Background and purpose:The cinobufacini injection is a traditional antitumor drug.However,its mechanism iS still unclear.The purpose of this study was to observe the effect of cinobufacini injections in DNA TOPO Ⅰ of human hepatocellular carcinoma HcpG-2 cells.Methods:The cells that were proliferated were assessed by MTT assay.Cell cycles were shown through FCM.TOPO Ⅰ mRNA expression was analyzed through RT-PCR.The activity of TOPO Ⅰ was measured by TOPO Ⅰ mediated super coiled PHR322 relaxation.Supercoiled PBR322 was also used to determine the direct DNA breakages.Results:Cinobufacini injections significantly inhibited HepG-2 cells proliferation in ways that were dependent on dosages and time.Induced tumor cells arrest at the S-phase.TOPO ⅠmRNA expression decreased in a manner that was dependent on dosages which inhibited the TOPO Ⅰ mediated DNA relaxations.However,the cinobufacini injections could not directly induce DNA breakage at any concentration.Conclusion:Cinobufacini injections can inhibit human hepatocellular carcinoma HepG-2 cells proliferation.The regulation of topoisomerase Ⅰ activity and mRNA expression may be one of the mechanisms that causes the cinobufacini injection to contribute against tumor.

Objective To explore protective effect of heparin on renal of children with Henoch-Schonlein purpura(HSP).Methods Two hundred and fifteen cases with HSP were divided into heparin-treated group(110 cases,male 64,female 46) and control group (105 cases,male 61,female 44).Serum IL-6 and IL-8 levels were examined by using radioimmunoassay respectively.These patients were followed up for more than 6 months.Results 1.The level of IL-6,IL-8 did not show significant difference between heparin-treated group and control group before treatment.The serum concentrations of IL-6,IL-8 in heparin-treated group were obviously lower than those in control group,after treatment,there was significantly different[IL-6(116.50?19.45)vs(123.88?22.55)ng /L,t=2.573 P=0.011;IL-8(0.161?0.043)vs(0.173?0.048)?g/L,t=2.024 P=0.044].2.During more than 6 months follow-up there were 26 cases suffering from purpura nephritis in heparin-treated group, the morbidity was 25%; the morbidity in control group was 39.8%,the morbidity in treatment group was significant lower than that in control group(?2=5.061 P=0.024).The time of renal injury was significantly delay in treatment group(35.0?13.2)d compared with that of control group (26.0?12.1)d(t=2.659 P=0.010).Conclusions The serum IL-6 and IL-8 concentrations in HSP obviously decrease after heparin treatment.Heparin therapy can decrease the morbidity of renal injury in children with HSP and delay the time of renal injury effectively.

Objective To evaluate chest CT features of microscopic polyangiitis(MPA).Methods Clinical data and chest CT images of 66 patients diagnosed as MAP had been collected.Depending on clinical manifestations.the 66 cases were divided into the active group and the stable group.The data of two groups were analyzed by x2 test.Results Forty-three of 66(65.2%)CT images were abnormal including 32 of them in active group and 11 in stable group. In these patients,CT images showed ground glass opacities(53.5%),lung consolidations(23.2%),scattered patchy opacities(44.2%),ground glass opacities and/or lung consolidations(76.7%),reticular opacities(65.1%),honeycomb(14.0%),pleural effusions(48.8%),emphysema(18.6%),and mediastinal adenopathies(58.1%).Lung consolidations,ground glass opacities,scattered patchy opacities,mediastinal adenopathies,and pleural effusion in the active group are more common than that in the stable group(X2=4.479,4.083,4.053,9.697,9.345 respectively,P<0.05).Conclusion Chest CT features of in patients with MPA have difference between active and stable periods.The chest CT scan is a useful tool to diagnose MAP in different periods and guide the treatment.

Objective To investigate the effects of substrate stiffness on the proliferation of human umbilical vein endothelial cells ( HUVEC) during dengue virus infection.Methods Polyacrylamide gels were prepared for cell culture [(0±4) kPa].The proliferation of HUVEC cultured on substrates with differ-ent stiffness was determined by using 3-(4,5-diethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfo-phenyl)-2H-etrazolium,inner salt ( MTS) assay.The cycle and apoptosis of HUVEC were determined by flow cytometry analysis.Dengue virus serotype 2 (DENV-2) strains were propagated and identified by con-ventional assays.The HUVEC were infected with DENV-2 strains at a MOI of 10 and cultured on traditional plastic and hydrogel substrates, respectively.The levels of nitric oxide (NO) and endothelin-1 (ET-1) were detected by nitric acid reductase assay and double antibody sandwich ELISA.Results Young′s modulus E value of the hydrogels was (3030 ±0.44) Pa.The proliferation of HUVEC and the expression of NO and ET-1 were enhanced along the increased substrate stiffness.However, no significant differences with the cell cycle and apoptosis were observed between cells cultured on different substrates.Conclusion The stiffness of substrates affected not only the proliferation of HUVEC, but also the release of cytokines during DENV-2 infection.The development of dengue fever was associated with the decreased secretion of vascular active substances as a result of blood vessel injury.The establishment of hydrogel substrates as the model of vascu-lar basement membranes might provide a new way for the in vitro investigation of the pathogenesis of DENV infection.

Objective To analyze the effects of dengue virus 2 ( DENV-2 ) infection on the ex-pression of IL-29 in primary human umbilical vein endothelial cells ( HUVECs) cultured on hydrogel sub-strates .Methods Primary HUVECs were isolated and cultured on hydrogel substrates .DENV-2 stains were used to infect the primary HUVECs at a multiplicity of infection( MOI) of 10.Flow cytometry analysis was performed to detect the apoptosis and infection rate of HUVECs after 48 hours of culturing .The gene chip profiling was performed to analyze mRNA expression .The expression of IL-29 at mRNA and protein levels were measured by real-time fluorescent quantitative PCR analysis and double antibody sandwich ELISA as -say, respectively.Results Compared with 96.36%of baby hamster kidney (BHK) cells that were infected with DENV-2 stains, only 4.71%primary HUVECs cultured on hydrogel substrates were infected .The pri-mary HUVECs cultured on hydrogel substrates with or without DENV-2 infection showed no significant differ-ences with the rates of cell apoptosis and infection (P>0.05).A significant difference was observed with the expression of IL-29 at mRNA level between primary HUVECs cultured on hydrogel substrates and the cells cultured in plastic bottles (P<0.05).The results of the real-time quantitative PCR analysis and ELISA as-say showed that IL-29 was highly expressed in DENV-2 infected primary HUVECs cultured on hydrogel sub-strates as compared with those in control groups (P<0.05).Conclusion The expression of IL-29 was de-tected in DENV-2 infected primary HUVECs cultured on hydrogel substrates , which was significantly differ-ent from that in DENV-2 infected primary HUVECs cultured in plastic bottles .The successful establishment of hydrogel substrates as the model of vascular basement membranes might provide a new way for the investi -gation of the pathogenesis of DENV infection .

Objective To explore the effects of coincident infection on treatment response and coronary artery lesion (CAL) outcome in children with Kawasaki disease(KD).Methods A retrospective study of 141 children diagnosed on KD between Jul.2005 and Dec.2006 were performed.Standardized clinical assessments,laboratory examinations microbiology test results plus treatment regimens were reviewed.CAL were visualized by using echocardiography.Infectious agents positive (INF+) and negative (INF-) groups were identified,and clinical assessments,laboratory and treatment data were analyzed.Results 1.Concurrent infections:41%(58/141) of children had one of above confirmed infection at KD diagnosis.2.Treatment response:the presence of infection did not alter the response to treatment with intravenous immunoglobulin (IVIG),with resolution of fever within 72 h in 85% (120/141) children after 1 dose of IVIG (2 g/kg) together with aspirin administration regardless of present or absent infection.3.CAL outcome:in total,56.0% (79/141) of children developed CAL at the time of diagnosis,involving dilatation (91.1%,72/79 cases) and aneurysm (8.9%,7/79 cases),and no giant aneurysm was found.Most CAL were recovered within 1 year after treatment.Incidence of aneurysm in INF+ group was significantly higher than that in INF-group (P=0.019).Conclusions Coincident infection would not affect on the clinical assessment,laboratory test results and treatment response to IVIG in children with KD,but would result in higher risk of serious CAL.Therefore,children with infection at diagnosis on KD will not only accept active treatment in acute phase,but also insist on convalescent care and follow-up visit.

Objective To explore the clinical significance of monocyte chemoattractant protein-1(MCP-1)in children with Henoch-Schonlein purpura nephritis(HSPN).At the same time compare the association between serum and urine MCP-1,to investigate the impact of the both on them in children with HSPN.Methods Serum and urine MCP-1 were measured by enzyme linked immunosorbent assay in 50 children with Henoch-Schonlein purpura(HSP)(25 cases of them patients with renal injures),and 25 healthy children,the changes of serum and urine MCP-1 were compared;at the same time serum urea nitrogen,creatinine,urinary albumin,urine N-acetyl-D-glucosaminidase(NAG),urine ?2-MG,24 hours urinary levels of protein were investigated in children with HSPN by analyzing the correlation between these indicators and serum and urine MCP-1;urine MCP-1 in HSPN group were measured in recovery period,and were compared with urine MCP-1 in HSP group and HSPN group in acute period.Results 1.The expressions of urine MCP-1 was significantly higher in HSPN group than those in HSP group and healthy controls(P0.05).2.Urine MCP-1 levels were associated with proteinuria in children with HSPN,but serum MCP-1 levels had nothing to do with HSPN.3.There was a close correlation between urine MCP-1 expression and urinary albumin,urine NAG,urine ?2-MG and 24 hours urinary levels of protein,but the expression of urine MCP-1 levels were not correlated with the serum urea nitrogen and creatinine.4.There was statistical significance in urine MCP-1 in acute and recovery periods with HSPN group(P

The nuclear transcription factor nuclear factor erythroid 2-related factor 2 (NRF2) plays a crucial role in maintaining cellular redox homeostasis. The aberrant NRF2 signaling confers enhanced antioxidant capacity, which is linked to tumor progression and therapeutic resistance. The current study investigates the biological effects and molecular mechanism of tribbles homolog 3 (TRIB3), a stress-induced protein, in regulating cell survival and apoptosis in lung cancer. This study first performed the RNA sequencing data analysis with 576 lung adenocarcinoma patients from the cancer genome atlas (TCGA) database. The NRF2- antioxidant response element (ARE) signature was enriched in patients with high TRIB3 expression. Dual-luciferase reporter assay and real-time quantitative polymerase chain reaction (PCR) were used to confirm the effect of TRIB3 on the kelch-like ECH-associated protein-1 (KEAP1)-NRF2 pathway. Abrogation of TRIB3 impaired NRF2 transcriptional activity and reduced the expression of its target genes. Moreover, TRIB3 enhanced NRF2 stability via blocking KEAP1-NRF2 interaction. TRIB3-depletion promoted reactive oxygen species (ROS) production, restrained cell proliferation, and enhanced carboplatin-induced apoptosis. In addition, NRF2 overexpression recovered the tumor inhibition effect of TRIB3-depletion. Consistently, TRIB3 failed to modulate apoptosis in NRF2 depletion cells. In summary, this study shows that TRIB3 inhibits the KEAP1-NRF2 interaction and upregulates the transcriptional activity of NRF2, thereby promoting lung cancer cell proliferation and reducing the sensitivity to chemotherapy. Targeting the TRIB3-NRF2 signal axis may become a new strategy for ROS homeostasis and lung cancer treatment.

Objective To investigate the effect of excessive fluoride,aluminum on Zn,Fe,Ca,Mg,Cuin rat blood.Methods Forty eight SD rats were randomly divided into 4 groups matched with their weights:control group,high aluminum group,high fluorine group and high fluorine-aluminum group.Aluminum content in their drinking water was 0,90,0,90 mg/L respectively.Fluorine content of their feed was 5.2,5.2,106.0,106.0 mg/kg and aluminum Was 6.8,6.8,19.7,19.7 mg/kg respectively.90 days later,the level of blood Zn,Fe,Ca,Mg, Cu Was detected by the atomic absorption spectrometry.Results Compared among these groups,Zn,Fe,Mg and Cu content of the whole blood had significant difierences(F=46.25,14.74,6.10,2.93,P<0.05),while Ca content of the whole blood did not significantly change(F=2.81.P>0.05).Factorial analysis showed that excessive intake of aluminum could significantly decreased Zn,Fe,Mg content of the blood(F=42.66,5.41,7.04,P<0.05)and excessive intake of fluorine could significantly decreased Zn,Fe,Mg,Cu content of the blood(F=64.50,37.90,9.75,6.74, P<0.05).The coexistence offluorine and Muminum had interaction to the level of Zn(F=31.59,P<0.05)and did not obviously interact with other elements(F=0.91,1.63,1.51.0.00,P>0.05).Compared with the control group [(131.30 ±13.86)μmol/L,(10.24 ±1.02),(1.71 ±0.19)mmol/L,(20.43 ±4.42)μmol/L],Zn content in the high aluminum group[(90.84±9.98)μmol/L]decreased significantly(P<0.05),so did Zn,Fe,Mg content in tlle high fluorine group[(85.85 ±10.92)μmol/L,(8.49 ±0.68),(1.52 ±0.13)mmol/L],the difference being statistically significant(P<0.05)0Zn,Fe,Mg,Cu content in the high fluorine-aluminum group,being(82.82 ±11.00)μmol/L, (8.16±0.45),(1.46±0.09)mmoL/L,(15.69±2.38)μmol/L,respectively,all decreased signitlcarIdy(P<0.05). Compared with the high aluminum group[(9.43±1.09)mmol/L],Fe content of the high fluorine aluminum group[(8.16±0.45)mmol/L]decreased significantly(P<0.05).Conclusions Excessive fluoride can cause blood zn, Fe,Mg,Cu decline,so can excessive aluminum.Combination of excessive fluofine and aiuminum has 8ignificant synergic effect on the level of Zn but have rio influence on Ca.

China ; epidemiology ; Cleft Lip ; epidemiology ; Cleft Palate ; epidemiology ; Female ; Humans ; Infant, Newborn ; Male