1.Molecular Mechanisms of RNA Modification Interactions and Their Roles in Cancer Diagnosis and Treatment
Jia-Wen FANG ; Chao ZHE ; Ling-Ting XU ; Lin-Hai LI ; Bin XIAO
Progress in Biochemistry and Biophysics 2025;52(9):2252-2266
RNA modifications constitute a crucial class of post-transcriptional chemical alterations that profoundly influence RNA stability and translational efficiency, thereby shaping cellular protein expression profiles. These diverse chemical marks are ubiquitously involved in key biological processes, including cell proliferation, differentiation, apoptosis, and metastatic potential, and they exert precise regulatory control over these functions. A major advance in the field is the recognition that RNA modifications do not act in isolation. Instead, they participate in complex, dynamic interactions—through synergistic enhancement, antagonism, competitive binding, and functional crosstalk—forming what is now termed the “RNA modification interactome” or “RNA modification interaction network.” The formation and functional operation of this interactome rely on a multilayered regulatory framework orchestrated by RNA-modifying enzymes—commonly referred to as “writers,” “erasers,” and “readers.” These enzymes exhibit hierarchical organization within signaling cascades, often functioning in upstream-downstream sequences and converging at critical regulatory nodes. Their integration is further mediated through shared regulatory elements or the assembly into multi-enzyme complexes. This intricate enzymatic network directly governs and shapes the interdependent relationships among various RNA modifications. This review systematically elucidates the molecular mechanisms underlying both direct and indirect interactions between RNA modifications. Building upon this foundation, we introduce novel quantitative assessment frameworks and predictive disease models designed to leverage these interaction patterns. Importantly, studies across multiple disease contexts have identified core downstream signaling axes driven by specific constellations of interacting RNA modifications. These findings not only deepen our understanding of how RNA modification crosstalk contributes to disease initiation and progression, but also highlight its translational potential. This potential is exemplified by the discovery of diagnostic biomarkers based on interaction signatures and the development of therapeutic strategies targeting pathogenic modification networks. Together, these insights provide a conceptual framework for understanding the dynamic and multidimensional regulatory roles of RNA modifications in cellular systems. In conclusion, the emerging concept of RNA modification crosstalk reveals the extraordinary complexity of post-transcriptional regulation and opens new research avenues. It offers critical insights into the central question of how RNA-modifying enzymes achieve substrate specificity—determining which nucleotides within specific RNA transcripts are selectively modified during defined developmental or pathological stages. Decoding these specificity determinants, shaped in large part by the modification interactome, is essential for fully understanding the biological and pathological significance of the epitranscriptome.
2.Research progress on mechanism of interaction between traditional Chinese medicine and intestinal flora
Jing WU ; Wei-Yi TIAN ; Kun CAI ; Su-Fang ZHOU ; Yao-Feng LI ; Xiang-Yun CHEN ; Hai-Bing QIAN ; Sha-Sha YANG
Chinese Pharmacological Bulletin 2024;40(10):1823-1829
Modern Chinese medicine studies have confirmed that the interaction between traditional Chinese medicine(TCM)and intestinal flora is the key to the treatment of diseases with tradi-tional Chinese medicine.This interplay includes such activities as:traditional Chinese medicine can be metabolized by intestinal flora into effective components with different biological activities from its precursors;TCM chemicals improve the composition of gut microbiota,consequently ameliorating its dysfunction as well as associated pathological conditions;and gut microbiota mediate the interactions between the multiple chemicals in TCM.There-fore,it becomes an important way to understand the modern sci-entific connotation of traditional Chinese medicine theory to study the pharmacological mechanism of the efficacy of traditional Chi-nese medicine by targeting Gut microbiota.
3.Bilateral coronary artery-right ventricular fistula with rare huge tortuosity entering the same site:case report
Wei-Song TANG ; Rong-Li XU ; Xing-Jiu CAI ; Xiao-Li FANG ; Guan-Liang CHEN ; Hai-Rong LI
Chinese Journal of Interventional Cardiology 2024;32(4):236-240
Coronary artery fistula(CAF)is defined as the direct connection between coronary artery and cardiac cavity,great vessel or other vascular structures.Most CAF are congenital and often present as persistent murmur in asymptomatic children.Although abnormal shunt of most coronary fistulas has little effect on hemodynamics,some larger fistulas can also lead to a series of complications,such as congestive heart failure.Therefore,closed CAF has been recommended to treat or prevent myocardial ischemia,congestive heart failure,endarteritis,arrhythmia,thromboembolism,aneurysm dilatation and rupture and other complications.CAF is a rare congenital heart disease,and bilateral CAF originating from two coronary arteries is even rarer.At present,there are rare systematic reports on bilateral CAF.Therefore,a case of huge bilateral CAF at the same site was reported,and systematically,this kind of case was summarized,so as to improve the clinical attention of diagnosis and treatment of this kind of CAF.Nowadays,some new interventional devices and technologies are emerging with the continuous progress of cardiovascular interventional technology,making the treatment more accurate,safe and effective.At the same time,there is also a clearer understanding of the indications and operating standards for interventional treatment,which is more operable and predictable during the treatment process.Therefore,interventional treatment of CAF may partially replace surgical treatment as the preferred treatment method.
4.Clinical Analysis of Philadelphia Chromosome-Like Acute Lymphoblastic Leukemia in Children
Tian-Dan LI ; Shao-Yan HU ; Zong ZHAI ; Guang-Hua CHEN ; Jun LU ; Hai-Long HE ; Pei-Fang XIAO ; Jie LI ; Yi WANG
Journal of Experimental Hematology 2024;32(1):78-84
Objective:To explore the clinical characteristics,molecular characteristics,treatment and prognosis of pediatric Philadelphia chromosome-like acute lymphoblastic leukemia(Ph-like ALL)with a therapeutic target.Methods:A total of 27 patients of Ph-like ALL with targeted drug target were initially diagnosed in Children's Hospital of Soochow University from December 2017 to June 2021.The data of age,gender,white blood cell(WBC)count at initial diagnosis,genetic characteristics,molecular biological changes,chemotherapy regimen,different targeted drugs were given,and minimal residual disease(MRD)on day 19,MRD on day 46,whether hematopoietic stem cell transplantation(HSCT)were retrospective analyed,and the clinical characteristics and treatment effect were summarized.Survival analysis was performed by Kaplan-Meier method.Results:The intensity of chemotherapy was adjusted according to the MRD level during induced remission therapy in 27 patients,10 patients were treated with targeted drugs during treatment,and 3 patients were bridged with HSCT,1 patient died and 2 patients survived.Among the 24 patients who did not receive HSCT,1 patient developed relapse,and achieved complete remission(CR)after treatment with chimeric antigen receptors T cells(CAR-T).The 3-year overall survival,3-year relapse-free survival and 3-year event-free survival rate of 27 patients were(95.5±4.4)%,(95.0±4.9)%and(90.7±6.3)%respectively.Conclusion:Risk stratification chemotherapy based on MRD monitoring can improve the prognosis of Ph-like ALL in children,combined with targeted drugs can achieve complete remission as soon as possible in children whose chemotherapy response is poor,and sequential CAR-T and HSCT can significantly improve the therapeutic effect of Ph-like ALL in children whose MRD is continuously positive during induced remission therapy.
5.Clinical Features and Prognosis of Patients with CD5+Diffuse Large B-Cell Lymphoma
Xiu-Juan HUANG ; Jian YANG ; Xiao-Fang WEI ; Yuan FU ; Yang-Yang ZHAO ; Ming-Xia CHENG ; Qing-Fen LI ; Hai-Long YAN ; You-Fan FENG
Journal of Experimental Hematology 2024;32(3):750-755
Objective:To analyze the clinical characteristics and prognosis of patients with CD5+diffuse large B-cell lymphoma(DLBCL).Methods:The clinical data of 161 newly treated DLBCL patients in Gansu Provincial Hospital from January 2013 to January 2020 were retrospectively analyzed.According to CD5 expression,the patients were divided into CD5+group and CD5-group.The clinical characteristics and prognosis of the two groups were statistically analyzed.Results:The median age of patients in CD5+group was 62 years,which was higher than 56 years in CD5-group(P=0.048).The proportion of women in CD5+group was 62.96%,which was significantly higher than 41.79%in CD5-group(P=0.043).The proportion of patients with IPI score>2 in CD5+group was 62.96%,which was higher than 40.30%in CD5-group(P=0.031).Survival analysis showed that the median overall survival and progression-free survival time of patients in CD5+group were 27(3-77)and 31(3-76)months,respectively,which were both shorter than 30(5-84)and 32.5(4-83)months in CD5-group(P=0.047,P=0.026).Univariate analysis showed that advanced age,positive CD5 expression,triple or double hit at initial diagnosis,high IPI score and no use of rituximab during chemotherapy were risk factors for the prognosis of DLBCL patients.Further Cox multivariate regression analysis showed that these factors were also independent risk factors except for advanced age.Conclusion:CD5+DLBCL patients have a worse prognosis than CD5-DLBCL patients.Such patients are more common in females,with advanced age and high IPI score,which is a special subtype of DLBCL.
6.Chinical application of synaptic vesicle protein 2A radioactive tracer 18F-SynVesT-1 in patients with Alzheimer′s disease
Kun HE ; Junpeng LI ; Hai SHA ; Yue QIAN ; Jie WANG ; Qi HUANG ; Jun ZHAO ; Qihao GUO ; Yihui GUAN ; Fang XIE
Chinese Journal of Nuclear Medicine and Molecular Imaging 2024;44(5):291-296
Objective:To investigate the application of (4R)-4-(3-[ 18F]fluoranyl-5-fluorophenyl)-1-((3-methylpyridin-4-yl)methyl)pyrrolidin-2-one( 18F-SynVesT-1), a synaptic vesicle glycoprotein 2A (SV2A) radioactive tracer, in patients with Alzheimer′s disease (AD). Methods:A total of 20 AD patients (2 males, 18 females, age (66.4±8.1) years) with positive β-amyloid (Aβ) deposition and 20 normal controls (NC; 9 males, 11 females, age (62.6±8.6) years ) without Aβ deposition were retrospectively recruited from Huashan Hospital, Fudan University between December 2021 and December 2022. All of them underwent 18F-SynVesT-1 PET/MR and 18F-Florbetapir (AV45) PET/CT scans. Preprocessing of brain 18F-SynVesT-1 PET images was carried out using statistical parametric mapping (SPM). The differences of the uptke of 18F-SynVesT-1 (synaptic density) between two groups based on ROI were compared by using either the independent-sample t test or Mann-Whitney U test. Spearman rank correlation analysis was performed to assess the relationship between synaptic density and cognitive performance. For voxelwise analysis, a general linear model was constructed to analyze differences in synaptic density between the two groups using the independent-sample t test. Furthermore, a multiple linear regression model was developed to explore the relationship between synaptic density and cognitive performance. Results:Compared to the NC group, the AD group exhibited significant widespread reduction in synaptic density across the cortical regions ( P<0.05, false discovery rate (FDR)-corrected), particularly in the medial temporal lobe (0.84±0.09 vs 1.04±0.09; t=-6.95, P<0.001), lateral temporal lobe (1.15±0.13 vs 1.31±0.08; t=-4.56, P<0.001), and lateral parietal lobe (1.24(1.04, 1.26) vs 1.32(1.23, 1.39); z=-3.25, P=0.001). Moreover, synaptic density in extensive cortical regions showed a positive correlation with mini-mental state examination (MMSE) and Montreal cognitive assessment-basic (MoCA-B) scores ( P<0.05, FDR-corrected). Notably, significant associations were observed between MMSE and MoCA-B scores and synaptic density in the lateral temporal lobe ( rs values: 0.71, 0.74, both P<0.001) and medial temporal lobe ( rs values: 0.71, 0.74, both P<0.001). Conclusions:18F-SynVesT-1 PET imaging is a valuable tool for evaluating synaptic density, specifically in the context of AD. The observed widespread reduction in synaptic density across cortical regions of patients with AD are closely related to cognitive decline.
7.Effects of long-term high-altitude exposure on the composition of gut microflora in different intestinal segments of rats
Zhi-Fang ZHAO ; Xu-Fei ZHANG ; Ning SUN ; Hao LI ; Hai-Lin MA
Modern Interventional Diagnosis and Treatment in Gastroenterology 2024;29(5):552-559
Objective To investigate the effects of long-term high altitude exposure on the composition and structure of the gut microbiota in rats in different intestinal segments,and to explore the key affected intestinal segments initially.Methods Six-week-old C57BL/6 mice were randomly divided into a control group(Control group)and a high altitude exposed group(HA group).The HA group was exposed to a low-pressure oxygen chamber at a simulated altitude of 3500-4000 m for 20 weeks,after which the microbiomes of both groups were analysed using high-throughput 16s rRNA sequencing and core changes in the duodenal,jejunal,ileal and colonic microflora communities were determined.Results The microbial abundance of the colon was significantly reduced in the hypoxic environment of high altitude,the microbial abundance and diversity of the foregut did not change significantly,and the AVD value of the colon was higher than that of the other intestinal segments,and it tended to be more stable after prolonged exposure to treatment in high altitude;At the Bray-curtis distance,the Microbial structure of the ileum and colon was significantly different between the Control and HA groups,whereas the duodenum and jejunum showed no significant changes;The predominant phylum in all intestinal segments was Firmicutes,but the dominant phyla varied in different intestinal segments and treatment groups,with Lactobacillus spp.contributing highly to the changes in the gut microflora;the complexity of the phylogenetic network of the ileum was higher than that of the other intestinal segments,whereas the colon had the fewest phylogenetic interactions;the jejunum and the ileum consisted mainly of abundant taxa,whereas the colon had a significantly smaller proportion of abundant taxa,mainly Conditionally rare taxa.The duodenum differed in taxa composition between the Control and HA groups.Conclusion High-altitude hypoxia can affect the microecological environment of the ileum and colon by remodelling the composition and structure of the intestinal microflora,especially in the ileum compared with the other three intestinal segments.In addition,the ileum is characterised by both lower complexity of the microflora structure and the prominent role of key genera in the high altitude hypoxia study,in which the changes of Lactobacillus spp.are worthy of more in-depth study at a later stage.Therefore,the ileal microbiota of rats may have a higher research value compared with other intestinal segments.
8.Design of emergency medical rescue information system based on microservices architecture
Jun-Jun WANG ; Xin ZHANG ; Ke-Yu FANG ; Hai-Long SI ; Xiao-Li QIN ; Ping CHEN
Chinese Medical Equipment Journal 2024;45(10):41-48
Objective To design an emergency medical rescue information system to ensure that emergency medical rescue institutions and teams at all levels can quickly access system support under emergency rescue conditions.Methods The emergency medical rescue information system was built with Browser/Server(B/S)architecture,microservices architecture,Java,JavaScript,Spring Boot,Spring Cloud and Alibaba framework,which used MySQL relational database,Redis cache database and Elasticsearch search engine for data storage and management.There were five functional modules involved in the system including the modules for triage,medical treatment,medical technical support,medical evacuation and command and management.Results The system developed behaved well in rapid deployment and response,and realized quick collection of casualty information and enhanced the efficiency and accuracy of casualty triage.Conclusion The system developed can be used in multi rescue scenarios to meet different requirements,which provides information system support for multi emergency medical rescue institutions and teams.[Chinese Medical Equipment Journal,2024,45(10):41-48]
9.Clinical characteristics and prognosis of childhood acute lymphoblastic leukemia with CD123 expression
Ke-Fu ZHU ; Hai-Jin LI ; Chuan-Fu QIAO ; Liu-Fang WANG ; Pei-Jing WU ; Ying CHEN ; Xin TIAN
Chinese Journal of Contemporary Pediatrics 2024;26(7):708-715
Objective To investigate the expression of CD123 in children with acute lymphoblastic leukemia(ALL)and its effect on the clinical characteristics and prognosis of children with B-lineage acute lymphoblastic leukemia(B-ALL).Methods A retrospective analysis was conducted on the clinical data of 251 children with ALL who were admitted to the Department of Hematology and Oncology,Children's Hospital of Kunming Medical University,from December 2019 to June 2022.According to the expression of CD123 at initial diagnosis,the children were divided into CD123+group and CD123-group,and the two groups were compared in terms of clinical characteristics and treatment outcome.The factors influencing the prognosis were analyzed.Results Among the 251 children with ALL,there were 146 children(58.2%)in the CD123+group.The B-ALL group had a significantly higher positive expression rate of CD123 than the acute T lymphocyte leukemia group(P<0.05).Compared with the CD123-group,the CD123+group had significantly lower peripheral blood leukocyte count and percentage of juvenile cells and a significantly higher proportion of children with high hyperdiploid karyotype or an age of 1-10 years,with a relatively low proportion of children with E2A-PBX1 fusion gene(P<0.05).The multivariate Cox proportional-hazards regression model analysis showed that compared with the>10 years group,the 1-10 years group had a significantly higher overall survival rate(P<0.05),and compared with the high risk group,the moderate risk group had a significantly higher event-free survival rate in children with B-ALL(P<0.05).Conclusions CD123 is widely expressed in children with B-ALL,and positive expression of CD123 might be an indicator for good prognosis in children with B-ALL,which is of great significance for evaluating the efficacy of remission induction therapy and survival prognosis of children with B-ALL.
10.Electroacupuncture at Sensitized Acupoints Relieves Somatic Referred Pain in Colitis Rats by Inhibiting Sympathetic-Sensory Coupling to Interfere with 5-HT Signaling Pathway.
Ying YANG ; Jin-Yu QU ; Hua GUO ; Hai-Ying ZHOU ; Xia RUAN ; Ying-Chun PENG ; Xue-Fang SHEN ; Jin XIONG ; Yi-Li WANG
Chinese journal of integrative medicine 2024;30(2):152-162
OBJECTIVE:
To investigate whether electroacupuncture (EA) at sensitized acupoints could reduce sympathetic-sensory coupling (SSC) and neurogenic inflammatory response by interfering with 5-hydroxytryptamine (5-HT)ergic neural pathways to relieve colitis and somatic referred pain, and explore the underlying mechanisms.
METHODS:
Rats were treated with 5% dextran sodium sulfate (DSS) solution for 7 days to establish a colitis model. Twelve rats were randomly divided into the control and model groups according to a random number table (n=6). According to the "Research on Rat Acupoint Atlas", sensitized acupoints and non-sensitized acupoints were determined. Rats were randomly divided into the control, model, Zusanli-EA (ST 36), Dachangshu-EA (BL 25), and Xinshu (BL 15) groups (n=6), as well as the control, model, EA, and EA + GR113808 (a 5-HT inhibitor) groups (n=6). The rats in the control group received no treatment. Acupuncture was administered on 2 days after modeling using the stimulation pavameters: 1 mA, 2 Hz, for 30 min, with sparse and dense waves, for 14 consecutive days. GR113808 was injected into the tail vein at 5 mg/kg before EA for 10 min for 7 consecutive days. Mechanical sensitivity was assessed with von Frey filaments. Body weight and disease activity index (DAI) scores of rats were determined. Hematoxylin and eosin staining was performed to observe colon histopathology. SSC was analyzed by immunofluorescence staining. Immunohistochemical staining was performed to detect 5-HT and substance P (SP) expressions. The calcitonin gene-related peptide (CGRP) in skin tissue and tyrosine hydroxylase (TH) protein levels in DRG were detected by Western blot. The levels of hyaluronic acid (HA), bradykinin (BK), prostaglandin I2 (PGI2) in skin tissue, 5-HT, tryptophan hydroxylase 1 (TPH1), serotonin transporters (SERT), 5-HT 3 receptor (5-HT3R), and 5-HT 4 receptor (5-HT4R) in colon tissue were measured by enzyme-linked immunosorbent assay (ELISA).
RESULTS:
BL 25 and ST 36 acupoints were determined as sensitized acupoints, and BL 15 acupoint was used as a non-sensitized acupoint. EA at sensitized acupoints improved the DAI score, increased mechanical withdrawal thresholds, and alleviated colonic pathological damage of rats. EA at sensitized acupoints reduced SSC structures and decreased TH and CGRP expression levels (P<0.05). Furthermore, EA at sensitized acupoints reduced BK, PGI2, 5-HT, 5-HT3R and TPH1 levels, and increased HA, 5-HT4R and SERT levels in colitis rats (P<0.05). GR113808 treatment diminished the protective effect of EA at sensitized acupoints in colitis rats (P<0.05).
CONCLUSION
EA at sensitized acupoints alleviated DSS-induced somatic referred pain in colitis rats by interfering with 5-HTergic neural pathway, and reducing SSC inflammatory response.
Rats
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Animals
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Electroacupuncture
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Rats, Sprague-Dawley
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Serotonin
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Acupuncture Points
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Pain, Referred
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Calcitonin Gene-Related Peptide
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Signal Transduction
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Colitis/therapy*
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Indoles
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Sulfonamides

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