Abstract: The activities of four CYP450 enzymes (CYP3A, 1A2, 2El and 2C) and the mRNA expression levels of CYP1A2, 2El, 2Cll and 3A1 in rat liver were determined after Wistar rats were orally administered with brucine (BR) at three dosage levels (3, 15 and 60 mg.kg-1 per day) and the high dose of BR combined with glycyrrhetinic acid (GA, 25 mg.kg-1 per day) or liquiritin (LQ, 20 mg.kg-1 per day) for 7 consecutive days. Compared with the control, brucine caused 24.5% and 34.6% decrease of CYP3A-associated testosterone 6beta-hydroxylation (6betaTesto-OH) and CYP2C-associated tolbutamide hydroxylation (Tol-OH), respectively, and 146.1% increase of CYP2El-associated para-nitrophenol hydroxylation (PNP-OH) at the high dose level. On the other hand, (BR+GA) caused 51.4% and 33.5% decrease, respectively, of CYP2El-associated PNP-OH and CYP1A2-associated ethoxyresorufin-O-de-ethylation (EROD) as compared with the high dose of BR group. Meanwhile, (BR+LQ) caused 41.1% decrease of CYP2El-associated PNP-OH and 37.7% increase of CYP2C-associated Tol-OH. The results indicated that the co-administration of BR with GA or LQ had effect on mRNA expression and activities of the CYP450 enzymes mentioned above to some extent, and the in vivo antagonism of LQ on BR-induced CYPs adverse effects and the in vivo inhibitory action of GA on CYP2E1 and 1A2 might play an important role in the detoxification of Radix Glycyrrhizae against Strychnos nux-vomica L.

Objective To assess the feasibility of applying intensity-modulated radiotherapy(IMRT)simultaneous integrated boost(SIB)to replace conventional radiotherapy(CR)plus brachytherapy of whole pelvis in locally advanced cervical eaneer(LACC).Methods Five LACC patients based difference position of uterus were chosen and worked out CR and IMRT SIB plans respectively.Dose distributions were compared between IMRT SIB and CR.Results When uterus was in ante-,neutral-,retro-pnsition and deviation respectively,IMRT SIB could provide enough and homogeneous dose distribution for target volume and reduce irradiated volumes and doses for organs at risk(recta,bladder and small intestine)than CR.The doses of the A,B,and fundus of uterus were higher in IMRT SIB than CR.However,in ease of small intestine was close to or encircled the uterus,the targets volume dose would be inadequacy.Conclusions LACC IMRT SIB's dose distribution is better than CR(except excess ante-position)and may help to treat those patients who couldn't be suitable with brachytherapy.

Objective To analyze MRI findings of the mitochondrial encephalopathy, in order to improve the understanding of this disease. Methods MR findings of 5 patients of clinically proved mitochondrial encephalopathy were retrospectively analyzed. Results Brain parenchymal lesions in all patients were low intensity on T1WI and high signal intensity on T2WI. One patient had bilateral globus pallidus involvement, while involvement of gray matter and white matter were observed in 4 patients. Three patients had enlargement of supratentorial ventricles, 2 patients had cerebellar atrophy and 1 patient had bilateral basal galia calcification. Conclusion MRI can show the intracranial lesions in patients with mitochondrial encephalomyopathy clearly, but accurate diagnosis should depend on clinical data.

The clinical features of 17 patients with benign urachal masses and 30 patients with urachal carcinoma treated at Sun Yat-sen University Cancer Center were analyzed retrospectively.Univariate analysis indicated that seven parameters differed significantly between the two groups.Binary logistic regression analyses showed that the rate of gross hematuria was significantly higher (P =0.042,Exp[B] =7.889) and the rate of fatty infiltration of the Retzius space was significantly lower (P =0.006,Exp[B] =0.028) in patients with urachal carcinoma than in those with benign urachal masses.Gross hematuria and fatty infiltration of the Retzius space may be indications of malignant and benign urachal masses,respectively.

Objective To explore the effect of chemokine CXCL12 and its receptor CXCR4 on proliferation,migration and invasion of epithelial ovarian cancer cells.Methods CXCR4 and CXCL12 mRNA and protein expression of human ovarian cancer cell line CAOV3 was detected by RT-PCR and immunocytochemistry.Integrin ?1 and vascular endothelial growth factor-C(VEGF-C)mRNA expression were detected in CAOV3 cells stimulated by CXCL12.The CAOV3 cells were divided into 6 groups:control group(un-stimulated),experimental group 1(stimulated by 100 ng/ml CXCL12),experimental group 2 (stimulated by 10 ng/ml CXCL12),experimental group 3(100 ng/ml CXCL12 and 10 ?g/ml neutralizing CXCR4 antibody),experimental group 4(100 ng/ml CXCL12 and 1 ?g/ml CXCR4 antagonist AMD3100),experimental group 5(10 ?g/ml neutralizing CXCR4 antibody or ascites).Methyl thiazolyl tetrazolium(MTT)was used to analyze the effects of different concentrations of CXCL12 on CAOV3 cell proliferation.Transwell invasion chamber and reconstructed basement membrane(Matrigel)were used to evaluate effect of various concentrations of CXCL12 and ascites on CAOV3 cell migration and invasion. Results CAOV3 cells expressed CXCR4 mRNA(0.70?0.10)and protein,but did not express CXCL12 mRNA or protein.Immunostaining of CXCR4 was mainly located in cytoplasm.CXCR4 mRNA was up- regulated after 100 ng/ml CXCL12 stimulation(1.24?0.14;t=-7.1088,P=0.0021).Integrin ?1 mRNA was greatly increased at 3 hours by stimulation of 100 ng/ml CXCL12(before and after stimulation 0.53?0.10,1.53?0.16;P0.05).Experimental group 1 stimulated the migration and invasion of CAOV3 cells in chemotaxis assay compared with control group and experimental group 2(number of cell migration respectively 523.3?25.2,108.0?7.2,211.7 ?24.7,number of cell invasion respectively 39.3?4.0,4.0?1.0,15.7?3.1;P

Objective To observe the biological characteristics of db/db mice, and to provide the basis for application of db/db mice in experimental research.Methods Spontaneous type 2 diabetes BKS.Cg-Dock7m +/+ Leprdb/JNju mice and wild type mice of the same age were used in this study.Their fasting blood glucose was determined at 8,12,16, 20 and 24 weeks of age, the body weight was recorded at 10, 12,16, 20 and 24 weeks of age, the levels of serum insulin, total cholesterol and triglyceride were measured, the organ weight and liver coefficient were determined, and the liver and pancreas were taken for pathological examination at 24 weeks of age.Results The db/db mice maintained a high level of fasting blood glucose and body weight.Levels of serum insulin, total cholesterol, and triglyceride were significantly higher than the wild type mice.Compared with wild type mice, liver weight and kidney weight were also significantly increased.Obvious pathological changes of liver and pancreas were observed in 24-week old db/db mice.Conclusions db/db mouse has obvious characteristics of type 2 diabetes, such as hyperglycemia, hyperlipidemia, and hyperinsulinemia, can maintain stable levels of high blood glucose,and is an ideal animal model for experimental study of type 2 diabetes mellitus.

A 27-year-old woman was admitted to a hospital due to intermittent fever for 20+ days and swelling pain in knee joint for 7 days.Patients was with persistent fever,the highest temperature to 40.1°C,the double knee joint swelling pain,a large number of scattered red needle-like rash were visible on bilateral hands and legs,lymph-adenectasis,splenectasis,bilateral hands interphalangeal joint and knee joint swelling pain,lymph nodes were con-fined to the bilateral axillary with soft texture,local tenderness,and good activity.Pathological results of left axil-lary lymph node showed the following finding:fragmental lymph node tissue with incomplete structure,lymphoid follicles existed,there were diffuse histocytes,immunoblasts,and a few small lymphocytes proliferation in the re-duced or disappeared area of follicular,caryokinesis could be easily seen,there were patches of necrosis foci with varied size,nucleus disintegrated,fibrinoid necrosis blood vessel with bleeding could be seen.Immunohistochemical detection showed the following results:CD3 (diffuse +);CD20 (follicular +);CD79α(follicular +);CD68 (+);EMA (-);ALK (-);CD15 (a small amount of cells +);CD30 (+),CD4 (-),CD5 (+);CD10 (-);bcl-2 (+);CD21 (+);telomerase B (-);TIA-1 (-);EBV(-)Ki-67 (+).Through a combination of clinical and immunohistochemical detection results,the diagnosis of histiocytic necrotizing lymphadenitis was made.Patient discontinued antimicrobial drugs,after she was treated with 5% glucose 100 mL + hydrocortisone sodium succinate 200 mg intravenous drip for 3 days,patients had no fever,axillary lymph node gradually dwindled.Then patients was treated with methylprednisolone 8 mg/d,twice a day,reduced 1 tablet every two weeks,and stopped eventual-ly.Patients was followed up for two years,repeated examination of blood routine,liver and kidney function were in the normal range,bilateral knee didn’t swell,could walk freely,there appeared no enlargement of lymph node.

In coal mines, main occupational hazard is coal-mine dust, which can cause health problem including coal workers' pneumoconiosis and lung cancer. Some heat shock proteins (Hsps) have been reported as an acute response to a wide variety of stressful stimuli. Whether Hsps protect against chronic environmental coal-mine dust over years is unknown. It is also interesting to know that whether the expression of Hsp27 and Hsp70 proteins as a marker for exposure is associated risk of lung cancer among coal miners. We investigated the association between levels of Hsp27 and Hsp70 expression in lymphocytes and plasma and levels of coal-mine dust exposure in workplace or risk of lung cancer in 42 cancer-free non-coal miners, 99 cancer-free coal miners and 51 coal miners with lung cancer in Taiyuan city in China. The results showed that plasma Hsp27 levels were increased in coal miners compared to non-coal miners (P<0.01). Except high cumulative coal-mine dust exposure (OR=13.62, 95%CI=6.05-30.69) and amount of smoking higher than 24 pack-year (OR=2.72, 95% CI=1.37-5.42), the elevated levels of plasma Hsp70 (OR=13.00, 95% CI=5.14-32.91) and plasma Hsp27 (OR=2.97, 95% CI=1.40-6.32) and decreased expression of Hsp70 in lymphocytes (OR=2.36, 95% CI=1.05-5.31) were associated with increased risk of lung cancer. These findings suggest that plasma Hsp27 may be a potential marker for coal-mine dust exposure. And the expression of Hsp27 and Hsp70 levels in plasma and lymphocytes may be used as biomarkers for lung cancer induced by occupational coal-mine dust exposure.

Objective: Investigation on the quality control method of bacterial endotoxin in betahistine hydrochloride injection.
Methods: The method of bacterial endotoxin gel test of 23 batches of betahistine hydrochloride injection from 5 manufacturers was studied.
Results: The limit value of endotoxin in this product was 3 EU·mg^-1, which was suitable for the bacterial endotoxin test of China Pharmacopoeia 2020.
Conclusion: The quality of betahistine hydrochloride injection can be controlled by bacterial endotoxin test, and the limit of bacterial endotoxin can be set as follows: the content of endotoxin in every 1mg of betahistine hydrochloride should not exceed 3 EU.

BACKGROUNDIn a previous study, we have verified that CXCR4 expression is correlated with tumor aggressive progression and poor prognosis in patients with epithelial ovarian cancer. The aim of this study was to explore the effect of CXCL12-CXCR4 axis on the metastasis of human ovarian cancer.

METHODSThe expressions of CXCR4 and CXCL12 mRNA and protein in human ovarian cancer cell line CAOV-3 was detected by RT-PCR and immunocytochemistry. Methythiazolyltetrazolium (MTT) was used to analyze the effect of different concentrations of CXCL12 on the proliferation of CAOV-3 cells. Transwell invasion chamber and matrigel were used to evaluate the effect of various concentrations of CXCL12 and ascites on the migration and invasion of CAOV-3 cells. The expressions of integrin beta(1) and vascular endothelial growth factor-C (VEGF-C) mRNA were detected by RT-PCR. Data were analyzed using ANOVA by SAS 6.12.

RESULTSUnder serum-free suboptimal culture conditions, CXCL12 (100 ng/ml) significantly enhanced the proliferation of CAOV-3 cells compared with the control and 10 ng/ml CXCL12 groups (0.428 +/- 0.051 vs. 0.325 +/- 0.045 and 0.328 +/- 0.039, P < 0.05). This enhancing effect of CXCL12 was significantly inhibited by 10 microg/ml neutralizing CXCR4 antibody or 1 microg/ml CXCR4 antagonist AMD3100. However, 10 microg/ml neutralizing CXCR4 antibody could not inhibit cell proliferation without CXCL12. The levels of migration and invasion of the CAOV-3 cells treated with 100 ng/ml CXCL12 were significantly higher than those in the control (migration: 523.3 +/- 25.2 vs 108.0 +/- 7.2; invasion: 39.3 +/- 4.0 vs. 4.0 +/- 1.0). The enhancing effect of CXCL12 on cell migration and invasion increased with the concentration of CXCL12 (100 ng/ml vs10 ng/ml: migration, 523.3 +/- 25.2 vs 211.7 +/- 24.7; invasion, 39.3 +/- 4.0 vs 15.7 +/- 3.1, P < 0.05), and was strongly inhibited by 10 microg/ml neutralizing CXCR4 antibody or 1 microg/ml AMD3100. The number of migrated and invading cells in the CAOV-3 added with ascites was significantly higher than those in the 100 ng/ml CXCL12 group (migration: 706.6 +/- 30.6 vs 523.3 +/- 25.2, invasion: 61.7 +/- 7.6 vs 39.3 +/- 4.0, P < 0.05). The level of integrin beta(1) mRNA was greatly increased at 3 hours after being treated with CXCL12 (0.53 +/- 0.10 vs. 1.53 +/- 0.16, P < 0.05), and VEGF-C mRNA displayed significant augment at 24 hours after being treated with CXCL12 (0.52 +/- 0.09 vs 1.11 +/- 0.15, P < 0.05).

CONCLUSIONSCXCL12 and its receptor CXCR4 can promote the proliferation, migration, invasion of ovarian cancer cell line CAOV-3 and enhance its secretion of integrin beta(1) and VEGF-C. These effects can be inhibited by neutralizing CXCR4 antibody or AMD3100. CXCL12-CXCR4 axis plays an important role in ovarian cancer growth and metastasis.

Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Chemokine CXCL12 ; Chemokines, CXC ; analysis ; physiology ; Female ; Humans ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Ovarian Neoplasms ; pathology ; Receptors, CXCR4 ; analysis ; physiology