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Lattice strain ruthenium nanoparticles uniformly and stably supported on nitrogen-modified carbon nanosheets(RuNPs/NC)were prepared via simple wet-chemical and subsequent pyrolysis method.The nitrogen doped NC could effectively improve their uniform dispersion and lattice compression of RuNPs.Through changing the pyrolysis temperature,the nitrogen content,types and degree of lattice strain of RuNPs could be effectively tuned,which could be used to adjust and control their peroxidase-like activity.The as-prepared RuNPs/NC-900 exhibited highest peroxidase-like activity,and could catalyze the oxidation of 3,3′,5,5′-tetramethylbenzidine(TMB)to produce a blue product with the maximum absorption at 652 nm in the presence of H2O2.The steady-state kinetic analysis indicated that the reaction catalyzed by RuNPs/NC followed the Michaelis-Menten kinetic model.Tannic acid(TA),gallic acid(GA)and ascorbic acid(AA)could effectively inhibit the RuNPs/NC-H2O2-triggered chromogenic reaction of TMB,resulting in color fading and decrease in absorbance.Based on this,a sensitive and accurate system was constructed for detection of TA,GA and AA.The detection limits(3σ/S)for TA,GA and AA were 0.014,0.014 and 0.29 μmol/L,respectively.This study not only developed a colorimetric sensing method based on RuNPs/NC nanozyme but also offered a new approach for the sensitive detection of antioxidants in food.
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Chronic pain has been a prominent public health issue in China for years,affecting over 30%of the population.The mechanism of chronic pain has always been a controversial and difficult topic of pain medicine research.The polarization of microglia inherent in the central nervous system when the external microenvironment changes and the subsequent neuroinflammatory response are critical in chronic pain.Microglia can polarize into pro-inflammatory M1 or anti-inflammatory M2 phenotypes during neuroin-flammatory reactions,exerting neurotoxic or neuroprotective effects in the nervous system,respectively.The aim of the article is proposed to provide an overview of the main mechanisms of microglial polarization and-how it might contribute to chronic pain.
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Based on the theory of "one qi circulation" founded by HUANG Yuanyu, the core disease mechanism of colorectal cancer is the innate spleen deficiency and stomach qi failing to bear downward, which leads to the turbidity assemble in large intestine, forming the carcinoma toxin, and ultimately transforms into colorectal cancer. The treatment should base on recovering the circulation of qi, Huangya Decoction (黄芽汤) as the basic formula, the circulation of qi ascending and descending as the base, adjusting ascending and descending together with Xiaqi Decoction (下气汤), and differentiating the syndrome on yin-yang excess-deficiency; for spleen-kidney yang deficiency syndrome, treated with Tianhun Decoction (天魂汤) to supplement liver, kidney and assist yang; for liver-kidney yin deficiency syndrome, treated wtih Dipo Decoction (地魄汤) to supplement lung, kidney, and assist yang. They jointly prompt one qi circulation to provide the thoughts for the treatment of colorectal cancer by traditional Chinese medicine.
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Objective:To evaluate the relationship between Sestrin2 and mitochondrial DNA (mtDNA)-NOD-like receptor associated protein 3 (NLRP3) inflammasome pathway during endotoxin-induced myocardial injury in mice.Methods:One hundred and eighty-four clean-grade healthy male ICR mice, aged 8-12 weeks, weighing 20-25 g, were used in this study. One hundred and sixty-eight mice were divided into 7 groups ( n=24 each) using the random number table method: normal control group (N group), lipopolysaccaride(LPS) group (L group), mtDNA group, LPS+ mtDNA group (M group), normal control+ negative control adeno-associated virus (AAV-NC)group (NC group), LPS+ mtDNA+ AAV-NC group (MC group), and LPS+ mtDNA+ Sestrin2 overexpression adeno-associated virus (AAV-Sestrin2) group (MSgroup). Another 10 mice were used to detect the transfection effect of AAV-Sestrin2, and the left 6 mice were used for mtDNA extraction. The model of endotoxemia was developed by intraperitoneal injection of LPS 10 mg/kg. mtDNA 5 mg/kg was intraperitoneally injected in mtDNA group, and mtDNA 5 mg/kg was intraperitoneally injected at 30 min after LPS injection in M group.AAV-Sestrin2 150 μl was injected via the tail vein in MS group, and the equal volume of AAV-NC was injected via the tail vein in MC and NC groups. Four weeks after virus injection, LPS 10 mg/kg was intraperitoneally injected and 30 min later mtDNA 5 mg/kg was intraperitoneally injected in MS and MC groups. Blood samples were collected at 24 h after LPS injection for determination of serum creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH) activities (by biochemical assay), concentrations of serum cardiac troponin I (cTnI), interleukin-18 (IL-18) and interleukin-1beta (IL-1β)(by enzyme-linked immunesorbent assay), and expression of mtDNA (by quantitative real-time polymerase chain reaction). The animals were sacrificed after the end of blood sampling and myocardial tissues were obtained for determination of the contents of reactive oxygen species (ROS), total antioxidant capacity (T-AOC), and adenosine triphosphate (ATP) and expression of NOD-like receptor associated protein 3 (NLRP3), active subunit p20 of caspase-1 (caspase-1p20) and apoptosis-associated microprotein (ASC) in myocardial tissues (by Western blot) and for microscopic examination of the pathological changes after HE staining (with a light microscope). Results:Compared with N group, the levels of CK-MB, LDH, cTnI, IL-1β and IL-18 in serum were significantly increased, the expression of mtDNA was up-regulated, the ROS content in myocardial tissues was increased, the T-AOC and ATP contents in myocardial tissues were decreased, the expression of NLRP3, caspase-1p20 and ASC in the myocardial tissues was up-regulated( P<0.05), and the pathological changes of myocardial tissues were aggravated in L group and mtDNA group.Compared with L group and mtDNA group, the levels of CK-MB, LDH, cTnI, IL-1β and IL-18 in serum were significantly increased, the expression of mtDNA was up-regulated, the ROS content in myocardial tissues was increased, the T-AOC and ATP contents in myocardial tissues were decreased, the expression of NLRP3, caspase-1p20 and ASC in the myocardial tissues was up-regulated( P<0.05), and the pathological changes of myocardial tissues were aggravated in M group. Compared with M group, the levels of CK-MB, LDH, cTnI, IL-1β and IL-18 in serum were significantly decreased, the expression of mtDNA was down-regulated, the ROS content in myocardial tissues was decreased, the T-AOC and ATP contents in myocardial tissues were increased, the expression of NLRP3, caspase-1p20 and ASC in the myocardial tissues was down-regulated( P<0.05), and the pathological changes of myocardial tissues were significantly attenuated in MS group. Conclusions:Sestrin2 can reduce endotoxin-induced myocardial injury in mice by alleviating mitochondrial damage, inhibiting oxidative stress, protecting mtDNA from oxidative damage, and then inhibiting mtDNA-NLRP3 inflammasome pathway.
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Epithelial basement membrane dystrophy(EBMD)is a common anterior corneal dystrophy with hidden and easily missed clinical manifestations. Patients usually complain of mild blurred vision or foreign body sensation, or occasional pain at night or immediately after opening the eyelid in the morning. Slit-lamp examination revealed irregular, amorphous corneal surfaces, fingerprint-like linear lesions, and punctate or bubble-like lesions. EBMD has a significant impact on preoperative biometrics and intraocular lens power calculation, which can lead to inaccurate measurement and postoperative refractive accident, and cataract surgeons must be aware of this. This article reviews recent research and conference reports on the impact of EBMD on cataract surgery, as a reference for refractive cataract surgeons, thus improving the preoperative diagnosis and detection rate, so as to provide the optimal treatment plan for patients.
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Molecularly imprinted polymers demonstrate outstanding performance in the research on trace ingredients because of their high selectivity. Stimuli-responsive molecularly imprinted polymers(STR-MIPs) with the introduction of different responsive groups on the basis of traditionally imprinted materials can undergo reversible transformations when exposed to external stimuli such as temperature, magnetism, pH or light. Such responsiveness, combined with the specific recognition, endows STR-MIPs with excellent perfor-mance in trace component studies. Traditional Chinese medicine(TCM) contains complex components with trace content, and thus STR-MIPs have broad application prospects in the enrichment analysis of trace components in TCM. This paper elaborates on the application of STR-MIPs in the enrichment analysis of trace components in TCM from the perspectives of different stimuli, summarized relevant research achievements in the recent five years to broaden the application fields of molecular imprinting, and proposed a few opi-nions about their future development.
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In the digital transformation of Chinese pharmaceutical industry, how to efficiently govern and analyze industrial data and excavate the valuable information contained therein to guide the production of drug products has always been a research hotspot and application difficulty. Generally, the Chinese pharmaceutical technique is relatively extensive, and the consistency of drug quality needs to be improved. To address this problem, we proposed an optimization method combining advanced calculation tools(e.g., Bayesian network, convolutional neural network, and Pareto multi-objective optimization algorithm) with lean six sigma tools(e.g., Shewhart control chart and process performance index) to dig deeply into historical industrial data and guide the continuous improvement of pharmaceutical processes. Further, we employed this strategy to optimize the manufacturing process of sporoderm-removal Ganoderma lucidum spore powder. After optimization, we preliminarily obtained the possible interval combination of critical parameters to ensure the P_(pk) values of the critical quality properties including moisture, fineness, crude polysaccharide, and total triterpenes of the sporoderm-removal G. lucidum spore powder to be no less than 1.33. The results indicate that the proposed strategy has an industrial application value.
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Teorema de Bayes , Mineração de Dados , Indústria Farmacêutica , Pós , Reishi , Esporos FúngicosRESUMO
Objective To investigate the role and molecular mechanism of Sirt1 in renal injury in diabetic mice under acute inflammatory state.Methods Forty SPF grade C57BL/6J male mice,8 weeks old,weighing 20-25 g were selected.The mice were divided into five groups by random number table meth-od:control group(group C),diabetic group(group D),lipopolysaccharide(LPS)+diabetic group(group L),LPS+diabetic+Sirt1 blocker EX527 group(group E),and LPS+diabetic+Sirt1 agonist ginkgoflavone sapogenins group(group G),8 mice in each group.After successful preparation of the diabet-ic mouse model,group L was injected intraperitoneally with LPS 10 mg/kg.Group E was injected intraper-itoneally with EX527 5 mg/kg(dissolved in DMSO 0.2 ml)1 hour before giving LPS treatment to diabetic mice.Group G was injected intraperitoneally with 200 mg/kg of ginkgoflavone sapogenins(dissolved in DMSO 0.2 ml)1 hour before LPS treatment was given to diabetic mice,groups C and D underwent an in-traperitoneal injection of 2%DMSO 0.15 ml at the same time point.24-hours urine volume was collected and 24-hours urinary protein concentration was determined,and blood was taken from the posterior eyes to detect serum Scr and BUN concentrations.After kidney tissues were removed,IL-1βand IL-18 concentra-tions were measured by ELISA,nitrate reductase assay for nitric oxide(NO)content in kidney,iron ion an-tioxidant capacity assay for total antioxidant capacity(T-AOC),qPCR and Western blot assay for Sirtl,caspase-1,NLRP3,and ASC mRNA expression and protein content.The acetylated FoxO3a protein content was detected by immunoprecipitation,the reactive oxygen species(ROS)content was calculated by di-hydroethidium staining,the pyroptosis rate was calculated by immunofluorescence double staining,HE stai-ning was performed,and the pathological results were observed under light microscope.Results Compared with group C,24-hours urine volume,urine protein concentration,serum Scr and BUN concentration,con-centrations of renal tissue IL-1β,IL-18,and NO,NLRP3,caspase-1,and ASC mRNA expressions and protein contents,ROS content and pyroptosis rate were significantly increased,T-AOC activity was signifi-cantly decreased in groups D,L,E,and G(P<0.05).Compared with group D,24-hours urine volume,urine protein concentration,serum Scr and BUN concentration,concentrations of renal tissue IL-1 β,IL-18,and NO,NLRP3,caspase-1,and ASC mRNA expressions and protein contents,ROS content and pyroptosis rate were significantly increased,T-AOC activity was significantly decreased in groups L,E,and G(P<0.05).Compared with group L,24-hours urine volume,urine protein concentration,serum Scr and BUN concentration,concentrations of renal tissue IL-1β,IL-18,and NO,NLRP3,caspase-1,and ASC mRNA expressions and protein contents,acetylated FoxO3a protein content,ROS content,and pyroptosis rate were significantly increased,T-AOC activity,Sirt1 mRNA expression and protein content,and FoxO3a mRNA expression were significantly decreased in group E(P<0.05),24-hours urine volume,urine pro-tein concentration,serum Scr and BUN concentration,concentrations of renal tissue IL-1β,IL-18,and NO,NLRP3,caspase-1,and ASC mRNA expressions and protein contents,acetylated FoxO3a protein con-tent,ROS content and pyroptosis rate were significantly decreased,T-AOC activity,Sirt1 mRNA expression and protein content were significantly increased in group G(P<0.05).Compared with group E,24-hours urine volume,urinary protein concentration,serum Scr and BUN concentration,concentrations of renal tissue IL-1β,IL-18,and NO,NLRP3,caspase-1,and ASC mRNA expressions and protein contents,acetylated FoxO3a protein content,ROS content,and pyroptosis rate were significantly decreased,T-AOC activity,Sirt1 mRNA expression and protein content were significantly increased in group G(P<0.05).Conclusion In diabetic mice under acute inflammatory state,elevated Sirt1 reduces kidney injury by de-creasing acetylated FoxO3a protein content,reduced urine volume,urine protein concentration,serum Scr and BUN concentration,inflammatory factor concentrations and apoptosis levels in renal tissue,and attenua-ted oxidative stress and inflammation levels.
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Objective:To evaluate the role of silencing regulatory protein (SIRT1) and its associated microRNAs (miRNAs) in dexmedetomidine-induced attenuation of renal damage in diabetic mice.Methods:SPF grade C57 male mice, aged 8 weeks, in which diabetes mellitus model was developed by intraperitoneal injection of 1% streptozotocin, were used.Thirty mice in which the model was successfully developed were divided into 5 groups ( n=6 each) using the random number table method: diabetes mellitus group (D group), diabetes mellitus + dexmedetomidine group (DD group), diabetes mellitus + dexmedetomidine + EX527 group (DDE group), diabetes mellitus + dexmedetomidine + miR-34a-3p-agomir group (DDH group), and diabetes mellitus + dexmedetomidine + miR-34a-3p-agomirNC group (DDC group). Six normal mice were selected as control group (C group). Dexmedetomidine 40 μg/kg was intraperitoneally injected once every 2 h, 3 times in total in DD, DDE, DDH and DDC groups.miR-34a-3p-agomir and miR-34a-3p-agomirNC 2.5 mmol were intraperitoneally injected via the tail vein at 72 h before dexmedetomidine administration once every 3 days, 2 times in total in DDH and DDC groups, respectively.SIRT1 inhibitor EX527 10 mg/kg was intraperitoneally injected at 1 h before dexmedetomidine administration in group DDE.At 24 h after the end of administration, serum concentrations of IL-6, IL-18, Cr and BUN, contents of nitric oxide (NO) and total antioxidant capacity (T-AOC), ROS activity, and expression of SIRT1, FoxO3a and P53 protein and mRNA, and expression of miR-217, miR-138 and miR-34a in renal tissues were determined. Results:Compared with group C, the serum IL-6, IL-18, Cr and BUN concentrations, contents of T-AOC and NO, and ROS activity were significantly increased, the expression of P53 protein and mRNA, miR-34a, miR-217 and miR-138 was up-regulated, and the expression of SIRT1 and FoxO3a protein and mRNA was down-regulated in group D ( P<0.05). Compared with group D, serum IL-6, IL-18, Cr and BUN concentrations, ROS activity and NO content were significantly decreased, T-AOC content was increased, the expression of SIRT1 and FoxO3a protein and mRNA was up-regulated, and the expression of miR-34a was down-regulated in group DD ( P<0.05). Compared with group DD, the serum IL-6, IL-18, Cr and BUN concentrations, NO content and ROS activity were significantly increased, T-AOC content was decreased, and the expression of SIRT1 and FoxO3a protein and mRNA was down-regulated in group DDE and group DDH ( P<0.05), no significant change was found in the expression of P53 protein and mRNA, miR-217, miR-34a and miR-138 in group DDE ( P>0.05), and the expression of P53 protein and mRNA and miR-34a was significantly up-regulated in group DDH ( P<0.05). Conclusions:The mechanism by which dexmedetomidine attenuates renal injury may be related to down-regulation of miR-34a expression, which further up-regulates SIRT1/FoxO3 expression and decreases oxidative stress in diabetic mice.
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In 2011, the FDA approved ipilimumab, the first immune checkpoint inhibitor(ICI), targeting CTLA-4, opening the field of immune checkpoint therapy (ICT). ICIs can induce durable clinical responses and improve survival in selected population. However, significant challenges still remain, including mechanisms of resistance, patient selection, management of serious immune-related adverse events, and rational therapeutic combinations. This review surveys the current understanding of response and resistance to ICIs and proposes a path forward to improving efficacy and minimizing toxicities.
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This study aims to explore the molecular mechanism of Ganoderma against gastric cancer based on network pharmacology, molecular docking, and cell experiment. The active components and targets of Ganoderma were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), and gastric cancer-related targets from GeneCards and Online Mendelian Inheritance in Man(OMIM). The protein-protein interaction(PPI) network of the common targets was constructed with STRING, followed by Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis of the common genes based on Bioconductor and R language. The medicinal-disease-component-target network and medicinal-disease-component-target-pathway network were established by Cytoscape. Molecular docking was performed between β-sitosterol(the key component in Ganoderma) and the top 15 targets in the PPI network. Cell experiment was performed to verify the findings. A total of 14 active components and 28 targets of Ganoderma were retrieved, and the medicinal and the disease shared 25 targets, including caspase-3(CASP3), caspase-8(CASP8), caspase-9(CASP9), and B-cell lymphoma-2(BCL2). The common targets involved 72 signaling pathways and apoptosis and p53 signaling pathway may play a crucial role in the effect of Ganoderma against gastric cancer. β-sitosterol had strong binding activity to the top 15 targets in the PPI network. The in vitro cell experiment demonstrated that β-sitosterol inhibited gastric cancer AGS cell proliferation by inducing cell apoptosis and cell cycle arrest in the S phase, which might be related to the regulation of the p53 pathway. This study shows the multi-component, multi-target, and multi-pathway characteristics of Ganoderma against gastric cancer, which lays a scientific basis for further research on the molecular mechanism.
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Humanos , Ganoderma , Medicina Tradicional Chinesa , Simulação de Acoplamento Molecular , Farmacologia em Rede , Neoplasias Gástricas/genéticaRESUMO
OBJECTIVE To explore t he protective mechanism of Yangxin dingji capsules on the cardiomyocytes of diabetic cardiomyopathy(DCM)model golden hamsters. METHODS In this study ,golden hamsters were divided into control group (n= 10,no modeling ,no drug administration ),model group (n=9,modeling,no drug administration ),TCM high-dose group [ n=8, modeling,Yangxin dingji capsules 2 g/(kg·d)],TCM low-dose group [ n=8,modeling,Yangxin dingji capsules 1 g/(kg·d)] and empagliflozin group [ n=9,positive control ,modeling,10 mg/(kg·d)]. All the golden hamsters were gavaged continuously for 8 weeks. The general conditions of golden hamsters were observed during the experiment. Blood glucose ,total cholesterol (TC)and creatine kinase MB (CK-MB),ejection fraction (EF),fractional shortening (FS),interleukin 1β(IL-1β)and transforming growth factor β1(TGF-β1)were detected ;the histopathological changes of myocardium were observed. mRNA and protein expression of nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3),caspase-1,aspirin D (GSDMD),nuclear factor κB (NF-κB)and IL- 1β were detected and observed;DNA damage in myocardial was detected. RESULTS Compared with control group,the blood glucose ,TC,CK-MB,serum IL- 1β,TGF-β1 levels,the mRNA expressions and positive protein expression of NLRP 3,caspase-1,GSDMD,NF-κ B and IL-1 β and protein expression of GSDMD in golden hamsters were significantly increased in model group (P<0.05 or P<0.01) EF and FS were significantly decreased (P<0.01);the fibers of myocardial cells was disordered , and the blue-stained collagen fibers between the myocardium increased ; DNA damaged positive cells in myocardial tiss ue of gold hamsters increased significantly. Compared with model group,the above indexes of administration groups were reversed to varying degrees ;the gap of myocardial cells were clear ,and the fibers disorder was improved ;the DNA damaged positive cells in the myocardial tissue were reduced to varying degrees. CONCLUSIONS Yangxin dingji capsule can inhibit the cardiomyocyte pyroptosis and relieve the inflammatory injury of DCM in DCM model golden hamsters by regulating the NLRP 3/caspase-1/GSDMD signaling pathway ,so as to protect the cardiomyocytes.
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Aim To explore the effeet of riboflavin on the establishment of pressure overload-induced heart failure model in mice by thoracic aortie constrietion (TAC ) and its preventive mechanism.Methods Eight-week-old SPF C57BL/6J mice were seleeted and divided into four groups; Sham group.Sham + ribofla¬vin group, TAC group and TAC + riboflavin group.A mouse heart failure model was constructed in the TAC group.The miee in the TAC + riboflavin group were given riboflavin by gavage one week before and eight weeks after the operation.The cardiac ultrasound inde¬xes, the changes of cardiac morphology and mitochon¬drial function indexes, the expression of apoptosis pro¬teins, ATP content, SCAD mRNA and protein expres¬sion, enzyme activity and flavin adenine dinucleotide (FAD) content in myocardial tissues were detected.Hie free fatty acid content in serum and myocardial tis¬sues were also detected.Results Compared with the sham group, the cardiac function indexes of the mice in the TAC group decreased, anrl typical heart failure occurred.Moreover, the expression of SCAD, enzyme activity, ATP and FAD content in the myocardium sig-nificantly decreased, and the free fatty acid content in myocardium and serum significantly increased.Com¬pared with the TAC group, after riboflavin treatment, the cardiac function of mice in TAC + Riboflavin group was significantly improved.In addition, ATP content, SCAD expression, enzyme activity and FAD content in myocardium all significantly increased, and free fatty acid content in myocardium and serum markedly de¬creased.Conclusions Riboflavin may improve myo-cardial energy metabolism by increasing FAD content and activating SCAD, thereby inhibiting pressure over¬load-induced heart failure in mice.
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Objective:To evaluate the effect of dexmedetomidine on pyroptosis in mice with acute renal injury induced by endotoxin and the relationship with miRNA-223-3p.Methods:Thirty-two clean-grade healthy male ICR mice, aged 8-12 weeks, weighing 20-25 g, were divided into 4 groups ( n=8 each) using the random number table method: control group (group C), lipopolysaccharide (LPS) group (group L), LPS plus dexmedetomidine group (group LD), and LPS plus dexmedetomidine plus atipamezole group (group LDT). The model of acute renal injury induced by endotoxin was established by intraperitoneal injection of LPS 400 μg/kg, followed by intraperitoneal injection of LPS 10 mg/kg 8 h later.Dexmedetomidine 40 μg/kg was intraperitoneally injected once every 2 h for 3 times in total starting from 30 min after establishing the model in group LD.Atipamezole 750 μg/kg was intraperitoneally injected immediately after establishing the model, and 30 min later dexmedetomidine 40 μg/kg was intraperitoneally injected once every 2 h for 3 times in total in group LDT.The equal volume of normal saline was intraperitoneally injected in group C. Blood samples were collected from the heart at 24 h after establishing the model, and serum creatinine (Cr) and blood urea nitrogen (BUN) concentrations were measured with an automatic biochemical analyzer.The animals were sacrificed and the left kidney tissues were obtained for microscopic examination of pathological changes after HE staining (with a light microscope) and for determination of the expression of caspase-1 p20, NOD-like receptor thermoprotein structural domain-related protein 3 (NLRP3) and ASC protein and mRNA (by quantitative real-time polymerase chain reaction and Western blot), contents of interleukin-1beta (IL-1β) and IL-18 (by enzyme-linked immunosorbent assay), and rate of pyroptosis in renal cortical cells (by TUNEL). Results:Compared with group C, the concentrations of serum Cr and BUN were significantly increased, the expression of NLRP3, caspase-1 p20 and ASC protein and mRNA in the renal tissues was up-regulated, the contents of IL-1β and IL-18 were increased, the rate of pyroptosis in renal cortical cells was increased ( P<0.05), no significant change was found in the expression of miRNA-223-3p ( P>0.05), and pathological changes of kidney were accentuated in group L. Compared with group L, the concentrations of serum Cr and BUN were significantly decreased, the expression of NLRP3, caspase-1 p20 and ASC protein and mRNA in the renal tissues was down-regulated, the contents of IL-1β and IL-18 were decreased, the rate of pyroptosis in renal cortical cells was decreased, the expression of miRNA-223-3p was up-regulated ( P<0.05), and pathological changes of kidney were attenuated in group LD.Compared with group LD, the concentrations of serum Cr and BUN were significantly increased, the contents of IL-1β and IL-18 were increased, the expression of NLRP3, caspase-1 p20 and ASC protein and mRNA in the renal tissues was up-regulated, the rate of pyroptosis in renal cortical cells was increased, the expression of miRNA-223-3p was down-regulated ( P<0.05), and the pathological changes of kidney were accentuated in group LDT. Conclusion:The mechanism by which dexmedetomidine reduces acute renal injury may be related to up-regulating the expression of miRNA-223-3p and inhibiting pyroptosis in mice.
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Objective:To investigate the effect of diabetes mellitus on pulmonary uptake of sevoflurane.Methods:Twenty patients with type 2 diabetes mellitus, aged 40-64 yr, with body mass index of 18.5-22.9 kg/m 2, of American Society of Anesthesiologists physical status Ⅰ or Ⅱ, undergoing elective surgery with general anesthesia, served as diabetes group (group D). Twenty non-diabetic patients matched by age, gender and surgery were selected as control group (group C). After anesthesia induction and tracheal intubation, sevoflurane was inhaled at a concentration of 2% (oxygen flow 2 L/min). The inhaled concentration (Fi) and exhaled concentration (Fa) at 1, 3, 5, 10, 15, 20 and 30 min of inhalation of sevoflurane were recorded, and the Fa/Fi ratio was calculated.The time required for the Fa/Fi ratio to reach 0.7 was recorded. Results:Compared with group C, the Fa/Fi ratio was significantly increased at each time point, and the time required for the Fa/Fi ratio to reach 0.7 was shortened in group D ( P<0.05). Conclusion:Diabetes mellitus can reduce pulmonary uptake of sevoflurane in the patients.
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Objective:To observe the expression levels of glial fibrillary acidic protein (GFAP), β-tubulin Ⅲ and synaptophsin, and explore the role of tripartite synapse in the mechanism of central nervous system (CNS) injury and the neuroprotective effect of chondroitin sulfate (CS).Methods:One month old clean grade, 48 female Sparague-Dawley rats and 48 male Sparague-Dawley rats, were randomly divided into 8 groups according to body weight (90 - 120 g) by random number table method, with 12 rats in each group, half male and half female. These rats were fed with water containing different concentrations of sodium fluoride (NaF) [ < 0.5 mg/L (control, CN), 10.0 mg/L (low dose fluoride, LF) and 50.0 mg/L (high dose fluoride, HF)]. Some rats were fed directly for 185 days (CN, LF and HF groups). In addition, rats of CN + normal saline (NS), LF + NS, HF + NS groups and LF + CS, HF + CS groups, were intraperitoneally injected with NS or 0.66 mg/kg CS for 5 consecutive days after 180 days of feeding. After the experiment, the pathological changes of hippocampal CA4 of brain tissue in each group were observed by hematoxylin eosin staining under light microscope, and the expression and distribution of GFAP, β-tubulin Ⅲ and synaptophsin in hippocampal CA4 of rats were detected by immunohistochemistry, the expression of GFAP, β-tubulin Ⅲ and synaptophsin at protein level in hippocampus of rats were detected by Western blotting.Results:Under light microscope, eosinophilic change, loss and irregular arrangement of neuron in the hippocampal CA4 were observed in LF, HF, LF + NS and HF + NS groups. The morphology of LF + CS and HF + CS groups was not significantly changed compared with CN group, but was significant changed compared with LF, HF, LF + NS and HF + NS groups. Immunohistochemical results showed that the rates of positive area of GFAP, β-tubulin Ⅲ and synaptophsin in female and male rats in LF and HF groups were significantly decreased than those in CN group ( P < 0.05); the positive area rates of female and male rats in LF + CS and HF + CS groups were higher than those in LF and HF groups, respectively ( P < 0.05). Western blotting results showed that the proten expression levels of GFAP, β-tubulin Ⅲ and synaptophsin of female and male rats in LF and HF groups (LF group: 0.90 ± 0.09, 0.82 ± 0.08, 1.43 ± 0.14, 0.92 ± 0.02, 1.21 ± 0.15, 0.87 ± 0.02, HF group: 0.58 ± 0.14, 0.73 ± 0.03, 0.63 ± 0.06, 0.67 ± 0.03, 0.87 ± 0.04, 0.70 ± 0.05) were lower than those in CN group (1.24 ± 0.08, 1.09 ± 0.10, 2.64 ± 0.30, 1.54 ± 0.09, 1.72 ± 0.10, 1.13 ± 0.06, P < 0.05). Conclusions:The tripartite synapse and extracellular matrix may take part in pathogenesis of the damages of CNS results from chronic fluorosis; CS may reduce the injury to a certain extent.
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Background@#Lumbar disc herniation (LDH) is a common cause of radicular pain, but the mechanism is not clear. In this study, we investigated the engagement of toll-like receptor 4 (TLR4) and the nuclear factor-kappa B (NF-κB) in radicular pain and its possible mechanisms. @*Methods@#An LDH model was induced by autologous nucleus pulposus (NP) implantation, which was obtained from coccygeal vertebra, then relocated in the lumbar 4/5 spinal nerve roots of rats. Mechanical and thermal pain behaviors were assessed by using von Frey filaments and hotplate test respectively. The protein level of TLR4 and phosphorylated-p65 (p-p65) was evaluated by western blotting analysis and immunofluorescence staining. Spinal microglia activation was evaluated by immunofluorescence staining of specific relevant markers. The expression of proand anti-inflammatory cytokines in the spinal dorsal horn was measured by enzyme linked immunosorbent assay. @*Results@#Spinal expression of TLR4 and p-NF-κB (p-p65) was significantly increased after NP implantation, lasting up to 14 days. TLR4 was mainly expressed in spinal microglia, but not astrocytes or neurons. TLR4 antagonist TAK242 decreased spinal expression of p-p65. TAK242 or NF-κB inhibitor pyrrolidinedithiocarbamic acid alleviated mechanical and thermal pain behaviors, inhibited spinal microglia activation, moderated spinal inflammatory response manifested by decreasing interleukin (IL)-1β, IL-6, tumor necrosis factor-α expression and increasing IL-10 expression in the spinal dorsal horn. @*Conclusions@#The study revealed that TLR4/NF-κB pathway participated in radicular pain by encouraging spinal microglia activation and inflammatory response.
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OBJECTIVE:To provide reference for the participation of clinical pharm acists in outpatient antibiotics management so as to promote the rational use of antibiotics in outpatient department. METHODS :The pharmacist reset medication rules , classified irrational medication levels ,formulated warning contents ,and established a diagnosis database of mild to moderate non- complex infections ,according to the problems found in the post review of outpatient antibiotics prescription through sorting out the previous rules of antibiotics use in the Yiyao Rational Drug Use Management Software (called“review software ”for short )in our hospital. The special pre-review was performed by using combination of system review and manual review. Pharmacists used the review saftware to count the data of outpatient antibiotics prescriptions before (the first quarter of 2020)and after (the second , third and fourth quarters of 2020)the implementation of special pre-review. The post review for antibiotics prescriptions in Dec. 2019(before the implementation of special pre-review )and Dec. 2020(after implementation of special pre-review )were performed by pharmacists to evaluate the impact of the implementation of special pre-review on promoting rational use of outpatient antibitics. RESULTS:Comared with before the implementation of special pre-review in the first quarter of 2020,the prompt rate of the review software for antibiotics prescriptions was decreased ,and the interception rate was increased after the implementation of special pre-review in the second quarter of 2020(P<0.05). Compared with before the implementation of special pre-review in Dec. 2019,the proportion of outpatient antibiotics prescriptions in all outpatient prescriptions ,the ratio of bi-antibiotics prescriptions in all antibiotics prescriptions in the same month ,the ratio of prescriptions with unsuitable indications in all antibiotics prescriptions in the same month were all decreased E-mail:phdloveyou@163.com significantly (P<0.01), while the ratio of prescriptions with rational antibiotics use in all antibiotics prescriptions in the same month was increased significantly (P<0.01). CONCLUSIONS:Pharmacists establishing a rule for rational use of antibiotics in outpatient department b ased o n the hospital ’s situation,implementing a special pre-review for antibiotics prescriptions with the help of review software ,can promote the rational use of antibiotics in outpatient department.
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Objective:To investigate the predicting value of high sensitivity C-reactive protein (hs-CRP) and albumin (Alb) ratio on prognosis of patients with in-hospital cardiac arrest (IHCA).Methods:A total of 107 patients with IHCA and spontaneous circulation recovery (ROSC) after cardiopulmonary resuscitation (CPR) in the Affiliated Hospital of Xuzhou Medical University during January 1, 2017 and September 30, 2020 were selected as the subjects and divided into the survival group and death group according to the survival condition on day 14 after IHCA. The correlation between ratio of high sensitivity C-reactive protein/albumin (hs-CRP/Alb) and the prognosis of patients was analyzed.Results:No statistical significant differences were found between the survival and death groups in sex, age, medical history, ECG monitoring, recovery ventilation mode, percentage of first monitoring of heart rate and pre-resuscitation Alb (all P > 0.05). However, there were significant differences in the percentage of non-cardiogenic CA and adrenaline dose > 5 mg, time of CPR, concentrations of blood lactic acid, Alb, hs-CRP, and ratio of hs-CRP/Alb (all P < 0.05). Logistic regression analysis showed that percentage of adrenaline dose > 5 mg, concentration of blood lactic acid, time of CPR, and ratio of hs-CRP/Alb were independent risk factors for predicting death. ROC curve analysis showed that hs-CRP/Alb ratio, and concentration of hs-CRP and Alb had predictive value on the death of patients with IHCA; the areas under the curves of hs-CRP/Alb ratio, hs-CRP and Alb concentration were 0.876, 0.864 and 0.745, respectively. The predictive efficiency of hs-CRP/Alb ratio was better than that of hs-CRP concentration or Alb concentration. Conclusions:hs-CRP/Alb ratio has predictive value for the prognosis of patients with IHCA and the predictive value is superior to that of hs-CRP and Alb concentration.
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Long tracheal lesions are mainly caused by stenosis, infection, trauma, malignant tumors and other factors. Resection of the diseased tissue or stenosis and end-to-end anastomosis is currently the gold standard for long tracheal lesions treatment. However, these treatment programs have proven to have major limitations. In recent years, tissue engineering technology has been regarded as a promising medical alternative treatment method, and the selection of scaffold materials is one of key parts. With the continuous exploration of domestic and foreign researchers, biological materials have been continuously developed and applied to the research of tissue engineering trachea. Tissue engineering degradable scaffold materials can be divided into natural polymer material scaffolds and synthetic polymer scaffolds according to the different sources. The scaffold material can be modified or compounded as needed to improve the biological properties of scaffolds. In addition, with the continuous development of biological printing technology, different scaffold materials can be better combined and used. Biodegradable scaffolds have become a new research direction in the field of tissue engineering trachea due to their polymer properties, and have good application prospects.