Osteolytic lesions as a presenting sign of acute myeloid leukemia: a case report.

Osteolytic lesions are infrequently observed in adult patients with acute myeloid leukemia (AML). This report details the case of a 66-year-old male patient who presented with myeloid sarcoma (MS), osteolytic lesion and pancytopenia. Effective treatments were delayed due to diagnostic challenges and the rapid progression of the disease. It is essential to consider AML in the differential diagnosis when faced with a patient presenting osteolytic lesions and pancytopenia.

Circulating plasma cells as a predictive biomarker in Multiple myeloma: an updated systematic review and meta-analysis.

BACKGROUND: Circulating plasma cells (CPCs) are defined by the presence of peripheral blood clonal plasma cells, which would contribute to the progression and dissemination of multiple myeloma (MM). An increasing number of studies have demonstrated the predictive potential of CPCs in the past few years. Therefore, there is a growing need for an updated meta-analysis to identify the specific relationship between CPCs and the prognosis of MM based on the current research status. METHODS: The PubMed, Embase, and Cochrane Library databases were screened to determine eligible studies from inception to November 5, 2023. Publications that reported the prognostic value of CPCs in MM patients were included. Hazard ratios (HRs) with 95% confidence intervals (CIs) of overall survival (OS) and progression-free survival (PFS) were extracted to pool the results. Subgroup analyses were performed based on region, sample size, cut-off value, detection time, initial treatment, and data type. The association between CPCs level and clinicopathological characteristics, including the International Staging System (ISS), Revised-ISS (R-ISS), and cytogenetic abnormalities were also evaluated. Statistical analyses were conducted using STATA 17.0 software. RESULTS: Twenty-two studies with a total of 5637 myeloma patients were enrolled in the current meta-analysis. The results indicated that myeloma patients with elevated CPCs were expected to have a poor OS (HR = 2.19, 95% CI: 1.81-2.66, p < 0.001) and PFS (HR = 2.45, 95% CI: 1.93-3.12, p < 0.001). Subgroup analyses did not alter the prognostic role of CPCs, regardless of region, sample size, cut-off value, detection time, initial treatment, or data type. Moreover, the increased CPCs were significantly related to advanced tumour stage (ISS III vs. ISS I-II: pooled OR = 2.89, 95% CI: 2.41-3.46, p < 0.001; R-ISS III vs. R-ISS I-II: pooled OR = 3.65, 95% CI: 2.43-5.50, p < 0.001) and high-risk cytogenetics (high-risk vs. standard-risk: OR = 2.22, 95% CI: 1.60-3.08, p < 0.001). CONCLUSION: Our meta-analysis confirmed that the increased number of CPCs had a negative impact on the PFS and OS of MM patients. Therefore, CPCs could be a promising prognostic biomarker that helps with risk stratification and disease monitoring.

There is a growing need for an updated meta-analysis to identify the specific relationship between CPCs and the prognosis of MM based on the current research status.Our meta-analysis revealed that a high CPCs level was significantly associated with worse OS and PFS in MM patients.CPCs could be a promising predictive biomarker that helps with risk stratification and disease monitoring.

Autophagy in Disease Onset and Progression.

Autophagy is a biological phenomenon whereby components of cells can self-degrade using autophagosomes. During this process, cells can clear dysfunctional organelles or unwanted elements. Autophagy can recycle unnecessary biomolecules into new components or sometimes, even destroy the cells themselves. This cellular process was first observed in 1962 by Keith R. Porter et al. Since then, autophagy has been studied for over 60 years, and much has been learned on the topic. Nevertheless, the process is still not fully understood. It has been proven, for example, that autophagy can be a positive force for maintaining good health by removing older or damaged cells. By contrast, autophagy is also involved in the onset and progression of various conditions caused by pathogenic infections. These diseases generally involve several important organs in the human body, including the liver, kidney, heart, and central nervous system. The regulation of the defects of autophagy defects may potentially be used to treat some diseases. This review comprehensively discusses recent research frontiers and topics of interest regarding autophagy-related diseases.

Identification of gene signatures related to hypoxia and angiogenesis in pancreatic cancer to aid immunotherapy and prognosis.

Background: One of the most diverse tumors is pancreatic cancer (PC), which makes predicting the prognosis challenging. PC development is directly related to hypoxia, angiogenesis, and immunotherapy. It is still unclear how the three features are related. Methods: The Genotype-Tissue Expression (GTEx) and the Cancer Genome Atlas (TCGA) database were employed to obtain sequencing data for healthy pancreatic tissues and PC tissues, respectively. According to the constructed hypoxic prognostic model (HPM) and angiogenic prognostic model (APM), 4 subtypes of PC were identified. Hypoxia and angiogenesis prognostic model (HAPM) was established based on differentially expressed genes (DEGs) between high-angiogenesis/high-hypoxia (HH) and low-angiogenesis/low-hypoxia (LL) subgroups. Base on the median risk score, PC patients were separated into high-risk and low-risk groups, and clinical traits, prognosis, percentage of immune cell infiltration, PD-1 expression, and the fraction of T-cell depletion were compared between the groups. Finally, the predictive accuracy of the tumor immune dysfunction and rejection (TIDE) and tumor inflammatory signature (TIS) models, as well as HAPM, was compared. Result: We analyzed the mRNA sequencing data from 178 PC tissues and 171 normal pancreatic tissues to obtain 9527 DEGs. We discovered 200 genes linked with hypoxia and 36 genes involved with angiogenesis through the literature. We found the core genes related with hypoxia and angiogenesis in PC by intersecting the DEGs of the HH and LL subgroups with those of PC via WGCNA. IL-17 signaling pathway, ECM-receptor interactions, cytokine receptor interactions, etc. were all enriched in the Kyoto Encyclopedia of Genes and Genomes (KEGG) results of core genes. HAPM has good predictive efficiency, according to an evaluation of KM survival curves and ROC curves. The external dataset also validated the model's ability to anticipate outcomes. Patients in the high- and low-risk groups were compared for PD1 expression and T-cell exclusion scores, which suggested that the model might be used to forecast which PC patients might benefit from immunotherapy. Conclusions: The probable molecular processes connecting hypoxia and angiogenesis are described in this work, and a model is developed that may be utilized to forecast the prognosis for PC patients and the benefits of immunotherapy.

m6A-modified circFNDC3B inhibits colorectal cancer stemness and metastasis via RNF41-dependent ASB6 degradation.

Colorectal cancer (CRC) is the third most frequently diagnosed cancer with unfavorable clinical outcomes worldwide. circFNDC3B plays as a tumor suppressor in CRC, however, the mechanism of circFNDC3B in CRC remains ambiguous. The stem-like properties of CRC cells were detected by the evaluation of stemness markers, sphere formation assay and flow cytometry. qRT-PCR, FISH, IHC, and western blotting assessed the expression and localization of circFNDC3B, RNF41, ASB6, and stemness markers in CRC. The metastatic capabilities of CRC cells were examined by wound healing and Transwell assays, as well as in vivo liver metastasis model. Bioinformatics analysis, RNA immunoprecipitation (RIP), RNA pull-down assay and co-IP were used to detect the associations among circFNDC3B, FXR2, RNF41, and ASB6. Downregulated circFNDC3B was associated with unfavorite survival in CRC patients, and circFNDC3B overexpression suppressed CRC stemness and metastasis. Mechanistically, studies revealed that YTHDC1 facilitated cytoplasmic translocation of m6A-modified circFNDC3B, and circFNDC3B enhanced RNF41 mRNA stability and expression via binding to FXR2. circFNDC3B promoted ASB6 degradation through RNF41-mediated ubiquitination. Functional studies showed that silencing of RNF41 counteracted circFNDC3B-suppressed CRC stemness and metastasis, and ASB6 overexpression reversed circFNDC3B- or RNF41-mediated regulation of CRC stemness and metastasis. Elevated ASB6 was positively correlated with unfavorite survival in CRC patients. In vivo experiments further showed that circFNDC3B or RNF41 overexpression repressed tumor growth, stemness and liver metastasis via modulating ASB6. Taken together, m6A-modified circFNDC3B inhibited CRC stemness and metastasis via RNF41-dependent ASB6 degradation. These findings provide novel insights and important clues for targeted therapeutic strategies of CRC.

Identification of Potential Molecular Mechanism Related to Infertile Endometriosis.

Objectives: In this research, we aim to explore the bioinformatic mechanism of infertile endometriosis in order to identify new treatment targets and molecular mechanism. Methods: The Gene Expression Omnibus (GEO) database was used to download MRNA sequencing data from infertile endometriosis patients. The "limma" package in R software was used to find differentially expressed genes (DEGs). Weighted gene co-expression network analysis (WGCNA) was used to classify genes into modules, further obtained the correlation coefficient between the modules and infertility endometriosis. The intersection genes of the most disease-related modular genes and DEGs are called gene set 1. To clarify the molecular mechanisms and potential therapeutic targets for infertile endometriosis, we used Gene Ontology (GO), Kyoto Gene and Genome Encyclopedia (KEGG) enrichment, Protein-Protein Interaction (PPI) networks, and Gene Set Enrichment Analysis (GSEA) on these intersecting genes. We identified lncRNAs and miRNAs linked with infertility and created competing endogenous RNAs (ceRNA) regulation networks using the Human MicroRNA Disease Database (HMDD), mirTarBase database, and LncRNA Disease database. Results: Firstly, WGCNA enrichment analysis was used to examine the infertile endometriosis dataset GSE120103, and we discovered that the Meorangered1 module was the most significantly related with infertile endometriosis. The intersection genes were mostly enriched in the metabolism of different amino acids, the cGMP-PKG signaling pathway, and the cAMP signaling pathway according to KEGG enrichment analysis. The Meorangered1 module genes and DEGs were then subjected to bioinformatic analysis. The hub genes in the PPI network were performed KEGG enrichment analysis, and the results were consistent with the intersection gene analysis. Finally, we used the database to identify 13 miRNAs and two lncRNAs linked to infertility in order to create the ceRNA regulatory network linked to infertile endometriosis. Conclusion: In this study, we used a bioinformatics approach for the first time to identify amino acid metabolism as a possible major cause of infertility in patients with endometriosis and to provide potential targets for the diagnosis and treatment of these patients.

Epidemiological features for primary lymphoma of the female genital tract patients and development of a nomogram to predict survival.

BACKGROUND: Primary lymphoma of the female genital tract (PLFGT) is a sporadic extranodal lymphoma. Its epidemiology and prognosis are not fully recognized. Our study aimed to construct and validate prognostic nomograms for predicting survival for patients with PLFGT. METHODS: Incidence rate from 1975 to 2017 and patients with PLFGT from 1975 to 2011 in the Surveillance, Epidemiology and End Results (SEER) database were retrospectively reviewed. The nomograms of overall survival (OS) and disease-specific survival (DSS) were established according to the multivariate Cox regression analyses. The concordance index (C-index) and calibration plots were used to demonstrate its robustness and accuracy. RESULTS: A total of 617 PLFGT patients were identified. The overall incidence of PLFGT is 0.437/1,000,000 (adjusted to the US standard population in 2000) from 1975 to 2017. Age, histological subtype, Ann Arbor Stage, and therapeutic strategy were identified as independent prognostic factors for OS and DSS by multivariate Cox regression (p < .05). Nomograms to predict 1-, 5-, and 10-year OS and DSS were established. The C-index and calibration plots showed a good discriminative ability and an optimal accuracy of the nomograms. Patients were divided into three risk groups according to the model of OS. CONCLUSIONS: The incidence of PLFGT has increased in the past 40 years, and the nomograms were developed and validated as an individualized tool to predict OS and DSS for all PLFGT patients and DLBCL patients. All patients are divided into three risk groups to assist clinicians to identify patients at high-risk and choose the optimal individualized treatments for patients.HighlightsThe incident of PLFGT and its subtypes were calculated and compared.Nomograms were constructed to predict the 1-, 5-, and 10-year OS and DSS.Patients are divided into the low-risk, medium-risk, and high-risk according total score of the nomogram.

International Prognostic Index-Based Immune Prognostic Model for Diffuse Large B-Cell Lymphoma.

Background: The International Prognostic Index (IPI) is widely used to discriminate the prognosis of patients with diffuse large B-cell lymphoma (DLBCL). However, there is a significant need to identify novel valuable biomarkers in the context of targeted therapy, such as immune checkpoint blockade (ICB). Methods: Gene expression data and clinical DLBCL information were obtained from The Cancer Genome Atlas and Gene Expression Omnibus datasets. A total of 371 immune-related genes in DLBCL patients associated with different IPI risk groups were identified by weighted gene co-expression network analysis, and eight genes were selected to construct an IPI-based immune prognostic model (IPI-IPM). Subsequently, we analyzed the somatic mutation and transcription profiles of the IPI-IPM subgroups as well as the potential clinical response to immune checkpoint blockade (ICB) in IPI-IPM subgroups. Results: The IPI-IPM was constructed based on the expression of CMBL, TLCD3B, SYNDIG1, ESM1, EPHA3, HUNK, PTX3, and IL12A, where high-risk patients had worse overall survival than low-risk patients, consistent with the results in the independent validation cohorts. The comprehensive results showed that high IPI-IPM risk scores were correlated with immune-related signaling pathways, high KMT2D and CD79B mutation rates, and upregulation of inhibitory immune checkpoints, including PD-L1, BTLA, and SIGLEC7, indicating a greater potential response to ICB therapy. Conclusion: The IPI-IPM has independent prognostic significance for DLBCL patients, which provides an immunological perspective to elucidate the mechanisms of tumor progression and sheds light on the development of immunotherapy for DLBCL.

A bispecific CAR-T cell therapy targeting BCMA and CD38 in relapsed or refractory multiple myeloma.

BACKGROUND: BCMA-specific chimeric antigen receptor-T cells (CAR-Ts) have exhibited remarkable efficacy in refractory or relapsed multiple myeloma (RRMM); however, primary resistance and relapse exist with single-target immunotherapy. Bispecific CARs are proposed to mitigate these limitations. METHODS: We constructed a humanized bispecific BM38 CAR targeting BCMA and CD38 and tested the antimyeloma activity of BM38 CAR-Ts in vitro and in vivo. Twenty-three patients with RRMM received infusions of BM38 CAR-Ts in a phase I trial. RESULTS: BM38 CAR-Ts showed stronger in vitro cytotoxicity to heterogeneous MM cells than did T cells expressing an individual BCMA or CD38 CAR. BM38 CAR-Ts also exhibited potent antimyeloma activity in xenograft mouse models. In the phase I trial, cytokine release syndrome occurred in 20 patients (87%) and was mostly grade 1-2 (65%). Neurotoxicity was not observed. Hematologic toxicities were common, including neutropenia in 96% of the patients, leukopenia in 87%, anemia in 43% and thrombocytopenia in 61%. At a median follow-up of 9.0 months (range 0.5 to 18.5), 20 patients (87%) attained a clinical response and minimal residual disease-negativity (≤ 10-4 nucleated cells), with 12 (52%) achieving a stringent complete response. Extramedullary plasmacytoma was eliminated completely in 56% and partially in 33% and of 9 patients. The median progression-free survival was 17.2 months. Two relapsed patients maintained BCMA and CD38 expression on MM cells. Notably, BM38 CAR-Ts cells were detectable in 77.8% of evaluable patients at 9 months and 62.2% at 12 months. CONCLUSION: Bispecific BM38 CAR-Ts were feasible, safe and significantly effective in patient with RRMM. TRIAL REGISTRATION: Chictr.org.cn ChiCTR1800018143.

Tumor-infiltrating B cells as a favorable prognostic biomarker in breast cancer: a systematic review and meta-analysis.

BACKGROUND: Tumor-infiltrating B lymphocytes (TIL-Bs) is a heterogeneous population of lymphocytes. The prognostic value of TIL-Bs in patients with breast cancer remains controversial. Here we conducted this meta-analysis to clarify the association of TIL-Bs with outcomes of patients with breast cancer. METHODS: We searched PubMed, Embase, and Web of Science to identify relevant studies assessing the prognostic significance of TIL-Bs in patients with breast cancer. Fixed- or random-effects models were used to evaluate the pooled hazard ratios (HRs) for overall survival (OS), breast cancer-specific survival (BCSS), disease-free survival (DFS), and relapse-free survival (RFS) in breast cancer. RESULTS: A total of 8 studies including 2628 patients were included in our study. Pooled analyses revealed that high level of TIL-Bs was associated with longer OS (pooled HR = 0.42, 95% CI 0.24-0.60), BCSS (pooled HR = 0.66, 95% CI 0.47-0.85), and DFS/RFS (pooled HR = 0.41, 95% CI 0.27-0.55). CONCLUSIONS: This meta-analysis suggests that TIL-Bs could be a promising prognostic marker for breast cancer. Novel therapeutic strategies for breast cancer treatment could be developed by enhancement of B cell-mediated antitumor immunity.

PiggyBac-Generated CAR19-T Cells Plus Lenalidomide Cause Durable Complete Remission of Triple-Hit Refractory/Relapsed DLBCL: A Case Report.

MYC/BCL2/BCL6 triple-hit lymphoma (THL) is an uncommon subset of high-grade B-cell lymphoma with aggressive clinical behavior and poor prognosis. TP53 mutation is an independently poor progonistic indicator in patients with THL, hence novel therapeutic strategies are needed for these patients. CD19-directed chimeric antigen receptor(CAR19)-T cell therapy has shown promising efficacy for relapsed/refractory diffuse large B cell lymphoma (RR DLBCL), but the majority of CAR19-T cell products to date have been manufactured using viral vectors. PiggyBac transposon system, with an inclination to memory T cells, offers a more convenient and economical alternative for transgene delivery. We herein report the first case of triple-hit RR DLBCL with TP53 mutation who was treated with piggyBac-generated CAR19-T cells and accompanied by grade 2 cytokine release syndrome. The patient obtained a complete remission (CR) in the 2nd month post-infusion and demanded maintenance therapy. Whether maintenance therapy is favorable and how to administrate it after CAR-T cell infusion remain controversial. Preclinical studies demonstrated that lenalidomide could enhance antitumor activity of CAR19-T cells. Therefore, we pioneered oral lenalidomide after CAR19-T therapy in the patient from the 4th month, and he discontinued after one cycle due to side effects. The patient has still kept sustained CR for over 24 months. Our case have firstly demonstrated the feasibility, preliminary safety and efficacy of piggyBac-produced CAR19-T cell therapy in triple-hit lymphoma. The innovative combination with lenalidomide warrants further investigation. Our findings shed new light on the possible solutions to improve short-term relapse after CAR19-T cell therapy in RR DLBCL. ChiCTR, number ChiCTR1800018111.

Prognostic value of FGFR1 expression and amplification in patients with HNSCC: A systematic review and meta-analysis.

Fibroblast growth factor receptor 1 (FGFR1) has recently been identified as a promising novel therapeutic target and prognostic marker in different types of cancer. In the present study, a meta-analysis was performed to clarify the correlation between FGFR1 and the survival outcomes of head and neck squamous cell carcinoma (HNSCC) patients. PubMed, Embase, and Web of Science were systematically searched for relevant studies in order to explore the prognostic significance of FGFR1 in HNSCC. Hazards ratios (HR) and 95% confidence intervals (CI) were collected to estimate the correlation between overexpression and amplification of FGFR1 and survival outcomes of HNSCC patients. Nine studies including 2708 patients with HNSCC were finally selected for the meta-analysis. The results indicated that FGFR1 predicted poor overall survival (OS) (HR, 1.97; 95% CI, 1.49-2.61, P<0.001) in HNSCC patients. Futhermore, FGFR1 was related to poor OS in human papillomavirus (HPV) negative HNSCC not in HPV positive HNSCC patients. Subgroup analysis stratified by molecular abnormalities, such as overexpression or amplification showed the similar results. The present study demonstrated that HNSCC patients with FGFR1 overexpression and amplification were more likely to exhibit poorer survival.

Epidemiological features of primary breast lymphoma patients and development of a nomogram to predict survival.

BACKGROUND: Studies on the epidemiology and prognosis of primary breast lymphoma (PBL) are lack for low incidence. Therefore, we aimed to investigate the epidemiological characteristics of PBL and develop nomograms to predict patient survival. METHODS: Data of patients who were diagnosed with PBL from 1975 to 2011 and incidence rate of PBL from 1975 to 2017 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Time-varying multivariable Cox regression analysis was performed to identify independent prognostic factors for overall survival (OS) and disease-specific survival (DSS). Nomograms were constructed based on the independent prognostic factors identified in multivariate Cox regression analysis. RESULTS: A total of 1427 patients diagnosed with PBL were identified with the average age of 67.1 years. The overall incidence of PBL is 1.35/1,000,000 (adjusted to the United States standard population in 2000) from 1975 to 2017, with a significant upward trend by an annual percentage change (APC) of 2.91 (95%CI 2.29-3.94, P < 0.05). Age, sex, race, year of diagnosis, marital status, histological subtype, Ann Arbor Stage, and treatment modality were assessed as independent prognostic factors for OS and DSS by multivariable Cox regression (P < 0.05). Nomograms were constructed to predict the 1-, 3-, 5-, and 10- year OS and DSS. The concordance index (C-index) and calibration plots showed robustness and accuracy of the nomogram. CONCLUSION: The overall incidence of PBL was steadily increasing over the past four decades. Nomograms constructed can predicting 1-, 3-, 5-, and 10-year OS and identify patients with high-risk PBL.

Studies Progression on the Function of Autophagy in Viral Infection.

Autophagy is a conservative lysosomal catabolic pathway commonly seen in eukaryotic cells. It breaks down proteins and organelles by forming a two-layer membrane structure of autophagosomes and circulating substances and maintaining homeostasis. Autophagy can play a dual role in viral infection and serve either as a pro-viral factor or an antiviral defense element dependent on the virus replication cycle. Recent studies have suggested the complicated and multidirectional role of autophagy in the process of virus infection. On the one hand, autophagy can orchestrate immunity to curtail infection. On the other hand, some viruses have evolved strategies to evade autophagy degradation, facilitating their replication. In this review, we summarize recent progress of the interaction between autophagy and viral infection. Furthermore, we highlight the link between autophagy and SARS-CoV-2, which is expected to guide the development of effective antiviral treatments against infectious diseases.

Predictive Nomogram for Severe COVID-19 and Identification of Mortality-Related Immune Features.

BACKGROUND: Patients with severe 2019 novel coronavirus disease (COVID-19) have a high mortality rate. The early identification of severe COVID-19 is of critical concern. In addition, the correlation between the immunological features and clinical outcomes in severe cases needs to be explored. OBJECTIVE: To build a nomogram for identifying patients with severe COVID-19 and explore the immunological features correlating with fatal outcomes. METHODS: We retrospectively enrolled 85 and 41 patients with COVID-19 in primary and validation cohorts, respectively. A predictive nomogram based on risk factors for severe COVID-19 was constructed using the primary cohort and evaluated internally and externally. In addition, in the validation cohort, immunological features in patients with severe COVID-19 were analyzed and correlated with disease outcomes. RESULTS: The risk prediction nomogram incorporating age, C-reactive protein, and D-dimer for early identification of patients with severe COVID-19 showed favorable discrimination in both the primary (area under the curve [AUC] 0.807) and validation cohorts (AUC 0.902) and was well calibrated. Patients who died from COVID-19 showed lower abundance of peripheral CD45RO+CD3+ T cells and natural killer cells, but higher neutrophil counts than that in the patients who recovered (P = .001, P = .009, and P = .009, respectively). Moreover, the abundance of CD45RO+CD3+ T cells, neutrophil-to-lymphocyte ratio, and neutrophil-to-natural killer cell ratio were strong indicators of death in patients with severe COVID-19 (AUC 0.933 for all 3). CONCLUSION: The novel nomogram aided the early identification of severe COVID-19 cases. In addition, the abundance of CD45RO+CD3+ T cells and neutrophil-to-lymphocyte and neutrophil-to-natural killer cell ratios may serve as useful prognostic predictors in severe patients.

Prognostic role of regulatory T cells in lymphoma: a systematic review and meta-analysis.

PURPOSE: The regulatory T cells (Tregs) are a subpopulation of lymphocytes that suppress the immune responses. The prognostic value of Tregs in lymphoma patients remains controversial. Thus, we conducted this meta-analysis to clarify the role of Tregs in the prognosis of lymphoma patients. METHODS: We searched PubMed, Embase, and Web of Science to obtain eligible studies that evaluated the prognostic factor of Tregs for lymphoma patients. Hazards ratios (HRs) with the matching 95% confidence intervals (95%CIs) were merged to estimate the prognostic value of Tregs. RESULTS: We finally retrieved 23 eligible studies, including a total of 2269 patients. The overall pooled analysis on all types of lymphomas showed that Tregs had a significantly positive association with prolonged overall survival (OS) (HR = 0.633, 95% CI 0.528-0.758) and progression-free survival (PFS) (HR = 0.451, 95% CI 0.261-0.779). Subgroup analysis indicated that high Tregs were significantly correlated with longer OS in Hodgkin lymphoma, diffuse large B cell lymphoma, and natural killer/T cell lymphoma. However, there was no significant association of Tregs with T cell lymphoma and follicular lymphoma. CONCLUSIONS: Increased Tregs indicates a better prognosis for patients with lymphoma. Tregs could be used as a valuable prognostic biomarker of lymphoma patients.

Role Of TP53 mutations in predicting the clinical efficacy of hypomethylating therapy in patients with myelodysplastic syndrome and related neoplasms: a systematic review and meta-analysis.

Hypomethylating agents (HMAs) are now a major treatment option for myelodysplastic syndrome (MDS) and related neoplasms, but 50% of patients still do not respond and realize poor outcomes. Mutational predictors of treatment efficacy attract continuous attention. Whether TP53 mutations can be used as predictors of HMA effectiveness has caused heated debate. Therefore, we performed a meta-analysis to investigate the predictive value of TP53 mutations to outcomes of HMA therapy in patients with MDS and related neoplasms. We systematically searched PubMed, Embase, the Cochrane Library, and the WanFang databases (published deadline: September 12, 2019). The primary endpoints were overall response rate (ORR) and overall survival (OS). Odds ratio (OR), hazard ratio (HR), and 95% confidence intervals (CI) were pooled to estimate the association between TP53 mutations and the clinical efficacy of HMAs. Four hundred fifteen papers were found, and 22 papers were included in this meta-analysis (N = 2020 participants). The results showed that the presence of TP53 mutation predicted an increased overall response rate with HMA treatment in the subsets that restricted patients in de novo disease, MDS by WHO (World Health Organization) criteria, or NGS (next-generation sequence) group (P = 0.005, P = 0.003, P = 0.0005, respectively). However, TP53 mutations remained poor factors for OS (P < 0.00001). Collectively, in HMA therapy, TP53 mutations can predict better ORR when setting more refined subgroups, but TP53 mutations still strongly correlated with poor survival in hypomethylating therapy.

Rational Design and Fabrication of ZnONPs Functionalized Sericin/PVA Antimicrobial Sponge.

The interests of developing antimicrobial biomaterials based on silk sericin from Bombyx mori cocoon, have been shooting up in the last decades. Sericin is a valuable natural protein owing to its hydrophilicity, biodegradability, and biocompatibility. Here, we fabricated a sponge with antibacterial capacities for potential wound dressing application. By co-blending of sericin, polyvinyl alcohol (PVA) and zinc oxide nanoparticles (ZnONPs), the ZnONPs-sericin/PVA composite sponge (ZnONPs-SP) was successfully prepared after freeze-drying. Scanning electron microscopy showed the porous structure of ZnONPs-SP. Energy dispersive spectroscopy indicated the existence of Zn in the sponge. X-ray diffractometry revealed the hexagonal wurtzite structure of ZnONPs. Fourier transform infrared spectroscopy showed the biologic coupling of ZnONPs and sericin resulted in a decrease of α-helix and random coil contents, and an increase of ß-sheet structure in the sponge. The swelling experiment suggested ZnONPs-SP has high porosity, good hydrophilicity, and water absorption capability. The plate bacterial colony counting coupled with growth curve assays demonstrated that the composite sponge has an efficiently bacteriostatic effect against Staphylococcus aureus and Escherichia coli, respectively. Furthermore, the cell compatibility analysis suggested the composite sponge has excellent cytocompatibility on NIH3T3 cells. In all, ZnONPs-SP composite sponge has significant potentials in biomaterials such as wound dressing and tissue engineering.