The slow rate of nerve regeneration after injury or recon- struction remains a clinical problem because it prohibits the timely reinnervation of distant target muscles be- fore the irreversible degeneration of the neu...The slow rate of nerve regeneration after injury or recon- struction remains a clinical problem because it prohibits the timely reinnervation of distant target muscles be- fore the irreversible degeneration of the neuromuscular junction and breakdown of muscle tissue. As such, high (proximal) nerve injuries result in the incomplete recovery of motor function and poor functional outcomes despite current and timely surgical management. Experimentally, several strategies have been shown to enhance nerve regen- eration and improve functional recovery in animal models but translation to clinical practice has not been realized. Two potential treatments, tacrolimus (immunosuppres- sant) and electrical stimulation are commonly used for other reconstructive indications and as such, are both read- ily available clinically. There is some evidence, which will be reviewed in subsequent sections, that these approaches may also be useful in enhancing neuronal regeneration.展开更多
What makes the acute optic neuritis model unique in an era of trials for neuroprotective and myelin repair agents?Acute optic neuritis(AON)is a common,and often the earliest manifestation of central nervous system...What makes the acute optic neuritis model unique in an era of trials for neuroprotective and myelin repair agents?Acute optic neuritis(AON)is a common,and often the earliest manifestation of central nervous system(CNS)inflammatory demyelinating disorders like multiple sclerosis (MS) and neuromyelitis optica (NMO).展开更多
Objective To study the clinical features and surgical strategies of thoracic spinal stenosis caused by ossification of posterior longitudinal ligament(OPLL).Methods From January 2004 to March 2009,21 cases of tho-raci...Objective To study the clinical features and surgical strategies of thoracic spinal stenosis caused by ossification of posterior longitudinal ligament(OPLL).Methods From January 2004 to March 2009,21 cases of tho-racic spinal stenosis展开更多
Immunoglobulin G4(IgG4)-related cholecystitis(IgG4-C)is often difficult to distinguish from gallbladder carcinoma(GBC).This study aimed to determine a practical strategy for differentiating between IgG4-C and GBC to a...Immunoglobulin G4(IgG4)-related cholecystitis(IgG4-C)is often difficult to distinguish from gallbladder carcinoma(GBC).This study aimed to determine a practical strategy for differentiating between IgG4-C and GBC to avoid unnecessary surgical resection.The expression of IgG4 in the gallbladder was detected by immunohistochemistry.The clinicopathological and radiological characteristics of IgG4-C patients and GBC patients were analyzed retrospectively.Immunohistochemistry revealed that IgG4 was upregulated in the plasma cells of IgG4-C tissues.The median serum total bilirubin levels were significantly higher in the patients with IgG4-C than in those with GBC(45.8μmol L^-1 vs.29.9μmol L^-1).The serumγ-GGT levels were higher in IgG4-C patients than in GBC patients,whereas the serum levels of CA125 were significantly higher in GBC patients than in IgG4-C patients.The imaging scans were helpful for differentiating IgG4-C from GBC based on the presence of a layered pattern and Rokitansky-Aschoff sinuses in the gallbladder wall.There were no statistically significant differences in age,presence of abdominal pain,level of emaciation between the two groups.Our study demonstrated that the combination of imaging with serum total bilirubin,γ-GGTand CA125 levels can offer added preoperative diagnostic value and reduce the rate of IgG4-C misdiagnosis.展开更多
Mutated and activated RAS is a key oncogene that drives various human cancers.RAS-targeted therapy has been an extensive research focus but has made little progress given its long history.Several novel binding sites,e...Mutated and activated RAS is a key oncogene that drives various human cancers.RAS-targeted therapy has been an extensive research focus but has made little progress given its long history.Several novel binding sites,especially the Cys12 mutation in KRAS G12C,have been identified,paving the way for irreversible inhibitor development.A series of clinical trials have proven their efficacies,and the first RAS G12C-targeting drug sotorasib(AMG-510)received approval for non-small cell lung cancer treatment in May,2021.In another approach,the development of indirect RAS inhibitors that target components of the RAS signaling pathway,including the upstream enzyme farnesyl transferase and the downstream effector molecules SOS1,MEK,AKT,and SHP2,has also made significant progress.This review systematically summarizes the latest progress in RAS signaling pathway-targeted drugs,discusses clinical challenges,and proposes beneficial strategies for RAStargeted therapy.展开更多
文摘The slow rate of nerve regeneration after injury or recon- struction remains a clinical problem because it prohibits the timely reinnervation of distant target muscles be- fore the irreversible degeneration of the neuromuscular junction and breakdown of muscle tissue. As such, high (proximal) nerve injuries result in the incomplete recovery of motor function and poor functional outcomes despite current and timely surgical management. Experimentally, several strategies have been shown to enhance nerve regen- eration and improve functional recovery in animal models but translation to clinical practice has not been realized. Two potential treatments, tacrolimus (immunosuppres- sant) and electrical stimulation are commonly used for other reconstructive indications and as such, are both read- ily available clinically. There is some evidence, which will be reviewed in subsequent sections, that these approaches may also be useful in enhancing neuronal regeneration.
文摘What makes the acute optic neuritis model unique in an era of trials for neuroprotective and myelin repair agents?Acute optic neuritis(AON)is a common,and often the earliest manifestation of central nervous system(CNS)inflammatory demyelinating disorders like multiple sclerosis (MS) and neuromyelitis optica (NMO).
文摘Objective To study the clinical features and surgical strategies of thoracic spinal stenosis caused by ossification of posterior longitudinal ligament(OPLL).Methods From January 2004 to March 2009,21 cases of tho-racic spinal stenosis
基金supported by the Special Research Foundation of the National Nature Science Foundation of China(81301865,81672412,81772597 and 81702904)the Guandong Natural Science Foundation(2016A030313840,2017A030311002 and 2018A030313645)+6 种基金the Guangdong Science and Technology Foundation(2016A020215199 and 2017A020215196)Science and Technology Program of Guangzhou,China(201607010111)Pearl River S&T Nova Program of Guangzhou,China(201610010022)the Fundamental Research Funds for the Central Universities(18ykpy22)Key Laboratory of Malignant Tumor Molecular Mechanism and Translational Medicine of Guangzhou Bureau of Science and Information Technology([2013]163)the Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes(KLB09001)Guangdong Science and Technology Department(2015B050501004,2017B030314026)。
文摘Immunoglobulin G4(IgG4)-related cholecystitis(IgG4-C)is often difficult to distinguish from gallbladder carcinoma(GBC).This study aimed to determine a practical strategy for differentiating between IgG4-C and GBC to avoid unnecessary surgical resection.The expression of IgG4 in the gallbladder was detected by immunohistochemistry.The clinicopathological and radiological characteristics of IgG4-C patients and GBC patients were analyzed retrospectively.Immunohistochemistry revealed that IgG4 was upregulated in the plasma cells of IgG4-C tissues.The median serum total bilirubin levels were significantly higher in the patients with IgG4-C than in those with GBC(45.8μmol L^-1 vs.29.9μmol L^-1).The serumγ-GGT levels were higher in IgG4-C patients than in GBC patients,whereas the serum levels of CA125 were significantly higher in GBC patients than in IgG4-C patients.The imaging scans were helpful for differentiating IgG4-C from GBC based on the presence of a layered pattern and Rokitansky-Aschoff sinuses in the gallbladder wall.There were no statistically significant differences in age,presence of abdominal pain,level of emaciation between the two groups.Our study demonstrated that the combination of imaging with serum total bilirubin,γ-GGTand CA125 levels can offer added preoperative diagnostic value and reduce the rate of IgG4-C misdiagnosis.
基金the National Natural Science Foundation of China(No.82173662,81772590 and 81572395)the Natural Science Foundation of Shanghai(No.20ZR1410400)the Extraordinary 2025 Elite Project of Fudan University,the Open Funding of Key Laboratory of Diagnosis and Treatment of Severe Hepato-pancreatic Diseases of Zhejiang Province,and the CAS Interdisciplinary Innovation Team JCTD-2019-07.
文摘Mutated and activated RAS is a key oncogene that drives various human cancers.RAS-targeted therapy has been an extensive research focus but has made little progress given its long history.Several novel binding sites,especially the Cys12 mutation in KRAS G12C,have been identified,paving the way for irreversible inhibitor development.A series of clinical trials have proven their efficacies,and the first RAS G12C-targeting drug sotorasib(AMG-510)received approval for non-small cell lung cancer treatment in May,2021.In another approach,the development of indirect RAS inhibitors that target components of the RAS signaling pathway,including the upstream enzyme farnesyl transferase and the downstream effector molecules SOS1,MEK,AKT,and SHP2,has also made significant progress.This review systematically summarizes the latest progress in RAS signaling pathway-targeted drugs,discusses clinical challenges,and proposes beneficial strategies for RAStargeted therapy.