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.

Objective To determine the acetylation level of nucleophosmin(NPM)in female breast cancer and to discuss its function through mutation of modified lysine sites.To construct positive and negative NPM mutants on its acetylated lysine sites and to express them in breast cancer cells.Methods Acetylation level and acetylated lysine sites of NPM in three breast cancer tissues and para-carcinoma tissues were detected by acetylome technology;NPM mutants were constructed by site-directed mutagenesis PCR,specific PCR products were digested by DpnI and transformed into Escherichia coli(E.coli)to obtain specific plasmids for mutants;The accuracy of mutants were verified by double restriction enzyme digestion and sequencing;The mutants were expressed in BT-549 cells by transient transfection and verified by RT-PCR method.Protein expression and acetylation level of NPM were validated by Western blotting;Function of NPM acetylation was analyzed by proteomic detection and bioinformatic analysis.Results The 27th and 32nd lysine of NPM were highly acetylated in breast cancer tissues,which were 2.76 and 2.22 times higher than those in adjacent normal tissues,respectively;The NPM mutants showed the same molecular weight as that of wild type NPM and contained expected mutation sites;Corresponding NPM mRNA levels of BT-549 cells transfected with NPM mutants were significantly increased.With the increase of wild type NPM expression level,NPM acetylation level increased,while decreased after 27th lysine underwent negative mutation.NPM acetylation can significantly change the expression levels of 101 proteins in BT-549 cells,which are enriched in regulation of cellular macromolecule biosynthesis,DNA-template transcription,RNA biosynthesis and RNA metabolism process.Conclusion NPM is highly acetylated in breast cancer and can play a key role in cellular macromolecule biosynthesis,DNA-templated transcription,RNA biosynthesis and RNA metabolism process.

Objective To analyze the characteristics and influencing factors of healthcare-associated bloodstream infection(HA-BSI)of carbapenem-resistant Enterobacterales(CRE).Methods Retrospective nested case-control study was adopted.Fifty-six patients with CRE HA-BSI in a tertiary general hospital from January 2020 to Decem-ber 2022 were selected as the CRE group.With a 1:1 ratio,56 patients with carbapenem-sensitive Enterobacterales(CSE)BSI during the same period was selected as the CSE group.Distribution of infection strains and departments was analyzed,and the relevant factors for CRE BSI were analyzed by univariate and multivariate logistic regression analyses.Results The distribution of CRE BSI was mainly in intensive care unit(ICU,n=23,41.07％)and de-partment of hematology(n=17,30.36％).The main infection strains were Klebsiella pneumoniae(n=32,57.14％)and Escherichia coli(n=16,28.57％).Univariate analysis showed that malignant tumor,hospitalization history within 60 days,stay in ICU for＞48 hours before infection,mechanical ventilation,indwelling central venous cathe-ter,combined use of at least two kinds of antimicrobial agents,and duration of antimicrobial use ≥10 days were all related to CRE BSI(all P＜0.05).Multivariate logistic regression analysis found that stay in ICU＞48 hours before infection and duration of antimicrobial use ≥10 days before infection were independent risk factors for CRE HA-BSI(P＜0.05).Conclusion Clinical departments,especially ICU,should pay attention to the epidemiological history of patients,identify patients with high-risk factors for CRE BSI as early as possible,use antimicrobial agents ratio-nally and standardize invasive procedure,so as to reduce the occurrence of CRE HA-BSI.

Objective: Based on 3D printing technology, explore the precision of a perforator vessel location guide plate for fibular musculocutaneous flaps before the transplantation of fibular osteocutaneous flaps and evaluate its application effects. Methods: This study was reviewed and approved by the ethics committee, and informed consent was obtained from the patients. From May 2019 to October 2022, 14 patients with jaw defects who needed to undergo fibular perforator flap transplantation at the First Affiliated Hospital of Xinjiang Medical University were selected. For the seven patients in the guide plate group, CTA was combined with Mimics software to reconstruct both lower limbs, and the perforator vessel positioning guide for locating perforator vessels was designed; the two ends of the guide plate were designed as fixed ends, with the upper end fixed to the knee joint and the lower end fixed to the ankle joint, and the guide plate was fabricated by a 3D printer. For the seven patients in the control group, a conventional handheld Doppler probe was used for perforator vessel location. The average operation time, bleeding volume, recovery time, deviation of perforator vessel location, postoperative flap-related complications, postoperative donor site shape satisfaction, and lower extremity functional scale (LEFS) score were recorded. SPSS 25.0 software was used for statistical analysis. Results: The average operation time, bleeding volume, recovery time, deviation of perforator vessel location and postoperative donor site shape satisfaction were significantly better in the guide plate group than in the control group (P<0.05); moreover, the differences in postoperative flap-related complications and LEFS scores were not statistically significant (P>0.05). Conclusion Based on 3D printing technology, fibular musculocutaneous flap perforator vessels can be more accurately located using a guide plate and the knee and ankle as fixed points, and this method can effectively stabilize the guide position, prevent soft tissue offset, and improve positioning accuracy and thus deserves to be generalized.

Objective Cognitive impairment(CI)in older individuals has a high morbidity rate worldwide,with poor diagnostic methods and susceptible population identification.This study aimed to investigate the relationship between different retinal metrics and CI in a particular population,emphasizing polyvascular status. Methods We collected information from the Asymptomatic Polyvascular Abnormalities Community Study on retinal vessel calibers,retinal nerve fiber layer(RNFL)thickness,and cognitive function of 3,785 participants,aged 40 years or older.Logistic regression was used to analyze the relationship between retinal metrics and cognitive function.Subgroups stratified by different vascular statuses were also analyzed. Results RNFL thickness was significantly thinner in the CI group(odds ratio:0.973,95%confidence interval:0.953-0.994).In the subgroup analysis,the difference still existed in the non-intracranial arterial stenosis,non-extracranial carotid arterial stenosis,and peripheral arterial disease subgroups(P<0.05). Conclusion A thin RNFL is associated with CI,especially in people with non-large vessel stenosis.The underlying small vessel change in RNFL and CI should be investigated in the future.

OBJECTIVE To provide a reference for pharmaceutical care in patients with hemorrhagic transformation after cerebral infarction complicated with atrial fibrillation. METHODS Clinical pharmacists participated in the treatment practice of a patient with hemorrhagic transformation after cerebral infarction complicated with atrial fibrillation. Because the patient had a hemorrhagic transformation after cerebral infarction after stent implantation and arterial thrombolysis， the clinical pharmacists recommended stopping antiplatelet drugs and giving plasma and cold precipitation； because D-dimer was significantly elevated， the clinical pharmacists recommended anticoagulant therapy with low-molecular heparin. Due to the patient’s recurrence of hemorrhagic transformation after cerebral infarction， the clinical pharmacists recommended discontinuing rivaroxaban and administering human prothrombin complex concentrate. RESULTS The physician adopted the clinical pharmacists’ recommendation. After treatment， the patient’s condition tended to improve steadily and was allowed to be discharged with medication. CONCLUSIONS The clinical pharmacists assessed the individualized risk and optimized the patient’s medication regimen by suggesting discontinuation of antiplatelet and anticoagulant drugs， carrying out pharmaceutical care such as coagulation index monitoring， determining the time and indications for restarting anticoagulation， and pharmaceutical monitoring， to ensure the safety and efficacy of the patient’s medication.

Objective:To evaluate the efficacy and safety of Xiao′er Huangjin Zhike Granules in the treatment of cough caused by acute bronchitis in children, which is defined in TCM terms as a syndrome of phlegm-heat obstructing the lung.Methods:This was a block-randomized, double-blind, placebo-controlled, multicenter clinical trial.From January 2022 to September 2023, 359 children aged 3 to 7 years old diagnosed as acute bronchitis (lung-obstructing phlegm-heat syndrome) were enrolled from 21 participating hospitals and randomly assigned to the experimental group and placebo group in a 3︰1 ratio, and respectively treated with Xiao′er Huangjin Zhike Granules and its matching placebo.Cough resolution/general resolution rate after 7 days of treatment was used as the primary efficacy outcome for both groups.Results:(1)On the seventh day of treatment, the rate of cough disappearance/basically disappearance in the experimental group and placebo group were 73.95% and 57.61% retrospectively, which had statistically significance ( P=0.001).(2)After 7 days of treatment, the median duration of cough disappearance/basic disappearance were 5 days and 6 days in the two groups , with a statistically significant difference ( P=0.006).The area under the curve of cough symptom severity time was 7.20 ± 3.79 in the experimental group and 8.20±4.42 in the placebo group.The difference between the two groups was statistically significant ( P=0.039).(3) After 7 days of treatment, the difference between TCM syndrome score and baseline was -16.0 (-20.0, -15.0) points in the experimental group and -15.0 (-18.0, -12.0) points in the placebo group, with significant difference between the two groups ( P=0.004).In the experimental group, the clinical control rate, the markedly effective rate, the effective rate and the ineffective rate were 49.04%, 28.35%, 16.48% and 6.13% severally; and in the placebo group, the clinical control rate, the markedly effective rate, the effective rate and the ineffective rate were 38.04%, 26.09%, 29.35%, and 6.52% separately, which had statistically significant ( P=0.014).(4) There was no significant difference in the incidence of adverse events or adverse reactions during the trial between both groups.Moreover, while adverse reactions in the form of vomiting and diarrhea were occasionally reported, no serious drug-related adverse event or adverse reaction was reported.(5)The tested drug provided good treatment compliance, showing no statistically significant difference from the placebo in terms of compliance rate. Conclusions:Based on the above findings, it can be concluded that Xiao′er Huangjin Zhike Granules provides good safety, efficacy, and treatment compliance in the treatment of cough caused by acute bronchitis, and lung-obstructing phlegm-heat syndrome, in children.

Hepatocellular carcinoma(HCC)is one of the most common malignant tumors globally.Programmed death protein-1(PD-1)/programmed death protein ligand-1(PD-L1)inhibitors promote the reactivation of anti-tumor immune response by bloc-king the negative modulatory signaling pathway of T cells'activa-tion and inhibiting the immune escape pathway of tumor cells.PD-1/PD-L1 inhibitors become a novel therapeutic strategy to treat HCC.However,long-term clinical outcomes show that HCC patients treated with anti-PD-1/PD-L1 monotherapy still have high rates of recurrence and metastasis.Combination immuno-therapy is a novel therapeutic strategy to treat advanced HCC pa-tients,among which PD-1/PD-L1 inhibitors in combination with anti-vascular endothelial growth factor(VEGF)agents have showed promising efficacy and better safety.PD-1/PD-L1 inhib-itors plus anti-VEGF agents combined therapy inhibit the growth of hepatoma cells by participating in the cancer immunity cycle pathway.This review focuses on the research progress of PD-1/PD-L1 inhibitors,anti-VEGF agents and their combined therapy in the clinical treatment of HCC.

Objective:To screen interleukin(IL)-1β secretion-related membrane transporters by macrophage experiment in vitro and conventional knockout mice.Methods:THP-1 cell line was differentiated to obtain human THP-1-derived macrophages,and the primary macrophages were obtained from human peripheral blood.FVB wild-type mice with the same sex and age were used as the controls of MRP1 knockout mice.The macrophages in abdominal cavity and bone marrow of mice were cultivated.The cells were treated with ABCC1/MRP1,ABCG2/BCRP,ABCB1/P-gp,OATP1B1,and MATE transporter inhibitors,then stimulated by lipopolysaccharide and adenosine triphosphate.The secretion level of IL-iβ was detected by ELISA,Western blot,and immunofluorescence.Results:After inhibiting ABCC1/MRP1 transporter,the secretion of IL-1β decreased significantly,while inhibition of the other 4 transporters had no effect.In animal experiment,the level of IL-1 β secreted by macrophages in bone marrow of MRP1 knockout mice was significantly lower than control group(P＜0.05).Conclusion:ABCC1/MRP1 transporter is a newly discovered IL-1β secretion pathway,which is expected to become a new target for solving clinical problems such as cytokine release syndrome.

Endodontic diseases are a kind of chronic infectious oral disease.Common endodontic treatment concepts are based on the removal of inflamed or necrotic pulp tissue and the replacement by gutta-percha.However,it is very essential for endodontic treatment to debride the root canal system and prevent the root canal system from bacterial reinfection after root canal therapy(RCT).Recent research,encompassing bacterial etiology and advanced imaging techniques,contributes to our understanding of the root canal system's anatomy intricacies and the technique sensitivity of RCT.Success in RCT hinges on factors like patients,infection severity,root canal anatomy,and treatment techniques.Therefore,improving disease management is a key issue to combat endodontic diseases and cure periapical lesions.The clinical difficulty assessment system of RCT is established based on patient conditions,tooth conditions,root canal configuration,and root canal needing retreatment,and emphasizes pre-treatment risk assessment for optimal outcomes.The findings suggest that the presence of risk factors may correlate with the challenge of achieving the high standard required for RCT.These insights contribute not only to improve education but also aid practitioners in treatment planning and referral decision-making within the field of endodontics.