care between the EGDT and usual care groups. CONCLUSIONS: EGDT significantly reduced mortality in patients with severe sepsis and/or septic shock over 15 years since its publication. Recent studies examining usual care with EGDT have similar mortality benefit because of the diminished treatment effect. This treatment effect is diminished for multiple reasons. With progress in the management of this disease the benefit of EGDT on overall mortality has become comparable with the usual care for sepsis patients. This is because many of the components of EGDT have been incorporated into usual care protocols. As a result, the conclusion that EGDT is ineffective cannot be made. A more rigorous RCT which adjusts for the factors that narrows the treatment effect between groups is required. Given the current state of sepsis care and equipoise that exist, this would be difficult.

Non-traumatic acute paraplegia associated with a CT-guided needle biopsy in a silicotic nodule: A case report.

The present study reports the case of an adult patient with non-traumatic acute paraplegia following a computed tomography (CT)-guided automated cutting needle biopsy (ACNB). Multiple nodules and masses were revealed on performing chest radiography and CT on a 45-year-old man. In order to make a pathological diagnosis, a CT-guided biopsy using an automatic cutting needle was performed. However, 10 min after the biopsy, a weakness of the lower extremities occurred, and the patient collapsed to the ground, albeit with clear consciousness. Spinal magnetic resonance imaging (MRI) performed subsequently revealed no abnormal findings in the spinal cord. An MRI performed 24 h later, however, revealed swelling of the thoracic spinal cord and a high-signal-intensity lesion in T2-weighted images at the level of T7, T8 and T9. The patient subsequently received hyperbaric oxygen therapy for a few days, and rehabilitative treatment over the course of a few weeks. At 6 months following the biopsy, the patient was unable to walk, although the patient could stand for 10 min and defecate independently. Currently, the patient remains active in daily life, in spite of confinement to a wheelchair. The present case study was reported to raise the awareness of the possibility of spinal cord ischemia and acute paraplegia following a CT-guided ACNB of the lungs. The mechanism underlying spinal cord ischemia remains to be fully elucidated, although is thought to be multifactorial, involving air embolism.

Graphene Oxide-Copper Nanocomposite-Coated Porous CaP Scaffold for Vascularized Bone Regeneration via Activation of Hif-1α.

Graphene has been studied for its in vitro osteoinductive capacity. However, the in vivo bone repair effects of graphene-based scaffolds remain unknown. The aqueous soluble graphene oxide-copper nanocomposites (GO-Cu) are fabricated, which are used to coat porous calcium phosphate (CaP) scaffolds for vascularized bone regeneration. The GO-Cu nanocomposites, containing crystallized CuO/Cu2 O nanoparticles of ≈30 nm diameters, distribute uniformly on the surfaces of the porous scaffolds and maintain a long-term release of Cu ions. In vitro, the GO-Cu coating enhances the adhesion and osteogenic differentiation of rat bone marrow stem cells (BMSCs). It is also found that by activating the Erk1/2 signaling pathway, the GO-Cu nanocomposites upregulate the expression of Hif-1α in BMSCs, resulting in the secretion of VEGF and BMP-2 proteins. When transplanted into rat with critical-sized calvarial defects, the GO-Cu-coated calcium phosphate cement (CPC) scaffolds (CPC/GO-Cu) significantly promote angiogenesis and osteogenesis. Moreover, it is observed via histological sections that the GO-Cu nanocomposites are phagocytosed by multinucleated giant cells. The results suggest that GO-Cu nanocomposite coatings can be utilized as an attractive strategy for vascularized bone regeneration.

A strontium-incorporated nanoporous titanium implant surface for rapid osseointegration.

Rapid osseointegration of dental implants will shorten the period of treatment and enhance the comfort of patients. Due to the vital role of angiogenesis played during bone development and regeneration, it might be feasible to promote rapid osseointegration by modifying the implant surface to gain a combined angiogenesis/osteogenesis inducing capacity. In this study, a novel coating (MAO-Sr) with strontium-incorporated nanoporous structures on titanium implants was generated via a new micro-arc oxidation, in an attempt to induce angiogenesis and osteogenesis to enhance rapid osseointegration. In vitro, the nanoporous structure significantly enhanced the initial adhesion of canine BMSCs. More importantly, sustained release of strontium ions also displayed a stronger effect on the BMSCs in facilitating their osteogenic differentiation and promoting the angiogenic growth factor secretion to recruit endothelial cells and promote blood vessel formation. Advanced mechanism analyses indicated that MAPK/Erk and PI3K/Akt signaling pathways were involved in these effects of the MAO-Sr coating. Finally, in the canine dental implantation study, the MAO-Sr coating induced faster bone formation within the initial six weeks and the osseointegration effect was comparable to that of the commercially available ITI implants. These results suggest that the MAO-Sr coating has the potential for future use in dental implants.

Enhanced Osseointegration of Hierarchical Micro/Nanotopographic Titanium Fabricated by Microarc Oxidation and Electrochemical Treatment.

Rapid osseointegration is recognized as a critical factor in determining the success rate of orthopedic and dental implants. Microarc oxidation (MAO) fabricated titanium oxide coatings with a porous topography have been proven to be a potent approach to enhance osteogenic capacity. Now we report two kinds of new hierarchical coatings with similar micromorphologies but different nanotopographies (i.e., MAO and MAO-AK coatings), and both coatings significantly promote cell attachment and osteogenic differentiation through mediating the integrin ß1 signaling pathway. In this study, titanium with a unique hierarchical micro/nanomorphology surface was fabricated by a novel duplex coating process, that is, the first a titanium oxide layer was coated by MAO, and then the coating was electrochemically reduced in alkaline solution (MAO-AK). A series of in vitro stem cell differentiation and in vivo osseointegration experiments were carried out to evaluate the osteogenic capacity of the resulting coatings. In vitro, the initial adhesion of the canine bone marrow stem cells (BMSCs) seeded on the MAO and MAO-AK coatings was significantly enhanced, and cell proliferation was promoted. In addition, the expression levels of osteogenesis-related genes, osteorix, alkaline phosphates (ALP), osteopontin, and osteocalcin, in the canine BMSCs, were all up-regulated after incubation on these coatings, especially on the MAO-AK coating. Also, the in vitro ALP activity and mineralization capacity of canine BMSC cultured on the MAO-AK group was better than that on the MAO group. Furthermore, 6 weeks after insertion of the titanium implants into canine femurs, both the bone formation speed and the bone-implant contact ratio of the MAO-AK group were significantly higher than those of the MAO group. All these results suggest that this duplex coating process is promising for engineering titanium surfaces to promote osseointegration for dental and orthopedic applications.

[Effects of lifestyle and quantitative nutrition interventions on individuals with prediabetes].

OBJECTIVE: To explore the impact of lifestyle and quantitative nutrition intervention on individuals with prediabetes. METHODS: A total of 214 prediabetic patients from epidemiologic survey in Ximazhuang and Guangrunmen community centers in Nanchang from January 2011 to January 2012 were enrolled in the study. All the participants were randomly divided into two groups: the intervention group and the control group, with 107 patients in each group. Intensified lifestyle and quantitative nutrition interventions were carried out in the intervention group, and routine lifestyle intervention was carried out in control group. Height and weight were measured, and the body mass index (BMI) was calculated. Blood glucose was tested by glucose oxidase method, and glycosylated hemoglobin (HbA1c) was detected by high performance liquid chromatography. Various parameter changes were compared between two groups after two year's follow-up, and the outcome data of patients was collected. The study was approved by the Ethics Committee of the Third Hospital of Nanchang. RESULTS: There were no significant differences in each parameter between two groups before intervention (all P>0.05). No obvious change was found for the parameters in the control group after two year's follow-up (all P>0.05), but weight, BMI, fasting blood glucose, postprandial two-hour blood glucose and HbA1c decreased in the intervention group (P<0.05). There were 11 (13.1%) diabetic cases and 1 (1.2%) participant with normal glucose tolerance in the control group, and 3 (3.4%) diabetic cases and 7 (8.0%) participants with normal glucose tolerance in the intervention group (P<0.05). The risk of diabetes in two groups was performed using cox regression model analysis, and the primary end-point was the incidence of diabetes. The risk of diabetes in the control group was significantly higher than that in the intervention group [HR=3.903, 95% CI: 1.089-13.992, P=0.037]. CONCLUSION: The lifestyle and quantitative nutrition interventions may improve the blood glucose control and delay the progression of diabetes in prediabetes patients.

Meta-analysis on radiofrequency ablation in combination with transarterial chemoembolization for the treatment of hepatocellular carcinoma.

To evaluate the efficacy and safety of transcatheter arterial chemoembolization (TACE) combined with radiofrequency ablation (RFA) and TACE alone for hepatocellular carcinoma (HCC), Pubmed, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI) and Wanfang Datebases were searched for the randomized controlled trials (RCTs) and retrospective cohort studies from the establishment of the databases to January 2014. The bibliographies of the included studies were searched, too. After study selection, assessment, data collection and analysis were undertaken, we performed this meta-analysis by using the RevMan5.2 software. Seventeen studies involving 1116 patients met the inclusion criteria with 530 treated with RFA-plus-TACE and 586 with TACE alone. The results of meta-analysis showed that the combination of TACE and RFA was obviously associated with higher 1-, 2-, and 3-year overall survival rates (OR1-year=3.98, 95% CI 2.87-5.51, P<0.00001; OR2-year=3.03, 95% CI 2.10-4.38, P<0.00001; OR3-year=7.02, 95% CI 4.14-11.92, P<0.00001) than TACE alone. The tumor complete necrosis rate in patients treated with TACE and RFA was higher than that of TACE alone (OR=13.86, 95% CI 8.04-23.89, P<0.00001). And there was a significant difference in local recurrence rate between two different kinds of treatment (OR=0.24, 95%CI 0.14-0.44, P<0.00001). Additionally, combination of TACE and RFA was associated with higher complete tumor necrosis rates than TACE mono-therapy in the treatment of HCC. However, RFA plus TACE was found to be associated with a lower local recurrence rate than TACE monotherapy. TACE-plus-RFA treatment was associated with a higher response rate (RR) than the TACE-alone treatment (OR=3.90, 95% CI=2.37-6.42, P<0.00001). TACE-plus-RFA treatment did not differ from the TACE-alone treatment in terms of stable disease (SD) rate (OR=0.38, 95% CI=0.11-1.26, P=0.11). Meta-analyses showed that the combination of RFA and TACE was associated with a significantly lower progressive disease (PD) rate (OR=0.15, 95% CI=0.05-0.43, P=0.0005). The rate of AFP reducing or returning to normal in serum in RFA plus TACE group was obviously lower than TACE alone group (OR=4.62, 95% CI 2.56-8.34, P<0.00001). The effect of TACE plus RFA for HCC is better than TACE mono-therapy. The combined therapy can elevate the patients' overall survival rate, tumor necrosis rate and the rate of AFP reducing or returning to normal in serum and decrease local recurrence rate, PD rate compared with TACE alone.

Reactivity of oxygen radical anions bound to scandia nanoparticles in the gas phase: C-H bond activation.

The activation of C-H bonds in alkanes is currently a hot research topic in chemistry. The atomic oxygen radical anion (O(-·)) is an important species in C-H activation. The mechanistic details of C-H activation by O(-·) radicals can be well understood by studying the reactions between O(-·) containing transition metal oxide clusters and alkanes. Here the reactivity of scandium oxide cluster anions toward n-butane was studied by using a high-resolution time-of-flight mass spectrometer coupled with a fast flow reactor. Hydrogen atom abstraction (HAA) from n-butane by (Sc2O3)(N)O(-) (N=1-18) clusters was observed. The reactivity of (Sc2O3)(N)O(-) (N=1-18) clusters is significantly sizedependent and the highest reactivity was observed for N=4 (Sc8O13(-)) and 12 (Sc24O37(-)). Larger (Sc2O3)(N)O(-) clusters generally have higher reactivity than the smaller ones. Density functional theory calculations were performed to interpret the reactivity of (Sc2O3)(N)O(-) (N=1-5) clusters, which were found to contain the O(-·) radicals as the active sites. The local charge environment around the O(-·) radicals was demonstrated to control the experimentally observed size-dependent reactivity. This work is among the first to report HAA reactivity of cluster anions with dimensions up to nanosize toward alkane molecules. The anionic O(-·) containing scandium oxide clusters are found to be more reactive than the corresponding cationic ones in the C-H bond activation.

Rhein lysinate decreases the generation of ß-amyloid in the brain tissues of Alzheimer's disease model mice by inhibiting inflammatory response and oxidative stress.

The protective effect of rhein lysinate (RHL) on Alzheimer's disease (AD) was explored in senescence-accelerated mouse prone-8 (SAMP8) mice. SAMP8 mice without treatment were used as the AD-positive control, and senescence-accelerated-resistant mice were used as the AD-negative control. In this study, 4-month-old male SAMP8 mice were orally administered 25 and 50 mg/kg RHL in drinking water for 6 months. The results of brain tissue enzyme-linked immunosorbent assay (ELISA), immunohistochemistry, and Western blot were demonstrated that compared with SAMP8 group, ß-amyloid1-40 and ß-amyloid1-42 were reduced; the levels of tumor necrosis factor-α and interleukin 6 of brain tissues were also significantly decreased; however, the level of sirtuin 1 (SIRT1) was increased in the RHL-treated group. Compared with SAMP8 group, the ROS levels and malondialdehyde levels were decreased; however, superoxide dismutase and glutathione peroxidase levels were increased in the brain tissues of SAMP8 25 and 50 mg/kg RHL-treated groups. In conclusion, the reduction of Aß induced by RHL was related to the increase of SIRT1 and the inhibition of the inflammatory response and oxidative stress in SAMP8 mice. It might be a promising biological therapeutic drug for AD.