Objective To study the effects of discoidin domain receptor 1 (DDR1) mediated phosphorylation of protein Tau on hypoxic-ischemic brain damage (HIBD) in neonatal rats and its possible mechanism.Methods Sixty-four seven-day-old male specific-pathogen-free Wistar rats were randomly divided into four groups with sixteen in each: Sham, HIBD, HIBD with normal saline (HIBD+NS) and HIBD with DDR1 inhibitor (HIBD+DI) groups. A rat model of HIBD was established by subjecting the rats to left common carotid artery ligation, followed by exposing them to hypoxia for two hours. In HIBD+DI group, the inhibitor of DDR1 was immediately injected into lateral cerebroventricles of the rats following modeling. Forty-eight hours after injection, tissues of left cerebral cortex were collected from each rat to evaluate histopathological changes with HE staining. Western-blotting was used to assess the phosphorylation levels of DDR1 and protein Tau. Enzyme-linked immunosorbent assay was performed to detect the concentrations of acetylcholine. Analysis of variance ort test were used for statistical analysis.Results (1) Damages in cerebral cortex: Percentages of abnormal neurons in the rats of HIBD group were higher than those in Sham group [(80.28±4.51)% vs (10.40±2.17)%,t=39.491,P<0.01]. Pyknotic or necrotic neurons in the rats of HIBD+DI group were less than those in HIBD+NS group [(31.91±3.05)% vs (82.01±7.20)%,t=18.123,P<0.01]. (2) Phosphorylation of DDR1 and protein Tau: Levels of phosphorylated DDR1 in the cerebral cortexes of rats in HIBD group were higher than those in Sham group (0.922±0.199 vs 0.095±0.023,t=10.379,P<0.01), and those levels in HIBD+NS group were higher than those in HIBD+DI group (1.200±0.171 vs 0.255±0.111,t=11.901, P<0.01). The phosphorylation of protein Tau was similar to that of DDR1 (0.919±0.228 vs 0.194±0.224 in HIBD and Sham groups,t=7.347; 1.100±0.167 vs 0.291±0.210 in HIBD+NS and HIBD+DI groups,t=9.447;bothP<0.01). (3) Levels of acetylcholine: Levels of acetylcholine in cerebral cortexes of rats in HIBD group were lower than those in Sham group [(3.685±0.472) vs (7.429±0.861) ng/g protein,t=10.781,P<0.01], and that levels in HIBD+DI group were higher than those in HIBD+NS group [(7.058±0.915) vs (2.521±0.723) ng/g protein,t=10.989,P<0.01].Conclusions Activation of DDR1 plays a key role in enhancing the phosphorylation of protein Tau and in reducing the secretion of acetylcholine in cerebral cortexes of rats with HIBD. Inhibitor of DDR1 could protect neonatal rats from HIBD through the decreasing of protein Tau phosphorylation and increasing of acetylcholine release by inhibiting the activation of DDR1.

Objective To study the effect of high-glucose-high-fat diet on expression and methylation of insulin receptor ( INSR) gene in F1 offspring. Methods Sixty 5-week-old male SD rats were randomly divided into two groups:normal diet group and high-glucose-high-fat diet group. After rats were fed for three months, all male rats were performed to copulate with normal female rats. The body weight, blood glucose, and blood insulin of neonatal rats of F1 offspring were measured. The genome DNA, total RNA, and total protein were extracted from livers, brains, and muscles of neonatal rats. Relative expression of INSR in both mRNA level and protein level were detected using a realtime PCR test and a Western blot test respectively. Methylation of INSR promoter was analyzed by a methylation specific PCR ( MSP ) . Results Both body weight and fasting glucose were without significant difference in two groups. In high-glucose-high-fat diet group, both the glucose tolerance and insulin tolerance of neonatal rats in F1 offspring were significantly decreased. Except that in brains, the expressions of INSR gene in livers and in muscles of neonatal rats in high-glucose-high-fat diet group were down-regulated in mRNA ( realtime PCR ) and protein levels ( Western blot) compared to the normal diet group. Meanwhile, the methylation of INSR gene in livers and muscles were strengthened in high-glucose-high-fat diet group. Conclusion A high-glucose-high-fat diet fed to male SD rats leads to the decrease in glucose tolerance, insulin tolerance, and the inhibition of expression of hepatic and muscle INSR gene in neonatal offspring. The methylation of INSR gene could be involved in this phenomenon.

Objective To evaluate the inverse distance weighted(IDW) in revealing the characteristics of spatial distribution of water fluoride in Heze City,Shandong Province.Methods A geographic information system (GIS) database of water fluoride was established in Heze City of Shandong Province using the data of endemic fluorosis surveys collected by Endemic Disease Prevention Institute in Shandong Province during 2005-2007.IDW spatial interpolation was applied to predict the distribution of fluoride in drinking water in 139 towns of Heze City.Sensitivity and specificity were calculated.Results Mean water fluoride levels in 10 counties of Heze City were all higher than 1.0 mg,/L,and the water fluoride in Cao County,Juye,Mudan District and Juancheng were higher than 2.0 mg/L.Of all 139 townships of Heze City,129 were higher fluoride townships where fluoride was ＞ 1.0 mg/L,10 were lower fluoride townships(≤ 1.0 mg/L).IDW spatial interpolation showed that the water fluoride of most areas in Heze City were ＞ 1.0-2.0 mg/L.The areas with water fluoride of ＞ 2.0-3.0 mg/L were mainly located in eastern Juancheng,northern Mudan District,north-central Chengwu,central and southern Juye,southeastern part of Caoxian and eastern part of Shan Town.Regions of water fluoride ＞ 3.0 mg/L were mainly distributed in Xieji and Wanfeng towns of Juye County,Jishan town of Juancheng County,Sunlaojia town of Caoxian and Dusi town of Mudan County.The internal verification results showed that the sensitivity,specificity and overall accuracy rate of IDW used for predicting water fluoride content was 100.00％ (129/129),10.00％ (1/10) and 93.53％ (130/139),respectively.While the external verification results showed that the sensitivity,specificity and overall accuracy rate of IDW for predicting water fluoride content was 100.00％(31/31),11.11％(1/9) and 80.00％(32/40),respectively.Conclusion With the application of IDW interpolation,it is feasible to infer the overall spatial distribution based on the monitoring data,and to reveal the spatial characteristics of water fluoride in Heze City,Shandong Province.

Objective To investigate the fluoride content in drinking water as well as the current status of endemic fluorosis in 5 counties of Shandong Province,in order to provide a scientific basis for making prevention and control strategies.Methods According to the survey data of fluoride content in drinking water in Shandong Province between 2005 to 2007,an epidemiological investigation was carried out in Mudan,Jiaxiang,Wucheng,Pingdu and Boxing Counties from September to November 2013.The fluoride content in drinking water and urine and dental fluorosis of children aged 8 to 12 were investigated in 3-4 major survey villages selected in the five counties.The fluoride content in drinking water was detected by fluoride ion selective electrode method,and dental fluorosis was diagnosed by Deans method.Results Fifty-eight drinking water samples were investigated in 16 villages of the five counties.Water fluorine content in Wucheng,Mudan,Pingdu,Boxing and Jiaxiang counties was 4.14,3.84,1.83,1.33 and 0.43 mg/L,respectively.There were 4 counties' fluorine content exceeding the national standard (1.20 mg/L) except Jiaxiang County.The exceeding rate was 100％ in Wucheng and Mudan counties.Urine fluorine content of 320 children aged 8 to 12 in Wucheng,Mudan,Boxing,Pingdu and Jiaxiang counties was 4.51,4.62,1.82,1.30,1.01 mg/L respectively;the total detection rate of dental fluorosis of 574 children was 61.85％ (355/574),the rate of dental damage was 12.89％ (74/574),and dental fluorosis index was 1.27;the detection rate of dental fluorosis in Wucheng,Mudan,Boxing,Pingdu and Jiaxiang Counties was 90.18％ (101/112),97.73％ (86/88),62.22％ (84/135),54.90％ (28/51) and 29.79％ (56/188),respectively.Conclusions The exceeding rate of water fluorine content is very high in 5 counties of severe endenic fluorosis areas in Shandong Province.The urinary fluorine level of the population is still high and the prevalence of dental fluorosis of children is high.Endemic fluorosis in Shandong Province has not yet been effectively controlled,control situation is still grim.

Objective To study the effect of perinatal hypothyroidism (PHT) on hippocampal neuronal structure and function of neonatal rats.Methods Sixteen pregnant SD rats were randomly divided into control group and PHT group (n=8).The pregnant rats were subjected to gavage by normal saline or 6-propyl-2-thiouracil (PTU) every day from 15 d of pregnant to the end of lactation.After parturition,38 male neonatal rats from each group were chosen for the following study.On the 7th d of birth,15 neonatal rats from each group were sacrificed,and the concentrations of free triiodothyronine (FT) 3,FT4 and thyroid stimulating hormone (TSH) in serum and acetylcholine (Ach) in the hippocampus were detected by ELISA.Real-time PCR,Western blotting and immunohistochemistry were used to assess the expressions of neuronal nuclei antigen (NeuN) and microtubule-associated protein tau (MAPT)in transcriptional and protein levels orderly.The left neonatal rats at one month old were performed morris water maze test to evaluate the learning and memory abilities.Results ELISA results showed that both FT3 and FT4 significantly decreased but TSH increased significantly in serum of PHT rats as compared with those in the control group (P＜0.05);Ach in the hippocampus of PHT rats was reduced three folds as compared with those in control group,with significant difference (P＜0.05).Real-time PCR and Western blotting results showed that the mRNA and protein expression levels of NeuN and MAPT in PHT rats were markedly down-regulated as compared with those in the control group:0.25 and 0.12 fold ofmRNA level in control group,and 0.35 and 0.22 fold of protein level in control group,with significant differences (P＜0.05).Immunohistochemistry indicated decreased NeuN and MAPT expression levels of varying degrees in PHT rats.In the morris water maze,one-month-old rats with PHT showed significantly prolonged escape latency ([10.18±3.02] s) and lengthened total distance ([365.28±41.77] cm) as compared with the control rats ([24.36±5.15] s,[790.36±72.53] cm,P＜0.05).Conclusion PHT could result in reduced expressions of neuron markers,axons dysfunction and decreased secretion of neurotransmitter in the hippocampus of neonatal rats,and it could weaken the learning and memory abilities in long term.

Objective To explore the effect of health education on endemic fluorosis in Shandong Province,and provide evidence for further development of health education measures.Methods From 2011 to 2015,using prospective method,19 endemic fluorosis counties (cities,districts) were selected as project counties in Shandong Province each year,and 3 townships (towns) were selected in each project county.Health educational activities on prevention and treatment of endemic fluorosis were carried out in the classes of grade 4-6 in the central primary school;3 administrative villages were selected in each township (town) to carry out community health education activities.Before and after the health education activities,questionnaire surveys on the health education of endemic fluorosis prevention knowledge were conducted among 30 students of grade 5 in the central primary school and 15 housewives lived near the schools in each township (town).Results The results of health education evaluation showed that the'awareness rate of prevention and treatment of endemic fluorosis in school students and housewives were 95.64％ (27 770/29 037) and 92.09％ (14 341/15 573),respectively,which were significantly higher than those before the intervention [69.40％ (20 157/29 043) and 67.40％ (10 375/15 393)],and the differences were statistically significant (x2 =6 926.73,2 928.85,P ＜ 0.05).Among the primary school students and housewives,the knowledge awareness rates of prevention and treatment of endemic fluorosis were increased by 26.24％ and 24.69％,respectively.Conclusion After implementation of endemic fluorosis health education intervention,the awareness rate of prevention and treatment knowledge in local fluorosis areas in Shandong Province is significantly increased,which means we can further expand the scope of health education.

Objective To analyze the influencing factors of water iodine in Shandong Province.Methods The county-based study set Shandong Province as a research site.The water iodine data of county (city) from 2008 to 2010 were obtained from Shandong Institute for Prevention and Control of Endemic Disease.Water iodine content was used as a dependent variable,and soil type,hydrogeological type,topography and distance to the Yellow River were analyzed as independent variables.Normality test and general linear regression analysis of the dependent variables were performed using SAS 9.3 software;geographically weighted regression (GWR) analysis was performed using SAM V4.0 software;related electronic maps were drawn using ArcGIS 9.3 software.Results A total of 108 164 water iodine content data were collected.General linear regression analysis showed that the constructed regression model was statistically significant (F =16.29,P ＜ 0.01),and the soil type was included in the model with a determination coefficient (R2) =0.51.GWR analysis showed that R2 =0.63 and the adjustive determination coefficient (R2adj) =0.59.Considering the autocorrelation of the variable space,the model's goodness of fit was better than that of the traditional general linear regression model.GWR analysis showed that soil type and distance to the Yellow River were major factors related to water iodine in Shandong Province.There was a negative correlation between soil type and spatial variability of water iodine in most areas of Shandong Province,the correlation coefficients weakened gradually from west to east,indicating a geographic gradient variability.The correlation coefficients of distance to the Yellow River and spatial variability of water iodine were negative in some areas,while they were positive in other areas,indicating a clear geographical variability from southwest to northwest.Conclusion The soil type and the distance to Yellow River are important factors affecting the spatial distribution of water iodine in Shandong Province.

Objective To analyze the relationship between blood glucose,blood lipid and body mass index (BMI) in elderly patients with hypertension.Methods Form January 2016 to December 2017,376 hypertensive patients over 65 year old in Jinan city were enrolled in this study.The sex,age,BMI,fasting blood glucose and blood lipid were investigated and tested.The prevalence of coronary heart disease and diabetes mellitus in hypertensive patients were investigated,and the relationship between BMI and blood glucose,blood lipid and liver function index were explored.Results Of 376 hypertensive patients,the detection rate of diabetes mellitus was 21.01％ (79/376),221 cases were diagnosed with coronary heart disease,with the detection rate of 58.78％.With the rise of BMI,fasting blood glucose showed an upward trend.Person correlation analysis showed that there was a significant positive correlation between BMI and fasting blood glucose(r =0.167,P =0.003).The difference between TG and TC in different BMI groups was statistically significant(FTG =12.48,P ＜ 0.001;Frc =4.83,P ＜ 0.001).The content of alanine transaminase in the overweight group and obese group was significantly higher than that in the normal body weight group,the difference was statistically significant(F =5.24,P =0.005).Conclusion For elderly hypertensive patients,it is urgent to test blood glucose and coronary heart disease screening.For people over the age of 65,obesity is still an important risk factor for hyperlipidemia and hyperglycemia.Therefore,body weight control is needed in elderly patients with hypertensive.

Objective:To dynamically monitor the prevalence and trend of dental fluorosis in children in Shandong Province, and to evaluate the prevention and control measures for drinking water-borne endemic fluorosis (referred to as drinking water-borne fluorosis), and to provide scientific basis for the next step.Methods:Totally 40 counties (cities, districts) were selected as project counties (cities, districts) from drinking water-borne fluorosis areas in Shandong Province in 2018, and all counties (cities, districts) were selected in 2019 and 2020, to investigate the situation of water improvement, detect water fluoride content, and investigate the prevalence of dental fluorosis in children aged 8 - 12 years.Results:From 2018 to 2020, the detection rates of dental fluorosis in children aged 8 - 12 years were 10.30% (503/4 884), 8.94% (25 895/289 539) and 8.66% (24 061/277 689), respectively, with statistically significant differences (χ 2 = 27.10, P < 0.001), and the dental fluorosis indexes were 0.21, 0.18 and 0.17, respectively. The total detection rates of dental fluorosis in children of different age groups in the 3 years were 7.26% (6 590/90 775), 7.97% (9 303/116 680), 9.29% (12 167/130 915), 9.29% (12 238/131 670) and 9.95% (10 161/102 072), the differences were statistically significant (χ 2 = 615.71, P < 0.001). In the 3 years, the total detection rate of dental fluorosis was 8.93% (28 101/314 737) in boys and 8.69% (22 358/257 375) in girls, the difference was statistically significant (χ 2 = 10.27, P = 0.001). In 2018 and 2019, the detection rates of dental fluorosis of children aged 8 - 12 years in water fluoride qualified villages [5.74% (235/4 095) and 7.98% (20 200/253 082)] were significantly lower than those in villages with excessive water fluoride [33.97% (268/789) and 15.62% (5 695/36 457), χ 2 = 570.61, 2 283.76, P < 0.001]. Conclusions:The prevalence of dental fluorosis among children aged 8 - 12 years has been effectively controlled, and remarkable results have been achieved in prevention and treatment of drinking water-borne fluorosis in Shandong Province. However, the detection rate of dental fluorosis among children in a few endemic villages is high, so it is necessary to continue to strengthen the monitoring of fluoride content in drinking water and the condition of dental fluorosis among children.