[Study on diagnostic value of extracellular volume imaging by magnetic resonance imaging for liver fibrosis of hepatitis B].

Objective: To investigate the diagnostic value of extracellular volume (ECV) imaging by magnetic resonance imaging for liver fibrosis of hepatitis B. Methods: A retrospective analysis was recruited in patients with chronic hepatitis B, who underwent liver surgery from April to October 2017 for pathological evaluation of liver tissues, and all patients underwent Gd-EOB-DTPA-enhanced T1 mapping to calculate the liver ECV score. The correlation between ECV and staging of hepatic fibrosis and inflammatory activity were compared to clarify the diagnostic value of staging of fibrosis. Results: 66 patients were enrolled in this study. Concerning the staging of liver fibrosis, there were 13, 4, 13, 10, and 26 cases with F0, F1, F2, F3 and F4 stages, respectively. ECV values had high interobserver consistency (correlation coefficient 0.860). The ECV difference between different stages of liver fibrosis was statistically significant (F = 15.02, P < 0.001). There was a significant positive correlation between ECV and fibrosis stage (r = 0.622, P < 0.001), and weak correlation with inflammatory activity (r = 0.332, P = 0.007). Fibrosis staging was an independent factor influencing ECV (P < 0.001). The area under the receiver operator characteristic curve for the diagnosis of liver fibrosis staging F≥1, F≥3 and F4 were 0.760, 0.846 and 0.873, respectively. The diagnostic sensitivity and specificity were 64.15%, 92.31%, 77.78%, 80.00% and 88.46, 72.50%, respectively. Conclusion: MRI-ECV imaging has great value for staging hepatic fibrosis of hepatitis B, and it can provide an effective method for diagnosis, staging, and evaluating the curative effect of fibrosis.

[Lack of progesterone receptor expression predicts poor prognosis in patients with operable ER-positive invasive breast cancer].

OBJECTIVE: To investigate the impact of lack of progesterone receptor (PR) expression on the prognosis of patients with operable ER (estrogen receptor)-positive invasive breast cancer. METHODS: We retrospectively analyzed the clinicopathological features, treatment and survival data of 318 women with ER+ /PR+ and ER+ /PR- invasive breast cancer. RESULTS: Among the 318 patients, there were 219 PR-positive and 99 PR-negative cases. The 5-year overall survival (OS) rate was 92.5%, and the 5-year disease-free survival (DFS) rate was 87.2% in the 318 ER-positive patients. Among them, the 5-year OS rates were significantly different between the PR-positive group (94.6%) and PR-negative group (87.8%, P=0.020), and the 5-year DFS rates were also significantly different from each other (89.8% and 81.6%, respectively, P=0.019). Univariate analysis showed that PR status, tumor size, T stage, axillary lymph node metastasis, and clinical stage were prognostic factors for OS (P<0.05 for all). Multivariate analysis showed that lack of PR expression, T stage ≥2, and positive axillary lymph node metastasis were independent risk factors for poor DFS and OS in ER-positive breast cancer patients (P<0.05 for all). Subgroup analysis showed that lack of PR expression was not significant in predicting poor DFS or OS when patients were in stage Ⅰ or with a small tumor (≤2 cm) (P>0.05 for all), and also showed that premenopausal women with PR-negative disease had poorer DFS and OS than PR-positive patients (P<0.05 for both). CONCLUSIONS: Lack of PR expression is an independent risk factor for poor prognosis in patients with operable ER-positive invasive breast cancer, especially in patients with a large tumor (>2 cm), advanced clinical stage (Stage Ⅱ or Ⅲ) or in premenopausal status.

AMFR gene silencing inhibits the differentiation of porcine preadipocytes.

Our study clarifies the role of the autocrine motility factor receptor (AMFR) gene in porcine preadipocyte differentiation. AMFR-siRNA was transfected into porcine preadipocytes and the preadipocytes were induced to differentiation. Subsequently, qRT-PCR was conducted to examine changes in mRNA expression of a series of genes in porcine preadipocytes, including AMFR, sterol-regulatory element-binding protein-1a (SREBP1a), SREBP2, insulin-induced gene 1 (Insig1), and Insig2. Expression changes in the mRNA of genes regulating adipocyte differentiation were also analyzed using qRT-PCR, including peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT/enhancer-binding protein alpha (C/EBPα), and Kruppel-like factor 2 (KLF2). Western blot analysis was conducted to examine the changes in AMFR protein expression in porcine preadipocytes. Additionally, morphological changes in differentiated porcine preadipocytes were examined by oil red O staining, and changes in optical density (OD) values were measured using an ultraviolet spectrophotometer. At 24 h after transfection with AMFR-siRNA, AMFR mRNA expression significantly reduced (P < 0.01), and AMFR protein expression markedly decreased (P < 0.05). The mRNA expression of SREBP1a, SREBP2, Insig1, and C/EBPα was significantly reduced (P < 0.01), whereas the expression of KLF2 mRNA was significantly elevated (P < 0.01). After induction of preadipocyte differentiation, the number of lipid droplets decreased in the AMFR-silenced group, and the OD value markedly reduced (P < 0.05). In addition, the expression of C/EBPα mRNA significantly decreased (P < 0.05), whereas the expression of KLF2 mRNA considerably increased (P < 0.05). Taken together, silencing of the AMFR gene inhibits the differentiation of porcine preadipocytes.

Liver fibrosis staging using T1 mapping on gadoxetic acid-enhanced MRI compared with DW imaging.

AIM: To evaluate the utility of T1 mapping on gadoxetic acid-enhanced magnetic resonance imaging (MRI) and diffusion-weighted imaging (DWI) for staging liver fibrosis. MATERIALS AND METHODS: This retrospective study was approved by the institutional review board and included 145 patients (mean age: 54 years old; 115 men and 30 women). Necro-inflammatory activity grade (G) and liver fibrosis stage (S) were histopathologically determined. T1 relaxation time and apparent diffusion coefficient (ADC) of the liver were measured and the reduction rate of the T1 relaxation time (Δ%) was calculated. T1 relaxation time measurements were compared with ADC values according to S/G scores. RESULTS: Unenhanced hepatobiliary phase (HBP) and Δ% of T1 relaxation times showed significant correlations with S/G scores (rho: 0.28, 0.51, -0.35 for the S score, 0.26, 0.39, -0.26 for the G score, respectively, p<0.05). ADC values showed significant correlation with the S score (rho: -0.17, p = 0.04) and did not correlate significantly with the G score (rho: -0.07, p = 0.39). The areas under receiver operator characteristics (AUC) curve of unenhanced HBP, Δ% T1 relaxation time, and the ADC value were 0.68, 0.82, 0.71, 0.61 for the identification of S ≥ 3, and 0.63, 0.68, 0.62, 0.52 for the identification of G ≥ 3, respectively. The HBP T1 relaxation time was better than that of ADC for identification of S ≥ 3 (p = 0.0005) and G ≥ 3 (p = 0.014). CONCLUSIONS: The HBP T1 relaxation time measurement on gadoxetic acid-enhanced MRI images might be a potential biomarker in the staging of hepatic fibrosis, and was more accurate than the ADC measurement.

Effect of cardiopulmonary bypass on leukocyte activation: changes in membrane-bound elastase on neutrophils.

BACKGROUND: Neutrophil elastase is known to be released from the activated leukocytes as a result of cardiopulmonary bypass (CPB). However, its biological effect on organ injury is questionable because it is quickly bound by natural proteinase inhibitors (PIs). Recently, membrane-bound elastase (MBE) was found to be able to resist the PIs' process and, thus, is biologically more active. This paper studies the effect of CPB on the kinetic change of MBE and its possible link to postoperative inflammation and organ function. METHOD: Ten consecutive patients undergoing elective coronary artery bypass grafting (CABG) surgery with CPB were recruited into the study. Blood samples were taken before sternotomy, after aortic declamping, at the end of CPB, three and six hours after CPB and on the first postoperative day. MBE was determined by substrate assay from isolated neutrophils. Inflammation and organ function markers methods. RESULTS: MBE slightly increased after aortic declamping, while it significantly increased and reached its peak at the end of CPB; it returned to its preoperative level on the first postoperative day. In contrast to lung sequestration of neutrophils, there was no transpulmonary gradient of MBE between left and right atria after aortic declamping. Neither MBE nor total MBE activity was positively correlated with postoperative inflammation markers such as blood lactate and C-reactive protein and organ function markers such as creatine phosphokinase and alanine aminotransferase. CONCLUSIONS: CPB induces increased MBE expression on neutrophils with its peak at the end of CPB. Lack of association between neutrophil MBE and clinical markers suggests that multiple systems might be involved in the post-CPB inflammatory reaction and organ dysfunction.

Quaternary ammonium functionalized poly(propylene imine) dendrimers as effective antimicrobials: structure-activity studies.

Quaternary ammonium functionalized poly(propyleneimine) dendrimers were synthesized and their antibacterial properties were evaluated using a bioluminescence method. These quaternary ammonium dendrimers are very potent biocides. The antibacterial properties depend on the size of the dendrimer, the length of hydrophobic chains in the quaternary ammonium groups, and the counteranion. Since these dendrimers are well characterized and monodisperse, they also serve as an effective system to study the structure-activity relationship. The antimicrobial properties of these dendrimer biocides have a parabolic dependence on molecular weight, which is different from the bell-shaped molecular weight dependence of conventional polymer biocides. The dependence on the hydrophobic chain of the quaternary ammonium structure is similar to conventional polymer biocides, and shows a parabolic relationship with dendrimer biocides carrying C10 hydrophobes the most potent. The antimicrobial properties of these novel biocides with bromide anions are more potent than those with chloride anions. Biocides derived from hyperbranched polymers were also synthesized and found to possess somewhat lower effectiveness.

Retrograde flush and cold storage for twenty-two to twenty-five hours lung preservation with and without prostaglandin E1.

BACKGROUND: Our previous study showed that retrograde flush through the left atrium is better than antegrade flush in 6-hour lung preservation. Whether it is feasible in long-term lung preservation is not clear. Several studies suggested that prostaglandin E1 may not be necessary in retrograde flush because of the low vascular resistance on the venous side. This study evaluates the effects of retrograde flush and prostaglandin E1 in 24-hour lung preservation. METHODS: Canine donor lungs were retrograde flushed with University of Wisconsin solution. Group A (n = 7) was pretreated with prostaglandin E1. No prostaglandin E1 was used in group B (n = 7). After flush and cold storage at 4 degrees C for 22 to 25 hours, left lung allotransplantation was performed. Measurements were taken before transplantation (baseline), and at 10, 30, 60, and 120 minutes after transplantation while the right pulmonary artery was occluded. RESULTS: After 120 minutes of reperfusion, the oxygen tension and carbon dioxide tension were 643 +/- 24 and 37 +/- 3 mm Hg in group A and 600 +/- 29 and 37 +/- 3 mm Hg in group B, respectively (p = NS). Pulmonary artery pressure (group A vs group B) was 20 +/- 1 versus 28 +/- 2 mm Hg (p < 0.01); right atrium pressure: 4 +/- 1 versus 8 +/- 1 mm Hg (p < 0.01); left pulmonary vascular resistance: 1109 +/- 51 versus 1525 +/- 133 dyne.sec.cm-5 (p < 0.05); airway resistance: 22 +/- 1 versus 24 +/- 1 cm H2O/L/sec (p = NS); lung dynamic compliance: 30 +/- 1 versus 26 +/- 1 cc/cm (p < 0.05) respectively. As compared with the baseline (19 +/- 1), airway resistance was significantly increased after 2 hours of reperfusion in group B (p < 0.05). Electron microscopy revealed that type I pneumocytes, capillary endothelial cells, and epithelial cells of bronchi were well preserved and the contents of lamellar bodies of type II pneumocyte were reduced. CONCLUSIONS: Canine lung was well preserved by retrograde flush and cold storage with University of Wisconsin solution after 24 hours preservation. Pretreatment of prostaglandin E1 is helpful in reducing pulmonary vascular resistance and airway resistance and improving lung dynamic compliance.

Pulsed brachytherapy as a substitute for continuous low dose rate: an in vitro study with human carcinoma cells.

PURPOSE: Pulsed dose rate (PDR) brachytherapy as a substitute for continuous low dose rate (CLDR) has the potential to be a useful option in brachytherapy. However, the frequency and duration of pulses that will produce results practically equivalent to CLDR is still an open and important question. This study was designed to compare the survival of human tumor cells, cultured in vitro, and exposed to continuous or pulsed irradiation where the pulse frequency was varied. METHODS AND MATERIALS: Three different human carcinoma cells, derived from cervical and breast cancers, were exposed to CLDR gamma rays, or to pulsed irradiations with the same overall dose rate. Pulsed regimens used were 3.8 min every hour, 7.6 min every 2 h, 11.4 min every 3 h, 15.2 min every 4 h, 22.8 min every 6 h, and 45.6 min every 12 h. For each comparison between CLDR and PDR, the overall dose and the overall time were the same. Experimental design was such that significant differences in biological effectiveness, if present, would be detected. RESULTS: For the cell lines investigated, hourly pulses resulted in cell survival indistinguishable from CLDR. However, as the pulse interval was increased, cell survival progressively decreased compared with CLDR, and the pulsed regimes were no longer equivalent to continuous low dose rate. CONCLUSIONS: This study provides some evidence to support the suggestion that a 10-min pulse, repeated every 1 to 2 h, would be functionally equivalent to a continuous low dose rate irradiation, at least in terms of early responding endpoints. Longer intervals between pulses might result in loss of equivalence in some cases.

Hypoxic preconditioning enhances functional recovery after prolonged cardioplegic arrest.

The purpose of this study was to assess the ability of hypoxic preconditioning to improve myocardial salvage after prolonged hypothermic cardioplegic arrest. Isolated working rat hearts were arrested at 4 degrees C with St. Thomas' Hospital cardioplegic solution and immersion stored for 4 or 6 hours. Two groups were studied, control and hypoxically preconditioned (HP) hearts. After 4 hours' preservation, aortic flow, coronary flow, and the first derivative of aortic pressure were 8.7 +/- 1.6 mL/min, 17.8 +/- 1.6 mL/min, and 2,064 +/- 123 mm Hg/s, respectively, in control hearts (n = 11) and 25.7 +/- 2.5 mL/min, 27.1 +/- 2.5 mL/min, and 2,655 +/- 93 mm Hg/s, respectively, in HP hearts (n = 11) (p < 0.05). After 6 hours' preservation, aortic flow, coronary flow, and the first derivative of aortic pressure were 3.5 +/- 1.2 mL/min, 18.8 +/- 0.4 mL/min, and 1,622 +/- 226 mm Hg/s, respectively, in control hearts (n = 6) and 21.5 +/- 3.2 mL/min, 25.5 +/- 2.3 mL/min, and 2,439 +/- 239 mm Hg/s, respectively, in HP hearts (n = 6) (p < 0.05). After 6 hours' preservation, adenine nucleotides and creatine phosphate levels were not significantly different between the two groups, but lactate dehydrogenase release was significantly increased (p < 0.05) in control versus HP hearts (4.66 +/- 0.58 IU/L versus 1.98 +/- 0.28 IU/L). We conclude that hypoxic preconditioning reduces cellular necrosis and preserves myocardial function after prolonged hypothermic cardioplegic arrest.

Radiopotentiation of human brain tumor cells by the spermine analog N1,N14-bis(ethyl)homospermine.

PURPOSE: To determine whether the cytotoxicity produced by radiation can be increased by the spermine analog N1,N14-bis(ethyl)homospermine (BE-4-4-4). METHODS AND MATERIALS: Two human tumor cell lines, SF-126 and U-251 MG, were either treated with 0.1 or 0.4 microM BE-4-4-4 for 3 or 4 days, or with 0.2 microM BE-4-4-4 for 4 days. At the end of BE-4-4-4 treatment, cells were irradiated and assayed immediately. Polyamine levels, cell survival, and cell number were determined. RESULTS: In SF-126 cells, treatment with 0.2 microM BE-4-4-4 for 4 days killed about 50% of the cells and also increased the cytotoxicity of radiation. The dose enhancement ratio was approximately 1.3:1.5, which is similar to that reported for alpha-difluoromethylornithine. Polyamine levels were partially depleted, and growth was inhibited to about 60% of control levels. Pretreatment of cells with either 0.1 or 0.4 microM BE-4-4-4 for 3 or 4 days produced less of an increase in radiation-induced cytotoxicity, even though these exposures killed 30-40% or 60-90% of the cells, respectively. Similar treatment with 0.1-0.4 microM BE-4-4-4 in U-251 MG cells had minimal effects on cytotoxicity and growth inhibition, while treatment with 1.0 microM and 2.0 microM BE-4-4-4 for 4 days produced more than a 50% depletion in polyamine levels and partial inhibition in growth, but failed to demonstrate radiopotentiation. CONCLUSION: The cytotoxic polyamine analog BE-4-4-4 can increase the cytotoxicity caused by radiation in at least one cell line. The amount of potentiation depends on the concentration of the analog, with the most occurring at the intermediate concentration. Because we did not observe potentiation in both cell lines, and because of the dose dependence seen in SF-126 cells, the clinical efficacy produced by combined BE-4-4-4 and radiation protocols may be limited.

Biophysical mechanism of radiation damage to mammalian cells by X- and gamma-rays.

Published information on the reproductive death in mammalian cells irradiated by a wide range of X- and gamma-ray energies has been re-analysed to extract intrinsic efficiencies of damage for the secondary electrons in transient equilibrium. On a log-log plot, a linear dependence on the track average l.e.t. and the average specific primary ionization is found, indicating that either serves as a good quality parameter. The soft X-ray data are consistent with this conclusion. Upon comparison with data for fast heavy ion irradiations, the average specific primary ionization is shown to be applicable independently of radiation type whereas track average l.e.t. is not. Furthermore it is revealed that electrons are most damaging near the end of their range but their efficiency is only about 10-20 per cent of that of fast ions at the same quality, possibly due to the influence of multiple scatter on the electron penetration depth. It is deduced that, for the dose rates involved, the damage by electrons is predominantly by intra-track action and not inter-track action. The results are consistent with the suggestion that optimum damage occurs when the mean free path between ionizations is equivalent to the strand separation in the double-stranded DNA.

X-ray photoelectron spectra study on the derivatives of N-beta-phenethyl amine and N-beta-phenethyl glycine.

The X-ray photoelectron spectra of sixteen derivatives of N-beta-phenethyl amine and N-beta-phenethyl glycine have been studied. The effect of different structures on N1s binding energy and that of their Pauling's atomic charge density on the nitrogen atoms are investigated. The experimental binding energy of N1s is proportional to the calculated Pauling's atomic charge density. It shows that the phosphoryl group is the strongest nitrogen lone pair electron localizing group as compared with the corresponding sulfonyl and acyl derivatives. The XPS results agree with the data that there is no decarbonylation during the synthesis of N-dialkylphosphoryl-tetrahydro-3-benzazepin-1-one. In addition, since the N1s in P-N bond is smaller than that in S-N and C-N bonds, the phosphoryl group can be removed under much milder conditions. These results provide a semi-empirical evidence for the synthesis of the skeleton of the cephalotaxine. It also differentiates the reaction paths for these three different amino protecting groups.