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Exosomal let-7a-5p derived from human umbilical cord mesenchymal stem cells alleviates coxsackievirus B3-induced cardiomyocyte ferroptosis via the SMAD2/ZFP36 signal axis

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Journal of Zhejiang university-Science B(Biomedicine & Biotechnology) 2024年第5期25卷 422-437页

作者： Xin LI Yanan HU Yueting WU Zuocheng YANG Yang LIU Hanmin LIU Department of Pediatric Pulmonology and Immunology West China Second University HospitalSichuan UniversityChengdu 610041China Key Laboratory of Birth Defects and Related Diseases of Women and Children(sichuan university) Ministry of EducationChengdu 610041China NHC Key Laboratory of Chronobiology(sichuan university) Chengdu 610041China The Joint Laboratory for Lung Development and Related Diseases of West China second university hospital Sichuan University and School of Life Sciences of Fudan UniversityWest China Institute of Women and Children's HealthWest China Second University HospitalSichuan UniversityChengdu 610041China sichuan Birth Defects Clinical Research Center West China Second University HospitalSichuan UniversityChengdu 610041China Department of Pediatrics the Third Xiangya HospitalCentral South UniversityChangsha 410013China

Viral myocarditis(VMC)is one of the most common acquired heart diseases in children and ***,its pathogenesis is still unclear,and effective treatments are *** study aimed to investigate the regulatory pathway by which exosomes alleviate ferroptosis in cardiomyocytes(CMCs)induced by coxsackievirus B3(CVB3).CVB3 was utilized for inducing the VMC mouse model and cellular *** echocardiography,left ventricular ejection fraction(LVEF),and left ventricular fractional shortening(LVFS)were implemented to assess the cardiac *** CVB3-induced VMC mice,cardiac insufficiency was observed,as well as the altered levels of ferroptosis-related indicators(glutathione) peroxidase 4(GPX4),glutathione(GSH),and malondialdehyde(MDA).However,exosomes derived from human umbilical cord mesenchymal stem cells(hucMSCs-exo)could restore the changes caused by CVB3 ***-7a-5p was enriched in hucMSCs-exo,and the inhibitory ffect of hucMSCs-exoa-ie-pmimo on CVB3-induced ferroptosis was higher than that of hucMSCs-exommie N(NC:negative control).Mothers against decapentaplegic homolog 2(SMAD2)increased in the VMC group,while the expression of zinc-finger protein 36(ZFP36)***-7a-5p was confirmed to interact with SMAD2 messenger RNA(mRNA),and the SMAD2 protein interacted directly with the ZFP36 *** SMAD2 and overexpressing ZFP36 inhibited the expression of ferroptosis-related ***,the levels of GPX4,solute carrier family 7,member 11(SLC7A11),and GSH were lower in the SMAD2 overexpression plasmid(oe-SMAD2)+let-7a-5p mimic group than in the oe-NC+let-7a-5p mimic group,while those of MDA,reactive oxygen species(ROS),and Fe^(2+)*** conclusion,these data showed that ferroptosis could be regulated by mediating SMAD2 ***-let-7a-5p derived from hucMSCs could mediate SMAD2 to promote the expression of ZFP36,which further inhibited the ferroptosis of CMCs to alleviate CVB3-induced VMC.

关键词： Exosome Let-7a-5p Mothers against decapentaplegic homolog 2(SMAD2) Coxsackievirus B3(CVB3) Ferroptosis

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RCAN family member 3 deficiency contributes to noncompaction of the ventricular myocardium

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Journal of Genetics and Genomics 2024年第5期51卷 543-553页

作者： Ting Hu Lan Liu He Wang Mei Yang Bocheng Xu Hanbing Xie Ziyuan Lin Xiaolei Jin Ping Wang Yanyan Liu Huaqin Sun Shanling Liu Department of Medical Genetics West China Second University HospitalSichuan UniversityChengduSichuan 610041China Key Laboratory of Birth Defects and Related Diseases of Women and Children(sichuan university) Ministry of EducationChengduSichuan 610041China Medical College Tibet UniversityLhasaTibet 850000China SCU-CUHK Joint Laboratory for Reproductive Medicine West China Second University HospitalSichuan UniversityChengduSichuan 610041China West China School of Medicine Sichuan UniversityChengduSichuan 610041China

Noncompaction of the ventricular myocardium(NVM),the third most diagnosed cardiomyopathy,is characterized by prominent trabeculae and intratrabecular ***,the genetic etiology of 40%–60%of NVM cases remains ***,we identify two infants with NVM,in a nonconsanguineous family,with a typical clinical presentation of persistent bradycardia since the prenatal period.A homozygous missense variant(R223L)of RCAN family member 3(RCAN3)is detected in both infants using whole-exome *** the zebrafish model,marked cardiac dysfunction is detected in rcan3 deficiency(MO-rcan3^(ATG)-injected)and rcan^(−/−) *** dysplasia of both endocardial and myocardial layers is also detected in rcan3-deficient ***3 R223L variant mRNAs can not rescue heart defects caused by rcan3 knockdown or knockout;however,hRCAN3 mRNAs rescue these ***-seq experiments show that several genes involved in cardiomyopathies are significantly regulated through multiple signaling pathways in the rcan3-knockdown zebrafish *** human cardiomyocytes,RCAN3 deficiency results in reduced proliferation and increased apoptosis,together with an abnormal mitochondrial ***,we suggest that RCAN3 is a susceptibility gene for cardiomyopathies,especially NVM and that the R223L mutation is a potential loss-of-function variant.

关键词： Cardiomyopathy NVM RCAN3 Mitochondrial structure Heartdefects

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Gabapentinoids for the treatment of stroke

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Neural Regeneration Research 2024年第7期19卷 1509-1516页

作者： Ying Zhang Chenyu Zhang Xiaoli Yi Qi Wang Tiejun Zhang Yuwen Li Department of Pharmacy West China HospitalSichuan UniversityChengduSichuan ProvinceChina Department of Neurosurgery West China HospitalSichuan UniversityChengduSichuan ProvinceChina

Gabapentinoid drugs(pregabalin and gabapentin) have been successfully used in the treatment of neuro pathic pain and in focal seizure *** research has demonstrated their potent activities in modulating neurotransmitter release in neuronal tissue,oxidative stress,and inflammation,which matches the mechanism of action via voltage-gated calcium *** this review,we briefly elaborate on the medicinal history and ligand-binding sites of *** systematically summarize the preclinical and clinical research on gabapentinoids in stroke,including ischemic stro ke,intracerebral hemorrhage,subarachnoid hemorrhage,seizures after stro ke,cortical spreading depolarization after stroke,pain after stroke,and nerve regeneration after stro *** review also discusses the potential to rgets of gabapentinoids in stroke;however,the existing results are still unce rtain regarding the effect of gabapentinoids on stroke and related *** preclinical and clinical trials are needed to test the therapeutic potential of gabapentinoids in ***,gabapentinoids have both opportunities and challenges in the treatment of stroke.

关键词： cortical spreading depolarization gabapentinoid intracerebral hemorrhage pain after stroke stroke subarachnoid hemorrhage

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Cell fate regulation governed by p53: Friends or reversible foes in cancer therapy

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Cancer Communications 2024年第3期44卷 297-360页

作者： Bin Song Ping Yang Shuyu Zhang Laboratory of Radiation Medicine West China Second University HospitalSichuan UniversityChengduSichuanP.R.China The second Affiliated hospital of Chengdu Medical College China National Nuclear Corporation 416 HospitalChengduSichuanP.R.China Laboratory of Radiation Medicine NHC Key Laboratory of Nuclear Technology Medical TransformationWest China School of Basic Medical Sciences&Forensic MedicineSichuan UniversityChengduSichuanP.R.China

Cancer is a leading cause of death *** therapies aimed at key oncogenic driver mutations in combination with chemotherapy and radiother-apy as well as immunotherapy have benefited cancer patients *** protein p53(TP53),a crucial tumor suppressor gene encoding p53,reg-ulates numerous downstream genes and cellular phenotypes in response to various *** affected genes are involved in diverse processes,includ-ing cell cycle arrest,DNA repair,cellular senescence,metabolic homeostasis,apoptosis,and ***,accumulating recent studies have contin-ued to reveal novel and unexpected functions of p53 in governing the fate of tumors,for example,functions in ferroptosis,immunity,the tumor microenvi-ronment and microbiome *** the possibilities,the evolutionary plasticity of p53 is the most controversial,partially due to the dizzying array of biological functions that have been attributed to different regulatory mechanisms of p53 *** 40 years after its discovery,this key tumor suppressor remains somewhat *** intricate and diverse functions of p53 in reg-ulating cell fate during cancer treatment are only the tip of the iceberg with respect to its equally complicated structural biology,which has been painstak-ingly ***,TP53 mutation is one of the most significant genetic alterations in cancer,contributing to rapid cancer cell growth and tumor ***,we summarized recent advances that implicate altered p53 in modulating the response to various cancer therapies,including chemotherapy,radiotherapy,and ***,we also discussed potential strategies for targeting p53 as a therapeutic option for cancer.

关键词： cancer chemotherapy drug targeting immunotherapy p53 tumor suppressor

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Establishment and validation of a predictive model for peripherally inserted central catheter-related thrombosis in patients with liver cancer

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World Journal of Gastrointestinal Surgery 2024年第7期16卷 2221-2231页

作者： Xiao-Fei Chen Hao-Jun Wu Tang Li Jia-Bin Liu Wen-Jie Zhou Qiang Guo Department of Thyroid Surgery West China Hospital of Sichuan UniversityChengdu 610041Sichuan ProvinceChina The second Department of General Surgery Chengdu Shangjinnanfu HospitalWest China Hospital of Sichuan UniversityChengdu 611730Sichuan ProvinceChina Department of Biliary Surgery West China Hospital of Sichuan UniversityChengdu 610041Sichuan ProvinceChina Department of Hepatobiliary and Pancreatic Surgery Chengdu Shangjinnanfu HospitalWest China Hospital of Sichuan UniversityChengdu 611730Sichuan ProvinceChina Department of Vascular Surgery West China Hospital of Sichuan UniversityChengdu 610041Sichuan ProvinceChina

BACKGROUND Peripherally inserted central catheters(PICCs)are commonly used in hospitalized patients with liver cancer for the administration of chemotherapy,nutrition,and other ***,PICC-related thrombosis is a serious complication that can lead to morbidity and mortality in this patient *** risk factors have been identified for the development of PICC-related thrombosis,including cancer type,stage,comorbidities,and catheter *** these risk factors and developing a predictive model can help healthcare providers identify high-risk patients and implement preventive measures to reduce the incidence of *** To analyze the influencing factors of PICC-related thrombosis in hospitalized patients with liver cancer,construct a predictive model,and validate *** Clinical data of hospitalized patients with liver cancer admitted from January 2020 to December 2023 were ***-five cases of PICC-related thrombosis in hospitalized patients with liver cancer were collected,and 220 patients who underwent PICC placement during the same period but did not develop PICC-related thrombosis were randomly selected as controls.A total of 255 samples were collected and used as the training set,and 77 cases were collected as the validation set in a 7:3 *** patient information,case data,catheterization data,coagulation indicators,and Autar Thrombosis Risk Assessment Scale scores were *** and multivariate unconditional logistic regression analyses were performed on relevant factors,and the value of combined indicators in predicting PICC-related thrombosis in hospitalized patients with liver cancer was evaluated using receiver operating characteristic(ROC)curve *** Univariate analysis showed statistically significant differences(P<0.05)in age,sex,Karnofsky performance status score(KPS),bedridden time,activities of daily living impairment,parenteral nutrition,catheter duration,d

关键词： Liver cancer Peripherally inserted central catheters Thrombosis Model Verify

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Precise genome-editing in human diseases:mechanisms,strategies and applications

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Signal Transduction and Targeted Therapy 2024年第3期9卷 1065-1085页

作者： Yanjiang Zheng Yifei Li Kaiyu Zhou Tiange Li Nathan J.VanDusen Yimin Hua Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE Department of PediatricsWest China Second University HospitalSichuan UniversityChengduSichuan 610041China Department of Cardiovascular Surgery West China HospitalSichuan UniversityChengduSichuan 610041China Department of Pediatrics Herman B Wells Center for Pediatric ResearchIndiana University School of MedicineIndianapolisIN 46202USA

Precise genome-editing platforms are versatile tools for generating specific,site-directed DNA insertions,deletions,and *** continuous enhancement of these tools has led to a revolution in the life sciences,which promises to deliver novel therapies for genetic *** genome-editing can be traced back to the 1950s with the discovery of DNA’s doublehelix and,after 70 years of development,has evolved from crude in vitro applications to a wide range of sophisticated capabilities,including in vivo ***,precise genome-editing faces constraints such as modest efficiency,delivery challenges,and off-target *** this review,we explore precise genome-editing,with a focus on introduction of the landmark events in its history,various platforms,delivery systems,and ***,we discuss the landmark events in the history of precise ***,we describe the current state of precise genome-editing strategies and explain how these techniques offer unprecedented precision and versatility for modifying the human ***,we introduce the current delivery systems used to deploy precise genome-editing components through DNA,RNA,and ***,we summarize the current applications of precise genome-editing in labeling endogenous genes,screening genetic variants,molecular recording,generating disease models,and gene therapy,including ex vivo therapy and in vivo therapy,and discuss potential future advances.

关键词： precise generating editing

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Heterogeneous body compositions and all-cause mortality in acute coronary syndrome patients:a ten-year retrospective cohort study

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Journal of Geriatric Cardiology 2024年第5期21卷 534-541页

作者： Guang-Zhi LIAO Lin BAI Yu-Yang YE Xue-Feng CHEN Xin-Ru HU Yong PENG Department of Cardiology West China HospitalSichuan UniversityChengduSichuanChina

BACKGROUND The association of different body components,including lean mass and body fat,with the risk of death in acute coronary syndrome(ACS)patients are *** We enrolled adults diagnosed with ACS at our center between January 2011 and December 2012 and obtained fol-low-up outcomes via telephone *** used restricted cubic splines(RCS)with the Cox proportional hazards model to analyze the associations between body mass index(BMI),predicted lean mass index(LMI),predicted body fat percentage(BF),and the value of LMI/BF with 10-year *** also examined the secondary outcome of death during *** During the maximum 10-year follow-up of 1398 patients,331 deaths(23.6%)occurred,and a U-shaped relationship was found between BMI and death risk(P_(nonlinearity)=0.03).After adjusting for age and history of diabetes,the overweight group(24≤BMIhospitalization,31 deaths(2.2%)were recorded,and the associations of the indicators with in-hospital mortality were consistent with the long-term outcome *** Our study provides new insight into the“obesity paradox”in ACS patients,highlighting the importance of considering body composition *** LMI and BF may serve as useful tools for assessing nutritional status and predicting the prognosis of ACS,based on their linear associations with all-cause mortality.

关键词： patients mortality coronary

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Epidemiology of congenital diaphragmatic hernia among 24 million Chinese births:a hospital-based surveillance study

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World Journal of Pediatrics 2024年第7期20卷 712-722页

作者： Zhi-Yu Chen Jing Tao Wen-Li Xu Yu-Yang Gao Wen-Yan Li Zhen Liu Jia-Yuan Zhou Li Dai National Center for Birth Defects Monitoring West China Second University HospitalSichuan UniversityNo.17 Section 3 RenminnanluChengdu 610041China The Joint Laboratory for Pulmonary Development and Related Diseases West China Institute of Women and Children’s HealthWest China Second University HospitalSichuan UniversityChengduChina Key Laboratory of Birth Defects and Related Diseases of Women and Children Ministry of EducationSichuan UniversityChengduChina NHC Key Laboratory of Chronobology Sichuan UniversityChengduChina Med‑X Center for Informatics Sichuan UniversityChengduChina

Background The prevalence of congenital diaphragmatic hernia(CDH)varies across countries,with limited information available on its epidemiology in *** study aimed to investigate the prevalence,time trends,and perinatal outcomes of CDH in China,as well as its associated malformations and potential associations with maternal and infant *** This study included all birth and CDH cases from the Chinese Birth Defects Monitoring Network between 2007 and 2019,with CDH cases classified as either isolated or *** employed the joinpoint regression model to calculate the trends of prevalence and the annual percent change,with Poisson regression used for adjusted prevalence rate ratios.A P value≤0.05 was considered statistically *** A total of 4397 CDH cases were identified among 24,158,029 births in the study period,yielding prevalence rates of 1.82,1.13 and 0.69 per 10,000 for overall,isolated,and associated CDH,*** prevalence of each type of CDH increased over *** prevalence of overall CDH varied significantly by infant sex(male ***,1.91/10,000 vs.1.63/10,000),maternal residence(urban ***,2.13/10,000 vs.1.45/10,000),maternal age(<20 years,1.31/10,000;20-24 years,1.63/10,000;25-29 years,1.80/10,000;30-34 years,1.87/10,000;≥35 years,2.22/10,000),and geographic region(central,1.64/10,000;east,2.45/10,000;west,1.37/10,000).Cardiovascular anomalies were the most common malformations associated with *** with associated CDH had a higher risk of premature birth and perinatal death than those with isolated *** The increasing prevalence and high perinatal mortality rate of CDH highlight the need for further etiological,epidemiological,and clinical studies among the Chinese population.

关键词： China Congenital diaphragmatic hernia Epidemiology Prevalence

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PCK1 attenuates tumor stemness via activating the Hippo signaling pathway in hepatocellular carcinoma

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Genes & Diseases 2024年第4期11卷 340-352页

作者： Rui Liu Yi Liu Wenlu Zhang Guiji Zhang Zhirong Zhang Luyi Huang Ni Tang Kai Wang Key Laboratory of Molecular Biology for Infectious Diseases(Ministry of Education) Institute for Viral HepatitisDepartment of Infectious DiseasesThe Second Affiliated HospitalChongqing Medical UniversityChongqing 400016China Department of Clinical Laboratory Sichuan Clinical Research Center for CancerSichuan Cancer Hospital&InstituteSichuan Cancer CenterAffiliated Cancer Hospital of University of Electronic Science and Technology of ChinaChengduSichuan 610041China

Liver cancer stem cells were found to rely on glycolysis as the preferred metabolic *** carboxylase 1(PCK1),a gluconeogenic metabolic enzyme,is down-regulated in hepatocellular carcinoma and is closely related to poor *** onco-genesis and progression of tumors are closely related to cancer stem *** is not completely clear whether the PCK1 deficiency increases the stemness of hepatoma cells and promotes the oncogenesis of hepatocellular ***,the results showed that PCK1 inhibited the self-renewal property of hepatoma cells,reduced the mRNA level of cancer stem cell markers,and inhibited ***,PCK1 increased the sensitivity of hepatocellular carci-noma cells to ***,we found that PCK1 activated the Hippo pathway by enhancing the phosphorylation of YAP and inhibiting its nuclear *** reduced the stemness of hepatoma cells and promoted the pro-apoptotic effect of ***,combined treatment with verteporfin and sorafenib may be a potential anti-tumor strat-egy in hepatocellular carcinoma.

关键词： Cancer stem cells Chemoresistance Gluconeogenesis Hepatocellular carcinoma YAP

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Low-molecular-weight heparin and preeclampsia—does the sword cut both ways?Three case reports and review of literature

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World Journal of Clinical Cases 2024年第9期12卷 1634-1643页

作者： Dan Shan Tao Li Xi Tan Ya-Yi Hu Department of Obstetrics and Gynecology West China Second University HospitalSichuan UniversityChengdu 610000Sichuan ProvinceChina Key Laboratory of Birth Defects and Related Diseases of Women and Children Sichuan UniversityMinistry of EducationChengdu 610000SichuanChina

BACKGROUND Low-molecular-weight heparins(LMWH)are the most commonly used anticoagulants during *** is considered to be the drug of choice due to its safety in not crossing *** the beneficial effect in the improvement of microcirculation,prophylactic application of LMWH in patients with preeclampsia became a ***,the bleeding risk related with LMWH in preeclampsia patients has seldomly been *** current study aimed to identify the potential risks regarding LMWH application in patients with *** SUMMARY Herein we present a case series of three pregnant women diagnosed with preeclampsia on LMWH therapy during *** the cases experienced catastrophic hemorrhagic *** reviewing the twenty-one meta-analyses,the bleeding risk related with LMWH seems *** one study analyzed the bleeding risk of LMWH and found a significantly higher risk of developing PPH in women receiving *** studies reported minor bleeding risks,none of these were serious enough to stop LMWH *** of bleeding either from uterus or from intrabdominal organs in preeclampsia patients on LMWH therapy should not be *** management of blood pressure even after delivery and homeostasis suture in surgery are *** Consideration should be given to the balance between benefits and risks of LMWH in patients with preeclampsia.

关键词： Pregnancy Preeclampsia Low-molecular-weight heparin Hemorrhage Case report

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