Spatial epidemiological analysis of the burden of liver cancer in China.

Background: Liver cancer is one of the most common cancers in the world, with unique regional variations in disability-adjusted life years (DALY) rate, nearly 50% of liver cancer cases occur in China. Therefore, understanding the epidemiological characteristics of liver cancer is of utmost importance. In this study, to analyze the spatial distribution characteristics and clustering of the DALY rate of liver cancer in 1990 and 2017 in China based on provincial administrative divisions, and to explore its possible influencing factor. Methods: The DALY rate data of liver cancer at the provincial level in China were collected, the global autocorrelation of the DALY rate was analyzed by Moran's I, the local autocorrelation of the DALY rate was analyzed by Getis-Ord-Gi*, and the influencing factors related to the DALY rate were analyzed by the least squares regression model. Results: The DALY rate of liver cancer in China generally showed an increasing trend. The DALY rate increased in 22 provinces and decreased in nine provinces. In 2017, the distribution of DALY rate in all provinces showed heterogeneity, with the highest DALY rate in Guangxi (1,363.37/100,000) and the lowest in Beijing (315.78/100,000). In 2017, the low and low clustering were mainly concentrated in Inner Mongolia, Ningxia, Shanxi, Hebei, and Tianjin. The low and high clustering in Yunnan, Guizhou, and Guangdong, were surrounded by the high clustering in neighboring provinces, high and high concentration is mainly concentrated in Hunan and neighboring provinces. The results of the least square regression model showed that the per capita years of education, hepatitis B incidence and the proportion of population over 65 years old had an impact on the DALY rate of liver cancer (P<0.05). Conclusions: The DALY rate of liver cancer in China showed an overall increasing trend. In 2017, the DALY rate of liver cancer in China had a spatial aggregation in the whole country, and the per capita years of education, the incidence of hepatitis B and the proportion of population over 65 years old had an impact on the DALY rate of liver cancer in space.

Burden of osteoarthritis in China, 1990-2019: findings from the Global Burden of Disease Study 2019.

This study aimed to report the most current data on the incidence and disability-adjusted life years (DALY) associated with osteoarthritis in China from 1990 to 2019. Publicly available modelled data from Global Burden of Disease Study (GBD) 2019 were used. The incidence and DALY, due to osteoarthritis in China, stratified by sex, trends of associated risk factors, assess the age, period, and cohort effects on the long-term trends of osteoarthritis incidence and DALY in China from 1990 to 2019. We found that the age-standardized incidence and DALY rates of osteoarthritis in China are higher than the average levels in Asia, Africa, and Oceania. In 2019, the number of cases of osteoarthritis in China was 10,681,311, an increase of 132.66% compared with 1990. the DALY of osteoarthritis in China was 4,724,885 person-years, which was 159.70% higher than that in 1990. In 2019, the incidence and DALY rates of osteoarthritis in China was 750.96/100,000,332.19/100,000. High body-mass as risk factors for osteoarthritis DALY with the population attributable proportion (PAF) increasing steadily from 1990 to 2019. The incidence and DALY rates of three types of osteoarthritis from high to low are osteoarthritis knee, osteoarthritis hand, and osteoarthritis hip. Age-period-cohort model showed that the incidence rate of osteoarthritis in China shows a trend of increasing first and then decreasing with age; concurrently, the DALY rate of osteoarthritis in China increased with age. For the period effect, we found that the period rate ratio (RR) of osteoarthritis incidence and DALY rates kept increasing in the cohort born before 2005-2009, and then, it was gradually reduced by year of birth in the cohort born after 2005-2009. As for cohort effect, the cohort RR of incidence rate of osteoarthritis almost has no change, while the cohort RR of DALY rate of osteoarthritis kept increasing from 1990 to 2019. The burden and impact of osteoarthritis in China are substantial and are increasing. Adopting suitable control and preventive community measures to reduce modifiable risk factors is needed to reduce the current and future burden of osteoarthritis in China. Key Points • This paper analyzes the disease burden of osteoarthritis in China for the first time and discusses the influence on the disease burden of osteoarthritis from the perspectives of age, period, and cohort.

Application of a Novel Miniaturized Histopathologic Microscope for Ex Vivo Identifying Cerebral Glioma Margins Rapidly During Surgery: A Parallel Control Study.

PURPOSE: The purpose of our study is to assess the clinical performance of the DiveScope, a novel handheld histopathologic microscope in rapidly differentiating glioma from normal brain tissue during neurosurgery. METHODS: Thirty-two ex vivo specimens from 18 patients were included in the present study. The excised suspicious tissue was sequentially stained with sodium fluorescein and methylene blue and scanned with DiveScope during surgery. The adjacent tissue was sent to the department of pathology for frozen section examination. They would eventually be sent to the pathology department later for hematoxylin and eosin staining for final confirmation. The positive likelihood ratio, negative likelihood ratio, sensitivity, specificity, and area under the curve of the device were calculated. In addition, the difference in time usage between DiveScope and frozen sections was compared for the initial judgment. RESULTS: The sensitivity and specificity of the DiveScope after analyzing hematoxylin and eosin -staining sections, were 88.29% and 100%, respectively. In contrast, the sensitivity and specificity of the frozen sections histopathology were 100% and 75%, respectively. The area under the curve of the DiveScope and the frozen sections histopathology was not significant ( P =0.578). Concerning time usage, DiveScope is significantly much faster than the frozen sections histopathology no matter the size of tissue. CONCLUSION: Compared with traditional pathological frozen sections, DiveScope was faster and displayed an equal accuracy for judging tumor margins intraoperatively.

Novel mutation in the NDP gene associated with Norrie disease in a Chinese pedigree.

PURPOSE: Norrie disease (ND) is a rare X-linked recessive disorder characteristic of early childhood blindness. While several mutations in the NDP gene have been reported as causative for ND, the genetic etiology remains unknown for many patients. This study aims to describe a novel mutation and explore the clinical manifestations in a Chinese family with two affected males. METHODS: Exome sequencing (ES) was employed to identify the causative gene in a four-generation pedigree. Sanger sequencing was subsequently utilized to validate the mutation detected by ES in additional family members. Ophthalmologic examination and diagnostic imaging relevant to ND were conducted. RESULTS: The proband (IV:2), an 8-month-old male infant, presented with binocular retinal detachment. DNA sequencing revealed a novel heterozygous missense mutation (c.174G>C) within the NDP gene in the proband. This mutation affected highly conserved residues and was predicted to disrupt the normal protein structure. Furthermore, the variant co-segregated with the disease phenotypes within the family. CONCLUSIONS: Our findings identified a novel missense mutation in the NDP gene associated with Norrie disease in China, expanding the mutation spectrum associated with ND. This discovery holds diagnostic, prognostic, and genetic counseling implications for affected individuals.

Assessing the Association of Self-Reported Sleep Duration and Metabolic Syndrome Among Middle-Aged and Older Adults in China from the China Health and Retirement Longitudinal Survey.

Objectives: We aim to investigate the correlation between sleep and metabolic syndrome (MS) among a community population 45 years of age and older in China. Methods: A cross-sectional analysis of 9096 participants from China health and longitudinal study was carried out. MS was defined by consensus criteria. Sleep durations were assessed by self-reported questionnaire. Odds ratio (OR) and 95% confidence intervals (CIs) for MS were obtained using multivariable-adjusted regression analysis. Results: Long habitual daytime sleep had a positive influence on MS (OR = 1.50, 95% CI = 1.10-2.06). For elderly, short daytime sleep significantly increased risk of MS (OR = 2.14, 95% CI = 1.25-3.67). Females with long daytime sleep was associated with increased risk of MS (OR = 1.54, 95% CI = 1.04-2.29). Conclusions: Daytime sleep significantly increased risk of MS for middle-aged and elderly Chinese. The hazard role of daytime sleep on MS was various between age and sex groups. Results of this study needed to be verified by future longitudinal studies.

Burden of Lung Cancer in China, 1990-2019: Findings from the Global Burden of Disease Study 2019.

BACKGROUND: Lung cancer is one of the most common malignant tumors in the world. It has become an increasingly important public health problem in China. In this study, we systematically assessed the lung cancer situation in China from 1990 to 2019 and provided an epidemiological knowledge base for the revision of health policies. The relevant data were extracted from the Global Burden of Disease (GBD) database. METHODS: Based on GBD 2019 data, we evaluated the incidence, prevalence, and death rates of lung cancer in China and their change trends from 1990 to 2019, making comparisons by gender and age. RESULTS: The age-standardized incidence and death rates (ASIR and ASDR, respectively) of lung cancer in China were higher than the average levels in Asia, Africa, Europe, and Oceania and also higher than those of neighboring Asian countries. Lung cancer rose from the seventh leading cause of death in 1990 to the fourth leading one in 2019, indicating that the disease burden of lung cancer is increasing. In 2019, the incidence, prevalence, and death rates of lung cancer were all higher in men than in women across all age groups. All three indices were lower in men and women <50 years old than in men and women >50 years. From 1990 to 2019, the ASIR, age-standardized prevalence rate (ASPR), and ASDR showed trends of increase (P < .05), and the rise in the ASPR (average annual percentage change [AAPC] = 1.9) was greater than those in the ASIR (AAPC = 1) and ASDR (AAPC = .8). CONCLUSIONS: From 1990 to 2019, the incidence, prevalence, and death rates of lung cancer continued to increase in China. To reduce this burden, prevention and management of known risk factors should be promoted through national policies.

Impact of the COVID-19 pandemic on the hospital attendance of patients with primary cervical cancer in Heilongjiang, China.

Information regarding the impact of the coronavirus disease 2019 (COVID-19) pandemic on cervical cancer in mainland China is lacking. We explored its impact on the hospital attendance of patients with primary cervical cancer. We included 1918 patients with primary cervical cancer who initially attended Harbin Medical University Cancer Hospital between January 23, 2019, and January 23, 2021. Attendance decreased by 31%, from 1135 in 2019 to 783 in 2020, mainly from January to June (𝜒2 = 73.362, P < .001). The percentage of patients detected by screening decreased from 12.1% in January-June 2019 to 5.8% in January-June 2020 (𝜒2 = 7.187, P = .007). Patients with stage I accounted for 28.4% in 2020 significantly lower than 36.6% in 2019 (𝜒2 = 14.085, P < .001), and patients with stage III accounted for 27.1% in 2020 significantly higher than 20.5% in 2019 (𝜒2 = 11.145, P < .001). Waiting time for treatment was extended from 8 days (median) in January-June and July-December 2019 to 16 days in January-June (𝜒2 = 74.674, P < .001) and 12 days in July-December 2020 (𝜒2 = 37.916, P < .001). Of the 179 patients who delayed treatment, 164 (91.6%) were for the reasons of the healthcare providers. Compared to 2019, the number of patients in Harbin or non-Harbin in Heilongjiang Province and outside the province decreased, and cross-regional medical treatment has been hindered. The COVID-19 pandemic has negatively impacted cervical cancer patient attendance at the initial phase. These results are solid evidence that a strategy and mechanism for the effective attendance of cervical cancer patients in response to public health emergencies is urgently needed.

Hair Selenium of Residents in Keshan Disease Endemic and Non-endemic Regions in China.

Few nationwide investigations on hair selenium (Se) and Keshan disease (KD) have been conducted. KD is closely associated with Se deficiency. Hair Se is an important biomarker for selenium nutrition. This research aimed to provide evidence for assessment of KD prevention, control, and elimination at the molecular level from the etiological perspective of selenium nutrition. The hair Se of the residents living in the KD endemic and non-endemic areas were determined through atomic fluorescence spectrometer. The median of the hair Se levels of the inhabitants living in KD endemic counties was significantly lower than that in KD non-endemic counties (0.34 vs 0.39 mg/kg, U = -10.03, P < 0.0001). The proportion of Se-deficient or Se-marginal residents in KD endemic counties was significantly higher than that in KD non-endemic counties (56.9% vs 36.6%, U = -9.57, P < 0.0001). The medians of the hair Se levels in KD endemic provinces of Shannxi, Heilongjiang, and Gansu were the lowest (0.35mg/kg), and in the category of Se-marginal status. The hair Se level featured a positive Spearman correlation with per capita disposable income (rs = 0.20, P < 0.0001). In conclusion, the median of the hair Se contents of residents living in KD endemic counties was significantly lower than that in KD non-endemic counties. The hair Se contents of nearly 57% of inhabitants living in KD endemic regions were in Se-deficient or Se-marginal status. The KD endemic provinces of Shannxi, Heilongjiang, and Gansu should be given high priority in KD prevention and control.

A county-level spatial epidemiological study of hair selenium and Keshan disease.

Background: No spatial analysis of hair selenium and Keshan disease (KD) on a nationwide county-level has been performed. Selenium deficiency is a recognized environmental risk factor for KD. Hair selenium is one of the recognized biomarkers of selenium nutrition. This study aimed to perform a geographically precise and visualized assessment of the achievement of KD prevention and control at the level of selenium nutrition in terms of etiology. Methods: A spatial ecological study was conducted. The hair selenium content of the residents was assayed using an atomic fluorescence spectrometer. The spatial analysis was performed using ArcGIS. Results: The median of the hair selenium levels of the 3,028 participants in the 1,174 counties was 0.38 mg/kg, and the content of inhabitants in KD endemic counties was significantly lower than that in KD non-endemic counties (0.34 vs. 0.39 mg/kg, z = -10.03, P < 0.0001). The proportion of Se-deficient and Se-marginal counties in KD endemic counties was significantly higher than that in KD non-endemic counties (59.4 vs. 29.0%, z = -7.45, P < 0.0001). The global autocorrelation analysis was not statistically significant (Moran's I = 0.0005, P = 0.68). Local autocorrelation analysis identified 174 low-low clusters of hair selenium levels, 83 (47.7%) of which are KD endemic counties located in KD endemic provinces of Henan, Gansu, Shaanxi, Inner Mongolia, Jilin, and Heilongjiang. The hair selenium featured a positive correlation with per capita GDP (r s = 0.20, P < 0.0001). Conclusion: The median of the hair selenium levels of inhabitants living in KD endemic counties was significantly lower than that in KD non-endemic counties. All the 83 KD endemic counties with low-low clusters of hair selenium levels should be prioritized in KD precision prevention and control. These findings are geographically precise and visualized evidence of the assessment of the effectiveness of KD prevention and control at the level of selenium nutrition in terms of etiology.

Clinicopathological and surgical comparisons of differentiated thyroid cancer between China and the USA: A multicentered hospital-based study.

Background: Thyroid cancer (TC), was the fastest-rising tumor of all malignancies in the world and China, predominantly differentiated thyroid cancer (DTC). However, evidence on TC stage distribution and influencing factors of late-stage were limited in China. Methods: We carried out a retrospective study and enrolled TC patients who were first diagnosed and hospitalized in 8 hospitals in China in 2017. Logistic regression was used to evaluate associations between influencing factors and DTC stage. We extracted eligible primary DTC records newly diagnosed in 2017 from the USA's Surveillance, Epidemiology, and End Results (SEER) database. We compared clinicopathological features and surgical treatment between our DTC records and those from the SEER database. Results: A total of 1970 eligible patients were included, with 1861 DTC patients with known stage. Among patients ≥45 years old, males (OR = 1.76, 95%CI 1.17-2.65) and those with new rural cooperative medical scheme insurance (NCMS) (OR = 1.99, 95%CI 1.38-2.88) had higher risks of late-stage DTC (stage III-IV). Compared with SEER database, over-diagnosis is more common in China [more DTC patients with onset age< 45 years old (50.3 vs. 40.7%, P < 0.001), with early-stage (81.2 vs. 76.0%, P < 0.001), and with tumors<2cm (74.9 vs. 63.7%, P < 0.001)]. Compared with the USA, TC treatment is more conservative in China. The proportion of lobectomy in our database was significantly higher than that in the SEER database (41.3 vs. 17.0%, P < 0.001). Conclusions: Unique risk factors are found to be associated with late-stage DTC in China. The differences in the aspect of clinicopathological features and surgical approaches between China and the USA indicate that potential over-diagnosis and over-surgery exist, and disparities on surgery extent may need further consideration. The findings provided references for other countries with similar patterns.

Spatial Epidemiological Analysis of Keshan Disease in China.

Objectives: Few researchers have studied the national prevalence of Keshan disease (KD) in China using spatial epidemiological methods. This study aimed to provide geographically precise and visualized evidence for the strategies for KD prevention and control. Methods: We surveyed and analyzed 237,000 people in 280 out of 328 KD-endemic counties (85.4%) in mainland China using a design of key investigation based on case-searching in 2015-2016. ArcGIS version 9.0 was used for spatial autocorrelation analysis, spatial interpolation analysis and spatial regression analysis. Results: Global autocorrelation analysis showed that global clustering of latent Keshan disease (LKD) prevalence was noted (Moran's I = 0.22, Z = 7.06, and P < 0.0001), no global clustering of chronic Keshan disease (CKD) prevalence (Moran's I = 0.03, Z = 1.10, and P = 0.27) was observed. Spatial regression analysis showed that LKD prevalence was negatively correlated with per capita disposable income (t = -4.36, P < 0.0001). Local autocorrelation analysis at the county level effectively identified the cluster areas of LKD prevalence in the provinces of Shaanxi, Gansu, Shanxi, Inner Mongolia, and Jilin. The high-high cluster areas should be given priority for precision prevention and control of Keshan disease. Conclusions: This spatial epidemiological study revealed that LKD prevention and control should be strengthened in areas with high values of clustering. Our findings provided spatially, geographically precise and visualized evidence for prioritizing KD prevention and control.

Sodium selenite inhibits cervical cancer growth via ROS mediated AMPK/FOXO3a /GADD45a axis.

Selenium is a trace element that has been shown to inhibit the growth of various cancer cell types. However, its role in cervical cancer and its underlying mechanisms remains largely unknown. Herein, we explored the anti-cervical cancer effect of selenium and its potential mechanisms through xenograft and in vitro experiments. HeLa cell xenografts in female nude mice showed tumor growth retardation, with no obvious liver and kidney toxicity, after being intraperitoneally injected with 3 mg/kg sodium selenite (SS) for 14 days. Compared to the control group, selenium levels in the tumor tissue increased significantly after SS treatment. In vitro experiments, SS inhibited the viability of HeLa and SiHa cells, blocked the cell cycle at the S phase, and enhanced apoptosis. RNA-sequencing, Kyoto encyclopedia of genes and genomes pathway analysis showed that forkhead box protein O (FOXO) was a key regulatory signaling pathway for SS to exhibit anticancer effects. Gene Ontology analysis filtered multiple terms associated with apoptosis, anti-proliferation, and cell cycle arrest. Further research revealed that SS increased intracellular reactive oxygen species (ROS) and impaired mitochondrial function, which activated adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) via phosphorylation at Thr172, resulting in activation of FOXO3a and its downstream growth arrest and DNA damage-inducible alpha (GADD45a). In summary, SS exhibited anti-cervical cancer effects, and their mechanisms may be that SS is involved in inducing cell cycle arrest and potentiating cell apoptosis caused by ROS-dependent activation of the AMPK/FOXO3a/GADD45a axis.

Long non-coding RNA HOXA-AS3 facilitates the malignancy in colorectal cancer by miR-4319/SPNS2 axis.

Growing evidence has shown the oncogenic role of long non-coding RNA HOXA-AS3 in the progression of several types of cancers, while the effect of HOXA-AS3 on colorectal cancer (CRC) remains unclear. In this study, HOXA-AS3 was significantly over-expressed in CRC clinical samples and human CRC cell lines (SW480, SW620, HCT116, COLO205, and LOVO). HOXA-AS3 knockdown was further achieved by specific siRNAs in COLO205 and LOVO cell lines. The depletion of HOXA-AS3 remarkably inhibited cell proliferation, induced cell cycle arrest, and promoted cell apoptosis in CRC cell lines. Additionally, HOXA-AS3 knockdown was determined to facilitate miR-4319 expression and reduce expression level of sphingolipid transporter 2 (SPNS2) in CRC cell lines. The dual luciferase reporter assay suggested that HOXA-AS3 acted as a sponge of miR-4319, and miR-4319 further directly targeted SPNS2 for expression regulation. Besides, HOXA-AS3 was determined to mediate CRC cell proliferation and apoptosis via miR-4319/SPNS2 axis. Moreover, tumorigenesis experiment validated that HOXA-AS3 promoted CRC progression in vivo by regulating miR-4319, SPNS2, and protein kinase B (AKT) signaling. In summary, this study reveals the novel role of HOXA-AS3 in pathogenesis of CRC and provides a candidate for CRC therapeutic target.

Methods used for the measurement of blood-brain barrier integrity.

The blood-brain barrier (BBB) comprises the interface between blood, brain and cerebrospinal fluid. Its primary function, which is mainly carried out by tight junctions, is to stabilize the tightly controlled microenvironment of the brain. To study the development and maintenance of the BBB, as well as various roles their intrinsic mechanisms that play in neurological disorders, suitable measurements are required to demonstrate integrity and functional changes at the interfaces between the blood and brain tissue. Markers and plasma proteins with different molecular weight (MW) are used to measure the permeability of BBB. In addition, the expression changes of tight-junction proteins form the basic structure of BBB, and imaging modalities are available to study the disruption of BBB. In the present review, above mentioned methods are depicted in details, together with the pros and cons as well as the differences between these methods, which maybe benefit research studies focused on the detection of BBB breakdown.

LincRNA-RoR/miR-145 promote invasion and metastasis in triple-negative breast cancer via targeting MUC1.

Triple-negative breast cancer (TNBC) was associated with high rates of cancer recurrence and metastasis and currently no available molecularly target. Accumulating evidences have established the importance of lincRNA-ROR as a marker of cancers. In order to better understand the mechanism of lincRNA-ROR in TNBC, we provided a novel molecular target into the regulatory invasion and metastasis in present research. We found that lincRNA-ROR was upregulated in TNBC cell lines and tissue samples. The aberrant expression of lincRNA-ROR was shown to increase invasion and metastasis in MDA-MB-231 and loss of function by siRNA reverse these process. Furthermore, lincRNA-ROR functions as a competing endogenous RNAs (ceRNA) which sponges miR-145 and therefore upregulate the expression of Mucin1 (MUC1). The expression of MUC1 impacted E-cadherin membrane localization. Together, MUC1 was a potential molecular target may help explain the role of lincRNA-ROR/miR-145 for invasion and metastasis in TNBC cell lines.

Incidence and mortality of cervical cancer in China, 2013.

OBJECTIVE: Estimating the incidence and mortality rate of cervical cancer became necessary to establish prevention measures and healthy policies. The aim of this study was to estimate the updated incidence and mortality rate of cervical cancer in 2013 in China. METHODS: According to the evaluation criteria developed by the National Central Cancer Registry of China, the data submitted from 255 cancer registries met the required standards in 2013. Cervical cancer cases were retrieved from the national database and combined with the 2013 national population data. The age-standardized incidence and mortality rates were based on the demographic structure of the national census 2000 and Segi's world population. RESULTS: In 2013, the estimated number of new cases and deaths from cervical cancer were 100,700 and 26,400, respectively. The crude incidence of cervical cancer was 15.17/100,000. The age-standardized incidence rates based on the Chinese standard population (ASIRC) and the world standard population (ASIRW) were 11.30/100,000 and 10.30/100,000, respectively. The incidence of cervical cancer in urban areas was 15.62/100,000 and the ASIRC was 11.12/100,000. The incidence of cervical cancer in rural areas was 14.65/100,000 and the ASIRC was 11.47/100,000. The mortality rate of cervical cancer was 3.98/100,000. The age-standardized mortality rates based on the Chinese (ASMRC) and world standard populations (ASMRW) were 2.76/100,000 and 2.62/100,000, respectively. The mortality rate of cervical cancer in urban areas was 3.85/100,000 and in rural areas was 4.14/100,000. Cervical cancer incidence and mortality increased with age. Urban areas had a higher incidence of cervical cancer and lower mortality rates when compared with rural areas. CONCLUSIONS: Dynamic monitoring of cervical cancer incidence and mortality is the fundamental work of cervical cancer prevention and control. Cervical cancer is a serious issue in women's health, and prevention strategies need to be enhanced, such as human papilloma virus (HPV) vaccination and screening programs.

Role of pigment epithelium-derived factor (PEDF) in arsenic-induced cell apoptosis of liver and brain in a rat model.

Although studies have shown that arsenic exposure can induce apoptosis in a variety of cells, the exact molecular mechanism of chronic arsenicosis remains unclear. Based on our previous study on human serum, the present study was to determine whether pigment epithelium-derived factor (PEDF) plays a role in the damage induced by chronic arsenic exposure in a rat model and to explore the possible signaling pathway involved. Thirty male Wistar rats were randomly divided into three groups and the arsenite doses administered were 0, 10, and 50 mg/L, respectively. The experiment lasted for 6 months. Our results showed that level of arsenic increased significantly in serum, liver, brain, and kidney in arsenic-exposed groups. It was indicated that PEDF protein was widely distributed in the cytoplasm of various types of cells in liver, brain, and kidney. PEDF protein level was only changed when the arsenite dose reached 50 mg/L in liver and brain, whereas it was not changed in the kidney. In order to investigate the possible mechanism of PEDF-exerted damages upon arsenite exposure, apoptosis in liver and brain was assessed. The proportion of apoptotic cells gradually increased with increasing arsenic administration. The ratio of Bax/Bcl-2 in the high arsenic group (50 mg/L) was significantly higher than that in the control group. Therefore, we thought PEDF played a role in cell apoptosis of liver and brain which induced by sodium arsenite exposure, and the results also demonstrated that Bax and Bcl-2 might be two key targets in the action of PEDF.

The relationships between low levels of urine fluoride on children's intelligence, dental fluorosis in endemic fluorosis areas in Hulunbuir, Inner Mongolia, China.

There has been public concern about children's intellectual performance at high levels of fluoride exposure, but few studies provide data directly to the question of whether low fluoride exposure levels less than 3.0 mg/L in drinking water adversely associated with children's intelligence. In this survey, we investigated the effects of low fluoride exposure on children's intelligence and dental fluorosis. 331 children aged from 7 to 14 were randomly recruited from four sites in Hulunbuir City, China. Intelligence was assessed using Combined Raven Test-The Rural in China while dental fluorosis was diagnosed with Dean's index. Mean value of fluoride in drinking water was 1.31±1.05 mg/L (range 0.24-2.84). Urine fluoride was inversely associated with IQ in the multiple linear regression model when children's age as a covariate variable was taken into account (P<0.0001). Each increase in 1 mg/L of urine fluoride associated with 0.59-point decrease in IQ (P=0.0226). Meanwhile, there was a dose-response relationship between urine fluoride and dental fluorosis (P<0.0001). In conclusion, our study suggested that low levels of fluoride exposure in drinking water had negative effects on children's intelligence and dental health and confirmed the dose-response relationships between urine fluoride and IQ scores as well as dental fluorosis.