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Chinese Journal of Integrative Medicine 2022年第6期28卷 560-566页

作者： SHEN Feng-lin ZHAO Yan-na YU Xiao-ling WANG Bo-lin WU Xiao-long LAN Gao-chen GAO Rui-lan Institute of Hematology Research The First Affiliated Hospital of Zhejiang Chinese Medical UniversityHangzhou310006China

Aberrant regulation of DNA methylation plays a crucial causative role in haematological malignancies(HMs).Targeted therapy,aiming for DNA methylation,is an effective mainstay of modem medicine;however,many issues remain to be addressed.The progress of epigenetic studies and the proposed theory of"state-target medicine"have provided conditions to form a new treatment paradigm that combines the"body state adjustment"of CM with targeted therapy.We discussed the correlation between Chinese medicine(CM)syndromes/states and DNA methylation in this paper.Additionally,the latest research findings on the intervention and regulation of DNA methylation in HMs,including the core targets,therapy status,CM compounds and active components of the Chinese materia medica were concisely summarized to establish a theoretical foundation of"state-target synchronous conditioning"pattern of integrative medicine for HMs,simultaneously leading a new perspective in clinical diagnosis and therapy.

关键词： haematological malignancies DNA methylation Chinese medicine state-target medicine

Risk Factors of Depression Screened by Two-Sample Mendelian Randomization Analysis:A Systematic Review

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Biomedical and Environmental Sciences 2024年第1期37卷 85-95页

作者： WANG Han lin XUE Yan feng CUI Bao Qiu LIU Hong shen Xin Xin Shandong Provincial Research Center for Bioinformatic Engineering and Technique School of Life SciencesShandong University of TechnologyZibo 255049ShandongChina Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical UniversityTaiyuan 030013ShanxiChina State Key Laboratory of Infectious Disease Prevention and Control National Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijing 102206China

Objective This study explored the potentially modifiable factors for depression and major depressive disorder(MDD)from the MR-Base database and further evaluated the associations between drug targets with MDD.Methods We analyzed two-sample of Mendelian randomization(2SMR)using genetic variant depression(n=113,154)and MDD(n=208,811)from Genome-Wide Association Studies(GWAS).Separate calculations were performed with modifiable risk factors from MR-Base for 1,001 genomes.The MR analysis was performed by screening drug targets with MDD in the DrugBank database to explore the therapeutic targets for MDD.Inverse variance weighted(IVW),fixed-effect inverse variance weighted(FE-IVW),MR-Egger,weighted median,and weighted mode were used for complementary calculation.Results The potential causal relationship between modifiable risk factors and depression contained 459 results for depression and 424 for MDD.Also,the associations between drug targets and MDD showed that SLC6A4,GRIN2A,GRIN2C,SCN10A,and IL1B expression are associated with an increased risk of depression.In contrast,ADRB1,CHRNA3,HTR3A,GSTP1,and GABRG2 genes are candidate protective factors against depression.Conclusion This study identified the risk factors causally associated with depression and MDD,and estimated 10 drug targets with significant impact on MDD,providing essential information for formulating strategies to prevent and treat depression.

关键词： Risk factors Drug targets Depression Major depressive disorder Two-sample Mendelian randomization

Proteomics study of Mycoplasma pneumoniae pneumonia reveals the Fc fragment of the IgG-binding protein as a serum biomarker and implicates potential therapeutic targets

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Frontiers of Medicine 2022年第3期16卷 378-388页

作者： Jinrong Liu Rongfang shen lin feng Shujun Cheng Jun Chen Ting Xiao Shunying Zhao Department of Respiratory Medicine Beijing Children’s HospitalCapital Medical UniversityNational Center for Children’s HealthBeijing 100045China State Key Laboratory of Molecular Oncology Department of Etiology and CarcinogenesisNational Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Beijing Engineering Research Center of Pediatric Surgery Engineering and Transformation CenterBeijing Children’s HospitalCapital Medical UniversityNational Center for Children’s HealthBeijing 100045China

Macrolide and corticosteroid resistance has been reported in patients with Mycoplasma pneumoniae(MP)pneumonia(MPP).MP clearance is difficult to achieve through antibiotic treatment in sensitive patients with severe MPP(SMPP).SMPP in children might progress to airway remodeling and even bronchiolitis/bronchitis obliterans.Therefore,identifying serum biomarkers that indicate MPP progression and exploring new targeted drugs for SMPP treatment require urgency.In this study,serum samples were collected from patients with general MPP(GMPP)and SMPP to conduct proteomics profiling.The Fc fragment of the IgG-binding protein(FCGBP)was identified as the most promising indicator of SMPP.Biological enrichment analysis indicated uncontrolled inflammation in SMPP.ELISA results proved that the FCGBP level in patients with SMPP was substantially higher than that in patients with GMPP.Furthermore,the FCGBP levels showed a decreasing trend in patients with GMPP but the opposite trend in patients with SMPP during disease progression.Connectivity map analyses identified 25 possible targeted drugs for SMPP treatment.Among them,a mechanistic target of rapamycin kinase(mTOR)inhibitor,which is a macrolide compound and a cell proliferation inhibitor,was the most promising candidate for targeting SMPP.To our knowledge,this study was the first proteomics-based characterization of patients with SMPP and GMPP.

关键词： severe Mycoplasma pneumoniae pneumonia children proteomics Fc fragment of the IgG-binding protein mechanistic target of rapamycin kinase inhibitor

MicroRNA-34c promotes neuronal recovery in rats with spinal cord injury through the C-X-C motif ligand 14/Janus kinase 2/signal transducer and activator of transcription-3 axis

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Chinese Medical Journal 2020年第18期133卷 2177-2185页

作者： Juan shen feng Gao lin Zhao Qin Hao Yan-ling Yang Department of Central Laboratory School of Medicine of Yan’an UniversityYan’anShaanxi 716000China

Background:Developing effective spinal cord repair strategies for spinal cord injury(SCI)is of great importance.Emerging evidence suggests that microRNAs(miRNAs)are closely linked to SCI recovery.This study aimed to investigate the function of miR-34c in the neuronal recovery in rats with SCI.Methods:A rat model with SCI was established.Differentially expressed miRNAs were identified by a microarray analysis.MiR-34c expression in rats was measured by reverse transcription quantitative polymerase chain reaction.Altered expression of miR-34c or C-X-C motif ligand 14(CXCL14)was introduced in SCI rats to measure their roles in neuronal recovery.Western blot analysis was performed to determine the phosphorylation of Janus kinase 2(JAK2)and signal transducer and activator of transcription-3(STAT3).Neuronal apoptosis in rat spinal cord tissues was detected.The concentrations of SCI recovery-related proteins thyrotropin releasing hormone(TRH),prostacyclin(PGI2),and ganglioside(GM)were evaluated by enzyme-linked immunosorbent assay.Data were analyzed using a t-test with a one-way or two-way analysis of variance.Results:Rats with SCI presented decreased grip strength(112.03±10.64 vs.17.32±1.49 g,P<0.01),decreased miR-34c expression(7 days:3.78±0.44 vs.0.95±0.10,P<0.05),and increased CXCL14 expression(7 days:0.61±0.06 vs.2.91±0.27,P<0.01).MiR-34c was found to directly bind to CXCL14.Overexpression of miR-34c increased grip strength(11.23±1.08 vs.31.26±2.99 g,P<0.01)and reduced neuronal apoptosis in spinal cord tissues(53.61%±6.07%vs.24.59%±3.32%,P<0.01),and silencing of CXCL14 also increased the grip strength(12.76±1.13 vs.29.77±2.75 g,P<0.01)and reduced apoptosis in spinal cord tissues(55.74%±6.24%vs.26.75%±2.84%,P<0.01).In addition,miR-34c upregulation or CXCL14 downregulation increased the concentrations of TRH,PGI2,and GM,and reduced phosphorylation of JAK2 and STAT3 in rats with SCI(all P<0.01).Conclusion:The study provided evidence that miR-34c could promote neuronal recovery in rats with SCI through inhibiting CXCL14

关键词： MIRN34C CXCL14 JAK2/STAT3 Spinal cord injury Apoptosis

Berberine Enhances Intestinal Mucosal Barrier Function by Promoting Vitamin D Receptor Activity

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Chinese Journal of Integrative Medicine 2024年第2期30卷 143-151页

作者： HUANG Yong-quan LIU Jia-lin CHEN Geng-xin shen Dan-ting ZHU Wang CHEN Xin-lin LIU feng-bin HOU Qiu-ke Graduate School Guangzhou University of Chinese MedicineGuangzhou(510405)China Department of Orthopedics the Second Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou(510006)China Department of Preventive Medicine and Health Statistics Guangzhou University of Chinese MedicineGuangzhou(510006)China Department of Gastroenterology the First Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou(510405)China

Objective:To evaluate if berberine can act on vitamin D receptors(VDR)and thereby regulate the expression of tight junction proteins(TJPs)in irritable bowel syndrome-diarrhea-predominant(IBS-D)rats.Methods:The newborn rats were induced into IBS-D rat model via neonatal maternal separation combined with acetic acid chemical stimulation.After modeling,the model was evaluated and rats were divided into the control group and berberine treatment groups(0.85,1.7 and 3.4 mg/kg,once a day for 2 weeks).The distal colon was obtained and colonic epithelial cells(CECs)were isolated and cultured after IBS-D model evaluation.The vitamin D receptor response element(VDRE)reporter gene was determined in the CECs of IBS-D rats to analyze the effect of berberine on the VDRE promoter.VDR overexpression or silencing technology was used to analyze whether VDR plays a role in promoting intestinal barrier repair,and to determine which region of VDR plays a role in berberine-regulated intestinal TJPs.Results:The IBS-D rat model was successfully constructed and the symptoms were improved by berberine in a dose-dependent manner(P<0.05).The activity of VDRE promoter was also effectively promoted by berberine(P<0.05).Berberine increased the expression of TJPs in IBS-D CECs(P<0.05).VDR expression was significantly increased after transfection of different domains of VDR when compared to normal control and basic plasmid groups(all P<0.05).RT-qPCR and Western blot results showed that compared with the blank group,expressions of occludin and zonula occludens-1 were significantly higher in VDR containing groups(all P<0.05).Berberine plus pCMV-Myc-VDR-N group exerted the highest expression levels of occludin and zonula occludens-1(P<0.05).Conclusion:Berberine enhances intestinal mucosal barrier function of IBS-D rats by promoting VDR activity,and the main site of action is the N-terminal region of VDR.

关键词： berberine Chinese medicine irritable bowel syndrome-diarrhea-predominant vitamin D receptors intestinal mucosal barrier tight junction proteins

A thermochemical model description of CaO-SiO2-Al2O3 silicate system

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China Foundry 2023年第6期20卷 480-490页

作者： Qiu-lin Wen feng-man shen Hai-yan Zheng Yun-bao Gao Yu Wang Yan-chun Lou National Key Laboratory of Advanced Casting Technologies Liaoning Academy of Materials 3. School of Metallurgy Northeastern University

A thermochemical model based on the ion and molecule coexistence theory(IMCT) was developed to calculate thermodynamic data in the CaO-SiO2-Al2O3slag system, considering the influential role of oxide activities on the thermodynamic properties of slags. Using this model, iso-activity contours were obtained for oxide components CaO, SiO2and Al2O3in this system at temperatures of 1,873 K and 1,773 K. When compared with the IMCT model, it is found that the predicted activities of oxide components in the CaO-SiO2-Al2O3system using the model developed in this study better matches experimental data from literature in terms of both trend and numerical value. Therefore, the model developed in this study can serve as a robust modeling tool for metallurgical processes, and the thermodynamic data predicted by this new model can be used to improve the metallurgical technology.

关键词： thermochemical model CaO-SiO 2 -Al 2 O 3 slag system thermodynamic properties molecule coexistence theory TG223 A

Modeling Method for Flexible Energy Behaviors in CNC Machining Systems

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Chinese Journal of Mechanical Engineering 2018年第1期31卷 156-166页

作者： Yu-feng Li Yu-lin Wang Yan He Yan Wang shen-Long lin Economics and Business Administration Chongqing University State Key Laboratory of Mechanical Transmission Chongqing University School of Mechanical Engineering Nanjing University of Science and Technology Department of Computing Mathematics and Engineering University of Brighton

CNC machining systems are inevitably confronted with frequent changes in energy behaviors because they are widely used to perform various machining tasks. It is a challenge to understand and analyze the flexible energy behaviors in CNC machining systems. A method to model flexible energy behaviors in CNC machining systems based on hierarchical objected-oriented Petri net(HOONet) is proposed. The structure of the HOONet is constructed of a high-level model and detail models. The former is used to model operational states for CNC machining systems, and the latter is used to analyze the component models for operational states. The machining parameters having great impacts on energy behaviors in CNC machining systems are declared with the data dictionary in HOONet models. A case study based on a CNC lathe is presented to demonstrate the proposed modeling method. The results show that it is effective for modeling flexible energy behaviors and providing a fine-grained description to quantitatively analyze the energy consumption of CNC machining systems.

关键词： Energy behaviors CNC machining systems Modeling method HOONet

New Insights into Genotype-phenotype Correlations in Chinese Facioscapulohumeral Muscular Dystrophy： A Retrospective Analysis of 178 Patients

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Chinese Medical Journal 2015年第13期128卷 1707-1713页

作者： feng lin Zhi-Qiang Wang Min-Ting lin shen-Xing Murong Ning Wang Department of Neurology and Institute of Neurology First Affiliated Hospital Fujian Medical University Fuzhou Fujian 350005 China

Background： Facioscapulohumeral muscular dystrophy （FSHD）, a common autosomal dominant muscular disorder, is caused by contraction of the D4Z4 repeats on 4q35. The complicated genotype-phenotype correlation among different ethnic population remains a controversial subject. We aimed to refine this correlation in order to provide new information for genetic counseling. Methods： Here, a cohort of[36 Chinese families including 178 affected individuals and 137 unaffected members were investigated. Genetic analyses were pertbrmed using the pl 3E-11, 4qA and 4qB probes after pulsed field gel electrophoresis separation and southern blotting. A I 0-grade FSHD clinical severity scale was adopted for clinical assessment. The genotype-phenotype correlation was established by linear regression analyses. Results： We observed a roughly inversed correlation between the short EcoRl fragment size and age-corrected clinical severity score in 154 symptomatic patients （P 〈 0.05）. Compared to male patients, a significant higher proportion of females in both asymptomatic carriers and severe patients showed larger variation in the size of short EcoRI fragment. A high incidence （ 19/42, 45.2%） ofasymptomatic （or minimally affected） carriers was found in familial members. Conclusions： Although the number of D4Z4 repeats is known as one of the critical influences on genotype-phenotype correlation, a rnajority ofphenotypic spectrum was still incompatible with their heterozygous contraction of the D4Z4 repeat, especial in female cases. Our resuhs suggest that there are multi-factors synergistically modulating the phenotypic expression.

关键词： Asymptomatic Facio-scapulohumeral Muscular Dystrophy Genetic Counseling Phenotype

Glycation of high-density lipoprotein in type 2 diabetes mellitus

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Chinese Medical Journal 2013年第21期126卷 4162-4165页

作者： Sun Jia-teng shen Ying Lu An-kang Lu lin shen Wei-feng Shanghai Jiao Tong Univ Sch Med Dept Cardiol Ruijin Hosp Shanghai 200025 Peoples R China Shanghai Jiao Tong Univ Sch Med Inst Cardiovasc Dis Shanghai 200025 Peoples R China

Objective To evaluate whether glycation of high-density lipoprotein （HDL） increases cardiovascular risk in patients with type 2 diabetes mellitus by altering its anti-atherogenic property.

关键词： glycation high-density lipoprotein atherosclerosis diabetes

Leukoaraiosis is associated with clinical symptom severity,poor neurological function prognosis and stroke recurrence in mild intracerebral hemorrhage:a prospective multi-center cohort study

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Neural Regeneration Research 2022年第4期17卷 819-823页

作者： Tian-Qi Xu Wei-Zhi lin Yu-Lan feng Fan-Xia shen Jie Chen Wei-Wen Wu Xiao-Dong Zhu lin Gu Yi Fu Department of Neurology Ruijin Hospital/Luwan BranchSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina The Third Affiliated People’s Hospital of Fujian University of Traditional Chinese Medicine FuzhouFujian ProvinceChina Department of Neurology Minhang HospitalFudan UniversityShanghaiChina Department of Neurology Ruijin North HospitalShanghaiChina Department of Neurology Zhongshan Hospital Qingpu BranchFudan UniversityShanghaiChina Department of Neurology The First Hospital of JiaxingJiaxingZhejiang ProvinceChina Department of Rehabilitation Shanghai Ruijin Rehabilitation HospitalShanghaiChina

Leukoaraiosis(LA)results from ischemic injury in small cerebral vessels,which may be attributable to decreased vascular density,reduced cerebrovascular angiogenesis,decreased cerebral blood flow,or microcirculatory dysfunction in the brain.In this study,we enrolled 357 patients with mild intracerebral hemorrhage(ICH)from five hospitals in China and analyzed the relationships between LA and clinical symptom severity at admission,neurological function prognosis at 3 months,and 1-year stroke recurrence.Patients were divided into groups based on Fazekas scale scores:no LA(n=83),mild LA(n=64),moderate LA(n=98)and severe LA(n=112).More severe LA,larger hematoma volume,and higher blood glucose level at admission were associated with more severe neurological deficit.More severe LA,older age and larger hematoma volume were associated with worse neurological function prognosis at 3 months.In addition,moderate-to-severe LA,admission glucose and symptom-free cerebral infarction were associated with 1-year stroke recurrence.These findings suggest that LA severity may be a potential marker of individual ICH vulnerability,which can be characterized by poor tolerance to intracerebral attack or poor recovery ability after ICH.Evaluating LA severity in patients with mild ICH may help neurologists to optimize treatment protocols.This study was approved by the Ethics Committee of Ruijin Hospital Affiliated to Shanghai Jiao Tong University(approval No.12)on March 10,2011.

关键词： clinical symptom severity functional dependence intracerebral hemorrhage leukoaraiosis modified Rankin scale National Institute Health of Stroke Scale prognosis stroke recurrence white matter hyperintensities