Induced pluripotent stem cells (iPSCs) are a type of pluripotent stem cells that can be generated from adult somatic cells.They have similar characteristics and function to embryonic stem cells (ESCs).Over the past decade,iPSCs were widely concerned in regenerative medicine and stem cell field.Especially the patient specific iPSCs have several advantages over ESCs,such as convenient source,do not exist immune rejection and ethical issues,even keep certain individual genotype.At present,tremendous progress have been made about the application of iPSCs in a variety of retinal diseases.Here,this article reviews pluripotent stem cell sources of RPE,photoreceptors and retinal ganglion cells and current transplantation strategies,the safety problems and prospects.

ObJeetive To report a simple and efficient method to label two different types of retinal ganglion cells (RGCs) in mouse retina.Methods Eyeballs were harvested from normal adult C57 BL/6 J mouse,the retinas were isolated,four radial cuts were done,the retinas were pasted on the nitrocellulose membrane with the ganglion cell layer upturned.The immunofluorescence double staining and laser confocal nmicroscope was used to reveal conventional retinal ganglion cells and intrinsically photosensitive retinal ganglion cells (ipRGCs) using Brn3a and Melanopsin.Results The double staining results of whole mount retina showed that conventional RGCs and melanopsin immunopositive ipRGCs had a complementary distribution in mouse retina,these two subtypes of RGCs were predominantly present in the ganglion cell layer.The numbers of ipRGCs was just about 1％-2％ of conventional RGCs,and the axons of ipRGCs toward the direction of the optic disc,several dendrites toward the inner plaximem layer.Conclusion The immunofluorescence double staining of whole mount retina is a simple,stable and efficient method to label two different types of mouse RGCs.

Objective To estabolish an optimal animal model of oxygen-induced retinopathy(OIR) suitable for examining pathogenesis and therapeutic intervention for retinopathy of prematurity(ROP). Methods Fifty-four 7-day-old C57BL/6J mice were devided into two groups. Twenty-seven mice in hyperoxic group were exposed to 75% oxygen for 5 days and then to room air for another 5 days. Twenty-seven mice in normoxic control were exposed to room air for 10 days. The proliferative neovascular response was estimated by observing the vascular pattern in adenosine diphosphate-ase(ADPase) stained retina flat-mounts and quantitated by counting the number of new vascular cell nuclei extending into the internal limiting membrane in cross-sections. Results Angiography in ADP ase stained retina flat-mounts delineated the entire vascular pattern. Hyperoxia-induced neovascularization occurred at the junction between the vascularized and avascular retina in the mid-periphery in all mice exposed to hyperoxia. After 5 days of exposure to hyperoxia at postnatal day 12(P12),the larger central radial vessels became tortuous and constricted and central perfusion became decreased obviously. After return to room air for 2 days at P14,neovascularization was seen. This response was maximal at P17. There was a mean of 44 neovascular nuclei per cross-section extending into the vitreous in hyperoxia compared to less than 2 nuclei in the normoxia control ( P

Objective To investigate clinical efficacy and adverse reactions of Citric acid tandospirone in treating generalized anxiety neurosis.By doing this study,we provide clinical evidence for citric acid tandospirone in treating generalized anxiety neurosis.Methods 92 patients with generalized anxiety were randomly divided into the control group and observation group according to the random number table.There were 46 cases in each group.In the observation group,the patients were given acid citrate edge tandospirone.At the starting the patients were taken 15mg/d. After 3 days the dose increased to 35mg/d by 5mg.The average dose was (31 ±3.4)mg/d.In control group,accord-ing to different patients sleep condition,oxazepam tablets were taken.The daily dosage does not exceed 30mg/d.After two weeks,the dose was gradually reduced to the end.The clinical efficacy,HAMA score and adverse reactions in the two groups were compared.Results Compared to prior treatment,after 2 weeks and 4 weeks the HAMA score in the two groups were significantly different (P<0.05).Compared with the control group,the score in the two group had significantly different after two weeks treatment (t=2.16,P<0.05).The total effective in the observation group was 86.9 %.In the control group the total effective rate was 82.6%.There was no significant difference between the two groups (χ2 =0.33,P>0.05).The rate of adverse reaction in the observation group was 32.6%.The rate of adverse reaction in the control group was 63%.The rate of adverse reaction in the control group and observation group had sig-nificantly different (χ2 =8.58,P<0.05) .Conclusion Acid citrate edge tandospirone on the treatment of general-ized anxiety neurosis showed obviously effect and had fewer adverse reactions.The clinical program is worth of further study and clinical application.

Objective To observe the effects of Sancaoanqian decoction on expression of cytokine IL-1?, IL-6 and TNF RⅡ in experimental autoimmune prostatitis rats, and explore the target protein of cytokine of Chinese herbal compound in treating chronic nonbacterial prostatitis. Methods Seventy-two male Wistar rats were divided randomly into six groups and 12 rats in each group. All groups were made experimental autoimmune prostatitis rat model by injecting SC purified prostate protein with FCA except normal group. The normal and model group were given saline, western medicine group was given indomethacin, large, medium and small doses decoction groups were treated with large, medium and small doses of Sancaoanqian decoction. All rats were sacrificed after 30 days. The mRNA and protein expression of cytokines were tested by methods of immunohistochemistry and fluorescent quantitation RT-PCR. Results Sancaoanqian decoction could reduce the mRNA and protein expression of IL-1?, IL-6 in experimental autoimmune prostatitis rats. There were no significant difference between large and medium doses decoction group, but had a better activity than small dose. The expression of TNF RⅡ were reduced in all doses groups and no difference among three doses of Sancaoanqian decoction. Conclusion Sancaoanqian decoction can regulate the immune function in chronic prostatitis rat model. Down-regulation of cytokines maybe one of important mechanisms in treating chronic prostatitis.

Objective To investigate the effect of di-2-ethylhexyl phthalate (DEHP) on the proliferation of SK-N-SH human neuroblastoma cells and its underlying mechanism. Methods Cells were cultured in estrogen-free improved Dulbecco's Modified Eagle's Medium and then divided into 5 groups: no treatment (control group); treated with 17β-estradiol (E_2 group); treated with DEHP (DEHP group); treated with both E_2 and phosphatidylinositol-3-kinases (PI3K) inhibitor LY294002 (E_2 + LY294002 group); treated with both DEHP and LY294002 (DEHP + LY294002 group). The absorbance value (AV) was measured on day 0, 2, and 5. DNA proliferation index (PI) and apoptotic index (AI) were determined by flow cytometry on day 5. Caspase-3 protein, protein-serine-threonine kinase (Akt) and phosphor-Akt (Ser473) protein expression were analyzed by Western blot on day 5. Results The AV of All groups increased on day 2, and 5. The AV of E_2 and DEHP groups were higher than that of the control group (P<0. 001), but the AV of E_2 + LY294002 and DEHP + LY294002 groups were lower than those of E_2 and DEHP groups (P<0.01) on day 2 and 5. On day 5, PI of E_2 and DEHP groups were also higher than that of control (P<0.01). However, PI of E_2 + LY294002 and DEHP + LY294002 groups were lower than those of E_2 and DEHP group (P<0.01) on day 5. There was no significant difference in AI and caspase-3 protein expression among the groups. At the same time, phosphor-Akt (Ser473) protein expression of E_2 and DEHP groups increased obviously, compared with the control group. Compared with E_2 and DEHP groups, E_2 + LY294002 and DEHP + LY294002 groups decreased significantly. However, Akt protein expression was equal among those groups. Conclusions DEHP can promote the growth of SK-N-SH cells to a level similar to that of E_2, with activation of the PI3K/Akt signaling pathway.

Background and purpose:Non-small cell lung cancer (NSCLC) patients who have good curative effect on epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) will inevitably acquired drug resistance. It will effect the survival directly. In contrast, few studies have found that EGFR-TKI effectively acquired drug resistance in patients with clinical characteristics. We investigated clinical characteristics of NSCLC patients who experienced acquired drug resistance during geiftinib therapy. Methods:To review the treatment from the beneift of patients with non-small cell lung cancer. All of the data were obtained from Jan. 2007 to Jan. 2014 in Xinjiang tumor hospital. The treatment for failure of acquired drug resistance of clinical manifestations, time to progress (TTP) and post-progression survival (PPS) were retrospectively analyzed. Results:The total collection of 417 patients. Median TTP was 10.2 months (95%CI:9.5-10.9). The TTP of women adenocarcinoma patients who didn’t smoke signiifcantly extended. When acquired drug resistance happened, 63.3%of patients appeared worse symptoms. The progress of the disease is as follows:209 cases (58.4%) from the primary lesion, 137 cases (38.3%) before the transfer, 194 cases (54.2%) of new happened. Patients of epidermal growth factor receptor (EGFR) wild type had more tendencies of symptomatic deterioration and new central nervous system (CNS) transfer than patients of EGFR mutation type. Patients of exon 19 deletion and L858R mutations on the new transfer were different (41.4%vs 6.3%, P=0.02). PPS was 8.9 months (95%CI:7.4-10.4). Smoking history, performance status (PS) score, new CNS lesions and the subsequent chemotherapy is independent factors of PPS. Conclusion:This study suggests that the clinical manifestations of acquired drug resistance according to EGFR mutation status and EGFR mutation genotype may be different. In addition, after the treatment of acquired drug resistance in patients with non-small cell lung cancer, the subsequent clinical beneift from chemotherapy are also associated with PPS.

Objective To investigate the clinical effect and safety of EEG biofeedback therapy combined with mirtazapine in the treatment of depressive disorder.Methods 124 patients with depressive disorder were selected and randomly divided into the observation group and the control group,62 cases in each group.The control group was given mirtazapine treatment,while the observation group was given EEG biofeedback therapy combined with mirtazapine.All the two groups were treated for 8 weeks.Before and 2,4,8 weeks after treatment,the clinical effects in the two groups were evaluated by Hamilton depression scale (HAMD),Montgomerie depression rating scale (MADRS) and the clinical global impression scale (CGI).The side effects scale(TESS) assessment was used to assess the side effects.And the serum norepinephrine (NE),5-hydroxytryptamine (5-HT) and dopamine (DA) levels were measured before and 8 weeks after treatment.Results The total effective rate of the observation group was 87.5％,which was significantly higher than 66.1％ in the control group (x2 =7.213,P ＜ 0.05).In the two groups,2,4,8 weeks after treatment,the HAMD scores were significantly lower than those before treatment (t =9.391,19.349,26.349,5.026,12.610,19.518,all P ＜ 0.05),the M ADRS scores were significantly lower than those before treatment (t =8.646,22.190,33.101,4.986,13.185,25.959,all P ＜ 0.05),and the CGI scores were significantly lower than those before treatment(t =17.471,29.482,42.256,13.136,28.358,35.661,all P ＜ 0.05).In the observation group,after treatment for 2,4,8 weeks,the HAMD scores were significantly lower than those in the control group(t =4.093,4.537,5.655,all P ＜ 0.05),and the MADRS scores were significantly lower than those in the control group (t =3.622,9.740,7.490,all P ＜ 0.05),while the CGI scores were significantly lower than those in the control group(t =8.608,11.024,12.598,all P ＜ 0.05).After treatment,the levels of 5-HT,NE and DA were (148.5 ± 4.9) ng/mL,(60.6 ± 4.2) ng/L and (78.0 ± 4.1) ng/L in the observation group,which were significantly higher than before treatment [(79.8 ± 4.3) ng/mL,(30.3 ± 4.0) ng/L and (43.5 ± 4.0) ng/L,t =82.977,41.134,46.837,all P ＜ 0.05].In the control group after treatment,the levels of 5-HT,NE and DA were (125.4 ± 4.1) ng/mL,(40.2 ± 4.0)ng/L and (50.3 ± 4.3)nig/L,which were significantly higher than those before treatment [(79.2 ± 3.9)ng/mL,(30.5 ±4.1)ng/L and (43.2 ±3.6)ng/L,t =64.287,13.334,9.969,all P ＜0.05],but which those in the observation group increased more significantly (t =28.469,27.695,36.286,all P ＜ 0.05).4 weeks and 8 weeks after treatment,the TESS scores in the observation group were (3.0 ± 1.0) points and (4.3 ± 1.2) points,which in the control group were (2.8 ± 1.2) points and (4.1 ± 1.3) points,there were no significant differences in terms of TESS scores (t =1.150,0.846,all P ＞ 0.05).Conclusion EEG biofeedback therapy combined with mirtazapine in the treatment of depression is better,the adverse reactions is not significantly increased,and it also has higher clinical safety compared with mirtazapine alone.

Objective To evaluate the relationship between lifestyle and development of Alzheimer's disease(AD).Methods Two hundred and thirty-eight AD patients(102 males and 136 females) and 476 healthy controls(204 males and 272 females) were recruited from Ningbo communities into this 1 ∶ 2 matched case-control study.Mini-Mental State Examination(MMSE) and Clinical Dementia Rating(CDR) were required to fill in.Chi-square test and conditional logistic regression were used for data analysis.We adopted Epidata 3.1 to establish the database and did statistical analysis by SPSS15.0.The count data were analysis by Chi-square test,meanwhile multiple factors analysis by conditional Logistic regression analysis.Results Through single factor analysis we found thatcigarette ≥20/day(F=8.687,P=0.003),children visiting(F=22.721,P＜0.05),friendship(F=16.784,P＜0.05),family gathering(≥1 times/week)(F=8.198,P=0.004),working after retirement(F=33.099,P＜0.05),travel(F=16.784,P＜0.05),social activities(F=24.919,P＜0.05),physical exercises(F=24.404,P＜0.05),eating pickles or pickled products(F=6.662,P=0.01),saturated fatty acid intake(F=23.069,P＜0.05),daily consumption of fruits and vegetables(F=8.401,P=0.004),chess(F=17.365,P＜0.05),reading(≥30 min/d)(F=36.390,P＜0.05),using computer(F=8.688,P=0.003) were related AD,the difference was statistically significant(P＜0.05).In multiple factors analysis,social activities,chess games or joke,travelling,working after retirement,reading,physical exercises,friendship,family gathering,saturated fatty acid intake and daily consumption of fruits and vegetables were risk factors of AD(odds ratio(OR) values were 0.571(0.342-0.753),0.623(0.343-0.889),0.686(0.461-0.942),0.534(0.326-0.714),0.276(0.175-0.438),0.538(0.336-0.738),0.585(0.385-0.765),0.466(0.316-0.745),0.527 (0.368-0.787) and 0.482(0.316-0.665),respectively; constant terms:OR=0.526).Conclusion A positive and leisure lifestyle and health reasonable diet could effectively reduce the risk of AD.