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

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

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Cognitive impairment in cerebral small vessel disease induced by hypertension

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Neural Regeneration Research 2024年第7期19卷 1454-1462页

作者： Weipeng Wei Denglei Ma Lin Li Lan Zhang Department of Pharmacy Xuanwu Hospital of Capital Medical UniversityBeijingChina Beijing geriatric medical Research center Beijing Engineering Research Center for Nervous System DrugsNational Center for Neurological DisordersNational Clinical Research Center for Geriatric DiseasesBeijingChina

Hypertension is a primary risk factor for the progression of cognitive impairment caused by cerebral small vessel disease,the most common cerebrovascular *** r,the causal relationship between hypertension and cerebral small vessel disease remains *** has substantial negative impacts on brain health and is recognized as a risk factor for cerebrovascular *** hypertension and lifestyle factors are associated with risks for stro ke and dementia,and cerebral small vessel disease can cause dementia and *** is the main driver of cerebral small vessel disease,which changes the structure and function of cerebral vessels via various mechanisms and leads to lacunar infarction,leukoaraiosis,white matter lesions,and intracerebral hemorrhage,ultimately res ulting in cognitive decline and demonstrating that the brain is the to rget organ of *** review updates our understanding of the pathogenesis of hypertensioninduced cerebral small vessel disease and the res ulting changes in brain structure and function and declines in cognitive *** also discuss drugs to treat cerebral small vessel disease and cognitive impairment.

关键词： blood-brain barrier cerebral small vessel disease cognitive impairment dementia endothelial dysfunction enlarged perivascular space hypertension lacunar infarction neuroinflammation treatment white matter high signal intensity

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Improving the value of molecular testing:current status and opportunities in colorectal cancer precision medicine

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Cancer Biology & Medicine 2024年第1期21卷 21-28页

作者： Haiyun Li Linwei Guo Chenchen Wang Xin Hu Ye Xu Department of Colorectal Surgery Fudan University Shanghai Cancer CenterShanghai 200032China Department of Oncology Shanghai Medical CollegeFudan UniversityShanghai 200032China Department of Gastrointestinal medical Oncology Fudan University Shanghai Cancer CenterShanghai 200032China Precision Cancer medical center Affiliated with Fudan University shanghai Cancer center Shanghai 201315China

Colorectal cancer(CRC)is the second leading cause of cancer-related deaths *** radical resection with adjuvant chemotherapy remains the primary treatment choice for CRC,but the 5-year postoperative survival rate is only approximately 60%,and approximately one-third of patients with CRC experience recurrence within 2 years of ***,the transformation of high-throughput sequencing has accelerated the development of precision *** example,KRAS mutations indicate resistance to anti-epidermal growth factor receptor(EGFR)-targeted therapies in ***,molecular-guided individualized therapy has brought new promise in major clinical areas and challenges,such as novel biomarkers predicting sensitivity and resistance to immunotherapy for microsatellite stable(MSS)CRC.

关键词： cancer chemotherapy colorectal

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Ketogenic diet therapy in children with epilepsy caused by SLC2A1 mutations:a single-center single-arm retrospective study

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World Journal of Pediatrics 2024年第5期20卷 517-524页

作者： Ying-Yan Wang Yun-Qing Zhou Li-Juan Luo Cui-Jin Wang Nan Shen Hao Li Ji-Wen Wang Department of Neurology Shanghai Children’s Medical CenterSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina Department of Infectious Diseases Shanghai Children’s Medical CenterSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina Clinical Research Ward Clinical Research CenterShanghai Children’s Medical CenterSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina

Background This retrospective study assessed the efficacy and safety of ketogenic diet therapies in children with epilepsy caused by SLC2A1 genetic mutations and glucose transporter type 1 deficiency *** Pediatric patients with epilepsy symptoms admitted to our medical center between January 2017 and October 2021 were included if they presented with an SLC2A1 genetic mutation on whole-exome *** analyzed the patients’convulsions and treatment with antiepileptic *** patients were followed up at different time periods after ketogenic diet *** Six patients with SLC2A1 mutations were included in this *** patients had seizures of different types and frequencies,and they took antiepileptic drugs to relieve their *** were then treated with a ketogenic diet for at least four *** analyzed epilepsy control rates at 1,2,3,6,and 12 months after ketogenic diet *** patients were seizure-free within a month of receiving the diet *** patients were followed up for six months,three were followed up for 12 months after the treatment,and there was no recurrence of epilepsy during this *** antiepileptic drug withdrawal,none of the patients experienced seizure relapse when receiving ketogenic diet treatment *** severe adverse events occurred during the *** Ketogenic diet therapy is very effective and safe for the treatment of epilepsy caused by SLC2A1 ***,patients with glucose transporter type 1 deficiency syndrome caused by SLC2A1 mutations should begin ketogenic diet treatment as soon as possible.

关键词： Epilepsy Glucose transporter type 1 Ketogenic diet SLC2A1

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Association of prealbumin with short-term and long-term outcomes in patients with acute ST-segment elevation myocardial infarction

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Journal of geriatric Cardiology 2024年第4期21卷 421-430页

作者： Jing TAN Jin SI Ke-Ling XIAO Ying-Hua ZHANG Qi HUA Jing LI Department of Cardiology Xuanwu Hospital Capital Medical UniversityBeijingChina Department of geriatric Medicine Xuanwu Hospital Capital Medical UniversityNational Clinical Research Center for Geriatric DiseasesBeijingChina

BACKGROUND Prealbumin is considered to be a useful indicator of nutritional status. Furthermore, it has been found to be associated with severities and prognosis of a range of diseases. However, limited data on the association of baseline prealbumin level with outcomes of patients with acute ST-segment elevation myocardial infarction(STEMI) are *** We analyzed 2313 patients admitted for acute STEMI between October 2013 and December 2020. In-hospital outcomes and mortality during the 49 months(interquartile range: 26–73 months) follow-up period were compared between patients with the low prealbumin level(< 170 mg/L) and those with the high prealbumin level(≥ 170 mg/L).RESULTS A total of 114 patients(4.9%) died during hospitalization. After propensity score matching, patients with the low prealbumin level than those with the high prealbumin level experienced higher incidences of heart failure with Killip class Ⅲ(9.9%vs. 4.4%, P = 0.034), cardiovascular death(8.4% vs. 3.4%, P = 0.035) and the composite of major adverse cardiovascular events(19.2%vs. 10.3%, P = 0.012). Multivariate logistic regression analysis identified that the low prealbumin level(< 170 mg/L) was an independent predictor of in-hospital major adverse cardiovascular events(odds ratio = 1.918, 95% CI: 1.250–2.942, P = 0.003). The cutoff value of prealbumin level for predicting in-hospital death was 170 mg/L(area under the curve = 0.703, 95% CI: 0.651–0.754, P< 0.001;sensitivity = 0.544, specificity = 0.794). However, after multivariate adjustment of possible confounders, baseline prealbumin level(170 mg/L) was no longer independently associated with 49-month cardiovascular death. After propensity score matching, Kaplan-Meier survival curves revealed consistent *** Decreased prealbumin level closely related to unfavorable short-term outcomes. However, after multivariate adjustment and controlling for baseline differences, baseline prealbumin level was not independently assoc

关键词： patients admitted infarction

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Integration of HiBiT into enteroviruses:A universal tool for advancing enterovirus virology research

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Virologica Sinica 2024年第3期39卷 422-433页

作者： Rui Yu Xiaohong Li Peng Zhang Minghao Xu Jitong Zhao Jingjing Yan Chenli Qiu Jiayi Shu Shuo Zhang Miaomiao Kang Xiaoyan Zhang Jianqing Xu Shuye Zhang School of Medicine Shanghai UniversityShanghai200444China Clinical center for Biotherapy Zhongshan HospitalFudan UniversityShanghai200433China Guangzhou Institutes of Biomedicine and Health The Chinese Academy of SciencesGuangzhou510530China Institutes of Biomedical Sciences Fudan UniversityShanghai200032China shanghai geriatric medical center Shanghai201104China Clinical center for Biotherapy Zhongshan Hospital/Zhongshan Hospital(Xiamen)Fudan University361015China shanghai Public Health Clinical center Fudan UniversityShanghai201508China

The utilization of enteroviruses engineered with reporter genes serves as a valuable tool for advancing our understanding of enterovirus biology and its applications,enabling the development of effective therapeutic and preventive *** this study,our initial attempts to introduce a NanoLuc luciferase(NLuc)reporter gene into recombinant enteroviruses were unsuccessful in rescuing viable *** hypothesized that the size of the inserted tag might be a determining factor in the rescue of the ***,we inserted the 11-amino-acid HiBiT tag into the genomes of enterovirus A71(EV-A71),coxsackievirus A10(CVA10),coxsackievirus A7(CVA7),coxsackievirus A16(CVA16),namely EV-A71-HiBiT,CVA16-HiBiT,CVA10-HiBiT,CVA7-HiBiT,and observed that the HiBiT-tagged viruses exhibited remarkably high rescue ***,the HiBiT-tagged enteroviruses displayed comparable characteristics to the wild-type viruses.A direct comparison between CVA16-NLuc and CVA16-HiBiT recombinant viruses revealed that the tiny HiBiT insertion had minimal impact on virus infectivity and replication ***,these HiBiT-tagged enteroviruses demonstrated high genetic stability in different cell lines over multiple *** addition,the HiBiT-tagged viruses were successfully tested in antiviral drug assays,and the sensitivity of the viruses to drugs was not affected by the HiBiT ***,our findings provide definitive evidence that the integration of HiBiT into enteroviruses presents a universal,convenient,and invaluable method for advancing research in the realm of enterovirus ***,HiBiT-tagged enteroviruses exhibit great potential for diverse applications,including the development of antivirals and the elucidation of viral infection mechanisms.

关键词： Enterovirus Infectious clones Reporter genes Luciferase Drug screening

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Decoupled deep hough voting for point cloud registration

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Frontiers of Computer Science 2024年第2期18卷 147-155页

作者： Mingzhi YUAN Kexue FU Zhihao LI Manning WANG Digital medical Research center School of Basic Medical SciencesFudan UniversityShanghai 200032China shanghai Key Laboratory of medical Image Computing and Computer Assisted Intervention Shanghai 200032China

Estimating rigid transformation using noisy correspondences is critical to feature-based point cloud ***,a series of studies have attempted to combine traditional robust model fitting with deep *** them,DHVR proposed a hough voting-based method,achieving new state-of-the-art ***,we find voting on rotation and translation simultaneously hinders achieving better ***,we proposed a new hough voting-based method,which decouples rotation and translation ***,we first utilize hough voting and a neural network to estimate *** based on good initialization on rotation,we can easily obtain accurate rigid *** experiments on 3DMatch and 3DLoMatch datasets show that our method achieves comparable performances over the state-of-the-art *** further demonstrate the generalization of our method by experimenting on KITTI dataset.

关键词： point cloud registration robust model fitting deep learning hough voting

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Lupenone improves motor dysfunction in spinal cord injury mice through inhibiting the inflammasome activation and pyroptosis in microglia via the nuclear factor kappa B pathway

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Neural Regeneration Research 2024年第8期19卷 1802-1811页

作者： Fudong Li Xiaofei Sun Kaiqiang Sun Fanqi Kong Xin Jiang Qingjie Kong Department of Orthopedics Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghaiChina Department of Orthopedic Surgery Spine CenterShanghai Changzheng HospitalNaval Medical UniversityShanghaiChina Department of Orthopedic Surgery Naval Medical CenterNaval Medical UniversityShanghaiChina Department of Anesthesiology Shanghai Changzheng HospitalNaval Medical UniversityShanghaiChina

Spinal cord injury-induced motor dysfunction is associated with *** have shown that the triterpenoid lupenone,a natural product found in various plants,has a remarkable anti-inflammatory effect in the context of chronic ***,the effects of lupenone on acute inflammation induced by spinal cord injury remain *** this study,we established an impact-induced mouse model of spinal cord injury,and then treated the injured mice with lupenone(8 mg/kg,twice a day)by intrape ritoneal *** also treated BV2 cells with lipopolysaccharide and adenosine5’-triphosphate to simulate the inflammatory response after spinal cord *** res ults showed that lupenone reduced IKBa activation and p65 nuclear translocation,inhibited NLRP3 inflammasome function by modulating nuclear factor kappa B,and enhanced the conve rsion of proinflammatory M1 mic roglial cells into anti-inflammatory M2 microglial ***,lupenone decreased NLRP3 inflammasome activation,NLRP3-induced mic roglial cell polarization,and microglia pyroptosis by inhibiting the nuclear factor kappa B *** findings suggest that lupenone protects against spinal cord injury by inhibiting inflammasomes.

关键词： inflammasome inflammation lupenone microglia polarization pyroptosis spinal cord injury

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Network meta-analysis of combination strategies in metastatic hormone-sensitive prostate cancer

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Asian Journal of Andrology 2024年第4期26卷 402-408页

作者： Shan-Shan Wang Xiao-Jie Bian Jun-Long Wu Bei-He Wang Sheng Zhang Ding-Wei Ye Department of Urology Fudan University Shanghai Cancer CenterShanghai 200032China Department of Oncology Shanghai Medical CollegeFudan UniversityShanghai 200032China Department of medical Oncology Fudan University Shanghai Cancer CenterShanghai 200032China.

This study compared different doublet and triplet therapies for efficacy and safety in metastatic hormone-sensitive prostate cancer(mHSPC).PubMed,EMBASE,and the Cochrane Library were comprehensively searched for eligible randomized controlled trials(RCTs)published from inception to October *** included abiraterone,apalutamide,enzalutamide,docetaxel,darolutamide,and androgen deprivation therapy(ADT),either as doublet or triplet *** outcomes examined were overall survival(OS),progression-free survival(PFS),castration-resistant prostate cancer(CRPC)-free survival,time to symptomatic skeletal event(SSE),and *** surface under the cumulative ranking curve(SUCRA)was determined to identify the preferred *** RCTs were *** combination of darolutamide,docetaxel,and ADT had the highest SUCRA of 84.3 for OS,followed by combined abiraterone,docetaxel,and ADT(SUCRA=71.6).The highest SUCRAs for PFS were observed for triplet therapies(abiraterone,docetaxel,and ADT[SUCRA=74.9],followed by enzalutamide,docetaxel,and ADT[SUCRA=74.3])and other androgen receptor axis-targeted therapy-based doublet therapies(SUCRAs:26.5–59.3).Darolutamide,docetaxel,and ADT had the highest SUCRAs,i.e.,80.8 and 84.0 regarding CRPC-free survival and time to SSE,*** Grade>3 adverse events(AEs),the SUCRAs of triplet therapies(SUCRAs:14.8–31.5)were similar to that of docetaxel and ADT(SUCRA=39.5).Three studies had a low risk of bias in all categories;the remaining studies had at least an unclear risk of bias in at least one *** therapy demonstrated potentially enhanced effectiveness than doublet therapy in mHSPC,with acceptable safety *** might be the optimal option for triplet therapy in combination with docetaxel and ADT.

关键词： androgen antagonist androgen receptor antagonist docetaxel meta-analysis prostatic neoplasm

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Efficacy of physiological seawater nasal irrigation for the treatment of children with SARS-CoV-2 Omicron BA.2 variant infection:a randomized controlled trial

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World Journal of Pediatrics 2024年第5期20卷 461-469页

作者： Ji-Lei Lin Fen Zhang Yan-Bo Li Shu-Hua Yuan Jin-Hong Wu Jing Zhang Lei Zhang Yi He Jie Chen Yong Yin Department of Respiratory Medicine Shanghai Children’s Medical CenterSchool of MedicineShanghai Jiao Tong University1678 Dongfang RoadPudong DistrictShanghaiChina University of British Columbia VancouverCanada Information Technology Department Shanghai Children’s Medical Center National Children’s Medical CenterSchool of MedicineShanghai Jiao Tong University1678 Dongfang RoadPudong DistrictShanghaiChina Department of Otorhinolaryngology Shanghai Children’s Medical CenterSchool of MedicineShanghai Jiao Tong University1678 Dongfang RoadPudong DistrictShanghaiChina Department of Respiratory Medicine Sanya Women and Children’s Hospital Affiliated to Hainan Medical CollegeHainan Branch of Shanghai Children’s Medical CenterSanyaChina Department of Respiratory Medicine Linyi Maternal and Child Healthcare HospitalLinyiChina shanghai Children’s medical center Pediatric medical Complex(Pudong) ShanghaiChina Pediatric AI Clinical Application and Research center Shanghai Children’s Medical CenterShanghaiChina

Background Saline nasal irrigation is an effective therapy for relieving common cold *** study aimed to investigate and explore the efficacy of physiological seawater nasal irrigation(PSNI)on children with mild and asymptomatic infection with *** This randomized controlled trial was conducted in shanghai,China,and 403 children with mild and asymptomatic infection with Omicron were *** children were allocated into the PSNI group and the control *** primary outcome was the duration of viral shedding(DVS),and the secondary outcome was the change in clinical *** The median age of all participants was 5.59(6.26)years *** DVS was significantly shorter in the PSNI group[2.40(1.13)]than in the control group[3.09(2.14)](P=0.014).The multivariable Cox regression model also showed that patients in the PSNI group had an increased probability of shorter DVS compared with patients in the control group[hazard ratio(HR),1.27;95%confidence interval(CI),1.04–1.55;P=0.017].Subgroup analysis suggested that the DVS of patients without full vaccination was significantly reduced in the PSNI *** proportions of runny nose and stuffy nose were apparently reduced in the first three days in the PSNI group or the control group,but there was no evidence showing that PSNI contributes to the benefit compared with the control *** PSNI can reduce the DVS of patients with mild and asymptomatic infection with SARS-CoV-2 Omicron BA.2 variant.

关键词： Children Duration of viral shedding Omicron Physiological seawater nasal irrigation

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