AIM To evaluate the pharmacokinetic properties and bioequivalency of Yexiazhu Formula Granules and Decoction.METHODS Twelve rats were randomly assigned into two groups and given intragastric administration of the solutions of Yexiazhu Formula Granules and Decoction(0.428 2,2.000 g/kg),respectively,after which blood collection was made at 0.083,0.167,0.25,0.5,0.75,1,2,3,4,8,12,24,36 h,UPLC-MS/MS was adopted in the plasma concentration determination of gallic acid,corilagin and ellagic acid,and main pharmacokinetic parameters were calculated.Subsequently,the bioequivalency of these two preparations was investigated.RESULTS No significant differences in AUC0-∞,AUC0-t,MRT0-∞,MRT0-t,t1/2,Tmax,CL and Cmax were observable between the two preparations(P＞0.05),whose Cmax,AUC0-∞ ratios or logarithmic mean differences accorded with bioequivalence standard at the 90%confidence level.CONCLUSION Yexiazhu Formula Granules and Decoction demonstrate approximate pharmacokinetic properties and display bioequivalency.

Odontogenic maxillary sinusitis(OMS)is a subtype of maxillary sinusitis(MS).It is actually inflammation of the maxillary sinus that secondary to adjacent infectious maxillary dental lesion.Due to the lack of unique clinical features,OMS is difficult to distinguish from other types of rhinosinusitis.Besides,the characteristic infectious pathogeny of OMS makes it is resistant to conventional therapies of rhinosinusitis.Its current diagnosis and treatment are thus facing great difficulties.The multi-disciplinary cooperation between otolaryngologists and dentists is absolutely urgent to settle these questions and to acquire standardized diagnostic and treatment regimen for OMS.However,this disease has actually received little attention and has been underrepresented by relatively low publication volume and quality.Based on systematically reviewed literature and practical experiences of expert members,our consensus focuses on characteristics,symptoms,classification and diagnosis of OMS,and further put forward multi-disciplinary treatment decisions for OMS,as well as the common treatment complications and relative managements.This consensus aims to increase attention to OMS,and optimize the clinical diagnosis and decision-making of OMS,which finally provides evidence-based options for OMS clinical management.

Humans ; Mitral Valve/surgery* ; Heart Valve Prosthesis ; Cardiac Surgical Procedures

Humans ; Mitral Valve/surgery* ; Heart Valve Prosthesis ; Cardiac Surgical Procedures

Objective: To explore the safety and feasibility of stereotactic radiation therapy (SBRT) strategy for irradiating porcine ventricular septum, see if can provide a preliminary experimental evidence for clinical SBRT in patients with hypertrophic obstructive cardiomyopathy (HOCM). Methods: Five male pigs (39-49 kg, 6 months old) were used in this study. Pigs were irradiated at doses of 25 Gy (n=2) or 40 Gy (n=3). Delineation of the target volume was achieved under the guidance of 3-dimensional CT image reconstruction, and SBRT was then performed on defined target volume of porcine ventricular septum. Blood biomarkers, electrocardiogram and echocardiography parameters were monitored before and after SBRT. Pathological examination (HE staining, Masson staining) was performed on the target and non-target myocardium at 6 months post SBRT. Results: SBRT was successful and all animals survived to the designed study endpoint (6 months) after SBRT. Serum cardiac troponin T (cTnT) level was significantly higher than the baseline level at 1 day post SBRT, and reduced at 1 week after SBRT, but was still higher than the baseline level(P<0.05). Serum N-terminal pro-B type natriuretic peptide (NT-proBNP) was also significantly increased at 1 day post SBRT (P<0.05) and returned to baseline level at 1 week post SBRT. The serum NT-proBNP level was (249±78), (594±37) and (234±46) pg/ml, respectively, and the cTnT was (14±7), (240±40) and (46±34) pg/ml, respectively at baseline, 1 day and 1 week after SBRT in the 40 Gy dose group. The serum NT-proBNP level was (184±20), (451±49) and (209±36) pg/ml, respectively, the cTnT values ​​were (9±1), (176±29) and (89±27) pg/ml, respectively at baseline, 1 day and 1 week after SBRT in the 25 Gy dose group. Both NT-proBNP and cTnT values tended to be higher post SBRT in the 40 Gy dose group as compared with the 25 Gy dose group, but the difference was not statistically significant (P>0.05). The left ventricular ejection fraction and the left ventricular end-diastolic diameter remained unchanged before and after SBRT (P>0.05). The interventricular septum thickness showed a decreasing trend at 6 months after SBRT, but the difference was not statistically significant ((9.54±0.24) mm vs. (9.82±8.00) mm, P>0.05). The flow velocity of the left ventricular outflow tract, and the valve function and morphology were not affected by SBRT. At 6 months after SBRT, HE staining revealed necrosis in the irradiated target area of ​​the myocardium in the 40 Gy dose group and the 25 Gy dose group, and the degree of necrosis in the irradiated interventricular septum was more obvious in the 40 Gy dose group as compared with the 25 Gy group. The combined histological analysis of the two groups showed that the necrotic area of ​​the irradiated target area accounted for (26±9)% of the entire interventricular septum area, which was higher than that of the non-irradiated area (0) (P<0.05). There was no damage or necrosis of myocardial tissue outside the target irradiation area in both groups. The results of Masson staining showed that the percentage area of myocardial fibrosis was significantly higher in the irradiated target area than non-irradiated area ((12.6±5.3)% vs. (2.5±0.8)%, P<0.05). Conclusion: SBRT is safe and feasible for irradiating porcine ventricular septum.
Animals ; Feasibility Studies ; Male ; Necrosis ; Radiosurgery/methods* ; Stroke Volume ; Swine ; Ventricular Function, Left ; Ventricular Septum

Objective: To compare the efficacy and safety of pro-urokinase and reteplase in the treatment of patients with acute ST elevation myocardial infarction (STEMI). Methods: STEMI patients, who received intravenous thrombolytic therapy in Henan STEMI registry between September 2016 and August 2018, were eligible for this study. A total of 5479 patients from 66 hospitals were screened and patients were divided into pro-urokinase group (n=638) and reteplase group (n=702) according to thrombolytic drugs. Data including patient demographics, risk factors, medical histories, patient information at admission, in-hospital treatment, time delays, and clinical events were collected. The clinical recanalization rate, in-hospital mortality, in-hospital death or treatment withdrawal, in-hospital main adverse cardiovascular and cerebrovascular events (MACCE, death or treatment withdrawal, congestive heart failure, reinfarction and ischemic stroke) and post-thrombolysis bleeding were compared between the two groups. Bleeding events were evaluated with Bleeding Academic Research Consortium (BARC) criteria. Results: The median age [61.8 (53.2, 69.0) vs. 62.6 (52.1, 69.8), P=0.833] or the proportion of women [23.0% (147/638) vs. 25.1% (176/702), P=0.385] were similar between the pro-urokinase and reteplase groups. Clinical recanalization rates were similar between the pro-urokinase and reteplase groups [82.1% (524/638) vs. 84.9% (596/702), P=0.172], and there was no difference in the median time from onset to thrombolysis [194.5 (135.0,290.0) min vs. 190 (126.0,292.0) min, P=0.431] and the median recanalization time [95 (67.5,120.0) min vs. 95 (71.0,119.0) min, P=0.561] between the two groups. There was no significant difference in in-hospital mortality [5.5% (35/638) vs. 5.1% (36/702), P =0.770], in-hospital all-cause mortality, treatment withdrawal [8.9% (57/638) vs.7.7% (54/702), P=0.410], and in-hospital MACCE [13.0% (83/638) vs. 10.4% (73/702), P=0.137] between pro-urokinase and reteplase groups. However, the incidence of post-thrombolysis bleeding was significantly higher in reteplase group than in pro-urokinase group [7.8% (55/702) vs. 3.8% (24/638), P=0.002]. Further analysis found that the incidence of oral bleeding and the BARC grades 1-2 bleeding were significantly higher in reteplase group than in pro-urokinase group, whereas the incidence of cerebral hemorrhage was similar between the two groups [0.6% (4/638) vs. 0.4% (3/702), P=0.715]. The comparison of efficacy and safety outcomes between the two groups after adjusting for baseline characteristics using general linear mixed models was consistent with those before the adjustment. There was no significant difference in in-hospital mortality, in-hospital death or treatment withdrawal, in-hospital MACCE after adjusting for baseline characteristics and post-thrombolysis bleeding between the two groups. Conclusions: Pro-urokinase and reteplase have similar clinical efficacy in the treatment of STEMI. In terms of safety, the incidence of cerebral hemorrhage is similar, while the incidence of BARC grades 1-2 bleeding and oral bleeding is higher in reteplase group than in pro-urokinase group, which has no impact on in-hospital outcomes.
Female ; Fibrinolytic Agents/therapeutic use* ; Hospital Mortality ; Humans ; Myocardial Infarction/drug therapy* ; Recombinant Proteins ; ST Elevation Myocardial Infarction/drug therapy* ; Thrombolytic Therapy ; Tissue Plasminogen Activator ; Treatment Outcome ; Urokinase-Type Plasminogen Activator

To study the binding capacity of active ingredients of Daidai lipid-lowering flavonoid extract and plasma protein,investigate the ways to improve the traditional formula for calculating protein binding rates based on ultrafiltration,and increase the stability and reliability of the experimental results. UPLC-MS/MS was used to establish a quantitative analysis method for simultaneous determination of active ingredients( neohesperidin and narngin) in ultrafiltrate. The protein binding rates were calculated by the traditional ultrafiltration formula. The correction factors( F) were introduced later,and the binding rates calculated with the correction factors were compared with those without the correction factors. The binding capacity of the extract and plasma protein was evaluated. The quantitative analysis method established by UPLC-MS/MS had a good specificity. The standard curve and linear range,method accuracy,precision and lower limit of quantitation all met the requirements. The method met the requirement for quantitative detection of the active ingredients in ultrafiltrate after the rat plasma was filtrated in the ultrafiltration tube. Under the experimental conditions,the binding rates of both active ingredients( neohesperidin and narngin) were higher than 90%. The active ingredients and rat plasma protein were bound in a concentration-dependent manner,with statistically significant differences( P<0. 01). There was no statistically significant difference between the protein binding abilities of the two active ingredients with rat plasma protein. Therefore,the active ingredients of Daidai lipid-lowering flavonoid extract had a relatively strong binding strength with rat plasma protein,and they were bound in a concentration-dependent manner. Additionally,when calculating protein binding rates by the traditional ultrafiltration formula,the correction factors could be introduced to effectively reflect the errors of multiple ingredient groups in traditional Chinese medicine extracts.This correction method could provide a reference thinking and practical reference for the improvement of the determination method of the traditional Chinese medicine plasma protein binding ability based on ultrafiltration.
Animals ; Blood Proteins ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; pharmacology ; Flavonoids ; pharmacology ; Hypolipidemic Agents ; pharmacology ; Lipids ; Rats ; Reproducibility of Results ; Tandem Mass Spectrometry

The paper studies and compares the metabolic difference of active ingredients of lipid-lowering flavonoid extract of Daidai in rat livers and intestinal microsomes,in order to explore the phase Ⅰ metabolism characteristics of active ingredients in livers and intestines. UPLC-MS/MS was used to establish a quantitative analysis method for active ingredients,neohesperidin and narngin,in a phase Ⅰ metabolism incubation system of liver and intestinal microsomes. Differential centrifugation was used to make liver and intestinal microsomes of rats. A phase Ⅰ metabolism incubation system was established,and the concentrations of the residual at different incubation time points were analyzed. Graphs were plotted to calculate the metabolic elimination half-life of the main active parts,with the natural logarithm residual percentage values ln( X) at different time points as the y axis,and time t as the x axis. The metabolism characteristics of the active ingredients were compared. The established UPLC-MS/MS quantitative analysis method has a good specialization,standard curve and linear range,accuracy and precision,with a satisfactory lower quantitative limit. The method allows quantitative detection of the active ingredients in a phase Ⅰ metabolism incubation system of liver and intestinal microsomes of rats. In the rats liver microsomes incubation system,the metabolic elimination half-life of neohesperidin and narngin were( 2. 20 ± 0. 28) h and( 1. 97±0. 28) h respectively. The elimination half-life of neohesperidin was larger than that of narngin,but with no statistically significant difference. In the rats intestinal microsomes incubation system,the metabolic elimination half-lives of neohesperidin and narngin were( 3. 68±0. 54) h and( 2. 26±0. 13) h respectively. The elimination half-life of neohesperidin was larger than that of narngin,with statistically significant differences( P<0. 05). The elimination half-lives of the active ingredients in liver microsomes were smaller than those in intestinal microsomes. The experiment results showed that the active ingredients of lipid-lowering flavonoid extract of Daidai had different elimination half-lives in phase Ⅰ rats liver and intestinal microsomes incubation system. This implied that they had different metabolic characteristics in rats liver and intestine,and liver may be the main metabolism site of the active ingredients. The phaseⅠ metabolism of narngin was stronger than that of neohesperidin. The differences between their metabolic characteristics may be related to the binding sites of B-ring hydroxyl in flavonoid glycosides and the number of methoxyl group. The results provided an important experimental basis for further development and clinical application of lipid-lowering flavonoid extract preparation of Daidai.
Animals ; Chromatography, Liquid ; Citrus sinensis ; Flavonoids ; Intestines ; Lipids ; Liver ; Microsomes, Liver ; Rats ; Rats, Sprague-Dawley ; Tandem Mass Spectrometry

Adolescent ; Adult ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Pituitary Neoplasms ; pathology ; Thyroid Dysgenesis ; diagnostic imaging ; pathology