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Neuronal regulated cell death in aging-related neurodegenerative diseases:key pathways and therapeutic potentials

Neural Regeneration Research 2025年第8期20卷 2245-2263页

作者： Run Song Shiyi Yin jiannan wu Junqiang Yan Department of Neurology The First Affiliated HospitalCollege of Clinical Medicine of Henan University of Science and TechnologyLuoyangHenan ProvinceChina Neuromolecular Biology Laboratory The First Affiliated HospitalCollege of Clinical Medicine of Henan University of Science and TechnologyLuoyangHenan ProvinceChina

Regulated cell death(such as apoptosis,necroptosis,pyroptosis,autophagy,cuproptosis,ferroptosis,disulfidptosis)involves complex signaling pathways and molecular effectors,and has been proven to be an important regulatory mechanism for regulating neuronal aging and ***,excessive activation of regulated cell death may lead to the progression of aging-related *** review summarizes recent advances in the understanding of seven forms of regulated cell death in age-related ***,the newly identified ferroptosis and cuproptosis have been implicated in the risk of cognitive impairment and neurodegenerative *** forms of cell death exacerbate disease progression by promoting inflammation,oxidative stress,and pathological protein *** review also provides an overview of key signaling pathways and crosstalk mechanisms among these regulated cell death forms,with a focus on ferroptosis,cuproptosis,and *** instance,FDX1 directly induces cuproptosis by regulating copper ion valency and dihydrolipoamide S-acetyltransferase aggregation,while copper mediates glutathione peroxidase 4 degradation,enhancing ferroptosis ***,inhibiting the Xc-transport system to prevent ferroptosis can increase disulfide formation and shift the NADP^(+)/NADPH ratio,transitioning ferroptosis to *** insights help to uncover the potential connections among these novel regulated cell death forms and differentiate them from traditional regulated cell death *** conclusion,identifying key targets and their crosstalk points among various regulated cell death pathways may aid in developing specific biomarkers to reverse the aging clock and treat age-related neurodegenerative conditions.

关键词： apoptosis autophagy cuproptosis disulfidptosis ferroptosis necroptosis neurodegenerative disease neurological aging diseases PANoptosis pyroptosis

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A novel mechanism of PHB2-mediated mitophagy participating in the development of Parkinson's disease

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Neural Regeneration Research 2024年第8期19卷 1828-1834页

作者： Yongjiang Zhang Shiyi Yin Run Song Xiaoyi Lai Mengmeng Shen jiannan wu Junqiang Yan Key Laboratory of Neuromolecular Biology The First Affiliated HospitalCollege of Clinical Medicine of Henan University of Science and TechnologyLuoyangHenan ProvinceChina Department of Neurology The First Affiliated HospitalCollege of Clinical Medicine of Henan University of Science and TechnologyLuoyangHenan ProvinceChina

Endoplasmic reticulum stress and mitochondrial dysfunction play important roles in Parkinson s disease,but the regulato ry mechanism remains ***-2(PHB2)is a newly discove red autophagy receptor in the mitochondrial inner membrane,and its role in Parkinson’s disease remains *** kinase R(PKR)-like endoplasmic reticulum kinase(PERK)is a factor that regulates cell fate during endoplasmic reticulum *** is regulated by PERK and is a target of the unfolded protein *** is unclear whether PERK regulates PHB2-mediated mitophagy thro ugh *** this study,we established a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced mouse model of Parkinson’s *** used adeno-associated virus to knockdown PHB2 *** res ults showed that loss of dopaminergic neurons and motor deficits were aggravated in the MPTP-induced mouse model of Parkinson’s *** rexpression of PHB2 inhibited these *** also established a 1-methyl-4-phenylpyridine(MPP+)-induced SH-SY5Y cell model of Parkinson’s *** found that ove rexpression of Parkin increased co-localization of PHB2 and microtubule-associated protein 1 light chain 3,and promoted *** addition,MPP+regulated Parkin involvement in PHB2-mediated mitophagy through phosphorylation of *** findings suggest that PHB2 participates in the development of Parkinson’s disease by intera cting with endoplasmic reticulum stress and Parkin.

关键词： endoplasmic reticulum dopaminergic neuron microtubule-associated protein 1 light chain 3 mitophagy oxidative stress Parkin Parkinson’s disease PKR-like endoplasmic reticulum kinase reactive oxygen species prohibitin-2

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In pursuit of a flawless aphrodite:paving the way to scarless oncoplastic breast surgery

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Cancer Communications 2019年第1期39卷 712-717页

作者： Liling Zhu Shunrong Li Luyuan Tan Xiaolan Zhang jiannan wu Fengxi Su Kai Chen Erwei Song Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation Sun Yat-Sen Memorial HospitalSun Yat-Sen UniversityGuangzhou 510120GuangdongP.R.China Breast Tumor Center Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510120GuangdongP.R.China Department of Breast Surgery Guangzhou Concord Cancer CenterGuangzhou 510045GuangdongP.R.China Sufengxi Clinic Guangzhou 510000GuangdongP.R.China

Introduction Breast cancer is the most commonly diagnosed malig-nancy in women worldwide[1,2]and in the twentieth century,mastectomy was the primary surgical treatment for breast cancer *** in breast-conserving surgery(BCS)propelled a change in treatment rational from“maximum tolerable”to“minimum effective”*** breast surgery aims to restore the shape of the breast and has been widely adopted since the past *** the cosmetic outcome has been sig-nificantly improved,the scar remaining on the surgeried breast skin is still a major pitfall that urges urgent *** this editorial,we review a series of techniques that can be incorporated in oncoplastic breast surgery to minimize scarring,signifying the beginning of an era for scarless oncoplastic surgery.

关键词： surgery breast scar

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Bidirectional differentiation of BMSCs induced by a biomimetic procallus based on a gelatin-reduced graphene oxide reinforced hydrogel for rapid bone regeneration

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Bioactive Materials 2021年第7期6卷 2011-2028页

作者： Delong Jiao Ao Zheng Yang Liu Xiangkai Zhang Xiao Wang jiannan wu Wenjun She Kaige Lv Lingyan Cao Xinquan Jiang Department of Prosthodontics Shanghai Engineering Research Center of Advanced Dental Technology and MaterialsShanghai Key Laboratory of Stomatology&Shanghai Research Institute of StomatologyNational Clinical Research Center for Oral DiseasesShanghai Ninth People’s HospitalCollege of StomatologyShanghai Jiao Tong University School of MedicineChina The State Key Laboratory of Bioreactor Engineering East China University of Science and Technology130 Meilong RoadShanghai 200237China

Developmental engineering strategy needs the biomimetic composites that can integrate the progenitor cells,biomaterial matrices and bioactive signals to mimic the natural bone healing process for faster healing and reconstruction of segmental bone *** prepared the gelatin-reduced graphene oxide(GOG)and constructed the composites that mimicked the procallus by combining the GOG with the photo-crosslinked gelatin *** biological effects of the GOG-reinforced composites could induce the bi-differentiation of bone marrow stromal cells(BMSCs)for rapid bone *** proper ratio of GOG in the composites regulated the composites’mechanical properties to a suitable range for the adhesion and proliferation of ***,the GOG-mediated bidirectional differentiation of BMSCs,including osteogenesis and angiogenesis,could be activated through Erk1/2 and AKT *** methyl vanillate(MV)delivered by GOG also contributed to the bioactive signals of the biomimetic procallus through priming the osteogenesis of *** the repair of the calvarial defect in vivo,the initial hypoxic condition due to GOG in the composites gradually transformed into a well-vasculature robust situation with the bi-differentiation of BMSCs,which mimicked the process of bone healing resulting in the rapid bone *** an inorganic constituent,GOG reinforced the organic photo-crosslinked gelatin hydrogel to form a double-phase biomimetic procallus,which provided the porous extracellular matrix microenvironment and bioactive signals for the bi-directional differentiation of *** show a promised application of the bio-reduced graphene oxide in biomedicine with a developmental engineering strategy.

关键词： Biomimetic procallus Bio-reduced graphene oxide Photo-crosslinked gelatin hydrogel Methyl vanillate Developmental engineering

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Sequential neoadjuvant chemotherapy using pegylated liposomal doxorubicin and cyclophosphamide followed by taxanes with complete trastuzumab and pertuzumab treatment for HER2-positive breast cancer: A phase Ⅱ single-arm study

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Chinese Journal of Cancer Research 2024年第1期36卷 55-65页

作者： Yaping Yang Liang Jin Yudong Li Nanyan Rao Chang Gong Shunrong Li jiannan wu Jinghua Zhao Linxiaoxiao Ding Fengxia Gan Jun Zhang Ruifa Feng Zhenzhen Liu Qiang Liu Breast Tumor Center Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene RegulationGuangzhou 510120China Department of Thyroid and Breast Surgery Shenzhen Qianhai Shekou Free Trade Zone HospitalShenzhen 518000China Breast and Thyroid Surgery Guilin Medical College Second Affiliated HospitalGuilin 541199China Department of Breast Disease Henan Breast Cancer Centerthe Affiliated Cancer Hospital of Zhengzhou University&Henan Cancer HospitalZhengzhou 450008China

Objective: Despite cardiotoxicity overlap, the trastuzumab/pertuzumab and anthracycline combination remains crucial due to significant benefits. Pegylated liposomal doxorubicin(PLD), a less cardiotoxic anthracycline, was evaluated for efficacy and cardiac safety when combined with cyclophosphamide and followed by taxanes with trastuzumab/pertuzumab in human epidermal growth factor receptor-2(HER2)-positive early breast cancer(BC).Methods: In this multicenter, phase II study, patients with confirmed HER2-positive early BC received four cycles of PLD(30-35 mg/m^(2)) and cyclophosphamide(600 mg/m^(2)), followed by four cycles of taxanes(docetaxel,90-100 mg/m^(2) or nab-paclitaxel, 260 mg/m^(2)), concomitant with eight cycles of trastuzumab(8 mg/kg loading dose,then 6 mg/kg) and pertuzumab(840 mg loading dose, then 420 mg) every 3 weeks. The primary endpoint was total pathological complete response(tp CR, yp T0/is yp N0). Secondary endpoints included breast p CR(bp CR),objective response rate(ORR), disease control rate, rate of breast-conserving surgery(BCS), and safety(with a focus on cardiotoxicity).Results: Between May 27, 2020 and May 11, 2022, 78 patients were treated with surgery, 42(53.8%) of whom had BCS. After neoadjuvant therapy, 47 [60.3%, 95% confidence interval(95% CI), 48.5%-71.2%] patients achieved tp CR, and 49(62.8%) achieved bp CR. ORRs were 76.9%(95% CI, 66.0%-85.7%) and 93.6%(95% CI,85.7%-97.9%) after 4-cycle and 8-cycle neoadjuvant therapy, respectively. Nine(11.5%) patients experienced asymptomatic left ventricular ejection fraction(LVEF) reductions of ≥10% from baseline, all with a minimum value of >55%. No treatment-related abnormal cardiac function changes were observed in mean N-terminal pro-BNP(NT-pro BNP), troponin I, or high-sensitivity ***: This dual HER2-blockade with sequential polychemotherapy showed promising activity with rapid tumor regression in HER2-positive BC. Importantly, this regimen showed an acceptable safety

关键词： Breast cancer HER2-positive breast cancer dual HER2 blockade neoadjuvant therapy sequential therapy

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肝动脉介入栓塞治疗肝癌合并门静脉瘤栓50例效果观察

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中国基层医药 2020年第23期27卷 2830-2834页

作者：吴建男舟山市普陀区人民医院消化科浙江省316100

目的:探讨放射介入栓塞治疗肝癌合并门静脉瘤栓的效果及其对患者生存质量的影响。方法:选取舟山市普陀区医院2017年7月至2019年7月就诊的肝癌合并门静脉瘤栓患者100例为研究对象,采用随机数字表法分为观察组和对照组各50例。对照组采用... 详细信息

目的:探讨放射介入栓塞治疗肝癌合并门静脉瘤栓的效果及其对患者生存质量的影响。方法:选取舟山市普陀区医院2017年7月至2019年7月就诊的肝癌合并门静脉瘤栓患者100例为研究对象,采用随机数字表法分为观察组和对照组各50例。对照组采用单纯肝动脉化疗药物灌注治疗,观察组采用放射介入肝动脉栓塞化疗。比较两组治疗效果、肝功能变化及生存质量评分。结果:观察组肝肿瘤缩小>50%25例(50%)、门静脉瘤栓消失10例(20%),对照组分别为16例(32%)、5例(10%),两组差异均有统计学意义(χ2=6.310、4.601,均P<0.05);治疗后,观察组血清白蛋白、丙氨酸氨基转移酶、白蛋白、血小板计数、白细胞计数分别为(23.80±10.60)μmol/L、(68.10±19.83)U/L、(338.60±50.16)g/L、(102.13±20.10)×109/L、(4.10±2.10)×109/L,对照组分别为(19.20±7.55)μmol/L、(64.10±11.25)U/L、(32.11±4.83)g/L、(110.45±28.64)×109/L、(4.83±2.83)×109/L,两组差异均有统计学意义(t=7.158、4.301、82.441、3.432、3.645,均P<0.05);观察组生存质量总健康评分为(69.20±3.94)分,高于对照组的(52.76±2.40)分(t=25.303,P<0.05)。结论:放射介入栓塞肝动脉治疗肝癌合并门静脉瘤栓能缩小肝癌或消除门静脉瘤栓,改善患者肝功能,提高患者生存质量,效果优于单纯肝动脉化疗药物灌注治疗。

关键词：肝肿瘤放射学,介入性栓塞,治疗性化学疗法,癌,局部灌注生活质量肝功能试验疗效比较研究

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以改革创新方法论引领区域协同治理

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探索与争鸣 2020年第10期 4-25,157页

作者：吴建南上海交通大学中国城市治理研究院上海交通大学国际与公共事务学院

改革开放以来,区域间竞争对于激发地方活力、实现经济快速增长曾经发挥了重要作用,但也带来了“行政区经济”的壁垒问题。随着社会主义市场经济体制的建立和完善,如何打破市场壁垒,促进资源在区域间的合理流动和有效配置,实现区域一体... 详细信息

改革开放以来,区域间竞争对于激发地方活力、实现经济快速增长曾经发挥了重要作用,但也带来了“行政区经济”的壁垒问题。随着社会主义市场经济体制的建立和完善,如何打破市场壁垒,促进资源在区域间的合理流动和有效配置,实现区域一体化发展,进而形成统一的国内市场,成为我国各级政府亟待解决的重大问题。尤其是近年来,我国已将实施区域协调发展确立为国家重大战略。为建立区域协调发展新机制,必须以破解区域间竞争的负面效应为问题导向,在跨域公共服务、跨域公共基础设施建设以及跨域环境保护等问题上实现区域协同治理。可以说,区域协同治理是实现区域协调发展的应有之义。

关键词：区域协调发展公共基础设施建设市场壁垒国家重大战略问题导向区域协同治理环境保护有效配置

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Successful Treatment of White Lung in Elderly Patients with COVID-19

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Proceedings of Anticancer Research 2023年第4期7卷 20-28页

作者： Chao Fang Nuan Xiao Shengnan Huang jiannan wu Lili Tan Hongmei Zhao Department of Geriatrics/Special Needs Ward Affiliated Hospital of Hebei UniversityBaoding 071000China

Novel coronavirus(SARS-CoV-2,hereby known as COVID-19)has the characteristics of rapid variation and multiple variants,which has caused a huge impact on human health *** the end of 2022,the Omicron variant was widely spread in China,and the patients infected with COVID-19 were mainly concentrated in the elderly over 80 years old and people with serious basic ***,diffuse lung injury can be seen in the advanced stage of severe and critical diseases,with a large number of inflammatory cells and fibrous mucus exudation,alveolar epithelial cells shedding and necrosis,severe pulmonary edema,hyaline membrane formation,and diffuse ground-glass shadow or consolidation on imaging,which is manifested as“white lung”[1],and its mortality rate has significantly *** study reported two cases of elderly patients admitted to the Affiliated Hospital of Hebei University for the treatment of COVID-19.

关键词： Advanced age COVID-19 White lung Treatment Experience

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A Case Study of Severe QT Interval Prolongation Caused by Antidepressants

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Journal of Clinical and Nursing Research 2023年第5期7卷 201-207页

作者： Chao Fang Nuan Xiao Hongmei Zhao Simin Ren Lili Tan jiannan wu Department of Geriatrics Hebei University Affiliated HospitalBaoding 071000Hebei ProvinceChina Department of Neurology Affiliated Hospital of Hebei UniversityBaoding 071000Hebei ProvinceChina

QT interval prolongation can be categorized into primary and secondary types according to its *** this paper,we report a case of severe asymptomatic QT interval prolongation secondary to *** follow-up and electrocardiogram monitoring is crucial when applying antidepressants,especially for patients without cardiac *** article presents case studies and examines existing literature on long QT syndrome to enhance the diagnosis and management of QT interval *** is especially relevant for non-psychiatric healthcare professionals who need to be attentive to the side effects of antidepressants to prevent potential adverse consequences resulting from oversight.

关键词： Antidepressant Asymptomatic QT interval extension Follow-up Electrocardiogram

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专栏导语:作为环境治理创新的环保督察:从定性到定量研究

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公共行政评论 2019年第2期12卷 1-4,M0003页

作者：吴建南上海交通大学国际与公共事务学院上海交通大学中国城市治理研究院

如果谈及改革开放以来环境治理中的创新,那么环保约谈和环保督察应该是非常值得研究的。先说环保约谈,最早的行政约谈实践肇始于税务部门,此后在工商管理、食品安全、环境保护等领域广泛应用(吴建南等,2018)。2014年5月环保部出台《环... 详细信息

如果谈及改革开放以来环境治理中的创新,那么环保约谈和环保督察应该是非常值得研究的。先说环保约谈,最早的行政约谈实践肇始于税务部门,此后在工商管理、食品安全、环境保护等领域广泛应用(吴建南等,2018)。2014年5月环保部出台《环境保护部约谈暂行办法》,明确环保约谈是指环保部或环保部与组织、监察等部门依法对于环保职责“未履行或履行不到位”的有关负责人进行“告诫谈话、指出问题、提出整改要求并督促整改”的行为。

关键词：环保督察治理创新环境治理导语专栏环境保护改革开放税务部门

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