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Immunoglobulin A nephropathy (IgAN), the most common primary renal disease, is characterized by abnormal IgA1 deposition. IgAN is caused by NOD-like receptor pyrin domain-containing-3 (NLRP3), which regulates innate immunity. Gubentongluo (GB) decoction, a traditional Chinese medicine, is an effective clinical treatment for IgAN in China. However, little is known about the underlying mechanisms. In this study, IgA1, which is separated from patients with IgAN, together with GB decoction was applied to treat human mesangial cells (HMCs). CCK-8 and the enzyme-linked immunosorbent assay were used to assess cell proliferation and the production of interleukin-1β (IL-1β), respectively. qPCR and Western blot were applied to detect the expression levels of NLRP3, IL-1β, and caspase-1. Our results showed that GB decoction inhibited IgA1-induced cell proliferation and IL-1β production. Furthermore, IgA1-induced upregulation of IL-1β, NLRP3, and caspase-1 was reduced after treatment with GB. Interestingly, MCC950, an NLRP3 inhibitor, showed similar effect as GB decoction. Additionally, NLRP3 overexpression stimulated cell proliferation, IL-1β secretion, and the expressions of IL-1β and caspase-1 in HMCs. But these effects could be alleviated by GB decoction. In conclusion, GB may play a protective role in IgAN cell model by inhibiting NLRP3. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has spread rapidly and significantly impacted most countries in the world. Providing an accurate forecast of COVID-19 at multiple scales would help inform public health decisions, but recent forecasting models are typically used at the state or country level. Furthermore, traditional mathematical models are limited by simplifying assumptions, while machine learning algorithms struggle to generalize to unseen trends. This motivates the need for hybrid machine learning models that integrate domain knowledge for accurate long-term prediction. We propose a three-layer, geographically informed ensemble, an extensive peer-learning framework, for predicting COVID-19 trends at the country, continent, and global levels. As the base layer, we develop a country-level predictor using a hybrid Graph Attention Network that incorporates a modified SIR model, adaptive loss function, and edge weights informed by mobility data. We aggregated 163 country GATs to train the continent and world MLP layers of the ensemble. Our results indicate that incorporating quantitatively accurate equations and real-world data to model inter-community interactions improves the performance of spatio-temporal machine learning algorithms. Additionally, we demonstrate that integrating geographic information (continent composition) improves the performance of the world predictor in our layered architecture. [ABSTRACT FROM AUTHOR]

Optimal post-remission treatment for individual favorable and intermediate risk acute myeloid leukemia (AML) patients has not yet been established. Human leukocyte antigen (HLA)-mismatched stem cell microtransplantation (MST), may improve outcomes and avoid graft-versus-host disease in patients with first complete remission of AML. We retrospectively analyzed the efficacy, safety, and survival of 63 patients with favorable- or intermediate-risk AML who received MST, autologous stem cell transplantation (ASCT), or cytarabine single agent (CSA) as post-remission treatment from January 2014 to August 2021. The neutrophil recovery time was shorter in the MST group than in the CSA group. The 2-year cumulative incidences of relapse in the MST, ASCT, and CSA groups were 27.27%, 29.41%, and 41.67%, respectively. During follow-up, 21 patients (33.30%) died of relapse, including six (9.52%), five (7.94%), and 10 (15.84%) in the MST, ASCT, and CSA groups, respectively. The estimated 2-year overall survival (OS) and relapse-free survival (RFS) were 62.20% vs. 50.00% (P = 0.101) and 57.10% vs. 50.00% (P = 0.136), in the >60 years MST and CSA groups (P = 0.101). The estimated 2-year OS was 100%, 66.20%, and 69.10% in the MST, ASCT, and CSA groups (MST vs CSA, P = 0.044), meanwhile, the estimated 2-year RFS was 100%, 65.40%, and 59.80% in patients ≤60 years. MST, ASCT, and CSA are acceptable post-remission treatments for patients with favorable- and intermediate-risk AML and may not only improve the prognosis of the elderly but also prolong the OS and RFS of favorable- or intermediate-risk patients ≤60 years. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the incidence and prognostic significance of common cytogenetic and molecular abnormalities in patients with TP53-mutated and non-TP53-mutated acute myeloid leukemia (AML). We retrospectively analyzed the clinical data of 326 patients with newly diagnosed AML hospitalized in our institution between October 2015 and June 2021. Classification variables were reported as percentages and compared by χ2 tests. Survival rates were evaluated by the Kaplan-Meier method. The incidence of TP53 mutations in AML patients in this clinic was 9.8%, of whom 87.5% patients were over 50 years old. The common concurrent mutations of TP53 were DNMT3A, IDH2, NRAS and TET2. Patients with a TP53 variant allele frequency (VAF) ≤ 40% had better overall survival (OS) than patients with a VAF >40%. Compared with non-TP53-mutated patients, significantly more TP53-mutated patients were gene-fusion negative, +mar, – 7/del (7q), – 5/del (5q), – 17/17p-, – 12/12p-, incomplete (inc) karyotype, or complex karyotype (CK), and had FLT3-ITD or IDH2 mutations, as well as a lower complete remission (CR) rate (31.3%) and higher recurrence rate (80.0%). The 2-year OS rates of TP53-mutated and non-TP53-mutated patients were 18.8% and 47.3%, respectively (P < 0.001). Univariate analysis showed that non-TP53-mutated patients with MLL family gene fusion, +mar or – 17/17p – karyotype, and FLT3-ITD mutations had a poor prognosis, while t(8; 21) karyotype was associated with a better prognosis. TP53-mutated patients with – 7/del (7q) or – 5/del (5q) karyotype had a poor prognosis. The cytogenetic and molecular landscapes differed between TP53-mutated and non-TP53-mutated patients, and some abnormalities had different values between them. [ABSTRACT FROM AUTHOR]

Previous studies validated the prognostic significance of lymphocyte to monocyte ratio (LMR) in patients with solid tumors and some hematologic malignancies. However, the correlation between LMR and Myelodysplastic Neoplasms (MDS) was unclear. The study intends to investigate the prognostic impact of LMR on MDS patients. 91 newly diagnosed MDS patients were included in this retrospective study. The cut-off of LMR was 3.2 by X-Tile. All patients were divided into the low LMR group (<3.2) and the high LMR group (≥3.2). Clinical characteristics were compared between the two groups. Patients in the high LMR group (n = 67) had better OS (P = 0.007) from the Kaplan-Meier survival curves. The results of the univariate analysis demonstrated that LMR was a prognostic factor for OS [hazard ratio (HR) = 2.070, 95%CI 1.201-3.571, P = 0.009]. After multivariate cox analysis, low LMR was confirmed to be an independent predictor of poor OS in MDS patients (HR = 1.872, 95%CI 1.084-3.230, P = 0.024). LMR, a representative marker of systematic inflammation and immune response, has potential prognostic significance in MDS patients. [ABSTRACT FROM AUTHOR]

To explore the clinical outcomes and characteristics of TP53-mutated primary myelodysplastic syndromes (MDS). A total of 74 de novo primary MDS patients who were diagnosed and treated in the Department of Hematology of our hospital from January 2018 and September 2021 were analyzed retrospectively. All patients had evaluable blood cell counts, mean corpuscular volume (MCV), lactate dehydrogenase (LDH), bone marrow (BM) morphology, biopsy, and MDS-related 20-gene mutations sequencing. In addition, 69 of 74 patients had complete cytogenetic analysis through conventional chromosome analysis and fluorescence in-situ hybridization. Patients were divided into two cohorts, the TP53-mutated type (TP53Mut) group (n = 19) and TP53 wild type (TP53WT) group (n = 55). Compared with the TP53WT group, patients in the TP53Mut group had higher ratios of cytogenetic abnormalities (82.4% vs. 30.8%, P < 0.001), with 5q- karyotype (64.70% vs. 38.5%, P < 0.001), complex karyotype(CK) (64.70% vs. 38.5%, P < 0.001), HR-MDS (94.7% vs. 61.8%, P = 0.008), and acute myelogenous leukemia (AML) transformation (26.3% vs. 12.7%, P < 0.001). Interestingly, patients in the TP53Mut group had lower median MCV than the TP53WT group (94.40 fl vs. 101.90 fl, P = 0.008). Furthermore, MCV = 100 fl as cutoff, and found that MCV ≤ 100 fl was more common in the TP53Mut group (73.7% vs. 38.2%, P < 0.001). After 1–4 courses of HMA ± chemotherapy, the overall response rate of the TP53Mut group was higher than the TP53WT group (83.3% vs. 71.4%, P = 0.012). With the median follow-up 12.0 months (1–46 months), the results show that the median OS and leukemia-free survival (LFS) of TP53Mut group was significantly shorter than the TP53WT group (P = 0.0018; P = 0.0310). Results of multivariate Cox proportional hazard analyses show TP53 mutation was an independent prognostic factor for the OS (HR 2.724, 95%CI 1.099–6.750, P = 0.030). TP53-mutated primary MDS patients were associated with higher frequency of cytogenetic abnormalities, with 5q- karyotype, CK, AML transformation, higher risk IPSS-R, lower MCV and sensitive to HMA treatment, but worse survival. [ABSTRACT FROM AUTHOR]

Prognostic nutritional index has been found to be related to the clinical outcomes of patients with cancer. However, its role in myelodysplastic syndromes (MDS) patients is unclear. We aimed to assess the value of nutritional status in predicting the prognosis of MDS patients. Totally 121 MDS patients were analyzed retrospectively. The prognostic nutritional index (PNI) was used to assess nutritional status of the patients. The bio-informatics tool X-tile was used to define the threshold, and accordingly patients were divided into PNIlow and PNIhigh groups, the characteristics were compared between two groups. The PNIhigh was associated with better OS (Overall Survival) than PNIlow in MDS patients (Median OS, 28.03 months versus 19.63 months, P = 0.0205). But there were no statistical differences in PFS (Progression-Free-Survival) between the two groups (P = 0.9373). The univariable and multivariable COX proportional hazard analysis adjusted for age, gender, platelet count, HB level and IPSS-R scores, and the results showed that PNI is a useful index in the evaluation of the OS of MDS (HR 0.588, 95%CI 0.374–0.926, P = 0.024). PNI would be a simple and immediately available tool for predicting the prognosis of MDS. [ABSTRACT FROM AUTHOR]

Shenling Baizhu Powder is a traditional Chinese medicine formula that has been used for thousands of years to invigorate spleen, nourish stomach and regulate immune function. The multi-herbal extracts, an improved formular from Shenling Baizhu Powder, were used in our study to investigate its immune-enhancing effects and underling mechanisms. Based on UPLC-Q-TOF-MS and SPME-GC-MS analysis, 106 chemical compounds were identified from the extracts. In vitro assays indicated that the extracts could promote cell proliferation and NO secretion of RAW264.7 cells. RNA-seq and RT-qPCR showed that RAW264.7 cells treated with extracts increased the expression of pro-inflammatory factors IL-1ß, iNOS, TNF-a, and TGF-ß. Western-Blot revealed that the extracts could significantly enhance ERK phosphorylation level, and slightly increased JNK and p38 phosphorylation levels. These data suggest that multi-herbal extracts have a potential of regulating immune response via the JNK/p38/ERK signalling of MAPK pathways in RAW264.7 cells. [ABSTRACT FROM AUTHOR]

Controlling nutritional status (CONUT) score, based on three indexes including serum albumin (ALB), total cholesterol (CHO), and absolute lymphocyte count (ALC), has been closely associated with the prognosis of cancer patients. Multiple studies revealed the significance of CONUT score in hematological malignancies, including diffuse large B-cell lymphoma (DLBCL), peripheral T-cell lymphoma (PTCL), multiple myeloma (MM), and leukemia. This review aimed to explore the prognostic role of CONUT score in hematological malignancies. We conducted this review through Pubmed to summarize the published studies on the CONUT score in hematological malignancies, using the terms: Controlling nutritional status, CONUT score, hematological malignancy, lymphoma, multiple myeloma, and leukemia. CONUT score can reflect not only the nutritional status but also the inflammatory status of patients with hematological malignancies. It can assist in predicting the survival of patients with DLBCL, PTCL, MM, adult T-cell leukemia (ATL), myelodysplastic syndrome (MDS), and acute myeloid leukemia with myelodysplasia related changes (AML-MRC). CONUT score plays an important role in predicting the prognosis of patients with hematological malignancies. [ABSTRACT FROM AUTHOR]

Nucleophosmin 1 (NPM1, also known as B23) is a multifunctional protein involved in a variety of cellular processes, including ribosomal maturation, centrosome replication, maintenance of genomic stability, cell cycle control, and apoptosis. NPM1 is the most commonly mutated gene in adult acute myeloid leukemia (AML) and is present in approximately 40% of all AML cases. The underlying mechanisms of mutant NPM1 (NPM1mut) in leukemogenesis remain unclear. This review summarizes the structure and physiological function of NPM1, mechanisms underlying the pathogenesis of NPM1-mutated AML, and the potential role of NPM1 as a therapeutic target. It is reported that dysfunctional NPM1 might cause AML pathogenesis via its role as a protein chaperone, inhibiting differentiation of leukemia stem cells and regulation of non-coding RNAs. Besides conventional chemotherapies, NPM1 is a promising therapeutic target against AML that warrants further investigation. NPM1-based therapeutic strategies include inducing nucleolar relocalisation of NPM1 mutants, interfering with NPM1 oligomerization, and NPM1 as an immune response target. [ABSTRACT FROM AUTHOR]

Objectives: Extramedullary multiple myeloma (EMM) is a relatively less frequent subentity of multiple myeloma (MM) and is generally considered to be a poor prognostic factor. Novel agents and hematopoietic stem cell transplantation (HSCT) have led to a significant improvement in the progression-free survival and overall survival of patients with MM, but outcomes of EMM remain dismal. Little is known regarding the role of novel therapies in this setting. This review summarizes the current available data regarding the roles of proteasome inhibitors, immunomodulators, monoclonal antibodies, chimeric antigen receptor (CAR)-T cell therapy and HSCT in EMM. Methods: A systematic literature review through PubMed was conducted to summarize the published evidence on the therapeutic developments of novel agents and HSCT in EMM. Literature sources published in English were searched, using the terms multiple myeloma, extramedullary and treatment. Results: Long-term outcomes of EMM patients remain dismal despite the utilization of novel agents and HSCT. The standard therapy of EMM has not been established. EMM should be managed as high-risk disease and treated accordingly. Discussion and conclusion: This review will provide an insight on the current and emerging treatment strategies as well as their efficacy in EMM. Further subgroup analyses in large prospective trials focusing on EMM is needed to help optimize the therapy. [ABSTRACT FROM AUTHOR]

To explore the relationship between platelet count and bleeding score in immune thrombocytopenia purpura (ITP) and compare the clinical practicability of two bleeding grading systems with adult patients with ITP. A total of 204 patients were retrospectively analyzed with the ITP bleeding scale (IBLS) and the ITP bleeding assessment tool (version 2016) (ITP-2016). The correlation between the two bleeding score systems and the relations among the platelet counts were respectively analyzed. (1) There is a linear relationship between platelet count and bleeding score, no matter which scoring system it is based on (rs = −0.429, p < 0.001; rs = −0.331, p < 0.001, the analysis of the number of sites of Grade 1/2 bleeding were done; and rs = −0.466, p < 0.05, the analysis between platelet count and bleeding score by ITP-2016 respectively). (2) Platelet count and bleeding scores are negatively correlated in those with extremely low platelet counts (< 10*109/L). The number of sites of Grade 2 bleeding and the ITP-2016 scores are negatively correlated with platelet counts (rs = −0.15 and rs = −0.244, p < 0.05, respectively). Significantly, there is no correlation between the platelet count and bleeding scores when the platelet count is more than 10*109/L. (3) It takes less time to score with ITP-2016 than IBLS (z = −3.825, P < 0.001). There is good responsiveness, strong assessment consistency, close correlation between ITP-2016 and IBLS. ITP-2016 takes less time-consuming in clinical application. It can be used as an effective tool of condition judgement, risk assessment and efficacy evaluation of patients with ITP. [ABSTRACT FROM AUTHOR]

Acute myeloid leukaemia (AML) is a haematopoietic malignancy with a dismal outcome. Consequently, risk stratification based on more effective prognostic biomarkers is crucial to make accurate therapy decisions. T cell receptor gamma alternative reading frame protein (TARP) has been reported in prostate and breast cancers, but its correlation with AML remains unclear. Differential expression of TARP mRNA in different AML subtypes was analysed using the UALCAN online platform. Its relationship with baseline clinical attributes, survival and efficacy were analysed based on three GSE1159, GSE425 and GSE6891 microarray datasets downloaded from Gene Expression Omnibus (GEO) and Oncomine databases. Quantitative real-time PCR was performed to determine mRNA levels of TARP in bone marrow mononuclear cells (BMMCs) isolated from AML patients. TARP was significantly overexpressed in AML patients. In AML, relatively low TARP expression was associated with the CBFβ-MYH11 fusion gene. The proportion of FLT3 mutations was significantly higher in non-adolescent and young adult (non-AYA, >39 years of age) AML patients who had high TARP levels but not in AYA (15–39 years) patients. High expression of TARP was related to poor outcome by univariate analysis but not by multivariate analysis and unsatisfactory therapeutic effects, which could be overcome by haematopoietic stem cell transplantation (HSCT). Our findings suggest that TARP might be a potential prognostic marker of AML and serve as a promising immunotherapeutic target. [ABSTRACT FROM AUTHOR]