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.

Vascular calcification is a highly regulated process of ectopic calcification in cardiovascular system while no effective intervention can be clinically performed up to date.As vascular calcification undergoes a common regulatory mechanism within bone formation,bone morphogenetic protein 7(BMP-7)main-tains contractile phenotype of vascular smooth muscle cells and further inhibits vascular calcification via promoting the process of osteoblast differentiation,reducing ectopic calcification pressure by increasing bone formation and reducing bone resorption.This work systematically reviews the role of BMP-7 in vascular calcifi-cation and the possible mechanism,and their current clinical application as well.The current proceedings may help develope early diagnostic strategy and therapeutic treatment with BMP-7 as a new molecular marker and potential drug target.The expec-tation could achieve early prevention and intervention of vascular calcification and improve poor prognosis on patients.

Aim To investigate the mechanism of icar-itin(ICT)on D-galactose(D-gal)-induced TM4 ser-toli cell junctional function damage in vitro.Methods TM4 cells were divided into the normal control group and D-gal treatment group with different concentra-tions.The expression changes of TM 4 cell junction function-related proteins(ZO-1,Occludin,β-catenin and Cx43)and ERα/FAK signaling pathway-related proteins(ERα,FAK and pY397-FAK)were detected by Western blot.The concentration of ICT was screened by MTT method.TM4 cells were divided into normal control group,D-gal treatment group,and D-gal treatment+different concentrations of ICT group.The expression levels of the above proteins were detected by Western blot.Molecular docking was used to study the interaction between ERα and ICT,meanwhile predict the affinity between them.Finally,TM4 cells were di-vided into normal control group,D-gal treatment group,ERα inhibitor group,D-gal+ICT group,and ERα inhibitor+ICT group.The expression levels of the above proteins were detected by Western blot.Re-sults Compared with the normal control group,the ex-pression of junctional function-related proteins(ZO-1,Occludin,β-catenin and Cx43)and ERα/FAK signa-ling pathway-related proteins(ERα,FAK and pY397-FAK)were significantly down-regulated.After treat-ment with ICT,the expression of above proteins were significantly up-regulated.The docking results of ERα and ICT molecules revealed the formation of two hydro-gen bonds between Asp351 amino acid residue of ERα and ICT,with bond distances measuring 3.4? and 2.4?.Additionally,the docking binding energy be-tween them was found to be lower than-7 kcal·mol-1.After TM4 cells were treated with ERα inhibi-tor,the expression of above proteins and ERα/FAK signaling pathway-related proteins were significantly down-regulated,while the expression levels of the a-bove proteins did not change significantly after being given ICT protected group.Conclusions D-gal can cause damage to the junctional function of TM4 cells,and ICT can improve this damage,which may be related to the up-regulation of ERα/FAK signaling pathway.

Objective To explore the clinical efficacy and safety of early surgical treatment for spinal thoracolumbar fracture without nerve injury.Methods The clinical data of 80 patients with spinal thoracolumbar fracture without nerve injury who were admitted to the department of spinal surgery in our hospital were retrospectively analyzed.According to the different operation timing,those who underwent surgery within 72 hours after fracture were included in the early operation group(n=41),and those who underwent surgery 72 hours to 2 weeks after fracture were included in the elective operation group(n=39).All operations were performed through the Wiltse approach for short-segment pedicle screw fixation on the injured vertebra.The operation time,intraoperative blood loss,hospital stay and incidence of complication of the two groups were compared.The visual analogue scale(VAS)scores,Oswestry disability index(ODI),compression rate of the anterior edge height of the injured vertebra,and the Cobb angle in the sagittal position of the injured vertebra before surgery,1 week after surgery and 1 year after surgery were compared between the two groups.The improvement rates of the anterior edge height compression and the Cobb angle in the sagittal position of the injured vertebra 1 week and 1 year after surgery were compared between the two groups.Results There was no significant difference in the operation time,intraoperative blood loss or total incidence of complications between the two groups(P>0.05).The hospital stay in the early operation group was shorter than that in the elective operation group,and the difference was statistically significant(P<0.05).The VAS scores and ODI 1 week and 1 year after surgery of the two groups were better than those before surgery,and the differences were statistically significant(P<0.05).There was no significant difference in the VAS scores or ODI at each time point before and after surgery between the two groups(P>0.05).The compression rate of the anterior edge height and Cobb angle in the sagittal position of the injured vertebra 1 week and 1 year after surgery in the two groups were lower/smaller than those before surgery,with statistically significant differences(P<0.05).There was no statistically significant difference in the compression rate of the anterior edge height or Cobb angle before surgery in the sagittal position of the injured vertebrae between the two groups(P>0.05).The compression rate of the anterior edge height and Cobb angle in the sagittal position of the injured vertebra 1 week and 1 year after surgery in the early operation group were lower/smaller than those in the elective operation group,and the differences were statistically significant(P<0.05).The improvement rates of the anterior edge height compression and the Cobb angle in the sagittal position of the injured vertebra 1 week and 1 year after surgery in the early operation group were better than those in the elective operation group,and the differences were statistically significant(P<0.05).Conclusion Early surgical treatment for spinal thoracolumbar fracture without nerve damage is safe,it can significantly shorten hospitalization time,obtain good fracture reduction quality and definite therapeutic effects.However,a comprehensive preoperative evaluation of the patients' condition is necessary to ensure surgical safety.

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.

The genomic island(GI)characteristics and virulence factor differences of clinical isolates of Burkholderia pseudomallei in Hainan Province,China were analyzed to provide a scientific basis for diagnosis and treatment of melioidosis.In total,52 B.pseudomallei isolates were collected for detection of virulence-related GIs by PCR.The whole genome sequence annotation format file was submitted on Islandviwer 4 platform,and the genomes of the same species and close relatives were added for comparison.Two algorithms,SIGI-HMM and IslandPath-DIMOB,were integrated to predict GIs and sequence a-lignments were conducted to identify specific GIs and differences in virulence factors.The genomes of 52 clinical strains could be divided into three branches based on evolutionary distance,with 82.69％(43/52)of strains concentrated in branch 1.In to-tal,828 GIs were identified among the 52 B.pseudomallei genomes,which formed 157 GI clusters based on sequence similari-ty.GIs accounted for 2.05％-6.38％of the genome content.While GI clusters 1 and 2 were present in all strains,a total of 84(53.50％)GI clusters only clustered within a single genome isolate.Of 10 GI likely specific clusters,five were from the same genus,two from another genus,and three with uncertain origins.Moreover,25 GI clusters were associated with virulence,which included eight shared by B.pseudomallei BP76 and BP169,which had the highest number of virulence-associated GIs among all isolates.O the 52 B.pseudomallei isolates,variations were identified in the virulence genes fhaB1,fhaB2,BPSL1661,cheY1,wzM,tssH-5/clpV,tssA-5,boaA,and boaB.Comparisons of these findings with clinical isolates from Thailand and Australia showed that B.pseudomallei isolates from Hainan had significant differences in the sequences of boaA,boaB,cheY1,and chbp.Additionally,fhaB1,fhaB3,and bimA displayed significant variations specifically within the Australian isolates.B.pseudomallei GI was conserved and specific to Hainan.The identification of specific GI and virulence factors was useful to clarify the source of horizontal gene transfer and differences in virulence at the molecular level.

A prokaryotic expression vector for the mutant diphtheria toxin CRM197 was constructed and expressed in Esch-erichia coli cells.Anti-CRM197 antibody concentrations were detected in serum samples of healthy volunteers.The crm 197 gene was codon-optimized in E.coli and cloned into the plasmid pET28a(+)under optimized expression conditions.CRM197 was purified using Ni-NTA spin columns and ion exchange chromatography,and confirmed by western blot analysis.The puri-fied CRM197 was used to detect specific anti-CRM197 antibody levels in serum samples of different age groups.The results showed that soluble codon-optimized CRM197 was successfully expressed under optimized expression conditions.The purity of CRM197 was more than 95％,as determined with Ni-NTA spin columns and ion exchange chromatography,consistent with the single specific bands obtained by western blot analysis and detection of serum levels of the anti-CRM197 antibody.Collec-tively,these results confirmed that the proposed expression strategy achieved high-yield production of soluble CRM197,al-though high levels in human serum may affect evaluation of immune interactions with glycan-CRM197 conjugates for applica-tion as a diagnostic antigen.The diphtheria mutant toxin CRM197 is used in many conjugate vaccines.The synthetic crm 197 gene with codon optimization in pET28a was transformed into E.coli Origami B(DE3)cells.CRM197 was induced by isopro-pyl β-d-1-thiogalactopyranoside and high level accumulation of soluble CRM197 was purified using Ni-NTA spin columns and ion exchange chromatography.The purity of the final prepara-tion reached 95％.CRM197 was used to detect the concentra-tions of the anti-CRM197 antibody in serum samples of healthy volunteers of different ages.The proposed expression strategy yielded high production of CRM197,which could interfere with evaluations of induced immune interactions by glycan-CRM197 conjugates and prohibit application as a diagnostic antigen.

This study was aimed at understanding the genomic characteristics of the Vibrio cholerae O1 group isolated from humans in Fujian Province,to provide essential data for the molecular epidemiological study of cholera.From 2008 to 2022,16 strains of the V.cholerae O1 group from patients and carriers were collected,and antibiotic sensitivity was determined accord-ing to the minimum inhibitory concentration(MIC).The whole genome sequences obtained through second generation sequen-cing were analyzed in open source software,including snippy,Roary,and Prokka,as well as online analysis websites,inclu-ding NCBI and BacWGSTdb,for core-genome multilocus sequence typing(cgMLST),core-genome single nucleotide polymor-phism analysis(cgSNP),virulence gene analysis,drug resistance gene prediction,and pan-genomic diversity analysis.The whole genome sequences of V.cholerae were divided into five sequence types(STs),among which the newly discovered ST182 and ST1480 were the evolutionary branches of the current dominant clonal group ST75 in China,and were highly related to two strains isolated from Taiwan in 2010 and 2013,respectively.Both toxigenic strains and non-toxigenic strains carried a variety of virulence factors and showed gene variation to varying degrees.Thirteen drug resistance genes in seven categories were predicted,among which the distribution of colistin and tetracycline resistance genes was consistent with the drug resistance phenotype.Pan-ge-nomic analysis indicated that V.cholerae had an open pan-genome,and Roary cluster analysis showed higher resolution than cgMLST.In summary,V.cholerae O1 group isolates from humans in Fujian Province have polymorphisms in genome structure and function,and the newly discovered ST1480 clone group has epidemic potential.Therefore,the monitoring of such strains must be strengthened.

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.

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.