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.Clinical Observation on Modified Shehuang Ointment for the Treatment of Facial Seborrheic Dermatitis
Man-Xin HUANG ; De-Jian DUAN ; Hai-Fang GAN ; Dan HUANG ; Jia-Yao NIE
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(1):110-115
Objective To observe the clinical efficacy of modified Shehuang Ointment(mainly composed of Cnidii Fructus,Phellodendri Chinensis Cortex,and Zanthoxyli Pericarpium)for the treatment of facial seborrheic dermatitis(SD).Methods Seventy-two patients with facial SD were randomly divided into observation group and control group,with 36 patients in each group.Both groups of patients were given oral use of Acrivastine Capsules and Vitamin B6 Tablets,and additionally,the observation group was given topical application of modified Shehuang Ointment and the control group was given topical application of 2%Ketoconazole cream.The course of treatment covered 4 weeks.The changes of clinical symptom scores and dermatology life quality index(DLQI)scores in the two groups were observed before and after treatment,and the clinical efficacy and safety of the two groups were also evaluated.Results(1)After 4 weeks of treatment,the total effective rate of the observation group was 88.89%(32/36),and that of the control group was 72.22%(26/36).The intergroup comparison showed that the efficacy of the observation group was significantly superior to that of the control group,and the difference was statistically significant(P<0.05).(2)After treatment,the clinical symptom scores of erythema,scales,grease,rash area,itchiness and other clinical symptoms of the patients in the two groups were significantly decreased compared with those before treatment(P<0.05),and the clinical symptom scores of the observation group were significantly lower than those of the control group,the differences being statistically significant(P<0.05).(3)After treatment,the DLQI scores of patients in the two groups were significantly lower than those before treatment(P<0.05),and the DLQI scores in the observation group were significantly lower than those in the control group after treatment,the difference being statistically significant(P<0.05).(4)During the treatment period,no significant adverse reactions occurred in the two groups of patients,with high safety.Conclusion The conventional western medicine treatment combined with topical application of modified Shehuang Ointment exerts certain effect in the treatment of facial SD,which can effectively relieve the clinical symptoms and improve the quality of life of patients.
3.Clinical Study on Dingxuan Decoction Combined with Vestibular Function Rehabilitation Training in the Treatment of Meniere's Disease
Yu-Fang ZHANG ; Yan-Fang SONG ; Ying-Zhe CHEN ; Xiang-Dong WU ; Jing-Jing HAI ; Wen-Qing SUN
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(3):646-652
Objective To investigate the efficacy of Dingxuan Decoction combined with vestibular function rehabilitation training in the treatment of Meniere's disease and to observe its effect on clinical symptoms and blood flow of vertebral artery.Methods A total of 100 patients with Meniere's disease of liver-kidney yin deficiency complicated with wind-water upward stirring type were randomly divided into an observation group and a control group,with 50 patients in each group.The control group was given conventional treatment and vestibular function rehabilitation training,and the observation group was treated with Dingxuan Decoction on the basis of treatment for the control group.The two groups were treated for 4 weeks and then were followed up for 6 months.The changes of traditional Chinese medicine(TCM)syndrome score,Dizziness Handicap Inventory(DHI)score,Tinnitus Handicap Inventory(THI)score,hearing visual analogue scale(VAS)score and vertebral artery blood flow in the two groups were observed before and after the treatment.After treatment,the TCM syndrome efficacy,hearing improvement and follow-up results were compared between the two groups.Results(1)After 4 weeks of treatment,the total effective rate for TCM syndrome efficacy of the observation group was 86.00%(43/50),and that of the control group was 62.00%(31/50),and the intergroup comparison showed that the TCM syndrome efficacy in the observation group was significantly superior to that in the control group(P<0.01).(2)After 4 weeks of treatment,the hearing of patients in both groups was improved,and the total effective rate for the efficacy of hearing improvement in the observation group was 76.00%(38/50),while that in the control group was 46.00%(23/50).The intergroup comparison showed that the efficacy of hearing improvement in the observation group was significantly superior to that in the control group(P<0.01).(3)After treatment,the TCM syndrome scores,DHI score,THI score and hearing VAS scores in the two groups were all decreased compared with those before treatment(P<0.05 or P<0.01),and the decrease in the observation group was significantly superior to that in the control group(P<0.01).(4)After treatment,the average blood flow velocity of the left vertebral artery(LVA)and the right vertebral artery(RVA)in the two groups were both increased compared with those before treatment(P<0.05),and the increase in the observation group was significantly superior to that in the control group(P<0.05 or P<0.01).(5)The results of 6-month follow-up after treatment showed that the incidence of Meniere's disease and the frequency of attack in the observation group were significantly reduced compared with those in the control group,and the episode duration in the observation group was significantly shorter than that in the control group,the differences being all statistically significant(P<0.05 or P<0.01).Conclusion Dingxuan Decoction combined with vestibular function rehabilitation training exert certain effect in treating patients with Meniere's disease of liver-kidney yin deficiency complicated with wind-water upward stirring type,and the therapy is effective on improving patients'clinical symptoms and vertebral artery blood flow,reducing the risk of recurrence and improving the quality of life of the patients.
4.Quantitative analysis of early lumbar disc degeneration in young adults by intravoxel incoherent motion in body diffusion-weighted imaging
Fang CHEN ; Mingzhe HU ; Hai WU ; Yaomeng CHEN ; Peipei ZHU
China Modern Doctor 2024;62(12):24-27,36
Objective To explore the predictive value of slow apparent diffusion coefficient(ADCslow),fast apparent diffusion coefficient(ADCfast)and perfusion fraction(f)value of intravoxel incoherent motion in body diffusion-weighted imaging(IVIM-DWI)sequence in early lumbar disc degeneration in young people.Methods The IVIM-DWI technique was used as quantitative magnetic resonance imaging for 120 patients(596 lumbar intervertebral discs)with lower back pain included in Wenzhou People's Hospital.The ADCslow,ADCfast and f values of all lumbar intervertebral discs were measured,and then they were divided into 3 groups according to the Pfirrmann grading standard.SPSS 20.0 statistical software was used to analyze the data.Results The ADCfast value has statistical significance in distinguishing the lumbar intervertebral discs of each group:The area under the curve(AUC)of the normal group vs.the early degenerative group was 0.766,with a sensitivity of 64.2%and a specificity of 78.5%;The AUC of the normal group vs.the mid to late stage degenerative group was 0.822,with a sensitivity of 67.9%and a specificity of 91.3%;The AUC of the early degeneration group vs.the middle and late stage degeneration group was 0.797,with a sensitivity of 62.1%and a specificity of 92.1%.The ADCslow value has statistical significance in distinguishing the lumbar intervertebral discs of each group:AUC=0.707 in the normal group vs.the early degenerative group,with a sensitivity of 83.6%and a specificity of 61.0%;The AUC of the normal group vs.the mid to late stage degenerative group was 0.701,with a sensitivity of 84.5%and a specificity of 58.6%;The AUC of the early degeneration group vs.the middle and late stage degeneration group was 0.668,with a sensitivity of 86.6%and a specificity of 51.0%.The f value cannot distinguish between different groups of lumbar intervertebral discs.Conclusion ADCslow and ADCfast of IVIM-DWI sequence have certain accuracy and specificity in distinguishing the early degeneration of lumbar intervertebral disc in young people,which provides a reliable basis for early clinical treatment.
5.Cellular Temperature Imaging Technology Based on Single-molecule Quantum Coherent Modulation
Hai-Tao ZHOU ; Cheng-Bing QIN ; Lian-Tuan XIAO ; Zhi-Fang WU ; Si-Jin LI
Progress in Biochemistry and Biophysics 2024;51(5):1215-1220
ObjectiveCellular temperature imaging can assist scientists in studying and comprehending the temperature distribution within cells, revealing critical information about cellular metabolism and biochemical processes. Currently, cell temperature imaging techniques based on fluorescent temperature probes suffer from limitations such as low temperature resolution and a limited measurement range. This paper aims to develop a single-cell temperature imaging and real-time monitoring technique by leveraging the temperature-dependent properties of single-molecule quantum coherence processes. MethodsUsing femtosecond pulse lasers, we prepare delayed and phase-adjustable pairs of femtosecond pulses. These modulated pulse pairs excite fluorescent single molecules labeled within cells through a microscopic system, followed by the collection and recording of the arrival time of each fluorescent photon. By defining the quantum coherence visibility (V) of single molecules in relation to the surrounding environmental temperature, a correspondence between V and environmental temperature is established. By modulating and demodulating the arrival times of fluorescent photons, we obtain the local temperature of single molecules. Combined with scanning imaging, we finally achieve temperature imaging and real-time detection of cells. ResultsThis method achieves high precision (temperature resolution<0.1°C) and a wide temperature range (10-50°C) for temperature imaging and measurement, and it enables the observation of temperature changes related to individual cell metabolism. ConclusionThis research contributes to a deeper understanding of cellular metabolism, protein function, and disease mechanisms, providing a valuable tool for biomedical research.
6.Raman Spectroscopy Analysis of The Temporal Heterogeneity in Lung Cell Carcinogenesis Induced by Benzo(a)pyrene
Hai-Tao ZHOU ; Wei YAO ; Cao-Zhe CUI ; Xiao-Tong ZHOU ; Xi-Long LIANG ; Cheng-Bing QIN ; Lian-Tuan XIAO ; Zhi-Fang WU ; Si-Jin LI
Progress in Biochemistry and Biophysics 2024;51(6):1458-1470
ObjectiveTemporal heterogeneity in lung cancer presents as fluctuations in the biological characteristics, genomic mutations, proliferation rates, and chemotherapeutic responses of tumor cells over time, posing a significant barrier to effective treatment. The complexity of this temporal variance, coupled with the spatial diversity of lung cancer, presents formidable challenges for research. This article will pave the way for new avenues in lung cancer research, aiding in a deeper understanding of the temporal heterogeneity of lung cancer, thereby enhancing the cure rate for lung cancer. MethodsRaman spectroscopy emerges as a powerful tool for real-time surveillance of biomolecular composition changes in lung cancer at the cellular scale, thus shedding light on the disease’s temporal heterogeneity. In our investigation, we harnessed Raman spectroscopic microscopy alongside multivariate statistical analysis to scrutinize the biomolecular alterations in human lung epithelial cells across various timeframes after benzo(a)pyrene exposure. ResultsOur findings indicated a temporal reduction in nucleic acids, lipids, proteins, and carotenoids, coinciding with a rise in glucose concentration. These patterns suggest that benzo(a)pyrene induces structural damage to the genetic material, accelerates lipid peroxidation, disrupts protein metabolism, curtails carotenoid production, and alters glucose metabolic pathways. Employing Raman spectroscopy enabled us to monitor the biomolecular dynamics within lung cancer cells in a real-time, non-invasive, and non-destructive manner, facilitating the elucidation of pivotal molecular features. ConclusionThis research enhances the comprehension of lung cancer progression and supports the development of personalized therapeutic approaches, which may improve the clinical outcomes for patients.
7.Conformational Engineering of Antibody Fragments on The Surface of Platinum Nanoparticles
Ling-Jie SHENG ; Jia XU ; Jing-Jing DAI ; Hai-Fang WANG ; Ao-Neng CAO
Progress in Biochemistry and Biophysics 2024;51(3):647-657
ObjectiveRecent successful restoration of the native conformation and function of the complementary-determining regions (CDRs) of antibodies on gold nanoparticles (AuNPs) demonstrates that the era of molecular conformational engineering is dawning. Basically, molecular conformational engineering aims to precisely tune flexible non-functional molecules into special conformations to carry out novel functions, in the same way as protein folding. In order to explore the general applicability of molecular conformational engineering, as well as to reveal the mechanism of protein structure-function relationship, the objective of this work is to restore the native conformation and function of the CDRs of an antibody on platinum nanoparticles (PtNPs). MethodsThe CDR fragment of the anti-lysozyme antibody cAB-lys3, which has no stable conformation or function in free state, was conjugated onto the surface of PtNPs through two Pt-S bonds. The original antigen-recognizing function of the CDR restored on PtNPs was assessed by the specific inhibition of the enzymatic activity of lysozyme by the PtNP-CDR conjugates. ResultsAfter optimization of the peptide density on the surface of PtNPs and modification of PtNPs with polyethylene glycol (PEG), the resulted PtNP-based hybrid artificial antibody (PtNP-10PEG-30P1), dubbed Platinumbody, could bind specifically to lysozyme and significantly inhibit the activity of lysozyme. ConclusionThis is the first time that the fragment of a protein could refold on PtNPs. Together with the previous Goldbody and Silverbody, current work demonstrates that artificial proteins could be generally created by restoration of the native conformation of natural proteins fragments on NPs.
8.Screening and identification of human monoclonal antibodies against low-calcium response V antigen of Yersinia pestis
Li ZHANG ; Bin-Yang ZHENG ; Qi ZHANG ; Hai-Lian WU ; Hong-Xin PAN ; Feng-Cai ZHU ; Hai-Sheng WU ; Jian-Fang ZHOU
Chinese Journal of Zoonoses 2024;40(1):15-20
To characterize human antibodies against low-calcium response V(LcrV)antigen of Yersinia pestis,the mono-clonal antibodies were screened and assayed.Antibody gene was derived from peripheral blood mononuclear cells of the vaccin-ees immunized by plague subunit vaccine in phase Ⅱb clinical trial.Human ScFv antibody library was constructed by phage dis-play.After panning library by using recombinant LcrV antigen,antibody variable genes were sequenced and converted into IgG1 format to evaluate its binding specificity and relevant parameters.An anti-plague human ScFv antibody library was estab-lished contained 7.54× 108 independent clones.After panning by LcrV antigen,3 human antibodies named as RV-B4,RV-D1 and RV-E8,respectively,were identified.Using indirect enzyme-linked immunosorbent assay(ELISA)and Western blot(WB),the specific bindings of the mAbs to LcrV antigen were confirmed.The dissociation constant(KD)of them to LcrV is 2.1 nmol/L,1.24 nmol/L and 42 nmol/L,respectively.Minor protective efficacy was found among 3 human antibodies in Y.pestis 141-infected mice.Three anti-LcrV monoclonal antibodies generated from immunized vaccinees were binding specific antibod-ies and could not block plague infection in mice.These antibodies are the potential candidate reagents for basic research of plague immunity and the application of plague diagnosis.
9.Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults (version 2024)
Qingde WANG ; Yuan HE ; Bohua CHEN ; Tongwei CHU ; Jinpeng DU ; Jian DONG ; Haoyu FENG ; Shunwu FAN ; Shiqing FENG ; Yanzheng GAO ; Zhong GUAN ; Hua GUO ; Yong HAI ; Lijun HE ; Dianming JIANG ; Jianyuan JIANG ; Bin LIN ; Bin LIU ; Baoge LIU ; Chunde LI ; Fang LI ; Feng LI ; Guohua LYU ; Li LI ; Qi LIAO ; Weishi LI ; Xiaoguang LIU ; Hongjian LIU ; Yong LIU ; Zhongjun LIU ; Shibao LU ; Yong QIU ; Limin RONG ; Yong SHEN ; Huiyong SHEN ; Jun SHU ; Yueming SONG ; Tiansheng SUN ; Yan WANG ; Zhe WANG ; Zheng WANG ; Hong XIA ; Guoyong YIN ; Jinglong YAN ; Wen YUAN ; Zhaoming YE ; Jie ZHAO ; Jianguo ZHANG ; Yue ZHU ; Yingjie ZHOU ; Zhongmin ZHANG ; Wei MEI ; Dingjun HAO ; Baorong HE
Chinese Journal of Trauma 2024;40(2):97-106
Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.
10.The Role of Mechanical Sensitive Ion Channel Piezo in Digestive System Diseases
Si-Qi WANG ; Xiang-Yun YAN ; Yan-Qiu LI ; Fang-Li LUO ; Jun-Peng YAO ; Pei-Tao MA ; Yu-Jun HOU ; Hai-Yan QIN ; Yun-Zhou SHI ; Ying LI
Progress in Biochemistry and Biophysics 2024;51(8):1883-1894
The Piezo protein is a non-selective mechanosensitive cation channel that exhibits sensitivity to mechanical stimuli such as pressure and shear stress. It converts mechanical signals into bioelectric activity within cells, thus triggering specific biological responses. In the digestive system, Piezo protein plays a crucial role in maintaining normal physiological activities, including digestion, absorption, metabolic regulation, and immune modulation. However, dysregulation in Piezo protein expression may lead to the occurrence of several pathological conditions, including visceral hypersensitivity, impairment of intestinal mucosal barrier function, and immune inflammation.Therefore, conducting a comprehensive review of the physiological functions and pathological roles of Piezo protein in the digestive system is of paramount importance. In this review, we systematically summarize the structural and dynamic characteristics of Piezo protein, its expression patterns, and physiological functions in the digestive system. We particularly focus on elucidating the mechanisms of action of Piezo protein in digestive system tumor diseases, inflammatory diseases, fibrotic diseases, and functional disorders. Through the integration of the latest research findings, we have observed that Piezo protein plays a crucial role in the pathogenesis of various digestive system diseases. There exist intricate interactions between Piezo protein and multiple phenotypes of digestive system tumors such as proliferation, apoptosis, and metastasis. In inflammatory diseases, Piezo protein promotes intestinal immune responses and pancreatic trypsinogen activation, contributing to the development of ulcerative colitis, Crohn’s disease, and pancreatitis. Additionally, Piezo1, through pathways involving co-action with the TRPV4 ion channel, facilitates neutrophil recruitment and suppresses HIF-1α ubiquitination, thereby mediating organ fibrosis in organs like the liver and pancreas. Moreover, Piezo protein regulation by gut microbiota or factors like age and gender can result in increased or decreased visceral sensitivity, and alterations in intestinal mucosal barrier structure and permeability, which are closely associated with functional disorders like irritable bowel sydrome (IBS) and functional consitipaction (FC). A thorough exploration of Piezo protein as a potential therapeutic target in digestive system diseases can provide a scientific basis and theoretical support for future clinical diagnosis and treatment strategies.

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