ObJective To evaluate the value of contrast-enhanced ultrasonography microflow imaging (MFI) in detecting prostate cancer. Methods Sixty-five patients with serum prostate-specific antigen levels higher than 4.00 μg/L were evaluated with transrectal gray-scale,power Doppler,and MFI ultrasonography and then biopsy guided by ultrasonography. Biopsy was performed at twelve sites in the base,the mid gland and the apex in each patient. In these three transverse sections, when any of the three methods showed abnormality,the biopsy site was directed to the abnormal foci. Diagnostic efficiency of the three methods for prostate cancer detection was compared based on biopsy results according to patient and biopsy site. Results Overall prostate cancers were detected in 230 (29.5 %) of 780 specimens in 36(55.4%) of 65 patients. MFI could detect more patients(34) than gray-scale(26) and power Doppler(28) (P = 0.021, P = 0.031), 6(16.7%)of the 36 patients diagnosed with cancer were identified only by MFI. By biopsy site, MFI had higher sensitivity and overall accuracy (80.0% and 83.0%) than gray-scale (47.0% and 76.8%) and power Doppler (37.4% and 74.6%) ultrasonography(P <0.001, P<0.001 ; P = 0.001, P <0.001), while the specificity of MFI was 84.4%, lower than gray-scale (89.3%) and power Doppler (90.2%) ultrasonography(P = 0.009, P < 0.001). Conclusions MFI could detect more patients and improve sensitivity and overall accuracy by biopsy site than conventional uhrasonography.

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Objective To investigate the correlation between plasma pentraxin 3 (PTX3)and cardiovascular disease(CVD) in maintenance hemodialysis(MHD) patients.Methods Plasma was obtained from 98 MHD patients before and after a session of HD and 50 age-matched healthy subjects.Plasma PTX3 was measured by enzyme-linked immunosorbant assay (ELISA).Spearman correlation and linear regression were used to examine the correlation between plasma PTX3 level and other laboratory parameters.Binary Logistic regression was used to assess the correlation between plasma PTX3 level and CVD.Receiver operator characteristic (ROC) curve was used to analyze the correlation among PTX3, high sensitive C-reactive protein(hsCRP) and CVD.Results Plasma PTX3 level was significantly higher in MHD patients compared to healthy controls [1.87 (1.34-2.50) μg/L vs 1.11(0.86-1.51) μg/L, P＜0.01], and increased after a single HD session[post-HD 2.18(1.80-3.14) μg/L vs pre-HD 1.87(1.34-2.50) μg/L, P＜0.01].Patients with CVD had higher concentrations of PTX3 than those without CVD[2.18 (1.48-2.74) μg/L vs 1.76 (1.25-2.26) μg/L, P＜0.05].High plasma PTX3 (＞1.87 μg/L) was positively and independently associated with CVD[OR=3.15, 95％CI(1.17-8.50), P＜0.05].ROC curve analysis showed the PTX3 was more closely correlated to CVD than hsCRP in MHD patients with hsCRP ＞3 mg/L, and the area under the curve of PTX3 and hsCRP was 0.655 ±0.083(P＜0.05) and 0.562±0.083(P＞0.05) respectively.Plasma PTX3 level was negatively correlated with body mass index (ρ=-0.248,P＜0.05), pre-albumin(ρ=-0.218, P＜0.05), total cholesterol(ρ=-0.265, P＜0.01), triglyceride (ρ=-0.246, P＜0.05), LDL-cholesterol (ρ=-0.254, P＜0.05), hemoglobin (ρ=-0.212, P＜0.05), and positively with erythropoietin dose per week(ρ=0.184, P＜0.01), cardiac troponin T (ρ=0.287,P＜0.01), carotid artery intima-media thickness (ρ=0.294, P＜0.05).Conclusions PTX3 level ismarkedly elevated in HD patients.HD procedure induces PTX3 elevation.Plasma PTX3 could be auseful marker of CVD risk factors in MHD patients.

OBJECTIVETo examine the possible role of aristolochic acid (AA) in transdifferentiation and apoptisis of human tubular epithelial cell line (HKC).

METHODSCultured HKC cells were divided into five groups: serum-free (negative control) and treatment with AA at the concentrations of 5 mg/L, 10 mg/L, 20 mg/L and 40 mg/L for 48 hours, respectively. Transdifferentiation of HKC cells was observed with the following methods: detection of the expression of vimentin and cytokeratin of HKC cells with indirect immunoflourescence, determination of expression of E-cadherin and alpha-smooth muscle actin (alpha-SMA) by indirect immunohistochemical double staining, and determination of the proportion of alpha-SMA (+) HKC cells by flow cytometry. The apoptosis of HKC cells was observed with Giemsa staining, TUNEL reaction and agarose gel electrophoresis, and the ratio of apoptotic HKC cells was quantitatively analyzed by flow cytometry with propidium iodide staining.

RESULTSThe expression of cytokeratin and E-cadherin reduced and that of vimentin increased in HKC cells treated with 10 mg/L of AA for 48 hours, and the expression of alpha-SMA (+) in HKC cells treated with 10 mg/L of AA (14.17 +/- 0.61)% was significantly higher than that in serum-free controls (3.57 +/- 0.52)%. Apoptosis of HKC cell treated with 40 mg/L of AA for 48 hours was 53.4%, significantly higher than that in serum-free controls (2%). Treatment with 5 mg/L of AA and 20 mg/L of AA could not induce apoptosis and transdifferentiation of cells.

CONCLUSIONSTreatment with relatively low concentration of AA (10 mg/L) might induce slight transdifferentiation in cultured HKC cells and that with higher concentration of AA (40 mg/L) for 48 hours might induce apparent apoptosis of these cells, which suggested that transdifferentiation and apoptosis of tubular epithelial cells probably played important roles in aristolochic acid-induced nephropathy.

Actins ; analysis ; Apoptosis ; drug effects ; genetics ; Aristolochic Acids ; pharmacology ; Carcinogens ; pharmacology ; Cell Differentiation ; drug effects ; Cell Line ; DNA Fragmentation ; drug effects ; Epithelial Cells ; drug effects ; metabolism ; ultrastructure ; Humans ; Immunohistochemistry ; In Situ Nick-End Labeling ; Kidney Tubules ; cytology ; drug effects ; ultrastructure ; Microscopy, Electron ; Muscle, Smooth ; chemistry

Objective: To analyze the clinical, laboratory characteristics and prognosis of adult early T-cell precursor acute lymphoblastic leukemia (ETP-ALL). Methods: The clinical data of 13 adult ETP-ALL patients from January 2009 to March 2017 were retrospectively analyzed and compared with non-ETP ALL patients. Results: 13 ETP-ALL patients (17.3%) were identified in 75 adult T-ALL patients, the median age of the patients was 35 years old (15 to 49 years) and 10 patients were male (76.9%). ETP-ALL patients had lower WBC count, LDH level, blasts in peripheral blood, lower incidence of thymic mass and higher PLT count compared to non-ETP ALL patients. The CR rate after one course induction chemotherapy for ETP-ALL and non-ETP ALL patients was 33.3% and 90.1%, respectively (χ²=26.521, P<0.001). The median overall survival(OS) was 11.33 (95%CI 0-28.46) and 25.69 (95%CI 11.98-39.41) months, respectively. The 3-year OS was 41.7% and 40.7%, respectively (P=0.699). The median event free survival (EFS) was 1.51 (95%CI 1.23-1.79) and 21.36 (95%CI 4.67-38.04) months, respectively. The 3-year EFS was 16.7% and 39.5%, respectively (P=0.002). The 3-year relapse free survival (RFS) was 53.0% and 52.0%, respectively (P=0.797). Multivariate analysis revealed that CNSL and allo-HSCT were independent risk factors affecting OS of T-ALL and ETP-ALL didn’t affect the prognosis of T-ALL. Conclusion To our knowledge, this study is the first report on characteristics and prognosis of adult ETP-ALL patients in China. At total of 13 T-ALL patients (17.3%) were classified as having ETP-ALL. These patients had a lower leukemia burden and lower CR rate after one course induction compared to non-ETP ALL patients. Allo-HSCT can improve the prognosis of ETP-ALL.

Objective: To analyze the clinical features and prognosis of acute lymphoblastic leukemia patients with immunophenotype of CD10^-pre-B (CD10^- pre B-ALL) . Methods: 6 adult cases with CD10^- pre B-ALL immunophenotypes were analyzed retrospectively, related literatures were reviewed to clarify these kind of patients’ clinical features and prognosis. Results: CD10^- pre B-ALL occurred in 1.5% of ALL, 1.8% of B-ALL and 11.5% of pre B-ALL respectively. All the 6 patients were male with the median age as 33.5 years old, the median white blood cells was 101.78×10⁹/L, MLL-AF4 fusion transcripts were evident in all cases. Complete remission (CR) was achieved in 5 patients after first induction chemotherapy, 1 patient failed to respond to induction therapy, and got CR after 3 courses of chemotherapy. 2 patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) in CR₁, 1 patient relapsed in the short term and underwent allo-HSCT in CR₂. 1 patient was still waiting for allo-HSCT. Of the 2 patients who didn’t receive transplantation, 1 died following a relapse, the other remained to be in CR. Conclusions CD10^- pre B-ALL was a rare but distinct subtype in adult ALL characterized by male dominance, high onset white blood cells and MLL rearrangement rate. Conventional chemotherapy produced a high response rate but more likely relapse, allo-HSCT may have the potential to improve the prognosis of these patients.

Objective: To evaluate the incidence of invasive fungal infections (IFI) and usage of intravenous antifungal drugs during remission induction chemotherapy in patients with acute myeloid leukemia (AML) under primary antifungal prophylaxis with posaconazole. Methods: Clinical records from newly diagnosed AML patients above 15 years old in one single center from February 2014 to January 2016 were retrospectively reviewed and analyzed, excluding acute promyelocytic leukemia. The incidence of IFI and usage of intravenous antifungal drugs were investigated between control group (not receiving any broad spectrum antifungal prophylaxis) and treatment group (receiving posaconazole as primary prophylaxis). Results: A total of 147 newly diagnosed AML patients were enrolled. Of them, 81 received prophylaxis with posaconazole, and 66 did not receive broad-spectrum antifungal treatment. 7 IFI occurred in posaconazole group, and all were possible cases; 19 IFI occurred in control group (3 proven, 4 probable, 12 possible). The incidence of IFI was significantly lower in treatment group than that in control group (8.6% vs 28.8%, χ²=10.138, P=0.001). Usage of intravenous antifungal drugs was significantly decreased in posaconazole group (18.5% vs 50.0%, χ²=16.390, P<0.001). Conclusion Prophylaxis with posaconazole coulf prevent IFI and reduce usage of intravenous antifungal drugs significantly during remission induction chemotherapy in AML patients.

Objective: To probe the potential utility of Wilms tumor 1 (WT1) as a marker of minimal residual disease (MRD) in acute myeloid leukemia (AML) to estimate the relapse-predicting cut-off value. Methods: Quantitative assessment of bone marrow WT1 mRNA level was preformed using real-time quantitative reverse transcription polymerase chain reaction (RQ-RT-PCR) assay. The expression levels of WT1 dynamically measured with RQ-RT-PCR were retrospectively analyzed in 121 AML cases (not including acute promyelocytic leukemia) achieving complete remission (CR) after induction therapy followed by consolidation therapy. By comparing WT1 levels of patients with different post-therapy outcomes, the investigators used the receiver operating characteristic (ROC) curve to determine WT1 threshold so as to predict their clinical relapses. Then prognoses and the significance of intervention were analyzed between WT1 positive and negative patients according to the cut-off value of WT1. Results: According to ROC curve, WT1 level higher than 2.98% predicted the possibility of relapse. For simplicity and clinical application, 3.00% was used as the cut-off value of WT1 level for relapse. WT1 levels in 41 patients at diagnosis were detected, meanwhile 3 patients whose WT1 levels at diagnosis below 3.00% were excluded, then the median WT1 level of the rest 38 patients at diagnosis was 44.09% (range 7.19%-188.06%) . The median WT1 level in remission was 0.48% (352 samples, range 0-8.41%) . The median WT1 level at diagnosis was higher than that in remission. Excluding the 3 patients with WT1 level at diagnosis under 3.00%, the relapse rate of WT1 positive group (>3.00% during consolidation phase and follow-up) and WT1 negative group (≤3.00%) was 70.0% (14/20) and 12.2% (12/98) respectively (P<0.001) . The median time from WT1 positivity to clinical relapse was 58 days. Conclusions WT1 expression level above 3.00% was associated with markedly high risk of relapse, which could be as a useful marker for monitoring MRD following consolidation therapy.

Objective: To analyze the clinical and laboratory characteristics, and prognosis of adult acute myeloid leukemia (AML) patients with MLL gene rearrangements. Methods: The medical records of 92 adult AML patients with MLL gene rearrangements from January 2010 to December 2016 were retrospectively analyzed. Results: 92 cases (6.5%) with MLL gene rearrangements were identified in 1 417 adult AML (Non-M₃) patients, the median age of the patients was 35.5 years (15 to 64 years old) with an equal sex ratio, the median WBC were 21.00(0.42-404.76)×10⁹/L, and 78 patients (84.8%) were acute monoblastic leukemia according to FAB classification. Eleven common partner genes were detected in 32 patients, 9 cases (28.1%) were MLL/AF9(+), 5 cases (15.6%) were MLL/AF6(+), 5 cases (15.6%) were MLL/ELL(+), 2 cases (6.3%) were MLL/AF10(+), 1 case (3.1%) was MLL/SETP6(+), and the remaining 10 patients’ partner genes weren’t identified. Of 92 patients, 83 cases with a median follow-up of 10.3 (0.3-74.0) months were included for the prognosis analysis, the complete remission (CR) rate was 85.5% (71/83), the median overall survival (OS) and relapse free survival (RFS) were 15.4 and 13.1 months, respectively. Two-year OS and RFS were 36.6% and 29.5%, respectively. Of 31 patients underwent allogeneic hematopoietic stem-cell transplantation (allo-HSCT), two-year OS and RFS for patients received and non-received allo-HSCT were 57.9% and 21.4%, 52.7% and 14.9%, respectively (P<0.001). Among patients with partner genes tested, 9 of 32 cases (28.1%) were MLL/AF9(+), the median follow-up was 6.0(4.1-20.7) months. 3 patients with MLL/AF9 underwent allo-HSCT. 23 cases (71.9%) were non- MLL/AF9(+), the median follow-up was 7.8 (0.3-26.6) months. 14 patients (60.1%) with non-MLL/AF9 underwent allo-HSCT. One-year OS for patients with MLL/AF9 and non-MLL/AF9 were 38.1% and 55.5%, respectively (P=0.688). Multivariate analysis revealed that high WBC (RR=1.825, 95% CI 1.022-3.259, P=0.042), one cycle to achieve CR (RR=0.130, 95% CI 0.063-0.267, P<0.001), post-remission treatment with allo-HSCT (RR=0.169, 95% CI 0.079-0.362, P<0.001) were independent prognostic factors affecting OS. Conclusions AML with MLL gene rearrangements was closely associated with monocytic differentiation, and MLL/AF9 was the most frequent partner gene. Conventional chemotherapy produced a high response rate, but likely to relapse, allo-HSCT may have the potential to further improve the prognosis of this group of patients.

Objectives: To investigate the influence of duration of antibiotic therapy on the prognosis of patients with AML who had Gram-negative bloodstream infection during consolidation chemotherapy. Methods: Data were collected retrospectively from 591 patients enrolled from the registered "A Phase III study on optimizing treatment based on risk stratification for acute myeloid leukemia, ChiCTR-TRC-10001202" treatment protocol between September 2010 and January 2016 in different treatment cycles. Results: A total of 119 episodes of Gram-negative bloodstream infection occurred during consolidation chemotherapy. Excluding the 5 episodes in which fever lasted longer than 7 days, 114 episodes of infection were analyzed. The median neutrophil count was 0 (0-5.62)×10⁹/L, median neutropenia duration was 9 (3-26) days, median interval of antibiotics administration was 7 (4-14) days. Logistic regression analysis showed that there is no significant difference on 3-day recurrent fever rate and reinfection by the same type bacteria between antibiotics administration ≤7 days or >7 days (1.2% vs 3.0%, P=0.522, OR=0.400, 95% CI 0.024-6.591; 18.5% vs 21.2%, P=0.741, OR=0.844, 95% CI 0.309-2.307). Propensity score analysis confirmed there was no significant difference on same pathogen infection rate between antibiotics application time ≤ 7 days or >7 days (P=0.525, OR=0.663, 95% CI 0.187-2.352). No infection associated death occurred within 7 or 30 days in both groups. Conclusion Discontinuation of therapy until sensitive antibiotics treated for 7 days does not increase the recurrent fever rate and the infection associated death rate. Indicating that, for AML who had Gram-negative bloodstream infection during consolidation chemotherapy, short courses of antibiotic therapy is a reasonable treatment option when the infection is controlled.