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
Multiple sclerosis(MS) is a chronic, autoimmune and neuroinflammatory disease of the central nervous system(CNS) with a neurodegenerative component, characterized by demyelination and degeneration of nerve fibers. It ...Multiple sclerosis(MS) is a chronic, autoimmune and neuroinflammatory disease of the central nervous system(CNS) with a neurodegenerative component, characterized by demyelination and degeneration of nerve fibers. It affects mainly young adults(aged 20 to 45 years) and its causes are still unknown, but it is thought that external factors such as viruses and environmental factors trigger the disease in people with a genetic susceptibility.展开更多
Background:Giant cell arteritis(GCA),the most common systemic vasculitis affecting elderly individuals,currently lacks specific therapies.This study aimed to systematically identify therapeutic targets for GCA through...Background:Giant cell arteritis(GCA),the most common systemic vasculitis affecting elderly individuals,currently lacks specific therapies.This study aimed to systematically identify therapeutic targets for GCA through integration of large-scale multi-omics datasets.Methods:We constructed a multi-stage analytical framework encompassing 32 proteomic datasets(covering 2914 unique plasma proteins)and 6 transcriptomic datasets.Multi-omics integration strategies,including two-sample Mendelian randomization,colocalization analysis,and functional enrichment analysis,were employed to identify and validate causal relationships between candidate targets and GCA risk across 4 independent European-ancestry GCA cohorts.Single-cell RNA sequencing analysis of peripheral blood mononuclear cells from untreated GCA patients was performed to characterize hub gene-immune cell relationships.Results:We identified 43 plasma proteins causally associated with GCA[false discovery rate(FDR)<0.05],with 17 representing novel therapeutic targets.Through dual validation using proteome-wide association studies and transcriptome-wide association studies,we identified 13 high-confidence candidate targets with distinct tissue-specific expression patterns.Unc-51 like kinase 3(ULK3)emerged as the strongest protective factor(odds ratio=0.47,95%confidence interval:0.37–0.71)through autophagy regulation,while SLAMF7 represents an immediate drug repositioning opportunity as the target of food and drug administration-approved elotuzumab.Five targets have existing approved drugs(SLAMF7,ICAM1,IL18,IL6ST,CTSS).Single-cell analysis revealed profound disruption of hub gene-immune cell relationships in untreated GCA patients,with cell-type-specific alterations in inflammatory gene expression,and TYMP as the most critical hub gene.Conclusions:This study provides a clinically-actionable atlas of 43 potential therapeutic targets in GCA,identifying novel mechanisms including autophagy modulation and metabolic reprogramming,with immediate drug repositioning opportunities and precision medicine strategies based on tissue-specific and cell-type-specific expression patterns.These findings require experimental validation before clinical translation.展开更多
Microglia are the resident macrophages of the central nervous system.They act as the first line of defense against pathogens and play essential roles in neuroinflammation and tissue repair after brain insult or in neu...Microglia are the resident macrophages of the central nervous system.They act as the first line of defense against pathogens and play essential roles in neuroinflammation and tissue repair after brain insult or in neurodegenerative and demyelinating diseases(Borst et al.,2021).Together with infiltrating monocyte-derived macrophages,microglia also play a critical role for brain tumor development,since immunosuppressive interactions between tumor cells and tumor-associated microglia and macrophages(TAM)are linked to malignant progression.This mechanism is of particular relevance in glioblastoma(GB),the deadliest form of brain cancer with a median overall survival of less than 15 months(Khan et al.,2023).Therefore,targeting microglia and macrophage activation is a promising strategy for therapeutic interference in brain disease.展开更多
Human cardiac organoids have revolutionized the study of cardiac development,disease modeling, drug discovery, and regenerative therapies. This review systematically discusses strategies and progress in the constructi...Human cardiac organoids have revolutionized the study of cardiac development,disease modeling, drug discovery, and regenerative therapies. This review systematically discusses strategies and progress in the construction of cardiac organoids, categorizing them into three main types:cardiac spheroids, self-organizing/assembloid organoids, and organoid-on-a-chip systems. This review uniquely integrates the advances in vascularization, organ-on-chip design, and environmental cardiotoxicity modeling within cardiac organoid platforms, offering a critical synthesis that is absent in the literature. In the context of escalating environmental threats to cardiovascular health, there is an urgent need for physiologically relevant models to accurately identify cardiac toxicants and elucidate their underlying mechanisms of action. This review highlights advances in cardiac organoid applications for disease modeling-including congenital heart defects and acquired cardiovascular diseases-drug development, toxicity screening, and the study of environmentally induced cardiovascular pathogenesis. In addition, it critically examines ongoing challenges and underscores opportunities brought by bioengineering approaches. Finally, we propose future directions for developing standardized cardiac organoid platforms with clinical predictability, aiming to expand the utility of this technology across broader research applications.展开更多
The mechanisms leading to neurological and neurodegenerative diseases are not completely known,and new,more effective,therapeutic treatments are necessary for most neurological pathologies.The treatment of neurologica...The mechanisms leading to neurological and neurodegenerative diseases are not completely known,and new,more effective,therapeutic treatments are necessary for most neurological pathologies.The treatment of neurological and neurodegenerative diseases is complicated due to the blood-brain barrier,which makes it difficult for drugs to access the brain areas in which they must act to improve the pathology.A tool that can help to overcome this difficulty is the use of extracellular vesicles,which can easily cross the blood-brain barrier.The extracellular vesicles are considered a main way of communication between the brain and the rest of the body,with important implications for the physiopathology and therapy of neurological diseases.In recent years,the involvement of microbiota in many neurological pathologies,as well as its possible therapeutic role,has also become evident.A key mediator in the pathologic and beneficial effects of microbiota seems to be the bacterial extracellular vesicles.There is an important communication between the brain and the intestinal microbiota(the gut-brain axis),by which the microbiota influences brain function,impacts on mental health,and plays a role in different neurological and neurodegenerative diseases.The identification of the mechanisms involved in this gut-brain axis is essential to understanding the mechanisms of neurological pathologies and to developing more effective treatments for these diseases.Bacterial extracellular vesicles would play a relevant role in these processes.This review compiles the recent information and evidence on the role of bacterial extracellular vesicles in brain pathologies and on the therapeutic utility of bacterial extracellular vesicles in neurological and neurodegenerative diseases.One advantage of bacterial extracellular vesicles compared to extracellular vesicles derived from other cell types,such as stem cells,is that bacterial extracellular vesicles are generally easier to produce and modify.Bacterial extracellular vesicles may be easily modified to target a specific pathology and/or to enhance its therapeutic efficacy.Although the studies are still scarce,they open a wide field of possibilities for future studies,which will lead to a deeper understanding of the role of microbiota and bacterial extracellular vesicles in neurological pathologies and the underlying mechanisms,as well as to the development of new treatments based on the use of bacterial extracellular vesicles in neurological diseases.展开更多
Male breast cancer(MBC)is rare,representing 0.5%–1%of all breast cancers,but its incidence is increasing due to improved diagnostics and awareness.MBC typically presents in older men,is human epidermal growth factor ...Male breast cancer(MBC)is rare,representing 0.5%–1%of all breast cancers,but its incidence is increasing due to improved diagnostics and awareness.MBC typically presents in older men,is human epidermal growth factor receptor 2(HER2)-negative and estrogen receptor(ER)-positive,and lacks routine screening,leading to delayed diagnosis and advanced disease.Major risk factors include hormonal imbalance,radiation exposure,obesity,alcohol use,and Breast Cancer Gene 1 and 2(BRCA1/2)mutations.Clinically,it may resemble gynecomastia but usually appears as a unilateral,painless mass or nipple discharge.Advances in imaging and liquid biopsy have enhanced early detection.Molecular mechanisms involve hormonal signaling,HER2/epidermal growth factor receptor(EGFR)pathways,tumor suppressor gene alterations,and epigenetic changes.While standard treatments mirror those for female breast cancer,emerging options such as cyclin-dependent kinase 4 and 6(CDK4/6),and poly(ADP-ribose)polymerase(PARP)inhibitors,immunotherapy,and precision medicine are reshaping management.Incorporating artificial intelligence,molecular profiling,and male-specific clinical trials is essential to improve outcomes and bridge current diagnostic and therapeutic gaps.展开更多
Stroke-induced alterations in cerebral blood flow trigger neurovascular remodeling,as manifested by the blood-brain barrier dysfunction and subs equent neurovascular repair activities such as angiogenesis.This process...Stroke-induced alterations in cerebral blood flow trigger neurovascular remodeling,as manifested by the blood-brain barrier dysfunction and subs equent neurovascular repair activities such as angiogenesis.This process involves neurovascular communication that facilitates the transport of mediators among cerebrovascular endothelial cells,pericytes,glial cells,and neurons,thereby transmitting signals from donor to recipient cells to elicit a collaborative response.展开更多
The retrospective study by Edwar et al reinforces the role of therapeutic penetrating keratoplasty(PK)as a vital intervention in severe,treatment-resistant infectious keratitis.In advanced cases—often complicated by ...The retrospective study by Edwar et al reinforces the role of therapeutic penetrating keratoplasty(PK)as a vital intervention in severe,treatment-resistant infectious keratitis.In advanced cases—often complicated by trauma,delayed presentation,and corneal perforation—PK restores globe integrity and provides limited visual recovery.However,its application is constrained by graft-related complications and donor shortages,particularly in low-resource settings.These limitations highlight the need for earlier,globe-sparing strategies to prevent progression and reduce surgical demand.Photoactivated chromophore for infectious keratitis-corneal collagen cross-linking(PACK-CXL)has emerged as a promising adjunct or alternative.With both antimicrobial and tissue-stabilizing effects,PACK-CXL may control infection and preserve corneal structure in earlier stages.A layered treatment framework that incorporates PACK-CXL as an initial intervention and reserves PK for refractory cases may help improve clinical outcomes.Further studies are needed to define their best use in practice.展开更多
Alzheimer’s disease(AD)remains an incurable neurodegenerative disorder with devastating societal and personal impacts.Despite decades of intensive research,therapeutic efforts targeting the clinical stages of AD have...Alzheimer’s disease(AD)remains an incurable neurodegenerative disorder with devastating societal and personal impacts.Despite decades of intensive research,therapeutic efforts targeting the clinical stages of AD have largely failed to halt or reverse disease progression.This has prompted a critical shift in focus toward the earlier,preclinical stages of AD,where interventions may hold greater promise for altering the disease trajectory.展开更多
In the words of the late Sir Colin Blakemore,neurologists have historically sought to infer brain functions in a manner akin to to king a hammer to a computeranalyzing localized anatomical lesions caused by trauma,tum...In the words of the late Sir Colin Blakemore,neurologists have historically sought to infer brain functions in a manner akin to to king a hammer to a computeranalyzing localized anatomical lesions caused by trauma,tumors,or strokes,noting deficits,and inferring what functions certain brain regions may be responsible for.This approach exemplifies a deletion heuristic,where the absence of a specific function reveals insights about the underlying structures or mechanisms responsible for it.By observing what is lost when a particular brain region is damaged,throughout the history of the field,neurologists have pieced together the intricate relationship between anatomy and function.展开更多
Ferroptosis,a type of cell death that mainly involves iron metabolism imbalance and lipid peroxidation,is strongly correlated with the phagocytic response caused by bleeding after spinal cord injury.Thus,in this study...Ferroptosis,a type of cell death that mainly involves iron metabolism imbalance and lipid peroxidation,is strongly correlated with the phagocytic response caused by bleeding after spinal cord injury.Thus,in this study,bulk RNA sequencing data(GSE47681 and GSE5296)and single-cell RNA sequencing data(GSE162610)were acquired from gene expression databases.We then conducted differential analysis and immune infiltration analysis.Atf3 and Piezo1 were identified as key ferroptosis genes through random forest and least absolute shrinkage and selection operator algorithms.Further analysis of single-cell RNA sequencing data revealed a close relationship between ferroptosis and cell types such as macrophages/microglia and their intrinsic state transition processes.Differences in transcription factor regulation and intercellular communication networks were found in ferroptosis-related cells,confirming the high expression of Atf3 and Piezo1 in these cells.Molecular docking analysis confirmed that the proteins encoded by these genes can bind cycloheximide.In a mouse model of T8 spinal cord injury,low-dose cycloheximide treatment was found to improve neurological function,decrease levels of the pro-inflammatory cytokine inducible nitric oxide synthase,and increase levels of the anti-inflammatory cytokine arginase 1.Correspondingly,the expression of the ferroptosis-related gene Gpx4 increased in macrophages/microglia,while the expression of Acsl4 decreased.Our findings reveal the important role of ferroptosis in the treatment of spinal cord injury,identify the key cell types and genes involved in ferroptosis after spinal cord injury,and validate the efficacy of potential drug therapies,pointing to new directions in the treatment of spinal cord injury.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
Peptides are a class of drugs that have become increasingly important and influential for the treatment of many human diseases. Compared to traditional small molecule drugs, peptides have the potential for higher targ...Peptides are a class of drugs that have become increasingly important and influential for the treatment of many human diseases. Compared to traditional small molecule drugs, peptides have the potential for higher target specificity and potency, along with better safety profiles. On the other hand, the complex and fragile nature of peptides poses significant challenges for their administration. Of particular concern is that they are often unstable and can be rapidly degraded by various proteases after dosing. To address these inherent problems of peptides, many different methods have been attempted. Here, we briefly review these methods, with an emphasis on the effect of each method.展开更多
To evaluate the therapeutic effect of a modified Devine procedure with a subcutaneous sliding fixation method for the treatment of congenital concealed penis,we retrospectively selected 45 patients with congenital con...To evaluate the therapeutic effect of a modified Devine procedure with a subcutaneous sliding fixation method for the treatment of congenital concealed penis,we retrospectively selected 45 patients with congenital concealed penises who were admitted to General Hospital of Ningxia Medical University(Yinchuan,China)between September 2020 and November 2023.In all cases,the penis was observed to be short,and retracting the skin at the base revealed a normal penile body,which immediately returned to its original position upon release.All patients underwent the modified Devine procedure with subcutaneous sliding fixation and completed a 12-week postoperative follow-up.A statistically significant increase in penile length was observed postoperatively,with the median length increasing from 4.0(interquartile range[IQR]:3.5–4.8;95%confidence interval[CI]:3.9–4.4)cm to 8.0(IQR:7.8–8.0;95%CI:7.7–7.9)cm,with P<0.001.The parents were satisfied with the outcomes,including increased penile length,improved hygiene,and enhanced esthetics.Except for mild foreskin edema in all cases,no complications(such as infections,skin necrosis,or penile retraction)were observed.The edema was resolved within 4 weeks after the operation.This study demonstrates that the modified Devine procedure utilizing the subcutaneous sliding fixation method yields excellent outcomes with minimal postoperative complications,reduced penile retraction,and high satisfaction rates among patients and their families.展开更多
OBJECTIVE:To study information gained by Traditional Chinese Medicine(TCM)four diagnostic methods and characteristics of syndrome development before and after treatment in patients with coronary heart disease,and to p...OBJECTIVE:To study information gained by Traditional Chinese Medicine(TCM)four diagnostic methods and characteristics of syndrome development before and after treatment in patients with coronary heart disease,and to probe into assessment indexes of therapeutic effects with distinctive TCM features.METHODS:Information from the four diagnostic methods before and after treatment in 100 patients with coronary heart disease was collected using the TCM interrogation scale,a pulse condition instrument,a tongue-face diagnosis instrument,anda voice diagnosis information collection system.Changes in the four diagnostic method results from before and after treatment were analyzed with frequency analysis and t-test methods.RESULTS:Before treatment,deficiency syndrome complicated with hyperactivity of pathogenic factors was most common.After treatment,deficiency syndrome was most common.This change from complex syndromes to single syndromes indicates disease and syndrome alleviation.Frequencies of symptoms gained by interrogation after treatment for syndrome of deficiency of heart-Qi,syndrome of deficiency of heart-Yin,and turbid phlegm syndrome were all less severe than those before treatment.Parameters of face color,color on all sub-regions of tongue,color of tongue fur,septic and greasy fur,and lip color after treatment all had significant changes.After treatment,part of the voice diagnosis parameters in the deficiency of heart-Yin and turbid phlegm syndromes had significant changes,but no significant changes were found in the deficiency of heart-Qi syndrome.CONCLUSION:Use of the TCM four diagnostic methods can provide an effective basis forTCM syndrome diagnosis,observation of development of state of illness,and evaluation of clinical therapeutic effects.展开更多
Background and Purpose: Therapeutic communication is a new term in family health care nursing, defined by Hohashi (2019) as a method of family intervention, and characterized by inclusion of not only verbal conversati...Background and Purpose: Therapeutic communication is a new term in family health care nursing, defined by Hohashi (2019) as a method of family intervention, and characterized by inclusion of not only verbal conversation but also nonverbal interaction. However, specific therapeutic communication methods have not been systematized. The purpose of this study was to clarify therapeutic communication methods for families/family members from the perspectives of verbal communication and non-verbal communication through a review of existing literature. Methods: We conducted a search using the medical literature databases PubMed and Ichushi-Web using the keywords “therapeutic communication”. Analysis was performed on seven articles from PubMed and 14 articles from Ichushi-Web that described therapeutic communication methods performed by healthcare professionals for families/family members. Through directed content analysis, therapeutic communication methods were subcategorized, and classified into three categories: verbal communication, non-verbal communication, and verbal/non-verbal communication. Results: A total of 23 subcategories were extracted. Verbal communication included 11 subcategories, such as “asking questions using the communicatee’s words as they are”. Non-verbal communication included five subcategories, such as “noticing changes in the content of the communicatee’s story”. And verbal/non-verbal communication featured seven subcategories, such as “making the communicatee aware of one’s own beliefs”. Conclusion: Therapeutic communication methods included basic care/caring in family interviews/meetings, as well as verbal communication and non-verbal communication that act on family/family members’ beliefs. It is believed that changes in family/family members’ beliefs can be used to eliminate, reduce, or improve problematic conditions in the family. .展开更多
Objective To search for effective methods of acupuncture therapy in treating chronic diarrhea. Methods Treatments were carried out on 52 patients with chronic diarrhea by using the left ascending and right descending ...Objective To search for effective methods of acupuncture therapy in treating chronic diarrhea. Methods Treatments were carried out on 52 patients with chronic diarrhea by using the left ascending and right descending method. Three acupoints at the left side, namely Xiàng （陷谷 ST 43）, Zúsānl （足三 里 ST 36） and Qūchí （曲池 LI 11）, and Lièqūe （列缺 LU 7） at the right side were selected, moxibustion was also carried out according to syndrome differentiation. The operation of left ascending and right descending method were firstly left and then right, first down and then up, firstly four limbs and then abdomen; the thumb moved backward and the index finger moved forward during needle twisting for the acupoints at the left side, and it was on the contrary for the right side. The needles were retained for 1 h for deficiency, and the pinholes were pressed when the needles were withdrawn; the needles were retained for 0.5 h for excess syndrome and newly-contracted disease, and the pinholes were enlarged by shaking the needles when they were withdrawn. Except that the needling was carried out twice a day for the patients with desertion following chronic diarrhea, the needling was carried out once a day, five days as a treatment course, the patients were given an interval for two days after every two treatment courses, and the therapeutic effect was observed after five treatment courses. Results totally 36 patients were cured, among which 11 patients were cured after one treatment course, 19 patients were cured after two to three treatment courses and 6 patients were cured after four to five treatment courses; eight patients were improved; six patients were not cured; the total effective rate was 88.0%. Conclusion the acupuncture with left ascending and right descending method has satisfactory therapeutic effect in treating chronic diarrhea.展开更多
It has been reported that the PI3K/AKT signaling pathway plays a key role in the pathogenesis of ischemic stroke.As a result,the development of drugs targeting the PI3K/AKT signaling pathway has attracted increasing a...It has been reported that the PI3K/AKT signaling pathway plays a key role in the pathogenesis of ischemic stroke.As a result,the development of drugs targeting the PI3K/AKT signaling pathway has attracted increasing attention from researchers.This article reviews the pathological mechanisms and advancements in research related to the signaling pathways in ischemic stroke,with a focus on the PI3K/AKT signaling pathway.The key findings include the following:(1)The complex pathological mechanisms of ischemic stroke can be categorized into five major types:excitatory amino acid toxicity,Ca^(2+)overload,inflammatory response,oxidative stress,and apoptosis.(2)The PI3K/AKT-mediated signaling pathway is closely associated with the occurrence and progression of ischemic stroke,which primarily involves the NF-κB,NRF2,BCL-2,mTOR,and endothelial NOS signaling pathways.(3)Natural products,including flavonoids,quinones,alkaloids,phenylpropanoids,phenols,terpenoids,and iridoids,show great potential as candidate substances for the development of innovative anti-stroke medications.(4)Recently,novel therapeutic techniques,such as electroacupuncture and mesenchymal stem cell therapy,have demonstrated the potential to improve stroke outcomes by activating the PI3K/AKT signaling pathway,providing new possibilities for the treatment and rehabilitation of patients with ischemic stroke.Future investigations should focus on the direct regulatory mechanisms of drugs targeting the PI3K/AKT signaling pathway and their clinical translation to develop innovative treatment strategies for ischemic stroke.展开更多
Regulated cell death is a form of cell death that is actively controlled by biomolecules.Several studies have shown that regulated cell death plays a key role after spinal cord injury.Pyroptosis and ferroptosis are ne...Regulated cell death is a form of cell death that is actively controlled by biomolecules.Several studies have shown that regulated cell death plays a key role after spinal cord injury.Pyroptosis and ferroptosis are newly discovered types of regulated cell deaths that have been shown to exacerbate inflammation and lead to cell death in damaged spinal cords.Autophagy,a complex form of cell death that is interconnected with various regulated cell death mechanisms,has garnered significant attention in the study of spinal cord injury.This injury triggers not only cell death but also cellular survival responses.Multiple signaling pathways play pivotal roles in influencing the processes of both deterioration and repair in spinal cord injury by regulating pyroptosis,ferroptosis,and autophagy.Therefore,this review aims to comprehensively examine the mechanisms underlying regulated cell deaths,the signaling pathways that modulate these mechanisms,and the potential therapeutic targets for spinal cord injury.Our analysis suggests that targeting the common regulatory signaling pathways of different regulated cell deaths could be a promising strategy to promote cell survival and enhance the repair of spinal cord injury.Moreover,a holistic approach that incorporates multiple regulated cell deaths and their regulatory pathways presents a promising multi-target therapeutic strategy for the management of spinal cord injury.展开更多
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.
基金supported by Italian Ministry of Health Ricerca Corrente [RC 2023] and RF-2016-02361294supported by#NEXTGENERATIONEU (NGEU)+3 种基金funded by the Ministry of University and Research (MUR)National Recovery and Resilience Plan (NRRP)project MNESYS (PE0000006)–A Multiscale integrated approach to the study of the nervous system in health and disease (DN. 1553 11.10.2022)(to FRG)partially supported by a grant from Fondazione Romeo ed Enrica Invernizzi (to FRG)。
文摘Multiple sclerosis(MS) is a chronic, autoimmune and neuroinflammatory disease of the central nervous system(CNS) with a neurodegenerative component, characterized by demyelination and degeneration of nerve fibers. It affects mainly young adults(aged 20 to 45 years) and its causes are still unknown, but it is thought that external factors such as viruses and environmental factors trigger the disease in people with a genetic susceptibility.
基金supported by grants from the Fundamental Research Funds for the Central Universities(No.2025ZFJH03)the Central Guidance Fund for Local Science and Technology Development(No.2024ZY01054)the CAMS Innovation Fund for Medical Sciences(No.2019-I2M-5-045).
文摘Background:Giant cell arteritis(GCA),the most common systemic vasculitis affecting elderly individuals,currently lacks specific therapies.This study aimed to systematically identify therapeutic targets for GCA through integration of large-scale multi-omics datasets.Methods:We constructed a multi-stage analytical framework encompassing 32 proteomic datasets(covering 2914 unique plasma proteins)and 6 transcriptomic datasets.Multi-omics integration strategies,including two-sample Mendelian randomization,colocalization analysis,and functional enrichment analysis,were employed to identify and validate causal relationships between candidate targets and GCA risk across 4 independent European-ancestry GCA cohorts.Single-cell RNA sequencing analysis of peripheral blood mononuclear cells from untreated GCA patients was performed to characterize hub gene-immune cell relationships.Results:We identified 43 plasma proteins causally associated with GCA[false discovery rate(FDR)<0.05],with 17 representing novel therapeutic targets.Through dual validation using proteome-wide association studies and transcriptome-wide association studies,we identified 13 high-confidence candidate targets with distinct tissue-specific expression patterns.Unc-51 like kinase 3(ULK3)emerged as the strongest protective factor(odds ratio=0.47,95%confidence interval:0.37–0.71)through autophagy regulation,while SLAMF7 represents an immediate drug repositioning opportunity as the target of food and drug administration-approved elotuzumab.Five targets have existing approved drugs(SLAMF7,ICAM1,IL18,IL6ST,CTSS).Single-cell analysis revealed profound disruption of hub gene-immune cell relationships in untreated GCA patients,with cell-type-specific alterations in inflammatory gene expression,and TYMP as the most critical hub gene.Conclusions:This study provides a clinically-actionable atlas of 43 potential therapeutic targets in GCA,identifying novel mechanisms including autophagy modulation and metabolic reprogramming,with immediate drug repositioning opportunities and precision medicine strategies based on tissue-specific and cell-type-specific expression patterns.These findings require experimental validation before clinical translation.
基金Deutsche Forschungsgemeinschaft(DFG,German Research Foundation),project numbers 324633948 and 409784463(DFG grants Hi 678/9-3 and Hi 678/10-2,FOR2953)to HHBundesministerium für Bildung und Forschung-BMBF,project number 16LW0463K to HT.
文摘Microglia are the resident macrophages of the central nervous system.They act as the first line of defense against pathogens and play essential roles in neuroinflammation and tissue repair after brain insult or in neurodegenerative and demyelinating diseases(Borst et al.,2021).Together with infiltrating monocyte-derived macrophages,microglia also play a critical role for brain tumor development,since immunosuppressive interactions between tumor cells and tumor-associated microglia and macrophages(TAM)are linked to malignant progression.This mechanism is of particular relevance in glioblastoma(GB),the deadliest form of brain cancer with a median overall survival of less than 15 months(Khan et al.,2023).Therefore,targeting microglia and macrophage activation is a promising strategy for therapeutic interference in brain disease.
基金supported by the Innovation Promotion Program of NHC and Shanghai Key Labs,SIBPT(grant number PT2025-01)。
文摘Human cardiac organoids have revolutionized the study of cardiac development,disease modeling, drug discovery, and regenerative therapies. This review systematically discusses strategies and progress in the construction of cardiac organoids, categorizing them into three main types:cardiac spheroids, self-organizing/assembloid organoids, and organoid-on-a-chip systems. This review uniquely integrates the advances in vascularization, organ-on-chip design, and environmental cardiotoxicity modeling within cardiac organoid platforms, offering a critical synthesis that is absent in the literature. In the context of escalating environmental threats to cardiovascular health, there is an urgent need for physiologically relevant models to accurately identify cardiac toxicants and elucidate their underlying mechanisms of action. This review highlights advances in cardiac organoid applications for disease modeling-including congenital heart defects and acquired cardiovascular diseases-drug development, toxicity screening, and the study of environmentally induced cardiovascular pathogenesis. In addition, it critically examines ongoing challenges and underscores opportunities brought by bioengineering approaches. Finally, we propose future directions for developing standardized cardiac organoid platforms with clinical predictability, aiming to expand the utility of this technology across broader research applications.
基金funded by the Ministerio de Ciencia e Innovación Spain(PID2020-113388RB-I00,AEI/10.13039/501100011033)Consellería de Innovación,Universidades,Ciencia y Sociedad Digital,Generalitat Valenciana(CIPROM/2021/082)+2 种基金co-funded with European Regional Development Funds(ERDF)(PID2020-113388RB-I00,and CIPROM/2021/082)PID2022-136874OB-C33 from MCIN/AEI/10.13039/501100011033by the European Union NextGenerationEU/PRTR(to VF).
文摘The mechanisms leading to neurological and neurodegenerative diseases are not completely known,and new,more effective,therapeutic treatments are necessary for most neurological pathologies.The treatment of neurological and neurodegenerative diseases is complicated due to the blood-brain barrier,which makes it difficult for drugs to access the brain areas in which they must act to improve the pathology.A tool that can help to overcome this difficulty is the use of extracellular vesicles,which can easily cross the blood-brain barrier.The extracellular vesicles are considered a main way of communication between the brain and the rest of the body,with important implications for the physiopathology and therapy of neurological diseases.In recent years,the involvement of microbiota in many neurological pathologies,as well as its possible therapeutic role,has also become evident.A key mediator in the pathologic and beneficial effects of microbiota seems to be the bacterial extracellular vesicles.There is an important communication between the brain and the intestinal microbiota(the gut-brain axis),by which the microbiota influences brain function,impacts on mental health,and plays a role in different neurological and neurodegenerative diseases.The identification of the mechanisms involved in this gut-brain axis is essential to understanding the mechanisms of neurological pathologies and to developing more effective treatments for these diseases.Bacterial extracellular vesicles would play a relevant role in these processes.This review compiles the recent information and evidence on the role of bacterial extracellular vesicles in brain pathologies and on the therapeutic utility of bacterial extracellular vesicles in neurological and neurodegenerative diseases.One advantage of bacterial extracellular vesicles compared to extracellular vesicles derived from other cell types,such as stem cells,is that bacterial extracellular vesicles are generally easier to produce and modify.Bacterial extracellular vesicles may be easily modified to target a specific pathology and/or to enhance its therapeutic efficacy.Although the studies are still scarce,they open a wide field of possibilities for future studies,which will lead to a deeper understanding of the role of microbiota and bacterial extracellular vesicles in neurological pathologies and the underlying mechanisms,as well as to the development of new treatments based on the use of bacterial extracellular vesicles in neurological diseases.
文摘Male breast cancer(MBC)is rare,representing 0.5%–1%of all breast cancers,but its incidence is increasing due to improved diagnostics and awareness.MBC typically presents in older men,is human epidermal growth factor receptor 2(HER2)-negative and estrogen receptor(ER)-positive,and lacks routine screening,leading to delayed diagnosis and advanced disease.Major risk factors include hormonal imbalance,radiation exposure,obesity,alcohol use,and Breast Cancer Gene 1 and 2(BRCA1/2)mutations.Clinically,it may resemble gynecomastia but usually appears as a unilateral,painless mass or nipple discharge.Advances in imaging and liquid biopsy have enhanced early detection.Molecular mechanisms involve hormonal signaling,HER2/epidermal growth factor receptor(EGFR)pathways,tumor suppressor gene alterations,and epigenetic changes.While standard treatments mirror those for female breast cancer,emerging options such as cyclin-dependent kinase 4 and 6(CDK4/6),and poly(ADP-ribose)polymerase(PARP)inhibitors,immunotherapy,and precision medicine are reshaping management.Incorporating artificial intelligence,molecular profiling,and male-specific clinical trials is essential to improve outcomes and bridge current diagnostic and therapeutic gaps.
基金supported by the National Natural Science Foundation of China,Nos.82171344(to ZY),82471313(to CKT)the Guangdong Basic and Applied Basic Research Foundation,China,Nos.2023B1515120035,2024A1515012035(to CKT)The Science and Technology Projects in Guangzhou Nos.2025A03J4169(to ZY)。
文摘Stroke-induced alterations in cerebral blood flow trigger neurovascular remodeling,as manifested by the blood-brain barrier dysfunction and subs equent neurovascular repair activities such as angiogenesis.This process involves neurovascular communication that facilitates the transport of mediators among cerebrovascular endothelial cells,pericytes,glial cells,and neurons,thereby transmitting signals from donor to recipient cells to elicit a collaborative response.
文摘The retrospective study by Edwar et al reinforces the role of therapeutic penetrating keratoplasty(PK)as a vital intervention in severe,treatment-resistant infectious keratitis.In advanced cases—often complicated by trauma,delayed presentation,and corneal perforation—PK restores globe integrity and provides limited visual recovery.However,its application is constrained by graft-related complications and donor shortages,particularly in low-resource settings.These limitations highlight the need for earlier,globe-sparing strategies to prevent progression and reduce surgical demand.Photoactivated chromophore for infectious keratitis-corneal collagen cross-linking(PACK-CXL)has emerged as a promising adjunct or alternative.With both antimicrobial and tissue-stabilizing effects,PACK-CXL may control infection and preserve corneal structure in earlier stages.A layered treatment framework that incorporates PACK-CXL as an initial intervention and reserves PK for refractory cases may help improve clinical outcomes.Further studies are needed to define their best use in practice.
基金supported by the Canadian Institutes of Health Research Project grant (PJT-169197) to QYsupported by a CGS-M fellowship from the Canadian Institutes of Health Research
文摘Alzheimer’s disease(AD)remains an incurable neurodegenerative disorder with devastating societal and personal impacts.Despite decades of intensive research,therapeutic efforts targeting the clinical stages of AD have largely failed to halt or reverse disease progression.This has prompted a critical shift in focus toward the earlier,preclinical stages of AD,where interventions may hold greater promise for altering the disease trajectory.
文摘In the words of the late Sir Colin Blakemore,neurologists have historically sought to infer brain functions in a manner akin to to king a hammer to a computeranalyzing localized anatomical lesions caused by trauma,tumors,or strokes,noting deficits,and inferring what functions certain brain regions may be responsible for.This approach exemplifies a deletion heuristic,where the absence of a specific function reveals insights about the underlying structures or mechanisms responsible for it.By observing what is lost when a particular brain region is damaged,throughout the history of the field,neurologists have pieced together the intricate relationship between anatomy and function.
基金supported by the National Natural Science Foundation of China,No.81972073(to HZ)a grant from the Taishan Scholars Program ofShandong Province-Young Taishan Scholars,No.tsqn201909197(to HZ)+1 种基金a grant from Tianjin Key Medical Discipline(Specialty)Construct Project,No.TJYXZDXK-027A(to SF)a grant from Academic Expert International Innovation Summit,No.22JRRCRC00010(to SF).
文摘Ferroptosis,a type of cell death that mainly involves iron metabolism imbalance and lipid peroxidation,is strongly correlated with the phagocytic response caused by bleeding after spinal cord injury.Thus,in this study,bulk RNA sequencing data(GSE47681 and GSE5296)and single-cell RNA sequencing data(GSE162610)were acquired from gene expression databases.We then conducted differential analysis and immune infiltration analysis.Atf3 and Piezo1 were identified as key ferroptosis genes through random forest and least absolute shrinkage and selection operator algorithms.Further analysis of single-cell RNA sequencing data revealed a close relationship between ferroptosis and cell types such as macrophages/microglia and their intrinsic state transition processes.Differences in transcription factor regulation and intercellular communication networks were found in ferroptosis-related cells,confirming the high expression of Atf3 and Piezo1 in these cells.Molecular docking analysis confirmed that the proteins encoded by these genes can bind cycloheximide.In a mouse model of T8 spinal cord injury,low-dose cycloheximide treatment was found to improve neurological function,decrease levels of the pro-inflammatory cytokine inducible nitric oxide synthase,and increase levels of the anti-inflammatory cytokine arginase 1.Correspondingly,the expression of the ferroptosis-related gene Gpx4 increased in macrophages/microglia,while the expression of Acsl4 decreased.Our findings reveal the important role of ferroptosis in the treatment of spinal cord injury,identify the key cell types and genes involved in ferroptosis after spinal cord injury,and validate the efficacy of potential drug therapies,pointing to new directions in the treatment of spinal cord injury.
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the support from the University of Colorado Boulder (Start-up Fund)the National Science Foundation CAREER Award (No. CHE-1454925)
文摘Peptides are a class of drugs that have become increasingly important and influential for the treatment of many human diseases. Compared to traditional small molecule drugs, peptides have the potential for higher target specificity and potency, along with better safety profiles. On the other hand, the complex and fragile nature of peptides poses significant challenges for their administration. Of particular concern is that they are often unstable and can be rapidly degraded by various proteases after dosing. To address these inherent problems of peptides, many different methods have been attempted. Here, we briefly review these methods, with an emphasis on the effect of each method.
基金supported by the National Natural Science Foundation of China(No.81860268,and No.82201000)Ningxia Natural Science Foundation(No.2021AAC02025)+2 种基金Ningxia science and technology innovation leading talent training project(No.2020GKLRLX06 and No.2020GKLRLX11)Ningxia Medical University research project(No.XTJKF240315)Ningxia Key Research and Development Project(No.2023BEG03021 and No.2021BEB04034).
文摘To evaluate the therapeutic effect of a modified Devine procedure with a subcutaneous sliding fixation method for the treatment of congenital concealed penis,we retrospectively selected 45 patients with congenital concealed penises who were admitted to General Hospital of Ningxia Medical University(Yinchuan,China)between September 2020 and November 2023.In all cases,the penis was observed to be short,and retracting the skin at the base revealed a normal penile body,which immediately returned to its original position upon release.All patients underwent the modified Devine procedure with subcutaneous sliding fixation and completed a 12-week postoperative follow-up.A statistically significant increase in penile length was observed postoperatively,with the median length increasing from 4.0(interquartile range[IQR]:3.5–4.8;95%confidence interval[CI]:3.9–4.4)cm to 8.0(IQR:7.8–8.0;95%CI:7.7–7.9)cm,with P<0.001.The parents were satisfied with the outcomes,including increased penile length,improved hygiene,and enhanced esthetics.Except for mild foreskin edema in all cases,no complications(such as infections,skin necrosis,or penile retraction)were observed.The edema was resolved within 4 weeks after the operation.This study demonstrates that the modified Devine procedure utilizing the subcutaneous sliding fixation method yields excellent outcomes with minimal postoperative complications,reduced penile retraction,and high satisfaction rates among patients and their families.
基金Supported by National Natural Science Fund of China(No.81173199)Shanghai City Excellent Discipline Leader Project(No.09XD1403700)+1 种基金Competitive Selection Entrusting Project of Shanghai City Science Committee(No.09DZ1907902)Key Discipline(Traditional Chinese Medicine Diagnostics)of State Administration of Traditional Chinese Medicine
文摘OBJECTIVE:To study information gained by Traditional Chinese Medicine(TCM)four diagnostic methods and characteristics of syndrome development before and after treatment in patients with coronary heart disease,and to probe into assessment indexes of therapeutic effects with distinctive TCM features.METHODS:Information from the four diagnostic methods before and after treatment in 100 patients with coronary heart disease was collected using the TCM interrogation scale,a pulse condition instrument,a tongue-face diagnosis instrument,anda voice diagnosis information collection system.Changes in the four diagnostic method results from before and after treatment were analyzed with frequency analysis and t-test methods.RESULTS:Before treatment,deficiency syndrome complicated with hyperactivity of pathogenic factors was most common.After treatment,deficiency syndrome was most common.This change from complex syndromes to single syndromes indicates disease and syndrome alleviation.Frequencies of symptoms gained by interrogation after treatment for syndrome of deficiency of heart-Qi,syndrome of deficiency of heart-Yin,and turbid phlegm syndrome were all less severe than those before treatment.Parameters of face color,color on all sub-regions of tongue,color of tongue fur,septic and greasy fur,and lip color after treatment all had significant changes.After treatment,part of the voice diagnosis parameters in the deficiency of heart-Yin and turbid phlegm syndromes had significant changes,but no significant changes were found in the deficiency of heart-Qi syndrome.CONCLUSION:Use of the TCM four diagnostic methods can provide an effective basis forTCM syndrome diagnosis,observation of development of state of illness,and evaluation of clinical therapeutic effects.
文摘Background and Purpose: Therapeutic communication is a new term in family health care nursing, defined by Hohashi (2019) as a method of family intervention, and characterized by inclusion of not only verbal conversation but also nonverbal interaction. However, specific therapeutic communication methods have not been systematized. The purpose of this study was to clarify therapeutic communication methods for families/family members from the perspectives of verbal communication and non-verbal communication through a review of existing literature. Methods: We conducted a search using the medical literature databases PubMed and Ichushi-Web using the keywords “therapeutic communication”. Analysis was performed on seven articles from PubMed and 14 articles from Ichushi-Web that described therapeutic communication methods performed by healthcare professionals for families/family members. Through directed content analysis, therapeutic communication methods were subcategorized, and classified into three categories: verbal communication, non-verbal communication, and verbal/non-verbal communication. Results: A total of 23 subcategories were extracted. Verbal communication included 11 subcategories, such as “asking questions using the communicatee’s words as they are”. Non-verbal communication included five subcategories, such as “noticing changes in the content of the communicatee’s story”. And verbal/non-verbal communication featured seven subcategories, such as “making the communicatee aware of one’s own beliefs”. Conclusion: Therapeutic communication methods included basic care/caring in family interviews/meetings, as well as verbal communication and non-verbal communication that act on family/family members’ beliefs. It is believed that changes in family/family members’ beliefs can be used to eliminate, reduce, or improve problematic conditions in the family. .
文摘Objective To search for effective methods of acupuncture therapy in treating chronic diarrhea. Methods Treatments were carried out on 52 patients with chronic diarrhea by using the left ascending and right descending method. Three acupoints at the left side, namely Xiàng （陷谷 ST 43）, Zúsānl （足三 里 ST 36） and Qūchí （曲池 LI 11）, and Lièqūe （列缺 LU 7） at the right side were selected, moxibustion was also carried out according to syndrome differentiation. The operation of left ascending and right descending method were firstly left and then right, first down and then up, firstly four limbs and then abdomen; the thumb moved backward and the index finger moved forward during needle twisting for the acupoints at the left side, and it was on the contrary for the right side. The needles were retained for 1 h for deficiency, and the pinholes were pressed when the needles were withdrawn; the needles were retained for 0.5 h for excess syndrome and newly-contracted disease, and the pinholes were enlarged by shaking the needles when they were withdrawn. Except that the needling was carried out twice a day for the patients with desertion following chronic diarrhea, the needling was carried out once a day, five days as a treatment course, the patients were given an interval for two days after every two treatment courses, and the therapeutic effect was observed after five treatment courses. Results totally 36 patients were cured, among which 11 patients were cured after one treatment course, 19 patients were cured after two to three treatment courses and 6 patients were cured after four to five treatment courses; eight patients were improved; six patients were not cured; the total effective rate was 88.0%. Conclusion the acupuncture with left ascending and right descending method has satisfactory therapeutic effect in treating chronic diarrhea.
基金supported by the National Natural Science Foundation of China,Nos.82274313(to YD),82204746(to ML),82003982(to TL).
文摘It has been reported that the PI3K/AKT signaling pathway plays a key role in the pathogenesis of ischemic stroke.As a result,the development of drugs targeting the PI3K/AKT signaling pathway has attracted increasing attention from researchers.This article reviews the pathological mechanisms and advancements in research related to the signaling pathways in ischemic stroke,with a focus on the PI3K/AKT signaling pathway.The key findings include the following:(1)The complex pathological mechanisms of ischemic stroke can be categorized into five major types:excitatory amino acid toxicity,Ca^(2+)overload,inflammatory response,oxidative stress,and apoptosis.(2)The PI3K/AKT-mediated signaling pathway is closely associated with the occurrence and progression of ischemic stroke,which primarily involves the NF-κB,NRF2,BCL-2,mTOR,and endothelial NOS signaling pathways.(3)Natural products,including flavonoids,quinones,alkaloids,phenylpropanoids,phenols,terpenoids,and iridoids,show great potential as candidate substances for the development of innovative anti-stroke medications.(4)Recently,novel therapeutic techniques,such as electroacupuncture and mesenchymal stem cell therapy,have demonstrated the potential to improve stroke outcomes by activating the PI3K/AKT signaling pathway,providing new possibilities for the treatment and rehabilitation of patients with ischemic stroke.Future investigations should focus on the direct regulatory mechanisms of drugs targeting the PI3K/AKT signaling pathway and their clinical translation to develop innovative treatment strategies for ischemic stroke.
基金supported by the Natural Science Foundation of Fujian Province,No.2021J02035(to WX).
文摘Regulated cell death is a form of cell death that is actively controlled by biomolecules.Several studies have shown that regulated cell death plays a key role after spinal cord injury.Pyroptosis and ferroptosis are newly discovered types of regulated cell deaths that have been shown to exacerbate inflammation and lead to cell death in damaged spinal cords.Autophagy,a complex form of cell death that is interconnected with various regulated cell death mechanisms,has garnered significant attention in the study of spinal cord injury.This injury triggers not only cell death but also cellular survival responses.Multiple signaling pathways play pivotal roles in influencing the processes of both deterioration and repair in spinal cord injury by regulating pyroptosis,ferroptosis,and autophagy.Therefore,this review aims to comprehensively examine the mechanisms underlying regulated cell deaths,the signaling pathways that modulate these mechanisms,and the potential therapeutic targets for spinal cord injury.Our analysis suggests that targeting the common regulatory signaling pathways of different regulated cell deaths could be a promising strategy to promote cell survival and enhance the repair of spinal cord injury.Moreover,a holistic approach that incorporates multiple regulated cell deaths and their regulatory pathways presents a promising multi-target therapeutic strategy for the management of spinal cord injury.
