Risk factors, outcomes and genotypes of carbapenem-nonsusceptible Klebsiella pneumoniae bloodstream infection: a three-year retrospective study in a large tertiary hospital in Northern China.

OBJECTIVE: To investigate the independent risk factors, outcomes and genotypes associated with carbapenem-non-susceptible K. pneumoniae bloodstream infections (BSIs) in northern China from 2014 to 2016. METHODS: Over a three-year period, a total of 289 K. pneumoniae BSI patients were identified. Medical records were extracted to obtain the clinical information. Polymerase chain reactions (PCRs) were performed to analyse the multilocus sequence typing (MLST) types, Klebsiella pneumoniae carbapenemase (KPC) and metallo-ß-lactamases (MBL) genes, for replicon typing of the 10 randomly selected carbapenem-non-susceptible K. pneumoniae. RESULTS: A total of 59 carbapenem-non-susceptible K. pneumoniae strains were identified. Resistance rates to imipenem, meropenem, ertapenem and amikacin were low. Multivariate analyses showed that a central venous catheter odds ratio (OR) of 4.021 (CI 1.002-16.134); mechanical ventilation of 7.587 (2.856-20.156); Pitt bacteraemia score of 1.481 (CI 1.218-1.800); hospitalization prior to culture of 1.026 (CI 1.001-1.053); and some antibiotic use 30 days prior to K. pneumoniae bacteremia, including carbapenem of 9.123 (CI 2.995-27.791), aminoglycoside of 34.079 (2.091-555.396), and tigecycline of 5.065 (CI 1.261-20.339) were associated with carbapenem-non-susceptible K. pneumoniae bacteremia. Sequence type 11 (ST11) was the most predominant MLST type, which accounted for 50% of the isolates. Eighty per cent of the isolates harbored the KPC-2 gene. The overall 28-day mortality rates of carbapenem-non-susceptible and carbapenem-susceptible K. pneumoniae were 54.24% and 19.56%, respectively. CONCLUSION: Central venous catheter, mechanical ventilation, high Pitt bacteraemia score, hospitalization prior to culture, and prior antibiotic use (carbapenem, aminoglycoside and tigecycline) were identified as independent risk factors for carbapenem-non-susceptible K. pneumoniae BSI, which was mostly caused by KPC-2 in northern China.

The relationship between UGT1A1 gene polymorphism and irinotecan effect on extensive-stage small-cell lung cancer.

AIMS: To analyze the distribution of uridine diphosphate glucuronosyltransferase (UGT)1A1 gene polymorphisms in Chinese patients with extensive-stage small-cell lung cancer (E-SCLC), and to evaluate correlations between the UGT1A1 gene polymorphisms and toxicity, and efficacy of irinotecan (CPT-11) based regimen in the patients with E-SCLC. METHODS: The study analyzed the distribution of UGT1A1*28/*6 gene polymorphisms by polymerase chain reaction amplification and pyrosequencing. The analysis of UGT1A1*28 and UGT1A1*6 gene polymorphisms was performed in 67 patients with E-SCLC admitted to the clinic in the Department of Oncology from June 2011 to January 2013. A total of 67 cases with E-SCLC treated with irinotecan (CPT-11)-based regimen were enrolled to observe the adverse events and efficacy during the chemotherapy, including objective response rate, progression-free survival (PFS) and overall survival (OS). The correlation between UGT1A1 gene polymorphisms and severe adverse events was analyzed. The influences of UGT1A1*6/*28 polymorphisms on objective response rate, PFS, and OS were also analyzed. RESULTS: The distribution of UGT1A1 genotypes among 67 patients was as follows: UGT1A1*28 wild-type (WT) genotype TA6/6 (56, 83.6%), heterozygous mutant genotype TA6/7 (11, 16.4%); UGT1A1*6 WT genotype G/G (45, 67.2%), heterozygous mutant genotype G/A (22, 32.8%); no significant difference of PFS and OS was observed between different genotypes. The incidence of grade 3 and 4 delayed diarrhea and neutropenia in the patients carrying UGT1A1*6 G/A mutation was higher than that in the WT genotype (36.4% vs 6.6% P=0.034; 27.2% vs 4.4% P=0.026, respectively). The incidence of grade 3 and 4 thrombocytopenia in the patients carrying UGT1A1*28 TA6/7 mutation was higher than that in the WT genotype (27.2% vs 1.8% P=0.017). The patients simultaneously carrying UGT1A1*28 TA6/7 and UGT1A1*6 G/A mutations were prone to suffering grade 3 and 4 delayed diarrhea and neutropenia. CONCLUSION: For irinotecan-based regimens in E-SCLC, the UGT1A1*28 and UGT1A1*6 locus mutations can be regarded as predictors for severe adverse events. We also found that neither clinical response nor prognosis was significantly associated with the UGT1A1 gene polymorphisms.

Ursodeoxycholic acid induces apoptosis of hepatocellular carcinoma cells in vitro.

OBJECTIVE: Ursodeoxycholic acid (UDCA) is widely used to treat chronic liver diseases, and its cytoprotective effect on normal hepatocytes has been shown. This study aimed to investigate the apoptotic effects of UDCA on hepatocellular carcinoma (HCC) cells and the underlying molecular events in vitro. METHODS: HCC cells were treated by UDCA at different doses and periods of time to assess cell morphology, viability, apoptosis and gene expression using methyl thiazolyl tetrazolium (MTT), Annexin V/propidium iodide (PI) stain, transferase dUTP nick end labeling (TUNEL), enzyme-linked immunosorbent assay (ELISA), immunocytochemistry and quantitative reverse transcription polymerase chain reaction, respectively. RESULTS: UDCA treatment reduced cell viability but induced HCC cell apoptosis in dose-dependent and time-dependent manners. UDCA arrested HepG2 cells at phase S of the cell cycle. At the gene levels, UDCA downregulated Bcl-2 and second mitochondria-derived activator of caspase (Smac) protein expressions, but upregulated Bax and Livin proteins in HCC cells. At the highest concentration, UDCA inhibited Livin mRNA expression but increased Smac and caspase-3 mRNA expressions as well as the activity of caspase-3 in HCC cells. CONCLUSIONS: The induction of HCC cell apoptosis by UDCA was dose-dependent and time-dependent and was mediated by the regulation of Bax to Bcl-2 ratio, the expressions of Smac and Livin, and caspase-3 expression and activity.

Relationship between the SER treatment period and prognosis of patients with small cell lung cancer.

PURPOSE: To explore the relationship between SER (time between the start of any treatment and the end of radiation therapy) and the survival of patients with limited-stage small cell lung cancer. MATERIALS AND METHODS: Between 2008 and 2013, 135 cases of limited-stage small cell lung cancer (LS-SCLC) treated with consecutively curative chemoradiotherapy were included in this retrospective analysis. In terms of SER, patients were divided into early radiotherapy group (SER<30 days, n=76) and late radiotherapy group (SER≥30 days, n=59) with a cut- off of SER 30 days. Outcomes of the two groups were compared for overall survival. RESULTS: For all analyzable patients, median follow-up time was 23.8 months and median overall survival time was 16.8 months. Although there was no significant differences in distant metastasis free survival between the two groups, patients in early radiotherapy group had a significantly better PFS (p=0.003) and OS (p=0.000). CONCLUSIONS: A short SER may be a good prognostic factor for LD-SCLC patients treated with concurrent chemoradiotherapy.

[Detection of SALL4 mRNA expression in leukemia by real-time fluorescent quantitative PCR].

This study was purposed to establish a real-time fluorescent quantitative PCR (FQ-PCR) for quantifying SALL4 mRNA and to investigate its expression in different types of leukemia patients. SALL4 mRNA expression were measured in 60 leukemia patients of different periods and 10 normal controls sequentially by FQ-PCR. The results showed that the expression of SALL4 mRNA in de novo leukemia patients and relapsed patients was higher than that in controls (P < 0.05), which was significantly decreased at complete remission (CR). In relapsed patients, the expression of SALL4 mRNA increased slightly higher than that in de novo leukemia group, but the difference was not statistically significant (P > 0.05). However, the expression of SALL4 mRNA was low in CLL, T-ALL and AML-M3. The expression pattern of BMI-1 was same as SALL4, and the expression of BMI-1 positively correlated with that of SALL4 in leukemia (r = 0.825, P < 0.01). It is concluded that the detection of SALL4 gene expression in acute and chronic leukemia by real-time gTR-PCR displays high sensitivity and specificity. SALL4 gene may be one of indicators for monitoring the therapeutic outcome of partial leukemia and minimal residual disease.

[Myocardial ultrastructural changes in rats following different levels of acute +Gz exposure].

OBJECTIVE: To observe the effects of different levels of acute +Gz exposure on myocardial ultrastructure of rats and provide experimental basis for further development of anti-G measures. METHOD: Twenty male Wistar rats were randomly divided into 4 groups (n=5): normal control group, +20 Gz group, +10 Gz group and +5 Gz group. Profile of the centrifuge +Gz exposure was trapezoidal, in which +20 Gz lasted for 30 s, +10 Gz for 1.5 min. +5 Gz exposure was repeated for 3 times with 30 min interval and each for 1.5 min. Myocardial tissue of left ventricle was sampled for transmission electron microscopy 5 h after exposure. RESULT: +20 Gz and +10 Gz exposure caused obvious edema of myocardial and endothelial cells, myofibril disorder and injuries of mitochondria and nucleus. Breaks of myocardial fiber, formation of contraction bands and rupture of mitochondria were also observed in +20 Gz group. In +5 Gz group, there was still slight edema of myocardial and endothelial cells, while organic changes of myocardial ultrastructure were not observed. CONCLUSION: High +Gz exposure can cause myocardial ultrastructural injury in rats. Slight reversible injured response can also be observed in myocardial cell after repeated moderate level of +Gz exposure. This indicates that attention should be paid to the study of the effect of high +Gz on heart in pilots.