RESUMO
OBJECTIVE: Cardiac surgery, especially when employing cardiopulmonary bypass and deep hypothermic circulatory arrest, is associated with systemic inflammatory responses that significantly affect morbidity and mortality. Intestinal perfusion abnormalities have been implicated in such responses, but the mechanisms linking local injury and systemic inflammation remain unclear. Intestinal mast cells are specialized immune cells that secrete various preformed effectors in response to cellular stress. We hypothesized that mast cells are activated in a microenvironment shaped by intestinal ischemia/reperfusion, and investigated local and systemic consequences. DESIGN: Rat model of deep hypothermic circulatory arrest. SETTING: University research laboratory. SUBJECTS: Twelve- to 14-week-old male Sprague-Dawley rats. INTERVENTIONS: Rats were anesthetized and cooled to 16°C to 18°C on cardiopulmonary bypass before instituting deep hypothermic circulatory arrest for 45 minutes. Specimens were harvested following rewarming and 2 hours of recovery. MEASUREMENTS AND MAIN RESULTS: Significant intestinal barrier disruption was found, together with macro- and microscopic evidence of ischemia/reperfusion injury in ileum and colon, but not in the lungs or kidneys. Immunofluorescence and toluidine blue staining revealed increased numbers of mast cells and their activation in the gut. In animals pretreated with the mast cell stabilizer, cromolyn sodium, mast cell degranulation was blocked, and intestinal morphology and barrier function were preserved following deep hypothermic circulatory arrest. Furthermore, cromolyn sodium treatment was associated with reduced intestinal neutrophil influx and blunted systemic release of proinflammatory cytokines. CONCLUSION: Our data provide primary evidence that intestinal ischemia/reperfusion is a leading pathophysiologic process in a rat model of deep hypothermic circulatory arrest, and that intestinal injury, and local and systemic inflammatory responses are critically dependent on mast cell activation. This identifies intestinal mast cells as central players in deep hypothermic circulatory arrest-associated responses, and opens novel therapeutic possibilities for patients undergoing this procedure.
Assuntos
Parada Circulatória Induzida por Hipotermia Profunda , Intestinos/irrigação sanguínea , Mastócitos/fisiologia , Traumatismo por Reperfusão/prevenção & controle , Síndrome de Resposta Inflamatória Sistêmica/fisiopatologia , Animais , Ponte Cardiopulmonar , Parada Circulatória Induzida por Hipotermia Profunda/efeitos adversos , Modelos Animais de Doenças , Hipotermia Induzida , Masculino , Mastócitos/imunologia , Ratos , Ratos Sprague-Dawley , Síndrome de Resposta Inflamatória Sistêmica/etiologiaRESUMO
With population aging and advances in dialysis technology, the proportion of elderly people among hemodialysis patients is getting higher, making concurrent geriatric syndromes an important issue that deserves particular consideration in the management of dialysis patients in clinical practice.Common geriatric syndromes, such as frailty, sarcopenia, malnutrition, physical dysfunction, cognitive impairment and depression, have a high prevalence in hemodialysis patients and are associated with poor prognosis.Comprehensive geriatric assessment of elderly hemodialysis patients can identify high-risk patients early, help implement stratified care, and serve as a valuable guide in the improvement of patients' prognosis and quality of life.
RESUMO
【Objective】 To observe the effect of deglycerolized red blood cells suspended in MAP on preservation and explore the most effective preservation method. 【Methods】 Concentrated red blood cells were prepared by centrifuging 400 mL of whole blood on the third day after collection. 40% compound glycerol solution was added using the ACP 215 automatic blood cell analyzer, and the resulting mixture was stored in an ultra-low temperature refrigerator at -65℃ for 30 days. After thawing and washing, it was equally separated into two bags. The control group received 0.9% sodium chloride solution, while the experimental group received MAP. Both groups were stored at 2-6℃. Hematological parameters, hemolysis indexes and cell metabolism indexes were measured on day 0, 1, 3, 5, 7 and 14 after storage. The quality changes of both groups were observed during the 14-day storage period. 【Results】 The quality of red blood cells in both groups was assessed through a panel of quality tests, including volume, hemoglobin content, free hemoglobin content, white blood cell residue, glycerin residue and sterility. These results met the Quality Requirements outlined in the "Quality Requirements of Whole Blood and Component Blood" (GB18469-2012), Hematocrit, red blood cell count, Hb recovery rate after washing and MCV meet the detection limit outlined in the "Expert Consensus on Quality Evaluation Indicators for Frozen Red Blood Cells", and the residual amount of platelets exceeds the detection limit(≤1%). There were no significant differences in RBC, Hct, MCV and hemoglobin between the two groups during the 14 day storage period. The level of free hemoglobin, hemolysis rate and K+ value increased in both groups over time. Significant differences in free hemoglobin were found on day 3, 5, 7 and 14 between the two groups(P<0.05). Hemolysis rate was significantly different on days 3, 5, 7 and 14, while K+ value was significantly different only on day 14(P<0.05). On day 14, the osmotic fragility of red blood cells was higher in the control group than in the experimental group(P<0.05); The ATP and pH values of both groups decreased as storage time increased, and significant differences in ATP and pH value were found on day 3, 5, 7 and on day 1, 3, 5, 7 and 14, respectively(P<0.05). 【Conclusion】 Deglycerolized red blood cells suspended in MAP additive solution can extend the storage period of blood to 7 days. This study provides a reference for the formulation of relevant standards.
RESUMO
Objective:To investigate the correlation between hyperuricemia and renal function in elderly who received health examination.Methods:A cross-sectional study. A total of 503 elderly individuals who received health examinations in Beijing Friendship Hospital from August 2020 to June 2021 were selected as the study subjects. The general data and laboratory test results were collected. The logistic regression analysis was applied to analyze the factors affecting hyperuricemia. Spearman correlation analysis and multivariate logistic regression were used to analyze the association between hyperuricemia and renal function in those subjects.Results:The prevalence of hyperuricemia in the elderly was 19.9%, and multivariate logistic regression analysis indicated that drinking( OR=1.785, 95% CI: 1.087-2.932), body mass index( OR=1.133,95% CI: 1.046-1.226), high-density lipoprotein cholesterol( OR=0.107,95% CI: 0.036-0.316) and estimated glomerular filtration rate (eGFR)( OR=3.290,95% CI: 1.699-6.370) were influencing factors of hyperuricemia. The Spearman correlation analysis showed that blood uric acid level was negatively correlated with eGFR in the elderly ( r=-0.278, P<0.001), and after adjusting for drinking history, age, body mass index and high-density lipoprotein cholesterol, multiple logistic regression analysis showed that hyperuricemia was an independent risk factor for eGFR<60 ml·min -1·(1.73 m 2) -1 ( OR=3.019; 95% CI: 1.450-6.284). Conclusion:Drinking, body mass index, high-density lipoprotein cholesterol and renal insufficiency increase the risk of hyperuricemia in the elderly, and hyperuricemia is an independent risk factor for renal insufficiency in the elderly.
RESUMO
With the increase of the elderly population, health problems of the elderly are more prominent and the health needs of the elderly are more complex and diverse, therefore, how to maintain their physical functional status has become the focus of research. Physical resilience and successful aging are closely related. This article reviews the concept of physical resilience, the relationship between physical resilience and frailty and intrinsic capacity, and its impact on the health status of the elderly. The aim of the article is to provide a reference for the assessment of physiological resilience and the related interventions to promote healthy aging.
RESUMO
Objective:To construct and validate a predictive model for the risk of excessive blood loss in pa-tients with ruptured tubal pregnancy,and to provide a basis and tool for the assessment of changes in the condi-tion of patients with ruptured tubal pregnancy.Methods:Clinical data of inpatients with ruptured tubal pregnancy from January 2014 to July 2021 were retrospectively analyzed,who underwent surgical treatment in the Depart-ment of Gynecology,Dongguan Maternal and Child Health Hospital.The pelvic blood volume was categorized into excessive blood loss and non-excessive blood loss groups based on whether the amount of pelvic blood was found to be≥750 ml intraoperatively.Factors influencing the occurrence of excessive blood loss were screened and modeled by univariate analysis,Lasso regression,and multi-factor Logistic stepwise regression.The area un-der the subject working characteristic curve(AUC)was used to evaluate the discrimination of the predictive mod-el,the model's consistency was evaluated by calibration curve and goodness-of-fit test,and the clinical utility of the model was evaluated and validated by the decision analysis curve.Finally,column line plots were drawn.Results:①A total of 386 patients with ruptured tubal pregnancy were included,of whom 124(32.12%)had blood loss≥750 ml.②The optimal predictors for predicting concomitant blood loss in patients with ruptured tubal preg-nancy were screened,including:days of abdominal pain,dizziness,pallor,fatigue,the maximum diameter of para-metrial mass,human chorionic gonadotropin(β-hCG),and hemoglobin(Hb)and the model and the column line graphswere constructed accordingly.③The prediction model AUC was 0.827(95%CI 0.781-0.873);the cut-off value was 0.391,at which point the specificity and sensitivity were 68.55%and 84.35%,respectively,and the AUC validated within the model by resampling was 0.804.Clinical decision curves showed that the threshold probability intervals for the maximum net benefit values ranged from 8.5%-97%,respectively.Conclusions:The constructed prediction model was validated to suggest good discriminatory efficacy and degree of consistency.As a tool,it has clinical application value in predicting the risk of hemorrhage in patients with ruptured tubal pregnan-cy.It can help to determine the occurrence of adverse events such as hemorrhagic shock at an early stage and improve the success rate of rescue treatment.
RESUMO
@#Objective To analyze the clinical characteristics of the Guang’an Omicron epidemic and summarize the management experiences and practices in pandemic prevention and control of major infectious diseases. Methods Retrospective analysis was performed on patients infected with coronavirus disease (COVID-19), afterwards treated and observed in the isolation ward of Guang’an People’s Hospital and the shelter of Guang’an City from May 9 to June 26, 2022. The characteristics of patients at different age stages and the related factors affecting the severity, re-positive and negative conversion was analyzed. Results Finally 1 278 patients were collected, including 508 males and 770 females, with an average age of 41.3±22.6 years. Among them, 1 054 patients were asymptomatic carriers. The overall severe rate was 0.86%, the severe rate of the high-risk group was 3.06%. The median negative conversion time was 10.0 days and re-positive rate was 7.36%. Patients aged>60 years were 2.589 times more likely to have a longer negative conversion time than those aged≤60 years (95%CI 1.921-3.489, P<0.001). Conclusion The clinical characteristics of Guang’an COVID-19 epidemic are mainly that the elderly with high risk factors are more likely to develop severe cases, have longer clearance time, and re-positve is more likely to occur.
RESUMO
Objective:To study the multi-locus sequence typing (MLST) gene characteristics of Brucella isolates in Guizhou Province. Methods:Brucella strains, which were isolated from 2017 to 2021 in Guizhou Province (preserved in the Bacterial and Viral Seed Bank of Guizhou Center for Disease Control and Prevention) were identified Brucella and species/types by BCSP31-PCR and AMOS-PCR methods, respectively. MLST method was used for genotyping, and Biometrics 8.0 software was used for cluster analysis of the typing results. Results:A total of 32 strains of Brucella were isolated in Guizhou Province and identified as Brucella melitensis ( B.melitensis) by BCSP31-PCR and AMOS-PCR methods. These strains were classified into 2 ST types (ST8 and ST39) by MLST method, with 28 strains of ST8 type(87.5%) and 4 strains of ST39 type (12.5%). The 28 strains of ST8 type were distributed in 7 cities (prefectures) of Guizhou Province, while the 4 strains of ST39 type were only found in Qianxinan Buyi and Miao Autonomous Prefecture. The cluster analysis results showed that ST8 and ST39 types strains were clustered in a group with the reference strain of B.melitensis, and there was only one nucleotide site difference between ST39 and ST8 types in the glk gene, indicating a close genetic relationship. Conclusions:B.melitensis is the main pathogen of the brucellosis epidemic in Guizhou Province in recent years. ST8 is the dominant MLST genotype in Guizhou Province.
RESUMO
OBJECTIVE: To understand the genotypes and nucleotide polymorphisms of Echinococcus granulosus metacestode from humans and sheep in Tianjun region, Qinghai Province. METHODS: The specific primers were designed according to the cox1 and nad1 genes of E. granulosus mitochondrial genome sequences accessed by GenBank. The primers were used to detect the cyst samples from 16 sheep and 2 humans infected with E. granulosus in Tianjun region of Qinghai Province by PCR, then the PCR amplification products were sequenced, the genotypes and nucleotide polymorphisms of the cox1 and nad1 genes were analyzed. RESULTS: The 18 isolated samples all belonged to E. granulosus G1 genotype. Among all the isolates, 9 haplotypes existed in the cox1 gene with 16 nucleotide mutation sites, and there were 0 to 5 nucleotide differences with the highest variation rate of 0.31%, whereas 7 haplotypes occurred with 15 nucleotide mutation sites, and there were 1 to 8 nucleotide differences with the highest variation rate of 0.89% for the nad1 gene. CONCLUSIONS: The epidemic genotype of E. granulosus is G1 in humans and sheep in Tianjun region of Qinghai Province, and the nucleotide polymorphisms of the cox1 gene were more abundant than those of the nad1 gene, and the resolution of the nucleotide polymorphisms of cox1 gene is higher than that of the nad1 gene used in E. granulosus isolates.
Assuntos
Equinococose/parasitologia , Echinococcus granulosus/genética , Ovinos/parasitologia , Animais , China , Análise Mutacional de DNA , DNA de Helmintos/genética , Genes de Helmintos , Genótipo , Haplótipos , Humanos , FilogeniaRESUMO
Objective: To evaluate the effect of postoperative radiotherapy and high-risk pathological factors on the prognosis of early-stage neuroendocrine carcinoma of cervix (NECC). Methods: A single-center retrospective cohort study of early-stage NECC in Peking Union Medical College Hospital from January 2011 to April 2022 were enrolled. The patients were treated with radical hysterectomy±adjuvant treatment. They were divided into postoperative non-radiation group and postoperative radiation group. The possible postoperative recurrence risk factors identified by univariate analysis were assessed using multivariate logistic regression. The Kaplan-Meier method was used to analyze the progression free survival (PFS), overall survival (OS), recurrence rate, and mortality rate. Results: (1) Sixty-two cases were included in the study, including 33 cases in postoperative non-radiation group and 29 cases in postoperative radiation group. (2) The median follow-up time was 37 months (ranged 12-116 months), with 23 cases (37%) experienced recurrences. There were 7 cases (11%) pelvic recurrences and 20 cases (32%) distant recurrences, in which including 4 cases (6%) both pelvic and distant recurrences. Compared with postoperative non-radiation group, the postoperative radiation group had a lower pelvic recurrence rate (18% vs 3%; P=0.074) but without statistic difference, a slightly elevated distant recurrence rate (24% vs 41%; P=0.150) and overall recurrence rate (33% vs 41%; P=0.513) without statistically significances. Univariate analysis showed that lymph-vascular space invasion and the depth of cervical stromal invasion≥1/2 were risk factors for postoperative recurrence (all P<0.05). Multivariate analysis showed lymph-vascular space invasion was an independent predictor for postoperative recurrence (OR=23.03, 95%CI: 3.55-149.39, P=0.001). (3) During the follow-up period, 18 cases (29%, 18/62) died with tumor, with 10 cases (30%, 10/33) in postoperative non-radiation group and 8 cases (28%, 8/29) in postoperative radiation group, without significant difference (P=0.814). The postoperative 3-year and 5-year survival rate was 79.2%, 60.8%. The depth of cervical stromal invasion≥1/2 was more common in postoperative radiation group (27% vs 64%; P=0.011), and postoperative radiation in such patients showed an extended trend in PFS (32.3 vs 53.9 months) and OS (39.4 vs 73.4 months) but without statistic differences (P=0.704, P=0.371). Compared with postoperative non-radiation group, the postoperative radiation did not improve PFS (54.5 vs 37.3 months; P=0.860) and OS (56.2 vs 62.4 months; P=0.550) in patients with lymph-vascular space invasion. Conclusions: Postoperative radiation in early-stage NECC patients has a trend to reduce pelvic recurrence but not appear to decrease distant recurrence and overall recurrence, and has not improved mortality. For patients with the depth of cervical stromal invasion≥1/2, postoperative radiation has a trend of prolonging OS and PFS but without statistic difference. Lymph-vascular space invasion is an independent predictor for postoperative recurrence, but postoperative radiation in such patients does not seem to have any survival benefits.
Assuntos
Feminino , Humanos , Colo do Útero/cirurgia , Prognóstico , Estudos Retrospectivos , Neoplasias do Colo do Útero/cirurgia , Carcinoma Neuroendócrino/cirurgia , RecidivaRESUMO
Cinnamomum camphora is an important economic tree species in China. According to the type and content of main components in the volatile oil of leaf, C. camphora were divided into five chemotypes, including borneol-type, camphor-type, linalool-type, cineole-type, and nerolidol-type. Terpene synthase(TPS) is the key enzyme for the formation of these compounds. Although several key enzyme genes have been identified, the biosynthetic pathway of(+)-borneol, which has the most economic value, has not been reported. In this study, nine terpenoid synthase genes CcTPS1-CcTPS9 were cloned through transcriptome analysis of four chemical-type leaves. After the recombinant protein was induced by Escherichia coli, geranyl pyrophosphate(GPP) and farnesyl pyrophosphate(FPP) were used as substrates for enzymatic reaction, respectively. Both CcTPS1 and CcTPS9 could catalyze GPP to produce bornyl pyrophosphate, which could be hydrolyzed by phosphohydrolase to obtain(+)-borneol, and the product of(+)-borneol accounted for 0.4% and 89.3%, respectively. Both CcTPS3 and CcTPS6 could catalyze GPP to generate a single product linalool, and CcTPS6 could also react with FPP to generate nerolidol. CcTPS8 reacted with GPP to produce 1,8-cineol(30.71%). Nine terpene synthases produced 9 monoterpene and 6 sesquiterpenes. The study has identified the key enzyme genes responsible for borneol biosynthesis in C. camphora for the first time, laying a foundation for further elucidating the molecular mechanism of chemical type formation and cultivating new varieties of borneol with high yield by using bioengineering technology.
Assuntos
Cinnamomum camphora/enzimologia , Alquil e Aril Transferases/químicaRESUMO
Aim To investigate the mechanism of Qizhu anti-cancer prescription ( QZACP) inthe treatment of primary liver cancer using network pharmacology and molecular docking. Methods Drugs and primary liver cancer ( PLC) -related targets were found according to TCMSP database and disease databases such as GeneCard, the key chemical components and core targets were screened by Cytoscape 3. 9. 1 and String platform respectively, and a network relationship diagram of traditional Chinese medicine-active component-target was constructed by using Cytoscape 3.9. 1. GO functional analysis and KEGG pathway analysis were performed using DAVID platform, visualized by R 4. 1. 1 software, and finally the core clustered proteins were analyzed by CytoNCA plug-in to obtain the core action targets, and the core components and key targets were verified by using molecular docking technology and the pharmacodynamic mechanism of QZACP was further verified by animal experiments. Results The active ingredients of QZACP in the treatment of primary liver cancer may be quercetin, glycyrrhizin, Denudatin B, isoflavanone, sanguinarol, etc. ; the potential targets were STAT3, EGFR, AKT1 etc. ; the related pathways were mainly PI3K-Akt signaling pathway,MAPK signaling pathway,etc. ; molecular docking showed that the core compounds had better integrating conformation with the key targets. In addition, QZACP could inhibit the growth of tumor in nude mice and decrease the expression of STAT3, EGFR and AKT1. Conclusions Qizhu anti-cancer prescription may have some positive significance in the treatment of primary liver cancer, which may be related to the regulation of PI3K/Akt signaling pathway.
RESUMO
OBJECTIVE To re-eval uate the systematic review and meta-an alysis of umeclidinium bromide and vilanterol trifenatate(UMEC/VIL)in the treatment of chronic obstructive pulmonary disease (COPD),so as to provide evidence-based basis for the treatment of COPD. METHODS Retrieved from PubMed (Medline),the Cochrane library ,Embase,CNKI,CBM,VIP and Wanfang database ,etc.,the systematic review and meta-analysis of UMEC/VIL in the treatment of COPD were collected from the inception to Apr. 2021. Two reviewers independently screened the literatures and extracted the data. AMSTAR 2 scale,PRISMA statement,and GRADE evaluation system were used to evaluate the methodological quality of the included studies ,the quality of reports and the grade of outcome indexes. The efficacy and safety of UMEC/VIL in the treatment of COPD were reported. RESULTS Six systematic reviews were finally included. The results of AMSTAR 2 scale showed that 1 study was of high quality , 2 were of medium quality and 3 were of low quality. The score of PRISMA statement was between 21.5 and 27,and the quality of the report was relatively perfect. The results of GRADE evaluation showed that more than 60% of the 134 outcome indicators were of medium to high quality of evidence. Comparison of effectiveness and safety showed that UMEC/VIL was superior to placebo , unilateral bronchodilator and salmeterol fluticasone in improving forced expiratory volume in one second (FEV1)trough,FEV1 peak and forced vital capacity (FVC). In the improvement of transition dyspnea index (TDI),SGRQ and SOBDA scores ,UMEC/ VIL was better than placebo ,unilateral bronchodilator and fluticasone propionate/salme terol. The adverse reaction rate ,acute exacerbation rate ,mortality rate ,withdrawal rate ,pneumonia rate and other negative indicators of UMEC/VIL were not inferior to placebo,unilateral bronchodilator and fluticasone propionate/salme terol. CONCLUSIONS Compared with placebo and unilateral bronchodilator,UMEC/VIL can significantly improve lung function ,symptoms and quality of life ,and has non-inferior effect for negative indicators. Compared with β2 adrenoceptor agonists combined with glucocorticoid ,UMEC/VIL can improve lung function of COPD patients ,but they are similar in other aspects.
RESUMO
Objective:To deeply understand the man′s feelings and psychological experience of temporary ejaculation disorder on the day of retrieving ova during in vitro fertilization-embryo transfer (IVF-ET) treatment, and to provide theoretical basis for targeted intervention measures.Methods:Using the phenomenological method,13 male patients with temporary ejaculation disorder were interviewed individually on the day of retrieving ova from July to October 2021 in the department of Reproductive Endocrinology, Women′s Hospital, School of Medicine Zhejiang University and a semi-structured interview was recruited with them. The interview data were analyzed, summarized and refined according to Colaizzi′s 7-step method.Results:Totally 6 classification topics were formed: Somatization discomfort; Negative emotion; Stress and frustration; Change of intimacy between infertile couples; Imperfect social support system; Fertility pressure.Conclusions:Medical staff should pay close attention to the emotional reaction and psychological state of patients, establish emotional support, improve the intimate relationship between infertile couples, provide effective psychological counseling, provide diversified and personalized information support and multi-dimension social support, arrange reasonably the sperm collection room, improve the medical environment and improve the quality of assisted reproductive services.
RESUMO
This study was aimed to explore the effect of Zingiberis Rhizoma extract on rats with antibiotic-associated diarrhea(AAD), and reveal the modulation of gut microbiota during alleviation of AAD. AAD rat model was successfully established by exposing rats to appropriate antibiotic mixed solution. Peficon(70 mg·kg~(-1)·d~(-1)) was used as positive control, then rats were treated with 200 mg·kg~(-1)·d~(-1) and 400 mg·kg~(-1)·d~(-1) of Zingiberis Rhizoma extract for low and high dosage groups of Zingiberis Rhizoma extract, respectively. The weight changes of the rats were observed, and the degree of diarrhea were evaluated by fecal score, 120 min fecal weight and fecal water content. Colon tissues for histopathological examination were stained with hematoxylin and eosin(HE), and 16 S rRNA sequencing analysis of gut microbiota was performed. The results showed that compared with the model group, the degree of diarrhea, indicated by fecal water content, fecal score, and 120 min fecal weight of positive control group, Zingiberis Rhizoma low-dose group and Zingiberis Rhizoma high-dose group were significantly ameliorated. And the treatment of Zingiberis Rhizoma could significantly improve the pathological condition of colon tissue in AAD rats, especially the high dose of Zingiberis Rhizoma. In addition, 16 S rRNA sequencing analysis of gut microbiota showed that the diversity and abundance of gut microbiota were significantly improved and the reco-very of gut microbiota was accelerated after given high-dose of Zingiberis Rhizoma, while no significant changes of alterations were observed after given Pefikon. Of note, compared with the pefikon group, the abundance and diversity of gut microbiota in Zingi-beris Rhizoma high-dose group were significantly elevated. At the phylum level, the abundance of Firmicutes in AAD rats increased and the abundance of Proteobacteria was decreased after the Zingiberis Rhizoma intervention. At the genus level, the abundance of Bacillus spp., Lachnoclostridium and Escherichia coli-Shigella were decreased, and the abundance of Lactobacillus spp., Trichophyton spp., and Trichophyton spp., etc., were increased. While compared with the AAD model group, there was no significant difference of gut microbiota after given Peficon. The results showed that Zingiberis Rhizoma exerted beneficial health effects against AAD, and positively affected the microbial environment in the gut of rats with AAD.
Assuntos
Animais , Ratos , Antibacterianos/efeitos adversos , Diarreia/tratamento farmacológico , Microbioma Gastrointestinal , Zingiber officinale , Extratos Vegetais , RizomaRESUMO
Two cardenolide glycosides, corotoxigenin 3-O-[β-D-glucopyranosyl-(1→4)-6-deoxy-β-D-glucopyranoside] (1) and coroglaucigenin 3-O-[β-D-glucopyranosyl-(1→4)-6-deoxy-β-D-glucopyranoside] (2), were isolated from the seed fairs of Asclepias curassavica. The structures of 1-2 were determined based on the combination of the analysis of their MS, NMR spectroscopic data and acid hydrolysis. The inhibitory effects of compounds 1 and 2 on human colorectal carcinoma cells (HCT116), non-small cell lung carcinoma cells (A549) and hepatic cancer cells (SMMC-7721) were evaluated. The results showed that both compounds 1 and 2 significantly inhibited the viability, proliferation, and migration of A549, HCT116 and SMMC-7721 cells, suggesting that compounds 1 and 2 can be applied in the treatment of lung, colon and liver cancers in clinical practice. This study may not only provide a scientific basis for clarifying the active ingredients in A. curassavica, but also help to understand its antitumor activity, which can promote the application of A. curassavica in clinical treatment of various cancers.
Assuntos
Humanos , Antineoplásicos/farmacologia , Asclepias/química , Cardenolídeos/farmacologia , Glicosídeos/farmacologia , SementesRESUMO
OBJECTIVE@#To assess the efficacy and safety of mulberry twig alkaloids (Sangzhi alkaloids, SZ-A) for treatment of type 2 diabetes in a randomized, double-blind, placebo-controlled multicenter clinical trial.@*METHODS@#A total of 200 patients were randomized to receive SZ-A (n=100) or placebo (n=100) for 16 weeks. The data analysis system for electronic data capture clinical trial central randomization system was used for randomization and dispensing of drugs. The primary outcome was the change in glycosylated hemoglobin (HbA1c) level. The secondary outcome included the proportions of cases with HbA1c <7.0% and HbA1c <6.5%, fasting blood glucose (FBG), postprandial blood glucose (PBG), area under curve for the PBG (AUC0-2h), body weight, and body mass index (BMI). Adverse events (AEs), severe adverse events (SAEs), treatment-related adverse events (TAEs), gastrointestinal disorders (GDs), blood pressure, routine blood tests, and liver and kidney function were monitored.@*RESULTS@#Compared with baseline, the change of HbA1c at week 16 was -0.80% (95% CI: -0.98% to -0.62%) and -0.09% (95% CI: -0.27% to 0.09%) in SZ-A group and placebo group, respectively. The proportion of patients with HbA1c <7% and <6.5% was higher in the SZ-A group than in the placebo group (46.8% vs. 21.6% and 29.9% vs. 10.8%). The observed values and changes in FBG, 1 h-PBG, 2 h-PBG, and AUC0-2h differed significantly between groups (P<0.001), but differences were not significant in body weight and BMI (P>0.05). The incidence rates of AEs, TAEs, and GDs differed significantly between groups (P=0.010, P=0.005, and P=0.006, respectively), whereas the incidence rates of SAEs showed no significant differences between groups (P=1.000).@*CONCLUSION@#SZ-A are effective and safe for treatment of type 2 diabetes. The protocol was registered in http://www.chictr.org.cn/showproj.aspx?proj=60117 (ChiCTR2000038550).
Assuntos
Humanos , Alcaloides , Glicemia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Método Duplo-Cego , Hemoglobinas Glicadas , Hipoglicemiantes/uso terapêutico , Morus , Comprimidos/uso terapêutico , Resultado do TratamentoRESUMO
INTRODUCTION: The use of moderate hypothermia during experimental cardiac surgery is associated with decreased expression of tumour necrosis factor (TNF)-alpha in myocardium and with myocardial protection. In order to identify the cellular mechanisms that lead to that repression, we investigated the effect of hypothermia during cardiac surgery on both main signalling pathways involved in systemic inflammation, namely the nuclear factor-kappaB (NF-kappaB) and activating protein-1 pathways. METHOD: Twelve female pigs were randomly subjected to standardized cardiopulmonary bypass with moderate hypothermia or normothermia (temperature 28 degrees C and 37 degrees C, respectively; six pigs in each group). Myocardial probes were sampled from the right ventricle before, during and 6 hours after bypass. We detected mRNA encoding TNF-alpha by competitive RT-PCR and measured protein levels of TNF-alpha, inducible nitric oxide synthase and cyclo-oxygenase-2 by Western blotting. Finally, we assessed the activation of NF-kappaB and activating protein-1, as well as phosphorylation of p38 mitogen-activated protein kinase by electrophoretic mobility shift assay with super shift and/or Western blot. RESULTS: During and after cardiac surgery, animals subjected to hypothermia exhibited lower expression of TNF-alpha and cyclo-oxygenase-2 but not of inducible nitric oxide synthase. This was associated with lower activation of p38 mitogen-activated protein kinase and of its downstream effector activating protein-1 in hypothermic animals. In contrast, NF-kappaB activity was no different between groups. CONCLUSION: These findings indicate that the repression of TNF-alpha associated with moderate hypothermia during cardiac surgery is associated with inhibition of the mitogen-activated protein kinase p38/activating protein-1 pathway and not with inhibition of NF-kappaB. The use of moderate hypothermia during cardiac surgery may mitigate the perioperative systemic inflammatory response and its complications.
Assuntos
Procedimentos Cirúrgicos Cardiovasculares/métodos , Hipotermia Induzida/métodos , Fator de Transcrição AP-1/antagonistas & inibidores , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Animais , Feminino , NF-kappa B/fisiologia , Transdução de Sinais/fisiologia , Suínos , Fator de Transcrição AP-1/biossíntese , Fator de Transcrição AP-1/fisiologia , Fator de Necrose Tumoral alfa/biossíntese , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases p38 Ativadas por Mitógeno/fisiologiaRESUMO
With the population ageing, the number of elderly patients with end-stage renal disease(ESRD)is increasing, and the proportion of elderly patients undergoing hemodialysis is also increasing year by year.The elderly patients undergoing hemodialysis are susceptible to frailty due to the comorbidities, polypharmacy, chronic inflammation, malnutrition and other factors.In addition, frailty can lead to a variety of adverse prognosis such as falls, fractures, cognitive decline, all-cause hospital readmissions and all-cause death in elderly patients undergoing hemodialysis.
RESUMO
Objective:To investigate the expression of urinary exosomal miR-150-5p in different age groups and its relationship with kidney aging.Methods:Seventy-six subjects were recruited at the geriatrics department of Beijing Friendship Hospital from January 2014 to December 2016, with 15 in the young group, 35 in the middle-aged group, and 26 in the elderly group.We detected the expression of urinary exosomal miR-150-5p by real-time PCR from urine samples of different age groups and used Logistic regression analysis to evaluate the correlation of different levels of miR-150-5p with age, gender, history of hypertension, history of coronary heart disease, and hyperlipidemia.Additionally after overexpression and knockdown of miR-150-5p in human renal tubular cells of the HK2 cell line, we analyzed the expression levels of epithelial-to-mesenchymal transition(EMT)-related proteins by Western blotting.Results:Logistic regression analysis showed that age was closely related to estimated urinary exosomal miR-150-5p levels( P<0.05), and estimated urinary exosomal miR-150-5p levels in the elderly group(1.33±0.41)were significantly higher than those in the young group(0.88±0.40)( P<0.05). In addition, estimated urinary exosomal miR-150-5p levels became inversely proportional to the glomerular filtration rate as age increased. In vitro experiments showed that the expression levels of ZO-1 and E-cadherin in epithelial cells were slightly decreased after knockdown of miR-150-5p in renal tubular epithelial cells of the HK-2 cell line. Conclusions:The expression of miR-150-5p in urinary exosomes may be slightly increased in the elderly.It could inhibit the occurrence of renal EMT, and its expression is correlated with renal function.Mir-150-5p may also affect the expression of adhesion molecule-related proteins in HK-2 cells.MiR-150-5p in urinary exosomes is expected to become one of the genetic markers associated with renal aging.