? amyloid protein(A?) including A?40 and A?42 are the important bioactive substances in vivo.Their toxic and beneficial attributes in the body depend on its concentration.The brain A? level is maintained by two balances under the physiological condition.The first balance is the generation involved in ?-secretase and ?-secretase and the degradation involved in neprilysin(NEP) and insulin-degrading enzyme(IDE) of A?. The second one is the balance between the receptor for advanced end glycation products(RAGE)-mediated influx and low-density lipoprotein receptor related protein 1(LRP1)-mediated efflux of A? across the blood-brain barrier(BBB).Breakdowning any one of the two balances would result in the aggregation and precipitation of A? in the brain,which is a crucial event in the pathogenesis of Alzheimer's disease(AD).This paper reviews the regulation of brain A? level under the physiological condition and the reducing strategies on the level of brain A? under the pathological condition for developing new drugs in the treatment of AD.

Objective To study the effects of pirfenidone on total enzyme and isoenzyme of liver microsomal cytochrome P450 in rats. Methods The activites of liver microsomal dimethyl nitrosamine N-demethylase( NDMA )and erythromycin demethylase( ERD ) were determined. Fifty-six SD rats were randomly divided into six groups,in which they received CMC,dexamethasone 100 mg·kg-1 ,ketoconazole 40 mg·kg-1 ,pirfenidone 25,50,100 mg·kg-1 ,respectively. After administration for 6 and 12 days,livers were prepared liver microsome,the concentration of proteinum in microsome and shade selection to plasma samples were determined by spectrophotometer. Results After administration of pirfenidone for 6 days, cytochrome P450 was significantly increased in 50 and 100 mg·kg-1 pirfenidone groups,as compared with solvent control group (1%sodium carboxymethylcellulose)(P﹤0. 01). After administration of pirfenidone for 6 and 12 days,NDMA of liver microsome was not changed significantly(P﹥0. 05). ERD of liver microsome was significantly increased in 100 mg·kg-1 pirfenidone group after administration for 12 days(P﹤0. 01). Conclusion Pirfenidone can induce P450 and ERD activities in a dose-and time-dependent manner.

A series of andrographolide derivatives with the structure of 12-N-substituted-14-deoxyandrographolide were synthesized from the parent compound andrographolide.Their antitumor activities were preliminarily evaluated on various cancer cell lines and compound 4d stood out due to its potent growth inhibitory effect in comparison with andrographolide.Compound 4d also demonstrated significant antitumor effect on human hepatoma HepG2cells in vitro and on sarcoma 180 (S180) and hepatoma 22(H22)-bearing mice in vivo.Then,the apoptosis induced by compound 4d in HepG2cells was detected by Annexin V/PI double staining assay.Further mechanic study showed that the expression of p53 and Bax was significantly elevated and that of Bcl-2was downregulated in 4d-treated HepG2cells.Collectively,these data suggested that compound 4d had remarkable antitumor effect both in vitro and in vivo and could effectively induce apoptosis via a p53-dependent pathway in HepG2 cells,thus deserving further investigation.

Objective To determine the relationship between cigarette smoking and the incidence of systemic lupus erythematosus.Methods Database including Cochrane Library,Pubmed,OVID and Elsevier were electronically searched to collect case-control and cohort studies on the relationship between cigarette smoking and incidence of systemic lupus erythematosus.The literatures were screened and the data were extracted independently according to the inclusion and exclusion criteria.The quantitative analysis were performed by using Stata 12.0 software.Results The pooled OR values (95％ confidence interval)of current smoking and ever smoking were 1.82 (95％CI 1.42～2.34) and 1.22 (95％CI 0.96～1.56) respectively.Conclusions Our Meta-analysis revealed a moderate but statistically significant association between current smoking and development of systemic lupus erythematosus.However,it is still not confirmed whether the past smoking is one of the risk factors of systemic lupus erythematosus.

Objective To assess the value of susceptibility weighted imaging (SWI)in the diagnosis of different cerebral diseases complicated with cerebral microbleeds (CVBs)and cerebral vascular malformations (CVMs).Methods The MRI data of 76 cases with CMBs and 25 cases with CVMs were retrospectively analyzed and the data were translated as follows:(1 )To compare the counts and detecting sensitivity of CMBs on routine MRI sequences (T1 WI,T2 WI,T2 FLAIR,DWI)with SWI.(2)To assess the difference of SWI,MIP and Phase in detecting the size,counts,intensity and edge features of CMBs.(3)To assess the advantages of SWI in the diagnosis of different CVMs.Results (1)In all 1 524 CMBs detected on SWI,294,87,361,391 CMBs were detected on T1 WI,T2 WI,T2 FLAIR and DWI respectively.The sensitivities were 19.3%,5.7%,23.7% and 5.7% on T1 WI,T2 WI,T2 FLAIR and DWI respectively.It was of statistical significance (P <0.05)in the counts and detecting sensitivity on different MRI sequences.(2) 1 524 and 1 539 CMBs were detected on SWI and MIP respectively.CMBs showed oval,dotted hypointensity or hypointensity domi-nated mixed intensity lesions which were ≤10 mm in size on SWI and MIP.1 521 CMBs were detected on Phase,which appeared as hyperintensity or hyperintensity dominated mixed intensity lesions.MIP and SWI were similar in detecting the size,counts and edge features of CMBs.And Phase was inferior compared with MIP and SWI .(3)12 cases of cerebral venous malformation were detec-ted,which all appeared as the classic Medusa head sign on SWI.6 cases of intracerebral capillary telangiectasia were detected , which were characterized as multiple small rounded even hypointense lesions ortarget signon SWI .2 cases of arteriovenous malformation (AVM)were detected on SWI,in which one case only showed multiple small vessels and gross drainage vein,and the other showed clear nidus and gross drainage veins into the sigmoid sinus.4 cases of cerebral cavernous angioma were detected.Mulberry sign, which was characterized as dotted mixed intensity lesion with hypointense ring,was noted in all the cases on SWI.One case of Sturge-Weber syndrome was detected,which showed gyriform low signal lesion on MIP imaging.And many broadened,tortuous veins in the cerebral hemispheres and near the tentorium were also noted.Conclusion SWI can be used as an important sequence for detecting CMBs.Different CVMs show their specific signs in SWI sequence.Combined with conventional MRI sequences an accurate diagnosis can be achieved most of the time.

OBJECTIVETo observe the inhibitory effect of gefitineb on the proliferation and its inducing effect on the apoptosis of mouse I-10 Leydig testicular cancer cells in vitro.

METHODSWe treated I-10 Leydig testicular cancer cells of mice with gefitineb at 0, 1.25, 2.5, 5, 10, 20, and 40 µmol/L. Then we determined the inhibitory effect of gefitineb on the growth of the cells by MTT, detected their early and late apoptosis by Annexin V-FITC/propidium iodide double staining and Hoechst 33258 nuclear staining, respectively, and observed the expressions of apoptosis-related proteins Bcl-2, Bax and caspase 3/9 by Western blot.

RESULTSCompared with the blank control group, gefitineb significantly inhibited the proliferation of the I-10 cells at 10 and 20 µmol/L (P < 0.05). The survival rate of the cells was (32.4 ± 2.8)% (P < 0.01) and their early and late apoptosis rates were (26.7 ± 4.2)% and (59.33 ± 10.2)% in the 40 µmol/L group, significantly different from those in the control (P < 0.05 and P <0.01). In comparison with the blank control group, gefitineb at 10, 20, and 40 µmol/L increased the expression of pro-apoptotic protein Bax by (41.9 ± 7.1), (60.1 ± 9.8), and (69.0 ± 11.3)% (all P < 0.05), decreased that of apoptosis-inhibitory protein Bcl-2 by (50.3 ± 8.9), (63.9 ± 6.9), and (88.7 ± 13.9)% (all P < 0.05), and elevated that of the cleft proteins caspase-3 by (69.0 ± 6.9)% (P < 0.05), (71.5 ± 8.1)% (P < 0.05), and (110.9 ± 14.2)% (P < 0.01) and caspase-9 by (51.8 ± 4.9), (54.7 ± 6.7), and (43.8 ± 11.8)% (all P < 0.05).

CONCLUSIONGefitineb can increase the cytotoxicity of I-10 Leydig testicular cancer cells of mice and induce their apoptosis via the mitochondria-mediated apoptosis signaling pathway.

Animals ; Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Apoptosis Regulatory Proteins ; metabolism ; Caspase 3 ; metabolism ; Caspase 9 ; metabolism ; Cell Proliferation ; drug effects ; Cell Survival ; Leydig Cell Tumor ; drug therapy ; metabolism ; pathology ; Male ; Mice ; Neoplasm Proteins ; metabolism ; Neoplasms, Germ Cell and Embryonal ; drug therapy ; metabolism ; pathology ; Quinazolines ; pharmacology ; Testicular Neoplasms ; drug therapy ; metabolism ; pathology ; bcl-2-Associated X Protein ; metabolism

Aim To study the effects of cycle arrest and molecular mechanism in human leukemia HL-60 cells induced by diallyl disulfide ( DADS ) . Methods Cell count, colony formation in soft agar experiments and flow cytometry analysis were employed to observe the DADS-induced cell growth inhibition and the effect of cycle arrest in HL-60 cells. The expressions of Chk1/2 and its downstream element in HL-60 cells were detected by Western blot. Results Cell count revealed that population doubling time increased to 35. 03 h and 71. 82 h, respectively, from 19. 14 h in HL-60 cells treated with 60 and 120 μmol·L-1 DADS ( P<0. 05 ) . Colony formation in soft agar experiments showed that colony formation inhibition rate of HL-60 cells exposed to 30, 60, 90 and 120μmol·L-1 DADS increased to 35. 06%, 62. 10%, 93. 79% and 99. 35%, respectively ( P<0. 05 ) . Flow cytometry a-nalysis exhibited that HL-60 cells treated with 60 and 120 μmol · L-1 DADS for 24 h and 48 h arrested in G2/M phase in a concentration-and time-dependent manner ( P <0. 05 ) . Western blot disclosed that the expression of p-Chk1 increased in a time-dependent manner ( P <0. 05 ); however, Chk1, Chk2 and p-Chk2 were not changed in HL-60 cells treated with 60μmol·L-1 DADS (P >0. 05). The expression of Cdc25C, CyclinB1 and CDK1 decreased after treated with 60 μmol·L-1 DADS in a time-dependent manner ( P<0. 05 ) , but the expression of 14-3-3 protein did not change ( P>0. 05 ) . Conclusion DADS can in-hibit the proliferation of HL-60 cells, and induce G2/M arrest through Chk1/Cdc25 C/CyclinB1/CDK1 path-way.

Objective To explore MRI manifestations of incomplete healing of the uterine incision after abdominal delivery.Methods Nine patients with clinical suspected incomplete healing of the uterine incision after abdominal delivery underwent cavitas pelvis MRI scans with 3.0T MRI.Results According to the characteristics of the MRI images,healing conditions of the uterine incisions were divides into 2 groups.GroupⅠwas showed that the uterine incision healed well,the uterine junctional zone and myometrium were continuous,and the incision scar was linear low signal intensity on T2 WI (2 cases,22%).GroupⅡwas showed that the uterine incisions healed incompletely,the uterine junctional zone and myometrium were discontinuous,and the myometrium edema was in some cases with high signal intensity on T2 WI (7 cases,78%).Conclusion MRI could directly displays incomplete healing of the uterine incision after cesarean section,provide the basis for clinical diagnosis and treatment.

BACKGROUND: Induced pluripotent stem cells (iPSCs) are a special type of cells with self-renewal and multi-differentiation potential, which can differentiate into intestinal organoids under certain conditions. OBJECTIVE: To explore whether iPSCs can differentiate into intestinal organoids under specific conditions in vitro.METHODS: iPSCs from B6J mice were recovered and cultured for 3 days until clone units covered about 80％ of the culture dish, and then the cells were cultured in the medium containing Activin A for 3 days until the deterministic endoderm formed. Further, the culture medium was replaced by the medium with fibroblast growth factor 4 and Wnt3A for 4 days to differentiate into the spheroids with CDX2+. After that, spheroids were collected and mixed with Matrigel,and then the mixture was dropped into the 4-well plate and cultured with Rspondin1, Noggin, epidermal growth factor, B27 and other growth factors to differentiate into intestinal organoids. Cell morphology was observed, FoxA2 and Sox17 expresson in the deterministic endoderm was detected, and CDX2, Sox9, CGA, MMP7 were measured.RESULTS AND CONCLUSION: iPSCs were cultured with Activin A for 3 days with higher cell fusion, initial differentiation and FoxA2/Sox17 expression (P < 0.05) than those of non-induced iPSCs. Spheroids began to appear at the 3rd day after culture with fibroblast growth factor 4 and WNT3A, and formed a lot at the 4th day. And CDX2 expression in spheroids was significantly increased compared with that in the deterministic endoderm (P < 0.05). Organoids gradually formed after 3 days culture, which contained all cell types of intestinal organoids, and expressions of specific markers, Sox9, CGA, MMP7, were significantly higher than those in spheroids (P < 0.05). To conclude, iPSCs can be induced to differentiate into intestinal organoids in three-dimensional niche in vitro.