Clear aligner treatment is a novel technique in current orthodontic practice.Distinct from traditional fixed orthodontic appliances,clear aligners have different material features and biomechanical characteristics and...Clear aligner treatment is a novel technique in current orthodontic practice.Distinct from traditional fixed orthodontic appliances,clear aligners have different material features and biomechanical characteristics and treatment efficiencies,presenting new clinical challenges.Therefore,a comprehensive and systematic description of the key clinical aspects of clear aligner treatment is essential to enhance treatment efficacy and facilitate the advancement and wide adoption of this new technique.This expert consensus discusses case selection and grading of treatment difficulty,principle of clear aligner therapy,clinical procedures and potential complications,which are crucial to the clinical success of clear aligner treatment.展开更多
Liver trauma,a common and severe surgical emergency,refers to injuries caused by various external forces acting on the liver.The causes of liver trauma are diverse,with direct external impacts such as traffic accident...Liver trauma,a common and severe surgical emergency,refers to injuries caused by various external forces acting on the liver.The causes of liver trauma are diverse,with direct external impacts such as traffic accidents,falls from heights,and violent collisions being frequent contributors.Additionally,iatrogenic procedures like improper liver biopsy techniques may also lead to liver trauma.Clinically,symptoms vary depending on the severity and extent of injury.Mild cases might present with localized symptoms like right upper abdominal pain and tenderness,while severe cases could result in massive intra-abdominal bleeding accompanied by shock symptoms,including pallor,rapid heart rate,and hypotension,along with gastrointestinal manifestations such as nausea and vomiting.Treatment approaches differ significantly:For minor injuries,conservative management typically involves bed rest,close monitoring of vital signs,hemostasis,and anti-infection measures.In critical scenarios involving liver rupture or massive hemorrhage,immediate surgical intervention is required to repair liver damage and control bleeding.展开更多
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
Objective:Hyper-progression recurrence(HPR)after hepatectomy is a specific recurrence pattern associated with extremely poor prognosis in patients with hepatocellular carcinoma(HCC).This study was aimed at investigati...Objective:Hyper-progression recurrence(HPR)after hepatectomy is a specific recurrence pattern associated with extremely poor prognosis in patients with hepatocellular carcinoma(HCC).This study was aimed at investigating the probable risk factors and establishing comprehensive models for formulating clinical strategies.Methods:Overall,16,158 patients with HCC from 8 hospitals were screened,among whom 3,125 patients who underwent R0 resection were included,and divided into development(n=2,113)and validation(n=1,012)cohorts.A comprehensive study of HPR predictive models and biological features was conducted.Results:Among the 3,125 enrolled patients,506(16.19%)developed HPR.The influence of HPR on extremely poor prognosis was reflected by recurrence features,adverse effects on systemic and liver function,and limited therapeutic options.Nine variables closely associated with HPR were identified,and incorporated into nomogram and conditional inference tree models,which successfully achieved pre-and post-operative HPR risk stratification and facilitated clinical decision-making.Multi-dimensional verification also confirmed the predictive accuracy of model combinations and their reliability in clinical applications.Furthermore,biological analyses revealed that HCCs with HPR exhibited hyperactive biological processes,inactive metabolism,and immune exhaustion features,together with high MYCN/HMGA2 co-expression,thereby enhancing understanding of the molecular events leading to HPR and providing valuable knowledge for HPR management.Conclusions:HPR after hepatectomy is associated with extremely poor prognosis and requires substantial attention.We constructed comprehensive predictive models and propose a clinical strategy for guiding HPR prevention and management.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
Targeted therapy has fundamentally altered the diagnosis and treatment of clinical cancers.By focusing on chromosomal abnormalities and various indications of cancer,these medications have paved the way for the precis...Targeted therapy has fundamentally altered the diagnosis and treatment of clinical cancers.By focusing on chromosomal abnormalities and various indications of cancer,these medications have paved the way for the precise treatment of malignant tumors.In addition to markedly reversing the status quo of reliance on radiotherapy,chemotherapy,and surgery,these drugs have radically transformed the clinical treatment of advanced malignant tumors and became the leading candidates in the fight against cancer.Significant advancements in new targeted medications,including small molecules(e.g.,KRASG12C inhibitors),bispecific antibodies,antibody drug conjugates,and cellular immunotherapy,are due to the advent of new technology and treatments.Notably,numerous difficulties have been encountered,although each medicine class has its own unique benefits and drawbacks.To serve as a key summary for the development of new treatment options for precision cancer medicine recently,this review aimed to summarize the most recent anti-tumor revolutionary medications with significant prospective therapeutic advantages.展开更多
Messenger RNA(mRNA)has emerged as an innovative therapeutic modality,offering promising avenues for the prevention and treatment of a variety of diseases.The tremendous success of mRNA vaccines in effectively combatti...Messenger RNA(mRNA)has emerged as an innovative therapeutic modality,offering promising avenues for the prevention and treatment of a variety of diseases.The tremendous success of mRNA vaccines in effectively combatting coronavirus disease 2019(COVID-19)evidences the unlimited medical and therapeutic potential of mRNA technology.Overcoming challenges related to mRNA stability,immunogenicity,and precision targeting has been made possible by recent advancements in lipid nanoparticles(LNPs).This review summarizes state-of-the-art LNP-mRNA-based therapeutics,including their structure,material compositions,design guidelines,and screening principles.Additionally,we highlight current preclinical and clinical trends in LNP-mRNA therapeutics in a broad range of treatments in ophthalmological conditions,cancer immunotherapy,gene editing,and rare-disease medicine.Particular attention is given to the translation and evolution of LNP-mRNA vaccines into a broader spectrum of therapeutics.We explore concerns in the aspects of inadequate extrahepatic targeting efficacy,elevated doses,safety concerns,and challenges of large-scale production procedures.This discussion may offer insights and perspectives on near-and long-term clinical development prospects for LNP-mRNA therapeutics.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
The coronavirus disease 2019(COVID-19),caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has high-lighted the pivotal role of the immune response in determining the progression and severity of ...The coronavirus disease 2019(COVID-19),caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has high-lighted the pivotal role of the immune response in determining the progression and severity of viral infections.In this paper,we review the most recent studies on the complicated dynamics between SARs-CoV-2 and the host immune system,highlight the importance of understanding these dynamics in developing effective treatments and formulate potent management strategies for CoVID-19.We describe the activation of the host's innate immunity and the subsequent adaptive immune response following infection with SARS-CoV-2.In addition,the review emphasizes the immune evasion strategies of the SARS-CoV-2,including inhibition of interferon production and induction of cytokine storms,along with the resulting clinical outcomes.Finally,we assess the efficacy of current treatment strategies,including antiviral drugs,monoclonal antibodies,and anti-inflammatory treatments,and discuss their role in providing immunity and preventing severe disease.展开更多
文摘Clear aligner treatment is a novel technique in current orthodontic practice.Distinct from traditional fixed orthodontic appliances,clear aligners have different material features and biomechanical characteristics and treatment efficiencies,presenting new clinical challenges.Therefore,a comprehensive and systematic description of the key clinical aspects of clear aligner treatment is essential to enhance treatment efficacy and facilitate the advancement and wide adoption of this new technique.This expert consensus discusses case selection and grading of treatment difficulty,principle of clear aligner therapy,clinical procedures and potential complications,which are crucial to the clinical success of clear aligner treatment.
文摘Liver trauma,a common and severe surgical emergency,refers to injuries caused by various external forces acting on the liver.The causes of liver trauma are diverse,with direct external impacts such as traffic accidents,falls from heights,and violent collisions being frequent contributors.Additionally,iatrogenic procedures like improper liver biopsy techniques may also lead to liver trauma.Clinically,symptoms vary depending on the severity and extent of injury.Mild cases might present with localized symptoms like right upper abdominal pain and tenderness,while severe cases could result in massive intra-abdominal bleeding accompanied by shock symptoms,including pallor,rapid heart rate,and hypotension,along with gastrointestinal manifestations such as nausea and vomiting.Treatment approaches differ significantly:For minor injuries,conservative management typically involves bed rest,close monitoring of vital signs,hemostasis,and anti-infection measures.In critical scenarios involving liver rupture or massive hemorrhage,immediate surgical intervention is required to repair liver damage and control bleeding.
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 National Natural Science Foundation of China(Grant Nos.NSFC 82273405,and 81972306)supported partly by the Guangxi Nature Sciences grants(Grant No.2018GXNSFAA138028)the Guangxi Medical University Training Program for Distinguished Young Scholars.
文摘Objective:Hyper-progression recurrence(HPR)after hepatectomy is a specific recurrence pattern associated with extremely poor prognosis in patients with hepatocellular carcinoma(HCC).This study was aimed at investigating the probable risk factors and establishing comprehensive models for formulating clinical strategies.Methods:Overall,16,158 patients with HCC from 8 hospitals were screened,among whom 3,125 patients who underwent R0 resection were included,and divided into development(n=2,113)and validation(n=1,012)cohorts.A comprehensive study of HPR predictive models and biological features was conducted.Results:Among the 3,125 enrolled patients,506(16.19%)developed HPR.The influence of HPR on extremely poor prognosis was reflected by recurrence features,adverse effects on systemic and liver function,and limited therapeutic options.Nine variables closely associated with HPR were identified,and incorporated into nomogram and conditional inference tree models,which successfully achieved pre-and post-operative HPR risk stratification and facilitated clinical decision-making.Multi-dimensional verification also confirmed the predictive accuracy of model combinations and their reliability in clinical applications.Furthermore,biological analyses revealed that HCCs with HPR exhibited hyperactive biological processes,inactive metabolism,and immune exhaustion features,together with high MYCN/HMGA2 co-expression,thereby enhancing understanding of the molecular events leading to HPR and providing valuable knowledge for HPR management.Conclusions:HPR after hepatectomy is associated with extremely poor prognosis and requires substantial attention.We constructed comprehensive predictive models and propose a clinical strategy for guiding HPR prevention and management.
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.
基金supported by the National Natural Science Foundation of China(82173662)Natural Science Foundation of Shanghai(20ZR1410400)+2 种基金State Key Basic Research Program of China(2018YFC0310905)Extraordinary 2025 Elite Project of Fudan UniversityOpen Funding of the Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province(2018E10008).
文摘Targeted therapy has fundamentally altered the diagnosis and treatment of clinical cancers.By focusing on chromosomal abnormalities and various indications of cancer,these medications have paved the way for the precise treatment of malignant tumors.In addition to markedly reversing the status quo of reliance on radiotherapy,chemotherapy,and surgery,these drugs have radically transformed the clinical treatment of advanced malignant tumors and became the leading candidates in the fight against cancer.Significant advancements in new targeted medications,including small molecules(e.g.,KRASG12C inhibitors),bispecific antibodies,antibody drug conjugates,and cellular immunotherapy,are due to the advent of new technology and treatments.Notably,numerous difficulties have been encountered,although each medicine class has its own unique benefits and drawbacks.To serve as a key summary for the development of new treatment options for precision cancer medicine recently,this review aimed to summarize the most recent anti-tumor revolutionary medications with significant prospective therapeutic advantages.
基金supported by the National Key Research and Development Program of China(2022YFE0202500)Distinguished Young Scholars of the National Natural Science Foundation of China(grant no.T2222022)+5 种基金National Key Research and Development Program of China(2021YFC2302402 and 2021YFC2302605)Major Program of the National Natural Science Foundation of China(grant no.T2394503)Key Project of the National Natural Science Foundation of China(grant no.32030062)CAS Project for Young Scientists in Basic Research(YSBR-010)the Foundation for Innovative Research Groups of the National Natural Science Foundation of China(grant no.21821005)Youth Innovation Promotion Association of the Chinese Academy of Sciences(no.2020000053).
文摘Messenger RNA(mRNA)has emerged as an innovative therapeutic modality,offering promising avenues for the prevention and treatment of a variety of diseases.The tremendous success of mRNA vaccines in effectively combatting coronavirus disease 2019(COVID-19)evidences the unlimited medical and therapeutic potential of mRNA technology.Overcoming challenges related to mRNA stability,immunogenicity,and precision targeting has been made possible by recent advancements in lipid nanoparticles(LNPs).This review summarizes state-of-the-art LNP-mRNA-based therapeutics,including their structure,material compositions,design guidelines,and screening principles.Additionally,we highlight current preclinical and clinical trends in LNP-mRNA therapeutics in a broad range of treatments in ophthalmological conditions,cancer immunotherapy,gene editing,and rare-disease medicine.Particular attention is given to the translation and evolution of LNP-mRNA vaccines into a broader spectrum of therapeutics.We explore concerns in the aspects of inadequate extrahepatic targeting efficacy,elevated doses,safety concerns,and challenges of large-scale production procedures.This discussion may offer insights and perspectives on near-and long-term clinical development prospects for LNP-mRNA therapeutics.
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supported by The Science and Technology Development Fund,Macao SAR(Grant Nos.0058/2020/A,0018/2023/AM).
文摘The coronavirus disease 2019(COVID-19),caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has high-lighted the pivotal role of the immune response in determining the progression and severity of viral infections.In this paper,we review the most recent studies on the complicated dynamics between SARs-CoV-2 and the host immune system,highlight the importance of understanding these dynamics in developing effective treatments and formulate potent management strategies for CoVID-19.We describe the activation of the host's innate immunity and the subsequent adaptive immune response following infection with SARS-CoV-2.In addition,the review emphasizes the immune evasion strategies of the SARS-CoV-2,including inhibition of interferon production and induction of cytokine storms,along with the resulting clinical outcomes.Finally,we assess the efficacy of current treatment strategies,including antiviral drugs,monoclonal antibodies,and anti-inflammatory treatments,and discuss their role in providing immunity and preventing severe disease.
