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Objective:To investigate the effects of centromere protein-A (CENP-A) on the invasion and migration of ovarian cancer (OC) cells and explore the related mechanism.Methods:OC cell line A2780 was cultured in vitro, and they were divided into Ng Group (Blank Control Group) , pcDNA group (negative transfection group:PCDNA vector plasmid) , pcDNA-CENP-A group (over-expression Group: pcDNA-CENP-A Vector Plasmid) and pathway inhibitor group (TRANSFECTION-CENP-A+ PI3K pathway inhibitor LY294002) . The cell proliferation was detected by CCK-8 method; the cell migration and invasion was detected by Scratch test and Transwell test; the expression of CENP-A, E-cadherin, N-cadherin and phosphatidylinositol 3-kinase/protein kinase B/nuclear factor-kappa B (PI3K/AKT/NF-κB) pathway related proteins was detected by Western blot.Results:A2780 cells were successfully transfected. After 24 hours, with the extension of culture time, compared with that in NG group [ (0.50±0.07) , (0.72±0.11) , (0.99±0.14) ] and pcDNA group [ (0.55±0.08) , (0.78±0.12) , (1.02±0.15) ], the viability of A2780 cells in pcDNA-CENP-A group [ (0.78±0.12) , (1.03±0.15) , (1.67±0.25) ] and pathway inhibitor group [ (0.63±0.09) , (0.87±0.13) , (1.39±0.20) ] increased significantly ( P<0.05) , compared with that in the pcDNA-CENP-A group, the viability of A2780 cells in the pathway inhibitor group was significantly decreased ( P<0.05) , in a time-dependent manner. Compared with those in NG group [ (15.83±1.46) %, (105.32±15.78) individual] and pcDNA group [ (16.79±1.46) %, (108.98±16.35) individual], the migration rate [ (37.96±5.80) %, (25.15± 2.19) %] and invasion number [ (327.87±49.18) individual, 206.53±30.97) individual] of A2780 cells, protein expression of CENP-A, N-cadherin, Vimentin, p-PI3K/PI3K, p-AKT/AKT, NF-κB, interleukin (IL-1β) , tumor necrosis factor-α (TNF-α) in pcDNA-CENP-A group and pathway inhibitor group were significantly higher ( P<0.05) , the expression of E-cadherin was significantly lower ( P<0.05) ; compared with those in the pcDNA-CENP-A group, the migration rate and invasion number of A2780 cells, protein expression of CENP-A, N-cadherin, Vimentin, p-PI3K/PI3K, p-AKT/AKT, NF-κB, interleukin (IL-1β) , tumor necrosis factor-α (TNF-α) in pathway inhibitor group were significantly lower ( P<0.05) , and the expression of E-cadherin was significantly higher ( P<0.05) . Conclusion:Overexpression of CENP-A can promote the proliferation, invasion and migration of ovarian cancer cells, which may be achieved by activating PI3K/AKT/NF-κB signaling pathway.
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OBJECTIVE：To study the effects of protocol deviation on the results of clinical trials ，and to provide reference for rising the quality management of drug clinical trials. METHODS ：Blind data review forms for clinical trials of a contract research organzation （CRO） company in Guangzhou from 2010 to 2019 were collected to analyze general characteristics of protocol deviation，the situation of protocol deviation before and after the “722 announcement”（Announcement on Carrying Out Self-inspection and Verification of Drug Clinical Trial Data issued by CFDA on July 22，2015）as well as the effects of protocol deviation on full analysis set （FAS）population division. The suggestions were put forward. RESULTS ：A total of 45 trials were included，involving 454 centers，14 304 disease cases and 5 562 cases of protocol deviation. The most common types of protocol deviations were over-window ，violation of criteria of the inclusion and exclusion ，and drop-out ，which accounted for 36.88％， 20.71％ and 18.43％ respectively. There was no statistical significance in protocol deviation degree of clinical trials with different stages or drug types （P＞0.05）；there was significant difference in the degree of protocol deviations in clinical trials with different stages before and after the “722 announcement”（P＜0.05）；the incidence of deviations from over-window ，violation of cirteria of the inclusion and exclusion ，and medication compliance had increased after the “722 announcement”；82.07％ of cases with protocol deviations could enter FAS ，and the population who included in FAS but did not enter per protocol set （PPS）accounted for 53.99％ of the total deviation ，of which deviations from drop-out and combined medication accounted for 19.51％ and 4.29％ respectively. All cases with deviation from medication compliance did not enter PPS. CONCLUSIONS ：Drop-out，violation of criteria of the inclusion and exclusion ，and over-window are the main factors that cause clinical trial protocol deviations. The “722 announcement”played a certain role on improving the quality management awareness of the personnel in drug clinical trial. Appropriate statistical methods should be selected to control bias ，and to strengthen the quality management of drug clinical trials and reduce protocol deviations ，by paying attention to trial design， staff training ， institutional management and 85223869。
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Cerebrolysin is an aqueous mixture of amino acids extracted from porcine brain, and mainly composed of 85% free amino acids and 15%small peptides. Cerebrolysin increase the metabolism of amino acids and glucose transport in the brain, improve the anti-anoxia ability of cells, and to enhance the brain's resistance to various types of malignant stimulation like stress and damage. Cerebrolysin can also promote synapse formation, induce neuronal differentiation, and help reverse brain injury. Because of its efficacy and safety, cerebrolysin has been widely used in the pediatric clinical practice, and primarily to treat neonatal hypoxic ischemic encephalopathy, childcerebral palsy, hyperactivity disorder, speech communication disorders, etc.The clinical symptoms were improved to some extent after the treatment of cerebrolysin. The recovery of consciousness, enhancement of comprehensionand memory, and improvement of the extremity motor function were observed. The treatment of cerebrolysincan not only enhance the cure rate, but also reduce the incidence of sequelae. This paper systematically summarized the clinical application of cerebrolysin in the pediatric population and relevant preclinical studies, to provide more guidance for clinical application of cerebrolysin in the treatment of pediatric diseases.
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Objective Systematic evaluation of cerebrolysin in the treatment of neonatal hypoxic -ischemic encephalopathy.Methods Computer search Cochrane Library, EMBase, PubMed, Chinese Journal Full-text Database (CNKI), Chinese Biomedical Literature Database (CBM), Wanfang Database ( each database retrieval time from its creation to May 2016 ) About cerebrolysin Randomized controlled clinical trial of neonatal hypoxic -ischemic encephalopathy.According to the inclusion and exclusion criteria of the literature, the methodological quality of the included research was evaluated and the data were extracted.Metadata was analyzed by RevMan 5.3 software.Results A total of 41 RCT patients were enrolled, with a total of 3695 patients, the experimental group was 1932 cases, the control group was 1763 cases.Meta analysis showed, the efficacy of cerebrolysin in the treatment of neonatal hypoxic-ischemic encephalopathy was significantly higher than that in the control group [OR=3.85, 95% CI (3.15,4.70), P<0.000001], for the impact of clinical symptoms, the number of primitive reflexes of neonatal hypoxic-ischemic encephalopathy in the treatment group was significantly higher than that in the control group [MD=-1.22, 95% CI ( -2.06,-0.38), P=0.004], muscle tension recovery days[MD=-1.69, 95% CI ( -1.80,-1.58), P<0.00001], conscious state recovery days[MD=-1.32, 95% CI ( -2.25,-0.40), P=0.005], seizure recovery days [MD=-2.36, 95% CI ( -3.70, -1.03), P =0.0005], and other indicators were shorter than the control group, the difference between the experimental group and the control group was statistically significant.Conclusion Cerebrolysin havean effective in treating HIE.
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OBJECTIVE:To systematically review the efficacy of Ginseng polysaccharideinjection combined with radiotherapy or chemotherapy in the treatment of malignancies,and provide evidence-based reference for clinical treatment. METHODS:Re-trieved from CNKI,CBM,VIP,Wanfang Database PubMed,EMBase,Web of Science,randomized controlled trials (RCT) about Ginseng polysaccharideinjection combined with radiotherapy or chemotherapy(test group)versus radiotherapy or chemothera-py alone(control group) in the treatment of malignancies were collected. Meta-analysis was performed by using RevMan5.3 soft-ware after data extract and quality evaluation by Cochrane 5.1.0. RESULTS:Totally 7 RCTs were enrolled,involving 567 patients. Results of Meta-analysis showed,the effective rate [OR=1.99,95%CI(1.27,3.14),P=0.003] and improvement rate of life quality [OR=2.95,95%CI(1.75,4.97),P<0.001] in test group were significantly higher than control group,cell abnormal rate [OR=0.26,95%CI(0.16,0.41),P<0.001] was lower than control group,the differences were statistically significant. There were no obvi-ous adverse reaction in 2 groups. CONCLUSIONS:Ginseng polysaccharideinjection combined with radiotherapy or chemotherapy is effective in the treatment of malignancies.
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OBJECTIVE:To establish a method for the rapid contents determination of potassium chloride and calcium chloride in Compound sodium chloride injection. METHODS:After diluted in appropriate way,Compound sodium chloride injection was sampled directly and contents of potassium chloride and calcium chloride were determined simultaneously by ICP-OES. The powder was 1 300 W,plasma gas flow rate was 15 L/min,auxiliary cooling gas flow was 0.2 L/min,atomizer flow rate was 0.8 L/min, the peristaltic pump rate was 0.8 L/min,atomizer pressure was 315 kPa,and the observation was axial observation,analysis spec-tral lines of potassium and calcium were 766.490 nm and 315.887 nm. RESULTS:The linear ranges of potassium and calcium were 1.0-12.0 mg/L (r=0.999 7 and 0.999 9);RSDs of precision and reproducibility tests were lower than 1%;recoveries were 98.5%-100.5%(RSD=0.59%,n=9)and 99.3%-102.3%(RSD=0.98%,n=9). CONCLUSIONS:The method is simple,rapid and simple,and can be used for the quality control of Compound sodium chloride injection.
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Objective To explore the role of white matter injuries in the schizophrenia induced by the NMDA re-ceptor antagonist. Methods Adult male C57BL/6J mice (8 week old) were equally divided into four groups. One group was sub-chronically treated with saline solution, and the other three groups were intraperitoneally treated with MK-801 at dose of 0.025 mg/mL (M1), 0.050 mg/mL (M2) and 0.100 mg/mL (M3) in a volume 10 ml per kilogram body weight. All ani-mals were tested using Morris water maze at the 9th-15th day and using the Hole Board exploration as well as Rota Rod performance tests on the 16th day. The myelin basic protein (MBP) and the ultrastructure of the myelin sheaths in the cor-pus callosum were then examined using immunohistochemical methods, transmission electron microscope technique and stereological methods. Results The repeated sub-chronic MK-801 treatment did not induce impairment of spatial learning and memory in Morris water maze. The MK-801 treatment at 0.25 mg/kg and 1.00 mg/kg but not at 0.50 mg/kg resulted in less exploration to a new environment. The myelin staining with anti-MBP antibody was less intense in all three schizo-phrenic groups when compared to saline control group (P<0.01). Furthermore, MK-801 treatment caused pathological al-terations of the myelin sheaths including segmental demyelination of myelinated fibers and splitting of myelin sheath lamel- lae in schizophrenic groups. The ratio of the injured myelinated nerve fibers in the corpus callosum of MK-801 treated mice [M3 group, (22.42 ± 4.24)%] was significantly higher when compared to the control mice [(3.84 ± 1.35)%,P<0.01)]. Conclusions The present study demonstrated the white matter damages, mainly low MBP expression and segmental demye-lization in the corpus callosum in the mice sub-chronic treated with MK-801, indicating that the white matter changes might be involved in the schizophrenia induced by NMDA antagonist.
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OBJECTIVE:The preparation of microspheres was optimized by central composite design in order to improve the lung targeting of tetrandrine chitosa microspheres. METHODS:Microspheres were prepared using an emulsion-chemical crosslink technique.Effects of three independent variables i.e. weight percent of tetrandrine and christon, volume percent of water phase and organic phase and christon concentration in aqueous phase were investigated on four response variables.Response variables selected in the research were yield,drug loading, envelop efficiency, mean diameter and span of dispersity.Second-order polynomial and linear equations were fitted to the data,and the resulting equations were used to produce three dimensional response surface graphs,by which optimal experimental conditions were selected. RESULTS:Five response variables were found to be dependent on three independent variables. According to optimal experimental conditions.An optimized formulation contained weight percent of tetrandrine and christon was 61.97%, volume percent of water phase and organic phase was 13.51% and christon concentration in aqueous phase was 2.37%. CONCLUSION:The central composite design can be used to optimazation of preparation formulation,diameter of the microspheres optimized by it can meet the demands of lung-targeting.
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OBJECTIVE:To provide scientific evidence for the microsphere's m etabolism in vivo of lung targeted tetran?drine polylactic acid(TET-PLA)microspheres.METHODS:Blood was sampled from carotid artery after microspheres were injected into rabbit through auricular vein,the concentration of TET in plasma was determined by RP-HPLC method;The pharmacokinetic parameters were obtained by using3p87program.RESULTS:Concentration-time curves of TET micro?spheres were fitted to a2-compartment model with t 1/2? of(286.49?237.55)min and AUC of(810.33?287.49)(?g?min)/ml.CONCLUSION:TET-PLA microspheres show sustained release effects in rabbits.
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OBJECTIVE:To study the lung targeted characteristic of tetrandrine polylactic acid microsphere(TPM).MET_HODS:TPM and tetrandrine injection were injected intravenously into mouse,an RP-HPLC was established to measure the content of TPM in biological samples,and the concentrations of tetrandrine in different tissues of mice were determined and compared.RESULTS:The determinable concentration of tetrandrine in plasma was in the linear range of 0.519～17.000?g/ml(r=0.9 996),the recovery was 97.32%,the mean value of RSD was 4.46%.After the use of TPM,the concentrations of tetrandrine in mouse tissues were significantly higher than tetrandrine injection,and the highest concentration was detected in lungs of mouse.CONCLUSIONS:TPM is distinguishingly lung targeted.