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Background The venous thromboembolism, which may be caused by increased platelet activation, is a risk factor for tumor prognosis. We determined the platelet activation status for diagnosis and predicting postoperative prognosis of hepatocellular carcinoma. Methods We conducted a prospective study of 191 patients diagnosed with HCC at Zhongshan Hospital from April 2016 to July 2016 as well as 99 healthy people. The platelet activation status was assessed by 2 platelet markers, PAC-1 and CD62p, using flow cytometry. The patients were treated with TACE or resection and monitored for ≥6 months. The diagnostic value of marker-positive platelets was determined by the receiver operating characteristic curve and the postoperative value were analyzed using the Kaplan-Meier method and COX regression model. Results All the 3 groups with high levels of marker-positive platelets were likely to be diagnosed with HCC and the PAC-1+ percentage had the best efficacy. The univariate analysis showed that the levels of PAC-1+ and CD62p+ platelets was risker factors for poor postoperative prognosis after both TACE and resection. Moreover, the multivariate analysis revealed that the level of PAC-1+ platelets was an independent risk factor for poor prognosis. Conclusions The PAC-1+ percentage of platelets is a new indicator for diagnosis and predicting postoperative prognosis.

Aim: To explore the prognostic value of the pretreatment platelet (PLT) count in patients undergoing transcatheter arterial chemoembolization (TACE) with hepatocellular carcinoma (HCC). Materials & methods: We prospectively analyzed 317 hepatitis B virus-related HCC patients undergoing TACE. Time to progression (TTP) was selected to evaluate the clinical significance of PLT level in HCC patients. Results: PLT was the only parameter showing statistical significance of all the clinical characteristics between two distinct tumor response groups. After ruling out cirrhosis as a potential major confounding factor, the conclusion was further established. Higher pretreatment PLT level, portal vessel invasion and higher stratification of α-fetoprotein level were independently associated with longer TTP. The prognostic score model combining the three risk factors revealed that higher risk scores might mean shorter TTP. Conclusion: The pretreatment PLT level is a potentially useful biomarker to predict the prognostic outcomes in HCC patients undergoing TACE and deserves to be further explored in subsequent works.

Immune thrombocytopenia (ITP) is an autoimmune-mediated disease characterized by decreased platelet counts. Cytokines play important roles in modulating the immune response and are involved in the pathogenesis of many autoimmune diseases. This study aimed at exploring the serum levels of a core set of cytokines that exert immune-regulatory functions in newly diagnosed ITP patients (both before and after treatment) and splenectomized ITP patients. Using the Bio-Plex suspension array system and ELISA, the serum levels of IL-10, IL-21, IL-27, IL-33, IL-35, IL-37, and TGF-β1 were detected. The data showed that the serum levels of the immune regulatory cytokines IL-10, IL-35, and TGF-β1 were significantly lower in newly diagnosed ITP patients. Decreased cytokine levels could be improved in patients with a complete response or a response after steroid-based treatment(s). The serum concentrations of TGF-β1 were positively correlated with the platelet counts both before and after treatment. All the detected immune-regulatory cytokines, except IL-37, showed significantly higher levels in splenectomized ITP patients than pretreatment ITP patients and healthy controls. In conclusion, these data suggest that lower levels of immune-regulatory cytokines are involved in the pathogenesis of ITP and that there is a long-lasting overexpression of immune-regulatory cytokines in ITP patients with splenectomy.

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare and life-threatening haematological emergency. Although therapeutic plasma exchange together with corticosteroids achieve successful outcomes, a considerable number of patients remain refractory to this treatment and require early initiation of intensive therapy. However, a method for the early identification of refractory iTTP is not available. To develop and validate a model for predicting the probability of refractory iTTP, a cohort of 265 consecutive iTTP patients from 17 large medical centres was retrospectively identified. The derivation cohort included 94 patients from 11 medical centres. For the validation cohort, we included 40 patients from the other six medical centres using geographical validation. An easy-to-use risk score system was generated, and its performance was assessed using internal and external validation cohorts. In the multivariable logistic analysis of the derivation cohort, three candidate predictors were entered into the final prediction model: age, haemoglobin and creatinine. The prediction model had an area under the curve of 0.886 (95% CI: 0.679-0.974) in the internal validation cohort and 0.862 (95% CI: 0.625-0.999) in the external validation cohort. The calibration plots showed a high agreement between the predicted and observed outcomes. In conclusion, we developed and validated a highly accurate prediction model for the early identification of refractory iTTP. It has the potential to guide tailored therapy and is a step towards more personalized medicine.

Primary immune thrombocytopenia (ITP) is a bleeding disorder commonly encountered in clinical practice. The International Working Group (IWG) on ITP has published several landmark papers on terminology, definitions, outcome criteria, bleeding assessment, diagnosis, and management of ITP. The Chinese consensus reports for diagnosis and management of adult ITP have been updated to the 4th edition. Based on current consensus positions and new emerging clinical evidence, the thrombosis and hemostasis group of the Chinese Society of Hematology issued Chinese guidelines for management of adult ITP, which aim to provide evidence-based recommendations for clinical decision making.

Background: Helicobacter pylori is one of the most widely distributed and most common bacteria in the world. There is a discrepancy in the H. pylori infection rate among different regions and countries that may be due to many factors. Objectives: The study aimed to determine the current status of H. pylori infection in the Tianjin Binhai area, China, and evaluate the factors related to H. pylori infection. Methods: We recruited a sample of 2235 cases and conducted the 14C or 13C breath tests and questionnaire surveys. The factors affecting H. pylori infection were analyzed using the chi-square test and multiple logistic regression. Results: The overall H. pylori infection rate was 45.6%, with the highest rate among male and married population and the lowest rate in the 11 - 20-year-old group. Moreover, populations with a high degree of culture or income had lower infection rates (P < 0.05). Populations who were smoking, drinking, eating seafood, or had more salt intake had higher infection rates (P < 0.05). Furthermore, the infection rate was higher in the population who had hypertension (P = 0.001) or dyspeptic symptoms (P < 0.05) in the last year. It was revealed that taking a previous H. pylori examination and education level were negatively correlated with H. pylori infection, and marital status was an important influential factor for H. pylori infection. Conclusions: The rate of H. pylori infection was lower in the Tianjin Binhai area than in the whole country, which may be related to socioeconomic status and marital status. Furthermore, it is also probably related to gender and hypertension.

Background Prospective randomized trials have not been used to evaluate the efficacy of adjuvant therapies after intrahepatic cholangiocarcinoma (ICC) resection. Methods We analyzed data from the Taiwan Cancer Registry database of ICC patients receiving resection. To compare outcomes, patients with ICC were enrolled and categorized into the following adjuvant treatment modality groups: group 1, concurrent chemoradiotherapy (CCRT); group 2, sequential chemotherapy (CT) and radiotherapy (RT); and group 3, CT alone. Results We enrolled 599 patients with resectable ICC who received surgery without distant metastasis. Of these patients, 174 received adjuvant CCRT (group 1), 146 received adjuvant sequential CT and RT (group 2), and 279 received adjuvant CT alone (group 3). Multivariate Cox regression analysis indicated that pathologic stage and positive margin were significantly poor independent predictors. After adjustment for confounders, adjusted hazard ratios (95% confidence intervals) for overall mortality at advanced pathologic stages III and IV were 0.55 (0.41–0.74) and 0.92 (0.70–1.33) in groups 1 and 2, respectively, compared with group 3. Conclusions Adjuvant CCRT improved survival in resected ICC with advanced pathologic stages or a positive margin in early pathologic stages compared with adjuvant CT alone or adjuvant sequential CT and RT.

Background and Aim: Regulatory T cells (Treg) play a vital role in immunosuppressive crosstalk; however, Tregs from different locations lead to different clinical outcomes. Our aim was, therefore, to compare the prevalences and suppressive phenotypes of Tregs in the peripheral blood, peritumor, and intratumor of patients with hepatocellular carcinoma (HCC). Methods: The frequencies and phenotypes of CD4 + CD25 + CD127 low/- CD49d - Tregs in the periphery, peritumor, and intratumor of 78 HCC patients and 12 healthy controls were evaluated by flow cytometry. Treg-cell suppressive activity was determined using an in vitro CD154 expression assay. Tregs from tumor and paired peritumor were then hybrid- ized using an Agilent whole genome oligo microarray, and selected genes were validated by real-time polymerase chain reaction. Functional analysis of the microarray data was performed using Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses. Results: Intratumoral Tregs exhibited higher frequencies and more suppressive pheno- typic functions than those in peritumor and periphery, whereas there was no difference between the latter two. Functional analysis showed that complement cascades, p53, and glycosylphosphatidylinositol-anchor biosynthesis pathways were significantly upregulated in intratumoral Tregs; the salivary secretion pathway was significantly downregulated in intratumoral Tregs, and immune cells and tumor-immuno-related Gene Ontology terms were significantly affected. Conclusions: Tregs in different locations exhibited different functional statuses. A higher prevalence and more suppressive phenotype suggested a critical role for intratumoral Tregs in the formation of multicellular immunosuppressive networks. HCC immunotherapy may be improved, therefore, by specific locational Tregs elimination or suppression.

Supplemental Digital Content is available in the text, Nucleoside triphosphate diphosphohydrolase-1 (ENTPD1/CD39) is the rate-limiting enzyme in a cascade leading to the generation of immunosuppressive adenosine and plays an important role in tumor progression. This study aimed to evaluate the expression of CD39 and CD39+Foxp3+ regulatory T cells (Tregs) and to determine their prognostic role in patients with hepatocellular carcinoma (HCC) after radical resection. Immunohistochemistry (IHC) and double IHC were used to analyze CD39 expression or the expression of CD39 and Foxp3 in a cohort of 324 HCC patients who underwent curative resection. The quantification of CD39 expression levels was determined using a computerized image analysis system and was evaluated by mean optical density (MOD), which corresponded to the positive staining intensity of CD39. The number of positive Foxp3 cells and both CD39 and Foxp3 positive cells in each 1-mm-diameter cylinder were counted under high-power magnification (×400). The “minimum P value” approach was used to obtain the optimal cutoff value for the best separation between groups of patients in relation to time to recurrence (TTR) or overall survival (OS). The expression of CD39 in HCC cell lines with stepwise metastatic potential and in human umbilical vein endothelial cells was determined by reverse transcription-polymerase chain reaction, Western blotting, and immunofluorescence. The SPSS 17.0 statistical package was used for statistics. CD39 was principally expressed on vascular endothelial cells, macrophagocytes, Tregs, and tumor cells in HCC. Compared with paired peritumoral tissues, tumoral tissues had a significantly higher expression level of CD39 (P

A study was conducted in 13 years of Organic Fertilizer (OF) and nofertilizer (U) field experiment in a winter wheat-summer maize rotation agroecosystem in the North China plain. The study was also included an Greenhouse (GH) experiment in cucumbers and kidney bean rotation in the North China Plain. Researchers aimed to evaluate the changes in soil physico-chemical parameters and the abundance and community structure of soil protozoan, under Greenhouse (GH), Organic Fertilizer (OF) and nofertilizer (U) different treatments, compared to difference management measure soil as the control (U). Soil organic matter content, available potassium (K) and hydrolyzable N were significantly higher in the plots under the GH treatment than under the other treatments. Available Phosphorus (P) content of OF was significantly higher than control treatment. After continuous many years organic application treatment and GH treatment which both increased the abundance soil protozoa. Both types of organic fertilizer and GH reduced the relative abundance of amoeba whereas increased relative abundance of flagellate in experiment. However, relative abundance of amoeba in the three treatments have occupied the overall majority. This result was positively related to the high level of phosphorus in this experiments which probably suppressed fungi thus increasing the food resources for bacterivorous protozoa, especially in flagellate. The GH and organic fertilizer treatments remarkably increased the overall abundance of protozoa. While the GH and organic fertilizer application treatments did not increase the relative abundance difference groups of soil protozoa, respectively especially amoeba increasing the relative abundance of flagellate, the increase in flagellate reflected enhanced biological activity and functioning of the bacterial decomposition pathway especially in the food web of this treatment.

Background and Aim: The high expression of the galectin-1 predicts poor patient outcome in several tumors. The aim of this study was to investigate its prognostic value in patients with hepatocellular carcinoma (HCC) after resection. Methods: Galectin-1 and tumor-infiltrating FoxP3+ regulatory T cells (Tregs) were validated by tissue microarrays from HCC patients (n = 386) and statistically assessed for correlations with the clinical profiles and the prognosis of the patients. Results: We found that galectin-1, which was prevalently upregulated in HCC, was significantly associated with tumor invasive characteristics (such as vascular invasion, incomplete encapsulation, poor differentiation, multiple number, and large tumor size). Patients with high galectin-1 expression had a significantly poorer tumor recurrence (P = 0.025) and overall survival (P = 0.021) than those with low galectin-1 expression. Even in early-stage disease, high galectin-1 expression was also independently associated with shortened survival (P

Hepatocellular carcinoma (HCC) is a typical inflammation‐related malignancy characterized by high postoperative recurrence and metastasis. Although several inflammatory cells and inflammatory signatures have been linked to poor prognosis, the inflammation‐associated molecular mechanisms of HCC development and progression are largely unknown. Here we show that triggering receptor expressed in myeloid cells (TREM)‐1, a transmembrane receptor expressing in myeloid cells, was also expressed in tumor‐activated hepatic stellate cells (HSCs) and associated with the aggressive behavior of HCC cells. Enzyme‐linked immunosorbent assay was used to measure the expression levels of soluble TREM‐1 (sTREM‐1) in activated hepatic stellate cells supernatant and 92 preoperative and postoperative plasmas of patients with malignancy and/or benign liver tumor/disease, respectively. Expression levels of TREM‐1 were assessed by immunohistochemistry in tissue microarray from 240 patients with HCC. As a result, increased secretion of sTREM‐1 from activated HSCs was observed after co‐culture with HCC cell lines (P

Objectives: TCR- gamma-delta + T cells (γδ T cells) are non-conventional T lymphocytes that can recognize and eradicate tumor cells. Our previous studies showed that infiltration and function of γδ T cells were substantially attenuated in hepatocellular carcinoma (HCC). However, their prognostic value was not clarified. Methods: The association between γδ T cells and the clinical outcomes was determined by immunohistochemistry (IHC) in a HCC patient cohort (n = 342). Results:Immunohistochemistry showed decreased infiltration of γδ T cells in tumoral tissues compared with paired peritumoral tissues. The counts of γδ T cells in peritumoral tissues were negatively correlated with tumor size (P = 0.005). Survival analysis showed that the levels of peritumoral γδ T cells were related to both time to recurrence (TTR) and overall survival (OS) (P = 0.010 and P = 0.036, respectively) in univariate analysis, and related to TTR in multivariate analysis (P = 0.014, H.R. (95% CI) = 0.682 (0.502-0.927)). Furthermore, the level of peritumoral γδ T cells showed independent prognostic value for TTR in Barcelona Clinic Liver Cancer (BCLC) stage A patients (P = 0.038, H.R. (95% CI) = 0.727 (0.537-0.984)). However, tumoral γδ T cells did not show independent prognostic value for either TTR or OS in HCC patients. Conclusions: Low counts of γδ T cells in peritumoral liver tissue are related to a higher incidence of recurrence in HCC and can predict postoperative recurrence, especially in those with early-stage HCC.

To evaluate the efficacy and safety of recombinant human thrombopoietin (rhTPO) combined with glucocorticoid in treatment of severe newly diagnosed primary immune thrombocytopenia (ITP).From June 2009 to December 2012, 24 male patients and 38 female patients with the diagnosis of severe primary ITP in our hospital were randomized into trial group (31 cases) or control group (31 cases), the median age was 50 years (range: 21-84 years). Trial group was treated with rhTPO combined with glucocorticoid, and control group was treated with glucocorticoid only.At the day 3, 7 and 14 from the beginning of treatment, the average platelet count (APC) in trial group[(35.5±24.9)×10⁹/L, (135.2±94.9)×10⁹/L and (192.0±109.1)×10⁹/L]were significantly higher than that in control group[(24.5±15.6)×10⁹/L, (78.2±121.9)×10⁹/L and (95.8±60.5)×10⁹/L, P=0.022, 0.009 and 0.001, respectively]. There was no significant difference in APC between the two groups at day 28 and 90 after treatment[(147.8±59.1)×10⁹/L vs (105.1±56.9)×10⁹/L, P=0.243; (137.4±52.3)×10⁹/L vs (104.3±59.8)×10⁹/L, P=0.568, respectively]. At the day 7, 14 and 28, the complete response rates in trial group were 61.3%, 87.1% and 80.6%, which were also significantly higher than that in control group (16.1%, 29.0% and 48.3%, P=0.000, 0.000 and 0.004, respectively). The median time to response in trial group was 3 days while in the control group was 5 days; the median duration of complete response in trial group was 76 days while in the control group was 54 days. In trial group, there were 4 cases treated with platelet transfusion, while in control group there were 11 cases, respectively.For patients with severe primary ITP, rhTPO combined with glucocorticoid could rapidly increase the platelet count, significantly improve the complete response rate and prolonged the effect with a low incidence of tolerable adverse events compared to single use of glucocorticoid. rhTPO combined with glucocorticoid could be a new therapeutic choice to those patients.

Regulatory T cells (Treg) play a vital role in immunosuppressive crosstalk; however, Tregs from different locations lead to different clinical outcomes. Our aim was, therefore, to compare the prevalences and suppressive phenotypes of Tregs in the peripheral blood, peritumor, and intratumor of patients with hepatocellular carcinoma (HCC). METHODS : The frequencies and phenotypes of CD4(+) CD25(+) CD127(low/-) CD49d(-) Tregs in the periphery, peritumor, and intratumor of 78 HCC patients and 12 healthy controls were evaluated by flow cytometry. Treg-cell suppressive activity was determined using an in vitro CD154 expression assay. Tregs from tumor and paired peritumor were then hybridized using an Agilent whole genome oligo microarray, and selected genes were validated by real-time polymerase chain reaction. Functional analysis of the microarray data was performed using Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses. RESULTS : Intratumoral Tregs exhibited higher frequencies and more suppressive phenotypic functions than those in peritumor and periphery, whereas there was no difference between the latter two. Functional analysis showed that complement cascades, p53, and glycosylphosphatidylinositol-anchor biosynthesis pathways were significantly upregulated in intratumoral Tregs; the salivary secretion pathway was significantly downregulated in intratumoral Tregs, and immune cells and tumor-immuno-related Gene Ontology terms were significantly affected. CONCLUSIONS : Tregs in different locations exhibited different functional statuses. A higher prevalence and more suppressive phenotype suggested a critical role for intratumoral Tregs in the formation of multicellular immunosuppressive networks. HCC immunotherapy may be improved, therefore, by specific locational Tregs elimination or suppression.

Background Sirtuin 3 (Sirt3), one of the seven Sirtuins family members, plays critical roles in the progression of multiple cancer types. However, its role in the prognosis of hepatocellular carcinoma (HCC) has not yet been investigated systematically. Methods The correlation of Sirtuins expression with prognosis of HCC was determined by immunohistochemistry (IHC) in a large HCC patient cohort (n = 342). Expression of Sirt3 in tumoral and peritumoral tissues of HCC patients were further determined by western blotting (WB). Results IHC and WB studies both showed a decreased expression of Sirt3 in tumoral tissues compared with peritumoral tissues (P = 0.003 for IHC, P = 0.0042 for WB). Decreased expression of Sirt3 in both tumoral and peritumoral tissues was associated with increased recurrence probability and decreased overall survival rate by univariate analyses (intratumoral Sirt3: P = 0.011 for TTR, P = 0.001 for OS; peritumoral Sirt3: P = 0.017 for TTR, P = 0.023 for OS), the prognostic value was strengthened by multivariate analyses (intratumoral Sirt3: P = 0.031 for TTR, P = 0.001 for OS; peritumoral Sirt3: P = 0.047 for TTR, P = 0.031 for OS). Intratumoral Sirt3 also showed a favorable prognostic value in patients with BCLC stage A (TTR, P = 0.011; OS, P Conclusions Down-regulation of intratumoral and peritumoral Sirt3 were both associated with poor outcome in HCC, moreover, intratumoral Sirt3 was a favorable prognostic predictor in early stage patients.

To investigate the number of peripheral blood CD5(+) B cells and their ability of secreting IL-10 in patients with immune thrombocytopenia (ITP).Peripheral blood lymphocytes were isolated from 57 pre-treated, 40 post-treated ITP patients and 25 controls using Ficoll-Hypaque density centrifugation and then stained with PE-CD5/FITC-CD19 for flow cytometric analysis. After 24-hour culture, lymphocytes were stained with APC-IL-10 for intracellular cytokine detection. ELISA assay was employed to determine IL-10 concentration in supernatants.The percentage and absolute number of CD5(+) B cells in peripheral blood from pre-treated ITP patients were significantly higher than that from normal controls (3.75 ± 2.37)% vs (2.10 ± 1.08)%, P0.01; (6.29 ± 5.77)× 10(7)/L vs (3.06 ± 1.90)× 10(7)/L, P0.01. CD5(+) B cells expressed more intracellular IL-10 than other lymphocyte subsets both in ITP patients and normal controls. The percentages of IL-10(+) cells within CD5(+) B cells in pre-treated ITP patients and normal controls were (29.51 ± 20.73)% and(15.90 ± 9.58)%, respectively(P0.01). Intracellular mean fluorescence intensity (MFI) of IL-10 in CD5(+) B cells was 27.95 ± 13.99 in pre-treated patients, which was significantly higher than that in controls (P0.01). In contrast, IL-10 concentration in supernatants was (173.05 ± 102.50) ng/L in pre-treated ITP group, which was lower than that (230.61 ± 76.96) ng/L in controls. In patients who achieved remission, the number of CD5(+) B cells decreased to level comparable to normal controls. While intracellular IL-10 MFI of CD5(+) B cells in post-treated ITP patients remained as high as in pre-treated ones, the IL-10 concentration in supernatants increased to level similar to controls.The significantly increased number of CD5(+) B cells and accumulated IL-10 in CD5(+) B cells suggested impaired IL-10 secretion in ITP patients. The number and the ability of secreting IL-10 of CD5(+) B cells could be restored after effective treatments in patients with ITP.

Background & Aims The immunosuppressive network within the tumor microenvironment is one of the major obstacles to the success of cancer immunotherapy. γδ T cells are attractive effectors for cancer immunotherapy. Nevertheless, the promising anti-tumor effect in vitro is partially if not totally mitigated in vivo . Thus, understanding the immune status of tumor-infiltrating γδ T cells is essential for orchestrating effective immunotherapy strategies. In this study, we have investigated the immunophenotype and function of γδ T cells in hepatocellular carcinoma (HCC) patients. Methods The phenotype of γδ T cells in peripheral blood, and peritumoral and tumoral tissues of HCC patients (n=61) was characterized by flow cytometry. Functional analysis of the HCC-infiltrating γδ T cells was conducted directly after γδ T cell isolation. Results The infiltration of γδ T cells in tumoral tissues was significantly reduced compared to paired peritumoral tissues. Impairment in degranulation of the granule pathway and downregulation of IFN-γ secretion were also demonstrated in HCC-infiltrating γδ T cells, which was in agreement with the results of gene microarray analysis, and further strengthened by the compromised specific cytotoxicity and IFN-γ secretion in vitro . Moreover, isolated HCC-infiltrating CD4 + CD25 + regulatory T cells (Treg cells) directly suppressed the cytotoxic function and IFN-γ secretion of γδ T cells in a TGFβ- and IL-10-dependent manner. Conclusions The effector function of γδ T cells was substantially impaired in HCC, which is partially mediated by Treg cells. We propose a new mechanism by which immune privilege develops within the tumor milieu.

To evaluate the efficacy, safety and prognostic impact of rituximab plus CHOP (R-CHOP) regimen on patients with diffuse large B-cell lymphoma (DLBCL), to access the impact of R-CHOP on patients' prognosis and to compare that with CHOP regimen.Five hundred and seven newly diagnosed DLBCL patients were enrolled from Jan. 1, 2000 to May 1, 2010. Patients were administered with 6 cycles of CHOP or at least 4 cycles of R-CHOP treatments. Rituximab was administered intravenously on day 1 at a dose of 375 mg/m(2). The typical CHOP regimen include cyclophosphamide (750 mg/m(2), IV), doxorubicin (50 mg/m(2), IV) and vincristine (1.4 mg/m(2), IV, maximum 2 mg) and prednisone (60 - 100 mg, oral, day 3 - 7). The complete response (CR) rates, overall response (OR) rates, and side events of these 2 groups were compared.Of the 411 analyzable patients, 224 received CHOP regimen and 187 received R-CHOP regimen. CR rate for R-CHOP group and CHOP group was 77.01% and 71.43%, respectively. OR rate in R-CHOP group was higher than that in the CHOP group (95.19% vs 87.95%, P = 0.007). The median follow-up time of R-CHOP group was 28.1 months vs that of 35.2 months in CHOP group. There was significant difference in progression free survival (PFS) and overall survival (OS) between 2 groups (P = 0.018 and 0.034, respectively). At the end of follow-up, the estimated median PFS in R-CHOP group had not been reached, while that was 84.8 months in CHOP group. The median OS in both groups had not yet been reached. The adverse events in R-CHOP group were similar with that in CHOP group.R-CHOP is a safe and effective regimen for management of newly diagnosed DLBCL, with a better remission rate, PFS and OS.

The high expression of the galectin-1 predicts poor patient outcome in several tumors. The aim of this study was to investigate its prognostic value in patients with hepatocellular carcinoma (HCC) after resection.Galectin-1 and tumor-infiltrating FoxP3(+) regulatory T cells (Tregs) were validated by tissue microarrays from HCC patients (n = 386) and statistically assessed for correlations with the clinical profiles and the prognosis of the patients.We found that galectin-1, which was prevalently upregulated in HCC, was significantly associated with tumor invasive characteristics (such as vascular invasion, incomplete encapsulation, poor differentiation, multiple number, and large tumor size). Patients with high galectin-1 expression had a significantly poorer tumor recurrence (P = 0.025) and overall survival (P = 0.021) than those with low galectin-1 expression. Even in early-stage disease, high galectin-1 expression was also independently associated with shortened survival (P0.001) and increased tumor recurrence (P = 0.005). Multivariate Cox proportional hazards analysis showed that galectin-1 was an independent marker for predicting the poor prognosis of HCC. The galectin-1 level was positively related to the number of tumor-infiltrating FoxP3(+) Tregs (r = 0.416, P0.001), and their combination served as a better prognosticator. The postoperative tumor recurrence and survival of HCC patients with galectin-1(high) and FoxP3(high) were significantly poorer than the other groups (both P0.001).Galectin-1 might be a new prognostic factor for HCC after resection and could potentially be a high-priority therapeutic target.

Interferon regulatory factor (IRF)-1 and IRF-2 are transcriptional factors that mediate interferons functions; the loss of IRF-1 expression and gain of IRF-2 expression were associated with malignant phenotype in multiple cancers. However, their roles in the progression of hepatocellular carcinoma (HCC) remain poorly described.Immunohistochemistry was used to analyze the nuclear expression of IRF-1/2 in a cohort of 332 HCC patients. The expression of IRF-1/2 in HCC cell lines with stepwise metastasis potential was determined by immunoblotting. Downregulation of IRF-1 or IRF-2 expression was mediated by shRNAs; a series of experiments were conducted to determine the changes of invasion ability and downstream molecular events.High expression of IRF-1 was associated with good outcome (p.001 for OS/TTR), while high expression of IRF-2 was relevant to increased recurrence probability (p=.049) in HCC patients. The combination of the 2 IRFs showed better predictive power than either factor alone. Immunoblotting analysis revealed that IRF-2/IRF-1 ratio was positively correlated with the metastatic potential in human HCC cell lines. Downregulation of IRF-2 led to sharply attenuated invasion ability, paralleled with a decreased expression of STAT3, p-STAT3(Ser727), and MMP9. While downregulation of IRF-1 caused a concurrent decrease in IRF-2, little or no change was displayed in IRF-2/IRF-1 ratio, invasion ability, and MMP9 expression.IRF-1 and IRF-2 expression were associated with prognosis of HCC patients with opposite predictive power. IRF-2/IRF-1 ratio was associated with tumor invasion, probably through modulation of MMP9 expression mediated by STAT3.

This study was aimed to investigate the T cell (helper T cells) immune status in ITP patients and its relation with therapeutic response. 20 de novo ITP patients were enrolled (8 males, 12 females) with a median age of 41 (20 to 81). Real-time RT-PCR method was used to measure the gene expression of Th cells including T-bet, IFN-γ, GATA-3, TGF-β, Foxp3, IL-2, IL-4 in PBMNC of ITP patients before and after conventional dose of prednisone therapy [1 mg/(kg·d)] and in PBMNC of 20 normal controls. The results showed that T-bet, IFN-γ and IL-2 were significantly over-expressed in PBMNC of ITP patients before treatment compared with that in normal controls (p0.01), and compared with that before treatment, T-bet, IFN-γ, and IL-2 were markedly down-regulated in ITP patients after treatment. Before treatment, the expressions of Foxp3, TGF-β, GATA3 and IL-4 in ITP patients did not show difference from normal controls, while after treatment Foxp3 were more up-regulated than that before treatment (p0.05). After treatment, TGF-β expression showed a different pattern between old and young patients. TGF-β expression was down-regulated (p0.05) among ITP patients younger than 60, while up-regulated in older patients. It is concluded that there is an imbalance of Th1/Th2/Treg cytokines in ITP patients, which can be reversed by glucocorticoid treatment. The conventional dose of glucocorticoid may be regarded as effective therapy for de novo ITP patients, it may correlate with improvement of imbalance between Th1/The2/Treg cytokines.

To design and synthesize new arylsubstituted imidazolin-2-one analogues as antitumor compounds.Arylsubstituted imidazolin-2-ones were prepared by condensation the appropriate omega-amino-acetophenone hydrochloride with arylisocyanate in toluene. The target compounds prepared in this study were tested for cytotoxicity against PC-3, A549, HO-8910, Hela, HL60, K562 and HL60R cancer cell lines, and mechanism of one of the products 4y was further evaluated with its mechanium.Thirty-six new compounds were synthesized and confirmed by 1H NMR, MS and elemental analysis. One of the synthesized products, compound 4y, displayed an encouraging selective activity against HL60 cells, and it was partlydue to the cell cycle arrest and cell apoptosis.Compound 4y is worthy to be intensively studied.

Background Peritumoral activated hepatic stellate cells (HSCs) are versatile myofibroblast-like cells closely related with hepatocellular carcinoma (HCC) progression. So far, comprehensive comparison of gene expression of human HSCs during hepatocarcinogenesis is scanty. Therefore, we identified the phenotypic and genomic characteristics of peritumoral HSCs to explore the valuable information on the prognosis and therapeutic targets of HBV related HCC. Methods A tissue microarray containing 224 HBV related HCC patients was used to evaluate the expression of phenotype markers of HSCs including α-SMA, glial fibrillary acidic protein (GFAP), desmin, vinculin and vimentin. HSCs and cancer associated myofibroblasts (CAMFs) were isolated from normal, peritumoral human livers and cancer tissues, respectively. Flow cytometry and gene microarray analysis were performed to evaluate the phenotypic changes and gene expression in HCC, respectively. Results Peritumoral α-SMA positive HSCs showed the prognostic value in time to recurrence (TTR) and overall survival (OS) of HCC patients, especially in early recurrence and AFP-normal HCC patients. Expression of GFAP positive HSCs cell lines LX-2 was significantly decreased after stimulation with tumor conditioned medium. Compared with quiescent HSCs, peritumoral HSCs and intratumoral CAMFs expressed considerable up- and down-regulated genes associated with biological process, cellular component, molecular function and signaling pathways involved in fibrogenesis, inflammation and progress of cancer. Conclusions Peritumoral activated HSCs displayed prognostic value in HBV related-HCC, and their genomic characteristics could present rational biomarkers for HCC risk and promising therapeutic targets.

Background Hepatocellular carcinoma (HCC) is a typical malignancy in a background of chronic inflammation. Th17 cells (a major source of IL-17) constitute crucial components of infiltrating inflammatory/immune cells in HCC and can amplify inflammatory response via binding to interleukin-17 receptor (IL-17R). Thus, we investigated the expression and clinical significance of IL-17 and IL-17 receptor family cytokines in HCC. Methods The expression and prognostic value of IL-17 and IL-17R (A-E) were examined in 300 HCC patients after resection. Six Th17 associated cytokines in serum (n = 111) were quantified using enzyme-linked immunosorbent assays. Phenotypic features of IL-17+ CD4+ T cells were determined by flow cytometry analysis. Results High expression of intratumoral IL-17 and IL1-7RE were significantly associated with poorer survival (p = 0.016 and + CD4+ T cells. Conclusions High expression of IL-17 and IL-17RE were promising predictors for poor outcome of HCC patients. The protumor power of IL-17 producing CD4+ T cells was probably involved in the crosstalk with different types of inflammatory/immune cells in HCC.