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Comprehensive characterization of metabolites and metabolic profiles in plasma has considerable sig-nificance in determining the efficacy and safety of traditional Chinese medicine(TCM)in vivo.However,this process is usually hindered by the insufficient characteristic fragments of metabolites,ubiquitous matrix interference,and complicated screening and identification procedures for metabolites.In this study,an effective strategy was established to systematically characterize the metabolites,deduce the metabolic pathways,and describe the metabolic profiles of bufadienolides isolated from Venenum Bufonis in vivo.The strategy was divided into five steps.First,the blank and test plasma samples were injected into an ultra-high performance liquid chromatography/linear trap quadrupole-orbitrap-mass spectrometry(MS)system in the full scan mode continuously five times to screen for valid matrix compounds and metabolites.Second,an extension-mass defect filter model was established to obtain the targeted precursor ions of the list of bufadienolide metabolites,which reduced approximately 39%of the interfering ions.Third,an acquisition model was developed and used to trigger more tandem MS(MS/MS)fragments of precursor ions based on the targeted ion list.The acquisition mode enhanced the acquisition capability by approximately four times than that of the regular data-dependent acquisition mode.Fourth,the acquired data were imported into Compound Discoverer software for identification of metabolites with metabolic network prediction.The main in vivo metabolic pathways of bufadienolides were elucidated.A total of 147 metabolites were characterized,and the main biotransformation reactions of bufadienolides were hydroxylation,dihydroxylation,and isomerization.Finally,the main prototype bufadienolides in plasma at different time points were determined using LC-MS/MS,and the metabolic profiles were clearly identified.This strategy could be widely used to elucidate the metabolic profiles of TCM preparations or Chinese patent medicines in vivo and provide critical data for rational drug use.
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Objectives: To explore the efficacy and safety of emergency transcatheter aortic valve replacement (TAVR). Methods: Data of patients who underwent emergency TAVR in eight centers, namely Fuwai Hospital, Wuhan Asia Heart Hospital, Xijing Hospital, Union Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology, Guangdong Provincial People's Hospital, Zhongshan Hospital Affiliated to Fudan University, the First Affiliated Hospital of Zhengzhou University, the Second Xiangya Hospital of Central South University, between May 2017 and December 2020 were retrospectively analyzed. The use of mechanical circulatory support system (MCS) and the results of laboratory tests (N-terminal B-type natriuretic peptide (NT-proBNP)) and echocardiography (mean aortic valve cross valve pressure difference and left ventricular ejection fraction) before and after operation were collected. The primary endpoint was all-cause death, and the secondary endpoints were stroke, major bleeding, major vascular complications, myocardial infarction, permanent pacemaker implantation, and acute renal injury. Device success was caculated, which refered to absence of procedural mortality and correct positioning of a single prosthetic heart valve into the proper anatomical location and intended performance of the prosthetic heart valve (mean aortic valve gradient<20 mmHg(1 mmHg=0.133 kPa) or peak velocity<3 m/s, with no moderate or severe prosthetic valve regurgitation). Kaplan-Meier survival curve was used to estimate the survival rate of patients during follow-up. Results: This study included 48 patients. The age was (72.5±8.1) years, and 34 patients were males (70.8%). Device success rate was 91.7% (44/48). The mean aortic valve transvalvular pressure was significantly decreased after operation ((12.3±6.4)mmHg vs. (60.2±23.8)mmHg, P<0.000 1). Left ventricular ejection fraction was significantly increased ((41.5±11.7)% vs. (31.0±11.3)%, P<0.000 1). NT-proBNP significantly decreased (3 492.0 (1 638.8, 7 165.5) ng/L vs. 12 418.5 (6 693.8, 35 000.0) ng/L, P<0.000 1). In-hospital all-cause mortality was 8.3% (4/48). During hospitalization, the rate of stroke was 2.1% (1/48), major bleeding was 6.3% (3/48), major vascular complications was 10.4% (5/48), myocardial infarction was 4.2% (2/48), permanent pacemaker implantation was 6.3% (3/48), and the rate of acute renal injury was 12.5% (6/48). MCS was used in 20 patients (41.7%). The median follow-up time was 196 days. During the follow-up, one patient died (due to systemic metastasis of pancreatic cancer), two cases suffered new myocardial infarction and one case received permanent pacemaker implantation. The survival rate of 30 days, 1 year and 2 years after the operation were 91.7% (44/48), 89.6% (43/48), 89.6% (43/48), respectively. Conclusion: Emergency TAVR may be a safe and effective treatment for patients with severe decompensated aortic valve stenosis.
Subject(s)
Acute Kidney Injury , Aged , Aged, 80 and over , Aortic Valve/surgery , Aortic Valve Stenosis/surgery , Female , Heart Valve Prosthesis , Humans , Male , Middle Aged , Myocardial Infarction/surgery , Retrospective Studies , Risk Factors , Stroke , Stroke Volume , Transcatheter Aortic Valve Replacement/methods , Treatment Outcome , Ventricular Function, LeftABSTRACT
Objective: To explore the short-term efficacy of fenestrated atrial septal defect (ASD) occulders in the treatment of pulmonary arterial hypertension (PAH). Methods: Thirty-six healthy dogs were divided into the balloon atrial septostomy (BAS)+fenestrated ASD occulders group (n=12), BAS group (n=12) and non-septostomy group (n=12). PAH was induced by intra-atrial injection of dehydrogenized monocrotaline (1.5 mg/kg) in all dogs. Animals in the BAS+fenestrated ASD occulders group underwent atrial septal puncture and fenestrated ASD occulders implantation. Animals in the BAS group underwent balloon atrial septostomy. The non-septostomy group received no surgical intervention. The hemodynamic indexes and blood N-terminal pro-B-type natriuretic peptide (NT-proBNP) of dogs were measured before modeling, 2 months after modeling, 1, 3, and 6 months after surgery, respectively. Echocardiography was performed to observe the patency of the shunt and atrial septostomy of the dogs in the BAS+fenestrated ASD occulders group and BAS group at 1, 3, and 6 months after surgery. Three dogs were sacrificed in each group at 1, 3, and 6 months after surgery, respectively. Atrial septal tissue and fenestrated ASD occulders were removed to observe the patency and endothelialization of the device. Lung tissues were obtained for hematoxylin-eosin (HE) staining to observe the inflammatory cells infiltration and the thickening and narrowing of the pulmonary arterials. Results: Among 36 dogs, 2 dogs died within 24 hours after modeling, and 34 dogs were assigned to BAS+fenestrated ASD occulders group (n=12), BAS group (n=11), and non-septostomy group (n=11). Compared with BAS group, the average right atrial pressure (mRAP) and NT-proBNP of dogs in the BAS+fenestrated ASD occulders group were significantly reduced at 3 months after surgery (P<0.05), and the cardiac output (CO) was significantly increased at 6 months after surgery, arterial oxygen saturation (SaO2) was also significantly reduced (P<0.05). Compared with non-septostomy group, dogs in the BAS+fenestrated ASD occulders group had significantly lower mRAP and NT-proBNP at 1, 3, and 6 months after surgery (P<0.05), and higher CO and lower SaO2 at 6 months after surgery (P<0.05). Compared with the non-septostomy group, the dogs in the BAS group had significantly lower mRAP and NT-proBNP at 1 month after surgery (P<0.05), and there was no significant difference on mRAP and NT-proBNP at 3 and 6 months after surgery (P>0.05). Echocardiography showed that there was a minimal right-to-left shunt in the atrial septum in the BAS group at 1 month after the surgery, and the ostomy was closed in all the dogs in the BAS group at 3 months after the surgery. There was still a clear right-to-left shunt in the dogs of BAS+fenestrated ASD occulders group. The shunt was well formed and satisfactory endothelialization was observed at 1, 3 and 6 months after surgery. The results of HE staining showed that the pulmonary arterials were significantly thickened, stenosis and collapse occurred in the non-septostomy group. Pulmonary microvascular stenosis and inflammatory cell infiltration in the pulmonary arterials were observed in the non-septostomy group. Pulmonary arterial histological results were comparable between BAS+fenestrated ASD occulders group and non-septostomy group at 6 months after surgery . Conclusions: The fenestrated ASD occulder has the advantage of maintaining the open fistula hole for a longer time compared with simple balloon dilation. The fenestrated ASD occulder can improve cardiac function, and it is safe and feasible to treat PAH in this animal model.
Subject(s)
Animals , Atrial Septum/surgery , Cardiac Catheterization/methods , Dogs , Familial Primary Pulmonary Hypertension , Heart Septal Defects, Atrial/surgery , Hypertension, Pulmonary , Pulmonary Arterial HypertensionABSTRACT
The high incidence of cardiovascular diseases is a serious threat to human health, and endovascular surgery has become the standard treatment for most interventional cardiovascular diseases. The robotassisted endovascular surgery system further enhances surgeons' ability to perform minimally invasive endovascular procedures in interventional cardiology. This study presents a new robotic technique for coronary intervention from the perspective of clinical application. Aiming at clinical application scenarios, this scheme proposed an intuitive guide wire catheter mechanism design, which accurately and perfectly simulates the doctor's hand movements, realizes the positive and negative direction translation of the guide wire catheter, accurate torque control of the guide wire rotation and locking. The results of animal test showed that the R-OneTM has a high degree of dexterity, accuracy and stability,and meets the clinical needs.
Subject(s)
Animals , Cardiovascular Diseases , Catheterization , Equipment Design , Robotic Surgical Procedures , RoboticsABSTRACT
OBJECTIVE@#To study the efficacy and safety of lactase additive in improving lactose intolerance in preterm infants.@*METHODS@#A total of 60 preterm infants with lactose intolerance who were admitted to the Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2018 to December 2019 were randomly divided into a lactase treatment group and a control group, with 30 infants in each group. The infants in the lactase treatment group were given 4 drops of lactase additive (180 mg) added into preterm formula or breast milk, and those in the control group were given placebo, oral administration of probiotics (live combined @*RESULTS@#Finally 29 infants in the lactase treatment group and 26 infants in the control group completed the trial. At the end of the first week after intervention, compared with the control group, the lactase treatment group had significantly lower frequency of daily milk vomiting and gastric retention amount (@*CONCLUSIONS@#Lactase additive can safely and effectively improve the clinical symptoms caused by lactose intolerance in preterm infants.
Subject(s)
China , Female , Humans , Infant , Infant, Newborn , Infant, Premature , Lactase , Lactose , Lactose Intolerance/drug therapy , Prospective StudiesABSTRACT
Objective:To investigate the protective effect and molecular mechanism of Angelicae Sinensis Radix-Chuanxiong Rhizoma medicated serum (ASRCRS) against oxidative damage of PC12 cells induced by H<sub>2</sub>O<sub>2</sub>. Method:Oxidative damage of PC12 cells was induced by H<sub>2</sub>O<sub>2</sub><italic> in vitro</italic>, and intervention was performed in the low-, medium-, and high-dose ASRCRS groups with a final volume fraction of 15%. The cell viability was determined by methyl thiazolyl tetrazolium (MTT) assay. Cell morphology was observed by an inverted fluorescence microscope. The content of lactate dehydrogenase (LDH) and malondialdehyde (MDA), the activity of superoxide dismutase (SOD), and the distribution of reactive oxygen species (ROS) in the cell supernatant were detected by the kits. Cell apoptosis was detected by Annexin V-FITC/PI double staining. The protein expression levels of nuclear factor E<sub>2</sub>-related factor 2 (Nrf2), Kelch-like epichlorohydrin associated protein-1 (Keap1), heme oxygenase-1 (HO-1), and SOD1 were detected by Western blot. Result:Oxidative damage was induced by 300 μmol·L<sup>-1</sup> H<sub>2</sub>O<sub>2</sub> for 24 hours. Compared with the normal group, the model group showed abnormal cell morphology, reduced cell viability (<italic>P</italic><0.01), increased LDH and MDA (<italic>P</italic><0.01), blunted SOD activity, elevated intracellular distribution of ROS, down-regulated protein expression of Nrf2, HO-1, and SOD1 (<italic>P</italic><0.05, <italic>P</italic><0.05), and up-regulated protein expression of Keap1 (<italic>P</italic><0.01). Compared with the model group, ASRCRS groups displayed improved cell morphology, increased cell viability, inhibited cell apoptosis, potentiated SOD activity (<italic>P</italic><0.01), suppressed release of LDH (<italic>P</italic><0.01) and generation of ROS, decreased content of MDA (<italic>P</italic><0.01), up-regulated protein expression of Nrf2, HO-1 and SOD1 (<italic>P</italic><0.05, <italic>P</italic><0.01), and down-regulated protein expression of Keap1 (<italic>P</italic><0.01). Conclusion:ASRCRS could protect PC12 cells from oxidative damage induced by H<sub>2</sub>O<sub>2</sub> by up-regulating the expression of Nrf2 to activate the Nrf2/antioxidant response element (ARE) signaling pathway, enhancing the ability to resist oxidative damage, and inhibiting cell apoptosis.
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OBJECTIVE@#To investigate the clinical features and prognosis of acute myeloid leukemia (AML) patients with the mixed lineage leukemia (MLL) gene rearrangements AF6 (MLL-AF6) positive.@*METHODS@#In the study, 11 patients who were newly diagnosed with MLL-AF6 positive AML were analyzed retrospectively, related literature was reviewed to clarify the clinical features and prognosis of MLL-AF6 positive patients.@*RESULTS@#Among the 11 patients, there were 6 males and 5 females, with a median age of 36 years. Six patients were diagnosed with AML M5 and five with M4 according to FAB classification (French-American-British classification systems). Gingival swelling and pain occurred in 6 cases and fever occurred in 5 cases. At first diagnosis, the median white blood cells were 55.5×109/L. Immunotype showed the expression of myeloid/monocyte and early stem cell series antigens. The expression level of MLL-AF6 fusion gene (real-time quantitative PCR) was 14.2%-214.5%, and 6/11 cases (54.5%) were associated with high EVI1 gene expression. Mutations of KRAS, TET2, ASXL1, TP53, DNMT3A, and FLT3-ITD were detected by next generation sequencing (NGS) in 4 patients. Chromosome G banding examination showed that 2 cases were t(6;11)(q27, q23) with complex karyotype abnormality, 4 cases with +8 abnormality and 2 cases with normal karyotype. Hematological complete remission (CR) was achieved in 8/11 patients (72.7%) after conventional induction chemotherapy, and primary drug resistance was observed in 3 patients. Two of the eight patients with CR were negative for minimal residual disease (MRD), with a median CR duration of 4.5 months. Two patients with positive MRD and three patients with refractory recurrence underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), but all died due to leukemia progression. At the end of follow-up on December 1, 2019, 2 patients were alive and 9 died, with median survival time of 9 months.@*CONCLUSION@#The AML patients with MLL-AF6 positive were mostly young, the majority of FAB types were M4 and M5, and most of the patients often had fever as the first symptom, with increased white blood cells, accompanied by organ infiltration, and high EVI1 gene expression. The hematological remission rate of routine chemotherapy is not low, but it is difficult to achieve molecular remission, most of which have early recurrence. Early allo-HSCT in a molecular negative state may prolong the CR duration.
Subject(s)
Adult , Female , Hematopoietic Stem Cell Transplantation , Humans , Leukemia, Myeloid, Acute/genetics , Male , Myeloid-Lymphoid Leukemia Protein/genetics , Oncogene Proteins, Fusion/genetics , Prognosis , Remission Induction , Retrospective StudiesABSTRACT
Objective: To explore the impact of transcatheter aortic valve replacement (TAVR) on renal function in patients with severe aortic stenosis. Methods: This is a single-center retrospective study. Consecutive patients with severe aortic valve stenosis and received TAVR in Zhongshan Hospital from December 2014 to December 2019 were included. The patients were divided into four groups according to the estimate glomerular filtration rate (eGFR) measured at one day before TAVR, namely eGFR>90 ml·min-1·1.73m-2 group, 60<eGFR≤90 ml·min-1·1.73m-2 group, 30<eGFR≤60 ml·min-1·1.73m-2 group and eGFR≤30 ml·min-1·1.73m-2 group. The patients were also divided into acute renal function recovery (AKR) group, acute kidney injury (AKI) group and no change in renal function group according to renal function changes at 72 hours after TAVR. AKR was defined as eGFR increased by more than 25% of the baseline value at 72 hours after TAVR, and AKI was defined as eGFR decreased more than 25% of the baseline value at 72 hours after TAVR. The clinical data of each group were compared, and multivariate logistic regression analysis was performed to analyze the determinants responsible for renal function changes after TAVR. Results: A total of 217 patients were enrolled in this study. The age was (76.7±7.4) years and there were 86 females. The Society of Thoracic Surgeons score was (9.5±5.8). The proportions achieved AKR after TAVR were 0, 30.2% (35/116), 58.6% (41/70) and 75.0% (9/12) respectively in eGFR>90 ml·min-1·1.73m-2 group, 60<eGFR≤90 ml·min-1·1.73m-2 group, 30<eGFR≤60 ml·min-1·1.73m-2 group and eGFR≤30 ml·min-1·1.73m-2 group. A total of 3 patients (1.4%) suffered AKI, including 2 patients in 30<eGFR≤60 ml·min-1·1.73m-2 group and 1 patient in 60<eGFR≤90 ml·min-1·1.73m-2 group. The incidence of AKI in eGFR<60 ml·min-1·1.73m-2 group was 2.4% (2/82). Among the 217 patients, AKR occurred in 85(39.2%) patients, 3(1.4%) experienced AKI and renal function remained unchanged in 129 (59.4%) patients post TAVR. Body mass index (BMI), left ventricular end diastolic dimension (LVEDD) and preoperative eGFR were statistically different between the 3 groups (P<0.05). Multivariate logistic regression analysis showed that BMI (OR=5.54, 95%CI 1.04-29.58, P=0.045), preoperative LVEDD (OR=1.22, 95%CI 1.09-1.38, P=0.001) and preoperative eGFR (OR=2.23, 95%CI 2.04-2.55, P=0.004) were associated with non-AKR post TAVR. Conclusions: After TAVR, most patients show no change or improvement of renal function. BMI, preoperative LVEDD and eGFR are related to renal function change after TAVR.
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The study of traditional Chinese medicine(TCM) syndrome model started late but developed rapidly. In recent years, with the deepening of the study of TCM diseases and prescriptions, to develop the modernization of TCM, the study of TCM syndrome model has been required to be more specific and went deeper. Qi deficiency and blood stasis syndrome, as a common clinical syndrome type, often occurs in cardiovascular and cerebrovascular diseases, digestive system diseases, chronic kidney disease, cancer and other diseases. With the increase in the aging of population in China, the research on Qi deficiency and blood stasis syndrome has become a hot topic in the field of TCM due to the physical characteristics of the elderly people with multiple Qi deficiency and blood stasis. The animal models of Qi deficiency and blood stasis syndrome established in recent years were classified into pathological model, etiological model and combined disease and syndrome model. By observing the macroscopical representation, limb behavior and hemorheology of experimental animals in line with the theory of TCM, this paper evaluates the method of modeling, and provides ideas and reference for the method of modeling for Qi-deficiency and blood-stasis syndrome. The research on the model of Qi-deficiency and blood-stasis syndrome should follow the thought of cause-pulse-syndrome-treatment, namely etiology-external manifestation-pathological mechanism-syndrome differentiation and treatment, and combine the study on the TCM syndrome model with modern science, so as to standardize the development of modeling methods and build relatively improved animal models of Qi deficiency and blood stasis, and provide model support for exploring the pathogenesis of Qi deficiency and blood stasis syndrome and new treatment ideas in the future.
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Schisandra is the mature fruit of Schisandra chinensis(known as "north Schisandra") or S. shenanthera(known as "south Schisandra"). S. chinensis contains a variety of lignans, volatile oils, polysaccharides, organic acids and other chemical constituents; among them, lignans are recognized as the characteristic active components. Clinical studies have found that Schisandra and Schisandra-related products have a better effect in the prevention and treatment of viral hepatitis, drug-induced liver injury, liver cirrhosis, liver failure and other liver diseases. Modern pharmacological studies have demonstrated that Schisandra has a variety of pharmacological activities, such as anti-inflammation, antioxidation, anticancer, regulation of nuclear receptor, antivirus, regulation of cytochrome P450 enzyme, inhibition of liver cell apoptosis and promotion of liver regeneration. This paper reviews the studies about the applications and mechanism of Schisandra in the prevention and treatment of liver diseases, in the expectation of providing guidance for the development of hepatoprotective drugs from Schisandra and the clinical applications of Schisandra-related products.
Subject(s)
Chemical and Drug Induced Liver Injury , Drugs, Chinese Herbal , Fruit , Chemistry , Humans , Lignans , Protective Agents , SchisandraABSTRACT
Yes-associated protein (YAP) is an important regulator of cellular proliferation and transdifferentiation. However, little is known about the mechanisms underlying myofibroblast transdifferentiation in dilated cardiomyopathy (DCM). We investigated the role of YAP in the pathological process of cardiac matrix remodeling. A classic model of DCM was established in BALB/c mice by immunization with porcine cardiac myosin. Cardiac fibroblasts were isolated from neonatal Sprague-Dawley rats by density gradient centrifugation. The expression levels of α-smooth muscle actin (α-SMA) and collagen volume fraction (CVF) were significantly increased in DCM mice. Angiotensin II (Ang II)-mediated YAP activation promoted the proliferation and transdifferentiation of neonatal rat cardiac fibroblasts, and this effect was significantly suppressed in the shRNA YAP + Ang II group compared with the shRNA Control + Ang II group in vitro (2.98±0.34 ×105 vs 5.52±0.82 ×105, P<0.01). Inhibition of endogenous Ang II-stimulated YAP improved the cardiac function by targeting myofibroblast transdifferentiation to attenuate matrix remodeling in vivo. In the valsartan group, left ventricular ejection fraction and fractional shortening were significantly increased compared with the DCM group (52.72±5.51% vs 44.46±3.01%, P<0.05; 34.84±3.85% vs 26.65±3.12%, P<0.01). Our study demonstrated that YAP was a regulator of cardiac myofibroblast differentiation, and regulation of YAP signaling pathway contributed to improve cardiac function of DCM mice, possibly in part by decreasing myofibroblast transdifferentiation to inhibit matrix remodeling.
Subject(s)
Animals , Male , Rats , Angiotensin II/pharmacology , Cardiomyopathy, Dilated/physiopathology , Adaptor Proteins, Signal Transducing/drug effects , Cell Transdifferentiation/drug effects , Myofibroblasts/drug effects , Phosphoproteins/antagonists & inhibitors , Phosphoproteins/physiology , Swine , Echocardiography , Cardiomyopathy, Dilated/pathology , Cell Differentiation , Blotting, Western , Rats, Sprague-Dawley , Cell Cycle Proteins , Adaptor Proteins, Signal Transducing/antagonists & inhibitors , Adaptor Proteins, Signal Transducing/physiology , Disease Models, Animal , Myofibroblasts/physiology , Mice, Inbred BALB C , Microscopy, FluorescenceABSTRACT
To characterize the chemical constituents of Huanbei Zhike Prescription by ultra-high performance liquid chromatography-time of flight mass spectrometry( UPLC-Q-TOF-MS/MS). A Thermo Syncronls C18 column( 2. 1 mm×100 mm,1. 7 μm) was used with methanol( A)-0. 1% formic acid solution( B) as the mobile phase for gradient elution. The injection volume was 2 μL; the column temperature was 40 ℃; the flow rate was 0. 3 m L·min-1; and electrospray ionization( ESI) source was used to collect data in positive and negative ion modes. The ion scanning range was m/z 50-1 200,with capillary voltage of 3 000 V,ion source temperature of100 ℃,atomization gas flow rate of 50 L·h-1,desolvent gas flow rate of 800 L·h-1,desolvent temperature of 400 ℃,cone hole voltage of 40 V,with argon as the collision gas and the collision energy was 20-35 V. The excimer ion peak information was analyzed by Waters UNIFI data processing software. The molecular formula with error within 1×10-5 was compared with the data in database to identify the compounds. The secondary fragment ion information of the target compound was selected,and then compared with the retention time and fragmentation patterns provided by the database and the existing literature to further confirm the compositions and structures of the compounds. A total of 68 main compounds in Huanbei Zhike Prescription were identified,including 38 flavonoids,10 organic acids,6 terpenoids and 10 nitrogen-containing compounds,of which 12 compounds were verified by the control substances. This method is rapid and accurate,which provides a new strategy for the qualitative analysis of the chemical constituents of Huanbei Zhike Prescription,and lays a foundation for the further study and quality control of the compound pharmacodynamic substance.
Subject(s)
Chromatography, High Pressure Liquid , Drugs, Chinese Herbal , Chemistry , Flavonoids , Tandem Mass Spectrometry , TerpenesABSTRACT
@#Objective To compare the clinical effect of single mediastinal drainage tube and both mediastinal drainage tube and closed thoracic drainage tube for the patients who received thoracoscopic radical resection of esophageal carcinoma. Methods We enrolled 96 esophageal carcinoma patients who received thoracoscopic radical resection from June 2016 to October 2018. Of them, 49 patients were indwelt with both mediastinal drainage tube and closed thoracic drainage tube (a chest & mediastinal drainage group, a CMD group) while the other 47 patients were indwelt with single mediastinal drainage tube (a single mediastinal drainage group, a SMD group). The total drainage volume, intubation time and incidence of postoperative complications (postoperative atelectasis, pulmonary infection, pleural effusion and anastomotic leakage) between the two groups were compared. The pain score and comfort score were also compared between the two groups. Results The total drainage volume and intubation time in the SMD group were not significantly different from those in the CMD group (1 321±421 mL vs. 1 204±545 mL, P=0.541; 6.1±3.7 d vs. 6.4 ±5.1 d, P=0.321). The incidence of postoperative complications (postoperative atelectasis, pulmonary infection, pleural effusion and anastomotic leakage) in the SMD group was not significantly different from that in the CMD group (10.6% vs. 6.1%, P=0.712; 4.3% vs. 10.2%, P=0.656; 6.4% vs. 12.2%, P=0.121; 2.1% vs. 4.1%, P=0.526). The numerical rating scale (NRS) pain scores on the first to the fifth day after surgery and during extubation in the SMD group were significantly lower than those in the CMD group (3.2±2.1 vs. 5.1±2.4, P=0.041; 2.8±0.6 vs. 4.8±1.4, P=0.015; 2.1±0.4 vs. 4.5±0.4, P=0.019; 1.7±0.7 vs. 4.0±0.8, P=0.004; 1.8±0.7 vs. 3.2±1.2, P=0.006; 1.4±0.2 vs. 2.5±3.4, P=0.012). The VAS comfort scores in the SMD group were significantly lower than those in the CMD group (3.6±1.7 vs. 6.6±3.7, P=0.018; 2.9±2.0 vs. 5.1±3.4, P=0.007; 2.1±1.4 vs. 5.5±2.4, P=0.004; 3.0±0.9 vs. 4.6±3.8, P=0.012; 1.8±1.1 vs. 4.2±2.7, P=0.003; 2.4±3.2 vs. 5.3±1.7, P=0.020). Conclusion The clinical effect of single mediastinal drainage tube in thoracoscopic resection of esophageal carcinoma is similar to that of both mediastinal drainage tube and closed thoracic drainage tube, but it can significantly improve the comfort of the patients.
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This study investigated the inhibitory effect of eight natural flavonoids in Chinese herb Scutellariae Radix on huamn cytochrome P450 1 A(CYP1 A), a key cancer chemo-preventive target. In this study, phenacetin was used as a probe substrate for CYP1 A, while human liver microsomes and recombinant human CYP1 A enzymes were used as enzyme sources. Liquid chromatography-tandem mass spectrometry was used to monitor the formation rates of acetaminophen, the O-deethylated metabolite of phenacetin. The dose-dependent inhibition curves were depicted based on the changes of the formation rates of acetaminophen, while the IC_(50) were determined. Inhibition kinetic analyses and docking simulations were used to investigate the inhibition modes and mechanism of wogonin(the most potent CYP1 A inhibitor in this herb), while the inhibition constants(K_i) of wogonin against both CYP1 A1 and CYP1 A2 were determined. Among all tested flavonoids, wogonin, 7-methoxyflavanone and oroxylin A displayed a strong inhibitory effect on CYP1 A(IC_(50)100 μmol·L~(-1)). Further investigations demonstrated that wogonin had a weak inhibitory effect on other human CYP enzymes, suggesting that it could be used as a lead compound for the development of specific inhibitors of CYP1 A. Furthermore, the inhibition kinetic analyses clearly demonstrated that wogonin could strongly inhibit phenacetin O-deethylation in both CYP1 A1 and CYP1 A2 in a competitive manner, with K_i values at 0.118 and 0.262 μmol·L~(-1), respectively. Molecular docking demonstrated that wogonin could strongly interact with CYP1 A1 and CYP1 A2 via hydrophobic and π-π interactions, as well as Ser120 and Ser116 in CYP1 A1 via hydrogen-bonding. In conclusion, this study found that some flavonoids in Scutellariae Radix displayed a strong inhibitory effect on CYP1 A, while wogonin is the most potent CYP1 A inhibitor with a relatively high selectivity towards CYP1 A over other human CYPs.
Subject(s)
Chromatography, Liquid , Cytochrome P-450 CYP1A1 , Cytochrome P-450 Enzyme Inhibitors , Pharmacology , Flavanones , Pharmacology , Flavonoids , Pharmacology , Humans , Molecular Docking Simulation , Scutellaria baicalensis , ChemistryABSTRACT
Sepsis is a kind of systemic inflammatroy response syndrome (SIRS) induced by severe infection,operation,and trauma,with high mortality rate,treatment cost,and high consumption of medical resources.It has caused a great burden to the medical industry and even the national economy.Therefore,it is urgent to find effective treatment methods for sepsis.At present,the sepsis has been treated with certain drugs pointing at its pathogenesis,such as antibiotics,glucocorticoids,and vasoactive drugs.,but the therapeutic effect is not ideal,with many side effects,poor prognosis,and high clinical mortality.Based on the overall macro-dialectical thinking mode,and with the unique effect and low side effect,traditional Chinese medicine (TCM) has attracted the attention from researchers and clinicians around the world for treatment of sepsis.In recent years,some traditional Chinese medicine prescriptions,Chinese patent medicines,single Chinese medicines and active ingredients are increasingly used as new drugs to prevent and treat sepsis.Such treatment methods have been widely recognized and have reduced the mortality and inflammatory indexes of patients to a certain extent,playing an important role in the prevention and treatment of sepsis.In this paper,the actions of nuclear factor kappa B (NF-κB) signal pathway in sepsis as well as the advances in research of NF-κB signal pathway-related proteins in Chinese medicine for sepsis were reviewed.
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Objective: To study the correlation between the fingerprint of different polar parts of Huanbei Zhike recipe and its antitussive effect,identify the chromatographic peaks greatly contributing to its pharmacological effect,and ascribe the chromatographic peaks. Method: Gradient elution method was used to establish the chromatographic peaks of different polar parts of Huanbei Zhike recipe. The common peaks and corresponding peak areas of each part were obtained by referring to the water extract chromatogram and after being processed by chromatographic workstation. The cough frequency,the latent period of cough and the contents of interleukin (IL)-4,interferon-γ(IFN-γ),immunoglobulin (Ig)E and IL-5 in lung lavage fluid of mice were used as the detection indexes to investigate the antitussive effect of different polar parts of Huanbei Zhike recipe. The correlation analysis among cough frequency,cough latent period and common peak area was carried out,and the peaks greatly contributing to the effect of medicine were pointed out,which were assigned according to the fingerprint of single drug. Result:Bivariate correlation analysis showed that seven chromatographic peaks, i.e. No.12,13,29,32,33,35 and 39,contributed significantly to the antitussive effect. The higher the content of the compounds represented by these peaks,the stronger the antitussive effect. There was a significant correlation between No. 32 peak and the latent period of cough,while No. 13 and No. 32 peaks were significantly correlated with cough frequency. These chromatographic peaks were assigned and found to be present in Scutellaria baicalensis,Crepis Herba, Aurantii Fructus,Glycyrrhiza uralensis,etc. Conclusion:The chromatographic peaks of No.13 and No.32 peaks contribute greatly to the antitussive effect of Huanbei Zhike recipe,while Crepis turczaniowii,S. baicalensis and Aurantii Fructus are of significant significance for the whole recipe.
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BACKGROUND@#Areal bone mineral density (aBMD) applied for osteoporosis diagnosis unavoidably results in the missingdiagnosis in patients with large bones and misdiagnosis in those with small bones. Therefore, we try to find a new adjusted index of bone mineral content (BMC) to make up shortcomings of aBMD in osteoporosis diagnosis.@*METHODS@#In this multi-center epidemiological study, BMC and aBMD of lumbar spines (n = 5510) and proximal femurs (n = 4710) were measured with dual energy X-ray absorptiometry (DXA). We analyzed the correlation between the bone mass and body weight in all subjects including four age groups (50 years). And then the body weight was used for standardizing BMC (named wBMC) and applied for the epidemiological analysis of osteoporosis.@*RESULTS@#The correlation of body weight and BMC is 0.839 to 0.931 of lumbar vertebra 1-4 (L1-4), and 0.71 to 0.95 of femoral neck in different age groups. When aBMD was applied for diagnosing osteoporosis, the prevalence was 7.55%, 16.39%, and 25.83% in patients with a high, intermediate, and low body weight respectively. However, the prevalence was 21.8%, 18.03%, and 11.64% by wBMC applied for diagnosing osteoporosis. Moreover, the prevalence of osteoporosis increased by 3.76% by wBMC with the body weight increased by 5 kg. The prevalence decreased by 1.94% when the body weight decreased by 5 kg.@*CONCLUSIONS@#wBMC can reduce the missed diagnosis in patients with large body weight and reduce misdiagnosis in those with small body weight. Including children, wBMC may be feasible for osteoporosis diagnosis individuals at any age.
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Absorptiometry, Photon , Adult , Age Factors , Body Weight , Physiology , Bone Density , Physiology , Female , Femur Neck , Diagnostic Imaging , Metabolism , Humans , Lumbar Vertebrae , Diagnostic Imaging , Metabolism , Middle Aged , Osteoporosis , Diagnostic Imaging , Metabolism , Prevalence , Young AdultABSTRACT
Objective To compare aortic root anatomical characteristics between severe aortic valve stenosis (AS) and aortic regurgitation (AR) patients, and to provide useful information for transcatheter aortic valve replacement (TAVR) device designs and procedural techniques for treatment of AR. Methods Consecutive patients admitted between April 2014 to May 2016 with severe AS or AR and planned to undergo transcatheter aortic valve replacement were included. There were a total of 57 AR and 113 AS patients. All patients underwent multi-detector computed tomographic imaging and echocardiography examinations. Results The mean aortic annulus diameter in AR patients was slightly but significantly larger than AS patients[ (26.4±3.7) mm vs. (25.2±2.9) mm, P=0.001]. The mean diameters of the ascending aorta[ (38.3±6.9) mm vs. (33.9±6.7) mm, P<0.001]and Valsalva sinus[ (38.9±6.9) mm vs. (32.7±4.5) mm, P<0.001] in AR patients were larger than in AS patients. The left coronary ostia height was of no significant difference between the 2 groups [ (12.5±3.7) mm vs. (13.4±3.2) mm, P=0.08] and the right coronary ostia height was higher in the AR group than in the AS group [ (17.5±5.0) mm vs. (15.3±3.3) mm, P=0.001]. Conclusions The anatomical aortic root data from patients with AS or AR in the present study may provide useful information for transcatheter aortic valve replacement device designs and procedural techniques for treatment of AR.
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Shenshao Tablet (SST), prepared from Paeoniae Radix Alba (PRA) and total ginsenoside of Ginseng Stems and Leaves (GSL), is a traditional Chinese medicine (TCM) preparation prescribed to treat coronary heart disease. However, its chemical composition and the components that can migrate into blood potentially exerting the therapeutic effects have rarely been elucidated. We developed an HPLC/DAD/ESI-MS approach aiming to comprehensively profile and identify both the chemical components of SST and its absorbed ingredients (and metabolites) in rat plasma and urine. Chromatographic separation was performed on an Agilent Eclipse XDB C column using acetonitrile/0.1% formic acid as the mobile phase. MS detection was conducted in both negative and positive ESI modes to yield more structure information. Comparison with reference compounds (t, MS), interpretation of the fragmentation pathways, and searching of in-house database, were utilized for more reliable structure elucidation. A total of 82 components, including 21 monoterpene glycosides, four galloyl glucoses, two phenols from PRA, and 55 ginsenosides from GSL, were identified or tentatively characterized from the 70% ethanolic extract of SST. Amongst them, seven and 24 prototype compounds could be detectable in the plasma and urine samples, respectively, after oral administration of an SST extract (4 g·kg) in rats. No metabolites were observed in the rat samples. The findings of this work first unveiled the chemical complexity of SST and its absorbed components, which would be beneficial to understanding the therapeutic basis and quality control of SST.
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Animals , Chromatography, High Pressure Liquid , Methods , Drugs, Chinese Herbal , Chemistry , Pharmacokinetics , Male , Rats , Rats, Sprague-Dawley , Spectrometry, Mass, Electrospray Ionization , Methods , Tablets , ChemistryABSTRACT
Aim To assess the effects of Trillium Tschonoskii Maxim ( TTM) decoction on learning and memory dysfunction in Alzheimer’ s disease ( AD ) model rats which induced by okadaic acid( OA) and its possible mechanism. Methods The SD rats were di-vided into ten groups,namely,d DMSO control group, OA group, TTM high-dose ( 0. 5 g·kg-1·d-1) group,TTM medium-dose ( 1 g·kg-1·d-1) group, TTM lower-dose (2 g·kg-1·d-1) group,and these groups were divided into one week and two weeks of gavage. Treatment groups were gavaged with TTM de-coction twice a day. After 5 days of Morris water maze training,treatment groups and AD model groups were injected with OA (0.392 mmol·L-1,1. 5 μL) in bi-lateral hippocampal of the rats. The DMSO groups were injected with 10% DMSO. The spatial memory reten- tion wereas detected by water maze at 24 h after injec-tion. After the test, we prepared sample for Western blot and Nissl’s staining. The Western blotting test was used to detect the PP2A activity and the phospho-rylation of Tau protein in the hippocampus. Nissl’'s staining was used to observe the changes of the number of Nissl’s bodies in the hippocampal CA1 and CA3 re-gions. Results The Morris water maze test showed that after injection of OA, the latency of TTM groups wereas shorter than that of OA groups. Western blot showed that the high dose TTM could increase the ac-tivity of PP2A and decrease the level of Tau phospho-rylation at PS-Tau396,,PT-Tau404. The Nissl’s stai-ning results showed that the number of Nissl’s bodies in the hippocampal CA1 and CA3 regions of OA groups wereas significantly attenuated compared with that of the number of Nissl's bodies in the hippocampal CA1 and CA3 regions than DMSO groups. The number of Nissl’s bodies in high groups were morewas larger than that of OA group. Conclusion The results show that TTM can improve the learning and memory dysfunction in AD model rats which induced by OA. The mecha- nism wasis probably that TTM can increase PP2A ac-tivity and then down-regulate the level of Tau phospho-rylation and improve neural development.