摘要：Dyspnea is a subjective sensation often described as a feeling of respiratory effort,tightness,or air hunger.The underlying mechanisms of this symptom are multifaceted and involve factors such as respiratory centers,cardiovas-cular system,airways,neuromuscular components,and metabolic factors,although not fully elucidated.The classical theory of imbalance between inspiratory neural drive(IND)and the simultaneous dynamic responses of the respiratory system posits that the disruption of a normal and harmo-nious relationship fundamentally shapes the expression of respiratory discomfort.Assessment and comprehensive treatment of dyspnea are crucial for patient rehabilitation,including subjective self-reporting and objective clinical measurements.Non-pharmacological interventions,such as pulmonary rehabilitation,fan therapy,exercise,chest wall vibration,virtual reality technology,traditional Chinese medicine(acupuncture and acupressure),and yoga,have shown promise in alleviating dyspnea symptoms.Addition-ally,oxygen therapy,has demonstrated short-term benefits for patients with pre-hospital respiratory distress and hyp-oxemia.This review provides a comprehensive overview of dyspnea,emphasizing the importance of a multifaceted approach for its assessment and management,with a focus on non-pharmacological interventions that contribute to enhanced patient outcomes and quality of life.

摘要：Regenerative rehabilitation is a novel and rapidly developing multidisciplinary field that converges regenerative medicine and rehabilitation science,aiming to maximize the functions of disabled patients and their independence.While regenerative medicine provides state-of-the-art technologies that shed light on difficult-to-treated diseases,regenerative rehabilitation offers rehabilitation interventions to improve the positive effects of regenerative medicine.However,regenerative scientists and rehabilitation professionals focus on their aspects without enough exposure to advances in each other's field.This disconnect has impeded the development of this field.Therefore,this review first introduces cutting-edge tech-nologies such as stem cell technology,tissue engineering,biomaterial science,gene editing,and computer sciences that promote the progress pace of regenerative medicine,followed by a summary of preclinical studies and examples of clinical investigations that integrate rehabilitative methodologies into regenerative medicine.Then,chal-lenges in this field are discussed,and possible solutions are provided for future directions.We aim to provide a platform for regenerative and rehabilitative professionals and clinicians in other areas to better understand the progress of regenerative rehabilitation,thus contributing to the clinical translation and management of innovative and reliable therapies.

摘要：The cyclic GMP-AMP synthase(cGAS)-stimulator of interferon genes(STING)pathway is an evolving DNA-sensing mechanism involved in innate immunity and pathogen defense that has been optimized while remaining conserved.Aside from recognizing pathogens through conserved motifs,these receptors also detect aberrant or misplaced self-molecules as possible signs of perturbed homeostasis.Upon binding external or self-derived DNA,a mobile sec-ondary messenger 2'3'-cyclic GMP-AMP(cGAMP)is produced by cGAS and in turn activates its adapter STING in the endo-plasmic reticulum(ER).Resting-state or activated STING protein is finely restricted by multiple degradation machin-eries.The post-translational changes of the STING protein,along with the regulatory machinery of the secret routes,limit the onset,strength and sustention of STING signal.STING experiences a conformational shift and relocates with TBK1 from the ER to perinuclear vesicles containing transcription factors,provoking the transcription activity of IRF3/IFN-Ⅰand NF-κB pathways,as well as to initiate a number of cellular processes that have been shown to alter the immune landscape in cancer,such as autophagy,NLRP3 inflamma-some,ER stress,and cell death.STING signal thus serves as a potent activator for immune mobilization yet also triggers immune-mediated pathology in tissues.Recent advances have established the vital role of STING in immune surveil-lance as well as tumorigenic process.This review provides an overview of the disparate outcomes of cancer attributed to the actions of pleiotropic and coordinated STING downstream signalosomes,along with the underlying mechanisms of STING function in pathologies,providing therapeutic impli-cations for new approaches in hunt for the next generation of cancer immunotherapy base on STING.

摘要：Angiogenesis,the process of formation of new capillaries from existing blood vessels,is required for multiple physiological and pathological processes.Complement factor H(CFH)is a plasma protein that inhibits the alternative pathway of the complement system.Loss of CFH enhances the alterna-tive pathway and increases complement activation fragments with pro-angiogenic capacity,including complement 3a,complement 5a,and membrane attack complex.CFH protein contains binding sites for C-reactive protein,malondialdehyde,and endothelial heparan sulfates.Dysfunction of CFH pre-vents its interaction with these molecules and initiates pro-angiogenic events.Mutations in the CFH gene have been found in patients with age-related macular degener-ation characterized by choroidal neovascularization.The Cfh-deficient mice show an increase in angiogenesis,which is decreased by administration of recombinant CFH pro-tein.In this review,we summarize the molecular mecha-nisms of the anti-angiogenic effects of CFH and the regulatory mechanisms of CFH expression.The therapeutic potential of recombinant CFH protein in angiogenesis-related diseases has also been discussed.

摘要：Alzheimer's disease(AD)is a gradually progres-sive neurodegenerative disease with tremendous social and economic burden.Therefore,early and accurate diagnosis is imperative for effective treatment or prevention of the disease.Cerebrospinal fluid and blood biomarkers emerge as favorable diagnostic tools due to their relative accessi-bility and potential for widespread clinical use.This review focuses on the AT(N)biomarker system,which includes biomarkers reflecting AD core pathologies,amyloid deposi-tion,and pathological tau,as well as neurodegeneration.Novel biomarkers associated with inflammation/immunity,synaptic dysfunction,vascular pathology,and α-synuclein-opathy,which might contribute to either the pathogenesis or the clinical progression of AD,have also been discussed.Other emerging candidates including non-coding RNAs,metabolites,and extracellular vesicle-based markers have also enriched the biofluid biomarker landscape for AD.Moreover,the review discusses the current challenges of biofluid biomarkers in AD diagnosis and offers insights into the prospective future development.

摘要：Persistent motor deficits are highly prevalent among post-stroke survivors,contributing significantly to disability.Despite the prevalence of these deficits,the pre-cise mechanisms underlying motor recovery after stroke remain largely elusive.The exploration of motor system reorganization using functional neuroimaging techniques represents a compelling yet challenging avenue of research.Quantitative electroencephalography(qEEG)parameters,including the power ratio index,brain symmetry index,and phase synchrony index,have emerged as potential prognostic markers for overall motor recovery post-stroke.Current evi-dence suggests a correlation between qEEG parameters and functional motor outcomes in stroke recovery.However,accurately identifying the source activity poses a challenge,prompting the integration of EEG with other neuroimaging modalities,such as functional near-infrared spectroscopy(fNIRS).fNIRS is nowadays widely employed to investigate brain function,revealing disruptions in the functional motor network induced by stroke.Combining these two methods,referred to as integrated fNIRS-EEG,neural activity and hemodynamics signals can be pooled out and offer new types of neurovascular coupling-related features,which may be more accurate than the individual modality alone.By harnessing integrated fNIRS-EEG source localization,brain connectivity analysis could be applied to characterize cortical reorganization associated with stroke,providing valuable insights into the assessment and treatment of post-stroke motor recovery.

摘要：Chronic pancreatitis(CP)is characterized by irreversible destruction of pancreatic parenchyma,inflam-matory cell infiltration and progressive fibrosis of pancre-atic tissue.Obstruction of pancreatic duct by pancreatic stone is the common pathological change in the course of CP with the incidence of over 50%at the diagnosis of CP.These ductal stones would cause pancreatic parenchymal hyper-tension and local ischemia,which was eventually followed by recurrent episodes of painful pancreatitis or other man-ifestations of pancreatic exocrine and endocrine insuffi-ciency.Removing pancreatic stones has been confirmed as the core to reduce pressure,improve drainage and lessen pain.Surgical therapy achieves satisfying pain relief with more complications,higher cost and less repeatability compared with endoscopic therapy.Endoscopic retrograde cholangiopancreatography,which used to be the standard endoscopic therapy for pancreatic stones,would fail if these stones are large or complex,while pancreatic extracorporeal shock wave lithotripsy(P-ESWL),which has been applied since 1987,could overcome this problem.Up to now,a large number of guidelines have recommended the P-ESWL as the first-line treatment strategy for radiopaque obstructive main pancreatic duct stones larger than 5 mm located in the head/body of the pancreas,and P-ESWL had completely changed the traditional treatment model for CP patients with pancreatic stones.In this article,we will focus on the technical progress,efficacy,safety and potential research areas of P-ESWL,we also give us suggestions for lithotripters improvement.

摘要：Taxanes,including paclitaxel,docetaxel,and cab-azitaxel,are key agents in cancer treatment,often used as front-line chemotherapy drugs in combination with other agent(s)(commonly carboplatin)and as second-line treatments alone.Generally,taxanes are highly effective,but drug resistance unavoidably develops following repeated treatment.Taxanes work by binding to and stabilizing microtubules,leading to mitotic arrest,mitotic catastrophe,and micronucleation.The long-recognized mechanisms of drug resistance generally can be classified into three categories:drug efflux,microtubule polymerization,and apoptotic pathway.A recent new addition to this list is a mechanism related to the nuclear envelope,as cancer cells undergo micronucleation and nuclear membrane rupture when treated with taxanes.All these mechanisms may operate simultaneously as taxane resistance is multi-factorial.Here,we review the cell biology understanding of nuclear envelope breaking in production of micronucleation,and nuclear membrane rupture and repair,and propose that these processes are involved in taxane resistance.

摘要：Objectives:Resistance to apoptosis in esophageal squa-mous cell carcinoma(ESCC)constitutes a significant impediment to treatment efficacy.Exploring alternative cell death pathways and their regulatory factors beyond apoptosis is crucial for overcoming drug resistance and enhancing therapeutic outcomes in ESCC. Methods:Mammalian Ste 20-like kinase 1(MST1)is impli-cated in regulating various cell deaths,including apoptosis,autophagy,and pyroptosis.Employing enhanced ascorbate peroxidase 2(APEX2)proximity labeling coupled with immunoprecipitation-mass spectrometry(IP-MS),we eluci-dated the interactomes of MST1 across these three cell death paradigms. Results:Proteomic profiling unveiled the functional roles and subcellular localization of MST1 and its interacting proteins during normal proliferation and various cell death processes.Notably,MST1 exhibited an expanded inter-actome during cell death compared to normal proliferation and chromosome remodeling functions consistently.In apoptosis,there was a notable increase of mitosis-associated proteins such as INCENP,ANLN,KIF23,SHCBP1 and SUPT16H,which interacted with MST1,alongside decreased expression of the pre-apoptotic protein STK3.During autophagy,the bindings of DNA repair-related proteins CBX8 and m6A reader YTHDC1 to MST1 were enhanced.In pyroptosis,LRRFIP2 and FLII which can inhibit pyroptosis increasingly binding to MST1. Conclusions:Our findings delineate potential mechanisms through which MST1 and its interactomes regulate cell death,paving the way for further investigation to validate and consolidate these observations.

摘要：Background Over the past few decades,the insidious proliferation of plastic contaminants has emerged as a pervasive environ-mental challenge,with far-reaching implications for the integrity of oceans and a myriad of natural ecosystems,even looming as a significant risk[1]to human health.

摘要：Bone injuries and diseases are associated with profound changes in the biophysical properties of living bone tissues,particularly their electrical and mechanical properties.The biophysical properties of healthy bone are attributed to the complex network of interactions between its various cell types(i.e.,osteocytes,osteoclast,immune cells and vascular endothelial cells)with the surrounding extracellular matrix(ECM)against the backdrop of a myriad of biomechanical and bioelectrical stimuli arising from daily physical activities.Understanding the pathophysiological changes in bone biophysical properties is critical to devel-oping new therapeutic strategies and novel scaffold bio-materials for orthopedic surgery and tissue engineering,as well as provides a basis for the application of various biophysical stimuli as therapeutic agents to restore the physiological microenvironment of injured/diseased bone tissue,to facilitate its repair and regeneration.These include mechanical,electrical,magnetic,thermal and ultrasound stimuli,which will be critically examined in this review.A significant advantage of utilizing such biophysi-cal stimuli to facilitate bone healing is that these may be applied non-invasively with minimal damage to sur-rounding tissues,unlike conventional orthopedic surgical procedures.Furthermore,the effects of such biophysical stimuli can be localized specifically at the bone defect site,unlike drugs or growth factors that tend to diffuse away after delivery,which may result in detrimental side effects at ectopic sites.

摘要：Adipose-derived mesenchymal stem cells(ADSCs)and bone marrow-derived mesenchymal stem cells(BMSCs)have shown great potential in clinical applications.Howev-er,the similarities and differences between these two cell types have not been fully elucidated.Recent advances in transcriptomic and metabolomic research have provided valuable insight into the characteristics and functions of ADSCs and BMSCs.In this perspective article,we review the key findings from these studies,including cellular het-erogeneity as well as differences in metabolic and secretory properties.We discuss how these insights can help guide the selection of the most suitable cell source for the clinic,and the optimization of preconditioning strategies prior to clinical deployment.Furthermore,we analyze the current landscape of products and clinical trials involving ADSCs and BMSCs,highlighting their therapeutic potential.We propose that the integration of multi-omics datasets will be crucial for establishing a comprehensive understanding of ADSC and BMSC identity and potency,and the provision of quality-assured stem cell-derived products for the clinic.

摘要：Cancer nanomedicine is defined as the application of nanotechnology and nanomaterials for the formulation of cancer therapeutics that can overcome the impediments and restrictions of traditional chemotherapeutics.Multidrug resistance(MDR)in cancer cells can be defined as a decrease or abrogation in the efficacy of anticancer drugs that have different molecular structures and mechanisms of action and is one of the primary causes of therapeutic failure.There have been successes in the development of cancer nanomedicine to overcome MDR;however,relatively few of these formulations have been approved by the United States Food and Drug Administration for the treatment of cancer.This is primarily due to the paucity of knowledge about nanotechnology and the fundamental biology of cancer cells.Here,we discuss the advances,types of nanomedicines,and the challenges regarding the translation of in vitro to in vivo results and their relevance to effective therapies.

摘要：As the crisp air of a new year washes over us,carrying with it the scent of possibilities and the whispers of unfinished endeavors,it is time for reflection and,of course,renewed dedication.Here at Medical Review,we stand tall amidst the constant churn of scientific discovery,witnessing firsthand the tireless efforts of researchers,clinicians,and healthcare professionals who relentlessly push the boundaries of medical knowledge.

摘要：Cardiovascular research has heavily relied on studies using patient samples and animal models.However,patient studies often miss the data from the crucial early stage of cardiovascular diseases,as obtaining primary tis-sues at this stage is impracticable.Transgenic animal models can offer some insights into disease mechanisms,although they usually do not fully recapitulate the phenotype of car-diovascular diseases and their progression.In recent years,a promising breakthrough has emerged in the form of in vitro three-dimensional(3D)cardiovascular models utilizing human pluripotent stem cells.These innovative models recreate the intricate 3D structure of the human heart and vessels within a controlled environment.This advancement is pivotal as it addresses the existing gaps in cardiovascular research,allowing scientists to study different stages of cardiovascular diseases and specific drug responses using human-origin models.In this review,we first outline various approaches employed to generate these models.We then comprehensively discuss their applications in studying car-diovascular diseases by providing insights into molecular and cellular changes associated with cardiovascular condi-tions.Moreover,we highlight the potential of these 3D models serving as a platform for drug testing to assess drug efficacy and safety.Despite their immense potential,chal-lenges persist,particularly in maintaining the complex structure of 3D heart and vessel models and ensuring their function is comparable to real organs.However,over-coming these challenges could revolutionize cardiovascu-lar research.It has the potential to offer comprehensive mechanistic insights into human-specific disease processes,ultimately expediting the development of personalized therapies.

摘要：To determine the definition,foundation,practice,and development of evidence-based rehabilitation medicine(EBRM)and point out the development direction for EBRM.Retrieve the database of PubMed,Cochrane Library,Embase,China national knowledge infrastructure(CNKI),Wanfang,and China science and technology journal data-base(CSTJ).The search was conducted from the establish-ment of the database to June 2023.The key words are"rehabilitation medicine and evidence based" in Chinese and English.After reading the abstract or full text of the literature,a summary analysis is conducted to determine the definition,foundation,practice,and development of EBRM.A total of 127 articles were included.The development of 14 sub majors in EBRM are not balanced,evidence-based musculoskeletal rehabilitation medicine(EBMRM)(31 arti-cles,mainly focuses on osteoarthritis,osteoporosis and musculoskeletal pain),evidence-based neurorehabilitation medicine(EBNM)(34 articles,mainly concentrated in stroke,traumatic brain injury and spinal cord injury)and evidence-based education rehabilitation medicine(EBEDRM)(17 ar-ticles,mainly focuses on educational methodology),evi-dence-based nursing rehabilitation medicine(EBNRM)(2 articles),evidence-based engineering rehabilitation medi-cine(EBENRM)(7 articles),evidence-based traditional Chi-nese rehabilitation medicine(EBTCRM)(3 articles),evidence-based internal rehabilitation medicine(EBIRM)(11 articles),evidence-based intensive care rehabilitation med-icine(EBICRM)(4 articles),evidence-based oncology reha-bilitation medicine(EBORM)(6 articles),evidence-based physical therapy medicine(EBPTM)(3 articles),evidence-based cardiopulmonary rehabilitation medicine(EBCRM)(6 articles),evidence-based speech therapy medicine(EBSTM)/evidence-based occupation therapy medicine(EBOTM)/evi-dence-based geriatric rehabilitation medicine(EBGRM)(1 article).The EBMRM,EBNM and EBEDRM are relatively well developed.The development of EBNRM,EBENRM,EBTCRM,EBIRM,EBICRM,EBGRM,EBORM,EBCRM,EBPTM,EBSTM and EBOTM is relatively slow,indicating these eleven fields should be pay more attention in future.

摘要：With the advent of improved tools to examine the astrocytes,which have been believed to play a supportive role in the central nervous system(CNS)for years,their participation in the operation of the CNS and drug addiction was unveiled.Assisting the formation and function of the CNS,astrocytes are involved in physiological and patholog-ical brain activities.Drug addiction is a pervasive psychiatric disorder,characterized by compulsive drug-taking behavior and high rate of relapse,impacting individual health and society stability and safety.When exposed to drugs of abuse,astrocytes go through a series of alterations,contributing to the development of addiction.Here we review how astrocytes contribute to the CNS and drug addiction.We hope that understanding the interaction between addictive drugs and astrocytes may help discover new mechanisms underlying the addiction and produce novel therapeutic treatments.

摘要：The brain is among the most essential organs of human beings. In human brain,there are about 100 billion neu-rons,and they form the basis of neural activity in the brain through synaptic connections [1]. The higher-level neural functions distinguish us from other animals,yet we still have not achieved a comprehensive knowledge of the brain. Therefore,understanding its structure and function is one of the most substantial and challenging frontier scientific questions of the 21st century.

摘要：Spontaneous pain occurring without apparent external stimuli,is a significant complaint of individuals with chronic pain whose mechanisms,somewhat surpris-ingly,remain poorly understood.Over the past decades,neuroimaging studies start to reveal brain activities accompanying spontaneous pain.Meanwhile,a variety of animal models and behavioral tests have been established,including non-reflexive tests and free-choice tests,which have been shown to be effective in assessing spontaneous pain.For the spontaneous pain mechanisms,multiple lines of research mainly focus on three aspects:(1)sensitization of peripheral nociceptor receptors and ion channels,(2)spontaneous neuronal firing and abnormal activity patterns at the dorsal root ganglion and spinal cord level,(3)func-tional and structural alterations in the brain,particularly the limbic system and the medial pain pathway.Despite accu-mulating evidence revealing distinct neuronal mechanisms from evoked pain,we are still far from full understanding of spontaneous pain,leaving a big gap between bench and bedside for chronic pain treatment.A better understanding of the neural processes in chronic pain,with specific linkage as to which anatomical structures and molecules related to spontaneous pain perception and comorbidities,will greatly improve our ability to develop novel therapeutics.

摘要：Trimethylamine-N-oxide (TMAO) is a metabolite produced from dietary nutrients by the gut microbiome, which was first discovered in 2011 and used to predict the risk of car-diovascular disease [1].