AIM: To investigate the physiological function of the novel serine protease SNC19 protein and its possible role in cancer invasion and metastasis. METHODS: Monoclonal antibodies directly against SNC19 extracellular domain was prepared. The protein and SNC19 mRNA expression were determined in different kinds of cell lines respectively by Western blot and Northern blot analysis. Cellular migration and adhesion abilities were assayed by monoclonal antibody blocking method. RESULTS: Western blot analysis showed there were two bands of SNC19 protein in BCAP37, COLO205, SW480 cells at about 120 kD and 60 kD while only one band in SW620 cells at 60 kD; Northern blots showed a approximate 3.4-kilobase fragment appearing in most epithelial-derived cell lines with this only form and high levels but no detection was obtained in OV, TCA8113, KB and SGC7901 cells. In antibody blocking experiments, the migration of SW480 cells was significantly inhibited compared with the control and the abilities of (SW480/SW480), SW480/NIH3T3 adhesion increased at the beginning of the experiments, but the difference reduced (along) with the time passed.CONCLUSION: SNC19 protein is closely related with cellular homogeneous and heterogeneous adhesion as well as cellular motility. As a novel serine protease, it may participate both in physiological and pathological processes, such as cell migration, tissue remodeling and cancer invasion and metastasis.

Cancer is still one of the major diseases threatening human life and health. At present, how to achieve precise diagnosis and treatment of tumors is the biggest challenge in cancer treatment. Prodrugs use the tumor specificity of targeting molecules to deliver anticancer drugs to tumor sites, which can effectively improve drug bioavailability, therapeutic efficacy and safety, and are currently a hot spot in the research and development of anticancer drugs. The targeting molecules of prodrugs mainly include nucleic acid aptamers, polymers, antibodies, polypeptides, etc. Among them, polypeptides have the advantages of good biocompatibility, controllable degradation performance, high in vivo responsiveness, and simple and easy preparation methods, and are widely used. It is used to construct peptide-drug conjugates (PDC) prodrugs to achieve targeted therapy of tumors. In recent years, with the development of phage peptide library technology and peptide standard solid-phase synthesis technology, more and more targeted peptides have been discovered and effectively synthesized and modified, providing strong support for the development of PDC. This review briefly introduces the types and functions of functional peptides and linkers in PDC, and discusses the application of PDC in chemotherapy, immunotherapy and photodynamic therapy in tumor targeted diagnosis and treatment, and finally summarizes the difficulties faced by PDC drug development.

Humans ; Infant ; Lead Poisoning, Nervous System, Childhood ; diagnosis ; therapy ; Male

China ; epidemiology ; Drug Resistance, Bacterial ; Electrophoresis, Gel, Pulsed-Field ; Humans ; Listeria monocytogenes ; physiology ; Listeriosis ; epidemiology ; Serotyping

OBJECTIVETo observe the effect of Zhenqing Recipe (ZQR) on non-alcoholic fatty liver (NAFL), and the expression of hepatic salt-inducible kinase 1 (SIK1) and sterol-regulatory element binding protein-ic (SREBP-lc) in type 2 diabetes rats.

METHODSA rat model of type 2 diabetes was established by high fat/sucrose diet combined with intraperitoneal injection of small dose streptozotocin (STZ) . Modeled rats were randomly divided into the model group, the ZQR group, and the metformin group, 8 in each group. Eight rats were recruited as a normal control group. ZQR at the daily dose of 12 g crude drugs/kg was administered to rats in the ZQR group by gastrogavage. Metformin suspension at the daily dose of 150 mg/kg was administered to rats in the metformin group by gastrogavage. Equal volume of distilled water was administered to rats in the normal control group and the model group. All medication lasted for 12 weeks. The levels of fasting blood glucose (FBG), free fatty acid (FFA), serum triglyceride (TG), serum total cholesterol (TC), serum alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were detected. The body weight and wet liver weight were weighed, and the liver weight index calculated. The liver TG content was measured. The pathological changes of liver and the expression of SIK1 were observed by HE staining and immunohistochemistry. The mRNA and protein expression of SIK1 and SREBP-1c were detected using RT-PCR and Western blot.

RESULTSCompared with the normal control group, FBG, FFA, TG, TC, ALT, AST, liver weight index, and liver TG contents significantly increased (P < 0.01); liver steatosis was severe, the mRNA and protein expression of SIK1 obviously decreased (P < 0.01); mRNA and protein expression of SREBP-1c increased (P < 0.01). After drug therapy, compared with the model group, FBG, FFA, TG, TC, ALT, AST, and liver weight index significantly decreased, liver TG contents significantly decreased, the mRNA and protein expression of SIK1 obviously increased, while mRNA and protein expression of SREBP-1c obviously decreased (P < 0.05, P < 0.01) in the ZQR group and the metformin group (P < 0.05, P < 0.01); and the pathological changes were also improved. All the indices were improved more in the ZQR group (all P < 0.05).

CONCLUSIONIn this experiment, we found that the expression of SIK1 decreased in NAFL rats with type 2 diabetes. ZQR could alleviate lesion of NAFL type 2 diabetes rats possibly by up-regulating hepatic SIK1 expression at mRNA and protein levels.

Animals ; Diabetes Mellitus, Type 2 ; complications ; drug therapy ; metabolism ; Disease Models, Animal ; Drugs, Chinese Herbal ; therapeutic use ; Fatty Liver ; complications ; drug therapy ; metabolism ; Liver ; metabolism ; Male ; Protein-Serine-Threonine Kinases ; metabolism ; Rats ; Rats, Wistar ; Sterol Regulatory Element Binding Protein 1 ; metabolism

Purpose:To study the effect of FasL gene on human lung adenocarcinoma cell lines and possibility of ex- ogenous FasL gene for gene therapy of lung cancer.Methods:An adenoviral expression vector with full length cDNA of FasL gene insert was constructed(Ad-FasL) and transfected into A549 cells.The effect of exogenous FasL gene on the growth of A549 cells was examined in vitro and in vivo.Results:Expression of FasL gene in A549 cells was confirmed by FCM and RT-PCR.The in vitro growth of the Ad-FasL transfected A549 cells was significantly inhibited (inhibition rate: 84%) as compared to mock (Ad-LacZ) transfected A549 cells.Colony-forming activity in vitro of the Ad-FasL transfected A549 cells was completely inhibited.The Ad-FasL transfected cells became apoptotic which was confirmed by the appear- ance of pre-G_1 on flow cytometry (FCM).The growth of A549 xenografts in nude mice was retarded by intra-tumol injection of Ad-FasL.Conclusions:FasL gene participates in the induction of cell apoptosis.Its use in gene therapy of cancer is promising.

Objective To summarize and analyze the results of our university graduates' participation in the national medical licensing examination in order to investigate the clinical medical teaching reform.Methods There were 770 candidates who took the NMLE from 2011 to 2013.Excel 2007 was used to statistically analyze the total score,passing rate,average score and mastery rate for each subject,and average score and mastery rate at different cognitive level.Results In these three years,our candidates' total pass rate was higher than the national average total pass rate,respectively higher 17.11％,18.10％,17.82％;the pass rate of practical skills examination was also higher than the national average pass rate,respectively higher 7.30％ and 7.19％ and 5.90％;the pass rate of theory examination was higher than the national average pass rate,respectively higher 12.91％,12.97％ and 14.29％.The average score and mastery rate for each subject,the average score and mastery rate at different cognitive level were also all higher than those of the national average of medical colleges.Conclusions National medical licensure examination can be used as an important reference,through optimization of medical curriculum and teaching mode,optimization of clinical practice skills training system and optimization of clinical practical skill evaluation system etc.,to further improve the clinical medical personnel training mode.

Objective To investigate the clinical characteristics and treatment of acute postrenal acute renal dysfunction associated with ceftriaxone.Methods Twenty-five cases of the ceftriaxione-associated acute postrenal renal insufficiency were reviewed.There were 16 males and 9 females,mean age 28years.The serum contents of BUN and Cr were ( 18.6 ± 7.0) mmol/L and (635.5 ± 248.7 ) μmol/L,respectively.All patients were divided into two groups depending on the therapy:11 patients accepted the drug therapy (alkalinization of the urine,antispasmodic,etc) and 14 patients accepted the intraureteral cannula.The clinical characteristics and the treatment effect were compared between the 2 groups.Results The patients of the intraureteral cannula group ( 1.4 ± O.7 d) went to hospital earlier than the drug therapy group (3.0 ± 1.4 d) ( P =0.045 ) after the symptom of oliguria or anuria appeared.There were no significant differences in serum creatinine,urea nitrogen,and the age between the 2 groups ( P ＞ 0.05 ).All the patients were cured after treatment.There were no significant differences in recovery time (2.9 ± 1.1 d and 3.2 ± 1.2 d,P =0.963) and hospitalization time (7.0 ±2.3 d and 5.9 +3.9 d,P =0.568) between the 2 groups.Conclusions The acute renal failure associated with ceftriaxone should have high attention.The prompt medical attention,including the intraureteral eannula and the drug therapy,can both achieve the satisfying curative effect.

Objective To observe the effect of underground part-obturated environment on human health. Methods 12 testees were chosen to undergo the experiment of 6 days in the part-obturated situation. The microclimate blood routine immunological items and the symptoms were investigated. Results In the part-obturated environment the average temperature was 15.2 ℃ the humidity was 75.5% the velocity of the wind was 0.06 m/s. Among the testees one was found had higher WBC number three had higher lymphocytes number. During the experiment the average value of CD3+ CD8+ and B cell were 60.05% 26.04% and 10.41% respectively the NK cell was higher compared with the controlbefore the experiment the differences were significant P

Functional constipation (FC) is a common functional bowel disorder disease that affects life quality of a large number of people. This study aimed to explore the impact of different intensities of electro-acupuncture (EA) treatment for FC patients. Totally, 111 patients with FC meeting the Rome III criteria were randomly assigned to different intensities of EA groups (low and high intensity of EA groups) and medicine-controlled (MC) group. In EA groups, patients were treated with EA at quchi (LI11) and shangjuxu (ST37) bilaterally for 4 weeks, 5 times/week in the first 2 weeks, and 3 times/week in the last 2 weeks. In MC group, 5 mg mosapride citrate was administered orally 3 times/day for 4 weeks. Spontaneous bowel movement frequency each day was recorded using a constipation diary. Self-rating anxiety scale (SAS) and self-rating depression scale (SDS) were used to assess the patients' psychological state. Cortisol (CORT), substance P (SP), and vasoactive intestinal polypeptide (VIP) were evaluated at baseline and at the end of 4 weeks after treatment. As compared with the baseline, there was statistically significant increase in stool frequency every week (P<0.01), but there was no statistically significant difference among the three groups. As compared with the baseline, after 4 weeks of EA therapy, the scores of SDS and serum levels of CORT were decreased significantly in low intensity of EA group (P<0.01), and the serum levels of SP and VIP were increased significantly (P<0.05); the scores of SAS and SDS and serum levels of CORT were decreased significantly in high intensity of EA group (P<0.05), and the serum levels of SP and VIP were increased significantly (P<0.05); the serum levels of CORT and VIP were increased significantly in MC group (P<0.05). As compared with MC group, after 4 weeks of treatment, the serum levels of SP were signifcicantly increased in low intensity of EA group (P<0.01). Low and high intensities of EA could increase the stool frequency, improve the FC patient's anxiety and depression, reduce the serum levels of CORT, and increase the serum levels of SP and VIP effectively. It is concluded that both low and high intensities of EA are effective for FC patients, but there is no significant difference between the low and high intensities of EA.