Clinical laboratory tests are basic elements that support healthcare tasks such as disease detection, diagnosis and monitoring of response to treatments. Current laboratory information systems focus on the patient dat...Clinical laboratory tests are basic elements that support healthcare tasks such as disease detection, diagnosis and monitoring of response to treatments. Current laboratory information systems focus on the patient database, tests and results, with multiple modules available, connecting with the various analytical systems or work areas. However laboratory information systems functioned as “islands of information”, because their design was fundamentally inward-looking and disconnected from other healthcare computer applications. Actually, the Electronic Health Register (EHR) is considered by clinicians as a tool with great potential healthcare benefits. The EHR, in the sense of a unique and complete record of a patient’s healthcare and state of health, regardless of the healthcare level used, is a real attempt to eliminate these “islands of information” and need modules to act as “bridges” with the laboratory information systems. This type of module, which in generic terms may be referred to as a laboratory test request module, has become an essential feature of the EHR. These modules need to use a laboratory coding system as a common language for exchanging information, ensuring that tests and results are unequivocally identified. The development of the laboratory test request module requires the commitment of professionals and political authorities, being necessary time for their design and an adequate pilot phase. The laboratory professionals have to assume a leadership role in the whole process of design, development and implementation of these modules, integrating in the equipment of information technologies of healthcare providers. In our manuscript we review the elements that may prove electronic systems for requesting clinical laboratory test into digital clinical records and the key elements to move from theory to practice.展开更多
Objective： Our aim was to investigate clinical and laboratory characteristics of osteoarthritic patients who had amyloid deposition in their knee joints. Methods： Synovial membranes were obtained from 36 patients wi...Objective： Our aim was to investigate clinical and laboratory characteristics of osteoarthritic patients who had amyloid deposition in their knee joints. Methods： Synovial membranes were obtained from 36 patients with knee osteoarthritis （OA） who underwent joint replacement surgery. From this sample, the diagnosis of amyloid was deter- mined by Congo red staining, which demonstrated apple-green birefringence under a polarized microscope. All syn- ovial membranes were immunohistochemically characterized for the expressions of amyloid immunoglobulin light chain （AL-K and AL-,k）, serum amyloid-A （SAA）, amyloidogenic transthyretin （ATTR）, and amyloidogenic 152- microglobulin （A152M）. Matrix-assisted laser desorption-ionizaton/time of flight mass spectrometry （MALDI-TOF MS） was used to analyze transthyretin （TTR） isoforms in the serum of each patient. Results： Nine cases （25%） were found to be amyloid-positive. Immunohistochemicaliy, eight cases （88.9%） had ATTR deposition, and one sample （11.1%） was shown to be AL-K-positive. MALDI-TOF MS identified that the TTR in the serum of the patients was unmodified wild-type TTR, TTR-Cys-S-S-Cys, and TTR-Cys-S-S-CysGly. The age at surgery and the disease duration were sig- nificantly higher in the ATTR-positive group than in the ATTR-negative group. Knee score and function score were significantly lower in the ATTR-positive group than in the ATTR-negative group. Conclusions： Amyloid deposition in synovial membranes of OA patients was found to be ATTR and AL-K. TTR in the serum of the patients was unmodified wild-type TTR together with two isoforms. The high age at surgery, long disease duration, and a deteriorated knee function were associated with ATTR amyloid deposition in the osteoarthritic knee joints.展开更多
1.Editor’s note In September 2024,a team of Australian experts in clinical laboratory medicine visited Shanghai Jiao Tong University School of Medicine and Shanghai University of Medicine&Health Sciences,which is...1.Editor’s note In September 2024,a team of Australian experts in clinical laboratory medicine visited Shanghai Jiao Tong University School of Medicine and Shanghai University of Medicine&Health Sciences,which is a dense 9-day agenda blending a superb scientific and educational communication program.Taking this opportunity,we are honored to have an interview with Prof.Greg,Head of Biochemistry and Endocrinology for Sullivan Nicolaides Pathology(SNP)in Brisbane Australia and President of Australian Association of Clinical Biochemistry and Laboratory Medicine(AACB),to share his experience in his clinical and scientific career and his insights on applied clinical laboratory medicine.展开更多
BACKGROUND In recent years,many studies have shown that proteasome 26S subunit non-ATPase 6(PSMD6)plays an important role in the occurrence and development of malignant tumours.Unfortunately,there are no reports on th...BACKGROUND In recent years,many studies have shown that proteasome 26S subunit non-ATPase 6(PSMD6)plays an important role in the occurrence and development of malignant tumours.Unfortunately,there are no reports on the evaluation of the potential role of PSMD6 in hepatocellular carcinoma(HCC).AIM To comprehensively evaluate the overexpression pattern and clinical significance of PSMD6 in HCC tissues.METHODS This study integrated PSMD6 mRNA expression profiles from 4672 HCC and 3667 non-HCC tissues,along with immunohistochemical scores from 383 HCC and adjacent tissues,to assess PSMD6 overexpression in HCC.Clustered regularly interspaced short palindromic repeats knockout technology evaluated PSMD6’s essential role in HCC cell growth.Functional enrichment analysis explored the molecular mechanism of PSMD6 abnormalities in HCC.Drug sensitivity analysis and molecular docking analysed the effect of abnormal expression of PSMD6 on the drug sensitivity of HCC cells.RESULTS The results of 41 external and two internal datasets showed that PSMD6 mRNA(SMD=0.26,95%CI:0.09-0.42,P<0.05)and protein(SMD=2.85,95%CI:1.19-4.50,P<0.05)were significantly overexpressed in HCC tissues.The integrated analysis results showed that PSMD6 had a significant overexpression pattern in HCC tissues(SMD=0.40,95%CI:0.15-0.66,P<0.05).PSMD6 knockout inhibited HCC cell growth(chronos scores<-1).Functional enrichment implicated ribosome biogenesis and RNA splicing.Significant enrichment of signalling pathways such as RNA degradation,ribosomes,and chemical carcinogenesis—reactive oxygen species.Drug sensitivity analysis and a molecular docking model showed that high expression of PSMD6 was associated with the tolerance of HCC cells to drugs such as ML323,sepantronium bromide,and GDC0810.Overexpressed PSMD6 effectively distinguished HCC tissues(AUC=0.75,95%CI:0.71-0.79).CONCLUSION This study was the first to discover that PSMD6 was overexpressed in HCC tissues.PSMD6 is essential for the growth of HCC cells and may be involved in ribosome biogenesis and RNA splicing.展开更多
Polyphenols,a diverse group of naturally occurring compounds found in plants,have garnered significant attention for their potential therapeutic properties in treating neurodegenerative diseases(NDs).The Wnt/β-cateni...Polyphenols,a diverse group of naturally occurring compounds found in plants,have garnered significant attention for their potential therapeutic properties in treating neurodegenerative diseases(NDs).The Wnt/β-catenin(WβC)signaling pathway,a crucial player in neurogenesis,neuronal survival,and synaptic plasticity,is involved in several cellular mechanisms related to NDs.Dysregulation of this pathway is a hallmark in the development of various NDs.This study explores multiple polyphenolic compounds,such as flavonoids,stilbenes,lignans,and phenolic acids,and their potential to protect the nervous system.It provides a comprehensive analysis of their effects on the WβC pathway,elucidating their modes of action.The study highlights the dual function of polyphenols in regulating and protecting the nervous system,providing reassurance about the research benefits.This review provides a comprehensive analysis of the results obtained from both in vitro studies and in vivo research,shedding light on how these substances influence the various components of the pathway.The focus is mainly on the molecular mechanisms that allow polyphenols to reduce oxidative stress,inflammation,and apoptotic processes,ultimately improving the function and survival of neurons.This study aims to offer a thorough understanding of the potential of polyphenols in targeting the WβC signaling pathway,which could lead to the development of innovative therapeutic options for NDs.展开更多
Hepatitis B virus(HBV)is a serious global public health concern.Although nucleoside drugs and interferons can significantly inhibit HBV replication,issues such as drug resistance and low clinical cure rates remain.Tra...Hepatitis B virus(HBV)is a serious global public health concern.Although nucleoside drugs and interferons can significantly inhibit HBV replication,issues such as drug resistance and low clinical cure rates remain.Traditional Chinese medicine(TCM)is widely used in the treatment of chronic hepatitis B(CHB)in China,with anti-inflammatory,anti-fibrotic,and liver-protective effects;however,reports on its antiviral effects are still inconsistent.We retrieved multicenter clinical studies and meta-analyses of TCM treatment for CHB over the past two decades.The results revealed that TCM has a certain anti-HBV effect,and when combined with antiviral drugs,it can significantly improve antiviral efficacy.It was demonstrated that TCM most effectively promotes serum HBV e antigen conversion to negative,followed by the ability to reduce HBV DNA levels,facilitating HBV surface antigen loss,and improving the treatment of CHB.展开更多
Objective Blood culture remains the gold standard for diagnosing bloodstream infections.Clinical laboratories must ensure the quality of blood culture processes from receipt to obtaining definitive results.We examined...Objective Blood culture remains the gold standard for diagnosing bloodstream infections.Clinical laboratories must ensure the quality of blood culture processes from receipt to obtaining definitive results.We examined laboratory analytical indicators associated with positive blood culture results.Methods Blood cultures collected from Peking Union Medical College Hospital between January 1,2020,and December 31,2022,were retrospectively analyzed.The mode of transportation(piping logistics delivery vs.staff),source of blood cultures(outpatient/emergency department vs.inpatient department),rotation of personnel,and time of reception(8:00–19:59 vs.20:00–07:59)were compared between blood culture-positive and-negative results.Results Between 2020 and 2022,the total positive rate of blood culture was 8.07%.The positive rate of blood cultures in the outpatient/emergency department was significantly higher than that in the inpatient department(12.46%vs.5.83%;P<0.0001).The time-to-detection of blood cultures was significantly affected by the delivery mode and personnel rotation.The blood culture positive rate of the total pre-analytical time within 1 h was significantly higher than that within 1–2 h or>2 h(P<0.0170).Conclusion Laboratory analytical indicators such as patient source,transportation mode,and personnel rotation significantly impacted the positive detection rate or time of blood culture.展开更多
Quorum sensing(QS)represents a mechanism through which bacteria engage in communication via chemical signals,a phenomenon prevalent across diverse bacterial species.Recent investigations have elucidated that QS signal...Quorum sensing(QS)represents a mechanism through which bacteria engage in communication via chemical signals,a phenomenon prevalent across diverse bacterial species.Recent investigations have elucidated that QS signaling pathways are pivotal in governing bacterial physiological processes,collective behaviors,and the emergence of drug resistance.Escherichia coli(E.coli),a prominent pathogenic bacterium,is increasingly exhibiting severe drug resistance issues,posing substantial hurdles for clinical interventions.Presently,a burgeoning body of research is exploring the connection between QS signaling pathways and the drug resistance mechanisms in E.coli,unveiling the coordinating function of QS within bacterial communities and its influence on antibiotic resistance.Despite some research advancements,the precise mechanisms underlying the QS signaling pathway remain ambiguous,and its potential applications are somewhat constrained.This article endeavors to systematically review the research progress concerning the QS signaling pathway in the context of clinical drug resistance mechanisms in E.coli,delving into its potential clinical applications and future research avenues,with the aim of offering novel insights and strategies to counteract drug resistance.展开更多
Alzheimer’s disease(AD),as the predominant form of neurodegenerative disorders,exerts a profound impact on the health of the global elderly population.For decades,the elucidation of AD pathogenesis and the developmen...Alzheimer’s disease(AD),as the predominant form of neurodegenerative disorders,exerts a profound impact on the health of the global elderly population.For decades,the elucidation of AD pathogenesis and the development of diagnostic and therapeutic approaches have been the focus of extensive research.Over recent years,a fundamental shift has occurred in AD diagnostics—transitioning from reliance on clinical diagnosis alone to biomarker-supported frameworks.AD biomarker research has transitioned from postmortem histopathology to in vivo detection paradigms,enabling precision diagnosis and intervention.This review synthesizes recent advances in molecular biomarkers across three domains:Fluid biomarkers,Molecular imaging and Innovative detection platforms,and also evaluates the challenges and prospects of the clinical transformation of molecular markers for AD.展开更多
Recent data suggest that vascular endothelial growth factor receptor inhibitor(VEGFRi)can enhance the anti-tumor activity of the anti-programmed cell death-1(anti-PD-1)antibody in colorectal cancer(CRC)with microsatel...Recent data suggest that vascular endothelial growth factor receptor inhibitor(VEGFRi)can enhance the anti-tumor activity of the anti-programmed cell death-1(anti-PD-1)antibody in colorectal cancer(CRC)with microsatellite stability(MSS).However,the comparison between this combination and standard third-line VEGFRi treatment is not performed,and reliable biomarkers are still lacking.We retrospectively enrolled MSS CRC patients receiving anti-PD-1 antibody plus VEGFRi(combination group,n=54)or VEGFRi alone(VEGFRi group,n=32),and their efficacy and safety were evaluated.We additionally examined the immune characteristics of the MSS CRC tumor microenvironment(TME)through single-cell and spatial transcriptomic data,and an MSS CRC immune cell-related signature(MCICRS)that can be used to predict the clinical outcomes of MSS CRC patients receiving immunotherapy was developed and validated in our in-house cohort.Compared with VEGFRi alone,the combination of anti-PD-1 antibody and VEGFRi exhibited a prolonged survival benefit(median progression-free survival:4.4 vs.2.0 months,P=0.0024;median overall survival:10.2 vs.5.2 months,P=0.0038)and a similar adverse event incidence.Through single-cell and spatial transcriptomic analysis,we determined ten MSS CRC-enriched immune cell types and their spatial distribution,including naive CD4+T,regulatory CD4+T,CD4+Th17,exhausted CD8+T,cytotoxic CD8+T,proliferated CD8+T,natural killer(NK)cells,plasma,and classical and intermediate monocytes.Based on a systemic meta-analysis and ten machine learning algorithms,we obtained MCICRS,an independent risk factor for the prognosis of MSS CRC patients.Further analyses demonstrated that the low-MCICRS group presented a higher immune cell infiltration and immune-related pathway activation,and hence a significant relation with the superior efficacy of pan-cancer immunotherapy.More importantly,the predictive value of MCICRS in MSS CRC patients receiving immunotherapy was also validated with an in-house cohort.Anti-PD-1 antibody combined with VEGFRi presented an improved clinical benefit in MSS CRC with manageable toxicity.MCICRS could serve as a robust and promising tool to predict clinical outcomes for individual MSS CRC patients receiving immunotherapy.展开更多
Regulatory T cells,a subset of CD4^(+)T cells,play a critical role in maintaining immune tolerance and tissue homeostasis due to their potent immunosuppressive properties.Recent advances in research have highlighted t...Regulatory T cells,a subset of CD4^(+)T cells,play a critical role in maintaining immune tolerance and tissue homeostasis due to their potent immunosuppressive properties.Recent advances in research have highlighted the important therapeutic potential of Tregs in neurological diseases and tissue repair,emphasizing their multifaceted roles in immune regulation.This review aims to summarize and analyze the mechanisms of action and therapeutic potential of Tregs in relation to neurological diseases and neural regeneration.Beyond their classical immune-regulatory functions,emerging evidence points to non-immune mechanisms of regulatory T cells,particularly their interactions with stem cells and other non-immune cells.These interactions contribute to optimizing the repair microenvironment and promoting tissue repair and nerve regeneration,positioning non-immune pathways as a promising direction for future research.By modulating immune and non-immune cells,including neurons and glia within neural tissues,Tregs have demonstrated remarkable efficacy in enhancing regeneration in the central and peripheral nervous systems.Preclinical studies have revealed that Treg cells interact with neurons,glial cells,and other neural components to mitigate inflammatory damage and support functional recovery.Current mechanistic studies show that Tregs can significantly promote neural repair and functional recovery by regulating inflammatory responses and the local immune microenvironment.However,research on the mechanistic roles of regulatory T cells in other diseases remains limited,highlighting substantial gaps and opportunities for exploration in this field.Laboratory and clinical studies have further advanced the application of regulatory T cells.Technical advances have enabled efficient isolation,ex vivo expansion and functionalization,and adoptive transfer of regulatory T cells,with efficacy validated in animal models.Innovative strategies,including gene editing,cell-free technologies,biomaterial-based recruitment,and in situ delivery have expanded the therapeutic potential of regulatory T cells.Gene editing enables precise functional optimization,while biomaterial and in situ delivery technologies enhance their accumulation and efficacy at target sites.These advancements not only improve the immune-regulatory capacity of regulatory T cells but also significantly enhance their role in tissue repair.By leveraging the pivotal and diverse functions of Tregs in immune modulation and tissue repair,regulatory T cells–based therapies may lead to transformative breakthroughs in the treatment of neurological diseases.展开更多
BACKGROUND:Breast hyperplasia is a common benign breast disease mainly caused by endocrine disorders,manifested as abnormal hyperplasia of breast tissue.In recent years,traditional Chinese medicine compounds and probi...BACKGROUND:Breast hyperplasia is a common benign breast disease mainly caused by endocrine disorders,manifested as abnormal hyperplasia of breast tissue.In recent years,traditional Chinese medicine compounds and probiotics have shown good potential in regulating the endocrine system and improving the intestinal microecology,providing new ideas for the treatment of breast hyperplasia.OBJECTIVE:To explore the effects and mechanisms of traditional Chinese medicine compounds and fermented probiotic compounds on breast hyperplasia in mice,providing new theoretical and experimental bases for the clinical treatment and prevention of breast hyperplasia.METHODS:(1)Network pharmacology tools were used to predict the anti-breast-hyperplasia activity of Herba Gueldenstaedtiae(Euphorbia humifusa),as well as its potential targets and signaling pathways.The databases included:TCMSP,OMIM,GeneCards database,UniProt website,Venny2.1.0 website,Metascape,HERB website,and STRING database,all of which are open-access databases.Network pharmacology can predict and screen key information such as the targets corresponding to the active ingredients of traditional Chinese medicine,disease targets,and action pathways through network analysis and computer-system analysis.Therefore,it has been increasingly widely used in the research of traditional Chinese medicine.(2)A breast hyperplasia model was induced in mice by injecting estrogen and progesterone.Mice in the normal blank group were injected intraperitoneally with normal saline every day.Mice in the model group and drugadministration groups were injected intraperitoneally with estradiol benzoate injection at a concentration of 0.5 mg/kg every day for 25 days.From the 26th day,the injection of estradiol benzoate injection was stopped.Mice in the normal blank group were injected intramuscularly with normal saline every day,and mice in the model group and drug-administration groups were injected intramuscularly with progesterone injection at a concentration of 5 mg/kg for 5 days.After the model was established,each group was given drugs respectively.The normal blank group and the model group were gavaged with 0.2 mL/d of normal saline;the positive blank group(Xiaozheng Pill group)was gavaged with an aqueous solution of Xiaozheng Pill at 0.9 mg/g;the low-,medium-and high-dose groups of Compound Herba Gueldenstaedtiae were gavaged with an aqueous solution of the compound medicine at 0.75,1.5,and 3.0 mg/(g·d)respectively;the low-,medium-and high-dose groups of traditional Chinese medicine-bacteria fermentation were gavaged with an aqueous solution of the compound medicine at 0.75,1.5,and 3.0 mg/(g·d)respectively.The administration was continuous for 30 days.RESULTS AND CONCLUSION:(1)The results of network pharmacology research showed that the Compound Herba Gueldenstaedtiae(Euphorbia humifusa)contained 46 active ingredients,which were related to 1213 potential targets.After comparison with 588 known breast-hyperplasia targets,it was speculated that 50 of these targets might be related to the direct effect of the compound on breast hyperplasia.(2)After drug intervention,there was no significant change in the high-dose group of Compound Herba Gueldenstaedtiae compared with the normal blank group.The liver indicators of the other intervention groups all significantly decreased(P<0.05).(3)In terms of kidney and uterine indicators,the medium-dose group of Compound Herba Gueldenstaedtiae decreased significantly compared with the normal blank group(P<0.05).In terms of the uterine index,the model group increased significantly compared with the normal blank group(P<0.01).(4)After 1-month drug treatment,the number of lobules and acini in the breast tissue of the Xiaozheng Pill group,the low,medium,and high-dose group of Compound Herba Gueldenstaedtiae,the low,medium,and highdose groups of traditional Chinese medicine-bacteria fermentation decreased,and the duct openings narrowed.With the increase of drug dose,diffuse hyperplasia of breast tissue was significantly improved.(5)The ELISA results showed that compared with the model group,the estrogen level was lower in the medium-dose group of traditional Chinese medicine-bacteria fermentation after the intervention(P<0.05).In addition,the follicle-stimulating hormone level in the low-dose group of Compound Herba Gueldenstaedtiae was lower than that of the model group(P<0.05).(6)The intervention in the mouse model led to changes in the abundance of short chain fatty acids and intestinal flora in all groups.To conclude,the Compound Herba Gueldenstaedtiae and its probiotic fermentation products significantly improved mammary gland hyperplasia in mice by regulating hormone levels,improving the structure of the gut microbiota,and increasing the content of shortchain fatty acids,providing new ideas and potential sources of drugs for the treatment of breast hyperplasia.展开更多
Objectives:The mechanism by which specific tumor subsets in colorectal cancer(CRC)use alternative metabolic pathways,particularly those modulated by hypoxia and fructose,to alter the tumor microenvironment(TME)remains...Objectives:The mechanism by which specific tumor subsets in colorectal cancer(CRC)use alternative metabolic pathways,particularly those modulated by hypoxia and fructose,to alter the tumor microenvironment(TME)remains unclear.This study aimed to identify these malignant subpopulations and characterize their intercellular signaling networks and spatial organization through an integrative multi-omics approach.Methods:Leveraging bulk datasets,single-cell RNA sequencing,and integrative spatial transcriptomics,we developed a prognostic model based on hypoxia-and fructose metabolism-related genes(HFGs)to delineate tumor cell subpopulations and their intercellular signaling networks.Results:We identified a specific subset of stanniocalcin-2 positive(STC2+)malignant cells spatially enriched within tumor regions and strongly associated with poor prognosis.This subset served as a key signaling hub in the TME,exhibiting increased epithelial–mesenchymal transition activity.STC2+cells engage in two spatially organized ligand–receptor interactions:the growth differentiation factor 15(GDF15)—transforming growth factor beta receptor 2(TGFBR2)pathway targeting endothelial cells and the migration inhibitory factor(MIF)—(cluster of differentiation 74[CD74]+C-X-C motif chemokine receptor 4[CXCR4])pathway targeting macrophages.Conclusion:This study identified a malignant cell state in CRC that is metabolically defined and spatially limited,including liver metastases,and is characterized by elevated STC2 expression and active immune-stromal interactions.Given the interplay between metabolic reprogramming and TME remodeling,STC2+malignant cells are a functionally significant subpopulation and a potential therapeutic target.展开更多
BACKGROUNDCancer stem cells(CSCs)drive recurrence and therapeutic resistance in triplenegativebreast cancer(TNBC),a highly aggressive breast cancer subtype.Intratumoralhypoxia,a common feature of solid tumors,promotes...BACKGROUNDCancer stem cells(CSCs)drive recurrence and therapeutic resistance in triplenegativebreast cancer(TNBC),a highly aggressive breast cancer subtype.Intratumoralhypoxia,a common feature of solid tumors,promotes CSCs enrichment,yet the mechanisms sustaining CSCs stemness remain poorly understood.Hypoxia-induced reactive oxygen species can oxidatively activate ataxia telangiectasiamutated(ATM)kinase(oxidized ATM,p-ATM)independently of DNA breaks.AIMTo investigate the role of hypoxia-induced oxidized ATM in sustaining TNBCCSCstemness through c-Myc-mediated regulation of one-carbon metabolism.METHODSHs578T and MDA-MB-231 TNBC cells were cultured under normoxia or hypoxia.CSC stemness was assessed by mammosphere assays and flow cytometry.ATMactivity was assessed by pharmacological inhibition(Ku60019)and short hairpinRNA knockdown.c-Myc binding to serine hydroxymethyltransferase 2(SHMT2)and methylenetetrahydrofolate dehydrogenase 2(MTHFD2)promoters was analyzedby dual-luciferase reporter assays and chromatin immunoprecipitation.NADPH/NADP+ratios were quantified,and metabolic reprogramming was profiledby liquid chromatography-tandem mass spectrometry metabolomics.RESULTSHypoxia significantly increased mammosphere formation in both Hs578T and MDA-MB-231 cells,as reflected byhigher numbers of mammospheres(Hs578T:214±18;MDA-MB-231:198±16;both P<0.01)and larger meandiameters(P<0.01).Hypoxia also elevated CD44+/CD24-cell proportions and stemness gene expression(P<0.01).Oxidized ATM was activated under hypoxia withoutγH2AX induction,confirming DNA damage independence.ATM inhibition reduced mammosphere growth and suppressed c-Myc,SHMT2,and MTHFD2.Luciferase and chromatin immunoprecipitation assays confirmed direct c-Myc binding to SHMT2 and MTHFD2promoters,while mutation of the binding sites abolished promoter activity.NADPH/NADP+ratios were significantlyelevated under hypoxia but reduced following ATM inhibition(P<0.05).Metabolomics revealed enrichmentof serine/glycine one-carbon pathways.CONCLUSIONHypoxia-induced oxidized ATM maintains TNBC-CSC stemness by promoting c-Myc-dependent upregulation ofMTHFD2 and SHMT2,linking hypoxia,redox signaling,and one-carbon metabolism.These findings suggest apotential therapeutic axis that could be exploited for TNBC treatment.展开更多
Metabolic reprogramming involving branched-chain amino acids(BCAAs)—leucine,isoleucine,and valine—is increasingly recognized as pivotal in cancer progression,metastasis,and immune modulation.This review comprehensiv...Metabolic reprogramming involving branched-chain amino acids(BCAAs)—leucine,isoleucine,and valine—is increasingly recognized as pivotal in cancer progression,metastasis,and immune modulation.This review comprehensively explores how cancer cells rewire BCAA metabolism to enhance proliferation,survival,and therapy resistance.Tumors manipulate BCAA uptake and catabolism via high expression of transporters like L-type amino acid transporter 1(LAT1)and enzymes including branched chain amino acid transaminase 1(BCAT1),branched chain amino acid transaminase 2(BCAT2),branched-chain alpha-keto acid dehydrogenase(BCKDH),and branched chain alpha-keto acid dehydrogenase kinase(BCKDK).These alterations sustain energy production,biosynthesis,redox homeostasis,and oncogenic signaling(especially mammalian target of rapamycin complex 1[mTORC1]).Crucially,tumor-driven BCAA depletion also shapes an immunosuppressive microenvironment,impairing anti-tumor immunity by limiting essential nutrients for T cells and natural killer(NK)cells.Innovative therapeutic strategies targeting BCAA pathways—ranging from selective small-molecule inhibitors(e.g.,LAT1 and BCAT1/2)to dietary modulation—have shown promising preclinical and early clinical efficacy,highlighting their potential to exploit metabolic vulnerabilities in cancer cells while bolstering immune responses.By integrating multi-omics data and precision targeting approaches,this review underscores the translational significance of BCAA metabolic reprogramming,positioning it as a novel frontier in cancer treatment.展开更多
Correction to“Liu QQ,Li YD,Chen JX,Zhang LL,Guan RC,Zhao W,Meng LY.Prognostic value of preoperative fibrinogen,neutrophil-to-lymphocyte ratio,serum alpha-fetoprotein,and prealbumin for patients with primary liver can...Correction to“Liu QQ,Li YD,Chen JX,Zhang LL,Guan RC,Zhao W,Meng LY.Prognostic value of preoperative fibrinogen,neutrophil-to-lymphocyte ratio,serum alpha-fetoprotein,and prealbumin for patients with primary liver cancer undergoing transarterial chemoembolization.World J Gastrointest Oncol 2025;17(6):103198 PMID:40547171 DOI:10.4251/wjgo.v17.i6.103198”.The funding number listed in the"Supported by"section of this article needs to be corrected.展开更多
Neuronal plasticity,the brain's ability to adapt structurally and functionally,is essential for learning,memory,and recovery from injuries.In neurodegenerative diseases such as Alzheimer's disease and Parkinso...Neuronal plasticity,the brain's ability to adapt structurally and functionally,is essential for learning,memory,and recovery from injuries.In neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease,this plasticity is disrupted,leading to cognitive and motor deficits.This review explores the mechanisms of neuronal plasticity and its effect on Alzheimer's disease and Parkinson's disease.Alzheimer's disease features amyloid-beta plaques and tau tangles that impair synaptic function,while Parkinson's disease involves the loss of dopaminergic neurons affecting motor control.Enhancing neuronal plasticity offers therapeutic potential for these diseases.A systematic literature review was conducted using databases such as PubMed,Scopus,and Google Scholar,focusing on studies of neuronal plasticity in Alzheimer's disease and Parkinson's disease.Data synthesis identified key themes such as synaptic mechanisms,neurogenesis,and therapeutic strategies,linking molecular insights to clinical applications.Results highlight that targeting synaptic plasticity mechanisms,such as long-term potentiation and long-term depression,shows promise.Neurotrophic factors,advanced imaging techniques,and molecular tools(e.g.,clustered regularly interspaced short palindromic repeats and optogenetics)are crucial in understanding and enhancing plasticity.Current therapies,including dopamine replacement,deep brain stimulation,and lifestyle interventions,demonstrate the potential to alleviate symptoms and improve outcomes.In conclusion,enhancing neuronal plasticity through targeted therapies holds significant promise for treating neurodegenerative diseases.Future research should integrate multidisciplinary approaches to fully harness the therapeutic potential of neuronal plasticity in Alzheimer's disease and Parkinson's disease.展开更多
Global environmental changes including climate warming,extreme weather events,ambient air pollution,freshwater contamination,and landscape transformation are reshaping the epidemiology of infectious diseases with unpr...Global environmental changes including climate warming,extreme weather events,ambient air pollution,freshwater contamination,and landscape transformation are reshaping the epidemiology of infectious diseases with unprecedented complexity,particularly in the post-COVID-19 era.This review synthesizes evidence from the past decade(2015-2024)to systematically elucidate how key environmental drivers modulate pathogen emergence,transmission dynamics,and clinical outcomes,with a focus on underlying mechanistic pathways.Specifically,we highlight:(1)the temperature-and precipitation-dependent transmission of vector-borne diseases(e.g.,malaria,dengue)via expanded vector habitats and accelerated pathogen incubation;(2)the exacerbation of respiratory infections(including COVID-19)by particulate matter(PM2.5)and nitrogen dioxide(NO2)through impaired mucosal immunity and enhanced inflammatory responses;(3)the persistence of diarrheal diseases in low-and middle-income countries(LMICs)linked to water insecurity and climate-induced infrastructure failure;and(4)zoonotic spillover risks amplified by urbanization and deforestation-driven human-wildlife interface disruption.Integrating the One Health socioecological framework,we further summarize methodological advances from high-resolution genomic surveillance to climate-informed machine learning models that have improved causal inference and predictive accuracy.Our synthesis confirms that environmental factors are not merely contextual but central,modifiable determinants of infectious disease risk,with disproportionate impacts on vulnerable populations.To mitigate future threats,we emphasize the urgency of interdisciplinary collaboration,integrated environmental-health monitoring platforms,and climate-resilient public health policies tailored to post-pandemic challenges.This review provides a timely roadmap for translating environmental epidemiology insights into actionable strategies to strengthen global health resilience.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
Objective： MicroRNA-21 （miR-21） has been shown to be a key regulator of carcinogenesis. There were few reports about the comparison of serum miR-21 with conventional tumor markers. This study aimed to explore the d...Objective： MicroRNA-21 （miR-21） has been shown to be a key regulator of carcinogenesis. There were few reports about the comparison of serum miR-21 with conventional tumor markers. This study aimed to explore the diagnostic value of circulating miR-21 as a tumor marker in breast cancer （BC） and compare it with CA15 3 and carcinoembryonic antigen （CEA）. Methods： Circulating miR-16 and miR-21 were amplified and quantitatively detected by real-time PCR in 89 BC patients and 55 healthy controls. The levels of CA153 and CEA were measured through assays. Then the sensitivity in diagnosis of BC was compared among miR-21, CA153 and CEA. Results： The level of serum miR-21 was significantly higher in BC patients than controls （P〈0.001）. The sensitivity and specificity of miR-21 were 87.6% and 87.3%, respectively, whereas the sensitivities of CEA and CA153 were only 22.47% and 15.73%. Con^lusions： Compared with CEA and CA153, serum miR-21 has a higher sensitivity in diagnosis of BC. Although not correlated with the status of ER, PR and clinical stages, serum miR-21 may be a potential diagnostic indicator for BC, especially for the early stage.展开更多
文摘Clinical laboratory tests are basic elements that support healthcare tasks such as disease detection, diagnosis and monitoring of response to treatments. Current laboratory information systems focus on the patient database, tests and results, with multiple modules available, connecting with the various analytical systems or work areas. However laboratory information systems functioned as “islands of information”, because their design was fundamentally inward-looking and disconnected from other healthcare computer applications. Actually, the Electronic Health Register (EHR) is considered by clinicians as a tool with great potential healthcare benefits. The EHR, in the sense of a unique and complete record of a patient’s healthcare and state of health, regardless of the healthcare level used, is a real attempt to eliminate these “islands of information” and need modules to act as “bridges” with the laboratory information systems. This type of module, which in generic terms may be referred to as a laboratory test request module, has become an essential feature of the EHR. These modules need to use a laboratory coding system as a common language for exchanging information, ensuring that tests and results are unequivocally identified. The development of the laboratory test request module requires the commitment of professionals and political authorities, being necessary time for their design and an adequate pilot phase. The laboratory professionals have to assume a leadership role in the whole process of design, development and implementation of these modules, integrating in the equipment of information technologies of healthcare providers. In our manuscript we review the elements that may prove electronic systems for requesting clinical laboratory test into digital clinical records and the key elements to move from theory to practice.
文摘Objective： Our aim was to investigate clinical and laboratory characteristics of osteoarthritic patients who had amyloid deposition in their knee joints. Methods： Synovial membranes were obtained from 36 patients with knee osteoarthritis （OA） who underwent joint replacement surgery. From this sample, the diagnosis of amyloid was deter- mined by Congo red staining, which demonstrated apple-green birefringence under a polarized microscope. All syn- ovial membranes were immunohistochemically characterized for the expressions of amyloid immunoglobulin light chain （AL-K and AL-,k）, serum amyloid-A （SAA）, amyloidogenic transthyretin （ATTR）, and amyloidogenic 152- microglobulin （A152M）. Matrix-assisted laser desorption-ionizaton/time of flight mass spectrometry （MALDI-TOF MS） was used to analyze transthyretin （TTR） isoforms in the serum of each patient. Results： Nine cases （25%） were found to be amyloid-positive. Immunohistochemicaliy, eight cases （88.9%） had ATTR deposition, and one sample （11.1%） was shown to be AL-K-positive. MALDI-TOF MS identified that the TTR in the serum of the patients was unmodified wild-type TTR, TTR-Cys-S-S-Cys, and TTR-Cys-S-S-CysGly. The age at surgery and the disease duration were sig- nificantly higher in the ATTR-positive group than in the ATTR-negative group. Knee score and function score were significantly lower in the ATTR-positive group than in the ATTR-negative group. Conclusions： Amyloid deposition in synovial membranes of OA patients was found to be ATTR and AL-K. TTR in the serum of the patients was unmodified wild-type TTR together with two isoforms. The high age at surgery, long disease duration, and a deteriorated knee function were associated with ATTR amyloid deposition in the osteoarthritic knee joints.
文摘1.Editor’s note In September 2024,a team of Australian experts in clinical laboratory medicine visited Shanghai Jiao Tong University School of Medicine and Shanghai University of Medicine&Health Sciences,which is a dense 9-day agenda blending a superb scientific and educational communication program.Taking this opportunity,we are honored to have an interview with Prof.Greg,Head of Biochemistry and Endocrinology for Sullivan Nicolaides Pathology(SNP)in Brisbane Australia and President of Australian Association of Clinical Biochemistry and Laboratory Medicine(AACB),to share his experience in his clinical and scientific career and his insights on applied clinical laboratory medicine.
基金Supported by National Natural Science Foundation of China,No.82160762Guangxi Zhuang Autonomous Region Administration of Traditional Chinese Medicine Scientific Research Project,No.GXZYA20230267+2 种基金China Undergraduate Innovation and Entrepreneurship Training Program,No.S202410598060XChina Undergraduate Innovation and Entrepreneurship Training Program,No.X202410598360Future Academic Star of Guangxi Medical University,No.WLXSZX24074.
文摘BACKGROUND In recent years,many studies have shown that proteasome 26S subunit non-ATPase 6(PSMD6)plays an important role in the occurrence and development of malignant tumours.Unfortunately,there are no reports on the evaluation of the potential role of PSMD6 in hepatocellular carcinoma(HCC).AIM To comprehensively evaluate the overexpression pattern and clinical significance of PSMD6 in HCC tissues.METHODS This study integrated PSMD6 mRNA expression profiles from 4672 HCC and 3667 non-HCC tissues,along with immunohistochemical scores from 383 HCC and adjacent tissues,to assess PSMD6 overexpression in HCC.Clustered regularly interspaced short palindromic repeats knockout technology evaluated PSMD6’s essential role in HCC cell growth.Functional enrichment analysis explored the molecular mechanism of PSMD6 abnormalities in HCC.Drug sensitivity analysis and molecular docking analysed the effect of abnormal expression of PSMD6 on the drug sensitivity of HCC cells.RESULTS The results of 41 external and two internal datasets showed that PSMD6 mRNA(SMD=0.26,95%CI:0.09-0.42,P<0.05)and protein(SMD=2.85,95%CI:1.19-4.50,P<0.05)were significantly overexpressed in HCC tissues.The integrated analysis results showed that PSMD6 had a significant overexpression pattern in HCC tissues(SMD=0.40,95%CI:0.15-0.66,P<0.05).PSMD6 knockout inhibited HCC cell growth(chronos scores<-1).Functional enrichment implicated ribosome biogenesis and RNA splicing.Significant enrichment of signalling pathways such as RNA degradation,ribosomes,and chemical carcinogenesis—reactive oxygen species.Drug sensitivity analysis and a molecular docking model showed that high expression of PSMD6 was associated with the tolerance of HCC cells to drugs such as ML323,sepantronium bromide,and GDC0810.Overexpressed PSMD6 effectively distinguished HCC tissues(AUC=0.75,95%CI:0.71-0.79).CONCLUSION This study was the first to discover that PSMD6 was overexpressed in HCC tissues.PSMD6 is essential for the growth of HCC cells and may be involved in ribosome biogenesis and RNA splicing.
基金financially supporting this work through the Large Research Group Project under Grant no.R.G.P.2/509/45
文摘Polyphenols,a diverse group of naturally occurring compounds found in plants,have garnered significant attention for their potential therapeutic properties in treating neurodegenerative diseases(NDs).The Wnt/β-catenin(WβC)signaling pathway,a crucial player in neurogenesis,neuronal survival,and synaptic plasticity,is involved in several cellular mechanisms related to NDs.Dysregulation of this pathway is a hallmark in the development of various NDs.This study explores multiple polyphenolic compounds,such as flavonoids,stilbenes,lignans,and phenolic acids,and their potential to protect the nervous system.It provides a comprehensive analysis of their effects on the WβC pathway,elucidating their modes of action.The study highlights the dual function of polyphenols in regulating and protecting the nervous system,providing reassurance about the research benefits.This review provides a comprehensive analysis of the results obtained from both in vitro studies and in vivo research,shedding light on how these substances influence the various components of the pathway.The focus is mainly on the molecular mechanisms that allow polyphenols to reduce oxidative stress,inflammation,and apoptotic processes,ultimately improving the function and survival of neurons.This study aims to offer a thorough understanding of the potential of polyphenols in targeting the WβC signaling pathway,which could lead to the development of innovative therapeutic options for NDs.
基金Supported by The Funding of Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences,No.CI2021A00810The Escort Project of Guang’anmen Hosital,China Academy of Chinese Medical Science-Backbone Talent Cultivation Project,No.9323013。
文摘Hepatitis B virus(HBV)is a serious global public health concern.Although nucleoside drugs and interferons can significantly inhibit HBV replication,issues such as drug resistance and low clinical cure rates remain.Traditional Chinese medicine(TCM)is widely used in the treatment of chronic hepatitis B(CHB)in China,with anti-inflammatory,anti-fibrotic,and liver-protective effects;however,reports on its antiviral effects are still inconsistent.We retrieved multicenter clinical studies and meta-analyses of TCM treatment for CHB over the past two decades.The results revealed that TCM has a certain anti-HBV effect,and when combined with antiviral drugs,it can significantly improve antiviral efficacy.It was demonstrated that TCM most effectively promotes serum HBV e antigen conversion to negative,followed by the ability to reduce HBV DNA levels,facilitating HBV surface antigen loss,and improving the treatment of CHB.
基金supported by grants from the National High Level Hospital Clinical Research Funding(2022-PUMCH-B-074)Peking Union Medical College Hospital Research Funding for Postdoc(kyfyjj202320).
文摘Objective Blood culture remains the gold standard for diagnosing bloodstream infections.Clinical laboratories must ensure the quality of blood culture processes from receipt to obtaining definitive results.We examined laboratory analytical indicators associated with positive blood culture results.Methods Blood cultures collected from Peking Union Medical College Hospital between January 1,2020,and December 31,2022,were retrospectively analyzed.The mode of transportation(piping logistics delivery vs.staff),source of blood cultures(outpatient/emergency department vs.inpatient department),rotation of personnel,and time of reception(8:00–19:59 vs.20:00–07:59)were compared between blood culture-positive and-negative results.Results Between 2020 and 2022,the total positive rate of blood culture was 8.07%.The positive rate of blood cultures in the outpatient/emergency department was significantly higher than that in the inpatient department(12.46%vs.5.83%;P<0.0001).The time-to-detection of blood cultures was significantly affected by the delivery mode and personnel rotation.The blood culture positive rate of the total pre-analytical time within 1 h was significantly higher than that within 1–2 h or>2 h(P<0.0170).Conclusion Laboratory analytical indicators such as patient source,transportation mode,and personnel rotation significantly impacted the positive detection rate or time of blood culture.
基金Research on the Resistance Mechanism of Carbapenem-Resistant Escherichia coli in Patients with Urosepsis Based on Bacterial Droplet Single-Cell RNA Sequencing(Project No.:MTyk2024-34,2024.01-2026-12)。
文摘Quorum sensing(QS)represents a mechanism through which bacteria engage in communication via chemical signals,a phenomenon prevalent across diverse bacterial species.Recent investigations have elucidated that QS signaling pathways are pivotal in governing bacterial physiological processes,collective behaviors,and the emergence of drug resistance.Escherichia coli(E.coli),a prominent pathogenic bacterium,is increasingly exhibiting severe drug resistance issues,posing substantial hurdles for clinical interventions.Presently,a burgeoning body of research is exploring the connection between QS signaling pathways and the drug resistance mechanisms in E.coli,unveiling the coordinating function of QS within bacterial communities and its influence on antibiotic resistance.Despite some research advancements,the precise mechanisms underlying the QS signaling pathway remain ambiguous,and its potential applications are somewhat constrained.This article endeavors to systematically review the research progress concerning the QS signaling pathway in the context of clinical drug resistance mechanisms in E.coli,delving into its potential clinical applications and future research avenues,with the aim of offering novel insights and strategies to counteract drug resistance.
基金funded by the Science and Technology Plan Project in the Medical and Health Field of Maanshan City(YL-2023-43).
文摘Alzheimer’s disease(AD),as the predominant form of neurodegenerative disorders,exerts a profound impact on the health of the global elderly population.For decades,the elucidation of AD pathogenesis and the development of diagnostic and therapeutic approaches have been the focus of extensive research.Over recent years,a fundamental shift has occurred in AD diagnostics—transitioning from reliance on clinical diagnosis alone to biomarker-supported frameworks.AD biomarker research has transitioned from postmortem histopathology to in vivo detection paradigms,enabling precision diagnosis and intervention.This review synthesizes recent advances in molecular biomarkers across three domains:Fluid biomarkers,Molecular imaging and Innovative detection platforms,and also evaluates the challenges and prospects of the clinical transformation of molecular markers for AD.
基金supported by the National Natural Science Foundation of China(No.81972012).
文摘Recent data suggest that vascular endothelial growth factor receptor inhibitor(VEGFRi)can enhance the anti-tumor activity of the anti-programmed cell death-1(anti-PD-1)antibody in colorectal cancer(CRC)with microsatellite stability(MSS).However,the comparison between this combination and standard third-line VEGFRi treatment is not performed,and reliable biomarkers are still lacking.We retrospectively enrolled MSS CRC patients receiving anti-PD-1 antibody plus VEGFRi(combination group,n=54)or VEGFRi alone(VEGFRi group,n=32),and their efficacy and safety were evaluated.We additionally examined the immune characteristics of the MSS CRC tumor microenvironment(TME)through single-cell and spatial transcriptomic data,and an MSS CRC immune cell-related signature(MCICRS)that can be used to predict the clinical outcomes of MSS CRC patients receiving immunotherapy was developed and validated in our in-house cohort.Compared with VEGFRi alone,the combination of anti-PD-1 antibody and VEGFRi exhibited a prolonged survival benefit(median progression-free survival:4.4 vs.2.0 months,P=0.0024;median overall survival:10.2 vs.5.2 months,P=0.0038)and a similar adverse event incidence.Through single-cell and spatial transcriptomic analysis,we determined ten MSS CRC-enriched immune cell types and their spatial distribution,including naive CD4+T,regulatory CD4+T,CD4+Th17,exhausted CD8+T,cytotoxic CD8+T,proliferated CD8+T,natural killer(NK)cells,plasma,and classical and intermediate monocytes.Based on a systemic meta-analysis and ten machine learning algorithms,we obtained MCICRS,an independent risk factor for the prognosis of MSS CRC patients.Further analyses demonstrated that the low-MCICRS group presented a higher immune cell infiltration and immune-related pathway activation,and hence a significant relation with the superior efficacy of pan-cancer immunotherapy.More importantly,the predictive value of MCICRS in MSS CRC patients receiving immunotherapy was also validated with an in-house cohort.Anti-PD-1 antibody combined with VEGFRi presented an improved clinical benefit in MSS CRC with manageable toxicity.MCICRS could serve as a robust and promising tool to predict clinical outcomes for individual MSS CRC patients receiving immunotherapy.
基金supported by the National Natural Science Foundation of China,Nos.32271389,31900987(both to PY)the Natural Science Foundation of Jiangsu Province,No.BK20230608(to JJ)。
文摘Regulatory T cells,a subset of CD4^(+)T cells,play a critical role in maintaining immune tolerance and tissue homeostasis due to their potent immunosuppressive properties.Recent advances in research have highlighted the important therapeutic potential of Tregs in neurological diseases and tissue repair,emphasizing their multifaceted roles in immune regulation.This review aims to summarize and analyze the mechanisms of action and therapeutic potential of Tregs in relation to neurological diseases and neural regeneration.Beyond their classical immune-regulatory functions,emerging evidence points to non-immune mechanisms of regulatory T cells,particularly their interactions with stem cells and other non-immune cells.These interactions contribute to optimizing the repair microenvironment and promoting tissue repair and nerve regeneration,positioning non-immune pathways as a promising direction for future research.By modulating immune and non-immune cells,including neurons and glia within neural tissues,Tregs have demonstrated remarkable efficacy in enhancing regeneration in the central and peripheral nervous systems.Preclinical studies have revealed that Treg cells interact with neurons,glial cells,and other neural components to mitigate inflammatory damage and support functional recovery.Current mechanistic studies show that Tregs can significantly promote neural repair and functional recovery by regulating inflammatory responses and the local immune microenvironment.However,research on the mechanistic roles of regulatory T cells in other diseases remains limited,highlighting substantial gaps and opportunities for exploration in this field.Laboratory and clinical studies have further advanced the application of regulatory T cells.Technical advances have enabled efficient isolation,ex vivo expansion and functionalization,and adoptive transfer of regulatory T cells,with efficacy validated in animal models.Innovative strategies,including gene editing,cell-free technologies,biomaterial-based recruitment,and in situ delivery have expanded the therapeutic potential of regulatory T cells.Gene editing enables precise functional optimization,while biomaterial and in situ delivery technologies enhance their accumulation and efficacy at target sites.These advancements not only improve the immune-regulatory capacity of regulatory T cells but also significantly enhance their role in tissue repair.By leveraging the pivotal and diverse functions of Tregs in immune modulation and tissue repair,regulatory T cells–based therapies may lead to transformative breakthroughs in the treatment of neurological diseases.
文摘BACKGROUND:Breast hyperplasia is a common benign breast disease mainly caused by endocrine disorders,manifested as abnormal hyperplasia of breast tissue.In recent years,traditional Chinese medicine compounds and probiotics have shown good potential in regulating the endocrine system and improving the intestinal microecology,providing new ideas for the treatment of breast hyperplasia.OBJECTIVE:To explore the effects and mechanisms of traditional Chinese medicine compounds and fermented probiotic compounds on breast hyperplasia in mice,providing new theoretical and experimental bases for the clinical treatment and prevention of breast hyperplasia.METHODS:(1)Network pharmacology tools were used to predict the anti-breast-hyperplasia activity of Herba Gueldenstaedtiae(Euphorbia humifusa),as well as its potential targets and signaling pathways.The databases included:TCMSP,OMIM,GeneCards database,UniProt website,Venny2.1.0 website,Metascape,HERB website,and STRING database,all of which are open-access databases.Network pharmacology can predict and screen key information such as the targets corresponding to the active ingredients of traditional Chinese medicine,disease targets,and action pathways through network analysis and computer-system analysis.Therefore,it has been increasingly widely used in the research of traditional Chinese medicine.(2)A breast hyperplasia model was induced in mice by injecting estrogen and progesterone.Mice in the normal blank group were injected intraperitoneally with normal saline every day.Mice in the model group and drugadministration groups were injected intraperitoneally with estradiol benzoate injection at a concentration of 0.5 mg/kg every day for 25 days.From the 26th day,the injection of estradiol benzoate injection was stopped.Mice in the normal blank group were injected intramuscularly with normal saline every day,and mice in the model group and drug-administration groups were injected intramuscularly with progesterone injection at a concentration of 5 mg/kg for 5 days.After the model was established,each group was given drugs respectively.The normal blank group and the model group were gavaged with 0.2 mL/d of normal saline;the positive blank group(Xiaozheng Pill group)was gavaged with an aqueous solution of Xiaozheng Pill at 0.9 mg/g;the low-,medium-and high-dose groups of Compound Herba Gueldenstaedtiae were gavaged with an aqueous solution of the compound medicine at 0.75,1.5,and 3.0 mg/(g·d)respectively;the low-,medium-and high-dose groups of traditional Chinese medicine-bacteria fermentation were gavaged with an aqueous solution of the compound medicine at 0.75,1.5,and 3.0 mg/(g·d)respectively.The administration was continuous for 30 days.RESULTS AND CONCLUSION:(1)The results of network pharmacology research showed that the Compound Herba Gueldenstaedtiae(Euphorbia humifusa)contained 46 active ingredients,which were related to 1213 potential targets.After comparison with 588 known breast-hyperplasia targets,it was speculated that 50 of these targets might be related to the direct effect of the compound on breast hyperplasia.(2)After drug intervention,there was no significant change in the high-dose group of Compound Herba Gueldenstaedtiae compared with the normal blank group.The liver indicators of the other intervention groups all significantly decreased(P<0.05).(3)In terms of kidney and uterine indicators,the medium-dose group of Compound Herba Gueldenstaedtiae decreased significantly compared with the normal blank group(P<0.05).In terms of the uterine index,the model group increased significantly compared with the normal blank group(P<0.01).(4)After 1-month drug treatment,the number of lobules and acini in the breast tissue of the Xiaozheng Pill group,the low,medium,and high-dose group of Compound Herba Gueldenstaedtiae,the low,medium,and highdose groups of traditional Chinese medicine-bacteria fermentation decreased,and the duct openings narrowed.With the increase of drug dose,diffuse hyperplasia of breast tissue was significantly improved.(5)The ELISA results showed that compared with the model group,the estrogen level was lower in the medium-dose group of traditional Chinese medicine-bacteria fermentation after the intervention(P<0.05).In addition,the follicle-stimulating hormone level in the low-dose group of Compound Herba Gueldenstaedtiae was lower than that of the model group(P<0.05).(6)The intervention in the mouse model led to changes in the abundance of short chain fatty acids and intestinal flora in all groups.To conclude,the Compound Herba Gueldenstaedtiae and its probiotic fermentation products significantly improved mammary gland hyperplasia in mice by regulating hormone levels,improving the structure of the gut microbiota,and increasing the content of shortchain fatty acids,providing new ideas and potential sources of drugs for the treatment of breast hyperplasia.
基金supported by the Joint Project of the Chongqing Science and Technology Commission(2025MSXM040).
文摘Objectives:The mechanism by which specific tumor subsets in colorectal cancer(CRC)use alternative metabolic pathways,particularly those modulated by hypoxia and fructose,to alter the tumor microenvironment(TME)remains unclear.This study aimed to identify these malignant subpopulations and characterize their intercellular signaling networks and spatial organization through an integrative multi-omics approach.Methods:Leveraging bulk datasets,single-cell RNA sequencing,and integrative spatial transcriptomics,we developed a prognostic model based on hypoxia-and fructose metabolism-related genes(HFGs)to delineate tumor cell subpopulations and their intercellular signaling networks.Results:We identified a specific subset of stanniocalcin-2 positive(STC2+)malignant cells spatially enriched within tumor regions and strongly associated with poor prognosis.This subset served as a key signaling hub in the TME,exhibiting increased epithelial–mesenchymal transition activity.STC2+cells engage in two spatially organized ligand–receptor interactions:the growth differentiation factor 15(GDF15)—transforming growth factor beta receptor 2(TGFBR2)pathway targeting endothelial cells and the migration inhibitory factor(MIF)—(cluster of differentiation 74[CD74]+C-X-C motif chemokine receptor 4[CXCR4])pathway targeting macrophages.Conclusion:This study identified a malignant cell state in CRC that is metabolically defined and spatially limited,including liver metastases,and is characterized by elevated STC2 expression and active immune-stromal interactions.Given the interplay between metabolic reprogramming and TME remodeling,STC2+malignant cells are a functionally significant subpopulation and a potential therapeutic target.
文摘BACKGROUNDCancer stem cells(CSCs)drive recurrence and therapeutic resistance in triplenegativebreast cancer(TNBC),a highly aggressive breast cancer subtype.Intratumoralhypoxia,a common feature of solid tumors,promotes CSCs enrichment,yet the mechanisms sustaining CSCs stemness remain poorly understood.Hypoxia-induced reactive oxygen species can oxidatively activate ataxia telangiectasiamutated(ATM)kinase(oxidized ATM,p-ATM)independently of DNA breaks.AIMTo investigate the role of hypoxia-induced oxidized ATM in sustaining TNBCCSCstemness through c-Myc-mediated regulation of one-carbon metabolism.METHODSHs578T and MDA-MB-231 TNBC cells were cultured under normoxia or hypoxia.CSC stemness was assessed by mammosphere assays and flow cytometry.ATMactivity was assessed by pharmacological inhibition(Ku60019)and short hairpinRNA knockdown.c-Myc binding to serine hydroxymethyltransferase 2(SHMT2)and methylenetetrahydrofolate dehydrogenase 2(MTHFD2)promoters was analyzedby dual-luciferase reporter assays and chromatin immunoprecipitation.NADPH/NADP+ratios were quantified,and metabolic reprogramming was profiledby liquid chromatography-tandem mass spectrometry metabolomics.RESULTSHypoxia significantly increased mammosphere formation in both Hs578T and MDA-MB-231 cells,as reflected byhigher numbers of mammospheres(Hs578T:214±18;MDA-MB-231:198±16;both P<0.01)and larger meandiameters(P<0.01).Hypoxia also elevated CD44+/CD24-cell proportions and stemness gene expression(P<0.01).Oxidized ATM was activated under hypoxia withoutγH2AX induction,confirming DNA damage independence.ATM inhibition reduced mammosphere growth and suppressed c-Myc,SHMT2,and MTHFD2.Luciferase and chromatin immunoprecipitation assays confirmed direct c-Myc binding to SHMT2 and MTHFD2promoters,while mutation of the binding sites abolished promoter activity.NADPH/NADP+ratios were significantlyelevated under hypoxia but reduced following ATM inhibition(P<0.05).Metabolomics revealed enrichmentof serine/glycine one-carbon pathways.CONCLUSIONHypoxia-induced oxidized ATM maintains TNBC-CSC stemness by promoting c-Myc-dependent upregulation ofMTHFD2 and SHMT2,linking hypoxia,redox signaling,and one-carbon metabolism.These findings suggest apotential therapeutic axis that could be exploited for TNBC treatment.
基金supported by a grant from the Dalian Science and Technology Innovation Fund Program(No.2024JJ13PT070)United Foundation for Dalian Institute of Chemical Physics,Chinese Academy of Sciences and the Second Hospital of Dalian Medical University(No.DMU-2&DICP UN202410)Dalian Life and Health Field Guidance Program Project(No.2024ZDJH01PT084).
文摘Metabolic reprogramming involving branched-chain amino acids(BCAAs)—leucine,isoleucine,and valine—is increasingly recognized as pivotal in cancer progression,metastasis,and immune modulation.This review comprehensively explores how cancer cells rewire BCAA metabolism to enhance proliferation,survival,and therapy resistance.Tumors manipulate BCAA uptake and catabolism via high expression of transporters like L-type amino acid transporter 1(LAT1)and enzymes including branched chain amino acid transaminase 1(BCAT1),branched chain amino acid transaminase 2(BCAT2),branched-chain alpha-keto acid dehydrogenase(BCKDH),and branched chain alpha-keto acid dehydrogenase kinase(BCKDK).These alterations sustain energy production,biosynthesis,redox homeostasis,and oncogenic signaling(especially mammalian target of rapamycin complex 1[mTORC1]).Crucially,tumor-driven BCAA depletion also shapes an immunosuppressive microenvironment,impairing anti-tumor immunity by limiting essential nutrients for T cells and natural killer(NK)cells.Innovative therapeutic strategies targeting BCAA pathways—ranging from selective small-molecule inhibitors(e.g.,LAT1 and BCAT1/2)to dietary modulation—have shown promising preclinical and early clinical efficacy,highlighting their potential to exploit metabolic vulnerabilities in cancer cells while bolstering immune responses.By integrating multi-omics data and precision targeting approaches,this review underscores the translational significance of BCAA metabolic reprogramming,positioning it as a novel frontier in cancer treatment.
基金Supported by Health Commission of Heilongjiang Province,No.20230404080031.
文摘Correction to“Liu QQ,Li YD,Chen JX,Zhang LL,Guan RC,Zhao W,Meng LY.Prognostic value of preoperative fibrinogen,neutrophil-to-lymphocyte ratio,serum alpha-fetoprotein,and prealbumin for patients with primary liver cancer undergoing transarterial chemoembolization.World J Gastrointest Oncol 2025;17(6):103198 PMID:40547171 DOI:10.4251/wjgo.v17.i6.103198”.The funding number listed in the"Supported by"section of this article needs to be corrected.
基金financially supported by King Abdulaziz University,Deanship of Scientific Research(DSR)。
文摘Neuronal plasticity,the brain's ability to adapt structurally and functionally,is essential for learning,memory,and recovery from injuries.In neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease,this plasticity is disrupted,leading to cognitive and motor deficits.This review explores the mechanisms of neuronal plasticity and its effect on Alzheimer's disease and Parkinson's disease.Alzheimer's disease features amyloid-beta plaques and tau tangles that impair synaptic function,while Parkinson's disease involves the loss of dopaminergic neurons affecting motor control.Enhancing neuronal plasticity offers therapeutic potential for these diseases.A systematic literature review was conducted using databases such as PubMed,Scopus,and Google Scholar,focusing on studies of neuronal plasticity in Alzheimer's disease and Parkinson's disease.Data synthesis identified key themes such as synaptic mechanisms,neurogenesis,and therapeutic strategies,linking molecular insights to clinical applications.Results highlight that targeting synaptic plasticity mechanisms,such as long-term potentiation and long-term depression,shows promise.Neurotrophic factors,advanced imaging techniques,and molecular tools(e.g.,clustered regularly interspaced short palindromic repeats and optogenetics)are crucial in understanding and enhancing plasticity.Current therapies,including dopamine replacement,deep brain stimulation,and lifestyle interventions,demonstrate the potential to alleviate symptoms and improve outcomes.In conclusion,enhancing neuronal plasticity through targeted therapies holds significant promise for treating neurodegenerative diseases.Future research should integrate multidisciplinary approaches to fully harness the therapeutic potential of neuronal plasticity in Alzheimer's disease and Parkinson's disease.
基金the Natural Science Basic Research Program of Shaanxi Province,China[2023-JC-QN-0858]the Free Exploration Program of the Second Affiliated Hospital,School of Medicine,Xi’an Jiaotong University[2020YJ(ZYTS)605]the National Natural Science Foundation of China[81900620].
文摘Global environmental changes including climate warming,extreme weather events,ambient air pollution,freshwater contamination,and landscape transformation are reshaping the epidemiology of infectious diseases with unprecedented complexity,particularly in the post-COVID-19 era.This review synthesizes evidence from the past decade(2015-2024)to systematically elucidate how key environmental drivers modulate pathogen emergence,transmission dynamics,and clinical outcomes,with a focus on underlying mechanistic pathways.Specifically,we highlight:(1)the temperature-and precipitation-dependent transmission of vector-borne diseases(e.g.,malaria,dengue)via expanded vector habitats and accelerated pathogen incubation;(2)the exacerbation of respiratory infections(including COVID-19)by particulate matter(PM2.5)and nitrogen dioxide(NO2)through impaired mucosal immunity and enhanced inflammatory responses;(3)the persistence of diarrheal diseases in low-and middle-income countries(LMICs)linked to water insecurity and climate-induced infrastructure failure;and(4)zoonotic spillover risks amplified by urbanization and deforestation-driven human-wildlife interface disruption.Integrating the One Health socioecological framework,we further summarize methodological advances from high-resolution genomic surveillance to climate-informed machine learning models that have improved causal inference and predictive accuracy.Our synthesis confirms that environmental factors are not merely contextual but central,modifiable determinants of infectious disease risk,with disproportionate impacts on vulnerable populations.To mitigate future threats,we emphasize the urgency of interdisciplinary collaboration,integrated environmental-health monitoring platforms,and climate-resilient public health policies tailored to post-pandemic challenges.This review provides a timely roadmap for translating environmental epidemiology insights into actionable strategies to strengthen global health resilience.
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 National High-Tech Research and Development(863)Program of China(No.2012AA02A504)
文摘Objective： MicroRNA-21 （miR-21） has been shown to be a key regulator of carcinogenesis. There were few reports about the comparison of serum miR-21 with conventional tumor markers. This study aimed to explore the diagnostic value of circulating miR-21 as a tumor marker in breast cancer （BC） and compare it with CA15 3 and carcinoembryonic antigen （CEA）. Methods： Circulating miR-16 and miR-21 were amplified and quantitatively detected by real-time PCR in 89 BC patients and 55 healthy controls. The levels of CA153 and CEA were measured through assays. Then the sensitivity in diagnosis of BC was compared among miR-21, CA153 and CEA. Results： The level of serum miR-21 was significantly higher in BC patients than controls （P〈0.001）. The sensitivity and specificity of miR-21 were 87.6% and 87.3%, respectively, whereas the sensitivities of CEA and CA153 were only 22.47% and 15.73%. Con^lusions： Compared with CEA and CA153, serum miR-21 has a higher sensitivity in diagnosis of BC. Although not correlated with the status of ER, PR and clinical stages, serum miR-21 may be a potential diagnostic indicator for BC, especially for the early stage.
