Objective By virtual screening in MDL,to search for a novel γ-secretase inhibitor.Methods A series of compounds were designed,synthesized,and evaluated based on pharmacophore model of γ-secretase inhibitors by virtual screening in MDL.Results The drug-likeness analytic data synthesized indicated that target compounds had drug-likeness.Each svnthesized compound was checked by IR spectroscopy,~1H and ~(13)C-NMR spectroscopy.Conclusion The designed compounds had better activity by model prediction.And the optimal compound showed a significant estimated activity value of 0.025 nmol/L and can be used as a lead for further drug development.

Objective To explore the measures to prevent recurrent laryngeal nerve (RLN)injury during thyroid surgery.Methods The clinical data of 223 patients undergone thyroid surgery were retrospectively analyzed.Among the 223 surgeries,69 sides were undergone regional protection act of RLN and 191 sides were performed RLN exposure.Results There were 2 cases of RLN injury from the regional protection operation of RLN,including 1 case of temporary nerve injury which could be resulted from surgery clamp and 1 case of permanent nerve injury which might be caused by mistaking ligation during surgery.There was only 1 case of temporary nerve injury in RLN exposure procedure which was probably caused by the postoperative nerve edema and was recovered 2 months after the operation.The total RLN injury rate was 1.35％.Conclusion For benign thyroid lesions and non-dorsal lesions or during partial excision of the gland,the regional protection of RLN is helpful to prevent RLN injury.In cases with dorsal lesions of thyroid or contralateral RLN injury,or during lobe subtotal resection,lobe resection and reoperation,exposing RLN to prevent injury is necessary.Taking different approaches based on the profiles of lesions and surgical procedures to prevent RLN injury can significantly reduce the risk of RLN injury.

OBJECTIVE:To evaluate the curative effect and safety of dexamethasone for severe asthma and severe sepsis systematically. METHODS:Randomized controlled trials about dexamethasone for severe asthma and severe sepsis were retrieved from database,such as Cochrane library(1996～2007),PubMed(1966～2007),EMCC(1995～2007),CHKD(1994～2007)and pertinent literatures. The qualities of included studies were evaluated and extracted data were analyzed by Meta-analysis respectively. RESULTS:11 trials containing 1 435 cases were up to included standard. Therapy results of severe asthma:(1)in remission rate of the total symptom,difference between dexamethasone and prednisone was not statistically significant [OR 1.44,95%CI(0.75, 2.75);P=0.27];(2)In the incidence rate of ADR,dexamethasone was lower than prednisone [OR 0.13,95%CI(0.04,0.44);P= 0.001];(3)In the recurrence rate,no statistical significance was noted in difference between dexamethasone and prednisone [OR 0.58,95%CI(0.25,1.31);P=0.19]. Therapy results of severe sepsis:(1)In the mortality,difference between dexamethasone and placebo was not statistically significant [OR 0.85,95%CI(0.41,1.78);P=0.67];(2)In the incidence rate of ADR,no statistical significance was noted in difference between hydrocortisone and placebo [OR 1.05,95%CI(0.51,2.19);P=0.89]. CONCLUSION: Dexamethasone is similar to prednisone in the treatment of severe asthma but better than prednisone in drug safety. The safety of dexamethasone is similar to placebo in the treatment of severe sepsis.

Humans ; Supranuclear Palsy, Progressive ; Acupuncture Therapy

Uridine diphosphate (UDP)-GalNAc : polypeptide N-acetylgalactosaminyltransfemse (ppGalNAcT) catalyzes the initial step in mucin type O-glycosylation in the Golgi apparatus. Here generation and characterization of a polyclonal antibody to human ppGalNAcT2 were described. The subcellular location of ppGalNAeT2 in SGC7901 cell line was investigated using Western blot analysis of fractionated cell extracts and confocal microscopy with this antibody and two Golgi markers: Golgi SNARE (soluble N-ethylmalemide-sensifive factor attachment protein receptor) of 28 ku (GS28) and trans-Golgi network (TGN) 38, markers for the c/s- and trans-Golgi apparatus, respectively. Morphometric analyses indicated that ～60% of the ppGalNAcT2 signal colocalized with the GS28, while～36% of the c/s-Golgi marker colocalized with the ppGalNAeT2. Approximately 34% of the ppGalNAcT2 signal colocalized with the TGN38, whereas 38% of the trans-Golgi marker colocalized with the ppGalNAcT2. The results provide unequivocal evidence for the location ofppGalNAcT2 within the Golgi apparatus, and further highlight the importance of this organelle in the initiation of O-linked glycosylation.

Objective To investigate whether HSP90α could be a sensitive and specific serum biomarker for the diagnosis and progression of lung cancer. Methods In the present study, different secretomic analy-ses on the two human lung adenocarcinoma cell lines CL1-0 and CL1-5 with low and high metastatic poten-tial, respectively, were performed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and ma-trix-assisted laser desorption/ionization time-of-flight mass spectrometry. The candidate biomarker was con-firmed by Western blotting, and was further analyzed in 224 serum samples including 141 lung cancer, 37 benign pulmonary diseases, as well as 46 healthy individuals using ELISA assay. Results HSP90α was sig-nificantly upregulated in the CM of CL1-5 cells. It was found that the levels of HSP90α were specifically ele-vated in the sera of non-small cell lung cancer compared with other groups. At the cut-off point 0.535 on the receiver operating oharacteristie curve, HSP90α could comparatively discriminate lung cancer from benign lung disease and healthy control groups with sensitivity of 0. 817, specificity 0. 919 and total accuracy 80. 14%. Conclusion HSP90α may be a potential useful serum biomarker for discriminating lung cancer from benign lung diseases and healthy individuals and staging of non-small cell lung cancer.

Objective:To measure vertical axis length of humerus head in patients with proximal hu-meral fractures and to evaluate the use of structure screws in proximal humerus internal locking osteosyn-thesis system ( PHILOS) .Methods:From January 2007 to February 2014,117 patients with proximal hu-merus fracture were treated by PHILOS plate.Preoperatively, all the patients tookanteroposterior X-ray of shoulder, and the vertical axis length of humerus head were measured, and the use of structure screws in PHILOS plate was observed.Results: There were 40 male and 77 female patients; The vertical axis length of humerus head in male patients was (47.64 ±3.44) mm, and the rate of structure screw use was 52.5%;The vertical axis length of humerus head in female patients was (42.46 ±3.21) mm, and the rate of structure screw use was 32 .5%.The vertical axis length of humerus head and the rate of structure screw use had significant difference in the male and female groups (P<0.05).Conclusion:The rate of structure screw use was low in the treatment of proximal humerus fracture by PHILOS plate, especially for women.We should improve the design of plate according to the anatomical characteristics of Chinese.

Objective:To evaluate the performance of RapidArc technique on cervical cancer patients with various filling status of the bladder. Methods: Conventional fixed field intensity modulation radiated therapy (IMRT) is used as the benchmark. In 10 fe-males suffering from cervical cancer, two CT scans were performed for treatment planning:one with an empty bladder and the other with filled bladder. The prescribed dose was 50 Gy. The images of that with an evacuated bladder and that with filled bladder were planned in the dual-arc RapidArc and the 7-field IMRT, respectively. The implementor of the plan was the Varian TrueBeam linear ac-celerator. Dose-volume histogram was used to evaluate the data from each plan. Results:When the bladder was filled, IMRT and Rapi-dArc homogeneity were 1.05 and 1.04 (P>0.05), respectively. When the bladder was emptied, the homogeneity was 1.04 for both plans (P>0.05). With or without bladder filling, the conformity index was 0.71 and 0.73 for IMRT and RapidArc (P>0.05), respectively. The effect of V30 and V40 (volume for receiving doses of 30 and 40 Gy) on the intestine and the bladder was more favorable in a full than in an empty bladder. No significant difference between the two plans was observed. IMRT exhibited improved V30 on the rectum and on the bladder. RapidArc was much better in terms of monitor unit (MU) and deliver time. Conclusion:No significant differences in the homogeneity and conformity index between dual-arc RapidArc and 7-field IMRT were observed. Filled bladder is better than empty bladder in intestine and bladder protection in both RapidArc and IMRT. IMRT is better on V30 of the rectum and the bladder, whereas RapidArc improved MU and deliver time.

In order to discriminate the crude and sweated Dipsaci Radix correctly and rapidly, the crude and sweated Dipsaci Radix were scanned by the NIR spectrometer, and an identifying model was developed by near infrared spectroscopy combined with principal component-Mahalanobis distance pattern recognition method. The pretreated spectra data of 129 crude samples and 86 sweated ones were analyzed through principal component analysis (PCA). The identifying model was developed by choosing the spectrum for 9 881.46-4 119.20 cm(-1) and "SNV + spectrum + S-G" to the original spectral preprocessing with 14 principal components, and then was verified by prediction set, identifying with 100% accuracy. The rapid identification model of the crude and sweated Dipsaci Radix by NIR is feasible and efficient, and could be used as an assistant means for identifying the crude and sweated Dipsaci Radix.
Chemistry, Pharmaceutical ; methods ; Dipsacaceae ; chemistry ; Plant Roots ; chemistry ; Principal Component Analysis ; methods ; Quality Control ; Spectroscopy, Near-Infrared ; methods

OBJECTIVETo study topiramate's new functions according to the medicinal property combinations, in order to apply the traditional Chinese medicinal theory in discovering new purposes of old drugs.

METHODAccording to New Traditional Chinese Medicinal Families--Chemical Traditional Chinese Medicines, the authors found out topiramate's property. Then based on the therapeutic principle of diabetes, hypertension, epilepsy and lung cancer, as well as the relations of efficacies and medicinal property combinations, they summarized the corresponding medicinal property combination modes, compared topiramate's medicinal property combination mode with corresponding medicinal property combination modes of these diseases, and predict topiramate's new functions.

RESULTAccording to the comparison, the corresponding medicinal property combinations were consistent with topiramate's medicinal property combinations as evidenced by corresponding literatures, whereas other medicinal property combinations were not.

CONCLUSIONBased on medicinal property combination modes, the authors screened topiramate's new functions according to e of TCM clinical experience, discovered topiramate's therapeutic effects on diabetes, hypertension and lung cancer in addition to epilepsy, and explore new drug function according to medicinal property combination modes, which could help greatly shorten the new drug R&D period.

Diabetes Mellitus ; drug therapy ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; chemistry ; therapeutic use ; Fructose ; analogs & derivatives ; chemistry ; therapeutic use ; Humans ; Hypertension ; drug therapy ; Lung Neoplasms ; drug therapy ; Phytotherapy