AIM: To explore the effects of angiotensin II on aortic calcification in the rat. METHODS: Arterial calcification of Sprague-Dawley rats was induced by vitamin D_3 plus nicotine. Calcification was confirmed by Von Kossa staining, measurement of calcium content, [~(45)Ca~(2+)] accumulation and alkaline phosphatase (ALP) activity of vascular tissue. RESULTS: The results showed that calcium content, [~(45)Ca~(2+)] accumulation and ALP activity in calcified arteries increased significantly compared with those of control. Ang Ⅱ levels in plasma and aortic tissues and the amount of angiotensinogen mRNA in calcified aorta were also increased as compared with control. Captopril (inhibitor of ACE) and losartan (Ang Ⅱ receptor inhibitor) decreased significantly the content of calcium, [~(45)Ca~(2+)] uptake and ALP activity in calcified aorta. Ang Ⅱ levels in plasma and aortic tissues and the amount of angiotensinogen mRNA in aortic tissue were down-regulated by captopril. The amount of angiotensinogen mRNA and the content of Ang Ⅱ in the calcified aorta were also decreased by losartan. CONCLUSION: The captopril and losartan significantly alleviate the vascular calcification. [

Objective To investigate the clinical value of glypican-3 (GPC3) in the diaganosis of hepatocellular carcinoma (HCC),the contents of GPC3 in the serum and tissues of HCC patients were detected.Methods ELISA and immunohistochemical staining were applied to detect GPC3 expressing level in the serum and tissues in 79 cases with HCC,35 cases with post-hepatitis cirrhosis and 30 normal liver specimens and the resuits were compared.The influential factor of GPC3 content in the patients with HCC was analyzed by logistic regression model.Results The serum level of GPC3 in patients with HCC was (143.02±40.26) μg/L which was signifcantly higher than that in patients with post-hepatitis cirrhosis [(6.15±4.31) μg/L] and healthy controls [(4.47±3.22) μg/L] (all P ＜ 0.01).The expression levels of GPC3 was signifeantly higher in post-hepatitis cirrhosis tumor-adjacent tissue and tumor-distant tissue.The expression levels of GPC3 was significantly positively correlated with tumor presence of distant mestasis (x2 =13.182,P ＜ 0.0) and clinical stage (x2 =4.250,P ＜ 0.05),and not correlated with sex,age,tumor size and the level of AFP inserum (P ＜ 0.01).Conclusion GPC3 is specific the diagnosis of HCC.The joint diagnosis of GPC3 and AFP will improve the sensitivity of HCC.Therefore,GPC3 could as a biomarker for evaluating HCC condition and prognsis.

Objective To find out the distribution of drinking-tea-borne fluorosis in the six ethnics in Qinghai Province, and to provide basic data for prevention and control of the disease. Methods In 2010, according to the requirement of “The National Surveillance Program of Drinking-Tea-borne Fluorosis”, six ethnics accounted for 99.59% of total population in Qinghai Province were investigated in 28 counties having brick-tea drinking habit. Three townships and a town in each county, two administrative villages(residents’ committee) in each township and town were chosen and 50 adults in each administrative village and residents ’ committee were selected to check skeletal fluorosis, dental fluorosis, urine fluoride and daily drinking amount of tea water. Five to six samples of drinking tea water were determined. Dental fluorosis was examined by Deans method; the fluoride content of brick-tea and urine were determined by fluoride ion selective electrode; the skeletal fluorosis was diagnosed based on “Endemic Osteofluorosis Clinical Indexing Diagnosis Standard”( WS 192-2008 ) . Results A total of 10 335 adults were surveyed, the number of Tibetan, Han, Hui, Mongolian, Tu and Salar ethnics were 4 972, 3 063, 1 196, 634, 235 and 235, respectively. The daily drinking amounts of tea water in Mongolian, Tibetan, Hui, Tu, Han and Salar ethnics were 2.53, 2.19, 1.74, 1.63, 1.22 and 1.07 L, respectively. Daily fluoride intakes in Tibetan, Mongolian, Tu, Hui, Han and Salar ethnics were 3.99, 2.78,2.27, 2.16, 1.78 and 1.28 mg, respectively. The medians of urinary fluoride concentration of the Tibetan, Tu, Hui, Han, Mongolian and Salar ethnics were 1.46, 1.19, 1.12, 0.98, 0.93 and 0.81 mg/L, respectively. The prevalence rates of dental fluorosis of the Hui, Han, Tibetan, Tu, Mongolian and Salar ethnics were 34.53%(413/1 196), 27.07%(829/3 063), 21.60%(1 074/4 972), 20.00%(47/235), 17.98%(114/634) and 6.38%(15/235), respectively. The incidence rates of clinical skeletal fluorosis of the Tibetan, Mongolian, Han, Hui, Tu and Salar ethnics were 13.42%(667/4 972), 11.04%(70/634), 9.31%(285/3 063), 7.61%(91/1 196), 5.53%(13/235) and 4.26%(10/235), respectively. Conclusions The distribution and prevalent status of drinking-tea-borne fluorosis in the six ethnics of Qinghai Province are different. Tibetan and Mongolian ethnics are the key population concerning the prevention and control of the disease.

Objective To observe the illness change trend of drinking water type endemic arsenic poisoning in Qinghai Province, comprehensively evaluate the effect of prevention and control measures, in order to provide a scientific basis for timely adjustment of the prevention and control measures. Methods From 2010 to 2013, according to the Drinking Water Type Endemic Arsenic Poisoning Monitoring Programs, 3 villages in 2 counties within Qinghai Province were randomly selected as monitoring sites. The arsenic content in drinking water of residents was measured, water improvement projects in all monitoring villages were investigated; at the same time an investigation of arsenic disease in resident population was conducted, and urinary arsenic content was monitored. Arsenic in drinking water and urine was determined by hydride generation atomic fluorescence spectrometry, and arsenic poisoning was diagnosed using Endemic Arsenic Poisoning Diagnostic Criteria (WS/T 211-2001). Results Of the three water improvement projects, two were water arsenic exceeded the standard, and one was intermittently operated. From 2010 to 2013, the arsenic poisoning detec tion rate in Baoning Village was 27.30% (193/707), 31.90%(245/768), 29.35%(221/753) and 28.22%(219/776); in Kecai Village was 32.62%(107/328), 34.83%(124/356), 31.26%(131/419) and 29.35%(118/402);and in Manimotai Village was 56.58%(43/76), 52.81%(47/89), 45.10%(46/102) and 34.69% (34/98), there was no significant difference statistically of the arsenic poisoning detection rates in the three monitored villages in the 4 years (χ2 =3.09, 0.04, 0.92, all P>0.05). From 2010 to 2013, women arsenic poisoning detection rate was 36.45%(203/557), 40.59%(246/606), 36.12%(225/623) and 34.77%(218/627), respectively;men was 25.27%(140/554), 28.01%(170/607), 26.57%(173/651) and 23.57%(153/649), respectively;women arsenic poisoning detection rates were higher than those of men (χ2 = 16.25, 21.32, 13.49, 19.38, all P < 0.05). Arsenic poisoning detection rate of people younger than 60 years old had a tendency to increase with age. In 2012 and 2013, 105 and 93 urine samples were tested, respectively; urinary arsenic geometric mean was 0.113 and 0.149 mg/L. Conclusions Water improvement projects and water quality are not optimistic, and prevalence of arsenic poisoning is still at a higher level. A sound long-term monitoring program should be established as soon as possible, the management and maintenance of water improvement projects should be strengthened, and the monitoring and prevention work should not be neglected.

Objective To find out the distribution and status of drinking-water-borne fluorosis in Qinghai,and to provide basic data for prevention and control of the disease.Methods According to the "Action Plan of Endemic Fluorosis and Arsenic Poisoning in Qinghai (2016-2020)",10 counties were selected to carry out the epidemiological study in 2016.The operation of the improvment project was investigated.The fluoride content of water was determined with fluoride ion-selective electrode,and dental fluorosis of 8-12 years old children was diagnosed by the Deans method.Results A total of 97 villages have been investigated,and all water was improved.The range of water fluoride was 0.20-2.13 mg/L.Normal operation rate of water-improving project was 83.33％ (50/60).The pass rate of water fluorine content was 96.67％ (58/60).The prevalence rate of dental fluorosis of the children was 18.70％ (774/4 140),and it was significantly lower than national standards (30％).Conclusions Water has been improved in all of the fluorosis villages.Most of the water-improving engineering projects to control drinking-water fluorosis has played a positive role,and drinking-water-borne fluorosis is under control.

Objective To explore the prevalence state of drinking brick-tea type fluorosis in children in Guoluo Prefecture,Qinghai Province.Methods According to the historical prevalence of drinking tea-type fluorosis in Guoluo Prefecture,in 2017,in 5 counties of Guoluo Prefecture,according to the pastoral area,agricultural area,semi-agricultural and semi-pastoral areas,each township (town) was selected,in each township (town) drawed a natural village in a ward as a survey point.At each survey site,drinking water samples of local residents were collected,and 10 households were selected,tea samples were collected,and dental fluorosis was investigated for children aged 8-12 years old.The mean of fluoride was determined by fluoride ion selective electrode method (GB/T 5750.5-2006,GB 19965-2005),and the dental fluorosis was diagnosed based on "Diagnosis of Dental Fluorosis" (WS/T 208-2011).Results The mean of fluoride in 85 water samples was 0.34 mg/L (0.20-0.77 mg/L),the mean of fluoride in 161 brick-tea samples was 579 mg/kg (110-1 278 mg/kg).The mean of daily fluoride intake of each person was 6.78 mg,among them,73.29％ (118/161) drank brick-tea,the detection rate of dental fluorosis of 2 083 children was 22.85％ (476/2 083),and the index of dental fluorosis was 0.42,the prevalence was weak.Conclusion The prevalence of drinking brick-tea type fluorosis of children in Guoluo Prefecture is less serious.

Objective:To analyze and screen microRNA (miRNA) related to the prognosis of gastric cancer(GC) by bioinformatics analysis, and to construct and validate a risk score model.Methods:The human genome miRNA sequencing data and corresponding clinicopathological data of the 491 samples (446 GC tissue samples and 45 normal gastric tissue samples) were downloaded from the cancer genome atlas (TCGA) database. The differentially expressed microRNA (DEM) was analyzed with edgeR package of R 4.0.2 software and the obtained DEM’s profile was randomly divided into training set and test set according to the ratio of 1∶1. The miRNA related to prognosis were analyzed and screened with univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression, and multivariate Cox regression analysis was further performed to analyze the screened prognostic-related miRNA and then the prognostic risk score model was constructed. Kaplan-Meier curve, receiver operating characteristic curve (ROC), and dynamic area under the ROC were drawn to evaluate the predictive power of the model.Results:A total of 175 DEM in GC tissues were screened out based on the cut-off criteria of |log2 Fold Change|>1.5 and P<0.01. Six DEMs related to the overall survival rate of patients with GC were screened out by univariate Cox regression and LASSO regression analysis, and then a five-miRNA risk score model was successfully constructed by multivariate Cox regression. The risk score=0.183×hsa-miRNA-184+ 0.086×hsa-miRNA-675-0.231×hsa-miRNA-2115+ 0.548×hsa-miRNA-3943-1.455×hsa-miRNA-1246. In the training set, test set and overall data set, the cumulative survival rates of the patients with higher risk score were lower than those of the patients with lower risk score, respectively, and the differences were statistically significant ( χ2=18.90, 9.50 and 26.70, all P<0.05). The prediction power of the model was better than that of TNM stage. And the results of stratified analysis showed the predictive ability of the model in patients with early GC. The results of univariate Cox regression and multivariate Cox regression demonstrated that the risk score of the model, gae and M stage were independent risk factors for poor prognosis in patients with GC (hazard ratio(95% confidence interval)1.19(1.07 to 1.32), 1.20(1.06 to 1.40), 1.50(1.01 to 2.23), 1.90(1.28 to 2.90), 1.34(1.15 to 1.57), 2.10(1.05 to 4.40); all P<0.05). Conclusion:The 5-miRNA risk score model based on 5 miRNAs which was an independent prognostic factor had high accuracy in predicting the prognosis of patients with GC.

Objective:To study the epidemic status of drinking tea type endemic fluorosis in Qinghai Province.Methods:In 2019, in counties (cities, districts, referred to as counties) that had the habit of drinking brick tea in 8 cities (prefectures) of Qinghai Province, epidemiological investigation of drinking tea type endemic fluorosis was carried out in villages. Ten households were randomly selected from each village, to investigate the demographic data of each household and the drinking situation of brick tea, residents' drinking water and brick tea samples were collected to determine the fluorine content, and calculate the daily per capita tea fluorine intake. At the same time, skeletal fluorosis was examined in all adults over 25 years old, and dental fluorosis was examined in all children aged 8 to 12 years old in survey sites. The content of fluorine in tea and water was detected by ion selective electrode method; the diagnosis of skeletal fluorosis was based on "Diagnostic Criteria for Endemic Skeletal Fluorosis" (WS 192-2008), the diagnosis of dental fluorosis was based on "Diagnosis of Dental Fluorosis" (WS/T 208-2011).Results:The mean (range) of fluorine of the 3 602 water samples was 0.31 (0.20 - 1.00) mg/L. The geometric mean (range) of fluorine of the 31 067 brick tea samples was 646 (40 - 2 295) mg/kg, the fluorine content of the brick tea ≤300 mg/kg accounted for 7.80% (2 422/31 067) of the total samples. The proportion of drinking Fu brick-tea was 89.97% (27 952/31 067); and the daily per capita tea fluorine intake was 1.93 mg, the daily per capita tea fluorine intake in Guoluo, Yushu and Hainan prefectures were higher than the health standard (3.50 mg). The detection rate of skeletal fluorosis in adults was 0.16% (2 357/1 484 907), Yushu Prefecture was the highest [29.23% (592/2 025)], followed by Guoluo Prefecture, which was 8.21% (771/9 393). The detection rate of dental fluorosis in children was 4.79% (8 076/168 623), Yushu Prefecture was the highest [32.61% (1 562/4 790)].Conclusion:Drinking tea type endemic fluorosis is prevalent in Qinghai Province, with obvious regional characteristics, covering a large population. The disease is relatively popular in Yushu Prefecture and Guoluo Prefecture.

Objective:To find out the variety, producing area, fluorine content of brick tea in Qinghai Province, and the drinking situation of brick tea among people, so as to provide basis for preventing and curing endemic fluorosis of drinking tea type.Methods:From April to November 2019, according to historical data, in 3 066 administrative villages in 39 counties (cities, districts, hereinafter referred to as counties) in Qinghai Province that had the habit of drinking brick tea, 10 families were randomly selected from each village to investigate the demographic data of each family and the drinking situation of brick tea, to collect brick tea samples to determine the fluorine content, and to calculate the daily average brick tea fluorine intake of the population > 16 years old.Results:A total of 31 067 brick tea samples were collected. The main brick tea consumed by the residents in the whole province was Fu brick tea, accounting for 89.97% (27 952/31 067), followed by Kang brick tea [5.12% (1 592/31 067)], Green brick tea [2.29% (710/31 067)], Black brick tea [1.85% (574/31 067)], and golden tip, mosaic, black wool and other brick tea [0.77% (239/31 067)]. There were 523 brands of brick tea in circulation in the province, among which there were 410 brands produced in Hunan Province, 26 brands in Sichuan Province, 11 brands in Hubei Province, and 76 brands in Henan Province and other provinces. The average content of fluorine in brick tea was 646.1 mg/kg, which ranged from 40.0 to 2 295.0 mg/kg. Brick tea with fluorine content ≤300 mg/kg accounted for 7.80% (2 422/31 067) of all samples. The annual average consumption of brick tea by population > 16 years old was 1.09 (0.35 - 7.40) kg, and the daily average brick tea fluorine intake was 1.93 (0.39 - 18.64) mg. There were 15 counties and 486 administrative villages in which the daily average brick tea fluorine intake exceeded the national standard (3.5 mg).Conclusion:The main brick tea in circulation in Qinghai Province is Fu brick tea, which has high fluorine content and is harmful to people, and prevention and control measures should be taken as soon as possible.

Objective:To observe the changes of serum C-terminal peptide of type Ⅰ collagen (CTX-1) and N-terminal lengthening peptide of type Ⅰ collagen (P1NP) in adult patients with skeletal fluorosis in the tea-drinking-borne endemic fluorosis area in Qinghai Province, and to find sensitive indicators for diagnosis of skeletal fluorosis.Methods:From April to August 2019, a case-control study was carried out in tea-drinking-borne endemic fluorosis area in Zhiduo County, Yushu Tibetan Autonomous Prefecture, and Gangcha County, Haibei Tibetan Autonomous Prefecture of Qinghai Province. According to the Diagnostic Standard for Endemic Skeletal Fluorosis (WS/T 192-2008), the clinical diagnosis and X-ray examination of skeletal fluorosis were carried out for permanent residents ≥25 years old and living for more than 10 years in the area, combined with face-to-face inquiry and investigation of past disease history, lifestyle and clinical manifestations. The patients with skeletal fluorosis and healthy people were selected as skeletal fluorosis group and control group, respectively. Randomized urine samples and fasting venous blood from the two groups were collected. The content of fluoride in urine was determined by ion selective electrode method, and the contents of CTX-1 and P1NP in serum were determined by enzyme-linked immunosorbent assay (ELISA).Results:A total of 127 people in the disease area were investigated, including 63 cases in skeletal fluorosis group and 64 cases in control group. There was no statistically significant difference in age and sex ratio between the two groups ( t = 0.42, χ 2 = 0.07, P > 0.05). The X-ray examination results showed that the patients with skeletal fluorosis were mainly mild, accounting for 71.43% (45/63); X-ray changes were mainly ossification of interosseous membrane and tendon. The urinary fluoride in control group and skeletal fluorosis group was 1.62 (1.12, 1.95) and 3.22 (2.38, 4.89) mg/L, respectively, with statistically significant difference between the two groups ( Z = 7.07, P < 0.001). The difference of serum CTX-1 and P1NP contents between the two groups was statistically significant ( Z = 2.00, 4.89, P < 0.05). Conclusions:The levels of serum CTX-1 and P1NP in patients with skeletal fluorosis are higher than those in healthy people. Serum CTX-1 and P1NP may be used as sensitive indicators for diagnosis of skeletal fluorosis.