OBJECTIVE To investigate the effect of icariin(ICA)on the ubiquitination modification of β-amy-loid precursor protein(APP)in Alzheimer's disease mice.METHODS In vitro,① HEK 293 cells stably overex-pressing human APP695(OE-hAPP)were treated with different concentrations of ICA(10-100 μmol·L-1)for 24 h and the cell viability was detected by MTT assay.②CHX(50 mg·L-1)was used to block protein synthesis and MG132(20 μmol·L-1)inhibits proteasome activity,then the level of APP in different time(0,0.5,1,2,3 and 4 h)and the ubiquitination were tested by Western blotting.③ E3 ubiquitin ligases HMG-CoA reductase degradation pro-tein 1(HRD1)protein expression in OE-hAPP was tested by Western blotting,as well as the level and ubiquitination of APP were tested under HRD1 silent condition by Co-IP and Western blotting.In vivo,① male APP/PS1 mice and wild type(WT)mice were randomly divided into 5 groups:WT,WT+ICA,APP/PS1,APP/PS1+ICA,and APP/PS1+donepezil(DPZ)groups.ICA(60 mg·kg-1·d-1)and DPZ(1 mg·kg-1·d-1)were treated for 3 months by gavage from 6 months of age,and WT mice were given equal volume of distilled water.②Morris water maze and Y-maze experiments were used to detect the alteration of spatial learning memory function.③ After then,the brain tissues were collected,total proteins were extracted,APP antibodies were subjected to Co-IP,and total ubiqui-tination(Ub),K48-linked polyubiquitination(UbK48)and K63-linked polyubiquitination of APP level,APP and HRD1 proteins were detected by Western blotting.RESULTS In vitro results showed that ICA significantly enhanced APP degradation(vs control,P＜0.01),up-reg-ulated HRD1 expression(vs control,P＜0.05;vs OE-hAPP,P＜0.05),elevated the level Ub and UbK48 of APP,as well as increased APP degradation.Moreover,silenced HRD1 gene abolished abovementioned effects of ICA(vs control-siRNA,P＜0.05;vs HRD1-siRNA,P＜0.05).In vivo results showed that ICA improved the spa-tial learning and memory function APP/PS1 mice by Mor-ris water maze and Y-maze tests,increased HRD1 expres-sion(vs APP/PS1 + vehicle,P＜0.05),enhanced APP ubiquitination and reduced APP protein level(vs APP/PS1 + vehicle,P＜0.01).CONCLUSION ICA promotes the ubiquitination and proteasome-dependent degrada-tion of APP by up-regulating HRD1,thereby improving the spatial learning and memory function of Alzheimer disease mice.

Objective:To investigate the changes of advanced glycosylation end product(AGEs)/sodium-glucose cotransporter-1(SGLT-1) in intestinal and renal tissues and intestinal flora of mice with diabetes kidney disease.Methods:Twenty KKay mice were divided into diabetic group(DM group, n=10) and diabetic kidney disease group(DKD group, n=10). The concentrations of serum AGEs, lipopolysaccharide(LPS), tumor necrosis factor-α(TNF-α), and intereukin-6(IL-6) were measured. Western blot technique was used to detect the protein expression of AGEs and SGLT-1 in kidney and intestinal tissue, and high-throughput sequencing was used to analyze the difference of intestinal flora. Results:The levels of inflammatory markers TNF-α, IL-6, and serum endotoxin in DKD group were significantly higher than those in DM group( P<0.05). The contents of AGEs in serum and intestine and kidney were increased, and the contents of SGLT-1 in intestine and kidney were increased( P<0.05). Metastats test showed that the abundance of Verrucomicrobia decreased and the abundance of Proteobacteria increased in DKD group( P<0.05). G - bacteria such as Aeromonas, Enterobacter, Morgan, Klebsiella, Serratia, and Burkholderia were relatively dominant, and the abundance of Akkermansia was significantly lower than that in DM group( P<0.05). Conclusion:The increase of AGEs in intestinal tract of DKD mice may induce intestinal dysbacteriosis, especially the increase of Proteobacteria, the decrease of Verrucosa and Wilhelm Ackermann, and the leakage of G-bacteria into the blood to produce intestinal endotoxemia and cause inflammatory reaction, this may be an important factor in the development of DKD. SGLT-1 is elevated in intestinal tissue, which may be involved in the development of DKD.

Objective To observe the effect of IcarisideⅡ (ICSⅡ) on spatial learning and memory impairments and axonal regeneration induced by chronic cerebral hypoperfusion (CCH) in rats.Methods 90 male SD rats were randomly divided into normal group,sham operation group,CCH group and ICS Ⅱ low,middle and high-dose treatment groups.The chronic cerebral hypoperfusion model was established by permanent bilateral common carotid artery occlusion.Then these rats in ICS Ⅱ low,middle and high-dose treatment groups were given ICS Ⅱ4,8 and 16 mg/(kg · d) by gavage on the 1st day after modeling.There were 5 rats in every group at each observing time(4,8 and 12 week).Morris water maze experiment was utilized to assess the escape latency and the target quadrant residence time while HE and immunohistochemistry analysis were applied to test the morphology change and expressions of GAP-43,MAP-2 and Nogo-A in hippocampal CA 1.Results Compared with those of sham operation groups at 4,8 and 12 week respectively,the escape latency in CCH group were significantly prolonged(40.02±4.95) s,(42.29±5.75) s,(53.68±6.14) s vs (26.43±2.68) s,(26.84±2.06) s,(31.53±4.12) s,P＜0.05;the target quadrant residence time were significantly reduced(28.53±2.40) s,(28.02±4.28) s,(22.60±4.03) s vs (33.34±2.89) s,(33.31 ±4.14) s,(31.63±2.20)s,P＜0.05);the expressions of GAP-43 and Nogo-A were increased with that of MAP-2 reduced(P＜0.05).Meanwhile,the neuropathological changes with more denatured neurons and less normal neurons were found in hippocampal CA1.However,compared with those of CCH group,the escape latency of ICS Ⅱ middle and high-dose groups (30.58±3.03) s,(29.19±4.23) s,(38.77±5.80) s;(28.90±2.98) s,(26.91 ±6.63) s,(36.51 ±3.98) s) were shortened (P＜0.05);the target quadrant residence time (32.54± 3.41) s,(32.69±3.47) s,(28.27±3.57) s;(32.69±3.54) s,(33.20±4.29) s,(28.07±4.04) s) were increased (P＜ 0.05);the expression of Nogo-A was decreased while those of GAP-43 and MAP-2 were conversely increased (P＜0.05).Moreover,few denatured neurons were observed in hippocampal CA1.But there were no differences for those indexs between CCH group and ICS Ⅱ low-dose treatment groups (P＞0.05).Compared with those in 8 week and 4 week,the escape latency and the target quadrant residence time were prolonged and reduced with the expression of Nogo-A increased in all groups except normal group and sham operation group(P＜0.05),the expressions of GAP-43 and MAP-2 were decreased in CCH group and ICS Ⅱ low-dose treatment group(P＜0.05),but there were no significant differences in ICS Ⅱ middle and high-dose treatment groups at 12 week(P＞0.05).However,there were no statistical significance of all indexes between 8 week and 4 week(P＞0.05).Conclusion ICS Ⅱ can improve the spatial learning and memory in chronic cerebral hypoperfusion rats,which may be achieved by neuroprotective effects and reducing the expression of Nogo-A consequently promotes the regeneration of axons.

Objective To observe the effects of icarisid Ⅱ (ICS Ⅱ)on cognitive deficits and expression of synaptophysin(SYN)in chronic cerebral hypoperfusion(CCH)rat models.Methods 40 male SD rats were randomly divided into four groups:normal group,sham operation group,model group and ICSⅡgroup.The model was established by permanent bilateral common carotid artery occlusion(BCCAO).ICS Ⅱ group was administered ICS Ⅱ at a dose of 8mg·kg -1 ·d -1 by gavage on 1st day after modeling.Sham group and CCH group were injected double -distilled water.The escape latency(s)and spatial probe times were measured by water maze test.Then,the morphology change and expression of SYN in hippocampal were assayed by HE and immunohistochemistry analysis.Results At the 1st month and 2nd month,the escape latency in the model group[(40.02 ±4.95)s,(42.29 ±5.75)s]were significantly prolonged compared with the sham operation group[(26.43 ±2.68)s,(26.84 ±2.06)s](t =4.89,5.06,all P <0.05).And those in the ICS Ⅱ group[(30.58 ±3.03)s,(29.19 ±4.23)s]were significantly decreased compared with the model group(t =3.63,4.10,all P <0.05).The space probe times in the model group[(2.6 ±0.89)times, (2.40 ±1.14)times]were significantly reduced compared with the sham operation group[(6.00 ±2.16)times, (5.75 ±2.16)times](t =3.23,4.18,P <0.05).And those in the ICS Ⅱ group[(4.40 ±1.34)times,(5.00 ± 1.58)times]were significantly increased compared with the model group (t =2.49,2.98,all P <0.05).The average optical density of SYN in hippocampal in the model group[CA1:(0.121 ±0.009),(0.122 ±0.008);CA3:(0.172 ± 0.028),(0.173 ±0.021 )]were significantly reduced compared with the sham operation group[CA1:(0.131 ± 0.006),(0.136 ±0.007);CA3:(0.218 ±0.035),(0.204 ±0.018)](t =2.43,2.53,3.12,2.34,P <0.05). Those in the ICS Ⅱ group[CA1:(0.131 ±0.006),(0.132 ±0.006);(0.212 ±0.02),(0.208 ±0.022)]were significantly increased compared with model group(t =2.41,2.41,2.31,2.77,all P <0.05).However,there was no statistically significant difference of those index between the normal group and sham operation group(P >0.05 ). Conclusion ICS Ⅱ can improve the cognitive deficits in CCH rat models and this effect may be associated with increased expressions of SYN in hippocampal.

Objective:To investigate the clinicopathological factors predictive of lymph node metastasis (LNM) in undifferentiat-ed early gastric cancer (EGC) and to expand the possibility of endoscopic therapy for treating undifferentiated EGC.Methods:The re-searchers collected the data of 90 undifferentiated EGC patients who had undergone surgery at the Xingtai People's Hospital, Xingtai, China. The relationship between LNM and clinicopathological factors was retrospectively analyzed using univariate and multivariate lo-gistic regression analyses. Results:Univariate analysis showed that tumor size, lymphatic vessel involvement (LVI), and cancer inva-sion depth were the significant and independent risk factors for LNM. The LNM rate was 57.1%in patients with the three clinicopatho-logical risk factors. LNM was not found in patients without the three risk factors. Conclusion:Tumor size, LVI, and invasion depth are independently associated with the presence of LNM in undifferentiated EGC. Endoscopic therapy can be used to treat the patients with-out risk factors.

Aim To investigate the effect of icariin ( ICA) on renal interstitial fibrosis in SHR and explore its mechanism. Methods Fourteen male SHR of 13-week-old were randomly divided into model group( n=7 ) and ICA group ( n=7 ) , and WKY as control group (n=7). One week after adaptive breeding,the rats in the ICA group were given ICA 40 mg·kg-1,ig,bid to 26-week-old. The other rats in the model group and control group were given the same amount of normal sa-line. Then, the morphological changes of the kidney were observed by HE and Masson staining,respective-ly. The contents of plasma aldosterone andⅢcollagen were measured by double antibody sandwich method. The mRNA expressions of TGF-β1 , Smad2 , CTGF and FN were examined by real time RT-PCR. Results Compared with the normal control group, the kidney structures of model group were disordered,the mesang-ial matrix and the tubular interstitial fibrosis were in-creased. The contents of plasma aldosterone and Ⅲcollagen were increased in model group ( P <0. 01 ) . And the mRNA expressions of TGF-β1 , Smad2 , CTGF and FN in kidney tissues were up-regulated in model group( P <0. 01 or P <0. 05 ) . Compared with the model group,the kidney structures were improved and the contents of plasma aldosterone and Ⅲ collagen were reduced, as well as the mRNA expressions of TGF-β1,Smad2,CTGF and FN in kidney tissues were down-regulated(P<0. 01 or P<0. 05)in ICA group. Conclusion ICA may have anti-renal interstitial fi-brosis effect on SHR,and the mechanism might be re-lated to the reduced plasma aldosterone levels and the down-regulated expression of TGF-β1 and Smad2 .

Objective To investigate the medical and pharmaceutical knowledge of patients with chronic diseases and analyse the influence factors of rational administration in patients ,to provid data to support the establishment of pharmaceutical service mode . Methods 386 cases of patients with chronic diseases were asked to finish the questionnaires for the medical and pharmaceutical knowledge ,and factors affecting the rational drug were analyzed by single factor and multiple factors Logistic regression analysis . Results Among the 386 patients ,cardiovascular and celebralvascular disease ratio was the highest(53 .3% ) ,followed by respiratory system diseases(13 .8% ) and the musculoskeletal system diseases (11 .50% );The averaged score of 386 patients was 1 .76 ± 0 .78 , medication knowledge was at a general level;single factor analysis results showed that there was significant difference(P<0 .05) between rational drug-use and abuse of drugs among patients in number ,form of payment ,marital status ,income ,education level , taking drug knowledge lectures ,combined treatment .Multivariate Logistic regression analysis showed that education level ,partici-pation in lectures ,drug combination ,disease species had a significant impact on the rational drug use among patients with chronic disease(P<0 .05) .Conclusion The pharmaceutical knowledge that patients with chronic disease mastered is unsatisfactory ;and unreasonable behavior of medication is common scence .Education level ,participation in lectures ,drug combination ,the number of diseases have great influence on the rational use of drugs in patients with chronic diseases .A kind of effective pharmaceutical service mode should be established for patients with chronic diseases by clinical pharmacists .This is a very meaningful work for rational ad-ministration .

Objective To evaluate the clinical value of speckle tracking imaging in the measurement of two-dimensional strain in patients with myocardial infarction. Methods High frame rate two-dimensional echocardiography were performed in 30 healthy subjects,21patients with anterior myocardial infarction and 15 patients with inferior myocardial infarction. Longitudinal strain (LS), radial velocity (Vs), regional shortening fraction (RFS),radial strain (RS) were measured in the apical two-chamber view and short-axis view(the level of papillary muscle) using two-dimensional strain software. Results Compared with healthy subjects, LS, Vs, RFS, RS decreased in the segments with infarction(P<0.05). LS, Vs, RFS, RS of the two myocardial infarction groups had partly differences(P<0.05). Conclusions Regional wall motion of left ventricle in patients with myocardial infarction can be evaluated accurately with speckle tracking imaging.

Objective To compare the curative effects of lumbar traction in supine position with hip flection and extension for prolapse of lumbar intervertebral disc (PLID).Methods 84 PLID patients were all treated by lumbar traction in supine position. But, group A (42 cases) with hip flection and group B (42 cases) with hip extension. Before and after three weeks therapy, all patients were assessed by Fairbank JC index and Visual Analogue Scales (VAS) to observe the symptom and pain condition.Results The scores of Fairbank JC index and VAS scale of the patients in group A were significantly lower than those in the group B (P<0.001).Conclusion Lumbar traction in supine position with hip flection for the PLID can obviously promote the curative effects.

Objective To evaluate the value of ultrasound-guided catheterization in the treatment of traumatic pericardial tamponade. Methods Nine patients with traumatic pericardial tamponade underwent ultrasound-guided catheterization from March 1998 to September 2003. After the drawing-off of fluid, the catheter was remained in the pericardium to drain the blood. Results The catheterization and drainage gave marked relief from symptoms. Surgical repairs of heart were performed in 4 patients within 4～ 8 h following drainage. Selective operations were required in 2 patients after the improvement of their conditions. Two patients were cured by drainage and 1 patient died of severe brain trauma. Conclusions The technique may produce prompt relief from symptoms of traumatic pericardial tamponade, being a safe and reliable procedure. It may create favorable conditions for further surgical repair or even freedom from operations.