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 analyze the clinical features and mutation of myeloid differentiation factor 88 (MYD88) L265P in patients with diffuse large B-cell lymphoma (DLBCL) of central nervous system (CNS).Methods:The clinicopathological materials of 45 cases of DLBCL of CNS were retrospectively collected in Xuanwu Hospital, Capital Medical University from September 2014 to February 2017. The clinicopathological data were retrospectively analyzed, combined with immunohistochemistry, EB virus in situ hybridization, imaging and medical history. The mutation of MYD88 L265P gene was detected by pyrosequencing and its clinical significance was analyzed. Results:The age of the patients ranged from 42 to 82 years [(57.6±8.8) years], including 24 males and 21 females. Totally 93.3% (42/45) of the patients had supratentorial tumours, which were single or multiple. The cerebral hemisphere (31/45, 68.9%) was the most common involved site, and 21 cases (21/45, 46.7%) had multiple lesions. Histologically, DLBCL in the CNS showed diffuse infiltration of tumor tissue, some of which grew around blood vessels in a "sleeve" arrangement. CD 20 and CD 79a were diffusely and strongly positive. Thirty-nine cases (39/45, 86.7%) were non-germinal center B cell (non-GCB) subtype and 6 cases (6/45, 13.3%) were germinal center B cell (GCB) subtype. MYD88 L265P mutation was found in 64.4% (29/45) patients. There was statistically significant difference between non-GCB type (71.8%, 28/39) and GCB type DLBCL (1/6, P=0.017). Compared with the operation/biopsy group without chemotherapy, operation+chemotherapy, biopsy+chemotherapy, operation/biopsy+chemotherapy+stem cell transplantation can improve the survival and prognosis ( HR=0.05, 95% CI 0.01-0.33 , P=0.002; HR=0.04, 95% CI 0.01-0.36 , P=0.004; HR=0.01, 95% CI 0.00-0.17 , P=0.001; respectively). Conclusions:DLBCL of the CNS is aggressive tumor with poor prognosis, the clinical manifestations are complex and diverse, and the diagnosis is challenging. MYD88 L265P is a common and specific gene mutation in primary CNS lymphoma(PCNSL), which is of great significance in the diagnosis and treatment of lymphoma. The MYD88 L265P mutation was more frequently detected in non-GCB than GCB subtype. Chemotherapy can improve the survival rate of PCNSL patients. If chemotherapy achieves complete remission and autologous hematopoietic stem cell transplantation is performed, there may be a chance of long-term survival.

Objective:To evaluate the effects of objective feedback teaching applied in the specialist nurses training of digestive endoscopy.Methods:Six-eighty nurses participating in the training of specialist nurses of digestive endoscopy in Chongqing were recruited in the study, among which, 30 trainees in 2019 were assigned to the observation group, taking objective feedback teaching, and 38 trainees in 2018 were assigned to the control group, receiving traditional teaching. After the training, the two teaching methods were assessed through theoretical results, operation skills and comprehensive evaluation, and meanwhile a self-designed satisfaction questionnaire on the satisfaction of trainees was conducted. SPSS 25.0 was used to perform t-test, Chi-square test and Mann-Whitney U test. Results:The operation skills (84.90±4.92) and comprehensive quality (86.30±4.62) of observation group were higher than those of the control group [(82.39±4.10), (83.86±5.10)], with statistically significant differences ( P<0.05), while there was no significant difference in theoretical knowledge [(85.80±5.63) vs. (83.68±4.51), P>0.05]. Trainees were satisfied with the new training mode. Conclusion:The objective feedback teaching mode can improve the training effect especially on operation skills and comprehensive quality of the specialist nurses of digestive endoscopy, and insure the satisfaction of specialist nurses with the training.

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

One patient with gallbladder mass had transient jaundice and was diagnosed with gallbladder carcinoma by abdominal ultrasonography， contrast-enhanced CT， MRCP， and PET-CT. Surgical exploration showed enlarged gallbladder and a mass in the neck of the gallbladder pressing against the hilum of the liver， with no manifestation of tumor invasion， and there were no signs of liver metastasis. Only cholecystectomy was performed for the patient. The pathological diagnosis was tubular adenoma of the gallbladder without carcinogenesis. This case is characterized by a large gallbladder tumor， without marginal infiltration on imaging or malignant transformation based on pathology.