OBJECTIVETo investigate the effect of apatinib, a small-molecule vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor, on the proliferation of human acute myeloid leukemia HL-60 cells and explore the possible mechanism.

METHODSMTT assay was used to assess the cytotoxicity of apatinib in HL-60 cells. The apoptosis and cell cycle changes of the cells in response to apatinib treatment were analyzed by flow cytometry, and Western blotting was used to assay P-Akt and P-Erk1/2 expressions in the cells.

RESULTSApatinib significantly inhibited the proliferation of HL-60 cells in vitro with an IC(50) of 4.96∓0.32 µmol/L. Apatinib treatment significantly increased the apoptotic rate of the cells in a dose-dependent manner, but produced no significant effect on the cell cycle (P>0.05). Western blotting showed that the expressions of P-Akt and P-Erk1/2 decreased in HL-60 cells after a 48-h apatinib treatment.

CONCLUSIONApatinib inhibits the proliferation of HL-60 cells by inducing cell apoptosis probably through the mechanism of inhibiting the expressions of the Akt/Erk1/2 signal transduction pathway.

Apoptosis ; drug effects ; Cell Proliferation ; drug effects ; HL-60 Cells ; Humans ; Protein-Tyrosine Kinases ; antagonists & inhibitors ; Pyridines ; chemistry ; pharmacology

Objective: To explore the determinants for health-seeking behavior of the residents after cough for more than 3 weeks in Yiwu, Zhejiang Province, in order to provide reference for prevention and control of respiratory diseases. Methods: A multi-stage cluster random sampling method was used to recruit the community residents aged 5 years and above in Yiwu. A face-to-face questionnaire survey was conducted to collect demographic information, features of cough and health-seeking behaviors in the past month. The multivariate logistic regression model was employed to analyze the associated factors for health-seeking behavior after a cough for more than 3 weeks. Results: Among 6 374 residents investigated, 152 cases had a cough for more than 3 weeks in the past month, accounting for 2.48%. They were( 45.00±21.15 ) years old, including 70 ( 46.05% ) males and 82 ( 53.95% ) females. About 58.55% ( 89 ) of them sought medical treatment. The results of multivariate logistic regression analysis showed that females ( OR=2.100, 95%CI: 1.005-4.391 ), middle school education level ( OR=0.406, 95%CI: 0.168-0.983 ), family annual income of 100 000 to 199 999 yuan ( OR=2.993, 95%CI: 1.215-7.373 ) were associated factors for health-seeking behavior after a cough for more than 3 weeks. Conclusion The rate of health-seeking behavior after a cough for more than 3 weeks among the residents in Yiwu is 58.55%, which is associated with gender, education level and income.

OBJECTIVETo analysis the changes of two chemical constituents, namely 2, 3-dihydro-3, 5- dihydroxy-6-methyl-4H-pyran-4-one (DDMP) and 5-hydryoxymethyl-furfural (5-HMF) produced in Radix Polygoni Multiflori after processing, with processing time, and to determine the contents of 5-HMF in samples of Radix Polygoni Multiflori and Radix Polygoni Multiflori preparata.

METHODAn HPLC method was applied with a Zobax SB-C18 (3.9 mm x 150 mm, 5 microm) column by a elution using methanol-water (10: 90) as the mobile phase. The detection was set at UV 280 nm.

RESULTThe contents of DDMP were increasing with the processing time until 24 hour, followed by a decrease until 60 hour process. The contents of 5-HMF were increasing gradually throughout the 60 hour steaming process. The contents of 5-HMF in 11 samples of Radix Polygoni Multiflori preparata were from 0.013% to 0.101%, and only one in 4 samples of Radix Polygoni Multiflori containing trace amount of 5-HMF.

CONCLUSIONThe chemical components in Radix Polygoni Multiflori were changed during the processing procedures. Therefore, the processing of Radix Polygoni Multiflori should be controlled and standardized.

Chromatography, High Pressure Liquid ; methods ; Drugs, Chinese Herbal ; chemistry ; Polygonaceae ; chemistry ; Reproducibility of Results

Objective To explore the influencing factors of insulin resistance among children in the mountainous area. Methods One middle school and 2 primary schools in Longquan city were randomly selected,47 classes of schoolchildren aged 1 0 -1 5 years were selected.Weight,height,waist circumstance (WC),blood pressure,blood glucose (FBG), serum insulin (FINS),triglycerides (TG),high -density lipoprotein (HDL -C)and total cholesterol (TC)were determined.Influencing factors of insulin resistance were analyzed by univariate and multiple logistic regression analysis. Results A total of 2 1 25 students were enrolled in this study.The 75th percentile of HOMA -IR was 2.59 respectively. The univariate analysis showed that HOMA -IR was significantly associated with HDL -C,TG,non HDL -C,BMI,WC, SBP,DBP and FPG (P <0.05).The multiple logistic regression analysis showed that WC (OR =1 .07,95%CI =1 .06 -1 .09),FPG (OR =2.29,95%CI =1 .78 -2.94),HDL -C (OR =0.34,95%CI =0.21 -0.56)and TG (OR =1 .43, 95%CI =1 .1 4 -1 .78)were the risk factors of insulin resistance.Conclusion WC,FPG,TG may be the risk factors of insulin resistance among children in the mountainous area,while HDL -C is the protective factor.

OBJECTIVETo investigate changes in serum insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-binding protein-3 (IGFBP-3) and their significance in children with left-to-right shunt congenital heart disease (CHD) associated with heart failure (HF).

METHODSTwenty healthy children (control group), 20 children with HF, without basic heart disease (HF group), 20 children with left-to-right shunt CHD, without HF (CHD group), and 30 children with left-to-right shunt CHD associated with HF (CHD+HF group) were included in the study. These groups were compared in terms of serum IGF-1 and IGFBP-3 levels. According to the New York Heart Association (NYHA) Functional Classification, the CHD+HF group was further divided into NYHA-II, NYHA-III and NYHA-IV subgroups and the subgroups were compared in terms of serum IGF-1, IGFBP-3, and cardiac troponin I (cTnI) levels. The correlation of serum IGF-1 and IGFBP-3 levels with serum cTnI level in the CHD+HF group was analyzed.

RESULTSThe CHD group showed decreased serum IGF-1 and IGFBP-3 levels compared with the control group (P<0.01). The CHD+HF group showed a significantly decreased serum IGF-1 level compared with the control group (P<0.01) and CHD group (P<0.05). The HF group had significantly increased serum IGF-1 and IGFBP-3 levels compared with other groups (P<0.01). The NYHA-II subgroup had the highest serum IGF-1 level and the NYHA-IV subgroup had the lowest serum IGF-1 level (P<0.01). In the CHD+HF group, serum IGF-1 and IGFBP-3 levels were negatively correlated with serum cTnI level (r=-0.692, P<0.05; r=-0.530, P<0.05).

CONCLUSIONSSerum IGF-1 level can be used as an objective condition evaluation indicator for CHD, and low serum IGF-1 level is a risk factor for HF. This also provides a clinical basis for treatment of HF using exogenous IGF-1.

Child, Preschool ; Female ; Heart Defects, Congenital ; blood ; Heart Failure ; blood ; Humans ; Infant ; Insulin-Like Growth Factor Binding Protein 3 ; blood ; Insulin-Like Growth Factor I ; analysis ; Male ; Troponin I ; blood

OBJECTIVETo investigate the relationship of lymphatic micovessel density (LMVD) detected by monoclonal antibody D2-40) with the VEGF-C expression in human breast cancer.

METHODSTissue samples of 102 breast cancers, 25 breast fibroadenomas and 10 normal breasts were collected. Immunohistochemical staining was used to detected the lymphatic micovessels with monoclonal antibody D2-40. The expression of VEGF-C was detect by SP immunohistochemistry, and VEGF-C mRNA by hybridization in situ.

RESULTSIn 102 breast cancers, the positive rate of D2-40 was 76.5% (78/102), higher than that in the breast fibroadenomas. LMVD in the periphery of breast cancer was 30.1 lymphatic microvessels per x 100 field of vision, which was significantly higher than that in the central area of the tumors (P = 0.000). The LMVD in the periphery of the breast cancers was correlated with the number of metastatic lymph nodes (r = 0.964, P < 0.01). The positive rates of VEGF-C protein and mRNA were 55.9% (57/102) and 59.8% (61/102), respectively, significantly higher than that in the breast fiberoadenomas and normal breast tissues (chi2 = 11.653, P = 0.003; chi2 = 10.345, P = 0.006), and were significantly correlated with the status of lymph node metastasis, clinical stage and the expressions of c-erbB-2 and p53 protein (P < 0.05). Both of VEGF-C protein and mRNA were significantly correlated with LMVD detected by D2-40 (P < 0.05), especially with the LMVD in the periphery of breast cancers (P < 0.05).

CONCLUSIONThe monoclonal antibody D240 can be used to detect the lymphatic endothelium in human breast cancer. The lymphatic microvessel density in the periphery of breast cancer is correlated with the lymph node metastasis and expression of VEGF-C. Therefore, VEGF-C may play a significant role in the lymphangiogenesis leading to metastasis of breast cancer.

Adult ; Aged ; Antibodies, Monoclonal ; Antibodies, Monoclonal, Murine-Derived ; Breast Neoplasms ; metabolism ; pathology ; Carcinoma, Ductal, Breast ; metabolism ; pathology ; Female ; Fibroadenoma ; metabolism ; pathology ; Humans ; Lymph Nodes ; pathology ; Lymphangiogenesis ; Lymphatic Metastasis ; Lymphatic Vessels ; pathology ; Microvessels ; pathology ; Middle Aged ; Neoplasm Staging ; RNA, Messenger ; metabolism ; Vascular Endothelial Growth Factor C ; genetics ; metabolism ; Young Adult

Objective To evaluate the efficacy and safety of memantine in the treatment of patients with Alzheimer' s disease (AD).Methods This was a 16-week,multi-center,randomized,double blind, placebo-controlled clinical trial (Study 10116).A total of 258 AD patients (MMSE score 5—18) were randomized in a 1:1 ratio into either memantine 10—20 mg/day (MEM,n=128) or placebo (PBO,n= 130) group for 16 weeks.Efficacy was primarily assessed in terms of changes of severe impairment battery (SIB) score in patients from baseline up to SIB assessment in the 16th week (16-week completers set, CS16).While ehanges of MMSE,ADCS-ADL_(19),and NPI (neuropsychiatric inventory) were evaluated as secondary efficacy parameters on both CSI6 and full-analysis set (FAS).Safety was assessed by physical examination,lab assays,ECG,and adverse events.Results 236 subjeets (CS16:MEM n=117,PBO n=119) were eligible for the efficacy assessment.No statistically significant difference between the treatments was observed on the primary and seeondary efficacy analysis,although both treatment groups had a slight increase from baseline in SIB total score.Post hoe evaluation of the data identified two bias factors that had a significant impact on the results of the pre-protoeol specified primary and secondary analyses.In a re-analysis of the data (CS16_(modified),MEM n=94,PBO n=95) excluding patient data affeeted by these factors,memantine-treated patients showed a statistically significant improvement related to placebo in the 16th week on the SIB (MEM 2.2 vs PBO 0.3,P=0.04),MMSE (MEM 1.0 vs PBO 0.1,P=0.03),and ADL (MEM 0.1 vs PBO-1.6,P=0.02) scales,indicating that memantine improved the cognitive function of AD patients and stabilized the activity of daily life.Memantine was well tolerated with an adverse event profile similar to that of placebo.Conclusion This study provides further support for pre-existing data,showing that memantine is efficacious,safe,and well-tolerated in patients with moderate to severe AD.

Objective To investigate clinical symptoms,pathophysiology and brain imaging features of Chinese familial cerebral cavernous angiomas.Methods Head MRI examination,clinical and pathophysiological examination were performed in a Chinese family with one proband of cerebral cavernous malformation.The disease atlas of the family was drawn.The patients indicative of a surgery underwent resection of hemangioma whose pathophysiology and microstructure were observed.Results Nine familial cerebral cavernous angiomas patients were found to have multiple intracranial lesion in the 18 family members,the penetrance being 50%,conforming to the feature of autosomal incomplete dominance inheritance.Four patients with skin cavernous hemangioma had familial cerebral cavernous angiomas.MRI was the most sensitive modality for the diagnosis of cavernous angioma.With T_2-Weighted sequences,the lesion was typically characterized by an area of mixed signal intensity,with a central reticulated core and a peripheral rim of decreased signal intensity related to deposition of hemosiderin.Gradient-echo(GRE)MRI could find microcavernous hemangiomas that would not be found in other sequences.Cavernous angiomas were typically discrete multilobulated berrylike lesions that contained hemorrhage in various stages of evolution.Histological homogeneity and overlap with other vascular malformations such as capillary telangictasia was common.Cavernous angiomas were composed of endothelial-linked sinusoidal spaces not separated by significant amounts of neural tissue.Hemorrhagic residua were common.Clots at different stages of evolution within the lesion were seen.The basic membranes of sinus became thick and soft.Parts of it were layered.Conclusions Familial cerebral cavernous angiomas is an autosomal incomplete dominance inheritance disease.Cavernous angiomas are composed of endothelial-linked sinusoidal spaces not separated by significant amounts of neural tissue.There are more than one focus in every patients and the skin cavernous angiomas is the foundation of diagnosing familial cerebral cavernous angiomas.Gradient-echo imagine sequence MRI(3.0 T)could be the"golden standard".

OBJECTIVETo explore the characters of the cervical lymph node metastasis in differentiated thyroid carcinoma, and to provide evidence for proper surgery of differentiated thyroid carcinoma.

METHODSFrom 1984 to 2000, 99 cases with differentiated thyroid carcinoma were performed thyroidectomy and neck dissection. The patients were followed up. A retrospective analysis was performed. Results In 99 cases with differentiated thyroid carcinoma, there were 61 papillary carcinoma, 13 papillary and follicular mixed carcinoma, 25 follicular carcinoma. According to 2002 UICC TNM classification, 60 cases were staged I, 1 case staged II, 5 cases staged III, 33 cases staged IV. Lobectomy and isthmectomy was performed in 80 cases, lobectomy was resected and opposite subtotal lobectomy in 15 cases, total thyroidectomy in 4 cases. One hundred and four neck dissection were performed in 99 cases (5 cases were bilateral neck dissection ). Among them, 66 (68 sides) were radical neck dissection, 33 (36 sides) were modified neck dissection. Pathological results showed that lymph nodes were positive in 86 sides of 83 cases. The rate of cervical lymph node metastasis was 83.8% (83/99). The positive rates of lymph node were 37.5% (39/104) in level VI and 76.9% (80/104) in II-V, which was statistically different (chi2 = 33.01, P < 0.01). The cervical lymph node metastasis in lateral area (level II-V) and that in VI had not relationship (chi2 = 2.08, P > 0.05). Ten and 15 year survival rates of all 99 cases were 88.3% and 84.5% respectively.

CONCLUSIONSThe occurrence of lymph node metastasis in level VI and level II was different and no relationship .One can not judge whether lateral neck metastasis by the lymph node statue in level VI only . Although they all had good prognosis, patients with positive nodes in level VI were not worse than that in lateral neck (II-V).

Adolescent ; Adult ; Aged ; Carcinoma, Papillary ; pathology ; Cell Differentiation ; Child ; Female ; Humans ; Lymph Nodes ; pathology ; Lymphatic Metastasis ; pathology ; Male ; Middle Aged ; Neck ; Neck Dissection ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Thyroid Neoplasms ; pathology ; Young Adult

We report a case of intractable circulatory failure event in a hypertensive patient during laparoscopy hepatectomy and analyze the diagnosis and treatment by multidisciplinary physicians. This case suggests that both surgeons and anesthesiologists should give attention to oral angiotensin II receptor antagonist during the preoperative period to avoid refractory hypotension. In addition, the use of EV1000 hemodynamic monitoring system in intensive care provides more convenience for clinical liquid management.