BACKGROUND: Plasminogen activator inhibitor 1 is the main regulator of the fibrinolytic system in vivo. The increase of plasminogen activator inhibitor 1 is closely related to thrombotic disease and it is also an independent risk factor for development of thrombotic disease.OBJECTIVE: To investigate the effect of huangqi(Astragalus), danggui (Angelica) and ligustrazine as medicines activating blood and eliminating stasis on the expression of plasminogen activator inhibitor 1 in HepG2 hepatocarcinoma cell strain.DESIGN: A randomized controlled study.SETTING: First Cadre Department of General Hospital of Chinese People' s Armed Police Force.MATERIALS: The experiment was completed in Academy of Military Medical Sciences of PLA from August to December 2004. HepG2 hepatocarcinoma cell strain was cultured. According to different drugs in culture medium, they were divided into six groups: control group, huangqi group,danggui group, huangqi + danggui group, compound danshen group and ligustrazine group.METHODS: Huangqi, danggui, huangqi + danggui, compound danshen and ligustrazine were added in HepG2 culture medium respectively. MTS assay was used to detect the effect of medicines activating blood and eliminating stasis on proliferation of HepG2 cells, plasminogen activator inhibitor 1 was assayed by specific enzyme-linked immunosorbent assays(ELISA),plasminogen activator inhibitor 1 activity was measured by amidolytical assay. 0.5 μg/mL of transforming growth factor β1 cells was added in HepG2 culture medium to stimulated production of plasminogen activator inhibitor 1. Control group was treated under the same conditions but without Chinese herbs.RESULTS: The inhibitory rates of cellular proliferation in huangqi and danggui groups werc(6.51 ±2. 66)% and (4.42 ±2. 19)%, but those in huangqi + danggui, compound danshen and ligustrazine groups were (12. 06 ±4. 98)%, (16. 38 ±4.06)% and(32. 83 ±9.8)% respectively,t = 2. 447 - 3. 707, P ＜ 0.05. Compared with the control group, huangqi,danggui, compound danshen and ligustrazine significantly inhibited plasminogen activator inhibitor 1 expression(22.68 ± 2.20, 11.11 ± 1.23,19.66±1.53, 15.45±1.27, 16.90±0.33, 14.01±0.74, t=2.447-3.707, P ＜ 0.05) and activity(2.16±0.014, 2.01 ±0.006, 1.95±0.014, 1.79±0. 104, 1.53±0.045, 1.48±0.012, t =2.447-3. 707,P ＜ 0.05) in HepG2 cells. The evident inhibitory effects were observed in the group of huangqi + danggui, especially in compound danshen and ligustrazine.CONCLUSION: The plasminogen activator inhibitor 1 expression and activity were inhibited effectively by huangqi, danggui, compound danshen and ligustrazine.

OBJECTIVETo investigate the expression of survivin mRNA in hematological malignancy cells and its correlation with HHT-induced cell apoptosis.

METHODSHematological malignancy cell lines MUTZ-1, K562, Jurkat, RPMI and HL60 were treated with HHT in vitro. Cell apoptosis was observed by flow cytometry (FCM) and the expression of surviving and XIAP mRNA was evaluated with semi-quantitative RT-PCR.

RESULTThe expression of survivin mRNA on cell lines was negatively correlated to HHT-induced cell apoptotic rate (r=-0.980, P=0.003). There were no significant differences in XIAP expression among these 5 cell lines.

CONCLUSIONSurvivin could be used as a new marker for drug-sensitivity and a new target for treatment of hematological malignancies.

Apoptosis ; drug effects ; HL-60 Cells ; Harringtonines ; pharmacology ; Humans ; Inhibitor of Apoptosis Proteins ; K562 Cells ; Microtubule-Associated Proteins ; biosynthesis ; genetics ; Myelodysplastic Syndromes ; metabolism ; pathology ; Neoplasm Proteins ; biosynthesis ; genetics ; RNA, Messenger ; biosynthesis ; genetics ; Tumor Cells, Cultured

Objective To investigate the role of oxidative stress-dependent Rasextracellular signal-regulated kinase (ERK1/2) signaling in aldosterone (ALDO)-induced mesangial cell proliferation. Methods The incorporation of 3H-thymidine (3H-TdR) and cell count were used as the measure of mesangial cell (MC) proliferation.Western blotting was used to detect the activation of Ki-RasA,c-Raf,MEK1/2,ERK1/2 and PI3K. Results Aldosterone significantly induced human mesangial cell proliferation,and anti-oxidant N-Acetylcysteine (NAC),catalase,and super oxide dismutase (SOD) significantly inhibited ALDO-induced mesangial cell proliferation (P＜0.01,respectively).Stimulation by ALDO for 3 h,Ki-RasA,c-Raf,MEK1/2,and ERK1/2 activity increased by 4.05-, 3.62-, 4.52-, and 3.40-fold compared with control group (P ＜0.01,respectively).NAC almost completely blocked ALDO-induced Ki-RasA,c-Raf,MEK1/2,and ERK1/2 activation (P＜0.01,respectively).Ki-RasA siRNA dose-dependently inhibited Ki-RasA expression, ALDO-induced Ki-RasA activation, and mesangial cell proliferation (P ＜0.01,respectively).c-Raf inhibitor GW5074 and MEK1/2 inhibitor PD98059 also reduced ALDO-induced mesangial cell proliferation by 65％ respectvely (P＜0.01).Ki-RasA siRNA had no effect on ALDO-induced PI3K phosphorylation.Combining LY294002 and PD98059 completely blocked ALDO-induced mesangial cell proliferation (P＜0.01). Conclusions ALDO-induced Ki-RasA-c-Raf-MEK-ERK signaling activation is dependent on reactive oxygen species (ROS) production,which mediates ALDO-induced mesangial cell proliferation.Inhibition of both ERK1/2 and PI3K signaling simultaneously completely blocks ALDO-induced mesangial cell proliferation.

This article was aimed to study the synergy effect of effective substances group and mechanisms of Qi-Zhi Wei-Tong (QZWT) Granules in promoting gastrointestinal dynamic effect in order to explore its mechanism. Rats were divided into 16 groups. Different component compatibility was given to promote the gastrointestinal dynamic ef-fect. The traditional semi-solid paste carbon propelling analysis method was used to observe gastrointestinal motility changes of rats after medication. After intragastric administration, changes of NO, cGMP and Ca2+content in gastroin-testinal tissues were observed. The results showed that fructus aurantii flavonoids and Cyperi flavonoids had the most prominent effect in promoting gastrointestinal motility in QZWT Granules (P< 0.01), which were followed by Cyperus oil and limonene (P< 0.05). Two-way interactions indicated that the combination of fructus aurantii flavonoids and limonene had prominently promoting action in gastrointestinal motility, which was followed by the combination of fructus aurantii flavonoids and Cyperus oil, Cyperi flavonoids and Cyperus oil, limonene and Cyperus oil. Each effec-tive component can reduce the NO and cGMP content in gastrointestinal tissues, and increase the Ca2+ content. It was concluded that the study defined the correlation and synergy between effective components and promoting effect of gastrointestinal motility. Mechanism of the effective component to promote gastrointestinal dynamic might be relat-ed to the reducing of NO and cGMP content in gastrointestinal tissues and increasing of Ca2+ content. This study also provided a theoretical basis for further research on quality control, compatibility and spectrum-effect correlation of gastrointestinal motility promotion medications.

Objective To explore the effect of nitric oxide (NO) on ?-aminobutyric acid B receptor (GABA_BR) subunits during recurrent febrile seizures (FS).Methods Twenty-four Sprague-Dawley rats aged 21 days were randomly divided into 4 groups: control group (37.0 ℃ water,n=8), FS group (45.2 ℃ water,n=8), FS + SNP group (45.2 ℃ water,n=8), FS+L-NMMA group (45.2 ℃ water,n=8). FS rats were induced 10 times in a warm-water bath, once every 2 days. The plasma level of NO was detected by the spectrophotometer. The expressions of GABA_BR subunit mRNA and c-fos gene were examined by in situ hybridization. The expressions of GABA_BR subunit and Fos protein were observed by immunohistochemistry. Results The plasma level of NO increased in FS + SNP group while decreased in FS+L-NMMA group compared with that in FS group. The expressions of GABA_BR_2 were down-regulated in FS+SNP group, while GABA_BR_1 hardly changed compared with those in FS group. In FS+L-NMMA group, both the expression of GABA_BR_2 and GABA_BR_1 up regulated compared with those in FS group. The expressions of c-fos gene and Fos protein were significantly enhanced after recurrent FS. SNP elevated the expressions of c-fos gene and Fos protein, while L-NMMA down regulated the expressions of them.Conclusion NO may play a regulatory role through modulating GABA_BR function in the pathogenesis of recurrent FS.

Objective To explore the influence of ?-aminobutyric acid B receptor(GABA_BR)on carbon monoxide (CO)/heme oxygenase(HO-1)system during recurrent febrile seizures (FS).Methods Sprague-Dawley rats aged 21 days were randomly divi- ded into 4 groups:control group and FS group,FS+baclofen group,FS+phaclofen group.FS in rats were induced 10 times in a bath of warm water, once every 2 days.The plasma level of CO was detected by the dual wave lengh spectrophotometer;the expressions of GABA_BR and HO-1 mRNA were examined by insitu hybridization;the expressions of GABA_BR and HO-1 protein were observed by immunohistochemistry.Results The plasma level of CO increased in FS+baclofen group,while decreased in FS+phaclofen group compared with FS group.The expressions of GABA_BR and HO-1 upregulated in FS+baclofen group,while decreased in FS+phaclofen group compared with FS group.There were significant difference (All P

Objective To discuss the predictive value of multiple ultrasonic features combination in diagnosis of thyroid papillary carcinoma (PTC) more than 1.0 cm in diameter. Methods The ultrasonic features of 258 PTC nodules from 251 patients and 207 nodular goiter (NG) nodules from 190 patients in the First People′s Hospital of Hangzhou were retrospectively analyzed. All the nodules were confirmed by pathological examination after surgery. The ultrasonic features included the shape of nodules, internal echo,anteroposterior/transverse diameter ratio (A/T), and microcalcification. The χ2 test was used to analyze the differences of ultrasonic features between PTC and NG. Multi-variate analyses (Logistic regression) was used to analyze the predictive risk ultrasonic features of PTC. The sensitivity and specificity of ultrasonic features were analyzed based on the gold standard of pathological results. Results There were significantly differences between 258 PTC nodules and 207 NG nodules in irregular shape, hypoechogenicity,A/T > 1 and microcalcification (χ2 values were 121.511, 105.411, 41.483, 121.072, all P < 0.01). The results of Logistic regression showed that irregular shape, hypoechogenicity, A/T>1 and microcalcification were risk ultrasonic features of PTC. And their OR values were 5.013 (95%CI 2.919-8.610), 5.811 (95%CI 3.411-9.901), 15.399 (95%CI 7.576-31.301), 4.141 (95%CI 1.687-10.164) respectively. The sensitivity and specificity of single ultrasonic feature were 26.0%-79.5% and 71.5%-96.1%; the sensitivity and specificity of two ultrasonographic features combination were 11.2%-57.0% and 92.3%-99.0%; and the sensitivity and specificity of three or four ultrasonographic features combination were 8.1%-31.8% and 99.0%-99.5%.Conclusions Irregular shape, hypoechogenicity, A/T> 1 and microcalcification of thyroid neoplasm are important ultrasonic features of PTC. Although the sensitivity of single ultrasonic feature in diagnosing PTC is higher than that of multiple features combination, it has a lower specificity. Therefore, combination of multiple ultrasonographic features can improve the specificity in diagnosing PTC and reduce the misdiagnosis of PTC.

Objective To measure the proximal femoral parameters which can provide anatomic evidence for the design of internal fixation components for intertrochanteric fractures of femur.Methods Femoral speci- mens were harvested randomly from 120 healthy adult cadavers(left 60,fight 60).The neck shaft angle,greater trochanter slope length,tilt angle of greater trochanter,axial length of head and neck,lengths of upper and lower borders of the neck,and the minimum transverse diameter of the neck were measured.On the basis of the anatomic study,a two-claw plate was designed to treat 145 cases of femoral intertrochanteric fractures.Results The femoral neck shaft angle was 128.59??6.31?,femoral greater trochanter slope length was(5.5?0.58)cm,tilt angle of femoral greater trochanter was 42.76??5.20?,and axial length of head and neck was(9.42?0.38)cm. There was a correlation between the parameters.All the patients were followed up for a mean time of 23.6 months. The fractures got clinic union in 3 to 6 months.Two cases experienced detachment of claws and hooks but their final outcome was not affected.Three cases suffered coxa vara.All the other cases obtained normal motion function of hips and normal neck shaft angle.No breakage of claw,hook or nail was found in them.Conclusions It is necessary to design an internal fixator that can fit the anatomical features of Chinese femurs in the treatment of intertrochanteric fractures of femur.The two-claw plate designed by us is a good attempt to improve the clinical effect.

The purpose of this study is to investigate the reversal effect and its mechanism of arsenic trioxide (As2O3) on multidrug resistance of gastric carcinoma cells. The concentration of vincristine (VCR) increased gradually to induce the drug resistance of gastric carcinoma cell SGC7901. MTT assay was used to determine the lethal effect of anticarcinogens on tumor cells and Western blotting assay was applied to determine the expression of P-glucoprotein (P-gp) and glutathione S-transferase (GST-s) in tumor cells. As a result, the resistance of SGC7901/VCR cells to VCR, fluorouracil and epirubicin was 16.56, 2.69 and 13.05 times, respectively, more than that of SGC7901 cells. After 24 h precondition with As2O3, RI of vincristine, fluorouracil and epirubicin decreased significantly (P < 0.05). Expression of P-gp and GST-s in resting SGC7901/VCR cells was significantly higher than that in carcinogen-sensitive SGC7901 cells. As2O3 decreased the expression of P-gp and GST-s in SGC7901/VCR cells significantly, while it showed no significant effect on carcinogen-sensitive SGC7901 cells. The result suggested that As2O3 could partly reverse drug resistance of SGC7901/VCR cells by probably the mechanism of decreasing the expression of P-gp and GST-s.
ATP-Binding Cassette, Sub-Family B, Member 1 ; metabolism ; Adenocarcinoma ; metabolism ; pathology ; Antineoplastic Agents ; pharmacology ; Arsenicals ; pharmacology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Drug Resistance, Multiple ; drug effects ; Drug Resistance, Neoplasm ; drug effects ; Epirubicin ; pharmacology ; Fluorouracil ; pharmacology ; Glutathione Transferase ; metabolism ; Humans ; Oxides ; pharmacology ; Stomach Neoplasms ; metabolism ; pathology ; Vincristine ; pharmacology

Objective To investigate the clinicopathological characteristics and prognosis of Henoch-Schonlein purpura nephritis with diffused endothelial cell proliferation (DEP-HSPN) in children. Methods Data of 8 DEP-HSPN cases in Nanjing Children's Hospital within recent ten years were retrospectively reviewed. The clinicopathological features, efficacy and prognosis were compared between DEP-HSPN cases and 48 cases of non-DEP-HSPN. Non-DEP-HSPN cases were divided into two groups according to the clinical classification or the pathological classification.Results (1) In DEP-HSPN, HSP developed nephritis within 4 to 15 days after the initial onset of purpuric rashes. Hematuria was present in all the 8 patients. The main clinical manifestation of DEP-HSPN was nephritic-nephrotic syndrome (4 cases), nephrotic level proteinuria (3 cases) and acute nephritic syndrome (1 case). Four cases had macrohematuria. Six cases had abdominal symptoms and two cases had arthritis. Pathology of all the cases showed grade Ⅲ-b lesion with diffused endocapillary proliferation and segmental necrotizing lesion of the capillary wall, always accompanied with intraglomerular inflammatory cell infiltration. Crescent was found in 4 cases. (2)Compared to non-DEP-HSPN grades Ⅲ, DEP-HSPN showed a shorter course of disease.Macrohematuria, heavy proteinuria, nephritic-nephrotic syndrome, and segmental necrotizing lesion of capillary wall were more common in DEP-HSPN. Compared to non-DEP-HSPN with nephrotic level proteinuria, DEP-HSPN had a lower rate of crescent. (3) Methylprednisolone pulse therapy in early stage, then prednisone combined with cyclophosphamide were used in the treatment of DEP-HSPN.After an average follow-up period of seven months, one patient showed complete remission, five showed persistent microhematuria, and two showed persistent microhematuria accompanied with minor proteinuria. No significant difference of prognosis was found between DEP-HSPN and nonDEP-HSPN. Conclusions DEP-HSPN has an acute onset. The main clinical manifestation of DEP-HSPN is nephritic-nephrotic syndrome and nephrotic level proteinuria, always accompanied with macrohematuria. Immunosuppressant treatment in the early stage of disease is effective for a short-term outcome.