Aim To observe the effect of the polymerization of HSF1 on the febrile response in fever rabbits,and further to investigate HSF1 action in thermoregulation and the possible central mechanism.Methods 70 rabbits were divided randomly into 4 groups:the control group(N),the quercetin group(Q),the LPS-feverish group(L),the quercetin+LPS-feverish group(Q+L).Changes in body temperature were continually observed;the expression of HSF1 and HSP70 in hypothalamus was detected by Western blot;the content of AVP in hypothalamus and VSA was measured by radioimmunoassay.Results ① The sequence of the maximum change of temperature(△Tmax)from low to high:group Q

Patient-derived xenograft models (PDXs) of lung cancer are obtained by directly implanting lung cancer tissue fragments in-to immunocompromised mice. The implanted tumor fragments can be proliferated and passaged in these mice models. The PDXs maintain the tumor microenvironment, histological and pathological characteristics, and tumor biomarkers of the original tumor tis-sues. The PDX also offers an ideal mice model that mimics the human tumor microenvironment. These models have important roles in the pre-clinical evaluation of cancer, the assessment of anti-tumor drug responses, and the analysis of biomarkers. These models also present a new direction for the individualized therapy of lung cancer patients.

Objective This experiment used the allogeneic bone marrow mesenchymal stem cells to cure the wound in rats .And to observe the effect and safety of bone marrow mesenchymal stem cells injection for wound heal -ing.Methods The rats with wound were divided into two groups .The rats bone marrow mesenchymal stem cells were isolated,cultured,purified,amplified and passaged.Flow cytometry instrument was used to identify the immune pheno-type of rats bone marrow mesenchymal stem cells .Local injected the rats-bone marrow mesenchymal stem cells in the rats.The difference of wound healing rate between the experimental group and control group were statistically ana -lyzed.Western blot was used to detect the expression of keratinocyte growth factor (KGF) in two groups.Histopatho-logical change of the wound was observed .Results The wound healing rate between the two groups had significantly statistical difference.After 3 days,7 days,14 days,the wound healing rates of the experimental group were (21.95 ± 8.11)%,(56.25 ±4.96)% and (79.85 ±5.44)%,respectively and which were better than those of the control group[(12.11 ±4.87)%,(30.24 ±1.53)%,(58.51 ±6.52)%](t=4.693,3.853,2.559,all P <0.05). According to the grading standards of the healing skin after HE staining ,the experimental group was better than the control group .According to the results of Western blot , the KGF protein expression of the experimental group was higher than the control group .Conclusion The allogeneic bone marrow mesenchymal stem cells may be an effective and safe method for the wound in rats .

Objective To evaluate the effect of penehyclidine hydrochloride (PHC) on the level of angiopoietin-1 (Ang-1) and tyrosine kinase receptor-2 (Tie-2) during endotoxin-induced acute lung injury (ALI) in rats.Methods Forty adult male Sprague-Dawley rats,weighing 180-220 g,were randomly divided into 4 groups using a random number table (n =10 each):control group (group C),ALI group,low-dose PHC group (group L-PHC) and high-dose PHC group (group H-PHC).ALI was induced with iv injection of lipopolysaccharide 5.0 mg/kg via the tail vein.In L-PHC and H-PHC groups,PHC 0.6 and 2 mg/kg were injected,respectively,via the tail vein at 1 and 24 h after lipopolysaccharide injection.The rats were sacrificed at 48 h after the initial injection of PHC to measure the lung water content,protein concentration in bronchoalveolar lavage fluid (BALF),and the expression of Ang-1,Tie-2 and phosphorylated Tie-2 in lung tissues.The morphological changes of lung tissues were observed under light microscope and the ultrastructural changes of alveolar epithelial barrier under transmission electron microscope.Results Compared with group C,the lung water content and protein concentrations in BALF were significantly increased,and the expression of Ang-1 and phosphorylated Tie-2 was down-regulated in the other three groups (P ＜ 0.05).Compared with group ALI,the lung water content and protein concentrations in BALF were significantly decreased,and the expression of Ang-1 and phosphorylated Tie-2 was up-regulated in H-PHC group (P ＜ 0.05),and no significant changes were found in the parameters mentioned above in group L-PHC (P ＞0.05).The damage to lung tissues was significantly reduced in group H-PHC as compared with group ALI.Conclusion PHC can improve the permeability of pulmonary microvascular and reduce injury to alveolar epithelial barrier,thus ameliorating endotoxin-induced ALI in rats,and the effect is dose-related and up-regulation of Ang-1 expression and inhancement of Tie-2 activity are involved in the mechanism.

To observe different expression patterns of β-catenin and its clinical significance in colorectal cancer (CRC).Methods A total of 181 cases of CRC tissues and 30 cases of normal colorectal tissue were investigated by immunohistochemistry for the expression of β-catenin.Results The expression rate of β-catenin was 56.9％ (103/181) in CRC,and higher than that in normal colorectal tissue (P ＜ 0.05).The overexpression of nuclear β-catenin was significantly correlated with histological differentiation,lymph node metastasis and Dukes' stage in CRC (P ＜ 0.05),and no relationship with other pathological parameters,such as age,gender and the depth of infiltration.The incomplete membranous expression of β-catenin was significantly correlated with histological differentiation,the depth of infiltration,lymph node metastasis and Dukes' stage in CRC (P ＜ 0.05).The high expression of nuclear β-catenin related to histological differentiation and Dukes' stage in CRC (P ＜ 0.05).In the follow-up data of 82 cases of CRC,the expression of nuclear β-catenin was associated with poor prognosis,and the 5-year survival rate was significantly lower than that of self-control groups (P ＜ 0.05).Conclusion β-catenin plays important roles in colorectal carcinogenesis.Abnormal expression of β-catenin was related to the aggressive progression of CRC and may be helpful for evaluating the prognosis of patients with CRC.β-catenin is expected to become a new target for diagnosis and treatment of CRC in future.

Objective To determine the level of interleukin (IL)-10 in sera and culture supernatants of CD4+CD25+T cells from children with atopic dermatitis (AD),and to evaluate its relationship with clinical course and severity of AD.Methods Totally,46 children with AD and 31 healthy controls were included in the study.All the patients were divided into 3 groups,i.e.,mild (n =10),moderate (n =16) and severe (n =20) group,according to severity scoring of atopic dermatitis (SCORAD) score.Venous blood samples were obtained from the patients and healthy controls.CD4+CD25+ regulatory T cells were separated from the blood samples by magnetic cell sorting (MACS) system in two steps and cultured in vitro.Enzyme linked immunosorbent assay (ELISA) was conducted to quantify the level of IL-10 in sera and culture supernatants of CD4+CD25 + T cells from these subjects.Analysis of variance was carried out to compare the level of supematant and serum IL-10 between the patients and controls,and Pearson correlation analysis to assess the relationship between the level of IL-10 and SCORAD score.Results The patients with mild,moderate and severe AD showed a similar serum IL-10 level compared with the healthy controls ((43.10 ± 25.07) pg/ml,(68.40 ± 36.65) pg/ml and (55.55 ± 41.97) pg/ml vs.(58.27 ± 36.84) pg/ml,all P ＞ 0.05).The level of supernatant IL-10 secreted by CD4+CD25+ T cells from the controls was significantly higher than that from the patients with severe AD ((55.15 ± 11.15) pg/ml vs.(27.25 ± 7.01) pg/ml,P ＜ 0.05),but similar to that from the patients with mild and moderate AD ((52.96 ± 11.69) pg/ml and (49.86 ± 9.18) pg/ml,respectively,both P ＞ 0.05).The level of secreted IL-10 was negatively correlated with SCORAD score (r =－0.757,P ＜ 0.01),whereas the serum level of IL-10 showed no statistical correlation with SCORAD score.Conclusion CD4+CD25+ T cells and IL-10 may be implicated in the development of AD.

Objective To investigate the effect of dexmedetomidine on acute kidney injury in endotoxemic rats.Methods Thirty adult male Sprague-Dawley rats,aged 4-6 months,weighing 180-220 g,were randomly divided into 3 groups (n =10 each) using a random number table:control group (group C),lipopolysaccharide group (group L),and dexmedetomidine (group D).Lipopolysaccharide (LPS) 5 mg/kg was injected slowly into the femoral vein to establish the model of endotoxemic in rats anesthetized with chloral hydrate.In group D,after LPS injection,a loading dose of dexmedetomidine 7 μg/kg was injected intravenously,and 15 min later dexmedetomidine was infused for 6 h at 5 μg · kg-1 · h-1,while the equal volume of normal saline was given in L and C groups.At 6 h after the end of LPS administration,blood samples were collected from the femoral vein for determination of serum creatinine (Cr),blood urea nitrogen (BUN),tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) concentrations.At 24 h after the end of LPS administration,the animals were sacrificed and kidneys were removed for microscopic examination and for determination of the expression of tight junction proteins ZO-1 and occludin in renal tissues by Western blot.Results Compared with group C,the serum Cr,BUN,TNF-α and IL-6 concentrations were significantly increased,and the expression of ZO-1 and occluding was down-regulated in L and D groups.Compared with group L,the serum Cr,BUN,TNF-α and IL-6 concentrations were significantly decreased,the expression of ZO-1 and occluding was up-regulated,and the pathological changes of kidneys were mitigated in D group.Conclusion Dexmedetomidine can alleviate acute kidney injury in endotoxemic rats.

Heat shock protein 90(Hsp90)is a highly conserved protein which have been proved to play an important role in the development and progression of malignant transformation .As one of small molecule inhibi-tors that has been detected to have potent antitumor activity in a wide range of malignancies ,NVP-AUY922 is a pyrazole scaffold drug with many advantages such as low toxicity and stable structure .As a result of this,NVP-AUY922 is extensively considered as a new promising kind of anti -tumor drug .This review intends to update the reader on advances made over the past four years in the clinical development of NVP -AUY922 in advanced cancers.

Objective To evaluate the effect of dexmedetomidine on acute liver injury in rats with endotoxemia.Methods Eighteen adult male Sprague-Dawley rats, aged 3-4 months, weighing 250-300 g, were randomly divided into 3 groups (n=6 each) using a random number table: control group (group C), endotoxin group (group E), and dexmedetomidine group (group D).In E and D groups, lipopo-lysaccharide 5 mg/kg was injected via the femoral vein of rats anesthetized with chloral hydrate.In group D, dexmedetomidine was infused with a 7 μg/kg loading bolus over 15 min after injection of lipopolysaccharide, followed by a 6 h continuous infusion of 5 μg · kg-1 · h-1.The equal volume of normal saline was given instead in E and C groups.After the end of administration, blood samples from the femoral vein were drawn for determination of tumor necrosis factor-alpha (TNF-α) and interleukin-1β (IL-1β) concentrations in serum (by using enzyme-linked immunosorbent assay), and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities in serum (using the International Federation of Clinical Chemistry and Laboratory Medicine reference procedures).Liver specimens were obtained for examination of pathologic changes with electron microscope.Results Compared with group C, the serum ALT and AST activities and TNF-α and IL-lβ concentrations were significantly increased in E and D groups.Compared with group E, the serum ALT and AST activities and TNF-α and IL-1β concentrations were significantly decreased in group D.The pathologic changes of livers were obvious in group E, and were significantly reduced in group D compared with group E.Conclusion Dexmedetomidine can alleviate acute liver injury in rats with endotoxemia, and the underlying mechanism is associated with inhibition of systemic inflammatory responses.

Objective To discuss the nonoperative management strategy to prevent the conversion of acute pancreatitis to the severe form.Methods In recent 4 years,286 patients with mild acute pancreatitis admitted to our hospital were divided into control group and treatment observation group;routine conservative management was performed in control group,and the strategy of improving pancreatic microcirculation and preventing cell Ca~2+ overload and inhibiting pancreatic protease was added to the treatment observation group.Results Among the 144 patients with mild acute pancreatitis in control group,conversion to severe acute pancreatitis occurred in 20 patients,and 14 of the 20 patients with severe acute pancreatitis developed systemic complications.Among the 142 cases in treatment observation group,the conversion of mild to severe acute pancreatitis occurred in 8 patients,and 2 of the 8 patients developed systemic complications.Serum C-reactive protein levels and Balthazar CT severity index were significantly decreased at each time point in treatment observation group compared to control group.Conclusions In addition to routine management,improving pancreatic microcirculation,preventing cell Ca~2+ overload and inhibiting pancreatic protease might serve as a benificial strategy for preventing the progression of mild acute pancreatitis to the severe form.