Our pre-clinical studies demonstrated that intratumoral vaccination with a recombinant oncolytic type 2 adenovirus overexpressing the heat shock protein (HSP)70 protein, designated as H103, can inhibit primary and metastatic tumors through enhanced oncolytic activity and HSPmediated immune responses against shared and mutated tumor antigens. In the pre-clinical studies of local H103 administration, no significant toxicity was observed in the animal trials with mice, cavy or rhesus monkeys. A phase I clinical trial of intratumoral injection of H103 was conducted in the patients with advanced solid tumors. A total of 27 patients were injected intratumorally with H103 in a dose-escalation study from a dose of 2.5 Â 10 7 to 3.0 Â 10 12 viral particles (VPs). The maximum tolerated dose of H103 was not defined. Two patients developed dose-limiting toxicities of grade III fever at the dose of 1.5 Â 10 12 VP and transient grade IV thrombocytopenia at the dose of 3.0 Â 10 12 VP. The common adverse events were mainly mild to moderate (grade I/II) in nature, including fever, mild injection-site reaction, leucopenia, lymphopenia, thrombocytopenia and hypochromia. The objective response (complete response+partial response) to H103-injected tumors was 11.1% (3/27), and the clinical benefit rate (complete response+partial response+minor response+stable disease) was 48.1%. Interestingly, transient and partial regression of distant, uninjected tumors was observed in three patients. The numbers of immune cells (CD4 + and CD8 + T cells, and natural killer cells) were elevated after H103 administration, but without statistical significance. This phase I trial demonstrates that intratumoral administration of H103 can be safely applied to cancer patients and shows promising clinical antitumor activity, warranting a further clinical investigation.

The maturation and developmental potential on cumulus-cell-free oocytes is of great importance theoretically and practically. The present study was to investigate the effects of l-ascorbic acid, alpha-tocopherol and co-culture on in vitro developmental potential of porcine denuded oocytes (DOs). Porcine DOs were cultured in maturation medium supplemented with vitamin C (0, 50, 100, 250, 500, 750 microM) and vitamin E (0, 10, 20, 50, 100, 250 microm), respectively. And they were also co-cultured with dispersed cumulus cells (group CCscoculture), intact cumulus cells oocyte complexes (COCs) (group COCscoculture), and COCs whose oocytes were removed (group OOXcoculture), respectively. After 44 h incubation, the maturation rates, cleavage rates and blastocyst rates after parthenogenetic activation in three experiments mentioned above were collected and analysed, respectively. L-Ascorbic acid promoted porcine DOs in vitro maturation and blastocyt development after parthenogenetic activation while alpha-tocopherol did not increase the in vitro maturation rates, but improved the blastocyst rate. None of the three co-culture manner promoted the in vitro maturation and the cleavage of porcine DOs after parthenogenetic activation, but all the co-culture manners improved the blastocyst rates. Both Vitamin C and E enhance the in vitro developmental potential of porcine DOs. Co-culture increases the developmental potential of porcine DOs.

The activation of hepatic stellate cells (HSCs) is the key event of the pathogenesis of hepatic fibrosis. Platelet-derived growth factor (PDGF) is the most potent mitogen for HSCs, and PDGF receptor-beta subunit (PDGFR-beta) is required for the proliferation of HSCs induced by PDGF. In this study, a high gene-silencing-efficacy PDGFR-beta small interference RNA (siRNA) was synthesized that could suppress the PDGFR-beta expression and inhibit the activation and proliferation but could not induce the apoptosis of HSCs in vitro. To avoid the side effect of nonspecific interference of PDGFR-beta, we constructed an HSCs-specific short hairpin RNA (shRNA) expression plasmid in which PDGFR-beta shRNA was driven by a glial fibrillary acidic protein (GFAP) promoter. The double-staining immunofluorescence examination indicated that GFAP promoter could target the transgene expression into HSCs in carbon tetrachloride induced acute injured rat's liver and bile duct ligation (BDL)-induced chronic injured rat's liver. Furthermore, HSCs-specific PDGFR-beta shRNA could relieve liver injury and hepatic fibrosis in the rat's model induced by BDL. This study demonstrates that PDGFR-beta siRNA may be presented as an antifibrogenic agent. The application of HSCs-specific RNA interference induced by the GFAP promoter might supply a new powerful tool for cell-specific gene therapy of hepatic fibrogenesis.

In this article, a supercritical CO2-based solar Rankine cycle system (SRCS) with a novel-concept thermally driven pump is studied. The thermally driven pump is a refrigerant-circulating pump composed of two expansion tanks and having merits of low power consumption and high reliability in comparison with conventional mechanical pump. The application of the present thermally driven pump in the supercritical CO2-based SRCS shows that an oscillatory flow is realized in the system and the system thermal efficiency is enhanced compared to the SRCS using the mechanical feed pump.

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The exact clinical significance of EGFR mutation status in NSCLC at the time of initial diagnosis remains disputable. The gene expression module in NSCLC for chemotherapy outcome prediction needs to be developed. We analyzed 56 patients with NSCLC received chemotherapy either with (n=20) or without EGFR-TKIs (n=36) between 2008 and 2012 in China. EGFR mutation test and gene expression profiling were performed in samples obtained before medication treatment by liquidchip platform. Significant association (P = 0.028) was seen between EGFR mutation status before first-line chemotherapy and EGFR-TKIs treatment outcomes, which even can be found from the status before second-or third-line treatment. A 14-gene expression profiling had been studied. Patients with low mRNA expression of ERCC1 or TYMS preferred higher DCR to cisplatin and pemetrexed than those with high expression (P = 0.39 and P = 0.11). Highly co-expression of TUBB3 and STMN1 gene has associated with the resistance to antimicrotubule drugs (P = 0.03). Our data suggest the EGFR mutations status, even at the time of initial diagnosis, is predictive of outcomes of TKIs treatment after chemotherapy. The mRNA expression profiling investigated in this study has a predictive value in NSCLC treatment, but further research with expanded samples is still required.

This retrospective study was designed to evaluate the value of contrast-enhanced harmonic ultrasonography (CEHU), diffusion-weighted magnetic resonance imaging (DW-MRI) and CEHU plus DW-MRI for the diagnosis of prostate transition-zone (TZ) cancer. In total, 31 TZ cancers in 28 patients and 25 peripheral zone (PZ) cancers in 21 patients without a TZ cancer were evaluated. All patients underwent DW-MRI and CEHU followed by radical prostatectomy. Predictors for the diagnosis of prostate cancer were evaluated in three protocols (CEHU, DW-MRI, CEHU plus DW-MRI). Statistical analysis of the differences between these protocols and receiver operating characteristic (ROC) curve analysis were carried out. CEHU plus DW-MRI had a significantly higher sensitivity, accuracy and negative-predictive value (90.3%, 73.2% and 81.3%, respectively) for TZ cancer than either method alone. The area under the ROC curve values were 0.659, 0.679 and 0.712 for CEHU, DW-MRI, and CEHU plus DW-MRI, respectively. In conclusion, CEHU plus DW-MRI might be a useful protocol for the detection and location of TZ cancer.

Significance Statement: Chronic cardiovascular risk factors damage cerebral small vessels yet the molecular pathways induced in injured cerebral endothelial cells that lead to tissue injury are unknown. Obesity-induced endothelial expression of CXCL5 in brain white matter disrupts normal myelination by forcing oligodendrocyte progenitor cells to associate with the cerebral vasculature and impedes brain repair after stroke.