Objective To explore neurobiological mechanisms of the withdrawal-induced aversion,the changes of protein kinase A(PKA) were measured in shell of accumbens nucleus (AcbSH) of CPA model rats.Methods 1.All 36 male SD rats were divided into three groups,model group ( MN group),and control group (MS group and SN group).MN group was injected with morphine,6.5 days,10mg/kg,intraperitoneally (IP),twice per day,naloxone injection,0.3 mg/kg,ip,along with conditioned place aversion training,to develop the CPA model.The MS group was administrated equivalent volume of morphine and saline.Also the SN group was injected with equivalent volume of saline and naloxone.2.During the development of CPA,the expression of protein kinase A was assayed with immunohistochemistry in the AcbSH.Results Before the development of CPA,PKA expressions were no significant differences among the three groups in the AcbSH (F=2.306,P=0.130).However,after development of CPA,PKA expressions showed significant differences among the three groups(F =36.516,P =0.000).The average gray intensity of MN group (109.50 ± 4.661 ) was apparently higher than the MS group (126.50 ±3.697,P＜0.01),than the SN group (133.50 ±6.364,P＜0.01).Conclusions 1.Protein kinase A expression,leading to the aversion in the AcbSH probably is a key pathway contributing to the development of CPA.2.The neuroadaptation mediated by PKA may be one of important molecular underpinnings of CPA.

Objective To investigate the clinical efficacy and safety of ziprasidone mesylate injection on the acute agitation symptom in mental retardation. Methods The total of 80 patients of mental retardation with acute agitation symptoms were randomly divided into two groups:the treatment group (40 patients) were intra-muscarly given with ziprasidone mesylate injection at the initial dose of 10 mg, 20 mg 4 h later, and 30 mg once on the second day and third day. And the control group (40 patients) were treated with haloperidol injection. The volume dose of haloperidol was 20 mg everyday. Other antipsychotic drugs, antimanic drugs and benzodiazepines were not allowed to be used during the observation, neither does the prophylactic use of drugs against parkinson's disease. Before and 1, 2, 4, 6, 8, 12, 24, 48, 72 h after treatment, the positive and negative scale ( PANSS) reduction rate, the end of the clinical global impression scale ( CGI) were assessed. By the end of the treatment, the adverse reactions symptom, cale ( TESS) was assessed for the safety. Results By the end of treatment PANSS reduction rate was 46. 31% in the test group and 48. 81% in the control group, the clinical improvement rate was 80. 00% in the treatment group and 82. 50% in the control group. No statistically significant difference on efficacy was found between two groups. The side reaction rate in the treatment group was 27. 5%, that in the control group was 40. 0%, there was significant difference ( P<0. 05) between two groups, but the extrapyramidal reaction in the control group was significantly more than that in the treatment group(P<0. 05). Conclusion Ziprasidone mesylate injection is effective on treating the symptoms of mental retardation, in corresponding to the effect of haloperidol injection,and with less extrapyramidal reactions.

Objective To evaluate bacteriophage therapy for gut-derived sepsis caused by Acinetobacter baumannii in mice.Methods Lyric phages of Acinetobacter baumannii were isolated from environment by using double-layer agar method.A murine model of gut-derived sepsis was established by oral administration of ampicillin-resistant Acinetobacter baumannii and injection of ampicillin and cyclophosphamide into peritoneal cavities of mice.Bacteriophage therapy were given 1 d before infection (group 1),2 d(group 2) and 6 d(group 3) after infection.The survival of the mice was observed,mice without bacteriophage therapy were as control.Independent-sample t test was performed to compare inflammatory cytokines levels in peripheral blood and liver,number of bacteria in liver and spleen between mice with and without bacteriophage therapy.Results The minimal lethal dose of Acinetobacter baumannii for mice with gut-derived sepsis was 1 × 107 CFU/mL.The survival of the mice in group 2 (4/6 survived),which were treated with bacteriophage 2 d after inoculation of Acinetobacter baumannii,was higher than those of group 1 (2/6 survived),group 3 (3/6 survived) and the control group (phage-untreated,0/6 survived).Interleukin (IL)-1 β,tumor necrosis factor (TNF)-α and IL-6 in peripheral blood in mice with bacteriophage therapy were (105 ±6) ng/L,(105 ± 11) ng/L and (104 ± 12)ng/L,which were lower than those in control group (t =5.04,9.05 and 9.33,P ＜ 0.01) ; IL-1 β and TNF-α in liver of mice with bacteriophage therapy were (104 ± 9) ng/L and (104 ± 11) ng/L,which were lower than those in the controls (t =13.70 and 12.80,P ＜0.01),but IL-6 levels were not of statistical difference between therapy and control groups (t =1.06,P ＞ 0.05).Number of bacteria in liver and spleen in mice with bacteriophage therapy were (2.9 ± 1.3) × 103CFU/g and (8.3 ±7.6) × 102 CFU/g,which were also lower than those in control group (t =9.16 and 8.96,P ＜ 0.01).Conclusions Bacteriophage therapy can be effective against gut-derived sepsis caused by Acinetobacter baumannii.

We have analyzed the current status of recognization and qualification of orphan drugs in China and abroad, looking at the aspects of the authority institutions, identification and qualification process, and the number of orphan drugs identified and available in the market. By comparing and analyzing horizontally the differences in orphan drugs identification between representative developed countries vs. some developing countries, we discuss the inadequacy of orphan drugs supervision in China. We introduce the advanced experience from the developed countries and some developing countries to provide suggestions for the identification and management of orphan drugs, hoping to speed up the process of development and market availability of orphan drugs and to maximize patient's accessibility to treatment in China.

This article combs and summarizes the entire process of rare disease selection and priority theme determination, including the application and preliminary review of rare diseases, standardization of disease theme information, the evaluation methods of evidence sorting and disease selection for priority selection of disease themes, and other aspects of the content were analyzed in depth. It is expected to provide reference for the subsequent selection of rare diseases, improve the fairness, rationality and scientificity of rare disease selection, and further promote research and decision-making in China′s rare disease-related fields.

Pharmacoeconomic evaluation is the essential supporting information for the inclusion of rare disease drugs into medical insurance in China. The accurate measurement of the health state utility of rare diseas is of practical significance to the development of rare disease pharmacoeconomic evaluation. Based on the review of pharmacoeconomic evaluation requirements for rare diseases in some countries/regions, we systematically retrieved the published studies on the measurement of health state utility for 121 rare diseases in China and other countries and regions. We identified 17 591 papers in the initial review, and later selected 230 after screening. We also made a comprehensive analysis of the quality of literature, evaluation content and use of tools for measuring health state utility in rare diseases in China. Finally, we analyzed the challenges in measurement in terms of population, instruments use, and application of results and made recommendations based on analysis, hoping to provide reference for the development of rare disease health state utility measurement studies in China.

【Objective】 To perform pre-transfusion examination and major crossmatch test using CD47 anti-idiotypic antibody (CD47 AID) (method 1) and reagent lack of anti-IgG4 anti-human globulin(method 2) in patients treated with CD47 monoclonal antibodies, and evaluate the feasibility of method 1 by comparing the transfusion efficacy of patients after cross matching with two methods. 【Methods】 Post-drug samples were collected from 18 clinical subjects treated with CD47 monoclonal antibody in our hospital. Antibody screening and major crossmatch test were performed using method 1 and method 2, and the difference of ΔHb (post-transfusion Hb minus pre-transfusion Hb) was compared after transfusion. The differences in ΔHb after transfusion were analyzed between the test group using method 1 and the control group without CD47 monoclonal antibody using ordinary microcolumn gel method. 【Results】 There was no significant difference in ΔHb between the test group using method 1 and test group using method 2 (8.40±0.71 vs 7.36±0.94, P>0.05). No significant difference was noticed in ΔHb between the test group using method 1 and the control group without CD47 monoclonal antibody (8.40±0.71 vs 6.59±0.77, P>0.05). 【Conclusion】 In the test group, major crossmatch test with method 1 has the same transfusion efficacy as the test with method 2. Method 1 is simple and easy to operate, and the results are objective and accurate. It is recommended to use method 1 for pre-transfusion antibody screening and major crossmatch tests for patients using CD47 monoclonal antibody.

【Objective】 To explore the feasibility of blood transfusion compatibility testing for multiple myeloma(MM) patients treated with anti-CD38 monoclonal antibody daratumumab (DARA) after DARA-Fab fragment blocking, and to evaluate the transfusion efficacy by comparing with dithiothreitol(DTT) method. 【Methods】 After DARA was prepared into DARA-Fab fragments using PierceFab preparation kit, the neutralization effects of different volumes (5, 10, 15, 30 μL) on screening cells and panel cells were confirmed. DARA-Fab fragments and screening cells with specific antigens and corresponding monoclonal antibody reagents were used as the experimental group and the control group with the same volume of saline for incubating and centrifugin.Twenty MM patients treated with DARA were selected for cross-matching with DARA-Fab and DTT respectively, and the laboratory indexes before and after transfusion were statistically analyzed, and the two blood matching methods were compared. 【Results】 After incubating and centrifuging, the results of DARA-Fab fragments(15, 30 μL) with screening cells and serum mixed with DARA were negative, while those of DARA-Fab(5, 10 μL) were positive. 15μL DARA-Fab treated antibody identification cells (2, 3, 4, 5, 7, 9, 11) were negative, antibody identification cells (1, 6, 8, 10, 12) were negative after 30 μL DARA-Fab fragments treatment; the results of MNS, Duffy, Kidd, Kell, Lewis, Rh blood group system of the experimental group were consistent with those of the control group; the hemoglobin (Hb) (g/L) of 20 patients after infusion of RBC (73.90±1.90) was significantly higher than that before transfusion (63.60±1.58), P<0.01. There was no significant difference in total bilirubin(TBil)(μmol/L)(16.25±3.54 vs 17.87±3.57), direct bilirubin(DBIL)(μmol/L)(6.31±2.32 vs 7.10±2.80)and indirect bilirubin(I-Bil)(9.94±1.38 vs 10.77±1.22) before and after infusion(P>0.05).And no statistical difference was noticed in Hb (10.75±1.04 vs 10.30±0.98), TBil (3.31±1.47 vs 3.31±0.55), DBIL(2.76±1.24 vs 2.60±0.83), and I-Bil(1.97±0.40 vs 2.82±0.53) between the DTT treatment method and the DARA Fab fragment treatment before and after transfusion(P>0.05). 【Conclusion】 DARA-Fab can remove the interference of RBC on cross matching by blocking CD38 antigen. This method has no effect on the antigens of common RBC blood group systems, and shows significant blood transfusion efficacy as that of DTT method.