Using a UPLC-MS/MS (MRM) and cocktail probe substrates method, the metabolic fingerprint of the compatibility of Radix Aconite (RA) and Radix Paeoniae Alba (RPA) and its effect on CYP450 enzymes were investigated. These main CYP isoforms include CYP 1A2, CYP 2C, CYP 2E1, CYP 2D and CYP 3A. Compared with the inhibition effect of RA decoctions on CYP450 isoforms, their co-decoctions of RA and RPA with different proportions can decrease RA' inhibition on CYP3A, CYP2D, CYP2C and CYP1A2, but can not reduce RA' effect on CYP2E1. The metabolic fingerprints of RA decoction and co-decoctions with different proportions of RPA in CYP450 of rat liver were analyzed by UPLC-MS. Compared with the metabolic fingerprints of RA decoction, the intensity of diester-diterpenoid aconitum alkaloids decreased significantly, while the intensity of monoester-diterpenoid alkaloids significantly increased in the metabolic fingerprints of co-decoctions of RA and RPA. The results suggest that RA coadministration with RPA increased the degradation of toxic alkaloid and show the effect of toxicity reducing and efficacy enhancing.

New-onset refractory status epilepticus is a rare and special clinical manifestation with high mortality. About half of the patients have no clear cause. At present, the pathogenesis is unclear, and the treatment plan is controversial. In recent years, it has been found that inflammatory and immune responses of the body may be involved in the pathogenic process, and it is called “inflammatory-immune mediated epileptic encephalopathy” based on the perspective of pathogenesis. There have also been many treatment attempts based on the inflammatory and immunological mechanisms, some of which have achieved satisfactory results. However, most of them are based on the review of small sample cases, and relevant guidelines are still lacking at present. In this paper, the definition, etiology, pathogenesis, clinical manifestations and treatment of persistent status of new-onset refractory status epilepticus are reviewed.

Objective To investigate the effect of bilateral limb function training on the rehabilitation of stroke patients with hemiplegia.Methods According to the random digit table,64 patients were divided into experiment group and control group,32 in each group.The control group was given lateral limb function training and the experiment group bilateral function training for one month. The two groups were compared in terms of the motor function of upper and lower extremities and the activity of daily living. Result In terms of the motor function of the lower extremities and the activity of daily living,the experiment group was superior to the control group(P<0.001).Conclusion The function training of bilateral limbs can promote the function rehabilitation of extremities of stroke patients with hemiplegia and improve the activities of daily living.

Objective To determine the prevalence of antibodies to cyclic citrullinated peptides (antiCCP) in patients with juvenile-onset systemic lupus erythematosus (JSLE) and its potential clinical significance. Methods Anti-CCP was measured in sera from patients with JSLE (n=47), juvenile idiopathic arthritis (JIA, n=54) and the sera from age-matched healthy children (n=40) using the third generation of anti-CCP ELISA commercial kit. The association of anti-CCP with other laboratory parameters and clinical features, especially arthritic symptoms in JSLE was also analyzed. T-test, Mann-Whitney U test, Chi-square and Fisher's exact test were used for statistical analysis. Results Out of the 47 JSLE patients, 6 (13%) were anti-CCP positive, which was significantly higher than that of the healthy controls( 13% vs 0, P＜0.05 ), but not different from that of the JIA group (26%, P=0.098). RF was more prevalent in JSLE patients with anti-CCP than patients without (83% vs 15%, P＜0.01 ), but there was no difference in other laboratory parameters and the clinical features ineluding the occurrence of arthritis (67% vs 51%, P＞0.05). As one of the initial symptoms, arthritis was observed in 25 of 47 JSLE patients and no one had developed deforming arthropathy.There was no statistical difference in anti-CCP positivity between JSLE patients with and without articular involvement ( 16% vs 9%, P＞0.05 ). Anti-CCP was not detected in any of the 3 patients with JSLE who had experienced joint pain and limited activity during 3 years follow-up. Conclusion Anti-CCP could be detected in patients with JSLE. It is noteworthy when differentiate from juvenile idiopathic arthritis, but the presence of anti-CCP does not relate with the occurrence of arthritis at presentation and persistence of arthritis in JSLE.

Immunohistochemistry was used to detect the protein expression of Snail in 5 specimens jusxta-eancerous normal breast tissues, 35 specimens of cancerous tissues without metastasis and 20 specimens of breast carcinoma with lymphonode metastasis. Breast carcinoma cell line MDA-MB-231 was transfected with antisense Snail. Results showed that the expression of Snail protein was significantly higher in breast carcinomas than in their normal tissues. The mRNA and protein expressions of Snail in the breast carcinoma cells treated with antisense Snail was significantly decreased while the E-cadherin protein significantly increased (both P < 0.05). The number of invasive ceils treated with antisense Snail was (10.5±1.3)%, while in treated with EGFP was (68.2±2.1)% (P < 0.05). The abnormal expression of Snail contribute to the invasiveness of breast carcinoma. The antisense Snail could prevent the cells ability to invade in vitro, and the effect is related with the up-regulated E-cadherin protein.

OBJECTIVE To study the antidepressant effects of ammoxetine(AMX)and the underlying mechanisms. METHODS Two behavioral despair models,the tail suspension test (TST) and the forced swimming test(FST),were used to evaluate the antidepressant-like effects of AMX 2.5-20 mg · kg-1 following oral administration. Monoamine neurotransmitter p-chloro-phenylalanine(p-CPA)andα-methyl-p-tyrosine(AMPT) depletion models in mice were used to investigate the effects of AMX on levels of 5-serotomin(5-HT)and norepinephrine(NE)in the brain. RESULLTS The results of behavioral study showed that compared with normal control group,AMX(10 and 20 mg · kg-1)reduced the immobility time of mice by 51.4% and 80.7% in the TST(P<0.05,P<0.01) or by 48.0% and 66.2% in the FST (P<0.05),respectively. Locomotion activity test indicated that AMX did not increase or decrease the movement distance of mice,demonstrating that AMX had no excitatory or inhibitory actions on the central nervous system. Moreover,AMX(5,10 and 20 mg·kg-1)exerted antidepressant effects in the p-CPA induced 5-HT depletion model and AMPT induced NE depletion model,as evidenced by the significantly reduced immobility time,ie,63.9%,93.4%,90.5% and 61.9%,77.2%,100% reduction in the TST (P<0.01),respectively,and AMX at the dose of 20 mg·kg-1 significantly increased the concentrations of 5-HT and NE by 144.7% and 57.2% in the mouse brain(P<0.05) ,respectively. CONCLUSION AMX has strong antidepressant-like effects in behavioral despair models and monoamine neurotransmitter depletion models in mice,which is involved in the increased levels of 5-HT and NE in the brain.

[ ABSTRACT] AIM: To explore whether autophagy is involved in the excessive death of renal tubular epithelial cells in subtotal nephrectomy ( SNx) rats and the relationship between autophagy and necroptosis in the kidney of SNx rats. METHODS:Male Sprague-Dawley rats were randomly assigned to control group ( n=6 ) and SNx group ( n=42 ) .The rats in SNx group were subjected to SNx.Sham surgery was performed in the rats in control group.The rats in SNx group were divided into subgroups at 0, 4, 8 and 12 weeks ( n=6) and the other rats in SNx group were divided into SNx+vehi-cle group, SNx+necrostatin-1 (Nec-1) group and SNx+3-methyladenine (3-MA) group.The expression of RIP1, RIP3, LC3 and beclin-1 at mRNA and protein levels was measured at 0, 4, 8 and 12 weeks by qPCR and immunohistochemistry. The effects of Nec-1 or 3-MA on the protein expression of LC3-I, LC3-II and beclin-1, and production of reactive oxygen species ( ROS) in the rat kidney were determined by Western blot and DCFH-DA staining.The death of renal tubular epi-thelial cells in the SNx rats was observed by TUNEL staining and electron microscopy.Finally, the effects of Nec-1 and 3-MA on blood urea nitrogen ( BUN) , serum creatinine ( SCr) and the pathological changes of the renal tissues were ana-lyzed.RESULTS:The highest mRNA and protein levels of RIP1, RIP3, LC3 and beclin-1 appeared at the 8th week after SNx (P<0.01).Compared with the rats in SNx+vehicle group, the protein over-expression of LC3-II/I and beclin-1, re-nal tubular epithelial cells with typical morphological features of necroptotic cell death and TUNEL-positive renal tubular
cells were decreased in the SNx rats treated with Nec-1 and 3-MA (P<0.01), but 3-MA did not reduce the increased con-centration of ROS.In addition, treatment with Nec-1 and 3-MA obviously reduced BUN, SCr (P<0.05), glomeruloscle-rosis index and tubulointerstitial injury score (P<0.01).CONCLUSION:Autophagy participates in the excessive death of renal tubular epithelial cells in SNx rats.Inhibition of autograph prevents necroptotic cell death of renal tubular cells, and alleviates chronic renal injury in SNx rats.

Aim To investigate the effects of dopamine(DA)on insulin secretion from rat islets and the possible mechanism.Methods Pancreatic islets were obtained from the pancreatic of male SD rats by collagenase P digestion and histopaque-1077 density gradient separation.Insulin secretion experiment was used to observe the change of insulin release after DA treatments.As to study the potential mechanisms of the effects of DA,patch-clamp experiment and calcuim image technique were applied to test the depolarization-evoked Ca2+ currents,action potential duration and intracellular Ca2+ concentration.Results In 2.8 mmol·L-1 glucose,DA had no effect on insulin secretion;in 16.7 mmol·L-1 glucose,dopamine inhibited insulin secretion in a dose-dependent manner.DA inhibited the inward calcium current,shorten the action potential duration,and reduced the intracellular Ca2+ concentration.Conclusion DA inhibits insulin secretion maybe by decreasing the inward calcium current leading to shorten the action potential duration and reduce the intracellular Ca2+ concentration.

Objective To divide computed tomography (CT) values into different ranges and investigate the influence of CT value division on dose calculation, and to propose a method to combine magnetic resonance imaging (MRI) with assigned CT values.Methods Ten CT images each were collected from patients with head and neck, chest, and pelvic tumors.Random sampling was performed for the CT values of main tissues or organs at the three parts, and then the mean CT value of each tissue or organ was calculated to divide the CT values into different ranges.A virtual phantom was built in the Varian Eclipse treatment planning system, and for the prescribed dose of 100 cGy, the machine output was recorded at different CT values.The influence of different CT value ranges on dose calculation was analyzed.The treatment plans of intensity-modulated radiotherapy were selected from 5 cervical cancer patients, and new CT values were assigned to the planning target volume (PTV) and organs at risk to obtain new CT images.The plans were transferred to the new CT images and compared with the results on the original CT images in terms of dosimetric parameters.Results After dividing the CT values into different ranges and verifying the results in dose calculation, the CT values corresponding to different human tissues or organs were-100 to 100 HU.The influence of CT value variation on dose calculation was within 3%.In the same treatment plan, there were small differences in dosimetric parameters between new CT images and original CT images.Dmax, Dmean, D98%, D95%, D5%, and D2% of PTV were all below 3%, and Dmax and Dmean of the bladder, rectum, small intestine, femoral head, and bone marrow were below 2%.Conclusions The influence of CT value division on dose calculation in the treatment planning for pelvic tumors is acceptable, so it can be used in combination with MRI.

Objective: To investigate the prevalence and risk factors of dyslipidemia among residents in Haining City, Zhejiang Province, so as to provide into the management of dyslipidemia. Methods: Totally 1 953 residents at ages of 15 to 69 years were recruited using a multi-stage stratified cluster sampling method in 5 townships (streets) of Hainan City. Subjects' demographic features, smoking status, alcohol consumption, family history of diseases and development of chronic diseases were collected. The height, body weight, waist circumstance and blood pressure were measured, and the fasting blood glucose, serum uric acid and blood lipid levels were determined. The prevalence of dyslipidemia was analyzed and standardized by the 7th population census data. The factors affecting dyslipidemia were identified using a multivariable logistic regression model. Results: Totally 1 893 valid questionnaires were recovered. The respondents included 949 males (50.13%) and 944 females (49.87%), and had a mean age of (47.90±14.34) years. A total of 513 participants were detected with dyslipidemia, and the prevalence and standardized prevalence of dyslipidemia were 27.10% and 27.01%, respectively. The prevalence of hypertriglyceridemia, hypercholesterolemia, hyperlipoproteinemia and hypolipoproteinemia was 16.53%, 3.22%, 1.74% and 15.27%, respectively. Multivariate logistic regression analysis showed that male (OR=1.571, 95%CI: 1.268-1.947), family history of stroke (OR=1.645, 95%CI: 1.192-2.270), hyperuricemia (OR=1.809, 95%CI: 1.370-2.388), central obesity (OR=1.423, 95%CI: 1.066-1.900), obesity (OR=1.736, 95%CI: 1.335-2.257), underweight (OR=0.171, 95%CI: 0.049-0.593) significantly correlated with dyslipidemia. Conclusions The prevalence of dyslipidemia is lower than the national level among residents at ages of 15 to 69 years in Haining City, and hypertriglyceridemia and hypolipoproteinemia are predominant types of dyslipidemia. Male, obesity, family history of stroke and hyperuricemia are risk factors of dyslipidemia.