An application of small-world network on predicting the behavior of infectious disease on campus.

Networks haven been widely used to understand the spread of infectious disease. This study examines the properties of small-world networks in modeling infectious disease on campus. Two different small-world models are developed and the behaviors of infectious disease in the models are observed through numerical simulations. The results show that the behavior pattern of infectious disease in a small-world network is different from those in a regular network or a random network. The spread of the infectious disease increases as the proportion of long-distance connections p increasing, which indicates that reducing the contact among people is an effective measure to control the spread of infectious disease. The probability of node position exchange in a network (p2) had no significant effect on the spreading speed, which suggests that reducing human mobility in closed environments does not help control infectious disease. However, the spreading speed is proportional to the number of shared nodes (s), which means reducing connections between different groups and dividing students into separate sections will help to control infectious disease. In the end, the simulating speed of the small-world network is tested and the quadratic relationship between simulation time and the number of nodes may limit the application of the SW network in areas with large populations.

Single-institution experience of venetoclax combined with azacitidine in newly diagnosed acute myeloid leukemia patients.

To retrospectively analyze the efficacy and safety of venetoclax combined with azacitidine (VEN + AZA) in the treatment of elderly patients with acute myeloid leukemia. The clinical data for 57 AML patients treated with the VEN + AZA regimen from December 2019 to November 2022 in the Department of Hematology, General Hospital of Tianjin Medical University, were collected. Of the 57 patients included in this study, the mean age of onset was 69.89 (±8.88) years. The median follow-up time was 8.57 months, and the median OS time was 11.50 months. The ORR, CR rate, and MRD (<0.1%) negativity rate were 87.5%, 68.8%, and 58.3%, respectively. The median OS was longer in patients who achieved CR/CRi and who were MRD-negative than in those who did not. MRD negativity was less likely to be achieved in patients aged ≥75 years and with ECOG scores of ≥3. Compared to traditional intensive chemotherapy, MRD negative was achieved more quickly with VEN + AZA regimens in patients with newly diagnosed AML. Advanced age and ECOG score were risk factors for negative MRD. The dominant adverse reactions were hematological adverse events. VEN + AZA regimens in elderly unfit patients with previously untreated newly diagnosed AML have sufficient efficacy and safety.

Infection risk in autoimmune hematological disorders with low-dose rituximab treatment.

BACKGROUND: Rituximab has been widely used in many autoimmune diseases. AIM: To evaluate the infection risk of rituximab in autoimmune hematological disorders. METHODS: Retrospectively studied and compared the clinical data of 89 patients in our hospital who used low-dose rituximab (group R) or pulse cyclophosphamide (group C) for their refractory/relapsed autoimmune hematological diseases from January 2011 to January 2017. The kinds of their diseases included autoimmune hemolytic disease (AIHA), Evans syndrome, and idiopathic thrombocytopenic purpura (ITP). All patients chose either rituximab treatment or cyclophosphamide treatment on their own considerations. FINDINGS: The median follow-up time was six months in group R and four months in group C. After treatments, the patients in group R showed higher white blood cell (WBC) count and neutrophil count than group C (P = .020, P = .037). CD20-positive B cells in group R remained at a very low level after rituximab treatment and need about 15 months to return to normal level, which was longer than group C (six months). The incidence of infection in these two groups has no significant difference, which was 34.7% (17/30) in group R and 32.5% (13/28) in group C (P = .976). Tuberculosis infections after rituximab treatment were found in three patients for the first time. CONCLUSION: The G-CSF, nadir WBC count, and IgA level were protective factors of infection during rituximab treatment. Low-dose rituximab therapy in autoimmune hematological diseases does not increase infection risk compared with cyclophosphamide.

Pseudo-monoclonal gammopathy due to autoimmune disease: a case report.

Hyperglobulinemia is a common manifestation of plasma cell disease, and it is sometimes caused by autoimmune diseases (AIDs). We report an uncommon presentation of hyperglobulinemia, with a high amount of plasma cells in bone marrow, pancytopenia, hematemesis, and splenomegaly in an 18-year-old woman. Some examinations were performed to determine the diagnosis, including serum protein electrophoresis, immunofixation electrophoresis, the free light chain assay, abdominal enhanced computed tomography (CT) and CT venography, and positron-emission tomography-CT. The patient was finally diagnosed with AID. Considerable improvement in her symptoms was observed after immunosuppressive therapy. Findings in this case highlight that not only differentiation of hyperglobulinemia caused by monoclonal or polyclonal immunoglobulin, but also AIDs, need to be considered to exclude non-Hodgkin's lymphoma and plasma cell disease.

Analysis of clinical characteristics of 92 patients with paroxysmal nocturnal hemoglobinuria: A single institution experience in China.

OBJECTIVES: We performed a retrospective analysis to investigate the clinical characteristics and therapeutic strategies of Chinese paroxysmal nocturnal hemoglobinuria (PNH) patients, and assessed the efficacy and safety of glucocorticoid in PNH patients. METHODS: The clinical data of 92 PNH cases in our hospital were analyzed, including clinical manifestation, laboratory examination, treatment efficacy, and survival. RESULTS: The main clinical manifestations of these patients included hemoglobinuria, anemia, fatigue, dyspnea, headache, abdominal pain, and erectile dysfunction. Glucocorticoid is still the first-line treatment for PNH patients to control hemolytic attack, and the short-term remission rate (12 months) is 79.01% (64/81). Meanwhile, the overall survival (OS) of 10 years after diagnosis was estimated as 70.77% (46/65). Moreover, Cox proportional risk model for multivariate analysis showed that the increase in LDH multiple, thrombosis complications, and complicated with bone marrow failure were the independent adverse prognostic factors affecting the survival of PNH patients. CONCLUSION: Paroxysmal nocturnal hemoglobinuria patients in mainland China have various clinical features, while lower incidences of thrombosis and renal damage. Thrombosis and bone marrow failure are two complications with worse prognosis.

Effect factors related to a high probability of hemodialysis independence in newly diagnosed multiple myeloma patients requiring hemodialysis.

BACKGROUND: Renal failure is a severe complication of symptomatic myeloma, related to higher mortality. Recovery from dialysis dependence can lead to enormous survival benefits. We investigated the effect factors for probability of dialysis independence. METHODS: Retrospective data on 45 newly diagnosed MM (NDMM) patients with serious renal impairment and requiring hemodialysis were analyzed. The statistical methods including logistic regression analysis, Kaplan-Meier survival curves, the log-rank test and the Cox proportional hazards model for survival analysis were used in our study. RESULTS: Twenty-two of the 45 patients, who were on hemodialysis at diagnosis, became dialysis independence. In the logistic regression analysis, serum level of ß2-microglobulin, kidney disease history, involved free light chain, and achieving at least VGPR were significantly associated with reversibility from dialysis dependence. In addition, achieving hemodialysis discontinuation was related to better survival. The multivariate analyses demonstrated that reversibility from dialysis dependence, proteinuria < 3.5 g/24 h, and achieving at least VGPR were significantly associated with OS among NDMM patients requiring hemodialysis. CONCLUSION: Lower serum level of ß2-microglobulin and lower level of free light chain at diagnosis, achieving at least VGPR, and shorter kidney disease history are related to a high probability of dialysis independence in NDMM patients with serious renal failure requiring dialysis.

Characteristics of patients with autoimmune haemolytic anaemia secondary to lymphoproliferative disorder: A single-centre retrospective analysis.

Autoimmune haemolytic anaemia (AIHA) is a kind of autoimmune diseases characterized by autoantibodies which produced and secreted by abnormal activated B lymphocytes directed against red blood cells (RBC). Study reveals that about 50% AIHA mainly occurs secondary to lymphoproliferative disorders (LPD) and autoimmune diseases. In this study, we aim to explore the characteristics of patients with AIHA secondary to LPD. Fifteen patients with AIHA secondary to LPD (secondary group) and 60 with primary AIHA (primary group) were retrospectively included. Patients in the secondary group [(59.40 ± 4.74) y] were older than those in the primary group [(47.53 ± 2.30) y] (p = 0.024). Reticulocyte counts were lower for the secondary group [(134.55 ± 20.67) × 109/L] than for the primary group [(193.88 ± 27.32) × 109/L] (p = 0.09). Haptoglobin was higher in the secondary (0.75 ± 0.19) g/L than in the primary group (0.34 ± 0.05) g/L (p = 0.004). The ratio of CD3+CD4+/CD3+CD8+ was higher in the secondary (1.81 ± 0.41) than in the primary (1.05 ± 0.12) group (p = 0.025). Duration of remission was shorter in the secondary [(23.52 ± 5.20) months] than in the primary [(40.87 ± 3.92) months] group (p = 0.013). Relapse rate was higher for the secondary (33.3%) than for the primary (8.3%) group (p = 0.003). Mortality rate was higher in the secondary (33.3%) than in the primary (8.3%) group (p = 0.003). Progression-free survival was shorter in the secondary than in the primary group (p = 0.021). In conclusion, patients with AIHA secondary to LPD showed higher age at diagnosis, shorter remission time, and higher recurrence and mortality rates than did those with primary AIHA.

Abnormal numbers of CD4+ T lymphocytes and abnormal expression of CD4+ T lymphocyte­secreted cytokines in patients with immune­related haemocytopenia.

In the past decade, a group of cases with persisting haemocytopenia were separated from those with idiopathic cytopenia of undetermined significance due to the optimal response of these patients to immunosuppression therapy and due to the detection of autoantibodies in the bone marrow of haemopoietic cells. This condition was termed immune­related haemocytopenia (IRH). However, the quantity of T lymphocytes remained unknown. In the present study, the percentage of CD4+ T­cell subsets and related cytokines was measured using flow cytometry and an enzyme­linked immunosorbent assay. An abnormal number of CD4+ T cell subsets was found, including increased percentages of T helper (Th)2, Th9 and Th17 cells and a decreased number of regulatory T (Treg) cells. In addition, the results showed downregulation in the levels of interleukin (IL)­2, transforming growth factor­ß and IL­35, and upregulation in the levels of IL­4, IL­6, IL­17, IL­23 and interferon­Î³ in patients who did not receive therapy (untreated patients). These levels were significantly associated with the number of peripheral blood cells and were recovered following treatment. In conclusion, an abnormal number of CD4+ T cell subsets and corresponding abnormal levels of regulatory cytokines resulted in the stimulation of B1 lymphocytes to produce autoantibodies in IRH, which may be considered as markers to evaluate disease prognosis and treatment strategies.

A Study of Immune Functionality of Newly Diagnosed Severe Aplastic Anemia Patients with Virus Infection.

BACKGROUND: Previous research showed that virus infection is correlated with the occurrence, development, and prognosis of AA. This study was designed to explore the influence of virus infection on the immune functionality and immunosuppressive therapy (IST) efficiency of newly diagnosed SAA patients. METHODS: Fifty-six newly diagnosed SAA patients combined with virus infection treated in the Hematology Department of Tianjin Medical University General Hospital from October 2004 to July 2014 were studied. Various immune parameters were tested and compared for SAA patients with and without virus infection. RESULTS: When compared with SAA patients without corresponding virus infection, SAA patients with CMV-IgM, PVB19-IgM, and EBV infection had increased CD8+ T cell percentage, decreased CD4+/CD8+ T cell ratios, and increased CD8+HLA-DR+/CD8+ percentage. The absolute value of CD8+ T cell of CMV-IgM group had increased as well. The CMV-IgM and PVB19-IgM groups showed decreased CD4+ T cell percentage, and decreased CD4+HLA-DR+/CD8+HLA-DR+ ratio. The PVB19-IgM group exhibited decreased CD4+HLA-DR+/CD4+ percentage, increased Th1 percentage and increased pDC percentage. Patients with EB virus infection showed lower NK cell percentage. Three years after IST, the treatment is significantly less effective for the SAA patients combined with virus infection than those without. CONCLUSIONS: CMV, PVB19, and EBV infection worsen the immune functionality abnormality of newly diagnosed SAA patients and reduce the IST efficiency.

Abnormal expression and mutation of the RBPJ gene may be involved in CD59- clonal proliferation in paroxysmal nocturnal hemoglobinuria.

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal proliferative disease of hematopoietic stem cells. Various gene mutations, including the phosphatidylinositol glycan anchor biosynthesis class A (PIG-A) gene, may contribute to the proliferation of PNH clones. In order to explore the mechanism of PNH clone proliferation, a study was performed on 13 patients with PNH who underwent whole exome sequencing. The frequency of mutations in these patients was explored, and an additional 30 patients with PNH were selected for analysis of cluster of differentiation 59-negative (CD59-) cells. The mRNA expression of 13 genes, which were selected based on their high frequency in patients with PNH and the fact that they met four screening conditions, was determined in these CD59- cells. Cell proliferation, apoptosis and cell cycle were evaluated upon knocking down the recombinant signal binding protein of immunoglobulin κJ region (RBPJ) gene in 5 patients in vitro. The detection rate of PIG-A gene mutation was 61.54% (8/13), and additional mutations in somatic genes were detected, including RBPJ, zinc finger protein 717, polycomb repressive complex 2 subunit and tet methylcytosine dioxygenase. Upon screening according to the mutation frequency and expression level, the present study focused on the RBPJ gene. The expression level of RBPJ in CD59- cells was apparently higher than that in CD59+ cells and normal controls which was significantly correlated with clinical data. Furthermore, the expression of RBPJ in PNH primary cells could be effectively inhibited by small interfering RNA-RBPJ. Once the expression of RBPJ decreased remarkably, the apoptotic rate increased gradually, while cell proliferation activity decreased with transfection time and cells were blocked in G0/G1 phase. In conclusion, mutations and abnormal expression of the RBPJ gene may participate in the abnormal proliferation of PNH clones.

Gene mutations associated with thrombosis detected by whole-exome sequencing in paroxysmal nocturnal hemoglobinuria.

BACKGROUND: Thrombosis is a most common and lethal complication of paroxysmal nocturnal hemoglobinuria (PNH), which is a complex progression and its mechanism remains unclear. We tried to explore the possible genetic background of thrombosis in PNH patients and provide potential gene mutations associated with thrombosis in PNH patients. METHODS: The CD59- cells of 7 PNH and 6 PNH- aplastic anemia (AA) patients were sorted by flow cytometry and sequenced by whole-exome sequencing (WES). The sequencing results and target mutation genes were analyzed and screened, respectively, and Kyoto Encyclopedia of Genes and Genomes (KEGG) signal pathway enrichment analysis was carried out. Finally, the expression of target genes was detected in 22 PNH (including seven cases with thrombus) and 20 normal controls, and the correlation between the expression of mRNA and the clinical thrombus-related indexes was analyzed. RESULTS: The mutation genes screened from 4 PNH with thrombus were BMPR2, F8, ITGA2B, THBD, and THBS1. The pathways enriched by these genes included Notch, Wnt, and arachidonic acid metabolism signaling pathways, which may be related to the pathogenesis of thrombosis in PNH. The BMPR2, THBD, and THBS1 gene expression was significantly different between PNH with and without thrombus group, and the THBS1 gene expression was positively correlated with D-Dimer and su-PAR levels. CONCLUSIONS: Genetic defects have a non-negligible effect on the incidence of thrombosis, and therefore, gene mutations maybe a genetic risk factor in PNH, which increase the incidence of thrombosis.

Clinical features and treatment outcome of elderly multiple myeloma patients with impaired renal function.

BACKGROUND: Renal impairment (RI) is a most common complication of multiple myeloma (MM), which is associated with an increased risk of early death and worse survival. METHODS: We retrospectively analyzed clinical features and outcomes of 77 MM patients over 70 years old and compared the differences between with and without RI groups. RESULTS: The percentage of elder MM patients with RI was 61%. Hemoglobin level was a protective factor (OR = 0.954, P = 0.033), while creatinine and hypertension were hazards (OR = 1.288, P < 0.001 and OR = 30.12, P = 0.008). And the percentages of patients with mild-to-moderate RI and moderate-to-severe RI were 40.4% and 59.6%. Complete remission (CR) rate was higher in patients treated with bortezomib (33.3%) than those with non-bortezomib treatment (3.33%) (P = 0.007). Meanwhile, CRrenal was higher in patients with bortezomib (58.3%) than non-bortezomib treatment (22.2%) (P = 0.025). The median OS of the patients with RI treated with bortezomib was longer than those with non-bortezomib regimens (15.0 vs 6.0 months, P = 0.001). The same result was observed in the patients with moderate-to-severe RI (13.0 vs 6.0 months, P = 0.007). The median OS of the patients with RI receiving the bortezomib regimens (15 months) was longer than those with non-bortezomib regimens (6.0 months) (P = 0.001). CONCLUSION: Hemoglobin is a protective factor in elder patients with RI, while creatinine and hypertension were hazards. The median OS of elderly patients with RI was worse, and bortezomib can improve the CR rate in these patients.

A cohort study of immune and hematopoietic functionality changes in severe aplastic anemia patients treated with immunosuppressive therapy.

To investigate if variations in immune and hematopoietic parameters correlated with immunosuppressive therapy (IST) in severe aplastic anemia (SAA) patients.A total of 115 SAA patients who received IST were included. Their immune and hematopoietic functionality changes had been evaluated at 0, 0.5, 1, 2, and 3-year(s) IST.For SAA patients with complete remission (CR), the CD4/CD8T cell ratio continued to increase after a year of IST. The T helper (Th)1/Th2 ratio continued to decrease after 6 months of IST, as did the activated CD8 T cell percentage. The myeloid dendritic cell (mDC)/plasmacytoid dendritic cell (pDC) ratio after 3 years of IST was significantly lower compared to that of untreated patients. The mDC/pDC and Th1/Th2 ratios exhibited positive correlation. The activated CD8 T cell percentage and the number of peripheral blood neutrophils showed inverse correlation. For SAA patients with partial remission (PR), the CD4T cell percentage increased at 1-year post-IST, but the later changes were not statistically significant. The other immune indexes of patients in partial remission group and nonremission (NR) group showed no obvious recovery. For all SAA patients, the percentage of T regulatory cells in CD4 lymphocyte was higher in post-IST group compared to the pretreatment group.For SAA patients responded well to IST, increase in peripheral neutrophils and improvement in bone marrow myeloid cells were first observed followed reduction in the activated CD8 T cell percentage, Th1/Th2 ratio, CD4/CD8T ratio, along with mDC/pDC ratio, all of which negatively correlated with the hematopoietic parameters. This demonstrates that IST prompts improvements of hematopoietic functionalities of the SAA patients by regulating their immune functionalities.

The clinical characteristics and therapy response of patients with acquired pure red cell aplasia.

OBJECTIVE: To summarize the clinical characteristics of acquired pure red cell aplasia (PRCA) patients diagnosed in our hospital in the last 10 years. METHOD: The clinical features, immune state and treatment response of acquired PRCA patients diagnosed in our hospital from January 2007 to January 2017 were retrospectively analyzed. RESULTS: The results showed that thymoma (13.21%) and parvovirus B19 (11.32%) were the most common causes for secondary PRCA. Ferritin (Fer) levels and erythropoietin (EPO) levels were increased in PRCA patients. The total CR and PR rate of immunosuppressive therapy in our studies was 68.29% and 12.20%, respectively. Patients with EPO level >400 U/L and Fer level >200 ng/ml had significantly lower CR rate than others. The patients with EPO level >400 U/L also had longer hemoglobin recovery time than patients with EPO level ≤400 U/L. Patients treated with corticosteroids (CS) + cyclosporine A (CsA) had lower relapse rate compared to the CS group (29.17% vs. 80.00%, P < .05). CONCLUSION: Our data showed that patients with PRCA had high EPO and Fer levels. Thymoma and viral infections are the most common causes for secondary PRCA. The CS+ CsA group had lower relapse rate than CS group although response rate was similar. Increased EPO and Fer levels might be the negative factors for prognosis of acquired PRCA.

Downregulation of Pim-2 induces cell cycle arrest in the G0/G1 phase via the p53-non-dependent p21 signaling pathway.

Pim-2 is a serine/threonine protein kinase that is highly expressed in various types of cancer, with essential roles in the regulation of signal transduction cascades, which promote cell survival and proliferation. The present study demonstrated that Pim-2 was expressed in cells lines derived from hematopoietic tumors and lung cancer. In vitro, downregulation of Pim-2 by short interfering RNA inhibited proliferation and delayed G0/G1 cell cycle progression in K562 leukemia, RPMI-8226 multiple myeloma, and H1299 and A549 non-small cell lung carcinoma cell lines. Furthermore, downregulation of Pim-2 resulted in upregulation of cyclin-dependent kinase (CDK) inhibitor p21, irrespective of the p53 status. In addition, the present study revealed that CDK2 and phosphorylated retinoblastoma (pRb) were significantly downregulated. This finding suggested that inhibition of CDK2 and pRb expression via upregulated p21 was involved in the downregulation of Pim-2-induced G0/G1 cell cycle arrest in lung cancer and hematopoietic malignancy cells. These results suggested that Pim-2 may serve a role in hematopoietic tumors, lung cancer proliferation and cell cycle progression by regulating the p21 signaling pathway. Downregulation of Pim-2 decreased cancer cell proliferation. Therefore, Pim-2 may be a potential therapy target in clinical cancer therapy.

Deficient invariant natural killer T cells had impaired regulation on osteoclastogenesis in myeloma bone disease.

Recent research showed that invariant natural killer T (iNKT) cells take part in the regulation of osteoclastogenesis. While the role of iNKT cells in myeloma bone disease (MBD) remains unclear. In our study, the quantity of iNKT cells and the levels of cytokines produced by them were measured by flow cytometry. iNKT cells and osteoclasts were induced from peripheral blood mononuclear cells after activation by α-GalCer or RANKL in vitro. Then, gene expressions and the levels of cytokines were determined by RT-PCR and ELISA, respectively. The results showed that the quantity of iNKT and production of IFN-γ by iNKT cells were significantly decreased in newly diagnosed MM (NDMM), and both negatively related with severity of bone disease. Then, the osteoclasts from healthy controls were cultured in vitro and were found to be down-regulated after α-GalCer-stimulated, while there was no significant change with or without α-GalCer in NDMM patients, indicating that the regulation of osteoclastogenesis by iNKT cells was impaired. Furthermore, the inhibition of osteoclastogenesis by iNKT cells was regulated by IFN-γ production, which down-regulated osteoclast-associated genes. In conclusion, the role of α-GalCer-stimulated iNKT cells in regulation of osteoclastogenesis was impaired in MBD, as a result of iNKT cell dysfunction.

Effects of microRNA-21 on apoptosis by regulating the expression of PTEN in diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is an aggressive malignancy and the most common subtype of non-Hodgkin lymphoma in China. However, many cases still remain biologically and clinically heterogeneous, indicating that the DLBCL mechanism remains unclear. MicroRNAs (miRNAs) are critically responsible for lymphomagenesis. We found that plasma miR-21 level was significantly higher in B-cell lymphoma. However, the exact contribution of miR-21 in DLBCL remains unknown.To determine the function and mechanism of miR-21 in DLBCL, miR-21 and phosphatase and tensin homolog (PTEN) expressions were examined through real-time PCR and immunohistochemical methods. Moreover, the effects of antisense oligonucleotide (ASO) targeting miR-21 (ASO-21) were observed in DLCBL cell line.MiR-21 expressions in cell line and tissues of patients were significantly higher than those in normal controls, which were inversely correlated with PTEN expression. MiR-21 expression was significantly higher in stage III/IV patients than in stage I/II patients. PTEN protein was expressed positively in only 6 patients with DLBCL (6/26). MiR-21 expression level in the PTEN-negative group was 11.73 (2.13-64.29), which was significantly higher than that in the PTEN-positive group (1.04, 0.67-15.15; P = .038). After down-regulating the miR-21 expression, apoptosis of DLBCL cells increased and PTEN protein was up-regulated in ASO-21-treated cells compared with SCO-21-treated cells by western blot.These results suggested that miR-21 affects apoptosis of lymphoma cells by regulating the expression of PTEN in DLBCL, which may be associated with increased poor prognosis for DLBCL patients and represents a useful approach for DLBCL treatment.

Plasma DNA methylation of p16 and shp1 in patients with B cell non-Hodgkin lymphoma.

BACKGROUND: Early diagnosis and treatment of non-Hodgkin lymphoma (NHL) are progressively important. It has been shown that aberrant promoter methylation contributes to the development and progression of lymphoma. We tried to explore the effect of methylation of p16 and shp1 genes in plasma in the diagnosis of B-NHL patients. METHODS: The methylation of p16 and shp1 genes in plasma were detected by methylation specific polymerase chain reaction in 103 patients with B-NHL, and compared with peripheral blood leukocytes (PBLs) and formaldehyde-fixed paraffin-embedded (FFPE) tumor tissues. RESULTS: The results showed that methylation frequency of p16 in plasma, PBLs, and FFPE tumor tissues of newly diagnosed B-NHL patients were 37% (27/73), 16% (12/73) and 39% (16/41), whereas those of shp1 were 47% (34/73), 25% (18/73) and 63% (26/41). High methylation consistency of p16/shp1 between plasma and FFPE tumor tissues were revealed (the values of kappa: 0.84, 0.80). Moreover, there were a higher frequency of methylated p16 in all three samples in patients with B symptoms and lower platelet count (<100 × 109/L), as well as in patients with stage III/IV in plasma and FFPE tumor tissues. Meanwhile, higher frequency of methylated shp1 was observed in patients with higher LDH level in all three samples. CONCLUSION: Methylation of p16/shp1 in plasma can represent their methylation status in tumor tissues, and may be promising biomarkers in early diagnosis and prognosis evaluation in B-NHL.

De-escalation empirical antibiotic therapy improved survival for patients with severe aplastic anemia treated with antithymocyte globulin.

We aimed to investigate the efficacy and safety of de-escalation empirical therapy for controlling infection in patients with severe aplastic anaemia (SAA) treated with antithymocyte globulin (ATG). Eighty-seven ATG-treated SAA patients who had microbiological culture-confirmed infections from 2006 to 2015 in our center were retrospectively analyzed. The efficacy of de-escalation and non-de-escalation therapy was compared. Among all 87 patients, 63 patients were treated with de-escalation therapy and 24 patients with non-de-escalation therapy. More patients showed response to anti-infection treatment in de-escalation group than in non-de-escalation group both on day 7 (60.32% vs. 25.00%, P = 0.003) and on day 30 (79.37% vs. 58.33%, P = 0.047) since the initial antimicrobial therapy. On day 30, more patients had increased absolute neutrophil count in de-escalation group compared with non-de-escalation group (76.19% vs. 45.83%, P = 0.007), and de-escalation group had lower morality rate (17.46% vs. 37.50%, P = 0.047) and better survival outcome (P = 0.023) on day 90. Twenty-three patients in de-escalation group and 5 patients in non-escalation group received granulocyte transfusions. Granulocyte transfusions helped to control infections in both de-escalation group (P = 0.027) and non-de-escalation group (P = 0.042) on day 7, but did not improve survival on day 90. We concluded that de-escalation antibiotics improved survival in SAA patients after ATG treatment. Early administration of broad-spectrum antibiotics pending microbiological cultures combined with a commitment to change to narrow-spectrum antibiotics should be recommended for controlling infections in SAA patients treated with ATG. Granulocyte transfusions might be an adjunctive therapy in controlling infections.

CYR61/CCN1 stimulates proliferation and differentiation of osteoblasts in vitro and contributes to bone remodeling in vivo in myeloma bone disease.

Cysteine-rich 61 (CYR61/CCN1), a secreted protein in bone marrow (BM) microenvironment, has diverse effects on many cellular activities such as growth and differentiation. However, the effect of CCN1 on osteoblasts (OBs) in myeloma bone disease remains unclear. In our study, the level of CCN1 in multiple myeloma (MM) patients was detected by ELISA and RT-PCR. The proliferation and differentiation of OBs from MM patients were observed after stimulated by CCN1 in vitro. The myeloma cells transduced with CYR61 gene (RPMI­8226/CYR61) were injected in a mouse model to evaluate the efficacy of CCN1 in vivo and compare with zoledronic acid. The results showed that CYR61/CCN1 levels in BM supernatant and OBs both elevated significantly in all newly diagnosed MM patients, especially in patients without bone disease (P=0.001 and P<0.001). After 30 ng/l CCN1 stimulation for 24 h, the quantity and mineralization of OBs increased significantly in vitro (P=0.046 and 0.048). The transcription factors of Wnt pathway, runt-related transcription factor 2 (Runx2) and ß-catenin were upregulated in OBs after CCN1 stimulation (P=0.012 and 0.011). After injection of RPMI­8226 cells, bone lesions were observed obviously by microCT and histochemistry at 7 weeks. Radiographic analysis of the bones showed decreased resorption in CCN1 overexpression group and zoledronic acid group, while severe resorption in negative control. Furthermore, trabecular bone volume in CCN1 overexpression group (1.7539±0.16949) was significantly higher than zoledronic acid group (1.2839±0.077) (P=0.012). In conclusion, CCN1 can stimulate the proliferation and differentiation of OBs in vitro and contribute to bone remodeling in vivo in MBD.