The key factor of chemotherapy for brain disorders is to penetrate brain blood barrier(BBB). Receptor mediated en-docytosis is one of the mechanisms for drug carriers to cross the BBB. Angiopep-2(ANG)can specifically bind to low density lipopro-tein receptor-related proteins 1(LRP-1)overexpressed on BBB and glioma cells,thus exhibits a higher LRP-mediated BBB penetra-tion capability. Its targeting efficiency is higher than that of other targeting molecules such as transferrin and(TF)lactoferrin(LF). This paper introduces the structure and function of ANG,and its application in brain targeting delivery systems,in order to provide references for research and development of brain targeting preparations and guidance for therapy of brain diseases.

Objective To construct bispecific antibody BsAb1/17 against both IL-1β and IL-17A,express and purify the biologically active BsAbl/17 protein in prokaryotic system for further studies and applications. Methods VH1VL17-CL and VL1VH17-CH1 gene segments were constructed by overlap-PCR.Restriction enzyme sites Nco Ⅰ and BamH Ⅰ were designed at the 5'and 3' end primers respectively. The products of overlap-PCR were ligated to the Nco Ⅰ/BamH Ⅰ -prepared pET-27b vector. The recombinant plasmids pET-27b-VH1 VL17-CL(petA) and pET-27b-VL1 VH17-CH1 ( petB ) were transformed into E. coliRosetta separately. The expressing products were analyzed by SDS-PAGE and Western blot. Neutralization activity of the bispecific antibody for blocking the induction of IL-18 expression by IL-1β in human T cells was determined by real-time PCR. Neutralization activity of the bispecific antibody for blocking the induction of IL-6 expression by IL-17A in HeLa cells was determined by ELISA assay. Results The structure of the plasmids pET-27b-VH1 VL17-CL(petA) and pET-27b-VL1 VH17-CH1 (petB)was confirmed by DNA sequencing. After induction, the fusion proteins were expressed mainly as inclusion bodies. The purity of the both proteins exceeded 90%. SDS-PAGE analysis suggests the relative molecular mass of both products expressed by petA and petB were approximately 38× 103, which is in accordance with the theoretical value. The results of Western blot and ELISA test demonstrated that BsAb1/17 molecule had binding ability to both IL-1β and IL-17A. The BsAb1/17 could block IL-1β to stimulate human T cell to express IL-18 and block IL-17A to stimulate HeLa cell to express IL-6. Conclusion We successfully constructed a novel bispecific antibody BsAb1/17 against both IL-1 β and IL-17A, and expressed biologically active BsAb1/17 protein in prokaryotic system.

Objective To investigate the relationship between carotid atherosclerotic plaque and multiple risk factors of angiocardiopathy,and to evaluate the injuries caused by different risk factors to subclinical target organ to control the general risk factors of angiocardiopathy.Methods Four hundred and twenty six outpatients and impatients,treated in our hospital from May 2007 to May 2009 with the results of color ultrasonic examination,were divided into carotid atherosclerotic plaque group(284 cases) and no carotid atherosclerotic plaque group( 142 cases).The clinical information including their age,body mass index,smoking condition,past medical history such as hypertension,diabetes mellitus and hyperlipoidemia were recorded,and the levels of total cholesterol(T C),high density lipoprotein cholesterol( HDL-C),low density lipoprotein cholesterol(LDL-C),triglyceride (TG),lipoprotein ( a ) ( LP (a) ),apolipoprotein A - 1 ( Apo A 1 ),apolipoprotein B ( Apo B ),highsensitivity C-reactive protein( hs-CRP),homocysteine ( HCY),microalbuminuria( MAU ) and uricacid(UA) were determined by lab tests.The independent variable and univariable data were processed and analyzed statistically to find out the risk factors of carotid atherosclerotic plaque.Results Age and drinking were significantly correlated with the carotid intima-media wall thickening(IMT) (P ＜ 0.001 ).Overweight,diabetes mellitus,increased LP (a),hyperlipoidemia,age,increased MAU and HCY could independently predict carotid atherosclerosis and plaque formation ( x2 =71.35,38.45,t =3.26,x2 =37.23,t =118.51,6.723 and 3.17respectively,Ps ＜ 0.05 ).The aggregated number of the risk factors was correlated to IMT and carotid atherosclerotic plaque ( P =0.0001 ).Conclusion Age,drinking,overweight,diabetes mellitus,increased LP (a),hyperlipoidemia,MAU and HCY are risk factors of carotid atherosclerosis and plaque formation,and the contribution of each factor can multiply and overlap,more risk factors means greater risk.

OBJECTIVETo establish a animal model of biliary leakage in pigs with laparoscopy.

METHODSEight healthy Bama minipigs were subject to laparoscopic surgery under general anesthesia.The cystic duct was resected at 0.5-1.0 cm from the root and the stump was left open with the gallbladder removed. Blood routine and hepatic functions of the pigs were tested before and 24 h after the surgery, and endoscopic retrograde cholangiography (ERC) was performed 24 h after the surgery. At 48 h after the surgery, the pigs were sacrificed for observation of the stump of the cystic duct.

RESULTSThe gallbladder, cystic duct, cystic artery, and the anatomical relations between the gallbladder and liver and between the cystic duct and common bile duct were fully exposed under laparoscopy. White blood cells, neutrophils and direct bilirubin increased significantly after the operation (P<0.05). The cystic ducts were resected at 0.5-1 cm away from the roots of the cystic ducts in 7 pigs and at 2 cm in 1 pig.

CONCLUSIONLaparoscopy is safe and feasible for establishing the porcine model of biliary leakage.

Animals ; Biliary Fistula ; Cystic Duct ; surgery ; Disease Models, Animal ; Female ; Laparoscopy ; Male ; Swine ; Swine, Miniature

Objective To investigate the expression of TFPT in non-small cell lung cancer (NSCLC), evaluate its clinical significance and study its influence on NSCLC. Methods Total of 50 specimens of carcinoma tissues and para-carcinoma tissue after surgery were collected.Then qRT-PCR was performed for TFPT expression. The correlations between the expression of TFPT and pathological characteristics were analyzed.pcDNA3.1-TFPT was transfected to up-regulate TFPT expression in A549 cells,and the transfection efficiency was evaluated by qRT-PCR.CCK8 assay was performed to evaluate the effects of ectopic TFPT on proliferation of A549 cells.The expression of TCF3 protein was determined by Western blot.Results The expression level of TFPT was up-regulated in tumor tissue compared with that in the para-carcinoma tissue. The expression of TFPT was associated with patients'gender, tumor size, differentiation degree, lymphatic metastasis and the distal metastasis (P < 0.01). Meanwhile, overexpression of TFPT increased the expression of TCF3 and the proliferation of A549 cells. Conclusions The expression of TFPT is obviously increased in NSCLC patients of female,larger tumor size, higher clinical stage or advanced histological grade. TFPT may promote cell proliferation by affecting the expression of TCF3 proteins.

OBJECTIVE: To explore the change and impact factors of craving for heroin in patients after 6 month methadone maintenance treatment (MMT). METHODS: The questionnaire of craving for heroin was used to measure the level of craving for heroin when patients just entered the study and were treated for 6 months. The influence of MMT on craving in patients were analyzed. RESULTS: The total score and score for other factors decreased except the factor "self-control" after MMT. The craving for high dose patients decreased significantly after 6 month treatment (P<0.05). The degree of craving for heroin in males and females all decreased after MMT, but no significant difference was shown (P>0.05). The craving degree for heroin in patients with long drug use was higher than that of patients with short drug use. After the treatment, the improvement of craving was more significant for the long drug users. CONCLUSION MMT can decline the craving for heroin in drug users. Dosage for methadone and gender may be the risk factors of craving change.
Adult ; China ; Female ; Heroin Dependence ; drug therapy ; psychology ; rehabilitation ; Humans ; Male ; Methadone ; therapeutic use ; Substance Withdrawal Syndrome ; drug therapy ; psychology ; Surveys and Questionnaires ; Young Adult

This paper is based on the theory of"internal diseases will be presented externally"in Traditional Chinese Medicine, combined with the idea of syndrome differentiation and grasping the main symptoms, and proposes the concept of"virtual special disease". It is extracted from ancient books and expert experience, and it is believed that it is widespread and can be tested by clinical practice. The application of virtual syndrome to diagnosis can achieve the purpose of simplifying the complexity TCM syndrome differentiation. On the one hand, it provides a new exploration for enriching the TCM syndrome differentiation system; on the other hand, it provides new ideas for supplementing the biological research of syndromes and developing the diagnosis of integrated traditional Chinese and Western medicine.

Objective To evaluate the risk of occupational noise-induced hearing loss in workers in a metal tool manufacturing enterprise, and to carry out risk classification and risk management. Methods A total of 91 male noise-exposed workers from a metal tool manufacturing enterprise in Hebei Province were selected as the research subjects using the convenience sampling method. The work site survey on occupational health and the measurement on individual noise exposure level were carried out. The ISO 1999：2013 (E) Acoustics-Estimation of Noise-Induced Hearing Loss was used to predict the risk of high frequency hearing loss (HFHL) and occupational noise-induced deafness (ONID). The risk classification and risk management were conducted using the WS/T 754-2016 Guideline for Risk Management of Occupational Noise Hazard (hereinafter referred to as WS/T 754-2016). Results The individual noise exposure intensity of workers in the six work sites of the enterprise, including blade workers, sheet punching workers, roller forging workers (hoe), hole punching workers, roller forging workers(shovels), and carpenters, exceeded the national occupational exposure limit, with the maximum volume of 91.2-104.1 dB(A). Among these workers, the positions of blade workers, sheet punching workers, and roller forging workers (hoe) were identified as critical control points for noise hazards in the enterprise. The detection rates of HFHL and ONID were 24.2% and 8.8%, respectively. The risk prediction results showed that, based on the actual noise exposure time and age of the study subjects, the risk of HFHL and ONID ranged from 1.7%-48.8% and 0.0%-29.5%, respectively. The risks of HFHL caused solely by occupational noise exposure when working up to 50.0, 55.0, and 60.0 years of age were 11.4% to 64.7%, 16.4% to 65.1%, and 17.2% to 59.4%, respectively. The risks of ONID caused solely by occupational noise exposure were 0.0% to 45.5%, 4.2% to 51.7%, and 5.9% to 57.4%, respectively. Except for the blade workers, the predicted median of potential noise-induced permanent threshold shifts (NIPTS) in the other five positions were lower than the actual values of NIPTS, with the difference ranging from 3.0-28.3 dB, and 73.3% of them underestimated by 10.0 dB or more. Conclusion The outcome of noise exposure on the hearing of workers in this enterprise are severe. Risk management should be conducted according to the WS/T 755-2016.

In order to obtain the lead compound for treatment of rheumatoid arthritis (RA), in this study, therapeutic efficacy of three bispecific antibodies (BsAB-1, BsAB-2 and BsAB-3) against both hIL-1beta and hIL-17 were compared on CIA model mice. First, by ELISA method we compared the binding capacity of the three bispecific antibodies to the two antigens. The results showed that all three antibodies could simultaneously bind both antigens, among these antibodies, BsAB-1 was superior over BsAB-2 and BsAB-3. CIA model was established with chicken type II collagen (CII) and developed RA-like symptoms such as ankle swelling, skin tight, hind foot skin hyperemia. The CIA mice were treated with three antibodies once every two days for total of 29 days. Compared with the CIA model mice, the RA-like symptoms of the antibody treated-mice significantly relieved, while the BsAB-1 treated-mice were almost recovered. CII antibody level in the serum and cytokines (IL-2, IL-1beta, IL-17A and TNF-alpha) expression in the spleen were examined. Compared with the CIA model mice, all three antibodies could significantly reduce CII antibody and cytokine expression levels. BsAB-1 antibody was more potent than BsAB-2 and BsAB-3. In summary, BsAB-1 is superior over BsAB-2 and BsAB-3 in amelioration of RA symptoms and regulation of CII antibody production and pro-inflammatory cytokine expression, therefore, BsAB-1 can be chosen as a lead compound for further development of drug candidate for treatment of RA.

Objective To explore the efficacy of standardized diabetes self-management education program. Methods A total of 200 cases of diabetes patients were divided into experimental group and control group with 100 cases each by random digits table method. For experimental group, the patients received standardized diabetes self-management education, for control group, traditional management and occasional telephone follow-up, for 6 months. Blood glucose metabolism, lipid, diabetes self-management ability were evaluated. Results The score in diet control, exercise therapy, medication, self-blood glucose monitoring, complication prevention and self-management ability of experimental group were (20.56 ± 1.23), (15.57 ± 1.62), (13.95 ± 1. 85), (14.62 ± 6.81), (31.65 ± 1.95) , (96.52 ± 1.28) points, and the score of control group were (19.74±1.36), (13.67±3.82), (12.66±1.03), (12.26±2.29), (29.56±1.76), (90.36± 1.94) points. Compliance of two group was improved, and experimental group much better ( t=3.53-5.82, all P<0.05). The fasting blood glucose, postprandial 2h blood glucose, glycosylated hemoglobin, triacylglycerol and total cholesterol of experimental group were (5.52±1.32) mmol/L, (7.69±3.62) mmol/L, (6.22±4.21)%, (1.42±1.28) mmol/Land (4.36±1.27) mmol/L, and those of control group were (6.56±1.23) mmol/L, (8.78±5.42) mmol/L, (7.12±4.29)%, (1.78±1.49) mmol/L and (4.71±2.14) mmol/L. Metabolism of two group was improved, and experimental group much better (t=4.93-6.78, all P<0.05). Conclusions Standardized diabetes self-management education is better than traditional management. It is worthy of clinical application.