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We aimed to explore the clinicopathological features and survival-related factors for intrahepatic cholangiocarcinoma (ICC). Eligible data were extracted from the Surveillance, Epidemiology and End Results (SEER) database from 2004 to 2015. Totally, 4595 ICC patients were collected with a male to female ratio of nearly 1:1. The higher proportion of ICC patients was elderly, tumor size ≥ 5 cm and advanced AJCC stage. Most patients (79.2%) have no surgery, while low proportion of patients receiving radiotherapy (15.1%). The median survival was 7.0 months (range 0–153 months). The 5-year CSS and OS rates were 8.96% and 7.90%. Multivariate analysis found that elderly age (aged ≥ 65 years old), male, diagnosis at 2008–2011, higher grade, tumor size ≥ 5 cm, and advanced AJCC stage were independent factors for poorer prognosis; while API/AI (American Indian/AK Native, Asian/Pacific Islander) race, married, chemotherapy, surgery and radiotherapy were independent favorable factors in both CSS and OS. Furthermore, stratified analysis found that chemotherapy and radiotherapy improved CSS and OS in patients without surgery. Age, sex, race, years of diagnosis, married status, grade, tumor size, AJCC stage, surgery, chemotherapy and radiotherapy were significantly related to prognosis of ICC. Chemotherapy and radiotherapy could significantly improve survival in patients without surgery.

RationaleThe volatile anesthetic isoflurane is suggested to produce a rapid and robust antidepressive effect in preliminary clinical trials. Recently, isoflurane was found to activate the tropomyosin receptor kinase B (TrkB) signaling which is the underlying mechanism of the rapid antidepressant ketamine.ObjectiveOur study investigated the effect of isoflurane anesthesia on chronic unpredictable mild stressed (CUMS) model in mice and verified the role of brain-derived neurotrophic factor (BDNF)/TrkB/ the mammalian target of rapamycin (mTOR) signaling in the antidepressant effect of isoflurane.MethodsWe employed the CUMS model of depression to assess the rapid antidepressant effect of isoflurane by the forced swimming test (FST), the sucrose preference test (SPT), and the novelty suppressed feeding test (NSFT). The protein expression of BDNF and TrkB/protein kinase B (PKB or Akt)/mTOR was determined through Western blot. The dendritic spine density in the hippocampus and medial prefrontal cortex (PFC) was measured by the Golgi staining.ResultsA brief burst-suppressing isoflurane anesthesia rapidly reversed the behavioral deficits caused by CUMS procedure, normalized the expression of BDNF and further activated the TrkB signaling pathway in CUMS-induced stressed mice in both prefrontal cortex (PFC) and hippocampus (HC). All of those behavioral and proteomic effects were blocked by K252a, a selective receptor inhibitor of TrkB. Isoflurane significantly promoted the formation of dendritic spines in both medial prefrontal cortex (mPFC), CA1, CA3, and DG of the hippocampus.ConclusionOur study indicates that isoflurane exerts a rapid antidepressant-like effect in CUMS depression animal model, and the activation of BDNF/TrkB signaling pathway plays an indispensable role in the biological and behavioral antidepressant effects of isoflurane. A single exposure to isoflurane could repair synaptic damage caused by chronic stimulation.

Methamphetamine (MAP) is the most widely used psychostimulant in the world, but the exact mechanisms underlying MAP addiction are not yet fully understood. Recent studies have identified the distribution of TRPV1 in several brain regions that are related to drug addiction, including nucleus accumbens (NAc) and dorsal striatum (DSt). In the present study, we performed conditioned place preference (CPP) and self-administration tests to examine the effects of capsazepine (CPZ) and SB366791 (SB) on MAP reward. We found that both CPZ and SB significantly inhibited MAP-induced CPP and self-administration; in contrast, TRPV1 knock-out (KO) mice did not develop MAP-induced CPP. Real-time RT-PCR, Western blot and quantitative autoradiographic tests showed up-regulation of TRPV1 mRNA and protein expression in the NAc and/or DSt regions of mice exhibiting MAP-induced CPP. In addition, an in vivo microdialysis experiment showed that CPZ dramatically reduced dopamine (DA) levels in the NAc region of MAP-treated mice. Furthermore, attenuated dopamine transporter (DAT) binding levels in the NAc and DSt regions of MAP-induced CPP mice were reversed by CPZ. Together, these data suggest that TRPV1 plays an important role in MAP reward via the modulation of DA release and DAT density, thereby providing a novel therapeutic target for MAP addiction.

The present study is aimed at testing the antidepressant--like effects and probable mechanisms of action of low molecular mass chondroitin sulfate (LMMCS) on depression induced by chronic unpredictable mild stress (CUMS) in mice. Four weeks of CUMS exposure resulted in depressive-like behavior, expressed by a significant decrease in the locomotor activity and sucrose consumption and increased immobility time in the forced swim test. Further, there was a significant reduction of 5-HT level in the hippocampus region of depressed mice. Treatment of mice for four weeks with LMMCS ameliorated significantly both the behavioral and biochemical changes induced by CUMS. These novel results suggest that LMMCS produces an antidepressant-like effect in mice subjected to CUMS, which might be related, at least in part, to the increase of 5-HT concentration in the hippocampus.

Under laser irradiation, photothermal therapy (PTT) effectively ablates tumors above 50 °C. However, hyperthermia can cause additional damage due to the inevitable heat spread to surrounding healthy tissue. Herein, nanoparticles named as GI@P NPs were designed for enhanced PTT with heat shock protein 90 (HSP90) inhibition at temperatures below 50 °C to achieve optimal cancer therapy and avoid surrounding damage. GI@P NPs were done by co-loading Garcinia cambogia acid (GA) and photosensitizer IR783 in polymer PLG- g -mPEG to form a nanomedicine, where IR783 with excellent photoacoustic (PA) signal acted as an excellent photothermal therapeutic agent that converted the laser energy into heat to kill tumor cells, GA was used as antitumor drug for chemotherapy and an inhibitor of HSP90 to overcome the heat resistance of tumors for efficient cryo-photothermal therapy, and PLG- g -mPEG can encapsulate IR783 and GA to increase biocompatibility and accumulate effectively in the tumor. After GI@P NPs were injected into the mice, we could observe that the PA signals gradually increased in the tumor region and showed the strongest PA signals at 12 h. Under laser irradiation, the tumor temperature of the mice could raise to about 43.5 °C, and the tumor was significantly inhibited after long-term monitoring by PA imaging. As a result, gentle PTT produced by GI@P NPs exhibited good antitumor effects at relatively low temperature and minimized nonspecific thermal damage to normal tissues. The GI@P NPs as nanomedicine enriched our understanding of various applications of polymeric carriers, especially in the biomedical field.

Polyethyleneimine (PEI), as a widely used polymer material in the field of gene delivery, has been extensively studied for modification and shielding to reduce its cytotoxicity. However, research aimed at preparing degradable PEI is scarce. In this work, the hydrogen peroxide (H 2 O 2 ) oxidation method was used to introduce degradable amide groups in the PEI and a series of oxidized PEI22k (oxPEI22k) with different degrees of oxidation were synthesized by regulating the dosage of H 2 O 2 . The relationship between the oxidation degree of oxPEI22k and the gene transfection efficiency of oxPEI22k was studied in detail, confirming that the oxPEI22k with oxidation degrees of 16.7% and 28.6% achieved improved transfection efficiency compared to unmodified PEI. These oxPEI22k also proved reduced cytotoxicity and improved degradability. Further, this strategy was extended to the synthesis of low-molecular-weight oxPEI1.8k. The oxPEI1.8k with suitable oxidation degree also achieved improved transfection efficiency and reduced cytotoxicity. In brief, this work provided high-efficiency and low-cytotoxicity degradable gene delivery carriers by regulating the oxidation degree of PEI, which was of great significance for promoting clinical applications of PEI.

The graft polymerization of acrylic acid (A) and acrylamide (B) was carried out onto bi-oriented polyester BOPET corona film. The influence of monomer concentration, reducer concentration and reaction time on the graft polymerization was investigated. The surface tension of the films increased with an increase of monomer concentration, till the concentration of monomer A reached 1.5 × 10^sup -2^ g/mL and the concentration of monomer B reached 4.0 × 10^sup -2^ g/mL. The surface tension of the films reached a maximum value at 7 × 10^sup -4^ M of reducer concentration and subsequently decreased with further increase in reducer concentration. The surface tension of the films increased with the increase of the reaction time apparently within 50min. The grafted corona BOPET films were characterized with IR and XPS. The presence of graft on the film surface was confirmed. The attenuation experiments on grafted corona BOPET films in air at 50°Cand in water were carried out to investigate the persistence of graft polymerization of acrylic acid and arylamide onto BOPET corona films.[PUBLICATION ABSTRACT]

Spherical carbamide particles were employed to produce porous Fe–Cr–C alloy with high porosity and large aperture via the space-holder leaching technique. A series of porous samples were prepared by regulating the processing parameters, which included the carbamide content and the compaction pressure. The pore characteristics and compression properties of the produced samples were investigated. The samples were characterized by scanning electron microscopy, image analysis, and compression tests. The results showed that the macro-porosity and the mean pore size were in the ranges 40.4%–82.4% and 0.6–1.5 mm, respectively. The compressive strength varied between 25.38 MPa and 127.9 MPa, and was observed to decrease with increasing total porosity.

This paper is aimed at comprehensively investigating the dynamic low-frequency electrical impedance (DLFI) of biological materials during the processes of freezing, thawing and heating, and combinations of them. Electrical impedance detection (EID) was proposed as a means of rapidly evaluating the viability of biological materials subject to freezing or thermal injury (processes expected to be significant in the practices of cryobiology and hyperthermia). Using two experimental setups, the DLFI for selected biological materials (fresh pork and fish) under various freezing and heating conditions was systematically measured and analyzed. Preliminary results demonstrate that damage that occurs to a biological material due to freezing or heating could result in a significant deviation in its electric impedance value from that of undamaged biomaterials. Monitoring impedance change ratios under various freezing and heating conditions may offer an alternative strategy for assessing the amount of damage sustained by biomaterials subject to cryosurgery, cryo-preservation and hyperthermia. Implementation of the present method in order to develop a new micro-analysis or biochip system is also suggested.

Forty-six patients with intractable urticaria were treated by acupuncture plus garlic-partitioned moxibustion. The results were compared with those of simple acupuncture in a control group of 30 patients. The total effective rate were 91.3%, in the observation group and 73.3%, in the control group. It is showed that acupuncture plus garlic-partitioned moxibustion has a better effect on intractable urticaria than simple acupuncture.