Eltrombopag plus diacerein vs. eltrombopag in patients with ITP: a multicenter, randomized, open-label, phase 2 trial.

This study aimed to compare the efficacy and safety of eltrombopag plus diacerein vs. eltrombopag alone in patients with primary immune thrombocytopenia (ITP) who were previously unresponsive to 14 days of eltrombopag treatment at the full dose. Recruited patients were randomly assigned 1:1 to receive either eltrombopag plus diacerein (n=50) or eltrombopag monotherapy (n=52). Overall response rate, defined as a platelet count at or above 30×109/L, at least doubling of the baseline platelet count, and no bleeding, was reached in 44% of patients in the eltrombopag plus diacerein group compared with 13% in the eltrombopag group at day 15 (P = .0009), and reached in 42% of patients in the combination group compared with 12% in the monotherapy group at day 28 (P = .0006). The addition of diacerein to eltrombopag also led to a longer duration of response (P = .0004). The two most common treatment-emergent adverse events were respiratory infection and gastrointestinal reactions in the combination group, and fatigue and respiratory infection in the eltrombopag group. In conclusion, eltrombopag plus diacerein was well tolerated, and induced higher overall response rates and longer duration of response than eltrombopag alone, offering a rejuvenating salvage therapy for ITP patients unresponsive to 14 days of full dosage eltrombopag. Our work has the potential to enhance the care of patients treated with thrombopoietin receptor agonists, reducing the need for rapid transitions to less-preferable therapies. This study is registered at ClinicalTrials.gov as NCT04917679.

Vitamin D receptor gene polymorphisms and multiple myeloma: a meta-analysis.

Vitamin D acts through the vitamin D receptor (VDR), and vitamin D level decreases in multiple myeloma (MM) patients. Single nucleotide polymorphisms in VDR alter its functions to affect the vitamin D status. This raises the question of whether VDR gene polymorphisms are associated with MM risk, which has been investigated in case‒control studies, but the results have been inconsistent. This meta-analysis aimed to investigate the relationship between VDR gene polymorphisms and MM risk. The PubMed, Web of Science, Medline, Embase, Chinese National Knowledge Infrastructure (CNKI), Chinese Scientific Journal (VIP), Wanfang Databases (WANFANG) were searched from inception to June 1, 2023, without language restriction or publication preference. Pooled odds ratio (OR) and 95% confidence interval (CI) for each variable were calculated. Leave-one-out sensitivity analysis was performed to determine the source of heterogeneity. Publication bias was assessed using Begg' and Egger's tests, and the trim-and-fill method was used to compensate for publication bias. The correlation meta-analysis was conducted using Comprehensive Meta-Analysis 3.0 and STATA 12.0 software. All the included studies were based on Asian populations and involved four VDR gene polymorphisms, TaqI (rs731236), ApaI (rs7975232), BsmI (rs1544410) and FokI (rs2228570). The results showed that TaqI (C vs. T: OR = 1.487, 95% CI 1.052, 2.104, P = 0.025; CC + CT vs. TT: OR = 1.830, 95% CI 1.138, 2.944, P = 0.013), ApaI (T vs. G: OR = 1.292, 95% CI 1.101, 1.517, P = 0.002; TT vs. GG: OR = 1.600, 95% CI 1.106, 2.314, P = 0.013; TG vs. GG: OR 1.305, 95% CI 1.050, 1.622; P = 0.016; TT + TG vs. GG: OR = 1.353, 95% CI 1.103, 1.662, P = 0.004), BsmI (GG vs. AA: OR = 1.918, 95% CI 1.293, 2.844, P = 0.001; GA vs. AA: OR = 1.333, 95% CI 1.058, 1.679, P = 0.015; G vs. A: OR = 1.398, 95% CI 1.180, 1.657, P = 0.000; GG vs. AA + GA: OR = 1.686, 95% CI 1.174, 2.423, P = 0.005), and FokI (T vs. C: OR = 1.687, 95% CI 1.474, 1.931, P = 0.000; TT vs. CC: OR = 2.829, 95% CI 2.066, 3.872, P = 0.000; TC vs. CC: OR = 1.579, 95% CI 1.304, 1.913, P = 0.000, TT + TC vs. CC: OR = 1.771, 95% CI 1.477, 2.125, P = 0.000; TT vs. CC + TC: OR = 2.409, 95% CI 1.814, 3.200, P = 0.000) are associated with MM risk. VDR gene polymorphisms including ApaI, BsmI, TaqI, and FokI are associated with MM risk in Asian populations. Additional studies with large sample sizes and different ethnicities are needed.

Acupuncture in Multiple Myeloma Peripheral Neuropathy: A Systematic Review.

Background: Peripheral neuropathy (PN) is a prevalent complication of multiple myeloma (MM), due to the disease itself or its treatment. Despite extensive research, the optimal treatment for multiple myeloma peripheral neuropathy (MMPN) remains unclear. Clinical practice has shown the potential efficacy of acupuncture in managing MMPN. This study aimed to conduct a comprehensive analysis of the literature to assess the effectiveness and safety of acupuncture as a treatment for MMPN. Methods: The PubMed, Web of Science, MEDLINE, Cochrane Library, and Embase databases were comprehensively searched from inception to November 1, 2023 to identify relevant studies pertaining to the use of acupuncture to treat MMPN. Results: A total of five studies, encompassing 97 patients diagnosed with drug-related PN, were ultimately included in this analysis. The literature lacks any reports pertaining to the utilization of acupuncture for disease-related PN. ST36, LI4, SP6, and EX-LE-10 were found to be the most frequently chosen acupoints. Following acupuncture treatment, there was a consistent reduction in scores on the Visual Analogue Scale (VAS), Neuropathic Pain Scale (NPS), Brief Pain Inventory-Short Form (BPI-SF), and Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) among MMPN patients. The results of Nerve Conduction Velocity (NCV) tests yielded conflicting results. No severe adverse effects were reported. Conclusion: The use of acupuncture for disease-related PN has not been studied to date. Acupuncture is safe for drug-related PN and is helpful for relieving pain. But uncertainty exists regarding the efficacy of this approach because there is substantial heterogeneity with respect to acupuncture treatment regimens, and more high-quality studies on this topic are warranted.

Disease-controlled multiple myeloma in a patient with 17p gain and t(4;14): A case report.

Cytogenetic karyotypes such as t(4; 14), del(17p), t(14; 16), t(14; 20), and TP53 mutations are associated with high-risk multiple-myeloma (MM) and indicate poor prognosis. Therefore, cytogenetic testing is extremely important for determining prognosis of MM. However, the aberrant karyotypes reported in the current literature are incomplete. The cytogenetic karyotype 17p gain has not received widespread attention, and its relationship with MM prognosis is unknown; additionally, the prognosis of 17p gain associated with t(4; 14) has not been studied in depth. Therefore, we introduce a special case in which a patient had both 17p gain and t(4; 14). An 81-year-old woman was admitted to the Affiliated Hospital of Shandong University of Traditional Chinese Medicine for stomach discomfort. The patient had no relevant medical history. Laboratory tests, immunophenotyping, and haematological results suggested MM, and cytogenetic tests indicated 17p gain and t(4; 14) with no other abnormalities. She was treated with two different chemotherapeutic regimens and achieved very good partial response, but eventually experienced biochemical relapses after discontinuing therapy. However, she eventually achieved good disease control with a bortezomib, lenalidomide, and dexamethasone-based regimen; she has survived longer than 5 years, much longer than the 1 year reported for MM patients with t(4:14), and been progression-free more than 3 years. We use this case to explore the possible relationship between the 17p gain and prognosis of patients with MM, as well as the treatment of MM with high-risk cytogenetic karyotypes. This case enriches the clinical application of cytogenetic analysis and adds important indicators for the prognosis of MM patients.

Developments of Fms-like Tyrosine Kinase 3 Inhibitors as Anticancer Agents for AML Treatment.

BACKGROUND: FMS-like tyrosine kinase 3 (FLT3) is a commonly mutated gene in acute myeloid leukemia. As a receptor tyrosine kinase (RTK), FLT3 plays a role in the proliferation and differentiation of hematopoietic stem cells. As the most frequent molecular alteration in AML, FLT3 has drawn the attention of many researchers, and a lot of small molecule inhibitors targeting FLT3 have been intensively investigated as potential drugs for AML therapy. METHODS: In this paper, PubMed and SciFinder® were used as a tool; the publications about "FLT3 inhibitor" and "Acute myeloid leukemia" were surveyed from 2014 to the present with an exclusion of those published as patents. RESULTS: In this study, the structural characterization and biological activities of representative FLT3 inhibitors were summarized. The major challenges and future directions for further research are discussed. CONCLUSION: Recently, numerous FLT3 inhibitors have been discovered and employed in FLT3-mutated AML treatment. In order to overcome the drug resistance caused by FLT3 mutations, screening multitargets FLT3 inhibitors has become the main research direction. In addition, the emergence of irreversible FLT3 inhibitors also provides new ideas for discovering new FLT3 inhibitors.

Zinc Oxide Nanoparticles Trigger Autophagy in the Human Multiple Myeloma Cell Line RPMI8226: an In Vitro Study.

Multiple myeloma (MM) is a malignant clonal proliferative plasma cell tumor. Zinc oxide nanoparticles (ZnO NPs) are used for antibacterial and antitumor applications in the biomedical field. This study investigated the autophagy-induced effects of ZnO NPs on the MM cell line RPMI8226 and the underlying mechanism. After RPMI8226 cells were exposed to various concentrations of ZnO NPs, the cell survival rate, morphological changes, lactate dehydrogenase (LDH) levels, cell cycle arrest, and autophagic vacuoles were monitored. Moreover, we investigated the expression of Beclin 1 (Becn1), autophagy-related gene 5 (Atg5), and Atg12 at the mRNA and protein levels, as well as the level of light chain 3 (LC3). The results showed that ZnO NPs could effectively inhibit the proliferation and promote the death of RPMI8226 cells in vitro in a dose- and time-dependent manner. ZnO NPs increased LDH levels, enhanced monodansylcadaverine (MDC) fluorescence intensity, and induced cell cycle arrest at the G2/M phases in RPMI8226 cells. Moreover, ZnO NPs significantly increased the expression of Becn1, Atg5, and Atg12 at the mRNA and protein levels and stimulated the production of LC3. We further validated the results using the autophagy inhibitor 3-methyladenine (3­MA). Overall, we observed that ZnO NPs can trigger autophagy signaling in RPMI8226 cells, which may be a potential therapeutic approach for MM.

TERC haploid cell reprogramming: a novel therapeutic strategy for aplastic anemia.

The telomerase RNA component (TERC) gene plays an important role in telomerase-dependent extension and maintenance of the telomeres. In the event of TERC haploinsufficiency, telomere length is often affected; this, in turn, can result in the development of progeria-related diseases such as aplastic anemia (AA) and congenital keratosis. Cell reprogramming can reverse the differentiation process and can, therefore, transform cells into pluripotent stem cells with stronger differentiation and self-renewal abilities; further, cell reprograming can also extend the telomere length of these cells, which may be crucial in the diagnosis and treatment of telomere depletion diseases such as AA. In this study, we summarized the effects of TERC haploid cell reprogramming on telomere length and the correlation between this alteration and the pathogenesis of AA; by investigating the role of cell reprogramming in AA, we aimed to identify novel diagnostic indicators and therapeutic strategies for patients with AA.

Advances in understanding the role of dendritic cells in aplastic anaemia.

Aplastic anaemia (AA) is an autoimmune disease characterized by haematopoietic failure in the bone marrow. Abnormal activation and hyperfunction of T lymphocytes are believed to cause bone marrow damage, which plays a major role in AA pathogenesis. Dendritic cells (DCs) play a vital role in the immune system by processing antigens for presentation to T cells and regulating their differentiation and function. DC dysfunction may cause abnormal T-cell activation. Recent studies have associated the occurrence and development of AA with DC function. In this review, we have discussed the role of DCs in AA pathogenesis and their potential as putative therapeutic targets for AA.

Zinc oxide nanoparticles induce toxicity in diffuse large B-cell lymphoma cell line U2932 via activating PINK1/Parkin-mediated mitophagy.

Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoma. Zinc oxide (ZnO) nanoparticles have excellent anti-tumor properties in the biomedical field. The present study aimed to explore the underlying mechanism by which ZnO nanoparticles induce toxicity in DLBCL cells (U2932) via the PINK1/Parkin-mediated mitophagy pathway. After U2932 cells were exposed to various concentrations of ZnO nanoparticles, the cell survival rate, reactive oxygen species (ROS) generation, cell cycle arrest, and changes in the expression of PINK1, Parkin, P62, and LC3 were monitored. Moreover, we investigated monodansylcadaverine (MDC) fluorescence intensity and autophagosome and further validated the results using the autophagy inhibitor 3-methyladenine (3-MA). The results showed that ZnO nanoparticles could effectively inhibit the proliferation of U2932 cells and induce cell cycle arrest at the G0/G1 phases. Moreover, ZnO nanoparticles significantly increased ROS production, MDC fluorescence intensity, autophagosome formation, and the expression of PINK1, Parkin, and LC3, and decreased the expression of P62 in U2932 cells. In contrast, the autophagy level was reduced after the intervention of the 3-MA. Overall, ZnO nanoparticles can trigger PINK1/Parkin-mediated mitophagy signaling in U2932 cells, which may be a potential therapeutic approach for DLBCL.

Functions and regulatory mechanisms of resting hematopoietic stem cells: a promising targeted therapeutic strategy.

Hematopoietic stem cells (HSCs) are the common and essential precursors of all blood cells, including immune cells, and they are responsible for the lifelong maintenance and damage repair of blood tissue homeostasis. The vast majority (> 95%) of HSCs are in a resting state under physiological conditions and are only activated to play a functional role under stress conditions. This resting state affects their long-term survival and is also closely related to the lifelong maintenance of hematopoietic function; however, abnormal changes may also be an important factor leading to the decline of immune function in the body and the occurrence of diseases in various systems. While the importance of resting HSCs has attracted increasing research attention, our current understanding of this topic remains insufficient, and the direction of clinical targeted treatments is unclear. Here, we describe the functions of HSCs, analyze the regulatory mechanisms that affect their resting state, and discuss the relationship between resting HSCs and different diseases, with a view to providing guidance for the future clinical implementation of related targeted treatments.

POEMS syndrome: origination from clonal plasma cells or B cells?

OBJECTIVES: POEMS syndrome is a rare disorder which has been increasingly recognized. The clonal origin is controversial. Some people argue that POEMS syndrome originates from abnormal plasma cell clones. So, treatment frequently targets the plasma cell clone. Nevertheless, others believe that both plasma cells and B cells can be the potential culprit in POEMS syndrome. METHODS: A 65-year-old male came to the emergency department of our hospital with the complaints of bilateral soles numbness and weight loss for half a year, abdominal distension for half a month, and chest tightness and shortness of breath for one day. He was then diagnosed as POEMS syndrome complicated with monoclonal B-cell lymphocytosis (non-CLL type). A standard bendamustine plus rituximab (BR) regimen combined with low dose of lenalidomide was administered. RESULTS: After four cycles of treatment, the ascites of the patient was absent and the neurological symptom disappeared. The renal function, the IgA level, and the VEGF level all returned to normal. DISCUSSION: POEMS syndrome, a multi-system disorder, is easily misdiagnosed. The clonal origin of POEMS syndrome is controversial and needs further study. For now, there are no approved treatment regimens. Treatments mainly target the plasma cell clone. This case suggested that other therapy besides anti-plasma cell treatment may also be effective in POEMS syndrome. CONCLUSION: We report a patient with POEMS syndrome who achieved complete response after treatment with the combination of a standard BR regimen and low dose of lenalidomide. POEMS syndrome's pathological mechanisms and therapies warrant further studies.

[The Latest Research Progress of Selinexor in the Treatment of Non-Hodgkin Lymphoma --Review].

Non-Hodgkin lymphoma (NHL) is a common lymphoid hematological malignancy, the treatment and prognosis of NHL have always been the focus of clinical attention. Chemotherapy is the main first-line treatment, but there is still no effective treatment for patients with poor response to chemotherapy, recurrence or progression within a short period of time after treatment, and new and effective drugs need to be developed clinically. As the only clinically validated oral selective inhibitor of nuclear export (SINE), Selinexor has been approved for the treatment of relapsed/refractory diffuse large B-cell lymphoma and multiple myeloma, clinical attempts are being made to apply it to the treatment of other hematological malignancies.This article reviews the anti-tumor mechanism of Selinexor and the latest research progress in its application in NHL, and provides ideas for a more diverse, standardized and effective applications of Selinexor in NHL.

Nutritional assessment of patients with aplastic anemia: comparison of four nutritional screening tools / Evaluación nutricional de los pacientes con anemia aplásica: comparación de cuatro instrumentos de detección nutricional

Introduction: Nutritional status can affect the treatment of hospitalized patients, and Malnutrition can even lead to death. However, the Nutritional status of patients with aplastic anemia (AA) is unclear. Objective: to assess the Nutritional status of aplastic anemia patients with body mass index (BMI) ≥ 24 kg/m2 (high BMI group) and BMI < 24 kg/m2 (low BMI group), and to compare the consistency between different Nutritional screening tools. Methods: patients with aplastic anemia hospitalized from January 2016 to December 2020 were collected. We used the combined index generated by Nutritional Risk Index (NRI), Prognostic Nutritional Index (PNI), Control Nutritional Status (CONUT) and Instant Nutritional Assessment (INA) to assess Nutritional status of patients with aplastic anemia. Kappa index was used to measure the consistency between different Nutritional screening tools. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of different Nutritional screening tools. Results: one hundred and ninety-five patients with aplastic anemia were enrolled. The overall prevalence of Malnutrition calculated by the combined index in patients with aplastic anemia was 51.3 %. The Malnutrition rates of patients in the low BMI group and high BMI group were 60.9 % and 38.8 %, respectively. The Malnutrition rates of very severe aplastic anemia (VSAA) patients, severe aplastic anemia (SAA) patients and ordinary patients were 76 %, 63.8 % and 45.1 %, respectively. Compared with the combined index, NRI had the highest consistency and area under the curve. (AU)

Introducción: el estado nutricional puede afectar el tratamiento de los pacientes hospitalizados y la malnutrición puede incluso causar la muerte. Sin embargo, el estado nutricional de los pacientes con anemia aplásica (AA) no está claro. Objetivo: evaluar el estado nutricional de pacientes con anemia aplásica con índice de masa corporal (IMC) ≥ 24 kg/m2 (grupo de IMC mayor) e IMC < 24 kg/m2 (grupo de IMC inferior), y comparar la consistencia entre diferentes herramientas de cribado nutricional. Métodos: se recogieron datos de pacientes con anemia aplásica hospitalizados entre enero de 2016 y diciembre de 2020. El estado nutricional de los pacientes con anemia aplásica se evaluó utilizando un índice compuesto por el índice de riesgo nutricional (NRI), el índice de pronóstico nutricional (PNI), el índice de estado nutricional controlado (CONUT) y la evaluación nutricional instantánea (INA). El índice Kappa se utilizó para medir la coherencia entre los diferentes instrumentos de detección nutricional. Las curvas de características operativas de los sujetos (ROC) se utilizaron para evaluar el valor diagnóstico de las diferentes herramientas de detección nutricional. Resultados: un total de 195 pacientes con anemia aplásica fueron incluidos en el estudio. La prevalencia global de desnutrición calculada por el índice combinado en pacientes con anemia aplásica fue del 51,3 %. Las tasas de desnutrición de los pacientes en el grupo de bajo IMC y el grupo de alto IMC fueron 60,9 % y 38,8 %, respectivamente. Las tasas de desnutrición en pacientes con anemia aplásica muy grave (VSAA), anemia aplásica grave (SAA) y pacientes comunes fueron del 76 %, 63,8 % y 45,1 %, respectivamente. En comparación con el índice compuesto, NRI tiene la mayor consistencia y área bajo la curva. (AU)

The Latest Research Advances of Danggui Buxue Tang as an Effective Prescription for Various Diseases: A Comprehensive Review.

Danggui Buxue Tang (DBT) is composed of Astragali Radix and Angelicae Sinensis Radix in a weight ratio of 5:1. The recipe of the decoction is simple, and DBT has been widely used in the treatment of blood deficiency syndrome for more than 800 years in China. Studies on its chemical constituents show that saponins, flavonoids, volatile oils, organic acids, and polysaccharides are the main components of DBT. Many techniques such as third-generation sequencing, PCR-denaturing gradient gel electrophoresis, and HPLC-MS have been used for the quality control of DBT. DBT has a wide range of biological activities, including blood enhancement, antagonizing diabetic nephropathy, cardiovascular protection, immunity stimulation, estrogen-like effect, and antifibrosis, among others. In this paper, we summarize the recent research advances of DBT in terms of its components, pharmacological activities, and possible mechanisms of action as well as provide suggestions for further research.

High Expression of ACOT2 Predicts Worse Overall Survival and Abnormal Lipid Metabolism: A Potential Target for Acute Myeloid Leukemia.

Acyl-CoA thioesterase (ACOT) plays a considerable role in lipid metabolism, which is closely related to the occurrence and development of cancer, nevertheless, its role has not been fully elucidated in acute myeloid leukemia (AML). To explore the role of ACOT2 in AML and to provide a potential therapeutic target for AML, the expression pattern of ACOT was investigated based on the TNMplot, Gene Expression Profiling Interactive Analysis (GEPIA), and Cancer Cell Line Encyclopedia (CCLE) database, and diagnostic value, prognostic value, and clinical phenotype of ACOT were explored based on data from The Cancer Genome Atlas (TCGA). Functional annotation and enrichment analysis of the common targets between ACOT2 coexpressed and AML-related genes were further performed by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) analyses. The protein-protein interaction (PPI) network of ACOT2 coexpressed genes and functional ACOT2-related metabolites association network were constructed based on GeneMANIA and Human Metabolome Database. Among ACOTs, ACOT2 was highly expressed in AML compared to normal control subjects according to TNMplot, GEPIA, and CCLE database, which was significantly associated with poor overall survival (OS) in AML (P=0.003). Moreover, ACOT2 exhibited excellent diagnostic efficiency for AML (AUC: 1.000) and related to French-American-British (FAB) classification and cytogenetics. GO, KEGG, and GSEA analyses of 71 common targets between ACOT2 coexpressed and AML-related genes revealed that ACOT2 is closely related to ACOT1, ACOT4, enoyl-acyl carrier protein reductase, mitochondrial (MECR), puromycin-sensitive aminopeptidase (NPEPPS), SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 (SMARCB1), and long-chain fatty acid-CoA ligase 1 (ACSL1) in PPI network, and plays a significant role in lipid metabolism, that is, involved in fatty acid elongation and biosynthesis of unsaturated fatty acids. Collectively, the increase of ACOT2 may be an important characteristic of worse OS and abnormal lipid metabolism, suggesting that ACOT2 may become a potential therapeutic target for AML.

Realgar (As4S4), a traditional Chinese medicine, induces acute promyelocytic leukemia cell death via the Bcl-2/Bax/Cyt-C/AIF signaling pathway in vitro.

Acute promyelocytic leukemia (APL) is a specific subtype of acute myelogenous leukemia (AML) characterized by the proliferation of abnormal promyelocytes. Realgar, a Chinese medicine containing arsenic, can be taken orally. Traditional Chinese medicine physicians have employed realgar to treat APL for over a thousand years. Therefore, realgar may be a promising candidate for the treatment of APL. Nevertheless, the underlying mechanism behind realgar therapy is largely unclear. The present study aimed to investigate the effect of realgar on cell death in the APL cell line (NB4) in vitro and to elucidate the underlying mechanism. In this study, after APL cells were treated with different concentrations of realgar, the cell survival rate, apoptotic assay, morphological changes, ATP levels and cell cycle arrest were assessed. The expression of Bcl-2, Bax, Cytochrome C (Cyt-C) and apoptosis-inducing factor (AIF) at the mRNA and protein levels were also measured by immunofluorescence, quantitative PCR (qPCR) and Western blotting. We found that realgar could significantly inhibit APL cell proliferation and cell death in a time- and dose-dependent manner. Realgar effectively decreased the ATP levels in APL cells. Realgar also induced APL cell cycle arrest at the S and G2/M phases. Following realgar treatment, the mRNA and protein levels of Bcl-2 were significantly downregulated, whereas the levels of Bax, Cyt-C, and AIF were significantly upregulated. In summary, realgar can induce APL cell death via the Bcl-2/Bax/Cyt-C/AIF signaling pathway, suggesting that realgar may be an effective therapeutic for APL.

Clinical significance and potential mechanism of heat shock factor 1 in acute myeloid leukemia.

BACKGROUND: Heat shock factor 1 (HSF1) is now considered to have the potential to be used as a prognostic biomarker in cancers. However, its clinical significance and potential function in acute myeloid leukemia (AML) remain underexplored. METHODS: In this study, the expression pattern and clinical significance of HSF1 in AML were examined by integrating data from databases including The Cancer Genome Atlas (TCGA), The Genotype-Tissue Expression (GTEx), Vizome, Cancer Cell Line Encyclopedia (CCLE) and Gene Expression Omnibus (GEO). Linkedomics was applied to collect HSF1-related genes in AML. GeneMANIA was applied to outline HSF1-related functional networks. CancerSEA analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and Gene Set Enrichment Analysis (GSEA) were performed to mine the potential mechanism of HSF1 in leukemogenesis. Single-sample Gene Set Enrichment Analysis (ssGSEA) was applied to explore the correlation between HSF1 and infiltrating immune cells in AML. RESULTS: HSF1 expression was elevated in AML compared to healthy controls and indicate a poor overall survival. HSF1 expression was significantly correlated with patients age, associated with patient survival in subgroup of bone marrow blasts (%) >20. Functional analyses indicated that HSF1 plays a role in the metastatic status of AML, and is involved in inflammation-related pathways and biological processes. HSF1 expression was significantly correlated with the immune infiltration of nature killer cells and T cell population. CONCLUSION: HSF1 plays a vital role in the molecular network of AML pathogenesis, and has the potential to be a biomarker for prognosis prediction.

Nutritional assessment of patients with aplastic anemia: comparison of four nutritional screening tools.

Introduction: Introduction: nutritional status can affect the treatment of hospitalized patients, and malnutrition can even lead to death. However, the nutritional status of patients with aplastic anemia (AA) is unclear. Objective: to assess the nutritional status of aplastic anemia patients with body mass index (BMI) ≥ 24 kg/m2 (high BMI group) and BMI < 24 kg/m2 (low BMI group), and to compare the consistency between different nutritional screening tools. Methods: patients with aplastic anemia hospitalized from January 2016 to December 2020 were collected. We used the combined index generated by Nutritional Risk Index (NRI), Prognostic Nutritional Index (PNI), Control Nutritional Status (CONUT) and Instant Nutritional Assessment (INA) to assess nutritional status of patients with aplastic anemia. Kappa index was used to measure the consistency between different nutritional screening tools. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of different nutritional screening tools. Results: one hundred and ninety-five patients with aplastic anemia were enrolled. The overall prevalence of malnutrition calculated by the combined index in patients with aplastic anemia was 51.3 %. The malnutrition rates of patients in the low BMI group and high BMI group were 60.9 % and 38.8 %, respectively. The malnutrition rates of very severe aplastic anemia (VSAA) patients, severe aplastic anemia (SAA) patients and ordinary patients were 76 %, 63.8 % and 45.1 %, respectively. Compared with the combined index, NRI had the highest consistency and area under the curve. Conclusions: the nutritional status of patients with aplastic anemia was very poor; the more serious the disease, the worse the nutritional status. Although the malnutrition rate in the low-BMI group was higher than in the high BMI group, the nutritional status of overweight or obese patients can not be ignored. NRI is the best tool for assessing the nutritional status of patients with aplastic anemia.

Introducción: Introducción: el estado nutricional puede afectar el tratamiento de los pacientes hospitalizados y la malnutrición puede incluso causar la muerte. Sin embargo, el estado nutricional de los pacientes con anemia aplásica (AA) no está claro. Objetivo: evaluar el estado nutricional de pacientes con anemia aplásica con índice de masa corporal (IMC) ≥ 24 kg/m2 (grupo de IMC mayor) e IMC < 24 kg/m2 (grupo de IMC inferior), y comparar la consistencia entre diferentes herramientas de cribado nutricional. Métodos: se recogieron datos de pacientes con anemia aplásica hospitalizados entre enero de 2016 y diciembre de 2020. El estado nutricional de los pacientes con anemia aplásica se evaluó utilizando un índice compuesto por el índice de riesgo nutricional (NRI), el índice de pronóstico nutricional (PNI), el índice de estado nutricional controlado (CONUT) y la evaluación nutricional instantánea (INA). El índice Kappa se utilizó para medir la coherencia entre los diferentes instrumentos de detección nutricional. Las curvas de características operativas de los sujetos (ROC) se utilizaron para evaluar el valor diagnóstico de las diferentes herramientas de detección nutricional. Resultados: un total de 195 pacientes con anemia aplásica fueron incluidos en el estudio. La prevalencia global de desnutrición calculada por el índice combinado en pacientes con anemia aplásica fue del 51,3 %. Las tasas de desnutrición de los pacientes en el grupo de bajo IMC y el grupo de alto IMC fueron 60,9 % y 38,8 %, respectivamente. Las tasas de desnutrición en pacientes con anemia aplásica muy grave (VSAA), anemia aplásica grave (SAA) y pacientes comunes fueron del 76 %, 63,8 % y 45,1 %, respectivamente. En comparación con el índice compuesto, NRI tiene la mayor consistencia y área bajo la curva. Conclusiones: el estado nutricional de los pacientes con anemia aplásica es muy deficiente; a mayor gravedad de la enfermedad, peor estado nutricional. Aunque la tasa de malnutrición en el grupo con bajo IMC es mayor que en el grupo con alto IMC, no se puede pasar por alto el estado nutricional de los pacientes con sobrepeso u obesidad. El NRI es la mejor herramienta para evaluar el estado nutricional de los pacientes con anemia aplásica.

The Identification of APOBEC3G as a Potential Prognostic Biomarker in Acute Myeloid Leukemia and a Possible Drug Target for Crotonoside.

The apolipoprotein B mRNA editing enzyme catalytic subunit 3G (APOBEC3G) converts cytosine to uracil in DNA/RNA. Its role in resisting viral invasion has been well documented. However, its expression pattern and potential function in AML remain unclear. In this study, we carried out a bioinformatics analysis and revealed that the expression of APOBEC3G was significantly upregulated in AML, and high expression of APOBEC3G was significantly associated with short overall survival (OS). APOBEC3G expression was especially increased in non-M3AML, and correlated with the unfavorable cytogenetic risks. Additionally, Cox regression analyses indicated APOBEC3G is a hazard factor that cannot be ignored for OS of AML patients. In molecular docking simulations, the natural product crotonoside was found to interact well with APOBEC3G. The expression of APOBEC3G is the highest in KG-1 cells, and the treatment with crotonoside can reduce the expression of APOBEC3G. Crotonoside can inhibit the viability of different AML cells in vitro, arrest KG-1 and MV-4-11 cells in the S phase of the cell cycle and affect the expression of cycle-related proteins, and induce cell apoptosis. Therefore, APOBEC3G could be a potential drug target of crotonoside, and crotonoside can be considered as a lead compound for APOBEC3G inhibition in non-M3 AML.

The Extensive Regulation of MicroRNA in Immune Thrombocytopenia.

MicroRNA (miRNA) is a small, single-stranded, non-coding RNA molecule that plays a variety of key roles in different biological processes through post-transcriptional regulation of gene expression. MiRNA has been proved to be a variety of cellular processes involved in development, differentiation, signal transduction, and is an important regulator of immune and autoimmune diseases. Therefore, it may act as potent modulators of the immune system and play an important role in the development of several autoimmune diseases. Immune thrombocytopenia (ITP) is an autoimmune systemic disease characterized by a low platelet count. Several studies suggest that like other autoimmune disorders, miRNAs are deeply involved in the pathogenesis of ITP, interacting with the function of innate and adaptive immune responses. In this review, we discuss emerging knowledge about the function of miRNAs in ITP and describe miRNAs in terms of their role in the immune system and autoimmune response. These findings suggest that miRNA may be a useful therapeutic target for ITP by regulating the immune system. In the future, we need to have a more comprehensive understanding of miRNAs and how they regulate the immune system of patients with ITP.