Agaricus blazei Murill (AbM) is a mushroom belonging to the Basidiomycetes family, which is believed to have antitumor and antioxidative activities. Proteoglycans and ergosterol are considered the key compounds of AbM for antitumor properties and so are used in complementary and alternative medicine as an anticancer drug. AbM is used to avoid serious side effects that would inevitably affect patients. Currently, the efficacy of AbM against chronic myeloid leukemia (CML) has not been established. The present study aimed to investigate the antitumor activities of the acidic RNA protein complex, FA-2-b-β, extracted from wild edible AbM. The CML K562 cells or primary CML bone marrow (BM) cells were treated with FA-2-b-β at different concentrations and time points. CML cell line proliferation and apoptosis were determined using the CCK-8 assay or Annexin V/propidium iodide (PI) labeling, RT-qPCR and western blotting was performed to determine the involvement of the Wnt/β-catenin-associated apoptotic pathway. The results of the present study demonstrated that FA-2-b-β has a high anti-proliferative potency and strong pro-apoptotic effects. Thus, daily intake of mushrooms containing FA-2-b-β may be an adequate source as an alternative medicine in the management of CML, and may provide useful information for the development of a novel therapeutic target in this area.
Ruxolitinib has demonstrated efficacy in patients with myelofibrosis (MF). However, substantial number of patients may not respond after 3-6 months of treatment or develop resistance over time. In this phase 2 trial, patients with a current diagnosis of intermediate or high-risk MF who either had an inadequate splenic response or spleen regrowth after ruxolitinib treatment were enrolled. All patients received jaktinib 100 mg Bid. The primary endpoint was the proportion of patients with ≥35% reduction in spleen volume (SVR 35) at week 24. The secondary endpoints included change of MF-related symptoms, anemic response, and safety profile. From July 6, 2021, to January 24, 2022, 34 ruxolitinib-refractory or relapsed patients were enrolled, 52.9% (18 of 34) were DIPSS intermediate 2 or high risk. SVR 35 at week 24 was 32.4% (11 of 34, 95% CI 19.1%-49.2%) in all patients and 33.3% (6 of 18, 95% CI 16.3%-56.3%) in the intermediate 2 or high-risk group. A total of 50% (8 of 16) transfusion-independent patients with hemoglobin (HGB) <100 g/L at baseline had HGB elevation ≥20 g/L within 24 weeks. Furthermore, 46.4% (13 of 28) of patients had a ≥ 50% decrease in the total symptom score (TSS 50) at week 24. The most common grade ≥3 treatment-emergent adverse events (TEAEs) were thrombocytopenia (32.4%), anemia (32.4%), and leukocytosis (20.6%). In total, 13 (38.2%) of 34 patients had serious adverse events (SAE), of which drug-related SAEs were found in 5 patients (14.7%). These results indicate that jaktinib can be a promising treatment option for patients with MF who have either become refractory to or relapsed after ruxolitinib treatment.
MicroRNA (miRNA) is a kind of highly conserved single-stranded small endogenous non-coding RNA associated with multiple diseases, particularly cancer. The miRNAs expression profile in multiple myeloma (MM) has been barely elucidated.The miRNAs expression profiles in bone marrow plasma cells of 5 MM individuals and 5 iron-deficiency anemia volunteers were analyzed using RNA-sequencing. Quantitative polymerase chain reaction (QPCR) was performed to validate the expression of selected miR-100-5p. The biological function of selected miRNA was predicated by bioinformatics analysis. Finally, the function of miR-100-5p and its target on MM cells were evaluated.MiRNA-sequencing showed that miR-100-5p was obviously upregulated in MM patients, which was further validated in an expanded cohort. Receiver operating characteristic curve analysis characterized miR-100-5p as a valuable biomarker of MM. Bioinformatics analysis predicted that miR-100-5p is targeted to CLDN11, ICMT, MTMR3, RASGRP3, and SMARCA5, and their low expression are associated with poor prognosis of MM patients. Kyoto encyclopedia of genes and genomes analysis suggested that the major interacting proteins of these five targets are mainly enriched in inositol phosphate metabolism and phosphatidylinositol signaling system pathway. In vitro study showed that miR-100-5p inhibition promoted the expression of these targets, especially MTMR3. In addition, miR-100-5p inhibition declined living number and metastasis, whereas promoted apoptosis of RPMI 8226 and U266 MM cells. The function of miR-100-5p inhibition was weakened by MTMR3 inhibition.These results indicates that miR-100-5p is a promising biomarker for MM, and that it may involve in the pathogenesis of MM by targeting MTMR3.
Dendritic cell (DC) vaccines have been shown to stimulate tumor antigen-specific CD8+ T cells; however, this strategy has demonstrated variable clinical efficacy likely due to immune escape mechanisms that can induce tumor-specific CD8+ T cell dysfunction. Herein, we evaluated the functional characteristics of DC vaccine-induced CD8+ T cells with regard to immune checkpoint inhibitors in gastric cancer patients who were administered Wilms tumor protein-1 (WT1)-targeted DC vaccine. We observed the upregulation of the inhibitory molecule, TIGIT and the inhibitory T cell co-receptors PD1 and Tim3 in limiting WT1-specific CD8+ T cell growth and function in GC patients. TIGIT-expressing PD1+Tim3- CD8+ T cells were the largest subset, while TIGIT+PD1+Tim3+ was the most dysfunctional subset of WT1-specific CD8+ T cells in gastric cancer patients. Importantly, the co-inhibition of TIGIT, PD1, and Tim3 pathways enhanced the growth, proliferation, and cytokine production of WT1-specific CD8+ T cells. In conclusion, our data suggests that targeting TIGIT, PD1, and Tim3 pathways may be important in reversing immune escape in patients with advanced gastric cancer.
Redundant carbapenemase-producing (RCP) bacteria, which carry double or multiple carbapenemases, represent a new and concerning phenomenon. The objective of this study is to conduct a comprehensive analysis of the epidemiology and genetic mechanisms of RCP strains to support targeted surveillance and control measures. A retrospective analysis was conducted using surveillance data from 277 articles. Statistical analysis was performed to determine and evaluate species prevalence, proportions of carbapenemases, antibiotic susceptibility profiles, sample information, and patient outcomes. Complete plasmid sequencing data were utilized to investigate potential antimicrobial resistance or virulence advantages that strains may gain from acquiring redundant carbapenemases. RCP bacteria are widely distributed globally, and their prevalence is increasing over time. Several countries, including China, India, Iran, Turkey, and South Korea, have reported more than 100 RCP strains. The most commonly reported RCP species are
OBJECTIVE To analyze the relationship between coagulation indexes and prognosis of patients with multiple myeloma (MM). METHODS A total of 99 newly diagnosed MM patients treated in Gansu Provincial Hospital from October 2017 to October 2019 were enrolled. Plasma thromboplastin time (TT), prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), D-dimer (D-D), platelet (PLT), and other laboratory indexes were detected. The relationship between coagulation indexes and clinical characteristics of MM patients was analyzed. The differences in survival rates among MM patients with different levels of coagulation indexes were compared, and the effect of each clinical index on the prognosis of MM patients was analyzed by univariate and multivariate. RESULTS Each coagulation index was correlated to sex, disease classification and stage, and β2-MG level of MM patients. Disease stage and β2-MG level were positively correlated with coagulation indexes, which means that patients with late-stage disease or high β2-MG, IgA and IgG levels were more likely to develop into coagulation disorders (P<0.05). The survival rate of patients with MM exhibiting elevated PT, FIB, and D-D levels was significantly lower (P<0.05). Univariate and multivariate analysis showed that each coagulation index was the influencing factor on the follow-up outcomes of MM patients, in which FIB was an independent prognostic factor. CONCLUSION Coagulation function is correlated with multiple clinical indicators of patients with MM and plays an important role in their prognosis.
Objective To investigate the effect of neutrophil/lymphocyte ratio (NLR) and monocyte/lymphocyte ratio (MLR) in the valuation prognosis of patients with multiple myeloma (MM). Methods The clinical data of 82 patients with initially diagnosed MM admitted to Gansu Provincial People's Hospital was analyzed retrospectively. NLR and MLR were calculated based on blood routine results respectively. The optimal cut-off point of NLR and MLR was determined according to the ROC curve, and the patients were divided into the high NLR/MLR group and the low NLR/MLR group. The general data, biochemical indicators and prognosis of the patients in each groups were compared respectively. The prognostic significance of the high NLR/MLR group and the low NLR/MLR group in patients between different treatment regimens and different clinical characteristics were analyzed. Risk stratification was designed based on NLR and high MLR as two risk factors, and the effect of risk factors, on the prognosis of MM patients were compared. Results ROC curve analysis determined that the optimal cut-off point of NLR was 3.1 (sensitivity 75%, specificity 70.7%) and the optimal cut-off point of MLR was 0.34 (sensitivity 83.3%, specificity 53.4%). The lactate dehydrogenase (LDH) and mean platelet volume (MPV) were correlated to NLR and MLR (P 0.05). The OS rate of patients with higher NLR and MLR was lower than those with low NLR and MLR and showed poor prognosis; Further analysis showed that there were statistically significant differences in OS time among patients with different MLR and NLR in the new drug treatment group and the traditional chemotherapy group, as well as patients in different age stratification groups, different β 2-MG stratification groups and different serum creatinine stratification groups. Patients with 2 risk factors showed a poorer prognosis than those with 0-1 risk factor. Conclusion Elevated NLR and MLR are associated with poor prognosis in MM patients and may serve as the cost-effective and readily available prognostic biomarkers.
To explore the correlation of body mass index (BMI), ABO blood group with multiple myeloma (MM).70 MM patients (MM group) and 10 healthy people (control group) were selected in the same period, the BMI of patients was calculated according to the height and weight, and the differences of BMI in 2 groups was compared. The distribution of age, sex, albumin (Alb), serum creatinine (Cr), hemoglobin (Hb) and red blood cell (RBC) in the two groups were analyzed. Differences in red blood cell distribution width (RDW), neutrophil/lymphocyte ratio (NLR), disease stage and lactate dehydrogenase (LDH) level, survival rate of MM patients with different BMI values and blood group were compared between two groups, and the differences in follow-up outcomes of MM patients were analyzed by univariate and multivariate logistic regression analysis.BMI level of MM patients was higher than that of control group (t=2.706, P＜0.01), but the difference of blood group was not significant (P＞0.05); The NLR value in obese patients was higher than that in non-obese patients, the staging was later and the Alb level was lower in obese patients than those in non-obese patients. the differences were statistically significant between obese patients and non-obese patients (P＜0.05). Univariate and multivariate analysis showed that BMI, Alb and LDH level could influence the follow-up outcome of MM patients, the patients with elevated BMI and LDH level had worse prognosis, while patients with elevated Alb had better prognosis. which means that all the three factors are independent factors affecting the prognosis of MM patrents.Increased BMI in MM patients can affect the outcome of follow-up, which is an independent influencing factor.体重指数、ABO血型与多发性骨髓瘤相关性研究.探索体重指数、ABO血型与多发性骨髓瘤（MM）的相关性.选取70例初发MM患者（MM组）和70例同期健康体检者（对照组），根据患者身高、体重计算得出体重指数（BMI），比较2组差异；将MM组患者分为非肥胖组（BMI＜28）和肥胖组（BMI≥28），分析2组患者在年龄、性别、白蛋白（Alb）、血肌酐（Cr）、血红蛋白（Hb）、红细胞分布宽度（RDW）、中性粒细胞/淋巴细胞比值（NLR）、疾病分期及乳酸脱氢酶（LDH）方面的差异；比较不同BMI值及不同血型MM患者生存率的差异，单因素及多因素Logistic回归分析各指标对MM患者随访结局的差异.MM患者BMI水平高于对照组（t=2.706, P＜0.01）,血型对比无显著差异（P＞0.05）；肥胖患者较非肥胖患者的NLR值偏高，分期偏晚，Alb水平偏低，与非肥患者差异有统计学意义（P＜0.05）。单因素及多因素分析显示，BMI、Alb及LDH水平对MM患者随访结局有影响，即BMI、LDH升高的患者预后更差，而Alb升高的患者预后较好，而且三者均是影响MM患者预后的独立影响因素.MM患者BMI升高可影响患者随访结局，是MM的独立影响因素.
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