1.The progress of the role and mechanisms of circadian rhythm and clock gene in the development of atherosclerosis
Wenlin LI ; Sainan LI ; Yao YANG ; Qinan MA ; Xiuqing HUANG ; Lin DOU ; Deping LIU ; Jian LI ; Tao SHEN
Chinese Journal of Arteriosclerosis 2025;33(5):369-377
With the extension of the global population's lifespan and the increasingly severe aging problem,cardio-vascular diseases have become the leading cause of death among the elderly population.Most cardiovascular diseases orig-inate from the formation of atherosclerotic plaques.In addition to common risk factors such as dyslipidemia,diabetes,hy-pertension,smoking,and obesity,circadian rhythm disruption is also regarded as an important but often overlooked risk factor for atherosclerosis.The circadian rhythm is involved in regulating key physiological processes such as inflammation and metabolism,which in turn affect the pathological processes of arteriosclerosis and thrombosis.In this process,the key genes that maintain the stability of the circadian rhythm,namely clock gene,play a crucial role.Clock gene have an important role in the pathological mechanism of atherosclerosis,and they may become potential new targets for the preven-tion and treatment of atherosclerosis.This paper reviews the latest research progress on the mechanism of action of clock gene in the occurrence and development of atherosclerosis.These findings may provide new ideas for the diagnosis and treatment of atherosclerosis.
2.Research progress of functions and mechanisms of tRNA-derived small RNA in aging-related diseases
Wenlin LI ; Yao YANG ; Que WANG ; Kun XU ; Mingjing YAN ; Xiuqing HUANG ; Lin DOU ; Weiqing TANG ; Jian LI ; Tao SHEN
Chinese Journal of Geriatrics 2025;44(1):92-98
The primary role of transfer RNA(tRNA)is to connect a specific amino acid to its 3' end, use its anticodon to match the codon on messenger RNA(mRNA), and deliver the corresponding amino acid to the ribosome for protein synthesis.tRNA exists in two forms: precursor tRNA and mature tRNA.When acted upon by enzymes like Dicer, elaC ribonuclease Z 2(ELAC2), angiopoietin(ANG), and other ribonucleases, tRNA is broken down into tRNA-derived stress-induced RNA(tiRNA)and tRNA-derived fragments(tRF).Recent advancements in RNA sequencing technology have led to increased interest in tiRNA and tRF, shedding light on their roles in various physiological and pathological processes.tRNA-derived small molecules(tsRNA)function similarly to microRNA(miRNA), influencing gene expression and protein synthesis.They show promise as diagnostic markers and potential therapeutic targets for age-related diseases.This review offers a comprehensive analysis of tsRNA classification, biological functions, research advancements, and clinical applications in age-related conditions.
3.Research progress of functions and mechanisms of tRNA-derived small RNA in aging-related diseases
Wenlin LI ; Yao YANG ; Que WANG ; Kun XU ; Mingjing YAN ; Xiuqing HUANG ; Lin DOU ; Weiqing TANG ; Jian LI ; Tao SHEN
Chinese Journal of Geriatrics 2025;44(1):92-98
The primary role of transfer RNA(tRNA)is to connect a specific amino acid to its 3' end, use its anticodon to match the codon on messenger RNA(mRNA), and deliver the corresponding amino acid to the ribosome for protein synthesis.tRNA exists in two forms: precursor tRNA and mature tRNA.When acted upon by enzymes like Dicer, elaC ribonuclease Z 2(ELAC2), angiopoietin(ANG), and other ribonucleases, tRNA is broken down into tRNA-derived stress-induced RNA(tiRNA)and tRNA-derived fragments(tRF).Recent advancements in RNA sequencing technology have led to increased interest in tiRNA and tRF, shedding light on their roles in various physiological and pathological processes.tRNA-derived small molecules(tsRNA)function similarly to microRNA(miRNA), influencing gene expression and protein synthesis.They show promise as diagnostic markers and potential therapeutic targets for age-related diseases.This review offers a comprehensive analysis of tsRNA classification, biological functions, research advancements, and clinical applications in age-related conditions.
4.The progress of the role and mechanisms of circadian rhythm and clock gene in the development of atherosclerosis
Wenlin LI ; Sainan LI ; Yao YANG ; Qinan MA ; Xiuqing HUANG ; Lin DOU ; Deping LIU ; Jian LI ; Tao SHEN
Chinese Journal of Arteriosclerosis 2025;33(5):369-377
With the extension of the global population's lifespan and the increasingly severe aging problem,cardio-vascular diseases have become the leading cause of death among the elderly population.Most cardiovascular diseases orig-inate from the formation of atherosclerotic plaques.In addition to common risk factors such as dyslipidemia,diabetes,hy-pertension,smoking,and obesity,circadian rhythm disruption is also regarded as an important but often overlooked risk factor for atherosclerosis.The circadian rhythm is involved in regulating key physiological processes such as inflammation and metabolism,which in turn affect the pathological processes of arteriosclerosis and thrombosis.In this process,the key genes that maintain the stability of the circadian rhythm,namely clock gene,play a crucial role.Clock gene have an important role in the pathological mechanism of atherosclerosis,and they may become potential new targets for the preven-tion and treatment of atherosclerosis.This paper reviews the latest research progress on the mechanism of action of clock gene in the occurrence and development of atherosclerosis.These findings may provide new ideas for the diagnosis and treatment of atherosclerosis.
5.Association between cardiovascular autonomic function and voiding symptoms in Parkinson disease
Ziqi GAO ; Rui YANG ; Wenlin HUANG ; Mengfei CAI ; Yuhu ZHANG
Chinese Journal of Nervous and Mental Diseases 2024;50(8):463-469
Objective To investigate the association between cardiovascular autonomic function and voiding symptoms in Parkinson disease(PD)patients.Methods We reviewed PD patients from the Department of Neurology of Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sciences)between November 2020 and July 2023.Patients with PD were diagnosed by movement disorder specialists and received motor symptoms assessment based on Movement Disorders Society-Unified Parkinson's Disease Rating Scale part Ⅲ(MDS-UPDRS Ⅲ).We included those patients who underwent 24-hour ambulatory blood pressure monitoring(ABPM),ultrasound measured post void residual(PVR)and uroflowmetry.Subjects were divided into two groups:PD patients with nocturnal hypertension(PD-NH)group and PD patients without nocturnal hypertension(PD-nNH)group,according to the average nocturnal blood pressure.General clinical features,clinical assessments and urinary evaluations were compared between the two groups.We calculated average real variability(ARV)and examined its correlation factors using generalized linear models.Results Among the total of 87 PD patients,46(52.87% )were found to have nocturnal hypertension(NH).The PD-NH group exhibited more PVR[1.00(0.00,21.25)mL]compared to the PD-nNH group[0.00(0.00,5.50)mL](P<0.05).Additionally,generalized linear model analysis which scale response is Gamma with log link showed in PD patients,ARV of 24-hour diastolic blood pressure was correlated with PVR(OR=1.003,95% CI:1.001-1.005,P=0.008)and sex(male,OR=1.234,95% CI:1.050-1.451,P=0.011).Conclusion Our study demonstrates the association between cardiovascular autonomic function and voiding symptoms in PD.
6.Stratified Treatment in Pediatric Anaplastic Large Cell Lymphoma: Result of a Prospective Open-Label Multiple-Institution Study
Tingting CHEN ; Chenggong ZENG ; Juan WANG ; Feifei SUN ; Junting HUANG ; Jia ZHU ; Suying LU ; Ning LIAO ; Xiaohong ZHANG ; Zaisheng CHEN ; Xiuli YUAN ; Zhen YANG ; Haixia GUO ; Liangchun YANG ; Chuan WEN ; Wenlin ZHANG ; Yang LI ; Xuequn LUO ; Zelin WU ; Lihua YANG ; Riyang LIU ; Mincui ZHENG ; Xiangling HE ; Xiaofei SUN ; Zijun ZHEN
Cancer Research and Treatment 2024;56(4):1252-1261
Purpose:
The risk stratification of pediatric anaplastic large cell lymphoma (ALCL) has not been standardized. In this study, new risk factors were included to establish a new risk stratification system for ALCL, and its feasibility in clinical practice was explored.
Materials and Methods:
On the basis of the non-Hodgkin’s lymphoma Berlin–Frankfurt–Munster 95 (NHL-BFM-95) protocol, patients with minimal disseminated disease (MDD), high-risk tumor site (multiple bone, skin, liver, and lung involvement), and small cell/lymphohistiocytic (SC/LH) pathological subtype were enrolled in risk stratification. Patients were treated with a modified NHL-BFM-95 protocol combined with an anaplastic lymphoma kinase inhibitor or vinblastine (VBL).
Results:
A total of 136 patients were enrolled in this study. The median age was 8.8 years. The 3-year event-free survival (EFS) and overall survival of the entire cohort were 77.7% (95% confidence interval [CI], 69.0% to 83.9%) and 92.3% (95% CI, 86.1% to 95.8%), respectively. The 3-year EFS rates of low-risk group (R1), intermediate-risk group (R2), and high-risk group (R3) patients were 100%, 89.5% (95% CI, 76.5% to 95.5%), and 67.9% (95% CI, 55.4% to 77.6%), respectively. The prognosis of patients with MDD (+), stage IV cancer, SC/LH lymphoma, and high-risk sites was poor, and the 3-year EFS rates were 45.3% (95% CI, 68.6% to 19.0%), 65.7% (95% CI, 47.6% to 78.9%), 55.7% (95% CI, 26.2% to 77.5%), and 70.7% (95% CI, 48.6% to 84.6%), respectively. At the end of follow-up, one of the five patients who received maintenance therapy with VBL relapsed, and seven patients receiving anaplastic lymphoma kinase inhibitor maintenance therapy did not experience relapse.
Conclusion
This study has confirmed the poor prognostic of MDD (+), high-risk site and SC/LH, but patients with SC/LH lymphoma and MDD (+) at diagnosis still need to receive better treatment (ClinicalTrials.gov number, NCT03971305).
7.Mechanism of Sanguis draconis flavones in treatment of myocardial ischemia-reperfusion injury based on network pharmacology
Sheng LI ; Liudan LIANG ; Yan LIU ; Gencheng LIANG ; Wenlin LUO ; Zhaohe HUANG
Chinese Journal of Pathophysiology 2024;40(10):1864-1873
AIM:To predict the mechanism of Sanguis draconis flavones(SDF)in the prevention and treat-ment of myocardial ischemia reperfusion injury(MIRI)based on network pharmacology and molecular docking methods.METHODS:The main chemical constituents of SDF were collected through literature search,and the targets of key con-stituents were screened by using the SwissTargetPrediction and TargetNet databases.Disease targets were also screened based on GeneCards,OMIM,TTD and PharmGkb databases,then targets were intersected with Cytoscape to construct the"drug-key constituent-target"network diagram,and the core target was obtained through visualization and analysis by Cytoscape software.Gene Ontology(GO)functional enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses were analyzed by the Metascape platform.By utilizing AutoDock Vina software and Pymol,molecular docking between core compounds and core targets was carried out.Further,animal experiments were performed to explore the pharmacodynamic mechanism of SDF.RESULTS:The active constituents of SDF included loureirin B and loureirin A,which were mapped to 391 targets.A total of 3 096 MIRI disease targets were obtained from the database,af-ter intersection,172 intersection targets were obtained,and 56 core targets were acquired through analysis.The core relat-ed pathways included the cancer pathway and cell death signaling pathway.The results of molecular docking verified the strong binding activity between key constituents and key targets.Animal experiments demonstrated that SDF effectively prevented and treated MIRI,significantly inhibited the arachidonic acid 15-lipoxygenase(ALOX15)mRNA and protein expression,and reduced the myocardial infarction size after MIRI.CONCLUSION:SDF may play a positive role in the treatment of MIRI,which may be related to the regulation of the ALOX15 factor.
8.Leaky Gut Plays a Critical Role in the Pathophysiology of Autism in Mice by Activating the Lipopolysaccharide-Mediated Toll-Like Receptor 4-Myeloid Differentiation Factor 88-Nuclear Factor Kappa B Signaling Pathway.
Fang LI ; Haoran KE ; Siqi WANG ; Wei MAO ; Cexiong FU ; Xi CHEN ; Qingqing FU ; Xiaori QIN ; Yonghua HUANG ; Bidan LI ; Shibing LI ; Jingying XING ; Minhui WANG ; Wenlin DENG
Neuroscience Bulletin 2023;39(6):911-928
Increased intestinal barrier permeability, leaky gut, has been reported in patients with autism. However, its contribution to the development of autism has not been determined. We selected dextran sulfate sodium (DSS) to disrupt and metformin to repair the intestinal barrier in BTBR T+tf/J autistic mice to test this hypothesis. DSS treatment resulted in a decreased affinity for social proximity; however, autistic behaviors in mice were improved after the administration of metformin. We found an increased affinity for social proximity/social memory and decreased repetitive and anxiety-related behaviors. The concentration of lipopolysaccharides in blood decreased after the administration of metformin. The expression levels of the key molecules in the toll-like receptor 4 (TLR4)-myeloid differentiation factor 88 (MyD88)-nuclear factor kappa B (NF-κB) pathway and their downstream inflammatory cytokines in the cerebral cortex were both repressed. Thus, "leaky gut" could be a trigger for the development of autism via activation of the lipopolysaccharide-mediated TLR4-MyD88-NF-κB pathway.
Mice
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Animals
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NF-kappa B
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Myeloid Differentiation Factor 88/metabolism*
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Lipopolysaccharides/pharmacology*
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Toll-Like Receptor 4/metabolism*
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Autistic Disorder/metabolism*
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Signal Transduction/physiology*
9.Bioinformatics analysis of genes related to chromophobe renal cell carcinoma
Genyi QU ; Maolin XIANG ; Yong XU ; Haibo NIE ; Guang YANG ; Wenlin HUANG ; Jiawei WANG ; Cheng TANG
Journal of Chinese Physician 2021;23(2):249-253
Objective:Bioinformatics was used to analyze the gene expression profile of renal chromophobe cell carcinoma (RCCC) to find out the key genes of RCCC.Methods:Chromophobe renal cell carcinoma gene chip data GSE15641 and GSE11151 were downloaded from the GEO database. Using R software packages such as " Affy" and " limma" in R software to screen differentially expressed genes, combining with David and STRING online bioinformatics tools to analyze the regulatory network of differentially expressed genes and construct protein-protein interaction (PPI) network, the Hub gene was screened through the Cytohubba plug-in of Cytoscape software.Results:A total of 261 differentially expressed genes were screened, including 194 down-regulated genes and 67 up-regulated genes. Gene enrichment (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed to explore their biological functions. In GO enrichment analysis, biological processes were mainly enriched in cell secretion, gluconeogenesis and cell proliferation regulation; in cell composition, they were mainly enriched in exosomes, plasma membranes and their components; in molecular function, they were mainly enriched in heparin binding; in KEGG pathway analysis, they were mainly enriched in metabolic pathway, antibody biosynthesis pathway and renin angiotensin system pathway. PPI network was constructed by using online bioinformatics tools. The top 10 Hub genes were screened by using cytohubba plug-in in Cytoscape software, which were pipecolic acid and sarcosine oxidase (PIPOX), hydroxyacid oxidase 2 (HAO2), kynurenine 3-monooxygenase (KMO), solute carrier family 2 member 2 (SLC2A2), formimidoyltransferase cyclodeaminase (FTCD), angiogenin (ANG), APOBEC1 complementation factor (A1CF), aldehyde dehydrogenase 8 family member A1 (ALDH8A1), vitamin D binding protein (GC), histidine rich glycoprotein (HRG).Conclusions:Bioinformatics analysis of differentially expressed genes in renal chromophobe cell carcinoma can effectively explore the interaction information of these differentially expressed genes, and provide new ideas for the treatment of renal chromophobe cell carcinoma.
10. Endovascular thrombectomy after intravenous recombinant tissue plasminogen activator (bridging therapy) for embolic stroke due to cardiac myxoma: a case report
Xiuqu CAI ; Haiqing XU ; Juanli LIU ; Yongwu DAI ; Wenlin HE ; Jiang LI ; Shaonian TANG ; Zhiyong HUANG ; Jinjin YAN
Chinese Journal of Neurology 2020;53(2):118-121
Myxomas are the most frequent, cardiac benign cardiac tumors which often present with stroke caused by tumorous orthrombotic emboli. The treatment of embolic stroke due to cardiac myxoma is still a clinical and technical challenge. A 61-year-old man who had an embolic stroke in the left middle cerebral artery was admitted to the Third Poeple′s Hospital of Huizhou. The initial National Institutes of Health Stroke Scale (NIHSS) score was 16. He received endovascular thrombectomy after intravenous recombinant tissue plasminogen activator (rt-PA) one hour after stroke onset. No intracranial hemorrhage developed. Pathological study of embolus showed a myxoma. A cardiac mass was found in the left atrium and removed surgically three weeks after stroke. Pathological study of the tumor showed a myxoma. At the one-month follow-up after excision of myxoma, the NIHSS score was 1 and the modified Rankin scale score was 0. No recurrence of embolism occurred after surgical resection. Endovascular thrombectomy after intravenous rt-PA (bridging therapy) for embolic stroke due to cardiac myxoma is safe and effective, and early resection of atrial myxoma can effectively avoid recurrence of cerebral infarction.

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