1.Prognostic factors and surgical approach selection for descending duodenal gastrointestinal stromal tumors
Xiaohan LIN ; Chao LI ; Xiaodong GAO ; Kuntang SHEN
Chinese Journal of Clinical Medicine 2026;33(2):250-259
Objective To explore the prognostic factors for patients with descending duodenum gastrointestinal stromal tumors (GIST), analyze the impact of different surgical approaches on prognosis, and develop a predictive model for surgical approach selection. Methods This single-center retrospective cohort study included patients with primary descending duodenum GIST treated in Zhongshan Hospital, Fudan University from January 2010 to January 2015, with follow-up until August 2025. The primary outcomes were incidence of postoperative complications, disease-free survival (DFS) rate, and overall survival (OS) rate. Cox regression and logistic regression were used to identify factors influencing prognosis and surgical approach selection, respectively. A nomogram model for selecting the surgical approach was constructed. Results A total of 78 patients with descending duodenum GIST were included, with age of (56.14±11.76) years. The 1-, 5-, and 10-year OS rates were 100%, 98.7%, and 85.7%, respectively, and the corresponding DFS rates were 100%, 90.9%, and 82.3%. Intraoperative blood loss, postoperative gastroparesis, mucosal ulceration, maximum tumor diameter, and Ki-67-positive cell ratio were independent risk factors for DFS, while maximum tumor diameter and mitotic figure were independent risk factors for OS (P<0.05). The 10-year DFS rate was higher in the local resection group than in the pancreaticoduodenectomy group (89.45% vs 74.24%; HR=0.300, P=0.013), but there was no statistical difference in OS between the two groups. The incidence of postoperative complications in the pancreaticoduodenectomy group was higher than that in the local resection group (P<0.001). Maximum tumor diameter and distance from tumor to the duodenal papilla were independent factors influencing surgical approach selection. The nomogram model based on these two indices demonstrated good discrimination and accuracy upon internal validation. Conclusions The long-term prognosis of patients with descending duodenal GIST is favorable, and surgical treatment achieves satisfactory outcomes. The nomogram model developed in this study can effectively guide individualized surgical approach selection and provide a reference for clinical decision-making.
2.Zuoguiwan Mitigates Oxidative Stress in Rat Model of Hyperthyroidism Due to Kidney-Yin Deficiency via DRD4/NOX4 Pathway
Ling LIN ; Qianming LIANG ; Changsheng DENG ; Li RU ; Zhiyong XU ; Chao LI ; Mingshun SHEN ; Yueming YUAN ; Muzi LI ; Lei YANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(2):43-51
ObjectiveTo decipher the mechanism by which Zuoguiwan (ZGW) treat hyperthyroidism in rats with kidney-Yin deficiency based on the dopamine receptor D4 (DRD4)/nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4) signaling pathway. MethodsThe rat model of kidney-Yin deficiency was induced by unilateral intramuscular injection of dexamethasone (0.35 mg·kg-1). After successful modeling, the rats were randomized into model, methimazole (positive control, 5 mg·kg-1), low-, medium-, and high-dose (1.85, 3.70, 7.40 g·kg-1, respectively) ZGW, and normal control groups. After 21 days of continuous gavage, the behavioral indexes and body weight changes of rats were evaluated. The pathological changes of the renal tissue were observed by hematoxylin-eosin staining. The serum levels of thyroid hormones [triiodothyronine (T3), thyroxine (T4), thyroid-stimulating hormone (TSH)], renal function indexes [serum creatine (Scr) and blood urea nitrogen (BUN)], energy metabolism markers [cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP)], and oxidative stress-related factors [superoxide dismutase (SOD), malondialdehyde (MDA), and NADPH)] were measured by enzyme-linked immunosorbent assay (ELISA). Western blot was employed to analyze the expression of DRD4, NOX4, mitochondrial respiratory chain complex proteins [NADH:ubiquinone oxidoreductase subunit S4 (NDUFS4) and cytochrome C oxidase subunit 4 (COX4)], and inflammation-related protein [tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), p38 mitogen-activated protein kinase (MAPK)] pathway in the renal tissue. ResultsCompared with the normal group, the model group showed mental malaise, body weight decreases (P<0.01), inflammatory cell infiltration in the renal tissue, a few residual parotid glands in the thyroid, elevations in serum levels of T3, T4, Scr, BUN, cAMP, cAMP/cGMP, MDA, and NADPH (P<0.01), down-regulation in protein levels of TSH, SOD, and DRD4 (P<0.05, P<0.01), and up-regulation in expression of NOX4, p-p38 MAPK/p38 MAPK, and inflammatory factors (P<0.01). Compared with the model group, ZGW increased the body weight (P<0.05, P<0.01), reduced the infiltration of renal interstitial inflammatory cells, restored the thyroid structure and follicle size, lowered the serum levels of T3, T4, Scr, BUN, cAMP, cAMP/cGMP, MDA and NADPH (P<0.05, P<0.01), up-regulated the expression of TSH, SOD and DRD4 (P<0.05, P<0.01), and down-regulated the expression of NOX4, p-p38 MAPK/p38 MAPK, and inflammatory factors (P<0.05, P<0.01). Moreover, high-dose ZGW outperformed methimazole (P<0.05). ConclusionBy activating DRD4, ZGW can inhibit the expression of NOX4 mediated by the p38 MAPK pathway, reduce oxidative stress and inflammatory response, thereby ameliorating the pathological state of hyperthyroidism due to kidney-Yin deficiency. This study provides new molecular mechanism support for the clinical application of ZGW.
3.Expert Consensus on Neurocritical Care Monitoring and Management in Beijing and Tibet(2025)
Drolma PHURBU ; Wenjin CHEN ; Heng ZHANG ; Jian ZHANG ; Xiaomeng WANG ; Guoying LIN ; Wenjun PAN ; Xiying GUI ; Xin CAI ; Chodron TENZIN ; Jianlei FU ; Qianwei LI ; TSEYANG ; Yijun LIU ; Bo LIU ; Tsering DROLMA ; Yudron SONAM ; KYILV ; Samdrup TSERING ; Wa DA ; Juan GUO ; Cheng QIU ; Huan CHEN ; Xiaoting WANG ; Yangong CHAO ; Dawei LIU ; Wenzhao CHAI ; Chenggong HU ; Wanhong YIN ; Shihong ZHU
Medical Journal of Peking Union Medical College Hospital 2026;17(1):59-72
Neurocritical care involves complex pathophysiological mechanisms, and its incidence is higher, injuries are more severe, and treatment is more challenging in high-altitude environments. This consensus, based on the latest domestic and international evidence-based medical data, establishes a standardized, goal-oriented framework for neurocritical care management applicable in high-altitude regions and nationwide. The consensus was developed following international standards for evidence quality assessment and underwent two rounds of Delphi expert consultation, resulting in 32 recommendation statements covering three parts: management systems, monitoring and assessment, and core strategies. Key updates include: advocating for the establishment of independent neurocritical care units and implementing precise tiered diagnosis and treatment based on the "Five Differences in Critical Care" concept; constructing a "trinity" multimodal brain monitoring system centered on cerebral blood flow, cerebral oxygenation, and brain function, emphasizing routine bedside transcranial Doppler ultrasound, cerebral oximetry, and continuous electroencephalography monitoring; shifting management strategies from mild hypothermia therapy to targeted temperature management, and defining the "446" target management pathway for the supercritical stage; emphasizing the assessment of static and dynamic cerebrovascular autoregulation functions through multimodal methods to achieve individualized optimal mean arterial pressure management; elevating cerebrospinal fluid management goals to the level of "glymphatic system" function maintenance; implementing a multidisciplinary collaborative, whole-process management model focusing on patients' long-term neurological functional outcomes; de-escalation criteria include multidimensional indicators such as recovery of brain structure, restoration of cerebrovascular autoregulation, improvement in cerebrospinal fluid dynamics, and reduction in biomarker levels; and integrating cutting-edge technologies like artificial intelligence into post-critical care management and rehabilitation planning. This consensus systematically integrates the entire process of neurocritical care management, reflecting the modern connotation of goal-oriented, dynamic, and multimodal integration in neurocritical care medicine. It aims to adapt to new trends such as deepening understanding of pathophysiological mechanisms, the integration of medicine and engineering, and the empowerment of artificial intelligence, thereby further advancing the discipline of critical care medicine.
4.Influencing Factors of Urate Crystal Deposition in Patients with Hyperuricemia and Prediction Model of TCM Syndrome Types-inflammatory Indicators
Jiaqi XU ; Bin AI ; Chao LIN ; Qiaoxuan LIN ; Changning LI ; Jing CAI ; Yan XIAO ; Jiemei GUO ; Youxin SU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(7):66-73
ObjectiveTo identify potential influencing factors of urate crystal deposition at ankle/foot in patients with hyperuricemia (HUA), and to analyze the predictive value of inflammatory indicators for urate crystal deposition in patients with different traditional Chinese medicine (TCM) syndromes, so as to provide potential reference for clinical risk assessment and individualized TCM intervention. MethodsA retrospective study was carried out with the enrollment of 231 HUA patients from The Third Affiliated People's Hospital of Fujian University of Traditional Chinese Medicine between January 2021 and December 2024. The enrolled patients were further divided into a crystal deposition-positive group (143 cases) and a crystal deposition-negative group (88 cases) according to the results of dual-energy computed tomography (CT). Sociodemographic data, living habits, serum uric acid levels, and inflammatory indicators of the enrolled patients were collcted, and TCM syndrome differentiation was performed. Furthermore, univariate analysis was used to compare inter-group differences in clinical characteristics. MMultivariate Logistic regression was applied to identify the influencing factors of urate crystal deposition. In addition, the receiver operating characteristic (ROC) curves were plotted to evaluate the predictive efficacy of inflammatory indicators for crystal deposition across different TCM syndromes. ResultsThere were statistically significant inter-group differences in the proportion of males, age, body mass index, proportion of mental labor, rate of low water intake, and rate of high-sugar beverage consumption (P<0.05),whereas no significant difference in low exercise intensity was found between the two groups. Furthermore, compared with the negative group, the positive group had higher serum uric acid level, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR), but lower systemic immune-inflammation index (SIRI) (P<0.05). Regarding the distribution of TCM syndromes, the positive group was dominated by the dampness-heat accumulation syndrome (55/143,38.46%), while the negative group was mainly characterized by the phlegm-turbidity obstruction syndrome (44/88,50.00%). Multivariate Logistic regression analysis revealed that high-sugar beverage consumption, elevated NLR, and elevated PLR were risk factors for urate crystal deposition [odd ratio (OR) = 8.002, 5.377, 1.034, respectively; 95% CI 1.572-40.732, 2.179-13.270, 1.013-1.054,all P<0.05], while SIRI was a protective factor (OR = 0.869, 95% CI 0.778-0.971, P<0.05). In the positive group, patients with the dampness-heat accumulation syndrome exhibited the highest NLR, while the lowest PLR and SIRI, showing statistically significant differences with those of other syndromes (all P<0.05). In addition, ROC curve analysis indicated that for the dampness-heat accumulation syndrome, the combined "NLR + PLR" model had an area under the curve (AUC) of 0.901 (95% CI 0.850-0.951, P<0.01), with a sensitivity of 89.1% and a specificity of 79.5%; for the blood stasis-heat obstruction syndrome, the combined "NLR + PLR" model had an AUC of 0.880 (95% CI 0.825-0.934, P<0.01), with a sensitivity of 100.0% and a specificity of 67.3%; for the liver-kidney Yin-deficiency syndrome, the single PLR model had an AUC of 0.842 (95% CI 0.731-0.952, P<0.01), with a sensitivity of 83.3% and a specificity of 84.0%. ConclusionUrate crystal deposition in HUA patients exhibits intimate associations with high-sugar beverage consumption as well as elevated NLR and PLR levels. Meanwhile, TCM syndrome differentiation has potential correlation with inflammatory characteristics. The inflammatory indicator-based prediction model constructed based on TCM syndromes exhibits good predictive value.
5.The Effects of Tai Chi Training on Bone Density,Bone Turnover Markers,and Heart Rate Variability in High-Risk Osteoporosis Population
Jiaming LIN ; Chao LI ; Wei ZHAO ; Jun ZHOU ; Xiaoying CHEN ; Xiangyu XI ; Haijun HE ; Baohong MI ; Yuefeng CHEN ; Weiheng CHEN
Journal of Traditional Chinese Medicine 2025;66(15):1566-1571
ObjectiveTo explore the effects of the Tai Chi training on bone density, bone turnover markers, and heart rate variability for people with high-risk osteoporosis, and to provide evidence for the prevention of osteoporosis at early stage. MethodsSixty-six cases of people with high risk of osteoporosis were included, and they were divided into 33 cases each in the intervention group and the control group using the random number table method. The control group received osteoporosis health education three times a week, and the intervention group received Tai Chi training under the guidance of a trainer three times a week for 40 mins each time on the basis of the control group, and both groups were intervened for 12 weeks. Dual-energy X-ray absorptiometry was used to measure the bone density of L1~L4 vertebrae, bilateral femoral necks and bilateral total hips in the two groups before and after the intervention; enzyme-linked immunosorbent assay was used to determine bone turnover markers before and after the intervention, including pro-collagen type Ⅰ pro-amino-terminal prepropyl peptide (P1NP) and β-collagen type Ⅰ cross-linking carboxy-terminal peptide (β-CTX). Seven cases with good compliance in the intervention group were selected. After wearing the heart rate sensor, they successively performed Tai Chi training and walking activities recommended by the guideline for 20 mins each, and the heart rate variability (HRV) during exercise was collected, including time-domain indexes such as standard deviation of normal sinus intervals (SDNN), root-mean-square of the difference between adjacent RR intervals (RMSSD), frequency-domain metrics such as low-frequency power (LF), high-frequency power (HF), and low-frequency/high-frequency power ratio (LF/HF), as well as nonlinear metrics such as approximate entropy (ApEn), sample entropy (SampEn). ResultsFinally, 63 cases were included in the outcome analysis, including 30 cases in the intervention group and 33 cases in the control group. After the intervention, the differences of L1~L4 vertebrae, bone density of bilateral femoral neck and bilateral total hip in the intervention group were not statistically significant when compared with those before intervention (P>0.05), while the bone density of all parts of the control group decreased significantly compared with that before intervention (P<0.05), and the difference in the bone density of the L1~L4 vertebrae, bilateral femoral neck, and the right total hip before and after the intervention of the intervention group was smaller than that of the control group (P<0.05). The differences in P1NP and β-CTX between groups before and after intervention was not statistically significant (P>0.05). Compared with walking exercise, LF decreased, HF increased and LF/HF decreased during Tai Chi exercise (P<0.05); the time domain indexes and non-linear indexes between groups had no statistically significant difference (P>0.05). ConclusionTai Chi exercise can maintain lumbar, hip, and femoral bone density and improve sympathetic/parasympathetic balance in people at high risk for osteoporosis, but cannot significantly improve bone turnover markers.
6.Effect of lncRNA MANCR on Proliferation, Migration, and Epithelial Mesenchymal Transition of Gastric Cancer Cells by Regulating miR-150-5p/GPNMB Axis
Chao LI ; Shihui WANG ; Jie LIN ; Fanke WANG ; Rui ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(17):135-142
ObjectiveTo investigate the effects of mitotically-associated long non-coding RNA (lncRNA MANCR) on the proliferation,migration, and epithelial mesenchymal transition (EMT) of gastric cancer (GC) cells by regulating the microRNA-50-5p (miR-150-5p)/non-metastatic melanoprotein B (GPNMB) axis. MethodsThe mRNA expressions of lncRNA MANCR,miR-150-5p, and GPNMB in 42 cases of GC tissue and adjacent tissue resected during surgery in the First Hospital of Hebei Medical University from June 2022 to September 2023 were detected by Real-time PCR. Human gastric mucosal epithelial cells GES-1 and human GC cells BGC-823 were cultured in vitro, and their lncRNA MANCR expression was detected. BGC-823 cells were randomly separated into control group (routine culture),sh-NC group (with sh-NC transfected),sh-MANCR group (with sh-MANCR transfected),sh-MANCR + anti-NC group (with sh-MANCR and anti-NC both transfected),and sh-MANCR + anti-miR-150-5p group (with sh-MANCR and anti-miR-150-5p both transfected). The mRNA expressions of lncRNA MANCR,miR-150-5p, and GPNMB in the BGC-823 cells of all groups were analyzed. EdU staining was used to detect the proliferation of BGC-823 cells. Transwell assay was used to detect the migration and invasion of BGC-823 cells. The expressions of EMT-related proteins E-cadherin,N-cadherin,Vimentin, and GPNMB were detected by Western blot. The interactions between lncRNA MANCR and miR-150-5p and between miR-150-5p and GPNMB were analyzed by dual luciferase reporter assay. ResultsThe mRNA expressions of lncRNA MANCR and GPNMB in GC tissue were higher than those in adjacent tissue,and the expression of miR-150-5p was lower than that in adjacent tissue (P<0.05). Compared with that in GES-1,lncRNA MANCR expression in BGC-823 cells was increased (P<0.05). Compared with those in the sh-NC group and control group,the EdU-positive cell rate,migration number,invasion number,the mRNA expressions of lncRNA MANCR and GPNMB, and the expressions of protein,N-cadherin protein, and Vimentin protein in the BGC-823 cells in the sh-MANCR group were lower ,and the protein expressions of miR-150-5p and E-cadherin were higher (P<0.05). Compared with those in the sh-MANCR group and the sh-MANCR + anti-NC group,the protein expressions of miR-150-5p and E-cadherin in the sh-MANCR + anti-miR-150-5p group were decreased. The EdU-positive cell rate,migration number,invasion number,mRNA expressions of GPNMB, and expressions of protein,N-cadherin protein, and Vimentin protein were increased (P<0.05). lncRNA MANCR could target the negative regulation of miR-150-5p,and miR-150-5p could target the negative regulation of GPNMB. ConclusionKnockout of lncRNA MANCR can inhibit the proliferation,migration, and EMT of GC cells by regulating the miR-150-5p/GPNMB axis.
7.Effect of lncRNA MANCR on Proliferation, Migration, and Epithelial Mesenchymal Transition of Gastric Cancer Cells by Regulating miR-150-5p/GPNMB Axis
Chao LI ; Shihui WANG ; Jie LIN ; Fanke WANG ; Rui ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(17):135-142
ObjectiveTo investigate the effects of mitotically-associated long non-coding RNA (lncRNA MANCR) on the proliferation,migration, and epithelial mesenchymal transition (EMT) of gastric cancer (GC) cells by regulating the microRNA-50-5p (miR-150-5p)/non-metastatic melanoprotein B (GPNMB) axis. MethodsThe mRNA expressions of lncRNA MANCR,miR-150-5p, and GPNMB in 42 cases of GC tissue and adjacent tissue resected during surgery in the First Hospital of Hebei Medical University from June 2022 to September 2023 were detected by Real-time PCR. Human gastric mucosal epithelial cells GES-1 and human GC cells BGC-823 were cultured in vitro, and their lncRNA MANCR expression was detected. BGC-823 cells were randomly separated into control group (routine culture),sh-NC group (with sh-NC transfected),sh-MANCR group (with sh-MANCR transfected),sh-MANCR + anti-NC group (with sh-MANCR and anti-NC both transfected),and sh-MANCR + anti-miR-150-5p group (with sh-MANCR and anti-miR-150-5p both transfected). The mRNA expressions of lncRNA MANCR,miR-150-5p, and GPNMB in the BGC-823 cells of all groups were analyzed. EdU staining was used to detect the proliferation of BGC-823 cells. Transwell assay was used to detect the migration and invasion of BGC-823 cells. The expressions of EMT-related proteins E-cadherin,N-cadherin,Vimentin, and GPNMB were detected by Western blot. The interactions between lncRNA MANCR and miR-150-5p and between miR-150-5p and GPNMB were analyzed by dual luciferase reporter assay. ResultsThe mRNA expressions of lncRNA MANCR and GPNMB in GC tissue were higher than those in adjacent tissue,and the expression of miR-150-5p was lower than that in adjacent tissue (P<0.05). Compared with that in GES-1,lncRNA MANCR expression in BGC-823 cells was increased (P<0.05). Compared with those in the sh-NC group and control group,the EdU-positive cell rate,migration number,invasion number,the mRNA expressions of lncRNA MANCR and GPNMB, and the expressions of protein,N-cadherin protein, and Vimentin protein in the BGC-823 cells in the sh-MANCR group were lower ,and the protein expressions of miR-150-5p and E-cadherin were higher (P<0.05). Compared with those in the sh-MANCR group and the sh-MANCR + anti-NC group,the protein expressions of miR-150-5p and E-cadherin in the sh-MANCR + anti-miR-150-5p group were decreased. The EdU-positive cell rate,migration number,invasion number,mRNA expressions of GPNMB, and expressions of protein,N-cadherin protein, and Vimentin protein were increased (P<0.05). lncRNA MANCR could target the negative regulation of miR-150-5p,and miR-150-5p could target the negative regulation of GPNMB. ConclusionKnockout of lncRNA MANCR can inhibit the proliferation,migration, and EMT of GC cells by regulating the miR-150-5p/GPNMB axis.
8.Study on the 90-day Feeding Experimental Background Data of SD Rats for Drug Safety Evaluation
Chao QIN ; Shuangxing LI ; Tingting ZHAO ; Chenchen JIANG ; Jing ZHAO ; Yanwei YANG ; Zhi LIN ; Sanlong WANG ; Hairuo WEN
Laboratory Animal and Comparative Medicine 2025;45(4):439-448
ObjectiveTo establish background data for a 90-day feeding trial of SD rats to ensure the reliability of research data. MethodsBackground data from six independent 90-day feeding trials of SD rats conducted by the National Center for Safety Evaluation of Drugs from 2020 to 2023 were summarized. These studies involved a blank control group of 120 SPF-grade 4-week-old SD rats, with an equal number of males and females, which were only given standard full-nutrient pelleted rat feed. After the quarantine period, the animals were observed for an additional 90 days, followed by intraperitoneal injection of Zoletil (50 mg/mL) for anesthesia, blood sampling, euthanasia, and necropsy. By analyzing the data from the blank control group, a relevant background database for SD rats was established. ResultsBoth male and female rats exhibited steady weight gain, with a more pronounced increase in male rats. Within 90 days, the average body weight of male and female rats increased to over 500 g and 300 g, respectively. Three weeks later, the average daily food intake of male rats stabilized at approximately 25~28 g per rat, while that of female rats remained stable at approximately 16~19 g per rat. The food utilization rate of all animals gradually decreased from the first week of the experiment. In the white blood cell (WBC) differential count results, significant differences were observed in the counts of WBCs, neutrophils (Neut), lymphocytes (Lymph), and monocytes (Mono) between males and females (P<0.001). However, there were no significant differences in the percentages of neutrophil (%Neut), lymphocyte (%Lymph), and monocyte (%Mono) between the sexes (P>0.05). The average red blood cell count (RBC), hemoglobin concentration (HGB), hematocrit (HCT), platelet count (PLT), prothrombin time (PT), and activated partial thromboplastin time (APTT) were higher in male animals than in female animals (P<0.05). The average values of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), creatine phosphokinase (CK), lactate dehydrogenase (LDH), glucose (GLU), and triglyceride (TG) in male rats were higher than those in female rats (P<0.05). The urinary pH range for male animals was 5.0 to 8.5, while for female animals it was 6.5 to 9.0. The majority of male animals had a urinary specific gravity lower than 1.020, and the majority of female animals had a urinary specific gravity lower than 1.015. The weights of various organs (excluding the adrenal glands and reproductive organs) in male animals were heavier than those in female animals (P<0.001), while the organ/body weight ratios (excluding the kidneys and reproductive organs) of female animals were higher than those of male animals (P<0.001). ConclusionThis study summarizes the background reference ranges for body weight, food intake, hematology, and serum biochemistry indicators in SPF-grade SD rats in the untreated control group from six 90-day feeding trials conducted by the National Center for Safety Evaluation of Drugs. It provides important reference data for related research. By summarizing the background and spontaneous histopathological changes in rats, this study aids in the standardization and normalization of subsequent research, as well as in the evaluation and analysis of abnormal results.
9.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.
10.Potential utility of albumin-bilirubin and body mass index-based logistic model to predict survival outcome in non-small cell lung cancer with liver metastasis treated with immune checkpoint inhibitors.
Lianxi SONG ; Qinqin XU ; Ting ZHONG ; Wenhuan GUO ; Shaoding LIN ; Wenjuan JIANG ; Zhan WANG ; Li DENG ; Zhe HUANG ; Haoyue QIN ; Huan YAN ; Xing ZHANG ; Fan TONG ; Ruiguang ZHANG ; Zhaoyi LIU ; Lin ZHANG ; Xiaorong DONG ; Ting LI ; Chao FANG ; Xue CHEN ; Jun DENG ; Jing WANG ; Nong YANG ; Liang ZENG ; Yongchang ZHANG
Chinese Medical Journal 2025;138(4):478-480

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