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MicroRNAs:A novel signature in the metastasis of esophageal squamous cell carcinoma

World Journal of Gastroenterology 2024年第11期30卷 1497-1523页

作者： Qi-Ying Wei Feng Jin Zhong-Yu Wang Bing-Jie Li Wen-Bo Cao Zhi-Yan Sun Sai-Jun Mo department of Pathophysiology School of Basic Medical SciencesZhengzhou UniversityZhengzhou 450001Henan ProvinceChina department of Perioperative Medicine The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052Henan ProvinceChina Division of special Service Department of Basic OncologySchool of Basic MedicineZhengzhou UniversityZhengzhou 450001Henan ProvinceChina department of Basic Science of Oncology School of Basic Medical SciencesZhengzhou UniversityZhengzhou 450001Henan ProvinceChina

Esophageal squamous cell carcinoma(ESCC)is a malignant epithelial tumor,characterized by squamous cell differentiation,it is the sixth leading cause of cancer-related deaths globally.The increased mortality rate of ESCC patients is predominantly due to the advanced stage of the disease when discovered,coupled with higher risk of metastasis,which is an exceedingly malignant charac-teristic of cancer,frequently leading to a high mortality rate.Unfortunately,there is currently no specific and effective marker to predict and treat metastasis in ESCC.MicroRNAs(miRNAs)are a class of small non-coding RNA molecules,approximately 22 nucleotides in length.miRNAs are vital in modulating gene expression and serve pivotal regulatory roles in the occurrence,progression,and prognosis of cancer.Here,we have examined the literature to highlight the intimate correlations between miRNAs and ESCC metastasis,and show that ESCC metastasis is predominantly regulated or regulated by genetic and epigenetic factors.This review proposes a potential role for miRNAs as diagnostic and therapeutic biomarkers for metastasis in ESCC metastasis,with the ultimate aim of reducing the mortality rate among patients with ESCC.

关键词： MicroRNAs Esophageal squamous cell carcinoma Metastasis Signaling pathway Epigenetics mechanism

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Reversal of tamoxifen resistance by artemisinin in ER+breast cancer:bioinformatics analysis and experimental validation

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Oncology Research 2024年第6期32卷 1093-1107页

作者： ZHILI ZHUO DONGNI ZHANG WENPING LU XIAOQING WU YONGJIA CUI WEIXUAN ZHANG MENGFAN ZHANG department of Oncology China Academy of Chinese Medical Sciences Guang’anmen HospitalBeijingChina

Breast cancer is the leading cause of cancer-related deaths in women worldwide,with Hormone Receptor(HR)+being the predominant subtype.Tamoxifen(TAM)serves as the primary treatment for HR+breast cancer.However,drug resistance often leads to recurrence,underscoring the need to develop new therapies to enhance patient quality of life and reduce recurrence rates.Artemisinin(ART)has demonstrated efficacy in inhibiting the growth of drug-resistant cells,positioning art as a viable option for counteracting endocrine resistance.This study explored the interaction between artemisinin and tamoxifen through a combined approach of bioinformatics analysis and experimental validation.Five characterized genes(ar,cdkn1a,erbb2,esr1,hsp90aa1)and seven drug-disease crossover genes(cyp2e1,rorc,mapk10,glp1r,egfr,pgr,mgll)were identified using WGCNA crossover analysis.Subsequent functional enrichment analyses were conducted.Our findings confirm a significant correlation between key cluster gene expression and immune cell infiltration in tamoxifen-resistant and-sensitized patients.scRNA-seq analysis revealed high expression of key cluster genes in epithelial cells,suggesting artemisinin’s specific impact on tumor cells in estrogen receptor(ER)-positive BC tissues.Molecular target docking and in vitro experiments with artemisinin on LCC9 cells demonstrated a reversal effect in reducing migratory and drug resistance of drug-resistant cells by modulating relevant drug resistance genes.These results indicate that artemisinin could potentially reverse tamoxifen resistance in ER-positive breast cancer.

关键词： Artemisinin Tamoxifen resistance Breast cancer

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Hypertension and human health:Evidence and prospects

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Chronic Diseases and Translational Medicine 2024年第2期10卷 89-91页

作者： Fangchao Liu Xiangfeng Lu department of Epidemiology Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Key Laboratory of Cardiovascular Epidemiology Chinese Academy of Medical SciencesBeijingChina

High blood pressure is a major public health issue and a leading risk factor for death worldwide,with the number of attributable deaths increased from 6.8 million in 1990 to 10.8 million in 2019.1,2 According to the World Health Organization,the age-standardized prevalence of hypertension was estimated to be 33%,affecting approximately 1.3 billion adults aged 30–79 years in 2019 worldwide,doubling from 1990.3 In addition to the heavy disease burden,the economic burden associated with hypertension is also substantial,accounting for approximately 10%of the global healthcare expenditure.4 Furthermore,despite improvements in diagnostic and treatment capacities,the status of hypertension care remains suboptimal,especially in low-and middle-income countries.For instance,in China,in 2019,the awareness,treatment,and control rates of hypertension were 38.3%,34.6%,and 12.0%,respectively.5 Accumulating evidence calls for more comprehensive and effective prevention and management of hypertension.

关键词： prevention treatment doubling

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Individualized brain mapping for navigated neuromodulation

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Chinese medical Journal 2024年第5期137卷 508-523页

作者： Chaohong Gao Xia Wu Xinle Cheng Kristoffer Hougaard Madsen Congying Chu Zhengyi Yang Lingzhong Fan Sino–Danish College University of Chinese Academy of SciencesBeijing 100190China Brainnetome Center National Laboratory of Pattern RecognitionInstitute of AutomationChinese Academy of SciencesBeijing 100190China School of Artificial Intelligence University of Chinese Academy of SciencesBeijing 100190China department of Applied Mathematics and Computer Science Technical University of DenmarkKongens Lyngby 2800Denmark Danish Research Centre for Magnetic Resonance Centre for Functional and Diagnostic Imaging and ResearchCopenhagen University Hospital Amager and HvidovreHvidovre 2650Denmark CAS Center for Excellence in Brain Science and Intelligence Technology Institute of AutomationChinese Academy of SciencesBeijing 100190China School of Health and Life sciences University of Health and Rehabilitation SciencesQingdaoShandong 266000China

The brain is a complex organ that requires precise mapping to understand its structure and function.Brain atlases provide a powerful tool for studying brain circuits,discovering biological markers for early diagnosis,and developing personalized treatments for neuropsychiatric disorders.Neuromodulation techniques,such as transcranial magnetic stimulation and deep brain stimulation,have revolutionized clinical therapies for neuropsychiatric disorders.However,the lack of fine-scale brain atlases limits the precision and effectiveness of these techniques.Advances in neuroimaging and machine learning techniques have led to the emergence of stereotactic-assisted neurosurgery and navigation systems.Still,the individual variability among patients and the diversity of brain diseases make it necessary to develop personalized solutions.The article provides an overview of recent advances in individualized brain mapping and navigated neuromodulation and discusses the methodological profiles,advantages,disadvantages,and future trends of these techniques.The article concludes by posing open questions about the future development of individualized brain mapping and navigated neuromodulation.

关键词： Brain atlas Individualization Navigated neuromodulation Multimodal magnetic resonance imaging Transcranial magnetic stimulation Deep brain stimulation

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IQGAP3 promotes the progression of glioma as an immune and prognostic marker

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Oncology Research 2024年第4期32卷 659-678页

作者： XIAOFENG GAO JUANJUAN GE XUZHENG GAO NA MEI YANTING SU SHIGANG SHAN WENBIN QIAN JIANGHENG GUAN ZHENWANG ZHANG LONG WANG Hubei Provincial Key Laboratory of Diabetic Cardiovascular Diseases Xianning Medical CollegeHubei University of Science and TechnologyXianning437100China School of Stomatology and Ophthalmology Xianning Medical CollegeHubei University of Science and TechnologyXianning437100China School of Basic medical sciences Xianning Medical CollegeHubei University of Science and TechnologyHubei University of Science and TechnologyXianning437100China School of Pharmacy Xianning Medical CollegeHubei University of Science and TechnologyXianning437100China department of Neurosurgery The General Hospital of Chinese PLA Central Theater CommandWuhan430070China

Background:IQGAP3 plays a crucial role in regulating cell proliferation,division,and cytoskeletal organization.Abnormal expression of IQGAP3 has been linked to various tumors,but its function in glioma is not well understood.Methods:Various methods,including genetic differential analysis,single-cell analysis,ROC curve analysis,Cox regression,Kaplan-Meier analysis,and enrichment analysis,were employed to analyze the expression patterns,diagnostic potential,prognostic implications,and biological processes involving IQGAP3 in normal and tumor tissues.The impact of IQGAP3 on immune infiltration and the immune microenvironment in gliomas was evaluated using immunofluorescence.Additionally,the cBioPortal database was used to analyze copy number variations and mutation sites of IQGAP3.Experimental validation was also performed to assess the effects of IQGAP3 on glioma cells and explore underlying mechanisms.Results:High IQGAP3 expression in gliomas is associated with an unfavorable prognosis,particularly in wild-type IDH and 1p/19q non-codeleted gliomas.Enrichment analysis revealed that IQGAP3 is involved in regulating the cell cycle,PI3K/AKT signaling,p53 signaling,and PLK1-related pathways.Furthermore,IQGAP3 expression may be closely related to the immunosuppressive microenvironment of glioblastoma.BRD-K88742110 and LY-303511 are potential drugs for targeting IQGAP3 in anti-glioma therapy.In vitro experiments showed that downregulation of IQGAP3 inhibits the proliferation and migration of glioma cells,with the PLK1/PI3K/AKT pathway potentially playing a crucial role in IQGAP3-mediated glioma progression.Conclusion:IQGAP3 shows promise as a valuable biomarker for diagnosis,prognosis,and immunotherapeutic strategies in gliomas.

关键词： IQGAP3 Tumor immune infiltration Prognosis Glioma Biomarker

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Honeymoon phase in type 1 diabetes mellitus: A window of opportunity for diabetes reversal?

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World Journal of Clinical Cases 2024年第1期12卷 9-14页

作者： Madhukar Mittal Pradakshna Porchezhian Nitin Kapoor department of Endocrinology and Metabolism All India Institute of Medical Sciences JodhpurJodhpur 342005India department of Endocrinology Diabetes and MetabolismChristian Medical College and HospitalVellore 632004Tamil NaduIndia

The knowledge of the pathogenesis of type 1 diabetes mellitus(T1DM)continues to rapidly evolve.The natural course of the disease can be described in four clinical stages based on the autoimmune markers and glycemic status.Not all individuals of T1DM progress in that specific sequence.We hereby present a case of T1DM with a classical third phase(honeymoon phase)and discuss the intri-cacies of this interesting phase along with a possible future promise of“cure”with the use of immunotherapies.We now know that the course of T1DM may not be in only one direction towards further progression;rather the disease may have a waxing and waning course with even reversal of type 1 diabetes concept being discussed.The third phase popularly called the“honeymoon phase”,is of special interest as this phase is complex in its pathogenesis.The honeymoon phase of T1DM seems to provide the best window of opportunity for using targeted therapies using various immunomodulatory agents leading to the possibility of achieving the elusive“diabetes reversal”in T1DM.Identifying this phase is therefore the key,with a lot of varying criteria having been proposed.

关键词： Diabetes reversal Diabetes remission Type 1 diabetes Honeymoon phase Immunomodulation

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Relationship between Phenotypic Changes of Dendritic Cell Subsets and the Onset of Plateau Phase during Intermittent Interferon Therapy in Patients with CHB

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Biomedical and Environmental sciences 2024年第3期37卷 303-314页

作者： YANG Liu WANG Shi Yu JIANG Ting Ting DENG Wen CHANG Min WU Shu Ling CAO Wei Hua LU Yao SHEN Ge LIU Ru Yu GAO Yuan Jiao XU Meng Jiao HU Lei Ping ZHANG Lu XIE Yao LI Ming Hui department of Hepatology Division 2 Beijing Ditan HospitalCapital Medical UniversityBeijing 100015China Center for Infectious Diseases Second Affiliated Hospital of Air Force Medical UniversityXi'an 710038ShaanxiChina department of Hepatology Division 2 Peking University Ditan Teaching HospitalBeijing 100015China

Objective This study aimed to evaluate whether the onset of the plateau phase of slow hepatitis B surface antigen decline in patients with chronic hepatitis B treated with intermittent interferon therapy is related to the frequency of dendritic cell subsets and expression of the costimulatory molecules CD40,CD80,CD83,and CD86.Method This was a cross-sectional study in which patients were divided into a natural history group(namely NH group),a long-term oral nucleoside analogs treatment group(namely NA group),and a plateau-arriving group(namely P group).The percentage of plasmacytoid dendritic cell and myeloid dendritic cell subsets in peripheral blood lymphocytes and monocytes and the mean fluorescence intensity of their surface costimulatory molecules were detected using a flow cytometer.Results In total,143 patients were enrolled(NH group,n=49;NA group,n=47;P group,n=47).The results demonstrated that CD141/CD1c double negative myeloid dendritic cell(DNmDC)/lymphocytes and monocytes(%)in P group(0.041[0.024,0.069])was significantly lower than that in NH group(0.270[0.135,0.407])and NA group(0.273[0.150,0.443]),and CD86 mean fluorescence intensity of DNmDCs in P group(1832.0[1484.0,2793.0])was significantly lower than that in NH group(4316.0[2958.0,5169.0])and NA group(3299.0[2534.0,4371.0]),Adjusted P all<0.001.Conclusion Reduced DNmDCs and impaired maturation may be associated with the onset of the plateau phase during intermittent interferon therapy in patients with chronic hepatitis B.

关键词： CHB Dendritic Cells Intermittent Interferon Therapy Plateau Phase

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Rhizoma Drynariae-derived nanovesicles reverse osteoporosis by potentiating osteogenic differentiation of human bone marrow mesenchymal stem cells via targeting ERα signaling

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2210-2227页

作者： Qing Zhao Junjie Feng Fubin Liu Qianxin Liang Manlin Xie Jiaming Dong Yanfang Zou Jiali Ye Guilong Liu Yue Cao Zhaodi Guo Hongzhi Qiao Lei Zheng Kewei Zhao Guangzhou Key Laboratory of Chinese Medicine Research on Prevention and Treatment of Osteoporosis the Third Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou 510378China Guangdong Engineering Research Center of Chinese Herbal-derived Vesicles Guangzhou University of Chinese MedicineGuangzhou 510006China department of Laboratory Medicine Nanfang HospitalSouthern Medical UniversityGuangzhou 510515China Guangdong Engineering and Technology Research Center for Rapid diagnostic Biosensors Nanfang HospitalSouthern Medical UniversityGuangzhou 510515China The Fifth Affiliated Hospital Sun Yat-sen University Zhuhai 519000China department of Blood Transfusion Guangdong Heyou International HospitalFoshan 528306China School of Pharmacy Nanjing University of Chinese MedicineNanjing 210023China

Although various anti-osteoporosis drugs are available,the limitations of these therapies,including drug resistance and collateral responses,require the development of novel anti-osteoporosis agents.Rhizoma Drynariae displays a promising anti-osteoporosis effect,while the effective component and mechanism remain unclear.Here,we revealed the therapeutic potential of Rhizoma Drynariae-derived nanovesicles(RDNVs)for postmenopausal osteoporosis and demonstrated that RDNVs potentiated osteogenic differentiation of human bone marrow mesenchymal stem cells(hBMSCs)by targeting estrogen receptor-alpha(ERα).RDNVs,a natural product isolated from fresh Rhizoma Drynariae root juice by differential ultracentrifugation,exhibited potent bone tissue-targeting activity and anti-osteoporosis efficacy in an ovariectomized mouse model.RDNVs,effectively internalized by hBMSCs,enhanced proliferation and ERαexpression levels of hBMSC,and promoted osteogenic differentiation and bone formation.Mechanistically,via the ERαsignaling pathway,RDNVs facilitated mRNA and protein expression of bone morphogenetic protein 2 and runt-related transcription factor 2 in hBMSCs,which are involved in regulating osteogenic differentiation.Further analysis revealed that naringin,existing in RDNVs,was the active component targeting ERαin the osteogenic effect.Taken together,our study identified that naringin in RDNVs displays exciting bone tissue-targeting activity to reverse osteoporosis by promoting hBMSCs proliferation and osteogenic differentiation through estrogen-like effects.

关键词： Rhizoma Drynariae-derived nanovesicles Bone marrow mesenchymal stem cells Bone targeting Osteogenic differentiation ERαsignaling Naringin Bone morphogenetic protein 2 Runt-related transcription factor 2

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Surgical intervention combined with weight-bearing walking training promotes recovery in patients with chronic spinal cord injury:a randomized controlled study

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Neural Regeneration Research 2024年第12期19卷 2773-2784页

作者： Hui Zhu James D.Guest Sarah Dunlop Jia-Xin Xie Sujuan Gao Zhuojing Luo Joe E.Springer Wutian Wu Wise Young Wai Sang Poon Song Liu Hongkun Gao Tao Yu Dianchun Wang Libing Zhou Shengping Wu Lei Zhong Fang Niu Xiaomei Wang Yansheng Liu Kwok-Fai So Xiao-Ming Xu Kunming Tongren Hospital KunmingYunnan ProvinceChina Neurological Surgery and the Miami Project to Cure ParalysisMiller School of MedicineUniversity of MiamiMiamiFLUSA School of Biological sciences The University of Western AustraliaPerthWAAustralia Minderoo Foundation PerthWAAustralia Clinical Center for Spinal Cord Injury Kunming General Hospital of Chengdu Military CommandKunmingYunnan ProvinceChina department of Biostatistics and Health Data Science Indiana University School of MedicineIndianapolisINUSA department of Orthopedic Spinal Surgery Xijing HospitalFourth Military Medical UniversityXi’anShaanxi ProvinceChina Spinal Cord and Brain Injury Research Center Department of Physical Medicine and RehabilitationUniversity of Kentucky College of MedicineLexingtonKYUSA Guangdong-HongKong-Macao Institute of CNS Regeneration Jinan UniversityGuangzhouGuangdong ProvinceChina W.M.Keck Center for Collaborative Neuroscience Rutgers UniversityPiscatawayNJUSA Neurosurgery department Chinese University of Hong KongPrince of Wales HospitalHong Kong Special Administration RegionChina Spinal Cord and Brain Injury Research Group Stark Neurosciences Research InstituteDepartment of Neurological SurgeryIndiana University School of MedicineIndianapolisINUSA

For patients with chronic spinal cord injury,the co nventional treatment is rehabilitation and treatment of spinal cord injury complications such as urinary tract infection,pressure sores,osteoporosis,and deep vein thrombosis.Surgery is rarely perfo rmed on spinal co rd injury in the chronic phase,and few treatments have been proven effective in chronic spinal cord injury patients.Development of effective therapies fo r chronic spinal co rd injury patients is needed.We conducted a randomized controlled clinical trial in patients with chronic complete thoracic spinal co rd injury to compare intensive rehabilitation(weight-bearing walking training)alone with surgical intervention plus intensive rehabilitation.This clinical trial was registered at ClinicalTrials.gov(NCT02663310).The goal of surgical intervention was spinal cord detethering,restoration of cerebrospinal fluid flow,and elimination of residual spinal cord compression.We found that surgical intervention plus weight-bearing walking training was associated with a higher incidence of American Spinal Injury Association Impairment Scale improvement,reduced spasticity,and more rapid bowel and bladder functional recovery than weight-bearing walking training alone.Overall,the surgical procedures and intensive rehabilitation were safe.American Spinal Injury Association Impairment Scale improvement was more common in T7-T11 injuries than in T2-T6 injuries.Surgery combined with rehabilitation appears to have a role in treatment of chronic spinal cord injury patients.

关键词： chronic spinal cord injury intensive rehabilitation locomotor training neurological recovery surgical intervention weightbearing walking training

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special electromyographic features in a child with paramyotonia congenita: A case report and review of literature

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World Journal of Clinical Cases 2024年第3期12卷 587-595页

作者： Hui Yi Chen-Xiang Liu Shu-Xin Ye Yu-Lin Liu department of Neuroelectrophysiology Qilu Children’s Hospital of Shandong UniversityJinan 250000Shandong ProvinceChina department of Neuroelectrophysiology University of Health and Rehabilitation Sciences(Qingdao Municipal Hospital)Qingdao 266000Shandong ProvinceChina

BACKGROUND Paramyotonia congenita(PMC)stands as a rare sodium channelopaty of skeletal muscle,initially identified by Eulenburg.The identification of PMC often relies on electromyography(EMG),a diagnostic technique.The child’s needle EMG unveiled trains of myotonic discharges with notably giant amplitudes,alongside irregular wave trains of myotonic discharges.This distinctive observation had not surfaced in earlier studies.CASE SUMMARY We report the case of a 3-year-old female child with PMC,who exhibited la-ryngeal stridor,muffled speech,myotonia from birth.Cold,exposure to cool water,crying,and physical activity exacerbated the myotonia,which was relieved in warmth,yet never normalized.Percussion myotonia was observable in bilateral biceps.Myotonia symptoms remained unchanged after potassium-rich food consumption like bananas.Hyperkalemic periodic paralysis was excluded.Cranial magnetic resonance imaging yielded normal results.Blood potassium remained within normal range,while creatine kinase showed slight elevation.Exome-wide genetic testing pinpointed a heterozygous mutation on chromosome SCN4A:c.3917G>A(p.G1306E).After a six-month mexiletine regimen,symptoms alleviated.CONCLUSION In this case revealed the two types of myotonic discharges,and had not been documented in other studies.We underscore two distinctive features:Giant-amplitude potentials and irregular waves.

关键词： Paramyotonia congenita Channelopathy Electromyography Child Case report

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