The composition of intestinal microflora is closely related to the occurrence and development of colorectal cancer (CRC). Among them, Fusobacterium nucleatum (Fn) has been proved directly related to the recurrence, metastasis and chemotherapy resistance of CRC. Therefore, it is of great significance for the prevention and treatment of colorectal cancer by the exploration potential anti-Fn drug targets and discovery small molecule drugs. However, no selective anti-Fn small molecule inhibitors have been reported so far as well as their anti-Fn thereby "anti-Fn further anticancer" mechanisms are unclear. Herein, this article reviews the potential therapeutic targets and small molecule ligands of Fn in order to provide a reference for the development of anti-Fn and anti-CRC small molecule drugs.

Objective To explore the activated brain region of acute epilepsy in cat model induced by pentylenetetrazol(FFZ)with manganese enhanced-functional MR imaging(ME-fMRI),and evaluate the application of ME-fMRI on localization of the activated brain.Methods Forty cats were divided into 4 groups by random number table method as epileptic A and B groups as well as control A and B groups. Cats of epileptic groups were injected with PTZ(55 mg/kg)intramuscularly,and those of control groups were injected with the saline at same dose.The behavior change in the epileptic and control group A was observed and electroencephalogram(EEG)was also undertaken.Cats of epileptic and control group B were performed ME-fMRI,and the percentage of the enhanced signal intensity was then calculated.Results After injection with PTZ(55 mg/kg)intramuscularly,epileptic seizure was all evoked,and then EEG recording showed spike-wave and polyspike-wave complexes.The neocortex of cats of epileptic group B was diffusely phanero-enhanced on ME-fMRI.The percent enhancement of signal intensity in cortex of frontal lobe,parietal lobe and occipital lobe was(34.6?5.7)% and that in cortex of temporal lobe with(22.9? 6.5)%,whereas those of control group B with(14.9?4.5)% and(11.6?3.2)% respectively.And there was significant difference between the above different localization of the brain in the two groups (t=-10.43,-5.46 respectively,P

OBJECTIVETo analyze the prevalence of asthma and asthma related symptoms among children aged 0-14 years in three Chinese cities and to obtain a crude estimation of the trend of childhood asthma prevalence in China.

METHODSA cross-sectional, population-based survey of prevalence of asthma was conducted in children aged from 0 to 14 years in 3 major cities of China (Beijing, Chongqing, and Guangzhou) with different geographic locations. All the subjects were randomly selected by a multi-stage sampling method. Three to five schools and kindergartens in 2 urban districts in each city were randomly selected for the survey, and a validated questionnaire that included the core questions of the International Study of Asthma and Allergies in Childhood, Phase III questionnaire and several additional questions were used. All questionnaires were completed by parents or guardians of the selected children. Children whose parents responded affirmatively to the question "Has your child ever been diagnosed as asthma by a doctor" were recognized as victims of asthma.

RESULTSThe prevalence of asthma in Beijing, Chongqing, and Guangzhou was 3.15%, 7.45%, and 2.09%, respectively. These values were significantly higher than those obtained 10 years ago in the national epidemiological survey in 2000 which used the same method of investigation and the same diagnotic criteria (χ²=3.938, P=0.047; χ²=73.506, P≤0.001; χ²=11.956, P=0.001, in each city). Of the asthmatic children 57.21%, 69.91%, and 60.00% had their first attack before the age of 3 in Beijing, Chongqing, and Guangzhou, respectively. Wheezing was the primary clinical manifestation for all asthmatic children, followed by persistent cough and repeated respiratory infections. Both the prevalence of asthma and asthma-related symptoms were statistically higher in males than in females.

CONCLUSIONThe prevalence of childhood asthma is statistically higher than that 10 years ago in the three Chinese cities.

Asthma ; epidemiology ; Child ; Child, Preschool ; China ; epidemiology ; Female ; Humans ; Male ; Prevalence

The present study was designed to test the hypothesis that a medium-term simulated microgravity can induce region-specific remodeling in large elastic arteries with their innermost smooth muscle (SM) layers being most profoundly affected. The second purpose was to examine whether these changes can be prevented by a simulated intermittent artificial gravity (IAG). The third purpose was to elucidate whether vascular local renin-angiotensin system (L-RAS) plays an important role in the regional vascular remodeling and its prevention by the gravity-based countermeasure. This study consisted of two interconnected series of in-vivo and ex-vivo experiments. In the in-vivo experiments, the tail-suspended, hindlimb unloaded rat model was used to simulate microgravity-induced cardiovascular deconditioning for 28 days (SUS group); and during the simulation period, another group was subjected to daily 1-hour dorso-ventral (-G(x)) gravitation provided by restoring to normal standing posture (S + D group). The activity of vascular L-RAS was evaluated by examining the gene and protein expression of angiotensinogen (Ao) and angiotensin II receptor type 1 (AT1R) in the arterial wall tissue. The results showed that SUS induced an increase in the media thickness of the common carotid artery due to hypertrophy of the four SM layers and a decrease in the total cross-sectional area of the nine SM layers of the abdominal aorta without significant change in its media thickness. And for both arteries, the most prominent changes were in the innermost SM layers. Immunohistochemistry and in situ hybridization revealed that SUS induced an up- and down-regulation of Ao and AT1R expression in the vessel wall of common carotid artery and abdominal aorta, respectively, which was further confirmed by Western blot analysis and real time PCR analysis. Daily 1-hour restoring to normal standing posture over 28 days fully prevented these remodeling and L-RAS changes in the large elastic arteries that might occur due to SUS alone. In the ex-vivo experiments, to elucidate the important role of transmural pressure in vascular regional remodeling and differential regulation of L-RAS activity, we established an organ culture system in which rat common carotid artery, held at in-vivo length, can be perfused and pressurized at varied flow and pressure for 7 days. In arteries perfused at a flow rate of 7.9 mL/min and pressurized at 150 mmHg, but not at 0 or 80 mmHg, for 3 days led to an augmentation of c-fibronectin (c-FN) expression, which was also more markedly expressed in the innermost SM layers, and an increase in Ang II production detected in the perfusion fluid. However, the enhanced c-FN expression and increased Ang II production that might occur due to a sustained high perfusion pressure alone were fully prevented by daily restoration to 0 or 80 mmHg for a short duration. These findings from in-vivo and ex-vivo experiments have provided evidence supporting our hypothesis that redistribution of transmural pressures might be the primary factor that initiates region-specific remodeling of arteries during microgravity and the mechanism of IAG is associated with an intermittent restoration of the transmural pressures to their normal distribution. And they also provide support to the hypothesis that L-RAS plays an important role in vascular adaptation to microgravity and its prevention by the IAG countermeasure.
Angiotensinogen ; genetics ; metabolism ; Animals ; Aorta, Abdominal ; pathology ; physiopathology ; Carotid Artery, Common ; pathology ; physiopathology ; Hindlimb Suspension ; Male ; Muscle, Smooth, Vascular ; metabolism ; pathology ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley ; Receptor, Angiotensin, Type 1 ; genetics ; metabolism ; Renin-Angiotensin System ; physiology ; Weightlessness Simulation

OBJECTIVETo investigate the correlation between MHC class I-related chain A (MICA) gene *008 allele and human cytomegalovirus (HCMV) infection.

METHODSMICA*008 allele was detected in 86 patients with chronic granulocytic leukemia and 81 unrelated normal individuals by way of sequence-specific primers (PCR-SSP). Anti-HCMV IgM was also detected in the sera of these subjects with enzyme linked immunosorbent assay (ELISA).

RESULTSMICA*008 allele frequency was lower in patients with chronic granulocytic leukemia than in the control group (22.2% vs 34.3%, Chi(2)=4.98, P<0.05). The infection rate of HCMV was significantly higher in those individuals with genotype of MICA*008 (-) than in those with MICA*008 (+), and moderate correlation was suggested between MICA*008 and HCMV infection (C=0.5829, 0.6142).

CONCLUSIONIndividuals with MICA*008 positivity is not liable to HCMV infection, but those with MICA*008 (-) can be vulnerable to HCMV infection, suggesting an inverse correlation between MICA*008 allele with HCMV.

Alleles ; Cytomegalovirus Infections ; genetics ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Histocompatibility Antigens Class I ; genetics ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; genetics ; virology

AIMTo investigate the molecular mechanisms of saponins from the rhizome of Anemarrhena asphodeloides Bunge.

METHODSOligonucleotide microarrays consisting of 87 probes representing 87 human cardiovascular disease-related genes were constructed. Effects of saponins on gene expression in human umbilical vein endothelial cells were analyzed by comparing hybridization of Cy 5-labeled cDNAs from saponins-treated human umbilical vein endothelial cells and Cy 3-labeled cDNAs from untreated human umbilical vein endothelial cells.

RESULTSThe results indicate that angiotensinogen gene, alpha 2A-adrenoceptor gene and endothelin-converting enzyme 1 gene were downregulated 2.8, 1.9 and 3.1 folds respectively after human umbilical vein endothelial cells were incubated in medium containing 80 mg.L-1 saponins.

CONCLUSIONThese results suggest that saponins may have beneficial effect on cardiovascular diseases by modulating the function of vein endothial cells and microarray can be used to investigate the biological action of extracts from traditional Chinese medicine.

Anemarrhena ; chemistry ; Angiotensinogen ; genetics ; metabolism ; Aspartic Acid Endopeptidases ; genetics ; metabolism ; Cells, Cultured ; Down-Regulation ; drug effects ; Endothelin-Converting Enzymes ; Endothelium, Vascular ; cytology ; metabolism ; Gene Expression ; drug effects ; Humans ; Metalloendopeptidases ; Oligonucleotide Array Sequence Analysis ; Plants, Medicinal ; chemistry ; Receptors, Adrenergic, alpha-2 ; genetics ; metabolism ; Rhizome ; chemistry ; Saponins ; isolation & purification ; pharmacology ; Umbilical Veins ; cytology ; metabolism

Objective　To investigate the effect of rapid fluid replacement on hemorheology in delayed resuscitation after burn. Methods　A total of 32 dogs inflicted with 40%TBSA full thickness scalding were randomly divided into 4 groups: scald control group(C group), delayed Gelofusion even replacement group (GE group), rapid fluid replacement group (GR group), and delayed plasma rapid fluid replacement group (PR group). The femoral arterial pressure, viscosity of blood and plasma, packed cell volume and aggregation of RBC were detected at the intervals of before and 2, 6, 8, 12, 24, 36 and 48 hours after scalding. Results　The viscosity of blood markedly increased at 2 hours after scalding, and the hemorheology parameters decreased after fluid resuscitation. The hemorheologic parameters were obviously lower in GR group than in GE group at 2 hours after rapid resuscitation, the viscosity of blood and RBC aggregation in GR group were obviously lower than those in PR group. Conclusion　Under the condition of delayed resuscitation after burn, rapid fluid replacement can quickly decreased the state of blood high viscosity and may play a role in improving microcirculation and treating burn shock.

OBJECTIVETo explore whether endothelin-1 and NO are involved in the instant changes in cardiac function at early stage of severe burn.

METHODS(1) Thirty-one Wistar rats were divided into sham burn A group (SA, n = 7), burn A group (BA, n = 10), non-selective endothelin A/B receptor antagonist PD142893 group (n = 7), and the selective endothelin A receptor antagonist BQ-123 group (n = 7) according to the random number table. Rats in the latter three groups were inflicted with 30% TBSA full-thickness burn. Immediately after injury, rats in PD142893 group and BQ-123 group were intravenously injected with PD142893 (0.1 mg/kg) and BQ-123 (30 nmol x kg(-1) x min(-1)) respectively. Rats in SA group were treated the same as rats in BA group except for sham injury. The cardiac function indexes of rats in BA and SA groups including left ventricular systolic pressure (LVSP) heart rate (HR) and LV + or - dp/dt max were monitored before injury and 10, 30, 60, 180 minutes post injury (PIM) using physiological signal acquisition and processing system. The respective changes in cardiac function indexes of rate in each group between PIM 10 and pre-injury in the value of percentage were calculated. (2) Another 20 Wistar rats were enrolled and divided into sham burn B group (SB, n = 4) and burn B group (BB, n = 16) according to the random number table, and they were subjected to above-mentioned injury. Heart tissues of rats in BB group were obtained at PIM 10, 30, 60, and 180 respectively (4 rats at each time point), and that in SB group were obtained immediately after injury. Endothelin-1 and NO contents in heart tissues were determined with ELISA.

RESULTS(1) Compared with the pre-injury value, LVSP, HR, LV +dp/dt max, LV -dp/dt max of rats in BA group decreased significantly since PIM 10 (with F value respectively 7.14, 16.40, 14.09 14.98, P < 0.05 or P < 0.01). No significant change was observed in above 4 indexes in rats of SB group between above mentioned two time points (with F value respectively 0.59, 0.51, 1.03, 1.04, P values all above 0.05). (2) In BA group, compared with the pre-injury value, LVSP decreased 27%, HR decreased 14%, LV +dp/dt max decreased 51%, LV -dp/dt max decreased 50% at PIM 10. Compared with those in BA group at PIM 10, cardiac function indexes were improved significantly in PD142893 group, with LVSP decreased 14% (F = 8.10, P < 0.01), HR increased 4% (F = 6.50, P < 0.01), LV +dp/dt max decreased 31% (F = 23.67, P < 0.05), LV -dp/dt max decreased 14% (F = 10.39, P < 0.01). In BQ-123 group, compared with the pre-injury value, HR increased 3%, LV -dp/dt max decreased 26% at PIM 10, which were obviously improved as compared with those in BA group (with F value respectively 6.50 and 10.39, P < 0.05 or P < 0.01); the percentage changes of LVSP and LV +dp/dt max in BQ-123 group were close to that in BA group (with F value respectively 8.10 and 23.67, P values both above 0.05). (3) Compared with those in SB group, myocardial tissue endothelin-1 content of rats in BB group increased significantly at PIM 10, 60, 180 (F = 2.85, P < 00.05 or P < 0.01), and NO content increased significantly at PIM 60, 180 (F = 1.87, with P values all below 0.05).

CONCLUSIONSEndothelin-1 may participate in the instant decline of cardiac function of rats at early stage of severe burn, and plays an important role in the instant myocardial damage after injury.

Animals ; Burns ; metabolism ; physiopathology ; Endothelin-1 ; metabolism ; Heart ; physiopathology ; Male ; Myocardium ; metabolism ; Nitric Oxide ; metabolism ; Rats ; Rats, Wistar

OBJECTIVETo investigate the instant changes in heart function and organ blood flow, and their relations in rats at early stage of severe burn.

METHODSThirty-six SD rats were divided into sham injury group (S, n = 6) and burn group (B, n = 30) according to the random number table. Rats in B group were subjected to 30% TBSA full-thickness burn. Five time points for observation: 10 and 30 minutes, and 1, 3, and 6 hour (s) post injury (PIM/H) were set up, with 6 rats at each time point. Rats in S group were sham scalded with 37 degrees C warm water. Hemodynamics indexes including heart rate (HR), mean artery pressure (MAP), left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), LV + or - dp/dt max were determined. Blood flow of heart, brain, kidney, spleen, stomach, and ileum was determined respectively with fluorescent microspheres method. The correlation between LV + or - dp/dt max and myocardial blood flow was analyzed.

RESULTS(1) Compared with those of S group, HR in B group decreased gradually after injury; MAP, LVSP, LV +dp/dt max, LV -dp/dt max and myocardial blood flow in B group decreased obviously at PIM 10 (with F value respectively 12.062, 12.629, 11.066, 18.374, 9.468, and P values all below 0.01). Among them, myocardial blood flow decreased from (6.8 + or - 0.8) mL x min(-1) g(-1) to (2.6 + or - 0.5) mL x min(-1) x g(-1). Above-mentioned indexes increased gradually as the time after injury went on, with the highest values (except for LV +dp/dt max) observed at PIH 1, which decreased again later, with values at PIH 3 and 6 significantly lower than those in S group (the same F values as above, P values all below 0.01). There was no obvious difference in LVEDP between S group and B group at each time point (F = 1.205, with P values all above 0.05). (2) Compared with those of S group, blood flow of kidney, spleen, stomach, and ileum of rats in B group at PIM 10 declined obviously (with F value respectively 22.694, 20.856, 12.653, 7.293, P < 0.05 or P < 0.01), but the decline range was smaller than that in heart. The lowest values of above-mentioned indexes were observed at PIH 1 or PIH 3. Brain blood flow of rats in B group at each time point was close to that in S group (F = 1.812, with P values all above 0.05). (3) The correlation coefficient r between LV +dp/dt max, LV -dp/dt max and myocardial blood flow was respectively 0.651 and 0.617, showing significant positive correlation (with t value respectively 4.456 and 4.222, and P values all below 0.01).

CONCLUSIONSThe myocardial ischemia and decrease in cardiac function may occur in a very short time after severe burn (PIM 10). The rapid decrease of heart blood flow plays an important role in the change in cardiac function. Myocardial damage and decrease of cardiac function may be one of the important factors result in the decline of blood flow in other organs.

Animals ; Brain ; blood supply ; Burns ; physiopathology ; Disease Models, Animal ; Heart ; physiopathology ; Hemodynamics ; Ileum ; blood supply ; Kidney ; blood supply ; Male ; Myocardial Ischemia ; physiopathology ; Rats ; Rats, Sprague-Dawley ; Regional Blood Flow ; Spleen ; blood supply ; Stomach ; blood supply

BACKGROUNDIncreased triglyceride (TG) occurs in patients with acute coronary syndrome (ACS), and apolipoprotein AV (apoAV) has been shown to lower TG levels. In the present study, we investigated plasma apoAV level and its relationship with TG and C-reactive protein (CRP) in ACS patients.

METHODSA total of 459 subjects were recruited and categorized into control group (n = 116), stable angina (SA) group (n = 115), unstable angina group (n = 116) and acute myocardial infarction group (n = 112). Plasma apoAV level was measured by a sandwich ELISA assay.

RESULTSCompared with controls ((100.27 +/- 22.44) ng/ml), plasma apoAV was decreased in SA patients ((76.54 +/- 16.91) ng/ml) but increased in patients with unstable angina ((330.89 +/- 66.48) ng/ml, P < 0.05) or acute myocardial infarction ((368.66 +/- 60.53) ng/ml, P < 0.05). Inverse correlations between apoAV and TG were observed in the control or stable angina groups (r = -0.573 or -0.603, respectively, P < 0.001), whereas positive correlations were observed in the patients with unstable angina or acute myocardial infarction (r = 0.696 or 0.690, respectively, P < 0.001). Furthermore, a positive relationship between apoAV and CRP was observed in the ACS patients but not in the non-ACS subjects.

CONCLUSIONThe plasma apoAV concentration is increased and positively correlates with TG and CRP in ACS patients.

Acute Coronary Syndrome ; blood ; metabolism ; Adult ; Aged ; Apolipoprotein A-V ; Apolipoproteins A ; blood ; C-Reactive Protein ; metabolism ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Male ; Middle Aged ; Triglycerides ; blood