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Chinese Medical Journal 2011年第6期124卷 947-950页

作者： ZHANG Zhi-ruo WEN Zhao-jun CHEN Sai-juan CHEN Zhu shanghai Jiao Tong University School of Public Health Shanghai 200025 China shanghai Institute of Hematology Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai 200025 China

This study is designed to serve as a reference for the establishment of health security systems for children＇s critical diseases. Through analysis of the operation of shanghai Children hospital Care Aid （SCHCA）, this study explored the financing model and management of a children＇s critical disease healthcare system and analyzed the possibility of expanding this system to other areas. It is found that a premium as Iow as RMB 7 per capita per year under SCHCA can provide high-level security for children＇s critical diseases. With the good experience in shanghai and based on the current basic medical insurance system for urban residents and the new rural cooperative medical scheme （NRCMS）, it is necessary and feasible to build a health security system for children＇s critical diseases at the national level.

关键词： children critical diseases health security system

Clinical experience of 3T intraoperative magnetic resonance imaging integrated neurosurgical suite in shanghai Huashan hospital

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Chinese Medical Journal 2012年第24期125卷 4328-4333页

作者： QIU Tian-ming YAO Cheng-jun WU Jin-song PAN Zhi-guang ZHUANG Dong-xiao XU Gen ZHU Feng-ping LU Jun-feng GONG Xiu ZHANG Jie YANG Zhong SHI Jian-bin HUANG Feng-ping MAO Ying ZHOU Liang-fu Glioma Surgery Division Department of Neurosurgery Huashan Hospital Fudan University Shanghai 200040 China

Background Intraoperative magnetic resonance imaging （iMRI） dates back to the 1990s and has been successfully applied in neurosurgery but they were low-field iMRI （〈1.0T）. This paper reports the clinical experience with a 3T iMRI-integrated neurosurgical suite in Huashan hospital, shanghai, China. Methods From September 2010 through March 2012, 373 consecutive patients underwent neurological surgery under guidance with 3T iMRI. A retrospective analysis was conducted regarding clinical efficiency. Results All surgery in the 373 patients was safe. The ratio of gross total resection for cerebral gliomas （n=161） was increased from 55.90% to 87.58%. The ratio of benefit in extent of resection was 39.13%. One hundred and fifty eight of the 161 glioma patients accomplished follow-up at 3 months postoperatively. Twenty of 161 patients （12.42%） suffered from early motor deficit after surgery. Late motor deficit was however observed in five of 158 patients （3.16%）. Twenty-one of 161 patients （13.04%） had early speech deficit and late speech deficit was only observed in six of 158 patients （3.80%）. The ratio of gross total resection for pituitary adenomas （n=49） was increased from 77.55% to 85.71%. The ratio of benefit in extent of resection was 10.2%. There were no iMRI-related adverse events even for patients who underwent awake craniotomy. Conclusion The 3T iMRI integrated neurosurgical suite provides high-quality intraoperative structural and functional imaging for real-time tumor resection control and accurate functional preservation, resulting in an improvement in maximal safe brain surgery.

关键词： intraoperative magnetic resonance imaging glioma pituitary adenoma

Human umbilical cord mesenchymal stem cells attenuate diabetic nephropathy through the IGF1R-CHK2-p53 signalling axis in male rats with type 2 diabetes mellitus

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第7期25卷 568-580页

作者： Hao ZHANG Xinshu WANG Bo HU Peicheng LI Yierfan ABUDUAINI Hongmei ZHAO Ayinaer JIEENSIHAN Xishuang CHEN Shiyu WANG Nuojin GUO Jian YUAN Yunhui LI Lei LI Yuntong YANG Zhongmin LIU Zhaosheng TANG Hua WANG Department of Endocrinology Shanghai East HospitalSchool of MedicineTongji UniversityShanghai 200120China Research Center for Translational Medicine Shanghai East HospitalSchool of MedicineTongji UniversityShanghai 200120China Department of Cardiology Shanghai East HospitalSchool of MedicineTongji UniversityShanghai 200120China Department of Biochemistry and Molecular Biology School of MedicineTongji UniversityShanghai 200331China shanghai Institute of Stem Cell Research and Clinical Translation Shanghai East HospitalShanghai 200120China Ji’an hospital Shanghai East HospitalJi’an 343000China

diabetes mellitus(DM)is a disease syndrome characterized by chronic hyperglycaemia.A long-term high-glucose environment leads to reactive oxygen species(ROS)production and nuclear DNA *** umbilical cord mesenchymal stem cell(HUcMSC)infusion induces significant antidiabetic effects in type 2 diabetes mellitus(T2DM)***-like growth factor 1(IGF1)receptor(IGF1R)is important in promoting glucose metabolism in diabetes;however,the mechanism by which HUcMSC can treat diabetes through IGF1R and DNA damage repair remains *** this study,a DM rat model was induced with high-fat diet feeding and streptozotocin(STZ)administration and rats were infused four times with *** glucose,interleukin-6(IL-6),IL-10,glomerular basement membrane,and renal function were *** that interacted with IGF1R were determined through coimmunoprecipitation *** expression of IGF1R,phosphorylated checkpoint kinase 2(p-CHK2),and phosphorylated protein 53(p-p53)was examined using immunohistochemistry(IHC)and western blot ***-linked immunosorbent assay(ELISA)was used to determine the serum levels of 8-hydroxydeoxyguanosine(8-OHdG).Flow cytometry experiments were used to detect the surface markers of *** identification of the morphology and phenotype of HUcMSC was performed by way of oil red“O”staining and Alizarin red *** rats exhibited abnormal blood glucose and IL-6/10 levels and renal function changes in the glomerular basement membrane,increased the expression of IGF1 and ***1R interacted with CHK2,and the expression of p-CHK2 was significantly decreased in IGF1R-knockdown *** cisplatin was used to induce DNA damage,the expression of p-CHK2 was higher than that in the IGF1R-knockdown group without cisplatin *** infusion ameliorated abnormalities and preserved kidney structure and function in DM *** expression of IGF1,IGF1R,p-CHK2,and p-p53,and the level of 8-OHdG in the DM group increased sign

关键词： Insulin-like growth factor 1 receptor(IGF1R) Checkpoint kinase 2(CHK2) Protein 53(p53) Diabetes mellitus Human umbilical cord mesenchymal stem cell(HUcMSC) DNA damage repair

Engineered plant extracellular vesicles for autoimmune diseases therapy

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Nano Research 2024年第4期17卷 2857-2873页

作者： Ruina Han Yan Wu Yafei Han Xiangfei Liu Han Liu Jiacan Su Institute of Translational Medicine Shanghai UniversityShanghai 200444China Organoid Research Center Shanghai UniversityShanghai 200444China National Center for Translational Medicine(shanghai)SHU Branch Shanghai UniversityShanghai 200444China Department of Orthopedics Shanghai Zhongye HospitalShanghai 200941China Department of Orthopedics Xinhua HospitalShanghai Jiao Tong University School of MedicineShanghai 200092China

Autoimmune diseases(AID)encompass a diverse array of conditions characterized by immune system dysregulation,resulting in aberrant responses of B cells and T cells against the body’s own healthy *** extracellular vesicles(PEVs)are nanoscale particles enclosed by phospholipid bilayers,secreted by plant cells,which facilitate intercellular communication by transporting various bioactive *** to their nanoscale structure,safety,abundant sources,low immunogenicity,high yield,biocompatibility,and effective targeting of the colon and liver,PEVs are regarded as a promising platform for the treatment of *** review provides a comprehensive summary of PEV biogenesis,physicochemical and biological properties,internalization mechanisms,isolation methods,and their applications in various diseases,with a specific focus on their potential roles in ***,we propose engineering approaches and administration methods for ***,we present an overview of the advantages and challenges associated with utilizing PEVs for the treatment of *** gaining a comprehensive understanding of PEVs,we anticipate the development of innovative therapeutic strategies for *** and engineered PEVs hold substantial promise as a valuable resource for innovative technologies in AID treatment.

关键词： autoimmune diseases plant extracellular vesicles extracellular vesicles engineering modification

Neoadjuvant camrelizumab(an anti-PD-1 antibody)plus chemotherapy or apatinib(a VEGFR-2 inhibitor)for initially unresectable stage II–III non-small-cell lung cancer:a multicentre,two-arm,phase 2 exploratory study

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Signal Transduction and Targeted Therapy 2024年第7期9卷 3015-3023页

作者： Haoran Xia Han Zhang Zheng Ruan Huibiao Zhang Liangdong Sun Hezhong Chen Yongxin Zhou Lele Zhang Dongliang Bian Xinsheng Zhu Jing Zhang Fenghuan Sun Huansha Yu Nan Song Xiaogang Liu Yuming Zhu Haiping Zhang Wenxin He Jian Chen Jie Yang Guohan Chen Shiliang Xie Dongfang Tang Xiaomiao Zhang Liang Duan Deping Zhao Qinchuan Li Peng Zhang Gening Jiang Department of Thoracic Surgery Shanghai Pulmonary HospitalTongji University School of MedicineShanghaiChina Department of Thoracic Surgery Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghaiChina Department of Thoracic Surgery Huadong Hospital Affiliated to Fudan UniversityShanghaiChina Department of Thoracic Surgery Changhai HospitalNaval Medical UniversityShanghaiChina Department of Thoracic-Cardiovascular Surgery Tongji HospitalTongji University School of MedicineShanghaiChina Central Laboratory Shanghai Pulmonary HospitalTongji University School of MedicineShanghaiChina Experimental Animal Center Shanghai Pulmonary HospitalTongji University School of MedicineShanghaiChina Department of Oncology Shanghai Pulmonary HospitalTongji University School of MedicineShanghaiChina Department of Thoracic Surgery Shanghai East HospitalTongji University School of MedicineShanghaiChina

This multicentre,two-arm,phase 2 study aimed to explore the efficacy and safety of neoadjuvant camrelizumab plus chemotherapy or apatinib in patients with initially unresectable stage II–III non-small-cell lung cancer(NSCLC).Eligible patients regardless of PD-L1 expression received neoadjuvant camrelizumab 200 mg and platinum-doublet chemotherapy every 3 weeks(arm A)or those with PD-L1-positive tumors received neoadjuvant camrelizumab and apatinib 250 mg once daily(arm B),for 2–4 cycles,followed by *** primary endpoint was major pathological response(MPR)*** patients in arm A and 21 in arm B were *** rates were 50.0%(15/30)in arm A and 42.9%(9/21)in arm B,with all patients achieving R0 *** these patients,the MPR and pathological complete response rates were both 20.0%(95%CI 4.3–48.1)in arm A and were 55.6%(95%CI 21.2–86.3)and 11.1%(95%CI 0.3–48.2)in arm B,*** corresponding objective response rates were 33.3%(95%CI 11.8–61.6)and 55.6%(95%CI 21.2–86.3).With a median follow-up of 22.4 months(95%CI 19.0–26.0),the median event-free survival was not reached(NR;95%CI 13.6-NR)in arm A and 16.8 months(95%CI 8.6-NR)in arm *** 3 or above treatment-related adverse events occurred in eight(26.7%)patients in arm A and three(14.3%)in arm *** analysis showed baseline TYROBP expression was predictive of treatment response in arm *** camrelizumab plus chemotherapy or apatinib exhibits preliminary efficacy and manageable toxicity in patients with initially unresectable stage II–III NSCLC.

关键词： Surgery chemotherapy treatment

Lipid nanovehicles overcome barriers to systemic RNA delivery: Lipid components, fabrication methods, and rational design

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Acta Pharmaceutica Sinica B 2024年第2期14卷 579-601页

作者： Jing Yan Hao Zhang Guangfeng Li Jiacan Su Yan Wei Can Xu Institute of Translational Medicine Shanghai UniversityShanghai 200444China Institute of Medicine Shanghai UniversityShanghai 200444China Department of Orthopedics Xinhua HospitalShanghai Jiao Tong University School of MedicineShanghai 200092China Department of Orthopedics Shanghai Zhongye HospitalShanghai 200941China Organoid Research Center Shanghai UniversityShanghai 200444China Department of Gastroenterology Changhai HospitalShanghai 200433China

Lipid nanovehicles are currently the most advanced vehicles used for RNA delivery,as demonstrated by the approval of patisiran for amyloidosis therapy in *** illuminate the unique superiority of lipid nanovehicles in RNA delivery,in this review,we first introduce various RNA therapeutics,describe systemic delivery barriers,and explain the lipid components and methods used for lipid nanovehicle ***,we emphasize crucial advances in lipid nanovehicle design for overcoming barriers to systemic RNA ***,the current status and challenges of lipid nanovehicle-based RNA therapeutics in clinical applications are also *** objective is to provide a comprehensive overview showing how to utilize lipid nanovehicles to overcome multiple barriers to systemic RNA delivery,inspiring the development of more high-performance RNA lipid nanovesicles in the future.

关键词： Lipid nanovehicles RNAtherapeutics Barriers to systemicRNA delivery Lipid components Fabricationmethods Lipid nanovehicledesign Extrahepatictissue targeting Organ tropism

Bromocriptine protects perilesional spinal cord neurons from lipotoxicity after spinal cord injury

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Neural Regeneration Research 2024年第5期19卷 1142-1149页

作者： Ying Peng Zhuoxuan Li Zhiyang Zhang Yinglun Chen Renyuan Wang Nixi Xu Yuanwu Cao Chang Jiang Zixian Chen Haodong Lin Trauma Center Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghaiChina Department of Orthopedics Zhongshan HospitalFudan UniversityShanghaiChina Department of Rehabilitation Medicine Shanghai Geriatric Medical CenterShanghaiChina

Recent studies have revealed that lipid droplets accumulate in neurons after brain injury and evoke lipotoxicity,damaging the ***,how lipids are metabolized by spinal cord neurons after spinal cord injury remains ***,we investigated lipid metabolism by spinal cord neurons after spinal cord injury and identified lipid-lowering compounds to treat spinal cord *** found that lipid droplets accumulated in perilesional spinal cord neurons after spinal cord injury in *** droplet accumulation could be induced by myelin debris in HT22 *** debris degradation by phospholipase led to massive free fatty acid production,which increased lipid droplet synthesis,β-oxidation,and oxidative *** oxidative phosphorylation increased reactive oxygen species generation,which led to increased lipid peroxidation and HT22 cell *** was identified as a lipid-lowering compound that inhibited phosphorylation of cytosolic phospholipase A2 by reducing the phosphorylation of extracellular signal-regulated kinases 1/2 in the mitogen-activated protein kinase pathway,thereby inhibiting myelin debris degradation by cytosolic phospholipase A2 and alleviating lipid droplet accumulation in myelin debris-treated HT22 *** function,lipid droplet accumulation in spinal cord neurons and neuronal survival were all improved in bromocriptine-treated mice after spinal cord *** results suggest that bromocriptine can protect neurons from lipotoxic damage after spinal cord injury via the extracellular signal-regulated kinases 1/2-cytosolic phospholipase A2 pathway.

关键词： bromocriptine central nervous system cytosolic phospholipase A2 high-content screening lipid droplet lipid metabolism lipotoxicity mitogen-activated protein kinase spinal cord injury spinal cord neurons

Chinese expert consensus on immunotherapy for advanced non-small cell lung cancer with oncogenic driver mutations(2023 edition)

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Chinese Medical Journal 2024年第9期137卷 1016-1018页

作者： The Society of Cancer Precision Medicine of Chinese Anti-Cancer Association The Lung Cancer Expert Group of Chinese Medical Association Publishing House Baohui Han Hua Zhong 不详 Department of Respiratory Medicine Shanghai Chest HospitalSchool of MedicineShanghai JiaoTong UniversityShanghai 20030China shanghai Chest hospital Shanghai Jiao Tong University School of Medicine

Non-small cell lung cancer(NSCLC)with oncogenic driver mutations was previously deemed“forbidden territory”for immunotherapy.[1]With the continuous generation of evidence,immunotherapy is expected to bring hope for such NSCLC with oncogenic driver mutations after acquired tyrosine kinase inhibitor(TKI)***,given the intricate interplay between driven mutations,targeted therapy,and immune microenvironment,the efcacy of immunotherapy in advanced NSCLC patients with diverse oncogenic driver mutations remains a topic of ongoing *** this context,Chinese Expert Consensus on Immunotherapy for Advanced NSCLC with Oncogenic Driver Mutations(2022 edition)wasrst launched in 2022 by the Society of Cancer Precision Medicine of Chinese Anti-Cancer Association and the Lung Cancer Expert Group of Chinese Medical Journals,aiming to provide standardized treatment guidance for clinical practice.

关键词： immunotherapy cancer lung

HIF-1αpromotes virus replication and cytokine storm in H1N1 virus-induced severe pneumonia through cellular metabolic reprogramming

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Virologica Sinica 2024年第1期39卷 81-96页

作者： Xiaoxiao Meng Yong Zhu Wenyu Yang Jiaxiang Zhang Wei Jin Rui Tian Zhengfeng Yang Ruilan Wang Department of Critical Care Medicine Shanghai General HospitalShanghai Jiaotong UniversitySchool of MedicineShanghai201620China Precision Research Center for Refractory Diseases Shanghai General HospitalShanghai Jiaotong UniversitySchool of MedicineShanghai201620China

The mortality of patients with severe pneumonia caused by H1N1 infection is closely related to viral replication and cytokine ***,the specific mechanisms triggering virus replication and cytokine storm are still not fully ***,we identified hypoxia inducible factor-1α(HIF-1α)as one of the major host molecules that facilitates H1N1 virus replication followed by cytokine storm in alveolar epithelial ***,HIF-1αprotein expression is upregulated after H1N1 *** of HIF-1αattenuates pulmonary injury,viral replication and cytokine storm in *** addition,viral replication and cytokine storm were inhibited after HIF-1αknockdown in ***,the invasion of H1N1 virus into alveolar epithelial cells leads to a shift in glucose metabolism to glycolysis,with rapid production of ATP and *** of glycolysis significantly suppresses viral replication and inflammatory *** analysis revealed that H1N1-induced HIF-1αcan promote the expression of hexokinase 2(HK2),the key enzyme of glycolysis,and then not only provide energy for the rapid replication of H1N1 virus but also produce lactate,which reduces the accumulation of the MAVS/RIG-I complex and inhibits IFN-α/β*** conclusion,this study demonstrated that the upregulation of HIF-1αby H1N1 infection augments viral replication and cytokine storm by cellular metabolic reprogramming toward glycolysis mainly through upregulation of HK2,providing a theoretical basis for finding potential targets for the treatment of severe pneumonia caused by H1N1 infection.

关键词： H1N1 Severe pneumonia Virus replication Hypoxia inducible factor-1α Glycolysis

Mitochondria-targeted nanoparticles overcome chemoresistance via downregulating BACH1/CD47 axis in ovarian carcinoma

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Chinese Chemical Letters 2024年第5期35卷 344-350页

作者： Ke Gong Jinghan Liao Jiangtao Lin Quan Wang Zhihua Wu Liting Wang Jiali Zhang Yi Dong Yourong Duan Jianhua Chen State Key Laboratory of Systems Medicine for Cancer Shanghai Cancer InstituteRenji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200032China Department of Ultrasound Xinhua HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200092China Department of Oncology Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai 200080China

The platinum-based chemotherapy is a routine strategy for the treatment of ovarian cancer,while it is prone to chemoresistance in clinical,which hinders the ***,it is urgently needed to elucidate the underlying mechanism of drug resistance and form the appropriate *** sequencing results showed that cisplatin(DDP)resistant ovarian cancer overexpressed BTB and CNC homology 1(BACH1),and up-regulated the“don’t eat me”signal *** identified that hemin,a BACH1 inhibitor,could effectively down-regulate BACH1 and simultaneously inhibit ***,hemin has a synergistic effect with *** designed a pH-responsive nanoparticle(H/D@FA-CaP-NPs)in which folic acid(FA)ensured targeting of ovarian cancer cells,while hemin inhibited BACH1 as well as down-regulated CD47,achieving the promotion of apoptosis of tumor cells and inducing phagocytosis of tumors by ***,hemin has a synergistic effect with DDP to promote apoptosis of tumor ***,hemin and DDP was encapsulated within hydrophobic 1,2-distearoyl-sn-glycero-3-phosphoethanolamine(DSPE)to form a tight core,and hydrophilic polyethylene glycol 2000(PEG2000)and calcium phosphate(CaP)formed the outside shell,and FA was modified on the surface of *** terms of function,(a)FA enhanced the active targeting of nanoparticles to tumors;(b)NPs targeted mitochondria to induce reactive oxygen species(ROS)production;(c)hemin encapsulated in nanoparticles could specifically target BACH1,thereby down regulating CD47;(d)hemin had a synergistic effect with DDP,thus augmenting the ***,mitochondria-targeted nanoparticles H/D@FA-CaP-NPs promoted tumor apoptosis and mobilized phagocytosis to treat tumor,providing a novel scheme for clinical treatment of cisplatin-resistant ovarian carcinoma.

关键词： Cisplatin-resistant Hemin BACH1 CD47 Phagocytosis ROS Synergistic effect