2.Metabolomics study of doxorubicin induced hepatotoxicity.
Qian-yun NIU ; Yue-tao LIU ; Zhen-yu LI ; Xue-mei QIN
Acta Pharmaceutica Sinica 2015;50(6):708-713
To reveal the underlying mechanism of doxorubicin induced hepatotoxicity, an NMR-based metabolomic approach combined with multivariate statistical analysis was used to observe its metabolic alternations of rat liver. Sixteen differential metabolites between model rats and normal rats were characterized as potential pathological biomarkers related to doxorubicin induced hepatotoxicity. Six pathways, including phenylalanine, tyrosine and tryptophan biosynthesis, valine, leucine and isoleucine biosynthesis, phenylalanine metabolism, glycine, serine and threonine metabolism, alanine, aspartate and glutamate metabolism, and tyrosine metabolism were regarded as the targeted metabolic pathways according to Metabolic Pathway Analysis (MetPA). The results suggested that the metabolic perturbations in rats with doxorubicin induced hepatotoxicity were mainly involved in amino acid metabolism, lipid pathways, purine metabolism, energy metabolism, dysfunction of biotransformation and oxidative stress. The investigation revealed the effects of doxorubicin on liver in a holistic metabolic way, which laid a foundation for further studies on its toxicity mechanism.
Animals
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Biomarkers
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metabolism
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Doxorubicin
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toxicity
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Energy Metabolism
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Liver
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drug effects
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metabolism
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Magnetic Resonance Imaging
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Magnetic Resonance Spectroscopy
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Metabolic Networks and Pathways
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Metabolomics
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Multivariate Analysis
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Oxidative Stress
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Rats
3.Analyses of Behavioral Hearing Thresholds in Children without ABR Responses
Zhen LI ; Kai WANG ; Ke XU ; Yong TAO ; Yueke KANG ; Zhaoli MENG ; Yun ZHENG
Journal of Audiology and Speech Pathology 2010;18(2):125-127
Objective To investigate residual hearing of children with sensorineural hearing loss in whom wave V was not found in ABR testing and to emphasize the importance of behavioral audiometry in determining the residual hearing.Methods Residual hearing obtained by behavioral audiometry of 101 children with SNHL was studied in relation to the absence of wave V in both click-ABR and tone burst-ABR tests.Results All children have residual hearing of different degrees at different frequencies.There appeared to be a higher percentage of lowfrequency residual hearing than middle and high frequencies.Also,the residual hearing at low frequencies appeared to be better than those in the middle and high frequencies.Average residual hearing thresholds in the right ears from 500 to 4 000 Hz were 106.81±7.13,110.00±7.90,111.78±5.22,112.06±7.08 dB HL and those in the left ears were 98.01±3.98,111.30±7.18,112.06±7.08,108.33±7.23 dB HL.Conclusion The absence of wave V in ABR does not mean total deafness.For those children with no wave V in ABR,behavioral audiometry must be conducted to determine children's behavioral hearing thresholds in order to know their residual hearing.
4.Urinary tract infections in the neonatal intensive care unit: clinical analysis of 229 cases.
Yu-Jie HAN ; Sheng-Lin YU ; Yun-Zhen TAO
Chinese Journal of Contemporary Pediatrics 2012;14(3):177-180
OBJECTIVETo study the clinical features, distribution of pathogens, drug susceptibility, and treatment effectiveness in neonates with urinary tract infection (UTI) and admitted to the neonatal intensive care unit (NICU).
METHODSThe clinical data of 229 neonates who developed UTI during their stay in the NICU were retrospectively studied.
RESULTSThe main clinical manifestations of these children included fever/irregular body temperature, refusing to milk feeding, jaundice, vomiting, diarrhea, poor weight gain, and lethargy. The top three pathogens were Escherichia coli, Enterococcus feces, and Klebsiella pneumoniae. Escherichia coli and Klebsiella pneumoniae were highly resistant to ampicillin and most cephalosporins (≥ 85%), and were highly sensitive to imipenem (100%), meropenem (100%), cefoperazone/sulbactam and piperacillin/tazobactam (>90%). Enterococcus feces were highly resistant to penicillin (100%), rifampicin (84%) and gentamicin (79%), but were sensitive to vancomycin.
CONCLUSIONSThe clinical manifestations of neonatal UTI are often atypical and manifested as systemic symptoms. The main pathogenic bacterium is Escherichia coli, and the isolation rate of enterococci can also be high. Most pathogenic bacteria are resistant to penicillin and cephalosporins, and therefore decision-making on drug administration must be based on the results of drug sensitivity tests.
Drug Resistance, Bacterial ; Humans ; Infant, Newborn ; Intensive Care Units, Neonatal ; Microbial Sensitivity Tests ; Retrospective Studies ; Urinary Tract Infections ; drug therapy ; microbiology
5.Progress of intersphincter resection with direct coloanal anastomosis for ultra-low rectal cancer.
Chinese Journal of Gastrointestinal Surgery 2013;16(12):1226-1229
In recent years, sphincter preservation and improvement of quality of life have become the primary goals in the management of low-lying rectal cancer. For lesions within 2 cm from the dentate line or more than 5 cm from the anal margin, abdominoperineal resection results in permanent stoma creation while intersphincteric resection (ISR) provides solution to sphincter function preservation and improved quality of life. This review was to summarize the current literature pertaining to this procedure, including current research progress, indications, development of ISR procedure, oncological and functional outcomes.
Anal Canal
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surgery
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Anastomosis, Surgical
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Humans
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Rectal Neoplasms
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surgery
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Sphincterotomy, Endoscopic
6.Comparative studies on the composition and antibiotic-resistance of pathogenic bacteria between children with community-acquired and hospital-acquired pneumonia.
Zhe WANG ; Wei JI ; Hong-bo GUO ; Yun-zhen TAO ; Yun-fang DING
Chinese Journal of Preventive Medicine 2011;45(3):211-216
OBJECTIVEThis research was to explore the difference between children with community-acquired pneumonia (CAP) and hospital-acquired pneumonia (HAP) in the composition and antibiotic-resistance of pathogenic bacteria.
METHODS241 CAP and 116 HAP with positive sputum culture who were hospitalized from January to December in 2008 in Children's Hospital Affiliated to Suzhou University were selected in this study. The bacteria were identified by traditionally manual method and antibiotic sensitivity tests were performed by K-B method. The chi-square or Fisher's exact test were used for statistical test.
RESULTSIn 241 CAP, Streptococcus pneumoniae and haemophilus influenza accounted for (42.2%, 106/251) and (12.4%, 31/251) infection, respectively; however in 116 HAP, Enterobacteriaceae and Non-fermenters accounted for (88.2%, 127/144). In addition, methicillin-resistant Staphylococcus aureus weren't isolated, however, its detection rate was 66.7% in HAP. The drug resistance was 1.5 times higher in HAP than that in CAP for several types of antibiotics, such as ceftazidime (37.5% (6/16) vs 75.6% (31/41)), cefepime (37.5% (6/16) vs 78.0% (32/41)), aztreonam (50.0% (8/16) vs 90.2% (37/41)), cefoperazone/sulbactam (12.5% (2/16) vs 51.2% (21/41)) and piperacillin/tazobactam (12.5% (2/16) vs 56.0% (23/41)). Klebsiella pneumoniae isolated from HAP had higher drug resistance than that isolated from CAP against some antibiotics, for example, gentamicin (0 vs 63.6% (7/11)), SMZ + TMP (20.0% (1/5) vs 63.6% (7/11)) and cefoperazone/sulbactam (0 vs 54.5% (6/11)). We also found Enterobacter cloacae isolated from HAP showed high drug resistance than that isolated from CAP against imipenem (0 vs 46.7% (7/15)), aztreonam (9.1% (1/11) vs 60.0% (9/15)) and cefoperazone (18.2% (2/11) vs 80.0% (12/15)) and Pseudomonas aeruginosa from HAP had higher resistance than that from CAP against gentamicin (0 vs 50.0% (9/18)), amikacin (0 vs 38.9% (7/18)), ceftazidime (0 vs 55.6% (10/18)), cefepime (0 vs 50.0% (9/18)) and cefoperazone (33.3% (2/6) vs 94.4% (17/18)). The detection rates of ESBLs for Escherichia coli were 84.6% (11/13) and 93.3% (14/15) in CAP and HAP, respectively (χ(2) = 0.553, P > 0.05); while for Klebsiella pneumoniae, they were 81.3% (13/16) and 95.1% (39/41), respectively (χ(2) = 2.767, P > 0.05).
CONCLUSIONCAP was mainly comprised of Streptococcus pneumoniae and haemophilus influenza; while HAP was mainly comprised of Enterobacteriaceae and Non-fermenters. The drug resistance of gram-negative bacilli was higher in HAP than that in CAP.
Child ; Child, Preschool ; Community-Acquired Infections ; microbiology ; Cross Infection ; microbiology ; Drug Resistance, Bacterial ; Female ; Gram-Negative Bacteria ; drug effects ; isolation & purification ; Haemophilus influenzae ; drug effects ; isolation & purification ; Humans ; Infant ; Infant, Newborn ; Male ; Microbial Sensitivity Tests ; Pneumonia, Bacterial ; microbiology ; Pseudomonas aeruginosa ; drug effects ; isolation & purification
7.Study on the molecule epidemiological between resistances of 7 genes interrelated 4 antibiotic to isolated Streptococcus pneumoniae in children.
Yun-fang DING ; Zu-huang MI ; Jian-hua ZHANG ; Yun-zhen TAO ; Ling QIN
Chinese Journal of Epidemiology 2005;26(6):435-439
OBJECTIVETo investigate the molecule epidemic for 7 genes interrelated penicillin, erythromycin, tetracycline, vancomycin resistance of isolated Streptococcus pneumoniae (SP) in children at Suzhou area.
METHODS(1) Thirty-one pneumococcal isolates were collected from respiratory tract secretions of children with respiratory diseases from Nov 2002 to Apr 2003 at the Children's Hospital of Suzhou University (reference strain ATCC49619). (2) Penicillin susceptibility was determined by E-test, while erythromycin, tetracycline, vancomycin were determined by K-B disk. (3) The detecting of pbp2B, ermA/B, mefA, tetM, vanA, vanB genes by PCR, Sequencing pbp2B genes, Contrasting pbp2B DNA sequences among pneumococcal isolates and SP R6 [penicillin sensitive (www.ncbi.nlm.gov/nucleotide, NC-003098)].
RESULTSOf thirty-one isolates studied, the results were shown as follows; (1) Penicillin sensibility 38.7% (n = 12), penicillin resistance 61.3% (n = 19), pbp2B mutation 64.5% (n = 20); (2) Erythromycin sensibility 9.7% (n = 3), erythromycin resistance 90.3% (n = 28), ermA/B 71% (n = 22), mefA 32.1% (n = 10), ermA/B + mefA 87.1% (n = 27); (3) Tetracycline sensibility 9.7% (n = 3), tetracycline resistance 90.3% (n = 28), tetM 90.3% (n = 28); (4) Vancomycin sensibility 100% (n = 31), vanA, vanB all 0%.
CONCLUSIONAmong pneumococcal isolates at our area, penicillin, erythromycin, tetracycline resistance were high, vancomycin was sensitive. Detecting 7 genes interrelated penicillin, erythromycin, tetracycline, vancomycin resistance expressed genotypies for antibiotic resistances in pneumococcal isolates.
Anti-Bacterial Agents ; pharmacology ; Child ; China ; epidemiology ; DNA, Bacterial ; genetics ; Drug Resistance, Multiple, Bacterial ; genetics ; Erythromycin ; pharmacology ; Female ; Humans ; Male ; Microbial Sensitivity Tests ; Molecular Epidemiology ; Penicillin Resistance ; genetics ; Pneumococcal Infections ; epidemiology ; microbiology ; Streptococcus pneumoniae ; drug effects ; genetics ; isolation & purification ; Tetracycline Resistance ; genetics ; Vancomycin ; pharmacology
8.Study on the molecular epidemiology of beta-lactamase TEM gene in isolated Streptococcus pneumoniae.
Yun-fang DING ; Jian-hua ZHANG ; Zu-huang MI ; Ling QIN ; Yun-zhen TAO ; Xiao QI
Chinese Journal of Epidemiology 2004;25(11):970-972
OBJECTIVETo investigate the beta-lactamase TEM gene of isolated Streptococcus pneumoniae (Sp) in Suzhou area.
METHODSTwenty-three strains of Sp were collected from respiratory tract secretions of children with respiratory diseases in Nov 2002 to Apr 2003 at Children's Hospital of Suzhou University (reference strain ATCC49619) to build TEM polymerase chain reaction (PCR) system (reference strain E. coli. 9-j53R1 with TEM gene) TEM gene of 23 strains was detected to comparo the sequences with published TEM gene sequences in GenBank for analyzing TEM gene model.
RESULTSTwenty-one strains had TEM gene with a positive rate of 91.3% (21/23). TEM-129 gene were confirmed from No.17 (SR017, penicillin resistance) TEM sequence. New discovered TEM-129 sequence had a modification (ATG[M]-->ATA[I]) at No.182 code and published (GenBank: www.ncbi.nlm.nih.gov/nucleotide, AY452662). TEM-1 genes were confirmed from other TEM sequences. New discovered TEM-1 gene of isolated Sp had been published (GenBank: www.ncbi.nlm.nih.gov/nucleotide, AY392531) too.
CONCLUSIONIsolated Sp had TEM gene (TEM-129, EM-1 genotype) with a positive rate of 91.3%. The result enriched the understanding of isolated Sp with penicillin resistance.
Base Sequence ; China ; epidemiology ; Drug Resistance, Bacterial ; genetics ; Female ; Genes, Bacterial ; genetics ; Humans ; Male ; Molecular Epidemiology ; Molecular Sequence Data ; Pneumonia, Bacterial ; epidemiology ; genetics ; microbiology ; Point Mutation ; Streptococcus pneumoniae ; enzymology ; genetics ; beta-Lactam Resistance ; beta-Lactamases ; genetics
9.Effects of amino acid substitutions of penicillin-binding proteins 2B, 1A, 2X on minimal inhibitory concentration of beta-lactams against Streptococcus pneumoniae.
Min XU ; Jian-hua ZHANG ; Yun-fang DING ; Yun-zhen TAO ; Zi-cai WANG
Chinese Journal of Pediatrics 2010;48(1):60-64
OBJECTIVETo observe the effect of amino acid substitution in conserved sequence of penicillin-binding protein (PBP) 1A, 2B, 2X on antimicrobial activity of beta-lactams against Streptococcus pneumoniae (SP).
METHODMinimal inhibitory concentration (MIC) of 6 beta-lactams was determined by the E-test in 59 SP strains. The penicillin-binding protein genes pbp1a, 2b, 2x in every SP strain were amplified by nested-polymerase chain reaction (nPCR), then the PCR products were sequenced using automatic genetic analyzer directly. To analyze the amino acid substitutions, the DNA sequences were converted to protein sequences and aligned by Clustalx software. According to amino acid substitution in conserved sequence of PBP2B, 3 phenotypes were observed, including: PBP2B phenotype I (no amino acid substitution); PBP2B phenotype II (Glutamine 432-->Leucine and/or Threonine 445/451-->Alanine/Serine, Glutamic 481-->Glycine, 1 strain had proline insertion between residues 431/432); PBP2B phenotype III (Alanine 624-->Glycine with the addition of phenotype II). According to amino acid substitution in conserved sequence of PBP1A, 3 phenotypes were observed, including: PBP1A phenotype I (no amino acid substitution); PBP1A phenotype II (Threonine 574-->Asparagine, Serine 575-->Threonine, Glutamine 576-->Glycine, Phenylalanine 577-->Tyrosine, 574TSQF-->NTGY); PBP1A III (Threonine 371-->Alanine/Serine, Proline 432-->Threonine with the addition of 574TSQF-->NTGY). According to amino acid substitution in conserved sequence of PBP2X, 4 phenotypes were observed, including: PBP2X phenotype I (no amino acid substitution); PBP2X phenotype II (Histidine 394-->Leucine or Threonine 338-->Alanine); PBP2X phenotype III (Threonine 338-->Alanine, Isoleucine 371-->Threonine, Arginine 384-->Glycine and Leucine 546-->Valine); PBP2X phenotype IV (Methionine 339-->Phenylalanine, Methionine 400-->Threonine with the addition of PBP2X phenotype III).
RESULTAmong 59 SP strains antibacterial activities distribution (sensitive strains, intermediate strains and resistant strains) of 6 beta-lactams were penicillin (12, 29, 18); amoxicillin(49, 9, 1); cefuroxime (16, 16, 27); ceftriaxone (47, 1, 11); cefotaxime (47, 3, 9); imipenem (49, 10, 0). beta-lactam antibiotics insensitive strains (intermediate + resistant strain) in PBP2B phenotype III, PBP1A phenotype III, PBP2X phenotype III and IV were significantly increased, the MIC(50) of these strains were significantly higher than that of the others.
CONCLUSIONThe amino acid substitutions in or vicinal conserved sequence of PBP of SP increase MIC for beta-lactam antibiotics.
Amino Acid Substitution ; Aminoacyltransferases ; genetics ; Anti-Bacterial Agents ; pharmacology ; Bacterial Proteins ; genetics ; Microbial Sensitivity Tests ; Penicillin-Binding Proteins ; genetics ; Peptidyl Transferases ; genetics ; Streptococcus pneumoniae ; drug effects ; beta-Lactam Resistance ; genetics ; beta-Lactams ; pharmacology
10.Relation of pbp2B, ermB, ermA/B, mefA genes with resistance to penicillin and erythromycin among Streptococcus pneumoniae isolates from children.
Yun-fang DING ; Jian-hua ZHANG ; Zu-huang MI ; Yun-zhen TAO ; Ling QIN
Chinese Journal of Pediatrics 2005;43(5):364-367
OBJECTIVETo investigate the relation of pbp2B, ermB, ermA/B and mefA genes to penicillin and erythromycin resistance among isolated Streptococcus pneumoniae (Sp) in children.
METHODSTwenty-six strains of Sp were collected from September 2002 to April 2003 at the Children Hospital of Suzhou University. (1) Twenty-six pneumococcal isolates were obtained from respiratory tract secretions of children with respiratory diseases. (2) Susceptibility of the isolates to penicillin, cefuroxime, ceftriaxone, cefotaxime and erythromycin was determined by E-test. (3) The genes pbp2B, ermB, ermA/B and mefA of the isolates were detected with PCR. (4) The PCR product of pbp2B gene was sequenced. (5) DNA sequences of pbp2B of pneumococcal isolates were compared with those of SpR6 [penicillin sensitive (www.ncbi.nlm.gov/nucleotide, NC-003098)].
RESULTSAmong the 26 isolates studied, pbp2B gene mutation was found in 15(58%) isolates, all were point mutation of A, B, C and D genotypes which were seen in 11(73%), 2(13%), 1(7%) and 1(7%), respectively. The numbers of isolates susceptible to penicillin, cefuroxime, ceftriaxone and cefotaxime were 9(82%), 10(91%), 11(100%) and 11(100%), of 11 non-mutation isolates;numbers of isolates resistant to penicillin, cefuroxime, ceftriaxone, and cefotaxime were 13(87%), 11(73%), 1(7%) and 1(7%) out of 15 isolates with mutation.ErmB, ermA/B, mefA and erm/mef genes were positive in 9(35%), 16(62%), 7(27%) and 21(81%)isolates. MIC of erythromycin was 2 to > 256 mg/L among pneumococcal isolates with erm/mef genes.
CONCLUSIONAmong antibiotic resistant pneumococcal isolates in the area, the main basis of penicillin resistance was the mutation of pbp2B genes. Genotype A mutation had the highest rate among the isolates with mutation and manifested as resistance to penicillin and cefuroxime. Expression of either all or any of the ermA, ermB and mef genes led to erythromycin resistance. Antibiotics resistant Sp strains in this area are forming a challenge to efficacy of penicillin and erythromycin.
Aminoacyltransferases ; genetics ; Anti-Bacterial Agents ; pharmacology ; Bacterial Proteins ; genetics ; Child ; Drug Resistance, Bacterial ; Erythromycin ; pharmacology ; Humans ; Membrane Proteins ; genetics ; Methyltransferases ; genetics ; Penicillin Resistance ; Penicillin-Binding Proteins ; genetics ; Streptococcus pneumoniae ; drug effects ; genetics