Kidney Transplantation and Clinical Outcomes in Patients With Multiple Myeloma: Evidence From the United States Nationwide Inpatient Sample / 대한배뇨장애요실금학회지

Purpose@#Patients with multiple myeloma (MM) are prone to developing persistent renal insufficiency. Novel therapeutic medications have improved long-term survival, making kidney transplantation (KT) a viable treatment option for MM survivors with end-stage renal disease. This study aimed to investigate the clinical outcomes in patients with MM who have received KT. @*Methods@#Data from hospitalized patients ≥ 40 years of age with MM in the Nationwide Inpatient Sample 2016–2018 of the United States were queried. Patients were classified as having or not having undergone KT, as well as the stage of chronic kidney disease (CKD) for those who had not received KT. Propensity-score matching (PSM) was applied to balance the characteristics between the groups. Binary logistic regression was utilized to determine the associations between study variables and inhospital mortality, unfavorable discharges, prolonged length of stay (LOS), and major complications. @*Results@#In total, 50,654 hospitalized patients with MM were identified, of whom 165 (0.3%) had received KT and 50,489 had not (5,905 at stage 5 CKD [CKD5D], 11,559 at stage 1–4 CKD [CKD1-4D], and 33,025 who were CKD-free). After PSM, between-group demographic and hospital-related characteristics were balanced. Binary regression analysis revealed that, compared to patients who were CKD-free, patients at CKD5D were significantly more likely to experience a prolonged LOS (odds ratio [OR], 1.31; 95% confidence interval [CI], 1.01–1.70) after adjusting for relevant confounders. Furthermore, compared to CKD-free patients, those who underwent KT were significantly more likely to have sepsis (OR, 1.48; 95% CI, 1.02–2.14). However, KT showed no association with the other adverse inpatient outcomes. @*Conclusions@#Although KT is not common in MM patients, those who had undergone KT had comparable hospital outcomes to CKD-free patients. These data will help clinicians deliver better consultations to MM patients attempting to receive KT.

Transcriptomic mechanisms and efficacy analysis of D-CAG regimen for treatment of acute myeloid leukemia after failure to initial induction of remission / 白血病·淋巴瘤

Objective:To investigate the transcriptomic mechanisms and clinical efficacy of D-CAG regimen for the treatment of acute myeloid leukemia (AML) after failure to initial induction of remission.Methods:The transcriptome data of AML cells before and after the use of dexitabine before August 28, 2021 was searched in Gene Expression Omnibus (GEO) database with "decitabine" as the search term. The R language package was used for differential expression analysis and Kyoto encyclopedia of genes and genomes (KEGG) and gene ontology (GO) enrichment analysis of the data. Protein-protein interaction network (PPI) analysis was conducted on the STRING online analysis website. The accurate treatment prediction platform designed based on logistic omics theory (EpiMed) was used to make drug-disease-target correlation analysis. The clinical data of 18 AML patients treated with D-CAG regimen after failure to induction of remission with standard anthracycline and cytarabine regimen ("3+7" regimen) in the 305th Hospital of Chinese PLA from October 8, 2015 to July 9, 2018 were searched and analyzed, and the curative effect was evaluated. The effects of the dose and duration of each drug on the efficacy were analyzed.Results:The transcriptome data of AML cells before and after the use of decitabine in GSE40442 dataset of the GPL5188 platform were finally selected, updated on July 10, 2014. A total of 366 differentially expressed genes were screened, including 201 up-regulated genes and 165 down-regulated genes. The differential genes were mainly related to cell cycle regulation, bone marrow leukocyte migration and differentiation, transcriptional regulation, bone marrow hematopoiesis and other signaling pathways. Ten core genes such as ANXA5, IL-10, THBS1, TLR4, JUN and CXCL12 were screened by PPI analysis. Drug-disease-target analysis showed that dexitabine had a potential therapeutic effect on various blood diseases such as diffuse large B-cell lymphoma, thrombocytopenia, T-cell acute lymphocytic leukemia, aplastic anemia, and AML. Of the 18 patients, after initial induction of remission, 7 (38.8%) patients achieved partial remission (PR), and 11 (61.2%) patients had no response (NR); after one cycle of re-induction remission therapy, 9 patients had complete remission (CR), 5 patients had PR, 4 patients had NR, and the overall response rate (ORR) was 77.8% (14/18). Compared with patients with NR, the CR rate was higher in patients with PR after initial induction therapy, which were 85.7% (6/7) and 27.3% (3/11), and the difference was statistically significant ( χ2=5.84, P = 0.025). The median duration of cytarabine in CR patients was longer than that in NR patients [10 d (7-14 d) vs. 5 d (2-8 d), Z = 3.89, P = 0.002] and the median ratio of the number of bone marrow blast cells to the duration cytarabine was lower in CR patients than that in NR patients [2.29 (0.89-9.10) vs. 8.10 (3.00-38.50), Z = -2.19, P = 0.006]; the median dose of cytarabine in CR patients was lower than NR patients, which were 50 mg·m -2·d -1 (30-150 mg·m -2·d -1) and 100 mg·m -2·d -1 (50-500 mg·m -2·d -1), and the difference was not statistically significant ( Z = -1.80, P = 0.074). Conclusions:AML patients with PR after initial induction and failure to initial induction of remission may be more likely to achieve CR after the treatment of D-CAG regimen, and this change may be related to the epigenetic regulation of decitabine.

Bioinformatics prediction of molecular mechanism and intervention drugs of SARS-related immune injury and their significance for COVID-19 treatment / 中华微生物学和免疫学杂志

Objective:To investigate the omics mechanism of SARS-related immune injury and predict targeted therapeutic drugs through clinical bioinformatics analysis of the transcriptome data of SARS virus in order to provide reference for clinical treatment of COVID-19.Methods:The transcriptome data of SARA virus were collected from the Gene Expression Oibus (GEO) and used to screen differential genes. Enrichment analysis and protein interaction analysis were performed to investigate the mechanism of immune damage associated with SARS. A platform of epigenetics in precision medicine (EpiMed) was established to predict potential therapeutic drugs.Results:The mechanism of SARS-related immune injury was complex, involving affecting the function of immune cells through signaling pathways such as Toll-like receptors, increasing cytokines in plasma through Th17 signaling pathway and inducing autoimmune responses after autoantibodies were generated by molecules such as IL-6, NF-κB, and TNF. Drugs such as Chuanqiong and Etanercept might have therapeutic effects on SARS-related immune damage.Conclusions:SARS virus could cause abnormal expression of many immune-related molecules and signaling pathways. Drugs such as Chuanqiong and Etanercept might have therapeutic effects on SARS-related immune damage. This study might provide reference for clinical treatment of COVID-19.

Omics analysis of angiotensin converting enzyme 2 inhibitory mutation-related inflammatory response and intervention drugs and its significance on corona virus disease 2019 / 中华传染病杂志

Objective:To analyze the inflammatory mechanism and potential intervention drugs related to angiotensin converting enzyme 2 (ACE2) inhibitory mutations in order to provide reference for the treatment of corona virus disease 2019 (COVID-19).Methods:The data of lung adenocarcinoma with ACE2 mutations were screened from the cancer genome atlas (TCGA) database. The data were analyzed by R program language edgeR package and cluster Profiler package, gene ontology (GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Using String online analysis website for protein-protein interaction (PPI) network analysis, screening out the core genes, and finally using the Epigenomic Precision Medicine Prediction Platform (EpiMed) for multi-group association analysis of key genes, and drug candidates prediction.Results:A total of 1 005 differential genes were obtained, of which 91 were up-regulated and 914 down-regulated. A total of 71 GO were enriched, including 45 items related to biological processes, 16 items related to cell components, and 10 items related to molecular function. A total of 13 KEGG pathways were enriched, mainly in inflammatory pathways, various viral infectious diseases, transcriptional regulation, drug metabolism and protein digestion and absorption pathways. The differentially expressed genes were introduced into String online analysis website for PPI network analysis, a total of 252 proteins were obtained, and 10 core genes were H2A clustered histone 16(HIST1H2AL), H3 clustered histone 2 (HIST1H3B), H3 clustered histone 7 (HIST1H3F), H3 clustered histone 11 (HIST1H3I), H3 clustered histone 3 (HIST1H3C), H2B clustered histone 3 (HIST1H2BB), H2B clustered histone 6 (HIST1H2BI), H4 clustered histone 2 (HIST1H4B), H1-4 linker histone (HIST1H1E), H2A clustered histone 4 (HIST1H2AB). Interferon-α, resveratrol, celecoxib, heartleaf houttuynia herb, weeping forsythia capsule, dexamethasone, Chinese pulsatilla root, tumor necrosis factor-α inhibitors, liquorice root and famciclovir might be drugs for the treatment of ACE2 mutation-related inflammation.Conclusions:Inflammation associated with ACE2 inhibitory mutations is similar to the pathogenesis of COVID-19, which could lead to disease by promoting the activation of inflammatory pathways such as mitogen-activated protein kinase (MAPK), the Janus kinase signal transducer and activator of transcription (JAK/STAT), mammalian target of rapamycin (mTOR). Celecoxib, interferon and resveratrol may have the potential therapeutic effects on COVID-19.

Effect of clopidogrel on development of chemically induced colitis-associated cancer in mice / 中国药理学与毒理学杂志

OBJECTIVE To investigate the effect of clopidogrel(Clog),a platelet aggregation inhibitor,on the development of colitis-associated colon cancer(CAC)and its possible mechanism. METHODS To establish a CAC model,male BALB/c mice were treated with single azoxymethane(AOM) 10 mg · kg-1 by ip. One week later,the mice drank 2.5% dextran sulfate sodium(DSS)for one week and water for two weeks,which lasted three cycles. From the first day mice received 2.5%DSS water, Clog 12.5,25.0 and 50.0 mg · kg-1 was ig administered once a day. Body mass,clinical symptoms,the number of colon tumor and tumor size in colon tissue were recorded. Hyperplasia of tumors was analyzed by HE staining. In the early inflammatory phase of the CAC model,the length of colons was measured, histological structure and epithelium cell proliferation of colon tissues were evaluated by HE staining and Ki67 staining,respectively. In the tumorigenesis and progression phase of the CAC model,epithe?lium cell proliferation of colon tissues was evaluated by Ki67 staining. The mRNA expression of tumor necrosis factor-α(TNF-α)was detected by real-time quantitative PCR. The expression of chemokine(C-X-C motif)ligand 2(CXCL2)and its receptor 2(CXCR2)in colon tissues was detected by PCR and immu?nohistochemistry. RESULTS Compared with model group,clinical symptoms of mice in Clog 12.5 mg · kg-1 group were alleviated,the size of colon tumors was decreased(P<0.05),and hyperplasia of tumors was reduced(P<0.05). During the inflammatory phase,the clinical symptoms of mice in Clog 12.5 mg·kg-1 group were significantly alleviated(P<0.05),the decrease of body mass was reduced(P<0.01),the colon shrinkage was ameliorated(P<0.01),the inflammatory injury and epithelium cell proliferation in colon tissues were reduced(P<0.05). During the tumorigenesis and progression phase,epithelium cell prolif?eration in colon tissues in Clog 12.5 mg·kg-1 group was reduced(P<0.01),and the mRNA and protein expression of TNF-α,CXCL2 and CXCR2 of colon tissues was decreased(P<0.05). CONCLUSION Clog can alleviate inflammation during the CAC early inflammatory phase and inhibit the formation of CAC. The antitumor effect of Clog may be related to the decrease in expression of CXCL2 and CXCR2.

Effect of amifostine on proliferation and differentiation of human megakaryocyte Dami cells / 中国药理学与毒理学杂志

OBJECTIVE To investigate the effect of amifostine(Amf)on the differentiation of human megakaryocyte cell line-Dami. METHODS Dami cells were treated with Amf 0.01-5.0 mmol · L-1 for 12 d. Dami cells were counted every day for the growth curve:only cells with a diameter>20μm. The platelet demarcation membrane system was observed by transmission electron microscopy. The expression of CD33,CD34,CD41a and DNA ploidy was detected by flow cytometry. RESULTS Amf 0.1-1.0 mmol · L-1 promoted the differentiation of Dami cells ,but inhibited their proliferation at a concentration>1.0 mmol · L-1. When these cells were treated with Amf 1.0 mmol · L-1 for 12 d,the platelet demarcation membrane system was observed,the percentage of cells with a diameter >20 μm was increased by 24.6%(P1.0 mmol·L-1).

Effect of clopidogrel combined with calcium-channel blocker on coronary artery disease in elderly patients: a propensity score-based retrospective cohort study / 南方医科大学学报

<p><b>OBJECTIVE</b>To compare the effects of clopidogrel combined with dihydropyridine calcium-channel blockers (CCBs) or non-dihydropyridine CCBs on coronary artery disease (CAD) in elderly patients.</p><p><b>METHODS</b>The study cohort was defined as all patients ≥60 years old hospitalized for CAD with the prescription of clopidogrel between January 2001 and February 2011. The primary endpoint was death of all causes, and the secondary endpoints were nonfatal myocardial infarction (MI), hospitalization for unstable angina, stroke, transient ischemic attack, or repeat revascularization (PCI or coronary artery bypass graft).</p><p><b>RESULTS</b>A total of 1021 patients were enrolled, among whom 402 patients were prescribed with clopidogrel and 619 with clopidogrel combined with CCB (dihydropyridine in 547 and non-dihydropyridine in 72). In clopidogrel group and clopidogrel with CCB group, the incidence density of death was 50.55 per thousand and 42.02 per thousand, respectively. The crude RR was 0.83 (95%CI: 0.55-1.26), and the multivariable-adjusted RR was 0.47 (95%CI: 0.14-1.6), showing no statistical significance in the rate of deaths of call causes between the two groups (P>0.05); the incidence density of composite thromboembolic events showed no significant difference between the two groups, either (P>0.05). After weighting of the propensity score, the patients with clopidogrel coadministered with non-dihydropyridine CCB showed a significant increase in composite thromboembolic events than those taking dihydropyridine CCB, with a SMRW-adjusted OR of 1.97 (95%: 1.2-3.23, P=0.007). No significant difference was observed in death or composite thromboembolic events between Pgp-inhibiting CCBs and non-Pgp-inhibiting CCBs.</p><p><b>CONCLUSION</b>Compared with clopidogrel without CCB, clopidogrel with CCB does not increase the mortality or composite thromboembolic events in elderly CAD patients, but clopidogrel combined with non-dihydropyridine CCB is associated with significantly increased composite thromboembolic events in comparison with dihydropyridine CCB.</p>

Effect of omeprazole on gene expression profile of human umbilical vein endothelial cell line and bioinformatics analysis / 南方医科大学学报

<p><b>OBJECTIVE</b>To characterize the effect of omeprazole on the spectrum of gene expression in the cultured human umbilical vein endothelial cell (HUVEC) line (EA.hy926), and explore the underlying molecular mechanism.</p><p><b>METHODS</b>Affymetrix U133 plus2.0 oligonucleotide microarray was used to detect the alteration in the gene expression profiles induced by 1×10(-5) mol/L omeprazole in HUVECs. Real-time PCR was employed to verify the results of selected differentially expressed genes, and Western blotting was performed to test the expression levels of the related proteins.</p><p><b>RESULTS</b>A total of 282 genes were found to show at least 1.5-fold changes in EA.hy926 cells after treatment with omeprazole for 48 h, including 236 up-regulated and 46 down-regulated ones. These genes were involved in the regulation of transcription, inflammatory response, immune response, cell adherence, anti-apoptosis, and signal transduction.</p><p><b>CONCLUSION</b>Omeprazole modulates the function of endothelial cells by regulating the gene expression profiles of multiple pathways.</p>

Inhibitory effects of traditional Chinese herbal medicine Tanreqing injection on proliferation of leukemia cells in vitro and the potential mechanisms / 中西医结合学报

Objective: The present study investigates the effects of Tanreqing injection, a compound Chinese herbal medicine, on the proliferation of leukemia cells in vitro and discusses the potential mechanisms. Methods: Tanreqing injection was diluted to a series of concentrations (1:2, 1:4, 1:8, 1:16, 1:32, 1:64, 1:128, 1:256 and 1:512) by volume and then independently applied to treat chronic myeloid leukemia K562 cells and T cell acute lymphocytic leukemia Molt4 cells at the proliferative stage. Cell growth was observed at different time intervals under a microscope. Cell proliferation was determined by cell counting kit-8 assay and the survival curve was delineated. The inhibitory rate and the half inhibitory concentration (IC50) were calculated. Molt4 cells were stained with propidium iodide (PI) and PI/Annexin V and then the cell cycle and apoptosis were analyzed by using flow cytometry. In addition, a real-time quantitative polymerase chain reaction was subjected to detect the expressions of apoptosis-related genes (bcl-2 and caspase-3) after Tanreqing treatment. Results: Tanreqing injection had inhibitory effects on the proliferation of K562 cells and Molt4 cells. The most toxic concentrations were observed between 1:2 and 1:16 where cells were almost necrotic. The inhibitory effect manifested in a concentration- and time-dependent manner. The IC50 of K562 and Molt4 was 1:333 and 1:142, respectively. After 1:32 Tanreqing injection treatment for 72 h, the number of Molt4 cells in the S phase significantly decreased (P<0.05), and the apoptosis rate markedly increased (P<0.05). In addition, increased caspase-3 expression and decreased bcl-2 expression were also observed (P<0.05). Conclusion: Tanreqing injection can both inhibit the proliferation and promote the apoptosis of leukemia cells in vitro, whereby the potential mechanism seems to be mediated in part by decreasing S phase ratio, down-regulating bcl-2 expression and up-regulating caspase-3 expression.

Influence of ABO-incompatible grafts in allogeneic hematopoietic stem cell transplantation / 中国组织工程研究

0.05).CONCLUSION:Pure red cell aplastic anemia appears after allogeneic hematopoietic stem cell transplantation in major ABO incompatibility between donor and recipient,which may lead to prolonged destruction of donor-derived erythrocytes and prolonged transfusion requirements.However,myeloid and megakaryocyte hematopoietic recovery,incidence of complications and survival rate are not influenced by ABO incompatibility.