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Journal of Environmental Sciences 2008年第9期20卷 1132-1137页

作者： WANG Dayong XING Xiaojuan Key Laboratory of Developmental Genes and Human disease Ministry of Education Southeast University Medical School Nanjing 210009 China department of genetics and Developmental Biology Southeast University Nanjing 210009 China

Locomotion behaviors are susceptible to disruption by a broad spectrum of chemicals and environmental stresses. However, no systematic testing of locomotion behavior defects induced by metal exposure has been conducted in the model organism of nematode Caenorhabditis elegans. In this study, the acute toxicity from heavy metal exposure on the locomotion behaviors was analyzed in nematodes. Endpoints of head thrash, body bend, forward turn, backward turn, and Omega/U turn were chosen to evaluate the locomotio...

关键词： locomotion behavior heavy metal acute exposure C. elegans

Apoer2/Lrp8:the undercover cop of synaptic homeostasis

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Neural Regeneration Research 2024年第12期19卷 2563-2564页

作者： Gordon C.Werthmann Joachim Herz department of Molecular genetics and center for Translational Neurodegeneration Research University of Texas Southwestern Medical Center at DallasDallasTXUSA department of Neuroscience department of Neurology University of Texas Southwestern medical center at Dallas DallasTXUSA

Apolipoprotein E receptor 2(ApoER2)is a receptor for the protein ApoE,the most common genetic risk factor for late-onset Alzheimer's disease(AD).It is also a key modulator of syna ptic homeostasis,in part through its effect on the expression of neuronal genes including those implicated in AD and other neuropsychiatric *** this perspective,we highlight several genes affected by ApoER2 and its alternatively spliced forms and how aberrant expression can be rescued by the reintroduction of the ApoER2 intracellular domain in the mouse hippocampus.

关键词： homeostasis ApoE Alzheimer

Development of a potential PET probe for HDAC6 imaging in Alzheimer's disease

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Acta Pharmaceutica Sinica B 2022年第10期12卷 3891-3904页

作者： Ping Bai Prasenjit Mondal Frederick A.Bagdasarian Nisha Rani Yan Liu Ashley Gomm Darcy R.Tocci Se Hoon Choi Hsiao-Ying Wey Rudolph E.Tanzi Can Zhang Changning Wang Athinoula A.Martinos center for Biomedical Imaging Department of RadiologyMassachusetts General HospitalHarvard Medical SchoolCharlestownMA 02129USA genetics and Aging Research Unit McCance Center for Brain HealthMassGeneral Institute for Neurodegenerative DiseaseDepartment of NeurologyMassachusetts General HospitalHarvard Medical SchoolCharlestownMA 02129USA

Although the epigenetic regulatory protein histone deacetylase 6(HDAC6)has been recently implicated in the etiology of Alzheimer’s disease(AD),little is known about the role of HDAC6 in the etiopathogenesis of AD and whether HDAC6 can be a potential therapeutic target for ***,we performed positron emission tomography(PET)imaging in combination with histopathological analysis to better understand the underlying pathomechanisms of HDAC6 in *** first developed[^(18)F]PB118 which was demonstrated as a valid HDAC6 radioligand with excellent brain penetration and high specificity to *** studies of[^(18)F]PB118 in 5xFAD mice showed significantly increased radioactivity in the brain compared to WT animals,with more pronounced changes identified in the cortex and *** translatability of this radiotracer for AD in a potential human use was supported by additional studies,including similar uptake profiles in non-human primates,an increase of HDAC6 in ADrelated human postmortem hippocampal tissues by Western blotting protein analysis,and our ex vivo histopathological analysis of HDAC6 in postmortem brain tissues of our ***,our findings show that HDAC6 may lead to AD by mechanisms that tend to affect brain regions particularly susceptible to AD through an association with amyloid pathology.

关键词： HDAC6 Alzheimer’s disease Radiotracer PET imaging Epigenetic

Analysis and prediction of research hotspots and trends in pediatric medicine from 2,580,642 studies published between 1940 and 2021

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World Journal of Pediatrics 2023年第8期19卷 793-797页

作者： Ze‑Ye Liu Yuan Huang Jing Xu Li Xiang Zhan‑Hao Su Yi‑Wei Liu Hao Zhang department of Structural Heart disease National Center for Cardiovascular DiseaseFuwai HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100037China State Key Laboratory of Cardiovascular disease Fuwai HospitalNational Center for Cardiovascular DiseasesPediatric Cardiac Surgery CenterFuwai HospitalChinese Academy of Medical Sciencesand Peking Union Medical CollegeBeijingChina State Key Laboratory of Cardiovascular disease Fuwai HospitalNational Center for Cardiovascular DiseasesFuwai HospitalChinese Academy of Medical Sciencesand Peking Union Medical CollegeBeijingChina Heart center and Shanghai Institute of Pediatric Congenital Heart disease Shanghai Children’s Medical CenterNational Children’s Medical CenterShanghai Jiaotong University School of MedicineNo.1678 Dongfang RoadShanghai 200127China department of Cardiovascular Surgery Guangdong Cardiovascular InstituteGuangdong Provincial People’s HospitalGuangdong Academy of Medical SciencesGuangzhou 510060China Shanghai Clinical Research center for rare Pediatric diseases Shanghai Children’s Medical CenterSchool of MedicineShanghai Jiao Tong UniversityShanghai 200127China

From 1990 to 2019,there has been a substantial increase in the global population from 5.3 billion to 7.7 billion(about 44.6%)[1,2].Simultaneously,the global death population among people under 20 years of age has increased from 6.22 million to 13.93 million,accounting for an increase of 124%[1,2,3].This means that the mortality rate of children/adolescents is almost three times higher than the growth rate of the global population.

关键词： mortality population. pediatric

Novel drug-delivery approaches to the blood-brain barrier

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Neuroscience Bulletin 2015年第2期31卷 257-264页

作者： Xiaoqing Wang Xiaowen Yu William Vaughan Mingyuan Liu Yangtai Guan department of Neurology Changhai Hospital Second Military Medical University Stem Cells and medical Research center Second Military Medical University department of Gerontology Changhai Hospital Second Military Medical University department of genetics Yale University

The blood-brain barrier （BBB） maintains homeostasis by blocking toxic molecules from the circulation, but drugs are blocked at the same time. When the dose is increased to enhance the drug concentration in the central nervous system, there are side-effects on peripheral organs. In recent years, genetic therapeutic agents and small molecules have been used in various strategies to penetrate the BBB while minimizing the damage to systemic organs. In this review, we describe several representative methods to circumvent or cross the BBB, including chemical and physical strategies.

关键词： drug delivery blood-brain barrier nanoparticles focused ultrasound

Insulin, longevity, and genetic analysis of metabolism

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Protein & Cell 2010年第7期1卷 605-606页

作者： Steven Y Cheng department of Developmental genetics center for Regenerative Medicine Nanjing Medical UniversityNanjing 210029China

In a 1989 Hollywood hit“Sex,Lies,and Videotapes”,director Steven Soderbergh told a story of an incestuous affair between a hot-shot lawyer and the sister of his married *** over-stayed visit by a drifter whose unusual fetish of videotaping conversations about sex lives of women deconvoluted this adulterous *** the biological life,persistent bias can also throw off a balance such as the homeostasis delicately constructed among metabolism,longevity,and the insulin signaling *** a recent paper published in Cell Metabolism,Yong Liu’s group at the Shanghai Institute of Nutritional Sciences and Liangyou Rui’s group at the University of Michigan medical School reported that alteration of metabolism through genetic deletion of SH2B,a gene encoding an adaptor protein required for insulin signaling,causes significant changes in the life span of affected fruitflies and *** the manmade and the god-made stories show only a slight superficial analogy in form,they both unfold through serendipitous analyses of seemingly unrelated events,a theme that reoccurringly underscores the importance of basic research.

关键词： metabolism analogy conversation

Gene therapy for monogenic disorders: challenges, strategies, and perspectives

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Journal of genetics and Genomics 2024年第2期51卷 133-143页

作者： Yi Zhang Zhi-Ying Wu department of medical genetics and center for rare diseases Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang 310009China department of Neurology Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang 310009China Key Laboratory of medical Neurobiology of Zhejiang Province HangzhouZhejiang 310009China

Monogenic disorders refer to a group of human diseases caused by mutations in single genes. While disease-modifying therapies have offered some relief from symptoms and delayed progression for some monogenic diseases, most of these diseases still lack effective treatments. In recent decades, gene therapy has emerged as a promising therapeutic strategy for genetic disorders. Researchers have developed various gene manipulation tools and gene delivery systems to treat monogenic diseases. Despite this progress, concerns about inefficient delivery, persistent expression, immunogenicity, toxicity, capacity limitation, genomic integration, and limited tissue specificity still need to be addressed. This review gives an overview of commonly used gene therapy and delivery tools, along with the challenges they face and potential strategies to counter them.

关键词： Gene therapy Monogenic diseases Geneediting Genedelivery Challenges

Criteria for level 1 and level 2 trauma codes: Are pelvic ring injuries undertriaged?

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World Journal of Orthopedics 2016年第8期7卷 481-486页

作者： Brittany E Haws Scott Wuertzer Laura Raffield Leon Lenchik Anna N Miller Wake Forest School of Medicine Medical Center Boulevard department of Radiology Medical Center Boulevard department of Molecular genetics and Genomics Medical Center Boulevard department of Orthopaedic Surgery Medical Center Boulevard

AIM: To determine the association of unstable pelvic ring injuries with trauma code ***: A retrospective review of all pelvic ring injuries at a single academic center from July 2010 to June 2013 was performed. The trauma registry was used to identify level 1 and level 2 trauma codes for each injury. The computed tomography scans in all patients were classified as stable or unstable using the Abbreviated Injury Scale. Pelvic injury classifications in level 1 and level 2 groups were compared. Patient disposition at discharge in level 1 and level 2 groups were also ***: There were 108 level 1 and 130 level 2 blunt trauma admissions. In the level 1 group, 67% of pelvic injuries were classified as stable fracture patterns and 33% were classified as unstable. In the level 2 group, 62% of pelvic injuries were classified as stable fracture patterns and 38% were classified as unstable. level 1 trauma code was not associated with odds of having an unstable fracture pattern(OR = 0.83, 95%CI: 0.48-1.41, P = 0.485). In the level 1 group with unstable pelvic injuries, 33% were discharged to home, 36% to a rehabilitation facility, and 32% died. In the level 2 group with unstable pelvic injuries, 65% were discharged to home, 31% to a rehabilitation facility, and 4% died. For those with unstable pelvic fractures(n = 85), assignment of a level 2 trauma code was associated with reduced odds of death(OR = 0.07, 95%CI: 0.01-0.35, P = 0.001) as compared to being discharged to ***: Trauma code level assignment is not correlated with severity of pelvic injury. Because an unstable pelvis can lead to hemodynamic instability, these injuries may be undertriaged.

关键词： Pelvic ring Trauma code Triage Unstable pelvis Abbreviated injury scale

Complete reprogramming to all-iPS mice

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Protein & Cell 2010年第1期1卷 2-3页

作者： Steven Y Cheng department of Developmental genetics and center for Regenerative Medicine Nanjing Medical UniversityNanjing 210029China

The landmark discoveries by Shinya Yamanaka in mice and later separately by James Thompson in humans that adult animal cells can be reprogrammed to a pluripotent state of embryonic stem(ES)cells by forced expression of just a few key transcription factors have permanently altered a long-held view about the stability of differentiated cells in developmental biology,and suggested a way of generating personalized replacement tissues from patients’own cells for the regenerative medical treatment.

关键词： programming generating permanent

Peritonitis with small bowel perforation caused by a fish bone in a healthy patient

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World Journal of Gastroenterology 2014年第6期20卷 1626-1629页

作者： Yonghoon Choi Gyuwon Kim Chansup Shim Dongkeun Kim Dongju Kim department of Internal Medicine Sahmyook Seoul Hospital department of Gastroenterology Sahmyook Seoul Hospital Digestive disease center Konkuk University Medical Center

Perforation of the gastrointestinal tract by ingested foreign bodies is extremely rare in otherwise healthy patients, accounting for < 1% of cases. Accidentally ingested foreign bodies could cause small bowel perforat... 详细信息

Perforation of the gastrointestinal tract by ingested foreign bodies is extremely rare in otherwise healthy patients, accounting for rarely reported, particularly in patients without intestinal disease. We report a case of 57-year-old female who visited the emergency room with periumbilical pain and no history of underlying intestinal disease or intra-abdominal surgery. Abdominal computed tomography and exploratory laparotomy revealed a small bowel micro-perforation with a 2.7-cm fish bone penetrating the jejunal wall.

关键词： Peritonitis Small bowel perforation Foreign body Fish bone Japanese red rock fish