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.

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.

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.

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.

OBJECTIVETo explore the effects of resuscitation with different kinds of colloids on oxygen metabolism of swine during shock stage of burn injury.

METHODSEighteen Guangxi Bama miniature swine were inflicted with 40% TBSA full-thickness burn on the back. And then they were divided into succinylated gelatin group (S) , hydroxyethyl starch group (H), and allogeneic plasma group (A) according to the random number table, with 6 swine in each group. The fluid resuscitation was begun at post injury hour (PIH) 2. The colloids used in groups S, H, and A were respectively succinylated gelatin, 60 g/L hydroxyethyl starch 130/0.4, and allogeneic plasma. The blood pressure, urine volume, heart rate, and central venous pressure (CVP) were recorded before injury and at the first and second PIH 24. The volume of resuscitation fluid was recorded at the first and second PIH 24. The changes in oxygen delivery., oxygen consumption, oxygen extraction ratio and D-lactate were determined and calculated before injury and at PIH 4, 8, 24, and 48. Data were processed with analysis of variance of repeated measurement, one-way analysis of variance and LSD test.

RESULTSThere were no statistically significant differences among the three groups in blood pressure, urine volume, heart rate, and CVP at each time point (with P values above 0. 05). There were no statistically significant differences in resuscitation fluid volume among the three groups at the first and second PIH 24 (with F values respectively 0. 239 and 2. 023, P values respectively 0. 790 and 0. 167). The oxygen consumption of swine in group S was (201 ± 38) L · min(-1) · m(-2) at PIH 48, which was significantly higher than that in group A [(150 ± 37) L · min(-1) · m(-2), P < 0.05], and the oxygen consumption was similar among the three groups at the rest time points (with P values above 0.05). The oxygen delivery of swine in group S was (484 ± 63) L · min(-1) · m(-2) at PIH 8, and it was significantly lower than that in group A [(652 ± 65) L(-1) min(-1) · m(-2), P < 0.01]. The oxygen delivery of swine in group S reached (903 ± 132) and (1,028 ± 98) L · min(-1) · m(-2) at PIH 24 and 48, respectively, and they were significantly higher than those in group A [(686 ± 72) and (720 ± 75) L · min(-1) · M(-2), with P values below 0.01]. Oxygen delivery in group H was similar to that of group A at each time point (with P values above 0.05). The oxygen extraction ratio in group S or group H was close to that of group A at each time point (with P values above 0.05). The D-lactate level in group S was (69 ± 9) mmol/L, and it was significantly higher than that in group A [(52 ± 4) mmol/L, P < 0.01] at PIH 48. The D-lactate level was similar among the three groups at the rest time points (with P values above 0.05).

CONCLUSIONSAccording to the changes in oxygen metabolism of swine during shock stage of burn injury resuscitated with different kinds of colloids, it is found that allogeneic plasma is better than artificial colloid, and 60 g/L hydroxyethyl starch 130/0.4 is superior to succinylated gelatin.

Animals ; Blood Pressure ; Burns ; China ; Colloids ; administration & dosage ; pharmacology ; Fluid Therapy ; Hydroxyethyl Starch Derivatives ; Oxygen ; metabolism ; Resuscitation ; methods ; Shock ; Swine

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.
Biotin ; metabolism ; Drug Delivery Systems ; Drug Design ; Drug Discovery ; methods ; Molecular Probe Techniques ; Molecular Probes ; chemistry ; Photoaffinity Labels ; Proteins ; metabolism ; Proteome ; chemistry ; Proteomics ; methods ; Small Molecule Libraries ; chemistry ; pharmacology

Psoriatic arthritis is an inflammatory joint disease associated with psoriasis. Due to difficulty for early diagnosis and lack of effective therapy, the disease leads to chronic course and frequent relapse. Patients may suffer from ankylosis,disability and even death. The past treatments neither can control the disease effectively, nor be capable of inhibiting the development of structural joint damage. Based on the current psoriasis pathogenesis, novel biologics have been developed,which can aim the specific targets, resulting in more effective and safer management for psoriatic arthritis.
Adalimumab ; Anti-Inflammatory Agents, Non-Steroidal ; therapeutic use ; Antibodies, Monoclonal ; therapeutic use ; Antibodies, Monoclonal, Humanized ; Arthritis, Psoriatic ; drug therapy ; etiology ; Dermatologic Agents ; therapeutic use ; Etanercept ; Humans ; Immunoglobulin G ; therapeutic use ; Receptors, Tumor Necrosis Factor ; therapeutic use ; Recombinant Fusion Proteins ; therapeutic use