[The Types and Laboratory Characteristics of Non-Hodgkin Lymphoma with Bone Marrow Invasion as the First Manifestation].

OBJECTIVE: To investigate the types and laboratory characteristics of non-Hodgkin lymphoma(NHL) with bone marrow invasion as the first manifestation. METHODS: 81 non-Hodgkin lymphoma patients with bone marrow invasion as the first manifestation treated in our hospital from January 2010 to July 2019 were selected. The clinical features, blood routine, lactate dehydrogenase (LDH), EB virus results, bone marrow features, immunophenotyping, gene and genetic characteristics of all patients were analyzed retrospectivel. RESULTS: Among 81 patients, 73 cases(90%) were B-cell lymphoma, 5 cases(6%) were T-cell lymphoma and 3 cases(4%) were NK/T-cell lymphoma, while the mantle cell lymphoma and diffuse large B-cell lymphoma were the highest, which accounted for 21%(17 cases) and 19.7%(16 cases), and lymphoma accounted for 8.6%(7 cases). There were 44 cases(54.3%) showed B symptoms, 65 cases (80.2%) showed abnormal blood routine. The MYD88 gene was detected in 5 of 17 cases. 25 cases of patients underwent chromosome examination, the result showed that 5 cases were t(8; 14) (q24; q32), 3 cases were complex karyotype and 17 cases were normal karyotype. 23 cases(23.4%) were EB virus positive, 42 cases(51.9%) were LDH increased. The proportion of bone marrow lymphoma cells was 1%-92%. Among them, 32 cases were diagnosed as lymphoma leukemia, and 6 cases of bone marrow lymphoma cells showed mass distribution similar to extramedullary tumor cells with bone marrow metastasis. CONCLUSION: B-cell lymphoma is the predominant NHL with bone marrow invasion as the first manifestation, while mantle cell lymphoma and diffuse large B-cell lymphoma are the most common pathological types with blood routine abnormalities. Bone marrow lymphoma cells can also present clusters of bone marrow metastasis, different types of lymphoma cells can make directional diagnosis.

[Clinical Characteristics and Risk Factors of Low Fibrinogenemia Induced by Hemocoagulase].

OBJECTIVE: To investigate the clinical characteristics and risk factors of low fibrinogenemia (LF) induced by hemocoagulase. METHODS: Clinical data of 57 patients with hypofibrinogenemia (LF group) treated with hemocoagulase during Jan.2015 to Oct. 2018 in our hospittal were analyzed retrospectively. The control group consisted of 60 patients who did not develop hypofibrinogenemia treated with hemocoagulase. The clinical characteristics were compared between these two groups, the univariate analysis and multivariate analysis were also performed. RESULTS: In LF group, the fibrinogenemia occurred on 5.4(σ=1.067) days after use of hemocoagulase，with the main manifestations as bleeding from the operation or wound site, the decrease of fibrinogen (0.694 g/L,σ=0.211), the increase of D-dimer (4.468µg/mL,σ=1.442) and the recovery of Fib on the day 3.93 (σ=0.563) after drug withdrawal. There were significant differences in age, sex, primary disease, origin of snake venom, course of treatment, complication of hepatic and renal insufficiency and route of administration between the 2 groups (P＜0.05). Multivariate logistic regression analysis showed that age(P=0.007,OR=11.248), course of treatment (P＜0.001,OR=72.104) and route of administration (P=0.049,OR=13.389) were risk factors for hypofibrinogenemia. CONCLUSION: The use of hemocoagulase should be vigilant against the occurrence of hypofibrinogenemia. Old age, long course of treatment and the intravenous administration may increase the risk of hypofibrinogenemia.

Analysis of the immunity effects after enhanced hepatitis B vaccination on patients with lymphoma.

The purpose of the study was to evaluate the immunity effects after vaccinating different doses and frequencies of hepatitis B vaccines by calculating the seroconversion rates of HBsAb in patients with lymphoma. Clinical data of 315 patients from January 2010 to August 2018 were analyzed. According to different doses and frequencies, the patients were divided into three groups: low-dose group, high-dose group, and high-dose and high-frequency group. The highest seroconversion rate of HBsAb was 82.3% in the high-dose and high-frequency group (p < .05). Multivariate logistic regression analysis showed that the dose and frequency of vaccination (p < .001, OR = 2.663), sex (p < .006, OR = 3.106), the Ann Arbor stage (p < .001, OR = 0.195) and whether the chemotherapy regimen contained ibrutinib or not (p < .008, OR = 8.115) are independent factors affecting the immunity effects of hepatitis B vaccine in patients with lymphoma. Increasing doses and frequencies of hepatitis B vaccination may improve the immune response in patients with lymphoma.

[Analysis of the Immune Efficacy and Influencing Factors of Different Dose of Hepatitis B Vaccine in Patients with Lymphoma].

OBJECTIVE: To investigate the conversion rate from negative to positive (positive rate) of HBsAb in lymphoma patients inoculated with different dose of hepatitis B vaccine, to evaluate the immune efficacy of different dose of hepatitis B vaccine, and to analyze the influencing factors. METHODS: Two hundred thirty six patients with lymphoma were selected, whose 5 indexes of hepatitis B (HBsAg, HBsAb, HBeAg, HBeAb and HBcAb) were all negative confirmed by ELISA. The hepatitis B vaccine was inoculated according to 0, 1 and 6 months immune procedures at 1-2 weeks before chemotherapy. The HBsAb level was detected at 1 month after the immunization, the differences in each indexes between HBeAb+ and HBeAb- patients were compared. RESULTS: The positive rate of HBsAb was 75% in all patients with lymphoma.The positive rate of high dose (20 µg) group was 81.4%, which was significantly higher than that of the low dose (10µg) group with 68.6% (χ2=5.09, P＜0.05). The positive conversion rate of HBsAb significantly higher in the patients of young, female, B-cell (except DLBCL subtype), early Ann Arbor stage, and the treatment regimens without glucocorticoid and rituximab. There were no statistical significances in systemic symptoms or no and treatment regimens with or without lenalidomide. Two doses of hepatitis B vaccine not displayed obvious adverse reactions. CONCLUSION: The high dose of hepatitis B vaccine can achieve better immune efficacy than that of the low dose in the patients with lymphoma.

Concurrent and reactivation of hepatitis B virus infection in diffuse large B-cell lymphoma: risk factors and survival outcome.

OBJECTIVE: To determine the clinical features and survival difference of HBV related and Non-HBV related diffuse large B-cell lymphoma (DLBCL) and to evaluate the occurrence of HBV reactivation in DLBCL patients and related risk factors for HBV reactivation after R-CHOP therapy. METHODS: A total of 246 patients diagnosed with CD20+ DLBCL were enrolled from June 2010 to June 2015. The medical records and survival data were analysed. Multivariate logistic regression analysis was used to identify predictors of HBV reactivation. Survival curves were performed by the Kaplan-Meier method. RESULTS: Among patients enrolled, 80 patients were HBsAg sero-positive and 166 patients were HBsAg sero-negative. Findings showed that HBsAg sero-negative patients were significantly older than that of patients with HBsAg sero-positive (P <  0.001). Proportion of B symptom positive patients in HBsAg sero-positive were higher (p = 0.002). Higher LDH level (P = 0.019) and late Ann Arbor stage (P = 0.010) were more often observed in patients with HBsAg sero-positive. The rate of complete response, partial response, stable disease and progress disease in HBsAg sero-negative group were 63.9, 16.9, 1.1 and 18.1%, respective, which is significantly higher than that in HBsAg sero-positive group (36.2, 18.8, 1.2 and 43.8%). Kaplan-Meier analysis showed that DLBCL patients with HBsAg sero-negative had better prognosis. In total, 17 patients showed HBV reactivation among 166 patients (10.2%) with HBsAg sero-negative after R-CHOP treatment, while a significant higher HBV reactivation 18.75% (9/48) in HBsAb negative group were observed, with 8.25% (8/97) patients in HBsAb level 10-100 U/mL group, and 0% patients in HBsAb level higher than 100 U/mL group. Multivariable analysis showed that serum HBsAb and serum HBcAb were independent risk factors for HBV reactivation in DLBCL patients. CONCLUSION: Our data revealed that characteristics and prognosis were significantly different between HBV related DLBCL than non-HBV related DLBCL patients. DLBCL patients with resolved hepatitis B are at a higher risk of developing HBV reactivation after R-CHOP chemotherapy compared with HBsAg-negative/HBcAb negative patients.

[Inhibitory Effect of High Concentration Insulin on the Proliferation of Human Leukemia Cell Strain K562].

OBJECTIVE: To study the impact of high concentration insulin on the proliferation and apoptosis of K562 cell strain. METHODS: K562 cells were treated with different concentrations of insulin. The proliferation activity was tested by CCK-8 assay, cytometry, and trypan blue exclusion. The alterations in glucose concentration of the culture media were monitored while the apoptosis of K562 cells was detected by flow cytometry. The effects of high concentration insulin on the proliferation of K562 cells were inhibited by varying concentrations of insulin-like growth factor-1 (IGF-1) and Suramin. RESULTS: Under the range of concentration (0.1-1 mU/mL), insulin facilitated the proliferation of K562 cells. In contrast, insulin at high concentrations (1.6-100 mU/mL) had the opposite effect, in a dose- and time-dependent manner. Different concentrations of glucose in the culture medium had no significant influence on the inhibitory effect of high concentration insulin on the proliferation of human leukemia cell strain K562. At low concentration insulin inhibited the apoptosis of K562 cells, in a dose-dependent manner. In contrast, insulin at high concentration had the opposite effect, in a dose-dependent manner. Furthermore, IGF-1 reversed the inhibitory effect of high concentration insulin on the proliferation of K562 cell in a dose- and time-dependent manner. Suramin, which is an IGF-1 receptor non-specific blocker, had the opposite effect on K562 cells, also in a dose- and time-dependent manner. CONCLUSION: These results indicate insulin has a dual effect on K562 cells. The dual effect is probably mediated by the binding of insulin and IGF-1R. Inhibitory effect of high concentration insulin on the proliferation of K562 cells is unrelated with the glucose metabolism in the culture media.

[Effect of midazolam on mantle cell lymphoma JeKo-1 cell line and its relevant mechanisms].

This study was aimed to explore the effect of midazolam on mantle cell lymphoma cell line JeKo-1 and the relevant mechanisms. Effects of midazolam on the proliferation and apoptosis of JeKo-1 cells were observed by CCK8 assay and flow cytometry, respectively. Effect of midazolam on the expression of BCL-2, cytochrome C (Cyto-C), pro-caspase-9, pro-caspase-8 and pro-caspase-3 protein were detected by Western blot. The results showed that midazolam could inhibit the growth of JeKo-1 cells significantly and the concentration of 50% growth inhibition (IC50) at 48 hours was approximately 40 µmol/L. After treatment with 20, 40, 80 µmol/L midazolam for 48 hours, a dose-dependent apoptosis of JeKo-1 cells could be observed. Meanwhile, a dose-dependent reduction of BCL-2, pro-caspase-9 and pro-caspase-3 protein expression and increase of Cyto-C protein expression in JeKo-1 cells were found, but the expression of pro-caspase-8 protein did not change. It is concluded that midazolam possibly initiates the mitochondrial pathway, not the death receptor pathway, by reducing the expression of BCL-2, leading in turn to the releasing of Cyto-C in mitochondria, then activating caspase-9 and caspase-3 protein, triggers the caspase cascade, and induces the apoptosis of JeKo-1 cells ultimately.

[Influence of insulin on human leukemia cell proliferation].

As a hormone with a number of biological effects, insulin not only displays the function of classic metabolic regulation, but also can regulate cell proliferation and differentiation, and ensure growth and development of embryos and young individuals. In vitro insulin can stimulate cell proliferation and differentiation. Insulin is also an important growth regulator in vivo, which has been proved in more and more studies. The role of insulin at the cellular level is triggered by the binding of insulin to its receptor located in the cell surface. However, insulin at the higher concentration can also been triggered by insulin-like growth factor-1 (IGF-1) receptor. Its role varies in different cell lines. Insulin receptor and insulin-like growth factor receptor-1 are widely expressed in human MDS and AML cell membranes. Recently, many studies related to the relationship between hyperinsulinemia and cancer have been reported. In this review the role and its possible mechanism in promoting human leukemia cell proliferation and inhibiting human leukemia cell proliferation are summarized. Furthermore, the potential application prospect of insulin analogues also will be described.