Objective To observe the protection of Caspase inhibitor(zVAD-fmk,benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone) on neonatal rat with hypoxic-ischemic brain damage(HIBD).Methods Thirty-six neonatal rats,7 days old,were randomly divided into hypoxic-ischemic(HI) control group(A),zVAD-fmk treated group(B) and sham group(C).Before HI insult,a pan-Caspase inhibitor,zVAD-fmk or normal buffer solution was injected into the cerebral ventricle.The water content of cerebral hemisphere was measured and the percentage of apoptofic cells in hippocampal neurons was measured by Flow cytometer(Annexin V/PI) at 24 hours after HI insult.The effect on body weights(percentage of increased weight,WIP) and macroscopical changes(percentage of cortox and hippocampal dead neurons) were assessed at 14 days.Results Compared with group A,the water content of ischemic hemisphere and apoptosis percentage of hippocampal neurons in group B reduced significantly.The difference of percentage of increased weight at 14 days in group B was not significantly.Microscopic examination showed that cortox and hippocampus neural death rate in group B was proved significantly reduced compared with that in group A.Conclusion Intracerebral administration of zVAD-fmk has protective effects on hypoxic-ischemic brain damage in neonatal rat.

Objective To investigate the expressions of cycloxygenase-2 (COX-2 ),vascular endothelial growth factor (VEGF),matrix metalloproteinase (MMP2 )and micro-vessel density (MVD)in papillary thyroid carcinoma (PTC)and the relationship between their expressions and clinicopathological features,so as to evaluate the malignancy and prognosis of PTC.Methods The expressions of COX-2,MMP2 and VEGF and MVD count in 32 cases of PTC and 18 cases of normal thyroid tissues were detected by immunohistochemical staining.Their relationship with clinicopathological characteristics was analyzed.Results ① The expression of COX-2,MMP2, VEGF and MVD in PTC was as follows:M(Q 3 -Q 1 )=5(1),M(Q 3 -Q 1 )=5.5(2),M(Q 3 -Q 1 )=5.5(1)and M (Q 3 -Q 1 )= 28 (5.75 ),respectively.It differed significantly from that in control group (P < 0.05 ).② The expression of COX-2 in PTC was related to the sex and age of patients,clinical stage and lymph node metastasis (P <0.05).The expression of VEGF in PTC was related to the sex and age of patients,tumor size,clinical stage and lymph node metastasis (P <0.05).The expression of MMP2 and MVD count in PTC were related to the age of patients,tumor size,clinical stage and lymph node metastasis (P <0.05 ).③ The expression of COX-2,MMP2, VEGF and MVD in PTC with invasion of thyroid capsules was as follows:M(Q 3 -Q 1 =6(2),M(Q 3 -Q 1 )=6.5 (2),M(Q 3 -Q 1 )=6(1.75)and M(Q 3 -Q 1 =30(7.75).The expression of these indexes in negative group was:M (Q 3 -Q 1 )=5(1.75),M(Q 3 -Q 1 )=5(1.75),M(Q 3 -Q 1 )=5 (1.75 )and M (Q 3 -Q 1 )=26.5 (4).There was a significant difference between the two groups (P < 0.05 ).④ There was a close positive correlation between the expressions of VEGF,COX-2,MMP2 and MVD in PTC (r >0.5).Conclusion The high expressions of COX-2, VEGF and MMP2 in thyroid tissues may result in the occurrence of PTC and lymph node metastasis,which is related to the regulation of tumor new vessels.Detecting these expressions are of value in evaluating the malignancy and prognosis of PTC.

Objective To explore the experience of thyroid cancer patients about the diagnosis and post-surgical radioactive iodine treatment. Methods A qualitative, descriptive study was used. Thirty-eight patients with thyroid cancer who were undergoing post-surgical radioactive iodine treatment participated in this study. Dairies about the participants′ experience were collected from them. Interpretative phenomenological analysis was used. Results Three superordinate themes emerged: the psychological process from distress to acceptance; the experience about post-surgical radioactive iodine treatment; and personal growth related to the cancer. Conclusions Understanding the psychological process of patients with thyroid cancer after the diagnosis and their experience about post-surgical radioactive iodine treatment can contribute to the clinical staff to improve the care quality for this group.

Ebola hemorrhagic fever is an acute infectious disease caused by Ebola virus,the mor-tality rate of which is up to 90% . Due to its high infection rate,high mortality rate as well as being a serious threat to public health and safety,Ebola virus is listed as a World Health Organization Risk Group 4 Patho-gen(requiring Biosafety Level 4-equivalent containment). However,there is no effective control method and treatment for Ebola virus infection. Different approaches have been used to develop vaccines and therapeutic drugs against Ebola virus infection and clinical trials of some products have been initiated,such as ZMapp, BCX-4430,GS-5734,DNA vaccines,and adenovirus vector vaccines. National Institutes of Health(NIH) announced a successful development of vaccine for Ebola virus which had passed the clinical trial by the end of 2014. At the meantime,the first anti-Ebola virus medicine had also been approved in China for emergency use only. Recent advances in the research and development of therapeutic drugs and vaccines against Ebola virus will be described in this review.

Objective To explore the effect and mechanism of local administration of thymosin β4 (Tβ4) on bone regeneration in a distraction osteogenesis model of rat fenur.Methods Sixty Sprague-Dawley rats were randomly divided into groups A,B and C in this study.A distraction osteogenesis model was established in the left femur after osteotomy.At the end of distraction period,the bone regeneration area in group A was subjected to no treatment,that in group B to injection of phosphate buffer saline (PBS),and that in group C to injection of Tβ4.On days 22,29 and 43 postoperatively,the rats from each group were randomly sacrificed and processed for observation of bone regeneration in the distraction osteogenesis area using radiography,Micro-CT,histology and immunohistochemical staining.RT-PCR was used to detect the expression of related genes as well.Results Radiography revealed that the bone regeneration in group C was superior to that in groups A and B on days 22,29 and 43 postoperatively.Micro-CT examination showed significantly increased bone volume (BV),bone mineral density (BMD) and ratio of bone volume to tissue volume (BV/TV) in group C on days 22,29 and 43 postoperatively,and significantly decreased ratio of bone surface area to bone volume on postoperative day 43 in comparison with groups A and B(P ＜ 0.05).HE staining indicated that local capillary density was significantly higher in group C than in groups A and B after local administration of Tβ4 in the distraction osteogenesis.Immunohistochemical staining showed that the capillary density and osteoblasts in group C were higher than in groups A and B.RT-PCR results revealed significantly higher expression of eNOS and Osterix mRNA in the local callus in group C on postoperative day 22 than in groups A and group B (P ＜ 0.05).Conclusion Local administration of thymosin β4 may promote bone formation,which is probably related to the increased expression of eNOS and Osterix.

OBJECTIVE:To establish the HPLC fingerprints for Herba clematidis in northeast. METHODS:HPLC was per-formed on the column of Hedera ODS-2 C18 with mobile phase of acetonitrile-0.5% phosphoric acid solution(gradient elution)at a flow rate of 1.0 mL/min,detection wavelength was 338 nm,column temperature was 30 ℃,and the injection volume was 20 μL. Using rutin as as a reference,the HPLC profiles of 10 batches of H. clematidis were determined,Similarity Evaluation Software for Chromatographic Fingerprint of Traditional Chinese Medicine(2004A edition) was used for the common peaks identification and similarity evaluation. RESULTS:There were 16 common peaks in the 10 batches of H. clematidis,similarity degree was higher than 0.9. It was proved that the HPLC profiles and control fingerprint profile of 10 batches of H. clematidis had good consistency. CONCLUSIONS:The established fingerprints can provide reference for the identification and quality evaluation of H. clematidis in northeast.

Objective To investigate the effect of flurbiprofen axetil on perioperative plasma levels of prostaglandin E2 (PGE2) and β-endorphine (β-EP) in patients after remifentanil-based anesthesia.Methods Sixty ASA Ⅱ patients of both sexes,aged 40-64 yr,weighing 50-75 kg,undergoing resection of esophageal cancer,were randomly divided into 3 groups (n =20 each):intralipid group (group A),flurbiprofen axetil pretreatment + postoperative analgesia with flurbiprofen axetil group (group B) and flurbiprofen axetil pretreatment group (group C).Anesthesia was induced with propofol,remifentanil and rocuronium and maintained with propofol,remifentanil and intermittent iv boluses of rocuronium.In group A,intralipid 0.2 ml/kg was injected intravenously at 30 min before operation and patient-controlled intravenous analgesia (PCIA) with fentanyl 15μg/kg + intralipid 0.2 ml/kg was used for postoperative analgesia.In group B,flurbiprofen axetil 2 mg/kg was injected intravenously at 30 min before operation and PCIA with fentanyl 15 μg/kg + flurbiprofen axetil 2 mg/kg was used for postoperative analgesia.In group C,flurbiprofen axetil 2 mg/kg was injected intravenously at 30 min before operation and PCIA with fentanyl 15 μg/kg + intralipid 0.2 ml/kg was used for postoperative analgesia.PCIA solution contained fentanyl 15 μg/kg,flurbiprofen axetil 2 mg/kg and intralipid 0.2 ml/kg in 100 ml of normal saline.The PCA pump was set up with a 0.5 ml bolus dose,a 10 min lockout interval and background infusion at a rate of 2 ml/h after a loading dose of 5 ml starting from 30 min before the end of operation.VAS score was maintained ＜ 3 after operation,and tramadol 50 mg was injected intravenously when VAS ≥ 4 after operation.The amount of remifentanil used during operation and the number of successfully delivered doses and the number of attempts,requirement for tramadol,apnea and severer hypotension were recorded within 48 h after operation.Blood samples were taken immediately before induction of anesthesia,at the end of operation,24 and 48 h after operation (T1-4) for determination of plasma β-EP and PGE2 concentrations.Results There was no significant difference in the amount of remifentanil used among the three groups (P ＞ 0.05).Compared with group A,the number of successfully delivered doses,the number of attempts and the requirement for tramadol were decreased,and the concentration of plasma PGE2 at T2,3 were significantly decreased in groups B and C,and the concentrations of plasma β-EP at T3,4 in group B and at T4 in group C were significantly increased (P ＜ 0.05).Compared with group B,the number of successfully delivered doses,the number of attempts and requirement for tramadol were significantly increased,and the concentration of plasma β-EP at T3,4 wassignificantly decreased in group C (P ＜ 0.05).Compared with the baseline value at T1,the concentrations of PGE2 were significantly increased at T2,3,and the concentration of plasma β-EP was significantly increased at T2,but decreased at T4 in group A,and the concentrations of β-EP at T3,4 were significantly increased in group B (P ＜ 0.05).There was no significant difference in the concentrations of PGE2 and β-EP between the four time points in group C (P ＞ 0.05).Apnea and severer hypotension were not found in the three groups.Conclusion The mechanism by which flurbiprofen axetil reduces postoperative opioid tolerance in patients after remifentanil-based anesthesia may be related to the decrease in PGE2 levels and increase in β-EP levels.

Heat shock proteins (HSPs) are a family of evolutionary conserved proteins that work as molecular chaperones for cellular proteins essential for cell viability and growth as well as having numerous cyto-protective roles. They are sub-categorised based on their molecular weights; amongst which some of the most extensively studied are the HSP90 and HSP70 families. Important members of these two families; Heat shock proteins 70 and heat shock proteins 90 (Hsp70/90), are the glucose regulated proteins (GRP). These stress-inducible chaperones possess distinct roles from that of the other HSPs, residing mostly in the endoplasmic reticulum and mitochondria, but they can also be translocated to other cellular locations. Their ability in adapting to stress conditions in the tumour microenvironment suggests novel functions in cancer. GRPs have been implicated in many crucial steps of carcinogenesis to include stabilization of oncogenic proteins, induction of tumour angiogenesis, inhibition of apoptosis and replicative senescence, and promotion of invasion and metastasis.

Objective:To investigate the effects of experimental periodontitis on serum C reactive protein(CRP) and insulin resistance in obese rats.Methods:4 week old SD rats (n=35)were fed with high fat diet for 16 weeks to establish the model of obesity.According to the obesity criteria,5 rats were screened out.According to the proportion of 1:2,10 rats were randomly selected as obese control group,20 obese rats were used for the establishment of the obesity with periodontitis model(combination group) by periodontal ligation using silk thread.4 rats died after ligation.Before periodontal ligation,1 and 4 weeks after periodontal ligation,orbital venous blood were collected for the detection of fasting blood glucose and fasting insulin.Homeostasis model assessments of insulin resistance index(HOMA-IR) and beta cell function index(HOMA-β) were calculated.The level of serum CRP was examined by ELISA.Results:The level of CRP in the combination group was increased 1 week after periodontal ligation,and then gradually decreased in the following 4 weeks(F=7.773,P=0.004).HOMA-IR in the combination group were higher than that in the obese group(F=-4.691,P=0.000),and beta cell function index was significantly lower(F=3.672,P=0.002) than that in the control group 4 weeks after periodontal ligation.Conclusion:The experimental periodontitis may affect the serum level of CRP in obese rats,aggravate insulin resistance and decrease the function of beta cells in obese rats.

OBJECTIVETo investigate the mechanism and the effects of intravenously injected tumor necrosis factor alpha (TNFalpha) on skeletal muscle protein degradation in rats and its relationship with glucocorticoid.

METHODSForty-five male Wistar rats were randomly divided into 3 groups as A (control), B (TNFalpha injection) and C (TNFalpha and glucocorticoid receptor antagonist injection) groups. TNFalpha in dose of 1x 10(6) units/kg was given to rats in B group intravenously. RU38486, a glucocorticoid receptor antagonist, was given by gavage in C group 2 hours before intravenous injection of TNFalpha in the same dose as in B group. the rat temperature was monitored 12 hours after the administration of the drugs. At the same time, the rat extensor digitorum longus muscles (EDL) were isolated, weighed and cultured under aerobic condition, and than the degradation rates of total and the myofibrillar proteins were determined with HPLC (high performance liquid chromatography), and the expression changes in C2 subunit mRNA and ubiquitin mRNA were detected by Northern blot.

RESULTSTwelve hours after the injection, the temperature of the rats in B and C group was much higher than that in A group (P < 0.01), while the weight of the extensor digitorum longus muscle in B and C groups was evidently lower than that in A group (P < 0.01) whereas that in C was higher than that in B groups (P < 0.05). The degradation rates of total and the myofibrillar proteins in B group were increased by 43% and 112%, respectively, when compared with those in A group (P < 0.01), while the rates in C group was decreased by 16% and 28%, respectively, when compared with those in B group (P < 0.01). In addition, the expressions of ubiquitin mRNA (2.4 kb) and C2 subunit mRNA in B group were increased 4.3 and 3.6 fold compared with those in A group, whereas those in C group were much lower than those in B group.

CONCLUSIONIntravenous injection of recombinant TNFalpha in large dose might enhance the activity of rat skeletal muscle ubiquitin-proteasome system pathway, which led to an increase in the degradation rate of rat total protein, especially the myofibrillar protein. Glucocorticoid was one of the mediating factors of that effect.

Animals ; In Vitro Techniques ; Male ; Muscle Proteins ; metabolism ; Muscle, Skeletal ; drug effects ; Rats ; Rats, Wistar ; Recombinant Proteins ; pharmacology ; Tumor Necrosis Factor-alpha ; pharmacology ; Ubiquitin ; metabolism