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Background/purpose: The disparate or irregular dental care was associated with acute clinical problems that may lead to care seeking for emergency visits. The aim of this study was to determine the time trends, demographics, and conditions of emergency dental (ED) visits in Taiwan. Methods: This cross-sectional study was conducted to analyze the insurance reimbursement of dental care services in National Health Insurance Research Database. The demographic characteristics and age-period effects of ED visits were estimated by multivariate Poisson regression. In addition, the top causes of ED visits were evaluated and stratified by traumatic and non-traumatic conditions. Results: The prevalence of ED visits were 3.18, 5.44, and 4.83 (per 10,000 persons) in 1997, 2002, and 2013, respectively. The primary diagnosis code for ED visits was 522 ‘pulp and periapical tissues’. Pulpitis (522.0), cellulitis (528.3), acute periodontitis (523.3), and caries (521.0) were the top 4 non-traumatic reasons for seeking ED visits. The top 3 traumatic conditions were open wound of internal structures of mouth without mention of complication (873.6), open wound of face without mention of complication (873.4), and loss of teeth due to trauma (525.1). The higher prevalence of ED visits were found in male (aRR = 1.50, 95% CI: 1.49–1.51), 6 y/o group (aRR = 1.56, 95% CI: 1.53–1.59), east region (aRR = 1.27, 95% CI: 1.25–1.29), and dependent coverage group (aRR = 1.16, 95% CI: 1.14–1.19). Conclusion: Taken together, these demographic data could serve as a reference for the authorities concerned to improve the current situation of ED in Taiwan. Keywords: Emergency dental visits, Taiwan, Nationwide population, National health insurance research database

Purpose: Tumor-associated PD-L1 expression is predictive of clinical response to PD-1–directed immunotherapy. However, PD-L1–negative patients may also respond to PD-1 checkpoint blockade, suggesting that other PD-1 ligands may be relevant to the clinical activity of these therapies. The prevalence of PD-L2, the other known ligand of PD-1, and its relationship to response to anti-PD-1 therapy were evaluated. Experimental Design: PD-L2 expression was assessed in archival tumor tissue from seven indications using a novel immunohistochemical assay. In addition, relationships between clinical response and PD-L2 status were evaluated in tumor tissues from patients with head and neck squamous cell carcinoma (HNSCC) with recurrent or metastatic disease, treated with pembrolizumab. Results: PD-L2 expression was observed in all tumor types and present in stromal, tumor, and endothelial cells. The prevalence and distribution of PD-L2 correlated significantly with PD-L1 (P = 0.0012– Conclusions: Clinical response to pembrolizumab in patients with HNSCC may be related partly to blockade of PD-1/PD-L2 interactions. Therapy targeting both PD-1 ligands may provide clinical benefit in these patients. Clin Cancer Res; 23(12); 3158–67. ©2017 AACR.

To explore the effect of electroacupuncture (EA) serum on expression of myogenic differentiation antigen (Myod) and autophagy-related protein Beclin 1 in cultured muscle satellite cells of rats under starvation conditions.The primary multifidus muscle satellite cells of one male SD rat were isolated and cultured to obtain the 3CCK-8 assay displayed that the proliferation levels were significantly higher at 12 h and 24 h after serum intervention in the 10% FBS, 10% EA serum, 20% EA serum and 30% EA serum groups than that in the blank control serum group (EA serum can promote proliferation of cultured muscle satellite cells under starvation conditions, which is related to its functions in regulating expression of Beclin 1 and cell-proliferation-related protein Myod.

Akt is frequently hyperactivated in human cancers and is targeted for cancer therapy. However, the physiological consequences of systemic Akt isoform inhibition were not fully explored. We showed that while combined Akt1 and Akt3 deletion in adult mice is tolerated, combined Akt1 and Akt2 deletion induced rapid mortality. Akt2(-/-) mice survived hepatic Akt1 deletion but all developed spontaneous hepatocellular carcinoma (HCC), which is associated with FoxO-dependent liver injury and inflammation. The gene expression signature of HCC-bearing livers is similar to aggressive human HCC. Consistently, neither Akt1(-/-) nor Akt2(-/-) mice are resistant to diethylnitrosamine-induced hepatocarcinogenesis, and Akt2(-/-) mice display a high incidence of lung metastasis. Thus, in contrast to other cancers, hepatic Akt inhibition induces liver injury that could promote HCC.

We have demonstrated that needle knife (acupotomy) treatment can improve knee osteoarthritis (KOA) in rabbits. The present study was designed to examine its effect on expression of phosphorylated focal adhesion kinase (p-FAK), phosphinositides 3 kinase (p-PI 3 K) and Aggrecan genes and proteins in the knee-joint cartilage tissues of KOA rabbits, so as to explore its partial molecular mechanism underlying improvement of KOA.Forty-nine New Zealand male rabbits were randomly divided into normal control, model, model +inhibitor, needle knife, needle knife+ inhibitor, electroacupuncture (EA), EA +inhibitor groups (After modeling, the expression levels of p-FAK and p-PI 3 K genes and proteins were significantly up-regulated (Needle knife intervention can up-regulate the expression levels of p-FAK, p-PI 3 K and Aggrecan proteins and mRNAs in the cartilage tissue of the knee-joint in KOA rabbits, suggesting an involvement of FAK-PI 3 K signaling in the needle knife-induced improvement of KOA.

Deer bone has been used as a health-enhancing food as well as an antiaging agent in traditional Oriental medicine. Recently, the water extract of deer bone (DBE) showed a neuroprotective action against glutamate or Aβ1–42-induced cell death of mouse hippocampal cells by exerting antioxidant activity through the suppression of MAP kinases. The present study is to examine whether DBE improves memory impairment induced by scopolamine. DBE (50, 100 or 200 mg/kg) was administered orally to mice for 14 days, and then scopolamine (2 mg/kg, i.p.) was administered together with DBE for another 7 days. Memory performance was evaluated in the Morris water maze (MWM) test and passive avoidance test. Also, brain acetylcholinesterase (AChE) and choline acetyltransferase (ChAT) activity, biomarkers of oxidative stress and the loss of neuronal cells in the hippocampus, was evaluated by histological examinations. Administration of DBE significantly restored memory impairments induced by scopolamine in the MWM test (escape latency and number of crossing platform area), and in the passive avoidance test. Treatment with DBE inhibited the AChE activity and increased the ChAT activity in the brain of memory-impaired mice induced by scopolamine. Additionally, the administration of DBE significantly prevented the increase of lipid peroxidation and the decrease of glutathione level in the brain of mice treated with scopolamine. Also, the DBE treatment restored the activities of antioxidant enzymes such as superoxide dismutase, glutathione peroxidase, and glutathione reductase to control the level. Furthermore, scopolamine-induced oxidative damage of neurons in hippocampal CA1 and CA3 regions were prevented by DBE treatment. It is suggested that DBE may be useful for memory improvement through the regulation of cholinergic marker enzyme activities and the suppression of oxidative damage of neurons in the brain of mice treated with scopolamine.

Periodontitis is one of the most prevalent oral diseases. In this study, we probed the nationwide registered database to assess the time trends of prevalence of periodontitis in Taiwan. A retrospective study was conducted to analyze the registered database compiled by the National Health Insurance provided by the Department of Health, Taiwan, from 1997 to December 2013. We found that the prevalence of periodontitis significantly increased from 11.5% in 1997 to 19.59% in 2013 (P for trend 65 years old decreased markedly. The proportion of individuals with periodontitis in age groups

To observe the effect of electroacupuncture (EA) serum on proliferation of multifidus muscle sa-tellite cells (SCs) and expression of paired box transcription factor Pax-7, MyoD and protein kinase B (PKB or Akt) proteins of SCs, so as to explore its underlying mechanism in promoting repair of multifidus muscles.Thirty-two SD rats were randomly assigned to control, model, EA-Weizhong (BL 40) and EA-Shenshu (BL 23) groups. The multifidus muscle injury (MFMI) model was established by injection of 0.5% bupivacaine hydrochloride (400 μL) into the bilateral LCompared with the normal serum group, the proliferation levels (detected by both CCK-8- and EdU) and the expression levels of MyoD and p-Akt proteins of SCs in the model serum group were significantly increased (Both EA-BL 40 and EA-BL 23 serum can promote proliferation of multifidus muscle SCs, which may contribute to the effect of EA intervention in promoting repair of the injured muscle, partially by way of Akt/PI 3 K signaling.

This study consisted of a site- and age-specific investigation linking children's blood lead level (BLL) to environmental exposures in a historic mining site in south China. A total of 151 children, aged 3–7 years, were included in this study. The geometric mean (GM) BLL was 8.22 μg/dl, indicating an elevated BLL. The Integrated Exposure Uptake Bio-Kinetic (IEUBK) model has proven useful at many sites for study of routes of exposure. Application of the IEUBK model to these children indicated that the GM difference between observed and predicted BLL levels was only 1.07 μg/dl. It was found that the key environmental exposure pathway was soil/dust intake, which contributed 86.3% to the total risk. Younger children had higher BLL than did older children. Therefore, of the various low risk-high benefit solutions, interventions for the children living near the site should be focused on the dust removal and soil remediation. Implementation of the China Eco-village Construction Plan and China New Rural Reconstruction Movement of the government may be a better solution.

Background Oral submucous fibrosis (OSF) is a one of the well-recognized oral potentially malignant disorders. In this study, we investigated the malignant transformation of OSF in a Taiwanese population. Methods A retrospective cohort study was analyzed from Taiwan's National Health Insurance Research Database. A comparison cohort that was randomly frequency-matched with the OSF cohort according to age, sex, and index year. Oral leukoplakia (OL) was further stratified to evaluate for the possible synergistic effects for OSF-associated malignant transformation. Results In this cohort, 71 (9.13%) of 778 cases of OSF were observed to transform into oral cancer. The malignant transformation rate was 29.26-fold in the OSF cohort than in the comparison cohort after adjustment (95% confidence intervals 20.55-41.67). To further stratify with oral leukoplakia (OL), OSF with OL (52.46; 95% confidence intervals 20.99-42.42) had higher risk of malignant transformation rate than OSF alone (29.84; 95% confidence intervals 20.99-42.42). The Kaplan-Meier plot revealed the rate free of malignant transformation was significant over the 13 years follow-up period (log-rank test, p

Objectives Breviscapine, a hydrophobic drug used for treating cardiovascular disease, was encapsulated in liposomes to improve its pharmaceutical characteristics. This study describes a novel liposome composition approach to specifically inhibit the P-glycoprotein efflux system. Methods Breviscapine-loaded Pluronic P85-coated liposomes were prepared by the thin film hydration technique. The particle size, zeta potential and encapsulation efficiency of the formulations were characterized. In-vitro drug release and permeability of Caco-2 cells were investigated. In-vitro characteristics and pharmacokinetics of the liposomes were evaluated in rat studies. Key findings The Pluronic P85-modified liposomes dispersed individually and had an approximate diameter of 118.8 ± 4.9 nm and a zeta potential of −35.4 ± 1.5 mV. Encapsulation efficiency was more than 90%. The use of the P85-coated liposomes resulted in significantly (P < 0.05) increased absorption of breviscapine in Caco-2 cells and in 5.6-fold enhancement in its oral bioavailability in rats. Conclusion The P85-modified liposomes for the oral delivery of breviscapine were prepared using l-α-phosphatidylcholine (soy-hydrogenated) and cholesterol with a narrow size distribution. This method seems to effectively enhance the bioavailability of breviscapine in rats.

Oral submucous fibrosis (OSF) has been regarded as a precancerous condition. Research examining the prevalence of OSF could be the first step in preventing or reducing malignant transformation. In this study, we probed a nationwide registered database to assess the prevalence, gender distribution, age, income, and urbanization status of OSF patients in Taiwan. Methods: A retrospective study was conducted to analyze the registered database compiled by the National Health Insurance provided by the Ministry of Health and Welfare, Taiwan. We identified dental visit patients diagnosed with OSF during the period between January 1, 1996 and December 31, 2013. In addition, demographic characteristics were analyzed by multivariate Poisson regression. Results: The prevalence of OSF increased significantly from 8.3 (per 105) in 1996 to 16.2 (per 105) in 2013 (p < 0.0001). Men had a significantly higher OSF prevalence than women (p < 0.001). The mean age of patients with OSF increased from 1996 to 2013. Individuals living in rural areas had a higher risk of OSF compared with those living in urban areas [relative risk (RR), 1.10; 95% confidence interval (CI), 1.07–1.13]. The higher income group had a lower risk of OSF compared with the lower income group (RR, 0.76; 95% CI, 0.73–0.80). Conclusion: This large-scale government-centered survey demonstrates that the prevalence of OSF in Taiwan significantly increased from 1996 to 2013. The prevalence was higher among men than among women.

To discuss the significance of calcineurin (CaN) and nuclear factor of active T cells 1 (NFATc1) in the damage mechanism of the testis of rats with chronic fluorosis.Eighteen clear class SD male rats, aging 6 week-old, were randomly divided into 3 groups, 6 rats in each. The rats of control group were fed with tap water (NaF1 mg/L) and the experimental rats were exposed to NaF (lower group: 5 mg/L, higher group: 50 mg/L) to established the chronic fluorosis model. After 8 months, we observed the occurrence of dental fluorosis among rats in different groups, and the contents of urine fluoride were detected by fluorine ion selective electrode method. The body of the rats were weighted as well as their testis. The testis tissues were stained with hematoxylin-eosin and observed under light microscope to find the morphological changes. The expression of CaN and NFATc1's protein and mRNA in testis were detected by Immunocytochemistry (IHC) and In-situ hybridization (ISH).The number of rats which was found dental fluorosis were separately 0, 4 and 5 in control group, low dose group and high dose group (χ(2) = 10.60, P0.05). The contents of urine fluoride were gradually increased in control group, low group and high group, which were (1.26 ± 0.17), (2.06 ± 0.64) and (7.69 ± 1.96)mg/L, respectively (F = 36.57, P0.05). The body weight were significantly different in all three groups(629.00 ± 16.00), (585.17 ± 17.27), (560.50 ± 16.07)g, F = 26.67, P0.05) and the testis weight were without statistical difference ((2.58 ± 0.17), (2.43 ± 0.31), (2.35 ± 0.38)g, F = 0.91, P0.05). Compared with the control group, the testicular structures were damaged in the experimental groups and especially significant in high dose group. The expression of CaN (59.10 ± 5.62, 77.93 ± 4.16, 101.69 ± 6.31, F = 74.18, P0.05) and NFATc1's (76.11 ± 4.41, 93.42 ± 3.85, 120.42 ± 9.31, F = 92.4, P0.05) protein in testis tissues were increased by the fluorine concentration. The mRNA expression of CaN and NFATc1 were separately (CaN: 58.76 ± 7.70, 82.01 ± 6.88, 99.47 ± 8.33, F = 42.65, P0.05 and NFATc1: 59.39 ± 4.74, 90.02 ± 5.37, 121.15 ± 7.69, F = 155.47, P0.05). There were positive correlation between the expression of CaN and NFATc1's protein and mRNA expression (r = 0.899, r = 0.908).The changes in the signaling pathway of expression of CaN may be involved in the injury mechanism of testis tissues of rats with chronic fluorosis.

To explore the changes of protein expression of mitochondrial fission gene dynamin-related 1(Drp 1) in the cortical neurons of rats with chronic fluorosis.A total of 120 one-month-old SD rats (each weighing approximately 100-120 g at the beginning of the experiment) were randomly divided into three groups, and fed with the different doses of fluoride containing in drinking water (untreated control containing 0 mg/L fluoride, and low-fluoridehigh-fluoride supplemented with 10 and 50 mg/L fluoride,respectively). After 3 or 6 months exposure, 20 rats from each group were killed. Then the protein expression of mitochondrial fission gene, Drp1, was detected by immunohistochemistry and western-blotting method.Dental fluorosis and urinary fluorosis were obviously found in the rats exposed to fluoride. At the experiment period of 3 months, the numbers of positive cells of Drp1 detected by immunohistochemistry changed. Compared with the control group (36.3 ± 5.8), the changes in low-fluoride group (34.7 ± 4.1) showed no significant difference (t = 1.5, P0.05),but the increase in high-fluoride group (45.0 ± 4.7) had statistical significance (t = 8.8, P0.05). The western-blotting method had consistent results. Compared with the control group (0.59 ± 0.03), a significant increase of the average topical density in low- fluoride (0.62 ± 0.03) and high-fluoride (0.71 ± 0.02) groups were found (t = 0.02,0.11, P0.05). At the experiment period of 6 months, the numbers of positive cells of Drp1 detected by immunohistochemistry significantly changed. Compared with the control group (33.2 ± 4.4), the number in low- fluoride and high-fluoride groups were separately (36.6 ± 3.8) and (39.4 ± 4.2),both increased significantly (t = 3.5,6.3, P0.05). Same results could be found in western-blotting method,compared with the control group (0.65 ± 0.06), the average topical density in low- fluoride (0.80 ± 0.09) and high-fluoride (0.76 ± 0.08) groups both increased significantly (t = 0.1,0.1, P0.05).Taking excessive amount of fluoride might result in the changes of expression of Drp1, and the neurons damage from the chronic fluorosis might be associated with the hyperfunction of mitochondrial fusion.

To observe the mitochondrial fragmentation and the expression of mito-fusion 1 gene in the cortical neurons of rats with chronic fluorosis, and to reveal their roles in mitochondria damage to neurons due to chronic fluorosis.SD rats were divided randomly into three groups of 20 each (a half females and a half males housed individually in stainless-steel cages), and fed with the different doses of fluoride containing in drinking water (untreated control containing 0 mg/L fluoride, and low-fluoride and high supplemented with 10 and 50 mg/L fluoride, respectively). After 3 or 6 months exposure, the mitochondrial morphology of the neurons in rat brains were observed by transmission electron microscopy (TEM), then the expression of mitochondrial fusion gene, Mfn1, were detected by immunohistochemistry and western-blotting, respectively.Dental fluorosis was obvious in the rats exposed to excessive fluoride in their drinking water, that is, (16 rats out of 20) numbers of I° detal fluorosis in the low-fluoride group, and (11 rats out of 20) numbers of I° and (9 rats out of 20) numbers of II° detal fluorosis in the high-fluoride group were observed after 3 months exposure. Moreover, (14 rats out of 20) numbers of I° and (6 rats out of 20) numbers of II° detal fluorosis in the low-fluoride group and (6 rats out of 20) numbers of Io, (13 rats out of 20) numbers of II°, and (1 rats out of 20) numbers of III° detal fluorosis in the high-fluoride group were observed after 6 months exposure. And both of untreated controls without detal fluorosis were also observed. The urinary level of fluoride in the low-fluoride group (3.30 ± 1.18) mg/L and in the high-fluoride group (5.10 ± 0.35) were observed after 3 months exposure (F = 3.18, P0.05). Moreover, the urinary level of fluoride in the low-fluoride group (4.16 ± 1.39) mg/L and in the high-fluoride group (5.70 ± 1.70) mg/L were also observed after 6 months exposure (F = 3.17, P0.05). The normal mitochondrial morphology of neurons in rats without fluorosis was observed after 3 and 6 months, while the abnormal mitochondrial morphology of neurons with fluorosis was shown, presenting mitochondrial fragmentation with swollen cristae and even the fragmented, shortened or stacked punctuate membranes (section observation of three bullous mitochondrial-mitochondrial fission process) by TEM. As compared with controls (53.0 ± 4.54 and 1.21 ± 0.18) at the experiment period of 3 months, Mif1 protein analysis with immunocytochemical (the numbers of positive cells: 51.09 ± 6.25) and western-blotting (1.22 ± 0.26) were no significant difference for low fluoride group (t = 1.7, 1.1, P0.05); Mif1 protein analysis with immunocytochemical (the numbers of positive cells: 59.71 ± 5.64) and western-blotting (1.66 ± 0.20) were significantly increasing for high fluoride group (t = 2.1, 2.1, P0.05). As compared with controls (36.43 ± 4.04 and 1.00 ± 0.13) at the experiment period of 6 months, Mif1 protein analysis with immunocytochemical (the numbers of positive cells 20.05 ± 4.55 and 17.10 ± 3.86) and western-blotting (0.64 ± 0.08 and 0.39 ± 0.06) were significantly decreasing for the two fluoride group (t = 2.1, 2.2; 2.2, 2.2 respectively, all P value were0.05).Taking excessive amount of fluoride might result in the mitochondrial fragmentation for the changed expression of Mfn1, and the neurons damage from the chronic fluorosis might be associated with the dysfunction of mitochondrial fusion.

To investigate the changes of mRNA and protein expression of CaN in the bone of rats with chronic fluorosis, and the mechanism of skeletal fluorosis.Thirty-six SD rats were divided into three groups (12 in each group, half male and half female selected according to body weight): control, low-dose and high-dose fluorosis groups. Controls were fed tap water (NaF0.5 mg/L), experimental animals in the low- or high-dose groups were fed water containing NaF of 5.0 and 50.0 mg/L, respectively. The rats were sacrificed after 6 months of treatment with fluoride. The serum was kept for testing bone metabolic marker bone gla protein (BGP) by enzyme-linked immunosorbent assay (ELISA), the protein and mRNA levels of CaN in distal femur of the rats with chronic flurosis were assessed by immunohistochemistry and in-situ hybridization.The levels of BGP (1.99 ± 0.62, 2.38 ± 0.16)µg/L in the low- or high-dose fluorosis groups were higher than that in the control group (0.15 ± 0.03) µg/L; and the high fluorosis group showed higher level than the low fluorosis group (all P0.05). Compared to the control group (131.11 ± 1.95, 111.82 ± 2.39), the protein and mRNA levels of CaN were higher in the low- or high-dose fluorosis groups (142.69 ± 1.17, 157.54 ± 1.88 and 121.28 ± 3.27, 134.63 ± 3.19, respectively), and the high fluorosis group showed higher levels than the low fluorosis group (all P0.05).BGP content could be used as a bone metabolic index in endemic fluorosis disease. Fluoride might up-regulate the mRNA and protein expression of CaN, and the changes in CaN level may be involved in the increase of the bone turnover and could be one of the pathogenetic factors in fluorosis.

To study the effect of fluoride on the oxidative stress of the rats in endemic fluorosis of coal burning and Mn-SOD expression at mRNA and protein levels.SD rats were divided into 2 groups (the number of female and male in each group was the same): control group and fluorosis group. All rats of the fluorosis group were fed corn dried by burning coal from endemic fluorosis areas with high fluoride content (fluoride 17 mg/kg in feed) to establish an animal model of fluorosis. In these rats, dental fluorosis was evaluated. The fluoride content in the urine was measured by fluorine ion-elective electrode method. The hepatic tissue and serum level of malonaldehyde (MDA) and the activities of superoxide dismutase (SOD) and glutathion reductase (GR) were measured by biochemical methods. The index signs of liver function were also measured from the serum. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blot were performed to detect the alterations of Mn-SOD expression in the liver at mRNA and protein levels.The dental fluorosis was observed in the fluorosis group, and the incidence was 11/11. The fluoride contents [(3.50 ± 2.58) mg/L] in the urine of fluorosis rats were increased as compared with the control [(1.42 ± 0.38) mg/L] (P0.05). AST [(223.74 ± 71.51) U/L] and total protein [(72.43 ± 5.59) g/L] of the hepatic function index in fluorosis rats showed obviously abnormal as compared with the control [(169.28 ± 53.74) U/L and (82.36 ± 7.31) g/L], respectively (P0.05). In the liver the content of MDA [(10.41 ± 0.59) µmol/g protein] increased as compared to the control [(5.80 ± 1.31) µmol/g protein, P0.01], and the activities of SOD [(62.60 ± 8.65) U/mg protein] and GR [ (1.17 ± 0.66) U/g protein] markedly decreased in the fluorosis group compared to the control [SOD (117.28 ± 8.64) U/mg protein and GR [(8.80 ± 1.59) U/g protein; P0.05, P0.01]. The level of Mn-SOD in the liver was markedly decreased in the fluorosis group [(14.83 ± 2.50) U/mg protein] as compared with the control [(34.05 ± 5.22) U/mg protein, P0.01]. The levels of mRNA (0.64 ± 0.15) and protein (0.84 ± 0.13) of Mn-SOD were markedly decreased in the fluorosis group as compared with the control [(0.86 ± 0.21) and (1.04 ± 0.14)], respectively (P0.05, P0.01).Fluorosis can decrease the activities of Mn-SOD, which is associated with decreased levels of mRNA and protein of Mn-SOD. Down-regulation of Mn-SOD expression may play an important role in the aggravation of oxidative stress in endemic fluorosis.

To analyze the prevalence rate of diabetic nephropathy (DN) and the related factors on DN among type 2 diabetic patients.A total number of 1758 type 2 diabetic patients who were hospitalized in the Beijing Hospital from 2003 to 2010 were analyzed retrospectively. Three groups were divided according to the rate of urinary albumin excretion (UAER). Patients whose UAER20 µg/min belonged to normal albuminuria (NA) group. The ones whose UAER from 20 to 200 µg/min belonged to microalbuminuria (MA) group, and the others whose UAER ≥ 200 µg/min belonged to large albuminuia (LA) group. The clinical characteristics were then compared. The related factors of DN were analyzed.(1) There were 1246 patients in NA group, 408 patients in MA group, and 104 patients in LA group. The constituent ratio of nephropathy was 29.1%. (2) The ages of NA group, MA group and LA group were (59.87 ± 12.77, 62.52 ± 12.74, 64.44 ± 12.74) years old, respectively, with body mass index (BMI) as (24.90 ± 3.42, 25.53 ± 4.00, 25.53 ± 3.91) kg/m(2) respectively; duration of diabetes as (8.39 ± 7.12, 10.77 ± 8.02, 12.84 ± 7.97) years; systolic blood pressure (SBP) as (133.42 ± 18.19, 142.72 ± 20.21, 151.12 ± 21.91) mm Hg; diastolic blood pressure as (78.75 ± 10.66, 80.79 ± 12.21, 83.33 ± 13.61) mm Hg; fasting blood sugar (FBS) as (8.25 ± 3.43, 9.02 ± 3.72, 9.22 ± 4.62) mmol/L; glycated hemoglobin (HbA1c) as (8.88 ± 2.10, 9.34 ± 2.36, 9.10 ± 2.36)%; uric acid (UA) as (288.04 ± 90.41, 307.23 ± 96.96, 374.28 ± 105.47) mmol/L; triglyceride as (1.72 ± 1.51, 2.06 ± 1.88, 1.94 ± 1.42) mmol/L, high density lipoprotein cholesterol as (1.08 ± 0.30, 1.02 ± 0.29, 1.07 ± 0.28) mmol/L; fasting insulin as (9.24 ± 9.02, 11.24 ± 9.74, 11.06 ± 9.29) µU/ml; fasting C peptide as (462.31 ± 289.94, 510.02 ± 350.08, 595.93 ± 445.86) pmol/L. There were significant differences between NA, MA and LA groups in all above items (P0.01 or P0.05). (3) Logistic regression analysis showed that DN were related with duration of diabetes, BMI, SBP, HbA1c, FBS, UA (OR values were 1.041, 1.055, 1.028, 1.116, 1.100, 1.004 respectively, P0.05 or P0.01).It would be helpful to prevent and retard progression of DN that comprehensively controlling high blood glucose, hypertension, hyperuricemia and body weight of type 2 diabetic patients.

To investigate the changes of mitochondrial distribution in axon/soma and the expression of mitochondrial fission 1 (Fis1) protein in the cortical neurons of rats with chronic fluorosis.Sixty SD rats were divided into 3 groups (20 each) according to weight hierarchy and fed with different concentrations of fluoride in drinking water (0, 10 and 50 mg/L, respectively) for 6 months. Images of mitochondria and tubulin labeled by immunofluorescence COXIV and tubulin-α were captured with fluorescence microscope. Fis1 protein expression in cortical neurons was analyzed with immunohistochemistry and Western blot. The expression of Fis1 mRNA was detected with real-time PCR.Varying degrees of dental fluorosis and increased fluoride contents in urine were observed in the rats receiving additional fluoride in drinking water. In the cortical neurons of rats fed with 10 mg/L and 50 mg/L fluoride, the numbers of neuronal soma stained with COXIV(34.8 ± 4.7 and 39.3 ± 3.0, respectively), and the expression of Fis1 protein (immunohistochemistry: 54.0 ± 3.6 and 51.3 ± 4.1, respectively; Western blot: 2.9 ± 0.4 and 2.6 ± 0.6, respectively) and mRNA (3773 ± 1292 and 1274 ± 162, respectively) was markedly increased as compared with controls (4.4 ± 2.3, 25.2 ± 2.5, 1.8 ± 0.2 and 277 ± 73) over the experimental period of 6 months.Excessive intake of fluoride results in an altered mitochondrial distribution in axon and soma in cortical neurons (i.e., the increase in soma and the decrease in axon), increased expression of Fis1 gene and enhanced mitochondrial fission. The altered mitochondrial distribution may be related to the high expression level of Fis1 and a functional disorder of mitochondria.

To explore the effect of endemic fluoride poisoning caused by coal burning on the oxidative stress in rat testis.Totally 40 male SD rats were equally randomized into four groups control group, low fluorosis group, middle fluorosis group, and high fluorosis group. Rats in all three fluorosis groups were fed with corn dried by burning coal obtained from endemic fluorosis areas with high fluoride, and thus the animal models of fluorosis were established. After 120 and 180 days, all the rats were sacrificed. Testis tissues were stained with hematoxylin eosin and observed under light microscope. The malonaldehyde (MDA) content, superoxide dismutase (SOD) activity, total nitric oxide synthase (TNOS), and inducible nitric oxidase synthase (iNOS) were measured by biochemical methods in the testis tissues. The content of NaF in testis was measured by fluorine selective electrode.The rat fluorosis models were successfully established. The fluoride content in testis was significantly increased in all the fluorosis groups(P0.01). Testicular structures were damaged in all of fluoride groups. The TNOS, iNOS activities, and MDA content of each fluoride group were significantly higher than that of the control group on day 120 and 180 (P0.05 or 0.01 ). The TNOS, iNOS activities, and MDA content significantly increased in a dose dependent manner (P0.05 or 0.01). The SOD activities significantly decreased in all the fluoride groups (P0.05 or 0.01).Endemic fluoride poisoning caused by coal burning can cause disorders in the oxidative system and antioxidative system in rat testis. The oxidative stress may play an important role in the fluorides induced reproductive toxicity in male rats.

To investigate mRNA and protein expressions of OPGL and M-CSF mRNA in bones of rats with experimental fluorosis induced by intake of fluoride in the drinking water, and to study the antagonizing effects of Danlan Xianpeng Liaofu capsules on the gene expression.Totally 72 SD rats were randomly assorted into 6 groups including the control group, the fluoride group, the high-dosage (0.8 g/kg×d), mid-dosage (0.4 g/kg×d) and low dosage (0.2 g/kg×d) medication groups and the borax group (borax, 0.8 g/kg×d). The distribution of female and male rats in each group was divided up on a fifty-fifty basis. Except the control group, a NaF containing water (NaF 50 mg/L in concentration) was supplied as the drinking water for all the experimental rats in order to establish experimental fluorosis. The thickness and density of trabecula and the thickness of bone cortex were measured by light microscopy. The fluoride content in urine and bone were analyzed by using fluoride ion selective electrode method. Expressions of OPGL and M-CSF mRNA and protein were studied using RT-PCR and immuno-histochemistry, respectively.(1) 10/12 of the experimental fluorosis rats developed dental fluorosis, and 2/12 of dental fluorosis rats occurred in the low-dosage medication group. Fluoride content in urine and bone of the fluorosis rats increased (P0.05). (2) Compared with that of the control rats, the bone trabecular depth, cortical thickness and trabecular density in experimental fluorosis rats were remarkably reduced. (3) Compared with that of the control group, mRNA expression of both OPGL and M-CSF was increased in the fluoride group rats. The difference was statistically significant (P0.05). (4) Compared with that of the fluoride group animals, the expression intensity of OPGL mRNA decreased in animals of the control group, the high, mid- and low- dosage medication groups and the borax group. Among them, except the low-dosage group, the difference between all the other groups and the fluoride group was statistically significant, respectively (P0.05). There was also a decrease of M-CSF mRNA in all the 3 medication groups and the borax group animals in comparing with that of the fluoride group and the difference was also statistically significant (P0.05), respectively. (5) Compared with that of the control group. There were an increase of OPGL and a decrease of M-CSF protein expression; and in addition, there were a decrease of OPGL and an increase of M-CSF protein expression in all 3 medication groups and the borax group in comparing with that of the fluoride group anima (P0.05).Excessive fluoride induces an accelerated bone turnover and may promote the absorption activity of osteoclasts by increasing the expression of OPGL and M-CSF. Danlan Xianpeng Liaofu capsule may be capable of regulating bone remodeling through a down-regulation on OPGL and M-CSF expression.

Maternal exposure to environmental tobacco smoke (ETS) has been reported to be associated with children's neurobehavioral development but there was no studies investigating the genetic susceptibilities to maternal ETS exposure on children's neurodevelopment. The aim of the study was to explore the modification effect of metabolic gene polymorphisms to cord blood cotinine on children's neurodevelopment at the 2 years of age. This study is one investigation of the Taiwan Birth Panel Study and a total of 145 pregnant women and their neonates were recruited between April 2004 and January 2005. We interviewed them by a structured questionnaire after delivery and collected umbilical cord blood at birth. Cotinine in umbilical cord blood as an indicator of environmental tobacco smoke was analyzed by using HPLC–MS/MS and the detection limited of this method was 0.05 ng/mL. Four metabolic genes, CYP1A1 MspI, CYP1A1 Ile462Val, GSTT1 and GSTM1 were identified. The Comprehensive Developmental Inventory for Infants and Toddlers (CDIIT) was used for assessing children's neurodevelopment at the 2 years of age accompanying with the measurement of Home Observation for Measurement of the Environment scale. We used multiple linear regression models to estimate the effects of cord blood cotinine and gene modification. Cotinine levels were significantly negatively associated with developmental quotients (DQs) of the whole test, and cognitive, language, fine-motor and social subtests of the CDIIT. Lower cognitive and language DQs were found in exposed group with absent type of GSTT1. In addition, the lowest scores in fine-motor and whole test DQs were detected in exposed group with CYP1A1 Ile462Val variant type and GSTT1 absent type. It can be concluded that CYP1A1 Ile462Val and GSTT1 metabolic genes can modify the effect of cord blood cotinine on early child neurodevelopment especially for language and fine motor development.