Acute myeloid leukemia (AML) was confirmed to be associated with hematopoietic insufficiency, as well as abnormal proliferation, differentiation or survival of myeloid progenitors. Multiple studies reported that microRNA-204 (miR-204) and Hepatocyte growth factor (HGF) played important roles in types of cancers. However, the potential molecular regulatory mechanism between miR-204 and HGF in AML remains to be further defined. Real-time PCR (RT-PCR) was adopted to detect the expression of miR-204 and HG. Relative protein levels were detected by western blot assay. The viability, cell cycle, apoptosis, migration, and invasion were analyzed by MTT, flow cytometry, and transwell assays. Moreover, the target relationship between miR-204 and HGF was predicted by MiRcode website and confirmed by luciferase reporter, RNA pull-down, and western blot assays. Our data suggested that miR-204 was downregulated in AML serum samples and cells. MiR-204 overexpression repressed cell proliferation, migration, invasion, and induced cell apoptosis in AML cells. HGF was upregulated in AML samples and cells, and HGF knockdown inhibited the malignancy of AML cells. In addition, HGF was directly targeted by miR-204. HGF overexpression reversed the effects of miR-204 mimic on AML cell proliferation, apoptosis, migration, and invasion. Besides, miR-204 regulated the c-Met signaling by targeting HGF, thereby regulating the downstream protein levels related to cell proliferation, apoptosis, migration, and invasion in AML cells. In conclusion, miR-204 could regulate AML progression through regulating the HGF/c-Met pathway.
Abstract Multiple studies have confirmed the occurrence of second tumors as a rare incidence of CAR-T therapy, but one of the complications that does warrant in-depth exploration. According, given the relatively small number of reported second tumor types thus far, additional comprehensive occurrence and characterization of a new second tumor type after CAR-T therapy remains essential for understanding the risk of potential tumors with this therapy, as well as for defining the role of immune microenvironment in malignant transformation. In this article, a new second tumor type CMML was identified in a patient who had received CD19 CAR-T therapy for DLBCL. The immune microenvironment of both the pre- and post-treatment of secondary CMML and primary CMML were deeply profiled by ScRNA-seq. Our results demonstrated an enhanced inflammatory cytokines, chemokines, and immunosuppression state of monocytes/macrophages, which may inhibit the cytotoxicity of T/NKs in secondary CMML. In contrast, the cytotoxicity of T/NKs were enhanced in secondary CMML after treatment. Collectively, our results highlight a new type of second tumor, CMML after CAR-T therapy and provide a framework for defining the immune microenvironment of second tumor occurrence after CAR-T therapy. Our results also provide a rationale for targeting macrophages to strengthen CMML treatment.
Mucormycosis is an angioinvasive fungal infection, associated with high mortality. The aim of our study was to explore the high-risk factors and predict the death of hematological disease complicated with mucormycosis. We retrospectively analyzed clinical data of 31 patients with hematological disease complicated with mucormycosis, adopted random forest to establish the death prediction model, and validated the model in another 15 patients. The median age of the 31 cases was 46 (28–51) years, male to female ratio 1.38:1, and 90-day mortality rate 54.8%. The most common underlying disease was acute myeloid leukemia (58.1%). The main clinical symptoms were fever (100%), cough (87.1%), sputum (80.6%), chest pain (61.3%), and hemoptysis (19.4%). Reversed halo sign (83.9%) was the most common computed tomography sign. A total of 48.4% of patients also had aspergillus or bacterial infections. Discriminative models were constructed by random forest with 17 non-survivors and 14 survivors. Procalcitonin, the duration of intravenous administration of amphotericin B or amphotericin B liposomes, and neutropenia at death or 90 days of survival were the leading risk factors for poor prognosis, with area under the curve of 0.975 (95% CI 0.934–1). We chose 0.6775 as death prediction threshold (with 82.3% sensitivity and 100% specificity) and validated the model successfully in another 15 patients. Chest pain and reversed halo sign are specific clinical and image signs of hematological disease complicated with mucormycosis. Neutropenia, elevated procalcitonin, and insufficient use time of amphotericin B or amphotericin B liposomes are risk factors for death.
In order to practice Knowles' contract learning method into nurse students of continuous education,we designed the course of nursing psychology as the application of learning contract,the undergraduates for the continuous education of Grade 2011 in Hainan Medical College were chosen as the trial group.The education activities were conducted according to Knowles' contract learning method,and then the researchers discussed the flexibility and the value of the continuing education on nursing in order to provide the future reference in the area of contract learning.
Key words:
Knowles; Contract learning method; Occupation teaching
Purpose: To investigate the prevalence, risk factors of intestinal carbapenem-resistant Enterobacteriaceae (CRE) colonization and bloodstream infection (BSI) caused by CRE in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Methods: We analyzed the clinical data of 185 patients with hematological malignancies who underwent allo-HSCT from May 2019 to December 2021. All patients received regular CRE monitoring by rectal swab during allo-HSCT, and some CRE strains were further identified for carbapenemase phenotypes. The rates, distribution and risk factors of CRE colonization, CRE-induced BSI were analyzed. Results: CRE was detected in 44 of 185 recipients, with colonization rate of 23.8%. A total of 46 strains of CRE were isolated, including 22 Escherichia coli , 17 Klebsiella pneumoniae , three Klebsiella oxytoca , two Enterobacter hormaechei , and two other Enterobacteriaceae. Among the 19 strains identified with carbapenemase phenotypes, eight strains of E. coli produced metal β-lactamase, five K. pneumoniae produced serine carbapenemase, two K. pneumoniae produced metal β-lactamase, two K. oxytoca produced metal β-lactamase, a Citrobacter malonic acid-free produced metal β-lactamase and a Citrobacter freundii produced metal β-lactamase. In 10 patients developed with CRE-related BSI, the types and combined drug sensitivity of strains detected by rectal swab were highly consistent with blood culture. Multivariate analysis revealed that pulmonary infection, perianal infection and carbapenem application in the 3 months pre-transplant were independent risk factors for rectal CRE colonization, while rectal colonization with carbapenem-resistant K. pneumoniae (CR-KP) was an independent risk factor for CRE-induced BSI. The mortality rate within 30 days of CRE-related BSI was 50.0%, and patients receiving multi-drug therapy within 24 hours showed slightly lower mortality than that in the single-drug treatment group. Conclusion: Allo-HSCT patients with CRE-induced BSI have poor prognosis, and CR-KP rectal colonization is an independent risk factor for CRE-related BSI. Rectal swab screening during allo-HSCT could provide early warning for later CRE-induced BSI. Keywords: allogeneic hematopoietic stem cell transplantation, carbapenem-resistant enterobacteriaceae, bloodstream infection, intestinal colonization
Cellular immunotherapy represented by CD19-directed chimeric antigen receptor T (CAR-T) cells has achieved great success in recent years. An increasing number of CAR-T therapies are being developed for cancer treatment, but the frequent and varied adverse events, such as "on-target, off-tumor toxicity", limit CAR-T application. Here, we identify the target antigen expression patterns of CAR therapies in 18 tissues and organs (peripheral blood mononuclear cells, bone marrow, lymph nodes, spleen, heart, ascending aortic tissue, trachea, lung, skin, kidney, bladder, esophagus, stomach, small intestine, rectum, liver, common bile duct, and pancreas) from healthy human samples. The atlas determines target antigens expressed on some normal cell types, which facilitates elucidating the cause of "on-target, off-tumor toxicity" in special tissues and organs by targeting some antigens, but not others. Moreover, we describe the target antigen expression patterns of B-lineage-derived malignant cells, acute myeloid leukemia (AML), and solid tumors. Overall, the present study indicates the pathogenesis of "on-target, off-tumor toxicity" during CAR therapies and provides guidance on taking preventive measures during CAR treatment.
To compare the gene mutational spectrum between elderly and young adults with acute myeloid leukemia(AML) based on next generation sequencing(NGS).The specimens of 250 AML patients in first affiliated hospital of Zhengzhou University from January 2018 to November 2018 were collected and analyzed retrospectively. The mutation of 22 related genes were detected by using AML NGS chips. Then, the differences between elderly (≥60 years old) and young adults (＜60 years old) were compared.The most frequent mutations of 250 patients were as follows: NPM1(22.4%), FLT3-ITD(18.8%), NRAS(17.2%), DNMT3A(14.4%), TET2(11.6%), IDH2(9.6%), Biallelic CEBPA(8.8%), Moallelic CEBPA(8.4%), KIT(8.4%), RUNX1(7.6%), IDH1(7.6%), ASXL1(6.0%), U2AF1(5.2%), SRSF2 (3.2%), SF3B1(3.2%), TP53(2.4%), KRAS(2.0%). The NPM1, CEBPA, DNMT3A mutation significantly increased in intermediate prognosis group while KIT significantly increased in favourable prognosis group. The TET2 and IDH2 mutation rate in elderly patients were significantly higher than that in young patients (21.8% vs 8.7%) (χ2=7.180, P=0.007) and (20.0% vs 6.7%) ( χ2=8.788, P=0.003) respectively. Compared with young patients, the frequencies of DNA methylation and demethylation mutations (including DNMT3A, TET2, IDH1, IDH2) and RNA splicing enzyme mutations (inc-luding SRSF2, SF3B1, U2AF1, ZRSR2) in elderly patients significantly increased(67.3% vs 36.4%) (χ2=16.653, P=0.000) and (23.6% vs 8.7%)(χ2=9.041, P=0.003) respectively.The gene mutational spectrum in elderly and young adult AML shows heterogeneity. Compared with young adults, the frequencies of DNA methylation and demethylation mutations and RNA splicing enzyme mutations in elderly patients significantly increase.基于二代测序的老年和年轻成人急性髓系白血病患者突变基因谱比较.比较基于二代测序（NGS）的老年和年轻急性髓系白血病（AML）患者突变基因谱，探讨老年AML的分子生物学特点.回顾性分析2018年1月至2018年11月在郑州大学第一附属医院进行了基于22个基因突变谱的NGS检测初治AML（非急性早幼粒细胞白血病）患者的突变基因数据，并比较老年（≥60岁）和年轻（＜60岁）AML患者之间的差异.250例患者常见突变频率依次为NPM1（22.4%）、FLT3-ITD（18.8%）、NRAS（17.2%）、DNMT3A（14.4%）、TET2（11.6%）、IDH2（9.6%）、CEBPA双突变（8.8%）、CEBPA单突变（8.4%）、KIT（8.4%）、RUNX1（7.6%）、IDH1（7.6%）、ASXL1（6.0%）、U2AF1（5.2%）、SRSF2 （3.2%）、SF3B1（3.2%）、TP53（2.4%）、KRAS（2.0%）。NPM1、CEBPA 、DNMT3A突变常见于患者预后中等组，而KIT突变在患者预后良好组更常见。老年患者较年轻患者更多出现TET2突变（21.8% vs 8.7%）（χ2=7.180，P=0.007）和IDH2突变（20.0% vs 6.7%）（χ2=8.788，P=0.003）。将突变基因按照功能进行分组显示，老年患者更多发生DNA甲基化和去甲基化突变（包括DNMT3A、TET2、IDH1、IDH2）（67.3% vs 36.4%，χ2=16.653，P=0.000），以及RNA剪切酶突变（包括SRSF2、SF3B1 、U2AF1、ZRSR2）（23.6% vs 8.7%）（χ2=9.041，P=0.003）.基于NGS技术发现，不同年龄的AML患者常见突变种类存在显著差异，老年患者更多发生DNA甲基化和去甲基化突变以及RNA剪切酶突变.
'/%3e%3cuse xlink:href='%23a' transform='rotate(23.036 .093 25.536)'/%3e%3cuse xlink:href='%23a' transform='rotate(45.87 1.273 16.18)'/%3e%3cuse xlink:href='%23a' transform='rotate(69.945 .996 12.078)'/%3e%3cuse xlink:href='%23a' transform='rotate(20.66 -19.689 31.932)'/%3e%3c/svg%3e)