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.

Breast cancer is one of the most common and fatal malignancies among women worldwide, and its treatment efficacy is often limited by drug resistance and the presence of undruggable targets. Traditional small-molecule drugs have difficulty effectively modulating certain critical targets such as transcription factors and non-coding RNAs, necessitating new therapeutic strategies. Proteolysis-targeting chimeras (PROTACs) function by recruiting pathogenic proteins to the cellular ubiquitin-proteasome system, thereby inducing their specific degradation. In contrast, ribonuclease-targeting chimeras (RIBOTACs) utilize small-molecule ligands but bind to RNA and direct endogenous RNases to selectively degrade pathogenic RNA molecules. By employing a "degradation rather than inhibition" mechanism, targeting chimera technology broadens the druggable landscape and offers a novel precision therapeutic strategy for breast cancer, particularly for refractory and drug-resistant cases. This approach not only overcomes the limitations of traditional drugs, such as the absence of suitable binding sites or poor selectivity, but also reduces required dosages and potential adverse effects. Recent studies have preliminarily demonstrated the therapeutic potential of PROTACs and RIBOTACs in breast cancer, encompassing target design, mechanistic investigation, and preclinical as well as early clinical applications. Research into these technologies reveals their ability to tackle previously undruggable targets, thereby providing theoretical support for the development of safer and more effective precision therapies for breast cancer. In the future, with advances in drug delivery systems and clinical trials, PROTACs and RIBOTACs are expected to be used synergistically with immunotherapy and chemotherapy, offering breast cancer patients more promising comprehensive treatment options and potentially driving oncology toward broader intervention of undruggable targets.
Humans ; Breast Neoplasms/drug therapy* ; Female ; Proteolysis ; Ribonucleases/metabolism* ; Molecular Targeted Therapy/methods* ; Antineoplastic Agents/therapeutic use*

OBJECTIVES: To explore the therapeutic mechanism of Guizhi Fuling (GZFL) Pellets against cervical cancer. METHODS: Publicly available databases were used to identify the targets of GZFL Pellets and cervical cancer to construct the protein-protein interaction (PPI) network, followed by GO biological process and KEGG pathway enrichment analysis of the hub genes. The "Traditional Chinese Medicine-Active Ingredients-Targets-Pathways" network for GZFL Pellets in cervical cancer treatment was generated using Cytoscape v10.0.0, and molecular docking of the drug and potential targets was performed to predict the specific targets of active components in Guizhi Fuling Pellets. The inhibitory effects of hederagenin, an active ingredient in GZFL Pellets, was tested in cultured cervical cancer cells and in nude mice bearing cervical cancer xenografts. RESULTS: GZFL Pellets contain 338 active components targeting 247 action sites. A total of 10127 cervical cancer-related targets were obtained, and among them 195 were identified as potential therapeutic targets of GZFL Pellets for cervical cancer treatment, including the key targets of GABRA1, PTK2, JAK2, HTR3A, GSR, and IL-17. Molecular docking study showed low binding energies of the active components such as hederagenin, campesterol, and stigmasterol for protein-molecule interaction. GO enrichment analysis suggested that GZFL Pellets inhibited cervical cancer primarily by regulating responses to steroid hormones, oxidative stress, and lipopolysaccharides. Among the active components of GZFL Pellets, hederagenin was found to inhibit cervical cancer cells in vitro and significantly reduced STAT3 phosphorylation level in the cancer cells. In nude mice bearing cervical cancer xenografts, hederagenin effectively inhibited tumor growth rate without causing obvious adverse effects. CONCLUSIONS GZFL Pellets inhibit cervical cancer cell growth through its multiple active components that target different pathways. Among these components, hederagenin inhibits tumor cell growth possibly by directly binding to JAK2 protein to inhibit STAT3 phosphorylation.
Female ; Animals ; Uterine Cervical Neoplasms/pathology* ; Mice, Nude ; Humans ; Mice ; Oleanolic Acid/therapeutic use* ; Drugs, Chinese Herbal/therapeutic use* ; Molecular Docking Simulation ; Xenograft Model Antitumor Assays ; Cell Line, Tumor ; STAT3 Transcription Factor/metabolism* ; Protein Interaction Maps ; Janus Kinase 2/metabolism*

Rheumatoid arthritis belongs to arthralgia syndrome in the theory of traditional Chinese medicine， and cold-dampness obstruction syndrome and dampness-heat obstruction syndrome are core syndromes and main syndrome differentiation types of this disease. Fine therapeutic effects have been obtained in the long-term clinical practice of many famous traditional Chinese medicine practitioners following the syndrome differentiation and treatment based on the guiding principles of cold and heat. To adapt to the clinical diagnosis practice of combining disease differentiation and syndrome differentiation， and to better carry out basic research on integrated Chinese and Western medicine and preclinical study on new traditional Chinese medicines， Guidelines for Establishing Animal Models of Rheumatoid Arthritis with Cold-Dampness Obstruction Syndrome and Dampness-Heat Obstruction Syndrome （hereinafter referred to as the Guidelines） were compiled by our research group， in cooperation with the renowned experts in research fields including traditional Chinese medicine， clinical medicine， zoology and evidence-based medicine， which provide a meaningful reference for scientific research， teaching and clinical applications. The compilation process of the Guidelines was guided by the theory of disease and syndrome integration and the principles of "evidence takes the main place， consensus plays an auxiliary role， and experience serves as the reference". Based on the comprehensive evaluation of pathogenesis homology， behavioral phenotypic consistency， and drug treatment predictability compared between animal models and human diseases， by the nominal group method， "recommendations" were formed for recommendations supported by evidence， and "consensus recommendations" were formed for recommendations not supported by evidence. Guidelines were formed involving content such as animal types， arthritis modeling methods， external stimulation conditions， and modeling assessment indicators during the establishment of the animal models of rheumatoid arthritis with cold-dampness obstruction syndrome and dampness-heat obstruction syndrome. The Guidelines are applicable for the disease and syndrome research on rheumatoid arthritis， investigation of therapeutic mechanisms， and development of new traditional Chinese medicine. The Guidelines also provide a reference for the establishment of guidelines on other types of diseases and syndromes combined with animal models to further promote the modernization of traditional Chinese medicine research and its integration with international academic development.

The Guidelines for Establishing Animal Models of Rheumatoid Arthritis with Cold-dampness Obstruction Syndrome and Dampness-heat Obstruction Syndrome （hereinafter referred to as the Guidelines） （No. T/CACM1567-2024） was published by Chinese Association of Chinese Medicine on January 11， 2024. To assist researchers and medical workers in understanding and applying the Guidelines more accurately， and also to provide reference and assistance for the establishment of guidelines on other types of diseases and syndromes combined with animal models， this paper made a declaration of the workflow， technological links， development references， promotion of its application and after-effect evaluation of the Guidelines that has been made according to the requirements of "Draft Group Standard of the Standardization Office of the Chinese Association of Traditional Chinese Medicine".

ObjectiveTo study the relationship between qi stagnation constitution and suboptimal health status (SHS) or lifestyle.MethodsFrom 2012 to 2013, we conducted a cross-sectional survey of 24 159 Chinese individuals aged 12–80 years. The qi stagnation constitution was assessed using the Constitution in Chinese Medicine Questionnaire. Health status was evaluated through medical records and the Subhealth Measurement Scale V1.0 (SHMS V1.0). Health-promoting lifestyles were measured using the Health-Promoting Lifestyle Profile II (HPLP-II).ResultsOf the 24 159 participants, 16.1% and 15.2% were classified as “always” and “sometimes” having the qi stagnation constitution, respectively. Those classified as “rarely” having the qi stagnation constitution scored higher on both the HPLP-II and SHMS V1.0. The participants classified as “always” having the qi stagnation constitution showed a significant association with SHS or disease compared to other imbalanced constitutions. Those in the “always” category were approximately 21 times more likely to be classified as having SHS (odds ratio [OR]: 21.17, 95% confidence interval [CI]: 15.74–28.45), whereas those in the “sometimes” category were approximately six times more likely (OR: 5.89, 95% CI: 5.04–6.90). Accordingly, the qi stagnation constitution score was significantly associated with the diagnosis of SHS, with an area under the curve of 0.77 (P .001). A score of 18.75 yielded the highest Youden Index (0.407), with a sensitivity of 60.5% and a specificity of 80.3%. Significant associations were observed between health-promoting lifestyles and qi stagnation constitution severity in an ordinal regression analysis (P .001). Protective factors included stress management (OR: 1.59), self-actualization (OR: 1.57), and exercise (OR: 1.36). In contrast, poorer interpersonal relationships (OR: 0.79), greater health responsibilities (OR: 0.86), and poorer nutrition (OR: 0.91) were associated with increased severity.ConclusionModulating the qi stagnation constitution through lifestyle interventions may help prevent the progression of SHS to disease, which aligns with core preventive principles in traditional Chinese medicine.

Objective To analyze the current status and latent profiles on the decision fatigue of nurses. Methods A total of 812 nurses from four public tertiary hospitals in Guangdong Province were selected as the research subjects using the convenience sampling method. The Decisional Fatigue Scale, the Nursing Work Environment Scale, the Nurses Job Stress Scale, and the Chinese version of 10-item Connor-Davidson Resilience Scale were used to assess the level of decision fatigue, work environment, job stress level, and resilience among nurses. The characteristics of latent profiles on the decision fatigue of nurses were analyzed, and multinomial logistic regression was used to analyze the influencing factors of latent profiles on the decision fatigue of nurses. Results The median and 25th and 75th percentiles of the scores of the decision fatigue of nurses were 10.0 (9.0, 15.0). The average scores for work environment, job stress, and resilience were (107.9±24.0), (86.1±23.8), and (23.6 ± 8.3), respectively. The result of latent profile analysis showed that the decision fatigue of nurses could be classified into three types: low fatigue-energetic, medium fatigue-avoidant and high fatigue-burnout, accounting for 15.0%, 59.6%, and 25.4%, respectively. The results of multinomial logistic regression showed that the risk of being classified as medium fatigue-avoidant was higher among practice nurse than nurse (P<0.05). Nurse with a monthly income of 5 000 to 10 000 yuan had higher risk of being classified as medium fatigue-avoidant than those with >10 000 yuan (P<0.05). And nurse with poorer work environment scores had higher risk of being classified as medium fatigue-avoidant than those with higher scores (P<0.01). Nurse with higher score on job stress and lower score on resilience had higher risk of being classified as medium fatigue-avoidant and high fatigue-burnout, than those with lower score of job stress and higher score on resilience (all P<0.01). Conclusion There is a heterogeneity in the decision fatigue of nurses, which can be categorized into three categories: low fatigue-energetic, medium fatigue-avoidant and high fatigue-burnout. The influencing factors of latent profile on the decision fatigue of nurses are job title, individual monthly income, work environment, job stress, and resilience.

{L-End}Objective To analyze the characteristics of hearing loss and the influencing factors of high-frequency hearing loss (HFHL) among noise-exposed workers in an urban rail transit enterprise over five consecutive years. {L-End}Methods A total of 1 268 noise-exposed workers, who exposed to the average noise intensity of <85.0 dB(A), in an urban rail transit enterprise was selected as the research subjects using a judgment sampling method. The pure-tone audiometry results from 2019 to 2023 were collected to analyze the result of hearing loss. The influencing factors of HFHL (average hearing threshold ≥40.0 dB at high frequencies in both ears) were analyzed using the generalized estimating equations (GEE). {L-End}Results The detection rates of threshold elevations at frequencies of 0.5-6.0 kHz increased with increasing frequency from 2019 to 2023 (all P<0.01), with the highest detection rate at 6.0 kHz. The detection rate of speech frequency hearing loss (hearing threshold weighted value≥26.0 dB in the better ear) was 0.1%, 0.0%, 0.4%, 0.2%, and 0.2%, respectively. The detection rate of HFHL from 2019 to 2023 was 2.4%, 2.8%, 2.8%, 2.1%, and 2.8%, respectively. The GEE analysis results showed that the risk of HFHL of the workers in 2022 and 2023 was lower than that in 2019 (all P<0.01), with the odds ratios and 95% confidence intervals ［OR (95%CI)］ of 0.57 (0.41-0.81) and 0.65 (0.48-0.87), respectively. The risk of HFHL was higher among vehicle maintenance worker than train drivers (P<0.05), with OR (95%CI) of 2.37 (1.18-4.77). The risk of HFHL increased with age and length of service among the workers (all P<0.05), with the OR (95%CI) of 2.05 (1.22-3.46) and 1.69 (1.12-2.54), respectively. No interaction was found between type of job and age, type of job and length of service, or age and length of service in the risk of HFHL among the research subjects(all P<0.05). {L-End}Conclusion Noise exposure below the national occupational exposure limits can lead to hearing loss in noise-exposed workers of urban rail transit enterprises, possibly affecting the hearing threshold at 6.0 kHz first. The influencing factors for HFHL in workers of rail transit are age, length of service, and type of job. There is a dose-effect relationship with age and length of service.

{L-End}Objective To explore the chain mediating effect of team psychological safety atmosphere and professional calling in the relationship between humble leadership and voice behavior. {L-End}Methods A total of 812 nurses from five medical institutions in Guangdong Province were selected as the research subjects using the convenience sampling method. The Team Psychological Safety Atmosphere Scale, the Professional Calling Scale, the Hospital Version of Humble Leadership Scale and the Voice Behavior Scale were used to investigate the perceived team psychological safety atmosphere and sense of professional calling, the perceived humble leadership style and voice behavior of the nurses. {L-End}Results The score of team psychological safety atmosphere, professional calling, humble leadership, and voice behavior of 812 nurses was (58.0±7.6), (44.6±8.0), (50.4±9.2) and (37.0±5.9), respectively, with the scoring rate of 72.5%, 74.3%, 80.0%, and 74.0%, respectively. Bootstrap analysis showed that humble leadership could positively influence voice behavior ［standardized effect value (β)=0.28, 95% confidence interval (CI) 0.20-0.35］. Humble leadership could influence voice behavior through the separate mediating effects of team psychological safety atmosphere (β=0.13, 95%CI 0.09-0.18), professional calling (β=0.07, 95%CI 0.04-0.11), and the chain mediating effect of team psychological safety atmosphere and professional calling(β=0.06, 95%CI 0.04-0.08). {L-End}Conclusion The voice behavior of clinical nurses is at a moderately high level. Humble leadership can directly influence voice behavior and can influence voice behavior through the mediating effects of team psychological safety atmosphere and professional calling. Nursing managers can inspire the work passion of clinical nurses by changing their own leadership style and creating a good atmosphere for voicing opinions.

OBJECTIVE: To explore method and clinical effect of microsurgical thinned anterolateral thigh perforator flap to repair soft tissue defects of foot and ankle. METHODS: From March 2017 to January 2022, totally 20 patients with soft tissue defects of ankle joint were treated with micro-thinning anterolateral perforator flap for free transplantation, included 13 males and 7 females, aged from 22 to 58 years old with an average of (36.45±12.36) years old. The size of flap ranged from 8.0 cm×5.0 cm to 20.0 cm×12.0 cm. Before operation, perforating vessels on the anterolateral thigh region were detected and marked with a portable Doppler detector. For the defect width less than 8 cm, 11 patients were repaired with a single flap. For the defect width more than 8 cm, the wound could not be sutured directly, and the lobulated flap technique was used in 9 patients, the width was converted to length, and the donor site was closed directly. Under the microscope, all flaps were thinened in a stepwise manner from the center of the pedicle to the periphery. After operation, survival of the flap, the shape, texture, sensory function recovery were observes, and recovery of foot function was evaluated by Maryland foot function evaluation standard. RESULTS: All 20 patients with microsurgical thinned anterolateral thigh perforator flaps were survived. Venous crisis occurred in 1 patient due to subcutaneous hematoma, after removal of the hematoma, the crisis was relieved and the flap survived successfully. The wounds in the donor and recipient sites healed well, and only linear scars left in the donor sites. Twenty patients were followed up for 3 to 26 months after operation, good shape of flaps without bloated, and good texture. The two-point discrimination of free flaps ranged from 9.0 to 16.0 mm, and the protective sensation was restored. The ankle flexion and extension function recovered well and patients could walk normally. According to Maryland foot function evaluation standard, 8 patients got excellent result, 10 patients good and 2 middle. CONCLUSION Microsurgical thinned anterolateral thigh perforator flap is an ideal method to repair soft tissue defects in functional area of foot and ankle, with good appearance and texture of the flap, no need for re-plastic surgery, reduced hospitalization costs, and less donor site damage.
Female ; Male ; Humans ; Young Adult ; Adult ; Middle Aged ; Ankle/surgery* ; Thigh/surgery* ; Ankle Joint ; Perforator Flap ; Hematoma