The prognostic relationship between CD56 expression and newly diagnosed multiple myeloma / 中华内科杂志

Objective:To evaluate the prognostic value of CD56 expression in newly diagnosed MM (NDMM).Methods:A total of 332 NDMM patients were enrolled in Beijing Chaoyang Hospital, Capital Medical University from January 1, 2011 to January 1, 2021, with a median age of 60 years and a male to female ratio of 1.2∶1. CD56 expression on myeloma cells was detected by flow cytometry before induction therapy. Overall survival (OS) and progression-free survival (PFS) data were collected. In order to reduce the confounding factors, the propensity score matching technique was used to match CD56 positive versus negative patients at a ratio of 1∶1.Results:Among 332 patients, CD56 positivity rate was 65.1% (216/332). Patients with CD56 expression had significantly longer median OS (58.4 vs. 43.1 months, P=0.024) and PFS (28.7 vs. 24.1 months, P=0.013) than those with negative CD56. Univariate Cox proportional hazards regression analyses showed that CD56 expression was positively correlated with OS ( HR=0.644, 95 %CI 0.438-0.947, P=0.025) and a favorable prognostic factor for PFS ( HR=0.646, 95 %CI 0.457-0.913, P=0.013). The favorable effect of CD56 expression on PFS was confirmed in multivariate analysis ( HR=0.705, 95 %CI 0.497-0.998, P=0.049), but OS was not affected ( P>0.05).In the propensity score matching analysis, 194 patients with 97 in each group were identified. CD56 positivity consistently predicted longer PFS (34.2 vs.25.1 months, P=0.047), but not OS (63.4 vs.43.1 months, P=0.056). Conclusion:These results demonstrate that CD56 expression is a favorable prognostic factor for PFS of newly diagnosed MM patients.

Sinoatrial node pacemaker cells share dominant biological properties with glutamatergic neurons

Activation of the heart normally begins in the sinoatrial node (SAN). Electrical impulses spontaneously released by SAN pacemaker cells (SANPCs) trigger the contraction of the heart. However, the cellular nature of SANPCs remains controversial. Here, we report that SANPCs exhibit glutamatergic neuron-like properties. By comparing the single-cell transcriptome of SANPCs with that of cells from primary visual cortex in mouse, we found that SANPCs co-clustered with cortical neurons. Tissue and cellular imaging confirmed that SANPCs contained key elements of glutamatergic neurotransmitter system, expressing genes encoding glutamate synthesis pathway (Gls), ionotropic and metabotropic glutamate receptors (Grina, Gria3, Grm1 and Grm5), and glutamate transporters (Slc17a7). SANPCs highly expressed cell markers of glutamatergic neurons (Snap25 and Slc17a7), whereas Gad1, a marker of GABAergic neurons, was negative. Functional studies revealed that inhibition of glutamate receptors or transporters reduced spontaneous pacing frequency of isolated SAN tissues and spontaneous Ca

Effects of storage time of bone marrow specimens on the detection results of plasma cells immunophenotyping by flow cytometry / 白血病·淋巴瘤

Objective To explore the effects of different storage time of bone marrow specimens on the expressions of different antigens in normal plasma cells (nPC) and clone plasma cells (cPC) by flow cytometry. Methods The bone marrow samples of 12 patients with multiple myeloma (MM) who were treated in Beijing Chaoyang Hospital from September 2017 to January 2018 were selected as MM group. The minimum residual disease (MRD) level in MM group was 10-3-10-2. The bone marrow samples of 12 patients without plasma cell diseases were used as control group. Bone marrow samples were anticoagulated with ethylenediaminetetraacetic acid dipotassium (EDTA-K2) and stored at 2-8 °C. The fluorescent antibodies CD56, CD138, CD45, CD38, CD117, CD81 and cκ, cλ, CD45, CD38, CD19, CD27 were labeled at 0, 24, 48 and 72 h, respectively. The average fluorescence intensity (MFI) of the above 10 antigens expressed in nPC and cPC was analyzed by Diva software. The proportion and absolute count of nPC in control group and cPC in MM group were analyzed. Results In control group, when stored for 24 h, compared with 0 h, the difference of MFI of antigens in nPC was not statistically significant (P ＞ 0.05). When stored for 48 h, compared with 0 h, the MFI of CD38, CD138, CD27, cκ and cλ in nPC decreased, and the differences were statistically significant (28 943±6 591 vs. 23 569±7 587, P＝ 0.018; 1 412±399 vs. 817±223, P＝ 0.014;12 855±3 734 vs. 9 210±3 660, P＝ 0.005; 26 712±9 025 vs. 17 247±5 078, P＝ 0.026; 17 707±8 633 vs. 8 307±3 158, P ＝ 0.049); the MFI of CD45 increased, and the difference was statistically significant (7 694± 2 525 vs. 9 184±1 332, P ＝ 0.037). When stored for 72 h, compared with 0 h, the MFI of cκ and cλ increased, but the differences were not statistically significant (both P ＞ 0.05). In MM group, when stored for 24 h, compared with 0 h, the difference in MFI of antigens in cPC was not statistically significant (P＞ 0.05). When stored for 48 h, compared with 0 h, the MFI of CD38, CD138, CD81, cκ and cλ decreased, and the differences were statistically significant (16 664±11 744 vs. 10 130±10 026, P＝ 0.003; 2 041±1 145 vs. 1 371±696, P＝ 0.047; 2 679±784 vs. 1 524±1 153, P＝ 0.025; 29 102±18 138 vs. 18 372±10 327, P＝0.038; 16 314±12 728 vs. 9 752±6 271, P＝0.034). When stored for 72 h, compared with 0 h, the MFI of cκ and cλ increased, but the differences were not statistically significant (both P＞ 0.05). The absolute count of nPC and cPC gradually decreased with the prolongation of the storage time, and the difference was statistically significant (both P<0.05) when stored for 0 h and 24 h. There was no significant difference in the percentage of nPC and cPC among different storage time (all P ＞ 0.05). Conclusion Different storage time of bone marrow samples has effects on the MFI of antigens and absolute count of nPC and cPC, and the detection should be completed within 48 h.

Comparison of minimal residual disease in multiple myeloma patients detected by 8-color panels and next generation flow cytometry / 中华血液学杂志

Objective@#To compare the sensitivity of 8-color panels and next generation flow cytometry (NGF) for detecting minimal residual disease of multiple myeloma patients.@*Methods@#8-color-membrane antigens (8C-Mem) panel was built including CD45, CD38, CD138, CD19, CD56, CD81, CD27 and CD117 to identify the plasma cells, while 8-color-cytoplasmic antigens (8C-Cyto) panel was built including CD45, CD38, CD138, CD19, CD56, CD81, cKappa (cK) and cLambda (cλ) , and 8-color-two-tubes (8C-2tubes) panel were built including 8C-Mem and 8C-Cyto panels, the data of three groups was analyzed by Diva software. NGF uses Infinicyt software to fuse 8C-2tubes data to further analyze the expression of plasma antigens. Bone marrow aspiration obtained from 20 controls and 76 multiple myeloma patients who achieved complete remission were measured and analyzed.@*Results@#Positive MRD samples were discriminated in 88.2% of the specimen evaluated through either abnormal plasma cells (aPCs) or clonal plasma cells (cPCs) by NGF antigens panel, Among of them, consistency was 94.7%. The median percentage of cPCs was 0.3530%, The lowest sensitivity of NGF was 0.0003%. In 8-color panels, the positive MRD rates of 8C-Mem, 8C-Cyto and 8C-2tubes panels were 84.2%, 85.5% and 86.8%, respectively, which lower than that of NGF (P<0.001) . The positive MRD rate of 8C-Mem and 8C-Cyto panels were lower than that of 8C-2tubes panel (P<0.001) , and the positive MRD rate of 8C-Mem panel was lower than that of 8C-Cyto panel (P<0.001) . Sensitivity and specificity of NGF was higher than that of 8-color panels. 8C-2tubes panel has the best sensitivity, accuracy, negative predicted value, positive predicted value and specificity than other 8-color panels. However, huge data and low efficiency for analysis is the disadvantage. 8C-Cyto panel was the second choice, and 8C-Mem panel was the last.@*Conclusions@#Membrane and cytoplasmic light chain is a better method for multiple myeloma-MRD detection and NGF panel is an ideal approach. 8C-Cyto panel is recommended in 8-MFC groups.

Research progress of therapy for elderly non-transplantation-eligible newly diagnosed multiple myeloma / 白血病·淋巴瘤

The mean age of multiple myeloma (MM) patients was 60 years old,most of whom are not eligible for transplantation.Goals for elderly patients is to prolong survival time and ensure quality of life by achieving the best response.Prolonged treatment or maintenance therapy in elderly patients could improve the quality of clinical response and extend progression-free survival.Further study is needed to determine whether novel treatment regimens could improve adverse prognosis of high-risk cytogenetic patients.Optimal individualized regimens should be found to improve tolerability and treatment efficacy.

Clinicopathological analysis on goblet cell carcinoid of the appendix / 肿瘤研究与临床

Objective To explore the clinicopathologic features,diagnostic criteria and clinical prognostic factors of Goblet cell carcinoid (GCC) of the appendix.Methods The clinical and pathological data from 6 GCC patients were analyzed including age,clinical stage,surgical procedure,outcome,macroscopic features,histological sections and immunohistochemistry.Results The median age was 49.67 years old.Clinically,4 patients presented the signs and symptoms of acute appendicitis,while 2 patients presented the signs and symptoms of abdominal pain.4 patients of them undergone the simple appendectomy,the other 2 undergone the right hemicolectomy.All patients who had undergone the operation treatment survived.One patient was lost to the follow-up.Macroscopically,no masses were found in the appendix.Microscopically,4 cases showed that the tumor cells were identical to the goblet cell normal small intestinal crypts morphologically.The atypia,necrosis and mitotic figures of neoplasm cells were absent.2 cases were composed of small,discrete acini,tubules lined by a single layer of cuboidal or columnar cell,the signet-ring cells were uniform with pattern of infiltration being nests,rosrttes,or clumps without a dintinct lumen.All GCC cases were positive to Syn,4 cases were positive to CgA,some cases expressed NSE,CD56,CK7,CK20,Ki-67 index of 5 cases was under 2 ％,the other 1 was 3 ％.None had lymph node metastases,intestinal metastases or ovary metastases.Conclusions GCC of appendix is a rare neoplasm,and has more aggressive behaviour than classic carcinoids.Positive expression of Syn and CgA is necessory for the diagnosis of GCC,Ki-67 index may suggest the grading of tumor.

Genetic evolution and heterogeneity of multiple myeloma: a report from the 2013 EHA annual meeting / 白血病·淋巴瘤

Recent studies have shown that multiple myeloma (MM) is preceded by a premalignant state called monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM).Some of the genetic changes of MM are also present in MGUS and SMM,including chromosomal translocations,copy number changes,somatic mutations and so on.This article discusses the genetic heterogeneity.

X-ray Analysis and Clinical Application of Galactography / 实用放射学杂志

Objective To observe the X-ray appearance and clinical value of galactography.Methods 600 cases of galactorrhea confirmed by pathologly underwent galactography,among them,298 cases were blood type(49.8%),150 cases were serum type(25%),106 were rinsing type(17.7%) and others were 46 cases(7.7%).Results On galactography,the ductsl were divided into 3 groups: 345 cases were foliar type(59%),127 were ramate type(26.2%),87 were trunk type(14.8%).The main radiographic characteristics of lesions were mammary ductal ectasia in 578(96.3%),ductal distortion in 561(93.5%),irregular filling defect in ducts in 349(58.2%),and ductal damage in 39(6.5%).42 cases were breast carcinomas(7%),312 were intraductal papillary tumors(52%),129 were mammary ductal ectasia(21.5%),26 were mammary ductal mastitis(4.3%),49 were proliferous disease(8.2%),25 were mammary cyst(4.2%),17 were negative anamnesis(2.8%).Conclusion Galactography is beneficial in diagnosis of the pathogenesis of galactorrhea.