AIMTo investigate the role and mechanism of mitochondrial calcium uniporter (MCU) in myocardial hypoxia/reoxygenation injury.

METHODSIsolated rat hearts were perfused with Langendorff apparatus. The hypoxia/reoxygenation injury was achieved by ligation of left anterior coronary artery for 30 min followed by release of ligation for 120 min. The left ventricular developed pressure (LVDP), the maximum rise/fall rate of left ventricular pressure (+/- dP/dt(max)), and the left ventricular end-diastolic pressure (LVEDP) were recorded. Activities of lactate dehydrogenase (LDH) in coronary effluent and reactive oxygen species (ROS) of myocardial mitochondria were spectrophotometrically assayed. Infarct size was determined by TTC staining method.

RESULTSCompared with the hypoxia/reoxygenation (H/R) group, ruthenium red (RR, 5 micromol/L), given at the on set of reoxygenation, significantly improved the contractile function of left ventricle, decreased the myocardial infarct size, alleviated the production of ROS in myocardial mitochondria and LDH release in coronary effluent. Spermine (20 micromol/L), given at the onset of reoxygenation, enhanced the production of ROS in the mitochondria and LDH release in coronary effluent at 5, 20 and 30 min of reoxygenation, however, there were no significant differences of ventricular contractile parameters and infarct size between groups subjected to hypoxia/reoxygenation with or without spermine treatment. Co-treatment of ROS scavenger N-2-mercaptopropionyl glycine (1 mmol/L) with spermine abolished the effect of spermine.

CONCLUSIONInhibition of mitochondrial calcium uniporter may refrain heart from hypoxia/reoxygenation injury via decreasing the production of ROS in heart mitochondria.

Animals ; Calcium Channels ; metabolism ; Cell Hypoxia ; In Vitro Techniques ; Male ; Mitochondria, Heart ; metabolism ; Myocardial Ischemia ; metabolism ; Rats ; Rats, Sprague-Dawley ; Reactive Oxygen Species ; metabolism

In order to identify the chemical constituents of Yushu tablets comprehensively, we studied the chemical constituents of CHCl3 extract from Yushu tablets by the ultra performance liquid chromatography-electrospray ionization-ion trap-time of flight mass spectrometry (UPLC-ESI-IT-TOF/MS). It showed that there were more than 100 compounds separated, and forty-nine peaks among these were identified on the basis of high resolution mass spectrometry data and literature data reported. Determination of twelve peaks was further confirmed by standard substances. These components assigned to the different plant sources mainly included phenylpropanoids, triterpenoids, quinones and m-trihydroxybenzene compounds. By analyzing the chemical components of CHCl3 extract from compound Chinese medicine Yushu tablets comprehensively, this study provided the foundation for studying chemical components, pharmacodynamic substance and quality control of Yushu tablets.
Chromatography, High Pressure Liquid ; Chromatography, Liquid ; Drugs, Chinese Herbal ; analysis ; Spectrometry, Mass, Electrospray Ionization ; Tablets ; Tandem Mass Spectrometry

To compare the pharmacokinetics of syringin, eleutheroside E and isofraxidin after intravenous administration of each monomer and Ciwujia injection. Twenty-four Sprague-Dawley rats were randomly divided into four groups and intravenously administrated with syringin, eleutheroside E, isofraxidin, and Ciwujia injection, respectively. The concentrations of the three components in rat plasma were determined by LC-MS/MS. DAS 2.0 software was applied to calculate the pharmacokinetic parameters while the SPSS 17.0 software was used for statistical analysis. Significant difference (P < 0.05) was found between each monomer and the injection on the main pharmacokinetic parameters such as AUC, CL and t1,/2. Compared with the injection, the group treated with the syringin has obvious decrease in AUC, and increase in CL while the group treated with eleutheroside E has obvious increase in AUC, and decrease in CL The t1/2 of isofraxidin was prolonged in Ciwujia injection. Pharmacokinetic characters of the ingredients in the injection varied greatly from the monomer. Other constituents in the injection may have an impact on the pharmacokinetic profiles of these three components.
Administration, Intravenous ; Animals ; Coumarins ; administration & dosage ; blood ; pharmacokinetics ; Drugs, Chinese Herbal ; administration & dosage ; pharmacokinetics ; Glucosides ; administration & dosage ; blood ; pharmacokinetics ; Lignans ; administration & dosage ; blood ; pharmacokinetics ; Male ; Phenylpropionates ; administration & dosage ; blood ; pharmacokinetics ; Rats ; Rats, Sprague-Dawley

To establish a method for the determination of cucurbitacin in plasma samples, in order to study the in vivo pharmacokinetic characteristics of cucurbitacin in rats. Rats were intravenously injected with cucurbitacin. With diphenhydramine as the internal standard (IS), the plasma concentrations of cucurbitacin in rat plasma at different time points were determined by liquid chromatography tandem mass spectrometry (LC-MS/MS). With electrospray ionization source, the positive ion detection in the multiple reaction monitoring mode was conducted to determine the ion-pairs for target compound and IS were m/z 503.2/113.1 and m/z 256.0/167.2, respectively. Agilent ZOBAX SB-C18 column (2.1 mm x 50 mm, 1.8 microm) was adopted and eluted with methanol and 0.1% formic acid (55:45), and the flow rate was 0.2 mL x min(-1). DAS 2.0 software was applied to fit the blood concentration and calculate corresponding pharmacokinetic parameters. The rats were intravenously injected with cucurbitacin at the concentration of 3.0 mg x kg(-1). The target blood quality concentration show good linear relations within the range of 10.5-3 150 microg x L(-1) (R2 = 0.996), the lower limit of the standard curve was 10.5 microg x L(-1), and the signal to noise ratio S/N = 12. Intra- and inter-day precisions RSD was less than 6.9% and 14%, respectively; The accuracy RE ranged between 0.20% and 3.7%; The extraction recoveries ranged between 92.7% and 97.1%. Regarding the pharmacokinetic parameters of tail intravenous injection of cucurbitacin, AUC (0-t) was (811.615 +/- 111.578) microg x h x L(-1), (t1/2) was (1.285 +/- 1.390) h, CL was (3.627 +/- 0.487) L x h x kg(-1), and V(d) was (6.721 +/- 7.429) L x kg(-1). In this study, researchers established a simple, accurate, sensitive and highly specific method for determining the blood concentration of cucurbitacin, and reported the in vivo pharmacokinetic characteristics of cucurbitacin in rats for the first time.
Administration, Oral ; Animals ; Cucurbitaceae ; chemistry ; Cucurbitacins ; administration & dosage ; blood ; pharmacokinetics ; Drugs, Chinese Herbal ; administration & dosage ; pharmacokinetics ; Male ; Rats ; Rats, Wistar

Objective To observe the motions of the rectum and bladder by image?guided radiotherapy ( IGRT) and to analyze their impact on treatment. Methods Eighteen patients with prostate cancer undergoing intensity?modulated radiotherapy ( IMRT) were enrolled in the study and 247 cone?beam computed tomography ( CBCT) images were obtained from this study. The clinical target volume, bladder, and rectum were contoured on all simulated CT and CBCT to examine their volume and position changes. The dose distributions were recalculated based on the data of the x?, y?, and z?axis setup errors. The doses to planning target volume ( PTV) and organs at risk were calculated in the replanning, and their impact on treatment was analyzed. Comparison of the planning and replanning results was made by paired t?test. The effects of displacements and volumes of the bladder and rectum on target doses were analyzed by Pearson correlation method. Results Great changes in the volumes of the bladder and rectum were observed during the treatment. For the planning and replanning results, PTVD95% was 7777. 37 cGy vs. 7628. 56 cGy ( P=0. 027), PTV Dmin was 87. 91 cGy vs. 83. 35 cGy (P=0. 000), and RVP was 5. 89% vs. 8. 31%(P=0. 000). There were correlations between PTVD95% and the motions of the bladder and rectum, with correlation coefficients of 0. 296 and 0. 177, respectively. The correlation coefficient between rectal volume and PTVD95% was 0. 115, indicating a certain correlation. There is a certain correlation between and PTV Dmin and bladder volume, with a correlation coefficient of?0. 128. Conclusions The recovery of the state during localization for the bladder and rectum, especially the latter, has great significance to ensure the target dose and reduce exposure of the rectum in the IMRT for prostate cancer.

Objective To analyze the data from intensity-modulated radiotherapy ( IMRT) for prostate cancer guided by kilovoltage cone-beam computed tomography (CBCT), and to provide a clinical basis for selecting the optimal image registration method and reasonable target volume margins.Methods A total of 16 patients with prostate cancer who received radical IMRT were enrolled, and CBCT for online position verification was performed 214 times.The images were obtained after conventional skin marking and laser alignment, and automatic registration, bone registration, soft tissue registration, and manual registration were performed for CBCT images and planned CT images.The differences between these four registration methods were evaluated, and the margins for extending clinical target volume into planning target volume (PTV) were calculated.Results The setup errors in left-right, anterior-posterior, and cranial-caudal directions for automatic registration, bone registration, soft tissue registration, and manual registration were-0.6±2.8 mm/-0.6±4.5 mm/-0.6±3.8 mm,-0.7±2.7 mm/-0.9±4.5 mm/-0.8±4.1 mm,-0.8± 2.6 mm/-0.3±4.4 mm/-1.1±4.0 mm, and-0.6±2.9 mm/-0.7±5.1 mm/-0.9±3.9 mm, respectively. There were no significant differences between the four registration methods.The margins for extension in the left-right, anterior-posterior, and cranial-caudal directions were calculated as 4.7 mm, 5.2 mm, and 6.5 mm, respectively.Conclusions With a comprehensive consideration of various factors, a default setting of automatic registration and manual fine adjustment is appropriate for CBCT-guided radiotherapy for prostate cancer.The margins for extension in the left-right, anterior-posterior, and cranial-caudal directions are 4.7 mm, 5.2 mm, and 6.5 mm, respectively.

Objective To investigate the effects of different stimulation of electroacupuncture on the protein expressions of SOCS1 and SOCS3 in rabbits with acute facial nerve injury; To determine the better stimulation. Methods New Zealand rabbits were treated with special hemostatic forceps for 5 min, and the length of the lesion was about 2.5 cm. The model of facial nerve injury was induced. The experiment was divided into blank group, sham-operation group, model group, and electoracupuncture weak-, medium-, and strong-stimulation group. The model group received no intervention after surgery. After treatment, the damaged facial nerve of each group was intercepted. The protein expressions of SOCS1 and SOCS3 mediated by negative feedback regulation of JAK-STAT were detected by ABC-ELISA. Results Compared with the blank group, the protein expressions of SOCS1 and SOCS3 in the model group increased (P<0.01). Compared with the model group, the protein expressions of SOCS1 and SOCS3 protein in electroacupuncture weak- stimulation group decreased (P<0.01). Conclusion Electroacupuncture can make SOCS1, SOCS3 protein expressions normal for acute facial nerve injury, and acupuncture treatment effect does not increase with the increase of stimulation.

Objective To evaluate the clinical efficacy and toxicity of intensity-modulated radiation therapy (IMRT) following prostatectomy for elderly patients with prostate cancer.Methods Ninety-eight prostate cancer patients receiving IMRT after prostatectomy were included in this study.The median age was 68 years old.The number of patients with low-,middle-and high-risk prostate cancer was 10,21 and 67,respectively.Two patients had oligometastases (pelvic bone metastases).Sixty-four patients were treated with IMRT combined with endocrine therapy.Among them,43 cases received adjuvant volumetric modulated arc therapy (VMAT),and 55 patients received salvage IMRT.The median radiotherapy dose was 72 Gy for the tumor bed.Twenty-nine patients received radiotherapy of the pelvic node region with a median dose of 50 Gy.Results The median follow-up time was 40 months.The 5-year overall survival (OS),biochemical recurrence-free survival (BRFS) and local control (LC) were 90％,76％ and 100％,respectively.The OS (88.8％ vs.90.8％,P=0.94),BRFS (75.9％ vs.71％,P=0.79) or LC (100％ vs.100％,P=0.32) did not significantly differ between the adjuvant and salvage radiotherapy groups,respectively.The incidence of grade Ⅰ-Ⅱ late rectal toxicities was 24.1％,and no ≥ grade 3 late toxicity was observed.The incidence of grade 1-2 late bladder toxicities was 29.9％,and 3.4％ for grade 3.Conclusion IMRT following prostatectomy yields high clinical efficacy and slight late toxicities in elderly patients with prostate cancer.

This article summarized the experience of Professor Xiong Jibai,a national TCM master,in treating pulmonary nodules based on the theory of"body fluids and blood stasis mixing"in Huang Di Nei Jing.Professor Xiong Jibai believes that the basic pathogenesis of pulmonary nodules is that"body fluids and blood stasis mixing"accumulate in lung collaterals,and the fundamental pathological factor is phlegm and blood stasis.Xiong's treatment is based on dissipating phlegm and activating qi,activating blood circulation and resolving masses,paying attention to syndrome differentiation and treatment,examining syndromes and seeking causes,flexibly selecting prescriptions and treating both symptoms and root causes;attaching importance to maintaining healthy qi,preventing both illness and change,and preventing recovery after illness.Clinical medical records were attached to prove the clinical thinking and medication characteristics.