Epilepsy is a common nervous system disease,with a morbidity of 4.8‰-11.2‰,so there has been about 50 million patients globally.Drug treatment is a major mean to treat epileptic patients.Recently,researches illustrated that cellular immunity disorder and humoral immunity disorder were coexist in epleptic patients,but there was no consensus on whether it was induced by anti-epileptic drugs(AEDs) or epilepsy itself up to now.This article is aimed to explain the impact of AEDs on immunity through review recent literature internal and abroad.

OBJECTIVE:To systematically review the efficacy of cetuximab combined with chemotherapeutics versus chemo-therapeutics alone in the treatment of metastatic colorectal cancer,and provide evidenced-based reference for clinical treatment. METHODS:Retrieved from Medline,PubMed,EMBase,CJFD,VIP,WanFang database and Cochrane Library,randomized con-trolled trials(RCT)about the efficacy of cetuximab combined with chemotherapeutics(test group)versus chemotherapeutics alone (control group) in the treatment of colorectal cancer were collected. Meta-analysis was performed by using Rev Man 5.2 software after data extract and quality assessment. RESULTS:A total of 12 RCTs were included,involving 8 514 patients. Results of Me-ta-analysis showed progression free survival in test group was significantly longer than control group,the difference was statistical-ly significant [HR=0.87,95%CI(0.79,0.95),P=0.002];compared with control group,there were no significant differences in the disease control rate[OR=1.06,95%CI(0.88,1.27),P=0.54] and overall survival[HR=0.92,95%CI(0.85,1.00),P=0.05] in test group. Results of subgroup analysis showed cetuximeb could significantly prolong the progression free survival of KRAS wild-type patients,the difference was statistically significant[HR=0.80,95%CI(0.66,0.98),P=0.03]. CONCLUSIONS:Compared with che-motherapeutics alone,chemotherapeutics combined with cetuximab can significantly prolong the progression free survival of pa-tients with metastatic colorectal cancer. Due to the limits of quality and sample size,more strict designed,long-term follow-up of large scale RCTs are needed for the further verification of the conclusion.

Objective To investigate relationship between utrophin and dystrophin in muscle of patients suffered from several neurological muscular diseases.Methods Muscle biopsies of 26 cases of patients suffered from 8 categories neurological muscular diseases and 2 cases of control were analysed for utrophin and dystrophin by immunofluorescence experiments.Results In a majority of Duchenne muscular dystrophy (DMD) patients,their sarcolemma revealed absent,weak or discontinuous fluorescence for dystrophin.In non-DMD muscular dystrophies,lipid storage myopathy,myotonic dystrophy,inflammatory myopathies, neurogenic amyotrophy, polymyositis, mitochondrial encephalomyopathy, myogenic amyotrophy,immunofluorescence reactivity for dystrophin were strongly exhibited in entire sarcolemma.In normal biopsy sample,strong immunofluorescence reactivity for dystrophin was identified in entire sarcolemma,while weak and discontinuous fluorescence was identified on a minority of sarcolemma of DMD patients with severely reduced dystrophin.There was no immunofluorescence reactivity for utrophin in sarcolemma of DMD patients with moderate decreased dystrophin,non-DMD muscular dystrophies and other 6 categories of neurological muscular diseases,nor in sarcolemma of normal biopsies.Conclusions utrophin is expressed in sarcolemma of DMD patients,who have severely reduced dystrophin simultaneously. utrophin is absent in sarcolemma of other categories of neurological muscular diseases including non-DMD muscular dystrophies with normal dystrophin expression and DMD patients with moderately decreased dystrophin.

ObjectiveTo observe production of vascular endothelial growth factor (VEGF) induced by granulocyte/macrophage colony-stimulating factor (GMCSF)via ERK nerve growth factor (NF)-κB singling pathway in human fibroblasts during wound healing and explore relating mechanism.MethodsHuman fibroblasts from the injured skin were used for this study and treated with GMCSF.RT-PCR was used for analyzing the protein and mRNA levels of VEGF and Western blotting was employed to determine the phosphorylation of ERK. The fibroblasts were pre-treated with ERK specific inhibitor PD98059 and further treated with GMCSF, then the fibroblasts and the supernatant were collected for detection of protein level of VEGF by means of Western blot. ERK signal pathway was inhibited to detect the activation of NF-κB by means of immunofluorescence staining. Furthermore, the nuclear and cytoplasmic extraction kit was used to separate the cytoplasm and nucleus and Western blot employed for observation of the NF-κB activation. ResultsThe mRNA level and protein level of VEGF were increased significantly with treatment with higher concentration of GMCSF in a dose-dependent manner. VEGF mRNA level was increased two hours after administration with GMCSF and reached peak at 4-6 hours. GMCSF could remarkably activate the ERK phosphorylation. Compared with GMCSF, the ERK specific inhibitor PD98059inhibited significantly the effect of GMCSF in inducing VEGF expression (P ＜ 0.05). Western blot and immunofluorescence staining analyses showed that the activation of NF-ΚB was inhibited with reduced production of VEGF after GMCSF treatment.Conclusion GMCSF up-regulates production of VEGF through activating NF-κB via ERK signal pathway in the human fibroblasts.

ObjectiveTo develop a new sutureless technique (photochemical tissue bonding,PTB ) for repair of corneal perforation. Methods A total of 60 rabbits were used for creating corneal perforation models.The corneal perforation on the left eye was repaired by sutures and the injury on the right eye was fixed with the use of amniotic membrane with PTB.The outcomes of the two mentioned repair methods were compared by observing the leakage of aqueous and the morphology of the anterior chamber at different instants,measuring the intraocular pressure (IOP) and observing the formation of neo-vessels and scars of cornea in the use of histological analysis. Results There was no leakage of aqueous and no difference for morphology evaluation in both treatments.PTB could adhere AM on the cornea to restore the corneal perforation.The peak IOP in the PTB treatment group at days 0,7 and 14 postoperative [ (531.2 ±49.5) mm Hg,(542.6 ±74.8) mm Hg and (603.9 ±69.1) mm Hg,respectively] was significantly higher than that in the suture group at the same instants [ (41.3 ±12.7) mm Hg,(142.6 ±25.4) mm Hg and (333.3 ± 66.7) mm Hg,respectively] (P ＜0.O1 ).Compared with suture repair,the treatment with PTB resulted in a better outcome of wound healing with less neo-vessels and less scars of cornea. Conclusion PTB treatment for repair of corneal perforation is superior to suture repair.

Objective To establish a stable animal model for sequentially dynamic and direct monitoring of the skin wound infection. Methods The mice with full-thickness skin incisions were replicated. After immediate subcutaneous suture,the mice were randomly divided into four groups,ie,Group A was inoculated with 50 μl sterile PBS solution),Groups B,C and D were inoculated with 50 μl suspension containing 1 × 106,1 × 108 and 1 × 1010 colony forming unit (CFU)/ml bioluminescent methicillin-resistant staphylococcus aureus (MRSA) respectively.Then,the diet behavior of each group was observed and the mean weight and mortality of each group were also recorded at different time points.The bioluminescent intensity of fluoresce in the wounds was recorded at different time points by using the charge-coupled device (CCD) based imaging system.Local wound tissues were incised at 24 hours after inoculation for HE staining so as to observe wound inflammatory reaction in each group.Wound healing time of each group was also recorded. Results ( 1 ) Average weight:Groups A and B showed unobvious changes in weight; Group C lightened until day 3 after inoculation and then recovered gradually to the preinoculation level at day 14; Group D lightened gradually until death.(2)Mortality:Groups A and B had no death; Group C had 10％ deaths at day 14; Group D had 100％ deaths.(3) Bioluminescent intensity of wounds:Groups A and B showed a gradual weakened luminescence since the day of inoculation and had almost complete disappearance at days 5 and 7 respectively; there was no sign of obvious increase or decrease in Group C from the day of inoculation till day 14 ; Group D had a gradual increase since the day of inoculation and the luminous area expanded until the death.(4) HE staining at 24 hours after inoculation:all the four groups showed inflammatory cell infiltration,especially in Groups C and D.(5) Wound healing time:wound healed at days 5 and 7 after inoculation in Groups A and B; the wounds showed no healing even at day 14 in the Group C,but the wounds length and area did not show obvious enlargement or diminishment ; the wounds extended gradually until the death in the Group D,since the day of inoculation. Conclusions The inoculation of 50 μl suspension with 1 × 108 CFU/ml bioluminescent MRSA to full-thickness skin incision rats allows direct,real-time dynamic and continuous detection of the occurrence and development of the wound infections.The infection model is easy to make and has stability and high repeatability.

OBJECTIVETo determine the expression of Skp2 in different prostate cancer (PCa) cell lines and tissues, and explore its influence on the androgen receptor (AR) signaling pathway and development of castration-resistant prostate cancer (CRPC).

METHODSThe expression levels of Skp2 and AR in different PCa cell lines were detected by Western blot. After knockdown of Skp2 in the C4-2 and 22RV1 cells transfected with shRNA, the expressions of AR and P27 were determined and the activity of ARR3-Luc measured by dual-luciferase reporter gene assay following treatment with dihydrotestosterone (DHT). The expressions of AR and Skp2 in human naïve PCa or CRPC specimens were detected by immunohistochemical staining followed by analysis of their differences and correlation.

RESULTSThe Skp2 protein expression level was significantly higher in the C4-2 or 22RV1 cells than in the LNCaP cells. DHT treatment increased the expression of Skp2 in the C4-2 cells, but knock-down of Skp2 significantly up-regulated the expression of the well-known downstream protein P27 and down-regulated that of AR. Consistently, DHT treatment increased the activity of ARR3-Luc, while knockdown of Skp2 remarkably decreased it in the C4-2 and 22RV1 cells (P < 0.05). In addition, significantly higher expressions of Skp2 and AR were observed in the CRPC than in the naïve specimens (P < 0.05), with a positive correlation between the two proteins (r = 0.658 1, P < 0.05).

CONCLUSIONSkp2 can enhance the expression and transcription activity of the AR protein in CRPC cells or tissues and is promising to be a critical molecular therapeutic target.

Androgens ; pharmacology ; Cell Line, Tumor ; Dihydrotestosterone ; pharmacology ; Disease Progression ; Gene Knockdown Techniques ; Humans ; Male ; Neoplasm Proteins ; genetics ; metabolism ; Prostatic Neoplasms, Castration-Resistant ; metabolism ; Receptors, Androgen ; genetics ; metabolism ; S-Phase Kinase-Associated Proteins ; physiology ; Transcriptional Activation ; Up-Regulation

To establish a method for the determination of astilbin, peoniflorin, rasmarinci acid, isofraxidin and liquiritin contained in Shaolin Xiaoyin tablets, in order to lay a foundation for designing late-stage dosage forms and clinical medication schemes. In this paper, efforts were made to establish a method for the determination of the blood concentration of the five components and study the in vivo pharmacokinetics in rats. The blood concentration was determined by HPLC. Phenomenex C18 column (4.6 mm x 250 mm, 5 microm) was adopted and eluted with methanol-acetonitrile-0.05% formic acid, the flow rate was 0.8 mL x min(-1), and the wavelength was 275 nm. The samples were processed by the solid phase extraction method. After oral administration of Shaoling Xiaoyin tablets, the rat bloods were collected at different time points to determine the blood concentrations. The experimental results showed that the baseline separation could be adopted for the five components, and astilbin, peoniflorin, rasmarinci acid, isofraxidin and liquiritin showed good linear relations within ranges of 2.48-248, 0.213 6-21.36, 0.531-53.1, 0.704-70.4, 0.253-25.3 mg x L(-1). All the five components could be absorbed in blood and excreted quickly. The method established in this paper is rapid and accurate, and could be used for in vivo analysis on preparations containing similar components. The main components in Shaoling Xiaoyin tablets could be absorbed and excreted quickly, and thus suitable to be made into sustained release tablets. Common preparations are required to be taken for 4-6 times a day.
Administration, Oral ; Animals ; Chromatography, High Pressure Liquid ; Cinnamates ; blood ; pharmacokinetics ; Coumarins ; administration & dosage ; blood ; pharmacokinetics ; Depsides ; blood ; pharmacokinetics ; Drugs, Chinese Herbal ; analysis ; pharmacokinetics ; Flavanones ; administration & dosage ; blood ; pharmacokinetics ; Flavonols ; administration & dosage ; blood ; pharmacokinetics ; Glucosides ; administration & dosage ; blood ; pharmacokinetics ; Male ; Monoterpenes ; administration & dosage ; blood ; pharmacokinetics ; Rats ; Rats, Sprague-Dawley

Objective To explore sub-clinical items in evaluating the prognosis of epileptic patients,the study on differences of regional cerebral blood flow (rCBF) in both effective treated and incomplete-controlled patients with idiopathic generalized tonic clonic seizure (GTCS) was carried out.Methods Interictal rCBF measurements using 99m Tc-ethyl cysteinates dimmer (ECD) SPECT was performed on 29 effective treated idiopathic GTCS patients and 12 incomplete controlled idiopathic GTCS patients. The rCBF distribution was semi-quantitatively analyzed by regions of interest (ROIs) comparing with abnormal rate of interictal hypoperfusion rCBF,clinical seizure time and EEG.Results ROI analysis showed that rCBF decreased in basal ganglia and thalamus of incomplete controlled patients with idiopathic GTCS compared to that of effective treated ones′ significantly ( P

Objective To explore the relative factors of unstable plaques of carotid atherosclerosis in ischemic eerebrovascular patients.Methods Carotid arteries of a total of 132 cases with ischemic cerebrovascular disease of carotid artery system were inspected by color Doppler ultrasound.The plaques discovered were classified according to ultrasonic appearance and their stability was judged.The relation between hypertension,diabetes,hyperlipemia, smoking and unstable plaques of carotid atheroselerosis was analyzed.Results The most common site of plaque for- mation was the bifurcate of the common carotid artery(56.99%),and the second commonest was carotid artery (23.12%).The incidence of unstable plaques in the patients with smoking,hypertension and diabetes was higher than those without them(P