Objective To evaluate the efficacy and safety of a new drug,human urinary kallidinogenase,against acute brain infarction.Method A 15-center,randomized,double-blinded and 3:1 placebo-controlled study was carried out.Acute brain infarction within 48 hours of onset in the territory of the middle cerebral artery were indicated as subjects;kallidinogenase or placebo which was dissolved in 50 ml saline,was slowly injected intraveousely within 30 minutes daily for 3 weeks.The European Stroke Scale and Barthel Index were used to evaluate the neurological deficit and the activities of daily living(ADL),followed by a follow-up at the end of the third month.Results 446 patients were enrolled,who completed ITT analysis,including 330 in kallidinogenase group and 116 in placebo group,meanwhile 421 proceeded with PP analysis(311 and 110 respectively).There were no significant differences of the baseline data between the 2 groups.At the end of treatment,the ESS scores increased by 55.1%?33.0% and 44.7%?32.8% respectively in kallidinogenase group(KG)and placebo group(PG,P=0.0022),the difference being significant.PP analysis had similar results.As for ADL,follow-up 90 days after the treatment showed 374 cases followed,280 in KG and 94 in PG;1 died in PG,while none in KG.In KG,the cases whose BI≥50 were significantly more than those in PG(P=0.0228).Adverse events possibly or definitely attributable to the drug were observed in 27 cases(7.74%),mostly were mild,such as palpitation,flush,dizziness, nausea etc,without special management needed.Only 2 died which was confirmed not correlated to kallidinogenase,and another 2 cases of sudden blood pressure drop were observed.The blood pressure drop, quickly restoring soon after the withdrawal of kallidinogenase and use of hemopiesic drugs,was considered to be caused by the combination use of anti-hypertensive drug ACEI and quick infusion speed.Conclusion Kallidinogenase is efficacious for acute brain infarction in improving the neurological deficits,which is safe in clinical use.

Mechanical ventilation (MV) with large tidal volumes can increase lung alveolar permeability and initiate inflammatory responses,resulting in ventilator-induced lung injury (VILI).The mechanisms of the injurious effects of MV and the genetic susceptibility remain unclear.VILI-related genes such as cysteine-rich angiogenic inducer 61 (Cyr61)have been demonstrated to play a detrimental role in the aggressive ventilation strategies.In the present study,we investigated the involvement of Cyr61 in the VIM and the underlying mechanism.A549 cells were exposed to cyclic stretch of varying durations and then the mRNA and protein levels of Cyr61 were measured by real-time PCR and Western blotting,respectively.Additionally,after exposure ofA549 cells to cyclic stretch for 5 min to 1 h,the expression levels of nuclear factor kappaB (NF-κB) and IL-8 were detected by ELISA and Western blotting.Thereafter,Cyr61 expression was depressed in A549 cells with the siRNA pGenesill.1-Cyr61-3 before the cyclic stretch,and IL-8 secretion and the activation of NF-κB pathways were probed by ELISA and Western blotting,respectively.Moreover,a NF-κB inhibitor (PDTC) and an activator (TNF) were used before mechanical stretch.Realtime PCR and ELISA were performed to detect the mRNA and protein of IL-8,respectively.The results showed that the mechanical cyclic stretch led to increased Cyr61 expression at mRNA and protein levels in A549 cells.Additionally,cyclic stretch also mobilized NF-κB from the cytoplasm to the nucleus and increased IL-8 secretion in A549 cells.The inhibition of Cyr61 blocked the NF-κB activation and IL-8 secretion in response to cyclic stretch.Inhibition of NF-κB attenuated the mRNA and protein expression of IL-8 in A549 cells transfected with Cyr61 siRNA.It was suggested that Cyr61/NF-κB signaling pathway mediates the upregulation of IL-8 in response to cyclic stretch in A594 cells.These findings support the hypothesis that Cyr61 plays a critical role in acute lung inflammation triggered by mechanical strain.

· AIM: To inspect and compare the functional vision of an aspheric intraocular lens (Tecnis) with those of conventional monofocal silicone and acrylic intraocular lens and multifocal intraocular lens (Array).· METHODS: The IOLs were tested in the eye model, which was designed to be optically equivalent to the theoretical eye model. The eye model is a combination of a spherical photographic lens with 35mm focal length ( IOL put in a water cell)and a charge coupled device (CCD) camera. The images constructed by the lenses are observed on a monitor of personal computer and the contrasts of the images are analyzed by using commercial image processing software.· RESULTS: The modulation transfer function of the eye model equals the scale produced by the theoretical eye model. The images constructed by changing the diameter of aperture stop and IOL.· CONCLUSION: The proposed eye model is useful for testing functional vision and for inspecting differences of intraocular lens.

Objective: The current study was designed to distinguish Phase G0/G1， S， G2/M cell groups in the whole cell cycle by DNA flow cytometry. Method: The authors developed a multiparameter flow cytometry of cyclin E＋ A/DNA for MOLT-4. Result: The data showed that the method could distinguish Phase G0, early G1, late G1, S, G2,and M cells. The method could be used in molecular cell biology, especially in cell kinetic study.

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

This study was purposed to investigate the intercellular cell adhesion molecule-1 (ICAM-1) gene K469E (A/G) (rs5498) and K56M (A/T) (rs5491) single nucleotide polymorphisms (SNP) and soluble ICAM-1 (sICAM-1) levels in plasma in three Chinese populations of Yugur, Tibetan and Han nationalities, to analyze comparatively the genotypes and allele frequencies distribution in different ethnic groups, and to explore the effects of ICAM-1 K469E and K56M polymorphism and sICAM-1 levels in plasma. EDTA-anticoagulant venous blood from Yugur(327 cases), Tibetan (400 cases) and Han (126 cases) people was collected, the DNA was extracted by using whole blood genomic DNA extraction kit, DNA SNP were analyzed by PCR-RFLP, genotype was judged by gel scan imaging system after agarose gel electrophoresis, the gene sequence was determined and the distribution of ICAM-1 genotypes and allele frequencies were compared among different ethnic groups, besides, the group representativeness was tested via the Hardy-Weinberg genetic equilibrium. Finally, the human sICAM-1 plasma levels were detected by using human ICAM-1 ELISA kit. The results showed that DNA sequencing result was consistent with PCR-RFLP analysis. In Yugur, Tibetan and Han nationalities, the KK, KE and EE three genotypes at ICAM-1 K469E gene locus were detected, the genotype distribution was not statistically significantly different, while the K, E allele frequency distribution was statistically significantly different (P < 0.05). Both of genotype and allele frequency distribution between Yugur, Tibetan and Han nationalities were statistically significantly different (P < 0.05). In K56M site only KK, KM two genotypes were detected, but the MM genotype was not detected in the three ethnic groups; the difference of two genotypes and K, M allele frequencies between Yugur and Han population was statistically significantly different (P < 0.05). Among three ethnic groups, the sex ratio and age distribution of K469E, K56M genotypes and allele frequencies of ICAM-1 gene were not significantly different, and distribution was in accordance with Hardy-Weinberg genetic equilibrium (P > 0.05). The plasma sICAM-1 level at ICAM-1 K469E allele locus in K individuals [(253 ± 122), (185 ± 97) µg/L] was higher than that at non-K allele [(145 ± 110) µg/L, P < 0.01]; the plasma sICAM-1 level of ICAM-1 K56M sites with KK genotype [(253 ± 122) µg/L] was higher than that of the KM genotypes [(168 ± 103) µg/L, P < 0.01]. In Yugur and Tibetan groups, the plasma sICAM-1 levels [(224 ± 80), (214 ± 111) µg/L] were higher than that in the Han group [(175 ± 125)µg/L, P < 0.05]. Pairwise comparison indicated that the plasma sICAM-1 levels between Yugur and Han group were statistically significantly different (P < 0.01), that was significantly different between Tibetan and Han group (P < 0.05). It is concluded that in Yugur, Tibetan and Han population, the genotypes and gene frequencies of two amino acid sites K469E and K56M in ICAM-1 were KK/KE-type, KK-type and K allele, moreover, the ratio of them in Yugur and Tibetan group was higher than that in Han, while there is not significant difference in sex ratio and age distribution, therefore, ICAM-1 genotype and allele frequency distribution in this study had ethnic representativeness. ICAM-1 gene K469E and K56M polymorphisms were likely to affect the plasma sICAM-1 expression level. K469E gene K allele may be a genetic risk factor, while K56M gene M allele a may be genetic protective factor for some diseases.
Adolescent ; Adult ; Aged ; Asian Continental Ancestry Group ; genetics ; Ethnic Groups ; genetics ; Female ; Gene Frequency ; Genotype ; Humans ; Intercellular Adhesion Molecule-1 ; blood ; genetics ; Male ; Middle Aged ; Plasma ; metabolism ; Polymorphism, Genetic ; Young Adult

The aim of this study was to investigate the similarities and differences of A1381T (rs216311) and -1793G/C (rs7966230) single nucleotide polymorphisms (SNP) in Chinese Yugur, Tibetan, and Han nationalities and their influence on plasma vWF concentration in order to explore the sensitivity of these 3 nationalities to vWF-related diseases. Peripheral venous blood was obtained from 322 Yugur, 399 Tibetan, and 120 Han healthy people. The DNA were then extracted. vWF gene A1381T and -1793G/C polymorphisms were analyzed by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and sequenced when it was necessary. The vWF:Ag level in plasma was determined by ELISA. The results showed that the genotype distribution of vWF gene at both A1381T and -1793G/C loci in Yugur, Tibetan and Han nationalities was different with statistically significance (P < 0.05). GG genotype of A1381T locus accounted for 69.9% in Yugur nationality, which was much higher than 56.6% and 53.3% in Tibetan and Han nationalities respectively(P < 0.01); AA genotype of A1381T locus expressed a low level of vWF in plasma. For the -1793G/C locus, the proportion of CG genotype in Yugur was much higher than that in Han, CC genotype expressed a high level of vWF in plasma. The plasma vWF levels with different nationalities and the polymorphism of vWF gene were significantly different. It is concluded that the polymorphisms of vWF gene at both A1381T and -1793G/C loci in Yugur, Tibetan and Han are significantly different; the polymorphism of vWF gene influences the plasma vWF level; the plasma vWF levels in Yugur and Tibetan are significantly higher than that in Han, which may be associated with the living environment and habits.
Adolescent ; Adult ; Aged ; Asian Continental Ancestry Group ; genetics ; China ; Ethnic Groups ; genetics ; Female ; Gene Frequency ; Genotype ; Humans ; Male ; Middle Aged ; Plasma ; chemistry ; Polymorphism, Genetic ; Young Adult ; von Willebrand Factor ; genetics ; metabolism

OBJECTIVETo investigate the independent predictors of postoperative mortality, morbidity, and long-term survival in patients with stage IV ( colorectal cancer.

METHODSClinical data of 189 patients with stage IV( colorectal cancer undergoing palliative resection of primary tumor in the presence of unresectable synchronous metastases were analyzed retrospectively.

RESULTSEighty-six (45.5%)patients developed postoperative complications. Preoperative predictors of medical complications included age(≥65, P=0.039) and emergency operations (P=0.001). Preoperative predictors of surgical complications included advanced local disease (T4, P=0.022) and lymph node spread (N2, P=0.009). Seventeen (9.0%) patients died in the postoperative period. Mortality was independently associated with age(P=0.013), peritoneal dissemination(P=0.010), emergency operations(P=0.001) and medical complications(P=0.008). The survival rates at 1-, 2-, and 3- year of 172 patients admitted in survival analysis were 41.2%, 22.7% and 7.7% respectively. Independent factors associated with poor overall survival included lymph node spread(N2, P=0.015) and poor tumor differentiation(P=0.038).

CONCLUSIONSEmergency operations should be avoid when palliative resection of primary tumor is considered for stage IV( colorectal cancer patients, especially for elderly patients and those with peritoneal dissemination. The significance of palliative resection is limited for stage IV ( colorectal cancer patients with lymph node spread and poor tumor differentiation.

Aged ; Colorectal Neoplasms ; pathology ; surgery ; Humans ; Lymph Nodes ; Neoplasm Staging ; Palliative Care ; Postoperative Complications ; Prognosis ; Retrospective Studies ; Survival Analysis

OBJECTIVETo investigate the renal function in newborns with birth asphyxia or intrauterine distress in the first week of life.

METHODSSixty full-term newborns born between June 2002 and February 2003 were assigned into three groups: Control group (healthy newborns), Intrauterine distress group (Apgar score > 7), and Birth asphyxia group without intrauterine distress (12 mild asphyxia and 8 severe asphyxia) (n=20 each). Urinary levels of alpha1-microglobulin (alpha1-MG), beta2-microglobulin (beta2-MG) and albumin (Alb) were detected by radioimmunoassay at 0-2, 3-4 and 6-7 days after birth.

RESULTSThe urinary levels of alpha1-MG, beta2-MG and Alb in the Asphyxia group were significantly higher than those in the Control group at all time points (P < 0.05), peaking at 3-4 days after birth. Statistically significant differences were found between the severely and mildly asphyxiated newborns for the urinary levels of alpha1-MG, beta2-MG and Alb at all time points (P < 0.05). There were no significant differences in the urinary levels of alpha1-MG, beta2-MG and Alb between the Intrauterine distress and the Control groups at each time point.

CONCLUSIONSBirth asphyxia may lead to renal glomerular and tubular impairments and it is speculated that the most serious impairment occurs at the 3rd and 4th days of life. The severity of renal impairments is associated with the degree of asphyxia. The renal function of the newborn appears to be normal following intrauterine distress.

Albuminuria ; urine ; Alpha-Globulins ; urine ; Asphyxia Neonatorum ; physiopathology ; Fetal Distress ; physiopathology ; Humans ; Infant, Newborn ; Kidney ; physiopathology ; beta 2-Microglobulin ; urine

OBJECTIVETo characterize DNA-PKcs and Ku70 expressions in hepato- and cholangio-neoplastic tissues and the association with the degree of malignancy and invasiveness of the tumors.

METHODSThe expression of DNA-PKcs and Ku70 was examined in 47 cases of hepato- or cholangio-neoplasm by immunohistochemistry.

RESULTSKu70 was expressed in all of the neoplastic tissues examined and with a little variation in levels. The highest expression was observed in adenocarcinomas and adenomas. There was no statistically significant association between Ku70 expression level and the degree of their malignancy extent or invasiveness. In contrast to Ku 70, a wide variation in expression levels of DNA-Pkcs was observed among different types of neoplastic tissues. The highest ratio of positive expressing cells was detected in hepatocellular carcinomas (92.1%), which was significantly higher than that in cholangioadeno carcinomas (65.3%) and biliary cystadenocarcinomas (51.9%). Low or no expression level was detected in papillary adenoma cases. DNA-PKcs expression of invasive adenomas and adeno-carcinomas (61.2%) was significantly higher than that of non-invasive adenomas and adeno-carcinomas (30.4%). There was no expression observed in the normal tissues adjacent to the tumors.

CONCLUSIONDNA-PKcs is expressed in hepato- and cholangio-neoplasms and its variable level of expression is associated with the types of the tumor and their degree of malignancy and invasiveness. DNA-PKcs could be recognized as a new biomarker for liver neoplasm.

Adenocarcinoma ; enzymology ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antigens, Nuclear ; biosynthesis ; genetics ; Bile Duct Neoplasms ; enzymology ; Bile Ducts, Intrahepatic ; enzymology ; Biomarkers, Tumor ; biosynthesis ; genetics ; Carcinoma, Hepatocellular ; enzymology ; DNA-Activated Protein Kinase ; biosynthesis ; genetics ; DNA-Binding Proteins ; biosynthesis ; genetics ; Female ; Humans ; Ku Autoantigen ; Liver Neoplasms ; enzymology ; Male ; Middle Aged