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基于FAERS数据库对恩曲替尼不良事件信号挖掘与分析

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中国新药杂志 2024年第13期33卷 1396-1402页

作者：丁楚凤王宇婷伍绮敏郑靖萍马麟宿凌暨南大学药学院广州中医药大学第二附属医院药学部

目的:基于美国FDA不良事件报告系统(FDA Adverse Event Reporting System, FAERS)数据库挖掘恩曲替尼的不良事件(adverse event, AE)信号，为临床安全用药提供参考。方法:利用OpenVigil 2.1数据平台，收集FAERS数据库中2004年第1季度—2... 详细信息

目的:基于美国FDA不良事件报告系统(FDA Adverse Event Reporting System, FAERS)数据库挖掘恩曲替尼的不良事件(adverse event, AE)信号，为临床安全用药提供参考。方法:利用OpenVigil 2.1数据平台，收集FAERS数据库中2004年第1季度—2023年第1季度的恩曲替尼相关AE报告，利用比例失衡法中的报告比值比(reporting odds ratio, ROR)法和比例报告比值(proportional reporting ratio, PRR)法进行数据挖掘。结果:共检索到目标药物恩曲替尼相关的AE报告600份，AE报告数呈波动上升趋势；共挖掘到82个AE信号，涉及16种系统器官分类(System Organ Class, SOC),主要为各类神经系统疾病和全身性疾病及给药部位各种反应，其次为肾脏及泌尿系统疾病、心脏系统疾病。报告例次排名靠前的AE信号涉及死亡、头晕、肾功能损坏等首选术语(preferred term, PT),肾功能损害、血肌酐升高、急性肾损伤、心肌炎等PT未被药品说明书收录；信号强度排名靠前的AE信号涉及构音困难、味觉障碍、共济失调等PT,其中构音困难、味觉障碍等大部分PT已被药品说明书收录，肌钙蛋白I升高等PT尚未被药品说明书收录。结论:恩曲替尼导致的AE包括各类神经系统疾病、心脏系统疾病、肾脏及泌尿系统疾病等；临床使用恩曲替尼治疗期间应重点关注患者的各类神经、肾脏和心脏毒性反应。

关键词：恩曲替尼不良事件美国FDA不良事件报告系统信号挖掘

Revealing the Structure-Property Difference of Natural Rubber Prepared by Different Methods: Protein and Gel Content are Key Factors

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Chinese Journal of Polymer Science 2024年第4期42卷 457-467页

作者： Shao-qi Huang Jun-qi Zhang Yong Zhu Ling-min Kong Lu-Sheng Liao Fu-Quan Zhang Zheng-Tian Xie Jin-Rong wu State Key Laboratory of Polymer Materials Engineering College of Polymer Science and EngineeringSichuan UniversityChengdu610065China Hainan Provincial Key Laboratory of Natural Rubber Processing Agricultural Products Processing Research Institute of Chinese Academy of Tropical Agricultural SciencesZhanjiang524001China

Natural rubber (NR) is widely used in various fields including aerospace, military industry and transportation due to its superior elasticity and comprehensive mechanical properties. Nonetheless, the commercial NR prepared by different methods usually exhibits different mechanical properties, primarily due to variations in processing conditions during the conversion from latex to bulk rubber material. Consequently, this poses challenges in scientific research and industrial production of NR. In order to assess the properties of various commercially available NR and identify key structural and compositional components, this study systematically compares and analyzes four representative NR raw materials: air dried sheet (ADS), ribbed smoked sheets (RSS), constant viscidity NR (CV), and whole field latex rubber (WF). The investigation focuses on evaluating their static mechanical behavior, SIC behavior, wear resistance, and fatigue resistance. The findings indicate that protein and gel content exhibit a crucial influence on the NR properties. These constituents contribute to the formation of a high-crosslinking density region, generating a heterogeneous network structure within the rubber. This structure amplifies strains during deformation, leading to earlier and stronger strain-induced crystallization (SIC). Among the four commercial NR brands, RSS demonstrates superior overall mechanical and dynamic properties owing to its high protein and gel content. This study serves as a valuable reference for comprehending the differences in properties among various commercial NR, thereby offering guidance for the actual processing and selection of NR.

关键词： Natural rubber Processingmethod Protein Gel content Property

Asperuloside Promotes Apoptosis of Cervical Cancer Cells through Endoplasmic Reticulum Stress-Mitochondrial Pathway

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Chinese Journal of Integrative Medicine 2024年第1期30卷 34-41页

作者： qi Zhi-min WANG Xia LIU Xia ZHAO Juan Medical Examination Center Hebei Province Hospital of Chinese MedicineShijiazhuang(050011)China Department of Gynaecology and Obstetrics Hebei Province Hospital of Chinese MedicineShijiazhuang(050011)China Experimental Center for Teaching Hebei Medical UniversityShijiazhuang(050017)China

Objective: To investigate the effects of asperuloside on cervical cancer based on endoplasmic reticulum(ER) stress and mitochondrial pathway. Methods: Different doses(12.5–800 μg/mL) of asperuloside were used to treat cervical cancer cell lines Hela and CaSki to calculate the half maximal inhibitory concentration(IC_(50)) of asperuloside. The cell proliferation was analyzed by clone formation assay. Cell apoptosis, intracellular reactive oxygen species(ROS) and mitochondrial membrane potential were determined by flow cytometry. The protein expressions of cleaved-caspase-3, Bcl-2, Bax, Cyt-c, cleaved-caspase-4 and glucose-regulated protein 78(GRP78) were analyzed by Western blot. And the inhibitor of ER stress, 4-phenyl butyric acid(4-PBA) was used to treat cervical cancer cells to further verify the role of ER stress in the apoptosis of cervical cancer cells induced by asperuloside. Results: Asperuloside of 325, 650, and 1300 μg/mL significantly inhibited the proliferation and promoted apoptosis of Hela and CaSki cells(P<0.01). All doses of asperuloside significantly increased intracellular ROS levels, reduced mitochondrial membrane potential, significantly reduced Bcl-2 protein expression level, and increased Bax, Cyt-c, GRP78 and cleaved-caspase-4 expressions(P<0.01). In addition, 10 mmol/L 4-PBA treatment significantly promoted cell proliferation and reduced apoptosis(P<0.05), and 650 μg/mL asperuloside could reverse 4-PBA-induced increased cell proliferation, decreased apoptosis and cleaved-caspase-3,-4 and GRP78 protein expressions(P<0.05). Conclusion: Our study revealed the role of asperuloside in cervical cancer, suggesting that asperuloside promotes apoptosis of cervical cancer cells through ER stress-mitochondrial pathway.

关键词： asperuloside Chinese medicine cervical cancer endoplasmic reticulum stress mitochondrial damage apoptosis

Efficacy and safety of Yiqi Peiyuan granules for improving the short-term prognosis of patients with acute kidney injury:A multicenter,double-blind,placebo-controlled,randomized trial

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Journal of Integrative Medicine 2024年第3期22卷 279-285页

作者： Jia-jia wu Tian-yi Zhang Ying-hui qi min-yan Zhu Yan Fang Chao-jun qi Li-ou Cao Ji-fang Lu Bo-han Lu Lu-min Tang Jian-xiao Shen Shan Mou Department of Nephrology Molecular Cell Lab for Kidney DiseaseShanghai Peritoneal Dialysis Research CenterUremia Diagnosis and Treatment CenterRenji Hospital Affiliated to Shanghai Jiaotong University School of MedicineShanghai 200127China Department of Nephrology Shanghai Pudong New Area Punan HospitalShanghai 200125China Department of Nephrology Ningbo Hangzhou Bay HospitalNingbo 315336Zhejiang ProvinceChina

Background:Yiqi Peiyuan(YQPY)prescription,a composite prescription of traditional Chinese medicine,has been used to prevent or delay the continued deterioration of renal function after acute kidney injury(AKI)in some institutions and has shown considerable efficacy.Objective:This is the first randomized controlled trial to assess efficacy and safety of YQPY for improving short-term prognosis in adult patients with AKI.Design,setting,participants and interventions:This is a prospective,double-blind,multicenter,randomized,and placebo-controlled clinical trial.A total of 144 enrolled participants were randomly allocated to two groups according to a randomization schedule.Participants,caregivers and investigators assessing the outcomes were blinded to group assignment.Patients in the YQPY group received 36 g YQPY granules twice a day for 28 days.Patients in the placebo group received a placebo in the same dose as the YQPY granules.Main outcome measures:The primary outcome was the change in the estimated glomerular filtration rate(eGFR)between baseline and after 4 and 24 weeks of treatment.The secondary outcomes were the change of serum creatinine(Scr)level between baseline and after treatment,and the incidence of endpoint events,defined as eGFR increasing by more than 25%above baseline,eGFR>75 mL/min per1.73 m2or the composite endpoint,which was defined as the sum of patients meeting either of the above criteria.Results:Data from a total of 114 patients(59 in the YQPY group and 55 in the control group)were analyzed.The mean changes in eGFR and Scr in weeks 4 and 24 had no difference between the two groups.In further subgroup analysis(22 in the YQPY group and 31 in the control group),the mean change in eGFR after treatment for 4 weeks was 27.39 mL/min per 1.73 m2in the YQPY group and 5.78 mL/min per1.73 m2in the placebo group,and the mean difference between groups was 21.61 mL/min per 1.73 m2(P<0.001).Thirteen(59.1%)patients in the YQPY group and 5(16.1%)in the placebo group reached the composite endpoints(P=0.002).Du

关键词： Chinese herbal medicine Randomized controlled trial Acute kidney injury Renal function

Discovering deaminases using AlphaFold2:a strategy to search for tool proteins for gene editing

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Signal Transduction and Targeted Therapy 2024年第3期9卷 822-824页

作者： Yongye Huang Jianxin Jiang min wu Key Laboratory of Bioresource Research and Development of Liaoning Province College of Life and Health SciencesNortheastern UniversityShenyang 110169China Wound Trauma Medical Center State Key Laboratory of TraumaBurns and Combined InjuryDaping HospitalArmy Medical UniversityChongqing 400042China Wenzhou Traditional Chinese Medicine Hospital of Zhejiang Chinese Medical University WenzhouZhejiang 325000China Wenzhou Institute University of Chinese Academy of SciencesWenzhou 325000China The Joint Research Center Affiliated Xiangshan Hospital of Wenzhou Medical UniversityNingboChina

A recent study by Huang et al.published in Cell reported the application of AlphaFold2 to forecast the structures of deaminase proteins and cluster them based on structural similarity,creating a truncated Sdd that can be used as a cytosine base editor(CBE)to be integrated into a single adeno-associated virus(AAV)1 This ground-breaking study aided by the artificial intelligence system would largely broaden the utility of tool proteins for gene editing.

关键词： CBE Alpha editor

Treatment of multisystem inflammatory syndrome in children

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World Journal of Pediatrics 2024年第4期20卷 325-339页

作者： Tong Tong Yi-Hua Jin min Wang Fang-qi Gong Department of Cardiology Children's HospitalZhejiang University School of MedicineNational Clinical Research Center for Child HealthNo.3333 Binsheng RoadHangzhou 310052China

Background Multisystem inflammatory syndrome in children(MIS-C),a relatively uncommon but severe pediatric complication,is associated with coronavirus disease 2019(COVID-19).A variety of treatment approaches,including intravenous immunoglobulins(IVIGs),glucocorticoids(GCs)and biologic agents,such as anakinra and infliximab,have been described for the management of COVID-19-related MIS-C.Anticoagulant therapy is also important.However,a well-developed treatment system has not been established,and many issues remain controversial.Several recently published articles related to the treatment of MIS-C have been released.Hence,in this review,we identified relevant articles published recently and summarized the treatment of MIS-C more comprehensively and systematically.Data sources We reviewed the literature on the treatment of MIS-C through 20 September 2023.The PubMed/Medline,Web of Science,EMBASE,and Cochrane Library databases were searched with the combination of the terms"multisystem inflammatory syndrome","MIS-C","PIMS-TS","therapy","treatment","drug","IVIG","GCs","intravenous immunoglobulin","corticosteroids","biological agent",and"aspirin".Results The severity of MIS-C varies,and different treatment schemes should be used according to the specific condition.Ongoing research and data collection are vital to better understand the pathophysiology and optimal management of MIS-C.Conclusions MIS-Cis a disease involving multiple systems and has great heterogeneity.With the accumulation of additional experience,we have garnered fresh insights into its treatment strategies.However,there remains a critical need for greater standardization in treatment protocols,alongside the pressing necessity for more robust and meticulously conducted studies to deepen our understanding of these protocols.

关键词： Coronavirus disease 2019-Corticosteroids Intravenous immunoglobulin Multisystem inflammatory syndrome in children-Treatment

Adaptive sampling for corrugated plate digitization using a laser displacement sensor

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Science China(Technological Sciences) 2024年第5期67卷 1510-1523页

作者： wu ChengXing qi qi CHEN BaiJin YANG JiXiang DING Han State Key Laboratory of Intelligent Manufacturing Equipment and Technology School of Mechanical Science and EngineeringHuazhong University of Science and TechnologyWuhan430074China State Key Laboratory of Intelligent Manufacturing Equipment and Technology School of Materials Science and EngineeringHuazhong University of Science and TechnologyWuhan430074China

The surface quality of a corrugated plate directly determines the heat transfer property of the thermal power mechanical apparatus.Traditional detection methods are impractical for real-world production,being slow and destructive.In contrast,the point laser displacement sensor,employing the optical triangle method,emerges as a promising device for assessing parts with variable curvature and highly reflective surfaces.Despite its benefits,high-density sampling by an innate frequency introduces challenges such as data redundancy and a poor signal-to-noise ratio,potentially affecting the efficiency and precision of subsequent data processing.To address these challenges,adjustable frequency data sampling has been developed for this sensor,allowing adaptive sampling for corrugated plate digitization.The process begins with surface digitization to extract discrete points,which are transformed into intersection curves using the B-spline fitting technique.Subsequently,dominant points are identified,considering multigeometric constraints for curvature and arch height.Finally,the sampling signal is adjusted based on the distribution information of dominant points.Comparative results indicate that the proposed method effectively minimizes redundant sampling without compromising the accurate capture of essential geometric features.

关键词： corrugated plate laser displacement sensor adaptive sampling dominant point curvature arch height

A GNSS Anti-Spoofing Technique Based on the Spatial Distribution Characteristic of the Residual Vectors

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Tsinghua Science and Technology 2024年第2期29卷 457-468页

作者： qi'an wu Xiaowei Cui mingquan Lu Pengxiang Yang Peng wu Department of Electronic Enginnering Tsinghua UniversityBeijing 100084China Xi’an Modern Control Technology Research Institute Xi’an 710065China

Anti-spoofing is becoming a crucial technique for applications with high navigation accuracy and reliability requirements.Anti-spoofing technique based on Receiver Autonomous Integrity Monitoring(RAIM)is a good choice for most Global Navigation Satellite System(GNSS)receivers because it does not require any change to the hardware of the receiver.However,the conventional RAIM method can only detect and mitigate a single spoofing signal.Some improved RAIM methods can deal with more spoofing signals,but the computational complexity increases dramatically when the number of satellites in view increase or need additional information.This paper proposes a new RAIM method,called the SRV-RAIM method,which has a very low computation complexity regardless of the number of satellites in view and can deal with any number of spoofing signals.The key to the new method is the spatial distribution characteristic of the Satellites'Residual Vectors(SRV).In replay or generative spoofing scenarios,the pseudorange measurements of spoofing signals are consistent,the residual vectors of real satellites and those of spoofing satellites have good separation characteristics in spatial distribution.Based on this characteristic,the SRV-RAIM method is proposed,and the simulation results show that the method can separate the real signals and the spoofing signals with an average probability of 86.55%in the case of 12 visible satellites,regardless of the number of spoofing signals.Compared to the conventional traversal-RAIM method,the performance is only reduced by 3.59%,but the computational cost is reduced by 98.3%,so most of the GNSS receivers can run the SRV-RAIM algorithm in time.

关键词： Global Navigation Satellite System(GNSS) anti-spoofing Receiver Autonomous Integrity Monitoring(RAIM) Satellites'Residual Vectors(SRV)

Ileal collision tumor associated with gastrointestinal bleeding: A case report and review of literature

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World Journal of Gastrointestinal Surgery 2024年第2期16卷 628-634页

作者： Yu-qi wu Hong-Yan Wang Mu-min Shao Lin Xu Xiao-Yan Jiang Shao-Ju Guo Department of Gastroenterology Shenzhen Traditional Chinese Medicine HospitalThe Fourth Clinical Medical College of Guangzhou University of Chinese MedicineShenzhen 518033Guangdong ProvinceChina Department of Pathology Shenzhen Traditional Chinese Medicine HospitalThe Fourth Clinical Medical College of Guangzhou University of Chinese MedicineShenzhen 518033Guangdong ProvinceChina

BACKGROUND Collision tumors involving the small intestine,specifically the combination of a hamartomatous tumor and a lipoma,are extremely rare.To our knowledge,no previous case report has described a collision tumor composed of two benign tumors of different origins in the small intestine.CASE SUMMARY Here,we present the case of an 82-year-old woman who presented with hemorrhagic shock and was found to have a mass measuring approximately 50 mm×32 mm×30 mm in the terminal ileum.Based on computed tomography scan findings,the mass was initially suspected to be a lipoma.A subsequent colonoscopy revealed a pedunculated submucosal elevation consisting of two distinct parts with a visible demarcation line.A biopsy of the upper portion suggested a juvenile polyp(JP).Owing to the patient’s advanced age,multiple comorbidities,and poor surgical tolerance,a modified endoscopic submucosal dissection was performed.Histopathological examination of the excised mucosal mass revealed a lipoma at the base and a JP at the top,demonstrating evidence of rupture and associated bleeding.The patient’s overall health remained satisfactory,with no recurrence of hematochezia during the six-month follow-up period.CONCLUSION This case report provides new evidence for the understanding of gastrointestinal collision tumors,emphasizing their diverse clinical presentations and histopathological characteristics.It also offers diagnostic and therapeutic insights as well as an approach for managing benign collision tumors.

关键词： Collision tumor Gastrointestinal bleeding Hamartomatous tumor Lipoma Modified endoscopic submucosal dissection Case report