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Magnetic resonance-guided focused ultrasound for essential tremor:a prospective,single center,single-arm study

Neural Regeneration Research 2024年第9期19卷 2075-2080页

作者： Rui Zong Xuemei Li Chunyu Yin Jianfeng He Dekang Zhang Xiangbing Bian Lichao Huang Jiayou Zhou Zhipei Ling Lin Ma xin lou Longsheng Pan xinguang Yu Seniro Department of Neurosurgery The First Medical Center of the PLA General HospitalBeijingChina Clinics of Cadre Department of OutpatientThe First Medical Center of the PLA General HospitalBeijingChina Department of Radiology The First Medical Center of the PLA General HospitalBeijingChina

The safety and effectiveness of magnetic resonance-guided focused ultrasound thalamotomy has been broadly established and validated for the treatment of essential tremor.In 2018,the first magnetic resonance-guided focused ultrasound system in Chinese mainland was installed at the First Medical Center of the PLA General Hospital.This prospective,single center,open-label,single-arm study was part of a worldwide prospective multicenter clinical trial(ClinicalTrials.gov Identifier:NCT03253991)conducted to confirm the safety and efficacy of magnetic resonance-guided focused ultrasound for treating essential tremor in the local population.From 2019 to 2020,10 patients with medication refractory essential tremor were recruited into this open-label,single arm study.The treatment efficacy was determined using the Clinical Rating Scale for Tremor.Safety was evaluated according to the incidence and severity of adverse events.All of the subjects underwent a unilateral thalamotomy targeting the ventral intermediate nucleus.At the baseline assessment,the estimated marginal mean of the Clinical Rating Scale for Tremor total score was 58.3±3.6,and this improved after treatment to 23.1±6.4 at a 12-month follow-up assessment.A total of 50 adverse events were recorded,and 2 were defined as serious.The most common intraoperative adverse events were nausea and headache.The most frequent postoperative adverse events were paresthesia and equilibrium disorder.Most of the adverse events were mild and usually disappeared within a few days.Our findings suggest that magnetic resonance-guided focused ultrasound for the treatment of essential tremor is effective,with a good safety profile,for patients in Chinese mainland.

关键词： efficacy essential tremor magnetic resonance-guided focused ultrasound(MRgFUS) movement disorder safety stereotactic therapy thalamotomy ventral intermediate nucleus

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Hemorrhagic cystitis in gastric cancer after nanoparticle albuminbound paclitaxel:A case report

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World Journal of Gastrointestinal Oncology 2024年第3期16卷 1084-1090页

作者： xin-Jie Zhang Jian lou Department of Cancer Center The Fifth Affiliated Hospital of Wenzhou Medical UniversityLishui 323000Zhejiang ProvinceChina

BACKGROUND The advanced first-line regimen for advanced gastric cancer is based on a combination of fluoropyrimidine and platinum and/or paclitaxel(PTX),forming a two-or three-drug regimen.Compared to conventional PTX,nanoparticle albumin-bound PTX(Nab-PTX)has better therapeutic effects and fewer adverse effects reported in studies.Nab-PTX is a great option for patients presenting with advanced gastric cancer.Herein,we highlight an adverse event(hemorrhagic cystitis)of Nab-PTX in advanced gastric cancer.CASE SUMMARY A 55-year-old male was diagnosed with lymph node metastasis after a laparo-scopic-assisted radical gastrectomy for gastric cancer that was treated by Nab-PTX and S-1(AS).On the 15th day after treatment with AS,he was diagnosed with hemorrhagic cystitis.CONCLUSION Physicians should be aware that hemorrhagic cystitis is a potential adverse event associated with Nab-PTX treatment.

关键词： Nanoparticle albumin-bound paclitaxel Hemorrhagic cystitis Gastric cancer Adverse event Case report

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Neutrophil extracellular traps mediate neuro-immunothrombosis

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Neural Regeneration Research 2024年第8期19卷 1734-1740页

作者： Jianbo lou Jianning Zhang Quanjun Deng xin Chen Department of Neurosurgery Tianjin Medical University General HospitalTianjinChina Tianjin Neurological Institute Key Laboratory of Post-Trauma Neuro-Repair and Regeneration in Central Nervous SystemMinistry of EducationTianjin Key Laboratory of InjuriesVariations and Regeneration of Nervous SystemTianjinChina

Neutrophil extracellular traps are primarily composed of DNA and histones and are released by neutrophils to promote inflammation and thrombosis when stimulated by various inflammato ry reactions.Neutrophil extracellular trap formation occurs through lytic and non-lytic pathways that can be further classified by formation mechanisms.Histones,von Willebrand factor,fibrin,and many other factors participate in the interplay between inflammation and thrombosis.Neuroimmunothrombosis summarizes the intricate interplay between inflammation and thrombosis during neural development and the pathogenesis of neurological diseases,providing cutting-edge insights into post-neurotrauma thrombotic events.The blood-brain barrier defends the brain and spinal cord against external assaults,and neutrophil extracellular trap involvement in blood-brain barrier disruption and immunothrombosis contributes substantially to secondary injuries in neurological diseases.Further research is needed to understand how neutrophil extracellular traps promote blood-brain barrier disruption and immunothrombosis,but recent studies have demonstrated that neutrophil extracellular traps play a crucial role in immunothrombosis,and identified modulators of neuro-immunothrombosis.However,these neurological diseases occur in blood vessels,and the mechanisms are unclear by which neutrophil extracellular traps penetrate the blood-brain barrier to participate in immunothrombosis in traumatic brain injury.This review discusses the role of neutrophil extracellular traps in neuro-immunothrombosis and explores potential therapeutic interventions to modulate neutrophil extracellular traps that may reduce immunothrombosis and improve traumatic brain injury outcomes.

关键词： inflammation neuro-immunothrombosis neurologic diseases neurotrauma neutrophil extracellular traps platelet thrombosis traumatic brain injury

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Regulation of AMPK activation by extracellular matrix stiffness in pancreatic cancer

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Genes & Diseases 2024年第3期11卷 338-350页

作者： xin Xu Yuan Fang Somaira Nowsheen Ye-Xiong Li Zhenkun lou Min Deng State Key Laboratory of Molecular Oncology and Department of Radiation Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Department of General Surgery Shanghai General HospitalShanghai Jiaotong University School of MedicineShanghai 200080China Department of General Surgery Zhongshan HospitalFudan UniversityShanghai 200032China Department of Dermatology University of California San DiegoSan DiegoCA 92093USA Department of Oncology Mayo ClinicRochesterMN 55905USA

The adenosine monophosphate(AMP)-activated protein kinase(AMPK)sits at a cen-tral node in the regulation of energy metabolism and tumor progression.AMPK is best known to sense high cellular ADP or AMP levels,which indicate the depletion of energy stores.Previous studies have shown that the low expression of phosphorylated AMPK is associated with a poor prognosis of pancreatic cancer.In this study,we report that AMPK is also highly sensitive to extracellular matrix(ECM)stiffness.We found that AMPK is activated in cells when cultured under low ECM stiffness conditions and is functionally required for the metabolic switch induced by ECM stiffness.This regulation of AMPK requires the Hippo kinases but not LKB1/CaMKKp.Hippo kinases directly phosphorylate AMPKa at Thr172 to activate AMPK at low ECM stiffness.Furthermore,we found AMPK activity is inhibited in patients with pancreatic ductal adenocarcinoma(PDAC)with high ECM stiffness and is associated with a poor survival outcome.The activation of Hippo kinases by ROCK inhibitor Y-27632 in combination with the mitochondrial inhibitor metformin synergistically activates AMPK and dramatically inhibits PDAC growth.Together,these findings establish a novel model for AMPK regulation by the mechanical properties of ECMs and provide a rationale for simultaneously targeting the ECM stiffness-Hippo kinases-AMPK signaling and low glucose-LKB1-AMPK signaling pathways as an effective therapeutic strategy against PDAC.

关键词： AMPKactivity Cellularmetabolic switch ECM stiffness Hippokinase signaling Pancreaticductal adenocarcinoma

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Research on Hepatocyte Regulation of PCSK9-LDLR and Its Related Drug Targets

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Chinese Journal of Integrative Medicine 2024年第7期30卷 664-672页

作者： LIU Su-su YU Tong QIAO Yan-fang GU Shu-xiao CHAI xin-lou School of Traditional Chinese Medicine Beijing University of Chinese Medicine

The prevalence of hyperlipidemia has increased significantly due to genetic, dietary, nutritional and pharmacological factors, and has become one of the most common pathological conditions in humans. Hyperlipidemia can lead to a range of diseases such as atherosclerosis, stroke, coronary heart disease, myocardial infarction, diabetes, and kidney failure, etc. High circulating low-density lipoprotein cholesterol(LDL-C) is one of the causes of hyperlipidemia. LDL-C in the blood binds to LDL receptor(LDLR) and regulates cholesterol homeostasis through endocytosis. In contrast, proprotein convertase subtilisin/kexin type 9(PCSK9) mediates LDLR degradation via the intracellular and extracellular pathways, leading to hyperlipidemia. Targeting PCSK9-synthesizing transcription factors and downstream molecules are important for development of new lipid-lowering drugs. Clinical trials regarding PCSK9 inhibitors have demonstrated a reduction in atherosclerotic cardiovascular disease events. The purpose of this review was to explore the target and mechanism of intracellular and extracellular pathways in degradation of LDLR and related drugs by PCSK9 in order to open up a new pathway for the development of new lipid-lowering drugs.

关键词： hyperlipidemia proprotein convertase subtilisin/kexin type 9 low-density lipoprotein receptor intracellular pathway extracellular pathway

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Orbit and clock products for quad-system satellites with undifferenced ambiguity fixing approach

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Satellite Navigation 2024年第1期5卷 125-139页

作者： Jiaqi Wu xingxing Li Yongqiang Yuan Keke Zhang xin Li Jiaqing lou Yun Xiong School of Geodesy and Geomatics Wuhan University129 Luoyu RoadWuhan430079China Hubei Luojia Laboratory 129 Luoyu RoadWuhan430079China German Research Centre for Geosciences GFZ Telegrafenberg14473PotsdamGermany Technische Universitat Berlin(TUB) Straße Des 17.Juni10623BerlinGermany

Integer Ambiguity Resolution(IAR)can significantly improve the accuracy of GNSS Precise Orbit Determination(POD).Traditionally,the IAR in POD is achieved at the Double Differenced(DD)level.In this contribution,we develop an Un-Differenced(UD)IAR method for Global Positioning System(GPS)+BeiDou Navigation Satellite System(BDS)+Galileo navigation satellite system(Galileo)+Global'naya Navigatsionnaya Sputnikovaya Sistema(GLONASS)quad-system POD by calibrating UD ambiguities in the raw carrier phase and generating the so-called carrier range.Based on this method,we generate the UD ambiguity-fixed orbit and clock products for the Wuhan Innovation Application Center(IAC)of the International GNSS Monitoring and Assessment System(iGMAS).One-year observations in 2020 from 150 stations are employed to investigate performance of orbit and clock products.Notably,the UD Ambiguity Resolution(AR)yields more resolved integer ambiguities than the traditional DD AR,scaling up to 9%,attributable to its avoidance of station baseline formation.Benefiting from the removal of ambiguity parameters,the computational efficiency of parameter estimation undergoes a substantial 70%improvement.Compared with the float solution,the orbit consistencies of UD AR solution achieve the accuracy of 1.9,5.2,2.8,2.1,and 2.7 cm for GPS,BeiDou-2 Navigation Satellite System(BDS-2),BeiDou-3 Navigation Satellite System(BDS-3),Galileo,and GLONASS satellites respectively,reflecting enhancements of 40%,24%,54%,34%,and 42%.Moreover,the standard deviations of Satellite Laser Ranging(SLR)residuals are spanning 2.5–3.5 cm,underscoring a comparable accuracy to the DD AR solution,with discrepancies below 5%.A notable advantage of UD AR lies in its capability to produce the Integer Recovered Clock(IRC),facilitating Precise Point Positioning(PPP)AR without requiring additional Uncalibrated Phase Delay(UPD)products.To assess the performance of quad-system kinematic PPP based on IRC,a network comprising 120 stations is utilized.In comparison to the float solution,the IR

关键词： Multi-GNSS Precise orbit determination Integer recover clock Undifferenced ambiguity resolution iGMAS innovation application center

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Current applications for magnetic resonance-guided focused ultrasound in the treatment of Parkinson’s disease

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Chinese Medical Journal 2023年第7期136卷 780-787页

作者： Haoxuan Lu Xiaoyu Wang xin lou Department of Radiology Chinese PLA General Hospital/Chinese PLA Medical SchoolBeijing 100853China School of Medicine Nankai UniversityTianjin 300071China

Magnetic resonance-guided focused ultrasound(MRgFUS)is a novel and minimally invasive technology.Since the US Food and Drug Administration approved unilateral ventral intermediate nucleus-MRgFUS for medication-refractory essential tremor in 2016,studies on new indications,such as Parkinson’s disease(PD),psychiatric diseases,and brain tumors,have been on the rise,and MRgFUS has become a promising method to treat such neurological diseases.Currently,as the second most common degenerative disease,PD is a research hotspot in the field of MRgFUS.The actions of MRgFUS on the brain range from thermoablation,blood-brain barrier(BBB)opening,to neuromodulation.Intensity is a key determinant of ultrasound actions.Generally,high intensity can be used to precisely thermoablate brain targets,whereas low intensity can be used as molecular therapies to modulate neuronal activity and open the BBB in conjunction with injected microbubbles.Here,we aimed to summarize advances in the application of MRgFUS for the treatment of PD,with a focus on thermal ablation,BBB opening,and neuromodulation,in the hope of informing clinicians of current applications.

关键词： Magnetic resonance-guided focused ultrasound Thermoablation Blood-brain barrier Parkinson’s disease Neuromodulation

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Fusobacterium nucleatum-induced imbalance in microbiome-derived butyric acid levels promotes the occurrence and development of colorectal cancer

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World Journal of Gastroenterology 2024年第14期30卷 2018-2037页

作者： Qi-Long Wu Xiao-Ting Fang xin-xin Wan Qing-Yong Ding Yan-Jun Zhang Ling Ji Yong-Liang lou Xiang Li School of Laboratory Medicine and Life Sciences Wenzhou Medical UniversityKey Laboratory of Laboratory MedicineMinistry of EducationWenzhou 325035Zhejiang ProvinceChina Department of Health Inspection and Quarantine School of Laboratory Medicine and Life SciencesWenzhou 325035Zhejiang ProvinceChina School of Laboratory Medicine and Life Sciences Wenzhou Medical UniversityZhejiang Provincial Key Laboratory of Medical GeneticsMinistry of EducationWenzhou 325035Zhejiang ProvinceChina Department of General Surgery The First Affiliated Hospital of Wenzhou Medical UniversityWenzhou 325035Zhejiang ProvinceChina School of Laboratory Medicine and Life Sciences Institute of One HealthWenzhou Medical UniversityZhejiang Provincial Key Laboratory of Medical GeneticsMinistry of EducationWenzhou 325035Zhejiang ProvinceChina Department of Health Inspection and Quarantine School of Laboratory Medicine and Life SciencesInstitute of One HealthWenzhou Medical UniversityZhejiang Provincial Key Laboratory of Medical GeneticsMinistry of EducationWenzhou 325035Zhejiang ProvinceChina

BACKGROUND Colorectal cancer(CRC)ranks among the most prevalent malignant tumors globally.Recent reports suggest that Fusobacterium nucleatum(F.nucleatum)contributes to the initiation,progression,and prognosis of CRC.Butyrate,a short-chain fatty acid derived from the bacterial fermentation of soluble dietary fiber,is known to inhibit various cancers.This study is designed to explore whether F.nucleatum influences the onset and progression of CRC by impacting the intestinal metabolite butyric acid.AIM To investigate the mechanism by which F.nucleatum affects CRC occurrence and development.METHODS Alterations in the gut microbiota of BALB/c mice were observed following the oral administration of F.nucleatum.Additionally,DLD-1 and HCT116 cell lines were exposed to sodium butyrate(NaB)and F.nucleatum in vitro to examine the effects on proliferative proteins and mitochondrial function.RESULTS Our research indicates that the prevalence of F.nucleatum in fecal samples from CRC patients is significantly greater than in healthy counterparts,while the prevalence of butyrate-producing bacteria is notably lower.In mice colonized with F.nucleatum,the population of butyrate-producing bacteria decreased,resulting in altered levels of butyric acid,a key intestinal metabolite of butyrate.Exposure to NaB can impair mitochondrial morphology and diminish mitochondrial membrane potential in DLD-1 and HCT116 CRC cells.Consequently,this leads to modulated production of adenosine triphosphate and reactive oxygen species,thereby inhibiting cancer cell prolif-eration.Additionally,NaB triggers the adenosine monophosphate-activated protein kinase(AMPK)signaling pathway,blocks the cell cycle in HCT116 and DLD-1 cells,and curtails the proliferation of CRC cells.The combined presence of F.nucleatum and NaB attenuated the effects of the latter.By employing small interfering RNA to suppress AMPK,it was demonstrated that AMPK is essential for NaB’s inhibition of CRC cell proliferation.CONCLUSION F.nucleatum can promote cancer progression through

关键词： Colorectal cancer Fusobacterium nucleatum Butyric acid Gut microbiota Adenosine monophosphate-activated protein kinase signal pathway

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What can we learn from quality assurance badges in open-source software?

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Science China(Information Sciences) 2024年第4期67卷 146-163页

作者： Feng LI Yiling lou xin TAN Zhenpeng CHEN Jinhao DONG Yang LI Xuanzhi WANG Dan HAO Lu ZHANG MoE Key Lab of HCST School of Computer SciencePeking University Department of Computer Science Purdue University School of Computer Science & Engineering Beihang University(BUAA) Department of Computer Science University College London(UCL)

In the development of open-source software(OSS), many developers use badges to give an overview of the software and share some key features/metrics conveniently. Among various badges, quality assurance(QA) badges make up a large proportion and are the most prevalent because QA is of vital importance in software development, and ineffective QA may lead to anomalies or defects. In this paper, we focus on QA badges in open-source projects, which present quality assurance information directly and instantly,and aim to produce some interesting findings and provide practical implications. We collect and analyze 100000 projects written in popular programming languages from GitHub and conduct a comprehensive empirical study both inside and outside QA badges. Inside QA badges, we build a category classification for all QA badges based on the properties they focus on, which shows the types of QA badges developers use. Then,we analyze the frequency of the properties that QA badges focus on, and property combinations, too, which present their use status. We find that QA badges focus on various properties while developers give different preferences to different properties. The use status also differs between different programming languages. For example, projects written in C focus on Security to a great extent. Our findings also provide implications for developers and badge providers. Outside QA badges, we conduct a correlation analysis between QA badges and some software metrics that have potential relationships with code quality, contribution quality, and popularity. We find that QA badges have statistically significant correlations with various software metrics.

关键词： quality assurance badge open-source software code quality empirical study

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Diagnosis of poorly differentiated adenocarcinoma of the stomach by confocal laser endomicroscopy:A case report

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World Journal of Clinical Cases 2024年第8期12卷 1481-1486页

作者： Jia-xin lou Yong Wu Muren Huhe Jing-Jie Zhang Dong-Wu Jia Zhen-Yu Jiang Department of Gastroenterology The Second Affiliated Hospital of Baotou Medical CollegeInner Mongolia University of Science and TechnologyBaotou 014030Inner Mongolia Autonomous RegionChina Medical Innovation Center The Fourth Military Medical UniversityXi'an 710000Shaanxi ProvinceChina

BACKGROUND In recent years,confocal laser endomicroscopy(CLE)has become a new endoscopic imaging technology at the microscopic level,which is extensively performed for real-time in vivo histological examination.CLE can be performed to distinguish benign from malignant lesions.In this study,we diagnosed using CLE an asymptomatic patient with poorly differentiated gastric adenocarcinoma.CASE SUMMARY A 63-year-old woman was diagnosed with gastric mucosal lesions,which may be gastric cancer,in the small curvature of the stomach by gastroscopy.She consented to undergo CLE for morphological observation of the gastric mucosa.Through the combination of CLE diagnosis and postoperative pathology,the intraoperative CLE diagnosis was considered to be reliable.According to our experience,CLE can be performed as the first choice for the diagnosis of gastric cancer.CONCLUSION CLE has several advantages over pathological diagnosis.We believe that CLE has great potential in the diagnosis of benign and malignant gastric lesions.

关键词： Confocal laser endomicroscopy Poorly differentiated gastric adenocarcinoma Diagnosis Early stage Case report

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