1.Conclusion ABR can evaluate the function of brainstem of patients with severe traumatic brain injury in PVS and provide evidence for prognosis.

A drug is composed of fragments with their functional and structural characteristics. Functional fragments contain structural elements known as pharmacophores which generate the bioactivity of the drugs, while structural fragments assemble the functional fragments into a specific skeleton also crucial for the activity. Although drug molecules possess structural diversity and complexity, the fragments usually have some similarity. They normally have simple texture, low molecular weight and log P. The aim of fragment-based drug discovery is to classify and screen the collections of fragments and subsequently expand, link, or merge them to obtain new chemical entities. This theory refines the traditional structure-based and the high throughput screen-based drug discovery strategy, and facilitates the reduction of molecular size and the improvement of drug-like properties, which will certainly increase the probability of developing new drugs. In this article, we reviewed the concept, methodology of fragment-based drug discovery and detailed a number of examples to illustrate the optimization strategies of this discovery method.

Objective This research examined the effect ofmicrobubble contrast agent plus ultrasound on the permeability of blood-brain barrier,and explored whether it affects the efficacy of chemotherapeutic drugs on cerebral glioblastoma.Methods Wistar rats were divided into three groups to find the optimal concentration of ultrasonic contrast agent.To identify the best ultrasound mode that affected the permeability of blood brain barrier,we employed transmission electron microscopy for study of brain ultrastructure.Western blotting was used to detect the tight junction protein claudin-5.Evans blue staining of brain tissues was utilized to identify the best ultrasonic contrast agent concentration and mode.Rat glioma cells (line 9L) were injected into Wistar rats.After temozolomide chemotherapy,the tumor size was measured and the tumor marker GFAP in serum was detected by ELISA.Results The best contrast agent concentration which increases permeability of BBB in rats was found to be lml/kg and the best ultrasound mode was intermittentlytriggered pulses lasting for 10min (with interval was set at 400ms).More Evans blue passed the blood-brain barrier in ultrasonic cavitation effect group than in control group (P＜0.05).After temozolomide chemotherapy,more tumor marker GFAP was detected in ultrasonic cavitation effect group than in control group (P＜0.05).Conclusion The permeability of BBB was increased and more temozolomide went through BBB when the rats were subjected to intermittently triggered ultrasonic pulses and were injected at contrast agent at lml/kg,which could help to achieve better therapeutic efficacy for glioblastoma.

Objective To study the influence of hierarchical model on the professional attitude and quality improvement of nurses and supply references for the apphcation of hierarchical model.Methods 310 nurses were divided into the control group(158 cases)and the practice group(152 cgses).The practice group adopted hierarchical model while the control group did not.Investigation was carried out in 15 aspects such as training requirement,choosing of nursing posts and departure intention,etc.Results The nursing teaching pest and nursing management post in the aspect of post requirement between the two groups had no statistical difference(P＞0.05),but statistical difference existed in other items(P＜0.05).In the aspect of training requirement evident difference existed in two groups(P＜0.05).Conclusion Application of hierarchical model proved to be a pivotal method to improve the professional passion and loyalty of nurses.

Due to the complicated pathogenesis of cardiac arrhythmia, the safe and effective therapeutic strategies for cardiac arrhythmia remain an urgent medical problems in the recent years. In this paper, we introduced the research practice of anti-arrhythmic agents targeting on potassium ion channel. The research progress of anti-arrhythmic agents in up-to-date literatures were also reviewed and prospected.

Objective To obtain the specific antigens of the expressed major capsid proteins from Noroviruses with different sub-genotypes in Beijing area. Methods The full-length genes of the major capsid proteins (VP1)were obtained through the amplification of the VP1 encoding gene in the recombinant plasmids pBST-CR2987(G Ⅱ-3)and pBST-CR2932(GⅡ-4),which represented different Norovirus geno-types. The full-length genes were sub-cloned into the expression vector pET-30a(+),resulting in a recombinant plasmid, with which the BL21 competent cells were transformed, and the expression of the gene was induced by adding IPTG to the growth culture. The expression of the major capsid proteins were analyzed with Coomassie blue staining after SDS-PAGE, and assayed by Western blot with serum from human. Results (1)The major capsid protein genes of CR2987 and CR2932 were sub-cloned into expression vector pET-30a(+). The VP1 encoding genes were 1647 bp in length for CR2987 and 1623 bp for CR2932. The open reading frames(ORF)coded for 549 and 541 amino acids for these two proteins, respectively. (2)The expressed VP1s were present primarily as inclusion bodies,and the maximal amount of the expressed proteins occurred at 4-6 h after IPTG induction.(3)These VP1s could be recognized by specific immune serum against VP1 of Norovirus as well as His-tag antibody. Conclusion The VP1s of CR2987 and CR2932 are expressed in BL21 E.coli cells.The expressed VP1s could react with specific immune serum against VP1 of Norovirus, indicating that the expressed VP1s are of antigenicity.

ve value and 68.0% total coincidence rate. Conclusion The PCR developed in this study is found to be a rapid and reliable method for the detection of adenoviruses in infant diarrheal stools samples.

Objective To investigate the CT characteristics of anaplastic thyroid carcinoma and evaluate the diagnostic value of CT in this disease.Methods The CT findings of 10 patients with pathologically proved anaplastic thyroid carcinoma were retrospectively reviewed.The patients included 7 females and 3 males.Their age ranged from 25.0 to 78 years with median of 61 years.Multi-slices plain and post contrast CT scans were performed in all patients.Results Unilateral thyroid was involved in 6 patients.Unilateral thyroid and thyroid isthmus were both involved in 2 patients due to big size.Bilateral thyroid were involved in 2 patients.The maximum diameter of anaplastic thyroid carcinoma ranged from 2.9-12.8 cm with mean of (4.5 ± 1.4) cm.All lesions demonstrated unclear margins and envelope invasion.The densities of all lesions were heterogeneous and obvious necrosis areas were noted on precontrast images.Seven lesions showed varied calcifications,and coarse granular calcifications were found in 5 lesions among them.All lesions showed remarkable heterogenous enhancement on post-contrast CT.The CT value of solid portion of the tumor increased 40 HU after contrast media administration.The ratios of CT value which comparing of the tumor with contralateral sternocleidomastoid muscle were 0.69-0.82 (0.76 ± 0.18)and 1.25-1.41 (1.33 ± 0.28)on pre and post CT,respectively.Enlarged cervical lymph nodes were found in 6 cases (60.0％).It showed obvious homogeneous enhancement or irregular ring-like enhancement on post-contrast images and dot calcifications were seen in 1 case.Conclusions Relative larger single thyroid masses with coarse granular calcifications,necrosis,envelope invasion,remarkable heterogeneous enhancing and enlarged lymph nodes on CT are suggestive of anaplastic thyroid carcinoma.

Objective To describe the natural history of cervical intraepithelial neoplasia(CIN)Ⅰand the biologic factors associated with the progression of CINⅠ and to analyze the predictive values of p16INK4a protein for the progression of CINⅠ. Methods From August 2010 to July 2013, 104 patients referred for abnormal cytology [≤ low-grade squamous intraepithelial lesion (LSIL); including negative for intraepithelial lesion or malignancy (NILM), atypical squamous cells of undetermined significance (ASCUS), LSIL] and high-risk (HR) HPV positive,and were diagnosed CINⅠ by colposcopy-assisted biopsy and followed at 1-year intervals in the First Affiliated Hospital of Nanjing Medical University. In order to analyze the relationship between the progression of CINⅠ with clinical biologic factors, including patient age, cervical cytology before colposcopy, loads of HR HPV, HPV L1 capsid protein, p16INK4a protein,χ2 tests was used to compare the different frequencies of factors in groups of progressed and persisted/regressed CINⅠ, then five factors with progressed CINⅠwere processed into binary logistic regression analysis. Results (1) In the first year of follow-up, among 104 patients(including 15 cases NILM,78 cases ASCUS,11 cases LSIL), 52 cases of them were NILM and HR HPV negative, 30 cases were negative for intraepithelial lesion, 10 cases were CINⅠ, 5 cases were CINⅡand 7 cases were CINⅢ. In total, 82 cases (78.8%,82/104) cases had regressed, 10 cases (9.6%,10/104) persisted, 12 cases (11.5%,12/104) progressed [including 5 cases (4.8%,5/104) progressed to CIN Ⅱ, 7 cases (6.7%,7/104) progressed to CIN Ⅲ, none progressed to invasive cancer]. (2) All patients, 88 cases of them accepted immunohistochemical detection the expression of p16INK4a protein. The result shown that 30 cases (34%,30/88) were positive and 58 cases (66%,58/88) were negative. And 94 cases accepted immunocytochemical detection the expression of HPV L1 capsid protein, 49 cases (52%,49/94) were positive and 45 cases (48%,45/94) were negative. (3) Univariate analysis showed that age of the patient, loads of HR HPV, cervical cytology before colposcopy and the expression of HPV L1 capsid protein were not risk factors of the progression of CINⅠ(all P>0.05) except for the expression of p16INK4a protein (P<0.05). Multivariable analysis found that p16INK4a protein positive was associated with progression of CINⅠ(OR=5.1,95%CI:1.162-22.387,P=0.031). (4) Thirty-one cases were p16INK4a protein positive, 8 cases (27%,8/30) of them progressed,while 4 cases (7%,4/58) of 58 cases with p16INK4a protein negative progressed,in which there were significant difference (P<0.05). The sensitivity was 75%, the specificity was 71%, the positive predictive value was 27%and the negative predictive value was 93%for progression to CINⅡ-Ⅲof p16INK4a protein staining. Conclusions The progression rate of CINⅠwith abnormal cytology (≤LSIL) and HR HPV positive was lower, and there was no progression to invasion at 1-year intervals. Immunostaining of p16INK4a protein as the risk factors of CINⅠprogression could have a role in prediction of CINⅠand the management of high-risk CINⅠ.

Objective To summary the clinical applied value of interventional therapy in hepatic venous outflow obstruction after orthotopic liver transplantation(OLT).Methods The clinical data of 27 patients suspect with hepatic outflow obstruction out of OLT patients were analyzed retrospec- tively.Most of them presented with liver dysfunction,like ascites,jaundice,or hydropsia of lower ex- tremity as BCS.These patients accepted venography and endovascular treatment if venous outflow ob- struction was found.Results By venography,one case of thrombus in inferior vena cava,one case of hepatic vein stenosis,13 cases of inferior vena cava stenosis(3 cases were associated with hepatic vein stenoses)were identified.Stent implantation was successfully performed on 10 patients,and balloon angioplasty on 4 patients.Rapid,dramatic resolution of symptoms was achieved in those patients. Hepatic vein restenosis occurred in one case 8 months after balloon dilatation,and treated with stent implantation.Inferior vena cava restenosis occurred in one case 2 years after balloon dilation,and trea- ted with another balloon expanding.Patients remained completely asymptomatic at 4 months to 5 years of follow-up.Conclusion The venacavographic balloon angioplasty and metallic stent replacement are safe and useful for post-OLT with venous outflow obstruction.