Protein tyrosine kinase genes are the largest family of oncogenes. This is not surprising since protein tyrosine kinases are important components of signal transduction pathways that control cell shapes, proliferation, differentiation, and migration. This review will address the recent progress in understanding the function of Eph receptor and ephrin ligands in normal development and how disregulation of these functions could promote tumorigenesis.

Acupuncture Points ; Acupuncture Therapy ; methods ; Antipsychotic Agents ; therapeutic use ; Combined Modality Therapy ; Electroacupuncture ; methods ; Female ; Humans ; Male ; Schizophrenia ; therapy

OBJECTIVE:To investigate effectiveness and safety of rh-endostatin in the treatment of keloid.METHODS:Sixty-four keloid patients in Nanchong Central Hospital during Jan.2015-Jan:2016 were divided into observation group and control group by random number table,with 32 cases in each group.Both group received fractional CO2 laser treatment.After surgery,control group was given antioxidant drug and antibiotics routinely.Observation group was additionally given Rh-endostatin injection 0.1-0.2 mg/cm2 via keloid body,once a month,for twice,on the basis of control group.Clinical efficacy,symptom score after laser treatment and 2 months after laser treatment,wound healing time,wound pigmentation area and keloid area before and after treatment,the occurrence of ADR were compared between 2 groups.RESULTS:There was no statistical significance in total re sponse rate (93.75％ vs.87.50％) and the incidence of ADR (15.63％ vs.12.50％) between observation group and control group (P＞0.05).There was no statistical significance in symptom score of control group between after laser treatment and after 2 months of treatment (P＞0.05).The erythema,edema and pigmentation scores of observation group were significantly lower than before treatment and control group,with statistical significance (P＜0.05);there was no statistical significance in skin itching and burning sensation score between 2 groups (P＞0.05).The wound incrustation time,decrustation time and wound healing time of observation group were significantly shorter than those of control group,with statistical significance (P＜0.05).Pigmentation area and keloid area of 2 groups were significantly smaller than before,and the observation group was significantly smaller than the control group,with statistical significance (P＜0.05).CONCLUSIONS:Rh-endostatin can alleviate erythema,edema,pigmenta tion and other symptoms effectively,shorten healing time,and inhibit pigmentation and keloid regeneration effectively with good safety.

Objective To investigate the expression of receptor tyrosine kinase EphB2 and its relationship with peritumoral brain edema (PTBE) in meningiomas and to explore the possible mechanism of PTBE in meningiomas. Methods A total of 44 meningioma tissue samples from patients undergoing surgery and 14 normal meninges samples as the control were collected for the examination of the immunoreactive EphB2 expression. The expressions of EphB2 in different types of meningiomas were determined by immunohistochemical method. Peritumoral brain edema was assessed on a subjective 5 point(0～4) scale based on the data from preoperative magnetic resonance imaging scan. Results ① The expressions of EphB2 in 44 cases of meningiomas were: scale 4 in 7 cases, scale 3.5 in 5 cases, scale 3 in 6 cases, scale 2.5 in 2 cases, scale 2 in 8 cases, scale 1 in 13 cases, scale 0 in 3 cases, mean scale 2.19 . ② No expression of EphB2 was found in 10 out of the 14 normal meninges samples, but minimal (scale 1) expression of EphB2 was found in only 4 cases. ③ Preoperative MRI results showed different levels of PTBE in 33 out of 44 cases. Conclusion There is expression of EphB2 in the cytoplasm in most meningiomas. The expression of EphB2 in meningnioma is positively correlated with peritumoral brain edema, suggesting that EphB2 participates in PTBE of meningiomas.

Objective To explore the distribution characteristics of high density lipoprotein (HDL) subclasses in elderly patients with type 2 diabetes mellitus (T2DM), and to evaluate the relationships of them with oxidative stress and carotid atherosclerosis. Methods The serum levels of HDL subclasses and 8-iso-prostaglandin (PG) F2α were assayed, the carotid ultrasound examinations were executed in 56 elderly patients with T2DM (male: 40, female: 16) and 41 elderly healthy controls (male: 31, female: 10). Results Compared with control group, the serum level of HDL3 was significantly lower in T2DM group [(0.51±0.21) mmol/L vs. (0.59±0.15) mmol/L,t=1.991, P＜ 0.05], and the serum levels of HDL and HDL2 were also decreased [(1.07±0.36)mmol/L vs. (1.18±0.32) mmol/L; (0.56±0.25) mmol/L vs. (0.64±0.33) mmol/L], but there were no statistical significances (t= 1.611 and 0.614 both P＞0.05). The HDL3 was negatively correlated with HbA1C (r=-0.503, P=0.005). The values of absorbance of serum 8-iso-PG F2αwere significantly decreased in T2DM group than in control group (0.017±0. 004 vs. 0. 021±0. 008,t=2.245, P＜0.05). The mean carotid intima-media thickness (IMT) was higher in T2DM group,but there was no statistically significance. The detection rate of carotid atherosclerotic plaques was significantly higher in T2DM group than in control group (63.3% vs. 36.0%, x2=4.076, P＜0.05). Conclusions The low level of small particles HDL3 as well as elevated oxidative stress may contribute to the development of atherosclerosis in elderly patients with T2DM.

A total of 105 patients with first-episode schizophrenia (male =51,female =54) and 99 normal controls (male =51,female =48) were included into this retrospective case-control study.Childhood trauma questionnaire-28 item short form (CTQ-SF) was used to assess the experience of childhood abuse.The result of binary logistic regression showed that emotional abuse (β =0.630,P ＜ 0.05) and emotional neglect(β =0.270,P ＜ 0.05) were included into the final model of predicting schizophrenia.It indicates that patients with first-episode schizophrenia experienced more early life stress than controls.Particularly emotional abuse and emotional neglect may play important roles in the onset of schizophrenia.

Objective To analyze the epidemiological features and influencing factors of human brucellosis in Qinghai province,and to provide scientific basis for prevention and control of brucellosis.Methods From 2006 to 2010,select the high incidence areas of brucellosis in Qinghai province and five counties(Henan,Dari,Tianjun,Ping'an and Haiyan counties) included in the “Central Subsidies to Local Public Health Special Fund Human Brucellosis Prevention and Control Projects” for the survey point,as well as high-risk employees from Qinghai Biological Pharmaceutical Factory were investigated.Combined with epidemiological questionnaire investigation [done according to the “National Human Brucellosis Surveillance Program(Trial)”],clinical symptoms and signs,confirmed human brucellosis patient were tested by intradermal allergy test,rose bengal plate agglutination test(RBPT) and standard tube agglutination test (SAT),in accordance with “Diagnostic Criteria and Principles of Management of Brucellosis” (GB 15988-1995) and“Diagnostic Criteria for Brucellosis” (WS 269-2007).Results Of 8368 serum samples detected,347 were RBPT positive,and the positive rate was 4.15％;5346 serum samples were tested by SAT,180 were positive,and the positive rate was 3.37％.In June 2009,112 employees in Qinghai Biological Pharmaceutical Factory were investigated on a follow-up survey,83 were RBPT positive,the positive rate was 74.11％; 58 were SAT positive,the positive rate was 51.79％.Eight of them were new cases and 4 were chronic brucellosis.Twenty five new cases were reported between 2006 and 2010.The peak incidence was from March to July.Most of the cases were herdsmen.ConclusionStrengthening animal quarantine,strengthening public education,and improving protection awareness,can effectively control the disease brucellosis.

Background Retinal pigment epithelium (RPE) cell transplantation is the primary means of human trial for the treatment of retinal degeneration.Induced pluripotent stem cells (iPSCs) will become an important source for cell transplantation.In addition,iPS-RPE cells may provide a personalized treatment platform for the patient's own cells treatment.Objective This study was to evaluate the feasibility of human fibroblasts differentiate toward iPSCs from retinitis pigmentosa (RP) patients and toward iPSC-RPE cells from non-RP individual by retroviral transfection of Oct4,Sox2,c-Myc and KLF4 genes.Methods Human thigh skin tissues were obtained from a RP patient with hotspot mutation of SNRNP200 p.S1087L and individual without SNRNP200 p.S1087L mutation,respectively,with the size 2 c m×3 cm.Human dermal fibroblasts were isolated and cultured by trypsin digestion and explant method.The fibroblasts were transfected by a series of retrovirus and cultured by human embyonic cellconditioned medium to generate and induce iPSCs,and then the iPSCs were identified by morphology,alkaline phosphatase (AP) staining and immunofluorescence assay of specific markers of pluripotent stem cells.iPSCs suspension were injected into SCID mouse to observe the tumorigenesis.The iPSCs from non-RP subject were induced to differentiate toward iPS-RPE cells by embryonic body (EB) inducing method,and iPS-RPE cells were identified by detecting the expression of RPE65,zonula occludens protein 1 (ZO-1) and lecithin retinol acyltransferase (LRAT).Results Cultured human dermal fibroblasts showed fusiform or polygon shape and intercellular close arrangement,and Vimentin was positively expressed in the cells.Small cell colonies were harvested 5-7 days after infected by retroviruses,and the morphology changed from spindle into round mass.The hESC-like iPSCs clonies appeared 20 days after cultivation,and the positive expressions of hESC-specific surface antigens including SSEA3,SSEA4,TRA-1-60,TRA-1-81 and Nanog were found in the cells 25-30 days after cultivation,and the positive staining of AP was obtained 12 weeks after cultivation.A teratoma was formed at the injection site of iPSCs suspension in SCID mouse.Immunofluorescence technique showed that RPE cell-specific proteins including RPE65,ZO-1 and LRAT proteins were positively expressed in iPS-RPE cells at 30 days after differentiation.Conclusions Mutation SNRNP200 p.S1087L of RP patient-specific iPSCs can be induced from human dermal fibroblast by retrovirus infection method.The function and morphology of the iPSCs were similar to hESCs.Human iPSCs cell line generated from the dermal fibroblasts of non-RP individuals can differentiate into iPS-RPE cells.

Objective To evaluate the clinical value of multiple bladder biopsies in the diagnosis and treatment of non-muscle invasive bladder cancer (NMIBC) during transurethral resection of bladder tumor(TURBT).Methods The data of 408 NMIBC patients from January 2009 to December 2013 was analyzed retrospectively.There were 302 males and 106 females.The mean age of these 408 patients was 65 years old from 33 to 86 years.Bladder multipoint biopsies were performed in 216 patients (biopsy group),and were not performed in the other 192 patients (control group).The multipoint biopsies were taken from right and left bladder walls,anterior and posterior walls,dome,trigone,prostatic urethra and abnormal mucosa.There were 127 males and 89 females in the biopsy group,with a mean age of 64 years old (from 18 to 87 years).In the control group,118 males and 74 females aged between 15 and 92 years have an average age of 66 years old.There was no statistically significant difference in regard to gender and age between the two groups.The positive rate of biopsy and whether the diagnosis and treatment plan changed in the study group were recorded and the recurrence and progression rates were compared between study and control groups.Results Of these 216 multiple mucosa biopsies,the total abnormal detection rate was 48.1％ (104/216).There were urothelial carcinoma in 12.5％ (39/216),carcinoma in situ in 5.6％ (12/216),dysplasia in 9.7％ (21/216),cystitis in 20.4％.The final diagnosis were changed in fifteen patients (6.9％) due to the biopsy results,and 38 patients(17.6％) treatment plans were changed.The 1-,3-,and 5-year recurrence-free survival rates (RFS) of biopsy group and control groups were 96.3％ vs.85.4％(x2 =14.955,P=0.000),85.2％ vs.69.8％ (x2 =13.183,P =0.000) and 69.9％ vs.64.1％ (x2 =1.574,P =0.245);progression-free survival(PFS) were 99.1％ vs.96.3％ (x2 =8.253,P =0.006),94.0％ vs.87.0％ (x2 =5.901,P=0.017) and90.3％ vs.85.4％ (x2 =2.273,P=0.169).The 1-and 3-year RFS and PFS of biopsy group were higher than control group.There was no significant difference in the 5-year RFS and PFS between the two groups.Conclusions Multiple bladder biopsies could be helpful for pathological diagnosis and the post-TUR treatment of NMIBC.Furthermore,it may reduce the early recurrence and progression rates of NMIBC,but have no effect on long-term prognosis.

Objective:To detect the effect of microRNA-7 ( miR-7 ) knockdown on pathology in murine acute lung injury ( ALI) model,and preliminarily explore its significance.Methods:Murine ALI model was performed by intraperitoneal injection of Li-popolysaccharide (LPS) (10 mg/kg) into miR-7KD mice and wild-type (wild type,WT) mice respectively.Then,the pathologic injury of lung tissue were observed by HE staining.And total cell count of bronchoalveolarlavage(BAL) was calculated.The relative expression of related cytokines in lung tissue was analyzed by Real-time PCR assay.Furthermore,the changes on proportion of innate immune cells (γδT cell and F4/80 macrophages cell) and adaptive immune cell ( CD4+T cell and CD8+T cell) were analyzed by FACS.Meanwhile, the expression of CD62L and CD69,as well as the absolute number,in CD4+T cell were also analyzed.Results: Compared with WT mice,pathological damage in lung tissues was significantly alleviated in miR-7KD mice.Real-time PCR analysis showed that the relative expression of IL-6 was obviously reduced (P<0.01),conversely,relative expression of IL-4 and TGF-βwere obviously increased (P<0.05).Furthermore,the total cell number in BAL also reduced significantly (P<0.05).Importantly,FACS analysis showed that the proportion and the absolute number of F4/80+Mφcells obviously reduced (P<0.05);however,the proportion of γδT cells increased (P<0.05).Moreover,the proportion and the absolute number of CD4+T cells and CD8+T cells were significantly reduced (P<0.05). Finally, the proportion and the absolute number of CD62L+in CD4+T cells were upregulated vigorously,contrastly,the proportion and the absolute number of CD69+in CD4+T cells were notably up-regulated (P<0.05).Conclusion:miR-7 defeciency could significantly ameliorate the pathology of murine ALI,suggesting that it may play an important regulatory role in the development of ALI.