Effectiveness of Antibiotic Use Management in Tianjin (2011-2013): A Quasi-Experimental Study.

BACKGROUND In this study we investigated changes in the status of antibiotic use in Tianjin since the implementation of the Antibiotic Stewardship Program (ASP) (2011-2013), as well as existing problems, strategies, and outcomes to promote rational clinical antibiotic use. MATERIAL AND METHODS A quasi-experimental study was performed to investigate situations of antibiotic use in secondary and tertiary general hospitals in Tianjin from April 2011 to 2013. Five major indicators were analyzed: percentage of antibiotic use in inpatient cases (%), antibacterial use density (AUD), proportion of prophylactic antibiotic application for type I surgical incision, compliance rate of medication administration 0.5-2.0 h before such procedures, and antibiotic prophylaxis for ≤24 h in patients receiving these surgeries. RESULTS There was a decrease in the percentage of antibiotic use across general hospitals (60.38% to 46.88%), in AUD (51.60% to 35.37%), and in the proportion of prophylactic antibiotic applications for type I incisions (86.67% to 25.08%). For patients undergoing these procedures, there was an increased compliance rate of medication administration of 0.5-2.0 h prior to surgery (86.38% to 100%), and of antibiotic prophylactic use for ≤24 h (40.30% to 96.37%). CONCLUSIONS Implementation of the ASP campaign has reduced irrational antibiotic use, promoted rational antibiotic use, and delayed antibiotic resistance.

MicroRNA-375 targets the 3-phosphoinositide-dependent protein kinase-1 gene in pancreatic carcinoma.

Pancreatic carcinoma (PC) is an aggressive malignancy with one of the poorest mortality rates. It is the sixth leading cause of mortality from malignant disease in China and the fourth leading cause of cancer-related mortality in the United States. The poor outcome reflects the requirement for an improved understanding of the transcriptional control of oncogenic signaling pathways. 3-phosphoinositide-dependent protein kinase-1 (PDK1) is a potent oncogenic driver of PC. The present study aimed to elucidate the transcriptional regulation of microRNA (miR)-375-targeted PDK1. miR-375 is a putative target and, in the present study, was observed to be significantly downregulated in the tumor compared with non-tumor tissues from patients with PC (n=44). As determined by a luciferase reporter assay, the ectopic expression of miR-375 was identified to diminish the transcriptional activity of PDK1. Furthermore, immunoblotting revealed that miR-375 suppressed endogenous PDK1 protein levels. Functional assays showed that miR-375 was able to inhibit proliferation and promote apoptosis of the PC cells. miR-375 is a significant regulator of the PDK1 oncogene, suggesting that it may have a potential therapeutic role in the treatment of PC.

[Association between -1654C/T and -1641A/G gene polymorphism of protein C susceptibility and prognosis in severe sepsis].

OBJECTIVE: To approach the allele frequency and genotypic distribution of protein C (PC) gene polymorphism on the susceptivity and prognosis in severe sepsis patients. METHODS: Eighty patients with severe sepsis were enrolled. They were divided into survival group (n=47) and non-survival group (n=33) according to 28-day prognosis. Seventy-two healthy volunteers were enrolled as controls. Allele-specific polymerase chain reaction (AS-PCR) was used to analyze -1654C/T and -1641A/G site genotypes polymorphism of PC gene, fragments containing alleles was analyzed by using DNA sequencing. RESULTS: All the samples of the PC gene in the -1654C/T site had three kinds of genotypes: in 80 cases of severe sepsis group, there were 16 homozygous CC type, 44 heterozygous CT type, 20 homozygous TT type. In 72 cases of healthy control group, there were 17 CC type, 34 CT type, 21 TT type. The -1654C/T allele frequency and genotypic distribution in the patients with severe sepsis was not significantly different from those in the healthy control group, and no statistically significant difference was observed between the survival group and the non-survival group (all P>0.05). All the samples of the PC gene in the -1641A/G site had three kinds of genotypes: in 80 cases of severe sepsis group, there were 60 homozygous AA type, 12 heterozygous AG type, 8 homozygous GG type. In 72 cases of healthy control group, there were 57 AA type, 10 AG type, 5 GG type. No statistically significant difference was observed between severe sepsis group and healthy control group, the survival group and the non-survival group (all P>0.05) in -1641A/G allele frequency and genotypic distribution (all P>0.05). Three kinds of haploid, including -1654T/-1641A, -1654C/-1641A, and -1654C/-1641G were found except -1654T/-1641G. The frequency of haploid -1654C/-1641A was significant higher in non-survival group than that in the survival group [42.42% (14/33) vs. 21.28% (10/47), P=0.038]. CONCLUSIONS: The correlation between PC haploid -1654C/-1641A gene polymorphisms and prognosis of severe sepsis was found.

A preliminary study on the efficacy and influencing factors of interferon for the treatment of genotype 1 chronic hepatitis C with different dosage forms.

BACKGROUND AND OBJECTIVE: Nowadays, interferon alfa-2b is still in widespread use for the treatment of chronic hepatitis C in China. In this study, peginterferon alfa-2a plus ribavirin was compared with interferon alfa-2b plus ribavirin for the initial treatment of genotype 1 chronic hepatitis C. MATERIALS AND METHODS: Overall, 168 patients with genotype 1 chronic hepatitis C were assigned peginterferon alfa-2a (135-180 µg subcutaneously/week) plus ribavirin (800-1200 mg/day orally) or interferon alfa-2b (300-500 million units, once every other day) plus ribavirin (800-1200 mg/day). According to HCV RNA levels at weeks 4 and 12, patients were reallocated to receive different interferon dosage forms or different courses of treatment. The primary endpoint was a sustained virological response (SVR). RESULTS: A total of 160 patients completed the entire study and eight cases were lost to follow-up. The SVR rates in patients treated with peginterferon alfa-2a plus ribavirin for 24 and 48 weeks were 67.9% (53/78) and 73.6% (14/19), respectively, whereas in patients treated with interferon alfa-2b plus ribavirin for 24 and 48 weeks the SVR rates were 52.4% (43/82) and 40% (8/20), respectively. The SVR rates in the groups with a rapid virological response (RVR) and without RVR were 68.8 and 16.9%, respectively. The SVR rates in the groups with an early virological response (EVR) and in the groups without EVR were 88.1 and 10.5%, respectively. CONCLUSION: Peginterferon alfa-2a plus ribavirin was more effective than interferon alfa-2b plus ribavirin, with similar safety. RVR can predict a greater chance of SVR. The duration of treatment should be shortened for patients with RVR. Treatment for patients without EVR should be discontinued.

Complete genome sequence of Acinetobacter baumannii MDR-TJ and insights into its mechanism of antibiotic resistance.

OBJECTIVES: To determine the genome sequence of Acinetobacter baumannii strain MDR-TJ and characterize the mechanisms of multidrug resistance in this strain. METHODS: The whole-genome sequence was determined using Roche 454 GS FLX Titanium. Subsequently, the gaps were closed by sequencing PCR products. The genome of strain MDR-TJ was annotated using IMG ER, the RAST annotation server and the BASys bacterial annotation system. The comM gene of MDR-TJ was examined to identify a possible antibiotic resistance island. Based on the results of multilocus sequence typing, we investigated seven multidrug-resistant A. baumannii strains belonging to global clone 2 (GC2) isolated from Asia, Australia and Europe to determine the backbone shared by resistance islands of GC2 isolates. RESULTS: The A. baumannii strain MDR-TJ genome consists of a circular chromosome and a plasmid, pABTJ1. Strain MDR-TJ was assigned to sequence type ST2. Strain MDR-TJ harbours a 41.6 kb resistance island designated RI(MDR-TJ), which can be derived from the backbone of Tn6167 through the insertion of a Tn6022 into the 3'-end of the tetA(B) gene. Comparative analysis showed that transposon Tn6022 and its truncated forms prevailed in the antibiotic resistance islands of GC2 isolates. The carbapenem resistance gene bla(OXA-23) carried by transposon Tn2009 is located on a putatively conjugative plasmid, pABTJ1. CONCLUSIONS: A. baumannii strain MDR-TJ belongs to GC2 and is resistant to multiple antibiotics. A. baumannii MDR-TJ harbours a genomic resistance island that interrupts the comM gene. The carbapenem resistance of MDR-TJ is mediated by a putatively conjugative plasmid, pABTJ1.

Clinical significance of expression and amplification of the DcR3 gene in pancreatic carcinomas.

This study aimed to investigate the clinical significance of expression and amplification of decoy receptor 3 (DcR3) in pancreatic carcinomas (PC). mRNA expression was detected by PQ-PCR, and amplification was determined. DcR3 protein expression was detected by immunohistochemistry and ELISA. Correlations between DcR3 expression and clinical pathological factors were analyzed. The relative amount of DcR3 in PC tissues and non-cancerous tissues showed a statistically significant difference, 21 cases displaying more than two fold DcR3 amplification, while no such amplification was found in normal pancreatic tissues. DcR3 positive cell staining was located in the cytoplasm. The positive rate of DcR3 in PC and non-cancerous tissues showed a significant difference. DcR3 mRNA expression was correlated with clinical staging, size of the tumor, lymph node metastasis and histological staging, while protein expression was correlated with clinical data like tumor size. DcR3 gene amplification only correlated with tumor size. The level of DcR3 in serum of the PC resectable group before operation was 72.2±10.2 pg/ml, showing a significant difference compared to gallbladder carcinoma group (GC) or pancreatic benign tumor (PBT) group (P <0.01). In conclusion, DcR3 amplification is correlated with DcR3 expression in PC tissues, especially those clinical pathological factors which reflect tumor progression. Assessment of DcR3 level in sera of PC patients may be helpful for the early diagnosis and prognostic judgement.

[Expression of soluble triggering receptor expressed on myeloid cells-1 in septic patients and its relation with prognosis].

OBJECTIVE: To approach the relationship between the contents of soluble form of triggering receptor expressed on myeloid cells-1 (sTREM-1) and prognosis in patients with sepsis. METHODS: Using prospective, control study design, a total of 50 patients with sepsis who were admitted in intensive care unit (ICU) of the Second Hospital of Tianjin Medical University from March to December in the year of 2009 were enrolled. Firstly, the patients were divided into sepsis (n=28) and severe sepsis (n=22) groups according to the patients' condition. Then the patients were divided into survival group (n=34) and death group (n=16) according to the clinical outcome at 28 days after onset of sepsis. Clinical and laboratory data including blood routine tests, blood chemistry, blood gas analysis, C-reactive protein (CRP) and procalcitonin (PCT) were collected on the 1st, 3rd and 7th day after onset. Acute physiology and chronic health evaluation II (APACHEII) score was determined. sTREM-1 levels were determined using enzyme linked immunosorbent assay (ELISA) method. Correlation analysis of the sTREM-1, APACHEII score, white blood cell count (WBC) and CRP, using Logistic regression analysis. A total of 30 healthy persons were enrolled into the control group. RESULTS: The sTREM-1 levels (ng/L) in 50 septic patients on the 1st day were higher than those of the healthy persons (52.80±9.30 vs. 23.29±6.22, P<0.01). The sTREM-1 levels (ng/L) in severe sepsis group on the 1st, 3rd and 7th day (58.25±10.59, 65.75±13.57, 50.18±21.73) were higher than those of the sepsis group (48.55±5.20, 42.85±8.54, 34.02±12.86, P<0.05 or P<0.01). The sTREM-1 levels (ng/L) of the survival group on the 1st, 3rd and 7th day (53.07±10.47, 45.04±9.89, 32.84±8.42) were decreased with the progression of the ailment. The sTREM-1 levels did not differ significantly between the control group and survival group on the 7th day (P>0.05). The sTREM-1 levels (ng/L) in the death group on the 1st, 3rd and 7th day were increased with the progression of the ailment (52.27±6.42, 69.67±12.83, 75.70±10.55), and the level was significantly higher than that in survival group on the 3rd and 7th day (both P<0.01). The contents of sTREM-1 were positive correlated with APACHEII score (r=0.657, P<0.01), but not correlated with WBC (r=0.023, P>0.05), while somewhat correlated with CRP (r=0.150, P<0.10). Logistic regression analysis showed that sTREM-1 [odds ratio (OR)=0.893,P=0.000] and APACHEII score (OR=0.771, P=0.000) might be potential prognostic factors for septic patients. The area under the receiver operator characteristic curve was 0.868 and 0.930. The sensitivity of prognostic evaluation was 81.1% and specificity was 74.5% with sTREM-1 50 ng/L, and the sensitivity was 83.8% and specificity was 86.3% with APACHEII score 20 to estimate the outcome. CONCLUSION: The serum sTREM-1 are elevated at early stage in sepsis patients. It can reflect the severity of the condition. The sTREM-1 level, which might be considered as a potential prognostic factor for septic patients, is significantly correlated with APACHEII score.

Genome sequence of Acinetobacter baumannii MDR-TJ.

Acinetobacter baumannii is a pathogenic species of bacteria, identified as an aerobic gram-negative bacterium, that is resistant to most antibiotics. In this study, the MDR-TJ strain was isolated at the Second Hospital of Tianjin Medical University, China, and was found to be resistant to penicillin, cephalosporins, aminoglycosides, quinolones, and also imipenem. The genome sequence of Acinetobacter baumannii strain MDR-TJ was determined by using a combination of 454 pyrosequencing and paired-end sequencing performed with the Roche Genome Sequencer FLX system to generate a scaffolded assembly.

[A clinical study of the serum vascular endothelial growth factor in patients with severe sepsis].

OBJECTIVE: To examine the dynamic changes in serum vascular endothelial growth factor (VEGF) levels in patients with severe sepsis, and to investigate its relationship with acute physiology and chronic health evaluation II (APACHE II) score and some clinical parameters of patients. METHODS: Using prospective, randomly control study design, 29 patients with severe sepsis admitted to the intensive care unit (ICU) of the Second Hospital of Tianjin Medical University from July 2006 to October 2007 were enrolled for study. Platelet (PLT) count and albumin (Alb) levels on the 1st, 3rd, 7th day were determined, and APACHE II score was assessed. VEGF levels of severe sepsis patients and healthy control volunteers (31 cases) were measured by enzyme linked immunoabsorbent assay (ELISA). The patients were divided into two groups according to survival or death, and the differences between two groups were compared. RESULTS: The VEGF level in the health control group was (78.77+/-8.15) ng/L. In 16 survivors, the VEGF levels gradually lowered along the course of the disease (F=40.32, P<0.01). There was no statistical difference between control group and survival group on the 7th day (P>0.05). Thirteen patients died, and their VEGF levels lowered on the 3rd day, but elevated again on the 7th day (F=29.61, P<0.01). The VEGF levels showed obvious positive correlation with APACHE II score (r=0.510, P=0.000), and negative correlation with PLT (r=-0.221, P=0.046), and no relation with Alb levels (r=-0.029, P=0.789). CONCLUSION: The VEGF levels are elevated at onset in severe sepsis patients. The VEGF levels lowered along with the course of the disease in survival group, but it lowers inconspicuously in death group. VEGF levels can reflect the severity of sepsis in certain degree.