Mitochondrial dysfunction is crucial in the pathogenesis and drug resistance of pediatric T-cell acute lymphoblastic leukemia (T-ALL), a malignant hematological disorder with unrestrained proliferation of immature T-cells. Therefore, the primary objective of this study is to elucidate the role of mitochondrial dysfunction-related differentially expressed genes (MDRDEGs) in pediatric T-ALL and to establish a diagnostic model based on the MDRDEGs. We obtained datasets from GEO on pediatric T-ALL patients and healthy controls. A comprehensive list of 843 mitochondrial dysfunction-related genes (MDRGs) was compiled from GeneCards database and PubMed literature. Subsequently, we identified significant MDRDEGs, also, performed functional enrichment and analysis immune infiltration analysis. Additionally, A mitochondrial dysfunction-based signature was created to predict pediatric T-ALL. The mRNA-miRNA and mRNA-TF Regulatory Network were constructed, and the molecular distributions of key genes were calculated. There were 8029 differentially expressed genes (DEGs) in pediatric T-ALL compared to controls. Intersecting these DEGs with MDRGs yielded 284 MDRDEGs. Enrichment analyses revealed that these MDRDEGs were involved in oxidative stress response, cellular respiration, mitochondrial inner membrane composition, and protein complexes. GSEA and GSVA highlighted significant enrichment in NF-κB and JAK-STAT pathways. The intersection of LASSO regression and RF algorithms highlighted two pivotal genes: RNLS and ULK1. Validation dataset demonstrated our diagnostic model's high accuracy. In conclusion, this study systematically investigated MDRDEGs' roles in pediatric T-ALL and constructed an effective diagnostic model. The findings provided new potential biomarkers for early diagnosis and therapeutic targets for pediatric T-ALL, offering promising directions for future research.

Objective The ETV6RUNX1 fusion is the most common genetic abnormality in childhood B-cell acute lymphoblastic leukemia (B-ALL), yet nearly 50 % of relapses occur in patients initially classified as low-risk with this alteration. This study aimed to unravel the underlying pathways driving relapse in ETV6RUNX1 positive B-ALL. Methods Single-cell RNA sequencing (scRNA-seq) was performed on a cohort of four B-ALL patients with the ETV6RUNX1 fusion (three newly diagnosed and one relapsed case, selected from 25 patients). Results we discovered that relapsed samples exhibited a decline in T cell populations, an increase in CD8 Tex cells and B cells, and a higher proportion of malignant cells. Gene enrichment analysis demonstrated that IFN-γ response signaling pathways and inflammatory responses were significantly enriched in newly diagnosed samples. Conversely, the relapsed samples showed enrichment in the oxidative phosphorylation and glycolysis pathways. Additionally, analysis of cellular interactions revealed that malignant B cells could interact with T cells through LGALS9-HAVCR2, potentially leading to the exhaustion of effector T cells. Moreover, NPDC1, LEF1, and ERG exhibited higher activity levels in malignant B cells from relapsed patients, highlighting their roles in the progression and maintenance of leukemia. Conclusion In summary, our study provides valuable insights into the potential causes of relapse in B-ALL patients with ETV6RUNX1, providing a foundation for the identification of prospective therapeutic targets.

Background: Systemic Epstein-Barr virus (EBV)-positive T-cell lymphoma of childhood (STCLC) is a rare disease with few clinical reports and high mortality. By exploring the clinical manifestations of a child with STCLC in our hospital auxiliary examination and diagnostic and therapeutic process, to deepen pediatricians' understanding of this disease. Case Description: This paper describes a 5-year-old Chinese girl who presented with acute fever and epistaxis. After admission, relevant ancillary tests indicated the presence of hemophagocytic lymphohistiocytosis (HLH) and the combination of EBV infection in this patient. Pathology of the cervical lymph node biopsy and bone marrow flow cytology examination indicated STCLC, and a diagnosis of STCLC combined with HLH was clear. Although the girl was clearly diagnosed within a few days and treated with chemotherapy and symptomatic support, she eventually died on the 6th day after admission due to progressive worsening of her disease. Conclusions: STCLC is a rare T-cell lymphoproliferative disorder that occurs primarily in the setting of acute EBV infection, usually presenting as HLH. It is a rapidly progressive and fatal disease of children and young adults characterized by monoclonal expansions of EBV-positive T-cells with an activated cytotoxic phenotype and by malignant proliferation. The mortality rate is close to 100%.

目的 分析乙型肝炎(乙肝)患者血清长链非编码RNA核富集转录体1(lncRNA NEAT1)表达与乙型肝炎病毒(HBV) DNA载量、肝功能及T淋巴细胞亚群的相关性.方法 按照血清HBV-DNA低、中、高载量1∶1∶1的比例收集2018年2月-2019年9月山东省千佛山医院诊治的慢性乙肝(CHB)患者324例,其中低、中和高载量组各108例.另取同期HBV携带者108例为对照组.采用实时荧光定量PCR(qRT-PCR)检测血清lncRNA NEAT1水平及HBV DNA载量,采用化学发光法检测血清谷丙转氨酶(ALT)和谷草转氨酶(AST)水平,采用流式细胞仪检测外周血CD3+、CD4+、CD8+细胞水平,计算CD4+ /CD8+值.采用Pearson法分析lncRNA NEAT1与血清肝功能指标水平及T淋巴细胞亚群的相关性.结果 与对照组比较,低、中、高HBV-DNA载量CHB患者血清lncRNA NEAT1、ALT、AST水平及CD8+细胞比例均显著增加(均P＜0.05),CHB患者外周血CD3+、CD4+细胞比例及CD4+/CD8+值均显著降低(均P＜0.05).Pearson分析显示,CHB患者血清lncRNA NEAT1水平与ALT、AST、CD8+细胞比例呈正相关(r分别为0.773、0.761、0.683,均P＜0.05,与CD3+、CD4+细胞及CD4+ /CD8+值呈负相关(r分别为-0.598、--0.719、--0.770,均P＜0.05).结论 CHB患者血清lncRNA NEAT1水平随HBV-DNA载量增加而升高,且与肝功能异常及炎症反应有关,检测血清lncRNA NEAT1可能对CHB患者病情进展及发病机制研究有一定指导价值.

Acute lymphoblastic leukemia (ALL) is a common malignancy in children. In this study, we aimed to explore putative mechanisms of microRNA-155-5p (miR-155-5p) involvement in childhood ALL (cALL) via interactions with casitas B-lineage lymphoma (CBL), interferon regulatory factor 4 (IRF4), and cyclin-dependent kinase 6 (CDK6). Bioinformatic analysis was performed initially to identify differentially expressed genes in cALL. The expression levels of miR-155-5p, CBL, IRF4, and CDK6 in peripheral blood lymphocytes from clinical ALL samples were determined using RT-qPCR and Western blot assays. A dual-luciferase reporter gene assay was used to ascertain a possible targeting relationship between miR-155-5p and CBL, CCK-8 assay and flow cytometry were used to measure cell activity and apoptosis of ALL cells. Co-IP was performed to investigate the interaction between CBL and IRF4 and the ubiquitination level of IRF4. Furthermore, in vivo validation was performed inducing xenograft tumor models with ALL cells in nude mice. As indicated by bioinformatic analysis, miR-155-5p and CDK6 were upregulated and CBL was downregulated in ALL. miR-155-5p was found to target CBL to inhibit CBL expression. miR-155-5p promoted the proliferation of ALL cells and inhibited their apoptosis by inhibiting the expression of CBL, which otherwise degraded IRF4 protein through ubiquitination, leading to inhibited CDK6 expression. Collectively, the results show that miR-155-5p can promote the development of cALL via the regulation on CBL-mediated IRF4/CDK6 axis.

In mainland China, the clinical, epidemiological and genetic features of non-O1/non-O139Vibrio cholerae(NOVC) bacteraemia have been scarcely investigated. Herein, we describe a patient with NOVC bacteraemia diagnosed in our hospital and present a retrospective analysis of literature reports of 32 other cases in China, detailing the clinical epidemiology, antibiotic resistance and molecular characteristics of isolates. Most patients were male (84.8%; median age, 53 years) and had predisposing factors, such as cirrhosis, malignant tumours, blood diseases and diabetes. In addition to fever, gastroenteritis was the most frequent presenting symptom. The mortality rate during hospitalisation was 12.1%. NOVC bacteraemia cases were more common in June-August, with the majority in coastal provinces and the Yangtze River basin. Only 42.4% of cases were attributed to consumption of marine (aquatic) products. Tetracycline, third-generation cephalosporins, and fluoroquinolones were the most effective antimicrobial agents, and the highest frequencies of resistance were recorded for ampicillin/sulbactam (37.5%), amoxicillin/clavulanic acid (33.3%), ampicillin (29.2%) and sulfamethoxazole (20%). Multi-drug resistant isolates were not detected. Limited data indicate thatctxABandtcpAgenes were absent in all NOVC isolates but other putative virulence genes (hlyA,toxR,hapandrtxA) were common. Ten multilocus sequence types were identified with marked genetic heterogeneity between different isolates. As clinical manifestations of NOVC bacteraemia may vary widely, and isolates exhibit genetic diversity, clinicians and public health experts should be alerted to the possibility of infection with this pathogen because of the high prevalence of liver disease in China.

In mainland China, the clinical, epidemiological and genetic features of non-O1/non-O139Vibrio cholerae(NOVC) bacteraemia have been scarcely investigated. Herein, we describe a patient with NOVC bacteraemia diagnosed in our hospital and present a retrospective analysis of literature reports of 32 other cases in China, detailing the clinical epidemiology, antibiotic resistance and molecular characteristics of isolates. Most patients were male (84.8%; median age, 53 years) and had predisposing factors, such as cirrhosis, malignant tumours, blood diseases and diabetes. In addition to fever, gastroenteritis was the most frequent presenting symptom. The mortality rate during hospitalisation was 12.1%. NOVC bacteraemia cases were more common in June-August, with the majority in coastal provinces and the Yangtze River basin. Only 42.4% of cases were attributed to consumption of marine (aquatic) products. Tetracycline, third-generation cephalosporins, and fluoroquinolones were the most effective antimicrobial agents, and the highest frequencies of resistance were recorded for ampicillin/sulbactam (37.5%), amoxicillin/clavulanic acid (33.3%), ampicillin (29.2%) and sulfamethoxazole (20%). Multi-drug resistant isolates were not detected. Limited data indicate thatctxABandtcpAgenes were absent in all NOVC isolates but other putative virulence genes (hlyA,toxR,hapandrtxA) were common. Ten multilocus sequence types were identified with marked genetic heterogeneity between different isolates. As clinical manifestations of NOVC bacteraemia may vary widely, and isolates exhibit genetic diversity, clinicians and public health experts should be alerted to the possibility of infection with this pathogen because of the high prevalence of liver disease in China.

The clinical features and laboratory tests results of two cases with Fanconi anemia (FA) who were admitted to the Department of Children′s Hematology and Endocrinology, the Provincial Hospital Affiliated to Shandong First Medical University in 2017 were analyzed.Sanger sequencing and multiplex ligation-dependent probe amplification(MLPA) of FA-related genes was carried out.One case was female, 4 years and 3 months old.The other case was a 6-year-old male.The main manifestations were recurrent fever, asthenia and bleeding points in both legs.The girl had milk coffee spots scattered on her legs and waist, and her left thumb nail was absent.The boy had no obvious physical examination abnormality, but his left atrium and left ventricle were large and segmental myocardial damage could be seen by echocardiography.Bone marrow biopsies of both cases showed hypo-proliferation (40%) or extremely low proliferation (10%), and no megakaryocyte was found.There were no significant abnormalities in chromosome aberration, single cell gel electrophoresis, cluster of differentiation(CD) 41, CD 55, and CD 59 and chromosome karyotype.Gene sequencing revealed that the two children had compound heterozygous mutations of Fanc A gene, which came from parents.The heterozygous mutation of c1838delT was found in the exon 21 of the female child and her father, which resulted in amino acid shift mutation pIi613Tfs*27.The heterozygous deletion mutations in exons 1-3 of Fanc A gene were found in the female child and her mother by the MLPA results.The gene sequencing analysis of the male child and his family members showed the heterozygous mutation of c4124_4125del in the exon 41 of the child and his mother, which resulted in amino acid shift mutation p. T1375Sfs*49.The heterozygous deletion mutations were observed in exons 23-40 of the male child and his father, according to the MLPA results.The main basis of diagnosis of FA is to sequence the related genes of suspected children.The c1838delT is a new mutation of Fanc A gene.

Non-O1/non-O139 Vibrio cholerae (NOVC) are increasingly being recognized as causes of sporadic cases of gastroenteritis and extra-intestinal invasive infections, such as bacteremia as well as skin and wound infections in immunosuppressed hosts. However, oral infections caused by these microorganisms have rarely been reported. We present a case of oral infection caused by NOVC in a patient undergoing chemoradiotherapy after esophagectomy for esophageal cancer. The patient recovered well after antibiotic treatment. The isolate from the patient was screened for phenotypic and genetic characteristics with reference to their major virulence genes. Our report provides supporting evidence for oral infection due to NOVC in a patient with esophageal cancer and suggests that some putative accessory virulence factors may be crucial in the pathogenicity of this strain. To the best of our knowledge, this is the first documented case of oral infection due to NOVC.

非O1、非O139群霍乱弧菌(non-O1 non-O139 Vibrio cholerae，NOVC)感染常与腹泻、肠道外感染有关，如菌血症、中耳炎、皮肤和软组织感染，口腔感染NOVC的病例极少被报道。现报道1例食管癌术后化学治疗患者口腔出现NOVC感染。患者以腹泻、腹痛伴发热起病，口唇和脸颊出现血疱，上下唇内侧和上腭黏膜出现广泛糜烂，舌底出现较大溃疡创面，经过抗菌药物治疗后腹泻好转，口腔感染症状消失。

目的:了解2019年山东千佛山医院临床细菌分离株的分布及耐药性,为临床合理使用抗生素提供依据.方法:通过Bruker MALDI-TOF、Walkaway 96 plus或VITEK-2 Compact自动化细菌鉴定仪进行细菌鉴定,纸片扩散法 、Walkaway 96 plus或VITEK-2 Compact自动化药敏系统进行药物敏感性测定.药敏按照2019年CLSI M100中规定的折点.使用WHONET 5.6软件分析数据.结果:2019年1月～12月共检出7634株临床分离株,其中革兰氏阴性菌和革兰阳性菌分别占70.5％和27.4％.前五种病原体分别是大肠杆菌、肺炎克雷伯菌、铜绿假单胞菌、金黄色葡萄球菌以及鲍曼不动杆菌.甲氧西林耐药金黄色葡萄球菌(MRSA)和凝固酶阴性葡萄球菌(MRCNS)占比分别为22.1％和31％.没有检测到对万古霉素,替考拉宁或利奈唑胺耐药的葡萄球菌.0.7％的屎肠球菌菌株对万古霉素耐药.分离出239株耐碳青霉烯的肠杆菌科细菌,占所有肠杆菌科分离株的7.6％.不动杆菌属对亚胺培南和美罗培南耐药率分别为72.2％和71.9％.铜绿假单胞菌对亚胺培南和美罗培南的耐药率分别为17.3％和14.3％.结论:我院的多重耐药细菌较前两年呈下降趋势,但形势仍较严峻,医院应做好抗菌药物临床使用管理,加强感染控制措施的落实,同时保持良好的细菌耐药性监测.

Hepatitis-associated aplastic anemia (HAAA) is a variant of acquired aplastic anemia in which bone marrow failure follows the development of an acute episode of seronegative hepatitis. HAAA occurs most frequently in male children and is lethal if left untreated. Antilymphocyte globulin, antithymocyte globulin, and allogeneic bone marrow transplantation have been used in the treatment of this disease. In this work, we report the case of a 3-year-old boy with HAAA treated successfully with immunosuppressive therapy.

Cluster of differentiation (CD)133 is considered to be a marker of leukemia stem cells (LSCs), which are one of the primary causes of occurrence, drug resistance and relapse of acute lymphoblastic leukemia (ALL). CD82, an adhesion molecule, performs an important role in the interaction between LSCs and their niche. The purpose of the present study was to assess CD133 and CD82 expression in patients with pediatric ALL, and to evaluate the association with the clinical data. Using flow cytometric assessment and reverse transcription-polymerase chain reaction, CD133 and CD82 expression levels were measured in the bone marrow (BM) of 37 patients with newly diagnosed (ND) pediatric ALL [ALL-ND; 30 B-cell-ALL (B-ALL) and 7 T-cell-ALL (T-ALL)], in 22 patients with complete remission pediatric ALL (ALL-CR) and in 16 age-matched children without BM disease. BM plasma CD82 concentrations were measured by ELISA. The CD82 mRNA expression level in the patients with ALL-ND was significantly higher compared with that in the controls. CD82 mRNA expression levels in pediatric patients with B cell-ALL (B-ALL) were higher than those in ALL-CR patients and controls. For T-ALL, CD82 expression in ND patients was higher than in controls. CD133 mRNA expression levels in patients with pediatric B-ALL-ND were higher than that of controls and patients with ALL-CR. The frequency of CD34+ cells in pediatric ALL was significantly higher than that in controls. Frequencies of CD34+CD133+ or CD34+CD82+ cells in pediatric ALL were higher than those in controls. A positive association was observed between CD133 and CD82 mRNA expression in patients with B-ALL. A significant association was observed between CD133 mRNA expression and the hyperdiploid karyotype. Therefore, it was considered that CD133 and CD82 may serve an important role in the evolution of pediatric ALL. CD133 and CD82 should be considered as potential markers for the prognosis of patients with ALL.

High mobility group box 1 (HMGB1) is a prototype damage-associated molecular pattern (DAMP) that can induce inflammatory and immune responses alone as well as in combination with other molecules such as DNA. However, the intricate molecular mechanisms underlying HMGB1-DNA complex-mediated innate immune response remains largely elusive. In this study, we demonstrated that HMGB1-DNA complex initially induced absent in melanoma 2 (AIM2)-dependent inflammasome activation, and promoted rapid release of inflammasome-dependent early proinflammatory cytokines such as interleukin 1β (IL-1β). Subsequently, HMGB1-DNA complex stimulated an ATG5-dependent cellular degradation process, autophagy, which was paralleled by a cessation of AIM2 inflammasome activation and IL-1β release. These HMGB1-DNA complex-induced inflammasome activation and autophagy were both dependent on the receptor for advanced glycation endproducts (RAGE) that recognizes a wide array of ligands (including HMGB1 and DNA). Thus, autophagy may function as a negative counter-regulatory mechanism for HMGB1-DNA complex-induced inflammasome activation, and provide a checkpoint to limit the development of inflammation.