Objective To investigate the correlation between Dishevelled protein expression and the proliferation and invasion of glioma cells.Methods 67 cases of brain glioma specimens were collected.The expression of Dishevelled protein was detected with immunohistochemical method.The immunoreactivity score (IRS) of Dishevelled protein,and proliferation index (PⅠ) and invasion index (Ⅱ) were measured and their correlations were analyzed.Results The positive rate of Dishevelled protein in glioma was 65.7 ％ (44/67).IRS,PⅠ and Ⅱ were 4.15±3.13,(30.93±17.92) ％,(20.38±13.36) ％,respectively.Both PⅠ and Ⅱ significantly increased with an increase in the pathological grade of brain glioma (P ＜ 0.001).Furthermore,PⅠ and Ⅱ were significantly higher in the Dishevelled protein-positive group than those in the Dishevelled protein-negative group [(38.27±17.60) ％ vs (16.02±8.92) ％ of PⅠ and (30.03±13.81) ％ vs (10.63±4.41) ％ of Ⅱ,respectively,P ＜ 0.001].PⅠ and Ⅱ of glioma cells were positively correlated with IRS of Dishevelled protein (r =0.940 between PⅠ and IRS,and r =0.953 between Ⅱ and IRS,respectively).Conclusion Dishevelled protein plays an important role in the proliferation and invasion of brain malignant glioma.

Atopic dermatitis (AD) is a chronic, relapsing, inflammatory dermatosis with a variety of clinical manifestations and difficult to cure. Currently, many AD drug candidates have entered the research and development pipeline. In order to provide technical specifications for the clinical development of AD drugs, the Center for Drug Evaluation of National Medical Products Administration released the "Technical Guidelines for Clinical Trials of Drugs for AD Treatment" (Draft for Comments) in November 2022. Non-clinical pharmacodynamics evaluation is an important research before the drug enters clinical trials. Oxazolone (OXA)- and 2,4-dinitro-fluorobenzene (DNFB)-induced models are the most popular classical hapten-induced AD murine models, but variations of modeling are existing in the methods from different studies, including sensitization sites, haptens' dosages, the period of challenges, and the skin lesions severity evaluation as well. In this study, the investigation of OXA- and DNFB-induced AD murine models with various conditions of modeling was performed to compare the characteristics of hapten-induced AD murine models in the pathological process and severity according to the appearance of AD patients, and the guidance of pharmacodynamics evaluation of AD-therapeutic drugs in clinical trials as well, which may provide a proposal for AD treatment drug candidates in the non-clinical pharmacodynamics evaluation. All animal experiments were approved by the Animal Care & Welfare Committee of Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College (approval No.: 00007782 and 00007784).

AIM: To observe the changes of polymorphonuclear leukocytes (PMN), neutrophil elastase (NE) and myeloperoxidase (MPO) expression in rat asthma. METHODS: Eighteen rats were randomly divided into two groups on average, including asthma group and control group. The rat model of asthma was established by the ovalbumin (OVA) challenge methods. Blood PMN were isolated and purified. The protein expression of MPO were detected by immunohistochemistry and chromatometry techniques. NE was detected by ELISA. RESULTS: (1) Immunohistochemistry showed that the levels of MPO expression around bronchus and in purified PMN in asthma group were significantly increased compared with those in control group (P

Aim To observe the effects of tetrahydro-biopterin ( BH4 ) on nitric oxide ( NO ) production in the kidney of type 2 diabetic nephropathy ( DN) mice, and to find a new target for the treatment of type 2 DN. Methods The 12 week-old db/db mice developed in-to DN phase were divided into 2 groups:DAHP group, subjected to intraperitoneal injection of 150 mg·kg-1 DAHP (n=8);DN group, subjected to intraperitone-al injection of same dose of normal saline containing 5% DMSO ( n = 6 ) . The age-matched db/m mice ( NS group) were subjected to intraperitoneal injection of same dose of normal saline containing 5% DMSO ( n =6 ) . Three groups of mice were treated for 7 days. Then the fasting blood-glucose, serum creatinine, u-rine protein and activity of iNOS were determined by chemical colorimetry. And the iNOS protein in renal cortex was determined by immunohistochemisty and western blot, respectively. BH4 was measured by HPLC method. NO level was determined by Griess method. Results The levels of fasting blood-glucose, serum creatinine, 24h urine volume, 24h urine pro-tein, BH4 , iNOS and NO in DN group were signifi-cantly higher than those in NS group;The levels of ser-um creatinine, urine volume, urine protein, BH4 , iN-OS and NO in DAHP group were significantly lower than those in DN group. Conclusion In the kidney of type 2 DN mice, the increased BH4 contributes to over-production of NO by the increased iNOS expression, and resultes in the increase of urine volume and urine protein.

Objective To validate the feasibility of the simulationmethod and the reliability of thesimulationresult through comparison between simulation and measurement of the energy spectrum from medical diagnostic X-ray (RQR-Radiation qualities in radiation beans emerging from the X-ray source assembly).Methods A simplified model of the medical diagnostic X-ray RQR radiation quality was established using code of BEAMnrc.The energy spectrum of the same RQR radiation quality were measured through a plane high-purity germanium spectrometer,and compared with the simulationresult.Results The difference of spectral distribution between measurement and simulation was less than 3％,in spite of the convolution processing not happened to the pulse height distribution measured by the spectrometer.And the spectral distribution,fluence,energy fluence,means energy distribution of the radiation was obtained using the code of BEAMDP.Conclusions As indicated above,it is possible to use the simulation of the energy distribution as a foundation for the establishment of X-ray RQR radiation quality.

Objective To investigate the effects of the microbubbles combined with different mechanical index ultrasound irradiation on ultrastmcture and migration of colon cancer cells.Methods The experimental study was conducted.Colon cancer cells inn vitro (Lovo ceils) were cultured and divided into 4 groups,ceils in the A group were not treated and cells in the B,C and D groups were treated by microbubbles combined with different mechanical index ultrasound irradiation (mechanical index were 0.20,0.80 and 1.45).The changes of ultrastructure and migration of cells were observed using laser scanning confocal microscope and MilliceIl-PCF cell culturechamber method,respectively.Measurement data with normal distribution were represented as (x)±s.Comparisons among groups were analyzed by the one-way ANOVA.Pairwise comparisons were done by the t test.Results (1)Effects of the microbubbles combined with different mechanical index ultrasound irradiation on ultrastructure of Lovo cells:Lovo cells in the A group showed big nucleus,less plasma,regular arrangement,jagged-like or more irregular varicosity surrounding nucleus,twisted euchmmatin,expansion of nucleus cisternal space,homogeneous distribution and normal development of granular soil and clear mitochondrial ridge-like structures.Lovo cells in the B group showed big nucleus with regular arrangement,obvious nucleolus margination,endoplasmic reticulum dilatation,normal development of mitochondrion and clear mitochondrial ridge-like structures.Lovo cells in the C group showed broadening nucleus space,abnormal nucleus with karyopycnosis,chromatin condensation,a few remaining or obvious dilatation of rough endoplasmic reticulum,typically consisting of different fragments or bubbles,cytoplasmic vacuoles changes and decreasing mitochondrial ridge-like structures.Lovo cells in the D group showed big and irregular nucleus,nucleolus margination,obvious endoplasmic reticulum dilatation,fewer mitochondrion with extended cell area and swelling shape,rare mitochondrial ridge-like structures with disordered or broken arrangement,even disappearing.(2) Effects of the microbubbles combined with different mechanical index ultrasound irradiation on migration of Lovo cells:Millicell-PCF cell culture chamber method showed that number of migration of Lovo cells were respectively 63±7,61±4,21±3 and 19±5 in the A,B,C and D groups,with a statistically significant difference (F=55.040,P＜0.05).There were no statistically significant difference in migration of Lovo cells between group A and B (t =1.571,P＞0.05) and between group C and D (t =2.013,P＞0.05).There were statistically significant differences in migration of Lovo cells between group A and C or D (t=7.861,10.652,P＜0.05) and between group B and group C or D (t=7.161,10.453,P＜0.05).Conclusion Microbubbles combined with high mechanical index ultrasound irradiation can make the ultrastructural alterations in the cancer cells,resulting in tumor cell degeneration and death,ultimately inhibit tumor cell migration and metastasis.

Objective To investigate the correlation between the serum resistin level and carotid artery atherosclerosis in elderly Chinese males. Methods The study enrolled 235 elderly Chinese males [median age 76 (range 60-97) years] scheduled for ultrasound examination of carotid artery plaque and determination of carotid artery intima-media thickness (CIMT). They were divided into carotid atherosclerotic plaque (CAP) and carotid atherosclerotic plaque-free (CAP-free) groups according to the ultrasound results. Their clinical profiles were col-lected, and the serum resistin and other blood biochemistry levels were determined.Results The CAP group was older and had a thicker mean CIMT than the CAP-free group. However, there was no difference in the serum resistin level between the groups. CIMT was positively correlated with age (r = 0.299,P< 0.001). The serum resistin level was not correlated with CIMT, even after controlling for age. Multiple linear regression analysis revealed that age (β = 0.001,P< 0.001) and body mass index (β = 0.002,P= 0.015) were significantly and posi-tively correlated with the mean CIMT. Only age [odds ratio (OR): 1.159; 95% confidence interval (CI): 1.078-1.183,P< 0.001] was associ-ated with the presence of carotid artery atherosclerotic plaque. The serum resistin level was not correlated with the mean CIMT or associated with the presence of carotid artery atherosclerotic plaque.Conclusion The results suggest that resistin might not be a risk factor for atherosclerosis in elderly Chinese males.

Objective Overexpressions of epidermal growth factor(EGF)and EGF receptor have been associ- ated with progression and invasive phenotype of pancreatic cancer.However,the underlying molecular mechanism by which EGF worked in pancreatic cancer cells has not been completely understood.In this study,effect of EGF on the invasion and metastasis of pancreatic cancer cells and its regulatory mechanism were investigated.Methods The effects of EGF on the proliferation,adhesion and invasion of pancreatic cancer cells were detected by WST-1 prolif- eration assay,adhesion assay and invasive assay,respectively.The activity and expression of MMP-2 and MMP-9 were examined by zymography,Western blot and RT-PCR,respectively.The activity of NF-?B was examined by EMSA.Results EGF could significantly promote the invasiveness of pancreatic cancer cells but did not affect cell proliferation or adhesion.The expressions of NF-?B and MMP-9 were significantly increased by EGF,but EGF did not affect the activity and expression of MMP-2.Furthermore,EGF stimulated the NF-?B binding activity.Pre- treatment with NF-?B inhibitors,pyrrolidine dithiocarbamate(PDTC),could significantly inhibit the activity of NF-?B induced by EGF.Meanwhile,the EGF-induced expression and activity of MMP-9,as well as cell invasiveness were also inhibited by NF-?B inhibitor.Conclusion EGF could increase the expression and promote the invasiveness of MMP-9 via the activation of NF-?B in pancreatic cancer cells,which implies that NF-?B inhibitant,such as PDTC,may diminish the invasiveness of pancreatic cancer cells.

ObjectiveTo evaluate the effects of intranasal administration of recombinant interleukin-17A(rIL-17A) on the expressions of β-Defensin-2(Defb2) and macrophage inflammatory protein(MIP) in pneumococcal pneumonia murine models.MethodsTwenty-four BALB/c mice were divided randomly into normal control,pneumococcal pneumonia,and rIL-17A intervention groups ( n =8 ).Before intranasal (i.n) infection with Streptococcus pneumoniae,the mouse was treated with PBS or rIL-17Ai.n respectively.The mRNA levels of Defb2,MIP-1α and MIP-2β expression in lung tissue were detected by real-time quantity PCR.The numbers of bacteria and leukocytes in bronchoalveolar lavage fluid (BALF) were counted as well.And the concentrations of MIP-1α,MIP-2β,IFN-γ and IL-4 in BALF and in supematants of spleen cells and mediastinal lymph node cells were assayed by ELISA.Changes in lung tissue histopathology were observed with HE staining through light microscope.ResultsNeutrophil and macrophage numbers are higher in BALF of rIL-17A group,while the numbers of bacteria were lower,when compared with those in pneumonia group( P＜0.01 ).The expression of Defb2 and MIP-1α mRNA were up-regulated in lung after rIL17A treatment(P＜0.01 ).When compared with rIL-17A non-treated mice,rIL-17A treated mice secretedhigher levels of MIP-1α in lymph node cell culture supernatants( P＜0.01 ),higher levels of MIP-2β were observed in spleen cell and lymph node cell culture supernatants( P＜0.01 ),higher levels of IFN-T were detected in BALF( P ＜ 0.01 ) and culture supernatants of spleen cell ( P ＜ 0.01 ) and lymph node cell ( P ＜0.05),and higher levels of IL-4 were detected in BALF and spleen cell culture supernatant(P＜0.01 ).Comparative analysis have not detect a significant irflammatory cell increases in rIL-17A treated mice lung tissue; however the histopathological lesions were decreased.ConclusionIntranasal inoculation of rIL-17A can promote pulmonary neutrophil and macrophage recruitment and bacterium clearance,Intranasal inoculation of riL-17enhances the host defense against Streptococcus pneumoniae infection partly through increasing the expression levels of defensins,MIP,IFN-T and IL-4 etc.

Objective To investigate the indications, techniques and results of laparoscopic hepatectomy. Methods The clinical data and follow-up results of 463 patients who received laparoscopic hepatectomy at our institute were retrospectively analyzed. Results From March 1, 2007 to March 31, 2011, 463 cases of laparoscopic hepatectomy were successfully carried out. Of the 463 patients,165 were with primary liver cancer, 29 with metastatic liver cancer, 143 with hepatic hemangioma, 81with hepatolithiasis and 45 with other benign liver diseases (including hepatic angiomyolipoma, hepatocellular adenoma, focal nodular hyperplasia and chronic liver abscess). The surgical approaches included laparoscopic left lateral lobectomy (93 cases), left hepatectomy (71 cases), extended left hepatectomy (4 cases), right hepatectomy (29 cases), right posterior lobectomy (24 cases), hepatectomy of segment Ⅵ (56 cases), extended right hepatectomy (2 cases), central hepatectomy (8 cases) and hepatectomy of segments Ⅶ/Ⅷ, Ⅳa, caudate lobe and the junction of segment Ⅵ and Ⅶ (41 case).Nonanntomic and wedge resection were performed on 121 patients, and combined resection on 14 patients. The mean operation time, blood loss, length of hospital stay and incidence of postoperative complications were (244.71 ± 105. 07) minutes, (460. 26±425.81) ml, (15.51 ±4.36) days and 9.29%, respectively. And no operative death occurred. In the 194 cases with malignant liver lesions,185 cases were followed up for 2 to 50 months. The 1 year and 3 year overall and disease free survival rate were 90. 8% and 87.9% , 84.2% and 73. 7% respectively. Conclusions As a means of minimally invasive surgical approach, laparoscopic hepatectomy can be selectively adopted for the treatment of all kinds of liver diseases which located at different parts of the liver, with the advantages of smaller trauma, quick recovery and cosmetic benefits. The short-term results of laparoscopic hepatectomy is superior to and its long-term results is equal to that of open surgery. Benign liver diseases, small hepatocellular carcinoma and metastatic liver cancer are the good indications for laparoscopic hepatectomy.