Objective To investigate the expressions of receptor for advanced glycation endproducts (RAGE) and nuclear factor κB(NF-κB) in brain hippocampus of rat with chronic fluorosis,and to reveal the mechanism of brain damage resulted from chronic fluorosis.Methods Sixty clean grade SD rats were randomly divided to three groups(20 rats in each group,10 female and 10 male) fed with different contents of fluoride,control group with normal tap-water(＜ 0.5 mg/L fluoride),small dosage of fluoride exposure group(10 mg/L fluoride in tap-water) and large dosage of fluoride exposure group(50 mg/L fluoride) for six months.Then the rats were killed by femoral artery bleeding and hippocampus was removed.Protein and mRNA levels of RAGE and NF-κB in the hippocampus were determined by Western blotting and quantitative real time PCR,respectively.Results As compared to the control groups[(100.00 ± 2.60)％,(100.00 ± 7.80)％],the expressions of RAGE and NF-κB at protein level in the hippocampus were significantly increased in the small dosage of fluoride exposure groups [(205.00 ± 15.30)％,(156.00 ± 12.20)％] and the large dosage of fluoride exposure groups[(232.00 ± 10.90)％,(162.00 ± 9.80)％,all P ＜ 0.05]; for the mRNA level of RAGE and NF-κB,the expressions were higher in the small dosage of fluoride exposure groups(1.27 ± 0.09,0.83 ± 0.15) and the large dosage of fluoride exposure groups (2.60 ± 0.19,1.27 ± 0.19) than those of the control groups(0.66 ± 0.18,0.32 ± 0.08,all P＜ 0.05).Conclusions The increased expressions of RAGE and NF-κB in the hippocampus of rat brain are caused by chronic fluorosis,and these changes may be associated with the mechanism of nerve injury.

Objective Aim of the study is to investigate the expression of syndecan-4 and nuclear factor κB(NF-κB) in the kidney of rat with chronic fluorosis,and to reveal the mechanism of kidney damage resulted from the toxicity of excessive amount of fluoride.Methods According to body mass and sex,sixty SD rats were randomly divided to three groups according to body mass and fed with different contents of fluoride:control group with normal tap-water(＜ 0.5 mg/L fluoride),small dosage of fluoride exposure group (adding 10 mg/L fluoride in tap-water) and large dosage of fluoride exposure group (50 mg/L fluoride) for six months.The protein level of syndecan-4 and NF-κB in the kidney was detected by Western blotting and syndecan-4 mRNA level by quantitative real time PCR.Results As compared to the control group[(100.0 + 8.1)％],the expression of syndecan-4 at protein level in the kidney of rat was significantly increased in the small dosage of fluoride exposure group [(198.5 + 5.6)％,P ＜ 0.05] and large dosage of fluoride exposure group [(209.2 + 13.0)％,P ＜ 0.05]; the protein levels of NF-κB in the small dosage of fluoride exposure group[(284.4 + 11.1)％,P ＜ 0.05] and in the large dosage of fluoride exposure group[(343.2 + 2.9)％,P ＜ 0.05] were significantly increased than that of the control group[(100.0 ± 10.7)％].The mRNA levels of syndecan-4 in the kidney in the small dosage of fluoride exposure group and large dosage of fluoride exposure group(0.431 + 0.058 and 0.453 ± 0.065,both P ＜ 0.05,respectively) were significantly increased than that of the control(0.128 + 0.026).Conclusions The increased expression of NF-κB in the kidney is induced by increased expression of syndecan-4,which may be involved in kidney damage of chronic fluorosis.

Avellino corneal dystrophy(ACD) is an autosomal dominant eye disorder caused by mutation of R124H in the transforming growth factor-beta induced gene (TGFBI) on chromosome 5,which was responsible for accumulating of abnormal TGFBI.Although the underlying mechanism by which mutations cause abnormal TGFBI deposition is not yet clear,but we have a better understanding of the etiology and possible pathogenesis of corneal dystrophy with the rapid development of human genetics and molecular biology,and summarizes the current achievement of this disease and understand the roles of TGFBI and its interaction with Periostin,which may contribute to further research in ACD.

Objective To investigate the value of temporary balloon occlusion of the abdominal aorta in the treatment of complete placenta previa with placenta accreta. Methods From January 2015 to February 2016, 24 cases of complete placenta previa with placenta accreta were treated with temporary balloon occlusion of the abdominal aorta (the study group) before cesarean, and 24 cases of complete placenta previa with placenta accreta did not receive balloon occlusion (the control group). The operation time, intraoperative blood loss, intraoperative blood transfusion volume, the perioperative hemoglobin level, the hysterectomy rate and the related complications were compared retrospectively.Also, the hospitalization time, the blood coagulation parameters after operation, including activated partial thromboplastin time (APTT), fibrinogen (FIB), D-Dimer and reperfusion injury parameters including creatine phosphokinase (CK), creatine phosphokinase isoenzyme (CK-MB), lactate dehydrogenase (LDH) and serum creatinine were compared between the 2 groups. Results The blood loss [750 ml (400-2 000 ml) vs 2 000 ml (1 500-2 375 ml);Z=-3.214, P=0.001] and blood transfusion volume [200 ml (0-800 ml) vs 800 ml (0-1 200 ml);173, P=0.030] in the study group were lower than in the control group. The hemoglobin difference between before and after operation in the study group was lower than the control group [(12.8±13.4) g/L vs (22.9±20.1) g/L;t=-2.041, P=0.047]. In the study group, there were still bleeding in 13 cases after releasing the balloon, 5 of them received uterine artery embolization, 5 cases received uterine artery ligation, and 3 cases received uterine packing. One case had venous thrombosis in the right lower limb. Two cases (8%,2/24) in the control group had hysterectomy, while none in the study group, there was no statistical significance (P=0.489). Conclusions Temporary balloon occlusion of the abdominal aorta can effectively reduce blood loss and blood transfusion in the treatment of complete placenta previa with placenta accreta, but there is still the risk of continuing bleeding after releasing the balloon. Other methods of hemostasis might be needed.

OBJECTIVETo study the effects of local application of allicin via gastroscopy on progressive gastric carcinoma, and to investigate its possible mechanisms.

METHODSEighty patients with progressive gastric adenocarcinoma, whose diagnosis was confirmed by gastroscopy and pathological examination, were assigned to 2 groups, 40 in each group. Forty-eight hours before operation, allicin was infused via gastroscopy to the lesion region of patients in the allicin group, and normal saline was infused instead to those in the control group. The gastric carcinoma tissue gotten from gastrectomy was taken to determine the percentage of cells in various cell cycle phases ( G0/ G1, S and G2/M), the cell apoptosis rate, proliferation index value and apoptosis related gene protein such as Fas, Bax and Bcl-2 by flow cytometry.

RESULTSIn the allicin group, the cell apoptosis rate was 9.60 +/- 1.52%, the percentage of cell in G0/G1 phase was 72.12 +/- 8.35%, in G2/M phase 9.54 +/- 3.20%, and PI 27.80 +/- 8.35, while in the control group, the corresponding data was 2.20 +/- 0.58%, 69.56 +/- 5.15%, 13.20 +/- 3.05%, and 30.40 +/- 5.15, respectively, and significant difference in all the 4 indexes could be found between the two groups (P < 0.05, P < 0.01). Moreover, allicin showed effects in up-regulating the protein expressions of apoptosis promoting gene Bax and apoptosis initiating gene Fas (P < 0.05, P < 0.01), and down-regulating that of anti-apoptosis gene Bcl-2 (P < 0.05).

CONCLUSIONLocal application of allicin via gastroscopy can inhibit the cell growth and proliferation of progressive gastric carcinoma, and can also promote gastric carcinoma cell apoptosis.

Adult ; Aged ; Anti-Infective Agents ; administration & dosage ; therapeutic use ; Apoptosis ; drug effects ; Cell Cycle ; drug effects ; Cell Proliferation ; drug effects ; Female ; Flow Cytometry ; Gastroscopy ; Humans ; Male ; Middle Aged ; Phytotherapy ; Stomach Neoplasms ; drug therapy ; metabolism ; pathology ; Sulfinic Acids ; administration & dosage ; therapeutic use ; bcl-2-Associated X Protein ; biosynthesis ; fas Receptor ; biosynthesis

Humans ; Lipoma ; diagnostic imaging ; pathology ; surgery ; Male ; Mediastinal Neoplasms ; diagnostic imaging ; pathology ; surgery ; Middle Aged ; Thymus Neoplasms ; diagnostic imaging ; pathology ; surgery ; Tomography, X-Ray Computed

AIM: To explore whether strontium ranelate ( Sr ) promotes osteogenic differentiation of rat bone mesenchymal stem cells (BMSCs) through the Hedgehog/Gli1 signaling pathway.METHODS:BMSCs were isolated from 4-week-old rats by adherent culture and induced to differentiate into osteoblasts .According to the experimental purposes , the cells were exposed to different concentrations of Sr , cyclopamine ( Cy, an inhibitor of Hedgehog receptor ) or Gli1-siR-NA.The expression of Gli1 and Runx2 in the cells was detected by Western blotting .The activity of alkaline phosphatase ( ALP) was measured by the method of colorimetry , and the mineralized nodules were observed under microscope with aliz-arin red staining .RESULTS:Exposure to Sr at concentrations of 0.1 to 5 mmol/L for 7 d markedly increased the expres-sion of Gli1 in the BMSCs , and the increase in Gli1 expression was the most obvious following Sr exposure at concentration of 3 mmol/L.Cy at concentration of 10 μmol/L inhibited Sr-induced up-regulation of Gli1 expression.Transfection of the BMSCs with Gli1-siRNA not only obviously inhibited Sr-induced up-regulation of Gli1 and Runx2 ( a downstream protein of Gli1) expression, but also antagonized Sr-induced enhancement of ALP activity and the formation of mineralized nodules . CONCLUSION:The Hedgehog/Gli1 pathway is involved in Sr-induced osteogenic differentiation of rat BMSCs .

Objective The aim of the study was to investigate the expression of P-glycoprotein (P-gp)and nuclear factor κB (NF-κB) in the cerebral cortex of rat with chronic fluorosis,and to reveal the mechanisms of damaged nervous system resulted from the toxicity of fluoride.Methods Sixty SD rats were randomly divided into three groups.The rats in each group were given drinking water containing different levels of fluoride:control group less than 0.5 mg/L,small amount of fluoride exposure group 10.0 mg/L and large amount of fluoride exposure group 50.0 mg/L.The animals were examined at the sixth month after initiating the experiment.Protein levels of P-gp and NF-κB in brain tissues were detected by immunocytochemistry and Western blotting,and the P-gp protein and mRNA level by quantitative real time PCR method.Results As compared to the control group(28.21 ±6.13),the numbers of positive staining cells by P-gp antibody in the cortex of rat brains were significantly increased in both the small and the large amount of fluoride exposure groups[(48.46 ± 8.00),(53.72 ± 9.15),respectively,all P ＜ 0.05] ; the protein levels in the control group(100.00 ± 3.86)％ detected by Western blotting were significantly increased in the cortex of rat brains treated with fluoride in both the small and the large amount of fluoride exposure groups[(189.47 ± 3.14)％,(191.36 ± 11.09)％,respectively,all P ＜ 0.05].The significantly increased expression of NF-κB at the protein level was observed in the cortex of rat brains of the small and the large amount of fluoride exposure groups[(365.97 ± 6.04)％ and (417.15 ± 10.89)％,respectively] as compared with the control group[(100.00 ± 10.07)％,all P ＜ 0.05].The mRMA level of P-gp in the cortex of rat brains of the small and the large amount of fluoride exposure groups(2396 ± 427,3479 ± 371,respectively) were higher than that of the control group(260 ± 106,all P ＜ 0.05).Conclusion The increased expressions of P-gp and NF-κB in the cortex of rat brains are induced by chronic fluorosis,which might be connected with the mechanism of brain damages.

Objective To investigate the changes of reactive oxygen species(ROS) level and mitochondria fission-fusion-balance in cortical neurons of rats with chronic fluorosis and reveal the correlation between these two factors. Methods One hundred and twenty rats were randomly divided into 3 groups(control group, low-dose fluorosis group, high-dose fluorosis group) and 40 rats were in each group according to body weight and the experiments were carried out for 3 months or 6 months. The rats were fed with different concentrations of fluoride (NaF) to establish fluorosis models. Controls were fed with tap water( < 0.5 mg/L), experimental animals in low- or high-dose group were fed with water containing NaF 10.0,50.0 mg/L, respectively. The level of ROS and the morphology in mitochondria fission-fusion balance in neurons of the cortex of rat brains prepared with cortical frozen sections were detected with ROS fluorescent probe and MitoTracker RED probe, respectively. Results Significant differences of the level of ROS and the numbers of abnormal mitochondria in morphology in the cortical neurons were found between 3 groups at the experiment period of 3 month and 6 month(F= 3.07,3.06,3.05,3.07, all P < 0.05). As compared with control group(10.43 ± 5.98,4.12 ± 3.86) at the experiment period of 3 month, the level of ROS and the numbers of abnormal mitochondria in morphology in the cortical neurons were obviously increased in high-dose fluorosis group(25.48 ± 6.09,20.47 ± 6.09, all P < 0.05), whereas no significant changes were found in low-dose fluorosis group(11.67 ± 3.49,6.68 ± 3.48, all P> 0.05). Furthermore, the increases in both ROS level and abnormal numbers of mitochondria were significant observed in the cortical neurons of low-dose fluorosis group (63.02 ± 8.15, 49.33 ± 8.61) and high-dose fluorosis group(65.60 ± 7.40,53.10 ± 6.95) as compared with the control group (25.26 ± 6.41,20.26 ± 6.41) at the experimental period of 6 month (all P < 0.05). The abnormal numbers of mitochondria correlated with ROS level(r = 0.93,0.81, all P < 0.05). Conclusions Taking excessive amount of fluoride results in high level of oxidative stress and impaired the balance of mitochondrial fission-fusion,which is dependent on the feeding times and doses of fluoride. The mechanism of the mitochondrial abnormalities might be associated with the high level of oxidative stress induced by chronic fluorosis.

Background Deficiency of neurotrophic factor is associated with the damage of optic nerve in glaucoma.Reaserches showed that ectopically applied neurotrophic factor has a transient neuroprotective effect in glaucoma model,and the viral expression of adeno-associated neurotrophie factor may provide long-term supplementation of neurotrophic factor and neuroprotection in tissues.Objective The present study Was to investigate the neuroproteetive effect of adeno-associated viral(AAV)-mediated brain-derived neurotrophic factor (BDNF)on retinal ganglion cells(RGCs)in DBA/2J mice with experimental glaucoma. Methods 10 clean DBA/2J mice were administered intravitreal injection with 1 microliter of AAV-BDNF-GFP in the left eyes at the age of 6 months,and the right eyes were injected with the same volume of saline solution as control.Intraocular pressure (IOP)was measured with Tonolab in the mice every month.Retinas were obtained after 3 months for the investigation of GFP expression in RGCs using fluorescence microscopy.Immunohistochemistry Was performed by applying TUJ1 and Cy3 antibodies to identify surviving RGCs. Results The IOP of DBA/2J mice were 11.90 mmHg and 11.40 mmHg in the right eyes and left eyes,respectively,at 4 months.The IOP of DBA/2J mice began to rise at 5 months and reached its peak in 8 month-old mice.There was no statistically significant difference in IOPs between the right eyes and the left eyes from 4 month-through 9 month-old mice(t=-1.78-0.61,P=0.11-0.90).Three months after intrlavitreal injection of AAV-BDNF-GFP,GFP was positively expressed in RGCs of retinas with the expression rate of 46.33%±8.08%.The over-expression of BDNF led to more RGCs survival than the control eyes (3168.13±1319.33/mm2 vs 2024.81±796.38/mm2,t=2.75,P=0.02). Conclusion These data suggest that BDNF can exert a protective effect in DBA/2J glaucoma mice.