Identification of the cellular targets of bioactive compounds is a major challenge and a key issue in chemical biology and drug discovery. As an important technology in functional proteomics, small molecule probes play a pivotal role in the identification of cellular targets of bioactive compounds. This review is intended to introduce the application principles and structural design philosophy of chemical probes for the purpose of mechanistic study. Recent cases of successful application were also discussed to further demonstrate the principles and significance ofbioactive small molecule-based probes.

Neural invasion is an important invasion pathway of pancreatic cancer.New research shows that neural invasion of pancreatic cancer related genes in the sequential role effect,through the cell signal transduction,regulation of specific growth factors,adhesion molecules,matrix metallopmteinase and other related systems,then changed in the generation,resulting in the cancer cells invasion of the nerve tissue eventually.We reviewed the progress of neural invasion of pancreatic cancer in this paper.

Objective To explore the key points of diagnosis,treatment and the reasonable surgical methods in 39 cases of pancreas trauma.Methods A retrospective review and analysis the cause and classification of injury,surgical methods of 39 cases of pancreatic trauma in the Department of General Surgery of Affiliated Provinical Hospital of Anhui Medical University during Jan.1990 to Dec.2011.Results In the 39 patients who underwent surgery,38 patients were cured,1 dead duing to craniocerebral injuries,3 patients with complications of pancreatic leakage cured after adequate drainage.Two patients with pancreatic pseudocyst pancreatic pseudocystcyst cured after pancreatic pseudocyst jejunum anastomosis.One patients with traumatic pancreatitis cured after conservative treatment.Conclusions Blunt injury is the most common cause of pancreas trauma.Imaging examination has high value in the early diagnosis of pancreas trauma.The reasonable surgical methods and careful examination during operation can improve the cure rate and reduce the mortality and incidence of complications of pancreatic trauma.If the patient's condition allowed,endoscopy not only contributes to the diagnosis of pancreatic trauma,but is an effective method for treatment of it.

BACKGROUND: Hyperhomocysteinemia has been suggested to be a possible independent risk factor for stroke.OBJECTIVE: To explore the relationship between hyperhomocysteinemia and cerebral infarction and hemorrhage, and analyze the factors that affect plasma homocysteine level.DESIGN: Case-controlled clinical trial.SETTING: Department of Neurology, Second Hospital Affiliated to Medical College of Zhejiang University.PARTICIPANTS: Totally 57 patients including 21 with cerebral hemorthage and 36 with brain infarction were treated in the Department of Neurology, Second Hospital Affiliated to Medical College of Zhejiang University Between January and November 2003. Twenty-eight healthy volunteers were also recruited from the subjects coming for routine physical examination.METHODS: Two milliliters of fasting venous blood was collected from all subjects in the morning for detecting the contents of plasma homocysteine,vitamin B12, folic acid, creatinine and so on. All patients were scored for clinical neurological impairment, with the hematoma volume calculated in patients with brain hemorrhage determined on the basis of CT scanning.acid, vitamin B12, clinical neurological impairment score and hematoma volume.RESULTS: Valid results were obtained from all the 57 stroke patients and in male and female patients of both cerebral infarction group and cerebral hemorrhage group than that of the subjects of the same gender in the control group [(25.2±21.4), (18.3±10.9), (11.5±2.9) μmol/L for male subjects;(22.8±18.9), (14.7±7.4), (10.8±2.6) μmol/L for female subjects, P＜ 0.05-0.01].The level of homocysteine was similar between cerebral infarction group and cerebral hemorrhage group, homocysteic acid level showed obvious inverse correlation with folic acid level (r=-0.442, -0.531, P ＜ 0.05), but without relation to vitamin B12 level (r=-0.086, -0.111, P ＞ 0.05). Homocysteine level was not obviously correlated to the neurological impairment scores in cerebral infarction group (r=-0.139, P ＞ 0.05), nor was it related to the scores or hematoma volume in cerebral hemorrhage group (r=0.225,0.425, P ＞ 0.05).CONCLUSION: Hyperhomocysteinemia is risk factor for cerebral infarction and hemorrhage. Plasma homocysteine level is inversely correlated with folic acid level, but not obviously related to vitamin B12, clinical neurologicla impairment score or hematoma volume.

Adult ; Condylomata Acuminata ; pathology ; Female ; Humans ; Laryngeal Diseases ; pathology

0.05 ), the postoperative complication and mortality rate of PG group were 13.7% and 6.8%, of TG group was all 6%.Conclusions:Proximal and total gastrectomy treatment does not significantly influence the prognosis of patients with cardia and esophgogastric junction cancer in progressive stage.

Objective:To explore the role of decoy receptor 3(DcR3) and its ligand tumor necrosis factor ligand-related molecule 1A(TL1A) in the treatment of pancreatic cancer implanted tumors in nude mice with CD 4 and CD 8 double negative T cells (DNT cells). Methods:DNT cells derived from peripheral blood of healthy volunteers were cultured in vitro by antibody adsorption method. A nude mouse model of pancreatic cancer implantation was established and randomly divided into DNT cell treatment group (tail vein injection of 1×10 8/ml DNT cell suspension), gemcitabine treatment group (tail vein injection of 50 mg/kg gemcitabine) and control group (no treatment). The tumor volume and weight in each group were measured after 50 days. Western blotting and qRT-PCR were used to detect the protein and mRNA expression of DcR3 and TL1A in nude mice implanted tumor tissues in each group, and TUNEL method was used to detect the apoptosis rate of nude mice implanted tumors in each group. Results:The tumor volume of the DNT cell treatment group, gemcitabine treatment group, and control group was (670.28±124.54), (604.60±179.16), (1738.80±391.39)mm 3, and the tumor weight was (225.60±8.12), (222.69±8.73), (265.07±10.76)mg, and the volume and weight of implanted tumors in the DNT cell treatment group and gemcitabine treatment group were significantly lower than those in the control group, and the differences were statistically significant (all P values <0.001). The expression levels of DcR3 protein and mRNA in the DNT cell treatment group and gemcitabine treatment group (0.56±0.02, 3.74±0.19; 0.57±0.03, 3.40±0.39) were significantly higher than those in the control group (0.39±0.04, 0.92±0.05), while the expression levels of TL1A protein and mRNA (0.41±0.03, 0.83±0.11; 0.40±0.05, 0.79±0.08) were significantly lower than those of the control group (0.81±0.05, 1.70±0.36), and the differences were statistically significant (all P values <0.001). The apoptotic rate of implanted tumors in the DNT cell treatment group was (53.2±11.2)%, and that in the gemcitabine treatment group was (56.2±8.6)%, which were significantly higher than the control group (10.3±3.2)%, and the differences were statistically significant ( all P values <0.001). Conclusions:DNT cells had a significant inhibitory effect on the growth of pancreatic cancer implanted tumors in nude mice. DcR3-TL1A may be involved in the anti-tumor mechanism of DNT cells.

Objective To determine the expression of brain-derived neurotrophic factor (BDNF) in pancreatic ductal adenocarcinoma and its clinical significance.Methods SP immunohistochemical staining method was used to detect the expression of BDNF in 46 cases of pancreatic ductal adenocarcinoma,38 cases of benign pancreatic diseases and 20 cases of normal pancreatic tissue.Real time PCR and Western blot was used to detect the protein and mRNA expression levels.The relationship between BDNF expression and clinicopathological parameters of pancreatic cancer was determined.Results The positive expression rate of BDNF was 52.2％ (24/46) in pancreatic ductal adenocarcinoma pancreatic ductal adenocarcinoma,7.8％ (3/38) in benign pancreatic diseases,and none of the normal pancreatic tissue was BDNF positive.The BDNF protein expression levels in pancreatic ductal adenocarcinoma,benign pancreatic diseases and normal pancreatic tissue were 0.38± 0.01,0.56± 0.01,0.97± 0.01,respectively,and the BDNF mRNA expression levels were 0.85 ± 0.14,1.67 ± 0.21,3.45 ± 0.67,respectively,and the expression levels in pancreatic ductal adenocarcinoma and benign pancreatic diseases were significantly higher than that in normal pancreatic tissue,while the expression level in pancreatic ductal adenocarcinoma was significantly higher than that in benign pancreatic diseases (P ＜0.05).Positive BDNF expression was correlated with nerve infiltration and lymph node metastasis of pancreatic ductal adenocarcinoma,but it was not related to age,sex,tumor size,location and differentiated degree (P ＞ 0.05).Conclusions BDNF is involved in the development and growth of pancreatic cancer,and it may be related with patient's prognosis.

Objective To investigate the relationship between HLA-B * 5801 allele and severe cutaneous adverse reactions caused by allopurinol or other drugs.The clinical value of HLA-B * 5801 as the marker of allopurinol-SCAR was evaluated.Methods Forty-three patients with allopurinol-SCAR,133 patients without SCAR after taking allopurinol for 3 months were included.Ninety-six patients with SCAR caused by other drugs and 148 healthy individuals were enrolled into the present study.HLA-B * 5801 allele was detected by PCR-SSP method.Data were analyzed by chi-square test.Results HLA-B * 5801 was present in 40 of 43 (93.0％) patients with allopurinol-SCAR,which was significantly higher than 19 of 148 (12.8％) in healthy subjects (x2=100.353,P＜0.01,OR=90.5,95％CI 25.5-321.8).But there were no significant differences between allopurinol-tolerant patients and healthy controls(10 of 133,7.5,x2=2.141,P＞0.05,OR=0.6,95％CI 0.2-1.2).And there were only 14 of 96 (7.5％) patients with SCAR caused by other drugs had HLA-B * 5801 (x2=0.152,P＞0.05,OR=1.2,95％CI 0.6-2.4).Conclusion The study indicates that people with HLA-B * 5801 have a high risk of allopurinol-SCAR.HLA-B * 5801 is a specific and predictive marker for guiding the selection of uric acid lowing drug allopurinol.

Objective To evaluate the clinical efficacy and safety of piperacillin and sulbactam sodium combinations in the treatment of common infections. Methods This was a multi-centre, prospective and open study. All subjects from 57 wards caught common infection like respiratory ( RTI) or urinary diseases ( UTI). The dosages of piperacillin and sulbactam sodium combinations 2. 5 g injection were determined according to indications:for adult, 2. 5 g or 5 g per time, 2 time/day; for severe or obstinate infection, 2.5 g or 5 g per time, 3 time/day. General information, clinical response pre- and posttreatment, infected locus, drug recipe and protocol, prognosis and adverse reaction were recorded. Results Data of 579 cases were collected with 388 males and 191 females. The average age was (66. 8 ± 17. 0) years. There were 500 patients who were suffering with RTI, with 362 cases of pneumonia, 102 of acute exacerbation of chronic bronchitis, and 36 of other infections. There were 50 cases with UTI, with 31 of simple urinary tract infection, and 19 of complex urinary tract infection. In addition, there were 9 cases of combined RTI and UTI, and 20 of other infections including peritonitis. The average duration of antimicrobial for RTI and UTI was (8. 65 ± 3. 78 ) days and (7. 45 ± 3. 46) days respectively with the total efficacy rate was 92. 6% and 98. 0% respectively for RTI and UTI. The incidence of adverse events was only 0.86% (5 cases), including nausea, rash, itching, ALT elevation and suspected drug induced fever in each one. Conclusion Piperacillin and sulbactam sodium compound had high clinical efficacy and safety in the treatment of common infections including RTI and UTI.