Ischemic stroke caused by intracranial vascular occlusion has become increasingly prevalent with considerable mortality and disability,which gravely burdens the global economy.Current relatively effective clinical tre...Ischemic stroke caused by intracranial vascular occlusion has become increasingly prevalent with considerable mortality and disability,which gravely burdens the global economy.Current relatively effective clinical treatments are limited to intravenous alteplase and thrombectomy.Even so,patients still benefit little due to the short therapeutic window and the risk of ischemia/reperfusion injury.It is therefore urgent to figure out the neuronal death mechanisms following ischemic stroke in order to develop new neuroprotective strategies.Regarding the pathogenesis,multiple pathological events trigger the activation of cell death pathways.Particular attention should be devoted to excitotoxicity,oxidative stress,and inflammatory responses.Thus,in this article,we first review the principal mechanisms underlying neuronal death mediated by these significant events,such as intrinsic and extrinsic apoptosis,ferroptosis,parthanatos,pyroptosis,necroptosis,and autophagic cell death.Then,we further discuss the possibility of interventions targeting these pathological events and summarize the present pharmacological achievements.展开更多
Transcorneal electrical stimulation （TES） is a novel therapeutic approach to activate the retina and related downstream structures. TES has multiple advantages over traditional treatments, such as being minimally in...Transcorneal electrical stimulation （TES） is a novel therapeutic approach to activate the retina and related downstream structures. TES has multiple advantages over traditional treatments, such as being minimally invasive and readily applicable in a routine manner. Series of animal experiments have shown that TES protects the retinal neuron from traumatic or genetic induced degeneration. These laboratory evidences support its utilization in ophthalmological therapies against various retinal and optical diseases including retinitis pigmentosa （RP）, traumatic optic neuropathy, anterior ischemic optic neuropathy （AION）, and retinal artery occlusions （RAOs）. Several pioneering explorations sought to clarify the functional mechanism underlying the neuroprotective effects of TES. It seems that the neuroprotective effects should not be attributed to a solitary pathway, on the contrary, multiple mechanisms might contribute collectively to maintain cellular homeostasis and promote cell survival in the retina. More precise evaluations y/a functional and morphological techniques would determine the exact mechanism underlying the remarkable neuroprotective effect of TES. Further studies to determine the optimal parameters and the long-term stability of TES are crucial to justify the clinical significance and to establish TES as a popularized therapeutic modality against retinal and optic neuropathy.展开更多
BACKGROUND The coexistence with patent ductus arteriosus(PDA),mitral valve prolapse(MVP),atrial fibrillation(AF)and hyperthyroidism is extremely rare and complex.The optimal therapeutic strategy is difficult to develo...BACKGROUND The coexistence with patent ductus arteriosus(PDA),mitral valve prolapse(MVP),atrial fibrillation(AF)and hyperthyroidism is extremely rare and complex.The optimal therapeutic strategy is difficult to develop.CASE SUMMARY A 27-year-old female with PDA,MVP,AF and hyperthyroidism presented with severe dyspnea.Given that a one-stage operation for PDA,MVP and AF is high risk,we preferred a sequential multidisciplinary minimally invasive therapeutic strategy.First,PDA transcatheter closure was performed.Hyperthyroidism and heart failure were simultaneously controlled via medical treatment.Video-assisted thoracoscopic mitral valve repair and left atrial appendage occlusion were performed when heart failure was controlled.Under this therapeutic strategy,the patient’s sinus rhythm was restored and maintained.Two years after the treatment,the symptoms of heart failure were relieved,and the enlarged heart was reversed.CONCLUSION Sequential multidisciplinary therapeutic strategies,which take advantage of both internal medicine and surgical approaches,might be reasonable for this type of disease.展开更多
Wolfram syndrome(WS)is a rare autosomal rece s s i ve disease characte r i zed by the development of diabetes insipidus,diabetes mellitus,optic atrophy,and deafness(often referred to as DIDMOAD),and overall severe neu...Wolfram syndrome(WS)is a rare autosomal rece s s i ve disease characte r i zed by the development of diabetes insipidus,diabetes mellitus,optic atrophy,and deafness(often referred to as DIDMOAD),and overall severe neurodegenerative fallback.The global prevalence of this disease is estimated at 1 in 770,000(Lee et al.,2023).It is most commonly caused by biallelic(point)mutations in the Wolframin endoplasmic reticulum(ER)transmembrane glycoprotein(WFS1)gene(in case of WS type 1),but mutations in the CDGSH Iron Sulfur Domain 2(CISD2)are also linked to WS(type 2).The latter,however,often present with less severe pathological manifestations(Lee et al.,2023).WFS1 is located on chromosome 4p16.1 and spans over 33 kilobases.Many mutation variants have been identified in WFS1,encompassing missense,nonsense,and frameshift mutations.These mutations are spread across the coding region of WFS1,but certain regions,such as exon 8,the largest exon,appear particularly mutation-prone and associated with the classical WS type 1 phenotype(Lee et al.,2023).展开更多
Liver metastases pose a serious challenge in the field of systemic cancer treatment,as this organ has a particular microenvironment that favours malignant cells disseminating to settle there.We outline major steps of ...Liver metastases pose a serious challenge in the field of systemic cancer treatment,as this organ has a particular microenvironment that favours malignant cells disseminating to settle there.We outline major steps of liver immune tolerance in metastasis including pre-metastatic niche formation,immune evasion during circulation,establishment of an intrahepatic immune desert and metabolism,myeloid cell networks and gut microbiome-mediated coordinated tolerance.We then combine new combination and integrative therapies that are intended to break this tolerance;these include immunochemotherapy regimens,synergistic antiangiogenics and immunotherapies,dual immune checkpoint blockade and myeloid-cell reprogramming,combined locoregional and systemic therapies and new microenvironmental targeting.Each strategy is assessed with regard to its potential disruption of hepatic immune quiescence,improved clinical translation and durable antitumour activity.We suggest a proposed solution termed Liver-metastasis-oriented shared-mechanism therapeutic strategy,which may target multiple metastatic bottlenecks due to similarities.This framework provides a basis for personalizing combination therapies and designing future clinical trials for treating liver metastases,with organ-specific considerations and will be the subject of a commentary.展开更多
Diabetic foot ulcer is a serious complication of diabetes.Excessive accumulation of advanced glycation end products(AGEs)is one of the critical pathogenic factors in postponing diabetic wound healing.The main pathogen...Diabetic foot ulcer is a serious complication of diabetes.Excessive accumulation of advanced glycation end products(AGEs)is one of the critical pathogenic factors in postponing diabetic wound healing.The main pathogenic mechanisms of AGEs include inducing cellular dysfunction,prolonging inflammatory response,increasing oxidative stress and reducing endogenous nitric oxide(NO)production.Combination therapy of blocking the deleterious effects of AGEs and supplementing exogenous NO is hypothesized to promote diabetic wound healing.Here,we presented nanoparticles/hydrogel composite dressings to co-delivery rosiglitazone and S-nitroso glutathione into the wound bed.The designed co-delivery system augmented the survival of fibroblasts,reduced oxidative stress levels,reversed the change of mitochondrial membrane potential and decreased the proinflammatory cytokine expression.Local sustained release of therapeutic agents significantly improved the wound healing of diabetic rats including increasing the wound closure rate,alleviating inflammation,promoting collagen fiber production and angiogenesis.Our finding indicated this local deliver strategy aimed at inhibiting the toxic effects of AGEs has great clinical potential for diabetic wound treatment.展开更多
N^(6)-methyladenosine RNA methylation,an essential post-transcriptional modification,dynamically regulates RNA metabolism and plays a crucial role in neuronal function.Growing evidence suggests that dysregulated N^(6)...N^(6)-methyladenosine RNA methylation,an essential post-transcriptional modification,dynamically regulates RNA metabolism and plays a crucial role in neuronal function.Growing evidence suggests that dysregulated N^(6)-methyladenosine modification contributes to the pathogenesis of neurodegenerative diseases,including Alzheimer’s disease,Parkinson’s disease,multiple sclerosis,and amyotrophic lateral sclerosis.However,the precise mechanisms by which N^(6)-methyladenosine modification influences these conditions remain unclear.This review summarizes the role of m6A modification and its associated regulators in neurodegeneration,focusing on their involvement in key pathological processes.In Alzheimer’s disease,m6A modification contributes to synaptic dysfunction,mitochondrial damage,and neuronal apoptosis.Evidence from APP/PS1,5xFAD,tau transgenic,and Drosophila models demonstrates that regulators such as methyltransferase-like 3 and fat mass and obesity-associated protein influence Alzheimer’s disease progression through neuroinflammation,circular RNAs dysregulation,and autophagy-related mechanisms.In Parkinson’s disease,altered N^(6)-methyladenosine regulator expression affects dopaminergic neuron survival and stress responses by modulating mRNA stability and autophagy-related lncRNAs.In multiple sclerosis and amyotrophic lateral sclerosis,N^(6)-methyladenosine affects immune activation,myelin repair,and the regulation of disease-associated genes such as TDP-43.Beyond N^(6)-methyladenosine,other RNA methylation modifications-such as m1A,m5C,m7G,uracil,and pseudouridine-are implicated in neurodegenerative diseases through their regulation of mitochondrial function,RNA metabolism,and neuronal stress responses.Additionally,N^(6)-methyladenosine exhibits cell type-specific functions:in microglia,it regulates inflammatory activation and phagocytic function;in astrocytes,it modulates metabolic homeostasis and glutamate-associated neurotoxicity;in neurons,it affects synaptic function and neurodegeneration-related gene expression;and in adult neural stem cells,it controls differentiation,neurogenesis,and cognitive plasticity.Recently,several small-molecule inhibitors targeting methyltransferase-like 3 or fat mass and obesity-associated protein have been developed to modulate N^(6)-methyladenosine modification,providing new opportunities for disease intervention,with the targeting of N⁶-methyladenosine-related pathways emerging as a promising therapeutic strategy.However,challenges persist in optimizing the specificity and delivery of these therapeutic approaches.展开更多
Cerebral small vessel disease encompasses a group of neurological disorders characterized by injury to small blood vessels,often leading to stroke and dementia.Due to its diverse etiologies and complex pathological me...Cerebral small vessel disease encompasses a group of neurological disorders characterized by injury to small blood vessels,often leading to stroke and dementia.Due to its diverse etiologies and complex pathological mechanisms,preventing and treating cerebral small vessel vasculopathy is challenging.Recent studies have shown that the glymphatic system plays a crucial role in interstitial solute clearance and the maintenance of brain homeostasis.Increasing evidence also suggests that dysfunction in glymphatic clearance is a key factor in the progression of cerebral small vessel disease.This review begins with a comprehensive introduction to the structure,function,and driving factors of the glymphatic system,highlighting its essential role in brain waste clearance.Afterwards,cerebral small vessel disease was reviewed from the perspective of the glymphatic system,after which the mechanisms underlying their correlation were summarized.Glymphatic dysfunction may lead to the accumulation of metabolic waste in the brain,thereby exacerbating the pathological processes associated with cerebral small vessel disease.The review also discussed the direct evidence of glymphatic dysfunction in patients and animal models exhibiting two subtypes of cerebral small vessel disease:arteriolosclerosis-related cerebral small vessel disease and amyloid-related cerebral small vessel disease.Diffusion tensor image analysis along the perivascular space is an important non-invasive tool for assessing the clearance function of the glymphatic system.However,the effectiveness of its parameters needs to be enhanced.Among various nervous system diseases,including cerebral small vessel disease,glymphatic failure may be a common final pathway toward dementia.Overall,this review summarizes prevention and treatment strategies that target glymphatic drainage and will offer valuable insight for developing novel treatments for cerebral small vessel disease.展开更多
Colorectal cancer(CRC)is the third most common malignancy worldwide and the second leading cause of cancer-related deaths,accounting for approximately 10%of all cancer cases.By 2050,CRC incidence is expected to rise s...Colorectal cancer(CRC)is the third most common malignancy worldwide and the second leading cause of cancer-related deaths,accounting for approximately 10%of all cancer cases.By 2050,CRC incidence is expected to rise substantially,driven by population aging and greater exposure to risk factors in developing countries.Despite advances in medicine and pharmacy,the effectiveness of available treatments remains limited,underscoring the urgent need for innovative therapeutic strategies.This review summarizes and critically evaluates currently available CRC therapies and explores new emerging directions.Particular attention is given to the role of immunotherapy,targeted therapies,nanotechnology-based approaches,metal-based compounds,PROTAC technology,and personalized medicine,with emphasis on their efficacy,safety,accessibility,and mechanisms of drug resistance.In conclusion,surgery and chemotherapy remain the backbone of CRC treatment,but novel therapeutic approaches are reshaping the treatment landscape.Emerging strategies may offer improved patient tolerability and survival outcomes by reducing the occurrence of burdensome adverse effects.Persistent challenges such as drug toxicity,the emergence of resistance mechanisms,and inequalities in access to innovative therapies underscore the need for further translational research.Integrating personalized therapeutic approaches will also be crucial to achieving more effective,safer,and accessible treatment strategies for CRC.展开更多
In this article,we make a comment on the recent article by Sun et al,focusing on the advances of neutrophil extracellular traps(NETs)formation in common osteoarticular diseases.Neutrophils are the first line to elimin...In this article,we make a comment on the recent article by Sun et al,focusing on the advances of neutrophil extracellular traps(NETs)formation in common osteoarticular diseases.Neutrophils are the first line to eliminate invading pathogens including fungal and bacterial infections via releasing hydrolytic enzymes and reactive oxygen species.Besides,neutrophils will accumulate at the inflammatory site and release NETs,which are composed of histones,DNA and granular proteins.Traumatic heterotopic ossification(THO)was generally believed to develop through four stages:Inflammation,chondrogenesis,osteogenesis,and bone maturation.Thus,it can be seen that THO was related to inflammation and bone formation.Apart from immune and infectious diseases,recent studies have also shown that NETs play a significant role in the pathogenesis of THO.This article focuses on elaborating the role of NETs in the onset of THO,discussing the existing problems in the current research and outlining future directions.展开更多
Precision medicine has become a cornerstone in modern therapeutic strategies, with nucleic acid aptamers emerging aspivotal tools due to their unique properties. These oligonucleotide fragments, selected through the S...Precision medicine has become a cornerstone in modern therapeutic strategies, with nucleic acid aptamers emerging aspivotal tools due to their unique properties. These oligonucleotide fragments, selected through the Systematic Evolution ofLigands by Exponential Enrichment process, exhibit high affinity and specificity toward their targets, such as DNA, RNA,proteins, and other biomolecules. Nucleic acid aptamers offer significant advantages over traditional therapeutic agents,including superior biological stability, minimal immunogenicity, and the capacity for universal chemical modifications thatenhance their in vivo performance and targeting precision. In the realm of osseous tissue repair and regeneration, a complexphysiological process essential for maintaining skeletal integrity, aptamers have shown remarkable potential in influencingmolecular pathways crucial for bone regeneration, promoting osteogenic differentiation and supporting osteoblast survival. Byengineering aptamers to regulate inflammatory responses and facilitate the proliferation and differentiation of fibroblasts,these oligonucleotides can be integrated into advanced drug delivery systems, significantly improving bone repair efficacywhile minimizing adverse effects. Aptamer-mediated strategies, including the use of siRNA and miRNA mimics or inhibitors,have shown efficacy in enhancing bone mass and microstructure. These approaches hold transformative potential for treatinga range of orthopedic conditions like osteoporosis, osteosarcoma, and osteoarthritis. This review synthesizes the molecularmechanisms and biological roles of aptamers in orthopedic diseases, emphasizing their potential to drive innovative andeffective therapeutic interventions.展开更多
Melatonin(N-acetyl-5 methoxytryptamine)is an indolic compound present in almost all fungi,plants,and animals.This neurohormone is synthesized and secreted into the internal environment mainly by the pineal gland,prese...Melatonin(N-acetyl-5 methoxytryptamine)is an indolic compound present in almost all fungi,plants,and animals.This neurohormone is synthesized and secreted into the internal environment mainly by the pineal gland,present in most vertebrates.Non-endocrine extrapineal locations have not been documented.This molecule with pleiotropic bioactions regulates the circadian rhythm,antioxidant,anti-inflammatory,immunostimulant,cardioprotective,antidiabetic,antiobesity,neuroprotective,and antiaging actions.Furthermore,in recent years,many studies have described the key role of melatonin in the prevention and development of cancer.The objective of this narrative review is to describe the different mechanisms through which melatonin exerts its action as an adjuvant in the modulation of carcinogenesis.The general anticarcinogenic mechanisms include epigenetic control,modulation of cell proliferation,regulation of cell cycle,induction of apoptosis,and telomerase inhibition.Melatonin also exerts antiestrogenic activity,which is particularly significant in hormone-dependent tumors,regulating the expression and transactivation of the estrogen receptor,and modulating the enzymes involved in the local synthesis of estrogens.Modulation of metastasis by melatonin includes increased expression of cell adhesion molecules such as E-cadherin andβ1-integrin,inhibition of angiogenesis,and control of fat metabolism by inhibiting the uptake of fatty acids by membrane transporters.Finally,immunomodulatory properties include enhanced production of anti-inflammatory interleukins and other cytokines in lymphocytes and monocytes and modulation of antioxidant activity by neutralizing free radicals.Despite all the mentioned properties,the use of melatonin in daily clinical practice is very limited,and additional studies are needed to better establish the role of this hormone in oncological clinical applications against different types of cancer.展开更多
We are deeply interested in the recent findings onβ-arrestin 2.Liu et al demonstrated thatβ-arrestin 2 knockout provides significant protection in diabetic nephropathy,underscoring its potential as a promising thera...We are deeply interested in the recent findings onβ-arrestin 2.Liu et al demonstrated thatβ-arrestin 2 knockout provides significant protection in diabetic nephropathy,underscoring its potential as a promising therapeutic target for diabetic nephropathy treatment.Furthermore,the role ofβ-arrestin 2 in metabolic regulation is equally critical,particularly in insulin signaling,hepatic glucose production,and adipose tissue function.Althoughβ-arrestin 2 plays a distinct role in metabolism and kidney protection,its tissue-specific regulation opens up valuable avenues for developing targeted therapeutic strategies centered onβ-arrestin 2.展开更多
This article explores the significant implications of the study by Ovadia et al,which innovatively compares the efficacy of a nutritional intervention(Modulen)to conventional pharmaceutical therapy(budesonide)in promo...This article explores the significant implications of the study by Ovadia et al,which innovatively compares the efficacy of a nutritional intervention(Modulen)to conventional pharmaceutical therapy(budesonide)in promoting mucosal healing in Crohn’s disease.Highlighting the paradox of a well-established yet underutilized nutritional approach,the findings suggest that Modulen may offer comparable therapeutic benefits despite its high withdrawal rate due to adherence challenges.This advancement underscores the evolving paradigm in inflammatory bowel disease treatment,shifting focus toward non-pharmacologic alternatives that target both clinical remission and endoscopic healing.The article advocates for the development of integrative treatment strategies that balance efficacy,patient adherence,and long-term disease management,emphasizing the need for further research to refine and optimize the role of nutritional therapies in clinical practice.展开更多
Pancreatic ductal adenocarcinoma(PDAC)is one of the most aggressive and fatal malignancies,with a 5-year survival rate of<15%.Despite significant advancements in targeted therapies and immunotherapy,these approache...Pancreatic ductal adenocarcinoma(PDAC)is one of the most aggressive and fatal malignancies,with a 5-year survival rate of<15%.Despite significant advancements in targeted therapies and immunotherapy,these approaches benefit only a limited subset of patients,leaving chemotherapy as the primary treatment modality for most patients.Chemotherapy is an essential adjunct to surgical resection,the only potentially curative option,playing a crucial role in reducing the tumor burden,delaying disease progression,and alleviating symptoms.However,its long-term efficacy is frequently undermined by the development of chemoresistance,wherein tumor cells adopt diverse strategies to evade or repair chemotherapy-induced damage.Addressing this critical barrier is imperative for improving the clinical outcomes of PDAC.This review comprehensively examines the multifaceted mechanisms of chemoresistance in PDAC and highlights innovative strategies designed to enhance chemosensitivity,thereby offering new hope for overcoming these challenges and improving patient survival.展开更多
Depression is a common comorbidity in gastric cancer(GC)patients,with prevalence rates reaching up to 57%,particularly in advanced stages and during active treatment.While prior studies have explored the bidirectional...Depression is a common comorbidity in gastric cancer(GC)patients,with prevalence rates reaching up to 57%,particularly in advanced stages and during active treatment.While prior studies have explored the bidirectional relationship between GC and depression,this editorial provides a structured synthesis of therapeutic strategies including pharmacological,psychotherapeutic,integrative,and biomarker-driven interventions,within a multidisciplinary care framework.Depression may exacerbate tumor progression through chronic stress and neurotransmitter dysregulation,such asβ2-adrenergic receptor activation,while the cancer burden deepens psychological distress.Antidepressants,especially selective serotonin reuptake inhibitors,have demonstrated efficacy in alleviating depressive symptoms in up to 70%of cases,particularly when used alongside chemotherapy.Psychotherapeutic modalities,including cognitive-behavioral therapy and family-based interventions,help reduce depressive symptoms,improve coping mechanisms,and prevent relapse.Integrative strategies like music therapy,mindfulness,and physical activity further support emotional wellbeing,particularly in mild-to-moderate depression.Multidisciplinary care that combines nutritional support,pain control,and psychosocial interventions is essential.Notably,the integration of interventional therapies with traditional Chinese medicine has shown potential in stabilizing tumor growth and improving mental health,enabling functional“tumor-bearing survival”.Emerging immunotherapies such as cadonilimab may also contribute indirectly to depression alleviation by enhancing treatment efficacy and extending survival.Future research should focus on biomarker-guided approaches,such as targetingβ2-adrenergic signaling,and developing personalized psychosocial care models.A holistic approach that integrates both physical and psychological care is vital to improving outcomes and quality of life in GC patients.展开更多
The interleukin-17 family is the key group of cytokines and displays a broad spectrum of biological functions,including regulating the inflammatory cascade in various autoimmune and inflammatory diseases,such as multi...The interleukin-17 family is the key group of cytokines and displays a broad spectrum of biological functions,including regulating the inflammatory cascade in various autoimmune and inflammatory diseases,such as multiple sclerosis,neuromyelitis optica spectrum disorder,myasthenia gravis,Guillain–Barre syndrome,acute disseminated encephalomyelitis,diabetes,inflammatory skin diseases,joint inflammation,and cancer.Although the function of the interleukin-17 family has attracted increasing research attention over many years,the expression,function,and regulation mechanisms of different interleukin-17 members are complicated and still only partially understood.Currently,the interleukin-17A pathway is considered a critical therapeutic target for numerous immune and chronic inflammatory diseases,with several monoclonal antibodies against interleukin-17A having been successfully used in clinical practice.Whether other interleukin-17 members have the potential to be targeted in other diseases is still debated.This review first summarizes the recent advancements in understanding the physicochemical properties,physiological functions,cellular origins,and downstream signaling pathways of different members and corresponding receptors of the interleukin-17 family.Subsequently,the function of interleukin-17 in various immune diseases is discussed,and the important role of interleukin-17 in the pathological process of immune diseases is demonstrated from multiple perspectives.Then,the current status of targeted interleukin-17 therapy is summarized,and the effectiveness and safety of targeted interleukin-17 therapy are analyzed.Finally,the clinical application prospects of targeting the interleukin-17 pathway are discussed.展开更多
Ischemic stroke is a major cause of neurological deficits and high disability rate.As the primary immune cells of the central nervous system,microglia play dual roles in neuroinflammation and tissue repair following a...Ischemic stroke is a major cause of neurological deficits and high disability rate.As the primary immune cells of the central nervous system,microglia play dual roles in neuroinflammation and tissue repair following a stroke.Their dynamic activation and polarization states are key factors that influence the disease process and treatment outcomes.This review article investigates the role of microglia in ischemic stroke and explores potential intervention strategies.Microglia exhibit a dynamic functional state,transitioning between pro-inflammatory(M1)and anti-inflammatory(M2)phenotypes.This duality is crucial in ischemic stroke,as it maintains a balance between neuroinflammation and tissue repair.Activated microglia contribute to neuroinflammation through cytokine release and disruption of the blood-brain barrier,while simultaneously promoting tissue repair through anti-inflammatory responses and regeneration.Key pathways influencing microglial activation include Toll-like receptor 4/nuclear factor kappa B,mitogen-activated protein kinases,Janus kinase/signal transducer and activator of transcription,and phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin pathways.These pathways are targets for various experimental therapies aimed at promoting M2 polarization and mitigating damage.Potential therapeutic agents include natural compounds found in drugs such as minocycline,as well as traditional Chinese medicines.Drugs that target these regulatory mechanisms,such as small molecule inhibitors and components of traditional Chinese medicines,along with emerging technologies such as single-cell RNA sequencing and spatial transcriptomics,offer new therapeutic strategies and clinical translational potential for ischemic stroke.展开更多
BackgroundFew studies have compared change in the health-related quality of life （HRQL） following treatment of non-ST-elevation acute coronary syndrome （NSTE-ACS） with either percutaneous coronary intervention （...BackgroundFew studies have compared change in the health-related quality of life （HRQL） following treatment of non-ST-elevation acute coronary syndrome （NSTE-ACS） with either percutaneous coronary intervention （PCI） or coronary artery bypass grafting （CABG）. This study is tocompare changes in HRQL six months after hospital discharge between NSTE-ACS pa-tients who underwent either PCI or CABG.Methods HRQL was assessed using the Seattle angina questionnaire at admission and six months after discharge in 1012 consecutive patients with NSTE-ACS. To assess associations of PCI and CABG with HRQL changes, logistic regression models were constructed treating changes in the score of each dimension of the Seattle angina question-naire as dependent variables.Results Although both the PCI and CABG groups experienced angina relief and other improvements at 6-month follow-up （P〈0.001）, the CABG relative to PCI group showed more significant improvements in angina frequency （P= 0.044） and quality of life （P= 0.028）. In multivariable logistic analysis, CABG also was an independent predictor for both im-provement of angina frequency （OR： 1.62, 95%CI： 1.09-4.63,P= 0.042） and quality of life （OR： 2.04, 95%CI： 1.26-6.92,P= 0.038） relative to PCI.Conclusions In patients with NSTE-ACS, both PCI and CABG provide great improvement in disease-specific health status at six months, with that of CABG being more prominent in terms of angina frequency and quality of life.展开更多
Hepatocellular carcinoma(HCC)is a pressing global health problem and is the sixth most common cancer and the third leading cause of cancer mortality worldwide.Despite continuous advances in treatment modalities,the 5-...Hepatocellular carcinoma(HCC)is a pressing global health problem and is the sixth most common cancer and the third leading cause of cancer mortality worldwide.Despite continuous advances in treatment modalities,the 5-year survival rate is low with a high propensity for recurrence and metastasis1.This clinical challenge in treating HCC is largely attributed to the heterogeneity and intrinsic therapy resistance of cancer stem cells(CSCs),which are a subpopulation of cells with self-renewal capability and multidirectional differentiation potential to induce tumorigenicity2.The behavior and maintenance of CSCs are not autonomous but critically dependent on the complex bidirectional crosstalk between CSCs and the tumor immune microenvironment(TIME)1.In this review we first summarize the recent progress in characterizing CSCs and the interactions between CSCs and the TIME in HCC.Next,we discuss the emerging therapeutic strategies targeting CSC populations with the ongoing challenges.Finally,we give our perspectives on the future directions in HCC CSC research.展开更多
基金This review was supported by the National Natural Science Foundation of China(81920108017,82130036,and 81630028)the Key Research and Development Program of Jiangsu Province of China(BE2020620)Jiangsu Province Key Medical Discipline(ZDXKA2016020).
文摘Ischemic stroke caused by intracranial vascular occlusion has become increasingly prevalent with considerable mortality and disability,which gravely burdens the global economy.Current relatively effective clinical treatments are limited to intravenous alteplase and thrombectomy.Even so,patients still benefit little due to the short therapeutic window and the risk of ischemia/reperfusion injury.It is therefore urgent to figure out the neuronal death mechanisms following ischemic stroke in order to develop new neuroprotective strategies.Regarding the pathogenesis,multiple pathological events trigger the activation of cell death pathways.Particular attention should be devoted to excitotoxicity,oxidative stress,and inflammatory responses.Thus,in this article,we first review the principal mechanisms underlying neuronal death mediated by these significant events,such as intrinsic and extrinsic apoptosis,ferroptosis,parthanatos,pyroptosis,necroptosis,and autophagic cell death.Then,we further discuss the possibility of interventions targeting these pathological events and summarize the present pharmacological achievements.
基金Supported by the National Key Basic Research Program of China (973 Program, No. 2013CB967001)
文摘Transcorneal electrical stimulation （TES） is a novel therapeutic approach to activate the retina and related downstream structures. TES has multiple advantages over traditional treatments, such as being minimally invasive and readily applicable in a routine manner. Series of animal experiments have shown that TES protects the retinal neuron from traumatic or genetic induced degeneration. These laboratory evidences support its utilization in ophthalmological therapies against various retinal and optical diseases including retinitis pigmentosa （RP）, traumatic optic neuropathy, anterior ischemic optic neuropathy （AION）, and retinal artery occlusions （RAOs）. Several pioneering explorations sought to clarify the functional mechanism underlying the neuroprotective effects of TES. It seems that the neuroprotective effects should not be attributed to a solitary pathway, on the contrary, multiple mechanisms might contribute collectively to maintain cellular homeostasis and promote cell survival in the retina. More precise evaluations y/a functional and morphological techniques would determine the exact mechanism underlying the remarkable neuroprotective effect of TES. Further studies to determine the optimal parameters and the long-term stability of TES are crucial to justify the clinical significance and to establish TES as a popularized therapeutic modality against retinal and optic neuropathy.
基金Supported by National Natural Science Foundation of China,No.81800342 and 81800138Zhejiang Provincial Natural Science Foundation of China,No.LQ20H020012.
文摘BACKGROUND The coexistence with patent ductus arteriosus(PDA),mitral valve prolapse(MVP),atrial fibrillation(AF)and hyperthyroidism is extremely rare and complex.The optimal therapeutic strategy is difficult to develop.CASE SUMMARY A 27-year-old female with PDA,MVP,AF and hyperthyroidism presented with severe dyspnea.Given that a one-stage operation for PDA,MVP and AF is high risk,we preferred a sequential multidisciplinary minimally invasive therapeutic strategy.First,PDA transcatheter closure was performed.Hyperthyroidism and heart failure were simultaneously controlled via medical treatment.Video-assisted thoracoscopic mitral valve repair and left atrial appendage occlusion were performed when heart failure was controlled.Under this therapeutic strategy,the patient’s sinus rhythm was restored and maintained.Two years after the treatment,the symptoms of heart failure were relieved,and the enlarged heart was reversed.CONCLUSION Sequential multidisciplinary therapeutic strategies,which take advantage of both internal medicine and surgical approaches,might be reasonable for this type of disease.
基金Research into Wolfram syndrome in the De Groef team has been supported by the Eye Hope Foundation(Belgium),Wolfram UK(UK)and The Snow Foundation(USA).
文摘Wolfram syndrome(WS)is a rare autosomal rece s s i ve disease characte r i zed by the development of diabetes insipidus,diabetes mellitus,optic atrophy,and deafness(often referred to as DIDMOAD),and overall severe neurodegenerative fallback.The global prevalence of this disease is estimated at 1 in 770,000(Lee et al.,2023).It is most commonly caused by biallelic(point)mutations in the Wolframin endoplasmic reticulum(ER)transmembrane glycoprotein(WFS1)gene(in case of WS type 1),but mutations in the CDGSH Iron Sulfur Domain 2(CISD2)are also linked to WS(type 2).The latter,however,often present with less severe pathological manifestations(Lee et al.,2023).WFS1 is located on chromosome 4p16.1 and spans over 33 kilobases.Many mutation variants have been identified in WFS1,encompassing missense,nonsense,and frameshift mutations.These mutations are spread across the coding region of WFS1,but certain regions,such as exon 8,the largest exon,appear particularly mutation-prone and associated with the classical WS type 1 phenotype(Lee et al.,2023).
文摘Liver metastases pose a serious challenge in the field of systemic cancer treatment,as this organ has a particular microenvironment that favours malignant cells disseminating to settle there.We outline major steps of liver immune tolerance in metastasis including pre-metastatic niche formation,immune evasion during circulation,establishment of an intrahepatic immune desert and metabolism,myeloid cell networks and gut microbiome-mediated coordinated tolerance.We then combine new combination and integrative therapies that are intended to break this tolerance;these include immunochemotherapy regimens,synergistic antiangiogenics and immunotherapies,dual immune checkpoint blockade and myeloid-cell reprogramming,combined locoregional and systemic therapies and new microenvironmental targeting.Each strategy is assessed with regard to its potential disruption of hepatic immune quiescence,improved clinical translation and durable antitumour activity.We suggest a proposed solution termed Liver-metastasis-oriented shared-mechanism therapeutic strategy,which may target multiple metastatic bottlenecks due to similarities.This framework provides a basis for personalizing combination therapies and designing future clinical trials for treating liver metastases,with organ-specific considerations and will be the subject of a commentary.
基金financially supported by the National Natural Science Foundation of China(no.82273878).
文摘Diabetic foot ulcer is a serious complication of diabetes.Excessive accumulation of advanced glycation end products(AGEs)is one of the critical pathogenic factors in postponing diabetic wound healing.The main pathogenic mechanisms of AGEs include inducing cellular dysfunction,prolonging inflammatory response,increasing oxidative stress and reducing endogenous nitric oxide(NO)production.Combination therapy of blocking the deleterious effects of AGEs and supplementing exogenous NO is hypothesized to promote diabetic wound healing.Here,we presented nanoparticles/hydrogel composite dressings to co-delivery rosiglitazone and S-nitroso glutathione into the wound bed.The designed co-delivery system augmented the survival of fibroblasts,reduced oxidative stress levels,reversed the change of mitochondrial membrane potential and decreased the proinflammatory cytokine expression.Local sustained release of therapeutic agents significantly improved the wound healing of diabetic rats including increasing the wound closure rate,alleviating inflammation,promoting collagen fiber production and angiogenesis.Our finding indicated this local deliver strategy aimed at inhibiting the toxic effects of AGEs has great clinical potential for diabetic wound treatment.
基金supported by the National Nature Science Foundation of China(General Program),Nos.82271237,82071218(both to JC),and 82230042(to ZY)the Foundation of Key Laboratory of Neurology,Hebei Medical University,Ministry of Education,China,No.2023001(to JC).
文摘N^(6)-methyladenosine RNA methylation,an essential post-transcriptional modification,dynamically regulates RNA metabolism and plays a crucial role in neuronal function.Growing evidence suggests that dysregulated N^(6)-methyladenosine modification contributes to the pathogenesis of neurodegenerative diseases,including Alzheimer’s disease,Parkinson’s disease,multiple sclerosis,and amyotrophic lateral sclerosis.However,the precise mechanisms by which N^(6)-methyladenosine modification influences these conditions remain unclear.This review summarizes the role of m6A modification and its associated regulators in neurodegeneration,focusing on their involvement in key pathological processes.In Alzheimer’s disease,m6A modification contributes to synaptic dysfunction,mitochondrial damage,and neuronal apoptosis.Evidence from APP/PS1,5xFAD,tau transgenic,and Drosophila models demonstrates that regulators such as methyltransferase-like 3 and fat mass and obesity-associated protein influence Alzheimer’s disease progression through neuroinflammation,circular RNAs dysregulation,and autophagy-related mechanisms.In Parkinson’s disease,altered N^(6)-methyladenosine regulator expression affects dopaminergic neuron survival and stress responses by modulating mRNA stability and autophagy-related lncRNAs.In multiple sclerosis and amyotrophic lateral sclerosis,N^(6)-methyladenosine affects immune activation,myelin repair,and the regulation of disease-associated genes such as TDP-43.Beyond N^(6)-methyladenosine,other RNA methylation modifications-such as m1A,m5C,m7G,uracil,and pseudouridine-are implicated in neurodegenerative diseases through their regulation of mitochondrial function,RNA metabolism,and neuronal stress responses.Additionally,N^(6)-methyladenosine exhibits cell type-specific functions:in microglia,it regulates inflammatory activation and phagocytic function;in astrocytes,it modulates metabolic homeostasis and glutamate-associated neurotoxicity;in neurons,it affects synaptic function and neurodegeneration-related gene expression;and in adult neural stem cells,it controls differentiation,neurogenesis,and cognitive plasticity.Recently,several small-molecule inhibitors targeting methyltransferase-like 3 or fat mass and obesity-associated protein have been developed to modulate N^(6)-methyladenosine modification,providing new opportunities for disease intervention,with the targeting of N⁶-methyladenosine-related pathways emerging as a promising therapeutic strategy.However,challenges persist in optimizing the specificity and delivery of these therapeutic approaches.
基金supported by the National Natural Science Foundation of China,No.82274304(to YH)the Major Clinical Study Projects of Shanghai Shenkang Hospital Development Center,No.SHDC2020CR2046B(to YH)Shanghai Municipal Health Commission Talent Plan,No.2022LJ010(to YH).
文摘Cerebral small vessel disease encompasses a group of neurological disorders characterized by injury to small blood vessels,often leading to stroke and dementia.Due to its diverse etiologies and complex pathological mechanisms,preventing and treating cerebral small vessel vasculopathy is challenging.Recent studies have shown that the glymphatic system plays a crucial role in interstitial solute clearance and the maintenance of brain homeostasis.Increasing evidence also suggests that dysfunction in glymphatic clearance is a key factor in the progression of cerebral small vessel disease.This review begins with a comprehensive introduction to the structure,function,and driving factors of the glymphatic system,highlighting its essential role in brain waste clearance.Afterwards,cerebral small vessel disease was reviewed from the perspective of the glymphatic system,after which the mechanisms underlying their correlation were summarized.Glymphatic dysfunction may lead to the accumulation of metabolic waste in the brain,thereby exacerbating the pathological processes associated with cerebral small vessel disease.The review also discussed the direct evidence of glymphatic dysfunction in patients and animal models exhibiting two subtypes of cerebral small vessel disease:arteriolosclerosis-related cerebral small vessel disease and amyloid-related cerebral small vessel disease.Diffusion tensor image analysis along the perivascular space is an important non-invasive tool for assessing the clearance function of the glymphatic system.However,the effectiveness of its parameters needs to be enhanced.Among various nervous system diseases,including cerebral small vessel disease,glymphatic failure may be a common final pathway toward dementia.Overall,this review summarizes prevention and treatment strategies that target glymphatic drainage and will offer valuable insight for developing novel treatments for cerebral small vessel disease.
文摘Colorectal cancer(CRC)is the third most common malignancy worldwide and the second leading cause of cancer-related deaths,accounting for approximately 10%of all cancer cases.By 2050,CRC incidence is expected to rise substantially,driven by population aging and greater exposure to risk factors in developing countries.Despite advances in medicine and pharmacy,the effectiveness of available treatments remains limited,underscoring the urgent need for innovative therapeutic strategies.This review summarizes and critically evaluates currently available CRC therapies and explores new emerging directions.Particular attention is given to the role of immunotherapy,targeted therapies,nanotechnology-based approaches,metal-based compounds,PROTAC technology,and personalized medicine,with emphasis on their efficacy,safety,accessibility,and mechanisms of drug resistance.In conclusion,surgery and chemotherapy remain the backbone of CRC treatment,but novel therapeutic approaches are reshaping the treatment landscape.Emerging strategies may offer improved patient tolerability and survival outcomes by reducing the occurrence of burdensome adverse effects.Persistent challenges such as drug toxicity,the emergence of resistance mechanisms,and inequalities in access to innovative therapies underscore the need for further translational research.Integrating personalized therapeutic approaches will also be crucial to achieving more effective,safer,and accessible treatment strategies for CRC.
文摘In this article,we make a comment on the recent article by Sun et al,focusing on the advances of neutrophil extracellular traps(NETs)formation in common osteoarticular diseases.Neutrophils are the first line to eliminate invading pathogens including fungal and bacterial infections via releasing hydrolytic enzymes and reactive oxygen species.Besides,neutrophils will accumulate at the inflammatory site and release NETs,which are composed of histones,DNA and granular proteins.Traumatic heterotopic ossification(THO)was generally believed to develop through four stages:Inflammation,chondrogenesis,osteogenesis,and bone maturation.Thus,it can be seen that THO was related to inflammation and bone formation.Apart from immune and infectious diseases,recent studies have also shown that NETs play a significant role in the pathogenesis of THO.This article focuses on elaborating the role of NETs in the onset of THO,discussing the existing problems in the current research and outlining future directions.
基金Key research and development projects of Sichuan Science and Technology Plan Project(2024YFFK0135)Fujian Provincial Natural Science Foundation of China(2024J011450).
文摘Precision medicine has become a cornerstone in modern therapeutic strategies, with nucleic acid aptamers emerging aspivotal tools due to their unique properties. These oligonucleotide fragments, selected through the Systematic Evolution ofLigands by Exponential Enrichment process, exhibit high affinity and specificity toward their targets, such as DNA, RNA,proteins, and other biomolecules. Nucleic acid aptamers offer significant advantages over traditional therapeutic agents,including superior biological stability, minimal immunogenicity, and the capacity for universal chemical modifications thatenhance their in vivo performance and targeting precision. In the realm of osseous tissue repair and regeneration, a complexphysiological process essential for maintaining skeletal integrity, aptamers have shown remarkable potential in influencingmolecular pathways crucial for bone regeneration, promoting osteogenic differentiation and supporting osteoblast survival. Byengineering aptamers to regulate inflammatory responses and facilitate the proliferation and differentiation of fibroblasts,these oligonucleotides can be integrated into advanced drug delivery systems, significantly improving bone repair efficacywhile minimizing adverse effects. Aptamer-mediated strategies, including the use of siRNA and miRNA mimics or inhibitors,have shown efficacy in enhancing bone mass and microstructure. These approaches hold transformative potential for treatinga range of orthopedic conditions like osteoporosis, osteosarcoma, and osteoarthritis. This review synthesizes the molecularmechanisms and biological roles of aptamers in orthopedic diseases, emphasizing their potential to drive innovative andeffective therapeutic interventions.
基金financed by the Department of Education of the Junta de Castilla-León and the European Regional Development Fund(FEDER)by TCUE Plan 2021-2023,134/2021,within the research project“Application of Genomics through the Study of Genetic polymorphisms in the treatment and prevention of chronic diseases in older adult patients”,(grant nos.SO002P23).
文摘Melatonin(N-acetyl-5 methoxytryptamine)is an indolic compound present in almost all fungi,plants,and animals.This neurohormone is synthesized and secreted into the internal environment mainly by the pineal gland,present in most vertebrates.Non-endocrine extrapineal locations have not been documented.This molecule with pleiotropic bioactions regulates the circadian rhythm,antioxidant,anti-inflammatory,immunostimulant,cardioprotective,antidiabetic,antiobesity,neuroprotective,and antiaging actions.Furthermore,in recent years,many studies have described the key role of melatonin in the prevention and development of cancer.The objective of this narrative review is to describe the different mechanisms through which melatonin exerts its action as an adjuvant in the modulation of carcinogenesis.The general anticarcinogenic mechanisms include epigenetic control,modulation of cell proliferation,regulation of cell cycle,induction of apoptosis,and telomerase inhibition.Melatonin also exerts antiestrogenic activity,which is particularly significant in hormone-dependent tumors,regulating the expression and transactivation of the estrogen receptor,and modulating the enzymes involved in the local synthesis of estrogens.Modulation of metastasis by melatonin includes increased expression of cell adhesion molecules such as E-cadherin andβ1-integrin,inhibition of angiogenesis,and control of fat metabolism by inhibiting the uptake of fatty acids by membrane transporters.Finally,immunomodulatory properties include enhanced production of anti-inflammatory interleukins and other cytokines in lymphocytes and monocytes and modulation of antioxidant activity by neutralizing free radicals.Despite all the mentioned properties,the use of melatonin in daily clinical practice is very limited,and additional studies are needed to better establish the role of this hormone in oncological clinical applications against different types of cancer.
基金Supported by National Natural Science Foundation of China,No.82471616,No.82170418,and No.82271618Natural Science Foundation of Hubei Province,No.2022CFA015+2 种基金Central Guiding Local Science and Technology Development Project,No.2022BGE237Key Research and Development Program of Hubei Province,No.2022BCE001,and No.2023BCB139Hubei Provincial Health Commission Project,No.WJ2023M151。
文摘We are deeply interested in the recent findings onβ-arrestin 2.Liu et al demonstrated thatβ-arrestin 2 knockout provides significant protection in diabetic nephropathy,underscoring its potential as a promising therapeutic target for diabetic nephropathy treatment.Furthermore,the role ofβ-arrestin 2 in metabolic regulation is equally critical,particularly in insulin signaling,hepatic glucose production,and adipose tissue function.Althoughβ-arrestin 2 plays a distinct role in metabolism and kidney protection,its tissue-specific regulation opens up valuable avenues for developing targeted therapeutic strategies centered onβ-arrestin 2.
文摘This article explores the significant implications of the study by Ovadia et al,which innovatively compares the efficacy of a nutritional intervention(Modulen)to conventional pharmaceutical therapy(budesonide)in promoting mucosal healing in Crohn’s disease.Highlighting the paradox of a well-established yet underutilized nutritional approach,the findings suggest that Modulen may offer comparable therapeutic benefits despite its high withdrawal rate due to adherence challenges.This advancement underscores the evolving paradigm in inflammatory bowel disease treatment,shifting focus toward non-pharmacologic alternatives that target both clinical remission and endoscopic healing.The article advocates for the development of integrative treatment strategies that balance efficacy,patient adherence,and long-term disease management,emphasizing the need for further research to refine and optimize the role of nutritional therapies in clinical practice.
基金supported by grants from the CAMS Innovation Fund for Medical Sciences(No.2024-I2M-ZD-001)National Key R&D Program of China(No.2023YFC2413400)+5 种基金National Natural Science Foundation of China(No.82272917,No.62133006,No.82203158,No.82473086,No.82473096,and No.82403006)Beijing Natural Science Foundation(No.7242104,No.7244385,and No.L248053)Research and Translational Application of Clinical Characteristic Diagnosis and Treatment Techniques in the Capital(No.Z221100007422070)Beijing Science and Technology Plan(No.Z231100007223006)National High Level Hospital Clinical Research Funding(No.2022-PUMCH-B-004)the Postdoctoral Fellowship Program of CPSF(No.GZB20240074).
文摘Pancreatic ductal adenocarcinoma(PDAC)is one of the most aggressive and fatal malignancies,with a 5-year survival rate of<15%.Despite significant advancements in targeted therapies and immunotherapy,these approaches benefit only a limited subset of patients,leaving chemotherapy as the primary treatment modality for most patients.Chemotherapy is an essential adjunct to surgical resection,the only potentially curative option,playing a crucial role in reducing the tumor burden,delaying disease progression,and alleviating symptoms.However,its long-term efficacy is frequently undermined by the development of chemoresistance,wherein tumor cells adopt diverse strategies to evade or repair chemotherapy-induced damage.Addressing this critical barrier is imperative for improving the clinical outcomes of PDAC.This review comprehensively examines the multifaceted mechanisms of chemoresistance in PDAC and highlights innovative strategies designed to enhance chemosensitivity,thereby offering new hope for overcoming these challenges and improving patient survival.
文摘Depression is a common comorbidity in gastric cancer(GC)patients,with prevalence rates reaching up to 57%,particularly in advanced stages and during active treatment.While prior studies have explored the bidirectional relationship between GC and depression,this editorial provides a structured synthesis of therapeutic strategies including pharmacological,psychotherapeutic,integrative,and biomarker-driven interventions,within a multidisciplinary care framework.Depression may exacerbate tumor progression through chronic stress and neurotransmitter dysregulation,such asβ2-adrenergic receptor activation,while the cancer burden deepens psychological distress.Antidepressants,especially selective serotonin reuptake inhibitors,have demonstrated efficacy in alleviating depressive symptoms in up to 70%of cases,particularly when used alongside chemotherapy.Psychotherapeutic modalities,including cognitive-behavioral therapy and family-based interventions,help reduce depressive symptoms,improve coping mechanisms,and prevent relapse.Integrative strategies like music therapy,mindfulness,and physical activity further support emotional wellbeing,particularly in mild-to-moderate depression.Multidisciplinary care that combines nutritional support,pain control,and psychosocial interventions is essential.Notably,the integration of interventional therapies with traditional Chinese medicine has shown potential in stabilizing tumor growth and improving mental health,enabling functional“tumor-bearing survival”.Emerging immunotherapies such as cadonilimab may also contribute indirectly to depression alleviation by enhancing treatment efficacy and extending survival.Future research should focus on biomarker-guided approaches,such as targetingβ2-adrenergic signaling,and developing personalized psychosocial care models.A holistic approach that integrates both physical and psychological care is vital to improving outcomes and quality of life in GC patients.
基金supported by the National Natural Science Foundational of China(Key Program),No.U24A20692(to CJZ)the National Natural Science Foundational of China,Nos.82101414(to MLJ),82371355(to CJZ)+4 种基金the National Natural Science Foundational of China for Excellent Young Scholars,No.82022019(to CJZ)Sichuan Special Fund for Distinguished Young Scholars,No.24NSFJQ0052(to CJZ)The Innovation and Entrepreneurial Team of Sichuan Tianfu Emei Program,No.CZ2024018(to CJZ)Funding for Distinguished Young Scholars of Sichuan Provincial People’s Hospital,No.30420230005(to CJZ)Funding for Distinguished Young Scholars of University of Electronic Science and Technology of China,No.A1098531023601381(to CJZ)。
文摘The interleukin-17 family is the key group of cytokines and displays a broad spectrum of biological functions,including regulating the inflammatory cascade in various autoimmune and inflammatory diseases,such as multiple sclerosis,neuromyelitis optica spectrum disorder,myasthenia gravis,Guillain–Barre syndrome,acute disseminated encephalomyelitis,diabetes,inflammatory skin diseases,joint inflammation,and cancer.Although the function of the interleukin-17 family has attracted increasing research attention over many years,the expression,function,and regulation mechanisms of different interleukin-17 members are complicated and still only partially understood.Currently,the interleukin-17A pathway is considered a critical therapeutic target for numerous immune and chronic inflammatory diseases,with several monoclonal antibodies against interleukin-17A having been successfully used in clinical practice.Whether other interleukin-17 members have the potential to be targeted in other diseases is still debated.This review first summarizes the recent advancements in understanding the physicochemical properties,physiological functions,cellular origins,and downstream signaling pathways of different members and corresponding receptors of the interleukin-17 family.Subsequently,the function of interleukin-17 in various immune diseases is discussed,and the important role of interleukin-17 in the pathological process of immune diseases is demonstrated from multiple perspectives.Then,the current status of targeted interleukin-17 therapy is summarized,and the effectiveness and safety of targeted interleukin-17 therapy are analyzed.Finally,the clinical application prospects of targeting the interleukin-17 pathway are discussed.
基金supported by the National Natural Science Foundation of China,82471345(to LC)the Key Research and Development Program for Social Development by the Jiangsu Provincial Department of Science and Technology.No.BE2022668(to LC).
文摘Ischemic stroke is a major cause of neurological deficits and high disability rate.As the primary immune cells of the central nervous system,microglia play dual roles in neuroinflammation and tissue repair following a stroke.Their dynamic activation and polarization states are key factors that influence the disease process and treatment outcomes.This review article investigates the role of microglia in ischemic stroke and explores potential intervention strategies.Microglia exhibit a dynamic functional state,transitioning between pro-inflammatory(M1)and anti-inflammatory(M2)phenotypes.This duality is crucial in ischemic stroke,as it maintains a balance between neuroinflammation and tissue repair.Activated microglia contribute to neuroinflammation through cytokine release and disruption of the blood-brain barrier,while simultaneously promoting tissue repair through anti-inflammatory responses and regeneration.Key pathways influencing microglial activation include Toll-like receptor 4/nuclear factor kappa B,mitogen-activated protein kinases,Janus kinase/signal transducer and activator of transcription,and phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin pathways.These pathways are targets for various experimental therapies aimed at promoting M2 polarization and mitigating damage.Potential therapeutic agents include natural compounds found in drugs such as minocycline,as well as traditional Chinese medicines.Drugs that target these regulatory mechanisms,such as small molecule inhibitors and components of traditional Chinese medicines,along with emerging technologies such as single-cell RNA sequencing and spatial transcriptomics,offer new therapeutic strategies and clinical translational potential for ischemic stroke.
文摘BackgroundFew studies have compared change in the health-related quality of life （HRQL） following treatment of non-ST-elevation acute coronary syndrome （NSTE-ACS） with either percutaneous coronary intervention （PCI） or coronary artery bypass grafting （CABG）. This study is tocompare changes in HRQL six months after hospital discharge between NSTE-ACS pa-tients who underwent either PCI or CABG.Methods HRQL was assessed using the Seattle angina questionnaire at admission and six months after discharge in 1012 consecutive patients with NSTE-ACS. To assess associations of PCI and CABG with HRQL changes, logistic regression models were constructed treating changes in the score of each dimension of the Seattle angina question-naire as dependent variables.Results Although both the PCI and CABG groups experienced angina relief and other improvements at 6-month follow-up （P〈0.001）, the CABG relative to PCI group showed more significant improvements in angina frequency （P= 0.044） and quality of life （P= 0.028）. In multivariable logistic analysis, CABG also was an independent predictor for both im-provement of angina frequency （OR： 1.62, 95%CI： 1.09-4.63,P= 0.042） and quality of life （OR： 2.04, 95%CI： 1.26-6.92,P= 0.038） relative to PCI.Conclusions In patients with NSTE-ACS, both PCI and CABG provide great improvement in disease-specific health status at six months, with that of CABG being more prominent in terms of angina frequency and quality of life.
基金supported by the Hong Kong Research Grants Council Theme-based Research Scheme(Grant No.T12-716/22-R)Innovation and Technology Commission grant for State Key Laboratory of Liver Research(Grant No.ITC PD/17-9)University Development Fund of The University of Hong Kong,and Loke Yew Endowed Professorship award.I.O.L.Ng is Loke Yew Professor in Pathology.
文摘Hepatocellular carcinoma(HCC)is a pressing global health problem and is the sixth most common cancer and the third leading cause of cancer mortality worldwide.Despite continuous advances in treatment modalities,the 5-year survival rate is low with a high propensity for recurrence and metastasis1.This clinical challenge in treating HCC is largely attributed to the heterogeneity and intrinsic therapy resistance of cancer stem cells(CSCs),which are a subpopulation of cells with self-renewal capability and multidirectional differentiation potential to induce tumorigenicity2.The behavior and maintenance of CSCs are not autonomous but critically dependent on the complex bidirectional crosstalk between CSCs and the tumor immune microenvironment(TIME)1.In this review we first summarize the recent progress in characterizing CSCs and the interactions between CSCs and the TIME in HCC.Next,we discuss the emerging therapeutic strategies targeting CSC populations with the ongoing challenges.Finally,we give our perspectives on the future directions in HCC CSC research.
