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.

Pulmonary fibrosis is a chronic and progressive lung disease that poses a threat to human health. Current treatment options are limited, highlighting the urgent need for more effective therapeutic strategies. Tetrandrine (TET), a bis-benzylisoquinoline alkaloid extracted from Stephania tetrandra, has been known for its anti-inflammatory and anti-fibrotic effects, but its specific mechanisms remain unclear. This study investigated the anti-fibrotic effects of TET in a chronic model of pulmonary fibrosis, aiming to delineate the molecular mechanisms underlying TET-mediated inhibition of fibroblast activation. The results showed that TET significantly alleviated the pathological changes in a murine model of multiple bleomycin-induced pulmonary fibrosis and effectively inhibited TGF-β1-induced fibroblast activation. Mechanistically, TET predominantly inhibited the TGF-β/SMAD signaling pathway and diminished intracellular reactive oxygen species (ROS) levels. Utilizing CRISPR-Cas9 library screening, we identified that angiotensin II type 1 receptor associated protein (AGTRAP) and membrane palmitoylated protein 6 (MPP6) played important roles in TET's suppressive impact of ROS levels, with the knockout of two genes attenuating TET's antifibrotic activity. All animal treatment procedures were approved according to the Committee on the Ethics of Animal Experiments of the Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences (IMB-20230406D507). This research not only elucidates the pharmacological mechanism of TET but also provides a novel therapeutic avenue for the treatment of pulmonary fibrosis.

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

Objective To evaluate the influence of ultrasound-mediated contrast agent microbubbles carrying kallidinogenase targeted therapy on neurogenesis and angiogenesis after experimental acute cerebral infarction.Methods Kallidinogenase-loaded microbubbles were prepared using mechanical shaking method.Middle cerebral artery occlusion (MCAO) model was established in male Wistar rats by sutureoccluded method.MCAO rats (n =120) were randomly divided into 5 groups:ultrasound-mediated kallidinogenase-loaded microbubbles group (group 1),ultrasound-mediated microbubbles group (group 2),ultrasound-mediated saline group (group 3),kallidinogenase group (group 4),saline group (group 5).Medication was given through tail vein daily for 2-6 consecutive days starting 24 h after MCAO.Ultrasound groups (groups 1,2 and 3) were given 2 MHz pulse ultrasonic irradiation on the ischemia lateral skull for 10 min after injection.Cell proliferation was examined using 5'-bromo-2'-deoxyuridine (BrdU,50 mg/kg).Infarction volume and neurological function were evaluated on the 3rd,7th day after MCAO respectively.Doublecortin (DCX) + cells in the subventricular zone and laminin + in the peri-infarction region were observed at the same time.Results The number of DCX + cells in the subventricular zone (under 20 × ocular) of groups 1-5 was 251.8 ± 13.1,125.7 ± 11.6,130.2 ± 13.7,234.5 ± 12.4 and 123.7 ± 10.0 respectively.The percentage of laminin + cells in the peri-infarction region (× 10 objective) of groups 1-5 was 10.0％ ± 0.8％,5.2％ ± 0.7％,5.0％ ± 1.0％,8.0％ ± 1.8％ and 5.0％ ± 0.9％ respectively.The number of DCX + cells in the subventricular zone and laminin + cells in the peri-infarction region of the group 1 and the group 4 was significantly more on the 7th day after MCAO compared with those of the other three groups (DCX:t values of group 1 vs groups 2,3,5 were 17.88,17.17 and 18.16,all P ＜ 0.01 ; t values of group 4 vs groups 2,3,5 were 15.42,14.78 and 15.70,all P ＜0.01.Laminin:t values of group 1 vs groups 2,3,5 were 7.01,6.71 and 7.11,all P ＜ 0.01 ; t values of group 4 vs groups 2,3,5 were 4.23,3.94 and 4.33,all P ＜0.01).Moreover,the number of DCX+ cells in the subventricular zone (t =2.46,P ＜ 0.05) and laminin + cells in the peri-infarction region (t =2.78,P ＜ 0.05) of the group 1 was much more than those of the group 4.Neurologic scores on the 7th day of groups 1-5 were 1.00 (0.75,1.25),2.0 (2.00,3.00),2.0 (1.00,2.00),1.5 (0.75,2.00),2.0 (2.00,2.50).Compared with other four groups,group 1 showed better functional improvement after stroke (U values of group 1 vs groups 2-5 were 2.0,4.0,7.5 and 2.5,all P ＜ 0.05).While there was no significant difference in infarction volume among five groups at all the time points after MCAO.Conclusions Our study demonstrates ultrasound-mediated kallidinogenase-loaded contrast agent microbubbles targeted therapy promotes neuroblasts proliferation and vascular regeneration compared with mediated and non-medicine-loaded microbubbles therapy,which attributes to functional improvement after MCAO.Therefore,ultrasound-mediated ultrasound contrast agent microbubbles carrying drugs targeted therapy may have a perspective on ischemic stroke.

Background Previous experimental and clinical studies have proved that elevated serum uric acid increased risk for developing hypertension.Whereas,there are a paucity of information on the relationship between serum uric acid and prehypertension.Objective The purpose of this research is to evaluate the association between the serum uric acid and prehypertension.Method A cohort of seven thousand eight hundred thirty-nine subjects without hypertension and other cardiovascular diseases were recruited from a cross sectional study in urban and rural place in 9 provinces during 2005-2006.Based on serum uric acid(324 ?mol/L for overall population,366 ?mol/L for male,285 ?mol/L for female),people were categorized into quartiles.The odds ratio for prehypertension was calculat ed with the lowest quartile as the reference.Results The prevalence of prehypertension increased with increasing uric acid in total population(P324 ?mol/L)to lowest quartile 1(