1.Clinical characteristics of neonatal necrotizing enterocolitis and analysis of risk factors for early-onset children
Jing WANG ; Mingqi SHEN ; Rongxiu ZHENG ; Yue XIN ; Yunxia MA ; Ying ZHANG ; Dejing WU ; Dan LIU
International Journal of Pediatrics 2025;52(9):629-633
Objective:To explore the clinical characteristics of neonatal necrotizing enterocolitis(NEC)and analyze the risk factors for early-onset NEC.Methods:A total of 220 children with NEC admitted to the Department of Pediatrics,Tianjin Medical University General Hospital from January 1st,2018 to February 29th,2024 were retrospectively selected as the research objects. According to the time of onset,the early-onset group( n=120)and the late-onset group( n=100)were established,and the clinical characteristics of the two groups were compared. Another 150 cases of normal healthy newborns born in this hospital in the same period were selected as the control group,and the clinical data of the control group were collected. The clinical characteristics of the early-onset group and the control group were compared,and the risk factors of early-onset NEC were analyzed by multivariate Logistic regression. Results:Compared with the late-onset group,the early-onset group had fever[50.0%(60/120)vs. 40%(40/100), χ2=7.333, P=0.007],apnea[39.17%(47/120)vs. 28%(28/100), χ2=7.568, P=0.006],no rise in body temperature[56.67%(68/120)vs. 39%(39/100), χ2=6.815, P=0.009],abdominal distension[25%(30/120)vs. 40%(40/100), χ2=13.200, P<0.001],vomiting[30.83%(37/120)vs. 45%(45/100), χ2=12.797, P<0.001]was significantly different(all P<0.05);Multivariate Logistic regression analysis:weight<1 500 g( OR=5.871,95% CI:3.153~9.673, P<0.001),gestational age<30 weeks( OR=4.256,95% CI:2.641~7.896, P=0.007),hemodynamically significant patent ductus arteriosus(hs-PDA)( OR=3.113,95% CI:1.865~5.133, P=0.033),severe anemia( OR=3.057,95% CI:2.165~4.802, P=0.001),feeding intolerance( OR=4.215,95% CI:1.579~10.802, P=0.005),amniotic fluid pollution( OR=2.452,95% CI:1.579~3.111, P<0.001)were the independent risk factors for early-onset NEC(all P<0.05). Conclusion:Weight<1 500 g,gestational age<30 weeks,hs-PDA,severe anemia,feeding intolerance,and amniotic fluid contamination are independent risk factors for early-onset NEC. In clinical practice,more attention should be paid to these factors for disease prevention,early identification,and timely intervention in newborns to reduce the occurrence of NEC.
2.Cation Channel TMEM63A Autonomously Facilitates Oligodendrocyte Differentiation at an Early Stage.
Yue-Ying WANG ; Dan WU ; Yongkun ZHAN ; Fei LI ; Yan-Yu ZANG ; Xiao-Yu TENG ; Linlin ZHANG ; Gui-Fang DUAN ; He WANG ; Rong XU ; Guiquan CHEN ; Yun XU ; Jian-Jun YANG ; Yongguo YU ; Yun Stone SHI
Neuroscience Bulletin 2025;41(4):615-632
Accurate timing of myelination is crucial for the proper functioning of the central nervous system. Here, we identified a de novo heterozygous mutation in TMEM63A (c.1894G>A; p. Ala632Thr) in a 7-year-old boy exhibiting hypomyelination. A Ca2+ influx assay suggested that this is a loss-of-function mutation. To explore how TMEM63A deficiency causes hypomyelination, we generated Tmem63a knockout mice. Genetic deletion of TMEM63A resulted in hypomyelination at postnatal day 14 (P14) arising from impaired differentiation of oligodendrocyte precursor cells (OPCs). Notably, the myelin dysplasia was transient, returning to normal levels by P28. Primary cultures of Tmem63a-/- OPCs presented delayed differentiation. Lentivirus-based expression of TMEM63A but not TMEM63A_A632T rescued the differentiation of Tmem63a-/- OPCs in vitro and myelination in Tmem63a-/- mice. These data thus support the conclusion that the mutation in TMEM63A is the pathogenesis of the hypomyelination in the patient. Our study further demonstrated that TMEM63A-mediated Ca2+ influx plays critical roles in the early development of myelin and oligodendrocyte differentiation.
Animals
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Cell Differentiation/physiology*
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Oligodendroglia/metabolism*
;
Mice, Knockout
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Mice
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Male
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Myelin Sheath/metabolism*
;
Humans
;
Child
;
Cells, Cultured
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Oligodendrocyte Precursor Cells/metabolism*
3.Langerhans Cell Histiocytosis of Bone:Report of Eight Cases and Review of the Literature.
Ya BI ; Dan-Dan WU ; Fang-Ying YU ; Zhen-Hong FANG ; Bo HUANG
Acta Academiae Medicinae Sinicae 2025;47(2):325-332
Langerhans cell histiocytosis of bone is a rare tumor disease characterized by the large accumulation of CD1a+ and CD207+ dendritic cells in tissues of unknown cause.It mainly occurs in children aged 1-4 years old,with incidences of 4-6 per million in children and 1-2 per million in adults.Due to its low incidence,diverse clinical manifestations,and no obvious specificity of imaging manifestations,the definitive diagnosis and early treatment of this type of tumor are challenging.In this paper,we report 8 cases of Langerhans cell histiocytosis of bone and review the relevant literature published in the past five years to summarize the clinical characteristics,pathological features,diagnosis,treatment,and prognosis of this disease.
Humans
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Bone Diseases/therapy*
;
Histiocytosis, Langerhans-Cell/therapy*
4.Listeria Brainstem Encephalitis With Myelitis Misdiagnosed as Acute Disseminated Encephalomyelitis:Report of One Case.
Dan-Ying WU ; Qin-Xue WANG ; Dong-Mei ZHU ; Yu-Jing GAN ; Min HUANG ; Su-Ming ZHOU
Acta Academiae Medicinae Sinicae 2025;47(4):673-678
Listeria brainstem encephalitis with myelitis is extremely rare in clinical practice.Since the clinical manifestations are non-specific,MRI is helpful for diagnosis.Positive cerebrospinal fluid culture is considered the gold standard for diagnosis.This article reports a case of an immunocompetent individual with listeria brainstem encephalitis with myelitis,aiming to enhance the awareness of this condition.
Humans
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Brain Stem/pathology*
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Diagnostic Errors
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Encephalitis/complications*
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Encephalomyelitis, Acute Disseminated/diagnosis*
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Listeriosis/complications*
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Myelitis/complications*
5.USP20 as a super-enhancer-regulated gene drives T-ALL progression via HIF1A deubiquitination.
Ling XU ; Zimu ZHANG ; Juanjuan YU ; Tongting JI ; Jia CHENG ; Xiaodong FEI ; Xinran CHU ; Yanfang TAO ; Yan XU ; Pengju YANG ; Wenyuan LIU ; Gen LI ; Yongping ZHANG ; Yan LI ; Fenli ZHANG ; Ying YANG ; Bi ZHOU ; Yumeng WU ; Zhongling WEI ; Yanling CHEN ; Jianwei WANG ; Di WU ; Xiaolu LI ; Yang YANG ; Guanghui QIAN ; Hongli YIN ; Shuiyan WU ; Shuqi ZHANG ; Dan LIU ; Jun-Jie FAN ; Lei SHI ; Xiaodong WANG ; Shaoyan HU ; Jun LU ; Jian PAN
Acta Pharmaceutica Sinica B 2025;15(9):4751-4771
T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.
6.Electrochemical biosensors with right-side-out-oriented cell membrane coating for the evaluation of AChE inhibitors as potential anti-Alzheimer's disease agents.
Ying ZHAO ; Xia LIU ; Shuning YANG ; Jiabo WANG ; Dan WU ; Yusi BU ; Xiaoyu XIE
Acta Pharmaceutica Sinica B 2025;15(11):5988-6000
Biosensors based on acetylcholinesterase (AChE) are crucial for early diagnosis, less invasive treatment, and drug evaluation of Alzheimer's disease (AD). However, existing technologies often suffer from enzyme conformational changes, leading to altered activity and loss and reduced sensor efficacy. To address this challenge, we developed a novel right-side-out-oriented red blood cell membrane-coated electrochemical biosensors (ROCMCBs) to evaluate AChE inhibitors from traditional Chinese medicines (TCMs) as potential anti-AD agents. The developed right-side-out-oriented coating based on immunoaffinity not only fully exposed the binding sites of AChE on the cell membrane but also ensured its conformation and stability as a peripheral membrane-anchoring protein, which was conducive to maintaining its biological activity and producing optimal interaction with drugs. At the same time, the biosensors exhibited a satisfactory sensitivity (limit of detection = 0.41 pmol/L). Ultimately, six potentially active compounds against AD (baicalin, geniposide, gastrodin, berberine, rhynchophylline, and senkyunolide A) were rapidly identified and evaluated from TCMs. This project provides a promising strategy for developing cell membrane-coated electrochemical biosensors. The application of cell membrane-coated electrochemical biosensors with well-defined cell membrane orientation further expands new perspectives and methods for AChE-targeted anti-AD research.
7.Atomic force microscopic observation of surface structure of purified protein molecules in vitro
Zhao-ying CHEN ; Xiao-feng FANG ; Dan-yan LIU ; Meng-qin CHEN ; Xi LING ; Jie-min ZHAO ; Wei WEI ; Yu-jing WU
Chinese Pharmacological Bulletin 2025;41(1):193-199
Aim To compare the observation results of atomic force microscopy(AFM)and scanning electron microscopy(SEM),and to summarize the main problems and solutions of AFM in observing biological macromolecules,using the observa-tion subjects of protein samples purified by our research group.Methods The protein samples were diluted to 15 nmol·L-1 with PBS,fixed on glass slides,silicon wafers,and mica sheets,dried,and made into solid-phase observation samples.SEM sam-ples were plated with platinum before observation.The surface structures of proteins were observed using AFM and SEM,sample heights were calculated,and differences in results were com-pared.Results Protein samples with positive charges tended to shift to the right during observation due to the repulsion of the AFM probe;mica sheets could effectively eliminate the positive charge of proteins to avoid sample movement;PBS provided a stable environment for protein samples,but the crystallization of PBS salts interfered with probe operation and imaging clarity;SEM samples needed to be plated with platinum before observa-tion and could not achieve the precision of AFM.Conclusions Both AFM and SEM can directly observe protein structures in vitro,with AFM providing higher precision results;when protein sample stability permits,ultrapure water is preferred as the sol-vent carrier,and volatile liquids such as ethanol can also serve as solvent carriers.The application of AFM offers a new approach for pharmacological studies on interactions between biological macromolecules.
8.Review of application scope of mobile medical devices combined with EMA method for lung cancer patient caring
Zi-dan WANG ; Hong-yue WU ; Bing LI ; Xin-tong ZHENG ; Jun-ling LIU ; Ying-nan ZHAO ; Yan LI
Chinese Medical Equipment Journal 2025;46(10):71-77
Relevant literature on mobile medical devices combined with the ecological momentary assessment(EMA)method applied to lung cancer patient caring was collected from some databases of CNKI,Wanfang,VIP,China Biomedical Literature Database,PubMed,Embase,Cochrane Library,CINAHL and Web of Science.The method of scoping review was used to sort out the general characteristics of the included literature,types and application of mobile medical devices,assessment content elements and outcome indicators.The feasibility and validity of mobile medical devices combined with the EMA method for the symptom assessment of lung cancer patients were described,whose advantages in monitoring during lung cancer caring and application prospects were elaborated.The problems of mobile medical devices during practical application were pointed out and some countermeasures were put forward accordingly.References were provided for personalized remote caring of lung cancer patients and development of intelligent multi-modal mobile devices.[Chinese Medical Equipment Journal,2025,46(10):71-77]
9.Differentiating bronchiolar adenoma from minimally invasive adenocarcinoma based on high-resolution CT features
Ziqian ZHAO ; Dan HAN ; Haiyan YANG ; Tengfei KE ; Wenyan WEI ; Yan WU ; Ying TAO ; Xinhui YANG ; Fengyi LI ; Wen ZHAO
Journal of Practical Radiology 2025;41(10):1633-1638
Objective To explore the pathological features of bronchiolar adenoma(BA)and its specific high-resolution computed tomography(HRCT)signs,and to differentiate BA from minimally invasive adenocarcinoma(MIA)using a non-invasive preoperative method.Methods A total of 80 patients with BA and 130 patients with MIA were retrospectively selected,and the clinical information and HRCT features were compared.All cases were divided into development set and test set at a 7︰3 ratio.Logistic regression analysis was used to screen the independent predictors of MIA and construct a model.Results There were significant differences in age,lobe distribution,density,vacuole sign,tumor-related vessels number(TVN),and distance to pleura(DTP)between BA and MIA patients(P<0.05).Age,density,TVN,DTP and long diameter were identified as independent predictors of MIA.A model was constructed,with area under the curve(AUC)of 0.887 and 0.884 in the development and test sets,respectively.Conclusion The model based on HRCT morphological features of BA and MIA demonstrates superior diagnostic performance compared to individual CT morphological features.
10.Anti-radiation effects of gene CCND1 activated by low-dose radiation
Dan CAI ; Ying FAN ; Yunqi MO ; Ruixue LIU ; Lei WU ; Jianan MA ; Qi WANG ; Zhenhua QI ; Zhidong WANG
Chinese Journal of Radiological Medicine and Protection 2025;45(9):840-850
Objective:To select low-dose radiation-activated genes with intrinsic radiation protection by developing a model for adaptive responses to low-dose ionizing radiation, in order to explore the mechanisms behind the radiation resistance of the candidate genes.Methods:The cells were divided into adaptive response induction group and whole transcriptome sequencing group. The level of DNA damage was assessed using the γ-H2AX immunofluorescence assay. The low-dose radiation-activated candidate genes with radiation protection were selected through whole transcriptome sequencing and quantitative reverse transcription PCR (RT-qPCR)-based validation. The anti-radiation effect of candidate gene CCND1 was assessed based on CCK-8 cell proliferation and γ-H2AX immunofluorescence assay. After up- and down-regulation of CCND1 expression, the anti-radiation mechanism of CCND1 was preliminarily explored through transcriptome sequencing analysis.Results:A model for low-dose ionizing radiation-induced adaptive responses of lymphocytes was constructed. Using this model, six candidate genes with radiation protection, including CCND1, ZMAT3, MGAT3, DFFB, CYP4F2, ITGA6, were selected. Compared to the control group, overexpressed CCND1 led to significantly enhanced proliferation ability of AHH-1 cells ( t = 7.92-14.76, P < 0.05) and distinctly lowered level of DNA damage ( t = 2.79-9.68, P < 0.05) after 2 Gy of X-ray irradiation. Furthermore, compared to the control group, the CCND1 knockdown caused significantly decreased cell proliferation ability ( t = 13.58-26.25, P < 0.05) and notably elevated level of DNA damage of cells ( t = 2.87-7.61, P < 0.05). Transcriptome sequencing revealed that up- and down-regulation of CCND1 expression resulted in the activation of pathways related to cell growth, death, and damage repair. Conclusions:By selecting six low-dose-activated candidate genes with radiation protection and revealing the function of CCND1 in radiation protection, this study provides a new perspective for the development of radiation protection agents from the perspective of adaptive responses to low-dose radiation.

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