Animals ; Antibodies, Monoclonal ; pharmacokinetics ; Iodine Radioisotopes ; pharmacokinetics ; Leukocyte Common Antigens ; immunology ; Male ; Mice ; Radiation Monitoring ; methods ; Rats ; Tissue Distribution

This study retrospectively reviewed the experimental clinical programs at The First Affiliated Hospital of Nanjing Medical University. Experience was summarized, and methods for improving clinical pharmaceutical research were discussed including recruiting talent people, managing resources and trail results, and establishing international cooperations.

OBJECTIVETo study relationship between daunorubicin (DNR) pharmacokinetics and efficacy and toxicity in children with acute leukemia.

METHODS(1) The concentration of DNR in plasma of children with acute leukemia was determined by high performance liquid chromatography (HPLC)-fluorescence detection method. Plasma was sampled frequently from the start of the infusion till the end of 24 h. DNR pharmacokinetics was studied by determination of the concentrations. (2) Efficacy and toxicity were monitored in each period after chemotherapy. Laboratory studies included examination of bone marrow, white blood cell count, electrocardiogram, echocardiogram, myocardial enzymogram, the liver and kidney function.

RESULTS(1) DNR was eliminated from plasma in a two-compartment manner. The maximum concentration was seen 1 - 3 h after infusion. Cmax was 63.50 microg/L. Tmax was 1.45 h. The concentration decreased quickly to a low level of about 11.52 microg/L from the end of 2 hours infusion. There was a large inter-individual difference in pharmacokinetic parameters of DNR. The difference of CL was 9-fold, AUC was 8-fold, Cmax was 5-fold. (2) CL of male patients [57.99 L/(h.m(2))] was significantly lower than that of female patients [93.71 L/(h.m(2))] (P < 0.05). Tmax of children older than 6 years was 1.1 h, and that of children younger than 6 years was 1.8 h (P < 0.05); Cmax of children older than 6 years was 90.77 microg/L, younger than 6 years was 57.44 microg/L (P < 0.05).

CONCLUSION(1) There is a large inter-individual difference in pharmacokinetic parameters of DNR in children. It may predict individual variety of efficacy and toxicity. Therapeutic drug monitoring is important. (2) Male patients and children older than 6 years had a higher bioavailability and lower metabolism, toxicity may easily occur in such children, therefore they may need lower dose.

Antibiotics, Antineoplastic ; adverse effects ; pharmacokinetics ; therapeutic use ; Child ; Child, Preschool ; Chromatography, High Pressure Liquid ; Daunorubicin ; adverse effects ; pharmacokinetics ; therapeutic use ; Drug Monitoring ; Female ; Humans ; Infant ; Leukemia ; drug therapy ; metabolism ; Male

ABC transporters on the intestinal barrier, blood-brain barrier and on tumor cells will affect drug bioavailability, transport across the blood-brain barrier and multidrug resistance. The active ingredients of traditional Chinese medicines can affect the function and expression of ABC transporters. When combined with pharmaceuticals the potential interaction between the two can change the efficacy of the medicines. We review the ABC transporter superfamily and their distribution with regard to their relationship and interactions with traditional Chinese medicine on the intestinal barrier and the blood-brain barrier, as well as their role in tumor multidrug resistance mediated by ABC transporters. We summarize the research progress over the past five years.

OBJECTIVETo investigate the relationship between genetic polymorphism in exon 12 C1236T, exon 21 G2677T/A and exon 26 C3435T of the multidrug resistance 1 (MDR1) gene and the risk of childhood acute lymphocytic leukemia (ALL).

METHODA total of 176 patients with ALL and a cohort of 170 matched healthy subjects were included. SNaPshot SNP typing was used to determine the genotypes of MDR1 C1236T, G2677T/A, C3435T. Based on the clinical data, the relationship between genetic polymorphism of MDR1 and the risk of childhood ALL was analyzed.

RESULTThere was significant difference in the distribution of genotype of MDR1 C3435T between the group of controls and cases. The mutant homozygous TT genotype was found to be associated with occurrence of ALL (P = 0.000; OR = 4.504). The data show evidence of pairwise linkage disequilibrium between the three common SNPs (C1236T-G2677T/A-C3435T). The haplotypes of TTT, TGC, CGC and CAC were predominant. The haplotype CGT distributed significantly differently between the groups of controls and cases (P = 0.034). The frequency of the haplotype TTT/TTT in the high risk group was higher than the other groups (P = 0.037).

CONCLUSIONThe present findings suggest that 3435C→T polymorphism in MDR1 gene may be a genetic susceptibility factor for ALL. The haplotype of MDR1 (C1236T-G2677T/A-C3435T) could be the clinical parameter at diagnosis.

ATP Binding Cassette Transporter, Sub-Family B ; ATP-Binding Cassette, Sub-Family B, Member 1 ; genetics ; Acute Disease ; Asian Continental Ancestry Group ; genetics ; Child, Preschool ; China ; ethnology ; Exons ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Haplotypes ; Humans ; Infant ; Linkage Disequilibrium ; Male ; Polymorphism, Single Nucleotide ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; genetics ; Risk Factors

BACKGROUNDNoise is widespread occupational hazard in iron and steel industry. Overhead-traveling cranes are widely used in this industry, but few studies characterized the overhead-traveling crane drivers' noise exposure level so far. In this study, we assessed and characterized personal noise exposure levels of overhead-traveling crane drivers in two steel-rolling mills.

METHODSOne hundred and twenty-four overhead-traveling crane drivers, 76 in the cold steel-rolling mill and 48 in the hot steel-rolling mill, were enrolled in the study. Personal noise dosimeters (AIHUA Instruments Model AWA5610e, Hangzhou, China) were used to collect full-shift noise exposure data from all the participants. Crane drivers carried dosimeters with microphones placed near their collars during the work shifts. Work logs had been taken by the drivers simultaneously. Personal noise exposure data were divided into segments based on lines in which they worked. All statistical analyses were done using SPSS 13.0.

RESULTSThe average personal noise exposure (L(Aeq.8h)) of overhead-traveling crane drivers in the hot steel-rolling mills ((85.03 +/- 2.25) dB (A)) was higher than that in the cold one ((83.05 +/- 2.93) dB (A), P < 0.001). There were 17 overhead traveling cranes in the hot steel-rolling mill and 24 cranes in the cold one, of which carrying capacities varied from 15 tons to 100 tons. The average noise exposure level based on different lines in the hot and cold steel-rolling mills were (85.2 +/- 2.61) dB (A) and (83.3 +/- 3.10) dB (A) respectively (P = 0.001), which were similar to the average personal noise exposure in both mills. The noise exposure levels were different among different lines (P = 0.021).

CONCLUSIONNoise exposure levels, depending upon background noise levels and the noise levels on the ground, are inconstant. As the noise exposure levels are above the 85 dB (A) criteria, these drivers should be involved in the Hearing Conservation Program to protect their hearing.

Environmental Monitoring ; instrumentation ; methods ; statistics & numerical data ; Female ; Humans ; Male ; Noise, Occupational ; Noise, Transportation ; Occupational Exposure ; analysis ; statistics & numerical data ; Occupational Health ; statistics & numerical data ; Steel

OBJECTIVE:To provide reference for the improvement of Chinese patent medicine instruction.METHODS:The outpatients were selected randomly from a Third Grade Class A hospital.A questionnaire survey was conducted on the attention degree of the outpatients to Chinese patent medicine instructions when taking medicine orally.The concern content label of patients in 221 Chinese patent medicine instructions were counted,analyzed and graded according to survey results.RESULTS:A total of 515 questionnaires were distributed,and 498 effective questionnaires were collected with effective recovery rate of 96.7％.The results of questionnaire survey showed that the highest concern from the patients was usage and dosage (92.4％),followed by attentions and taboos (88.0％,70.3％).The following items were drug interaction,pregnant and lactating women medication,children medication and the elderly medication (56.2％,46.4％,45.2％,42.4％).Among the description of medication methods (usage and dosage) in 221 Chinese patent medicine instructions,203 prescriptions clearly marked medication times (91.9％),160 clearly marked drug dosage (72.4％) and 36 clearly marked medication course (16.3％).In matters of taboos (attentions,taboos,pregnant and lactating women medication,children medication and the elderly medication),124 prescriptions clearly marked population taboos (56.1％),82 clearly marked symptom taboos (37.1％) and 71 clearly marked diet taboos (32.1％).According to the scoring statistics of 221 Chinese patent medicine instructions,there were 52 instructions with score of 6,followed by 47 instructions with score of 8;there were only 4 instructions with full score (12).CONCLUSIONS:At present,related contents of medication methods highly concerned by the patients are well marked in Chinese patent medicine instructions,especially its guidance is basically able to meet the requirements in respect of medication times.The related contents of medication taboos,which is next only to attention degree of medication methods by patients,is poorly marked.Its guidance remains to be improved.

AIM To explore the effects of Rosa roxburghii Radix on ulcerative colitis(UC)in rats based on pyroptosis and neutrophil extracellular traps(NETs).METHODS Rats were randomly divided into the normal group and the model group.The successfully established UC rat models by trinitrobenzene sulfonic acid(TNBS)/ethanol enema were then randomly divided into the model group,the sulfasalazine group(0.3 g/kg)and the low,medium and high dose R.roxburghii Radix groups(2,4,8 g/kg),followed by dosing of corresponding drugs by gavage.21 days later,the rats had their disease activity index(DAI)score calculated;their pathological changes of colon tissue observed by HE staining;their levels of serum interleukin(IL)-18,IL-1β and myeloperoxidase(MPO)detected by ELISA;and their protein expressions of NE,MPO,NLRP3,caspase-1 and GSDMD in colon tissue detected by Western blot and immunohistochemistry.RESULTS Compared with the normal group,the model group displayed increased DAI score(P＜0.01),increased serum levels of IL-1β,IL-18 and MPO(P＜0.01),and increased protein expressions of NE,MPO,caspase-1,NLRP3 and GSDMD in colon tissue(P＜0.01).Compared with the model group,the groups intervened with sulfasalazine,or medium,or high dose R.roxburghii Radix demonstrated with decreased DAI scores(P＜0.05,P＜0.01),decreased serum levels of IL-1β,IL-18 and MPO(P＜0.01),and decreased protein expressions of NE,MPO,caspase-1,NLRP3 and GSDMD in colon tissue(P＜0.05,P＜0.01).CONCLUSION R.roxburghii Radix may alleviate the inflammatory reaction in a rat model of UC and improve its pathological injury of colon via regulating pyroptosis and NETs.

OBJECTIVEIn childhood acute lymphoblastic leukemia (ALL), cytogenetics plays an important role in diagnosis, allocation of treatment and prognosis. On the basis of the conventional cytogenetic analysis, molecular methods have improved pediatric hematologists/oncologist's ability to accurately and rapidly perform risk-stratification on patients with childhood ALL during the last few years. The aim of the present study was to assess the demography of cytogenetic abnormalities in childhood ALL.

METHODThe study subjects consisted of 124 newly diagnosed ALL patients younger than 16 years of age, who were diagnosed at the Department of Pediatric Hematology/Oncology, Soochow University Children's Hospital. The diagnosis and FAB subtypes of ALL was determined by Wright-Giemsa-stained bone marrow smears and cytochemical staining. Immunophenotyping of the bone marrow samples was performed by flow cytometry. Multiplex polymerase chain reaction (Multiplex PCR) analysis was performed to detect the 29 most common leukemia translocations for routine molecular diagnostic hematopathology practice, and complement the information gained from conventional cytogenetic analysis.

RESULTSCytogenetic analysis was successful in 112 of 124 children with ALL. Sixty-eight (60%) of them had clonal chromosomal abnormalities. Numerical imbalances consisted of hyperdiploid (> 47 chromosomes, 36 cases), hypodiploid (< 46 chromosomes, 14 cases), pseudodiploidy (18 cases). Chromosomal translocations were observed in 13 patients by conventional cytogenetic analysis. Three cases were found positive for 4; 11 translocation, 3 cases for 9; 22 translocation, 1 case for 1; 19 translocation and 6 cases for other rare translocations. Multiplex-PCR analysis detected 116 of the 124 ALL patients. Thirteen cases of TEL-AML1, 10 cases of rearrangement in the MLL gene, 4 cases of E2A-PBX1, 4 cases of E2A-HLF, 3 cases of BCR-ABL, 2 cases of TLS-ERG, 32 cases of HOX11 were detected by Multiplex PCR in B-lineage leukemias. SIL-TAL1 had been found in 4 of 7 of T-lineage leukemias.

CONCLUSIONSSixty-eight cases of ALL showed chromosomal aberrations. Multiplex PCR positivity was detected in 59 (50%) of the 116 ALL patients studied. Multiplex PCR combined with chromosomal analysis uncovered chromosomal abnormalities in 95 of 124 (77%) of ALL patients and supplemented each other in detecting chromosomal abnormalities.

Adolescent ; Basic Helix-Loop-Helix Transcription Factors ; genetics ; Child ; Child, Preschool ; Chromosome Aberrations ; Core Binding Factor Alpha 2 Subunit ; genetics ; Cytogenetic Analysis ; DNA-Binding Proteins ; genetics ; Female ; Fusion Proteins, bcr-abl ; genetics ; Gene Fusion ; genetics ; Homeodomain Proteins ; Humans ; Immunophenotyping ; methods ; Infant ; Karyotyping ; Male ; Myeloid-Lymphoid Leukemia Protein ; genetics ; Oncogene Proteins, Fusion ; genetics ; Polymerase Chain Reaction ; Pre-B-Cell Leukemia Transcription Factor 1 ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; genetics ; Proto-Oncogene Proteins ; genetics ; Reverse Transcriptase Polymerase Chain Reaction ; methods ; T-Cell Acute Lymphocytic Leukemia Protein 1 ; Translocation, Genetic

Objective To detect the expression of DJ-1 in laryngeal squamous cell carcinoma (LSCC) and to study the relationship between DJ-1 expression and clinical indexes of LSCC. Methods The expressions of DJ-1 protein in 71 LSCC samples and 9 cases control samples from laryngeal mucosa tissues of non-LSCC patients were detected using streptavidin peroxidase immunohistochemistry stainin and the relationships between DJ-1 protein expression and clinicopathologic characteristics were analyzed. Results ( 1 ) The positive expression rate of DJ-1 protein in LSCC was 85.9% (61/71), which was significantly higher than the rate (55.5% ,5/9) in control laryngeal mucosa tissues (P<0.05). (2) DJ-1 expression was related to tumor recurrence (P <0. 05) ,but not to sex,age,primary cancer position,T stage, clinical stage, lymph node metastasis and tumor differentiation. Tumor recurrence rate (53. 3% ) in the patients with higher expression of DJ-1 protein was higher than the rate ( 26. 8% ) in the patients with lower expression of DJ-1 protein ( X2 = 5. 164, P < 0. 05 ). (3 ) With Kaplan-Meier curves and Cox regression analysis,the cumulative 5-year survival rates were correlated with DJ-1 expression levels in laryngeal cancer tissues or cervical lymph node metastasis (all P < 0. 05 ), but not to sex, age, primary cancer position, T stage, clinical stage and tumor differentiation. Conclusions The expression of DJ-1 protein in LSCC is higher than that in control laryngeal mucous tissues. Overexpression of DJ-1 is associated with poor overall survival in ISCC patients.