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Severe coronavirus disease 2019 (COVID-19) is commonly complicated with coagulopathy, the difference of coagulation features between severe pneumonia induced by SARS-CoV2 and non-SARS-CoV2 has not been analyzed. Coagulation results and clinical features of consecutive patients with severe pneumonia induced by SARS-CoV2 (COVID group) and non-SARS-CoV2 (non-COVID group) in Tongji hospital were retrospectively analyzed and compared. Whether patients with elevated D-dimer could benefit from anticoagulant treatment was evaluated. There were 449 COVID patients and 104 non-COVID patients enrolled into the study. The 28-day mortality in COVID group was approximately twofold of mortality in non-COVID group (29.8% vs. 15.4%, P = 0.003), COVID group were older (65.1 ± 12.0 vs. 58.4 ± 18.0, years, P < 0.001) and with higher platelet count (215 ± 100 vs. 188 ± 98, ×109/L, P = 0.015), comparing to non-COVID group. The 28-day mortality of heparin users were lower than nonusers In COVID group with D-dimer > 3.0 μg/mL (32.8% vs. 52.4%, P = 0.017). Patients with severe pneumonia induced by SARS-CoV2 had higher platelet count than those induced by non-SARS-CoV2, and only the former with markedly elevated D-dimer may benefit from anticoagulant treatment.

Acute myeloid leukemia (AML) is the most prevalent form of leukemia among adults, characterized by aggressive behavior and significant genetic diversity. Despite decades of reliance on conventional chemotherapy as the mainstay treatment, patients often struggle with achieving remission, experience rapid relapses, and have limited survival prospects. While intensified induction chemotherapy and allogeneic stem cell transplantation have enhanced patient outcomes, these benefits are largely confined to younger AML patients capable of tolerating intensive treatments. DNMT3A, a crucial enzyme responsible for establishing de novo DNA methylation, plays a pivotal role in maintaining the delicate balance between hematopoietic stem cell differentiation and self-renewal, thereby influencing gene expression programs through epigenetic regulation. DNMT3A mutations are the most frequently observed genetic abnormalities in AML, predominantly in older patients, occurring in approximately 20–30% of adult AML cases and over 30% of AML with a normal karyotype. Consequently, the molecular underpinnings and potential therapeutic targets of DNMT3A mutations in AML are currently being thoroughly investigated. This article provides a comprehensive summary and the latest insights into the structure and function of DNMT3A, examines the impact of DNMT3A mutations on the progression and prognosis of AML, and explores potential therapeutic approaches for AML patients harboring DNMT3A mutations.

T-cells are a core component of tumor immunotherapy because of their potent ability to identify and kill cancer cells. Yet efficacy is limited by exhaustion, senescence, metabolic dysregulation, an immunosuppressive tumor microenvironment (TME), and limited persistence. This review analyzed these key issues and proposed targeted improvement strategies. Emerging approaches encompass pharmacological modulation of T cell activation and survival pathways, epigenetic reprogramming to reverse exhaustion and senescence, metabolic engineering, combinatorial targeting of immunosuppressive TME components and advanced genetic tools, notably CRISPR-Cas9–based CAR-T optimization, which exemplifies how precise genome editing can enhance therapeutic efficacy. We review the progress and prospects of T-cell improvement strategies in tumor immunotherapy, emphasizing the need for further exploration to enhance the broader application and long-term efficacy of T-cell therapies. This review highlights recent advances and future directions in T-cell engineering, metabolic modulation, and microenvironment targeting, aiming to translate innovations into effective cancer immunotherapies.

Background Acute myeloid leukemia (AML), as the most common subtype of leukemia in adults, is characterised by rapid progression and poor prognosis. In the context of the rapid development of medical technology and the complexity of social factors, a detailed report describing the latest epidemiological patterns of AML is important for decision makers to allocate healthcare resources effectively. Methods Our research utilized the latest data sourced from the Global Burden of Disease (GBD) 2021. To delineate the burden of AML, we comprehensively described the incidence, deaths, disability-adjusted life years (DALYs), and the associated age-standardized rates per 100,000 persons (ASR) spanning from 1990 to 2021 stratifies according to age, sex, socio-demographic index (SDI), and nationality. Additionally, we extracted and analyzed data about the risk factors that contribute to AML-related deaths and DALYs. Results According to our study, the incidence of AML has continued to rise globally from 79,372 in 1990 to 144,645 in 2021 and AML affected the male and the elderly populations disproportionately. Furthermore, there was a significant positive correlation between the burden of AML and the SDI value. Developed nations generally exhibited higher age-standardized incidence rate, age-standardized death rate, and age-standardized disability-adjusted life year rate than the developing nations. We also analyzed the prevalence of smoking, high body mass index, and occupational benzene and formaldehyde exposure in the AML population in different SDI regions. Moreover, smoking and high body mass index were more prevalent in developed countries, whereas occupational exposure to these chemicals was the predominant risk factor in developing countries. Conclusion The global burden of AML has increased over the past 32 years, with rising morbidity and mortality. The incidence of AML is differentially distributed across different SDI countries or regions. AML incidence is higher in the elderly and in men. The proportions of smoking, high body mass index, and occupational exposure to benzene and formaldehyde varied by region. The findings highlight the need for region-specific prevention and call for future research on preventive strategies and new treatments to lower AML incidence and improve patient outcomes.

Background: Markedly elevated D-dimer levels can occur in emergency patients with various clinical situations, and is likely to indicate the presence of coagulopathy, rapid differential diagnosis was crucial for them. Methods: D-dimer was detected in consecutive 813 patients entering the emergency department of our hospital, for the patients with D-dimer levels above 5.0 µg/mL, the final diagnoses and 28-day mortality were confirmed, and the levels of thrombomodulin (TM), thrombin-antithrombin complex (TAT) and plasmin-antiplasmin complex (PAP) on admission were detected. Results: There were 148 emergency patients with D-dimer levels higher than 5.0 µg/mL mainly due to sepsis, malignancy, trauma, venous thromboembolism (VTE), cerebrovascular accident, and so on. Both of the TM and TAT levels among these diagnoses were significantly different ( p  < 0.001). The elevated TM (>13.3 TU/mL) had a predictive value of 96.0% for excluding VTE, and the normal TM had a predictive value of 90.4% for excluding sepsis. The overall 28-day mortality of these patients with D-dimer >5.0 ug/mL was 14.2%, the TAT level on admission was independently associated with 28-day mortality (odds ratio 1.014, 95% CI 1.001–1.027, P  = 0.030). Conclusions: The medical emergencies associated with markedly elevated D-dimer levels were revealed, specific markers of endothelial dysfunction and thrombin generation measured by automatic analyzer have the potential to distinguish diagnoses and predict outcomes in these patients.

Chimeric antigen receptor T-cell (CAR-T) therapy has shown remarkable effects in treating various hematological malignancies. However, hematotoxicity, specifically neutropenia, thrombocytopenia, and anemia, poses a serious threat to patient prognosis and remains a less focused adverse effect of CAR-T therapy. The mechanism underlying lasting or recurring late-phase hematotoxicity, long after the influence of lymphodepletion therapy and cytokine release syndrome (CRS), remains elusive. In this review, we summarize the current clinical studies on CAR-T late hematotoxicity to clarify its definition, incidence, characteristics, risk factors, and interventions. Owing to the effectiveness of transfusing hematopoietic stem cells (HSCs) in rescuing severe CAR-T late hematotoxicity and the unignorable role of inflammation in CAR-T therapy, this review also discusses possible mechanisms of the harmful influence of inflammation on HSCs, including inflammatory abrasion of the number and the function of HSCs. We also discuss chronic and acute inflammation. Cytokines, cellular immunity, and niche factors likely to be disturbed in CAR-T therapy are highlighted factors with possible contributions to post-CAR-T hematotoxicity.

Purpose Quercetagetin, a flavonoid derived from the natural herb Flos eriocauli, is used in traditional Chinese medicine for its fire-purging (anti-inflammation) and wind-expelling (pain-alleviating) properties. However, its potential effects concerning rheumatoid arthritis (RA) remain underexplored. This study was designed to elucidate the potential associations between Quercetagetin and RA, establishing the therapeutic potential of Quercetagetin and related mechanisms in RA treatment. Methods Network pharmacology was conducted to decipher related targets and signaling pathways between Quercetagetin and RA. In vitro assays were then conducted to explore the effects of Quercetagetin on osteoclast cell behaviors and corresponding signaling pathways. In vivo study further validated the therapeutic effect of Quercetagetin in collagen antibody-induced arthritis (CAIA) mice. Results The network pharmacological analysis indicated an intimate correlation of Quercetagetin with RA-related inflammatory osteolysis treatment. Pertaining to biological validations, 2 µM of Quercetagetin successfully inhibited LPS-driven osteoclast differentiation and function. qPCR assay and Western blot analyses denoted parallel changes in osteoclastic marker genes and proteins. Further mechanism study uncovered the effect of Quercetagetin in stimulating the Nrf2/Keap1 signaling pathway and moderating the Pten/AKT/Nfatc1 axis in osteoclasts. In vivo study revealed 40 mg/kg Quercetagetin every day could significantly relief joint destruction in CAIA mice. Conclusions Our study presents Quercetagetin ‘s therapeutic potential in treating RA, outlining its effects and potential mechanisms in suppressing LPS-induced osteoclast activity, and alleviating inflammatory bone destruction in CAIA model, thereby laying the groundwork for further translational research on Quercetagetin and Flos eriocauli in RA treatment. Highlights Quercetagetin extracted from Flos eriocauli displayed brilliant anti-osteoclast and anti-inflammation potential during rheumatoid arthritis. Quercetagetin significantly repressed lipopolysaccharide-stimulated osteoclast behavior from phenotypical and molecular level. Quercetagetin mitigated inflammatory bone destruction in collagen antibody-induced arthritis.

Background Rapid and accurate identification of carbapenemase-producing organism (CPO) intestinal carriers is essential for infection prevention and control. Molecular diagnostic methods can produce results in as little as 1 h, but require special instrumentation and are expensive. Therefore, it is urgent to find an alternative method. The broth enrichment-multiplex lateral flow immunochromatographic assay was recently reported, but using it to directly detect CPO intestinal carriers in rectal swabs still requires the evaluation of many samples. The aim of this study was to compare the performance of these two methods, and to explore the control measures of CPO infection. Methods Through CPO selective culture, PCR and DNA sequencing, 100 rectal swabs confirmed to be CPO-positive and 100 rectal swabs with negative results were collected continuously. After eluting the rectal swabs with saline, three aliquots were used: one for counting, one for detection by Xpert Carba-R, and one for culture in broth for 0 h, 1 h, 2 h, 3 h and 4 h, followed by NG-Test CARBA 5 assessment. The sensitivity and specificity of the NG-Test CARBA 5 method after different incubation times were calculated. The limit of detection (LoD) of this assay after 4 h broth incubation was estimated by examining the bacterial suspensions and simulated faecal suspensions prepared with CPOs producing different types of carbapenemases. Results Xpert Carba-R demonstrated a combined sensitivity of 99.0% and specificity of 98.0%. The sensitivity and specificity were higher than 90.0% for the different enzyme types. The specificities of five common carbapenemases detected by the broth enrichment NG-Test CARBA 5 combined method after different incubation times were 100%. The sensitivities increased with increasing incubation time. At 4 h, the Klebsiella pneumoniae carbapenemase (KPC), New Delhi metallo-beta-lactamase (NDM), imipenemase (IMP), Verona integron-encoded metallo-beta-lactamase (VIM), and oxacillinase (OXA) -48 detection sensitivities were 93.0%, 96.3%, 100%, 100% and 85.7%, respectively. The LoDs were between 10 2 and 10 4  CFU/mL for all five enzymes after 4 h of incubation. Conclusions This investigation highlighted that the broth enrichment-multiplex lateral flow immunochromatographic assay can be used as a new method for screening CPOs in rectal swabs.