Objective To evaluate the efficacy and safety of dipeptidyl peptidase-4 inhibitor,linagliptin,in subjects aged 60 years or older with type 2 diabetes mellitus (T2DM).Methods Data from eight 24-week,multinational,multicenter,randomized,double-blind,placebo-controlled,parallel-group studies were analyzed.Patients aged 60 years or older with T2DM were received oral linagliptin (5 mg/d) or placebo in combination with mefformin,or metformin plus sulfonylurea.Efficacy was assessed by the changes in glycosylated hemoglobin A1c (HbA1c) and fasting plasma glucose (FPG) from baseline to 24 weeks of treatment.Safety endpoint included the frequency and intensity of adverse events.Results A total of 1 421 patients (placebo 429,linagliptin 992) were included in the full analysis set (FAS).Mean ages of the subjects were (67.4 ± 5.6) years in the linagliptin group and (66.7-± 5.6) years in the placebo group.Baseline HbA1c was (8.0 ±0.8) ％ in the linagliptin group and (8.1 ±0.9) ％ in the placebo group.At the end of 24-week,placebo-adjusted reduction in HbAlc in subjects with linagliptin was (0.7 ±0.1)％ (95％ CI 0.6-0.8,P ＜0.000 1),and placebo-adjusted reduction in FPG in subjects with linagliptin was (0.88 ±0.12) mmol/L(95％ CI 0.65-1.11,P ＜0.000 1).Overall safety and tolerability in the two groups were similar.Adverse events occurred in 57.1％ of patients in the placebo group and 61.1％ of patients in the linagliptin group,and the incidence of adverse events leading to discontinuation was 3.2％ in the placebo group and 3.8％ in the linagliptin group.Serious adverse events occurred in 1.6％ of patients in the placebo group and 2.8％ of patients in the linagliptin group.Investigator-defined hypoglycaemia occurred in 7.3％ of patients in the placebo group and 11.9％ of patients in the linagliptin group.Among them,most were mild or moderate hypoglycaemia,and severe hypoglycaemia only occurred in 0.2％ of patients in the placebo and 0.5％ in the linagliptin groups.Overall incidence of hypoglycaemia in linagliptin group was slightly higher than that in placebo group,which might be due to the fact that more patients were taking sulfonylureas in linagliptin group than in placebo group (26.8％ linagliptin;18.4％ placebo).No difference could be viewed in hypoglycaemia between the two groups in patients without sulfonylureas (1.2％ linagliptin,1.1％ placebo)Moreover,no severe hypoglycaemia was reported in subjects without sulfonylureas.The incidences of other adverse events were similar in both groups.Conclusion Linagliptin was efficacious in lowering glucose with a safety profile similar to placebo in type 2 diabetic patients aged 60 years or older.

ZHANG Lin-hua, GAO Rui-chang, XU Ming-li (School of Chemical Engineering, Tianjin University, Tianjin 300072, China)

Objective Gastrointestinal dysfunction is closely correlated with the impairment of intestinal barrier caused by serious infection.We focused on the role of platelet activating factor(PAF)in the intestinal impairment caused by endotoxemia by studying on the morphology of intestinal epithelial ceils and diamine oxidase (DAO)levels with the application of Ginkgolide B(PAF receptor antagonist).Method Eighteen-day-old Wistar rats were randomized into lipopolysaccharide(LPS)(5 mg/kg),PAF receptor antagonist(pretreatment and treatment)and normal saline(Control)groups(n=8 at each time point).Ginkgolide B(PAF receptor antagonist BN52021)5 mg/kg was administered 30 minutes before(in pretreatment group)and after LPS injection(in treatment group).The ileum specimens(n=8)were harvested at 1.5,3,6,24,48 and 72 hours after LPS or NS injection.The ultrastructures of intestinal epithelial cells were studied by transmission electron microscopy (TEM)and with hematoxylin and erosin staining.The contents of DAO in ileum tissue and plasma were measured respectively with spectrophotometer.According to data Normality and Variance equality,ANOVA analysis and LSD (least significant difference)-t test were used for multiple group difference.The whole test Was performed in the animal laboratory,pathological laboratory,biochemical laboratory of our hospital and electron microscopy laboratory of Liao-ning University of Traditionary Chinese Medicine.Results Histologic examination of intestinal injury in LPS group showed the edema of intestinal villi,the capillary congestion in lamina propria,the dilation of interstitial lymphatic vessel.and the polymorphonuclear infiltration in enteric cavity in LPS group at 1.5,3,6,24 hours.The edema of the intestinal villi were shown in antagonist group.Ultrastructural study showed microvilli and tight junctions were intact in the control group.The tight junctions enlarged and the microvilli were thin,rare or disrupted in the experimental group.The pathological changes in PAF antagonist group were slightly lighter than that in the LPS group.The DAO content in the ileum tissue was obviously decreased in the LPS group compared with that in the control group.It reached to a nadir at 6 hrs[from(0.172±0.004)U/mg to(0.096±0.010)U/mg,F=13.372,P＜0.01).The DAO content in plasma was obviously higher in the LPS group than that in the control group.The patterns of DAO changes in the PAF antagonist group were as the same as that in the LPS group at each time point.Conclusions PAF may play a certain role in the injury of intestinal barrier in endotoxemia.Preventive and remedial administration of Ginkgolide B may relieve intestinal injury.The activity changes of DAO in plasma synchronized with that in ileum tissue.It may be deduced that the alterations of DAO in plasma may indicate the destruction of intestinal mucosa in the early stage sensitively.

Objective:To establish an HPLC method for the determination of genistein in genistein-loaded Eudragit nanoparticles. Methods:The HPLC analysis was carried out on a DiamonsilTM C18(250 mm ×4.6 mm,5μm)column with the mobile phase of meth-anol-water (85∶15) at the flow rate of 1. 0 ml·min-1 . The detection wavelength was set at 261nm and the column temperature was 25℃. Results: A good separation was displayed between the drug peak and the excipient peaks. An excellent linearity range for genistein was obtained from 1.0 μg·ml-1 to 100.0 μg·ml-1(r =0.999 8). The recovery of genistein was 99.85%(RSD =0. 65%,n=9). Conclusion:The method is simple, rapid, accurate and specific, which is suitable for the determination of content and encapsulation efficiency of genistein-loaded nanoparticles.

As one of the important founders of GAO's acupuncture academic school in YanZhao area, Professor GAO Yuchun 's experience of acupuncture for headache is summarized in this paper. In the opinion of Professor GAO, the treatment of headache should focus on eliminating evil and relieving pain, and the syndrome differentiation should be based on meridian differentiation, especially on three yang meridians of foot as well as liver meridian and kidney meridian. In the acupoint prescription, attention should be placed on strengthening the spleen and stomach. The midnight-midday ebb flow acupuncture is advocated. The combination between acupuncture order and movement of qi is emphasized. In the manipulation, the role of pressing hand, the stimulation during reinforcing and reducing methods, and needle-retention time are important. The breathing reinforcing and reducing method of acupuncture are also advocated.
Acupuncture Points ; Acupuncture Therapy ; methods ; Female ; Headache ; therapy ; Humans ; Meridians ; Middle Aged

0 (P<0.01).Conclusions HERG1 was over expressed in PANC1 cells and tissues of human pancreatic cancer.The HERG1 K+ channel was related to the proliferation,migration and invasion of PANC1.

Objective Henoch-Sch?nlein purpura(HSP)is a common multisystemic vasculitis in children ,but the exact pathogenesis remains unknown. Pentraxin 3(PTX3),a new kind of inflammatory cytokines,has a strong inflammatory effect,and is involved in occurrence and develop-ment of a variety of autoimmune diseases. The objective of this study is to evaluate the expression of PTX3,interleukin-8(IL-8),tumor necrosis fac-tor-α(TNF-α)and high sensitivity C-reactive protein(hs-CRP)in children with HSP,and explore the clinical significance of PTX3 in HSP devel-opment. Methods Thirty-six children(HSP group)and 17 healthy children(control group)were enrolled in the study. Serum levels of PTX3,IL-8 and TNF-α were detected by enzyme-linked immunosorbent assay. Serum hs-CRP levels were measured by automatic biochemical analyzer. Re-sults The serum levels of PTX3,IL-8,TNF-α,and hs-CRP were up-regulated in HSP group compared with the control group(P<0.05). The levels of PTX3,IL-8,TNF-α,and hs-CRP in patients with joint symptoms,or/and gastrointestinal symptoms,or/and kidney injury were significant-ly higher than those patients without joint symptoms,or/and gastrointestinal symptoms,or/and kidney injury(P<0.05). The expression of PTX3 was positively correlated with the expression of IL-8 and TNF-α(r=0.514,0.833,all P<0.05),but there was no correlation between PTX3 and hs-CRP(r=0.292,P>0.05). The expression of PTX3,IL-8,TNF-α and hs-CRP in HSP patients had no gender difference(all P>0.05). Con-clusion The high expression of PTX3 is related to the degree of inflammation in children with HSP. The up-regulated expression of PTX3 may play an important role in pathogenesis of HSP in children.

Objective To explore the activity of thioredoxin reductase (TrxR) in chronic myeloid leukemia cell line K562 and the anti-leukemia effect of BBSKE (a novel inhibitor of TrxR) in vitro. Methods The activity of TrxR on K562 cell lineage and fresh bone marrow cell from healthy adult was analyzed by insulin reduction assay. The inhibition of proliferation was measured by CCK-8 assay. The anti-leukemia effect of BBSKE was detected by laser scanning confocal microscope,agarose gel electrophoresis and flow cytometry with Annexin V -FITC/PI staining. Results TrxR activity of K562 cell lineage was significantly higher than that of normal bone marrow mononuclear cells. The apoptosis of K562 cells could be induced at concentrations of 10 μmol/L BBSKE after treated for 24 hours. The typical DNA ladder bans were observed by agarose gel electrophoresis. The apoptotic rates of K562 cells were (10.28±2.74) %. Application of 10 μmol/L BBSKE for 48 hours could also induce apoptosis of fresh bone marrow cell from chronic myeloid leukemia patients, and the apoptotic rates were (5.70±0.48) %. Conclusion TrxR activity in chronic myeloid leukemia cells was significantly higher than that of normal cells. BBSKE inhibits the TrxR activity and the proliferation of K562 by inducing apoptosis.It might be a potential medication for chronic myeloid leukemia.

Objective:To determine the inhibitory effect of Rupixiao ( RPX) granule on mammary gland hyperplasia ( HMG) in rabbits and explore the possible mechanism to provide reference for clinical medication. Methods:Rabbit model of mammary hyperpla-sia was established by estradiol benzoate and progesterone. Xiaoyao pills and tamoxifen were used as the positive control, and the RPX granule group was respectively at low, medium and high dose (0. 525,1. 05,2. 1 g·kg-1). Each group was with intragastric adminis-tration for 30 days. The levels of E2 , PROG, FSH, LH and PRL in serum and the expression of VEGF in the homogenate tissue were determined by an Elisa method. The breast tissue of rabbits in each group was withdrawn to observe the structure changes after Hema-toxylin-eosin staining ( HE) . Results:Ovarian preservation-benzoic acid, estradiol combined with progesterone could be used to estab-lish mammary gland hyperplasia in rabbits. RPX granule could significantly decrease the serum levels of E2 and PRL (P<0. 01)and increase that of PROG (P<0. 01 or P<0. 001). The results of pathological section showed that the breast structure in RPX granule high dose group could be restored to the level of the blank control group, which showed its therapeutic effect on HMG was better than that of tamoxifen and Xiaoyao pills. The expression of VEGF in each treatment group significantly decreased compared with that in the model group by the Elisa reagent (P<0. 001). Conclusion:RPX granule has good efficacy in HMG rabbits. The inhibitory effects of RPX granule on HMG in rabbits maybe related to the inhibition of VEGF in rabbit breast tissues, and the inhibition of RPX granule was similar to that of tamoxifen and Xiaoyao pills.

Objective To establish three methods of DNA extraction from Cryptosporidium parvum oocysts and test by PCR. Methods After three freeze-thaw cycles, three kinds of templates were extracted from the oocysts by Chelex-100, phenol/chloroform or genomic DNA purification system kit, and used for PCR detection. According to the sequence of a C.parvum gene (L16996), a pair of primers was designed and synthesized, and used for PCR. The sensitivity of the template by Chelex-100 method was also tested by PCR. Results One 446 bp PCR product was observed by agarose gel electrophoresis for all three kinds of templates. The PCR sensitivity by Chelex-100 extracted DNA reached for detection of a specimen containing only 1/2 oocyst. Conclusion The three kinds of extraction can all be served as templates for PCR detection of C.parvum oocysts, while Chelex-100 method is simpler, quicker and more reliable for DNA extraction of the parasite.