Female ; Humans ; Methotrexate ; Pregnancy ; Pregnancy, Ectopic

Objective To investigate the effects of different abstinent duration on brain functional network of heroin addicts at resting state.Methods Sixteen heroin addicts during protracted abstinence for 11-13 months (PA12 group) and twenty heroin addicts during protracted abstinence for 5-7 months (PA6 group) were recruited in the resting-state functional MRI study.Graph theoretical methods were applied to construct topological organization of whole brain network and nodes betweenness of the networks in all subjects,and the between-group differences were analyzed.The correlation of the node betweenness with the abstinence duration was conducted.Results There was no significant difference (P＞0.05) in the small world characteristic (γ≈1,λ》1) between two groups.Compared with the PA6 group,the PA12 group demonstrated significantly decreased nodal betweenness in regions of left parahippocampal gyrus,left precentral gyrus,and significantly enhanced nodal betweenness in regions of the left cuneus,left temporal and right middle occipital gyrus (all P＜0.05).Moreover,the betweenness of the left precentral gyrus (r =-0.52,P =0.001) and parahippocampal gyrus (r=-0.49,P=0.002) were negatively related with the abstinence duration,the betweenness of the right middle occipital was positively correlated with the abstinence duration (r=0.49,P=0.003).Conclusion The brain network small world topology of heroin addicts tend to be stable after 5-7 months of abstinence.Long-term abstinence may minimize the addicfs memory of drugs and potential drug seeking behavior,and recover addicts' visual spatial attention function.

Objective To examine the cognitive function in healthy first-degree relatives (FDRs) of patients with bipolar Ⅰ disorder.Methods Cognitive function were studied in one hundred twenty healthy FDRs of patients with bipolar Ⅰ disorder and one hundred normal controls using digital symbol, digital span, visual reproduction, trail making test A (TMT-A) and trail making test B (TMT-B).Results Compared with normal controls, FDRs showed impairment in all indexes of the tests, including digital symbol, digital span (forward, reversed and forward + reversed), visual reproduction, TMT-A and TMT-B (t=-3.44、-4.23、-4.32、-4.98、-2.59、4.32、3.78, respectively, Ps≤0.01).By analysis of covariance (covariant: age and years of education), FDRs were still impaired in these indexes (P<0.05).Compared with sex-matched normal controls, male FDRs showed impairment in all indexes of the tests, but female FDRs only showed impairment in digital span (reversed, forward + reversed), TMT-A and TMT-B (P<0.05).Conclusions Attention, memory and executive function are impaired in healthy first-degree relatives of patients with bipolar Ⅰ disorder.

Objective To investigate the effect of Pingfei Oral Liquid (POL) on the distribution of mast cells (MCs) and the expression of interleukin 6 (IL-6) in the lung tissue of radiation pneumonia rats. MethodsForty-five SD rats were randomized into 3 groups : normal control,model group and POL group. The rat model of radiation lung fibro-sis was set up by a single X-ray dose of 20Gy irradiation over the whole chest of the rats. POL (20 g·kg-1·d-1,once a day, five times a week) was given orally one week before irradiation and the treatment lasted 5 weeks. MCs in the lung tissue were stained with toluidine blue firstly and then were counted 2, 4 and 8 weeks after irradiation. IL-6 protein expression of lung tissue was measured by immunohistochemical assay 8 weeks after irradiation, and mRNA ex-pression was determined with RT-PCR 4 weeks after irradiation. ResultsIt's showed the aggregation of large amount of pulmonary mast cells and increase of IL-6 protein expression 8 weeks after irradiation (P < 0.01).IL-6 mRNA expression in the irradiated lung of rats increased 4 weeks after irradiation (P < 0. 01). POL could reduce the aggrega- tion of MCs (P < 0. 01) and the expression of IL-6 protein (P < 0. 01) and mRNA (P < 0. 05) in the lung tissue. ConclusionPOL can prevent radiation pneumonia in rats by reducing the aggregation of mast cells and inhibiting IL-6 expression in the lung tissue.

Objective To evaluate the relationship between newly developed depression after mild traumatic brain injury (mild-TBI)and abnormality on susceptibility-weighted imaging (SWI).Methods One hundred and eighty patients after mild-TBI,who had normal findings at conventional CT and MRI were enrolled in our study.All cases underwent conventional MRI and SWI.Ac-cording to SWI,the number and volume of microbleed lesions were calculated.All patients were followed up within 1 year after TBI,and divided into depressive group and non-depressive group based on SCID-IV.The difference in microbleed lesions on SWI was compared between the depressive group and non-depressive group.Results The incidence rate of microbleed on SWI in depres-sive group was higher than that in non-depressive group (P < 0.001 ).Among patients with microbleed lesions,the volume and number of lesions in depressive group were more than those in non-depressive group (P <0.001),and these differences were only found at the frontal,parietal and temporal lobes (P < 0.001 ).No significantly difference between depressive and non-depressive group was found in other areas (P >0.05).Conclusion SWI is useful to identify the microbleed lesions after mild TBI.The depres-sion after TBI is correlated with the location and distribution range of microbleed lesions.

Anesthetics, Intravenous ; administration & dosage ; pharmacology ; Animals ; Animals, Newborn ; Cerebral Cortex ; cytology ; metabolism ; Drug Synergism ; Female ; Fentanyl ; administration & dosage ; pharmacology ; Male ; Midazolam ; administration & dosage ; pharmacology ; Neurons ; metabolism ; Patch-Clamp Techniques ; Primary Cell Culture ; Rats ; Rats, Sprague-Dawley ; Voltage-Gated Sodium Channels ; drug effects

To investigate the protective effect of preconditioning with hyperoside ( Hyp) against myocardial ischemia-reperfusion injury (MIRI) in rats and the role of PI3K/Akt signaling pathway. MIRI was established by ligation of left anterior descending coronary artery for 30 min followed by reperfusion for 120 min in rats. Male SD rats were randomly divided into five groups: sham group,model group (MIRI),Hyp preconditioning group(Hyp), Hyp preconditioning + LY294002 (a PI3K/Akt signaling pathway inhibitor) group (Hyp + LY), and LY294002 group (LY). At the end of reperfusion, hemodynamic parameters were recorded as left ventricular systolic pressure (LVSP) , left ventricular end-diastolic pressure ( LVEDP) and maximal rate of increase and decrease of left ventricular pressure (± dP/dt(max)). Myocardial infaret size, the oxidative stress markers, myocardial enzymes indicators and inflammatory factors were also analyzed. The expressions of Akt, p-Akt, Bax and Bcl-2 proteins was detected by using Western blot method. The results showed that Hyp preconditioning remarkably improved cardiac constriction and relaxation function, reduced myocardial infarct size and enhanced the activities of oxidative stress markers about correlated to MIRI, such as superoxide dismutase (SOD), catalase (CAT) and glutathione-peroxidase (GSH-Px) and decreased the contents of malondialdehyde (MDA) as compared with MIRI group. Simultaneouly, the levels of myocardial enzymes, i. e. creatine kinase ( CK) and creatine kinase MB isoenzyme (CK-MB), and inflammatory factors, for instance tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) were decreased. Hyp pretreatment apparently restrained myocardial apoptosis as evidenced by decreasing the level of Bax expression, increasing the levels of phosphorylation of Akt and Bcl-2 expression. These effects were inhibited by LY294002, a blocker of PI3K/Akt signaling pathway. These findings indicated that the cardioprotection of Hyp preconditioning against MIRI may be related to activating PI3K/Akt signaling pathway, upregulating the expression of BCL-2 protein and down-regulating the expression of Bax protein.
Animals ; Creatine Kinase ; genetics ; metabolism ; Drugs, Chinese Herbal ; administration & dosage ; Heart ; drug effects ; Humans ; Interleukin-6 ; genetics ; metabolism ; Ischemic Preconditioning, Myocardial ; Male ; Malondialdehyde ; metabolism ; Myocardial Reperfusion Injury ; drug therapy ; enzymology ; genetics ; prevention & control ; Phosphatidylinositol 3-Kinases ; genetics ; metabolism ; Proto-Oncogene Proteins c-akt ; genetics ; metabolism ; Quercetin ; administration & dosage ; analogs & derivatives ; Rats ; Rats, Sprague-Dawley ; bcl-2-Associated X Protein ; genetics ; metabolism

To investigate the effects and potential mechanisms of hyperoside (Hyp) on the vascular endothelium function in middle cerebral artery (MCA) ex vivo in rats. Isolated arterial segments from MCAs of rats were used for surveying vasomotoricity in a pressurized chamber. Transmembrane potential was recorded by using glass microelectrodes to evaluate hyperpolarization. Hyp (1 x 10(-6)-1 x 10(-4) mol . L-1) was utilized to observe the effect on 1 x 10(-7) mol . L-1 U46619-preconstricted MCA in rats. The results showed that 1 x 10(-6)-1 x 10(-4) mol . L-1 Hyp significantly induced concentration-dependent vasodilatation and hyperpolarization, leading to the maximal diastolic ratio of (73. 2 ± 6. 1)% and maximal changes in membrane potentials of (-13. 2 ± 2. 2) mV. Hyp still elicited vasorelaxation and hyperpolarization by removal of endothelium in MCA of rat, which was notably attenuated as compared with vascular endothelium-intact group (P <0. 01). In the MCAs preconstricted by U46619 (1 x 10(-7) mol . L-1), Hyp (1 x 10(-6)-1 x 10(-4) mol . L-1) produced concentration-dependent vasorelaxation and hyperpolarizition that were partially attenuated by 3 x 10(-5) mol . L-1 L-NAME(a NOS inhibitor) plus 1 x 10(-5) mol . L-1 PGI2 ,(a synthetase inhibitor). The residual effects were further decreased by 1 x 10(-3) mol . L-1 TEA (an inhibitor of Ca2+-activated potassium channel) or 1 x 10(-5) mol . L-1 PPG (a blocker of endogenous H2S synthese-CSE). Similarly, 1 x 10(-5)-1 x 10(-3) mol . L-1 NaHS (a donor of exogenous H2S) or 1 x 10(-5)-1 x 10(-3) mol . L-1 L-Cys (the substrate of endogenous H2S synthesis) obviously evoked dose-dependent vasodilatation and hyperpolarization of MCA in rats. These findings indicated that Hyp may induce endothelium-dependent and endothelium-independent responses. And the endothelium-dependent vasodilatation may be related to the increases of endogenous H2S that has been promoted Hyp in the endotheliocyte of MCAs, and activated Kca and opening of Kca channels, resulting in the hyperpolarization of vascular smooth muscle cell membrane and subsequent reduction of Ca2+ influx and vasodilation.
Animals ; Endothelium, Vascular ; drug effects ; Enzyme Inhibitors ; pharmacology ; Female ; Male ; Middle Cerebral Artery ; Muscle, Smooth, Vascular ; drug effects ; Nitric Oxide ; metabolism ; Potassium Channels ; metabolism ; Quercetin ; analogs & derivatives ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Sulfides ; metabolism ; Vasodilation ; drug effects ; Vasodilator Agents ; pharmacology

Chinese traditional medicine has provided, since ancient times, a basis for health care and medicine to the Chinese nation and for China's national stability. Identification of the constituents responsible for therapeutic and undesired effects of Chinese herbal medicines is a type of key research facilitating the modernization of these medicines. For a complex Chinese herbal medicine, multi-compound pharmacokinetic research is a useful approach to identifying its constituents that are bioavailable (in their unchanged and/or metabolized forms) at loci responsible for the medicine's therapeutic action and to characterizing the compounds' disposition and pharmacokinetics related to the action. In addition, such pharmacokinetic research is also useful for identifying herbal compounds associated with the medicine's adverse effects and drug-drug interaction potential. Over the past decade, great advances have been achieved in the theory, methodology, associated techniques, and their application of such multi-compound pharmacokinetic research, which has become an emerging field in pharmacokinetics. In this perspective, we elaborate on the methodology, technical requirements, and key analytical techniques of multi-compound pharmacokinetic research on Chinese herbal medicines, describe research examples regarding investigation of pharmacokinetics and disposition of a class of bioactive herbal constituents (ginsenosides of Panax notoginseng root) and pharmacokinetics-based identification of potential therapeutic compounds from a dosed Chinese herbal medicine (LianhuaQingwen capsule), and discuss follow-up development for the multi-compound pharmacokinetic research.

50?mol/L induced markedly oncotic cell death,but no apoptosis was observed.TEM examination indicated that a form of cell death accompanied by cellular swelling,organelle swelling and vacuolization,mitochondrial swelling and cristae membrane loss,and nucleus swelling, chromatin scattering or karyolysis,which characterized as oncosis.When treated with 50,200?mol/L of ART for 5 h, the intracellular ROS level of Panc-1 cells markedly increased to 1.60 and 4.49 fold compared with that of untreated cells,respectively.Pretreatment with TCEP effectively attenuated ART-induced intracellular ROS level and decrease the oncosis in Panc-1 cells.Conclusions:ART exerts profound cytotoxic effects on Panc-1 cells and induces an oncosis- like cell death,which is quite different from apoptosis.The cellular generation of ROS and its peroxidation damage may be one of the mechanisms for its anti-tumor effect on pancreatic cancer.