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Cancer immunotherapy has become a promising strategy. However, the effectiveness of immunotherapy is restricted in "cold tumors" characterized with insufficient T cells intratumoral infiltration and failed T cells priming. Herein, an on-demand integrated nano-engager (JOT-Lip) was developed to convert cold tumors to hot via "increased DNA damage and dual immune checkpoint inhibition" strategy. JOT-Lip was engineered by co-loading oxaliplatin (Oxa) and JQ1 into liposomes with T-cell immunoglobulin mucin-3 antibodies (Tim-3 mAb) coupled on the liposomal surface by metalloproteinase-2 (MMP-2)-sensitive linker. JQ1 inhibited DNA repair to increase DNA damage and immunogenic cell death (ICD) of Oxa, thus promoting T cells intratumoral infiltration. In addition, JQ1 inhibited PD-1/PD-L1 pathway, achieving dual immune checkpoint inhibition combining with Tim-3 mAb, thus effectively promoting T cells priming. It is demonstrated that JOT-Lip not only increased DNA damage and promoted the release of damage-associated molecular patterns (DAMPs), but also enhanced T cells intratumoral infiltration and promoted T cell priming, which successfully converted cold tumors to hot and showed significant anti-tumor and anti-metastasis effects. Collectively, our study provides a rational design of an effective combination regimen and an ideal co-delivery system to convert cold tumors to hot, which holds great potential in clinical cancer chemoimmunotherapy.
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To investigate the factors affecting the rate of improvement in endurance exercise performance following pre-cooling with ice slurry, we focused on individual physical characteristics and thermoregulatory capacity. Twenty-four healthy adults (12 males and 12 females) ingested 7.5g kg-1 of either ice slurry at -1°C (ICE) or control water at 20°C (CON) before cycling at 55% VO2max and continued cycling until the rectal temperature reached 38.5°C or untill exhaustion in a hot environment (controlled at 38°C, 40% relative humidity). The relationship between the rate of improvement in exercise performance and physical characteristics and thermoregulatory factors (changes in rectal temperature, the rate of rectal temperature increase, whole body sweat loss, mean metabolic heat production, and heat storage) was investigated. No correlation was noted between the rate of improvement in exercise performance and physical characteristics and heat storage. On the other hand, the rate of improvement in exercise performance showed significant correlations with changes in rectal temperature (r = -0.497), the rate of rectal temperature increases during exercise (r = -0.784), whole body sweat loss (r = 0.407), and mean metabolic heat production (r = -0.436). The rate of inhibition of sweating and the rate of increase in metabolic heat production by ice slurry ingestion during exercise have been suggested to be related to the rate of improvement in exercise performance. On the other hand, there was no relationship between body composition or VO2max and the rate of improvement in exercise performance.
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Statins have multiple anti lipid effects, such as anti-inflammatory, anti-oxidation and anti arteriosclerosis, which are beneficial to improve cardiac function. Statins can effectively improve left ventricular remodeling and protect ventricular diastotic function. In this study, the effects of statin therapy on diastolic function and BNP level and exercise tolerance after exercise were observed by statins in patients with diastolic dysfunction. The results showed that after atorvastatin treatment, the exercise BNP decreased in the treatment group, which was significantly different from that before treatment and in the control group [P<0.05]. This study demonstrated that atorvastatin was used to treat patients with diastolic dysfunction and exercise hypertension ny lowering blood pressure and reducing exercise SBP, anti-inflammatory and improving vascular endothelial function
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Objective To determine whether the supplementation of ω-3 polyunsaturated fatty acids in parenteral nutrition (PN) confers treatment benefits to outcomes of septic patients.Methods The databases of MEDLINE,EMBASE,Cochrane central register of controlled trials,the CNKI and the Wanfang biomedicine were searched to identify prospective randomized controlled trials (RCTs) which compared the ω-3 polyunsaturated fatty acids supplemented with the standard PN on outcomes of adult patients with sepsis from January 1996 to June 2013.The methodological quality of the included studies was evaluated,and the Cochrane Collaboration RevMan 5.0 was used for data analysis.Results A total of 12 studies enrolling 721 patients were included.Significant reduction in 28-day mortality [relative risk (RR) 0.77,95％ confidence interval (95％CI) 0.59 to 0.99,P=0.04],short intensive care unit [ICU,weighted mean difference (WMD)=-3.10,95％CI-5.98 to-0.21,P=0.04] and hospital length of stay (WMD =-3.12,95％CI-4.65 to-1.60,P＜0.000 1) were observed in patients receiving ω-3 polyunsaturated fatty acids supplemented PN.There was no differences in days of mechanical ventilation between patients with or without adding ω-3 polyunsaturated fatty acids in PN (WMD =1.33,95％ CI-5.09 to 7.75,P=0.69).Conclusions Meta-analysis results demonstrated that PN supplemented with ω-3 polyunsaturated fatty acids was beneficial in improving the outcomes of patients with sepsis.However,this conclusion must be interpreted with caution due to the low quality of the enrolled trials.
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<p><b>OBJECTIVE</b>To develop an HPLC method for determination of clemastanin B which has anti-viral activity in Radix Isatidis and compare the contents of clemastanin B in the drugs from different origins.</p><p><b>METHOD</b>The samples were separated on an ZORBAX SB-C18 (4.6 mm x 250 mm, 5 microm) column with the mobile phase of acetonitrile-water (11:89). Flow rate was 1.0 mL x min(-1). The detection wavelength was set at 225 nm. Column temperature was 30 degrees C.</p><p><b>RESULT</b>The linear range of clemastanin B was 0.0615-1.8441 microg (r = 0.9995), the average recovery was 97.74%, RSD was 1.4% (n=9). The contents of clemastanin B were in the range of 0.269-0.900 mg x g(-1) in Radix Isatidis from different origins.</p><p><b>CONCLUSION</b>The method for quantitation of clemastanin B in Radix Isatidis was accurate and reliable, which can be used to evaluate the quality of Radix Isatidis.</p>
Subject(s)
China , Furans , Isatis , Chemistry , Plant ExtractsABSTRACT
OBJECTIVE:To probe into the status quo and the trend of the utilization of the oral stasis-eliminating Chinese patent medicine in our hospital in order to provide scientific basis for rational use of this medicine.METHODS:The consumption amount and consumption sum of the oral stasis-eliminating Chinese patent medicine in our hospital during 2006-2008 were reviewed in respect of the DDDs and DDC using DDDs ranking method.RESULTS:During 2006～2008,the consumption amount of the oral stasis-eliminating Chinese patent medicine in our hospital had a steady increase,and the DDDs showed a good synchronism.CONCLUSION:The use of stasis-eliminating Chinese patent medicine is rational in our hospital.
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Objective To explore the role of oval cells in hepatic injure and to study its mechanism.Methods Fifty male SD rats were randomly divided into control group(20 cases)and model group(30 cases).Hepatic pathologic changes were observed through optical microscope and electron microscope.Vimentin and PCNA were detected by immunohistochemistry,Notch1、RBP-J?、HES1 mRNA were detected by semi-quantitative RT-PCR method.Results The histological morphology was normal in the control group,the positive cells of vimentin and PCNA were found on occasion,the expression of Notch1、RBP-J?、HES1 mRNA was low.In the model group,the oval cells were discovered in portal duct regions massively.The tonofilaments and desmosome juntion which were the distinctive structure of oval cells were observed by electron microscopy.The positive cells of vimentin and PCNA were increased(P
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Objective To explore the characteristics of gastric myoelectrical activity induced by meal in obese people.Methods Fourty-one cases of obese subjects were investigated with Digitrapper electrogastrography(EGG) before and after test meal,32 healthy volunteers with normal body mass index were matched as control.Results①Before the meal, the percentage of normal slow waves(N%)in obese group was lower than that in control subjects(55.52?15.7 vs 70.83?14.31,P
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Objective:To explore the expression of GITR/GITRL in rheumatoid arthritis(RA)and its correlation with clinical features of the disease.Methods:Fifty three RA patients,35 osteoarthritis(OA)patients and 35 healthy volunteers were included in the study.The real-time-fluorescence quantitative PCR method was used to analyze the expression level of GITR/GITRL mRNA.Using fluorescence-activated cell sorting(FACS),the expression of GITR on CD4+CD25+ T cells in peripheral blood monouuclear cells(PBMC)was detected.The levels of Anti-CCP antibody,C-reactive protein(CRP),erythrocyte sedimentation rate(ESR)and rheumatoid factor(RF)of the RA patients were measured at the same time.Results:It was shown that the level of GITR/GITRL mRNA and the percentage of GITR+ T cells in the CD4+CD25+ T cell subpopulation[12.38?5.72/16.41?10.16,(28.12?16.85)%] were significantly higher than those of the OA group [9.59?5.87/12.09?7.53,(21.01?14.42)%,P