Objective To explore the protective effects of dipeptidyl peptidase-4 inhibitor (DPP-4I) on AD-like neurodegenerative changes and its mechanism. Methods The human neuroblastoma cell line SH-SY5Y on the logarithmic phase was divided into six groups:control group (CON group, treated with PBS contained 1‰DMSO for 12 h), wortmannin intervention group (W group, treated with 0.03 μmol/L wortmannin for 12 h), DPP-4I intervention group (DPP-4I group, treated with 10μmol/L DPP-4I for 12 h), both DPP-4I and wortmannin intervention group (DPP-4I+W group, pre-treated with 10 μmol/L DPP-4I for 2 h, then 0.03 μmol/L wortmannin for 12 h), DPP-4I, wortmannin and Ex9-39 intervention group (DPP-4I+W+Ex9-39 group, pre-treated with 10μmol/L Ex9-39 for 2 h, then 10μmol/L DPP-4I for 2 h followed by 0.03μmol/L wortmannin for 12 h), and Ex9-39 intervention group (Ex9-39 group, treated with 10μmol/L Ex9-39 for 12 h). MTT assay was used to detect the cell vitality. Western blot assay was used to detect the level of total tau protein (tau-5) and phosphorylated tau at different sites (pSpS199/202, pT231 and pS396), the level of phosphorylated neurofilaments (NF-H, NF-M) and phosphorylation of critical enzyme in PI3K/Akt/GSK-3β signaling pathway. Results (1) The cell vitality decreased, the levels of pSpS199/202, pT231, pS396 and NF-H/M increased significantly in W group than those in CON group. However, comparing with CON group, the above mentioned parameters reversed in DPP-4I group. Comparing with W group, the cell vitality increased and phosphorylated levels of above mentioned indices were decreased in DPP-4I+W group. (2) The cell vitality showed a decline trend while the levels of phosphorylation tau at three different sites and NF-H/M were higher in Ex9-39 group than those in CON group. Comparing with DPP-4I+W group, the results of the phosphorylated levels showed the same changes in DPP-4I+W+Ex9-39 group. (3) Comparing with CON group, the expression levels of phosphorylated PI3K, Akt and GSK3β increased significantly in DPP-4I group, while those decreased in W group. Additionally, the expression levels of phosphorylated PI3K, Akt and GSK3β were significantly increased in DPP-4I+W group than those in W group. Conclusion DPP-4I can enhance the level of GLP-1 and activate PI3K/Akt/GSK-3βinsulin signaling pathway to improve the hyperphosphorylated tau and NFs induced by wortmannin, and to protect AD-like neurodegeneration.

To evaluate the efficacy and accuracy of photorefractive keratectomy (PRK) for myopia and myopic astigmatism .SVS APEX excimer laser with a wave length of 193 nm(Sumit Technology Inc. Waltham, Mass, USA) was applied. 316 myopic eyes of 168 patients were treated with PRK between September, 1996 and October, 1997, and 260 eyes (84%) of 150 patients were followed for more than three months, including male 68(116 eyes, 40.1%) and female 82(144 eyes, 59.9%). The preoperative spherical equivalent refractive errors ranged from -1.25D to -10.00 (mean -4.67±1.63D), and astigmatism ranged from 0 to -2.00D (means -0.33±0.45D). We divided the patients into two groups according to the referaction: group A (from -1.25D to -5.90D) and group B(from -6.00 to -10.00D). The number of eyes in the two groups were 220 and 40 respectively. In group A, on the 10th day, 68.9% has the uncorrected visual acuity (UCVA) equal to or one line better or lower than the preoperative best corrected visual acuity (BCVA). In 1,3,6 and 12 months, 90%, 96%, 95% and 94% had the UCVA equal to or one line better or lower than the preoperative BCVA respectively. In group B, on the 10 th day, in 1,3,6 and 12 months, UCVA equal to or one line better or lower than the preoperative BCVA occurred in 35.9%, 83%, 87%, 86%, and 84% of the cases respectively. Most of the haze showed 0.5～1 grades except 3 eyes with the haze of 2 grade in 3 or 6 months and it changed to 1 and 0.5 grade respectively within one year. In 10 days and 1,3,6,12 months postoperatively, the corneal haze was noted in 32.9%, 84.8%, 62.8%,9.0% and 2.8% of the treated eyes respectively. We found that 193 nm excimer laser PRK was a predictable, safe, stable, and effective refractive surgery for correcting myopia up to -10.00D in Chinese patients, and the effect was better in myopia lower than -6.00D.

Oblective To evaluate the corneal healing of non-epuality diopter response histopathologically,immunohistochemically and ultrastructurally after excimer laser photorefractive keratectomy(PRK) with SVS APEX PLUS(Summit Technology Inc. USA) excimer laser, and the effects of corticosteroid on the healing. Methods PRK on 6 white rabbits(12 eyes) was performed on right eye of the rabbit for an attampted correction of -4.00 diopter and on left eye for an attempted correction of -8.00 diopter. The rabbits were divided into 2 groups randomly and each group included 6 eyes: Group FLM (3 rabbits, 6 eyes) and group CM (3 rabbits, 6 eyes). Fluoromethalone was given to group FLM,and chloromycetin to group CM. On 10d, 30d and 100d ,the eyes of one rabbit in each group were enucleated randomly. Half of each cornea was prepared for electron microscope observation (SEM and TEM)and the rest embedded in OCT compound for immunohistochemical study to examine Ⅲ -C and FN. Results All eyes were reepithelialized within 3d after PRK. Subepithelial corneal haze was observed on 15d,which was dominant on 30 or 60d. On 100d postoperatively,corneal hazes of 11 eyes were grades 0 or 0. 5,only 1 eye(the left eye of group CM) was denser haze (grade 1). On 3d postoperatively, one or two layers of corneal epithelial cell covered the ablation zone. On 30d after PRK,the epithelial cells showed hyperplastic changes. The cells were larger and increased from normal 5 or 6 layers to 7 or 8 layers of cells on 100d after PRK,epithelium was clear with more bright epithelium. Microplicae and microvilli were less than before. The expression of Ⅲ -C and FN in group CM was significantly more evident than that in group FLM. Conclusion The study show that despite recovery of a continuous and smooth epithelial layer and nearly normal corneal tissues on 100d after PRK,abnormalities of both epithelium and superficial stroma can be detected in the area of ablation. The ablation depth of stroma can influence the appearance of corneal haze after PRK. The microplicae and microvilli of rabbit cornea epithelium become less after PRK,which can be one of cause leading to ocular dry sensation in some patients.

Objective To evaluate the efficacy and toxicity of the combination of oxaliplatin and S-1 in the treatment of patients with advanced breast cancer.Methods A total of 72 patients with advanced breast cancer after the treatment failuer of anthracycline and taxane were treated with oxaliplatin and S-1.The first day,they were given oxaliplatin,135 mg/m2,with the 5％ glucose injection 500 ml,the time of intravenous drip should be more than 2 hours.And the S-1 was taken after breakfast and dinner,the dose was 40-60 mg,and the time of duration was 2 weeks,then they had 7 days to rest.The cycle was 21 days.Every 2 cycles,we estimated the efficacy.Patients who were effective and stable kept that chemotherapy regimens,the maximum duration was 6 cycles.The efficacy and toxicities were evaluated after cycles of chemotherapy.Results Two cases (2.8％) had complete response (CR),26 cases (36.1％) had partial response (PR).The response rate (RR) was 38.9％ and the disease control rate (DCR) was 69.4％.The median progress free survival (PFS) was 7.7 months and the median overall survival (OS) was 12.3 months.Subgroup analysis showed that the OS of patients who belong to stage Ⅳ,had two or more metastases or with failure treatment after being treated with anthracycline and taxane was notably shorter than the patients who belong to stage Ⅲ C,only one metastasis,with effective treatment after being treated with anthracycline and taxane,and the differences were statistically significant (10.5 months vs.15.0 months,x2 =4.469,P =0.035;9.3 months vs.15.0 months,x2 =8.297,P=0.004;10.0 months vs.14.0 months,x2 =4.077,P=0.043).The main side effects were neutropenia (19.4％),nausea (8.3％) and nerve toxicity (2.8％),mainly 3-4 degree,and could be welltolerated.The others were diarrhea,impaired liver function,stomatitis,anemia and hand-foot syndrome,mainly 1-2 degree.Conclusion Oxaliplatin combined with S-1 is effective and tolerable in treatment of patients with advanced breast cancer,the adverse reactions can be tolerated.

Objective To investigate the relevance ratio of abnormal electrocardiogram (ECG) and describe the abnormal ECG index among the residents in Keshan disease (KD) area.To assess the KD illness severity and provide comparable quantitative indicators,provide the scientific basis for elimination of KD.Methods Non probability sampling method was used,and monitoring stations with the highest incidence of KD at the county level were selected in 2012.Clinical examination and 12 lead ECG was carried out.According to The KD Diagnosis Standard (WS/T 210-2011),eight common changes in ECG of KD were scored.According to age and sex group,check the abnormal rate of ECG detection of Keshan disease,while analysed the changes of abnormal ECG index score in latent KD patients and chronic KD patients.Abnormal ECG index to determine:If there was one change,the score was 1 and the abnormal ECG index was 1.And so on,the highest score was 8.Results Totally 61 831 residents were surveyed and 9 634 were found with abnormal ECG,and the relevance ratio of abnormal ECG was 15.58％;totally 3 862 residents had eight ECG changes of KD and the relevance ratio was 6.25％;totally 508 residents were diagnosed with KD and the relevance ratio was 0.82％.The relevance ratio of abnormal ECG among all age groups was statistically different (x2 =3 065.64,P ＜ 0.05).The relevance ratio of abnormal ECG in women was higher than that of men [3.91％ (2 419/61 831) vs 2.33％ (1 443/61 831),x2 =86.30,P＜ 0.05].Abnormal ECG index score was (1.06 ± 0.25) which was not statistically different between gender [men:(1.07 ± 0.27) vs women:(1.06 ± 0.24),t =1.41,P ＞ 0.05].The abnormal ECG index score in latent KD patients was lower than that of chronic KD patients [(1.09 ± 0.30) vs (1.60 ± 0.69),t =-4.87,P ＜ 0.05].In eight ECG changes,the most check out items were T wave and/or ST segment changes (2 816).Conclusions The relevance ratio of abnormal ECG in KD area is at a higher level.The abnormal ECG index can be used to assess the KD illness severity and provide comparable quantitative indicators,in order to provide a new train of thought for the evaluation of KD elimination.

Objective To describe the status of prevalence,awareness,treatment,and control of hypertension among the residents in severe historical endemic areas of Keshan Disease in Heilongjiang Province,and to provide scientific evidence for prevention and control of hypertension.Methods In December 2015,Yongjin,Yongli groups of Yongjin Village,and Fengnian,Fengtian,Fengfu groups of Fengnian Village in Fanrong Township,Fuyu County,Qiqihaer City,Heilongjiang Province were selected via the cross-sectional method.The residents aged 18 years or older were surveyed as respondents by cluster sampling.Demography,risk factors,hypertension related information were collected through questionnaire survey.Blood pressure,height and weight were measured through physical examination.Blood pressure measurement was conducted with Omron HEM-1020 electronic sphygmomanometer,the diagnostic criteria was Chinese Guidelines for Prevention and Treatment of Hypertension (revised in 2010).Results Totally 683 residents were surveyed,the valid participants were 669,the prevalence of hypertension was 49.2％ (329/669),the standardized prevalence was 37.9％,the prevalence of men [58.0％ (164/283)] was higher than that of women [42.7％ (165/386),x2 =15.103,P ＜ 0.01],the prevalence increased with increasing age (total,men,women:x2tendency =9.044,4.560,7.789,all P ＜ 0.01).The awareness of hypertensive patients was 60.8％ (200/329),the standardized awareness was 41.2％,the awareness of men [54.3％ (89/164)] was lower than that of women [67.3％ (111/165),x2 =5.836,P ＜ 0.05],the awareness of hypertensive patients increased with increasing age (total,men,women:x2tendency =3.638,2.686,2.419,all P ＜ 0.05).The treatment of hypertensive patients was 51.1％ (168/329),the treatment of men [43.9％ (72/164)] was lower than that of women [58.2％ (96/165),x2=6.711,P ＜ 0.05],the treatment of hypertensive patients increased with increasing age (total,men,women:x2tendency =4.422,2.704,3.633,all P ＜ 0.01).The control rate of hypertensive patients was 5.5％ (18/329),the control rate among the treatment was 10.7％ (18/168).Conclusions The standardized prevalence of hypertension among the residents of the severe historical endemic areas of Keshan disease in Heilongjiang Province is higher than the national average (25.2％),the standardized awareness is lower than the national average (46.5％),the treatment and the control are low.We should pay more attention to the hypertension in the severe historical endemic areas of Keshan disease.

Objective To evaluate the efficacy and accuracy of photorefractive keratectomy(PRK) for myopia and myopic astigmatism.Methods SVS APEX PLUS excimer laser with a wave length of 193nm(Summit Technology Inc.Waltham,Mass,USA) was applied.Three hundred and sixteen myopic eyes of 168 patients were treated with PRK from Suptember 1996 to October 1997,and 260 eyes(84%) of 150 patients were followed-up for more than three month,including male 68(116 eyes,40.1%) and female 82(144 eyes,59.9%).The preoperative spherical equivalent refractive errors ranged from -1.25D to -10.00D(mean -4.67D± 1.63D),and astigmatism ranged from 0 to -2.00D(mean -0.33D±0.45D). The patients were divided into two groups according to the refraction:group A(from -1.25D to -5.90D) and group B(from -6.00D to -10.00D).The number of eyes in the two groups were 220 and 40,respectively.Results In group A,After 10 days,68.9% had the uncorrected visual acuity(UCVA) equal to or one line better or lower than the preoperative best corrected visual acuity(BCVA).After 1 ,3,6 and 12 months,90%,96%,95% and 94% had the UCVA equal to or one line better or lower than the preoperative BCVA,respectively.In group B,after 10 days,1,3,6 and 12 months,UCVA equal to or one line better or lower than the preoperative BCVA occurred in 35.9%,83.0%,87.0%,86.0% and 84.0% of the patients respectively. Most of the haze showed 0.5～1 grades except 3 eyes with the haze of 2 grade at 3 or 6 months and it changed to l and 0.5 grade respectively at one year.after 10 days and 1,3,6,12 months postoperatively,the corneal haze was noted in 32.9%,84.8%,62.8%,9.0%and 2.8% of the treated eyes respectively.Conclusion We found that the 193nm excimer laser PRK is a predictable,safe,stable,and effective refractive surgery for correcting myopia up to-10.00D in Chinese patients,and the effect is better in myopia lower than -6.00D.

Objective To label granulocytes in a state of differentiation in mouse bone marrow (BM) with EdU (5-ethynyl-2′-deoxyuridine) for further understanding the changes in granulocyte produc-tion at different stages of differentiation during inflammation. Methods C57BL/6 mice were intraperitoneal-ly (i.p.) injected with EdU and heat-inactivated Escherichia coli(HI E.coli). BM cells were harvested at different time points after HI E.coli injection and then stained with fluorescent-conjugated antibodies(Abs). Myeloblasts,promyelocytes,myelocytes, metamyelocytes and band and segmented neutrophils were identi-fied by fluorescence-activated cell sorting(FACS). The percentage of EdU-positive cells in each population was recorded. Results The percentage of EdU-positive myeloblasts in mice increased by 10.0% at 24 h af-ter intraperitoneal injection with HI E.coli,but decreased by 75.0% and 23.0% at 48 h and 72 h,respec-tively. The percentage of EdU-positive promyelocytes declined by 23.0%,54.5%,64.3% and 77.8% at 24 h,48 h,72 h and 96 h,respectively. The percentage of EdU-positive myelocytes increased by 60.0% and 10.0% at 24 h and 48 h,but decreased by 80.0% and 90.0% at 72 h and 96 h. The percentage of EdU-positive metamyelocytes increased by 50.0% at 24 h,but decreased by 33.3%,61.5% and 66.7% at 48 h,72 h and 96 h. The percentage of EdU-positive band and segmented cells increased by 14.0% at 24 h,but decreased by 50.0%, 77.8% and 88.0% at 48 h, 72 h and 96 h. Conclusion Emergency granulopoiesis occurred 24 h after the establishment of HI E.coli-induced model of acute peritonitis, which meant that the proliferation of myeloid precursor cells,especially that of myelocytes and metamyelocytes,was accelerated and resulted in increasing number of mature neutrophils immigrating to sites of inflammation.