RESUMO
Objective:To evaluate the effect of febutostat on vascular endothelial function, intima-media thickness(C-IMT) and elasticity of the carotid artery in patients with asymptomatic hyperuricemia.Methods:This study was a randomized controlled clinical trial that enrolled asymptomatic hyperuricemia patients from the outpatient and inpatient departments of Huai′an First People′s Hospital from October 2018 to October 2020. The participants were randomly divided into two groups: the Febuxostat group and the control group. Serum triglyceride(TG), total cholesterol(TC), low-density lipoprotein cholesterol(LDL-C), high-density lipoprotein cholesterol(HDL-C), fasting blood glucose(FBG), fasting insulin(FINS), nitric oxide(NO), endothelin-1(ET-1), malondialdehyde(MDA), and superoxide dismutase(SOD) were measured at baseline and 1, 3, and 6 months after treatment, and brachial artery flow-mediated dilation(FMD) was quantified by color Doppler ultrasound. The following parameters of the common carotid artery were detected at baseline and 12 months after treatment: C-IMT, arterial compliance(AC), one-point pulse wave velocity(PWV), stiffness index(β), and pressure-strain elasticity modulus(Ep). The differences before and after treatment and between the two groups were compared. Pearson correlation was used to analyze the correlation between ΔUA and ΔNO, ΔET-1, ΔC-IMT, ΔAC, Δβ, ΔEp, and ΔPWVβ after treatment with febuxostat. Results:Compared with baseline, TG, HOMA-IR, ET-1 and MDA were significantly lower, while FMD, NO and SOD were significantly higher after 3-months treatment with febuxostat. After 12-months treatment, there was no significant difference in C-IMT or Ep, but there was an increase in AC and a decrease in PWVβ or β compared with baseline. There was a negative correlation between ΔFMD and ΔUA( r=-0.403, P=0.004), but there were no correlations between ΔNO and ΔUA( r=-0.187, P=0.194), ΔET-1 and ΔUA( r=0.038, P=0.791) after 6-months treatment. And ΔUA was an independent factor for ΔFMD( F=2.94, P=0.003, adjusted R2=0.139). After 12-months treatment, there was a negative correlation between ΔAC and ΔUA, and a positive correlation between ΔPWVβ and ΔUA, but there were no correlations between the following indicators: ΔC-IMT and ΔUA( r=0.169, P=0.240), Δβ and ΔUA( r=-0.214, P=0.136), ΔEp and ΔUA( r=-0.077, P=0.597). In the control group, there were no differences among the above indicators between each follow-up time and baseline. Conclusion:Febuxostat improves vascular endothelial function and elasticity in patients with asymptomatic hyperuricemia, which may be related to the decreased oxidative stress response.
RESUMO
Objective::To establish differential metabolites between different varieties of Angelica sinensis, and provide reference for breeding, introduction, regional cultivation and ecological cultivation of new varieties of A. sinensis. Method::Comprehensive non-target metabonomics analysis was conducted for five new varieties of A. sinensis collected at the same time from the same origin: Mingui No. 1 (MG1), Mingui No. 2 (MG2), Mingui No. 4 (MG4), Mingui No. 5 (MG5), and Mingui No. 6 (MG6). The 50% methanol extract of each variety was taken, and then the differential metabolites among varieties were found by using ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS), software Progenesis QI, principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), and non-targeted metabonomics analysis. Differential metabolites were identified based on precise molecular weight, secondary fragments, KEGG database, HMDE database and related literature information. Result::The results of UPLC-Q-TOF-MS and multivariate statistical analysis showed that there were significant differences in the metabolites of five Angelica varieties. As compared with MG1, the contents of chlorogenic acid, ferulic acid, tryptophan and ferulic aldehyde were significantly lower in MG2, MG4, MG5 and MG6, while the contents of ligustilide, coumarin, bovine keratin, palmitin, protocatechualdehyde and linolenic acid were significantly higher (P<0.05). The results of multivariate statistical analysis showed that the metabolites of MG2 and MG5 were similar with those of MG6, but were significantly different from those of MG4.In addition, 38 distinct metabolites were identified, involving 7 potential targeted metabolic pathways. Different varieties of A. sinensis could regulate the synthesis of their metabolites through phenylpropanoid biosynthesis and sesquiterpene-like compounds metabolism, lipid metabolism, amino acid metabolism, carbohydrate metabolism, nucleotide metabolism, carotenoids, linolenic acid, linoleic acid and some other metabolic pathways. Conclusion::UPLC-Q-TOF-MS and Progenesis QI metabonomics techniques were used to compare the chemical constituents of different varieties of A. sinensis from the overall level. The differences and their regularities were found, which could provide reference for quality control, variety sorting, identification, breeding and ecological planting of A. sinensis.
RESUMO
Objective To observe the influence of edaravin combined with cerebroside-kinin on the level of glial fiber acidic protein (GFAP) and ubiquitin carboxyl terminal-L1 (UCH-L1) in the treatment of severe craniocerebral injury.Methods From January 2016 to December 2017,a total of 123 patients with severe craniocerebral injury were selected in our hospital,and randomly(random number) assigned to the observation group (61 cases) and control group (62 cases).Patients in the control group were given cerebroside-kinin,and patients in the observation group were given cerebroside-kinin and edaravone.The acute physiology and chronic health evaluation score (APACHE Ⅱ),activities of daily living (ADL) score,serum malonaldehyde (MDA),superoxide dismutase (SOD),myeloperoxidase (MPO),matrix metalloprotein 9 (MMP-9),GFAP and UCH-L1 before and after treatment were observed.The side effects were also recorded.Results The APACHE Ⅱ score was significantly reduced in both groups after treatment (P=0.008;P=0.003),and was lower in the observation group than that in the control group (P=0.013).The ADL score of both groups increased after treatment (P=0.025;P=0.008),and was higher in the observation group than that in the control group (P=0.012).After treatment the levels of MDA,SOD and MPO in the observation group were significantly higher than those in the control group (P＜0.05);the level of MMP-9 in the observation group was significantly lower than that in the control group (P=0.012);the levels of GFAP and UCH-L 1 in the observation group were significantly higher than those in the control group (P=0.014;P=0.035).There was no significant difference of the total side effect incidence between the observation group and the control group (8.06％ vs 9.83％,x 2=0.088,P=0.719).Conclusions The treatment by edaravone combined with cerebroside-kinin on severe craniocerebral injury may effectively protect the nerve cells,improve nerve function,clinical efficacy and the body's antioxidant capacity,reduce the serum levels of GFAP,UCH-L1,and have better safety.
RESUMO
Objective To investigate the value of early trophic feeding on maintenance of the integrity of intestinal mucosa barrier in severe traumatic patients.Methods The seriously traumatic patients were eligible for enrollment to this study from January 1st,2014 to March 31st,2015 in the intensive care unit of Xiangcheng People's Hospital.All patients were randomly divided into early enteral nutrition (EEN)group and the control group.Within 12 to 24 hours after ICU admission,all patients were fed on enteral nutrition.In the EEN group,the nutrient was reached to 25％ of target nutrient amount [104.6 kJ/ (kg · d)],and in the control group,the nutrition was reached to 60％ of the target nutrient amount.Comparisons of feeding intolerance,incidence of newly developed lung infection,the total length of hospital stay,ICU medical costs,and the markers of mucosa barrier function including lactulose/mannitol ratios (L/M),serum lactic acid level,and diamine oxidase (the first day,the third day and the seventh day) between two groups were carried out.Results Of them,56 patients were treated with early enteral nutrition.Early enteral feeding intolerance and ICU associated infection complications were significantly lower in EEN group than those in control group (P =0.012,P =0.046).There were no significant differences in ICU associated infection complications,the length of ICU stay,the length of hospital stay,ICU medical costs,L/M ratios,D-lactic acid level and diamine oxidase concentration between the two groups (P=0.135,P=0.126,P =0.223,P =0.235).Conclusions Under the seriously traumatic stress,the significantly increased intestinal mucosal permeability will be occurred early.In patients with early trophic feeding,the intestinal mucous membrane barrier function can be improved,thus decreasing ICU associated infection complications and incidence of feeding intolerance.
RESUMO
Objective To investigate the value of early trophic feeding on maintenance of the integrity of intestinal mucosa barrier in severe traumatic patients.Methods The seriously traumatic patients were eligible for enrollment to this study from January 1st,2014 to March 31st,2015 in the intensive care unit of Xiangcheng People's Hospital.All patients were randomly divided into early enteral nutrition (EEN)group and the control group.Within 12 to 24 hours after ICU admission,all patients were fed on enteral nutrition.In the EEN group,the nutrient was reached to 25％ of target nutrient amount [104.6 kJ/ (kg · d)],and in the control group,the nutrition was reached to 60％ of the target nutrient amount.Comparisons of feeding intolerance,incidence of newly developed lung infection,the total length of hospital stay,ICU medical costs,and the markers of mucosa barrier function including lactulose/mannitol ratios (L/M),serum lactic acid level,and diamine oxidase (the first day,the third day and the seventh day) between two groups were carried out.Results Of them,56 patients were treated with early enteral nutrition.Early enteral feeding intolerance and ICU associated infection complications were significantly lower in EEN group than those in control group (P =0.012,P =0.046).There were no significant differences in ICU associated infection complications,the length of ICU stay,the length of hospital stay,ICU medical costs,L/M ratios,D-lactic acid level and diamine oxidase concentration between the two groups (P=0.135,P=0.126,P =0.223,P =0.235).Conclusions Under the seriously traumatic stress,the significantly increased intestinal mucosal permeability will be occurred early.In patients with early trophic feeding,the intestinal mucous membrane barrier function can be improved,thus decreasing ICU associated infection complications and incidence of feeding intolerance.
RESUMO
DNA topoisomerases-mediated DNA damages are generated from exogenous and endogenous effects, which need to be metabolized or repaired to maintain genome stability involving in many of repair enzymes. Tyrosyl-DNA phosphodiesterase 1 (TDP1) and tyrosyl-DNA phosphodiesterase 2 (TDP2) are two DNA repair enzymes discovered recently. TDP1 and TDP2 have the ability to hydrolyze the tyrosyl-phosphodiester bond of the phenol of tyrosine with 3'-and 5'-DNA end, respectively, which are contained in the metabolites of the damaged DNA mediated by topoisomerase 1 and topoisomerase 2, respectively. The abnormal activation and expression of TDP1 or TDP2 is the important reason for cancer development. Therefore, TDP1 and TDP2 have been regarded as potential targets in cancer therapy. In this review, we discuss the rationales of their potential as targets and development of their inhibitors together with topoisomerase poisons or DNA damaging agents.
RESUMO
Objective Carbonic anhydrase 1 (CA1) not only enhances the hydration reaction but also promotes the formation of CaCO3,which is an essential step for new bone formation in vitro.However,there is no direct evidence to demonstrate the involvement of CA1 in bio-mineralization in cells and tissues.This study is aimed to evaluate the important role of CA1 in bio-mineralization and ossification in cultured cells.Methods Calcification in Saos-2 cells was induced using osteogenic medium (OM) and the calcification was determined by Alizarin Red-S staining.The expressions of ossification protein marker Runt-related transcription factor-2 (Runx2),osterix (OSX),alkaline phosphatase (ALP),osteocalcin (OCN) and bone sialoprotein (BSP) were detected in the process of bone formation by real-time PCR.The expression of CA 1 in the calcified cells were measured using real-time PCR and Western blotting.We also detected calcification in Saos-2 cells in the presence of acetazolamide,an anti-carbonic anhydrase drug to CA1,to determine the role of CA1 in biomineralization in culture cells.T test analysis was used to compare the two groups,M-ANOVA of repeated measurs was conducted for different time point.Results Following the stimulation of OM,Saos-2 cells produced a great amount of calcium-rich deposits [0.68±0.03 vs 2.76±0.13,P＜0.01].Increased transcriptions of ossification protein markers were also detected in these stimulated Saos-2 cells,indicating that the OM launched the process of bone formation in the cells.CA1 had a significantly increased expression during this process [0.25±0.03 vs 0.94±0.06,P＜0.01].Following treatment with acetazolamide,the expression of CA1 evidently declined [1.09±0.05 vs 0.55±0.07,P＜0.05],and the mineralized nodule formation was declined [2.76±0.13 vs 2.19±0.07,P＜0.01].Conclusion These findings indicate that CA1 participates in the biomineralization and ossification,and may play an important roles in bone formation.
RESUMO
Cardiovascular reactions to acrylic bone cement in patients with total hip replacement are a common complication. Hypotension and arrhythmias are the most frequently observed symptoms. Elderly patients with fractures of the femoral neck constitute a special risk group. In some patients these reactions will be fatal. The mechanisms suggested to explain these reactions are embolism of air, polymer or fat, reaction to the heat, and toxic or vasodilating effects of the acrylic monomer. It may be that potentially lethal complications only occur if two or more of the predisposing factors (hypovolemia, myocardial insufficiency, arrhythmia, embolism, histamine release) are present simultaneously. We have experienced a case of complication following bone cement insertion under spinal anesthesia. This female patient was 91 years old with old myocardial infarction on EKG.