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 investigate the correlations between circulating tumor cells(CTCs)in peripheral blood and clinicopathological characteristics and the effect of neoadjuvant chemotherapy on patients with gastric cancer.Methods A total of 112 patients with gastric cancer admitted to the Third Affiliated Hospital of Xinxiang Medical University from March 2015 to February 2016 were selected as the research subjects.All patients were drawn 4 mL of fasting peripheral venous blood on the first day before treatment,and peripheral blood CTCs were detected by using negative enrichment combined with immunofluorescence.Based on the CTC detection results,the patients were divided into the CTC-positive group and the CTC-negative group.Patients in both groups were treated with neoadjuvant chemotherapy,including intravenous infusion of oxaliplatin 130 mg·m-2 on the first day and oral administration of capecitabine 1 000 mg·m-2,twice a day,on days 1-14;21 days was taken as one course of treatment,and a total of 3 courses of treatment was adopted.The clinicopathological characteristics of patients in the two groups were compared.The consistency of Response Evaluation Criteria in Solid Tumors(RECIST)and evaluation criteria of CTC count was analyzed by the Kappa test.The 3-year cumulative survival rate and 5-year cumulative survival rate of patients were calculated by the Kaplan-Meier survival analysis,and the 3-year cumulative survival rate and 5-year cumulative survival rate were compared by log-rank test between the CTC-positive group and the CTC-negative group.Results Among the 112 gastric cancer patients,64 patients(57.14％)tested positive for peripheral blood CTCs,and 48 patients(42.86％)tested negative for peripheral blood CTCs.After neoadjuvant chemotherapy,the number of patients with complete remission,partial remission,stable disease and progression of disease was 0,76,21 and 15 patients,respectively;and the effective rate of treatment was 67.86％(76/112).There were statistically significant differences in the depth of tumor invasion and TNM staging between the CTC-positive group and the CTC-negative group(P＜0.05);there was no statistically significant difference in gender,age,pathological type,size,location and differentiated degree of tumor,and vascular tumor embolus in the two groups(P＞0.05).The total effective rate in the CTC-positive group was 59.38％(38/64),and the total effective rate in the CTC-negative group was 79.17％(38/48);the total effective rate in the CTC-positive group was significantly lower than that in the CTC-negative group(x2=4.926,P＜0.05).RECIST and CTC count evaluation criteria were moderately consistent(Kappa=0.546).The 3-year cumulative survival rate and 5-year cumulative survival rate in the CTC-positive group were 75.6％and 26.7％,respectively;and the 3-year cumulative survival rate and 5-year cumulative survival rate in the CTC-negative group were 85.2％and 46.6％,respectively.There was no statistically significant difference in the 3-year cumulative survival rate of patients between the CTC-positive group and the CTC-negative group(P＞0.05).The 5-year cumulative survival rate of patients in the CTC-positive group was significantly lower than that in the CTC-negative group(P＜0.05).Conclusion The detection of CTCs helps assess the degree of tumor invasion and clinical staging of patients with gastric cancer and can evaluate the effect of neoadjuvant chemotherapy,showing certain predictive value for the long-term survival of gastric cancer patients.

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.

Objective To explore the mechanism of the treatment of primary dysmenorrhea(PD)by mild moxibustion on"Shenque"and"Guanyuan"acupoints based on the regulation of cAMP-PKA signaling pathway on TRPV1.Methods Totally 32 female non-pregnant Wistar rats were randomly divided into blank group,model group,mild moxibustion group and capsazepine group,with 8 rats in each group.Except for the blank group,the other groups all used estradiol benzoate intraperitoneal injection combined with ice water bath to establish a PD cold-dampness stagnation syndrome rat model.Intervention began on the first day of modeling,the mild moxibustion group selects"Shenque"and"Guanyuan"for mild moxibustion,20 min per time,the capsazepine group was injected capsazepine 2 mg/kg,once a day for 10 consecutive days.ELISA was used to detect uterine PGF2α and cAMP content,immunofluorescence staining was used to detect TRPV1 expression in uterine tissue,Western blot was used to detect PKA,p-PKA and TRPV1 protein expression.Results Compared with the blank group,the latency period of body twisting in the model group rats decreased,and the body twisting score increased(P<0.01);the contents of PGF2α and cAMP in uterine tissue increased(P<0.01),and the expressions of TRPV1 and p-PKA proteins increased(P<0.01).Compared with the model group,the mild moxibustion group and capsazepine group showed an increase in the latency period of body twisting and a decrease in the body twisting score(P<0.01);the content of PGF2α and cAMP in uterine tissue decreased(P<0.01),and the expressions of TRPV1 and p-PKA proteins decreased(P<0.05,P<0.01).Compared with the mild moxibustion group,the capsazepine group showed an increase in the latency period of body twisting and a decrease in the body twisting score(P<0.01);the contents of PGF2α and cAMP in uterine tissue decreased(P<0.05,P<0.01),and the expressions of TRPV1 protein decreased(P<0.05).Conclusion Mild moxibustion at"Shenque"and"Guanyuan"acupoints has obvious analgesic effect on PD rats,and its mechanism may be related to the regulation of uterine cAMP-PKA signaling pathway mediated TRPV1 protein expression.

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.