Epilepsy is a serious neurological disorder;however,the effectiveness of current medications is often suboptimal.Recently,stem cell technology has demonstrated remarkable therapeutic potential in addressing various ne...Epilepsy is a serious neurological disorder;however,the effectiveness of current medications is often suboptimal.Recently,stem cell technology has demonstrated remarkable therapeutic potential in addressing various neurological diseases,igniting interest in its applicability for epilepsy treatment.This comprehensive review summarizes different therapeutic approaches utilizing various types of stem cells.Preclinical experiments have explored the use and potential therapeutic effects of mesenchymal stem cells,including genetically modified variants.Clinical trials involving patientderived mesenchymal stem cells have shown promising results,with reductions in the frequency of epileptic seizures and improvements in neurological,cognitive,and motor functions reported.Another promising therapeutic strategy involves neural stem cells.These cells can be cultured outside the body and directed to differentiate into specific cell types.The transplant of neural stem cells has the potential to replace lost inhibitory interneurons,providing a novel treatment avenue for epilepsy.Embryonic stem cells are characterized by their significant capacity for self-renewal and their ability to differentiate into any type of somatic cell.In epilepsy treatment,embryonic stem cells can serve three primary functions:neuron regeneration,the maintenance of cellular homeostasis,and restorative activity.One notable strategy involves differentiating embryonic stem cells intoγ-aminobutyric acidergic neurons for transplantation into lesion sites.This approach is currently undergoing clinical trials and could be a breakthrough in the treatment of refractory epilepsy.Induced pluripotent stem cells share the same genetic background as the donor,thereby reducing the risk of immune rejection and addressing ethical concerns.However,research on induced pluripotent stem cell therapy remains in the preclinical stage.Despite the promise of stem cell therapies for epilepsy,several limitations must be addressed.Safety concerns persist,including issues such as tumor formation,and the low survival rate of transplanted cells remains a significant challenge.Additionally,the high cost of these treatments may be prohibitive for some patients.In summary,stem cell therapy shows considerable promise in managing epilepsy,but further research is needed to overcome its existing limitations and enhance its clinical applicability.展开更多
Background:Neurological disorders(NDs),including ischemic stroke(IS),Parkinson’s disease(PD),and Alzheimer’s disease(AD),are major contributors to global morbidity and mortality.Boswellia extract has demonstrated ne...Background:Neurological disorders(NDs),including ischemic stroke(IS),Parkinson’s disease(PD),and Alzheimer’s disease(AD),are major contributors to global morbidity and mortality.Boswellia extract has demonstrated neuroprotective properties,yet a comprehensive systematic review assessing its efficacy remains absent.This study aims to evaluate the efficacy of Boswellia extract in treating NDs,with a particular focus on its effects in AD and its potential for long-term neurorestoration,thereby supporting further investigation into Boswellia’s therapeutic role in ND management.Methods:A systematic literature search was performed in PubMed,Web of Science,ScienceDirect,and Google Scholar for English-language studies published up to March 2024.Eighteen studies met the inclusion criteria and were included in the meta-analysis.The study protocol was registered on PROSPERO(CRD42024524386).Eligible studies involved rodent models of IS,PD,or AD with post-operative interventions using Boswellia extract.Data extraction focused on mechanisms of action,dosages,treatment durations,and therapeutic outcomes.Studies were excluded if they involved non-ND models,combined treatments,or had incomplete data.Two researchers independently conducted literature screening and data extraction.Statistical analyses were conducted using Stata(version 17)and RevMan(version 5.4),employing fixed or random-effects models based on heterogeneity assessments.Result s:Boswellia extract significantly improved the mean effect size for NDs(ES=1.28,95%CI(1.05,1.51),P<0.001).Specifically,it reduced cerebral infarct volume in IS(SMD=−2.87,95%CI(−3.42,−2.32))and enhanced behavioral outcomes in AD(SMD=3.26,95%CI(2.07,5.14))and PD(SMD=5.37,95%CI(3.93,6.80)).Subgroup analyses revealed that Boswellia extract exhibited superior efficacy in AD when administered orally and via intra-cerebroventricular injection.Long-term treatment with Boswellia extract suggested potential neurorestorative effects.Additionally,Boswellia extract was more effective than its monomeric constituents,highlighting its promising role in ND treatment.Conclusion:Boswellia extract demonstrates significant neuroprotective effects across various NDs,particularly in AD and in promoting long-term neurorestoration.These findings support the need for further research into Boswellia’s potential as a therapeutic agent in the management of neurological disorders.展开更多
It has been reported that the PI3K/AKT signaling pathway plays a key role in the pathogenesis of ischemic stroke.As a result,the development of drugs targeting the PI3K/AKT signaling pathway has attracted increasing a...It has been reported that the PI3K/AKT signaling pathway plays a key role in the pathogenesis of ischemic stroke.As a result,the development of drugs targeting the PI3K/AKT signaling pathway has attracted increasing attention from researchers.This article reviews the pathological mechanisms and advancements in research related to the signaling pathways in ischemic stroke,with a focus on the PI3K/AKT signaling pathway.The key findings include the following:(1)The complex pathological mechanisms of ischemic stroke can be categorized into five major types:excitatory amino acid toxicity,Ca^(2+)overload,inflammatory response,oxidative stress,and apoptosis.(2)The PI3K/AKT-mediated signaling pathway is closely associated with the occurrence and progression of ischemic stroke,which primarily involves the NF-κB,NRF2,BCL-2,mTOR,and endothelial NOS signaling pathways.(3)Natural products,including flavonoids,quinones,alkaloids,phenylpropanoids,phenols,terpenoids,and iridoids,show great potential as candidate substances for the development of innovative anti-stroke medications.(4)Recently,novel therapeutic techniques,such as electroacupuncture and mesenchymal stem cell therapy,have demonstrated the potential to improve stroke outcomes by activating the PI3K/AKT signaling pathway,providing new possibilities for the treatment and rehabilitation of patients with ischemic stroke.Future investigations should focus on the direct regulatory mechanisms of drugs targeting the PI3K/AKT signaling pathway and their clinical translation to develop innovative treatment strategies for ischemic stroke.展开更多
The sleep-wake cycle stands as an integrative process essential for sustaining optimal brain function and,either directly or indirectly,overall body health,encompassing metabolic and cardiovascular well-being.Given th...The sleep-wake cycle stands as an integrative process essential for sustaining optimal brain function and,either directly or indirectly,overall body health,encompassing metabolic and cardiovascular well-being.Given the heightened metabolic activity of the brain,there exists a considerable demand for nutrients in comparison to other organs.Among these,the branched-chain amino acids,comprising leucine,isoleucine,and valine,display distinctive significance,from their contribution to protein structure to their involvement in overall metabolism,especially in cerebral processes.Among the first amino acids that are released into circulation post-food intake,branched-chain amino acids assume a pivotal role in the regulation of protein synthesis,modulating insulin secretion and the amino acid sensing pathway of target of rapamycin.Branched-chain amino acids are key players in influencing the brain's uptake of monoamine precursors,competing for a shared transporter.Beyond their involvement in protein synthesis,these amino acids contribute to the metabolic cycles ofγ-aminobutyric acid and glutamate,as well as energy metabolism.Notably,they impact GABAergic neurons and the excitation/inhibition balance.The rhythmicity of branchedchain amino acids in plasma concentrations,observed over a 24-hour cycle and conserved in rodent models,is under circadian clock control.The mechanisms underlying those rhythms and the physiological consequences of their disruption are not fully understood.Disturbed sleep,obesity,diabetes,and cardiovascular diseases can elevate branched-chain amino acid concentrations or modify their oscillatory dynamics.The mechanisms driving these effects are currently the focal point of ongoing research efforts,since normalizing branched-chain amino acid levels has the ability to alleviate the severity of these pathologies.In this context,the Drosophila model,though underutilized,holds promise in shedding new light on these mechanisms.Initial findings indicate its potential to introduce novel concepts,particularly in elucidating the intricate connections between the circadian clock,sleep/wake,and metabolism.Consequently,the use and transport of branched-chain amino acids emerge as critical components and orchestrators in the web of interactions across multiple organs throughout the sleep/wake cycle.They could represent one of the so far elusive mechanisms connecting sleep patterns to metabolic and cardiovascular health,paving the way for potential therapeutic interventions.展开更多
A microgravity environment has been shown to cause ocular damage and affect visual acuity,but the underlying mechanisms remain unclear.Therefore,we established an animal model of weightlessness via tail suspension to ...A microgravity environment has been shown to cause ocular damage and affect visual acuity,but the underlying mechanisms remain unclear.Therefore,we established an animal model of weightlessness via tail suspension to examine the pathological changes and molecular mechanisms of retinal damage under microgravity.After 4 weeks of tail suspension,there were no notable alterations in retinal function and morphology,while after 8 weeks of tail suspension,significant reductions in retinal function were observed,and the outer nuclear layer was thinner,with abundant apoptotic cells.To investigate the mechanism underlying the degenerative changes that occurred in the outer nuclear layer of the retina,proteomics was used to analyze differentially expressed proteins in rat retinas after 8 weeks of tail suspension.The results showed that the expression levels of fibroblast growth factor 2(also known as basic fibroblast growth factor)and glial fibrillary acidic protein,which are closely related to Müller cell activation,were significantly upregulated.In addition,Müller cell regeneration and Müller cell gliosis were observed after 4 and 8 weeks,respectively,of simulated weightlessness.These findings indicate that Müller cells play an important regulatory role in retinal outer nuclear layer degeneration during weightlessness.展开更多
BACKGROUND Excessive endoplasmic reticulum(ER)stress in intestinal epithelial cells can lead to damage to the intestinal mucosal barrier,activate the signal transducer and activator of transcription 3(STAT3)/nuclear f...BACKGROUND Excessive endoplasmic reticulum(ER)stress in intestinal epithelial cells can lead to damage to the intestinal mucosal barrier,activate the signal transducer and activator of transcription 3(STAT3)/nuclear factor kappa B(NF-κB)signaling pathway,and exacerbate the inflammatory response,thus participating in the pathogenesis of ulcerative colitis(UC).Mesalazine is a commonly used drug in the clinical treatment of UC.However,further studies are needed to determine whether mesalazine regulates the ER stress of intestinal epithelial cells,downregulates the STAT3/NF-κB pathway to play a role in the treatment of UC.AIM To study the therapeutic effects of mesalazine on spontaneous colitis in interleukin-10(IL-10)-/-mice.METHODS The 24-week-old IL-10-/-mice with spontaneous colitis were divided into the model group and the 5-amino salicylic acid group.Littermates of wild-type mice of the same age group served as the control.There were eight mice in each group,four males and four females.The severity of symptoms of spontaneous colitis in IL-10-/-mice was assessed using disease activity index scores.On day 15,the mice were sacrificed.The colon length was measured,and the histopathological changes and ultrastructure of colonic epithelial cells were detected.The protein expressions of STAT3,p-STAT3,NF-κB,IκB,p-IκB,and glucoseregulated protein 78 were identified using Western blotting.The STAT3 and NF-κB mRNA expressions were identified using real-time polymerase chain reaction.The glucose-regulated protein 78 and C/EBP homologous protein expressions in colon sections were detected using immunofluorescence.RESULTS Mesalazine reduced the symptoms of spontaneous colitis in IL-10 knockout mice and the histopathological damage of colonic tissues,and alleviated the ER stress in epithelial cells of colitis mice.Western blotting and quantitative real-time polymerase chain reaction results showed that the STAT3/NF-κB pathway in the colon tissue of model mice was activated,suggesting that this pathway was involved in the pathogenesis of UC and might become a potential therapeutic target.Mesalazine could down-regulate the protein expressions of p-STAT3,NF-κB and p-IκB,and down-regulate the mRNA expression of STAT3 and NF-κB.CONCLUSION Mesalazine may play a protective role in UC by reducing ER stress by regulating the STAT3/NF-κB signaling pathway.展开更多
Recent advances in research on extracellular vesicles have significantly enhanced their potential as therapeutic agents for neurological diseases.Owing to their therapeutic properties and ability to cross the blood–b...Recent advances in research on extracellular vesicles have significantly enhanced their potential as therapeutic agents for neurological diseases.Owing to their therapeutic properties and ability to cross the blood–brain barrier,extracellular vesicles are recognized as promising drug delivery vehicles for various neurological conditions,including ischemic stroke,traumatic brain injury,neurodegenerative diseases,glioma,and psychosis.However,the clinical application of natural extracellular vesicles is hindered by their limited targeting ability and short clearance from the body.To address these limitations,multiple engineering strategies have been developed to enhance the targeting capabilities of extracellular vesicles,thereby enabling the delivery of therapeutic contents to specific tissues or cells.Therefore,this review aims to highlight the latest advancements in natural and targeting-engineered extracellular vesicles,exploring their applications in treating traumatic brain injury,ischemic stroke,Parkinson's disease,Alzheimer's disease,amyotrophic lateral sclerosis,glioma,and psychosis.Additionally,we summarized recent clinical trials involving extracellular vesicles and discussed the challenges and future prospects of using targeting-engineered extracellular vesicles for drug delivery in treating neurological diseases.This review offers new insights for developing highly targeted therapies in this field.展开更多
Rectal neuroendocrine tumor(rNET)is an indolent malignancy often detected during colonoscopy screening.The incidence of rNET has increased approximately 10-fold over the past 30 years.Most rNETs detected during screen...Rectal neuroendocrine tumor(rNET)is an indolent malignancy often detected during colonoscopy screening.The incidence of rNET has increased approximately 10-fold over the past 30 years.Most rNETs detected during screening endoscopy are small,measuring<10 mm.Current guidelines recommend endoscopic resection for small,well-differentiated rNET using modified endoscopic submucosal resection(mEMR)or endoscopic submucosal dissection.However,the optimal endoscopic treatment method remains uncertain.This paper summarizes the evidence on mEMR with submucosal stretching,mEMR without submucosal stretching,endoscopic submucosal dissection and endoscopic full-thickness resection.Given that rNETs often exhibit submucosal invasion,achieving adequate resection depth is crucial to ensure histological complete resection.mEMR with submucosal stretching appears favorable due to its high rate of histological complete resection,safety and convenience.Risk factors associated with lymph node and distant metastases are also discussed.A treatment algorithm is proposed to facilitate clinical decision-making.展开更多
Autologous bone marrow-derived mesenchymal stem cells(BMSCs)have been shown to promote osteogenesis;however,the effects of allogeneic BMSCs(allo-BMSCs)on bone regeneration remain unclear.Therefore,we explored the bone...Autologous bone marrow-derived mesenchymal stem cells(BMSCs)have been shown to promote osteogenesis;however,the effects of allogeneic BMSCs(allo-BMSCs)on bone regeneration remain unclear.Therefore,we explored the bone regeneration promotion effect of allo-BMSCs in 3D-printed autologous bone particle(ABP)scaffolds.First,we concurrently printed scaffolds with polycaprolactone,ABPs,and allo-BMSCs for appropriate support,providing bioactive factors and seed cells to promote osteogenesis.In vitro studies showed that ABP scaffolds promoted allo-BMSC osteogenic differentiation.In vivo studies revealed that the implantation of scaffolds loaded with ABPs and allo-BMSCs into canine skull defects for nine months promoted osteogenesis.Further experiments suggested that only a small portion of implanted allo-BMSCs survived and differentiated into vascular endothelial cells,chondrocytes,and osteocytes.The implanted allo-BMSCs released stromal cell-derived factor 1 through paracrine signaling to recruit native BMSCs into the defect,promoting bone regeneration.This study contributes to our understanding of allo-BMSCs,providing information relevant to their future application.展开更多
DNA2,a multifunctional enzyme with structure-specific nuclease,5'-to-3'helicase,and DNA-dependent ATPase activities,plays a pivotal role in the cellular response to DNA damage.However,its involvement in cerebr...DNA2,a multifunctional enzyme with structure-specific nuclease,5'-to-3'helicase,and DNA-dependent ATPase activities,plays a pivotal role in the cellular response to DNA damage.However,its involvement in cerebral ischemia/reperfusion(I/R)injury remains to be elucidated.This study investigated the involvement of DNA2 in cerebral I/R injury using conditional knockout(cKO)mice(Nestin-Cre)subjected to middle cerebral artery occlusion(MCAO),an established model of cerebral I/R.Results demonstrated a gradual up-regulation of DNA2 expression,peaking at 72 h post-MCAO.Notably,DNA2 cKO mice exhibited more pronounced brain injury,neurological deficits,and neuronal apoptosis within the penumbra following MCAO.Additionally,DNA2 expression was elevated in an oxygen-glucose deprivation/reoxygenation(OGD/R)cell culture model,and DNA2 knockdown(KD)exacerbated neuronal apoptosis and oxidative stress.Transcriptome analysis of ischemic penumbra tissues via RNA sequencing revealed significant down-regulation of Homer1 in DNA2 cKO mice.Furthermore,in vitro experiments demonstrated that overexpression of Homer1a ameliorated DNA2 KD-induced neuronal apoptosis.Collectively,these findings demonstrate that DNA2 deficiency exacerbates cerebral I/R injury through the down-regulation of Homer1a,highlighting a novel regulatory axis in ischemic neuroprotection.展开更多
Hepatocellular carcinoma(HCC),which is essentially primary liver cancer,is closely related to CD8^(+)T cell immune infiltration and immune suppression.We constructed a CD8^(+)T cells related risk score model to predic...Hepatocellular carcinoma(HCC),which is essentially primary liver cancer,is closely related to CD8^(+)T cell immune infiltration and immune suppression.We constructed a CD8^(+)T cells related risk score model to predict the prognosis of HCC patients and provided therapeutic guidance based on the risk score.Using integrated bulk RNA sequencing(RNA-seq)and single-cell RNA sequencing(scRNA-seq)datasets,we identified stable CD8^(+)T cell signatures.Based on these signatures,a 3-gene risk score model,comprised of KLRB1,RGS 2,and TNFRSF1B was constructed.The risk score model was well validated through an independent external validation cohort.We divided patients into high-risk and low-risk groups according to the risk score and compared the differences in immune microenvironment between these two groups.Compared with low-risk patients,high-risk patients have higher M2-type macrophage content(P<0.0001)and lower CD8^(+)T cells infiltration(P<0.0001).High-risk patients predict worse response to immunotherapy treatment than low-risk patients(P<0.01).Drug sensitivity analysis shows that PI3K-β inhibitor AZD6482 and TGFβRII inhibitor SB505124 may be suitable therapies for high-risk patients,while the IGF-1R inhibitor BMS-754807 or the novel pyrimidine-based anti-tumor metabolic drug Gemcitabine could be potential therapeutic choices for low-risk patients.Moreover,expression of these 3-gene model was verified by immunohistochemistry.In summary,the establishment and validation of a CD8^(+)T cell-derived risk model can more accurately predict the prognosis of HCC patients and guide the construction of personalized treatment plans.展开更多
During the process of organizing our original data,we unfortunately identified two error in the figures within our published article.In Fig.1,the online version incorrectly labels the SNI+NAC group as the sham+NAC gro...During the process of organizing our original data,we unfortunately identified two error in the figures within our published article.In Fig.1,the online version incorrectly labels the SNI+NAC group as the sham+NAC group.We have revised the grouping annotations in Fig.1 and have labeled the DHE staining in the figure to present the experimental design more clearly.展开更多
Qin Medicine,referring to the traditional medicinal system and geo-authentic herbs originating from Shaanxi Province and its surrounding regions,has played a pivotal role in the evolution of Chinese medicine.Rooted in...Qin Medicine,referring to the traditional medicinal system and geo-authentic herbs originating from Shaanxi Province and its surrounding regions,has played a pivotal role in the evolution of Chinese medicine.Rooted in the distinct biogeographical landscape of the“Three Qin”region-comprising northern Shaanxi’s Loess Plateau,the Guanzhong Plain,and the southern Qinling-Bashan Mountains-Qin Medicine embodies the synergistic convergence of endemic biodiversity,empirical therapeutic traditions,and regional cultural identity[1].The distinct biogeographical landscape of the“Three Qin”region profoundly shaped Qin Medicine’s development.The arid Loess Plateau of northern Shaanxi,characterized by drought-tolerant flora,yields herbs such as Huangqi(Astragalus membranaceus)and Dahuang(Rheum palmatum)in harsh environments.In contrast,the biodiverse,humid Qinling-Bashan Mountains fostered a wealth of herbs for clearing heat,resolving dampness,and calming the spirit,such as Huanglian(Coptis chinensis),Fuling(Poria cocos),and Tianma(Gastrodia elata).The fertile Guanzhong Plain supported the cultivation of herbs such as Baishao(Paeonia lactiflora)and Danggui(Angelica sinensis)[2].This article traces the historical trajectory of Qin Medicine,systematically analyzing its formation,development,and modern advancements.展开更多
Hypertrophic cardiomyopathy(HCM)is the most common genetic cardiovascular disease,mostly inherited in an autosomal dominant manner.It is a global heart disease with complex clinical phenotypes and gene expression.The ...Hypertrophic cardiomyopathy(HCM)is the most common genetic cardiovascular disease,mostly inherited in an autosomal dominant manner.It is a global heart disease with complex clinical phenotypes and gene expression.The prevalence rate in the population is 1:500-1:200.This article mainly introduces the diagnostic criteria,pathological manifestations,and genetic basis of HCM,which is the leading cause of sudden death in adolescents and athletes due to exercise,with 60%-70%showing familial clustering.It also discusses the latest progress in the relationship between different genotypes and clinical phenotypes of HCM pa-tients.展开更多
Background:QiShenYiQi(QSYQ)is commonly accepted to treat ischemic stroke(IS)in clinical settings,yet the underlying mechanism of action of QSYQ is largely unknown.Methods:By combining systems pharmacology with experim...Background:QiShenYiQi(QSYQ)is commonly accepted to treat ischemic stroke(IS)in clinical settings,yet the underlying mechanism of action of QSYQ is largely unknown.Methods:By combining systems pharmacology with experimental assessment,we examined the key targets,bioactive components,and mechanisms of QSYQ against IS.Results:Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform predicted a total number of 254 targets that were potentially related to QSYQ,whereas 699 targets associated with IS were gathered from Therapeutic Target Database,Comparative Toxicogenomics Database,Gene Cards,Online Mendelian Inheritance in Man,and National Center for Biotechnology Information databases,and 83 of these targets overlap with QSYQ-related targets.Importantly,through the analysis of Gene Ontology functional annotation,Kyoto Encyclopedia of Genes and Genomes pathway enrichment,and protein-protein interaction network,we identified 20 related signaling pathways along with 4 hub genes.Subsequently,our molecular docking results revealed that QSYQ might interact with PTGS2,PTGS1,SCN5A,and HSP90AB1.We observed dose-dependent beneficial effects of QSYQ in significantly improving neurological function and alleviating histopathological damage in middle cerebral artery occlusion model,while decreasing infarct volume.Notablely,QSYQ markedly downregulates tumor necrosis factor-α,interleukin-6,and interleukin-1 beta.Overall,this study demonstrates the synergetic effects of QSYQ on regulating multi-targets in IS through inhibiting inflammatory processes and neuronal apoptosis,these findings may expand the understanding of QSYQ and provide guidance for its clinical application in treating IS.Conclusion:Current study reveals the protective roles of QSYQ against IS through modulating PTGS2/PTGS1/SCN5A/HSP90AB1 and TNF signaling pathways.展开更多
BACKGROUND Hepatic artery infusion chemotherapy(HAIC)is a widely used local therapeutic approach for intermediate to advanced-stage hepatocellular carcinoma(HCC),exhibiting considerable efficacy.However,the prevalence...BACKGROUND Hepatic artery infusion chemotherapy(HAIC)is a widely used local therapeutic approach for intermediate to advanced-stage hepatocellular carcinoma(HCC),exhibiting considerable efficacy.However,the prevalence of postoperative pain highlights the importance of pain management.Owing to the limitations inherent in existing pain management strategies,this study investigates and assesses the analgesic effectiveness of a multimodal treatment protocol in mitigating pain after HAIC procedures.AIM To provide patients with a more comprehensive and effective pain management strategy.METHODS A total of 100 patients with primary HCC who underwent HAIC were randomly assigned to a control group(n=50)and a multimodal group(n=50).Baseline characteristics and perioperative data were collected.Upon enrollment,patients in the multimodal group received parecoxib(40 mg)30 minutes before HAIC,followed by 48 hours of patient-controlled analgesia with sufentanil.In contrast,the control group underwent standard preoperative preparation(psychological support)and received dezocine(5 mg)intraoperatively,with intravenous flurbiprofen(100 mg)administered every 12 hours for 48 hours postoperatively.RESULTS Compared to the control group,the multimodal analgesia group exhibited significantly lower resting and movement visual analog scale pain scores at postoperative 0,2,4,6,and 12 hours(P<0.05).Furthermore,the multimodal group experienced a reduced incidence of postoperative nausea and vomiting,as well as a lower overall frequency of adverse events,compared to the control group(P<0.05).Patient satisfaction was also significantly higher in the multimodal group than in the control group(P<0.05).CONCLUSION Our study demonstrates that multimodal analgesia is effective in reducing postoperative pain,minimizing adverse reactions,and improving patient satisfaction in HCC patients undergoing HAIC.This approach provides valuable clinical strategies for optimizing pain management in this patient population.展开更多
Objective Hepatocellular carcinoma(HCC),a lethal cancer with high global mortality,may be targeted through ferroptosis,an iron-dependent form of cell death.Despite its potential,the prognostic value of ferroptosis in ...Objective Hepatocellular carcinoma(HCC),a lethal cancer with high global mortality,may be targeted through ferroptosis,an iron-dependent form of cell death.Despite its potential,the prognostic value of ferroptosis in HCC is underexplored.Methods Our study leveraged single-cell and bulk sequencing datasets to identify ferroptosis-related genes and developed a prognostic model via Cox and LASSO regression analyses.Survival and mutation analyses led to the creation of a nomo-gram for predicting patient prognosis.Furthermore,we investigated the role of GRINA,a ferroptosis-related gene,through functional assays,including cell proliferation,colony formation,and metastatic potential analyses.We also assessed mito-chondrial abnormalities,intracellular iron,and ROS levels in GRINA-knockdown cells.Results The developed ferroptosis-related model classified HCC patients into risk groups,revealing notable survival dispari-ties.High-risk patients presented increased immune checkpoint gene expression.The nomogram revealed robust prognostic accuracy.Additionally,we found that GRINA suppression reduced HCC cell proliferation,colony formation,and metastatic potential.Cells with GRINA knockdown presented mitochondrial abnormalities and increased intracellular iron and ROS levels.Conclusions By analysing multiomics sequencing data,we established a connection between ferroptosis-related risk groups and the tumor immune microenvironment.These findings provide novel insights into the role of ferroptosis in HCC and suggest that GRINA inhibition is a potential therapeutic strategy,leading to mitochondrial damage and the induction of fer-roptosis in HCC cell lines.展开更多
BACKGROUND Colorectal cancer(CRC)is a prevalent gastrointestinal malignancy with a typi-cally unfavorable prognosis following the onset of liver metastases.AIM To develop and validate a new clinical prediction model t...BACKGROUND Colorectal cancer(CRC)is a prevalent gastrointestinal malignancy with a typi-cally unfavorable prognosis following the onset of liver metastases.AIM To develop and validate a new clinical prediction model to accurately forecast overall survival(OS)in CRC patients following surgical treatment for liver metastasis.METHODS This study included 1059 patients diagnosed with CRC liver metastases(CRLM)at the Xijing Hospital between 2010 and 2022.The patients were randomly divided into training and validation cohorts at a 7:3 ratio.Key clinical predictors were identified using least absolute shrinkage and selection operator(LASSO)regression combined with a Cox proportional hazards model,leading to the establishment of a prediction model and preparation of a nomogram to enhance its clinical utility.Decision curve analysis(DCA)and Kaplan-Meier survival analysis were employed to evaluate the precision and predictive performance of the model.RESULTS The LASSO-Cox regression analysis revealed multiple pivotal clinical biomarkers significantly linked to CRLM,including gamma-glutamyl transferase levels,blood chloride concentration,activated partial thromboplastin time,N stage,and vascular invasion.The model's receiver operating characteristic curve area under the curve exceeded 0.7 for both the training and validation groups with moderate-to-good predictive accuracy.Furthermore,DCA validated the nomogram's effectiveness for OS prediction.Kaplan-Meier risk stratification demonstrated markedly improved OS among patients classified as low-risk compared to those categorized as high-risk(P<0.001),highlighting its clinical utility for risk assessment and treatment guidance.CONCLUSION The nomogram prediction model constructed in this study has good predictive value and can effectively assess the survival rate of patients with CRLM.展开更多
Background The association of systemic inflammatory response index(SIRI)with prognosis of coronary artery disease(CAD)patients has never been investigated in a large sample with long-term follow-up.This study aimed to...Background The association of systemic inflammatory response index(SIRI)with prognosis of coronary artery disease(CAD)patients has never been investigated in a large sample with long-term follow-up.This study aimed to explore the association of SIRI with all-cause and cause-specific mortality in a nationally representative sample of CAD patients from United States.Methods A total of 3386 participants with CAD from the National Health and Nutrition Examination Survey(NHANES)1999-2018 were included in this study.Cox proportional hazards model,restricted cubic spline(RCS),and receiver operating characteristic curve(ROC)were performed to investigate the association of SIRI with all-cause and cause-specific mortality.Piecewise linear regression and sensitivity analyses were also performed.Results During a median follow-up of 7.7 years,1454 all-cause mortality occurred.After adjusting for confounding factors,higher lnSIRI was significantly associated with higher risk of all-cause(HR=1.16,95%CI:1.09-1.23)and CVD mortality(HR=1.17,95%CI:1.05-1.30)but not cancer mortality(HR=1.17,95%CI:0.99-1.38).The associations of SIRI with all-cause and CVD mortality were detected as J-shaped with threshold values of 1.05935 and 1.122946 for SIRI,respectively.ROC curves showed that lnSIRI had robust predictive effect both in short and long terms.Conclusions SIRI was independently associated with all-cause and CVD mortality,and the dose-response relationship was Jshaped.SIRI might serve as a valid predictor for all-cause and CVD mortality both in the short and long terms.展开更多
Objective:Pancreatic cancer is a global health challenge,yet the Western Pacific Region(WPR)lacks comprehensive analysis of its burden and human resources for health(HRH)distribution.This study aims to assess trends i...Objective:Pancreatic cancer is a global health challenge,yet the Western Pacific Region(WPR)lacks comprehensive analysis of its burden and human resources for health(HRH)distribution.This study aims to assess trends in pancreatic cancer and HRH density in the WPR and investigate their relationship.Methods:Pancreatic cancer data from GBD 2021 and annual HRH density from GBD 2019 were analyzed.Joinpoint regression was used to analyze temporal trends of pancreatic cancer burden and HRH density across 31countries of the WPR.Spearman's rank correlation analysis and generalized linear models were applied to investigate the association between HRH density and pancreatic cancer burden.Results:From 1990 to 2021,pancreatic cancer incidence in the WPR increased by 209%,from 59,766 to184,612 cases,with a 201%rise in mortality and a 152%increase in disability-adjusted life years(DALYs).In 2021,smoking and high fasting plasma glucose were major risk factors,responsible for 16.43%and 23.29%of deaths,respectively.HRH density was positively correlated with the age-standardized incidence(P=0.767),death(P=0.752),and DALYs(P=0.726)rates of pancreatic cancer,and in 2019,most countries'HRH densities were below the Universal Health Coverage targets.Conclusions:Despite improvements in HRH,notable distribution inequalities and shortages persist,limiting capabilities in pancreatic cancer diagnosis and treatment.The positive association between burden and HRH density reflects improved diagnostics from HRH growth but persistent treatment insufficiency due to shortages,and suggests that targeted HRH investment,strengthened primary care,and integration of palliative care are crucial to alleviating the burden.展开更多
基金supported by the National Natural Science Foundation of China,Nos.82471471(to WJ),82471485(to FY)Shaanxi Province Special Support Program for Leading Talents in Scientific and Technological Innovation,No.tzjhjw(to WJ)+1 种基金Shaanxi Key Research and Development Plan Project,No.2023-YBSF-353(to XW)the Joint Fund Project of Innovation Research Institute of Xijing Hospital,No.LHJJ24JH13(to ZS)。
文摘Epilepsy is a serious neurological disorder;however,the effectiveness of current medications is often suboptimal.Recently,stem cell technology has demonstrated remarkable therapeutic potential in addressing various neurological diseases,igniting interest in its applicability for epilepsy treatment.This comprehensive review summarizes different therapeutic approaches utilizing various types of stem cells.Preclinical experiments have explored the use and potential therapeutic effects of mesenchymal stem cells,including genetically modified variants.Clinical trials involving patientderived mesenchymal stem cells have shown promising results,with reductions in the frequency of epileptic seizures and improvements in neurological,cognitive,and motor functions reported.Another promising therapeutic strategy involves neural stem cells.These cells can be cultured outside the body and directed to differentiate into specific cell types.The transplant of neural stem cells has the potential to replace lost inhibitory interneurons,providing a novel treatment avenue for epilepsy.Embryonic stem cells are characterized by their significant capacity for self-renewal and their ability to differentiate into any type of somatic cell.In epilepsy treatment,embryonic stem cells can serve three primary functions:neuron regeneration,the maintenance of cellular homeostasis,and restorative activity.One notable strategy involves differentiating embryonic stem cells intoγ-aminobutyric acidergic neurons for transplantation into lesion sites.This approach is currently undergoing clinical trials and could be a breakthrough in the treatment of refractory epilepsy.Induced pluripotent stem cells share the same genetic background as the donor,thereby reducing the risk of immune rejection and addressing ethical concerns.However,research on induced pluripotent stem cell therapy remains in the preclinical stage.Despite the promise of stem cell therapies for epilepsy,several limitations must be addressed.Safety concerns persist,including issues such as tumor formation,and the low survival rate of transplanted cells remains a significant challenge.Additionally,the high cost of these treatments may be prohibitive for some patients.In summary,stem cell therapy shows considerable promise in managing epilepsy,but further research is needed to overcome its existing limitations and enhance its clinical applicability.
基金supported by the National Natural Science Foundation of China,specifically through grants(No.8227431382304947)Key Research and Development Project of Shaanxi Province(2023GHZD43).Peer re v iew information。
文摘Background:Neurological disorders(NDs),including ischemic stroke(IS),Parkinson’s disease(PD),and Alzheimer’s disease(AD),are major contributors to global morbidity and mortality.Boswellia extract has demonstrated neuroprotective properties,yet a comprehensive systematic review assessing its efficacy remains absent.This study aims to evaluate the efficacy of Boswellia extract in treating NDs,with a particular focus on its effects in AD and its potential for long-term neurorestoration,thereby supporting further investigation into Boswellia’s therapeutic role in ND management.Methods:A systematic literature search was performed in PubMed,Web of Science,ScienceDirect,and Google Scholar for English-language studies published up to March 2024.Eighteen studies met the inclusion criteria and were included in the meta-analysis.The study protocol was registered on PROSPERO(CRD42024524386).Eligible studies involved rodent models of IS,PD,or AD with post-operative interventions using Boswellia extract.Data extraction focused on mechanisms of action,dosages,treatment durations,and therapeutic outcomes.Studies were excluded if they involved non-ND models,combined treatments,or had incomplete data.Two researchers independently conducted literature screening and data extraction.Statistical analyses were conducted using Stata(version 17)and RevMan(version 5.4),employing fixed or random-effects models based on heterogeneity assessments.Result s:Boswellia extract significantly improved the mean effect size for NDs(ES=1.28,95%CI(1.05,1.51),P<0.001).Specifically,it reduced cerebral infarct volume in IS(SMD=−2.87,95%CI(−3.42,−2.32))and enhanced behavioral outcomes in AD(SMD=3.26,95%CI(2.07,5.14))and PD(SMD=5.37,95%CI(3.93,6.80)).Subgroup analyses revealed that Boswellia extract exhibited superior efficacy in AD when administered orally and via intra-cerebroventricular injection.Long-term treatment with Boswellia extract suggested potential neurorestorative effects.Additionally,Boswellia extract was more effective than its monomeric constituents,highlighting its promising role in ND treatment.Conclusion:Boswellia extract demonstrates significant neuroprotective effects across various NDs,particularly in AD and in promoting long-term neurorestoration.These findings support the need for further research into Boswellia’s potential as a therapeutic agent in the management of neurological disorders.
基金supported by the National Natural Science Foundation of China,Nos.82274313(to YD),82204746(to ML),82003982(to TL).
文摘It has been reported that the PI3K/AKT signaling pathway plays a key role in the pathogenesis of ischemic stroke.As a result,the development of drugs targeting the PI3K/AKT signaling pathway has attracted increasing attention from researchers.This article reviews the pathological mechanisms and advancements in research related to the signaling pathways in ischemic stroke,with a focus on the PI3K/AKT signaling pathway.The key findings include the following:(1)The complex pathological mechanisms of ischemic stroke can be categorized into five major types:excitatory amino acid toxicity,Ca^(2+)overload,inflammatory response,oxidative stress,and apoptosis.(2)The PI3K/AKT-mediated signaling pathway is closely associated with the occurrence and progression of ischemic stroke,which primarily involves the NF-κB,NRF2,BCL-2,mTOR,and endothelial NOS signaling pathways.(3)Natural products,including flavonoids,quinones,alkaloids,phenylpropanoids,phenols,terpenoids,and iridoids,show great potential as candidate substances for the development of innovative anti-stroke medications.(4)Recently,novel therapeutic techniques,such as electroacupuncture and mesenchymal stem cell therapy,have demonstrated the potential to improve stroke outcomes by activating the PI3K/AKT signaling pathway,providing new possibilities for the treatment and rehabilitation of patients with ischemic stroke.Future investigations should focus on the direct regulatory mechanisms of drugs targeting the PI3K/AKT signaling pathway and their clinical translation to develop innovative treatment strategies for ischemic stroke.
基金supported by a grant from the French Society of Sleep Research and Medicine(to LS)The China Scholarship Council(to HL)The CNRS,INSERM,Claude Bernard University Lyon1(to LS)。
文摘The sleep-wake cycle stands as an integrative process essential for sustaining optimal brain function and,either directly or indirectly,overall body health,encompassing metabolic and cardiovascular well-being.Given the heightened metabolic activity of the brain,there exists a considerable demand for nutrients in comparison to other organs.Among these,the branched-chain amino acids,comprising leucine,isoleucine,and valine,display distinctive significance,from their contribution to protein structure to their involvement in overall metabolism,especially in cerebral processes.Among the first amino acids that are released into circulation post-food intake,branched-chain amino acids assume a pivotal role in the regulation of protein synthesis,modulating insulin secretion and the amino acid sensing pathway of target of rapamycin.Branched-chain amino acids are key players in influencing the brain's uptake of monoamine precursors,competing for a shared transporter.Beyond their involvement in protein synthesis,these amino acids contribute to the metabolic cycles ofγ-aminobutyric acid and glutamate,as well as energy metabolism.Notably,they impact GABAergic neurons and the excitation/inhibition balance.The rhythmicity of branchedchain amino acids in plasma concentrations,observed over a 24-hour cycle and conserved in rodent models,is under circadian clock control.The mechanisms underlying those rhythms and the physiological consequences of their disruption are not fully understood.Disturbed sleep,obesity,diabetes,and cardiovascular diseases can elevate branched-chain amino acid concentrations or modify their oscillatory dynamics.The mechanisms driving these effects are currently the focal point of ongoing research efforts,since normalizing branched-chain amino acid levels has the ability to alleviate the severity of these pathologies.In this context,the Drosophila model,though underutilized,holds promise in shedding new light on these mechanisms.Initial findings indicate its potential to introduce novel concepts,particularly in elucidating the intricate connections between the circadian clock,sleep/wake,and metabolism.Consequently,the use and transport of branched-chain amino acids emerge as critical components and orchestrators in the web of interactions across multiple organs throughout the sleep/wake cycle.They could represent one of the so far elusive mechanisms connecting sleep patterns to metabolic and cardiovascular health,paving the way for potential therapeutic interventions.
基金supported by the Army Laboratory Animal Foundation of China,No.SYDW[2020]22(to TC)the Shaanxi Provincial Key R&D Plan General Project of China,No.2022SF-236(to YM)the National Natural Science Foundation of China,No.82202070(to TC)。
文摘A microgravity environment has been shown to cause ocular damage and affect visual acuity,but the underlying mechanisms remain unclear.Therefore,we established an animal model of weightlessness via tail suspension to examine the pathological changes and molecular mechanisms of retinal damage under microgravity.After 4 weeks of tail suspension,there were no notable alterations in retinal function and morphology,while after 8 weeks of tail suspension,significant reductions in retinal function were observed,and the outer nuclear layer was thinner,with abundant apoptotic cells.To investigate the mechanism underlying the degenerative changes that occurred in the outer nuclear layer of the retina,proteomics was used to analyze differentially expressed proteins in rat retinas after 8 weeks of tail suspension.The results showed that the expression levels of fibroblast growth factor 2(also known as basic fibroblast growth factor)and glial fibrillary acidic protein,which are closely related to Müller cell activation,were significantly upregulated.In addition,Müller cell regeneration and Müller cell gliosis were observed after 4 and 8 weeks,respectively,of simulated weightlessness.These findings indicate that Müller cells play an important regulatory role in retinal outer nuclear layer degeneration during weightlessness.
基金Supported by Xi’an Science and Technology Plan Project,No.23YXYJ0162Shaanxi Province Traditional Chinese Medicine Research and Innovation Talent Plan Project,No.TZKN-CXRC-16+2 种基金Project of Shaanxi Administration of Traditional Chinese Medicine,No.SZYKJCYC-2025-JC-010Shaanxi Province Key Research and Development Plan Project-Social Development Field,No.S2025-YF-YBSF-0391the Science and Technology Innovation Cultivation Program of Longhua Hospital affiliated to Shanghai University of Chinese Medicine,No.YD202220。
文摘BACKGROUND Excessive endoplasmic reticulum(ER)stress in intestinal epithelial cells can lead to damage to the intestinal mucosal barrier,activate the signal transducer and activator of transcription 3(STAT3)/nuclear factor kappa B(NF-κB)signaling pathway,and exacerbate the inflammatory response,thus participating in the pathogenesis of ulcerative colitis(UC).Mesalazine is a commonly used drug in the clinical treatment of UC.However,further studies are needed to determine whether mesalazine regulates the ER stress of intestinal epithelial cells,downregulates the STAT3/NF-κB pathway to play a role in the treatment of UC.AIM To study the therapeutic effects of mesalazine on spontaneous colitis in interleukin-10(IL-10)-/-mice.METHODS The 24-week-old IL-10-/-mice with spontaneous colitis were divided into the model group and the 5-amino salicylic acid group.Littermates of wild-type mice of the same age group served as the control.There were eight mice in each group,four males and four females.The severity of symptoms of spontaneous colitis in IL-10-/-mice was assessed using disease activity index scores.On day 15,the mice were sacrificed.The colon length was measured,and the histopathological changes and ultrastructure of colonic epithelial cells were detected.The protein expressions of STAT3,p-STAT3,NF-κB,IκB,p-IκB,and glucoseregulated protein 78 were identified using Western blotting.The STAT3 and NF-κB mRNA expressions were identified using real-time polymerase chain reaction.The glucose-regulated protein 78 and C/EBP homologous protein expressions in colon sections were detected using immunofluorescence.RESULTS Mesalazine reduced the symptoms of spontaneous colitis in IL-10 knockout mice and the histopathological damage of colonic tissues,and alleviated the ER stress in epithelial cells of colitis mice.Western blotting and quantitative real-time polymerase chain reaction results showed that the STAT3/NF-κB pathway in the colon tissue of model mice was activated,suggesting that this pathway was involved in the pathogenesis of UC and might become a potential therapeutic target.Mesalazine could down-regulate the protein expressions of p-STAT3,NF-κB and p-IκB,and down-regulate the mRNA expression of STAT3 and NF-κB.CONCLUSION Mesalazine may play a protective role in UC by reducing ER stress by regulating the STAT3/NF-κB signaling pathway.
基金supported by the National Natural Science Foundation of China,Nos.82171363,82371381(to PL),82171458(to XJ)Key Research and Development Project of Shaa nxi Province,Nos.2024SF-YBXM-404(to KY)。
文摘Recent advances in research on extracellular vesicles have significantly enhanced their potential as therapeutic agents for neurological diseases.Owing to their therapeutic properties and ability to cross the blood–brain barrier,extracellular vesicles are recognized as promising drug delivery vehicles for various neurological conditions,including ischemic stroke,traumatic brain injury,neurodegenerative diseases,glioma,and psychosis.However,the clinical application of natural extracellular vesicles is hindered by their limited targeting ability and short clearance from the body.To address these limitations,multiple engineering strategies have been developed to enhance the targeting capabilities of extracellular vesicles,thereby enabling the delivery of therapeutic contents to specific tissues or cells.Therefore,this review aims to highlight the latest advancements in natural and targeting-engineered extracellular vesicles,exploring their applications in treating traumatic brain injury,ischemic stroke,Parkinson's disease,Alzheimer's disease,amyotrophic lateral sclerosis,glioma,and psychosis.Additionally,we summarized recent clinical trials involving extracellular vesicles and discussed the challenges and future prospects of using targeting-engineered extracellular vesicles for drug delivery in treating neurological diseases.This review offers new insights for developing highly targeted therapies in this field.
基金Supported by Nanchang High-Level Scientific and Technological Innovation Talents‘Double Hundred Plan’Project,China,No.2022-312.
文摘Rectal neuroendocrine tumor(rNET)is an indolent malignancy often detected during colonoscopy screening.The incidence of rNET has increased approximately 10-fold over the past 30 years.Most rNETs detected during screening endoscopy are small,measuring<10 mm.Current guidelines recommend endoscopic resection for small,well-differentiated rNET using modified endoscopic submucosal resection(mEMR)or endoscopic submucosal dissection.However,the optimal endoscopic treatment method remains uncertain.This paper summarizes the evidence on mEMR with submucosal stretching,mEMR without submucosal stretching,endoscopic submucosal dissection and endoscopic full-thickness resection.Given that rNETs often exhibit submucosal invasion,achieving adequate resection depth is crucial to ensure histological complete resection.mEMR with submucosal stretching appears favorable due to its high rate of histological complete resection,safety and convenience.Risk factors associated with lymph node and distant metastases are also discussed.A treatment algorithm is proposed to facilitate clinical decision-making.
基金supported by the Science and Technology Development Fund of the Fourth Military Medical University(No.2016XB051)the Military Medical Promotion Plan of the Fourth Military Medical University(No.2016TSA-005)+2 种基金the Science and Technology Program of Guangzhou(No.201604040002)the Youth Development Project of Air Force Medical University(No.21QNPY072)the Xijing Hospital Booster Program(No.XJZT24CZ10).
文摘Autologous bone marrow-derived mesenchymal stem cells(BMSCs)have been shown to promote osteogenesis;however,the effects of allogeneic BMSCs(allo-BMSCs)on bone regeneration remain unclear.Therefore,we explored the bone regeneration promotion effect of allo-BMSCs in 3D-printed autologous bone particle(ABP)scaffolds.First,we concurrently printed scaffolds with polycaprolactone,ABPs,and allo-BMSCs for appropriate support,providing bioactive factors and seed cells to promote osteogenesis.In vitro studies showed that ABP scaffolds promoted allo-BMSC osteogenic differentiation.In vivo studies revealed that the implantation of scaffolds loaded with ABPs and allo-BMSCs into canine skull defects for nine months promoted osteogenesis.Further experiments suggested that only a small portion of implanted allo-BMSCs survived and differentiated into vascular endothelial cells,chondrocytes,and osteocytes.The implanted allo-BMSCs released stromal cell-derived factor 1 through paracrine signaling to recruit native BMSCs into the defect,promoting bone regeneration.This study contributes to our understanding of allo-BMSCs,providing information relevant to their future application.
基金supported by the National Natural Science Foundation of China (32070979)Shenzhen Science and Technology Program (JCYJ20220530161604009,JCYJ20240813150734043)+3 种基金Key Research and Development Program of Shaanxi (2024SF,YBXM,050)Fundamental Research Funds for the Central Universities (31020190QD004,3102019YX01001)Double First-Class Project of China Pharmaceutical University (CPUQNJC22_02)Global Pharmaceutical Development Alliance Plan of China Pharmaceutical University (1302090024-05)。
文摘DNA2,a multifunctional enzyme with structure-specific nuclease,5'-to-3'helicase,and DNA-dependent ATPase activities,plays a pivotal role in the cellular response to DNA damage.However,its involvement in cerebral ischemia/reperfusion(I/R)injury remains to be elucidated.This study investigated the involvement of DNA2 in cerebral I/R injury using conditional knockout(cKO)mice(Nestin-Cre)subjected to middle cerebral artery occlusion(MCAO),an established model of cerebral I/R.Results demonstrated a gradual up-regulation of DNA2 expression,peaking at 72 h post-MCAO.Notably,DNA2 cKO mice exhibited more pronounced brain injury,neurological deficits,and neuronal apoptosis within the penumbra following MCAO.Additionally,DNA2 expression was elevated in an oxygen-glucose deprivation/reoxygenation(OGD/R)cell culture model,and DNA2 knockdown(KD)exacerbated neuronal apoptosis and oxidative stress.Transcriptome analysis of ischemic penumbra tissues via RNA sequencing revealed significant down-regulation of Homer1 in DNA2 cKO mice.Furthermore,in vitro experiments demonstrated that overexpression of Homer1a ameliorated DNA2 KD-induced neuronal apoptosis.Collectively,these findings demonstrate that DNA2 deficiency exacerbates cerebral I/R injury through the down-regulation of Homer1a,highlighting a novel regulatory axis in ischemic neuroprotection.
基金国家自然科学基金项目(No.81902513)山西省应用基础研究计划项目(No.202303021211114 and 202103021224228)山西省高等教育百亿工程“科技引导”专项(No.BYJL047)资助。
文摘Hepatocellular carcinoma(HCC),which is essentially primary liver cancer,is closely related to CD8^(+)T cell immune infiltration and immune suppression.We constructed a CD8^(+)T cells related risk score model to predict the prognosis of HCC patients and provided therapeutic guidance based on the risk score.Using integrated bulk RNA sequencing(RNA-seq)and single-cell RNA sequencing(scRNA-seq)datasets,we identified stable CD8^(+)T cell signatures.Based on these signatures,a 3-gene risk score model,comprised of KLRB1,RGS 2,and TNFRSF1B was constructed.The risk score model was well validated through an independent external validation cohort.We divided patients into high-risk and low-risk groups according to the risk score and compared the differences in immune microenvironment between these two groups.Compared with low-risk patients,high-risk patients have higher M2-type macrophage content(P<0.0001)and lower CD8^(+)T cells infiltration(P<0.0001).High-risk patients predict worse response to immunotherapy treatment than low-risk patients(P<0.01).Drug sensitivity analysis shows that PI3K-β inhibitor AZD6482 and TGFβRII inhibitor SB505124 may be suitable therapies for high-risk patients,while the IGF-1R inhibitor BMS-754807 or the novel pyrimidine-based anti-tumor metabolic drug Gemcitabine could be potential therapeutic choices for low-risk patients.Moreover,expression of these 3-gene model was verified by immunohistochemistry.In summary,the establishment and validation of a CD8^(+)T cell-derived risk model can more accurately predict the prognosis of HCC patients and guide the construction of personalized treatment plans.
文摘During the process of organizing our original data,we unfortunately identified two error in the figures within our published article.In Fig.1,the online version incorrectly labels the SNI+NAC group as the sham+NAC group.We have revised the grouping annotations in Fig.1 and have labeled the DHE staining in the figure to present the experimental design more clearly.
基金supported by the National Natural Science Foundation of China(Grant No.82274313)Project of Shaanxi Administration of Traditional Chinese Medicine(Grant No.2022-SLRH-YQ-010).
文摘Qin Medicine,referring to the traditional medicinal system and geo-authentic herbs originating from Shaanxi Province and its surrounding regions,has played a pivotal role in the evolution of Chinese medicine.Rooted in the distinct biogeographical landscape of the“Three Qin”region-comprising northern Shaanxi’s Loess Plateau,the Guanzhong Plain,and the southern Qinling-Bashan Mountains-Qin Medicine embodies the synergistic convergence of endemic biodiversity,empirical therapeutic traditions,and regional cultural identity[1].The distinct biogeographical landscape of the“Three Qin”region profoundly shaped Qin Medicine’s development.The arid Loess Plateau of northern Shaanxi,characterized by drought-tolerant flora,yields herbs such as Huangqi(Astragalus membranaceus)and Dahuang(Rheum palmatum)in harsh environments.In contrast,the biodiverse,humid Qinling-Bashan Mountains fostered a wealth of herbs for clearing heat,resolving dampness,and calming the spirit,such as Huanglian(Coptis chinensis),Fuling(Poria cocos),and Tianma(Gastrodia elata).The fertile Guanzhong Plain supported the cultivation of herbs such as Baishao(Paeonia lactiflora)and Danggui(Angelica sinensis)[2].This article traces the historical trajectory of Qin Medicine,systematically analyzing its formation,development,and modern advancements.
基金Supported by National Natural Science Foundation of China,No.82230065,No.82371974 and No.82272009.
文摘Hypertrophic cardiomyopathy(HCM)is the most common genetic cardiovascular disease,mostly inherited in an autosomal dominant manner.It is a global heart disease with complex clinical phenotypes and gene expression.The prevalence rate in the population is 1:500-1:200.This article mainly introduces the diagnostic criteria,pathological manifestations,and genetic basis of HCM,which is the leading cause of sudden death in adolescents and athletes due to exercise,with 60%-70%showing familial clustering.It also discusses the latest progress in the relationship between different genotypes and clinical phenotypes of HCM pa-tients.
基金supported by the National Natural Science Foundation of China(No.82274313)Projects of Shaanxi Administration of Traditional Chinese Medicine(2022-SLRH-YQ-010)Key Laboratory of Traditional Chinese Medicine and Pharmacology.
文摘Background:QiShenYiQi(QSYQ)is commonly accepted to treat ischemic stroke(IS)in clinical settings,yet the underlying mechanism of action of QSYQ is largely unknown.Methods:By combining systems pharmacology with experimental assessment,we examined the key targets,bioactive components,and mechanisms of QSYQ against IS.Results:Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform predicted a total number of 254 targets that were potentially related to QSYQ,whereas 699 targets associated with IS were gathered from Therapeutic Target Database,Comparative Toxicogenomics Database,Gene Cards,Online Mendelian Inheritance in Man,and National Center for Biotechnology Information databases,and 83 of these targets overlap with QSYQ-related targets.Importantly,through the analysis of Gene Ontology functional annotation,Kyoto Encyclopedia of Genes and Genomes pathway enrichment,and protein-protein interaction network,we identified 20 related signaling pathways along with 4 hub genes.Subsequently,our molecular docking results revealed that QSYQ might interact with PTGS2,PTGS1,SCN5A,and HSP90AB1.We observed dose-dependent beneficial effects of QSYQ in significantly improving neurological function and alleviating histopathological damage in middle cerebral artery occlusion model,while decreasing infarct volume.Notablely,QSYQ markedly downregulates tumor necrosis factor-α,interleukin-6,and interleukin-1 beta.Overall,this study demonstrates the synergetic effects of QSYQ on regulating multi-targets in IS through inhibiting inflammatory processes and neuronal apoptosis,these findings may expand the understanding of QSYQ and provide guidance for its clinical application in treating IS.Conclusion:Current study reveals the protective roles of QSYQ against IS through modulating PTGS2/PTGS1/SCN5A/HSP90AB1 and TNF signaling pathways.
基金Supported by Beijing Medical Award Foundation of China,No.YXJL-2023-0638-0048.
文摘BACKGROUND Hepatic artery infusion chemotherapy(HAIC)is a widely used local therapeutic approach for intermediate to advanced-stage hepatocellular carcinoma(HCC),exhibiting considerable efficacy.However,the prevalence of postoperative pain highlights the importance of pain management.Owing to the limitations inherent in existing pain management strategies,this study investigates and assesses the analgesic effectiveness of a multimodal treatment protocol in mitigating pain after HAIC procedures.AIM To provide patients with a more comprehensive and effective pain management strategy.METHODS A total of 100 patients with primary HCC who underwent HAIC were randomly assigned to a control group(n=50)and a multimodal group(n=50).Baseline characteristics and perioperative data were collected.Upon enrollment,patients in the multimodal group received parecoxib(40 mg)30 minutes before HAIC,followed by 48 hours of patient-controlled analgesia with sufentanil.In contrast,the control group underwent standard preoperative preparation(psychological support)and received dezocine(5 mg)intraoperatively,with intravenous flurbiprofen(100 mg)administered every 12 hours for 48 hours postoperatively.RESULTS Compared to the control group,the multimodal analgesia group exhibited significantly lower resting and movement visual analog scale pain scores at postoperative 0,2,4,6,and 12 hours(P<0.05).Furthermore,the multimodal group experienced a reduced incidence of postoperative nausea and vomiting,as well as a lower overall frequency of adverse events,compared to the control group(P<0.05).Patient satisfaction was also significantly higher in the multimodal group than in the control group(P<0.05).CONCLUSION Our study demonstrates that multimodal analgesia is effective in reducing postoperative pain,minimizing adverse reactions,and improving patient satisfaction in HCC patients undergoing HAIC.This approach provides valuable clinical strategies for optimizing pain management in this patient population.
基金supported by the National Natural Science Foundation of China(No.82102512).
文摘Objective Hepatocellular carcinoma(HCC),a lethal cancer with high global mortality,may be targeted through ferroptosis,an iron-dependent form of cell death.Despite its potential,the prognostic value of ferroptosis in HCC is underexplored.Methods Our study leveraged single-cell and bulk sequencing datasets to identify ferroptosis-related genes and developed a prognostic model via Cox and LASSO regression analyses.Survival and mutation analyses led to the creation of a nomo-gram for predicting patient prognosis.Furthermore,we investigated the role of GRINA,a ferroptosis-related gene,through functional assays,including cell proliferation,colony formation,and metastatic potential analyses.We also assessed mito-chondrial abnormalities,intracellular iron,and ROS levels in GRINA-knockdown cells.Results The developed ferroptosis-related model classified HCC patients into risk groups,revealing notable survival dispari-ties.High-risk patients presented increased immune checkpoint gene expression.The nomogram revealed robust prognostic accuracy.Additionally,we found that GRINA suppression reduced HCC cell proliferation,colony formation,and metastatic potential.Cells with GRINA knockdown presented mitochondrial abnormalities and increased intracellular iron and ROS levels.Conclusions By analysing multiomics sequencing data,we established a connection between ferroptosis-related risk groups and the tumor immune microenvironment.These findings provide novel insights into the role of ferroptosis in HCC and suggest that GRINA inhibition is a potential therapeutic strategy,leading to mitochondrial damage and the induction of fer-roptosis in HCC cell lines.
文摘BACKGROUND Colorectal cancer(CRC)is a prevalent gastrointestinal malignancy with a typi-cally unfavorable prognosis following the onset of liver metastases.AIM To develop and validate a new clinical prediction model to accurately forecast overall survival(OS)in CRC patients following surgical treatment for liver metastasis.METHODS This study included 1059 patients diagnosed with CRC liver metastases(CRLM)at the Xijing Hospital between 2010 and 2022.The patients were randomly divided into training and validation cohorts at a 7:3 ratio.Key clinical predictors were identified using least absolute shrinkage and selection operator(LASSO)regression combined with a Cox proportional hazards model,leading to the establishment of a prediction model and preparation of a nomogram to enhance its clinical utility.Decision curve analysis(DCA)and Kaplan-Meier survival analysis were employed to evaluate the precision and predictive performance of the model.RESULTS The LASSO-Cox regression analysis revealed multiple pivotal clinical biomarkers significantly linked to CRLM,including gamma-glutamyl transferase levels,blood chloride concentration,activated partial thromboplastin time,N stage,and vascular invasion.The model's receiver operating characteristic curve area under the curve exceeded 0.7 for both the training and validation groups with moderate-to-good predictive accuracy.Furthermore,DCA validated the nomogram's effectiveness for OS prediction.Kaplan-Meier risk stratification demonstrated markedly improved OS among patients classified as low-risk compared to those categorized as high-risk(P<0.001),highlighting its clinical utility for risk assessment and treatment guidance.CONCLUSION The nomogram prediction model constructed in this study has good predictive value and can effectively assess the survival rate of patients with CRLM.
基金National Key Research and Development Program of China(2022YFC2503500 and 2022YFC2503504)。
文摘Background The association of systemic inflammatory response index(SIRI)with prognosis of coronary artery disease(CAD)patients has never been investigated in a large sample with long-term follow-up.This study aimed to explore the association of SIRI with all-cause and cause-specific mortality in a nationally representative sample of CAD patients from United States.Methods A total of 3386 participants with CAD from the National Health and Nutrition Examination Survey(NHANES)1999-2018 were included in this study.Cox proportional hazards model,restricted cubic spline(RCS),and receiver operating characteristic curve(ROC)were performed to investigate the association of SIRI with all-cause and cause-specific mortality.Piecewise linear regression and sensitivity analyses were also performed.Results During a median follow-up of 7.7 years,1454 all-cause mortality occurred.After adjusting for confounding factors,higher lnSIRI was significantly associated with higher risk of all-cause(HR=1.16,95%CI:1.09-1.23)and CVD mortality(HR=1.17,95%CI:1.05-1.30)but not cancer mortality(HR=1.17,95%CI:0.99-1.38).The associations of SIRI with all-cause and CVD mortality were detected as J-shaped with threshold values of 1.05935 and 1.122946 for SIRI,respectively.ROC curves showed that lnSIRI had robust predictive effect both in short and long terms.Conclusions SIRI was independently associated with all-cause and CVD mortality,and the dose-response relationship was Jshaped.SIRI might serve as a valid predictor for all-cause and CVD mortality both in the short and long terms.
基金supported by the Noncommunicable Chronic Diseases-National Science and Technology Major Project(No.2023ZD0510500)National Natural Science Foundation of China(No.82403392)。
文摘Objective:Pancreatic cancer is a global health challenge,yet the Western Pacific Region(WPR)lacks comprehensive analysis of its burden and human resources for health(HRH)distribution.This study aims to assess trends in pancreatic cancer and HRH density in the WPR and investigate their relationship.Methods:Pancreatic cancer data from GBD 2021 and annual HRH density from GBD 2019 were analyzed.Joinpoint regression was used to analyze temporal trends of pancreatic cancer burden and HRH density across 31countries of the WPR.Spearman's rank correlation analysis and generalized linear models were applied to investigate the association between HRH density and pancreatic cancer burden.Results:From 1990 to 2021,pancreatic cancer incidence in the WPR increased by 209%,from 59,766 to184,612 cases,with a 201%rise in mortality and a 152%increase in disability-adjusted life years(DALYs).In 2021,smoking and high fasting plasma glucose were major risk factors,responsible for 16.43%and 23.29%of deaths,respectively.HRH density was positively correlated with the age-standardized incidence(P=0.767),death(P=0.752),and DALYs(P=0.726)rates of pancreatic cancer,and in 2019,most countries'HRH densities were below the Universal Health Coverage targets.Conclusions:Despite improvements in HRH,notable distribution inequalities and shortages persist,limiting capabilities in pancreatic cancer diagnosis and treatment.The positive association between burden and HRH density reflects improved diagnostics from HRH growth but persistent treatment insufficiency due to shortages,and suggests that targeted HRH investment,strengthened primary care,and integration of palliative care are crucial to alleviating the burden.
