OBJECTIVE:To provide reference for prevention of nosocomial drug-induced liver injury(DILI),early diagnosis of DILI and appropriate disposal of DILI.METHODS:4 975 medical records were randomly collected from a grade three class A hospital during 2008～2009.The incidence of DILI,hospitalization costs,extended time of hospital stay and prevention of DILI were analyzed retrospectively and economic evaluation was carried out.RESULTS:DILI occurred in 63 cases with the incidence rate of 1.27%.Among these cases,10 cases(15.87%) were preventable.For each DILI,average increased medical cost was 3 220.26 yuan and average extended time of hospital stay was 4.38 d.For the preventable DILI,the average increased medical cost was 6 239.85 yuan,and average extended time of stay was 8.30 d.The top 3 drugs which caused liver injury were anti-infective drugs(including antitubercular agent,41.27%),antineoplastic agents(28.57%) and cardiovascular drugs(7.94%).Types of DILI were as follows:live cell injury accounted for 65.08%,cholestasis accounted for 25.40%,and mixed type accounted for 9.52%.CONCLUSION:DILI is characterized with high incidence rate among patients and high medical cost.Some of DILI cases are preventable.Therefore,There is advantage both in clinical and economic aspects to reduce the incidence rate of preventable DILI by emphasizing rational use of drugs.

No abstract available.
Base Sequence ; Cell Cycle Proteins/*genetics ; Chromosomes, Human, Pair 11 ; Chromosomes, Human, Pair 22 ; Female ; Gene Rearrangement ; Histone-Lysine N-Methyltransferase/*genetics ; Humans ; Immunophenotyping ; In Situ Hybridization, Fluorescence ; Karyotype ; Leukemia, Myeloid, Acute/*diagnosis/metabolism ; Male ; Myeloid-Lymphoid Leukemia Protein/*genetics ; Oncogene Proteins, Fusion/genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Septins/*genetics ; Sequence Analysis, DNA ; Translocation, Genetic ; Young Adult

OBJECTIVETo investigate the clinical and genetics characteristics of patients with monosomal karyotype acute myeloid leukemia (MK-AML).

METHODSThe karyotypes of 3743 patients with newly-diagnosed de novo AML were analyzed, which had identified 153 cases with MK-AML, for whom the clinical and genetics characteristics were analyzed.

RESULTSThere were 2056 patients (54.9%) among all patients. A total of 153 patients fulfilling the criteria for MK-AML were identified, which comprised 93 males and 60 females, with a median age of 54. The median white blood cell count on presentation was 4.4×10 (9)/L. One hundred and forty-five cases (94.8%) have fulfilled the criteria for complex karyotype (≥ 3 chromosomal abnormalities). Although the monosomy could be found with all autosomes, chromosome 7 has been most frequently involved (38.56%, 59/153).

CONCLUSIONMK-AML is a distinct cytogenetic subtype of AML. Monosomy 7 is frequently detected among MK-AML patients. The monosomal karyotype is common among elder patients with AML.

Adult ; Aged ; Chromosomes, Human, Pair 7 ; genetics ; Female ; Humans ; Karyotype ; Leukemia, Myeloid, Acute ; genetics ; Male ; Middle Aged ; Monosomy ; Young Adult

OBJECTIVETo investigate whether CpG-oligodeoxynucleotide (CpG-ODN) can improve the detection rate of the karyotypic abnormalities in chronic lymphocytic leukemia (CLL).

METHODSThe bone marrow (BM) or peripheral blood (PB) cells from 57 cases of CLL were collected and cultured with CpG-ODN DSP30+interleukin-2 (IL-2), phytohemagglutinin (PHA), pokeweed (PWM) or IL-2, respectively. Five days later cells were harvested for chromosome preparation. Karyotypic analysis was done using R banding technique. Panel fluorescence in situ hybridization (FISH) was carried out on 19 cases of CLL with normal karyotypes using the following probes: Cen12, D13S25, Rb1, ATM, p53, MYB and IgH. Genomic DNA from 21 cases of them was extracted from BM or PB leukocytes. The immunoglobulin variable heavy chain (IgVH) was amplified by polymerase chain reaction (PCR) and sequenced. CD38 and ZAP70 expressions in the leukemic cells were determined by flow cytometry (FCM).

RESULTSThe detection rate of karyotypic abnormalities in the CpG-ODN+IL-2 group (43.85%) was obviously higher than that in the PHA (15.09%), PWM (17.31%) and IL-2 (3.13%) groups (P<0.01). Fifty-two types of karyotypic abnormalities were found. Among them, trisomy12 (+12) or +12 with other abnormalities were the most common, while translocations were the most frequent structural abnormalities including 3 unbalanced and 11 balanced translocations, among them 7 had rearrangements involving 14q32. Thirteen cases showed one or more abnormalities on FISH including trisomy 12 and p53 deletion each in one case, IgH rearrangement and partial deletion each in one case, 13q14.3 deletion in 11 cases of which 5 cases also had Rb1 deletion, 1 case had Rb1 partial deletion. No case with ATM or MYB deletions was found. PCR detected IgVH mutations in 10/21 cases. FCM showed 10/45 cases were CD38 positive, but 35 /45 were CD38 negative, 11/27 cases expressed ZAP70, but 16/27 did not. Among the 26 cases examined for CD38 and ZAP70 expressions simultaneously, 5 cases were CD38+ZAP70+, 13 were CD38-ZAP70-, 6 were CD38-ZAP70+, and 2 were CD38+ZAP70-, respectively. Statistic analysis showed a correlation between complex karyotype and IgVH without mutation, but no association between karyotype and CD38 or ZAP70 expression was observed.

CONCLUSIONCpG-ODN immunostimulation can obviously raise the detection rate of abnormal karyotypes, especially translocations in CLL. FISH is an important complement to conventional karyotypic analysis. The combination of both methods can provide more comprehensive genetic information for CLL.

Adjuvants, Immunologic ; genetics ; Adult ; Aged ; Aged, 80 and over ; Bone Marrow Cells ; cytology ; immunology ; Cells, Cultured ; Chromosome Aberrations ; Female ; Humans ; Immunoglobulin Heavy Chains ; genetics ; In Situ Hybridization, Fluorescence ; Interleukin-2 ; genetics ; Karyotyping ; methods ; Leukemia, Lymphocytic, Chronic, B-Cell ; diagnosis ; genetics ; immunology ; Male ; Middle Aged ; Oligodeoxyribonucleotides ; genetics ; immunology ; Phytolacca americana ; genetics

Objective:To evaluate the intestinal function in rats with exertional heat stroke (EHS) and explore the protective role of Ruifuping pectin (RFP) against heat related intestinal mucosal injury.Methods:One hundred and twenty healthy special pathogen free (SPF) male Sprague-Dawley (SD) rats were randomly divided into normothermic control group, EHS model group, hyperthermic plus drinking water group (H 2O+EHS group) and hyperthermic plus pectin group (RFP+EHS group) with 30 rats in each group. The rats in the H 2O+EHS group and RFP+EHS group were given water 20 mL/kg or RFP 20 mL/kg orally for 5 days during adaptive training period. After 1 week, the temperature control range was adjusted to (37±1)℃ using the temperature control treadmill, and the rat model of EHS was reproduced by one-time high temperature exhaustive exercise. No rehydration intervention was given during the training adaptation period in the EHS model group. The rats in the normothermic control group were maintained to room temperature (25±2)℃ and humidity (55±5)% without other treatment. Behavior tests including withdraw response, righting, and muscle strength were performed immediately after onset of EHS. Blood of inferior vena cava was collected, and the serum inflammatory cytokines [tumor necrosis factor-α (TNF-α) and interleukins (IL-6, IL-1β, IL-10)] and activity of diamine oxidase (DAO) were detected by enzyme linked immunosorbent assay (ELISA). The intestinal mucosa was collected, after hematoxylin-eosin (HE) staining, and Chiu score was performed to assess EHS induced pathological changes under light microscope. Results:The rats in the EHS model group had behavioral, inflammatory and pathological changes, such as delayed withdraw response and righting, decreased forelimb pulling, increased inflammatory index, and obvious intestinal mucosal injury, which indicated that the reproduction of the EHS model was successful. There was no significant difference in above parameters between the H 2O+EHS group and the EHS model group except that the inflammatory index in the RFP+EHS group was improved. Compared with the EHS model group, the withdraw reflex to pain and righting after RFP pretreatment in the RFP+EHS group were significantly improved (righting score: 1.4±0.2 vs. 0.3±0.2, withdraw reflex to pain score: 1.0±0.1 vs. 0.2±0.1, both P < 0.05), the muscle strength was significantly increased (N: 13.0±0.5 vs. 8.2±0.6, P < 0.01). The levels of pro-inflammatory factors in the RFP+EHS group were significantly lower than those in the EHS model group [TNF-α (ng/L): 67.5±9.2 vs. 194.3±13.7, IL-6 (ng/L): 360.0±54.1 vs. 981.2±84.4, IL-1β (ng/L): 33.7±9.0 vs. 88.7±6.1, all P < 0.01], while the level of anti-inflammatory factor IL-10 was higher than that in the EHS model group (ng/L: 208.7±10.5 vs. 103.7±7.0, P < 0.01). The degree of intestinal mucosal injury in the RFP+EHS group was less severe than that in the EHS model group, and the Chiu score and DAO were significantly lower than those in the EHS model group [Chiu score: 1.5±0.2 vs. 3.8±0.0, DAO (U/L): 83.7±6.7 vs. 128.7±10.5, both P < 0.05]. Conclusions:High temperature training can damage the intestinal barrier function, and induce endotoxemia and systemic inflammatory response syndrome (SIRS) in rats. Oral prophylactic RFP can protect the intestinal barrier function, alleviate SIRS, and promote the recovery of basic nerve reflex and muscle strength after the occurrence of EHS in rats.

Objective: To evaluate the clinical characteristics and prognosis of 3q26 rearrangements in chronic myeloid leukemia (CML) patients. Methods: The clinical and laboratory data of 1 075 patients with CML diagnosed from 2010 to 2016 were retrospectively analyzed, and they were divided into 3q26 rearrangement positive group (n=19) and 3q26 rearrangement negative group (n=1 056). The expression of EVI1, ABL kinase region mutation and survival time between the two groups were compared. Meanwhile, the prognostic effects of three treatment methods, including tyrosine kinase inhibitors (TKIs), TKIs combined with chemotherapy and allogeneic hematopoietic stem cell transplantation, on the patients with 3q26 rearrangements were compared. Results: Most of the patients with 3q26 rearrangements were in the advanced phase (χ 2 =181.233, P＜0.01), and the median time to enter the acute phase was shorter (9.5 months). The mutation ratio of ABL kinase region and expression levels of EVI1 in 3q26 rearrangement positive group were significantly higher than that in the negative group (χ 2 =16.758, P＜0.01; Z/U=-0.331 9, P＜0.01). After treatment with TKIs, the median survival time of the 3q26 rearrangement positive group was significantly shorter than that of the negative group (χ 2 =313.229, P＜0.01). The prognosis of the patients treated with hematopoietic stem cell transplantation was better than that with TKIs (P=0.049). Conclusion The CML patients with 3q26 rearrangements have a higher risk of sudden change, shorter survival time and poor prognosis. Hematopoietic stem cell transplantation may improve their prognosis.

OBJECTIVETo explore the clinical and laboratory features of chronic myeloid leukemia (CML) with atypical e14a3 and e19a2 BCR-ABL fusion gene subtypes.

METHODSWe retrospectively analyzed a cohort of CML patients with Ph chromosome positive confirmed by cytogenetic and FISH but classical e13a3(b2a2), e14a2(b3a2)and e1a2 fusion transcripts negative identified by conventional real-time quantification RT-PCR (RQ-PCR). Further RQ-PCR was done with the forward primer and reverse primer designed to detect rare atypical BCR-ABL fusion genes including e14a3 and e19a2 transcripts. Direct sequencing analysis was performed on the PCR products and mutations in the BCR-ABL kinase domain were detected. The clinical data of patients were retrospectively analyzed.

RESULTSSix CML patients were found to carry t(9;22) abnormality and BCR-ABL rearrangement confirmed by FISH but classical BCR-ABL fusion genes negative detected by RQ-PCR. Further RQ-PCR and sequencing analysis confirmed the fusion of BCR exon 14 and ABL exon 3 in five CML patients (case 1-5) and the fusion of BCR exon 19 and ABL exon 2 in one CML patient (case 6). E255K and I293T IM-resistant mutations were detected in case 1 and 2, respectively. Among five cases with e14a3 transcripts, four were CML-CP, one CML-AP. Four patients were male and one was female. The median age was 48 years. The patient (case 6) with e19a2 transcripts was 40-year-old female with a diagnosis of CML-CP and PLT count was more than 1 000×10⁹/L. Imatinib (IM) therapy was administer in case 1, 2, 3, 4 and hematopoietic stem cell transplantation (HSCT) was undergone in case 5 after hydroxyurea (Hu) or interferon failure. Case 1 who had E255K IM resistant mutation, responded poorly to IM but obtained a complete cytogenetic remission (CCyR) after a substitution of dasatinib for IM. Case 2 and 3 achieved CCyR 6 months later after IM treatment and had been maintained well with IM despite I293T mutation in case 2. Case 4 attained CCyR 3 months later after IM treatment but relapsed and died soon. Case 5 was still in CCyR after HSCT. Case 6 with e19a2 transcripts got complete hematologic response after Hu treatment and CCyR was achieved soon after IM therapy.

CONCLUSIONIncidence of CML with atypical transcripts is extremely low. They could benefit from tyrosine kinase inhibitors or HSCT. Rare and atypical BCR- ABL fusion gene subtypes could be missed by conventional RQ-PCR.

Adult ; Female ; Fusion Proteins, bcr-abl ; genetics ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; classification ; diagnosis ; genetics ; Male ; Middle Aged ; Retrospective Studies