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Aspirin Enhances the Protective Effect of Progesterone on Trophoblast Cell from Oxidative Stress and Apoptosis

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Reproductive and Developmental Medicine 2021年第1期5卷 1-8页

作者： Jia-Wei Shi Hui-Li Yang zhen-zhen lai Hui-Hui Shen Lu-Yu Ruan Yan Wang Xue-Min Qiu Feng Xie Ming-Qing Li Laboratory for Reproductive Immunology Institute of Obstetrics and GynecologyHospital of Obstetrics and GynecologyShanghai Medical SchoolFudan UniversityShanghai 200080China Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases Shanghai200080China

Objective:Clinically,low-dose aspirin and progesterone are frequently used to prevent pregnancy loss.We investigated the effect of these drugs on the biological behavior of human extravillous trophoblasts in vitro.Methods:HTR-8/SVneo cells were cultured in vitro and treated with different concentrations of aspirin and progesterone.The proliferation,invasion,and apoptosis of HTR-8/SVneo cells were assessed using a cell counting Kit-8 assay,Matrigel Transwell assay,and Hoechst staining,respectively.Reverse transcriptase polymerase chain reaction was used to verify the expression of related genes.Reactive oxygen species(ROS)levels were detected using the 2,7-dichlorofluorescin diacetate assay.Results:Low-dose aspirin alone,progesterone alone,or aspirin plus progesterone upregulated the proliferation and invasion and decreased the apoptosis of HTR-8/SVneo cells.Moreover,the expression of marker of proliferation Ki-67(MKI67),matrix metalloproteinases 2(MMP2),and MMP9 was increased.In addition,low-dose aspirin plus progesterone exerted stronger anti-apoptosis effects than low-dose aspirin and progesterone alone.Interestingly,aspirin upregulated the expression of progesterone receptor(PGR).Treatment with hydrogen peroxide(H_(2)O_(2))promoted ROS production in HTR-8/SVneo cells;however,low-dose aspirin plus progesterone significantly restricted H_(2)O_(2)-mediated ROS production and apoptosis in HTR-8/SVneo cells.Conclusions:These data suggest that low-dose aspirin and progesterone promote proliferation and invasion and cooperatively reduce oxidative stress and apoptosis in trophoblasts in vitro.These results may provide an experimental basis for the combined application of aspirin and progesterone to prevent unexplained recurrent spontaneous miscarriage,especially in patients with trophoblast dysfunction.

关键词： Apoptosis Aspirin Invasion Miscarriage Progesterone Progesterone Receptor Proliferation Reactive Oxygen Species Trophoblasts

The Application of Aspirin in Pregnancy-Related Complications

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Reproductive and Developmental Medicine 2020年第3期4卷 184-190页

作者： Lu-Yu Ruan zhen-zhen lai Hui-Li Yang Shao-Liang Yang Si-Yao Ha Jia-Wei Shi Hui-Hui Shen Ming-Qing Li Laboratory for Reproductive Immunology Institute of Obstetrics and GynecologyHospital of Obstetrics and GynecologyFudan UniversityShanghai 200080China Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases Hospital of Obstetrics and GynecologyFudan UniversityShanghai 200011China NHC Key Lab of Reproduction Regulation(Shanghai Institute of Planned Parenthood Research) Fudan UniversityShanghai 230032China

Aspirin,one of the most widely applied medicines,not only possesses the effects on reducing fever,anti-vascular hyperplasia,and anti-inflammation,but also has the capacity of preventing platelet aggregation.So far,it is acceptable to adopt aspirin,especially low-dose aspirin(LDA),to prevent pregnancy-related complications,such as pregnancy complicated by antiphospholipid syndrome,systemic lupus erythematosus,or preeclampsia;unexplained recurrent spontaneous abortion;fetal growth restriction;and preterm birth.In this article,we reviewed the possible mechanism of action and applications of aspirin in these pregnancy-related complications.

关键词： Abortion Antiphospholipid Antibodies Aspirin Fetal Growth Restriction Preeclampsia Pregnancy Preterm Birth Systemic Lupus Erythematosus

Cyclooxygenase-2 and Decidual Immune Cells

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Reproductive and Developmental Medicine 2019年第3期3卷 177-184页

作者： Si-Yao Ha Hui-Li Yang zhen-zhen lai Lu-Yu Ruan Jia-Wei Shi Ming-Qing Li Laboratory for Reproductive Immunology Institute of Obstetrics and GynecologyHospital of Obstetrics and GynecologyFudan UniversityShanghai 200080China Laboratory for Reproductive Immunology Shanghai Key Laboratory of Female Reproductive Endocrine Related DiseasesHospital of Obstetrics and GynecologyFudan UniversityShanghai 200011China Laboratory for Reproductive Immunology NHC Key Laboratory of Reproduction Regulation(Shanghai Institute of Planned Parenthood Research)Fudan UniversityShanghai 230032China

Cyclooxygenase-2(COX-2)is a rate-limiting enzyme in arachidonic acid(AA)metabolism.COX-2 and its products(prostanoids)serve versatile biological functions during pregnancy.Numerous evidences demonstrate special reprogramming of COX-2-catalyzing AA metabolism in decidual immune cells(DICs),particularly in decidual macrophages,corresponding to special gestational phases.This review summarizes the reprogramming of COX-2-catalyzing AA metabolism in DICs as well as the immunoregulation of diverse COX-2-generating prostanoids in DICs during the different phases of gestation.

关键词： Cyclooxygenase-2 Decidual Immune Cell Metabolism Pregnancy Prostanoid

Pathogenesis, diagnosis, and treatment of epilepsy: electromagnetic stimulation-mediated neuromodulation therapy and new technologies

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Neural Regeneration Research 2025年第4期20卷 917-935页

作者： Dian Jiao lai Xu zhen Gu Hua Yan Dingding Shen Xiaosong Gu Academy of Medical Engineering and Translational Medicine Tianjin UniversityTianjinChina Key Laboratory of Advanced Drug Delivery Systems of Zhejiang Province College of Pharmaceutical SciencesZhejiang UniversityHangzhouZhejiang ProvinceChina Affiliated Hospital of Nantong University NantongJiangsu ProvinceChina

Epilepsy is a severe,relapsing,and multifactorial neurological disorder.Studies regarding the accurate diagnosis,prognosis,and in-depth pathogenesis are crucial for the precise and effective treatment of epilepsy.The pathogenesis of epilepsy is complex and involves alterations in variables such as gene expression,protein expression,ion channel activity,energy metabolites,and gut microbiota composition.Satisfactory results are lacking for conventional treatments for epilepsy.Surgical resection of lesions,drug therapy,and non-drug interventions are mainly used in clinical practice to treat pain associated with epilepsy.Non-pharmacological treatments,such as a ketogenic diet,gene therapy for nerve regeneration,and neural regulation,are currently areas of research focus.This review provides a comprehensive overview of the pathogenesis,diagnostic methods,and treatments of epilepsy.It also elaborates on the theoretical basis,treatment modes,and effects of invasive nerve stimulation in neurotherapy,including percutaneous vagus nerve stimulation,deep brain electrical stimulation,repetitive nerve electrical stimulation,in addition to non-invasive transcranial magnetic stimulation and transcranial direct current stimulation.Numerous studies have shown that electromagnetic stimulation-mediated neuromodulation therapy can markedly improve neurological function and reduce the frequency of epileptic seizures.Additionally,many new technologies for the diagnosis and treatment of epilepsy are being explored.However,current research is mainly focused on analyzing patients’clinical manifestations and exploring relevant diagnostic and treatment methods to study the pathogenesis at a molecular level,which has led to a lack of consensus regarding the mechanisms related to the disease.

关键词： diagnosis drug treatment electroencephalography epilepsy monitoring epilepsy nerve regeneration neurostimulation non-drug interventions pathogenesis prediction

Teneligliptin mitigates diabetic cardiomyopathy by inhibiting activation of the NLRP3 inflammasome

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World Journal of Diabetes 2024年第4期15卷 724-734页

作者： Gu-Lao Zhang Yuan Liu Yan-Feng Liu Xian-Tao Huang Yu Tao zhen-Huan Chen Heng-Li lai Department of Cardiology Jiangxi Provincial People's HospitalThe First Affiliated Hospital of Nanchang Medical CollegeNanchang 330000Jiangxi ProvinceChina

BACKGROUND Diabetic cardiomyopathy(DCM),which is a complication of diabetes,poses a great threat to public health.Recent studies have confirmed the role of NLRP3(NOD-like receptor protein 3)activation in DCM development through the inflammatory response.Teneligliptin is an oral hypoglycemic dipeptidyl peptidase-IV inhibitor used to treat diabetes.Teneligliptin has recently been reported to have anti-inflammatory and protective effects on myocardial cells.AIM To examine the therapeutic effects of teneligliptin on DCM in diabetic mice.METHODS Streptozotocin was administered to induce diabetes in mice,followed by treatment with 30 mg/kg teneligliptin.RESULTS Marked increases in cardiomyocyte area and cardiac hypertrophy indicator heart weight/tibia length reductions in fractional shortening,ejection fraction,and heart rate;increases in creatine kinase-MB(CK-MB),aspartate transaminase(AST),and lactate dehydrogenase(LDH)levels;and upregulated NADPH oxidase 4 were observed in diabetic mice,all of which were significantly reversed by teneligliptin.Moreover,NLRP3 inflammasome activation and increased release of interleukin-1βin diabetic mice were inhibited by teneligliptin.Primary mouse cardiomyocytes were treated with high glucose(30 mmol/L)with or without teneligliptin(2.5 or 5μM)for 24 h.NLRP3 inflammasome activation.Increases in CKMB,AST,and LDH levels in glucose-stimulated cardiomyocytes were markedly inhibited by teneligliptin,and AMP(p-adenosine 5‘-monophosphate)-p-AMPK(activated protein kinase)levels were increased.Furthermore,the beneficial effects of teneligliptin on hyperglycaemia-induced cardiomyocytes were abolished by the AMPK signaling inhibitor compound C.CONCLUSION Overall,teneligliptin mitigated DCM by mitigating activation of the NLRP3 inflammasome.

关键词： Diabetic cardiomyopathy Teneligliptin NLRP3 AMPK Interleukin-1β

NLRP3 activation in macrophages promotes acute intestinal injury in neonatal necrotizing enterocolitis

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World Journal of Pediatrics 2024年第2期20卷 153-164页

作者： Bo Shi Cheng-Jie Lyu zhen-Kai Le Hao-Sen Ji Yi Xiao Yuan-Yuan Zhang Shou-Jiang Huang Lin-Jun Yu Qiang Shu Jin-Fa Tou Deng-Ming lai Department of Neonatal Surgery Children’s HospitalZhejiang University School of MedicineNational Clinical Research Center for Child HealthHangzhou 310052China Department of Pulmonology Children’s HospitalZhejiang University School of MedicineNational Clinical Research Center for Child HealthHangzhou 310052China Department of Thoracic and Cardiovascular Surgery Children’s HospitalZhejiang University School of MedicineNational Clinical Research Center for Child HealthHangzhou 310052China

Background Macrophages are involved in various immune inflammatory disease conditions.This study aimed to investigate the role and mechanism of macrophages in regulating acute intestinal injury in neonatal necrotizing enterocolitis(NEC).Methods CD68,nucleotide-binding oligomerization domain,leucine-rich repeat,and pyrin domain-containing 3(NLRP3),cysteine aspartate-specific protease-1(caspase-1),and interleukin-1β(IL-1β)in paraffin sections of intestinal tissues from NEC and control patients were detected with immunohistochemistry,immunofluorescence,and western blot.Hypertonic pet milk,hypoxia and cold stimulation were used to establish a mouse(wild type and Nlrp3^(-/-))model of NEC.The mouse macrophage(RAW 264.7)and rat intestinal epithelial cell-6 lines were also cultured followed by various treatments.Macrophages,intestinal epithelial cell injuries,and IL-1β release were determined.Results Compared to the gut“healthy”patients,the intestinal lamina propria of NEC patients had high macrophage infiltration and high NLRP3,caspase-1,and IL-1β levels.Furthermore,in vivo,the survival rate of Nlrp3^(-/-)NEC mice was dramatically improved,the proportion of intestinal macrophages was reduced,and intestinal injury was decreased compared to those of wild-type NEC mice.NLRP3,caspase-1,and IL-1β derived from macrophages or supernatant from cocultures of macrophages and intestinal epithelial cells also caused intestinal epithelial cell injuries.Conclusions Macrophage activation may be essential for NEC development.NLRP3/caspase-1/IL-1β cellular signals derived from macrophages may be the underlying mechanism of NEC development,and all these may be therapeutic targets for developing treatments for NEC.

关键词： Caspase-1 Interleukin-1β Macrophage Necrotizing enterocolitis NLRP3

Novel PIKfyve/Tubulin Dual-target Inhibitor as a Promising Therapeutic Strategy for B-cell Acute Lymphoblastic Leukemia

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Current Medical Science 2024年第2期44卷 298-308页

作者： zhen LU Qian lai Zhi-feng LI Meng-ya ZHONG Yue-long JIANG Li-ying FENG Jie ZHA Jing-wei YAO Yin LI Xian-ming DENG Bing XU Department of Hematology The First Affiliated Hospital of Xiamen University and Institute of HematologySchool of MedicineXiamen UniversityXiamen361005China Key Laboratory of Xiamen for Diagnosis and Treatment of Hematological Malignancy Xiamen361005China Department of Oncology The First Affiliated Hospital of Jinan UniversityJinan UniversityGuangzhou510630China State Key Laboratory of Cellular Stress Biology Innovation Center for Cell Signaling NetworkSchool of Life SciencesXiamen UniversityXiamen361003China

Objective:In B-cell acute lymphoblastic leukemia(B-ALL),current intensive chemotherapies for adult patients fail to achieve durable responses in more than 50%of cases,underscoring the urgent need for new therapeutic regimens for this patient population.The present study aimed to determine whether HZX-02-059,a novel dual-target inhibitor targeting both phosphatidylinositol-3-phosphate 5-kinase(PIKfyve)and tubulin,is lethal to B-ALL cells and is a potential therapeutic for B-ALL patients.Methods:Cell proliferation,vacuolization,apoptosis,cell cycle,and in-vivo tumor growth were evaluated.In addition,Genome-wide RNA-sequencing studies were conducted to elucidate the mechanisms of action underlying the anti-leukemia activity of HZX-02-059 in B-ALL.Results:HZX-02-059 was found to inhibit cell proliferation,induce vacuolization,promote apoptosis,block the cell cycle,and reduce in-vivo tumor growth.Downregulation of the p53 pathway and suppression of the phosphoinositide 3-kinase(PI3K)/AKT pathway and the downstream transcription factors c-Myc and NF-κB were responsible for these observations.Conclusion:Overall,these findings suggest that HZX-02-059 is a promising agent for the treatment of B-ALL patients resistant to conventional therapies.

关键词： B-cell acute lymphoblastic leukemia dual-target inhibitor NF-kB c-Myc PI3K/AKT p53

Low-noise and low-power pixel sensor chip for gas pixel detectors

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Nuclear Science and Techniques 2024年第3期35卷 142-152页

作者： Zhuo Zhou Shi-Qiang Zhou Dong Wang Xiang-Ming Sun Chao-Song Gao Peng-zhen Zhu Wei-Ping Ren Jun Liu Mu-Xian Li Chen Lian Chun-lai Dong PLAC Key Laboratory of Quark and Lepton Physics(MOE)Central China Normal UniversityWuhan 430079China

Topmetal-M2 is a large-area pixel sensor chip fabricated using the GSMC 130 nm CMOS process in 2021.The pixel array of Topmetal-M2 consists of pixels of 400 rows×512 columns with a pixel pitch of 45μm×45μm.The array is divided into 16 subarrays,with pixels of 400 rows×32 columns per subarray.Each pixel incorporates two charge sensors:a diode sensor and a Topmetal sensor.The in-pixel circuit primarily consists of a charge-sensitive amplifier for energy measurements,a discriminator with a peak-holding circuit,and a time-to-amplitude converter for time-of-arrival measurements.The pixel of Topmetal-M2 has a charge input range of~0-3 k e-,a voltage output range of~0-180 mV,and a charge-voltage conversion gain of~59.56μV∕e-.The average equivalent noise charge of Topmetal-M2,which includes the readout electronic system noise,is~43.45 e-.In the scanning mode,the time resolution of Topmetal-M2 is 1 LSB=1.25μs,and the precision is^()7.41μs.At an operating voltage of 1.5 V,Topmetal-M2 has a power consumption of~49 mW∕cm~2.In this article,we provide a comprehensive overview of the chip architecture,pixel working principles,and functional behavior of Topmetal-M2.Furthermore,we present the results of preliminary tests conducted on Topmetal-M2,namely,alpha-particle and soft X-ray tests.

关键词： Charge collection Gas detectors Semiconductor detectors X-ray detectors

An Improved Thermal Conductivity Measurement Scheme for Macroscopic Graphitic Films Using the Laser Flash Method

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Journal of Thermal Science 2024年第4期33卷 1480-1490页

作者： ZHANG Peijuan MING Xin LIU Yingjun WANG Xuelong SHI Hang HAO Yuanyuan LU Jiahao LIU zheng lai Haiwen ZHANG Ying GAO Weiwei XU zhen GAO Chao MOE Key Laboratory of Macromolecular Synthesis and Functionalization Department of Polymer Science and EngineeringKey Laboratory of Adsorption and Separation Materials & Technologies of Zhejiang ProvinceZhejiang University Shanxi-Zheda Institute of Advanced Materials and Chemical Engineering Special Equipment Safety Supervision and Inspection Institute of Jiangsu Province National Graphene Products Quality Inspection and Testing Center (Jiangsu) Hangzhou Gaoxi Technol Co. Ltd China Academy of Aerospace Aerodynamics

Achieving efficient thermal management urges to exploit high-thermal-conductivity materials to satisfy the boosted demand of heat dissipation.It is critical to adopt standardized characterization protocols to evaluate the intrinsic thermal conductivity of thermal management materials.However,for the most representative laser flash method,the lack of standard measurement methodology and systematic description on the thermal diffusivity and influencing factors has led to significant deviations and confusion of the thermal conduction performance in the emerging thermal management application.Here,the measurement error factors of thermal diffusivity by the common laser flash analyzer(LFA) are discussed.Taking high-thermal-conductivity graphitic film(GF) as a typical case,the key factors are analyzed to guide the measurement protocol of related carbon-based thermal management materials.The basic principle of the LFA measurement,actual pre-processing conditions,instrument parameters setting,and data analysis are elaborated for accurate measurements.Furthermore,the graphene thick films and common isotropic materials are also extended to meet various thermal measurement requirements.Based on the existing practical problems,we propose a feasible test flow to achieve a unified and standardized thermal conductivity measurement,which is beneficial to the rapid development of carbon-based thermal management materials.

关键词： thermal management graphitic film laser flash method thermal conductivity thermal diffusivity