Autocrine motility factor (AMF) plays an important role in the stimulation of the migration and motility of cells, especially the generation, migration and angiogenesis of tumor. Recently, it has been found that AMF has three isoforms, ATX-t, ATX-m and PD-I alpha. The PD-I alpha isoform is specifically expressed in the brain, which plays extensive functions in nervous system, such as regulating neural development and differentiation, promoting neurotrauma repair, inducing neuropathic pain, even contributing neurodegeneration under some circumstances. This indicates the close relationship of AMF/AMFR and the pathophysiology of the nervous system. This paper mainly reviews the function of AMF and AMFR and its possible mechanism in the nervous system.

Objective To explore the common clinical features and mechanism of HenochSchonlein purpura (HSP) in children,and provide evidence and guidance for clinical diagnosis,therapy and prognosis of HSP.Methods Prospective study.Totally 1 232 HSP children blood samples were collected during January 2010 to December 2013 in the Children's Hospital of Zhejiang University School of Medicine,and the levels of immunoglobulin,complement,T lymphocyte subsets and CRP were detected in the acute phase of HSP.The clinical data were analyzed with these indexes to explore the function of cellular and/or humoral immunity in the pathogenesis of HSP.In addition,this study detected serum IgA levels in 200 cases of sepsis rash,200 cases of urticarial and 200 cases of thrombocytopenic purpura patients and 400 cases of healthy children over the same period to our hospital respectively,in order to find out whether IgA is capable of differentiating allergic purpura rash from other similar skin rashes.Results Compared with healthy children,the IgA level was significantly higher [IgA:2.0 (0.6-7.5) g/L vs 1.1(0.6-2.1) g/L,Z =5.928,P =0.03].When IgA ＞ 1.44 g/L,the diagnostic sensitivity and specificity to differentiate allergic purpura patients from sepsis patients were 77.43 ％ (954/1 232) and 80.00％ (160/200),respectively.When IgA ＞ 1.53 g/L,the diagnostic sensitivity and specificity to distinguish from allergic purpura with urticaria patients were 72.57％ (894/1 232) and 74.51％ (149/200).When IgA ＞0.91 g/L,it had a 95.14％ sensitivity (1 172/1 232) and a 79.45％ specificity (159/200) for the differential diagnosis of allergic purpura and thrombocytopenic purpura patients.When IgA ＞ 1.33 g/L,the sensitivity of distinguishing allergic purpura patients from healthy children was 81.25％ (1 001/1 232),while the specificity was 95.00％ (380/400).Conclusions HSP children show cellular immune dysfunction.Th1/Th2 imbalance and over-activation of Th2 cells result in the increased synthesis and release of immune globulin,causing abnormalities in humoral immune.An increase in serum IgA level of HSP patients can differentiate HSP from other similar rashes.

OBJECTIVE：To provide refe rence for improving the moni toring system of simplified registration system of Chinese classical formulas. METHODS ：A comparative study was conducted on the simplified registration system of traditional herbal medicines in the European Union and Chinese classical formulas from the aspects of regulatory agencies ，regulatory systems ， simplified registration conditions ，simplified registration catalogs and registration data. On the basis of the experience of the simplified registration system of traditional herbal medicines in the European Union ，some suggestions were put forward to improve the simplified registration system of Chinese classical formulas. RESULTS & CONCLUSIONS ：The European Union establishes special committee on traditional herbal medicine for registration and supervision ；has established a complete regulatory system from directives to specific guidelines ；focuses on the history and conditions of the use of traditional herbal medicine ；has published the European Union monographs and European Union list ，which are used as a basis for safety and effectiveness to further reduce or exempt registration data. In China ，National Medical Products Administration and the National Administration of Traditional Chinese Medicine are jointly responsible for the registration and supervision of classical formulas. At present ，the relevant documents to simplify the registration and approval have been issued ，but there is no corresponding implementation rules and guidelines. China also attaches great importance to the clinical experience of classical formulas ，and emphasizes the consistency of preparation methods and dosage forms with ancient classics. Recently ，China has published the Catalogue of Ancient Classic Formula（the First Batch ），including 100 classical formulas ，and the classic formulas in the catalogue can be exempted from relevant registration materials when applying for registration. Our country can learn from the experience of the European Union and combine the actual situation of classic formulas supervision to establish an expert committee ，focus on quality control and risk control to improve registration and supervision system ，optimize the selection conditions of classic formulas ，and explore the classic formulas monographs ， to further stimulate the innovation vitality of traditional Chinese medicine industry.

OBJECTIVE：To analyze the application of health technology as sessment（HTA）for the selection of essential medicine in Thailand ，and to provide reference for optimizing the selection system of essential medicine in China. METHODS ：By retrieving related literatures and official websites ，the situation （selection mode ，institution and HTA institution ），process（main selection process of selection for essential medcine ，HTA process ） and supporting measures （HTA guideline ，HTA research database，standard cost list ）in the selection of essential medicine in Thailand were analyzed comprehensively. Suggestions to essential medicine selection in China were put forward. RESULTS & CONCLUSIONS ：The current selection model of essential medicines in Thailand is based on the application of stakeholders （pharmaceutical manufacturers ，healthcare providers ，patients or patient organizations ，etc.）through expert selection combined with HTA ，which is charged by essential medicine list subcommittee. The Health Intervention and Technology Assessment Program Center of its health economics working group is responsible for the specific work of essential medicine HTA. Its main process include the submission of applications by pharmaceutical manufacturers ， screening by essential medicine list committee ，expert selection ，and the coordination working group of essential medicine list to form the proposed list ，which is then examined and approved by the subcommittee ，minister of Health and National Drug System Development Committee ；finally the list was released. The high-price but necessary drugs are selected by the subcommittee and then the priority is assessed by the health economics working group. Non-profit organization or other interested organizations conduct HTA ；health economics working group and external audit experts evaluate the research quality ，and the health economics working group forms policy recommendations ； NLEMcommittee will carry out list access or price negotiation which then were considered by the subcommittee. In HTA supporting measures of Thailand ， HTA guidelines include HTA methodology guidelines （ensuring high quality economic evaluation and prom oting standardization of research fr amework）and HTA process guidelines （HTA is strictly regulated from transparency，accountability，inclusiveness，timeliness，quality，consistency，competitiveness）. HTA database include 4 kinds of economic evaluation researches （cost minimization analysis ，cost-benefit analysis ，cost-effectiveness analysis and cost-utility analysis），result evaluation ，quantitative research of life quality ，which supplied reference for research staff. The standard cost list makes the economical evaluation process more accurate and convenient. The selection of essential medicine in China can refer to the relevant experience of Thailand ，gradually establish health technology assessment system ，strengthen international cooperation and personnel training ；introduce the concept of priority ，and reasonably allocate evaluation resources ；formulate HTA guidelines ， improve supporting measures ；emphasize the participation of stakeholders to ensure the standard and transparent selection process ， so as to continuously improve corresponding selection system in China from aspects of the system construction ，resource allocation，supporting measures ，program optimization ，etc.

OBJECTIVE：To improve the willin gness of chinese pharmaceutical enterprises to participate in drug patient assistance programs ，improve the level of drug use and access to innovative drugs in China and fully evaporate the supplementary role of the medical security system. METHODS ：Through grounded theoretical analysis of the interview results ，the theoretical framework of the factors affecting the implementation of drug patient assistance programs by pharmaceutical companies was proposed. The above theoretical framework was empirically studied through questionnaire survey on the personnel who understood or participated in drug patient assistance program in Chinese pharmaceutical enterprises. Based on partial least squares structural equation model ，Smart PLS 3.0 software was used for data processing to analyze the influence of different factors on the willingness of pharmaceutical companies to participate in drug patient assistance programs ，and the relevant suggestions were put forward. RESULTS & CONCLUSIONS ：Economic benefits ，market competition ，social benefits and policy environment have significants impacts on the willingness of pharmaceutical enterprises to implement drug patient assistance programs. The path coefficients were 0.244 （P＜0.01），0.236 （P＜0.01），0.235 （P＜0.05），0.228 （P＜0.01）. Human resource efficiency and cooperation unit have no significant effects on the willingness of pharmaceutical enterprises to implement drug patient assistance programs（P＞0.05）. Economic benefits are in line with the nature of enterprises ’profit-making and have the most close influence. Therefore，the pricing strategy of drugs and the tax policies of government departments are very important for enterprises. Participation in market competition is also an important factor for enterprises to participate in patient assistance programs. The earlier the implementation of patient assistance ，the more opportunities of relevant drugs will be to seize more markets. The social benefits manifest as reducing the economic burden of patients ，improving the quality of life ，and promoting the social and economic development. At the same time ，enterprises have set up good social image and forms a word-of-mouth effect. The policy environment generally includes the legal environment and medical insurance policies. The legal provisions restrict the donations of pharmaceutical enterprises to a certain extent ，but corresponding regulatory measures are still essential. Medical insurance policies are closely related to the establishment and adjustment of patient assistance programs ，and the connection between medical insurance access and patient assistance programs needs to be further improved. Therefore ，from the perspective of enterprises ，it is recommended to establish a cost and benefit calculation system for drug patient assistance programs ，and broaden the publicity channels and increase the publicity intensity of patient assistance programs. From the perspective of the government ，it is recommended that tax incentives for donations should be increased，the patient assistance supervision system should be improved ，the access and adjustment rules for the drugs of patient assistance programs in medical insurance list should be clarified ，so as to promote pharmaceutical enterprises to actively participate in patient assistance programs and improve the drug use level and drug accessibility of patients.

OBJECTIVE：To pro vide reference f or resolving structural imbalance of “supply and demand dislocation ”in each stage of new drug R&D funds in China. METHODS ：Through analyzing the fund demand in each stage of new drug R&D and the problem of “supply and demand dislocation ”in detail ，a financing scheme matching the fund demand of each stage was designed ， and analyzed with the financing process of “Wanke”. RESULTS & CONCLUSIONS ：In the basic stage of new drug R&D ，there was a large demand for funds ，but there were great technical risks ，transformation risks and investment risks ，little attention and support from investors ，resulting in the lack of R&D funds in this stage. It is suggested to increase the investment of R&D enterprises themselves. In the stage of new drug discovery ，the risks of R&D and investment were still high ，more funds were needed and funds were in short supply. It is suggested to attract more venture capital into this stage. From preclinical stage to clinical stage Ⅱ，there was a greater demand for funds. It is suggested that this stage should mainly rely on venture capital and pledge financing with patents. From the clinical stage Ⅲ to pre-marketing ，R&D had entered the mature stage with less investment risk. Therefore ，more venture capital could be obtained in this stage ，and there was a situation of excess capital. At this time ，in addition to venture capital ，R&D enterprises can also choose listing financing. In the post-marketing stage ，the sales right of a certain region in the product sales link could be transferred to provide new reserve funds for the next round of new drug R&D ，so as to achieve a virtuous circle of R&D activities. One of the reasons for the success of “Wanke”R&D financing lied in the combination of various financing methods in the financing process. It is suggested that China should improve the financial financing system and patent value evaluation system at the national level ，so as to promote the drug patent pledge financing in China as soon as possible. Finally ，new drug R&D institute must establish the concept of independent innovation ，speed up the output of technological innovation results ，so as to achieve the improvement of China ’s independent R&D capability.

Objective: To investigate the safety and long-term efficacy of a new treatment, echocardiography-guided transthoracic laser ablation of the animal interventricular septum (IVS), for obstructive hypertrophic cardiomyopathy (HOCM). Methods: Ten healthy sheep were randomly divided into two groups: experimental group: sheath puncture with laser ablation (energy: 3 W, 1000 J), sham control group: sheath puncture only without laser ablation. Echocardiography and electrocardiogram (ECG) were recorded before operation, immediately after operation, and 1, 3 and 6-month after the operation. Left ventricular systolic and diastolic function, longitudinal strain, difference of time to peak between the ablation segment and the surrounding segments were analyzed. Blood samples were collected before and one hour after the operation to examine the serological results. Results: Immediately and 6 months after the operation, all animals survived with normal cardiac function. No severe complications such as cardiac tamponade or bundle branch block occurred. The Troponin I level was significantly elevated immediately after the operation(P<0.05). The thickness of the ablated IVS was significantly reduced 6 months after the operation compared with before the operation[(3.23±1.21)mm vs (8.53±0.44)mm, P<0.05]. M-mode echocardiography showed that the amplitude of movement of the ablated region of the experimental group 6 months after the operation was significantly decreased compared with the control group(P<0.05). Three dimensional strain analysis showed that for the experimental group, the longitudinal strain of the ablation segment was significantly reduced and the difference of time to peak was significantly delayed, compared with the control group(P<0.05). Conclusions Echocardiography-guided transthoracic laser ablation of IVS is a safe, effective, and minimally invasive method. It is capable to reduce the volume of IVS without influencing the cardiac function, which makes it a potential alternative for HOCM treatment.

Pancreatic adenocarcinoma (PAAD) is one of the most lethal malignancies. Although gemcitabine (GEM) is a standard treatment for PAAD, resistance limits its application and therapy. Secoemestrin C (Sec C) is a natural compound from the endophytic fungus Emericella, and its anticancer activity has not been investigated since it was isolated. Our research is the first to indicate that Sec C is a broad-spectrum anticancer agent and could exhibit potently similar anticancer activity both in GEM-resistant and GEM-sensitive PAAD cells. Interestingly, Sec C exerted a rapid growth-inhibiting effect (80% death at 6 h), which might be beneficial for patients who need rapid tumor shrinkage before surgery. Liquid chromatography/mass spectrometry and N-acetyl-l-cysteine (NAC) reverse assays show that Sec C sulfates cysteines to disrupt disulfide-bonds formation in endoplasmic reticulum (ER) proteins to cause protein misfolding, leading to ER stress and disorder of lipid biosynthesis. Microarray data and subsequent assays show that ER stress-mediated ER-associated degradation (ERAD) ubiquitinates and downregulates YAP to enhance ER stress via destruction complex (YAP-Axin-GSK-βTrCP), which also elucidates a unique degrading style for YAP. Potent anticancer activity in GEM-resistant cells and low toxicity make Sec C a promising anti-PAAD candidate.