Purpose:To study the expression of CD44v6 protein in breast carcinoma and its prognostic significance. Methods:100 cases of formalin-fixed paraffin-embeded female breast invasive ductal carcinoma tissues were retrospectively analyzed using EnVision~(TM) immunohistochemical method with the monoclonal antibody CD44v6.Statistical analysis was based on the Log-rank test and Cox analysis.Results:Sixty-six of 100 cancer tissues expressed CD44v6.Positive staining was mainly on the cell membranes.There was significant correlation between CD44v6 immunoreactivity and lymph node me- tastasis and TNM stage.The 5-and 10-year survival rates were 82.76% and 78.37% of patients with CD44v6 low-expres- sion tumors,and 64.1% and 49.88% of those with CD44v6 high-expression tumors,respectively;the difference between the two groups of patients was significant(P

OBJECTIVETo observe the effects of Mongolian pharmaceutical Betel shisanwei ingredients pill on AC-cAMP-PKA signal transduction pathways in hippocampus and prefrontal cortex of depressive rats.

METHODSixty male Wistar rats were randomly divided into six groups according to the sugar consumption test (10 rats in each group), normal control group,model group,fluoxetine group (3.3 mg x kg(-1)) and low dose, medium dose and high dose group (0.25, 0.5, 1 g x kg(-1)) of Betel shisanwei ingredients pill. Except the normal control,the other groups were treated with the chronic unpredictable mild stress stimulation combined with lonely raising for 28 days. 10 mL x kg(-1) of drugs were given to each rat once daily,continuously for 28 days. The AC activity of the hippocampus and prefrontal cortex were determined by radiation immunity analysis (RIA), while cAMP and PKA quantity were determinated by Enzyme-linked immunosorbent (ELISA).

RESULTThe AC activity, cAMP and PKA quantity of hippocampus and prefrontal of mouse model of Chronic stress depression decreased significantly than those of control group (P < 0.05 or P < 0.01). However, the AC activity, cAMP and PKA quantity of rat hippocampus and prefrontal cortex in the fluoxetine group and the Mongolian pharmaceutical Betel shisanwei ingredients pill group indecreased significantly than those of model group (P < 0.01 or P < 0.05). Especially for the high dose group of Mongolian pharmaceutical Betel shisanwei ingredients pill.

CONCLUSIONThe AC-cAMP-PKA signal transduction pathways in hippocampus and prefrontal cortex of depression model of rats is down-regulated, whereas Mongolian pharmaceutical Betel shisanwei ingredients pill could up-regulated it to resist depression.

Adenylyl Cyclases ; genetics ; metabolism ; Animals ; Cyclic AMP ; metabolism ; Cyclic AMP-Dependent Protein Kinases ; genetics ; metabolism ; Depression ; drug therapy ; genetics ; metabolism ; Drugs, Chinese Herbal ; administration & dosage ; Hippocampus ; drug effects ; metabolism ; Humans ; Male ; Mice ; Prefrontal Cortex ; drug effects ; metabolism ; Rats ; Rats, Wistar ; Signal Transduction ; drug effects

Objective To explore the present condition of endemic arsenism, the implementation of control measures and the effect of the monitored county (Tongyu County) and the monitoring spot (Baiyintuhai Village) in 2006 and 2007. Methods According to the National Survey Scheme of Endemic Arsenism, the progress of anti-arsenic water in Tongyu, and the management and running of all engineering projects and the arsenic content in water were surveyed. The patients with endemic arsenism in Tongyu were generally surveyed. The arsenic content of the improved drinking water in Tongyu and the arsenic in urine of children aged 8-12 and adults over 18 years of age were determinted. The causes of resident death in the monitoring spot from the year of 2006 and 2007 were investigated. Arsenic content of drinking water and the urine of local residents was examined with "Model AFS-930 Double-Channel Atomic Fluorescence Spectrometer". Results There were 30 endemic arsenism areas, 157 areas with high arsenic content and all population of 57 576 in Tongyu. Six areas had improved water till 2006, where 20.0% of water had improved, and six water-improving projects were all running normally, benefiting a population of 1670. Eight high arsenic areas changed water, in a rate of 5.09%. Eight water-improving projects were functioning well, benefiting a population of 4350. Until 2007, 28 areas had improved water in Tongyu, accounting for 93.33%. These 28 projects were well running, covering a population of 7980. One hundred and fouty-eight high arsenic areas had changed water, reaching a rate of 94.27%. One hundred and fouty-eight projects changedg water were running normally, benefiting a population of 46 214. In the surveyed spots, arsenic content was between 0.004 mg/L and 0.005 mg/L in 2006 and between 0.010 mg/L and 0.021 mg/L in 2007, all in the normal range to the time being. The arsenic contents in urine of the children aged 8-12 in the monitoring spots were determinted, averaging at 0.024 mg/L in 15 samples, fluctuating between 0.005 mg/L and 0.048 mg/L in 2006. The average content in urine from adults was 0.019 mg/L in 53 samples, fluctuating between 0.005 mg/L and 0.087 mg/L in 2007. The arsenic contents in urine were all in the normal range in 2006 and 2007. In 2006 14 endemic arsenism patients, all in light symptoms, had been checked out, the morbidity being 6.19%. In 2007, 17 patients who were all in light symptoms were identified in a rate of 6.94%. There was no significant difference of morbidity between the two years(χ2=0.1059, P>0.05). Two patients died, unrelating with drinking high arsenic water in 2006 and 2007. Conclusions The prevention and control measures are well implemented in Tongyu. The water-improving projects are functioning well. The condition of endemic arsenism is slight and hasn't changed so much in these two years. The arsenic contents in urine of children and adults within the normal range, showing that improving water can control the occurrence and the development of endemic arsenism.

BACKGROUNDThe lung functional status could be displayed on lung perfusion images. With the images, the radiotherapy plans of lung cancer could be guided to more optimized. This study aimed to assess quantitatively the impact of incorporating functional lung imaging into 3-dimensional conformal radiotherapy (3DCRT) and intensity-modulated radiation therapy (IMRT) planning for non-small cell lung cancer (NSCLC).

METHODSTen patients with NSCLC who had undergone radiotherapy were included in this study. Before radiotherapy, each patient underwent CT simulation and lung perfusion imaging with single photon emission computed tomography (SPECT). The SPECT images were registered with simulation planning CT and used to contour functional lung (lung-F) and non-functional lung (lung-NF). Two 3DCRT plans and two IMRT plans were designed and compared in each patient: two anatomic plans using simulation CT alone and two functional plans using SPECT-CT in addition to the simulation CT. Dosimetric parameters of the four types of plans were compared in terms of tumor coverage and avoidance of normal tissues. Total radiation dose was set at 66 Gy (2 Gy x 33 fractions).

RESULTSIn incorporating perfusion information in 3DCRT and IMRT planning, the reductions on average in the mean doses to the functional lung in the functional plan were 168 cGy and 89 cGy, respectively, compared with those in the anatomic plans. The median reductions in the percentage of volume irradiated with > 5 Gy, > 10 Gy, > 20 Gy, > 30 Gy and > 40 Gy for functional lung in the functional plans were 6.50%, 10.21%, 14.02%, 22.30% and 23.46% in 3DCRT planning, respectively, and 3.05%, 15.52%, 14.16%, 4.87%, and 3.33% in IMRT planning, respectively. No greater degree of sparing of the functional lung was achieved in functional IMRT than in 3DCRT.

CONCLUSIONFunction-guided 3DCRT and IMRT plannings both appear to be effective in preserving functional lung in NSCLC patients.

Carcinoma, Non-Small-Cell Lung ; diagnostic imaging ; pathology ; radiotherapy ; Humans ; Radiography ; Radiotherapy, Conformal ; methods ; Radiotherapy, Intensity-Modulated ; methods ; Tomography, Emission-Computed, Single-Photon ; methods

OBJECTIVETo investigate the impact of PET/CT on the clinical staging, target volume delineation and precise radiotherapy (PAR) planning for patients with non-small cell lung cancer (NSCLC).

METHODSPET/CT scanning was performed in 58 histologically proven NSCLC patients for radical radiotherapy or surgery. The clinical staging of all patients was determined by PET/CT according to 1997 World Health Organization (WHO) staging system. The gross tumor volume (GTV) was delineated and three-dimensional conformal radiotherapy (3D-CRT) planning was established with identical parameters based on CT image and PET/CT fused image, respectively. The indexes including volume of GTV (V(GTV)), percentage of the total lung volume which received more than 20 Gy (V(20)), mean lung dose (MLD), tumor control probability (TCP), normal tissue complication probability (NTCP), and dose to spinal cord (Ds) were selected and evaluated. The quality of the two plans and the impact of PET/CT on PAR planning was compare and analyzed.

RESULTS1. PET/CT image results changed the clinical stages in 21 of 58 (36.2%) patients with 14 upstaged and 7 downstaged, therefore, the management decisions were modified in 16 (27.6%) patients. 2. Among 32 patients who underwent surgery, PET/CT staging result was consistent with pathologic staging in 29 with one false negative and 2 false positive in lymph node staging. The sensitivity of PET/CT was 96.9% and accuracy 90.6%. 3. The differences of indexes including V(GTV) (P = 0.004), V(20) (P = 0.000) and MLD (P = 0.004) between the two radiotherapy plannings were statistically significant, whereas, the Ds, TCP and NTCP (left lung, right lung, skin and spinal cord) was not.

CONCLUSION1. The impact PET/CT on clinical staging of NSCLC and PAR planning was remarkable. 2. PET/CT is more consistent with pathology in staging than CT and, therefore, is an important compensatory staging measure. 3. Compared with CT, PET/CT can reduce the V(GTV) in patients with atelectasis and obstructive pneumonitis when contouring the target volume, so can provide better protection for normal surrounding lung tissue. On the other hand, PET/CT is more sensitive in detecting mediastinal lymph node metastasis than CT, and the V(GTV) can be more precise and guaranteed. 4. Radiopneumonitis may be more effectively prevented because of significant decrease in V(20) and MLD by more precise planning based on PET/CT results. 5. PET/CT not only can provide satisfactory Ds, TCP and NTCP within clinical demand, but also more precise delineation of the radiation target volume and precise radiotherapy planning for NSCLC.

Adult ; Aged ; Aged, 80 and over ; Carcinoma, Non-Small-Cell Lung ; diagnostic imaging ; pathology ; radiotherapy ; surgery ; Female ; Humans ; Lung Neoplasms ; diagnostic imaging ; pathology ; radiotherapy ; surgery ; Male ; Middle Aged ; Neoplasm Staging ; Positron-Emission Tomography ; methods ; Radiotherapy Dosage ; Radiotherapy Planning, Computer-Assisted ; Radiotherapy, Conformal ; methods ; Tomography, X-Ray Computed

OBJECTIVETo look for the evidences of motilin receptor expression on interstitial cells of Cajal (ICC) of the rabbit.

METHODSmooth muscle segments with ICC were isolated from the small intestine of 10-day old rabbits. The tissue segments equilibrated in Ca(2+)-free Hanks' solution were dispersed with an enzyme solution containing collagenase type II and then Ficoll density centrifugation was used to dissociate ICC. The cells were suspended and cultured in the M199 medium. The c-kit antibody was applied to distinguish the cultured ICC. The motilin receptor was identified by immunocytochemical assay with GPR38 antibody, c-kit antibody and hoechst 33342 combined to label ICC. Cells cultured for a few days were sorted for ICC with c-kit stained green fluorescent through flow cytometry. The total RNA and proteins extracted from the sorted ICC were respectively used to verify motilin receptor on the ICC by reverse-transcriptase polymerase chain reaction (RT-PCR) and Western blotting.

RESULTWe had successfully dissociated and cultured ICC of rabbit small intestine in vitro. Fluorescent staining with c-kit antibody confirmed that the culture ICC was successful. Triple-labeled immunofluorescent staining had detected the motilin receptor on membrane of ICC. Flow cytometry analysis showed that the ratio of c-kit positive cell in the cultured cells was 64.3%. The number of sorted ICC was 6.7 × 10(5) and 5.6 × 10(6). The results of RT-PCR and Western blot confirmed that the ICC had motilin receptor expression.

CONCLUSIONOur study demonstrated presence of motilin receptor on ICC of the rabbit. The present results may suggest that ICC play an important role in gastrointestinal movement induced by motilin.

Animals ; Cells, Cultured ; Interstitial Cells of Cajal ; metabolism ; Intestine, Small ; cytology ; Rabbits ; Receptors, Gastrointestinal Hormone ; metabolism ; Receptors, Neuropeptide ; metabolism

BACKGROUNDResearches in arterial elasticity have increased over the past few years. We investigated the effects of simvastatin on vascular stiffness in fat fed rabbits by ultrasonography.

METHODSThirty rabbits were assigned randomly to 3 groups: normal control group (A), the cholesterol group (B), simvastatin group (C: high fat diet for 4 weeks and high fat diet + simvastatin for further 4 weeks). Stiffness coefficient, pressure strain elastic modulus and velocity of pulse waves in abdominal aorta and femoral artery were measured by ultrasonographic echo tracking at the end of the 4th and the 8th weeks.

RESULTSAt the end of the 4th week, stiffness coefficient, pressure strain elastic modulus and pulse wave velocity of femoral artery were significantly increased in group B compared with those in group A. Similarly, at the end of the 8th week, the same parameters of abdominal aorta were significantly increased in group B compared with those in group A. In contrast, stiffness coefficient, pressure strain elastic modulus and pulse wave velocity of femoral artery were significantly decreased in group C compared with those in group B, however, there was no significant difference in parameters of abdominal aorta between groups B and C.

CONCLUSIONShort term administration of simvastatin can improve the elasticity of femoral artery but not abdominal aorta.

Animals ; Anticholesteremic Agents ; therapeutic use ; Aorta, Abdominal ; drug effects ; Blood Flow Velocity ; drug effects ; Dietary Fats ; adverse effects ; Femoral Artery ; drug effects ; Rabbits ; Random Allocation ; Simvastatin ; therapeutic use

BACKGROUNDPrevious reports have confirmed that edaravone has protective effects against ischemia-reperfusion (IR) injury of many organs. In this study, we investigated the effect of edaravone on preventing IR injury of the lung in a canine lung transplantation model.

METHODSTwelve weight-matched pairs of random-bred dogs were randomized into two groups. Within each pair, one dog served as donor and the other as recipient. In the study group, prostaglandin E1(PGE1)(8 microg/kg) was injected into the donor pulmonary artery (PA) before occlusion and the donor lungs were flushed with 1.0 L of LPD solution containing edaravone (10 mg/kg) and stored in the same LPD solution at a temperature of 1 degrees C for 8 hours. The left single lung transplantation was then performed and recipients received intravenous injection with edaravone (10 mg/kg) at the onset of reperfusion. In the control group, edaravone was substituted by the same volume of sterile saline solution. Another six dogs were obtained as normal control group in which left lungs were dissected after thoracotomy without an IR injury. One hour after reperfusion, or after dissection of the left lung, the right lung was excluded from perfusion and ventilation after which, cardiopulmonary parameters were measured. Wet/dry ratios, malondialdehyde (MDA) and myeloperoxidase (MPO) levels were assessed and histological analysis of lung tissue performed at the same time.

RESULTSAll animals survived until the end of the experiment. The study group showed significantly decreased wet/dry ratios (treated: (74.1 +/- 4.2)% vs control: (86.8 +/- 5.2)%, P < 0.01), MDA levels (treated: 0.50 +/- 0.08 vs. control: 0.88 +/- 0.15, P < 0.01) and MPO activity (treated: 0.23 +/- 0.05 vs. control: 0.43 +/- 0.07, P < 0.01) compared to the control group two hours after occlusion of the right side. In the control group, pulmonary vascular resistance (PVR) was increased markedly and arterial oxygen partial pressure deteriorated significantly after exclusion of the right side compared to those in the treatment group.

CONCLUSIONSEdaravone attenuates IR-induced lung injury and preserves lung function by inhibiting oxidative stress and decreasing leukocyte extravasation in a canine lung transplantation model.

Animals ; Antipyrine ; analogs & derivatives ; pharmacology ; therapeutic use ; Disease Models, Animal ; Dogs ; Lipid Peroxidation ; Lung ; metabolism ; pathology ; Lung Transplantation ; adverse effects ; Nitric Oxide ; biosynthesis ; Oxidative Stress ; drug effects ; Peroxidase ; metabolism ; Reperfusion Injury ; prevention & control

BACKGROUNDA novel anti-rheumatic drug, T-614, has been shown to have an anti-inflammatory effect and to improve abnormal immunological findings in rheumatoid arthritis (RA). To assess the safety and efficacy of T-614 versus placebo in patients with active RA we conducted a 24-week clinical study in 280 Chinese patients.

METHODSIn a multicenter, randomized, double blind, placebo controlled study, 280 patients were randomly assigned to receive placebo (n = 95) or T-614 at 50 mg (n = 93) or 25 mg (n = 92) daily. Active disease was defined by 4 of the following 5 criteria: >or= 5 tender joints, >or= 3 swollen joints, morning stiffness lasting for >or= 60 minutes, and Westergren erythrocyte sedimentation rate (ESR) >or= 28 mm/h, the assessment of pain at the rest by patient as moderate or severe. Clinical and laboratory parameters were analyzed at baseline, 2, 4, 6, 12, 18 and 24 weeks. The primary efficacy variable at week 24 was the American College of Rheumatology (ACR) response rate using the intent-to-treat population.

RESULTSThe ACR response rate was significantly higher in the T-614 treatment group compared with the placebo group within 8 weeks after the initiation of treatment. After 24 weeks, the 25 mg/d and 50 mg/d dosage groups and the placebo group showed 39.13%, 61.29% and 24.21% in ACR20 and 23.91%, 31.18% and 7.37% in ACR50, respectively. A time-response in ACR response was observed, with clear superiority for the 25 mg/d and 50 mg/d dosage groups compared to placebo (P < 0.0001), and the 50 mg/d dose compared to the 25 mg/d dose (P < 0.05) when using the ACR response analyses after 24 weeks. ESR and c-reactive protein (CRP) were significantly different in the treatment groups after 24 weeks. The incidence of adverse events (AEs) was not significantly higher with T-614 than with placebo, but upper abdominal discomfort, leucopenia, elevated serum alanine aminotransferase (sALT), skin rash and/or pruritus were more common in the 50 mg and 25 mg dosage groups.

CONCLUSIONT-614, a new slow-acting drug, is effective in treatment of rheumatoid arthritis and is well tolerated.

Adult ; Aged ; Antirheumatic Agents ; therapeutic use ; Arthritis, Rheumatoid ; drug therapy ; Benzopyrans ; adverse effects ; therapeutic use ; Double-Blind Method ; Female ; Humans ; Male ; Middle Aged ; Sulfonamides ; adverse effects ; therapeutic use

BACKGROUNDTelbivudine, one of the five nucleos(t)ide antiviral drugs, was reported to be superior to lamivudine in a better biochemical, virological, and histological response for treatment-naive patients in the GLOBE trial. The aim of this study was to determine the antiviral potency, viral resistance, and the signifcance of early response for long-term telbivudine treatment.

METHODSWe recruited 161 patients of chronic hepatitis B (CHB) on telbivudine between January 2009 and September 2011 in Macau, China. The serum hepatitis B virus DNA levels, hepatitis B e antigen (HBeAg) seroconversion, alanine aminotransferase (ALT) normalization, and viral resistance were analyzed.

RESULTSThe median age and follow-up duration were 48 years and 16.9 months. All patients were followed up for at least 6 months, while data were collected for 132, 120, 95, and 53 patients at 12, 24, 48, and 96 weeks respectively. The cumulative HBeAg seroconversion rate was 20.8% and only three patients (1.9%) presented with telbivudine low level resistance. The ALT normalization rates were 76.9% at 48 weeks and 77.6% at 96 weeks. Undetectable HBV DNA was achieved by 1.8%, 31.6%, 60%, and 74.1% in HBeAg positive patients and 29.3%, 60.3%, 84%, and 84.6% in HBeAg negative patients at each time point. Week 12 HBV DNA level < 1000 copies/ml (< 200 IU/ml) was a better predictor of viral suppression at 2-year follow-up (P = 0.001, OR = 27.00) than undetectable HBV DNA level at week 24 (P = 0.120, OR = 4.81).

CONCLUSIONSTwo-year telbivudine treatment yielded high rates of viral suppression and ALT normalization. Serum HBV DNA level at week 12 is a superior predictor for long-term viral suppression.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Alanine Transaminase ; blood ; Antiviral Agents ; therapeutic use ; DNA, Viral ; blood ; Drug Resistance, Viral ; Female ; Hepatitis B, Chronic ; drug therapy ; virology ; Humans ; Male ; Middle Aged ; Thymidine ; analogs & derivatives ; therapeutic use ; Time Factors