Assessment of 2022 European LeukemiaNet risk classification system in real-world cohort from China.

BACKGROUND: The European LeukemiaNet (ELN) risk classification system for acute myeloid leukemia (AML) patients has been used worldwide. In 2022, the ELN risk classification system modified risk genes including CEBPA mutation status, myelodysplasia-related (MR) gene mutations and internal tandem duplications of FLT3 (FLT3-ITD). METHODS: We include newly diagnosed de novo AML patients at our center from January 2017 to December 2021, regardless of the further treatment received. Clinical data and date of survival were included. Survival analysis were performed using the Kaplan-Meier method, and the log-rank test was used to compare survival between different risk groups. RESULTS: We include 363 newly diagnosed de novo AML patients from 2017 to 2021 to assess the accuracy of the ELN risk classification system. Their survival results show that the ELN-2022 risk classification system is not superior to the ELN-2017 version; for patients with FLT3-ITD mutations but without FLT3 inhibitor treatment, their survival is similar to the ELN-2022 adverse risk group. The ELN-2022 risk classification system cannot accurately clarify ECOG performance status (PS) 2-4 patients, especially in the ELN-2022 favorable risk group. CONCLUSION: The ELN-2022 risk stratification system may not be appropriate for patients unable to receive intensive therapy or FLT3 inhibitor; more real-world data is needed to straify patients with worse ECOG PS and inferior intensive therapy.

Neuroprotective potentials of ferulic acid against intracerebral hemorrhage COVID-19 through using network pharmacology approach and molecular docking analysis.

Intracerebral hemorrhage (ICH) refers to severe stroke subtype that may be life-threatening or even cause death. It is clinically observed that coronavirus disease 2019 (COVID-19) may be associated with the high mortality in ICH patients. Ferulic acid, one of the functional bioactive ingredients from medicinal herbs, has been preclinically proven with beneficial activities, including neuroprotection and anti-inflammation actions. Based on current findings, we assumed that ferulic acid may play the potentials against COVID-19 when ICH. In this study, preclinical approach including network pharmacology and molecular docking was applied to detect and identify the core targets and pharmacological mechanisms involved in ferulic acid on COVID-19 and ICH. The network pharmacology analysis identified total eleven core targets in ferulic acid and COVID-19/ICH. The molecular mechanisms of ferulic acid against COVID-19 and ICH were mostly involved in induction of antiviral activity, modulation of inflammatory reaction. Molecular docking model revealed that ferulic acid might effectively bind to epidermal growth factor receptor (EGFR) protein based on strong binding capability. Current findings reflected the preclinical pharmacological activities of ferulic acid that might use for management of COVID-19 and ICH. Although there are the limitations that are absence of experimental validation, these bioinformatic results underline that ferulic acid may exert simultaneous potentials against COVID-19 and ICH through modulating integrative mechanisms and key biotargets.

Dexamethasone enhances venetoclax-induced apoptosis in acute myeloid leukemia cells.

Acute myeloid leukemia (AML) therapies have been significantly improved by the development of medicines that can target BCL-2. On the other hand, non-recurrent alterations in oncogenic pathways and gene expression patterns have already been linked to therapeutic resistance to venetoclax therapy. Bone marrow mesenchymal stromal cells (BM-MSCs) support leukemic cells in preventing chemotherapy-induced apoptosis by mitochondrial transfer in leukemic microenvironment. In this study, we investigated the enhancement of the antitumor effect of BCL-2 inhibitor venetoclax by dexamethasone. In particular, dexamethasone had no significant effect on the viability of AML cells, but dexamethasone combined with venetoclax could significantly increase the apoptosis of AML cells induced by venetoclax. When AML cells were co-cultured with BM-MSCs, dexamethasone combined with venetoclax showed additional anti-tumor effect compared to venetoclax alone. Venetoclax increased reactive oxygen species level in co-cultured AML cells, contributed to transfer more mitochondria from BM-MSCs to AML cells and protect AML cells from apoptosis. Dexamethasone combined with venetoclax induced more apoptosis, but dexamethasone reduced the venetoclax-induced reactive oxygen species level in AML cells and reduced the transfer of mitochondria from BM-MSCs to AML cells. This may lead to a diminished protective effect of BM-MSCs on AML cells. Together, our findings indicated that venetoclax in combination with dexamethasone could be a promising therapy in AML.

A food poisoning caused by ST7 Staphylococcal aureus harboring sea gene in Hainan province, China.

ST7 Staphylococcus aureus is highly prevalent in humans, pigs, as well as food in China; however, staphylococcal food poisoning (SFP) caused by this ST type has rarely been reported. On May 13, 2017, an SFP outbreak caused by ST7 S. aureus strains occurred in two campuses of a kindergarten in Hainan Province, China. We investigated the genomic characteristics and phylogenetic analysis of ST7 SFP strains combined with the 91 ST7 food-borne strains from 12 provinces in China by performing whole-genome sequencing (WGS). There was clear phylogenetic clustering of seven SFP isolates. Six antibiotic genes including blaZ, ANT (4')-Ib, tetK, lnuA, norA, and lmrS were present in all SFP strains and also showed a higher prevalence rate in 91 food-borne strains. A multiple resistance plasmid pDC53285 was present in SFP strain DC53285. Among 27 enterotoxin genes, only sea and selx were found in all SFP strains. A ФSa3int prophage containing type A immune evasion cluster (sea, scn, sak, and chp) was identified in SFP strain. In conclusion, we concluded that this SFP event was caused by the contamination of cakes with ST7 S. aureus. This study indicated the potential risk of new emergencing ST7 clone for SFP.

Regeneration of Activated Sludge into SiO2-Decorated Heteroatom-Doped Porous Carbon as Advanced Electrodes for Li-S Batteries.

The regeneration of harmful activated sludge into an energy source is an important strategy for municipal sludge treatment and recycling. Herein, SiO2-modified N,S auto-doped porous carbon (NSC@SiO2) with high conductivity (70 S m-1) is successfully obtained through a simple calcination method of the activated sludge from wastewater treatment. Further, P-doped NSC@SiO2 (NSPC@SiO2) is designed to achieve a higher surface area (891 m2 g-1 vs 624 m2 g-1), a larger pore volume (0.87 cm3 g-1 vs 0.08 cm3 g-1), and more carbon defects. Due to its special structure, NSPC@SiO2 is used as a sulfur host of lithium-sulfur batteries. The results of polysulfide adsorption experiments, S 2p X-ray photoelectron spectra (XPS), Li2S nucleation experiments, polysulfide symmetric cells, measurement of the galvanostatic intermittent titration (GITT), polarization voltage difference, lithium-ion diffusion rate, and Tafel slope verified that NSPC@SiO2 greatly improved the adsorption capacity of polysulfides, lowered the barrier to Li2S formation and the internal resistances of cells, and accelerated Li+ ion diffusion and the reaction kinetics of polysulfide conversion, resulting in the excellent performance of polysulfide capture and superior rate performance and cyclic stability. By comparing NSPC@SiO2 with NSC@SiO2, a higher initial capacity (1377 mAh g-1 vs 1150 mAh g-1 at 0.1C), better rate capacity (912 mAh g-1 vs 719 mAh g-1 at 2C), and low capacity decay (0.094% per cycle within 200 cycles) are obtained. Our work provides direction for the treatment, disposal, and resource utilization of activated sludge.

TIM-3 Expression Level on AML Blasts Correlates With Presence of Core Binding Factor Translocations Rather Than Clinical Outcomes.

Background: T-cell immunoglobulin and mucin domain-containing molecule 3 (TIM-3) expresses on leukemic stem and progenitor populations of non-M3 acute myeloid leukemia (AML) as well as T lymphocytes. TIM-3 is thought to be involved in the self-renewal of leukemic stem cells and the immune escape of AML cells, however its correlation with AML prognosis is still controversial and worthy of further investigation. Methods: we simultaneously assessed TIM-3 expression levels of leukemic blasts and T lymphocytes in the bone marrow of de novo AML patients using flow cytometry. The correlations of TIM-3 expression between leukemic blasts and T lymphocytes and the correlations of TIM-3 expression with various patient parameters were analyzed. In addition, the Cancer Genome Atlas (TCGA) data of AML patients were acquired and analyzed to verify the results. Results: TIM-3 expression of CD34+ leukemic blasts (R2 = 0.95, p<0.0001) and CD34+CD38- leukemic stem cells (R2 = 0.75, p<0.0001) were significantly and positively correlated with that of the whole population of leukemic blasts. In addition, TIM-3 expression level of leukemic blasts correlated significantly and positively with that of CD8+ (R2 = 0.44, p<0.0001) and CD4+ (R2 = 0.16, p=0.0181) lymphocytes, and higher TIM-3 expression of leukemic blasts was significantly associated with a greater proportion of peripheral CD8+ T lymphocytes (R2 = 0.24, p=0.0092), indicating that TIM-3 on leukemic blasts might alter adaptive immunity of AML patients. Regarding clinical data, the presence of core binding factor (CBF) translocations was significantly correlated with higher TIM-3 expression of leukemic blasts (CBF versus non-CBF, median 22.78% versus 1.28%, p=0.0012), while TIM-3 expression levels of leukemic blasts were not significantly associated with the remission status after induction chemotherapy (p=0.9799), overall survival (p=0.4201) or event-free survival (p=0.9873). Similar to our results, TCGA data showed that patients with CBF translocations had significantly higher mRNA expression level of HAVCR2 (the gene encoding TIM-3) (median, 9.81 versus 8.69, p<0.0001), and as all patients in the cohort were divided into two groups based on the median HAVCR2 expression level, 5-year overall survivals were not significantly different (low versus high, 24.95% versus 24.54%, p=0.6660). Conclusion: TIM-3 expression level on AML blasts correlates with presence of CBF translocations rather than clinical outcomes.

Efficacy and safety of CD22-specific and CD19/CD22-bispecific CAR-T cell therapy in patients with hematologic malignancies: A systematic review and meta-analysis.

Background: CD22 single and CD19/CD22 bispecific targeted chimeric antigen receptor T (CAR-T) cell therapy are promising immunotherapy modalities for the treatment of hematologic malignancies. The aim of this study was to assess the efficacy and safety of CD22 and CD19/CD22 targeted CAR-T cell therapy by summarizing the existing evidence. Methods: Electronic databases including PubMed, Embase, and Scopus were comprehensively searched from inception up to November 30, 2022. Pooled response rates and minimal residual disease (MRD) negative response rates, cytokine release syndrome (CRS) rates and neurotoxicity rates were calculated. Subgroup analysis was performed based on the type of immunotherapy. Results: Ten clinical studies including 194 patients with hematologic malignancies were included after a systematical screening of literature. The pooled complete response (CR) rates of CD22 and CD19/CD22 CAR-T cell therapy for relapsed or refractory B-cell lymphoblastic leukemia (B-ALL) were 0.75 (95% CI: 0.60 - 0.88) and 0.87 (95% CI: 0.76 - 0.96). The overall MRD negative response rates of CD22 and CD19/CD22 CAR-T were 0.54 (95% CI: 0.42 - 0.66) and 0.91 (95% CI: 0.47 - 0.88). Pooled CRS rates of CD22 targeted and CD19/CD22 targeted immunotherapy were 0.92 (95% CI: 0.82 - 0.98) and 0.94 (95% CI: 0.82 - 1.00), respectively. Conclusion: Both CD22 and CD19/CD22 CAR-T immunotherapy demonstrated favorable efficacy and acceptable adverse events in the treatment of hematologic malignancies. Well-designed and large sample-sized clinical trials are warranted.

Exosomal LINC00355 derived from cancer-associated fibroblasts promotes bladder cancer cell resistance to cisplatin by regulating miR-34b-5p/ABCB1 axis.

Cisplatin resistance is a major challenge for bladder cancer (BC). Evidence indicates that exosome derived from cancer-associated fibroblasts (CAF-Exo) can promote chemotherapy resistance in various human tumors by delivering bioactive molecules. We have previously demonstrated that CAF-derived exosomal LINC00355 promotes BC cell proliferation and invasion. However, the underlying mechanisms are still unclear. In this study, we aimed to investigate the role and mechanisms of CAF-derived exosomal LINC00355 in BC cell resistance to cisplatin. Exosomes were isolated from normal fibroblasts (NFs) and BC tumor-derived CAFs, namely, NF-Exo and CAF-Exo. CAFs were transfected with si-Ctrl or si-LINC00355 and then different exosomes were isolated, namely, CAFsi-Ctrl-Exo and CAFsi-LINC00355-Exo. The human BC cell lines (T24 and 5367) were incubated with NF-Exo, CAF-Exo, CAFsi-Ctrl-Exo, and CAFsi-LINC00355-Exo in the presence of cisplatin. MTT proliferation assay and flow cytometric analysis showed that CAF-Exo promoted BC cell resistance to cisplatin and upregulated ABCB1 expression in BC cells by transferring LINC00355 to BC cells. Luciferase activity assay confirmed the interaction between miR-34b-5p and LINC00355 or ABCB1. qRT-PCR and western blot analysis further showed that LINC00355 sponged miR-34b-5p to upregulate ABCB1 expression. However, the promoting effects of CAF-Exo on BC cell resistance to cisplatin were abolished by miR-34b-5p overexpression and ABCB1 silencing. In conclusion, exosomal LINC00355 derived from CAFs promotes BC cell resistance to cisplatin by regulating the miR-34b-5p/ABCB1 axis.

[Significance of Detecting the Plasma Levels of MMP-13 in Patients with Multiple Myeloma].

OBJECTIVE: To study the significance of detecting the plasma level of matrix metalloproteinase-13(MMP-13) in patients with multiple myeloma(MM) and to investigate the correlation of MMP-13 levels in MM patients with myeloma bone disease(MBD). METHODS: The plasma level of MMP-13 was quantitatively analyzed in 53 newly diagnosed MM patients and 30 healthy controls by enzyme-linked immunosorbent assay(ELISA). Imaging examination was used to determine bone damage in patients with MM. At the same time, using a dual-energy X-ray absortionmetry(DXA), the bone mineral density was examined on vertebra L2 to L4 in the anteroposterior position and the proximal left femur in 17 MM patients and 15 healthy controls. RESULTS: The plasma level of MMP-13 in MM patients was significantly higher than that in the controls(P<0.01), and the MMP-13 level in MM patients with stage III of International Staging System(ISS) was significantly higher than that in patients with stage I-II(P<0.01). The MMP-13 level in MM patients without MBD was significantly higher than that in the controls(P<0.05). According to bone disease grading, 53 patients were divided into group A(bone grade 0-2, n=18)and group B(bone grade 3-4, n=35). Compared with group A, MMP-13 level group B was enhanced significantly (P<0.01). Further analyses revealed that the level of MMP-13 negatively correlated with the bone mineral density on L2 to L4, greater trochanter and Ward's triangle(r values were -0.693, -0.575 and -0.575, respectively, P<0.05), but not correlated with left femoral neck(r= -0.339)(P>0.05). CONCLUSION: The level of MMP-13 in MM patients is significantly high, and closely relates with ISS clinical stage, degree of MBD and the bone mineral density of MM patients. MMP-13 plays an important role in the development of MBD.

Determination of volatile organic compounds exhaled by cell lines derived from hematological malignancies.

Background: The gas human exhaled contains many volatile organic compounds (VOCs), which is related to the health status of body. Analysis of VOCs has been proposed as a noninvasive diagnostic tool for certain cancers. Detailed research on the VOCs in gas exhaled by cell can characterize cell type specific metabolites and may be helpful to detect the cancer markers in clinical practice.Methods: Solid-phase microextraction (SPME) gas chromatography-mass spectrometry was used to detect VOCs in the headspace of tissue culture flask in non-Hodgkin's lymphoma (NHL) cell line JEKO and acute mononuclear leukemia cell line SHI-1, to elaborate the characteristic gaseous biomarkers of hematological malignancies. While macrophage cells and lymphocytic cells were acted as control. The blank group was only the RPMI 1640 medium containing 10% fetal calf serum that without cells.Results: Comparing with control group, the concentration of dimethyl sulfide, 2,4-dimethylheptane, methylbenzene, o-xylene, dodecane, and 1,3-di-tert-butylbenzene in JEKO cells was relatively higher, while the concentration of ethanol, hexanal, and benzaldehyde was lower. In SHI-1 cells, the levels of 2,4-dimethylheptane, benzene, 4-methyldecane, chloroform, 3,7-dimethyl dodecane, and hexadecane were significantly elevated, but the levels of hexanol and cyclohexanol were distinctly reduced. CONCLUSIONS: This pilot study revealed that the malignant hematological cells could change the components of VOCs in the cell culture flask in a cell type-specific pattern. The traits of VOCs in our setting offered new strategy for hematological malignancies tracing, and would act as potential biomarkers in diagnosis of malignant hematological diseases.

Relationships among hope, coping style and social support for breast cancer patients.

BACKGROUND: Breast cancer is one of the most common cancers in women, and its incidence seems to have gradually increased every year. During the treatment of breast cancer, patients suffer psychological morbidity, and hope is one important factor in maintaining psychological health. Therefore, in this study, we investigated the level of hope in Chinese women with breast cancer during chemotherapy and confirmed the relationships among hope, coping style, and social support. METHODS: One hundred and fifty-nine inpatients with breast cancer who were undergoing chemotherapy in two affiliated hospitals of Harbin Medical University were recruited and investigated. Each patient completed the Herth Hope Index (HHI), Jalowiec Coping Scale (JCS), and the social support scale made by XIAO Shui-yuan, and provided general demographic data. RESULTS: The mean hope level of the 159 patients with breast cancer was 38.62 ± 4.56. There was a statistical difference between the hope level and monthly income. Analysis of results from the Pearson test showed no relationship between the hope level and coping style; however, there were positive relationships between hope and optimism, hope and self-reliance, and hope and palliative coping styles. In contrast, negative relationships were found between hope and the fatalistic and emotional coping styles. The total score of hope and social support had significantly positive relationship for the three scales. CONCLUSIONS: Patients with breast cancer achieved high levels of hope, with the level of hope being proportional to increase in the income. During chemotherapy, patients with breast cancer had adopted many coping styles.