A novel series of bis-nicotine derivatives (3a-3i) were designed, synthesized and evaluated as bivalent anti-Alzheimer's disease agents. The pharmacological results indicated that compounds 3e-3i inhibited both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in the micromolar range (IC50, 2.28-117.86 micromol x L(-1) for AChE and 1.67-125 micromol x L(-1) for BChE), which was at the same potency as rivastigmine. A Lineweaver-Burk plot and molecular modeling study showed that these derivatives targeted both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. Besides, these compounds could significantly inhibit the self-induced Abeta aggregation with inhibition activity (11.85%-62.14%) at the concentration of 20 micromol x L(-1).

Aim To explore the protective effect of Sertoli cells on the co-transplanted allogeneic renal cells in male and female recipient rats. Methods Testicular Sertoli cells were prepared by digestion with trypsin， collagenase and DNase， while renal cells were prepared by digestion with trypsin alone. FasL and Fas expressions were detected respectively by FCM before transplantation. About 106 cells were injected into the allogeneic renal subcapsule. In order to demonstrate the survival of renal cells， the expression of g-PG in graft was examined by SABC method. Apoptosis of the lymphocytes surrounding the graft was observed by TUNEL(terminal deoxynucleotidyl transferase-mediated X-dUTP nick end labeling). Results The grafts were analyzed histologically 20 days after transplantation. The renal cells transplanted alone were all rejected, while the survival rates of the mixed cell transplantation were 87.5％ and 77.8％ in male and female recipients respectively. When the renal cells co-transplanted with Sertoli cells treated by anti-FasL mAb， only 30.0％ grafts were survived. Apoptosis of lymphocytes surrounding the graft were quite evident. Conclusion Sertoli cells expressing FasL can protect renal cells from allograft rejection by inducing apoptosis of Fas expressing T cells surrounding the grafts.

Adolescent ; Anal Canal ; physiopathology ; Child ; Constipation ; physiopathology ; Female ; Gastrointestinal Motility ; physiology ; Humans ; Male ; Rectum ; physiopathology

In the study, to explore the anti-tumor effects and mechanisms of chlorpromazine (CPZ) and perphenazine (PPZ) combined with temozolomide (TMZ) on human glioma cell lines, we performed MTT assays to determine the growth inhibitory rate of CPZ, PPZ and TMZ in mono and combined treatments. The anti-tumor effects of CPZ and PPZ alone or in combination with TMZ were determined by colony formation, cell apoptosis, cell cycle arrest, reactive oxygen species (ROS) production and mitochondrial membrane potential (MMP) detection (JC-1). The expression level of p53 was detected by immunofluorescence assay. Furthermore, autophagy under different administrations was detected by flow cytometry and confocal imaging to explore the anti-tumor mechanism of CPZ and TMZ. Protein phosphatase 2A (PP2A), cancerous inhibitor of protein phosphatase 2A (CIP2A) and proto-oncogene protein (c-Myc) were detected by immunofluorescence assay, tumor stem cell markers (CD44, CD133) and aldehyde dehydrogenase (ALDH) were detected by flow cytometry to explore the anti-tumor mechanism of PPZ and TMZ. The results showed that after 72 h treatments of combinations, the values of half maximal inhibitory concentration (IC₅₀) of TMZ on U87 and U251 cells were reduced, and the ability of TMZ to induce apoptosis and cycle arrest was improved. In addition, the combination of CPZ and TMZ could induce an increased effect of autophagy via activating the relevant pathway of p53 gene in glioma cells. The combination of PPZ and TMZ increased the sensitivity of glioma cells to TMZ, and the underlying mechanism might be related to the inhibition of CIP2A/PP2A/c-Myc signaling pathway. In conclusion, CPZ and PPZ combined with TMZ, showed the significant synergistic effects in cancer treatment, which are the novel and potential therapeutic regimens providing a new treatment strategy for human glioma.

Objective:To investigate frequencies of microsatellite instability(MSI)and loss of heterozygosity(LOH)in renal ceil carcinoma(RCC),and to discuss the relationship of clinicopathological characteristics of RCC with MSI and LOH. Methods:Twelve microsatellite markers located at chromosomes 3p,9p and 14q were selected to investigate microsatellite alterations(MSI and LOH)in 31 RCC specimens and their paired metastasis specimens by polymerase chain reaction- polyacrylamide gel elect rophoresis-ethylene dibromide(PCR-PAGE-EB)staining and sequencing.Results:The frequency of MSI could reached 61.3% and that of LOH could reach 54.8%.The highest frequency of MSI was at locus of D9S168(32.3%);the highest frequency of LOH was at locus of D3S1289(21.4%).No correlation was found between MSI or LOH and the patients' age,sex,pathology type and metastastis,except that MSI was correlated with TNM stage of RCC(P

Abstract: Objective　A survey on the plague foci in Qiaojia County of Jinsha River Basin was conducted to understand the composition of plague host vectors and the prevalence of plague among animals, to explore the occurrence and epidemic risk of plague, and to provide scientific basis for plague monitoring and control in this area. Methods　Seven villages and towns in Qiaojia County were selected as the research areas, and the cage night method and the clamp line method were used to investigate the small mammals and their surface parasitic fleas. The host animal organs, serum and surface parasitic flea's samples were collected. The plague indicator animal serum was collected simultaneously on the spot, and the collected host animal organs and flea's samples were cultured and detected for Yersinia pestis. The indirect hemagglutination test (IHA) was used to detect the fraction 1 capsular antigen (F1) antibody of the host animal and the indicator animal serum samples. Results　A total of 525 small mammals belonging to 3 orders, 6 families, 12 genera and 23 species were captured. The dominant species in farming areas were Apodemus chevrieri (31.05%), Niviventer confucianus (13.90%) and Anourosorex squamipes Milne-Edwards (11.43%). The dominant species in residential areas were Rattus norvegicus (66.67%) and Rattus tanezumi (20.00%). The rat densities in agricultural and residential areas were 20.98% and 1.00%, respectively. A total of 277 external parasitic fleas belonging to 15 species, 13 genera, 5 families were collected. The dominant species were Palaeopsylla remota (22.02%), Neopsylla specialis specialis (20.58%), Frontopsylla diqingensis (18.77%) and Ctenophthalmus (Sinoctenophthalmus) quadratus (11.55%), and the rat fleas index was 0.53. No Yersinia pestis was isolated from all rodent organs and flea samples. A total of 167 serum samples from dogs and 15 serum samples from rats were collected, and plague F1 antibody was detected by IHA. IHA detection of plague F1 antibody were negative. Conclusions　Qiaojia County has the distribution of the main host and main vector of plague, and the rat density is high, but the rat body flea index is low. There is no positive detection of plague host animals, vector fleas and indicator animals. It can be considered that the risk of plague occurrence and epidemic in the region is not high in the near future. It is necessary to further strengthen the monitoring and control of plague and other rodent-borne diseases in the region.

Objective To evaluate the chnical features and prognosis of traumatic benign paroxysmal positional vertigo (t-BPPV).Methods By retrospectively analyzing the results of clinical features and prognosis in 19 patients with t-BPPV from January 2003 to September 2006,the results were compared with 51 patients with idiopathic benign paroxysmal positional vertigo (i-BPPV).Results The mean ages were (51.3?19.1) years in t-BPPV group and (63.2?16.5) years in i-BPPV group,the difference was significant (t=2.57,P0.05).The one-stage success rates were 62.5% in t-BPPV group and 83.6% in i-BPPV group,the difference was significant (x~2=4.94,P

Objective To analyze the recuperation of lungs after TECAB, and probe more effective nursing care for the lungs of patients after TECAB. Methods 20 cases received the treatment of TECAB were collected during the period of January 2009 to July 2010. Due to the reason of ventilation with single lung, patients were demanded to strength breath and take right lateral position and treated with back-tapping in left lung. Meanwhile, patients were treated with back-tapping with lower intensity and more times and lower frequency vibration ( 10 - 15 time/s). The recuperation of patients were observed and analyzed. Results After treatment, the value of PaO2 and PaCO2 were in normal range, and no complications were occurred and all of them recovered from illness. Conclusions Effective and well-targeted lungs nursing is an important assurance that helps the sufferer to recover from illness and the new lungs nursing after one-lung ventilation in TECAB is effective.

Objective To investigate the effects ofYangyin Yiqi Mixture on pulmonary fibrosis caused by bleomycin in rats;To discuss its possible mechanism.Methods SD rats were randomly divided into normal control group, model group, dexamethasone acetate group, low-dose, middle-dose and high-doseYangyin Yiqi Mixture groups. Bleomycin was used to establish pulmonary fibrosis rat models through endotracheal instillation. One day after molding, each medication group received gavage with relevant medicine. Lung tissues were taken on the 7th, 14th and 28th day. Masson staining was used to observe pathological change;alkalinehydrolysis was used to detect HYP content;Western blot was used to detect the protein expressions of MMP-2 and TIMP-1.Results Compared with the normal control group, on 7th day, collagen in lung tissue of rats in model group markedly increased;the content of HYP in lung tissue significantly increased (P<0.01). On 28th day, collagen was deposited diffusely and the alveolar was destroyed;content of HYP in lung tissue increased significantly (P<0.01). Compared with model group, deposited collagen in lung tissue was alleviated, and the content of HYP were remarkable reduced in middle and high doseYangyin Yiqi Mixture groups and displayed dose-dependent. Western blot results showed that the protein expressions of MMP-2 and TIMP-1 increased quickly compared with the low expression of normal lung tissue in the 7th day of molding (P<0.05), and reached high expression in the 28th day. Compared with the model group, the level of MMP-9 in high-dose Yangyin Yiqi Mixture group decreased significantly in the 14th day;the expression of TIMP-1 decreased significantly in the 7th, 14th and 28th day (P<0.05).ConclusionYangyin Yiqi Mixture can effectively resist pulmonary fibrosis, which may be realized by inhibiting the expressions of TIMP-1 and MMP-9, regulating and promoting collagenic hydrolysis and restraining deposition of collagen.

Objective To evaluate the application of three-dimensional measurement and computer-aided navigation system in treatment of orbitozygomatic complex fiacture.Methods Pre-and post-operative three-dimensional measurements were taken by Mimics software to locate the zygomatic bones of 15 patients with orbitozygomatic complex ftacture to determine distance of optical foramen to zygomaticotemporal suture (On-Zm)/ zygomaticofrontal suture (On-Or)/zygomaticomaxillary suture (OnTz),horizontal angle of zygomatic arch,horizontal angle of the zygomatic process,and inferior angel of the frontal process of zygomatic bone.Preoperative design and simulation,intraoperative real time navigation and postoperative evaluation were applied using computer assisted navigation system.Results OnTz,On-Or,and On-Zm was (48.6-±4.5)mm,(42.5±2.2)mm,and (47.5±3.2)mmin the unaffected side,but was (50.4 ± 2.2) mm,(37.2 ± 1.0) mm,and (53.4 ± 3.6) mm in the affected side before operation (P ＜ 0.05).Whereas On-Tz,On-Or,and On-Zm improved to (46.4 ± 3.7) mm,(41.2 ± 1.8) mm,and (46.4 ± 2.5) mm in the affected side after operation,similar with the values in the unaffected side (P ＜ 0.05).Horizontal angle of zygomatic arch,horizontal angle of the zygomatic process,and inferior angel of the frontal process of zygomatic bone was (144.7 ±4.1)°,(132.5 ± 2.3)°,and (112.0 ± 3.4)° in the affected side,with significant differences from (150.3 ± 8.0)°,(141.1 ±4.2)°,and (114.9 ±5.1)° in the affected side before operation (P ＜0.05),but they were improved to almost the normal values (144.6 ± 4.1) o,(132.8 ± 2.0) °,and (111.9 ± 3.6) ° after operation.Satisfactory surgical outcomes,such as three dimensional symmetry and recovery of normal mouth-openingand occlusion,had been achieved.Conclusions Three-dimensional measurement is a quantitative study on the spatial displacement of orbitozygomatic complex.Combined with computer-assisted navigation system with preoperative design and simulation,intraoperative real time navigation and postoperative evaluation,three-dimensional measurement attains the overall management of orbitozygomatic complex fracture.