Costimulatory signals have become a hot field in immunological researches. As co-inhibitory molecules, programmed death-1 ( PD-1) and its ligands (PD-1/PD-L) have been demonstrated to play an important role in autoimmune disease, organ transplant rejection, microorganism infection, tumor immune escapes etc. . In recent years,some studies about PD-1/PD-L pathway in ophthalmology have been curried out and reported. Some changes were found in PD-1/PD-L pathway, such as ocular immunologic diseases, ocular infectious diseases, ocular tumors, immune privilege in ocular tissues and so on. Through the research on PD-1/PD-L pathway,we can further understand the pathogenesis of some ocular diseases and find new methods for their prevention and treatments. This article reviewed the recent advances in PD-1/PD-L pathway in ophthalmological physiopathology.

A rapid detection method of active pharmaceutical ingredients( API) in weak API signal drugs by surface enhanced Raman scattering ( SERS) technology combined with paper substrate was established in this work. By soaking the filter paper in silver nanoparticles solution ( Ag NPs) to synthesize Ag NPs-paper as the substrate, and then the sample solution was dropping on the substrate with SERS detection. On the basis of strengthen ability of Ag NPs-paper, result of SERS detection and optimal preparation conditions, the fast identification method of weak API signal drugs was established. In this case, the SERS spectra of weak API signal drugs and their standards SERS spectra were obtained, where the correlation coefficient of weak API signal drug SERS spectra and its standard was more than 0. 9. The result showed that by this method, the low content API in weak API signal drugs could be well investigated, and the deficiencies of the normal Raman spectroscopy efficiently was also overcome. In conclusion, the synthesize method of Ag NPs-paper was simple, and the strengthen effect of this Ag NPs-paper on the intensity was obviously observed. Paper substrate-SERS method was simple, rapid and sensitive, and could be used to detect weak API signal drugs, presenting broad application prospects in the rapid detection of weak API signal drugs.

Objective To investigate the role of miR?193a?3p in the radioresistance of esophageal squamous cell carcinoma ( ESCC) . Methods MTT assay was used to identify the cell lines with the highest radiosensitivity and radioresistance in four esophageal cancer cell lines exposed to irradiation of 6 MV X?ray. Stem?loop quantitative real?time PCR was used to measure the expression levels of miR?193a?3p, miR?155, and miR?22?3P in the two cell lines. Further studies were performed on miR?193a?3p because of the substantial difference in its expression between the two cell lines. The mimic (3PM) and antagomiR (3PA) of miR?193a?3p as well as siRNA ( si?LOXL4) were synthesized and transfected into cells to elevate and inhibit miR?193a?3p expression. MTT assay and flow cytometry were used to evaluate the effects of miR?193a?3p and its downstream gene LOXL4 on radiosensitivity. Results KYSE510 and KYSE410 were characterized as cell lines with the highest radiosensitivity and radioresistance, respectively. miR?193a?3p had a substantially larger difference in expression between the two cell lines than miR?155 or miR?22?3P (1. 00 ∶ 21. 00). Transfection of 3PM resulted in elevated expression of miR?193a?3p in KYSE510, which had a significantly lower radiosensitivity and a significantly reduced apoptosis ratio by 11. 01% compared with the control group ( P<0. 05) . KYSE410 transfected with 3PA had a significantly higher radiosensitivity ( P<0. 05) . The expression of LOXL4, a downstream gene of miR?193a?3p, was negatively correlated with miR?193a?3p expression. Transfection with si?LOXL4 inhibited the expression of LOXL4, which resulted in a significantly lower radiosensitivity and a significantly reduced apoptosis ratio by 7. 07% compared with the control group ( P<0. 05) . Conclusions miR?193a?3p promotes the radioresistance of esophageal cancer cells probably by regulation of LOXL4.

Background Some aboard studies showed that polyatomic pathway play an important role in the microsvasculopathy of type 2 diabetes,and sorbitol dehydrogenase (SDH) gene is involved in the pathogenesis of diabetic retinopathy(DR).There is no relevant research at home up to now.Objective This study was to investigate the correlation of sorbitol dehydrogenase (SDH) G-888C gene polymorphism with diabetic retinopathy (DR) in type 2 diabetes mellitus.Methods The SDH genotypes were determined by polymerase chain reactionreaction fragment length polymorphism (PCR-RFLP) in 187 patients with diabetes and 123 normal contrels.Patients were divided into two groups depending on the presence or absence of DR(DR:n=118;NDR:n=69).The frequencies of SDH genotype and allele were assayed and compared among these groups.This study was approved by Ethic Committee of Guangdong General Hospital.Written informed consent was obtained from each individual prior to any relevant medical procedure.Results The disease course in the DR group was significantly longer than that in NDR group(t=2.070,P=0.042),and other clinical features in both groups were non-significant (all P>0.05).The genotype frequencies in the DR group,NDR group and normal control group were 24.6%,8.7% and 8.1%,respectively,and frequencies of the G allele were 42.4%,25.4% and 29.7%,showing statistically significant differences among these three groups.The GG genotype and G allele frequencies were significantly higher in the DR group than those in the NDR group and normal control group (GG:P=0.007,P=0.001;G:P=0.001,P=0.004).There were no significant differences in the frequencies of the GG genotype and G allele between the NDB group and normal control group ( P>0. 05) as well as the proliferative DR group and non-proliferative DR group (P>0.05).Conclusion SDH G-888C gene polymorphism is associated with the development of diabetic retinopathy in southern Chinese.

Objective To summarize radiographic manifestations of granulocytic sarcoma (GS),in order to investigate its radio-graphic feature.Methods Nine patients of GS confirmed by surgery pathology and immunohistochemistry were collected.There were four cases underwent CT scan,2 underwent MRI,3 underwent CT and MRI meanwhile.Results There were 4 cases in the lymph nodes,4 cases in the bone,1 case in the enterocoelia.The density of enlarged lymph node was inhomogeneous,and smaller lymph node was homogeneous density,both enhanced obviously.The density or intensity of the lesions occurred in the canalis verteb-ralis and paravertebra was also homogeneous,slightly enhanced,with bone and medulla ossea invasion.Lesions in the enterocoelia was inhomogeneous desity with clear boundary,enhanced inhomogeneously.Conclusion GS is a rare extramedullary malignant tumor composed of immature myeloid cells.CT and MRI can provide a certain diagnostic value.The perplexity in diagnosing such lesions highlighted the need of careful interpretation of all clinacal,radiographic,histopathological and immunochistochemical details as it is one of the most frequently misdiagnosed disorder.

Objective To analyze the clinical characteristics,pathological classification and therapy strategy of rectal carcinoid and its prognostic factors.Methods Forty four patients with rectal carcinoid were diagnosed and treated in Ruijin Hospital Shanghai Jiaotong University from January 2006 to November 2013,among whom 21 patients (19 males and 2 females) were followed-up for 1-7.5 years.The clinical data of these cases were retrospectively analyzed.Results The patients underwent colonoscopy because of changed bowel habits and/or abnormal digital rectal examination,none of them had carcinoid syndrome.Colonoscopy showed that most lesions presented yellowish in color and smooth in surface; the diameter of the tumor was ≤ 1.0 cm in 12 cases (57％) ; the tumors were located at the rectum within 8 cm from anal rim in 17cases (76％); most of them were well differentiated.Immunohistochemistry demonstrated that NSE expression was highly positive.The 1 year-and 3year-survival rate were both 100％.Among 8 cases who were followed up for over 5 year,2 relapsed.Conclusions The digital rectal examination plays a key role in detecting rectal carcinoid.Though prognosis is relatively good,we should keep close following-up to detect the recurrence.The main risk factors influencing the prognosis are tumor size,depth of invasion and clinical stage.The combination measurement of CEA,TSGF,CA19-9 and NSE will either increase the sensitivity or the specificity of early detection.

Objective To investigate the prevalence and attitude of smoking and its influencing factors among residents in Hongkou District of Shanghai,so as to provide evidence for tobacco control. Methods Nine hundred and sixty residents in Hongkou District of Shanghai aged 15 to 69 years were selected by multi-level random sampling,among whom 958 completed the investigations on smoking status. Results The smoking rate and standardized smoking rate were 20.04% and 18.73%,respectively.The smoking rate and standardized smoking rate of males were 41.05% and 30.07%,and those of females were 0.80% and 1.70%,respectively.The smoking rate of males was higher than that of females(RR=0.02,95%CI: 0.01-0.03).The smoking rates of age groups of 25 years old and over were higher than those of 15 to 24 years old,and the smoking rate of subjects with or above junior college education was lower than that of subjects with or below middle school education(RR=0.45,95%CI: 0.25-0.79).Subjects who drank alcohol smoked more than those did not(RR=2.68,95%CI: 1.76-4.09).Lower annual per capita income and higher knowledge on smoking hazard led to more tendance to object to smoking and agree with anti-smoking. Conclusion The prevalence of smoking of residents aged 15 to 69 years in Hongkou District of Shanghai was relatively lower.Age,gender,education status and alcohol drinking were influencing factors of smoking.Education on tobacco control among subjects aged more than 35 years should be strengthened,and more attention should be paid to those with lower education.Besides,education on alcohol control should be managed together with tobacco control.

AIM:To investigate the maturation of mice immature myeloid dendritic cells (mDCs) induced by antigen(Ag)85B of mycobacterium tuberculosis, and the expression of TSLPR and OX40L mediated by TSLP in vitro. METHODS:Recombinant mouse GM-CSF ( rmGM-CSF) and rmIL-4 were used to induce bone marrow precursor cells of C57BL/6 mice to differentiate into immature mDCs in vitro.mDCs were identified followed by purification using CD 11c binding magnetic beads .The morphological characteristic of mDCs was observed under inverted phase-contrast microscope and scanning electron microscope .The surface phenotypes of mDCs were determined by flow cytometry .To obtain the opti-mal concentrations of Ag85B and TSLP, immature mDCs were cultured with different concentrations of Ag 85B or TSLP at 0 (control group), 50, 100 and 200 μg/L for 24 h, and the expression of cell surface molecules CD 80, CD86, TSLPR and OX40L was detected by flow cytometry.In addition, the expression of TSLPR and OX40L in Ag85B and TSLP-co-stimula-ted mDCs was determined by flow cytometry .RESULTS:After 7 d of culture in vitro, the cells showed irregular dendritic protrusions under the inverted-phase contrast microscope , and had wrinkles and dendritic splits under scanning electron mi-croscope , conformed to the morphological characteristics of immature mDCs .The mDCs cells expressed higher level of spe-cific marker CD11c, lower level of co-stimulatory molecules CD80 and CD86, which conformed to the phenotype of imma-ture mDCs.The CD80 +and CD86 +cell ratios of mDCs displayed significant increases in 50, 100 and 200μg/L Ag85B or TSLP groups compared with control group (P<0.05).The ratios of TSLPR +and OX40L+cells did not differ among dif-ferent concentrations of Ag 85B groups.The ratios of TSLPR +and OX40L+cells were significantly increased in 100 μg/L and 200μg/L TSLP groups compared with control group and 50μg/L TSLP group (P<0.05).Under the circumstance of optimal Ag85B or TSLP treatment concentration at 200 μg/L, there was significantly decreased in TSLPR and OX 40L cell ratio of mDCs in Ag85B group or Ag85B combined with TSLP group when compared with TSLP group (P<0.05), and no significant difference among Ag85B group, Ag85B combined with TSLP group and control group was observed .CONCLU-SION: Ag85B enhances mDCs maturation by up-regulating the expression of co-stimulatory molecules CD80 and CD86, and inhibit the expression of pro-inflammatory specific molecules TSLPR and OX40L on TSLP-activated mDCs, indicating that Ag85B modifies the development of asthmatic airway inflammation through the pathway of TSLP -activated mDCs.

[ABSTRACT]OBJECTIVEThe purpose of this study was to analyze the screened miRNAs related to the chemosensitivity for the TPF regimen of hypopharyngeal squamous cell carcinoma by miRNA array, and provide a set of miRNAs that may be useful for the development of novel diagnostic markers and more effective therapeutic strategies from the screened miRNAs.METHODSA total number of 21 patients who underwent TPF induction chemotherapy for primary hypopharyngeal squamous cell carcinoma were recruited for miRNA array analysis. 12 patients are sensitive to chemotherapy, and 9 patients are not. Moreover, the selected putative regulated miRNAs were also validated by RT-PCR in another 24 patients (14 patients are sensitive to chemotherapy, and others are not).RESULTSThere were 24 miRNA significantly differencial to the sensitivity to chemotherapy, and 6 miRNAs were up-regulated in the TPF group while 18 miRNA were down-regulated (P<0.05). To identify typical miRNA, mirfocus 3.0 database selected four miRNAs hsa-miR-211-3p, hsa-miR-4253, hsa-miR-4443, and hsa-miR-193b-3p, which were significant down-regulated in TPF-sensitive group. QRT-PCR further validated that only three miRNA (hsa-miR-4253、hsa-miR-4443、hsa-miR-193b-3p) were under-expressed in TPF-sensitive group of another 24 tissue samples (P<0.05).CONCLUSIONMiRNA hsa-miR-193b-3p, hsa-miR-4253, hsa-miR-4443 were identified in TPF-sensitive tissues by microarrays, and further validated by RT-PCR. These down-regulated miRNAs may act as novel biomarkers to classify TPF sensitivity of hypopharyngeal squamous cell carcinoma patients and will contribute to the understanding of the molecular basis of the chemosensitivity in the disease.

Objective To investigate the antagonistic effect of ω-3PUFAs on cognitive impairment in MK-801-induced schizophrenia (SZ) rats and its mechanism.Methods Rat model of schizophrenia was induced by MK-801.Morris water maze was used to detect the change of cognitive function in rats.The number of neonatal neurons in hippocampus was detected by Brdu staining.CREB,p-CREB,BDNF,TrkB and p-TrkB levels were detected by Weston Blot.Results MK-801 induced schizophrenia-like cognitive impairment (the escape latency in the water maze test was (6.51±3.10)s for Ctr group,(15.27±6.20)s for Mod group;acrossing times was (4.63±1.06) times for Ctr group,(2.00±1.15) times for Mod group),reduced the number of neonatal neurons in hippocampus (the relative level of neonatal neuron number per unit area,Mod/Ctr was 0.656±0.066) and impaired the CREB/BDNF/TrkB pathway (the relative level of gray value,Mod/Ctr:CREB was 0.393±0.065,p-CREB was 0.591±0.015,BDNF was 0.716±0.115,TrkB was 0.787±0.029,p-TrkB was 0.586±0.013).ω-3PUFAs improved the CREB/BDNF/TrkB pathway activity by increasing CREB and TrKB level and their phosphorylation (the relative level of gray value,Pre/Ctr:CREB was 1.139±0.111,p-CREB was 0.845±0.243,BDNF was 0.864±0.133,TrkB was 0.916±0.022,p-TrkB was 0.952±0.047),and then recovered the number of neonatal neurons in hippocampus (the relative level of neonatal neuron number per unit area,Pre/ Ctr was 1.183±0.101),thereby reduced the cognitive dysfunction in schizophrenia rats(the escape latency in the water maze was (7.44±4.55)s for Pre;acrossing times was (3.86±1.68) times for Pre).Conclusion ω-3PUFAs can relieve the MK-801-induced schizophrenia-like cognitive impairment.