Objective To investigate the role of mitochondrial permeability transition pore (mPTP) in attenuation of myocardial ischemia-reperfusion (I/R) injury by delayed preconditioning with sevoflurane in rats.Methods Eighty male SD rats, weighing 250-300 g, were randomly assigned into 5 groups ( n = 16 each): Ⅰsham operation group (group S), Ⅱ group I/R, Ⅲ sevoflurane delayed preconditioning group (group SP), Ⅳ the mPTP opener atractyloside + sevoflurane delayed preconditioning group (group A + SP), and Ⅴ atractyloside group (group A). Myocardial I/R was induced by ligation of anterior descending branch of left coronary artery for 30 min followed by 120 min of reperfusion in group I/R, SP, A + SP and A. In group SP and A + SP, 2.5%sevoflurane was inhaled for 1 h, while pure oxygen was inhaled for 1 h in the other groups, and then myocardial ischemia was performed 24 h later. In group A + SP and A, atractyloside 5 mg/kg was injected intravenously via caudal vein 15 min before ischemia. Blood samples were taken from carotid arteries for detection of serum cardiac troponin-Ⅰ (cTnI) concentrations at the end of reperfusion. Then the rats were sacrificed and hearts removed. The myocardial infarct size (IS) and expression of Bcl-2 and Bax in the myocardium were determined. Myocardial ultrastructure was examined with the electron microscope. Results Serum cTnI concentrations and Bax expression were significantly higher, the myocardial IS was significantly larger and Bcl-2 expression was significantly lower in the other groups than in group S ( P ＜ 0.05). Serum cTnI concentrations and Bax expression were significantly lower, the myocardial IS was significantly smaller and Bcl-2 expression was significantly higher in group SP than in group I/R ( P ＜ 0.05). Microscopic examination showed less damage in group SP than in group I/R. The protection provided by sevoflurane preconditioning was abolished by atractyloside. Conclusion Inhibition of mPTP opening can result in an up-regulation of Bcl-2 expression and down-regulation of Bax expression, which plays a role in attenuation of myocardial I/R injury by delayed preconditioning with sevoflurane in rats.

OBJECTIVE: To determine the effect of Gingkgo biloba leaf extract (EGb761) induced delayed preconditioning on cytochrome c oxidase (CcO) expression during myocardial ischemia-reperfusion in rats. METHODS: Four groups (10 in each) of Sprague-Dawley male rats were studied. In the sham group, the rats received no treatment. Rats in the ischemia-reperfusion (IR) group were treated with NS (1.0 mL/kg intravenously) 24 h before ischemia. Rats in the M group were treated with EGb761 (100 mg/kg intravenously) 24 h before the ischemia. In the D group , EGb761-treated rats that received the 5-hydroxydecanoate (5-HD), an inhibitor of mitochondrial KATP channels 15 min before the ischemia. The IR, M, and D groups were subjected to ischemia by 30 min of coronary artery occlusion before 2 h of reperfusion. At the end of the reperfusion, myocardial infarct size was measured. CcO was measured by Western blot. The myocardial ultrastructure was observed under the electron microscope. RESULTS: The infarct size was significantly smaller in the M group [(23.78 ± 4.82)%] than in the I/R group [(37.87 ± 5.92)%] (P<0.05). The CcO protein expression in the myocardium was significantly higher in the M group than in the I/R group(P<0.05). Microscopic examination showed less myocardial damage in the M group than that in the I/R group. The infarct size, CcO protein expression, and myocardial damage had no significant difference between the D group and the I/R group (P>0.05). CONCLUSION EGb761 induced delayed preconditioning attenuates myocardial ischemia-reperfusion injury possibly through up-regulating CcO expression in rats.
Animals ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Electron Transport Complex IV ; metabolism ; Ginkgo biloba ; chemistry ; Ischemic Postconditioning ; methods ; Ischemic Preconditioning, Myocardial ; methods ; Male ; Myocardial Ischemia ; physiopathology ; Myocardial Reperfusion Injury ; metabolism ; prevention & control ; Phytotherapy ; Plant Leaves ; chemistry ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo study the effects of beta-amyloid peptide (Abeta) on cell membrane lipids and cholinergic receptors of human neuroblastoma cells.

METHODSHuman SH-SY5Y neuroblastoma cells were treated with different concentrations of Abeta(1-42) with and without pretreatment of vitamin E. MTT [3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide] reduction, lipid peroxidation, protein oxidation and phospholipids were measured by spectrophotometry. Levels of cholesterol and unbiquinone were determined by high-performance liquid chromatography (HPLC). The numbers of cholinergic receptor binding sites were determined by receptor binding assay and the protein levels of nicotinic receptor alpha3 and alpha7 subunits were studied by Western blotting.

RESULTSSH-SY5Y cells showed decreased reduction rates of MMT and phospholipids, and increased lipid peroxidation and protein oxidation after exposure to Abeta (0.1 micromol/L) as compared to the control. The number of cholinergic receptor binding sites, the protein level of nicotinic receptor alpha3 and alpha7 subunits and the content of ubiquinone decreased in cells treated with high dose of Abeta (1 micromol/L). Although the level of cholesterol was not changed in any way, vitamin E partially prevented the neurotoxic effects of Abeta.

CONCLUSIONbeta-amyloid peptide reduces the level of cell membrane lipids and cholinergic receptors in human SH-SY5Y neuroblastoma cells, likely through the induction of an enhanced oxidative stress.

Amyloid beta-Peptides ; administration & dosage ; metabolism ; toxicity ; Cell Line, Tumor ; Cell Membrane ; metabolism ; Cholesterol ; metabolism ; Dose-Response Relationship, Drug ; Humans ; Lipid Peroxidation ; drug effects ; Malondialdehyde ; metabolism ; Membrane Lipids ; metabolism ; Neuroblastoma ; metabolism ; pathology ; Oxidative Stress ; drug effects ; Peptide Fragments ; administration & dosage ; metabolism ; toxicity ; Phospholipids ; metabolism ; Receptors, Nicotinic ; metabolism ; Ubiquinone ; metabolism ; Vitamin E ; metabolism ; pharmacology

In the treatment of aortic arch dissections involving left subclavian artery (LSA), a double stent implantation is sometimes required to treat the disease of each branch. In this study, aortic arch and LSA were modeled by using Pro/engineer wildfire3. 0. Two deployed stents were inserted in the aortic arch and LSA. There are 3 kinds of model according to the stent struts protruding into the inlet of the collateral branch, and the healthy aortic arch model without any stent was provided as a reference case. We used computational fluid dynamics (CFD) to investigate the flows in the model stents and focused on the changes of blood speed and wall shear stress caused by the implanted stents of different models. The results showed that the stent strcuts protruding into the inlet of LSA induced the conspicuous decrease of blood speed and the emergence of large-scale low shear stress,which would cause thrombogenesis, neointimal hyperplasia and result in in-stent restenosis, so it would be judicious to use dedicated bifurcated stents for treatment of bifurcation lesions.
Aneurysm, Dissecting ; physiopathology ; surgery ; Aorta ; physiopathology ; Aortic Aneurysm ; physiopathology ; surgery ; Hemodynamics ; Humans ; Prosthesis Implantation ; methods ; Shear Strength ; Stents ; Stress, Mechanical ; Subclavian Artery ; surgery

OBJECTIVETo study the possible immunological mechanism of wheezing attack in children with cytomegalovirus (CMV) infection.

METHODSA total of 25 under-5-year-old children with wheezing following CMV infection were enrolled. The expression of serum regulatory T cells (Treg)/T helper 17 (Th17) cytokines interleukin (IL)-10, IL-6, and IL-17, and peripheral blood lymphocyte subsets were determined. Twenty age-matched healthy children were selected as the control group.

RESULTSThe wheezing group had a significantly reduced serum IL-10 level, significantly increased IL-6 and IL-17 levels, significantly reduced levels of natural killer cells, and significantly increased levels of CD8+ T cells and CD19+ B cells, as compared with the control group.

CONCLUSIONSWheezing children with CMV infection have Treg/Th17 imbalance and cellular immune dysfunction, which may be an important immunological mechanism of the development of wheezing in children after CMV infection.

Child, Preschool ; Cytokines ; blood ; Cytomegalovirus Infections ; immunology ; Female ; Humans ; Infant ; Male ; Respiratory Sounds ; etiology ; immunology ; T-Lymphocytes, Regulatory ; immunology ; Th17 Cells ; immunology

Objective To investigate the effect of fibronectin type Ⅲ and SPRY domain containing 1 (FSD1) protein on the invasion of glioma stem cells (GSCs), so as to probe into the new biomarkers or potential therapeutic targets for gliomas. Methods The Cancer Genome Altas (TCGA) database data were used to analyze and compare the FSD1 gene expression (the FSD1 mRNA level) in the glioblatoma (also known as glioblastoma multiforme, GBM) and normal brain tissues as well as in the different grade glioma tissues, and the correlation of the FDS1 gene expression (mRNA level) with the survival prognosis of patients was also analyzed using the TCGA database data. The lentivirus was used to overexpress the FSD1 protein in the GSCs, T4121 and D456. The effect of the overexpressed FSD1 protein on the invasive ability of the GSCs, T4121 and D456 was evaluated by Transwell invasion assay. Results The FSD1 gene expression (mRNA level) was significantly lower in GBM than in normal brain (P＜0.01). The FSD1 gene expression (the mRNA level) in gliomas significantly decreased with the increase of the gliomas grade (gradeⅡvs Ⅲ, P＜0.05;gradeⅢvs Ⅳ, P＜0.01). The survival prognosis of patients with gilomas was well associated with the level of FSD1 gene expression (the FSD1 mRNA level), as indicated by the overall survival rate of the patients, which was significantly lower in the patients with the low FSD1 mRNA level than in the patients with the high FSD1 mRNA level (P＜0.01). In the Transwell invasion assay, the count of the invasive cell numbers significantly decreased in the FSD1 protein-overexpressed T421 and D456 groups than in the corresponding control group (P＜0.01 in both T4121 and D456 cell lines). Conclusion There is a clinical relevance of the FSD1 expression for the malignant progression of gliomas (the grade of gliomas). The low level FSD1 is favorable for keeping the invasive ability in GSCs.

The safety of Chinese patent medicine has become a focus of social. It is necessary to carry out work on post-marketing clinical safety evaluation for Chinese patent medicine. However, there have no criterions to guide the related research, it is urgent to set up a model and method to guide the practice for related research. According to a series of clinical research, we put forward some views, which contained clear and definite the objective and content of clinical safety evaluation, the work flow should be determined, make a list of items for safety evaluation project, and put forward the three level classification of risk control. We set up a model of post-marketing clinical safety evaluation for Chinese patent medicine. Based this model, the list of items can be used for ranking medicine risks, and then take steps for different risks, aims to lower the app:ds:risksrisk level. At last, the medicine can be managed by five steps in sequence. The five steps are, collect risk signal, risk recognition, risk assessment, risk management, and aftereffect assessment. We hope to provide new ideas for the future research.
Clinical Trials as Topic ; Drug-Related Side Effects and Adverse Reactions ; epidemiology ; etiology ; Drugs, Chinese Herbal ; adverse effects ; chemistry ; economics ; therapeutic use ; Herbal Medicine ; economics ; legislation & jurisprudence ; Humans ; Patents as Topic ; Product Surveillance, Postmarketing ; Quality Control

OBJECTIVE: To develop the visual uroflow scale (VUS), analyze the relationship of VUS score and index of free uroflowmetry, assess urination function preliminarily and improve the work efficiency in the clinic. METHODS: Male lower urinary tract symptoms (LUTS) patients, who attended the Department of Urology in Peking University People's Hospital from March 2016 to March 2017, were assessed for their urination function according to the Visual Uroflow Scale without help from clinicians before undertaking a free uroflowmetry test. And afterwards, a free uroflowmetry was undertaken, and variables including maximal flow rate (Qmax), the average flow rate (Qave) and voiding volume (VV) was obtained. During the study, 124 cases were collected and 53 cases met the inclusion and exclusion criteria and were included in the study cohort. The Spearman correlation analysis was used for analyzing the correlation of VUS scores with free uroflowmetry variables and age. The validity of VUS was evaluated. RESULTS: Most of the patients could choose the very figure matched with self-condition by first instinct without any help from the clinician. The data were analyzed by Spearman correlation analysis. In the present study, voiding time was positively correlated with the VUS score (correlation coefficient, 0.62, P < 0.05). In the present cohort, the patients chose the third and fourth figures to take longer time to urinate, implying worse LUTS situation. Flow time and VUS scores were positively correlated (correlation coefficient, 0.61, P < 0.05). The patients with higher VUS scores would spend more time on urinate, no matter how long urinary hesitation was. Both Qmax and Qave were negatively correlated with the VUS score (correlation coefficient －0.54, －0.62, P < 0.05). The study illustrated that the VUS score suggested that the Qmax basically and further reflected the urination function. And its relationship to age revealed the decreased urination function of aging male, which had reached a consensus. CONCLUSION Development of VUS has helped the clinician assess the urination function preliminarily at the first time. Patients are assessed for a VUS score before getting surgery or receiving the drug for treatment, and can be re-assessed after. The VUS score can provide an objective quantitative basis to evaluate the treatment efficacy. In addition, considering that it is convenient, timesaving and easy to understand, the VUS is available for follow-up.
Cohort Studies ; Humans ; Lower Urinary Tract Symptoms ; Male ; Urination ; Urodynamics

Complete healing of the intestinal mucosa is the most ideal goal in the treatment of inflammatory bowel disease (IBD). The intestinal mucosa healing not only significantly alters the course of the disease and relieves clinical symptoms, but also markedly reduces the occurrence of complications and prevents recurrence of IBD. As chronic inflammation associated with peptic ulcer damage is the main pathological feature of IBD, clinical treatment is mainly based on anti-inflammatory therapy, but such therapy cannot promote the healing of the intestinal mucosa of patients. Therefore, how to achieve long-term remission of IBD is still an urgent challenge. In the process of intestinal mucosal repair, the polarization of macrophages maintains the homeostasis of the intestinal microenvironment, which is a representative process that promotes mucosal inflammatory-repair. It is a key part of initiating tissue regeneration that should not be underestimated. In this paper, we reviewed the literature of the past decade, focusing on the promotion of intestinal mucosal healing in IBD. The discussion will highlight the importance and feasibility of regulating macrophages to promote intestinal mucosal repair. Following this thought, we discuss the shortcomings of current clinical treatments and summarize the relevant drugs which have potential to promote intestinal mucosal repair. The aim is to provide effective potential drugs and therapeutic targets for the treatment of IBD.

[Objective]To ascertain the drug resistance for pulmonary tuberculosis in Taizhou City, and to provide basis for tuberculosis prevention and control strategy. [Methods] The sputum samples were collected form 267 smear positive pulmonary tuberculosis patients who registered in a drug susceptibility testing (DST) monitoring site in Taizhou City form 2015 to 2017. Then with culture, identification of Mycobacterium and DST for 9 anti-tuberculosis drugs [isoniazid (INH) , rifampicin (RFP) , ethambutanol (EMB) , streptomycin (SM) , kanamycin (KAM) , ofloxacin (OFX) , crinkledmycin (CPM) , promethylamine (PTO) and para amino salicylate (PAS) ] by using proportion method performed on all sputum specimens. [Results]Of the 267 smear positive cases, 220 were cultured with 190 culture positive (17 were identified as nontuberculous mycobacterial infections) , 28 culture negative, and 2contaminated. Among 160 cases with the result of DST to 9 drugs, the overall drug resistance rate was22.5％. The overall drug resistance rates were 21.4％ and 33.3％ in the newly diagnosed patients and retreated patients respectively. There was no significant difference between the two groups (P>0.05). The multidrug resistance rate was 3.1％, and had a significant difference between the new and retreated patients (0.7％ vs. 26.7％, P<0.01). Drug resistances rates of the 9 drugs ranged from high to low as:INH (8.1％) , PTO (8.1％) , SM (6.9％) , RFP (6.3％) , OFX (2.5％) , PAS (2.5％) , EMB (2.5％) , CPM (2.5％) and KAM (2.5％). There was no gender difference found in drug resistance rates (P> 0.05). Neither was there age difference (P> 0.05). [Conclusion] The epidemic of drugresistant of tuberculosis in Taizhou City are still high, especially that of acquired multi-drug resistance of tuberculosis. We must continue to improve the "three-in-one"management model, improve the quality of clinical diagnosis and treatment, and strengthen community medication management.