Objective:To investigate the structural alterations of mitochondria and its role in neutrophil death induced by ONO-AE-248.Methods:Human neutrophils were cultured in vitro with ONO-AE-248(5?10-5 mol/L)and medium alone. Transmission electron microscopy(TEM) was used to detect the structural alterations of mitochondria and the level of mitochondria membrane potential by flow cytometry using mitocapture dying.Results:ONO-AE-248 resulted in extremely swollen mitochondria within 6 hours. Meanwhile, a rapid loss of mitochondrial membrane potential of neutrophils occurred, especially in 3 hours and 6 hours. There were obviously differences between spontaneous apoptosis and non-apoptosis programmed cell death induced by ONO-AE-248.Conclusion:The experiment results suggest that changes of mitochondrial structure and function be typically morphological, physiological and biochemical features in this unique form of neutrophil death, and that the mitochondrial pathway might play a more important role in ONO-AE-248-induced death of neutrophils.

Objective To observe the effect of lovastatin on plasminogen activator inhibitor -1 (PAI-1) and collagen type Ⅳ in rats with glomerularsclerosis induced by adriamycin,and to discuss its mechanism of protective effects on kidneys.Methods Twenty-four male Wistar nephritic rats induced by adriamycin were randomly divided into 3 groups:control,hyperlipidemia and lovastatin treatment group.They were fed 12 weeks.Urinary protein excretion and serum lipid were assayed,then renal glomerularsclerosis index,the expression of PAI-1 and collagen type Ⅳ were observed.Results Serum total cholesterol,triglycerides,low-density lipoprotein,urinary protein excretion,renal glomerularsclerosis index were significantly lower in treatment group than those in hyperlipidemia group.Expression of PAI-1 and collagen type Ⅳ,and number of foamcells were also sharply lower in treatment group than those in hyperlipidemia group.Conclusions Lovastatin not only reduces proteinuria,improves renal function,but also modulates glomerularsclerosis by inhibiting activity of PAI-1 and decreasing accumulation of collagen type Ⅳ.The mechanism of renal protective effect is independent of a reduction of circulating cholesterol.

Objective To explore the influence of brain-derived neurotrophic factor (BDNF) on the differentiation of nerve stem cells (NSCs) from neonatal rat hippocampus in vitro and to find new revulsant of NSCs,which can improve the percentage of NSCs differentiating into neurons.Methods Twenty-four hours neonatal rats were selected to obtain hippocampus tissue to culture NSCs in serum-free culture medium by suspending culture.The high pure NSCs were obtained after passing 2 generations.The culture cells were identified as NSCs by staining of nestin,which was NSCs special marker.After passaged three generations,the NSCs were randomly classified into 2 groups:test group and control group.There were 15 pieces per group.There was 2 mL per piece,which contains 1?105 cells.50 g/L fetal bovine serum(FBS) and 20 ?g/L BDNF were added into foundational culture medium in test group;only 50 g/L FBS was added into foundational culture medium in control group.The neurons and their percentage were tested using the immunofluorescence labeling and flow cytometer after 7 days of differentiated cultivation.Results The hippocampus tissue cells grew in globular in serum-free culture medium by suspending culture,which expressed highly positive by nestin immunofluorescence staining.Its purity was above 90%.The percentage of neurone specific enolase(NSE)-positive cells in test group was 60.45%,which was obviously higher than that of control group (23.67%).The difference was significant between 2 groups(?2=27.75 P

Objective To explore the protective effect of selenium, an antioxidant, on fluoride-induced renal injury in rats and find out the optimal level of selenium against fluoride toxicity and its valid molecular target.Methods All 80 male weanling SD rats were randomly divided into 8 groups by body weight as follows: normal control group(drinking tap water), fluoride exposed group (drinking water containing 50 mg/L of NaF), low, middle,high selenium exposed groups(drinking water containing 0.375, 0.750, 1.500 mg/L of Na2SeO3) and low, middle,high Se-fluoride groups (drinking water containing both 50 mg/L NaF and three doses of Na2SeO3 as abovementioned, respectively). After 6 months, the rats were killed then the oxidation level and nuclear factor κB(NF-κB)expression level in kidney were measured. Results The weight of the fluoride exposed group[(695.95 ± 55.89 )g]was significantly deceased than the controls[(782.69 ± 56.12)g, P ＜ 0.01]. Glutathione peroxidase(GSH-Px)activity of fluoride exposed group[(55.86 ± 5.09)U/mgprot] was not significantly different but decreased. Tatal antioxidant capacity (T-AOC) activity in fluoride exposed group [(7.54 ± 1.35)U/mgprot] significantly decreased than the controls[(9.03 ± 0.37 )U/mgprot, P ＜ 0.05]. In addition, a significant increase of malondialdehyde ( MDA )in fluoride exposed group[(3.86 ± 0.31 )mnol/mgprot, P ＜ 0.05] was observed than the controls[(3.14 ± 0.32)nmol/mgprot, P ＜ 0.05]. GSH-Px activity of high Se-fluoride group[(74.99 ± 8.41 )U/mgprot] was significantly higher than the fluoride exposed group[(55.86 ± 5.09)U/mgprot, P ＜ 0.05] and its MDA level[(3.17 ± 0.20)nmol/mgprot] was lower than the fluoride exposed group[(3.86 ± 0.31 ) nmol/mgprot, P ＜ 0.05]. NF-κB expression levels of fluoride group, high selenium group and low Se-fluoride group(0.360 ± 0.015,0.367 ± 0.007,0.376 ± 0.006,respecyively) were obviously increased compared with the controls(0.312 ± 0.022, P ＜ 0.05); it was significantly lower in high Se-fluoride group(0.312 ± 0.005) than in fluoride exposed group(0.360 ± 0.015, P ＜ 0.05). Conclusions Na2SeO3 of 1.5 mg/L is the optimal dose against chronic fluorosis on kidney injury under this experimental condition.NF-κB is likely to be a target molecule of the selenium as an antagonist on fluorosis.

Autoimmune diseases (AID) are characterized by autoimmune disorder, as autologous tissue is attacked by the autoimmune system. It is reported that the imbalance of autoimmune tolerance and ingrained inflammatory response are the core events of AID undoubtedly. Peroxisome proliferator-activated receptor γ (PPARγ) which belongs to the nuclear hormone receptor superfamily is a ligand activated transcription factor. PPARγ combines with retinoid X receptor (RXR) to form heterodimer. When PPARγ is activated, the complex regulates gene expression by binding to a specific peroxisome proliferator response element (PPRE). In addition, PPARγ has diversified biological functions, playing important roles in regulating metabolism, controling inflammation, modulating glucose and lipid metabolism, ameliorating atherosclerosis, anti-tumor, and regulating immune response. However, recently researches indicate that PPARγ participates in the pathogenesis of AID. PPARγ plays key roles in regulating activation and polarization of macrophages, function of dendritic cells, proliferation and differentiation of T cells, and modulation of the function of related stromal cells. This article summarizes the biological functions and signal transduction pathways of PPARγ and the protective effects of agonists of PPARγ on AID, aiming to provide theoretical support for the research of mechanism and prevention and treatment of AID.

Objective To analyze clinical features and sum up experience for the treatment of ischemic bowel disease. Methods Clinical data of 73 patients with the diagnosis of ischemic bowel disease were retrospectively analyzed. ResultsTwenty-eight patients were male and 45 patients were female. The median of age was 65 years (range of 38 to 89 years). Forty-eight patients were associated with hypertension, 23%(17/73) patients had a history of coronary disease and 15% (11/73) had diabetes. Seventy patients presented symptom of abdominal pain and 93% (68/73) had hematochezia. Symptoms relieved by conservative treatment in 96% (63/66) patients. Nine patients underwent a surgery. One patient died of sepsis postoperatively. One suffered from colostomy necrosis and leakage of the rectum segment. Conclusion 1. Elder patients presenting symptoms of abdominal pain and hematochezia, especially with a history of cardio-cerebrovascular disease and diabetes should be considered for the possibility of ischemic bowel disease. 2. Most patients with ischemic bowel disease could be successfully treated by conservative therapy. 3. Surgery for patients with chronic relapsing and nonresponsible symptoms was difficult and patients often suffer from high postoperative complications.

Objective To investigate the current status of coal-burning endemic fluorosis and the fluoride content in foods and drinking water in Hongya County,Sichuan Province.Methods Dental fluorosis and urinary fluoride were suveyed in children of 8～12 years old in two schools which repectively located in Gaomiao and Wawushan Town.The adults above 20 years old underwent clinical examination.At the same time,fifty adults above 20 years old in Garden Village were chosen to take forearm and calf X-ray films to find out the evidence of skeletal fluorosis.The content of fluoride in food such as bacon,corn,dry capsicum in Sanxing Village in Gaomiao Town and Futian Village in Wawushan Town as well as drinking water in five families in Sanxing Village were determined.Results The dental fluorosis rate of children was 40.76%(161/395),the dental fluorosis index was 0.86 in Gaomiao Town.The dental fluorosis rate of children was 14.36%(82/571),the dental fluorosis index was 0.31 in Wawushan Town.The medium value of the urine fluoride was 0.81 mg/L.ranged 0.16～3.89 mg/L.The positive rate oi the clinical examination of skeletal fluorosis was 5.27%(27/512),the X-rays detective rate was 4.00%(2/50).The medium value in bacon,corn,dry capsicum were 6.00,0.64,1.49 mg/kg.The averaged content of the fluoride in drinking water(0.14±0.06)mg/L of local household was within the eligible limitation.Conclusions It is currently a mild endemic disease in Hongya Country,its incidence is reduced apparently,pathogenetic environmental fluoride content is reduced.The main source of fluoride is from the preserved ham contaminated with fluoride,which is epidemiologically significant in endemic area of Hongya County.Defluoriding countermeasures should be taken in the endemic areas.

Objective To analyze the heterogeneous variation of serum free fatty acid (FFA) and lipids during early second trimester in women with or without uterine artery notch in pre-eclampsia (PE).Methods This is a prospective cohort study of 4 000 women with singleton pregnancies registered in early pregnancy and in whom regular check-ups were performed in Haidian Maternal & Child Health Hospital.Blood specimens were collected at gestational age 14-18 weeks at the same time of screening for Down's syndrome.One hundred and one cases with early diastolic notch of the uterine artery were included in the N+ group,and 172 cases without notch but at high risk of PE were included in the N-group at 22-24 weeks.In addition,205 women who were selected randomly at a ratio of 1 ∶ 5,without notch or PE high-risk factors,were also included in the N group.Both groups were subgrouped according to the outcomes of pregnancy complications:early-onset PE group EPE,late-onset PE (LPE),gestational hypertension (GH) group,gestational diabetes mellitus (GDM) group with normal blood pressure,and no complications (NC) group.The variation in FFA and other lipid metabolism indicators in the PE subgroups were compared and analyzed by two independent-sample t-test,one-factor analysis of variance,Chi-square test (or Fisher's exact) and Logistic regression.Results History of PE and pre-hypertension at first visit differed significantly between the N+ and N-groups [3.9％ (4/101) vs.0.8％ (3/377),x2=5.52,P＜0.05; pre-hypertension at first visit,42.2％ (43/101) vs.25.7％ (97/377),x2=10.91,P＜0.05].In the N+ group,23.8％ (n=24) of women had PE,of which 37.5％ (n=8) were early onset.In the N group,2.1％ (n=8) had PE,and all were late onset.The incidence of PE differed significantly between the N+ and N-groups (x2=59.72,P＜0.05).In the N+ group,FFA gradually decreased among the ePE,IPE,GH and NC groups [(0.68±0.27),(0.58±0.21),(0.57±0.21) and (0.49±0.19) mmol/L,F=2.78,P＜0.05]; Multivariate regression analysis showed that FFA (OR=135.68,95％CI:3.78-4 873.00) and PE history (OR=123.25,95％CI:9.27-i 638.00) were risk factors of ePE.Pre-hypertension at registration (OR=4.69,95％CI:2.08-10.58) and pre-pregnancy body mass index (BMI) 24-28 (OR=3.69,95％CI:1.26-10.83) were risk factors ofGH.FFA (OR=9.08,95％CI:2.49-33.01) and pre-pregnancy BMI ≥ 28 (OR=5.08,95％CI:2.16-11.92) were risk factors for GDM.Conclusions Serum FFA and TG levels in early second trimester are correlated with PE,especially the early-onset PE.The onset of PE is heterogeneous and affected by many factors,and occurs in patients with or without early diastolic notch of the uterine artery in the second trimester.Patients with notch are more likely to have early-onset PE,which is correlated with blood FFA and TG levels.

In recent years, more and more research shows that the pharmacokinetic parameter of traditional Chinese medicine can be affected by the disease states. It's possible that drug metabolic enzymes, transporters, cell membrane permeability and the change of microbes group could be interfered with physiological and pathological changes, which enables the pharmacokinetics of traditional Chinese medicine in the body to be altered, including the process of absorption, distribution, metabolism and excretion, and then the pharmacokinetic parameters of traditional chinese medicine are altered. It's found that investigating the pharmacokinetic of traditional Chinese medicine in the pathological state is more useful than that of in normal state because the great part of traditional Chinese medicine is mainly used to treat disease. This article reflects the latest research on the pharmacokinetic of traditional Chinese medicine in the disease state such as diabete, cerebral ischemia, liver injury, inflammatory disease, nervous system disorders and fever in order to provide certain reference for clinicians designing reasonable administration dose.
Animals ; Brain Ischemia ; drug therapy ; Chemical and Drug Induced Liver Injury ; drug therapy ; Humans ; Inflammation ; drug therapy ; Medicine, Chinese Traditional ; Nervous System Diseases ; drug therapy

Objective The purpose of this study was to investigate the expression of human mitochondrial transcription termi-nation factor-3 ( hMTERF3) in non-small cell lung cancer ( NSCLS) and to analyze its clinicopathological significance. Methods The paraffin block samples used in this study included 65 cases of NSCLC and 32 cases of normal alveolar epithelial tissues. We determined the expressions of hMTERF3 in NSCLC and normal alveolar epithelial tis-sues by immunohistochemistry, calculate the survival rate using the Kaplan-Meier method, and analyzed the risk factors affecting the prognosis of NSCLC using the Cox Proportional Hazard Model. Results In the 65 cases of NSCLC, 31 ( 47. 69%) showed positive expression of hMTERF3. The total survival time was significantly shor-ter in the patients with a high than in those with a low hMTERF3 ex-pression ([30.39±3.35] vs [57.61±7.12] mo, P<0.05). The riskfactors affecting the prognosis of NSCLC included positive expression of hMTERF3 (HR=3.302, 95% CI:1.598-6.905) and lymph node metastasis (HR=4.052, 95% CI: 1.212-12.398). Conclusion hMTERF3 is overexpressed in NSCLC. Highly expressed hMTERF3 and lymph node metastasis reduce the survival time of NSCLC patients, suggesting that hMTERF3 may be a potential bio-marker for the prognosis of NSCLC.