Comparative study on the main active components of Baoyuan decoction in plasma and urine of normal and heart failure rats.

The global morbidity and mortality of heart failure has been increasing in recent years. Traditional Chinese medicine (TCM) was increasingly used to treat cardiovascular diseases. Baoyuan decoction (BYD) was a famous classical prescription in China. Modern pharmacological studies showed that it had obvious therapeutic effects on cardiovascular diseases, but its pathological pharmacokinetic studies were unclear. In this research, the absorption of 16 bioactive components in plasma and the excretion of 9 representative components in urine of control rats and isoproterenol (ISO)-induced heart failure rats were studied using the large-volume direct-injection LC-MS method established by our research group. The results indicated that flavonoid constituents exhibited quicker absorption and elimination than saponin constituents after oral administration of BYD. The half-life period of some bioactive compounds in the model group was increased, which contributed to the longer therapeutic effect. The cumulative excretion rate of major flavonoid components of BYD decreased significantly in the ISO-induced heart failure rats.

Heart rate variability-derived features based on deep neural network for distinguishing different anaesthesia states.

BACKGROUND: Estimating the depth of anaesthesia (DoA) is critical in modern anaesthetic practice. Multiple DoA monitors based on electroencephalograms (EEGs) have been widely used for DoA monitoring; however, these monitors may be inaccurate under certain conditions. In this work, we hypothesize that heart rate variability (HRV)-derived features based on a deep neural network can distinguish different anaesthesia states, providing a secondary tool for DoA assessment. METHODS: A novel method of distinguishing different anaesthesia states was developed based on four HRV-derived features in the time and frequency domain combined with a deep neural network. Four features were extracted from an electrocardiogram, including the HRV high-frequency power, low-frequency power, high-to-low-frequency power ratio, and sample entropy. Next, these features were used as inputs for the deep neural network, which utilized the expert assessment of consciousness level as the reference output. Finally, the deep neural network was compared with the logistic regression, support vector machine, and decision tree models. The datasets of 23 anaesthesia patients were used to assess the proposed method. RESULTS: The accuracies of the four models, in distinguishing the anaesthesia states, were 86.2% (logistic regression), 87.5% (support vector machine), 87.2% (decision tree), and 90.1% (deep neural network). The accuracy of deep neural network was higher than those of the logistic regression (p < 0.05), support vector machine (p < 0.05), and decision tree (p < 0.05) approaches. Our method outperformed the logistic regression, support vector machine, and decision tree methods. CONCLUSIONS: The incorporation of four HRV-derived features in the time and frequency domain and a deep neural network could accurately distinguish between different anaesthesia states; however, this study is a pilot feasibility study. The proposed method-with other evaluation methods, such as EEG-is expected to assist anaesthesiologists in the accurate evaluation of the DoA.

A survey of current practices, attitudes and demands of anaesthesiologists regarding the depth of anaesthesia monitoring in China.

BACKGROUND: In this study, we aimed to analyse survey data to explore two different hypotheses; and for this purpose, we distributed an online survey to Chinese anaesthesiologists. The hypothetical questions in this survey include: (1) Chinese anaesthesiologists mainly use the depth of anaesthesia (DoA) monitors to prevent intraoperative awareness and (2) the accuracy of these monitors is the most crucial performance factor during the clinical daily practice of Chinese anaesthesiologists. METHODS: We collected and statistically analysed the response of a total of 12,750 anesthesiologists who were invited to participate in an anonymous online survey. The Chinese Society of Anaesthesiologists (CSA) trial group provided the email address of each anaesthesiologist, and the selection of respondents was random from the computerized system. RESULTS: The overall response rate was 32.0% (4037 respondents). Only 9.1% (95% confidence interval, 8.2-10.0%) of the respondents routinely used DoA monitors. Academic respondents (91.5, 90.3-92.7%) most frequently used DoA monitoring to prevent awareness, whereas nonacademic respondents (88.8, 87.4-90.2%) most frequently used DoA monitoring to guide the delivery of anaesthetic agents. In total, the number of respondents who did not use a DoA monitor and whose patients experienced awareness (61.7, 57.8-65.6%) was significantly greater than those who used one or several DoA monitors (51.5, 49.8-53.2%). Overall, the crucial performance factor during DoA monitoring was considered by 61.9% (60.4-63.4%) of the respondents to be accuracy. However, most respondents (95.7, 95.1-96.3%) demanded improvements in the accuracy of the monitors for DoA monitoring. In addition, broad application in patients of all ages (86.3, 85.2-87.4%), analgesia monitoring (80.4, 79.2-81.6%), and all types of anaesthetic agents (75.6, 74.3-76.9%) was reported. In total, 65.0% (63.6-66.5%) of the respondents believed that DoA monitors should be combined with EEG and vital sign monitoring, and 53.7% (52.1-55.2%) believed that advanced DoA monitors should include artificial intelligence. CONCLUSIONS: Academic anaesthesiologists primarily use DoA monitoring to prevent awareness, whereas nonacademic anaesthesiologists use DoA monitoring to guide the delivery of anaesthetics. Anaesthesiologists demand high-accuracy DoA monitors incorporating EEG signals, multiple vital signs, and antinociceptive indicators. DoA monitors with artificial intelligence may represent a new direction for future research on DoA monitoring.

Evaluation of the effects of notoginseng total saponins (NS), safflower total flavonoids (SF), and the combination of NS and SF (CNS) on the activities of cytochrome P450 enzymes using a cocktail method in rats.

Notoginseng total saponins (NS), safflower total flavonoids (SF), and the combination of NS and SF, namely CNS, are used for the treatment of cardiovascular diseases in clinic. This study developed a cocktail assay involving seven cytochrome P450 (CYP) enzymes to elucidate the effect of NS, SF, and CNS on CYP enzymes and to explore the synergistic effect of CNS in terms of CYP enzymes. Ultra-performance liquid chromatography-MS and reverse-transcription polymerase chain reaction were applied to detect the activities and mRNA expression levels of CYP enzymes. SF exhibited inhibitory effects on CYP1A2, 2B1, 2E1, and 2C11 and induction effects on CYP2C19 and 2D4. NS exhibited induction effects on CYP1A2, 2B1, 2E1, 2C11, 2C19, and 2D4. CNS exhibited induction effects on CYP1A2, 2B1, 2E1, 2C19, and 2D4 and inhibitory effects on CYP3A1 in vivo. Moreover, mRNA expression results were consistent with pharmacokinetic results. Potential herb-drug interactions should be studied closely when SF, NS, or CNS with clinical drugs are metabolized by CYP1A2, 2B1, 2E1, 2C11, 2C19, 2D4, and 3A1. CNS could change the inhibition or induction effects of CYP compared to the NS group, which might be one of the causes for the synergistic effects of the combination of NS and SF.

Fault Identification of Chemical Processes Based on k-NN Variable Contribution and CNN Data Reconstruction Methods.

Data-driven fault detection and identification methods are important in large-scale chemical processes. However, some traditional methods often fail to show superior performance owing to the self-limitations and the characteristics of process data, such as nonlinearity, non-Gaussian distribution, and multi-operating mode. To cope with these issues, the k-NN (k-Nearest Neighbor) fault detection method and extensions have been developed in recent years. Nevertheless, these methods are primarily used for fault detection, and few papers can be found that examine fault identification. In this paper, in order to extract effective fault information, the relationship between various faults and abnormal variables is studied, and an accurate "fault⁻symptom" table is presented. Then, a novel fault identification method based on k-NN variable contribution and CNN data reconstruction theories is proposed. When there is an abnormality, a variable contribution plot method based on k-NN is used to calculate the contribution index of each variable, and the feasibility of this method is verified by contribution decomposition theory, which includes a feasibility analysis of a single abnormal variable and multiple abnormal variables. Furthermore, to identify all the faulty variables, a CNN (Center-based Nearest Neighbor) data reconstruction method is proposed; the variables that have the larger contribution indices can be reconstructed using the CNN reconstruction method in turn. The proposed search strategy can guarantee that all faulty variables are found in each sample. The reliability and validity of the proposed method are verified by a numerical example and the Continuous Stirred Tank Reactor system.

Increased serum 2-oxoglutarate associated with high myocardial energy expenditure and poor prognosis in chronic heart failure patients.

Myocardial energy expenditure (MEE) and 2-oxoglutarate are elevated in chronic heart failure (CHF) patients compared with healthy controls. To explore whether 2-oxoglutarate could reflect the levels of MEE and predict the prognosis of CHF, 219 CHF patients and 66 healthy controls were enrolled. 2-Oxoglutarate was assayed with Liquid Chromatography-Mass Spectrometry/Mass Spectrometry (LC/MS/MS). CHF patients were divided into 4 groups according to interquartile range of MEE and followed for death or recurrent hospital admission due to CHF for the mean follow-up time 6.64±0.16months. 2-Oxoglutarate was increased in CHF patients compared with controls (P<0.01) and correlated with estimated glomerular filtration rate (r=0.142, P=0.036), age (r=-0.269, P<0.01) and MEE levels (r=0.307, P<0.01) in a multiple linear correlation analysis in CHF patients. Furthermore, 2-oxoglutarate (OR=3.470, 95% CI=1.557 to 7.730, P=0.002), N-terminal pro-B-type natriuretic peptide (OR=4.013, 95% CI=1.553 to 10.365, P=0.004), age (OR=1.611, 95% CI=1.136 to 2.283, P=0.007) and left ventricular ejection fraction (OR=7.272, 95% CI=3.110 to 17.000, P<0.001) were independently associated with MEE on multiple logistic regression analysis. Kaplan-Meier event curves showed that high 2-oxoglutarate levels were associated with adverse outcomes (Log Rank, Chi(2)=4.026, P=0.045). This study showed that serum 2-oxoglutarate is associated with MEE levels, which can be used as potential biomarkers for MEE, and it can reflect the clinical severity and short-term outcome of CHF.

Leonurus japonicus Houtt. modulates neuronal apoptosis in intracerebral hemorrhage: Insights from network pharmacology and molecular docking.

ETHNOPHARMACOLOGICAL RELEVANCE: Leonurus japonicus Houtt. (Labiatae), commonly known as Chinese motherwort, is a herbaceous flowering plant that is native to Asia. It is widely acknowledged in traditional medicine for its diuretic, hypoglycemic, antiepileptic properties and neuroprotection. Currently, Leonurus japonicus (Leo) is included in the Pharmacopoeia of the People's Republic of China. Traditional Chinese Medicine (TCM) recognizes Leo for its myriad pharmacological attributes, but its efficacy against ICH-induced neuronal apoptosis is unclear. AIMS OF THE STUDY: This study aimed to identify the potential targets and regulatory mechanisms of Leo in alleviating neuronal apoptosis after ICH. MATERIALS AND METHODS: The study employed network pharmacology, UPLC-Q-TOF-MS technique, molecular docking, pharmacodynamic studies, western blotting, and immunofluorescence techniques to explore its potential mechanisms. RESULTS: Leo was found to assist hematoma absorption, thus improving the neurological outlook in an ICH mouse model. Importantly, molecular docking highlighted JAK as Leo's potential therapeutic target in ICH scenarios. Further experimental evidence demonstrated that Leo adjusts JAK1 and STAT1 phosphorylation, curbing Bax while augmenting Bcl-2 expression. CONCLUSION: Leo showcases potential in mitigating neuronal apoptosis post-ICH, predominantly via the JAK/STAT mechanism.

Anesthetic management of conjoined twins undergoing one-stage surgical separation: A single center experience.

OBJECTIVE: To summarize our experience in the anesthetic management of conjoined twins undergoing one-stage surgical separation. METHODOLOGY: Medical records of conjoined twins admitted to our hospital for treatment and considered for surgical separation from 1996 to present were retrospectively reviewed. Four cases of conjoined twins underwent one-stage surgical separation under general anesthesia. Preoperative evaluation was performed to determine the extent of anatomical conjunction and associated anomalies. Anesthesia was simultaneously induced in all conjoined twins. The intubation procedure was successfully performed with the head slightly rotated to each baby's side, followed by the administration of vecuronium. Anesthetic agents were administered according to the estimated weight of each baby. One case of conjoined twins underwent surgical separation with cardiopulmonary bypass due to shared hearts. Results : All conjoined twins were successfully separated. No significant respiratory or cardiac events occurred during surgery except for one twin, which died after separation because of complicated congenital heart disease. Conclusions : Accurate preoperative evaluation, respiratory and circulatory management, and close cooperation of the multidisciplinary team are important aspects of anesthetic management of conjoined twins surgery.

Cognitive function and delirium following sevoflurane or propofol anesthesia for valve replacement surgery: A multicenter randomized controlled trial.

Cognitive dysfunction is a common postoperative neurological complication in patients undergoing valve replacement surgery. This study aimed to compare the effects of sevoflurane versus propofol-based total intravenous anesthesia on the incidence of cognitive dysfunction following valve replacement surgery. This multicenter, randomized, controlled double-blinded study was conducted in three teaching hospitals in China. Patients receiving on-pump valve replacement surgery were enrolled. Stratified block randomization was used to randomly assign patients 1:1 to receive sevoflurane (1.0-1.5 MAC) or propofol (2.0-3.0 mg/kg/h) for anesthesia maintenance. The primary outcome was the incidence of cognitive dysfunction assessed by four cognitive tests before, as well as 7-14 days after surgery. Patients were randomly assigned to receive sevoflurane anesthesia (n = 144) or propofol-based total intravenous anesthesia (n = 145). The incidence of postoperative cognitive dysfunction in the sevoflurane anesthesia group (31.9%) was significantly lower than that in the total intravenous anesthesia group (43.4%; relative risk 0.61, 95% confidence interval [CI]: 0.38-0.97, p = 0.044). There was no difference in the incidence of delirium between patients receiving sevoflurane and total intravenous anesthesia (27.8% [35/144] vs. 25.9% [35/145], 1.10, 95% CI: 0.64 to 1.90, p = 0.736). There was a significant difference in the Katz Index on day 3 after surgery (3 [0.9) vs. 3 (1.0], 0.095, 95% CI: 0.05 to 0.43, p = 0.012). No difference was observed in other outcomes between the two groups. For patients undergoing on-pump valve replacement surgery, sevoflurane anesthesia had a smaller effect on cognitive function and independence in daily life activities compared with propofol anesthesia.

[A clinical analysis of morning blood pressure surge in middle and old aged male hypertensive patients].

OBJECTIVE: To investigate the morning blood pressure surge (MBPS) and its relationship with 24-hour blood pressure variability and anti-hypertensive drugs in middle-aged and elderly hypertensive patients. METHODS: A total of 521 middle-age and elderly men were surveyed with ambulatory blood pressure monitoring and ambulatory electrocardiograms recordings as well as questionnaire investigation from January 2009 to December 2010. Subjects were divided into MBPS positive group and MBPS negative group according to the level of MBPS [> 35 mm Hg (1 mm Hg = 0.133 kPa) or ≤ 35 mm Hg]. RESULTS: In all the cases, the prevalence of MBPS was 19.4%, of which the elderly and very elderly had higher prevalences (18.9% and 21.8%, respectively) than the middle-aged (5.6%, both P < 0.01). Significant differences could be found in age[(81.6 ± 6.4) years vs (78.7 ± 9.7) years], day mean systolic blood pressure [(132.8 ± 13.3) mm Hg vs (128.8 ± 13.3) mm Hg], fasting blood glucose [(5.96 ± 1.59) mmol/L vs (5.68 ± 1.22) mmol/L] and 24-hour blood pressure variability between the two groups (all P < 0.05). Significant difference could be observed in the prevalence of MBPS between the diuretics-taking group and non-taking group (27.4% vs 17.6%, P < 0.05). CONCLUSIONS: The elderly hypertensive patients are prone to appear MBPS phenomenon. Fasting blood glucose level, 24-hour blood pressure variability may be associated with MBPS. Diuretic antihypertensive treatment may not be conductive for MBPS control.

Advances in Diagnostic Imaging of Hepatopulmonary Syndrome.

Hepatopulmonary syndrome (HPS) is a serious pulmonary complication of progressive liver disease that leads to a poor clinical prognosis. Patients with HPS may develop acute respiratory failure, which requires intensive care and therapy. At present, the only effective treatment is liver transplantation; therefore, early diagnosis and timely treatment are of considerable significance. The three main features of HPS are liver disease, oxygenation disorder, and intrapulmonary vascular dilatation (IPVD). Diagnosing HPS is challenging due to the difficulty in detecting the presence or absence of IPVD. As such, imaging examination is very important for detecting IPVD. This paper reviews the imaging methods for diagnosing HPS such as ultrasound, dynamic pulmonary perfusion imaging, pulmonary angiography, and computed tomography.

Comparison of Murraya exotica and Murraya paniculata by fingerprint analysis coupled with chemometrics and network pharmacology methods.

There are two source plants for the traditional Chinese medicine Murrayae Folium et Cacumen (MFC) in Chinese Pharmacopoeia, i.e. Murraya exotica L. and M. paniculata (L.) Jack. Herein, a chemical comparison of M. exotica and M. paniculata by high performance liquid chromatography (HPLC) fingerprint analysis coupled with chemometrics and network pharmacology was performed. The main peaks in the fingerprints were identified by liquid chromatography coupled with ion trap/time-of-flight mass spectrometry (LC-IT-TOF-MS) and authenticated by references. The chemometrics results showed that the HPLC fingerprints of these two species were clearly divided into two categories using hierarchical cluster analysis (HCA) and principal component analysis (PCA), and a total of 13 significantly differentiated markers were screened out by orthogonal partial least squares-discriminant analysis (OPLS-DA). However, the following network pharmacology analysis showed that these discriminated markers were found to act via many common targets and metabolic pathways, indicating the possibly similar pharmacological effects and mechanisms for M. exotica and M. paniculata. The above results provide valuable evidence for the equivalent use of these two plants in clinical settings. Moreover, the chromatographic fingerprint analysis coupled with chemometrics and network pharmacology supplies an efficient approach for the comparative analysis of multi-source TCMs like MFC.

[Value of Doppler echocardiography derived myocardial energy expenditure measurements in chronic heart failure patients].

OBJECTIVE: To evaluate the relationship between myocardial energy expenditure (MEE) level and cardiac function in chronic heart failure (CHF) patients. METHODS: A total of 99 CHF patients were divided into 3 groups according to the LVEF (HFNEF > or = 50%, n = 37; HFREF1 35.1% - 49.9%, n = 30; HFREF2 < or = 35%, n = 32) or the New York Heart Association (NYHA II, n = 26; III, n = 42; IV, n = 31) criteria. Thirty patients with cardiovascular disease and without CHF served as controls. Routine examinations including serum CRP (ELISA) and plasma NT-proBNP (chemiluminescence sandwich ELISA) were made on the next morning after admission; echocardiography was performed on the third day after admission. LVMW, LVMWI, RWT, LVIDd, LA, LV, LVEF, LVFS, E/A, EDT, IVRT, Tei index and MEE were measured or calculated. RESULTS: MEE was significantly higher in HFREF patients than in controls (P < 0.01) and similar between HFNEF patients and controls (P > 0.05). MEE increased in proportion to decrease of LVEF and increase of NYHA grades in CHF patients (all P < 0.05). Bivariate analysis confirmed that MEE was significant correlated with LVMW, LVMWI, RWT, LVIDd, LA, LV, LVEF (r = -0.540, P < 0.01), LVFS (r = -0.454, P < 0.01), E/A, EDT, IVRT, Tei index, NYHA grades, CRP and NT-proBNP. CONCLUSION: MEE derived from standard echocardiographic measurements is an effective indicator for myocardial bioenergetics and significantly correlated with cardiac function in CHF patients, especially in CHF patients with reduced LVEF.

Allosteric regulation of protein 14-3-3ζ scaffold by small-molecule editing modulates histone H3 post-translational modifications.

Background: Histone post-translational modifications (PTMs) are involved in various biological processes such as transcriptional activation, chromosome packaging, and DNA repair. Previous studies mainly focused on PTMs by directly targeting histone-modifying enzymes such as HDACs and HATs. Methods and Results: In this study, we discovered a previously unexplored regulation mechanism for histone PTMs by targeting transcription regulation factor 14-3-3ζ. Mechanistic studies revealed 14-3-3ζ dimerization as a key prerequisite, which could be dynamically induced via an allosteric effect. The selective inhibition of 14-3-3ζ dimer interaction with histone H3 modulated histone H3 PTMs by exposing specific modification sites including acetylation, trimethylation, and phosphorylation, and reprogrammed gene transcription profiles for autophagy-lysosome function and endoplasmic reticulum stress. Conclusion: Our findings demonstrate the feasibility of editing histone PTM patterns by targeting transcription regulation factor 14-3-3ζ, and provide a distinctive PTM editing strategy which differs from current histone modification approaches.

Pharmacokinetics study of 16 representative components from Baoyuan Decoction in rat plasma by LC-MS/MS with a large-volume direct injection method.

BACKGROUND: Baoyuan decoction (BYD), a well-known traditional Chinese medicine (TCM) formula, is clinically used for the treatment of aplastic anemia, chronic renal failure, coronary heart disease, etc. PURPOSE: The purpose of this study was to develop a large-volume direct injection liquid chromatography-mass spectrometry (LC-MS) method for simultaneous determination of 16 representative flavonoids and saponins in rat plasma after oral administration of BYD. METHODS: The rat plasma sample was injected directly into a pre-column, which was eluted firstly by 0.05% formic acid in water. Then, the accumulated components were eluted from the pre-column and transferred into a Waters BEH C18 column with acetonitrile and water system (contain 0.05% formic acid) as the mobile phase at a rate of 0.3 ml/min. The detection was accomplished in a negative mode using the schedule multiple-reaction monitoring (sMRM). RESULTS: The correlation coefficients for calibration curves were all higher than 0.9920 for formononetin, ononin, calycosin, liquiritigenin, isoliquiritigenin, glycyrrhizic acid, glycyrrhetinic acid, liquiritin, isoliquiritin, liquiritin apioside, isoliquiritin apioside, ginsenoside Rb1, ginsenoside Re, ginsenoside Rd, ginsenoside Rg1 and astragaloside. The intra- and inter-day precisions (RSD) and accuracy (RE) for the investigated components were in the range of -10.9 to 13.7%. The average recoveries were in the range of 75.7-108.6%. This method was successfully applied to investigate the pharmacokinetics of 16 compounds of BYD in rats. The absorption and elimination rates of the representative saponins were significantly slower than most of the targeted-flavonoids after oral administration of BYD in rats. CONCLUSION: The results demonstrated that the large-volume direct injection LC-MS method provided a rapid and efficient approach for multi-components pharmacokinetics of TCM.

CRISPR/Cas9­mediated hypoxia inducible factor­1α knockout enhances the antitumor effect of transarterial embolization in hepatocellular carcinoma.

Transarterial embolization (TAE) is a palliative option commonly used for the treatment of advanced, unresectable hepatocellular carcinoma (HCC). However, patient prognosis in regards to overall survival has not improved with this method, mainly due to hypoxia­inducible factor­1α (HIF­1α)­induced angiogenesis and invasiveness. Thus, it is hypothesized that HIF­1α may be an ideal knockout target for the treatment of HCC in combination with TAE. Thus, in the present study, HIF­1α knockout was conducted in human liver cancer SMMC­7721 cells and a xenograft HCC model was established using a lentivirus­mediated CRISPR/Cas system (LV­Cas) with small guide RNA­721 (LV­H721). Furthermore, hepatic artery ligation (HAL) was used to mimic human transarterial chemoembolization in mice. The results revealed that HIF­1α was highly expressed in both HCC patient tissues and SMMC­7721­induced tumor tissues. The HIF­1α knockout in SMMC­7721 cells significantly suppressed cell invasiveness and migration, and induced cell apoptosis under CoCl2­mimicking hypoxic conditions. Compared with the control groups, HAL + LV­H721 inhibited SMMC­7721 tumor growth in orthotopic HCC and markedly prolonged the survival of HCC­bearing mice, which was accompanied by a lower CD31 expression (tumor angiogenesis) and increased apoptosis in the tumor cells. These findings demonstrated a valuable antitumor synergism in combining CRISPR/Cas9­mediated HIF­1α knockout with TAE in mice and highlighted the possibility that HIF­1α may be an effective therapeutic knockout target in combination with TAE for HCC treatment.

Effects of Baoyuan decoction, a traditional Chinese medicine formula, on the activities and mRNA expression of seven CYP isozymes in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Baoyuan decoction (BYD), a traditional Chinese medicine (TCM) formula, is composed of four herbs and widely used with western drugs to treat coronary heart disease, aplastic anemia and chronic renal failure in clinic. However, no study of the effect of BYD on the cytochrome P450 (CYP) activities has been reported. AIM OF THE STUDY: The purpose of the present study was to evaluate the potential influences of BYD on the activities of seven CYP isozymes (CYP1A2, 2B6, 2C9, 2C19, 2D6, 2E1, and 3A4) in rats. MATERIALS AND METHODS: A sensitive and selective UPLC-MS/MS method for simultaneous determination of seven probe drugs and internal standard (IS) in rat plasma was developed and validated. The influence of BYD on the activities of CYP isozymes and mRNA expression levels were carried out by comparing plasma pharmacokinetics and real-time reverse transcription-polymerase chain reaction (RT-PCR) of probe drugs between control and BYD treatment groups respectively. RESULTS: The calibration curve were linear, with correlation coefficient (r) > 0.99 for seven probe drugs. The intra and inter-assay accuracy and precision of the method were within ±â€¯14.9% and the recoveries ranged from 83.2% to 106.1%. Compared with control group, BYD at low (1.46 g/kg) and high (7.30 g/kg) dosages could significantly increase Cmax and AUC0-t of chlorzoxazone and testosterone, while decrease AUC0-t of phenacetin at high dosage and increase AUC0-t of tolbutamide and metoprolol. Additionally, BYD had increased AUC0-t of bupropion at low dosage and decreased it at high dosage. The mRNA expression results were in accordance with those of pharmacokinetic. CONCLUSION: BYD exhibited inhibitory effects on CYP2C9, CYP2E1, and CYP3A4. Moreover, BYD had induction effects on CYP1A2, and CYP2D6 activities. However, no significant change in CYP2C19 activity was observed. It would be useful for the safe and effective usage of BYD in clinic.

Prognostic significance of urothelial carcinoma with divergent differentiation in upper urinary tract after radical nephroureterectomy without metastatic diseases: A retrospective cohort study.

To evaluate the impact of urothelial carcinoma with divergent differentiation (UCDD) on the prognosis of patients for primary upper urinary tract urothelial carcinoma (UTUC) with pN0/x status treated with radical nephroureterectomy (RNU) and to evaluate the prognostic value of UCDD in different tumor locations (renal pelvis and ureter).Data from a total of 346 patients with UTUC who received RNU between January 2012 and March 2016 in the institution were retrospectively analyzed. Clinicopathological features and prognostic factors age, sex, complaint, height, weight, blood pressure, tumor grade, stage, smoking status, history of adjuvant chemotherapy, tumor location, history of bladder cancer, tumor necrosis, degree of hydronephrosis, tumor size, tumor focality, and preoperative anemia were compared between patients with pure UTUC and patients with UCDD. The endpoints were cancer-specific survival (CSS), overall survival (OS), and intraluminal recurrence-free survival (IRFS).Overall, divergent differentiation was present in 50 patients (14.5%). UCDD was related to different tumor location (P = .01), smoking (P = .04), higher body mass index (P = .02), and advanced tumor grade (P = .01). By Kaplan-Meier analysis, UCDD was found to be significantly correlated with worse IRFS, CSS, and OS (all P < .01). Multivariate analysis demonstrated that UCDD was an independent predictor of IRFS (P < .01), CSS (P = .01), and OS (P = .01). However, 40 patients died for various reasons and the 5-year OS rates were 91.9% in UCDD- group and 68.0% in UCDD+ group, respectively. In patients with ureteral tumors, UCDD was the significant predictor for IRFS, CSS, and OS. However, the prognostic value of UCDD was not observed in pyelocaliceal tumors.The presence of divergent differentiation is associated with inferior survival. UCDD may identify patients at high risks for poor prognosis especially in patients with ureteral tumors. As a result, more attention and follow-up should be given to patients with ureteric urothelial carcinoma.

Effect of terbutaline on alveolar liquid clearance after oleic acid-induced lung injury in rats.

OBJECTIVE: To investigate whether terbutaline affects alveolar liquid clearance after oleic acid-induced lung injury in rats. METHODS: Forty healthy Wistar rats (weighing 250-280 g) were randomly divided into five groups (n=8 in each group): the normal control group (control group), oleic acid injury group (injury group), terbutaline-treated group (terbutaline group), terbutaline plus amiloride-treated group (terbutaline+amiloride group) and terbutaline plus ouabain-treated group (terbutaline+ouabain group). Acute lung injury model was induced by intravenous oleic acid (0.25 ml/kg body weight). 24 hours later, 1.5 microCi (125) I-labeled 5% albumin solution (5 ml/kg body weight) was dripped into the lungs through trachea. The alveolar liquid clearance rate, extravascular lung water content, and arterial blood gas were measured 1 hour thereafter. RESULTS: At 24 hours after infusion of oleic acid, the rats developed pulmonary edema and severe hypoxemia, with the alveolar liquid clearance rate decreased by 49.2% and the extravascular lung water content elevated by 47.9%. Compared with the rats in the injury group, terbutaline (10(-4) mol/L) significantly increased the alveolar liquid clearance rate, decreased the extravascular lung water content and improved hypoxemia. The effect of terbutaline was partly blocked by amiloride and ouabain, which were inhibitors of sodium transport. Terbutaline increased the alveolar liquid clearance rate by 63.7%, and amiloride and ouabain reduced the alveolar liquid clearance rate by 54.7% and 56.8%, respectively. CONCLUSIONS: Terbutaline can accelerate alveolar liquid clearance through increasing sodium transport to attenuate pulmonary edema, thus improving gas exchange, which may have therapeutical effect on pulmonary edema after acute lung injury.

Diurnal brooding behavior of long-tailed tits (Aegithalos caudatus glaucogularis).

Brooding is a major breeding investment of parental birds during the early nestling stage, and has important effects on the development and survival of nestlings. Investigating brooding behavior can help to understand avian breeding investment strategies. From January to June in 2013 and 2014, we studied the brooding behaviors of long-tailed tits (Aegithalos caudatus glaucogularis) in Dongzhai National Nature Reserve, Henan Province, China. We analyzed the relationships between parental diurnal brooding duration and nestling age, brood size, temperature, relative breeding season, time of day and nestling frequencies during brooding duration. Results showed that female and male long-tailed tit parents had different breeding investment strategies during the early nestling stage. Female parents bore most of the brooding investment, while male parents performed most of the nestling feedings. In addition, helpers were not found to brood nestlings at the two cooperative breeding nests. Parental brooding duration was significantly associated with the food delivered to nestlings (F=86.10, df=1, 193.94, P<0.001), and was longer when the nestlings received more food. We found that parental brooding duration declined significantly as nestlings aged (F=5.99, df=1, 50.13, P=0.018). When nestlings were six days old, daytime parental brooding almost ceased, implying that longtailed tit nestlings might be able to maintain their own body temperature by this age. In addition, brooding duration was affected by both brood size (F=12.74, df=1, 32.08, P=0.001) and temperature (F=5.83, df=1, 39.59, P=0.021), with it being shorter in larger broods and when ambient temperature was higher.