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Chlorogenic acid alleviates hypoxic-ischemic brain injury in neonatal mice

Neural Regeneration Research 2023年第3期18卷 568-576页

作者： Lu-Yao Li Qi Wang Lu Deng zhen lin Jing-Jing lin Xin-Ye Wang Tian-Yang Shen Yi-Hui zheng Wei lin Pei-Jun Li Xiao-Qin Fu Zhen-Lang lin Department of Pharmacy The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityWenzhouZhejiang ProvinceChina Department of Neonatology The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityWenzhouZhejiang ProvinceChina Department of Geriatrics The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityWenzhouZhejiang ProvinceChina Department of Orthopedics The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityWenzhouZhejiang ProvinceChina Department of Neurology The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityWenzhouZhejiang ProvinceChina

Recent studies have shown that chlorogenic acid(CGA),which is present in coffee,has protective effects on the nervous system.However,its role in neonatal hypoxic-ischemic brain injury remains unclear.In this study,we established a newborn mouse model of hypoxic-ischemic brain injury using a modified Rice-Vannucci method and performed intraperitoneal injection of CGA.We found that CGA intervention effectively reduced the volume of cerebral infarct,alleviated cerebral edema,restored brain tissue structure after injury,and promoted axon growth in injured brain tissue.Moreover,CGA pretreatment alleviated oxygen-glucose deprivation damage of primary neurons and promoted neuron survival.In addition,changes in ferroptosis-related proteins caused by hypoxic-ischemic brain injury were partially reversed by CGA.Furthermore,CGA intervention upregulated the expression of the key ferroptosis factor glutathione peroxidase 4 and its upstream glutamate/cystine antiporter related factors SLC7A11 and SLC3A2.In summary,our findings reveal that CGA alleviates hypoxic-ischemic brain injury in neonatal mice by reducing ferroptosis,providing new ideas for the treatment of neonatal hypoxic-ischemic brain injury.

关键词： chlorogenic acid ferroptosis glutathione peroxidase 4 lipid peroxidation neonatal hypoxic-ischemic brain injury neurons neuroprotection oxidative stress oxygen-glucose deprivation system Xc^(-)

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Reperfusion after hypoxia-ischemia exacerbates brain injury with compensatory activation of the antiferroptosis system:based on a novel rat model

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Neural Regeneration Research 2023年第10期18卷 2229-2236页

作者： Tian-Lei Zhang Zhi-Wei Zhang Wei lin Xin-Ru lin Ke-Xin lin Ming-Chu Fang Jiang-Hu Zhu Xiao-ling Guo Zhen-Lang lin Department of Pediatrics the Second School of Medicinethe Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityWenzhouZhejiang ProvinceChina Second Clinical Medical College Wenzhou Medical UniversityWenzhouZhejiang ProvinceChina Key Laboratory of Children Genitourinary Diseases of Wenzhou the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityWenzhouZhejiang ProvinceChina Key Laboratory of Perinatal Medicine of Wenzhou the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityWenzhouZhejiang ProvinceChina Basic Medical Research Center the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityWenzhouZhejiang ProvinceChina

Hypoxic-ischemic encephalopathy,which predisposes to neonatal death and neurological sequelae,has a high morbidity,but there is still a lack of effective prevention and treatment in clinical practice.To better understand the pathophysiological mechanism underlying hypoxic-ischemic encephalopathy,in this study we compared hypoxic-ischemic reperfusion brain injury and simple hypoxic-ischemic brain injury in neonatal rats.First,based on the conventional RiceVannucci model of hypoxic-ischemic encephalopathy,we established a rat model of hypoxic-ischemic reperfusion brain injury by creating a common carotid artery muscle bridge.Then we performed tandem mass tag-based proteomic analysis to identify differentially expressed proteins between the hypoxic-ischemic reperfusion brain injury model and the conventional Rice-Vannucci model and found that the majority were mitochondrial proteins.We also performed transmission electron microscopy and found typical characteristics of ferroptosis,including mitochondrial shrinkage,ruptured mitochondrial membranes,and reduced or absent mitochondrial cristae.Further,both rat models showed high levels of glial fibrillary acidic protein and low levels of myelin basic protein,which are biological indicators of hypoxic-ischemic brain injury and indicate similar degrees of damage.Finally,we found that ferroptosis-related Ferritin(Fth1)and glutathione peroxidase 4 were expressed at higher levels in the brain tissue of rats with hypoxic-ischemic reperfusion brain injury than in rats with simple hypoxic-ischemic brain injury.Based on these results,it appears that the rat model of hypoxic-ischemic reperfusion brain injury is more closely related to the pathophysiology of clinical reperfusion.Reperfusion not only aggravates hypoxic-ischemic brain injury but also activates the anti-ferroptosis system.

关键词： ferroptosis hypoxic-ischemic brain injury hypoxic-ischemic encephalopathy hypoxic-ischemic reperfusion brain injury mitochondria model proteomic analysis reperfusion Rice-Vannucci transmission electron microscopy

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Transseptal approach for catheter ablation of left-sided accessory pathways in children with Marfan syndrome:A case report

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World Journal of Clinical Cases 2023年第9期11卷 2084-2090页

作者： Zi-Yan Dong Wei Shao Yue Yuan Li lin Xia Yu lang Cui zhen zhen Lu Gao Department of Cardiology Beijing Children's HospitalCapital Medical UniversityBeijing 100045China National Center for Children’s Health Beijing Children's HospitalCapital Medical UniversityBeijing 100045China

BACKGROUND Left-sided accessory pathways(APs)can be accessed with either a transaortic(TA)or transseptal approach(TS).For children with Marfan syndrome(MFS)who have aortic disease,the use of TA can aggravate the disease,making TS the best choice for these patients.CASE SUMMARY A 10-year-old girl was hospitalized because of intermittent heart palpitations and chest tightness.She was diagnosed with MFS,supraventricular tachycardia,Wolff-Parkinson-White syndrome,and left-sided AP was detected by cardiac electrophysiological.Catheter ablation was successfully performed via TS under the guidance of the Ensite system.During the follow-up,no recurrence or complications occurred.CONCLUSION The TS for catheter ablation of left-sided APs can be considered in children with MFS.Adequate evaluation and selection of the appropriate puncture site are particularly important.

关键词： Transseptal approach Left-sided accessory pathway Catheter ablation Pediatric Marfan syndrome Case report

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氯喹通过抑制NF-κB和MAPK信号通路减轻脂多糖诱导的BV2小胶质细胞炎症反应

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中国病理生理杂志 2020年第7期36卷 1320-1326页

作者：方明楚林振浪温州医科大学附属第二医院、育英儿童医院新生儿科浙江温州325027

目的:探究氯喹(CQ)对脂多糖(LPS)刺激的BV2小胶质细胞活化的抑制作用及可能机制。方法:将小鼠BV2小胶质细胞分为对照组、LPS组和LPS+CQ组。LPS+CQ组预先给予CQ(10μmol/L)处理30 min再给予LPS刺激,在LPS组和LPS+CQ组中给予LPS(500μg/L... 详细信息

目的:探究氯喹(CQ)对脂多糖(LPS)刺激的BV2小胶质细胞活化的抑制作用及可能机制。方法:将小鼠BV2小胶质细胞分为对照组、LPS组和LPS+CQ组。LPS+CQ组预先给予CQ(10μmol/L)处理30 min再给予LPS刺激,在LPS组和LPS+CQ组中给予LPS(500μg/L)刺激后,各组细胞分别培养30 min、6 h和24 h。倒置显微镜下观察BV2细胞的形态学改变;RT-qPCR和ELISA法检测白细胞介素6(IL-6)和肿瘤坏死因子α(TNF-α)的mRNA和蛋白表达水平来评估BV2细胞的活化情况;用免疫荧光染色检测NF-κB蛋白核转移情况;用Western blot检测核因子κB抑制蛋白α(IκB-α)蛋白的表达情况及c-Jun氨基末端激酶(JNK)和p38蛋白的磷酸化水平。结果:LPS刺激后,BV2细胞形态由圆形或椭圆形向多极或纺锤样转变,而预先给予CQ能抑制BV2细胞的形态转变。LPS刺激后,BV2细胞中TNF-α和IL-6的mRNA水平和培养上清液中的蛋白水平明显增加,但预先给予CQ则明显抑制TNF-α和IL-6的mRNA和蛋白表达,可见CQ能减轻LPS诱导的BV2细胞炎症反应。此外,LPS刺激后,BV2细胞内IκB-α蛋白大量降解,细胞核内的NF-κB蛋白显著增多,MAPK信号通路中JNK和p38蛋白磷酸化水平明显升高;而预先给予CQ可显著减少IκB-α蛋白的降解,明显抑制NF-κB蛋白向细胞核内转移,显著降低JNK和p38蛋白的磷酸化水平,可见CQ能抑制LPS诱导下BV2细胞内NF-κB和MAPK信号通路的激活。结论:氯喹显著减轻LPS诱导的BV2细胞炎症反应,其机制与抑制NF-κB和MAPK信号通路有关。

关键词：氯喹小胶质细胞脂多糖炎症 NF-κB信号通路 MAPK信号通路

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THEORETICAL STUDY OF A COMPACT PROJECTOR AND HYDROPHONE ARRAY

THEORETICAL STUDY OF A COMPACT PROJECTOR AND HYDROPHONE ARRA...

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2015全国压电和声波理论及器件技术研讨会

作者： Xin-ran XU lin-lang BAI zhen-yu zhenG Hangzhou Applied Acoustics Research Institute

In this paper,a design of a compact projector and hydrophone array is proposed.The FEM is utilized to simulate the performance of the projector and hydrophone,and several design parameters are optimized to achieve higher and flatter sensitivity/TVR response over the working frequency band.The measured performance of the manufactured compact array verifies the validity of the design.

关键词： Compact projector and hydrophone array Piezoelectric polymer film Finite element method

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环境规制对企业绿色技术创新的影响特征与异质性——基于中国上市公司绿色专利数据

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科学学研究 2021年第5期39卷 909-919,929页

作者：王珍愚曹瑜林善浪同济大学经济与管理学院上海200092

基于2004-2015年中国沪深股市上市公司绿色专利数据,建立环境规制综合衡量指标,运用系统GMM估计方法,研究环境规制对企业绿色技术创新的影响特征与作用机理,分析绿色专利类型、企业所有制性质与行业类型的异质性。环境规制对企业绿色创... 详细信息

基于2004-2015年中国沪深股市上市公司绿色专利数据,建立环境规制综合衡量指标,运用系统GMM估计方法,研究环境规制对企业绿色技术创新的影响特征与作用机理,分析绿色专利类型、企业所有制性质与行业类型的异质性。环境规制对企业绿色创新有先抑制后促进的"U"型影响特征;企业绿色技术创新活动中,环境规制会促进价值更高的绿色发明专利创新;非国有企业对于环境规制容忍度较低,"U"型拐点到来较早,且倾向于价值更高的绿色发明专利创新;环境规制对清洁行业与污染行业绿色技术创新的"U"型影响特征存在差异,清洁行业多体现"U"型曲线右半段,拐点较早,污染行业则完整体现了"U"型曲线全过程,拐点较迟。因此,采取灵活性差异化的环境规制政策对促进企业绿色技术创新具有积极作用。

关键词：环境规制企业绿色技术创新绿色专利异质性

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Surgical treatment of hepatocellular carcinoma with inferior vena cava tumor thrombus: a new classification for surgical guidance

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Hepatobiliary & Pancreatic Diseases International 2013年第3期12卷 263-269页

作者： Ai-Jun Li Wei-Ping Zhou Chuan lin Xi-Long lang zhen-Guang Wang Xiao-Yu Yang Qing-He Tang Ran Tao Meng-Chao Wu Division of Special Treatment Ⅱ Eastern Hepatobiliary Surgery Hospital Second Military Medical University Division of Hepatic Surgery Third Eastern Hepatobiliary Surgery Hospital Second Military Medical University Department of Cardiothoracic Surgery Changhai Hospital Second Military Medical University Center for Organ Transplantation and Department of General Surgery Ruijin Hospital

BACKGROUND: Hepatic resection is the main treatment modality for hepatic tumors. Advances in diagnostic technique, preoperative preparation, surgical technique, and postoperative management increased the success rate. The present study aimed to evaluate hepatectomy and resection of inferior vena cava tumor thrombus (IVCTT) in patients with hepatocellular carcinoma, and the relationship between IVCTT classification and selection of surgical technique. METHODS: We retrospectively reviewed 13 patients with hepatocellular carcinoma who had undergone hepatectomy with IVCTT resection between May 1997 and August 2009. Age, gender, diagnosis, findings of physical examination, results of preoperative laboratory investigations, radiological examination, criteria for resection, postoperative pathological results, incisions, operative technique, intraoperative transfusion, drains, and intraoperative and postoperative complications were evaluated for all patients. RESULTS: Type Ⅰ IVCTT (10 patients) was posterior to the liver and below the diaphragm; type Ⅱ IVCTT (2 patients) was above the diaphragm but still outside the atrium; and type Ⅲ IVCTT (1 patient) was above the diaphragm and in the right atrium. Type Ⅰ was treated by radical hepatectomy and removal of IVCTT with total hepatic vascular exclusion. Type Ⅱ was treated by radical hepatectomy and removal of IVCTT by incision of the diaphragm. Type Ⅲ was treated by hepatectomy and resection of the thrombus from the right atrium under cardiopulmonary bypass. There were no surgical complications and one patient has been survived for 4 years with cancer-free status. The median survival time was 18.2 months, and the 1-and 2-year survival rates were 53.8% and 15.4%, respectively. CONCLUSION: Surgical treatment is safe and feasible for treatment of IVCTT in patients with hepatocellular carcinoma, and surgical resectability can be judged according to the classification of tumor thrombus.

关键词： liver tumor inferior vena cava hepatectomy tumor thrombus total hepatic vascular exclusion

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新生儿肠穿孔101例临床分析

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中国当代儿科杂志 2015年第2期17卷 113-117页

作者：董亚徐银权林振浪温州医科大学附属第二医院、育英儿童医院新生儿重症监护病房浙江温州325027

目的分析新生儿肠穿孔的临床特点,为改善新生儿肠穿孔的预后提供理论依据。方法回顾性分析2000年1月至2014年6月入住新生儿重症监护病房的101例新生儿肠穿孔患儿的临床资料。结果新生儿肠穿孔的主要病因是新生儿坏死性小肠结肠炎(NEC,41... 详细信息

目的分析新生儿肠穿孔的临床特点,为改善新生儿肠穿孔的预后提供理论依据。方法回顾性分析2000年1月至2014年6月入住新生儿重症监护病房的101例新生儿肠穿孔患儿的临床资料。结果新生儿肠穿孔的主要病因是新生儿坏死性小肠结肠炎(NEC,41例,40.6%),其次为特发性肠穿孔(17例,16.8%)、先天性巨结肠(10例,9.9%)。特发性肠穿孔组患儿平均出生体重和平均胎龄明显高于NEC组(P<0.05);NEC组致病菌以肠球菌为主,特发性肠穿孔组以革兰阴性菌为主,两组病原菌分布不同(P<0.05)。Logistic多元回归分析显示,酸中毒、多部位肠穿孔、穿孔至手术时间较长是新生儿死亡的独立危险因素。结论新生儿肠穿孔病因多样,以NEC为主;NEC所致肠穿孔与特发性肠穿孔具有不同的致病菌,两者可能是相互独立的疾病;早期诊断、尽早手术是挽救新生儿肠穿孔患儿生命的主要措施。

关键词：肠穿孔坏死性小肠结肠炎预后新生儿

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Recent progress in self-propelled particles

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Journal of Hydrodynamics 2024年第1期36卷 61-77页

作者： zhen-yu Ouyang Jian-zhong lin Laboratory of Impact and Safety Engineering Ministry of EducationNingbo UniversityNingbo315201China Department of Mechanics State Key Laboratory of Fluid Power and Mechatronic SystemsZhejiang UniversityHangzhou310027China

Self-propelled particles are commonly found in a large number of planktonic organisms such as bacteria,fungi,and algae in nature,and researchers have taken a long interest in exploring their swimming mechanisms for more than a century.Especially in the past 20 years,with the development of computational fluid dynamics and flow display technology,as well as the need for the design of synthetic self-propelled particles and micro-swimming devices,self-propelled particles have become the forefront and hotspot of current research in the field of fluid mechanics.This paper first introduces the swimming characteristics of common self-propelled particles,leading to a classic“squirmer”type self-propelled particle model.On this basis,a systematic introduction and summary of the theoretical and numerical simulation research of“squirmer”will be conducted.Finally,the main challenges and opportunities faced by the current research will be summarized.

关键词： Self-propelled particles multiphase flow hydrodynamic interaction

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促红细胞生成素对新生儿坏死性小肠结肠炎的炎症干预研究

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中华全科医学 2019年第8期17卷 1340-1343页

作者：周丽林振浪温州医科大学定理临床学院温州市中心医院新生儿科浙江温州325000 温州医科大学附属第二医院新生儿科温州医科大学第二临床医学院浙江温州325000

目的分析促红细胞生成素(erythropoietin,EPO)治疗新生儿坏死性小肠结肠炎(NEC)的临床疗效,基于Toll样受体(TLR)4/NF-κB信号通路分析其可能作用机制。方法选择2016年8月-2018年8月温州市中心医院诊断为坏死性小肠结肠炎的患儿共94例,... 详细信息

目的分析促红细胞生成素(erythropoietin,EPO)治疗新生儿坏死性小肠结肠炎(NEC)的临床疗效,基于Toll样受体(TLR)4/NF-κB信号通路分析其可能作用机制。方法选择2016年8月-2018年8月温州市中心医院诊断为坏死性小肠结肠炎的患儿共94例,随机数字法分为对照组和观察组,其中对照组42例、观察组52例,对照组给予标准医学治疗方案,观察组联合应用重组EPO肌注治疗,剂量为200 IU/kg,每周2次,疗程为1周。比较2组患儿并发症发生率和病死率,治疗前后血清TNF-α和IL-6水平,TLR-4和NF-κB mRNA表达水平。结果对照组患儿有21例发生相关并发症,其中败血症7例、急性肠穿孔6例、感染性腹膜炎6例、其他2例。观察组有15例,其中败血症5例、急性肠穿孔5例、感染性腹膜炎4例、其他1例,观察组患儿并发症发生率和病死率均显著低于对照组(均P<0.05)。观察组治疗后血清TNF-α和IL-6水平显著低于干预前,且明显低于对照组(均P<0.05)。观察组血清TLR-4和NF-κB mRNA表达水平显著低于干预前,且明显低于对照组(均P<0.05)。结论 EPO可能通过TLR-4/NF-κB信号通路,减轻炎症反应TNF-α和IL-6表达水平,进而改善NEC临床症状和预后。

关键词：促红细胞生成素新生儿坏死性小肠结肠炎炎症反应 Toll样受体-4/NF-κB信号通路

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