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Introduction: The present study was to investigate the clinical role of miR-330-3p in acute cerebral infarction (ACI), including its diagnostic and prognostic potential. Preliminary exploration of its target genes was archived by bioinformatics analysis. Methods: miR-330-3p in plasma of the patients with ACI and controls were quantified by real-time quantitative PCR. The 1-month prognosis of the ACI patients was evaluated by the Glasgow Outcome Scale (GOS). The correlation between the plasma levels of miR-330-3p and the GOS scores was tested by Pearson correlation analysis. The receiver operating characteristic (ROC) curves were established based on the expression level of miR-330-3p in different groups. The miR-330-3p-targeting genes were analyzed using Venn diagram, protein-protein interaction network, and Gene Ontology enrichment analysis. Results: miR-330-3p was significantly increased in the plasma of ACI patients compared with that in healthy controls, and ROC curve revealed its diagnostic value for ACI. miR-330-3p was significantly increased in the plasma of patients with poor 1-month prognosis compared with those with good 1-month prognosis. miR-330-3p expression was negatively correlated with GOS score, suggesting its potential to predict the 1-month prognosis for ACI. One-year survival analysis revealed surviving patients had lower levels of miR-330-3p than the deceased. miR-330-3p was proven to predict the death of patients with ACI. The miR-330-3p-targeting genes were associated with synapse-related Gene Ontology terms. Conclusion: miR-330-3p was upregulated in the plasma of patients with ACI, making it a promising diagnostic and prognostic marker for patients with ACI. miR-330-3p could facilitate synaptic plasticity following cerebral infarction. [ABSTRACT FROM AUTHOR]

Hematological malignant tumors (HMTs) are serious diseases that threaten human health and life with high mortality. Therefore, it is necessary to develop novel strategies for diagnosis and treatment. Human endogenous retroviruses (HERVs) have recently attracted increasing attention as potential targets for cancer diagnosis and therapy. In this study, we explored the association between HERV-K expression levels and HMTs development. Clinical data and peripheral blood samples were collected from 236 leukemia, 384 lymphoma patients, and 69 healthy controls. Quantitative polymerase chain reaction was used to detect the expression of HERV-K gag, pol, and env genes in peripheral blood mononuclear cells or different cell subpopulations. Differently expressed HERV-K genes were further tested by using deep sequencing method, and further analyzed with gene ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. B cell- and T cell-related cytokines in patients were also detected by enzyme-linked immunosorbent assay (ELISA). The results showed that the expression levels of the HERV-K gag, pol, and env genes in patients were significantly higher than in healthy controls. There was a correlation between the expression level of HERV-K and the clinicopathological parameters of leukemia patients. HERV-K expression was increased in the B lymphocytes of leukemia and lymphoma patients, but not in the T cells or neutrophils. The GO and KEGG analyses showed that abnormal expression of the HERV-K locus in patients affected immune regulation. The analysis of cytokines proved that the B cell-related cytokines, including interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-10, tumor necrosis factor (TNF)-α, and interferon-gamma, were significantly decreased in patients, while the T cell-related cytokines, including IL-3, IL-12, and TNF-β, were not significantly changed. In conclusion, HERV-K genes might participate in the occurrence and development of leukemia and lymphoma, and might be biomarkers for the detection or evaluation of leukemia and lymphoma. [ABSTRACT FROM AUTHOR]

To date, the predictive role of laboratory indicators for the phenomenon of no flow is unclear. Hence, our objective was to conduct a meta‐analysis to investigate the association between laboratory parameters and the risk of the no‐reflow phenomenon in patients with ST‐elevation myocardial infarction (STEMI) following primary percutaneous coronary intervention (PCI). This, in turn, aims to offer valuable insights for early clinical prediction of no‐reflow. We searched Pubmed, Embase, and Cochrane Library from the establishment of the database to October 2023. We included case‐control or cohort study that patients with STEMI following primary PCI. We excluded repeated publication, research without full text, incomplete information or inability to conduct data extraction and animal experiments, reviews, and systematic reviews. STATA 15.1 was used to analyze the data. The pooled results indicated that elevated white blood cell (WBC) count (odds ratio [OR] = 1.061, 95% confidence interval [CI]: 1.013–1.112), neutrophil count (OR = 1.324, 95% CI: 1.128–1.553), platelet (PLT) (OR = 1.002, 95% CI: 1.000–1.005), blood glucose (OR = 1.005, 95% CI: 1.002–1.009), creatinine (OR = 1.290, 95% CI: 1.070–1.555), total cholesterol (TC) (OR = 1.022, 95% CI: 1.012–1.032), d‐dimer (OR = 1.002, 95% CI: 1.001–1.004), and fibrinogen (OR = 1.010, 95% CI: 1.005–1.015) were significantly associated with increased risk of no‐reflow. However, elevated hemoglobin was significantly associated with decreased risk of no‐reflow. In conclusion, our comprehensive analysis highlights the predictive potential of various parameters in assessing the risk of no‐reflow among STEMI patients undergoing PCI. Specifically, WBC count, neutrophil count, PLT, blood glucose, hemoglobin, creatinine, TC, d‐dimer, and fibrinogen emerged as significant predictors. This refined risk prediction may guide clinical decision‐making, allowing for more targeted and effective preventive measures to mitigate the occurrence of no‐reflow in this patient population. [ABSTRACT FROM AUTHOR]

Donor lymphocyte infusion (DLI) cures relapsed hematologic malignancies after allogeneic hematopoietic stem cell transplantation through the graft‐versus‐tumor (GVT) effect. Although the important role of magnesium in enhancing immunity has been mentioned in studies, limited clinical data have explored how magnesium affects the efficacy of DLI. Besides, although laboratory data demonstrate that magnesium can enhance CD8+ T cells effector function, whether magnesium regulates the tumor killing effect of peripheral blood mononuclear cells (PBMCs) remains to be explored. Here, for the retrospective study, we collected clinical data of relapsed patients receiving DLI and explored the relationship between different serum magnesium levels and patient outcomes. For in vitro studies, we investigated the effect of magnesium on the cytotoxicity of DLI cells which were PBMCs and preliminarily explored the mechanism. Eighty‐one patients were enrolled in this study. It was found that the high post‐DLI magnesium level was significantly associated with a higher incidence of complete remission (CR) or partial remission (CR/PR) and a higher possibility of survival. The magnesium level after DLI was an independent risk factor of overall survival. In vitro studies proved that increased magnesium enhanced the cytotoxic function of PBMCs on hematologic malignancies. Besides, magnesium modulated LFA‐1 headpiece opening. When blocking the integrin‐ligand interaction between LFA‐1 and ICAM‐1, the regulation effect of magnesium on PBMCs was weakened. Therefore, it was possible that magnesium regulated PBMCs effector function by stimulating LFA‐1. These results show that serum magnesium levels affect immunological responses mediated by donor lymphocytes in hematologic malignancies. [ABSTRACT FROM AUTHOR]

Acute graft‐versus‐host disease (aGVHD) causes significant morbidity and mortality. While most studies focus on classic or late aGVHD, some patients with previous aGVHD achieve complete remission and later develop another episode of aGVHD. Data on recurrence of aGVHD (RaGVHD) are lacking. This study aimed to identify the incidence, risk factors, and impacts of RaGVHD after T‐cell‐replete haploidentical hematopoietic cell transplantation (haplo‐HCT) without posttransplantation cyclophosphamide. We evaluated patients with RaGVHD after haplo‐HCT between 2017 and 2019 and compared their outcomes to those of patients with no aGVHD and those of patients with one episode of de novo aGVHD. Of 199 patients included in the analysis, 45 experienced 50 cases of RaGVHD with a 1‐year cumulative incidence of 19.0% (95% CI: 14.5–24.6). Grade III–IV aGVHD was more common in RaGVHD than in previous aGVHD (22.2% vs. 4.4%, p = 0.01). Female donor to male recipient was strongly associated with RaGVHD (HR: 2.5, p = 0.009). The most common death in patients with RaGVHD was GVHD‐related, which was different from controls who mostly died from relapse (p = 0.008). RaGVHD was an independent risk factor for chronic GVHD (HR: 2.6, p = 0.006) and nonrelapse mortality (HR: 2.4, p = 0.019) and a significant predictor of lower GVHD relapse‐free survival (HR: 1.9, p = 0.020) and cGVHD relapse‐free survival (HR: 2.1, p = 0.007). In conclusion, clinical manifestations and negative impacts of RaGVHD needs to be recognized independently. [ABSTRACT FROM AUTHOR]

Early T-cell precursor (ETP) lymphoblastic leukemia/lymphoma is a high-risk T lymphoblastic leukemia/lymphoma (T-ALL/LBL) subgroup. We performed a real-world multicenter study to explore the clinical characteristics and prognosis of adolescent and young adults (AYA) and older adult ETP leukemia/lymphoma. A total of 103 patients with ETP-ALL/LBL in five centers in China between January 2016 and February 2021 were included in this study. The median age was 29 years (range, 15–70 years). Next-generation sequencing was performed in 94 patients and revealed that NOTCH1 (35.1%, 33 cases) was the most frequently mutated gene, followed by JAK3 (16.0%, 15 cases), PHF6 (13.80%, 13 cases) and EZH2 (11.70%, 11 cases). Complete remission (CR) was obtained in 74.2% (72/97) of patients, and 6 relapsed/refractory patients received a decitabine combined with AAG priming regimen as reinduction therapy with a CR rate of 50%. With a median follow-up of 18 months (0.5–60 months), the 2-year overall survival (OS) and relapse-free survival (RFS) rates for the entire cohort were 54% and 57.7%, respectively. Allogeneic stem cell transplantation (allo-SCT) was performed in 59.8% (58/97) of patients. After landmark analysis at 6 months, the 2-year OS rates was 77% of patients with allo-SCT at CR1 and 25% of patients with chemotherapy alone (p < 0.001). A multivariate analysis suggested that allo-SCT and CR after the first course induction were independent prognostic factors for OS. Collectively, we reported the largest cohort study with AYA and older adult ETP-ALL/LBL, and we found that ETP-ALL/LBL was highly invasive and had a poor long-term prognosis. Allo-SCT could significantly improve ETP-ALL/LBL patient survival. [ABSTRACT FROM AUTHOR]

Acute myeloid leukemia (AML) is one of the most aggressive hematopoietic malignancies. Patients still suffer from refractory/relapsed disease after anthracycline-based therapy, which leads to a poor prognosis. N6-Methyladenosine (m6A) is the most abundant post-transcriptional modification in eukaryotes, the imbalance of which is reported to be associated with various pathological processes, including drug resistance. However, the relationship between m6A modification and drug resistance has not been well defined in AML. In this study, we analyzed the sequencing data of HL60 and its Adriamycin-resistant cell line HL60/ADR. We found a total of 40,550 m6A-methylated peaks, representing 15,640 genes in HL60, and 38,834 m6A-methylated peaks, representing 15,285 genes in HL60/ADR. KEGG pathway analysis showed that pathways were enriched in the FoxO signaling pathway, p53 signaling pathway, and Notch signaling pathway. MeRIP-seq results showed that the fold enrichment of the global m6A level in HL60/ADR was higher than that in HL60, and dot blot assay results indicated that the global m6A level was elevated in HL60/ADR cells compared with that in HL60 cells. Further analysis revealed that the expression level of METTL3 was elevated in HL60/ADR cells compared with that in HL60 cells. After a combined treatment of STM2457 (an inhibitor of METTL3) and Adriamycin, the proliferation of HL60/ADR was inhibited. Thus, we hypothesized that the abnormality of m6A modification played an important role in Adriamycin-resistant AML. [ABSTRACT FROM AUTHOR]

BACKGROUND: The correlation between intestinal microbiota and clinical outcomes after allogeneic hematopoietic stem cell transplantation (allo‐HCT) has been reported in platforms with T‐cell depletion or postcyclophosphamide‐based graft‐vs‐host disease (GVHD) prophylaxis regimens. It is still unclear whether it is the same in platforms of antithymocyte globulin (ATG)–based myeloablative allo‐HCT. METHODS: A total of 603 fecal specimens from 100 consecutive patients receiving allo‐HCT were collected between December 2018 and July 2020. Fetal samples were profiled with next‐generation sequencing of bacterial 16S ribosomal RNA (rRNA) genes. RESULTS: The diversity decreased to the lowest level at approximately day 12 after allo‐HCT and then increased over time. According to the diversity of 314 samples that were collected from 86 patients during the engraftment period, patients were grouped into the low‐ and high‐diversity groups. Two‐year overall survival in the high‐diversity group was significantly longer than that in the low‐diversity group (83.7% vs 60.6%, P =.026). Further analysis revealed that worse outcomes for patients with low diversity were associated with increased risk of worse outcomes for patients with low diversity (adjusted hazard ratio, 4.95; P =.046). Its association with relapse and GVHD was not found. Compositional analysis of fecal microbiota revealed that the abundance of bacteroides decreased greatly during allo‐HCT, whereas that of Enterococcus, Klebsiella, and Escherichia was found to be increased. CONCLUSIONS: This study indicates that gut dysbiosis in platforms of ATG‐based myeloablative allo‐HCT featured loss of bacterial diversity. The diversity of the intestinal flora at the engraftment period was an independent predictor of longer survival. LAY SUMMARY: The correlation between intestinal microbiota and clinical outcomes after allogeneic hematopoietic stem cell transplantation (allo‐HCT) is reported in platforms with T‐cell depletion or postcyclophosphamide‐based graft‐vs‐host disease (GVHD) prophylaxis regimens.It is still unclear whether it is the same pattern in platforms of antithymocyte globulin (ATG)–based T‐cell repletion myeloablative allo‐HCT.Our study indicated that gut dysbiosis in platforms of ATG‐based myeloablative allo‐HCT also features loss of bacterial diversity. The diversity of the intestinal flora at the engraftment period is an independent predictor of longer survival. Gut dysbiosis in platforms of antithymocyte globulin–based myeloablative allogeneic hematopoietic stem cell transplantation featured loss of bacterial diversity. The diversity of the intestinal flora at the engraftment period was an independent predictor of longer survival. [ABSTRACT FROM AUTHOR]

Background: Population-based studies have consistently showed an increased incidence of coronary heart disease and cardiac mortality in patients with type 2 diabetes mellitus (T2DM). Tongmai Jiangtang capsules (TJC) are Chinese patent medicines that have been approved in China for the treatment of diabetic vascular complications. However, the evidence supporting the efficacy of Tongmai Jiangtang capsules in type 2 diabetic coronary heart disease (T2DM-CHD) remains unclear. Herein, we designed a randomized, parallel-controlled clinical trial to investigate a new complementary therapy for T2DM-CHD patients. Methods: A total of 360 T2DM-CHD subjects (aged 18–75 years) will be randomly assigned to the TJC group or the placebo group at a 2:1 ratio. On the basis of western medicine therapy, all the participants will receive TJC or placebo, orally, three capsules/treatment, three per day for 12 weeks. The primary outcomes will be assessed according to the Canadian Cardiovascular Society (CCS) classification. All statistical analyses will be performed setting a two-sided 0.05 significance level, using SAS 9.4 statistical software. Discussion: The efficacy of TJC for the treatment of T2DM-CHD patients will be evaluated. The study will provide reliable clinical research evidence for application of TJC in treating T2DM-CHD patients. Clinical Trial Registration: https://www.chictr.org.cn/enIndex.aspx, Chinese Clinical Trial Registry ChiCTR2000037491. [ABSTRACT FROM AUTHOR]

Relapse is the main cause of treatment failure for leukaemia patients with unfavourable gene mutations who receive allogeneic haematopoietic stem cell transplantation (allo‐HSCT). There is no consensus on the indication of donor lymphocyte infusion (DLI) for prophylaxis of relapse after allo‐HSCT. To evaluate the tolerance and efficacy of prophylactic DLI in patients with unfavourable gene mutations such as FLT3‐ITD, TP53, ASXL1, DNMT3A or TET2, we performed a prospective, single‐arm study. Prophylactic use of decitabine followed by DLI was planned in patients with TP53 or epigenetic modifier gene mutations. The prophylaxis was planned in 46 recipients: it was administered in 28 patients and it was not administered in 18 patients due to contraindications. No DLI‐associated pancytopenia was observed. The cumulative incidences of grade II–IV and III–IV acute graft‐versus‐host disease (GVHD) at 100 days post‐DLI were 25.8% and 11.0%, respectively. The rates of chronic GVHD, non‐relapse mortality and relapse at 3 years post‐DLI were 21.6%, 25.0% and 26.1%, respectively. The 3‐year relapse‐free survival and overall survival (OS) rates were 48.9% and 48.2%, respectively. Acute GVHD (HR: 2.30, p = 0.016) and relapse (HR: 2.46, p = 0.003) after DLI were independently associated with inferior OS. Data in the current study showed the feasibility of prophylactic DLI with/without decitabine in the early stage after allo‐HSCT in patients with unfavourable gene mutations. [ABSTRACT FROM AUTHOR]

Background: Acute myeloid leukemia (AML) is a heterogeneous disease of the hematopoietic system, for which identification of novel molecular markers is potentially important for clinical prognosis and is an urgent need for treatment optimization. Methods: We selected C-type lectin domain family 11, member A (CLEC11A) for study via several public databases, comparing expression among a variety of tumors and normal samples as well as different organs and tissues. To investigated the relationship between CLEC11A expression and clinical characteristics, we derived an AML cohort from The Cancer Genome Atlas (TCGA); we also investigated the Bloodspot and HemaExplorer databases. The Kaplan-Meier method and log-rank test were used to evaluate the associations between CLEC11A mRNA expression, as well as DNA methylation, and overall survival (OS), event-free survival (EFS), and relapse-free survival (RFS). DNA methylation levels of CLEC11A from our own 28 de novo AML patients were assessed and related to chemotherapeutic outcomes. Bioinformatics analysis of CLEC11A was carried out using public databases. Results: Multiple public databases revealed that CLEC11A expression was higher in leukemia. The TCGA data revealed that high CLEC11A expression was linked with favorable prognosis (OS p -value = 2e-04; EFS p -value = 6e-04), which was validated in GSE6891 (OS p -value = 0; EFS p -value = 0; RFS p -value = 2e-03). Methylation of CLEC11A was negatively associated with CLEC11A expression, and high CLEC11A methylation level group was linked to poorer prognosis (OS p -value = 1e-02; EFS p -value = 2e-02). Meanwhile, CLEC11A hypermethylation was associated with poor induction remission rate and dismal survival. Bioinformatic analysis also showed that CLEC11A was an up-regulated gene in leukemogenesis. Conclusion: CLEC11A may be used as a prognostic biomarker, and could do benefit for AML patients by providing precise treatment indications, and its unique gene pattern should aid in further understanding the heterogeneous AML mechanisms. [ABSTRACT FROM AUTHOR]

Chidamide, a novel histone deacetylase inhibitor, has exerted effects in T-cell tumors through various mechanisms. Seventeen patients with refractory or relapsed T-cell acute lymphoblastic lymphoma/leukemia (T-LBL/ALL) received Chidamide combined with chemotherapy as salvage treatment. Historical data was analyzed as comparison as chemotherapy group. Complete response (CR) rate and overall response rate (ORR) of Chidamide + chemotherapy group were higher than that of chemotherapy group after one course. Chidamide + chemotherapy group had a better progress-free survival (PFS) compared to chemotherapy group. No difference in overall survival (OS) was observed. Grade 3/4 nonhematological adverse events (>10%) of patients in Chidamide + chemotherapy group included febrile neutropenia (64.7%), drug-induced liver failure (17.6%), decreased fibrinogen (11.8%), sepsis (11.8%), pneumonitis (11.8%), and oral mucositis (11.8%). This study demonstrates that Chidamide included regimen may be a new treatment strategy with an acceptable safety profile for refractory or relapsed T-LBL/ALL patients but requires further investigation. [ABSTRACT FROM AUTHOR]

Purpose: The chemotherapeutic regimen DCAG (decitabine with cytarabine, aclarubicin hydrochloride, and granulocyte colony-stimulating factor) is effective for elderly patients with acute myeloid leukemia, but recommendations for young patients remain controversial. This study investigated the tolerance and efficacy of DCAG for patients with newly diagnosed acute myeloid leukemia (aged 14–60 years). The clinical features or molecular markers that may predict response to DCAG were identified. Patients and methods: One-hundred sixty-one consecutive patients with newly diagnosed acute myelogenous leukemia received DCAG or standard (idarubicin plus cytarabine, IA) induction chemotherapy (n=64 and 97, respectively). Results: The rates of complete remission after the first cycle, overall survival (OS), and event-free survival (EFS) were comparable. After the second cycle, the complete remission rate of the DCAG group (54.7%) was significantly lower than that of the reference (78.35%, P=0.005). The following were associated with significantly worse OS, and EFS, in the DCAG group: Eastern Cooperative Oncology Group (ECOG) score ≥3 and no response after the second induction therapy; and FLT3-ITD. The multivariate analysis showed the DCAG group with significantly shorter OS associated with ECOG ≥3 and FLT3-ITD. In the DCAG group, after the first cycle of induction chemotherapy the median recovery times of neutrophils and platelets were 15.8 and 13 days. Conclusion: The DCAG and IA groups were similar with regard to complete remission rate after the first cycle, OS, and EFS. The complete remission rate after the second cycle of the DCAG was significantly lower than that of the IA. Grade 4 neutropenia and thrombocytopenia were a major adverse event associated with DCAG. [ABSTRACT FROM AUTHOR]