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OBJECTIVE@#To evaluate the long-term prognosis of patients with ST-segment elevation myocardial infarction (STEMI) treated with different reperfusion strategies in Chinese county-level hospitals.@*METHODS@#A total of 2,514 patients with STEMI from 32 hospitals participated in the China Acute Myocardial Infarction registry between January 2013 and September 2014. The success of fibrinolysis was assessed according to indirect measures of vascular recanalization. The primary outcome was 2-year mortality.@*RESULTS@#Reperfusion therapy was used in 1,080 patients (42.9%): fibrinolysis ( n= 664, 61.5%) and primary percutaneous coronary intervention (PCI) ( n= 416, 38.5%). The most common reason for missing reperfusion therapy was a prehospital delay > 12 h (43%). Fibrinolysis [14.5%, hazard ratio ( HR): 0.59, 95% confidence interval ( CI) 0.44-0.80] and primary PCI (6.8%, HR= 0.32, 95% CI: 0.22-0.48) were associated with lower 2-year mortality than those with no reperfusion (28.5%). Among fibrinolysis-treated patients, 510 (76.8%) achieved successful clinical reperfusion; only 17.0% of those with failed fibrinolysis underwent rescue PCI. There was no difference in 2-year mortality between successful fibrinolysis and primary PCI (8.8% vs. 6.8%, HR = 1.53, 95% CI: 0.85-2.73). Failed fibrinolysis predicted a similar mortality (33.1%) to no reperfusion (33.1% vs. 28.5%, HR= 1.30, 95% CI: 0.93-1.81).@*CONCLUSION@#In Chinese county-level hospitals, only approximately 2/5 of patients with STEMI underwent reperfusion therapy, largely due to prehospital delay. Approximately 30% of patients with failed fibrinolysis and no reperfusion therapy did not survive at 2 years. Quality improvement initiativesare warranted, especially in public health education and fast referral for mechanical revascularization in cases of failed fibrinolysis.
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Humanos , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Intervenção Coronária Percutânea , População do Leste Asiático , Resultado do Tratamento , Reperfusão Miocárdica , Infarto do Miocárdio , Sistema de Registros , HospitaisRESUMO
Objective: To evaluate the acute and long-term outcome of patients with ST segment elevation myocardial infarction (STEMI) concurrent with chronic total occlusion (CTO) undergoing primary percutaneous coronary intervention (PCI). Methods: 11 905 STEMI patients from the China Acute Myocardial Infarction Registry were enrolled in this study and divided into CTO group and non-CTO group according to the angiography results of primary PCI. 1∶3 propensity score matching was used to match the patients between the two groups. The primary endpoint was in-hospital mortality and mortality at 1-year post PCI. The secondary endpoint was major adverse cardiovascular events (MACE) including death, re-myocardial infarction, revascularization, heart failure associated readmission, stroke and major bleeding at 1-year post PCI. Results: There were 931 CTO patients (7.8%) in this cohort (male=755 (81.1%), mean age (62.2±11.4 years)). The rest 10 974 patients were STEMI without CTO (male=8 829 (80.5%),mean age (60.0±11.8) years). After propensity score matching, 896 patients were enrolled in CTO group and 2 688 in non-CTO group. In-hospital mortality was significantly higher in the CTO group than in non-CTO group (4.2% vs. 2.4%, P=0.006). The ratio of all cause death, cardiac death, and MACE at 1-year follow up was also significantly higher in the CTO group than in non-CTO group (8.5% vs. 4.4%, P<0.001, 5.3% vs. 2.6%, P=0.001, 35.1% vs. 23.3%, P<0.001, respectively). Multiple regression analysis showed that CTO (HR=1.54, 95%CI 1.06-2.22, P=0.022), advanced age (HR=1.06, 95%CI 1.04-1.08, P<0.001), and previous heart failure history (HR=4.10, 95%CI 1.90-8.83, P<0.001) were independent risk factors of 1-year mortality. Conclusions: The in-hospital and 1-year mortality increased significantly in STEMI patients concurrent with CTO. CTO, advanced age and history of heart failure are independent risk factors of 1-year death among STEMI patients.
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Idoso , Humanos , Masculino , Pessoa de Meia-Idade , China , Doença Crônica , Oclusão Coronária/complicações , Infarto do Miocárdio , Intervenção Coronária Percutânea , Fatores de Risco , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Resultado do TratamentoRESUMO
This study was to determine the expression of the cell cycle inhibitor p21 in alveolar macrophages (AMs) and the role of p21 in activation of AMs in bleomycin (BLM) injury-induced lung fibrosis. The expression of CD206 in AMs was measured by immunofluorescence staining. Reverse transcription-polymerase chain reaction (RT-PCR) assay was used to detect the expression of macrophage activation markers. The coculture assay for macrophage and fibroblast was employed to explore the effect of macrophage on fibroblast activation. Immunofluorescence staining and western blotting assay were adopted to detect the expression of p21 in fibrotic tissues. AMs were treated with p21 knockdown or overexpression virus, RT-PCR and the co-culture system were used to explore the effect of p21 expression on macrophage activation. The Experimental Animal Welfare Ethics Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College approved all of the protocols for this research. Our results showed that the expression of CD206 and macrophage activation markers was increased in AMs from fibrotic mice, indicating that AMs from fibrotic mice were associated with a profibrotic phenotype. Moreover, the expression of p21 was upregulated in AMs after BLM treatment. Depletion of p21 suppressed macrophage activation, while overexpression of p21 promoted the profibrotic phenotype of AMs from healthy mice. In summary, BLM injury causes the progressive accumulation of p21 in AMs, which induces the production of a number of profibrotic factors promoting the development of pulmonary fibrosis.
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This article reported the clinical characteristics and SRD5A2 gene mutation pattern of a child with steroid 5-α reductase type 2 deficiency. The 2-month-old boy showed hypospadias and short penis shortly after birth. DNA was extracted from the peripheral blood of the child and his parents. The endocrine disease-related genes were captured and sequenced by high-throughput sequencing technology, and the family DNA samples were verified by Sanger sequencing. The results showed that c.680G>A(p.R227Q) and c.608G>A(p.G203D) compound heterozygous mutations existed in the SRD5A2 gene of the child. The c.680G>A mutation inherited from his father, which was a known pathogenic mutation. The c.608G>A mutation originated from his mother, which was a novel mutation discovered in this study. These results provide molecular evidence for the etiological diagnosis of the child and genetic counseling for the family, as well as extend the mutation spectrum of SRD5A2 gene.
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Criança , Feminino , Humanos , Lactente , Masculino , 3-Oxo-5-alfa-Esteroide 4-Desidrogenase , Genética , Sequência de Bases , Hipospadia , Proteínas de Membrana , Genética , MutaçãoRESUMO
The present study was aimed to clarify the signaling molecular mechanism by which fibroblast growth factor 21 (FGF21) regulates leptin gene expression in adipocytes. Differentiated 3T3-F442A adipocytes were used as study object. The mRNA expression level of leptin was detected by fluorescence quantitative RT-PCR. The phosphorylation levels of proteins of signal transduction pathways were detected by Western blot. The results showed that FGF21 significantly down-regulated the mRNA expression level of leptin in adipocytes, and FGF21 receptor inhibitor BGJ-398 could completely block this effect. FGF21 up-regulated the phosphorylation levels of ERK1/2 and AMPK in adipocytes. Either ERK1/2 inhibitor SCH772984 or AMPK inhibitor Compound C could partially block the inhibitory effect of FGF21, and the combined application of these two inhibitors completely blocked the effect of FGF21. Neither PI3K inhibitor LY294002 nor Akt inhibitor AZD5363 affected the inhibitory effect of FGF21 on leptin gene expression. These results suggest that FGF21 may inhibit leptin gene expression by activating ERK1/2 and AMPK signaling pathways in adipocytes.
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Animais , Camundongos , Células 3T3 , Adenilato Quinase , Adipócitos , Metabolismo , Regulação para Baixo , Fatores de Crescimento de Fibroblastos , Metabolismo , Leptina , Metabolismo , Sistema de Sinalização das MAP Quinases , Fosforilação , Transdução de SinaisRESUMO
Facilitative glucose transporters (GLUT) are proteins that mediate glucose transmembrane transport in the form of facilitated diffusion, which play an important role in regulating cell energy metabolism. There are many breakthroughs in researches of facilitative GLUT in recent years. It has been known that there are 14 subtypes of facilitative GLUT with obvious tissue specificity in distribution and physiological function. In the present review, the tissue and cellular distribution, subcellular localization, expression regulation, physiological function and the relationship to diseases of facilitative GLUT subtypes were summarized, in order to further understand their physiological and pathophysiological significances.
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Humanos , Transporte Biológico , Doença , Metabolismo Energético , Glucose , Proteínas Facilitadoras de Transporte de Glucose , FisiologiaRESUMO
OBJECTIVE@#Identification of new risk factors is needed to improve prediction of adverse outcomes in patients with three-vessel disease (TVD). The present study aimed to evaluate the prognostic values of serum chloride and sodium levels in patients with TVD.@*METHODS@#We used data from a prospective cohort of consecutive patients with angiographically confirmed TVD. The primary endpoint was all-cause death. Cox proportional hazard regression was used to analyze the relationship of serum chloride and sodium levels with long-term outcomes of TVD patients.@*RESULTS@#A total of 8,318 participants with available serum chloride and sodium data were included in this analysis. At baseline, patients in the low tertiles group of serum chloride level (⪕ 102.0 mmol/L) or serum sodium level (⪕ 139.0 mmol/L) had more severe disease conditions. During a median follow-up of 7.5-year, both low serum chloride level and low serum sodium level were found to be associated with an increased risk for mortality in univariate analysis. However, when both parameters were incorporated into a multivariate model, only low serum sodium level remained to be an independent predictor of all-cause death (hazard ratio: 1.16, 95% confidence interval: 1.01-1.34, P = 0.041). Modest but significant improvement of discrimination was observed after incorporating serum sodium level into the Synergy between percutaneous coronary intervention (PCI) with Taxus and Cardiac Surgery score.@*CONCLUSION@#Serum sodium level is more strongly associated with long-term outcomes of TVD patients compared with serum chloride level. Low serum sodium level is an independent risk factor for mortality, but only provides modest prognostic information beyond an established risk model.
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Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , China , Epidemiologia , Cloretos , Sangue , Doença da Artéria Coronariana , Sangue , Diagnóstico , Mortalidade , Prognóstico , Estudos Prospectivos , Sódio , SangueRESUMO
Objective To investigate the expression of calreticulin and its correlation with autoantibodies and inflammatory cytokines in patients with early rheumatoid arthritis (RA). Methods Serum samples were obtained from 106 patients with early active RA, 95 patients with stable RA, 85 osteoarthritis (OA) and 80 healthy controls (HC). Serum levels of calreticulin, anti- cyclic peptide antibody (CCP), interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α were measured by enzyme-linked immnuosorbent assay (ELISA). The serum level of rheumatoid factor (RF) was detected by immunoturbidimetry. The correlations between serum calreticulin and inflammatory cytokines were evaluated using Spearman's rank correlation test. Results Serum levels of calreticulin were significantly higher in patients with early active RA [(5.84±2.62)μg/L] than those in patients with stable RA [(4.26±1.42)μg/L], patients with OA [(3.92±1.10)μg/L] and HC [(3.86 ± 0.91)μg/L] (P<0.001). There were no statistical differences in serum levels of calreticulin between stable RA, OA and HC groups (P>0.05). Serum levels of calreticulin were significantly higher in RF-positive RA patients than those of RF-negative RA patients [(6.12±2.87)μg/L vs. (4.92±1.22)μg/L, P=0.045]. Serum calreticulin levels were also significantly higher in anti-CCP-positive RA patients than those of anti-CCP-negative RA patients [(6.39±2.93)μg/L vs. (4.69±1.17)μg/L, P=0.002]. The serum level of calreticulin was positively correlated with IL-1β (rs=0.386, P=0.009), IL-6 (rs=0.405, P=0.006) and TNF-α(rs=0.428, P=0.003) in early active RA patients. Conclusion The elevated serum level of calreticulin is related to autoantibodies and inflammatory cytokines in early RA patients, suggesting that calreticulin can be used as a potential biomarker for early diagnosis and prognosis of RA.
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Objective To study the clinical data of patients with locally advanced cervical cancer(LACC)treated with preoperative radiotherapy plus chemotherapy combined with surgery. Methods Seventy patients with LACC(stage ⅠB2,ⅡA2 andⅡB)who were treated in our hospital from January 2012 to December 2016 were selected in this study.All the cases were randomly divided into two groups.The observation group(n=35)was treated with three-dimensional intracavitary brachytherapy plus chemotherapy combined with surgery, while the control group (n=35) was treated with radical radiotherapy.Patients of the two groups were followed up after the treatment.The recent and long term complications were recorded and observed in the two groups.Meanwhile,the survival curves were drawn by Kaplan-Meier,and the difference of total survival rate was compared with the Log-rank method between the two groups. Results The incidence of rectal reaction was less in the observation group than that in the control group(14.3% vs.37.1%,χ 2=4.786,P<0.05).There were no significant differences in bone marrow suppression,gastrointestinal reaction and bladder reaction between the two groups (P>0.05). The incidence rates of radioactive bladder injury (8.6% vs. 31.4%) and radionuclide injury (11.4% vs. 34.2%) were less in the observation group than those in the control group(χ2=5.714 and 5.185 respectively,P<0.05).The survival analysis showed that there was no significant difference in the total survival rate between the two groups of stageⅠB2+ⅡA2 and stageⅡB patients(Log rank χ2=0.081 and 0.376,P>0.05).Conclusion For patients with locally advanced cervical cancer, preoperative radiotherapy plus chemotherapy combined with surgery can reduce the incidence of related complications, meanwhile, there is no significant difference in the total survival rate and the mean survival time after the treatment of the two methods.
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Objective: Residual SYNTAX score (rSS) can be used as the independent predictor for clinical prognosis and the tool for quantifying incomplete revascularization (IR) in coronary artery disease (CAD) patients with percutaneous coronary intervention (PCI). Our work assessed the prognostic value of rSS on large-scale PCI patients in China. Methods: A total of 10 724 CAD patients undergoing PCI in our hospital in 2013 were studied; 381 patients with previous CABG and hybrid procedure were excluded, 10 343 patients were finally enrolled. Baseline SYNTAX score (bSS) and rSS were calculated before and after PCI. Complete revascularization (CR) was defined by rSS=0 and IR was defined by rSS≥1. The patients were followed-up for 30 months. Clinical endpoint events included MACE, a composite event of all-cause death, myocardial infarction (MI) and revascularization; all-cause death, cardiac death, MI, all-cause death/MI and revascularization.Results: There were 5 050/10 343 (48.8%) patients having CR and 5 293 having IR including 1 908 (18.4%) patients with 1≤rSS≤4, 1 777 (17.2%) with 4<rSS≤9 and 1608 (15.5%) with rSS>9. Patients with the higher rSS had more clinical comorbidity and more complicated coronary lesions. Compared with CR patients, IR patients had the higher incidences of 30-month clinical endpoint events. As rSS increasing, the incidence of MACE was elevating accordingly. Multivariate regression analysis indicated that rSS was the independent predictor for MACE and all other endpoints occurrence. Conclusion: IR patients especially those with rSS>9 had the higher incidence of adverse clinical outcomes. rSS has been a good tool for quantifying revascularization and assessing prognosis in PCI patients in China.
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Objective: To assess the relationship between bicycle ownership status and physical activity, time of sitting, overweight or obesity in China. Methods: Based on the information of China cohort from Prospective Urban Rural Epidemiology (PURE) study, we conducted a cross-sectional description. Multivariable linear and multivariable Logistic regression analysis were respectively used to distinguish the differences of physical activity, time of sitting, overweight or obesity status between bicycle owners and non-bicycle owners. Results: A total of 42 677 participants were analyzed, the average age was (51.23±9.72) years including 40.9% male. There were 27 744 (65.0%) bicycle owners, their MET-min/week for total physical activity, work, transportation,domestic and recreation time were 2513.00 (1114.00, 5271.00), 444.00 (0.00, 735.00), 420.00 (0.00, 990.00), 600.00 (180.00,1260.00) and 198.00 (0.00, 693.00) respectively; time of sitting was (1397.03±832.13) min/week and waist circumference was (81.03±10.53) cm. With adjusted potential confounders, bicycle owners had more transportation activity, while less total physical activity, work, domestic and recreation time than non-bicycle owners; bicycle owner had more time of sitting and less risk of obesity; BMI and waist-to-hip ratio were similar between bicycle owners and non-bicycle owners. Conclusion: Bicycle owners had more transportation related physical activity and less risk of obesity; while the total physical activity, domestic and recreation related physical activity might be reduced in them.
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Objectives: To observe the prevalence of bleeding and to explore the independent predictors of bleeding in ST-segment elevation acute myocardial infarction patients with fibrinolysis therapy in China. Methods: From January 2013 to June 2014, 1 568 patients undergoing fibrinolysis in the Chinese Acute Myocardial Infarction Registry (CAMI) were prospectively included. Patients were divided into bleeding group (bleeding after fibrinolysis, n=55) and no bleeding group (without bleeding after fibrinolysis, n=1 513). Logistic regression analysis was performed to define the independent predictors of bleeding. Results: The prevalence of bleeding with fibrinolysis in these patients was 3.5% (55/1 568). The fibrinolysis success rate is 86%. Among them, the rate of intracranial bleeding was 0.6%, and the rate of gastrointestinal bleeding was 1.9%. The fibrinolysis success tended to be higher in patients with bleeding (94.1% vs 85.7%, P=0.0589) ,and the mortality rate was significantly higher in patients with bleeding (20.0% vs 7.1%, P=0.0019) . Logistic regression analysis showed that age≥75 years (OR=2.45, 95%CI:1.10-5.46, P=0.0290) and use of rtPA (HR=3.41, 95%CI:1.48~7.86, P=0.0040) were independent predictors of bleeding after fibrinolysis in this patient cohort. Conclusions: The prevalence of bleeding after fibrinolysis in Chinese STEMI patients is low. Older age and rtPA use are independent predictors of bleeding after fibrinolysis in this patient cohort.
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Objectives: To investigate the association between acquired thrombocytopenia and long-term clinical outcome among stable coronary artery disease patients undergoing elective percutaneous coronary intervention (PCI). Methods: We analyzed clinical data of 8 271 consecutive patients who underwent elective PCI in Fuwai Hospital from January 2013 to December 2013. Acquired thrombocytopenia was defined as platelet count <150×109/L after PCI in patients with normal baseline platelet count value. We compared data on demographic, clinical, laboratory, and 30-month outcome between non-thrombocytopenic and thrombocytopenic patients and identified the independent predictors of acquired thrombocytopenia post PCI. Results: Acquired thrombocytopenia developed in 654 (7.91%) patients (634 [7.67%] patients had mild thrombocytopenia, 20 [0.24%] patients had moderate or severe thrombocytopenia). Patients who developed thrombocytopenia had higher 30-month rate of all cause death (2.3% vs 1.0%, P=0.0086) and cardiogenic death (1.2% vs 0.5%, P=0.0261). Moderate or severe thrombocytopenia was associated with a 13-fold increased risk for cardiogenic death, 7-fold increased risk for stent thrombosis,11-fold increased risk for myocardial infarction compared with patients without thrombocytopenia. Conclusions: Acquired thrombocytopenia after PCI is common in stable coronary artery disease patients and is independently associated with increased risk of long-term adverse outcome in these patients.
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<p><b>OBJECTIVE</b>To investigate the effect of estradiol on the expression of antioxidant enzymes in osteoblasts and its role in postmenopausal osteoporosis.</p><p><b>METHODS</b>Rat models of osteoporosis established by ovariectomy were treated with estradiol for 3 months, and the changes in serum levels of reactive oxygen species (HO) and antioxidant enzymes (γ -GCS, GSH-ST and GSH-px) were detected. The effects of estradiol on the expression of γ -GCS mRNA and protein in osteoblast-like cells MC3T3-E1, MG63 and OB were examined with PCR and Western blotting. Using a mRNA microarray, we analyzed the changes in the expressions of 84 antioxidant enzymes in the osteoblast cell line MC3T3-E1 following estradiol treatment, and the enzymes with significant changes were verified by PCR. CCK-8 kit was used to evaluate the effect of estradiol and antioxidant NAC on the proliferation of MC3T3-E1 cells.</p><p><b>RESULTS</b>Rat models of osteoporosis were successfully established with ovariectomy. The osteoporotic rats showed significantly increased serum level of reactive oxygen species (H2O2) and decreased levels of antioxidant enzymes. Estrogen treatment of the osteoporotic rats obviously reversed the phenotype of osteoporosis, lowered serum level of reactive oxygen species, and increased the level of γ -GCS. In MC3T3-E1, MG63 and OB cells, estradiol treatment significantly upregulated the expression levels of γ -GCS mRNA and protein. In MC3T3-E1 cells treated with estrogen, the mRNA chip identified 6 upregulated antioxidant enzymes (Gpx6, Gstk1, Nos2, Prdx2, Ngb and Ccs), and the results of PCR verified that estradiol upregulated Ccs and Ngb mRNAs in MC3T3-E1, MG63 and OB cells. Estradiol and antioxidant NAC obviously promoted the proliferation of MC3T3-E1 cells.</p><p><b>CONCLUSION</b>Estradiol significantly increases the expression of antioxidase γ -Gcs, Ccs and Ngb in osteoblasts in vitro. Postmenopausal osteoporosis is closely related with the increase of reactive oxygen species and the decrease of antioxidant levels. In osteoblasts, estrogen deficiency may increase the level of reactive oxygen species, decrease the level of antioxidant enzymes, activate the oxidative stress cascade, and consequently inhibit the proliferation of osteoblasts to aggravate the condition of osteoporosis.</p>
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<p><b>OBJECTIVE</b>To establish a method for gene delivery in murine renal tissue using lentivirus vector encoding miR-483-5p.</p><p><b>METHODS</b>Thirty-five C57BL/6J mice were randomly divided into control group, low-dose treatment group (5 µL each kidney) , and high?dose treatment group (20 µL each kidney), and in the latter two groups, the lentivirus vector encoding miR-483-5p were injected in the renal cortex. The tissue samples were collected at 7 and 21 days after the injection. A transgenic mouse model with inducible systemic overexpression of miR-483-5p was established in TG483 mice. The Cre-loxp system was used to create a mouse model with renal tubule-specific expression of miR-483-5p. The levels of BUN in the mice were detected and HE staining and fluorometric TUNEL assay were used to observe the morphological changes of the kidneys; real-time qPCR was used to detect miR-483-5p expression in the renal cortex.</p><p><b>RESULTS</b>The mice with overexpression of miR-483-5p had normal renal function without obvious pathological changes or apoptosis in the renal tissue. Renal cortex injection of 20 µL lentivirus resulted in obviously increased level of miR-483-5p at 21 days (1.2∓0.43 vs 8.6∓1.09, P<0.001). miR-483-5p showed a low expression (0.9∓0.09 vs 1.7∓0.19, P<0.05) in TG483 mice and a high expression in the kidney of the transgenic mice established using the Cre-loxp system (1.6∓1.13 vs 12.36∓3.89, P<0.05).</p><p><b>CONCLUSION</b>The transgenic mice with renal tubule-specific expression of miR-483-5p show normal renal function, and this model facilitates further study of the role of miR-483-5p in the kidney.</p>
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<p><b>BACKGROUND</b>Patients with premature triple-vessel disease (PTVD) have a higher risk of recurrent coronary events and repeat revascularization; however, the long-term outcome of coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI), and medical therapy (MT) alone for PTVD patients is controversial. The aim of this study is to evaluate the long-term outcome of PTVD patients among these three treatment strategies, to find out the most appropriate treatment methods for these patients.</p><p><b>METHODS</b>One thousand seven hundred and ninety-two patients with PTVD (age: men ≤50 years and women ≤60 years) were enrolled between 2004 and 2011. The primary end point was all-cause death. The secondary end points were cardiac death, myocardial infarction, stroke, or repeat revascularization.</p><p><b>RESULTS</b>PCI, CABG, and MT alone were performed in 933 (52.1%), 459 (25.6%), and 400 (22.3%) patients. Both PCI and CABG were associated with lower all-cause death (4.6% vs. 4.1% vs. 15.5%, respectively, P < 0.01) and cardiac death (2.8% vs. 2.0% vs. 9.8%, respectively, P < 0.01) versus MT alone. The rate of repeat revascularization in the CABG group was significantly lower than those in the PCI and MT groups. After adjusting for baseline factors, PCI and CABG were still associated with similar lower risk of all-cause death and cardiac death versus MT alone (all-cause death: hazard ratio [HR]: 0.35, 95% confidence interval [CI]: 0.23-0.53, P < 0.01 and HR: 0.35, 95% CI: 0.18-0.70, P = 0.003, respectively, and cardiac death: HR: 0.32, 95% CI: 0.19-0.54, P < 0.01 and HR: 0.36, 95% CI: 0.14-0.93, P = 0.03, respectively).</p><p><b>CONCLUSIONS</b>PCI and CABG provided equal long-term benefits for all-cause death and cardiac death for PTVD patients. Patients undergoing MT alone had the worst long-term clinical outcomes.</p><p><b>TRIAL REGISTRATION</b>ClinicalTrials.gov; Identifier: NCT02634086. https://www.clinicaltrials.gov/ct2/show/record/NCT02634086?term=NCT02634086&rank=1.</p>
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Notwithstanding the noteworthy advances in its treatment, malignant tumor remains one of the main diseases threatening human health. Therefore, it is urgent to search and develop novel anticancer drugs with high curative effect and less side effect. In this review, we focus on summarizing the physio-chemical properties, preparation processes, anti-tumor activity mechanisms, clinical effects, side effects, and main isomers, especially the research progress of temsirolimus, with the hope to provide some reference for the further research.
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OBJECTIVE: To determine and compare the contents of principal component and related substances of ammonium glycyrrhizinate by methods contained in different pharmacopoeias and a new method established by our lab. METHODS: The methods for quality control of ammonium glycyrrhizinate in the latest edition of European Pharmacopoeia, British Pharmacopoeia, national drug standards of China, and the method established by our laboratory were employed to determine the contents of the principal component isomers and related substances of ammonium glycyrrhizinate in its raw materials and pharmaceutical products. The methods were evaluated and compared regarding the chromatographic features, resolution of principal component isomers, experimental cost, content determination results, and the advantages and disadvantages of each method were discussed. RESULTS: The mobile phases adopted in aforementioned pharmacopoeias are all acidic, which could not effectively separate 18α-glycyrrhizinic acid and 18β-glycyrrhizinic acid, thus could not truly reflect the contents of 18α-glycyrrhizinic acid, 18β-glycyrrhizinic acid, related substances A, and the related substances in the raw materials and pharmaceutical products. The resolution of principal component isomer by our method was 1.5, complying to the pharmacopoeia requirement. The content determination results of ammonium glycyrrhizinate raw materials by the four methods had no significant difference. CONCLUSION: Among the four methods, the method established by our laboratory performed best in terms of accuracy and practicability. This method has shorter detection time, lower cost, reduced toxicity and pollution, and the results are accurate and reliable, which suggests that it can be used for the chiral resolution of 18α-glycyrrhizinic acid and 18β-glycyrrhizinic acid and the content determination of principal component and related substances of the raw material and pharmaceutical products of ammonium glycyrrhizinate. This study provideds reference for further revision of the quality control method in Pharmacopoeia.
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A simple, fast and sensitive analytical method for the simultaneous separation and detection of 18alpha-glycyrrhizinic acid, 18beta-glycyrrhizinic acid, related substance A and related substance B by RP-HPLC and drug quality standard was established. The structures of principal component isomer and related substances of raw material drug of ammonium glycyrrhizinate have been confirmed. Reference European Pharmacopoeia EP7.0 version, British Pharmacopoeia 2012 version, National Drug Standards of China (WS 1-XG-2002), domestic and international interrelated literature were referred to select the composition of mobile phase. The experimental parameters including salt concentration, pH, addition quantities of organic solvent, column temperature and flow rate were optimized. Finally, the assay was conducted on a Durashell-C18 column (250 mm x 4.6 mm, 5 microm) with 0.01 mol x mL(-1) ammonium perchlorate (add ammonia to adjust the pH value to 8.2) -methanol (48 : 52) as mobile phase at the flow rate of 0.8 mL x min(-1), and the detection wavelength was set at 254 nm. The column temperature was 50 degrees C and the injection volume was 10 microL. The MS, NMR, UV and RP-HPLC were used to confirm the structures of principal component isomer and related substances of raw material drug of ammonium glycyrrhizinate. Under the optimized separation conditions, the calibration curves of 18 alpha-glycyrrhizinic acid, 18beta-glycyrrhizinic acid, related substance A and related substance B showed good linearity within the concentration of 0.50-100 microg x mL(-1) (r = 0.999 9). The detection limits for 18alpha-glycyrrhizinic acid, 18beta-glycyrrhizinic acid, related substance A and related substance B were 0.15, 0.10, 0.10, 0.15 microg x mL(-1) respectively. The method is sensitive, reproducible and the results are accurate and reliable. It can be used for chiral resolution of 18alpha-glycyrrhizinic acid, 18Pbeta-glycyrrhizinic acid, and detection content of principal component and related substances of raw material drug of ammonium glycyrrhizinate. It is concluded that the separation of principal component isomer of raw material drug of ammonium glycyrrhizinate and the validity of the substance's structure assignments of retention time being 1.2 in the European pharmacopoeia EP7.0 version, British pharmacopoeia 2012 version remains open to question. It may be of practical value for the quality control of raw material drug, preparation, and Chinese herbal medicine of ammonium glycyrrhizinate.
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Compostos de Amônio , Química , Cromatografia Líquida de Alta Pressão , Ácido Glicirrízico , Química , Isomerismo , Imageamento por Ressonância Magnética , Espectrometria de Massas , Estrutura Molecular , Análise de Componente Principal , Controle de Qualidade , Padrões de Referência , Espectrofotometria UltravioletaRESUMO
The metabolomic analysis of three Cimicifuga species was performed using H-NMR spectroscopy and pattern recognition (PR) techniques. A broad range of metabolites could be detected by 'H-NMR spectroscopy without any chromatographic separation. The analysis using principal component analysis (PCA) and discriminant partial least square (DPLS) of the 1H-NMR spectrum showed a clear discrimination between C. foetida and the other two species. The major metabolites responsible for the discrimination were triterpenoid saponins and saccharides. These results indicated that the combination of 1H-NMR and PR provides a useful tool for chemotaxonomic analysis and authentification of Cimicifuga species, and could used for the quality control of plant materials.