OBJECTIVE: To compare the setting methods for biologics data protection period between America and Japan, in order to provide suggestions for China. METHODS: We made a contrastive study of American "break even" model and Japanese "risk management evaluation" model by using method introduction and characteristic analysis. RESULTS: The two setting methods in the US and Japan focus on different system objectives, respectively. The Chinese choice of setting method needs to combine the feasibility of setting methods and the national conditions and policy goals for comprehensive consideration. CONCLUSION: At present and the future for a long time, China's pharmaceutical industry is still in the "imitation to innovation" stage, and drug safety issues remain the core task. Therefore, the period of biologics data protection should be rationally set up by using "risk management evaluation" model as the base, "break even" model as supplement, so as to bring the three policy effects such as innovation incentive, the improvement of innovative drugs availability and strengthening the drug post-market safety monitoring.

OBJECTIVE: To make a comparative analysis on the expedited approach for new drug review in the USA, the European Union, and Japan, and to provide references for China. METHODS: Through analyzing the mechanism and implementation performance of each expedited approach, and summarizing its characteristics, this paper puts forward some suggestions according to the situation of the reform for new drug review in China. RESULTS: Compared with the US, EU and Japan, our country is gradually laying emphasis on the value of clinical curative effect when to apply expedited approach, but there is still a large gap on system setting. CONCLUSION: Hence this paper suggests to draw lessons from foreign "multi-channel, full coverage" concept, and gradually to establish a new multi-channel system of expedited review approach on the basis of perfecting our country's priority review approach, thereby accelerating the process of new drugs which have high clinical value.

Objective To observe the clinical efficacy ofXing Nao Kai Qiao (brain-awakening and orifice-opening) needling plus thunder-fire moxibustion in treating vertebrobasilar ischemia.Method Fifty-five patients with vertebrobasilar ischemia were randomized into a treatment group of 26 cases and a control group of 29 cases. The treatment group was intervened byXing Nao Kai Qiao needling plus thunder-fire moxibustion, while the control group was by oral administration ofYangxue Qingnao granules. The blood flow of vertebrobasilar arteries were observed by using ultrasonic Doppler blood-flow detector before and after intervention, and the clinical efficacies were compared between the two groups.Result The recovery and markedly-effective rate and total effective rate were respectively 61.5% and 96.2% in the treatment group, versus 34.5% and 89.7% in the control group, and the differences were statistically significant (P<0.01,P<0.05). The VS and VD of vertebral arteries and VS of basilar arteries were significantly changed after intervention in the treatment group (P<0.05). The VS of basilar arteries was significantly changed after intervention in the control group (P<0.05). After treatment, The VS of vertebral and basilar arteries in the treatment group was significantly different from that in the control group (P<0.05).ConclusionXing Nao Kai Qiao needling plus thunder-fire moxibustion is an effective approach in treating vertebrobasilar ischemia.

Objective To compare the effectiveness and safety of raltitrexed and fluorouracil(FU)/leucovorin (LV) combined with oxaliplatin for advanced colorectal cancer. Methods Fifty patients with advanced colorectal cancer diagnosed by histopathology or cytology were randomly divided into two groups with 25 cases each by envelope, but 1 case lost. Patients in experimental group were treated with raltitrexed (3 mg/m2, ≥ 15 min intravenously) combined with oxaliplatin (130 mg/m2 on day 1 ), patients in control group were treated with FU/LV combined with oxaliplatin:LV 100 mg/m2 infusion (over 2 h, from day 1 to day 3 ) followed by FU (400 mg/m2 infusion in 2 h and 600 mg/m2 continuous infusion from day 1 to day 3 ),combined with oxaliplatin ( 130 mg/m2 on day 1 ), 3 weeks were as one cycle. Patients received 6 or less cycles until disease progressed or toxicity could not be tolerated. Results Effective rate was 37.50%(9/24)and 33.33%(8/24) in experimental group and control group respectively (P＞ 0.05). Disease control rate in experimental group was 83.33% (20/24) while in control group was 70.83% ( 17/24 ) (P ＞ 0.05 ). The median time of progression-free survival (PFS) in experimental group and control group was 11.0 months and 9.0 months respectively (95%CI 8.643-11.357,P =0.015). Main adverse effects were anorexia, vomiting, neutropenia, thrombopenia, anemia, neurotoxicity, fatigue, aminotransferase abnormality, and so on. There was no statistic difference between two groups in side effects(P ＞ 0.05). Conclusions Raltitrexed combined with oxaliplatin is an effective regimen for the advanced colorectal cancer. Compared with traditional FU-based regimen, it is more convenient. Patients will have less venous exposure time and hospital days.Effective rate and mean survival time are superior or not inferior in raltitrexed treatment to that of FU-based regimen. Raltitrexed combined with oxaliplatin is worthy to be recommended in treating colorectal cancer.

Objective To analyze the inappropriate use of oral drugs in elderly patients admitted in internal medicine, and to guide clinical rational drugs use in elderly patients. Methods One hundred inpatients′ data over 65 years were collected in the department of geriatrics. The potentially inappropriate use of oral drug were analyzed according to the Beers criteria published in 2012 and drugs instructions. Results In 100 patients, (5.81 ± 2.78) kinds of oral drugs had been taken per inpatient. One patient was involved out-of-label usage. There were potentially inappropriate uses of oral drugs in 21 patients. Inappropriate use of oral drugs in three patients were not related to diagnosis or disease, and in 4 patients were related to morbid state, 14 patients used drugs that need to be used with caution in older adults. Conclusions There are off-label uses and potentially inappropriate medications in clinical practice, so clinical doctors should examine and assess the uses of drugs. Clinical doctors should strengthen the understanding and application of the comprehensive geriatric assessment.

OBJECTIVETo build a type 2 diabetes mellitus rat model with cardiac ischemia.

METHODSMale Wistar rats were fed high sucrose and high fat diet for four weeks and then injected with streptozoticin (STZ) (40 mg/kg .i.p.). The levels of fasting blood glucose and serum insulin were monitored every week. The body weights of rats were also measured every week. The blood levels of creatine kinase and lactate dehydrogenase (LDH) were measured following the electrocardiograph used BL-410 biological experiment system.

RESULTSThe serum insulin levels of diabetic rats were 4.05 ng/ml after four weeks high sucrose and high fat diet. The fasting blood glucose levels of diabetic rats were 17.9 mmol/L after injection. Compared with normal group, there was obvious change of S-T segment in the electrocardiograph of diabetic group at the fourteenth week. The levels of creatine kinase and lactate dehydrogenase in diabetic group significantly increased in comparison with those in normal group.

CONCLUSIONThe cardiac ischemia of diabetic rats model is suitable for investigating cardiac disease of diabetes mellitus.

Animals ; Creatine Kinase ; blood ; Diabetes Mellitus, Experimental ; physiopathology ; Diabetes Mellitus, Type 2 ; chemically induced ; physiopathology ; Diet, High-Fat ; adverse effects ; Dietary Sucrose ; adverse effects ; Disease Models, Animal ; L-Lactate Dehydrogenase ; blood ; Male ; Myocardial Ischemia ; physiopathology ; Rats ; Rats, Wistar ; Streptozocin

[Objective] To investigate the anti-proliferative and apoptosis effect induced by Honokiol (HNK) on human myeloid leukemia cell line U937 cells in vitro.[Methods] After treated with different concentration of HNK,Hoechst33342 fluorescent staining was used to detect cell apoptosis;the growth inhibition ration of U937 cells and PBMCs were analyzed by MTT assay;the apoptosis ration was detected by flow cytometry;mitochondrial membrane potential was explored by rhodamine 123 stain;Caspase3/7 protein activity kit was used to test the Caspase3/7 activity;the Caspase-3 and Caspase-7 mRNA levels were detected by real-time fluorescent relative-quantification reverse transcriptional PCR (FQ-PCR).[Results] Honokiol could significantly inhibit the proliferation of U937 cells in terms of the indexes of IC50/U937 11.8 μg/mL and IC50/PBMCs 40.3 μg/mL,and the anti-proliferative effect was in a time and concentration dependent manner;Flow cytometry analysis manifested that Honokiol could induce U937cells apoptosis by Annexin V/PI double Annexin V/PI fluorescein stain;Honokiol significantly inhibited the mitochondrial membrane potential of U937 cells and enhanced the ability of Caspase3/7 and the mRNA expression levels,but not the PBMCs.[Conclusion] HNK can inhibit U937 cells proliferation and induce cells apoptosis via activating Caspase 3/7.

Objective Schistasoma japonicum(S.japonicum)lysophospholipase gene(Sjl539)from cDNA of S japonicum adult worms was amplified and subcloned into eukaryotic expression vector pcDNA3.1(+)for expression of recombinant antigen and immunogenicity analysis.Methods Total RNA of S.japonicum was extracted to generato cDNA by RT-PCR.The Sj1539 gent was amplified.The DNA fragment was subcloned into eukaryofic expression vector pcDNA3.1(+)following insertion and amplification in pGEM-T.The recombinant plasmid was transfected into human cervical carcinoma cell strain(Hela cells)and expression products were identified by Western blotting.Results The size of PCR product was approximately 684 bp.It was confirmed that Sj1539 gene had been inserted successfully by the recombinant plasmid digested with two enzymes and PCR.It was verified that the expression product could react with S.japonicum-infected rabbit serum by Western blotting and the molecular weight was approximately 25×103.Conclusions The eukaryotie expression vector carrying Sj1539 gene has been established and the expression product has been obtained.

Objective:Taking Chongyang county of Hubei Province as an example, the paper describes the in-tegration of the maternal and child health ( MCH) and family planning ( FP) service system and analyses the key ele-ments to provide reference for promoting integration. Methods: qualitative interviews and quantitative questionnaire were used to collect data. The software QSR Nvivo 8. 0 and SPSS 17. 0 were used for qualitative and quantitative data analysis. Results:Based on the correct understanding of integration, Chongyang implements the supporting policies actively, maintains the original compensation mode unchanged, follows the principle of“no reducing headcounts and no downsizing” strictly, promotes the merger of institutions rapidly, adjusts the service contents and methods reasona-bly, and integrates the maternal and child and family planning information platform. Conclusion:The correct concept of integration, appropriate staffing, and stable funding in Chongyang provide rich experiences for future research. However, there is room for improvement in staffing, incentive mechanisms, service content, and forms.

To explore the antibacterial activity and mechanism of total alkaloids and berberine from Coptidis Rhizoma on Aeromonas hydrophila, and determine the effect of total alkaloids and berberine from Coptidis Rhizoma on minimum inhibitory concentrations, permeability and fluidity of cell membrane, conformation of membrane proteins and virulence factors of A. hydrophila. The results showed that both total alkaloids and berberine from Coptidis Rhizoma had antibacterial activities on A. hydrophila, with minimum inhibitory concentrations of 62.5 and 125 mg · L(-1), respectively. Total alkaloids and berberine from Coptidis Rhizoma could increase the fluidity of membrane, change the conformation of membrane porteins and increase the permeability of bacteria membrane by 24.52% and 19.66%, respectively. Besides, total alkaloids and berberine from Coptidis Rhizoma significantly decreased the hemolysis of exotoxin and the mRNA expressions of aerA and hlyA (P < 0.05, P < 0.01), the secretion of endotoxin and the mRNA expression of LpxC (P < 0.05, P < 0.01). The results suggested that the antibacterial activity of total alkaloids and berberine from Coptidis Rhizoma on A. hydrophila may be related to the bacteria membrane injury. They inhibited the bacterial growth by increasing membrane lipid fluidity and changing conformation of membrane proteins, and reduced the secretion of virulence factors of A. hydrophila to weaken the pathogenicity.
Aeromonas hydrophila ; drug effects ; genetics ; metabolism ; Alkaloids ; pharmacology ; Anti-Bacterial Agents ; pharmacology ; Bacterial Proteins ; genetics ; metabolism ; Bacterial Toxins ; biosynthesis ; Berberine ; pharmacology ; Cell Membrane ; drug effects ; genetics ; metabolism ; Coptis ; chemistry ; Drugs, Chinese Herbal ; pharmacology ; Membrane Fluidity ; drug effects ; Rhizome ; chemistry