5.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.
6.Efficacy and safety of omental wrapping technique for pancreaticojejunal anastomosis in preventing complications after pancreaticoduodenectomy: A Meta-analysis
Yabo SHI ; Yang LI ; Huabing LIU ; Zhicong WANG ; Changwen HUANG
Journal of Clinical Hepatology 2024;40(1):129-137
ObjectiveTo systematically evaluate the efficacy and safety of omental wrapping technique for pancreaticojejunal anastomosis in preventing complications after pancreaticoduodenectomy. MethodsThis study was conducted according to the PRISMA guideline. English and Chinese databases including CNKI, Wanfang Data, VIP, CBM, the Cochrane Library, PubMed, Embase, and Web of Science were searched for clinical studies on omental wrapping technique for pancreaticojejunal anastomosis in preventing complications after pancreaticoduodenectomy published up to November 2022, and Stata 16 and Review Manager 5.4 were used to perform the meta-analysis. ResultsA total of 15 studies with 1 830 patients were included in this study. The meta-analysis showed that the omental wrapping group had a significantly lower overall incidence rate of postoperative pancreatic fistula (POPF) than the non-omental wrapping group (odds ratio [OR]=0.30, 95% confidence interval [CI]: 0.22 — 0.41, P<0.001), and the subgroup analysis showed that the omental wrapping group had a significantly lower incidence rate of grade B/C POPF than the non-omental wrapping group (OR=0.29, 95%CI: 0.21 — 0.39, P<0.001). Compared with the non-omental wrapping group, the omental wrapping group had significantly lower incidence rates of postoperative bile leakage (OR=0.30, 95%CI: 0.16 — 0.56, P<0.001), postoperative hemorrhage (OR=0.35, 95%CI: 0.24 — 0.53, P<0.001), delayed gastric emptying (OR=0.45, 95%CI: 0.31 — 0.64, P<0.001), abdominal infection (OR=0.55, 95%CI: 0.40 — 0.75, P<0.001), reoperation (OR=0.31, 95%CI: 0.18 — 0.54, P<0.001), and death within 30 days after surgery (OR=0.42, 95%CI: 0.22 — 0.80, P=0.009), a significantly earlier time to diet (mean difference [MD]=-0.98, 95%CI: -1.84 to -0.11, P=0.03), and a significantly shorter length of postoperative hospital stay (MD=-2.44, 95%CI: -4.10 to -0.77, P=0.004). There were no significant differences between the two groups in the time of operation (MD=-13.68, 95%CI: -28.31 to -0.95, P=0.07) and intraoperative blood loss (MD=-17.26, 95%CI: -57.55 to -23.03, P=0.40). ConclusionOmental wrapping can reduce the incidence rates of postoperative complications such as pancreatic fistula, bile leakage, postoperative hemorrhage, abdominal infection, and delayed gastric emptying, improve the prognosis of patients, and shorten the length of hospital stay, without increasing surgical difficulty or time of operation.
7.Conical beam CT measurement of alveolar bone structure remodeling in patients with skeletal class Ⅲ malocclusion after orthodontic-orthognathic treatment
Qihang ZHAO ; Xin LU ; Lei TONG ; Yonghui SHANG ; Shuai LI ; Wen LIU ; Jianhua ZHOU ; Rongtao YUAN ; Qingyuan GUO
Chinese Journal of Tissue Engineering Research 2024;28(23):3729-3735
BACKGROUND:Most of the studies on combined orthodontic-orthognathic treatment of skeletal class Ⅲ malocclusions have focused on the improvement of the patient's lateral appearance and recovery in the later stages of the treatment,while there are fewer studies observing the microcosmic nature of the alveolar bone remodeling of the lower anterior teeth. OBJECTIVE:To evaluate the therapeutic effect of lower anterior tooth decompensation and alveolar bone remodeling in patients with skeletal class Ⅲ malocclusion before and after orthodontic-orthognathic treatment based on oral X-ray lateral films and oral cone-beam CT. METHODS:From January 2015 to May 2023,15 patients with skeletal class Ⅲ malocclusion who underwent orthodontic-orthognathic surgery at Qingdao Hospital of Rehabilitation University were enrolled.All patients underwent lateral cephalography and cone beam computed tomography before and after treatment.Cephalometric measurement items related to the angle and line distance,lip/lingual bone cracking length(d-La/d-Li)and bone cracking/bone fenestration of the lower anterior teeth before and after treatment were measured. RESULTS AND CONCLUSION:Lateral X-ray films showed that the amount of alveolar bone remodeling after decompensation of the lower anterior teeth showed significant changes compared to before treatment.The root of the tooth moved significantly towards the center of the alveolar bone,and the specific data was closer to normal data,but there were still some differences compared with normal individuals.Based on the cone-beam CT measurement,the bone cracking/bone fenestration length and width of the alveolar bone were improved in almost all the teeth after orthodontic-orthognathic combined treatment,alveolar bone remodeling in some teeth even reached the level of healthy individuals.Before treatment,most patients often experienced bone fenestration/cracking on the lip/lingual side of the lower incisor due to compensatory tooth growth.However,during the preoperative orthodontic stage,decompensation triggered alveolar bone remodeling and significant changes in tooth angle.Preoperative orthodontic treatment caused the upper anterior teeth to retract and the lower anterior teeth to tilt and control the root,but the amount of decompensation before surgery was often insufficient.In the orthognathic surgery stage,the jaw was removed through the positioning guide plate,the maxilla moved forward,and the mandible retreated.During the postoperative orthodontic process,the effect of fine adjustment was better.Although there is a certain degree of recurrence trend in the position of teeth and jawbones,the postoperative orthodontic treatment is closer to the normal value.
8.Modified calcaneal plate combined with suture anchors in treatment of comminuted fracture of split-type greater tuberosity of humerus(Liu-Gang type IV)
Gang LIU ; Baolu ZHANG ; Ruichen LI ; Xiaomei HOU ; Hong LUO ; Canhao LAI ; Qingyuan LI ; Xia LIANG ; Dingsu BAO ; Shijie FU ; Shengqiang ZENG
Chinese Journal of Tissue Engineering Research 2024;28(24):3855-3861
BACKGROUND:Numerous scholars have previously researched certain greater tuberosity fractures and the procedures used to treat them.Few researchers,however,have studied the comminuted split fracture of the greater tuberosity of the humerus(Liu-Gang type IV)with rotator cuff tear in great detail. OBJECTIVE:To compare the clinical therapeutic effect of open repair position modified calcaneal plate combined with suture anchors and proximal humeral internal locking system(PHILOS)plate in the treatment of comminuted fracture of split-type greater tuberosity of humerus combined with rotator cuff tears(Liu-Gang type IV). METHODS:Case data of 30 patients with comminuted fracture of split-type greater tuberosity of humerus combined with rotator cuff tears(Liu-Gang type IV)from May 2012 to May 2022 were retrospectively analyzed.They were divided into the modified calcaneal plate combined with suture anchor group(group A)and the PHILOS with#2 Johnson group(group B),with 15 cases in each group.Intraoperative blood loss,surgical time,and incision length of all patients were recorded.Pain visual analog scale score,Constant-Murley score,as well as shoulder joint abduction,forward flexion,external rotation,and dorsal expansion activities during the last follow-up(>1 year)were evaluated. RESULTS AND CONCLUSION:(1)The surgical incision length and operation time were shorter,and blood loss was less in group A than those in group B(P<0.05).(2)No significant difference in visual analog scale score and Constant-Murley score was detected between the two groups(P>0.05).(3)During the last follow-up,forward flexion in group A was better than that in group B(P<0.05).No significant difference in abduction,external rotation,and dorsal expansion was determined between group A and group B(P>0.05).(4)In terms of complications,there was 1 case of shoulder joint pain and discomfort in group A(7%),2 cases of subacromial impingement syndrome,2 cases of upward movement of nodules,and 2 cases of shoulder joint pain(40%)in group B.There were significant differences in complication rates between the two groups(P=0.031).(5)In summary,the modified calcaneal plate combined with suture anchors in the treatment of comminuted fracture of split-type greater tuberosity of humerus combined with rotator cuff tears(Liu-Gang type IV)could better restore the forward flexion function of the shoulder joint and has a small incision,less blood loss,shorter operation time and fewer complications.
9.Practice of Value-based Payment in US.and Its Enlightenment to China
Qingyuan YU ; Yuchang LI ; Xinyu DU ; Yuanli LIU
Chinese Health Economics 2024;43(7):86-92
The reform of medical insurance payment is a critical part of deepening the medical reform.It plays an important role in guiding the behavior of healthcare providers.The latest progress in the reform of health insurance payment in the US.is the imple-mentation of value-based payment models.The literature research method is applied to review the development of value-based pay-ment practices in the US.It finds the main value-based payment models in the United States are targeted hospitals and physicians as the incentive object,with the characteristics of the combination of reward and punishment,the combination of horizontal and ver-tical evaluation,the continuous improvement of evaluation system,and the full use of information means.On this basis,combined with the national conditions of China,it puts forward four suggestions on establishing effective incentive mechanism,formulating scientific evaluation system,insisting on continuous improvement mechanism and strengthening medical information construction for future reform of medical insurance.
10.A preliminary in vivo and in vitro study of endothelial cell pyroptosis in the periodontal inflammatory environment
Rui LI ; Xiaoyu WANG ; Qingyuan YE ; Yazheng WANG ; Xige ZHANG ; Xiaotong GE ; Qintao WANG
Chinese Journal of Stomatology 2024;59(5):486-495
Objective:To observe whether endothelial cells undergo pyroptosis in the inflammatory periodontal environment by using a model in vivo and in vitro, providing an experimental basis for indepth understanding of the underlying pathogenesis of periodontitis. Methods:According to the classification of periodontal diseases of 2018, gingival tissues were collected from periodontally healthy subjects and patients with stage Ⅲ-Ⅳ, grade C periodontitis, who presented Department of Oral and Maxillofacial Surgery and Department of Periodontology, School of Stomatology, The Fourth Military Medical University from April to May 2022. Immunohistochemical staining was performed to detect the expression level and distribution of gasdermin D (GSDMD), a hallmark protein of cell pyroptosis, in gingival tissues. Periodontitis models were established in each group by ligating the maxillary second molar teeth of three mice for 2 weeks (ligation group). The alveolar bone resorption was determined by micro-CT (mice without ligation treatment were used as the control group), and the colocalization of GSDMD and CD31 were quantitatively analyzed by immunofluorescence staining in gingival tissues of healthy and inflammatory mice. Human umbilical vein endothelial cells (HUVECs) were cultured in vitro and treated with lipopolysaccharide (LPS) of Porphyromonas gingivalis (Pg) combined with adenosine triphosphate (ATP) at various concentrations of 0.5, 1.0, 2.5, 5.0, and 10.0 mg/L, respectively, and the 0 mg/L group was set as the control group at the same time. Scanning electron microscopy was used to observe the morphology of HUVECs. Western blotting was used to detect the expression of gasdermin D-N terminal domains (GSDMD-N) protein and immunofluorescence cell staining was used to detect the expression and distribution of GSDMD. Cell counting kit-8 (CCK-8) was used to detect the proliferative ability of HUVECs, and propidium iodide (PI) staining was used to detect the integrity of cell membrane of HUVECs. Results:Immunohistochemistry showed that GSDMD in gingival tissues of periodontitis was mainly distributed around blood vessels and its expression level was higher than that in healthy tissues. Micro-CT showed that alveolar bone resorption around the maxillary second molar significantly increased in ligation group mice compared with control subjects ( t=8.88, P<0.001). Immunofluorescence staining showed significant colocalization of GSDMD with CD31 in the gingival vascular endothelial cells in mice of ligation group. The results of scanning electron microscopy showed that there were pores of different sizes, the typical morphology of pyroptosis, on HUVECs cell membranes in the inflammatory environment simulated by ATP combined with different concentrations of LPS, and 2.5 mg/L group showed the most dilated and fused pores on cell membranes, with the cells tended to lyse and die. Western blotting showed that the expression of GSDMD-N, the hallmark protein of cell pyroptosis, was significantly higher in 2.5 and 5.0 mg/L groups than that in the control group ( F=3.86, P<0.01). Immunofluorescence cell staining showed that the average fluorescence intensity of GSDMD in 2.5 mg/L group elevated the most significantly in comparison with that in the control group ( F=35.25, P<0.001). The CCK-8 proliferation assay showed that compared to the control group (1.00±0.02), 0.5 mg/L (0.52±0.07), 1.0 mg/L (0.57±0.10), 2.5 mg/L (0.58±0.04), 5.0 mg/L (0.55±0.04), 10.0 mg/L (0.61±0.03) groups inhibited cell proliferation ( F=39.95, P<0.001). PI staining showed that the proportion of positive stained cells was highest [(56.07±3.22)%] in 2.5 mg/L group ( F=88.24, P<0.001). Conclusions:Endothelial cells undergo significant pyroptosis in both in vivo and in vitro periodontal inflammatory environments, suggesting that endothelial cell pyroptosis may be an important pathogenic factor contributing to the pathogenesis of periodontitis.

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