Explore the vast range of titles available.

Experimental and acute exposure studies imply that manganese affects red blood cell production. Nevertheless, the association between environmental exposure and red blood cell distribution width (RDW) has yet to be explored. This research sought to assess the correlation between blood manganese levels and RDW within the general population of the United States. Employing weighted multiple linear regression models, data from the 2011-2018 National Health and Nutrition Examination Survey (NHANES) were utilized to assess the correlation between manganese levels in the blood and RDW. Restricted cubic spline plots and two-piecewise linear regression models were also employed. The analysis included a total of 15882 participants in which we determined an independent positive relationship between blood manganese levels and RDW among participants(β = 0.079, P<0.001). Moreover, we identified a J-shaped association between blood manganese levels and RDW in total participants (inflection point for blood manganese: 7.32 ug/L) and distinct subgroups following adjusted covariates. Women exhibited a more pronounced association, even after controlling for adjusted covariates. We determined a J-shaped relationship between blood manganese levels and RDW with an inflection point at 7.32 ug/L for blood manganese. Nevertheless, fundamental research and large sample prospective studies are needed to determine the extent to which blood manganese levels correlate with RDW.

Chimeric antigen receptor (CAR) technology has revolutionized cancer treatment, particularly in malignant hematological tumors. Currently, the BCMA-targeted second-generation CAR-T cells have showed impressive efficacy in the treatment of refractory/relapsed multiple myeloma (R/R MM), but up to 50% relapse remains to be addressed urgently. Here we constructed the BCMA-targeted fourth-generation CAR-T cells expressing IL-7 and CCL19 (i.e., BCMA-7 × 19 CAR-T cells), and demonstrated that BCMA-7 × 19 CAR-T cells exhibited superior expansion, differentiation, migration and cytotoxicity. Furthermore, we have been carrying out the first-in-human clinical trial for therapy of R/R MM by use of BCMA-7 × 19 CAR-T cells (ClinicalTrials.gov Identifier: NCT03778346), which preliminarily showed promising safety and efficacy in first two enrolled patients. The two patients achieved a CR and VGPR with Grade 1 cytokine release syndrome only 1 month after one dose of CAR-T cell infusion, and the responses lasted more than 12-month. Taken together, BCMA-7 × 19 CAR-T cells were safe and effective against refractory/relapsed multiple myeloma and thus warranted further clinical study.

The survival and death cause in elderly acute promyelocytic leukemia (APL) patients were analyzed and a prognosis model was constructed. Retrospectively, the medical data of elderly APL patients ( N  = 1723, from year 2000 to 2020) were gained from surveillance, epidemiology, and end results (SEER) database, and patients were randomly divided into train set and test set 1 (7:3). Test set 2 was composed of 17 APL patients from our hospital. Single factor and multi-factor analyses were performed by COX regression analysis. Death causes were analyzed among dead APL patients. Prognosis prediction model was constructed and verified. Single factor analysis results showed that age, marital status, income, year of diagnosis, months from diagnosis to treatment and chemotherapy were highly correlated with the death of APL patients. Multi-factor analysis results indicated that age, year of diagnosis and chemotherapy could independently serve as predictors to the death of APL patients. More patient succumbed to APL relative to other causes. The prognosis model had a higher diagnostic value for 0.5-year (AUC = 0.797) overall survival in train set, and for 2-year (AUC = 0.784) overall survival in test set 1. 1-year survival prediction in train set and test set 1 indicated the stability of the model. Age, year of diagnosis and chemotherapy are the independent risk factors, and APL is the leading cause of death in elderly APL patients. The prognosis model has a good clinical prediction value for elderly APL patients.

The present study determined the role and mechanism of miR-138 in non-small cell lung cancer (NSCLC). In total, 45 freshly resected clinical NSCLC tissues were collected. The expression of miR-138 in tissues and cell lines were determined by real-time quantitative PCR. miR-138 mimics were transfected into A549 and Calu-3 cells in vitro, and then the effects of miR-138 on lung cancer cell proliferation, cell cycle, invasion and metastasis were investigated by CCK-8 assay, Transwell and flow cytometry, respectively. The protein expression of the potential target gene Sirt1 in lung cancer cells were determined by western blot analysis. Dual-Luciferase reporter assay was performed to further confirm whether Sirt1 was the target gene of miR-138. The expression of miR-138 was significantly lower in lung cancer tissues and was negatively correlated to the differentiation degree and lymph node metastasis of lung cancer. In vitro experiment results showed that miR-138 inhibited lung cancer cell proliferation, invasion and migration. It was verified that miR-138 could downregulate Sirt1 protein expression, inhibit epithelial-mesenchymal transition (EMT), decrease the activity of AMPK signaling pathway and elevate mTOR phosphorylation level. Dual-Luciferase reporter assay demonstrated that miR-138 could directly regulate Sirt1. Downregulation of Sirt1 alone can also cause the same molecular and biological function changes. Western blot analysis and confocal microscopy results indicated that overexpression of miR-138 or interference of Sirt1 expression could inhibit lung cancer cell autophagy activity possibly through AMPK-mTOR signaling pathway. miR-138 plays a tumor suppressor function in lung cancer. It may inhibit the proliferation, invasion and migration of lung cancer through downregulation of Sirt1 expression and activation of cell autophagy. The downregulation of miR-138 is closely related to the development of lung cancer.

Hereditary spherocytosis (HS) and Chronic myelocytic leukemia (CML) are both life threatening hemotologic diseases. They are rarely seen to occur simultaneously in one individual patient. Here we demonstrate a case of HS associated with CML in this study. The patient is a young female, diagnosed with HS in 2005, and was given partial embolization of the splenic artery. She got significant remission after the procedure. In 2008, she was found abnormal in blood routine test, after bone marrow routine, chromosome and fusion gene tests, she was diagnosed with CML (chronic phase). She did not receive regular treatment until 3 months prior, and is currently being treated with Dasatimib. She achieved hematological remission, but had no significant improvement in chromosome and fusion gene figures. Due to her severe condition of hemolysis, a splenectomy or an allogeneic hematopoietic stem cell transplantation is considered.

Curcumin, a polyphenol derived from the rhizome of Curcuma, is a potential tumor inhibitor through affecting signaling pathways and epigenetic regulation. The mammalian target of rapamycin (mTOR) gene serves a crucial role in the carcinogenesis of multiple myeloma. The curcumin-induced epigenetic regulation of mTOR, including promoter DNA methylation in multiple myeloma, has not yet been fully elucidated. In the present study, antitumor effects of curcumin were investigated in RPMI-8226 and NCI-H929 cells using an MTT assay and flow cytometry. The expression of mTOR and DNA methyltransferase proteins were determined by western blot analysis, and the methylation status of the mTOR promoter were detected by sequencing following bisulfite conversion. The results of the present study revealed that the half-maximal inhibitory concentration of curcumin was 10 µM in myeloma cells. Following curcumin treatment, the mRNA and protein expression levels of mTOR were decreased by 43.31 and 39.34% in NCI-H929 cells, respectively. The promoter of mTOR, located in chromosome 1 (chromosome position, 11262153-11263153), contains a CpG island that was hypermethylated in myeloma cells following curcumin treatment. The expression levels of DNA methyltransferase (DNMT)3a and DNMT3b were increased in curcumin-treated cells. Collectively, these results indicate that curcumin serves a role in the epigenetic regulation of mTOR expression, and that mTOR downregulation is due to promoter hypermethylation, which may be associated with DNMT3a and DNMT3b upregulation. The results of the present study contribute towards improving the understanding of curcumin treatment in multiple myeloma and provide novel insights into the molecular mechanisms underlying the epigenetic regulation of mTOR.

Objective. Primary hepatic lymphoma is a rare disease. And the clinical manifestations of this disease are nonspecific. The objective of this paper is to improve clinicians’ understanding of this disease. Methods. We analyzed the clinical characteristics of a case of primary hepatic lymphoma in association with hepatitis B virus infection and reviewed the literature. Conclusion. The clinical manifestations of primary hepatic lymphoma are nonspecific. And it is easily misdiagnosed. Postoperative radiotherapy of patients with early stage was previously speculated to achieve favorable improvement. The application of targeted therapeutic drugs, chemotherapy, or combined local radiotherapy has become the first-line treatment strategy.

Objective: The aim of this study was to evaluate the clinical efficacy and safety of high-dose imatinib (IM) for chronic myeloid leukemia (CML) patients by pooled published studies. Methods: Through searching the databases of PubMed, EMBASE, ASCO, ESMO, CNKI, and Wanfang, we collected open published clinical controlled trials-related high-dose IM treatment of CML. The pooled complete cytogenetic response (CCyR) and hematologic toxicities were calculated by the statistical software. Results: Seven studies were included in this study with 1137 cases received high-dose IM treatment and 958 cases received regular-dose IM treatment. The pooled results showed that patients received high-dose IM had higher CCyR compared with regular-dose with the odds ratio (OR) of 1.75 (95% confidence interval [95% CI]: 1.44-2.1, P < 0.05) and 1.58 (95% CI: 1.38-1.81, P < 0.05) in 6 and 12 months. However, the hematologic toxicities risk of neutropenia (OR = 1.76, 95% CI: 1.22-2.54) and thrombopenia (OR = 1.88, 95% CI: 1.42-2.50) were much higher in the high-dose group. Conclusion: High-dose IM for CML treatment was superior to standard-dose IM in the aspects of CCyR, but the risk of developing neutropenia and thrombopenia was much higher.

Objective: The aim of this study was to evaluate the clinical efficacy of Aidi injection combined with CHOP chemotherapy regimen in the treatment of malignant lymphoma. Methods: We made an electronic search in the database of Wanfang, CNKI, and PubMed. All the clinical studies related to Aidi injection combined with CHOP chemotherapy regimen in the treatment of malignant lymphoma were screened and reviewed. The combined objective response rate (ORR), life quality improvement, and hematological toxicity were pooled by random- or fixed-effect model according to the heterogeneity across the included study. Moreover, the publication bias was evaluated by Begg's funnel plot and Egger's line regression test. Results: Eight prospective clinical trials with 513 subjects (273 in the Aidi injection plus CHOP group and 240 in the CHOP group) were included in this meta-analysis. The pooled results showed that Aidi injection combined with CHOP chemotherapy regimen can significantly improve the ORR (odds ratio [OR] =1.68, 95% confidence interval [CI]: 1.09-2.60, P < 0.05), improve the life quality (OR = 3.32, 95% CI: 1.97-5.58, P < 0.05), and decrease the risk of developing leukopenia (OR = 0.25, 95% CI: 0.17-0.39, P < 0.05) and thrombocytopenia (OR = 0.34, 95% CI: 0.22-0.53, P < 0.05). Conclusion: With the present evidence, Aidi injection combined with CHOP chemotherapy regimen can improve the treatment response and quality of life and decrease the risk of developing severe leukopenia or thrombocytopenia.