[摘 要] 目的：探讨lncRNA DLEU2通过EZH2/H3K27me3途径调控IKKα介导甲状腺癌（TC）放射性碘抵抗的作用机制。方法：利用TCGA数据库分析TC中DLEU2的表达及其与EZH2的相关性。构建放射性碘抵抗的TPC-1细胞（RR-TPC-1细胞）模型及裸鼠移植瘤模型，通过敲低或过表达DLEU2（si-DLEU2/OE-DLEU2）、抑制EZH2（UNC1999）、过表达IKKα（OE-IKKα）进行干预，采用qPCR、WB、RIP、ChIP、CCK-8、流式细胞术、TUNEL染色及体内成瘤实验检测基因与蛋白表达、表观修饰、细胞增殖、凋亡及肿瘤生长。结果：TCGA分析显示，DLEU2在TC组织中显著上调（P < 0.001），与患者不良预后相关（P = 0.008 4），且与EZH2表达呈正相关（r = 0.390, P < 0.001）；RIP证实EZH2与DLEU2存在相互作用/结合（P < 0.05）。体外实验表明，敲低DLEU2可显著下调RR-TPC-1细胞中EZH2、IKKα表达及H3K27me3修饰水平，抑制NF-κB通路活化（P < 0.05或P < 0.01），抑制细胞增殖、促进凋亡（均P < 0.05）。联合敲低DLEU2与抑制EZH2进一步增强上述效应，而过表达IKKα则可部分逆转上述效应（P < 0.05或P < 0.01）。体内实验进一步证实，敲低DLEU2联合抑制EZH2可显著抑制移植瘤生长，增加肿瘤细胞凋亡（均P < 0.01）；IKKα过表达则部分逆转上述抗肿瘤效应（P < 0.05或P < 0.01）。结论：lncRNA DLEU2通过招募EZH2催化H3K27me3修饰，间接激活IKKα/NF-κB信号并形成正反馈环路，介导TPC-1细胞131I抵抗。

ObjectiveTo investigate the association of the single nucleotide polymorphism （SNP） of the insulin-like growth factor binding protein-3 （IGFBP3） gene at rs10225396 （A>G） locus with the susceptibility to hepatocellular carcinoma， as well as its potential molecular regulatory mechanisms， and to provide novel genetic biomarkers and a theoretical basis for early screening and precise targeted therapy for hepatocellular carcinoma. MethodsA total of 192 patients with hepatocellular carcinoma who were admitted to The Affiliated Hospital of Yanbian University and Yanbian Cancer Hospital from January 2009 to August 2016 were enrolled as experimental group， and 190 healthy individuals who underwent physical examination in Physical Examination Center of Yanbian Hospital during the same period of time were enrolled as control group. Peripheral blood samples were collected from all subjects， and after DNA was extracted from whole blood， the DNA samples meeting quality standards were sent to Beijing Genomics Institute Research Center Co.， Ltd.， for Mass ARRAY mass spectrometry， while genotyping was completed. The independent-samples t test was used for comparison of continuous data between two groups， and the chi-square test was used for comparison of categorical data between two groups. A binary Logistic regression model was used to analyze the association of the SNP of the IGFBP3 gene at rs10225396 locus with the susceptibility to hepatocellular carcinoma， and odds ratio （OR） and 95% confidence interval （CI） were calculated to assess the risk of developing hepatocellular carcinoma in individuals carrying different genotypes. ResultsThere were two alleles （G and A） at the rs10225396 locus of the IGFBP3 gene， yielding the three genotypes of AA， AG， and GG， and its genotype distribution was consistent with the Hardy-Weinberg equilibrium （χ²=0.072， P=0.789）. The stratified genetic analysis showed that carriers of the IGFBP3 rs10225396 AA genotype had a significant increased risk of hepatocellular carcinoma among individuals of age <63 years， male sex， smoking history， drinking history， and the Chinese Korean population （all P<0.001）. The binary Logistic regression analysis showed that after adjustment for related risk factors in the codominant model， the population with genotype AG and GG had a significant reduction in the risk of hepatocellular carcinoma compared with the population with genotype AA （P<0.001）， and in the dominant model， the population with genotype AG+GG had a significant reduction in the risk of hepatocellular carcinoma compared with the population with genotype AA （P<0.001）. ConclusionThrough a genotyping analysis of hepatocellular carcinoma patients and healthy individuals in Yanbian Korean Autonomous Prefecture of Jilin Province， China， this study shows that genotype AA at rs10225396 locus of the IGFBP3 gene is significantly associated with the susceptibility to hepatocellular carcinoma， and this genotype can significantly increase the risk of developing hepatocellular carcinoma with the presence of specific risk factors， which provides a potential genetic marker for early screening and precise treatment of hepatocellular carcinoma.

Antibiotics are chemicals with bactericidal or bacteriostatic activity produced by microorganisms and artificially synthesized. Since the discovery of penicillin by Alexander Fleming in 1928, antibiotics have been widely used in clinical treatments as well as in the animal husbandry and aquaculture, leading to antibiotic residues in soil, water, food and other environments. At the same time, antibiotic resistance is increasingly serious, which necessitates the discovery of novel antibiotics. In recent years, with the development of synthetic biology, researchers have developed a variety of whole-cell biosensors that can respond to antibiotics. These whole-cell biosensors use microbial cells to convert antibiotic signals into readable signals, which can not only perform dynamic detection of antibiotics simply, quickly, sensitively and accurately but also effectively discover novel antibiotics. This review comprehensively summarizes the reported whole-cell biosensors for antibiotics, classifies them into two types (specific and general), and elaborates on the design principles and applications of the two types of antibiotic biosensors. This review will provide reference for the construction and application of other whole-cell biosensors for antibiotics.
Biosensing Techniques/methods* ; Anti-Bacterial Agents/pharmacology*

This paper presents a rare renal biopsy-confirmed case of enoxaparin-induced anticoagulant-related nephropathy (ARN). A 62-year-old male was admitted with microscopic hematuria, massive albuminuria, and elevated serum creatinine following postoperative right shoulder joint infection. The serum creatinine level decreased after surgical debridement and antibiotic therapy. Enoxaparin (4 000 U daily) was initiated for thromboembolism prevention. The patient developed acute kidney injury with serum creatinine 517 μmol/L accompanied by gross hematuria. Renal biopsy revealed characteristic features of ARN coexisting with infection-related glomerulonephritis. After antibiotic therapy, urinary alkalinization, hemodialysis, and glucocorticoids (prednisone acetate 30 mg daily) of therapeutic interventions, the renal function partially recovered with dialysis discontinuation. The paper reviews the relevant literature on the risk factors, clinical manifestations, pathological features, diagnosis and treatment of ARN to improve clinicians' understanding.

Acromegaly is a rare disease characterized by the overproduction of growth hormone(GH)and insulin-like growth factor-1(IGF-1), which affects multiple organ systems and increases mortality risk.As the population ages, the number of elderly patients with acromegaly is rising annually, leading to more pronounced systemic complications and significantly impacting quality of life(QoL). However, there is limited data in the literature regarding the assessment of acromegaly complications in the elderly.Therefore, to enhance our understanding of acromegaly in this demographic, the present review focuses on the epidemiology, diagnosis, complication assessment, and therapeutic prognosis of acromegaly in elderly patients.

Objective To investigate the clinical and radiological features of osteofibrous dysplasia(OFD),and to improve the diagnostic accuracy of OFD and reduce the misdiagnosis rate.Methods A retrospective analysis was conducted on the clinical and radiological data of 21 patients with OFD confirmed by surgical pathology.Results Among the 21 patients,the imaging manifestations showed that the lesions were mainly located within the anterior cortex of the tibia,presenting as cystic expansile bone destruction with corti-cal expansion and thinning,protruding into the medullary cavity.Within the lesions,unequal thickness linear bony septations were visible,resembling soap-bubble changes,along with patchy ground-glass density shadow.A sclerotic rim was observed surrounding the lesions,with a clear boundary from normal tissue.No obvious soft tissue mass or periosteal reaction was noted in all cases.On MRI,the majority of the lesions exhibited prolonged T,and T2 signals,with linear hypointense separations observed within the lesions.No significant edema was noted in the surrounding bone and soft tissues,although a minor degree of bone marrow edema was present.All patients underwent surgical treatment.Fifteen patients were followed up for review,ranging from 3 to 38 months postoperatively.Among them,9 patients had no recurrence,while 6 patients experienced recurrence,manifesting as new lytic bone destruction in the surgical area.Conclusion The radiological manifestations of OFD are characteristic,and an accurate diagnosis can be made for typical cases in combination with the patient's age,location of the lesion and clinical presentation.Due to the high recurrence rate after OFD sur-gery,regular follow-up is recommended.

Children undergoing hematopoietic stem cell transplantation(HSCT)often experience car-diopulmonary dysfunction,reduced muscle strength,and other complications due to the disease itself and treatment adverse effects.Multiple studies indicate that exercise intervention can promote immune reconstitu-tion,improve physiological functions,and enhance quality of life;however,insufficient exercise remains preva-lent among these children.This review summarizes the current status,influencing factors,exercise outcomes,and management approaches of exercise interventions for pediatric HSCT recipients,aiming to provide refer-ences for developing exercise intervention research suited to China's healthcare context.

Objective To investigate the sputum metabolic profiles of patients with occupational coal workers' pneumoconiosis (CWP) by an untargeted metabolomics method, and to identify relevant differential metabolic pathways and potential biomarkers. Methods A total of 12 male patients with stage Ⅰ CWP were selected as the CWP group, and 16 healthy male individuals were selected as the control group, using a judgmental sampling method. Sputum metabolites of individuals in both groups were detected to perform non-targeted metabolomic analysis using the ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Differential metabolites (DMs) and their pathways were screened using principal component analysis, partial least squares discriminant analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Potential biomarkers were analyzed and identified via the receiver operating characteristic curve (ROC). Results There were apparent metabolic alterations observed in sputum of CWP patients compared with healthy controls. In the positive ion mode, a total of 42 DMs were identified in sputum from CWP patients, including 19 downregulated and 23 upregulated metabolites. In the negative ion mode, a total of 25 DMs were identified in sputum from CWP patients, including 16 downregulated and 9 upregulated metabolites. KEGG enrichment analysis of sputum from CWP patients showed that seven DMs pathways were enriched in ABC transporters, histidine metabolism, phenylalanine metabolism, arachidonic acid metabolism, linoleic acid metabolism, purine metabolism, and oxidative phosphorylation, involving 26 DMs. ROC analysis indicated that 16(R)-hydroxyarachidonic acid, pyrophosphate, and 2-hydroxyphenylacetate of these 26 DMs may serve as potential biomarkers for CWP. Conclusion Sputum metabolomic profiles were altered in CWP patients compared with healthy controls. The potential biomarkers of CWP prevention and treatment are 16(R)-hydroxyarachidonic acid, pyrophosphate, and 2-hydroxyphenylacetate.

BACKGROUND: Several studies have demonstrated the occurrence of secondary tumors as a rare but significant complication of chimeric antigen receptor T (CAR-T) cell therapy, underscoring the need for a detailed investigation. Given the limited variety of secondary tumor types reported to date, a comprehensive characterization of the various secondary tumors arising after CAR-T therapy is essential to understand the associated risks and to define the role of the immune microenvironment in malignant transformation. This study aims to characterize the immune microenvironment of a newly identified secondary tumor post-CAR-T therapy, to clarify its pathogenesis and potential therapeutic targets. METHODS: In this study, the bone marrow (BM) samples were collected by aspiration from the primary and secondary tumors before and after CD19 CAR-T treatment. The CD45 + BM cells were enriched with human CD45 microbeads. The CD45 + cells were then sent for 10× genomics single-cell RNA sequencing (scRNA-seq) to identify cell populations. The Cell Ranger pipeline and CellChat were used for detailed analysis. RESULTS: In this study, a rare type of secondary chronic myelomonocytic leukemia (CMML) were reported in a patient with diffuse large B-cell lymphoma (DLBCL) who had previously received CD19 CAR-T therapy. The scRNA-seq analysis revealed increased inflammatory cytokines, chemokines, and an immunosuppressive state of monocytes/macrophages, which may impair cytotoxic activity in both T and natural killer (NK) cells in secondary CMML before treatment. In contrast, their cytotoxicity was restored in secondary CMML after treatment. CONCLUSIONS This finding delineates a previously unrecognized type of secondary tumor, CMML, after CAR-T therapy and provide a framework for defining the immune microenvironment of secondary tumor occurrence after CAR-T therapy. In addition, the results provide a rationale for targeting macrophages to improve treatment strategies for CMML treatment.
Humans ; Lymphoma, Large B-Cell, Diffuse/therapy* ; Tumor Microenvironment/genetics* ; Antigens, CD19/metabolism* ; Leukemia, Myelomonocytic, Chronic/genetics* ; Immunotherapy, Adoptive/adverse effects* ; Male ; Single-Cell Analysis/methods* ; Female ; Sequence Analysis, RNA/methods* ; Receptors, Chimeric Antigen ; Middle Aged

Objective To investigate the clinical and radiological features of osteofibrous dysplasia(OFD),and to improve the diagnostic accuracy of OFD and reduce the misdiagnosis rate.Methods A retrospective analysis was conducted on the clinical and radiological data of 21 patients with OFD confirmed by surgical pathology.Results Among the 21 patients,the imaging manifestations showed that the lesions were mainly located within the anterior cortex of the tibia,presenting as cystic expansile bone destruction with corti-cal expansion and thinning,protruding into the medullary cavity.Within the lesions,unequal thickness linear bony septations were visible,resembling soap-bubble changes,along with patchy ground-glass density shadow.A sclerotic rim was observed surrounding the lesions,with a clear boundary from normal tissue.No obvious soft tissue mass or periosteal reaction was noted in all cases.On MRI,the majority of the lesions exhibited prolonged T,and T2 signals,with linear hypointense separations observed within the lesions.No significant edema was noted in the surrounding bone and soft tissues,although a minor degree of bone marrow edema was present.All patients underwent surgical treatment.Fifteen patients were followed up for review,ranging from 3 to 38 months postoperatively.Among them,9 patients had no recurrence,while 6 patients experienced recurrence,manifesting as new lytic bone destruction in the surgical area.Conclusion The radiological manifestations of OFD are characteristic,and an accurate diagnosis can be made for typical cases in combination with the patient's age,location of the lesion and clinical presentation.Due to the high recurrence rate after OFD sur-gery,regular follow-up is recommended.