Objective To determine the frequency of polymorphism at exon 26 (C3435T) of muhidrug resistance 1 gene (MDR1) in epileptic patients in the southern Chinese and to study the association of this polymorphism with pharmacoresistance.Methods DNA samples were obtained from 134 patients,of whom 72 were resistant to antiepileptic drug treatment and 62 were responsive to the treatment. Genotypes of the C3435T polymorphism were determined by polymerase chain reaction (PCR) followed by restriction digestion and gel electrophoresis.Genotype and allele frequencies in the drug resistant group were compared to those in the response group by Chi-square analysis.Results Of all 134 patients,33 (24.6%) had CC genotype,72 (53.7%) had CT genotype,and 29 (21.6%) had TT genotype.The frequency of CC genotype was significantly higher in the pharmaeoresistance group (33.3%) than that in the responsive group (14.5%,P=0.012).The frequency of the C allele was also significantly higher in the pharmacoresistance group (57.6%) than that in the responsive group (44.4%,P=0.03).When patients were divided by types of seizure into three groups:generalized seizure group,partial seizure group,and undefined seizure group,the CC genotype and C allele were associated with pharmacoresistance in the partial seizure group.Conclusions In the southern Chinese,the CC genotype and C allele are associated with resistance to the antiepileptic treatment.This finding needs to be verified in studies with larger sample size.

Objective:To investigate the role of C3a,C5a and their receptors in the pathogenesis of IgA nephropathy (IgAN). Methods:A total of twenty-eight 6-8 weeks old female BALB/c mice were investigated.And they were negative control group , WT group,C3aR-/-group,C5aR-/-group(the latter three groups were named as experimental groups ),seven mice in each group.All the mice were infected through respiratory tract with infectious SV (experimental groups) or PBS(negative control group),combined with tail vein challenge to make IgAN animal model.Testing 24 h total urinary protein , serum urea nitrogen ( BUN ) and creatinine ( Cr ) , using direct immunofluorescence to test the renal deposition of IgA and C 3,observing renal pathologic lesion under PAS staining with light microscopy.RT-qPCR was used to test the relative mRNA expression of TNF-α,TGF-β,IL-1β,IL-6,MCP-1.Results: After 15 weeks,the level of UTP in experimental group was significantly higher than negative control group ,and the same results as WT group than C3aR-/-group and C5aR-/-group.There was no significant difference among groups for BUN and Cr.Combined with negative control group , experimental groups had significant renal pathological lesions , and the changes of WT group was more severe than C3aR-/-group and C5aR-/-group.The results of relative mRNA expression of TNF-α,TGF-β,IL-1β,IL-6,MCP-1 was the same as the level of 24 h UTP,at the same time,the relative mRNA expression of IL-1β,IL-6,MCP-1 in C3aR-/-group was significantly less than C5aR-/-group.Conclusion:The deficiency of C3a/C5a receptors can protect kidney from injury in IgAN ,and C3a receptor has more significant role in protect kidney from injury in IgAN.

BACKGROUND: Osteoporosis is a genetic disease associated with many enes. To date, the genes that regulate bone mass are incompletely defined.OBJECTIVE: To investigate the relationship between polymorphisms of steoprotegerin (OPG) gene promoter with bone mineral density (BMD) in remenopausal and postmenopausal women.DESIGN: Prospective study.SETTING: Peking Union Medical College Hospital.PARTICIPANTS: In July 2002, 495 Han nationality women selected from Peking Union Medical College Hospital were non-related volunteers and gave their informed consent prior to the study, which included 306 premenopausal women aged 20-39 years, 189 postmenopausal women aged 50-84 years.METHODS: ① BMD measurement: BMD was measured at the Lumbar Spine and Femoral Neck, trochanter, Ward's triangle by dual-energy X-ray absorptiometry. ② Genotyping: Whole blood genome DNA was extracted by QIAGEN DNA extraction kit. The PCR product and the result of endonuclease digest were confirmed by sequencing (Bioasia Biotechnology,Shanghai, China). The impact of the polymorphisms on BMD was also investigated using multiple Logistic regression.MAIN OUTCOME MEASURES: ① Distribution of OPG genotypes and the relationship with BMD. ② Association between OPG polymorphisms and osteoporosis.RESULTS: All 495 subjects were involved in the final analysis. ① These polymorphisms were in Hardy-Weinberg equilibrium (χ2= 0.056 -0.222, P＞ 0.05). The frequencies of genotypes of these subjects were as follows: AA (70.1%), AG (26.9 %), GG (3.0 %) for 163A→G polymorphism; TT (71.3 %), TG (25.9 %), GG (2.8 %) for 245T→G polymorphism. BMD was lower in premenopausal women with GG +AG genotype than AA genotype for 163A→G polymorphism, so did GG+TG genotype than TT genotype for 245T→G polymorphism. But there was no significant difference. BMD was lower in postmenopausal women with AG+GG genotype than AA genotype for 163A→G polymorphism at Lumbar Spine 2-4, Femoral Neck, Ward's triangle and Trochanter (P ＜ 0.05). For 245T→G polymorphism, BMD of postmenopausal women with TG+GG genotype was lower at Femoral Neck,Ward's triangle and Trochanter than TT genotype (P ＜ 0.05). For 245T→G polymorphism, BMD of postmenopausal women with TG+GG genotype was lower at Femoral Neck, Ward's triangle, and Trochanter than TT genotype (P ＜ 0.05). ② Age, weight, height, years since menopause, and 163A→G/245T→G genotypes were sewed as covariates. AG+GG genotype was contributed to low BMD at Lumbar Spine 2-4 and Ward's triangle (OR =2.045, OR=2.956, P ＜ 0.05, 95% CI 1.05-6.7). TG+GG genotype was risk factor for osteoporosis at Lumbar Spine 2-4, Ward's triangle,and Trochanter (OR=2.059, OR=2.859, OR=2.123, P ＜ 0.05, 95% CI 1.04-6.5).CONCLUSION: BMD was lower in postmenopausal women with the variant G allele for 163A→G and 245T→G polymorphisms at Femoral Neck,Ward's triangle, and Trochanter. The variant allele G may associate with lower BMD in postmenopausal women.

Objective To survey the prevalence of greenhouse farmer's lung and related risk factors in part of rural areas of Liaoning Province.Methods Using uniform scheme,procedures and questionnaire,a survey for 5420 farmers(2660 men and 2760 women)with complete data who work inside greenhouses was performed in Shenyang,Xinmin,Chaoyang,and Jinzhou between August 2006 and June 2009.Pulmonary function tests was performed for every active farmer.Results Greenhouse farmer's lung was diagnosed in 308 cases,205 men(66.55%,205/308)and 103 women(33.44%,103/308),a prevalence of 5.7%(308/5420).The prevalence rate of greenhouse farmer's lung in males was significantly higher than that in females(?2=39.93,P0.05).In the 308 cases,the number of patiernts presented with fever chill,cough/sputum,chest tightness/shortness of breath were 180(58.44%),192(62.34%),160(51.95%)respectively,and the number of crepitations,radiological changes,spirometry abnormalities and serum IgE antibodies(+)was 164(53.25%),153(49.68%),147(47.73%)and 136(44.16%)at the time of the study.62.34%(192/308)of patients with greenhouse farmer's lung were mild and 38.66%(116/308)were severe.Conclusion The total prevalence rate of greenhouse farmer's lung in part of rural areas of Liaoning Province was 5.7% and multiple risk factors were associated with the disease.

In atherosclerosis, chronic inflammatory processes in local diseased areas may lead to the accumulation of reactive oxygen species (ROS). In this study, we devised a highly sensitive H₂O₂-scavenging nano-bionic system loaded with probucol (RPP-PU), to treat atherosclerosis more effectively. The RPP material had high sensitivity to H₂O₂, and the response sensitivity could be reduced from 40 to 10 μmol/L which was close to the lowest concentration of H₂O₂ levels of the pathological environment. RPP-PU delayed the release and prolonged the duration of PU in vivo. In Apolipoprotein E deficient (ApoE^‒/‒) mice, RPP-PU effectively eliminated pathological ROS, reduced the level of lipids and related metabolic enzymes, and significantly decreased the area of vascular plaques and fibers. Our study demonstrated that the H₂O₂-scavenging nano-bionic system could scavenge the abundant ROS in the atherosclerosis lesion, thereby reducing the oxidative stress for treating atherosclerosis and thus achieve the therapeutic goals with atherosclerosis more desirably.

Protein corona (PC) has been identified to impede the transportation of intravenously injected nanoparticles (NPs) from blood circulation to their targeted sites. However, how intestinal PC (IPC) affects the delivery of orally administered NPs are still needed to be elucidated. Here, we found that IPC exerted "positive effect" or "negative effect" depending on different pathological conditions in the gastrointestinal tract. We prepared polystyrene nanoparticles (PS) adsorbed with different IPC derived from the intestinal tract of healthy, diabetic, and colitis rats (H-IPC@PS, D-IPC@PS, C-IPC@PS). Proteomics analysis revealed that, compared with healthy IPC, the two disease-specific IPC consisted of a higher proportion of proteins that were closely correlated with transepithelial transport across the intestine. Consequently, both D-IPC@PS and C-IPC@PS mainly exploited the recycling endosome and ER-Golgi mediated secretory routes for intracellular trafficking, which increased the transcytosis from the epithelium. Together, disease-specific IPC endowed NPs with higher intestinal absorption. D-IPC@PS posed "positive effect" on intestinal absorption into blood circulation for diabetic therapy. Conversely, C-IPC@PS had "negative effect" on colitis treatment because of unfavorable absorption in the intestine before arriving colon. These results imply that different or even opposite strategies to modulate the disease-specific IPC need to be adopted for oral nanomedicine in the treatment of variable diseases.