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 explore the effect of Xinwei Granules on cell proliferation in rats with precancerous lesions of gastric cancer based on CyclinD1-CDK4/6-P16 pathway.Methods 180 Wistar rats were randomly divided into 6 groups,30 rats in each group:blank control group(blank),model group,Weifuchun control group,Xinwei Granule(low,medium and high dose)group.The PLGC rat model was made by MNNG method.Xinwei granule low,medium and high dose group were 0.72 g·kg-1,1.44 g·kg-1,2.88 g·kg-1;weifuchun group was given 0.52 g·kg-1,once a day by intragastric administration,and the blank group and the model group were given the same amount of normal saline by intragastric administration.The experimental period was 16 weeks.After the end of the experiment,the general condition of the rats was observed,and the mRNA and protein expressions of CyclinD1,CDK4/6 and P16 in gastric mucosa were detected by RT-PCR and Western blotting.Results The activity and diet of rats in each group of Xinwei Granules and Weifuchun group were improved to varying degrees compared with the model group.Compared with the blank control group,the mRNA and protein expression levels of CyclinD1,CDK4 and CDK6 in the model group were significantly increased.The mRNA and protein expression levels of P1 6 were significantly decreased(P＜0.05).The expression levels of CyclinD1,CDK4,CDK6 mRNA and protein in Xinwei granule(low,medium and high dose)group and Weifuchun group were lower than those in model group.The mRNA and protein expression levels of P16 were significantly increased(P＜0.05),and the effect of Xinwei granule medium dose group was the most significant.Conclusion Xinwei granules participate in the regulation of cell cycle through the CyclinD1-CDK4/6-P16 pathway,thereby inhibiting the proliferation of PLGC cells.

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.

With dwindling number of new antibiotics and inappropriate use of antibiotics, the emergence and spread of antibiotics resistance occurs commonly in healthcare institutions worldwide. In China, antibiotics are commonly overprescribed and misused. This study is to assess the effect of the nationwide special campaign on antibiotic stewardship program (ASP) at specialized hospitals in China by investigating prescription information from 2011 to 2012. Data on the hospital consumption and prescription of systemic antibiotics were obtained from four specialized hospitals, including maternity, children's, stomatological and cancer hospitals. Systematic random sampling was used to select outpatient prescriptions and inpatient cases. A total of 105 specialized hospitals in 2011 and 121 specialized hospitals in 2012 were analysed. The defined daily doses (DDDs) per 100 inpatient days, the percentage of antibiotic use in outpatient prescriptions, and the percentage of antibiotic use in inpatient cases were used as measurements of antibiotic use. The overall antibiotic use density in the selected hospitals decreased between 2011 and 2012 from 39.37 to 26.54 DDD/100 inpatient days (P<0.001). The percentage of antibiotic use in outpatient prescriptions (range: 24.12%-18.71%, P=0.109) and inpatient cases (64.85%-60.10%, P=0.006) also decreased within the two years. Significant changes were observed among regions and different hospitals within the two years. And antibiotic consumption was correlated with the type and size of specialized hospital in 2012, but not with the regions. This analysis of antibiotic consumption of specialized hospitals allows relevant comparisons for benchmarking and shows that national ASP has improved antibiotic rational use in China. The data will assist policymakers in formulating effective strategies to decrease antibiotic overuse and identify areas that require further work.

OBJECTIVETo observe the changes of proximal femoral geometry after femoral neck fracture treated with THA, analyze the existent of differences and their manifestation.

METHODSAll patients of femoral neck fracture (FNF) and osteonecrosis of femoral head (ONFH) were treated with THA by the same operating team from January to December of 2014, including 22 patients with FNF (11 males and 11 females,with age from 44 to 83 years old (means 66.18 ± 11.47) and 23 patients with ONFH (12 males and 11 females, with age from 19 to 68 years old (means 51.91 ± 11.76). After THA, height of femorals, offsets, osteotomy position and adjusting modes were measured and the statistic analysis was done.

RESULTSAfter THA, all patients were measured. Decreased femoral height, offsets and lower osteotomy positions were found in patients with FNF than those with ONFH, and 3 kinds of adjustments because of lower-positional osteotomy were found.

CONCLUSIONAfter THA, lower-positional osteotomy and decreased femoral offsets may occur on patients with FNF. The adjustments caused by lower-positional osteotomy may lead to negative results.

Adult ; Aged ; Aged, 80 and over ; Arthroplasty, Replacement, Hip ; methods ; Female ; Femoral Neck Fractures ; pathology ; surgery ; Femur ; pathology ; Femur Head Necrosis ; pathology ; surgery ; Humans ; Male ; Middle Aged