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Multidrug resistance (MDR) is the main factor of tumor recurrence and chemotherapy failure in clinical practice. Its mechanism is relatively complex, and one of the most thoroughly studied mechanism is the overexpression of P-glycoprotein (P-gp) on tumor cell membrane. Most of the chemotherapy drugs are p-gp substrates, and tumor cells will transport the chemotherapy drugs to the extracellular through p-gp mediated active transport, so that the concentration of effective drugs in the cell is reduced, resulting in drug resistance, leading to the decline of clinical efficacy. The reversal agent of P-gp can reduce the intracellular pumping of chemotherapeutic drugs by regulating the expression and transport activity of P-gp, and enhance the sensitivity of tumor cells to chemotherapeutic drugs, thus improving the therapeutic effect. In this paper, we will summarize the natural plant active ingredients that can reverse P-gp mediated MDR to provide reference for clinical and related studies.
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Interleukin (IL)-17A, a pro-inflammatory cytokine, is a fundamental function in the onset and advancement of multiple immune diseases. To uncover the primary compounds with IL-17A inhibitory activity, a large-scale screening of the library of traditional Chinese medicine constituents and microbial secondary metabolites was conducted using splenic cells from IL-17A-GFP reporter mice cultured under Th17-priming conditions. Our results indicated that some aureane-type sesquiterpene tetraketides isolated from a wetland mud-derived fungus, Myrothecium gramineum, showed remarkable IL-17A inhibitory activity. Nine new aureane-type sesquiterpene tetraketides, myrogramins A-I ( 1, 4- 11), and two known ones ( 2 and 3) were isolated and identified from the strain. Compounds 1, 3, 4, 10, and 11 exhibited significant IL-17A inhibitory activity. Among them, compound 3, with a high fermentation yield dose-dependently inhibited the generation of IL-17A and suppressed glycolysis in splenic cells under Th17-priming conditions. Strikingly, compound 3 suppressed immunopathology in both IL-17A-mediated animal models of experimental autoimmune encephalomyelitis and pulmonary hypertension. Our results revealed that aureane-type sesquiterpene tetraketides are a novel class of immunomodulators with IL-17A inhibitory activity, and hold great promise applications in treating IL-17A-mediated immune diseases.
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Extracorporeal membrane oxygenation (ECMO), a kind of life support technology that can replace lung and heart function, is widely used in critical respiratory and circulatory exhaustion. Because of the serious diseases and the use of interventional catheters, patients receiving ECMO life support are often administrated with broad-spectrum antimicrobial agents, which increase the risk of fungal infection. Fungal infection during ECMO can increase mortality. How to effectively control fungal infection is a thorny problem faced by clinicians. During the treatment of ECMO, the patient's physiological status, ECMO oxygenation membrane, circulation pipeline and other factors may change the pharmacokinetic profiles of antifungal drugs, thereby affect the clinical efficacy of drugs. This artical reviews the pharmacokinetic characteristics of antifungal drugs during ECMO support, in order to provide references for clinical antifungal treatment.
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Objective To analyze retrospectively the death pattern, risk factors, and death time of 253 patients at the Respiratory Care Unit of General Hospital of PLA in order to improve care quality and reduce mortality.Methods The information of patients was extracted from the hospital information system ( HIS) , and then classified and calculated accord-ing to different time points.Results Between November and next March,the mortality rate was higher than in other months (P<0.05), accounting for 19.5%.Mortality of those admitted between 8∶01 and 9∶00 or between 23∶01 and 24∶00 was higher than at other times(P<0.05), accounting for 41.7%and 50.0%, respectively.There was statistically significant difference(P<0.01) in mortality between days of the week,with the highest on Saturday, accounting for 43.1%.Mortality on non-work days was higher than on workday(P<0.01), accounting for 38.3% and 13.2%, respectively.Mortality at off-hour was higher than at office time(8∶00-11∶30 and 14∶30-18∶00 on workday) (P<0.01), accounting for 31.3%and 5.2%, respectively.Logistic regression analysis showed that age, month of admission, and the hour of discharge were associated with the outcome.Conclusion The high mortality between November and next March may be related to the higher incidence of respiratory diseases in winter, air pollution and cold weather.High mortality is also significantly associ-ated with the care quality of the medical staff.
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Objective To investigate the effect of Zhali Nusi Recipe ( ZNR) on hemorheological parameters, blood - lipid metabolism, the activities of superoxide dismutase ( SOD) and glutathione peroxidase ( GSH-Px) , and the content of malondialdehyde (MDA) in brain tissues of cerebral ischemia-reperfusion rats with the syndrome of phlegm blended with blood stasis. Methods Ninety rats were randomly divided into sham operation group, model group, nimodiping (10.8 mg/kg) group, high-, middle- and low-dose ZNR groups ( in the dosage of 30, 15, 7.5 g/kg, respectively) , 15 rats in each group. Except the sham operation group, the other groups were given intragastric administration of intralipid for 4 weeks, and then were induced into focal cerebral ischemia-reperfusion by middle cerebral artery occlusion with thread-obstruction method. After post-operation medication for 7 days, the rat general situations, the neurological deficiency symptoms, and the water content in brain tissues were observed. The morphological features of brain tissues were observed after HE staining. The blood was taken from the ab dominal aorta to detect the hemorheological parameters and blood lipid levels. Metabolic levels of free radicals in the brain tissue homogenate were also determined. Results Compared with the sham operation group, neurological deficiency scores of the rats and the water content in the brain tissues of model group were significantly enhanced. The hippocampal neurons of model rats presented typical ischemic changes. In the model group, the hemorheological parameters such as whole blood viscosity, plasma viscosity, hematocrit ( HCT) , and erythrocyte aggregation in dexes ( EAI) were significantly increased, and erythrocyte deformation indexes were significantly decreased; the serum levels of total cholesterol ( TC) , triglyceride ( TG) , low-density lipoprotein cholesterol (LDL-C) were significantly increased, and high-density lipoprotein cholesterol ( HDL-C) level was significantly decreased; the activities of SOD and GSH-Px in brain tissues were significantly decreased, and MDA content was increased significantly ( P<0.05 or P<0.01). Compared with the model group, high-, middle-and low-dose ZNR improved the general situations of the cerebral ischemia-reperfusion rats, increased the neurological deficiency scores, reduced the water content in brain tissues, improved the recovery of morphology of cells in cerebral ischemia tissues, reduced whole blood viscosity, plasma viscosity, HCT and EAI of the model rats, promoted erythrocyte deformation indexes, decreased serum TG, TC, LDL-C levels, increased the activities of SOD and GSH-Px in cerebral ischemic tissues, and sig nificantly decreased MDA content (P<0.05 or P<0.01). And high-dose ZNR had the best effect. Conclusion ZNR has certain protective effect on cerebral ischemia-reperfusion rats with the syndrome of phlegm blended with blood stasis, and the mechanism may be closely related with the improvement ofhemorheology, blood lipid and free radical metabolism in model rats.
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Objective:To establish a method for the content determination of tetrahydropalmatine and imperatorin in Yuanhu Zhi-tong tablets by HPLC. Methods:An AKZONOBEL Kromasil 100-5 C18 column (250 mm × 4. 6 mm , 5μm) was used and the mobile phase consisted of methanol and 0. 1% phosphoric acid (52∶48) (adjusting pH to 6. 5 with triethylamine),the flow rate was 1. 0 ml· min-1 at the column temperature of 40℃, the detection wavelength was at 284 nm, and the injection volume was 10 μl. Results:The linear range of tetrahydropalmatine was 0.004 2-0.084 0 mg·ml-1(r=1.000 0). The average recovery was 97.72% with RSD of 1.10%(n=6). The linear range of imperatorin was 0.003 6-0.072 0 mg·ml-1(r=0.999 7). The average recovery was 97.99%with RSD of 0. 96%(n=6). The measurement results of 10 batches were stable and reliable. Conclusion:The method is simple and accurate, which can be used to improve the quality standard.
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D-psicose 3-epimerase (DPEase) is demonstrated to be useful in the bioproduction of D-psicose, a rare hexose sugar, from D-fructose, found plenty in nature. Clostridium cellulolyticum H10 has recently been identified as a DPEase that can epimerize D-fructose to yield D-psicose with a much higher conversion rate when compared with the conventionally used DTEase. In this study, the crystal structure of the C. cellulolyticum DPEase was determined. The enzyme assembles into a tetramer and each subunit shows a (β/α)(8) TIM barrel fold with a Mn(2+) metal ion in the active site. Additional crystal structures of the enzyme in complex with substrates/products (D-psicose, D-fructose, D-tagatose and D-sorbose) were also determined. From the complex structures of C. cellulolyticum DPEase with D-psicose and D-fructose, the enzyme has much more interactions with D-psicose than D-fructose by forming more hydrogen bonds between the substrate and the active site residues. Accordingly, based on these ketohexose-bound complex structures, a C3-O3 proton-exchange mechanism for the conversion between D-psicose and D-fructose is proposed here. These results provide a clear idea for the deprotonation/protonation roles of E150 and E244 in catalysis.
Subject(s)
Binding Sites , Biocatalysis , Catalytic Domain , Clostridium cellulolyticum , Hexoses , Chemistry , Manganese , Chemistry , Protein Structure, Quaternary , Racemases and Epimerases , Chemistry , Metabolism , Substrate SpecificityABSTRACT
Objective This article analyzed the characteristics of the health service in medium cities and the impact on community health service.Methods Summary and statistical analysis of the outcomes from the Fourth National Health Service Survey by the category of metropolitans,sub-provincial cities and provincial capital cities,and non-provincial-capital cities.Results In the medium cities,the geographical accessibility is high against low economic and technology accessibility.These cities have lower 2-week morbiditv rate but high children morbidity rate.These cities also feature high self-rated health status among residents and high health risk factors prevalence at the sarne time.Conclusion Medium cities are recommended to further build their CHS system,enhance their ties with larger cities,so as to elevate their technical competence,for meeting such public health needs of the people in infectious disease control,health promotion and vulnerable population healthcare.