Objective To investigate the current prevalent status of endemic fluorosis in the alluvial plain area of the Yellow River in Shandong Province,in order to provide a scientific basis for developing control measures against the disease.Methods Six counties were selected as survey counties by random sampling,ten improvedwater projects were selected in each survey county,for the projects,the operating effect was investigated and water fluoride content was tested;three epidemic villages were chosen as survey villages in each county,the operating condition and the fluoride level of water were investigated in the villages with water improvement projects.Dental fluorosis of children aged 8 to 12 was surveyed,the urinary fluoride and skeletal fluorosis X-ray diagnosis were checked of adults over the age of 25.Water fluoride and urinary fluoride contents were detected via the F-ion selective electrode method,and the prevalence of dental fluorosis of all children aged 8 to 12 was diagnosed based on Clinical Diagnostic Criteria of Dental Fluorosis (WS/T 208-2011),skeletal fluorosis X-ray diagnosis was done based on the National Standard for Diagnosis of Endemic Skeletal Fluorosis (WS 192-2008).Results ①In the six counties,58 improved-water defluoridation projects were investigated,all projects were operated normally,the qualified rate of water fluoride content was 44.83％ (26/58).②A total of 19 villages that had water-improving and defluoridation projects were investigated,and all projects were operated normally,the qualified rate of water fluoride content was 42.11％ (8/19).③The overall rate of dental fluorosis among children aged 8 to 12 years old was 49.28％ (480/974),with the index of dental fluorosis as 1.01 in 19 villages,the prevalence of dental fluorosis was mild.In the qualified villages of water fluoride concentration,the positive rate of dental fluomsis among children aged 8 to 12 was 33.41％ (148/443),dental fluorosis index was 0.65,and the prevalence of dental fluorosis was extremely low;in the exceeding-standard villages of water fluoride content,the positive rate of dental fluorosis among children aged 8 to 12 was 62.52％ (332/531),dental fluorosis index was 1.36,and the prevalence of dental fluorosis was mild;the detection rate of dental fluorosis among children aged 8 to 12 of the villages with qualified fluoride content was lower than the rate of the villages with excessive fluoride (x2 =81.91,P ＜ 0.01).④X-ray detection rate of skeletal fluorosis in adults over the age of 25 was 6.14％ (53/863) in 17 villages,there was no statistically significant difference between the qualified villages and the exceeding-standard villages of water fluoride concentration (x2 =1.55,P ＞ 0.05),X-ray detection rate of skeletal fluorosis in adults was 5.04％ (20/397) and 7.08％ (33/466),respectively.In the qualified villages and the exceeding-standard villages of water fluoride,urinary fluoride geometric average and the exceeding rate of urinary fluoride were 1.50 mg/L,44.16％ (170/385) and 2.09 mg/L,62.58％ (286/466),respectively.In the qualified villages of water fluoride,the exceeding rate of adult urinary fluoride was lower than that in the exceeding-standard villages (x2 =28.58,P ＜ 0.01).Conclusions The prevention and control measures on endemic fluorosis have had some effects in the alluvial plain area of the Yellow River in Shandong Province.But the water fluoride content of water improving defluoridation projects still exceeds the national standard seriously,and endemic fluorosis has not been effectively controlled.Prevention measures should be further strengthened.

Objective To understand the schedule and effectiveness of water-improving defluoridation projects comprehensively of control of fluorosis in drinking-water-borne endemic fluorosis areas in Shandong Province,and to provide a scientific basis for making strategies for prevention and control of the disease.Methods In accordance with the requirements of Shandong Provincial Survey Scheme for Implementation of Prevention and Control Measures of Endemic Fluorosis,the progress of water-improving defluoridation projects was investigated in Shandong Province.The types of water source,scale and operating conditions for water-improving defluoridation projects in 17 cities of the province were investigated.Water fluoride contents of the normal operating projects were detected by F-ion selective electrode.Results ① By the end of 2012,a total of 3 539 water-improving defluoridation projects were built that covered 9 856 fluorosis villages,113 counties,17 cities in the province,and the water-improving rate was 91.01％ (9 856/10 830).The type of water source of water-improving project was mainly groundwater,accounted for 93.78％ (3 319/3 539) of the total projects.As for the scale of the water-improving projects,small centralized water supply projects were the main projects,accounted for 92.96％(3 290/3 539) of the total projects.\)Of all the water-improving defluoridation projects,normal operating projects accounted for 89.12％(3 154/3 539),intermittent and scrapped projects accounted for 3.25％(115/3 539) and 7.63％ (270/3 539),respectively.③Among normal operating projects,the number of projects with water fluoride content ≤ 1.20 mg/L was 1 925,accounted for 72.40％(1 925/2 659).The number of projects with water fluoride content ＞ 1.20 mg/L was 734,accounted for 27.60％ (734/2 659); among them water fluoride contents between 2.01-4.00 mg/L and ＞ 4.00 mg/L were 233 and 65,respectively,and the highest water fluoride value was 9.71 mg/L.Conclusions The progress of water-improving projects in some cities (counties) of Shandong Province is still slow.Some of the water-improving projects can not be operated normally or have been scrapped,and water fluoride content has exceeded the standard seriously.So the prevention and control measures need to be further strengthened,funding should be increased,and the operating conditions and water quality of the water-improving defluoridation projects in Shandong need to be further improved.

Objective To understand the status quo of the illness situation and the implementation of prevention and control measures on Kashin-Beck disease( KBD ) in Shandong Province , and provide a scientific basis for assessment and acceptance of the work on eliminating KBD. Methods In accordance with the requirements of the national “Implementation Scheme for Endemic Disease Control in 2012” and the “Shandong Provincial Technical Scheme for KBD Control in 2012”. In four towns of Qingzhou, three epidemic villages were selected as the surveying villages in each town in order to understand the implementation of measures for prevention and control of KBD; information such as population of investigating villages, per capita income, farming, food and the implementation of control measures,etc were included. In each investigating village, 7 - 12 years old children were selected to receive clinical and X-ray examination. When fewer than 50 people in a investigating village , one additional endemic village was included near the investigating village , and all children aged 7 to 12 of the village were checked. The number of cases of clinical degree Ⅰ, Ⅱ, Ⅲand the detection rates, X-ray positive detection rate, the number of cases of metaphysis, epiphysis, distal end of phalanx, carpal bone, triad and the detection rates were calculated, respectively. Clinical and X-ray diagnosis were based on “The Diagnostic Criteria of Kaschin-Beck disease”(WS/T 207-2010). Results A total of 14 epidemic villages were selected to survey in four towns of Qingzhou. In the recent three years in the epidemic areas, measures of supplying Se had not been implemented;measures of resettlement and off-site education had not been implemented either. In the epidemic areas , the main crops were wheat and corn; the staple food was flour which accounted for more than 80%, and the foreign food bought accounted for only 11%. The areas of returning farmland to forest (grass) accounted for 0.32%(36/11 151) of the original arable land, and the areas of replanting economic crops accounted for 1.17%(131/11 151) of the original farmland. A total of 536 children aged 7 to 12 were examined by clinical and X-rays. Patient of KBD was not detected clinically. Six positive patients with metaphyseal changes of KBD were detected by X-rays, and the average X-ray detection rate was 1.12%(6/536). Patients with abnormal epiphysis, distal end of phalanx and carpal bone were not detected by X-rays. Conclusions KBD in Shandong Province has been effectively controlled. Since the cause of KBD is still unknown, it is necessary to build a sustainable long-term control mechanism of KBD;further improve the monitoring system and dynamic monitoring work still need to be strengthened.

Objective To study the prevalence of drinking water type of endemic fluorosis in Shandong Province,and to provide a scientific basis in making strategies for prevention and control of the disease.Methods Ten counties (cities,districts) were selected by random number table method to carry out the epidemiological study,and to study the progress and effect of water-improving and defluoridation projects.Three villages in each county (city,district) were chosen to determine fluoride content of drinking water and to check the prevalence of dental fluorosis of children 8 to 12 years old.Water fluoride content was determined with fluoride ion-selective electrode,and dental fluorosis was diagnosed by the Deans method.Results In the 10 counties (cities,districts),a total of 515 water-improving and defluoridation projects were built covering 3 207 fluorosis villages,and the waterimproving rate was 81.71％ (3 207/3 925).A total of 85 water-improving and defluoridation projects were investigated in the 10 counties (cities,districts),and all of the projects were operating normally.The number of projects that water fluoride concentration ≤ 1.20 mg/L was 51; the qualified rate of water fluoride concentration was 60.00％ (51/85),and the maximum value of water fluoride was 4.38 mg/L.A total of 29 villages that had waterimproving and defluoridation projects were investigated in the 10 counties (cities,districts),and the number of villages that mean of water fluoride ≤ 1.20 mg/L was 21,accounting for 72.41％ (21/29); ＞ 1.20 mg/L was 8,accounting for 27.59％ (8/29),and the maximum value of water fluoride was 4.02 mg/L.In the 21 qualified villages of water fluoride concentration,a total of 1 023 children aged 8 to 12 were examined; the positive rate of dental fluorosis was 38.12％ (390/1 023); dental fluorosis index was 0.67,and the prevalence of dental fluorosis was extremely low.In the 8 exceeding-standard villages of water fluoride content,a total of 449 children aged 8 to 12 were examined; the positive rate of dental fluorosis was 54.79％ (246/449); dental fluorosis index was 1.18,and the prevalence of dental fluorosis was mild.Conclusion In Shandong Province,the water fluoride content of waterimproving and defluoridation projects exceeds the national standard seriously,and the condition of children's dental fluorosis is still serious,and the measures of water-defluoridation should be further strengthened.

Objective To understand the status of endemic fluorosis in Shandong Province.Methods In accordance with the requirements of the National Surveillance Scheme of Drinking-Water-Type Endemic Fluorosis (Trial) and Shandong Provincial Surveillance Scheme of Drinking-Water-Type Endemic Fluorosis (Trial),ten counties (cities,districts) were chosen in the province,and ten water-improvement projects were selected in each county (city,district).The operating effect of water-improvement projects was investigated; one peripheral water sample of each project was collected,and water fluoride content was tested.Three epidemic villages were chosen as fixed monitoring villages in each county (city,district).In the villages that had changed water source,one peripheral water sample was collected; in unchanged water source villages,one water sample was collected following five different directions of the east,the west,the south,the north and the center of the water source location; and the water fluoride content was tested.All students aged 8 to 12 were checked for dental fluorosis in the monitoring villages.The fluoride content in drinking water was detected by fluoride ion selective electrode method,and dental fluorosis was diagnosed by Dean's method.Results ① In the 10 counties (cities,districts),a total of 85 water-improving projects were monitored,and all the projects were in normal operation; the water fluoride contents of 47 projects were qualified,and the qualified rate of water fluoride content was 55.29％(47/85),with the maximum of water fluoride content was 4.74 mg/L.② In the 30 fixed monitoring villages,27 monitored villages had water-improving projects; water fluoride contents of 19 villages were qualified,the qualified rate of water fluoride content was 70.37％ (19/27),with the maximum of water fluoride content was 4.77 mg/L.In the 3 monitored villages without water-improving projects,villages of mean water fluoride contents ≤ 1.20 mg/L and ＞ 1.20 mg/L were two and one,respectively,with the maximum of water fluoride content was 1.55 mg/L.③ In the 19 monitored villages with water-improving projects that in normal operating condition with qualified water fluoride content,the detected rates of dental fluorosis and the defect type of dental fluorosis among children aged 8 to 12 years old were 52.37％(508/970) and 6.39％(62/970),respectively,and the index of dental fluorosis was 1.02.In the 8 monitored villages with water-improving projects that in normal operating condition with water fluoride content that exceeded the national standard,the detected rates of dental fluorosis and the defect type of dental fluorosis were 62.39％ (297/476) and 8.82％ (42/476),respectively,and the index of dental fluorosis was 1.67.In the 3 monitored villages without water-improving projects,the detected rates of dental fluorosis and the defect type of dental fluorosis were 49.45％ (90/182) and 7.14％ (13/182),respectively,and the index of dental fluorosis was 1.25.Conclusions In Shandong Province,the water fluoride content of water-improving defluoridation projects exceeds the national standard seriously,and water quality of the projects still need to be further improved.The projects of water-improving defluoridation play a certain role in control of dental fluorosis condition,but the condition of children' s dental fluorosis is still very serious.So preventive and control measures for endemic fluorosis should be further strengthened.

Objective To supply a scientific basis for laying out a unified standard of reference value of Chinese newborn boys' hemoglobin. Methods After the reference values of 5169 Chinese healthy newborn boys' hemoglobin tested in 78 areas were collected, a research was made on the relationship between the reference value of Chinese newborn boys' hemoglobin and altitude by using curvilinear regression analysis. Results As the altitude gradually increased, the reference value of Chinese newborn boys' hemoglobin gradually increased by index law, with significant correlation (R=0.601, F=43.05, P= 0.0000). One curvilinear regression model was given out: =176.9e 0.00008662x?25.3. Conclusion If altitude of a particular area is known, the reference value of Chinese newborn boys' hemoglobin in this area can be established by using regression model. According to the correlation between Chinese newborn boys' hemoglobin and altitude, China can be divided into three regions: Qinghai-Tibet Region, Central Region, Eastern Region.

Objective To determine the prevalence of penicillinase-producing Neisseria gonorrhoeae(PPNG) and the distribution of blaTEM-135 gene variants in PPNG at several gonococcal antimicrobial surveillance sites in China, to compare N. gonorrhoeae multi-antigen sequence typing(NG-MAST)types of PPNG and its blaTEM-135 gene variants, and to assess the difference and association in NG-MAST types of blaTEM-135 gene variants among different regions. Methods A total of 572 N. gonorrhoeae isolates were collected at 6 gonococcal antimicrobial surveillance sites from Jiangsu, Shanghai, Zhejiang, Tianjin, Guangdong and Guangxi in 2012. After isolation, purification, and identification, cefalotin paper discs were used for detection of PPNG. DNA was extracted by QIAxtractor DX kits after cultivation of the PPNG strains. Then, mismatch amplification mutation assay (MAMA) PCR was performed to identify blaTEM-135 variants, and NG-MAST analysis to determine N. gonorrhoeae genotypes. Results Among the 572 N. gonorrhoeae strains, 38.1%(218/572) were identified as PPNG, and of the PPNG strains, 52.3% (114/218) were blaTEM-135 variants. The detection rate of PPNG at these surveillance sites from high to low was as follows: 51.7% (45/87, Zhejiang), 45.6%(36/79, Shanghai), 38.0% (78/205, Guangdong), 37.5% (12/32, Guangxi), 31.2% (24/77, Jiangsu) and 25.0%(23/92, Tianjin), and that of blaTEM-135 variants was as follows: 68.9%(31/45, Zhejiang), 58.3%(14/24, Jiangsu), 50.0%(39/78, Guangdong), 47.2%(17/36, Shanghai), 39.1%(9/23, Tianjin)and 33.3%(4/12, Guangxi). NG-MAST analysis showed that the ST2318, ST1768, ST1866, ST1053 and ST8726 types predominated among these bla TEM-135 variants, and a strong correlation was found between blaTEM-135 variants and some NG-MAST types, such as ST1768, ST1053 and ST8726 types. The distribution of NG-MAST types was significantly different between the surveillance site in Tianjin (in the Northern part of China) and the other sites (in the Southern part of China), but highly similar among the surveillance sites in Jiangsu, Zhejiang and Shanghai regions. Conclusions There is a high prevalence of PPNG and its blaTEM-135 variants at several gonococcal antimicrobial surveillance sites in China, with significant differences in NG-MAST genotype distribution of PPNG and its blaTEM-135 variants among different regions.

OBJECTIVE To explore mecha-nisms of imperatorin on regulating P-glycoprotein(P-gp)in blood-brain barrier(BBB)based on net-work pharmacology combined with in vitro experi-ment.METHODS Drug targets were predicted using the Pharmapper and Swiss targets data-bases;disease targets were obtained through the Genecards database;intersections between drugs and disease targets were screened by Cytoscape software;the obtained core targets were used to construct protein-protein interaction(PPI)network,gene ontology(GO)functions,and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis.The effects of imperatorin(20,50,100 μ mol·L-1)on P-gp activity were monitored in hCMEC/D3in vitro BBB model,and the effects of imperatorin on the expression of target proteins were verified using Western blot method.RESULTS 55 drug targets and 3102 disease targets were obtained from the network pharmacology screening,and 37 core targets were obtained after the combination.Enrichment analysis showed that core targets were closely related to chemical synaptic trans-mission regulation,neurotransmitter receptor activity,proteinkinaseregulationactivity,G protein-coupled receptor signaling pathway,neural active ligand receptor interaction pathway,PI3K-Akt sig-naling pathway,VEGF signaling pathway,etc..In vitro experimental validation suggested that all tested concentration groups of imperatorin signifi-cantly reduced the activity and expression of P-gp,which were achieved by significantly downregu-lating the phosphorylation levels of PI3K and Akt,and repressing the expression of VEGFR2 pro-tein.CONCLUSION Network pharmacology was used to predict the core targets and signaling pathways of imperatorin on regulating P-gp in BBB and relevant validation was conducted through in vitro experiments,providing a refer-ence basis for further exploration of the mecha-nisms of imperatorin on regulating P-gp in BBB.

Objective To detect the spatial distribution characteristics of water fluoride in Shandong Province.Methods The county-based study set Shandong Province as a research site.The county level fluoride database was matched with electronic maps to build geographic information system (GIS) spatial data platform.Global Moran's I and Local Moran's I index were calculated,respectively,and the cluster range of water fluoride distribution in Shandong Province was studied through SaTScan software.Results The water fluoride was normal (≤ 1.0 mg/L) in 54 counties in Shandong Province,mainly located in Weihai and Yantai in the eastern,Dongying in northern,and vast region in middle and southeastern of Shandong Province.Eighty-six counties were high water fluoride counties (＞ 1.0 mg/L),mainly distributed in the southwest,northwest and north-central of Shandong Province,showing a significant geographical feature.Global spatial autocorrelation analysis showed that the distribution of water fluoride content in Shandong Province showed significant positive spatial autocorrelation (Moran's I =0.44,Z =6.83,P ＜ 0.01).Local Moran's I analysis showed water fluoride in 13 counties had local spatial autocorrelation,being all high-high clusters.And these results were statistically significant (P ＜ 0.05).A cluster area was detected through SaTScan spatial analysis software,including 15 counties.The center was located in Dongming County of Heze City,with radius of 130.08 km.The results and the local spatial autocorrelation results were basically consistent.Conclusions There are apparent spatial autocorrelation and spatial cluster in water fluoridation in Shandong Province.Spatial autocorrelation and SaTScan software can be combined in exploring the spatial distribution of water fluoride.

As an important means of treating heart failure (HF), cardiac assist device has been widely used in clinic. This paper reviews the application status, existing problems and future development trend of cardiac assist devices, including the classification of cardiac assist devices, representative research achievements and indications of the assist devices. It also summarizes the biomechanical indexes of the heart and the new approaches and methods for treating heart failure, as well as the hemodynamic studies of cardiac assist devices in recent years. The research findings provide references for further optimization of cardiac assist device structure and clinical application of the device.
Heart Failure ; Heart-Assist Devices ; Hemodynamics ; Humans