Notch signal pathway can regulate the morphogenesis,apoptosis and cellular proliferation of normal tissues and organs,which plays an important role in regulating hematopoietic cells proliferation and differentiation in bone marrow microenvironment.The occurrence and development of multiple myeloma(MM)are closely related to the bone marrow microenvironment in which many signal pathways are involved.Recent studies show that Notch signal pathway promotes the development and progression of many cancers including MM,which plays key roles in tumor invasion and drug resistance.This review focus on the recent findings on Notch signal pathway in MM,and reveals that Notch signal pathway will be identified as a potential new therapeutic target in MM.

Recently numerous studies have demonstrated that Notch signaling pathway plays a critical role in regulating cell proliferation and differentiation in hematopoietic microenvironment,which is associated with MM occurrence and the drug resistance.The latest researches show that there are close relations between hypoxia and Notch signaling pathway in tumor occurrence and progression.Exploring the interactions of microenvironment of hypoxia,HIF-1α and Notch signaling pathway will provide theoretical basis for MM targeted therapy.

Hypoxia environment plays an important role in the pathogenesis of multiple myeloma such as stimulating angiogenesis,increasing bone destructiong,epithelial-mesenchymal transition and drug resis-tance.Thus,there are many therapeutic strategies targeting the hypoxic environment of multiple myeloma,such as hypoxia-activated prodrug and molecular targeting inhibitors.Targeting the hypoxic environment is a promis-ing therapy for multiple myeloma in the future.

Objective To explore the expression and its significance of Notch1、Notch2、Notch3 transmembrane receptor protein in different types of lymphoma tissues. Methods By employing immunohistochenistry SP staining,the expres-sions of Notch in 59 lymphomas were detected, and 21 cases of lymph-node reactive hyperplasia served as control group. Results The expression of Notch1 was significantly higher in T-cell lymphoma and NK/T-cell lymphoma than that in the B-cell lymphoma and the control group, the difference was statistically significant (P<0.01). The expres-sion of Notch2 was obviously higher in B-cell lymphoma and NK/T-cell lymphoma than that in the T-cell lymphoma and the control group,the difference was statistically significant(P<0.01). The expression of Notch3 in NK/T-cell lym-phoma group was significantly higher than that in the other three groups,the difference was statistically significant (P<0.01). Conclusion Abnormal activation of Notch signaling pathway is closely related to the occurrence and develop-ment of lymphoma. The occurrence and development of NK/T-cell lymphoma is probably associated with the high ex-pression of Notch1, Notch2 and Notch3; The occurrence and development of T- cell lymphoma is probably related to the high expression of Notch1; The occurrence and development of B-cell lymphoma is probably associated with the high expression of Notch2.

Objective:To analyze the data of clinical characteristics, hospitalization actual cost and hospital stay of inpatients with lymphoma, and to provide references for local epidemiological research, hospital optimization management, and appropriate resource allocation.Methods:The quadratic programming was performed based on hospital information management system and case system, as well as the information from inpatients with lymphoma in Shandong Tai'an Central Hospital between January 1, 2004 and November 30, 2019, and then they were derived and collected into the SQL server database. The gender, onset age, age distribution, and hospital stay of all inpatients with lymphoma were retrospectively analyzed. The patients were divided into the young group (< 45 years old), middle-aged group (≥45 years old and < 60 years old) and elderly group (≥ 60 years old) according to the age. The hospitalization cost and hospital stay of these inpatients in different age groups were collected and compared.Results:The number of admissions for inpatients with lymphoma between January 1, 2004 and November 30, 2019 was 3 866, accounting for 0.38% (3 866/1 011 627) of the total inpatient admissions. There were 817 newly-diagnosed lymphoma inpatients, including 499 males and 318 females (male to female ratio was 1.57:1). The median onset age of the newly-diagnosed lymphoma inpatients was 58 years old (7 months to 86 years old). Among the newly-diagnosed lymphoma patients, the proportion of them with age ≥ 45 years old was increased, and peaked at 60-65 years old, and decreased after 75 years old. There were 180, 270 and 367 cases in the young group, middle-aged group and elderly group respectively; the median hospital stay was 13.5 d, 13.0 d and 14.0 d, respectively (χ 2 = 0.419, P = 0.811). The median total cost of hospitalization was 9 846.39 yuan, 12 232.16 yuan and 14 022.36 yuan, respectively (χ 2 = 9.443, P = 0.009); and the median drug cost was 3 423.37 yuan, 3 523.62 yuan and 3 654.54 yuan, respectively (χ 2 = 2.202, P = 0.333); the ratio of median drug cost to the total cost was 44.80%, 40.49% and 34.58%, respectively (χ 2 = 6.512, P = 0.039). Conclusions:The number of lymphoma inpatients in Shandong Tai'an Central Hospital is on the rise. The incidence of inpatients with lymphoma is increased annually with older onset age. The total cost of inpatients was increased with the aging, but it has no obvious relevance with hospital stay. Middle-aged and elderly people are the target populations for disease control and prevention. Measures including screening, early diagnosis and early treatment should be enhanced.

Chronic lymphocytic leukemia (CLL) is a clonal malignant disease of B lymphocytes (T lymphocytes are rare) and usually occurs in elderly people. CLL has a highly variable clinical course, with a median survival of 35 to 63 months. In the era of immunochemotherapy, the survival of CLL patients has improved significantly, but most patients still have primary drug resistance and relapse after the treatment. The emergence of Bruton tyrosine kinase inhibitor has completely changed the treatment mode of CLL, making the treatment of CLL into the era of targeted therapy. Ibrutinib combined with CD19 chimeric antigen receptor T-cell has good efficacy and can improve the prognosis of patients.

Objective To investigate risk factors for early death in acute promyelocytic leukemia patients. Methods The clinical characteristics including leucocyte counts at onset,platelet count and fibrinogen content of 42 patients with APL were evaluated. The factors of immunophenotype, genes fusion as well as gene mutations were compared. Results Among the 42 patients with APL,6 cases were observed early death with the early mortality rate of 14.3%. To be spe-cific,4 deaths were attributable to cerebral hemorrhage,whereas the other two were linked with disseminated intravas-cular coagulation complicated with multiple organ failure and myocardial infarction respectively. The leukocyte counts of dead patients were significantly more than complete remission group. At the same time, the blood platelet counts and the fibrinogen counts were all less than those of complete remission patients. 5 patients were confirmed as CD2+,5 cases were CD34 and/or HLA-DR+,and FLT3-ITD gene mutation was found in 4 subjects. Difference between the two groups was statistically significant(P<0.05). Conclusion Acute promyelocytic leukemia patients with leukocytosis,low platelet count, hypofibrinogenemia, CD2+, CD34 and/or HLA-DR+as well as FLT3-ITD gene mutation are at an increased risk of early death in the risk factor analysis.

Objective: To evaluate the efficacy and safety of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in prophylaxis neutropenia after chemotherapy in patients with lymphoma. Methods: This was a multicenter, single arm, open, phase Ⅳ clinical trial. Included 410 patients with lymphoma received multiple cycles of chemotherapy and PEG-rhG-CSF was administrated as prophylactic. The primary endpoint was the incidence of Ⅲ/Ⅳ grade neutropenia and febrile neutropenia (FN) after each chemotherapy cycle. Meanwhile the rate of antibiotics application during the whole period of chemotherapy was observed. Results: ①Among the 410 patients, 8 cases (1.95%) were contrary to the selected criteria, 35 cases (8.54%) lost, 19 cases (4.63%) experienced adverse events, 12 cases (2.93%) were eligible for the termination criteria, 15 cases (3.66%) develpoed disease progression or recurrence, thus the rest 321 cases (78.29%) were into the Per Protocol Set. ②During the first to fourth treatment cycles, the incidences of grade Ⅳ neutropenia after prophylactic use of PEG-rhG-CSF were 19.14% (49/256) , 12.5% (32/256) , 12.18% (24/197) , 13.61% (20/147) , respectively. The incidences of FN were 3.52% (9/256) , 0.39% (1/256) , 2.54% (5/197) , 2.04% (3/147) , respectively. After secondary prophylactic use of PEG-rhG-CSF, the incidences of Ⅳ grade neutropenia decreased from 61.54% (40/65) in the screening cycle to 16.92% (11/65) , 18.46% (12/65) and 20.75% (11/53) in 1-3 cycles, respectively. The incidences of FN decreased from 16.92% (11/65) in the screening cycle to 1.54% (1/65) , 4.62% (3/65) , 3.77% (2/53) in 1-3 cycles, respectively. ③The proportion of patients who received antibiotic therapy during the whole period of chemotherapy was 34.39% (141/410) . ④The incidence of adverse events associated with PEG-rhG-CSF was 4.63% (19/410) . The most common adverse events were bone pain[3.90% (16/410) ], fatigue (0.49%) and fever (0.24%) . Conclusion During the chemotherapy in patients with lymphoma, the prophylactic use of PEG-rhG-CSF could effectively reduce the incidences of grade Ⅲ/Ⅳ neutropenia and FN, which ensures that patients with lymphoma receive standard-dose chemotherapy to improve its cure rate.

Apoptosis ; Cell Hypoxia ; Cell Line, Tumor ; Cell Proliferation ; Humans ; Multiple Myeloma ; pathology