Myocardial injury caused by Doxorubicin has limited its clinical application. Our research has demonstrated that doxorubicin induces various forms of cell death, oxidative stress, and metabolic abnormalities. We have confirmed, through both in vitro and in vivo studies, that apoptosis, iron overload, inflammatory responses, and arachidonic acid metabolism contribute to doxorubicin's cardiotoxic effects. Treatment with quercetin effectively reduces iron accumulation and preserves mitochondrial structural integrity by inhibiting oxidative stress and inflammatory responses. Using molecular docking and surface plasmon resonance (SPR) techniques, our study suggests that quercetin activates the HO-1/PGC-1α pathway, which may involve downregulation of ALOX5 expression, thereby alleviating oxidative stress, inhibiting iron-dependent lipid peroxidation and ferroptosis-like changes, mitigating inflammatory responses, and modulating arachidonic acid metabolism. Additionally, quercetin enhances energy availability and supports mitochondrial function. We propose quercetin, a promising active compound derived from traditional Chinese medicine, as a potential mitigator of doxorubicin-induced cardiotoxicity.

Background Novel biomarkers and therapeutic target identification are required to improve the cure rate of relapsed/refractory leukemia. Aberrant glycosylation is present during tumorigenesis, so glycosylation-related genes may be ideal candidates. This study aimed to explore the prognostic potential of glycosylation-related genes in B-cell acute lymphoblastic leukemia (B-ALL).Methods The expression of 220 glycosylation-related genes based on the transcriptome was determined in patients with primary B-ALL (n=183) using the Therapeutically Applicable Research to Generate Effective Treatments project. Kaplan–Meier survival analysis identified 174 statistically significant genes that strongly predicted prognosis. Their prognostic value was analyzed in acute myeloid leukemia (AML) to determine their universal application in acute leukemia cases. We focus on genes with independent prognostic value in ALL and AML, as well as genes that contradict experimental data through bioinformatics analysis, and analyze their causes or mechanisms.Results Eighteen prognostic genes could be applied to both B-ALL and AML. A panel of five glycosylation-related genes (favorable: CHST15 and ST3GAL1; adverse: B3GNT7, CHPF, and HAS2) was identified as an independent biomarker for the risk stratification of patients with B-ALL, complementing traditional clinicopathological prognostic factors. In addition, transcriptome sequencing data indicates that FUT4 has a good prognosis in ALL, which is inconsistent with previous research results in our laboratory. Analysis of the reasons suggests that it is highly likely related to tumor burden.Conclusions CHST15, ST3GAL1, B3GNT7, CHPF, and HAS2 were acted as an independent biomarker for B-ALL and AML. Based on the single-cell transcriptomic analysis, we propose that the inconsistency of FUT4 may result from a lower tumor load and a higher proportion of myeloid cells. Thus, our data emphasizes the benefits of selecting glycosylation-related genes as prognostic markers of B-ALL and provides new insights into mechanism exploration, prognosis prediction, and drug development for leukemia. Revealed the reasons for the inconsistency between the big data analysis results of clinical queues and the research conclusions of laboratory cell models. Bioinformatics analysis can provide directional effects, and the specific role of genes needs further verification.

Purpose. To investigate the role and mechanism of N-fucosyltransferase VII (FUT7) in acute lymphoblastic leukemia (ALL). Methods. Bone marrow tissues were collected from patients with ALL and children with immune thrombocytopenic purpura (control) hospitalized in our hospital during the same period. Then, the FUT7 expression in bone marrow tissues was detected by qRT-PCR and western blotting. Human ALL cell strain Jurkat was cultured, and after knockdown or overexpression of FUT7, cell proliferation, apoptosis, adhesion and invasion were examined by MTT assay, flow cytometry, fibronectin adhesion assay and transwell, respectively; the protein expression level of integrin α5, integrin β1, p-FAK, and p-AKT was tested by western blotting. Results. The FUT7 expression was up-regulated in bone marrow cells of ALL patients. After knockdown of FUT7, the proliferation, adhesion and migration ability of ALL cells were significantly reduced, and apoptosis was increased, while the overexpression of FUT7 obtained the opposite results. Moreover, the overexpression of FUT7 also promoted the protein expression of integrin α5, integrin β1, p-FAK, p-AKT. Conclusion. FUT7 can promote the adhesion and invasion of ALL cells by activating the integrin/FAK/AKT pathway.

患儿,女,出生后8 h因"生后发现肛门闭锁8 h"入我院新生儿外科.患儿母亲孕1产1,胎龄37周,羊膜早破7 h,因"胎位不正"剖宫产娩出,羊水清.患儿无宫内窘迫史,出生时无窒息抢救史,1-min Apgar评分10分,出生体重3.45 kg.患儿入院后完善术前检查拟手术治疗.

Unveiling the mechanism of the relapse of acute lymphoblastic leukemia (ALL) is the key to improve the prognosis of ALL and remains a huge challenge. Glycan-based interactions play a vital role in immune surveillance, cell-cell adhesion and cell-matrix interaction, contributing to treatment failure in tumor. However, the glycan essential for leukemia development and its upstream regulatory mechanism by oncogenic drivers were rarely reported. Here, we demonstrated that LeX, a well-characterized cancer-related glycan epitope, strengthened the cell-matrix interaction via glycosylating α5β1 integrin under the control of the driver oncogenic Ikaros isoform (IK6) in ALL. By analyzing the expression profile of Ikaros and the level of FUT4/LeX in clinical samples, we found that FUT4/LeX was positively correlated with dysfunctional Ikaros isoforms. IK1 (Full length Ikaros) regulates the level of FUT4 as a transcription repressor, while IK6 abolished the wild-type Ikaros mediated transcriptional repression and resulted in higher level of FUT4 expression. Moreover, we demonstrated that FUT4 could activate α5β1-mediated sequential signal transduction and accelerate adhesion and invasion between integrin α5β1 in leukemia cells and fibronectin in extracellular matrix (ECM) via increasing glycosylation. Together, our study provides a new insight into the mechanisms by which Ikaros mutation induced ALL cells invasion and a potential strategy for drug-resistance ALL by blocking LeX in combination with common chemotherapy.

OBJECTIVE:To explore the genetic cause for a child with congenital ichthyosis.METHODS:The child was subjected to next generation sequencing using a specific gene panel. Suspected mutation was validated by Sanger sequencing.RESULTS:The proband was found to harbor compound heterozygous mutations c.327delG (p.Met109Ilefs*2) and c.791G>A (p.Arg264Gln) of the TGM1 gene, which were respectively inherited from his mother and father. The same mutations were not found among 101 healthy controls. c.327delG was not reported previously. By bioinformatic analysis, both mutations are likely to impair the function of TGase-1 protein.CONCLUSION:The compound heterozygous mutations of c.327delG and c.791G> A of the TGM1 gene probably underlie the ichthyosis in the proband. The result has facilitated prenatal diagnosis for this pedigree.

This paper reported the diagnosis and treatment of two neonates with Kabuki syndrome (KS).Neither of them had typical facial features of KS during the neonatal period,but poor response,abnormal appearance and multiple organ dysplasia were observed in both.Case 1 was lost to follow up after discharge,while typical KS facial features were gradually appeared in Case 2 including eversion of lower lateral eyelids,arched eyebrows,sparse eyebrow arch,flattened nasal tip,prominent ears,during a three-month follow-up after birth.Next-generation sequencing revealed that both neonates were KS caused by lysine methyltransferase 2D (KMT2D) gene mutation,of which case 1 had a heterozygous deletion mutation ofc.13895delC (p.P4632HfsTer8) in KMT2D gene,while case 2 had a heterozygous repeat mutation of c.12809dupA (p.T4271Dfs*63) in KMT2D gene.Both cases were defined as de novo mutations and the one carried by case 2 was a newly discovered pathogenic mutation.

Biliary atresia (BA) is a rare and severe disease that affects infants where a fibroinflammatory process destroys the bile ducts, leading to fibrosis and biliary cirrhosis, and mortality if untreated. Bone marrow‑derived mesenchymal stem cells (BMMSCs) have been considered as a promising therapy in fibrotic diseases. The aim of the present was to investigate the anti‑fibrotic roles of BMMSC transplantation in a BA mouse model. Mouse BA models were established by Rhesus rotavirus administration to neonatal mice. The results revealed that the liver enzyme and bilirubin metabolism levels, and the levels of the oxidative stress marker malondialdehyde (MDA) and the fibrosis marker were all increased in the BA model, while the liver tissue levels of superoxide dismutase and glutathione peroxidase were reduced. The hematoxylin and eosin and Masson's trichrome staining revealed severe liver fibrosis and collagen accumulation in BA livers. However, these indicators were all reversed once the BA mice were administered the BMMSC inoculation. In conclusion, the present study demonstrated the anti‑fibrotic potential of BMMSCs in BA mice, which may provide a novel approach to ameliorate the fibrotic response in BA patients.

An algorithm for distributed mining association rules with constraints called DMCASE is presented using Sampling and constraint-based Eclat algorithm. At each database site, Sampling algorithm and constraint-based Eclat algorithm are implemented. And the local frequent itemsets satisfying constraints are developed They then are combined to global frequent itemsets satisfying constraints based on inductive learning method DMCASE algorithm scans the whole database only once. It is also an algorithm with high efficiency. Results from our experiments show that the algorithm is an effective way to resolve the problem of distributed mining association rules with constraints.