OBJECTIVETo observe the central nervous system symptoms and alterations in the blood indicators in rats within a short term after benzene poisoning.

METHODTwenty-four female SD rats were randomized into 4 equal groups to receive intraperitoneal injection of low-, medium- or high-dose benzene (39.05, 78.11, and 234.33 mg/kg, respectively) or peanut oil. Blood samples were taken from the rats via the femoral artery 24 h after the injections for routine blood test and liver and kidney function test.

RESULTSIntraperitoneal injection of benzene at a high dose, but not at a low or medium dose, caused obvious symptoms in the central nervous system. Benzene either at a low or medium dose did not produce obvious changes in routine blood test or liver and kidney function test as compared with the control group, but a high dose resulted in significant changes in WBC, PLT, ALT and AST (P<0.05). Abnormalities in the renal function were found in none of the groups (P>0.05).

CONCLUSIONExposure to high-dose benzene can result in abnormalities in the central nervous system, routine blood indicators and liver function, but does not obviously affect the kidney function in rats.

Alanine Transaminase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Benzene ; toxicity ; Blood Cell Count ; Central Nervous System Diseases ; chemically induced ; Female ; Kidney ; drug effects ; Liver ; drug effects ; Rats ; Rats, Sprague-Dawley

Objective To track the catabolic route and clearance of ena-lapril maleate tablets in vivo by surface -enhanced Raman scattering spectrometry , and put forward proposal to its safe medication.Methods The urine and feces of 15 patient exemplars was collected , pre-processed , blended with an equal volume of surface -enhancer , and tested at the identified peak of enalapril maleate of (1470 ±2 ) /cm.Then the clearance of active pharmaceutical ingredient was calculated and analyzed .Results The methodical recovery was high and the relevant standard deviation was within 3%.The active pharmaceutical ingredient was in good linear at the concentration of 5~100μg· mL-1 in urine and in feces, and the limit of detection was 0.5 μg · mL-1 and 1.3μg· mL-1 , respectively.Enalapril was effective to 11 exemplars, while its clinical effect was not responded on 4 exemplars.Conclusion The method is proved to be prompt and rapid , appropriate to the catabolic analysis in vivo and clinical evaluation to angiotensin -converting -enzyme Ⅰinhibitors.

OBJECTIVE: To find the mutation of disease-causing genes of sudden unexplained death syndrome (SUDS) in the young by whole exome sequencing in one case. METHODS: One SUDS case was found no obvious fatal pathological changes after conventional autopsy and pathological examination. The whole exome sequencing was performed with the Ion Torrent PGM™ System with hg19 as reference sequence for sequencing data. The functions of mutations were analyzed by PhyloP, PolyPhen2 and SIFT. A three-step bioinformatics filtering procedure was carried out to identify possible significative single nucleotide variation (SNV), which was missense mutation with allele frequency < 1% of myocardial cell. RESULTS: Four rare suspicious pathogenic SNV were identified. Combined with the analysis of conventional autopsy and pathological examination, the mutation MYOM2 (8_2054058_G/A) was assessed as high-risk deleterious mutation by PolyPhen2 and SIFT, respectively. CONCLUSION Based on the second generation sequencing technology, analysis of whole exome sequencing can be a new method for the death cause investigation of SUDS. The gene MYOM2 is a new candidate SUDS pathogenic gene for mechanism research.
Autopsy ; Brugada Syndrome/genetics* ; Cause of Death ; DNA Mutational Analysis/methods* ; Death, Sudden/etiology* ; Exome ; Gene Frequency ; Genetic Testing/methods* ; High-Throughput Nucleotide Sequencing/methods* ; Humans ; Molecular Biology ; Molecular Diagnostic Techniques/methods* ; Molecular Sequence Data ; Mutation

OBJECTIVETo investigate the normal range of (CAG)n in spinocerebellar ataxia type 1 (SCA1) gene and spinocerebellar ataxia type 3 (SCA3/MJD) gene in 110 normal subjects of Han population in Northeastern China, to assess the genotypes for clinically diagnosed spinocerebellar ataxia(SCA) individuals including 25 patients from 8 families and 6 sporadic patients, and to make presymptomatic and prenatal diagnosis.

METHODSDNA fragments from the normal subjects and the patients were detected by fluorescence-PCR. Homozygosities were selected for DNA sequencing.

RESULTSThe normal ranges of (CAG)n of SCA1 and SCA3/MJD were 20-39 and 14-38 repeats respectively, SCA1 was found mostly to be 26 and 27 repeats, allele frequency 34.09% and 20.91%; heterozygosity was 84.55%, SCA3/MJD was found mostly to be 14 repeats, allele frequency 39.55%, heterozygosity was 78.18%.(CAG)(68) of SCA3/MJD gene of one affected individual had been found in a family but no CAG mutative expansion in related members was observed.

CONCLUSIONThe normal ranges of CAG repeats vary with areas and races. SCAs genotyping is the first choice in presymptomatic and prenatal diagnosis.

Ataxin-1 ; Ataxin-3 ; Ataxins ; China ; DNA ; chemistry ; genetics ; Family Health ; Female ; Gene Frequency ; Genotype ; Humans ; Machado-Joseph Disease ; diagnosis ; genetics ; Male ; Nerve Tissue Proteins ; genetics ; Nuclear Proteins ; genetics ; Pedigree ; Repressor Proteins ; Sequence Analysis, DNA ; Spinocerebellar Ataxias ; diagnosis ; genetics ; Trinucleotide Repeat Expansion ; genetics ; Trinucleotide Repeats ; genetics

OBJECTIVETo construct cDNA subtracted libraries from gastric dysplasia and further screen differentially expressed genes.

METHODSRelatively pure dysplasia and normal tissue were procured by manual microdissection, and amplified by cDNA-PCR, which was used to carry on for suppression subtractive hybridization (SSH). Subtracted cDNA fragments were linked with vector, cloned, screened, sequenced, and made homologous search. Differentially expressed fragments were verified by dot hybridization.

RESULTSTwo subtracted cDNA libraries were constructed. Among 26 sequenced clones, 15 fragments corresponded to known genes, 3 fragments were known EST and 8 fragments were unknown EST (GenBank BQ164614-BQ164616, BQ291516-BQ291520). Fifteen fragments were verified to be differentially expressed in gastric dysplasia.

CONCLUSIONSSubtracted cDNA libraries from gastric dysplasia are constructed using combination of microdissection-cDNA PCR and SSH setup in our laboratory. Some fragments have been screened and verified to help to search for novel associated genes with gastric carcinogenesis.

Cloning, Molecular ; DNA, Complementary ; genetics ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Gene Library ; Humans ; Microdissection ; Nucleic Acid Hybridization ; methods ; Polymerase Chain Reaction ; Precancerous Conditions ; genetics ; pathology ; Sequence Analysis, DNA ; Stomach Neoplasms ; genetics ; pathology

OBJECTIVETo explore the relationship between the changes of trace elements and lymphatic metastasis in gastric carcinoma.

METHODSTrace elements including Fe, Mg, Mn, Ca, Cu, Zn, Se were measured in primary gastric carcinoma and regional lymph nodes from 40 patients with gastric carcinoma, and compared among the primary tumor, metastatic, and non-metastatic nodes.

RESULTSThere were no significant differences in the contents of Fe, Mg, Mn and Ca among primary gastric tumors, regional lymph nodes with or without metastasis (P=0.372 - 0.741, P > 005), and no significant differences in the contents of all 7 trace elements between primary tumors and metastatic lymph nodes (P=0.15 - 0.59, P > 005). Compared with metastatic lymph nodes, the contents of Zn, Se significantly decreased, while Cu and Cu/Zn significantly increased (P=0.001 - 0.009, P< 0.01) in non-metastatic lymph nodes. The content of Zn in N2 positive lymph nodes was significant lower than that in N1 positive nodes (P=0.027). There were no significant difference in the contents of all 7 elements between intestinal type and diffuse type (P=0.149 - 0.758, P > 0.05).

CONCLUSIONSLymphatic metastasis of gastric cancer is concomitant with the changes of trace elements, and the changes of Zn, Cu, Se may be related with lymphatic metastasis.

Adult ; Aged ; Female ; Humans ; Lymph Nodes ; metabolism ; Lymphatic Metastasis ; Male ; Middle Aged ; Stomach Neoplasms ; metabolism ; pathology ; Trace Elements ; metabolism

Objective To analyze the related pathogenicity gene mutations in a sudden death of hypertrophic cardiomyopathy (HCM) on whole exome level.Methods Whole exome sequencing (WES) was been performed on a sudden death case sample with pathological features of HCM by Illumina(R) Hiseq 2500 platform.Using hgl9 as the reference sequences,the sequencing data were analyzed.Suspicious single nucleotide variants (SNV) were screened,and the conservatism and function were analyzed by the software such as PhyloP,PolyPhen-2,SIFT,etc.Results After screening,a heterozygous mutation C719R was finally identified in the gene MYBPC3 of this case.Conclusion The molecular anatomy on whole exome level by second generation sequencing technology can help to define the molecular mechanism of HCM and provide a new mothed and thought for analysis of death cause.

OBJECTIVETo clarify whether A1166C polymorphism of the angiotensin II type 1 receptor (AT(1)R) gene is associated with susceptibility to essential hypertension in Han, Tibetan and Yi populations in China.

METHODSThis study involved 302 normotensive and 446 hypertensive subjects. The polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism in genomic DNA. The data were analyzed by ANCOVA, chi-square test, and multiple logistic regression.

RESULTSIn normotensive controls, the A1166 allele frequencies were 0.979, 0.939 and 0.965 in Han, Tibetan and Yi participants, respectively. There was no significant intergroup variation in frequency of the allele in normotensives (chi-square=4.166, P=0.125). The frequency of the A1166 allele in Tibetan male hypertensives was significantly higher than that in normotensives (chi-square=11.46, P=0.001). There was no significant difference in A1166C genotype distribution and allele frequency between normotensives and hypertensives either in the Han (P=0.465) or Yi (P=0.357) populations. Body mass index in the Han and Yi populations (P=0.0001), age in the Tibetan and Yi populations (P=0.0001), and AA genotype in the Tibetan male population (P=0.0034) all were independent risk factors for hypertension. Diastolic blood pressure levels were significantly higher in Tibetan male subjects with the AA genotype than in those with the AC+CC genotype (P=0.0040).

CONCLUSIONThe A1166 allele is very common in Han, Tibetan and Yi populations, approximately 1.35-fold more common than in Caucasians. The A1166 allele of the AT(1)R gene may be a predisposing factor for essential hypertension in Tibetan males. A1166C polymorphism of the AT(1)R gene is probably not involved in the pathogenesis of essential hypertension in Han and Yi populations.

Alleles ; Asian Continental Ancestry Group ; genetics ; Blood Pressure ; genetics ; China ; ethnology ; DNA ; analysis ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genetics, Population ; Genotype ; Humans ; Hypertension ; genetics ; Male ; Polymorphism, Genetic ; Polymorphism, Single Nucleotide ; Receptor, Angiotensin, Type 1 ; genetics ; Tibet

OBJECTIVE: To explore the toxicity of 1,2-dichloroethane( 1,2-DCE) and its metabolites on human astrocytes( HAs). METHODS: Different doses of 1,2-DCE( 5. 00,10. 00,25. 00,50. 00 and 100. 00 mmol/L),2-chlorohydrins( 5. 00,25. 00,50. 00,100. 00 and 200. 00 mmol/L),2-chloroacetaldehyde( 1. 00,5. 00,10. 00,20. 00 and 50. 00 mmol / L) and chloroacetic acid( 0. 01,0. 05,0. 10,0. 50 and 1. 00 mmol / L) were used for treating HAs in vitro during their logarithmic phase. After 24 hours of culture,the morphology of HAs was observed by fluorescent inverted phase contrast microscope. The survival rate and the inhibition ratio of HAs were detected by CCK-8 colorimetry to estimate the50% inhibiting concentration in 24 hours( 24 h-IC50). The apoptosis of HAs was tested by double-labeling and flow cytometry using Annexin Ⅴ-fluorescein isothiocyanate and propidium iodide. RESULTS: The morphology of HAs changed in varying degrees after 24 hours exposure to 1,2-DCE,2-chlorohydrins,2-chloroacetaldehyde and chloroacetic acid. The changes included smaller size of cells,pseudopodia tapering,increased intracellular particles and suspension of circular cells and decreased transparency of cells. With the increasing does of 1,2-DCE,2-chlorohydrins,2-chloroacetaldehyde and chloroacetic acid exposure,the survival rates of HAs decreased( P < 0. 01),while its inhibition ratios increased( P <0. 01). They all showed dose-effect relationship. 24 h-IC50 of the above 4 chemicals were 56. 25,235. 00,26. 43 and1. 38 mmol / L,respectively. The 1,2-DCE,2-chlorohydrins and chloroacetic acid could induce the apoptosis of HAs and the apoptosis rate of HAs was positively correlated with the 3 kinds of chemicals( P < 0. 01). CONCLUSION: 1,2-DCE and its metabolites 2-chloroacetaldehyde,2-chlorohydrins and chloroacetic acid can lead to toxic damage and induce the apoptosis of HAs. Chloroacetic acid has the strongest toxicity among the metabolites.

Poly (ADP-ribose) polymerase 1/2(PARP1/2) can catalyze the poly (ADP ribose) (PAR) substrate protein modification and play an important role in the regulation of DNA damage repair, cell death and transcriptional activity. The PARP inhibitor olaparib (AZD2281) can be used as a sensitizer of radiotherapy and chemotherapy in the cancer treatment. Through establishment of biological fluorescent labeled 4T1 ectopic breast tumor model, we found that olaparib exhibited a poor effect on 4T1 breast cancer alone. However, in the combination with Taxol, olaparib significantly increased the anti-tumor effect of Taxol, and reduced the PAR levels of the tumor tissues. Importantly, olaparib did not amplify the toxicity of chemotherapy drugs. This study suggests that olaparib is a representative of the PARP inhibitor that can enhance Taxol 's antitumor effect in the 4T1 ectopic breast tumor model, which sets the foundation for future study of the mechanism of olaparib action.