Objective To detect the osteopontin(OPN)expression in renal tissue of rats with fluorosis and low calcium diet,and study the role of OPN in renal injury of fluorosis.Methods Forty-eight aged 1 month Wistar rats,80-120 g,were randomly divided into 4 groups by 2×2 factorial design(the number of female and male in each group was equal):the control group,high-flluoride group,low-calcium group and low-calcium with high-fluoride group.All rats of the fluorosis groups were fed with feed containing corn exposed to coal-burning from endemic fluorosis areas with high fluoride(100 mg/kg,corn),the other two groups were fed with feed containing coru from nonendemic fluorosis areas(fluoride 5 mg/kg,corn).After 16 weeks,the rats were killed.The change of teeth was examined,and the incidence rate of dental fluorosis was calculated.The expressions of both protein and mRNA of OPN in rat renal tissue were determined by RT-PCR and immunohistochemistry after four-month experimentation.Results The growth of teeth was very well in the control group and the low-calcium group.The two high-fluoride groups showed evident dental fluorosis(100%).The results of immunohistochemistry showed that the OPN protein was localized in renal tubule cytoplasm.The OPN-positive cells from renal tissue were lightly and scatteredly stained in control and low-calcium groups.The OPN-positive cells had deeper color in high-fluoride group and low-calcium with high-fluoride group,widely distributed in the renal tubular epithelial cells.The protein expression of OPN in the two groups exposed to fluoride(168.64±13.21,169.26±8.92)was significantly higher than those of the corresponding control group(145.78±10.26,all P<0.01)and low-calcium group(149.60±16.84,all P<0.01).The mRNA expression of OPN in the two groups exposed to fluoride(1.89±0.37,1.94±0.22)was significantly higher than those of the corresponding control group(1.32±0.26,all P<0.05)and low-calcium group(1.30±0.186,P<0.05),respectively.High fluoride influenced the expression of protein and mRNA of OPN(F=13.821,4.24,all P<0.05).Low calcium did not affect the expression of protein and mRNA of OPN(F=2.164,0.58,all P>0.05).However,high fluoride and low calcium had a cross interaction on the expression of protein and mRNA of OPN(F=6.257,432,all P<0.05).Conclusions Over-dose fluoride enhances the expression of OPN.The higher expression observed in the cases exposed to high fluoride concentration is associated with serious renal injury.OPN may he a potential marker for renal injury in fluorosis.Moreover,over-dose fluoride and low calcium make the renal injury worse,indicating low calcium plays an important part in renal injury by fluoride.

AIM: To investigate the signaling mechanisms involved in the priming effects of lipopolysaccharide(LPS) on heat killed Staphylococcus aureus(HKSa)-induced nitric oxide(NO) production in macrophages.METHODS: Murine macrophage RAW264.7 was used in the experiment.Griess reagent was used to measure the content of nitrite in culture medium.Real-time PCR and Western blot was utilized to examine the mRNA and protein levels of toll-like receptor 2(TLR2),respectively.Dual luciferase reporter assay was used to assess the transcriptional activity of nuclear factor of activated T cells(NF-AT).RESULTS: The RAW264.7 cells pretreated with LPS for 24 h significantly enhanced NO production induced by HKSa,suggesting that LPS primed the macrophages and increased the reactivity of the cells to HKSa.LPS increased the mRNA and protein levels of TLR2 in a dose-dependent manner in RAW264.7 cells.The RAW264.7 cells pretreated with LPS enhanced NO production induced by peptidoglycan,one of the specific ligand of TLR2.The priming effect of LPS on HKSa-induced NO production was partly blocked by TLR2 neutralizing antibody.LPS significantly enhanced the transcriptional activity of NF-AT,which was inhibited by BAPTA/AM(a cell-permeable cytosolic calcium chelator) and cyclosporine A(CsA,an inhibitor for calcineurin).Both BAPTA/AM and CsA inhibited the priming effect of LPS on HKSa-induced NO production in RAW264.7 cells.CONCLUSION: The present study confirms the priming effect of LPS on the reactivity of RAW264.7 cells to HKSa.Pattern recognition receptor TLR2 and calcium/calcineurin/NF-AT signaling pathway may be involved in the priming process initiated by LPS.

In order to solve the problem of selection and in vivo delivery problem in siRNA treatment, hepatitis B virus (HBV) HBx gene which could be targeted by siRNA was studied. The siRNA expression plasmid which specific inhibits HBx expression was obtained by in vitro selection via a dual-luciferase plasmid including HBx-Fluc fusion protein expression domain. The selected siRNA expression plasmid was then encapsulated in PEG-modified cationic liposome, which was devoted into pharmacodynamic studies at both cellular and animal level. The results illustrated that the cationic liposome which encapsulated siRNA expression plasmid could effectively inhibit HBx gene expression both in vitro and in vivo.

Animals ; Disease Models, Animal ; Hypoglycemia ; chemically induced ; metabolism ; Hypothalamus ; drug effects ; metabolism ; Insulin ; pharmacology ; Intracellular Signaling Peptides and Proteins ; metabolism ; Male ; Neuropeptides ; metabolism ; Orexins ; Rats ; Rats, Sprague-Dawley

Langerhans cell tumor is a kind of tumor that originates from Langerhans cells (LC) and maintain their specific phenotype profile and ultrastructural features. Based on cell morphology, immunohistochemical and ultrastructural characteristics, Langerhans cell tumor has two main subcategories: Langerhans cell histiocytosis (LCH) and Langerhans cell sarcoma (LCS). LCH is a benign clonal proliferative disease of the LC, whereas LCS is an extremely rare neoplastic proliferation of Langerhans cells with overtly malignant cytologic features and spreads aggressively, which is considered to be a high level malignant type of LCH. Both LCH and LCS can involved various tissues and organs and have complex and diverse clinical manifestation, which cause different severity. The diagnosis depends on histopathological morphology and immunohistochemistry; the electron microscopy was used to assists diagnosis when necessary. The treatment includes surgery, chemotherapy, radiotherapy, immunotherapy and hematopoietic stem cell transplantation, etc, but lack of generally accepted optimal treatment options currently, individualized treatment is needed. The prognosis of LCH is primarily related to the number of damaged organ, while LCS has a poor overall prognosis as its invasion and rapid progress. This article reviews the pathogenesis, clinical manifestations, diagnosis, treatment and prognosis of both LCH and LCS.
Histiocytosis, Langerhans-Cell ; Humans

Objective To investigate the expression of hypoxia-inducible 1 alpha(HIF-lα)and glucose transporter 1(Glut1)in human breast cancer and its relationship to proliferating cell nuclear antigen (PCNA)protein and clinical pathologic factors.Methods Immunohistochemical staining was used to measure the expression of HIF-lα.Glut1 and PCNA in human breast fibroadenoma,usual hyperplasia and breast carcinoma.Results HIF-1α expression was not found in breast fibroadenoma and hyperplastic Iesions.In contrast.the positive rate of HIF-1α was found in the ductal carcinoma in situ 55%(DCIS,11/20)and the invasive breast carcinoma 85%(51/60).Glut1 positivity in breast carcinoma was 58.8%(47/80).The totsl positive rate of PCNA in breast carcinoma was 75%(60/80),that in DCIS was 65%(13/20)and that in invasive carcinoma was 78.3%(47/60).There was a positive correlation between HIF-lα and Glut 1 level (r=0.653,P＜0.01),a positive correlation between HIF-1α and PCNA level(r=0.693,P＜0.01);and also a positive correlation between Glutl and PCNA level(t=0.742.P＜0.01).conclusion The overexpression of HIF-lα and its target gene Glut1 played important roles in carcinogenesis and progression of breast carcinoma and closely correlated with cell proliferation of breast carcinoma and may become a new target for treatment of breast carcinoma.

Objective To determine the risk factors for post-operative delirium(POD)and post-operative cognitive dysfunction(POCD)in patients undergoing spine surgery.Methods One hundred and twenty ASA Ⅰ-Ⅲ of both sexes aged 50-76 yr undergoing elective spine surgery under general anesthesia were studied.POD was assessed by Delirium Rating Scale revised 98 at 2 days after operation and the patients were assigned into POD and nonPOD group.Cognitive function was assessed by Mini-Mental State Examination(MMSE)at 1 day before and 3 days after operation.The patients were diagnosed as having POCD if MMSEpre-MMSEpost ≥ 3.The palients were assigned into POCD and nonPOCD group.Executive function and depression were assessed by stroop interference test and Beck Depression Inventory(BDI)at 1 day before operation.Age,sex,education,alcohol consumption per week,a history of psychiatric disease,ASA physical status,Charlson comorbidity score,type of anesthesia,anticholinergic drug administration and VAS score at 1 day after operation were recorded.If there was signifirant difference between the 2 groups,the factor was analyzed using multi-factor logistic regression to select risk factor for incidence of POD and POC).Results Eleven patients developed POD(9.2％)and 30 patients developed POCD(25.0％).Logistic regression model showed that lower Stroop-CW,higher BDI score,higher Charlson comorbidity score and a history of psychiatric disease were risk factors for POD,while lower Stroop-CW,higher BDI score,higher Charlson comorbidity score and higher alcohol consumption per week were risk factors for POCD.Conclusion Preoperative executive dysfunction,depression and greater preoperative comorbidity are risk factors for both POD and POCD.A history of psychiatric disease is a risk factor for POD and higher alcohol consumption is a risk factor for POCD in patients undergoing spine surgery.

Objective To assess the relationship of serum prealbumin level with the severity of acute ischemic stroke (AIS).Methods The clinical data of 2522 AIS patients who were admitted in Peking Union Medical College Hospital from 2000 to 2008 were retrospectively analyzed.The serum prealbumin and hypersensitive C-reactive protein (hs-CRP) levels were evaluated by immunoturbidimetric assay within 24 hours after admission.The AIS severity was evaluated at admission using modified Rankin Scale (mRS).Patients were divided into mild AIS group (mRS score ≤ 3 ) and severe AIS group (mRS score ＞ 3 ).The levels of serum prealbumin and hs-CRP were compared between these two groups,and the relationship between praalbumin and hs-CRP was also analyzed.Results There were 1697 patients in the mild group (average mRS score:1.67) and 825 patients in the severe group ( average mRS score:4.53 ).The severe group had significantly lower prealbumin level [ ( 191.20,82.00)versus (219.18,72.00) mg/L,P =0.000] and higher hs-CRP level [ (6.01,8.22) versus (4.15,6.93) mg/L,P =0.000 ] than the mild group,respectively.Partial regression analysis showed that the stroke severity was negatively correlated with serum prealbumin level (r =-0.115,P =0.000) and positively correlated with hs-CRP level (r =0.098,P =0.000).Serum prealbumin level was inversely correlated with hs-CRP level ( r =- 0.396,P =0.000).Conclusion The prealbumin level is relevant with the severity of AIS and inflammation.

Objective To examine the recurrent ischemic stroke(RIS)in hospitalized patients predicted by Essen Stroke Risk Score(ESRS)and investigate the effect of intensive antiplatelet therapy in patients with high risk of RIS. Methods Retrospective analysis of patients with acute noncardioembolic ischemic stroke consecutively admitted to Peking Union Medical College Hospital(PUMCH)during 2001-2008. All 1008 patients were included in this study, 377 hospitalized in 2001-2002, 315 in 2005 and 316 in 2008. High risk of RIS was defined as ESRS ≥3. The average ESRS score in three groups and percentage of patients with high risk of RIS in each group were calculated. Risk of RIS was evaluated by comparing the average ESRS score in these three groups. Patients with high risk and taking clopidogrel treatment were also evaluated. Results Average ESRS score was 2. 67 ± 1.47,3.55 ± 1.40 and 3.93 ± 1.48(F= 150. 85,P=0.000)in groups of patients hospitalized in 2001-2002, 2005 and 2008 respectively. A significant difference was shown in percentage of high risk patients with ESRS ≥3 in three groups: as 51.64% in 2001-2002,77. 19% in 2005 and 85. 45% in 2008(X2=98.30,P=0. 000),showing a trend of increasing risk of RIS. Except for patients age, rates of having the risk factors in patients increased significantly, including hypertension, diabetes, myocardial infarction, myocardial diseases, smoking,vascular disease and stroke history. Clopidogrel usage has been increasing to 25.63% in 2008, but was far behind high ratio of high risk RIS patients(85.45%). Conclusions This retrospective study showd an increasing trend in RIS risk during 2001-2008. Identifying high risk patients and applying intensified antiplatelet therapy might play an important role in reducing the risk of RIS.

Adrenalectomy ; Adult ; Angiomyolipoma ; pathology ; surgery ; Follow-Up Studies ; Humans ; Kidney ; pathology ; Kidney Neoplasms ; pathology ; surgery ; Lymph Node Excision ; Lymph Nodes ; pathology ; Lymphatic Metastasis ; Male ; Nephrectomy ; Ureter ; surgery