Neuronal cell death is a common outcome of multiple pathophysiological processes and a key factor in neurological dysfunction after subarachnoid hemorrhage.Neuronal ferroptosis in particular plays an important role in...Neuronal cell death is a common outcome of multiple pathophysiological processes and a key factor in neurological dysfunction after subarachnoid hemorrhage.Neuronal ferroptosis in particular plays an important role in early brain injury.Bromodomain-containing protein 4,a member of the bromo and extraterminal domain family of proteins,participated in multiple cell death pathways,but the mechanisms by which it regulates ferroptosis remain unclear.The primary aim of this study was to investigate how bromodomain-containing protein 4 affects neuronal ferroptosis following subarachnoid hemorrhage in vivo and in vitro.Our findings revealed that endogenous bromodomain-containing protein 4 co-localized with neurons,and its expression was decreased 48 hours after subarachnoid hemorrhage of the cerebral cortex in vivo.In addition,ferroptosis-related pathways were activated in vivo and in vitro after subarachnoid hemorrhage.Targeted inhibition of bromodomain-containing protein 4 in neurons increased lipid peroxidation and intracellular ferrous iron accumulation via ferritinophagy and ultimately led to neuronal ferroptosis.Using cleavage under targets and tagmentation analysis,we found that bromodomain-containing protein 4 enrichment in the Raf-1 promoter region decreased following oxyhemoglobin stimulation in vitro.Furthermore,treating bromodomain-containing protein 4-knockdown HT-22 cell lines with GW5074,a Raf-1 inhibitor,exacerbated neuronal ferroptosis by suppressing the Raf-1/ERK1/2 signaling pathway.Moreover,targeted inhibition of neuronal bromodomain-containing protein 4 exacerbated early and long-term neurological function deficits after subarachnoid hemorrhage.Our findings suggest that bromodomain-containing protein 4 may have neuroprotective effects after subarachnoid hemorrhage,and that inhibiting ferroptosis could help treat subarachnoid hemorrhage.展开更多
A recently published study(Xin et al.,Prog Biochem Biophys,2026,53(2):431-441.DOI:10.3724/j.pibb.2025.0508)addresses the therapeutic challenges of pancreatic ductal adenocarcinoma(PDAC)by innovatively developing an or...A recently published study(Xin et al.,Prog Biochem Biophys,2026,53(2):431-441.DOI:10.3724/j.pibb.2025.0508)addresses the therapeutic challenges of pancreatic ductal adenocarcinoma(PDAC)by innovatively developing an orally administered nanogene delivery system.Designed to achieve in situ,efficient delivery of chimeric antigen receptor(CAR)genes to tumor sites,this approach offers a novel strategy for CAR-macrophage(CAR-M)based immunotherapy.Its key highlights are as follows.展开更多
Ischemia–reperfusion injury is a common pathophysiological mechanism in retinal degeneration.PANoptosis is a newly defined integral form of regulated cell death that combines the key features of pyroptosis,apoptosis,...Ischemia–reperfusion injury is a common pathophysiological mechanism in retinal degeneration.PANoptosis is a newly defined integral form of regulated cell death that combines the key features of pyroptosis,apoptosis,and necroptosis.Oligomerization of mitochondrial voltage-dependent anion channel 1 is an important pathological event in regulating cell death in retinal ischemia–reperfusion injury.However,its role in PANoptosis remains largely unknown.In this study,we demonstrated that voltage-dependent anion channel 1 oligomerization-mediated mitochondrial dysfunction was associated with PANoptosis in retinal ischemia–reperfusion injury.Inhibition of voltage-dependent anion channel 1 oligomerization suppressed mitochondrial dysfunction and PANoptosis in retinal cells subjected to ischemia–reperfusion injury.Mechanistically,mitochondria-derived reactive oxygen species played a central role in the voltagedependent anion channel 1-mediated regulation of PANoptosis by promoting PANoptosome assembly.Moreover,inhibiting voltage-dependent anion channel 1 oligomerization protected against PANoptosis in the retinas of rats subjected to ischemia–reperfusion injury.Overall,our findings reveal the critical role of voltage-dependent anion channel 1 oligomerization in regulating PANoptosis in retinal ischemia–reperfusion injury,highlighting voltage-dependent anion channel 1 as a promising therapeutic target.展开更多
Phosphodiesterase 4 is a key enzyme involved in the regulation of cell signal transduction,but its role in subarachnoid hemorrhage remains unclear.Neuronal pyroptosis has been reported to be involved in early brain in...Phosphodiesterase 4 is a key enzyme involved in the regulation of cell signal transduction,but its role in subarachnoid hemorrhage remains unclear.Neuronal pyroptosis has been reported to be involved in early brain injury after subarachnoid hemorrhage.This study aimed to investigate whether phosphodiesterase 4 contributes to early brain injury after subarachnoid hemorrhage by mediating neuronal pyroptosis and its related mechanisms.Endovascular perforation of male C57BL/6J mice was performed to model subarachnoid hemorrhage in vivo,and oxyhemoglobin was added to the culture medium of primary neurons to model subarachnoid hemorrhage in vitro.A phosphodiesterase 4-specific inhibitor,etazolate,was intraperitoneally injected 30 minutes after subarachnoid hemorrhage induction.Small interfering RNA(siRNA)was administered intracerebroventricularly 72 hours before subarachnoid hemorrhage to achieve genetic knockdown of phosphodiesterase 4.To investigate the mechanism,a nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3(NLRP3)-specific agonist,nigericin,was intracerebroventricularly injected 60 minutes before subarachnoid hemorrhage.Neuronal phosphodiesterase 4 expression increased after subarachnoid hemorrhage and reached the highest point at 24 hours.Etazolate treatment reduced neurological deficits and brain edema in mice,alleviated neuronal pyroptosis and inflammatory response,and improved neuronal injury.Treatment with phosphodiesterase 4 siRNA had the same neuroprotective effects as etazolate.Mechanistically,phosphodiesterase 4 triggered the nuclear factor kappa-B pathway,and simultaneously caused lysosomal and mitochondrial dysfunction after subarachnoid hemorrhage,which promoted NLRP3 inflammasome activation and induced neuronal pyroptosis.Blocking of phosphodiesterase 4 inhibited the nuclear factor kappa-B pathway,and improved lysosome and mitochondrial function.Activation of NLRP3 reversed the neuroprotective effects of etazolate without affecting phosphodiesterase 4 expression.Together,the results indicate that phosphodiesterase 4 regulates NLRP3-mediated neuronal pyroptosis in early brain injury after subarachnoid hemorrhage.Phosphodiesterase 4 may be a potential therapeutic molecular target for subarachnoid hemorrhage.展开更多
Central venous catheterization(CVC)is a fundamental clinical procedure widely performed across medical specialties.However,the complication rate of subclavian vein catheterization ranges from 6%to 11%.[1]Common compli...Central venous catheterization(CVC)is a fundamental clinical procedure widely performed across medical specialties.However,the complication rate of subclavian vein catheterization ranges from 6%to 11%.[1]Common complications include hemothorax,pneumothorax,air embolism,arterial puncture,and aortic perforation.[2]Herein,we report a rare case of accidental puncture of the aorta during subclavian CVC,which was successfully managed with a ventricular septal defect(VSD)occluder.展开更多
Alzheimer’s disease,a devastating neurodegenerative disorder,is characterized by progressive cognitive decline,primarily due to amyloid-beta protein deposition and tau protein phosphorylation.Effectively reducing the...Alzheimer’s disease,a devastating neurodegenerative disorder,is characterized by progressive cognitive decline,primarily due to amyloid-beta protein deposition and tau protein phosphorylation.Effectively reducing the cytotoxicity of amyloid-beta42 aggregates and tau oligomers may help slow the progression of Alzheimer’s disease.Conventional drugs,such as donepezil,can only alleviate symptoms and are not able to prevent the underlying pathological processes or cognitive decline.Currently,active and passive immunotherapies targeting amyloid-beta and tau have shown some efficacy in mice with asymptomatic Alzheimer’s disease and other transgenic animal models,attracting considerable attention.However,the clinical application of these immunotherapies demonstrated only limited efficacy before the discovery of lecanemab and donanemab.This review first discusses the advancements in the pathogenesis of Alzheimer’s disease and active and passive immunotherapies targeting amyloid-beta and tau proteins.Furthermore,it reviews the advantages and disadvantages of various immunotherapies and considers their future prospects.Although some antibodies have shown promise in patients with mild Alzheimer’s disease,substantial clinical data are still lacking to validate their effectiveness in individuals with moderate Alzheimer’s disease.展开更多
The neuroinflammatory response mediated by microglial activation plays an important role in the secondary nerve injury of traumatic brain injury.The post-transcriptional modification of N^(6)-methyladenosine is ubiqui...The neuroinflammatory response mediated by microglial activation plays an important role in the secondary nerve injury of traumatic brain injury.The post-transcriptional modification of N^(6)-methyladenosine is ubiquitous in the immune response of the central nervous system.The fat mass and obesity-related protein catalyzes the demethylation of N^(6)-methyladenosine modifications on mRNA and is widely expressed in various tissues,participating in the regulation of multiple diseases’biological processes.However,the role of fat mass and obesity in microglial activation and the subsequent neuroinflammatory response after traumatic brain injury is unclear.In this study,we found that the expression of fat mass and obesity was significantly down-regulated in both lipopolysaccharide-treated BV2 cells and a traumatic brain injury mouse model.After fat mass and obesity interference,BV2 cells exhibited a pro-inflammatory phenotype as shown by the increased proportion of CD11b^(+)/CD86^(+)cells and the secretion of pro-inflammatory cytokines.Fat mass and obesity-mediated N^(6)-methyladenosine demethylation accelerated the degradation of ADAM17 mRNA,while silencing of fat mass and obesity enhanced the stability of ADAM17 mRNA.Therefore,down-regulation of fat mass and obesity expression leads to the abnormally high expression of ADAM17 in microglia.These results indicate that the activation of microglia and neuroinflammatory response regulated by fat mass and obesity-related N^(6)-methyladenosine modification plays an important role in the pro-inflammatory process of secondary injury following traumatic brain injury.展开更多
Objectives Dysregulated osteoclast function contributes to skeletal diseases.However,the specific ubiquitination regulators of the osteoclastogenesis repressor MafB,particularly at the post-translational level,remain ...Objectives Dysregulated osteoclast function contributes to skeletal diseases.However,the specific ubiquitination regulators of the osteoclastogenesis repressor MafB,particularly at the post-translational level,remain undefined.This study aims to identify ubiquitin-specific proteases(USPs)that deubiquitinate MafB and enhance its stability.Methods We constructed a MafB-conjugated luciferase and overexpressed 40 individual USPs,measuring changes in luciferase activity.The identified USP was overexpressed in human CD14^(+) peripheral blood mononuclear cells(PBMCs)to evaluate its effect.Osteoclast differentiation was assessed through osteoclast marker Integrin alpha-V(CD51)staining and Western blot analysis.Co-immunoprecipitation(co-IP)was performed to assess the interplay.The influence on MafB ubiquitination and degradation was evaluated via immunoprecipitation and Western blot.Finally,MafB was knocked down in the USP-overexpressing PBMCs to analyze its effect on osteoclast differentiation.Results Overexpression of ubiquitin-specific protease 29(USP29)significantly increased MafB expression by approximately 75%(p<0.0001).Elevated USP29 levels strongly inhibited osteoclastic differentiation in CD14^(+) PBMCs(p<0.0001).USP29 was found to interact with MafB,markedly reducing its ubiquitination and subsequent degradation in PBMCs(p<0.001).Knocking down MafB in USP29-overexpressing PBMCs alleviated the inhibitory effect of USP29 on osteoclastogenesis.Conclusion USP29 acts as a potent stabilizer of MafB,inhibiting osteoclastogenesis in human CD14^(+) PBMCs,at least in part,by enhancing MafB stability.These findings expand our understanding of USP29’s role and the post-translational regulation of MafB.Furthermore,USP29 serves as a vital factor that controls osteoclast differentiation,and its regulatory function is at least partially mediated by deubiquitinating and stabilizing MafB.展开更多
Diabetic retinopathy(DR),a common complication of diabetes,is characterized by retinal angiogenesis and inflammation.The role of hepatoma-derived growth factor(HDGF)in mediating inflammation during DR remains unclear....Diabetic retinopathy(DR),a common complication of diabetes,is characterized by retinal angiogenesis and inflammation.The role of hepatoma-derived growth factor(HDGF)in mediating inflammation during DR remains unclear.We measured HDGF levels in the aqueous humor and found that HDGF was increased in DR but decreased after anti-angiogenesis treatment.Using public single-cell RNA sequencing datasets,we found that elevated HDGF in DR was mainly produced by Müller cells and targeted microglia.Additionally,integrin beta 2(Itgb2),a target gene of HDGF that induces microglial activation,was significantly upregulated in DR.To verify these results,we performed enzyme-linked immunosorbent assays,quantitative reverse transcription-PCR,Western blotting,and fluorescence immunostaining in cultured Müller and microglial cells treated with HDGF or anti-HDGF,as well as in DR mice receiving intravitreal injections of HDGF or its antibody.Exogenous HDGF further promoted microglial activation,migration,and secretion of pro-inflammatory cytokines,while neutralization of HDGF suppressed these effects caused by high glucose.Furthermore,the HDGF receptor nucleolin was overexpressed in microglia under high glucose stimulation.Therefore,blocking HDGF from Müller cells in DR reduced the excessive inflammatory response in microglia,highlighting HDGF as a potential therapeutic target.展开更多
Based on the Bismuth-Corlette classification of hilar cholangiocarcinoma,the patients with types I,II,and III can undergo radical resection in the absence of extensive intrahepatic metastasis and vascular invasion[1]....Based on the Bismuth-Corlette classification of hilar cholangiocarcinoma,the patients with types I,II,and III can undergo radical resection in the absence of extensive intrahepatic metastasis and vascular invasion[1].Depending on the scope of tumor invasion in bile duct,a combined resection of parts of the liver,hepatic ducts,common bile ducts,regional lymph nodes,and even parts of the duodenum and pancreas is necessary,along with biliary and gastrointestinal reconstructions[2].The surgical plan is complex,involving a large resection area and significant trauma.In recent years,laparoscopic or robot assisted radical resection of hilar cholangiocarcinoma has been applied clinically[3,4].With the advanced laparoscopic equipment,many patients undergo hepatopancreatoduodenectomy successfully[5].The limitations of traditional laparoscopic techniques restrict their wide application in clinical practice.However,the Da Vinci robot has been widely applied due to its clear field of vision and flexible manipulation.However,its utilization in hepato-pancreatoduodenectomy for hilar cholangiocarcinoma is still relatively rare.Here,we report a case with hilar cholangiocarcinoma at clinical stage IIIb who underwent robot-assisted hepato-pancreatoduodenectomy.展开更多
Background:Sarcomatoid carcinoma of the ureter(SCU)is a highly aggressive and relatively uncommon malignant tumor of the urinary tract.Its frequency is quite low,and its prognosis is very bad when compared to other ca...Background:Sarcomatoid carcinoma of the ureter(SCU)is a highly aggressive and relatively uncommon malignant tumor of the urinary tract.Its frequency is quite low,and its prognosis is very bad when compared to other cancers of the urinary system.SCU clinical reports are still hard to come by.MRI and PEI/CT imaging of ureteral sarcomatoid cancer is presented in this case to promote diagnostic awareness and comprehension of the imaging characteristics of this uncommon illness.Method:The patient had ureteral sarcomatoid cancer,which was verified by pathological investigation after ureteroscopic biopsy.The patient’s clinical information,imaging results,surgical outcomes,and pathological findings were gathered.A retrospective study was carried out in combinationwith pertinent national and international literature.Results:An 84-year-old female patient was admitted for“left flank discomfort lasting over one month.”MRI revealed an irregular soft tissue mass in the middle-lower segment of the left ureter.T2-weighted imaging showed an unevenly slightly hyperintense signal.Diffusion-weighted imaging demonstrated restricted diffusion.Contrastenhanced imaging exhibited heterogeneous enhancement.PET/CT demonstrated significantly increased fluorodeoxyglucose metabolism in the mass with secondary left upper urinary tract obstruction.Concurrent findings included a solitary metastatic lesion in hepatic segment S6 and multiple lymph node metastases along the left common iliac and external iliac arteries.Preoperative diagnosis suggested a malignant tumor of the ureter.The patient underwent left nephroureteroscopy with biopsy,and the postoperative pathological diagnosis was ureteral sarcomatoid carcinoma.Conclusion:Ureteral sarcomatoid carcinoma is a rare,highly malignant,and aggressive tumor with nonspecific imaging features,typically presenting as an invasively growing mass.Diagnosis relies on postoperative pathology and immunohistochemical examination.MRI and PET/CT scans are valuable for preoperative localization and characterization,tumor staging,treatment planning,and postoperative follow-up.The prognosis is extremely negative.The main treatment option is radical surgery,although constant monitoring is necessary since early recurrence and metastases are frequent after surgery.展开更多
Organophosphate pesticide poisoning is an acute form of poisoning primarily found in underdeveloped regions.Its main clinical manifestations include muscarinic symptoms,nicotinic symptoms,and central nervous system di...Organophosphate pesticide poisoning is an acute form of poisoning primarily found in underdeveloped regions.Its main clinical manifestations include muscarinic symptoms,nicotinic symptoms,and central nervous system disturbances.This report presents a case of a middleaged female who developed extremely rare symptoms of optic nerve damage after ingesting a large amount of an organophosphate pesticide.展开更多
Micro/nanoplastics(M/NPs)have become pervasive environmental pollutants,posing significant risks to human health through various exposure routes,including ingestion,inhalation,and direct contact.This review systematic...Micro/nanoplastics(M/NPs)have become pervasive environmental pollutants,posing significant risks to human health through various exposure routes,including ingestion,inhalation,and direct contact.This review systematically examined the potential impacts of M/NPs on ocular health,focusing on exposure pathways,toxicological mechanisms,and resultant damage to the eye.Ocular exposure to M/NPs can occur via direct contact and oral ingestion,with the latter potentially leading to the penetration of particles through ocular biological barriers into ocular tissues.The review highlighted that M/NPs can induce adverse effects on the ocular surface,elevate intraocular pressure,and cause abnormalities in the vitreous and retina.Mechanistically,oxidative stress and inflammation are central to M/NP-induced ocular damage,with smaller particles often exhibiting greater toxicity.Overall,this review underscored the potential risks of M/NPs to ocular health and emphasized the need for further research to elucidate exposure mechanisms,toxicological pathways,and mitigation strategies.展开更多
Oxidative stress significantly contributes to secondary damage after spinal cord injury.Despite its importance,research on oxidative stress in spinal cord injury remains limited.Investigating the expression and regula...Oxidative stress significantly contributes to secondary damage after spinal cord injury.Despite its importance,research on oxidative stress in spinal cord injury remains limited.Investigating the expression and regulation of oxidative stress-related genes could enhance the diagnosis and treatment of spinal cord injury.In this study,we analyzed the sequencing data of human blood samples and injured mouse spinal cord tissue that were sourced from GEO databases and identified diagnostic biomarkers associated with the severity of spinal cord injury.We also explored the expression patterns of oxidative stress-related genes,potential regulatory mechanisms,and therapeutic drugs.To validate our findings,we performed immunofluorescence and quantitative polymerase chain reaction to assess gene expression in the injured spinal cord.Our results revealed biomarkers associated with oxidative stress and immune responses across different levels of spinal cord injury in humans.We identified differentially expressed oxidative stress-related genes and key hub genes in injured mouse spinal cord tissue and revealed their temporal expression patterns at both the tissue and single-cell levels.We also clarified the signaling pathways associated with oxidative stress and identified ligand-receptor pairs among various cell types at different time points after injury.Furthermore,we discovered microRNAs,long non-coding RNAs,and transcription factors that regulate these hub genes and revealed their roles in modulating gene expression at various stages after spinal cord injury.We also identified drugs targeting these hub genes.The findings from this study not only aid in identifying diagnostic biomarkers that reflect the severity of spinal cord injury,but also provide insights into the expression dynamics of oxidative stress-related genes.In addition,the study reveals potential regulatory mechanisms and identifies potential drugs to treat patients with spinal cord injury.展开更多
Diabetes mellitus is an escalating global health issue,with 463 million adults affected in 2019.Without intervention,this number is projected to increase to 578 million by 2030 and 700 million by 2045[1].Diabetic woun...Diabetes mellitus is an escalating global health issue,with 463 million adults affected in 2019.Without intervention,this number is projected to increase to 578 million by 2030 and 700 million by 2045[1].Diabetic wound,a significant complication,is characterized by delayed healing,high disability rates,and elevated mortality[2].The challenges of wound healing in diabetic patients,compounded by their high morbidity and mortality rates,have drawn growing attention in biomedical research.展开更多
Despite effective antiretroviral therapy(ART),many individuals with human immunodeficiency virus(HIV)/acquired immune deficiency syndrome(AIDS)achieve viral suppression but fail to fully restore cluster of differentia...Despite effective antiretroviral therapy(ART),many individuals with human immunodeficiency virus(HIV)/acquired immune deficiency syndrome(AIDS)achieve viral suppression but fail to fully restore cluster of differentiation 4(CD4)^(+)T lymphocyte(CD4 cell)counts—a condition known as immunological non-response(INRs).INRs are associated with elevated health risks,including increased susceptibility to AIDS-related and non-AIDS-related complications.The pathogenesis of INRs remains incompletely understood,and no established therapeutic interventions exist,posing a major challenge in contemporary HIV/AIDS management.Emerging evidence indicates that INRs exhibit significant alterations in gut microbiota composition.Dysbiosis of the gut microbiota may contribute to persistent immune activation,cytokine imbalance,and cellular pyroptosis,all of which could impair immune reconstitution in people living with HIV/AIDS.Traditional Chinese medicine(TCM)has demonstrated potential immunomodulatory effects and is increasingly utilized in the management of INRs.Targeting the gut microbiota and elucidating the mechanisms by which TCM modulates this microbial ecosystem may offer new avenues for preventing and treating INRs.This review explores the interplay between gut microbiota and TCM,examines the association between gut dysbiosis and INRs,discusses the mechanistic pathways through which microbiota imbalance contributes to INRs development,and highlights how TCM interventions regulate gut microbiota to promote immune recovery.By focusing on the gut microbiota as a therapeutic interface,this article provides novel insights into TCM-based strategies for improving outcomes in INRs and supports the development of innovative treatment approaches.展开更多
BACKGROUND Perimenopausal women are prone to anxiety and depression due to fluctuating hormone levels,which significantly impair their quality of life.The current treatments have certain limitations.In traditional Chi...BACKGROUND Perimenopausal women are prone to anxiety and depression due to fluctuating hormone levels,which significantly impair their quality of life.The current treatments have certain limitations.In traditional Chinese medicine,liver-soothing formulas are commonly prescribed for mood-related disorders,but their overall efficacy in perimenopausal anxiety and depression remains uncertain and requires verification through meta-analysis.AIM To provide evidence-based support for clinical decision-making and research,a meta-analysis was conducted to evaluate the effectiveness of liver-soothing formulas in treating perimenopausal anxiety and depression.METHODS Relevant studies published up to April 2025 were retrieved from ClinicalTrials.gov,PubMed,Web of Science,EMBASE,and the Cochrane Library.Eligible studies were screened according to predefined inclusion and exclusion criteria.Data were extracted and analyzed using the Stata 12.0 software.RESULTS After searching and screening,12 articles involving 1798 patients(922 in the treatment group and 876 in the control group)were included in the analysis.Meta-analysis showed that the standardized scores for anxiety[standardized mean difference(SMD)=-0.71,95%confidence interval(95%CI):-1.06 to-0.36]and depression(SMD=-0.67,95%CI:-1.06 to-0.27)of the treatment group were lower than those of the control group.Subgroup analysis results revealed that for anxiety,liver-soothing formulas used alone(SMD=-0.34,95%CI:-0.50 to-0.18)or in combination(SMD=-0.88,95%CI:-1.43 to-0.34)both significantly reduced scores compared with the control group.For depression,monotherapy of liversoothing formulas showed no significant statistical difference between the treatment and control groups(SMD=-0.47,95%CI:-1.11 to 0.17),whereas combination therapy produced significantly lower standardized scale scores in the treatment group than in the control group,with a statistically significant difference(SMD=-0.83,95%CI:-1.39 to-0.28).Regarding Greene scores,no statistically significant difference was observed with monotherapy(SMD=0.87,95%CI:-0.32 to 2.06),whereas combination therapy had significantly lower Greene scores(SMD=-0.24,95%CI:-0.44 to-0.04).No statistically significant difference was found between the groups in the occurrence of adverse reactions(odds ratio=0.90,95%CI:0.57-1.43).However,liver-soothing formulas did not affect estrogen levels in perimenopausal women.CONCLUSION Compared with placebo,conventional Western medicine,or other interventions,the monotherapy of liver-soothing formulas demonstrates superior efficacy in treating perimenopausal anxiety.When used as an adjuvant,they exert a synergistic effect in alleviating negative emotions and improving overall perimenopausal symptoms.展开更多
Mesenchymal stromal cell transplantation is an effective and promising approach for treating various systemic and diffuse diseases.However,the biological characteristics of transplanted mesenchymal stromal cells in hu...Mesenchymal stromal cell transplantation is an effective and promising approach for treating various systemic and diffuse diseases.However,the biological characteristics of transplanted mesenchymal stromal cells in humans remain unclear,including cell viability,distribution,migration,and fate.Conventional cell tracing methods cannot be used in the clinic.The use of superparamagnetic iron oxide nanoparticles as contrast agents allows for the observation of transplanted cells using magnetic resonance imaging.In 2016,the National Medical Products Administration of China approved a new superparamagnetic iron oxide nanoparticle,Ruicun,for use as a contrast agent in clinical trials.In the present study,an acute hemi-transection spinal cord injury model was established in beagle dogs.The injury was then treated by transplantation of Ruicun-labeled mesenchymal stromal cells.The results indicated that Ruicunlabeled mesenchymal stromal cells repaired damaged spinal cord fibers and partially restored neurological function in animals with acute spinal cord injury.T2*-weighted imaging revealed low signal areas on both sides of the injured spinal cord.The results of quantitative susceptibility mapping with ultrashort echo time sequences indicated that Ruicun-labeled mesenchymal stromal cells persisted stably within the injured spinal cord for over 4 weeks.These findings suggest that magnetic resonance imaging has the potential to effectively track the migration of Ruicun-labeled mesenchymal stromal cells and assess their ability to repair spinal cord injury.展开更多
Objective:The contribution of long non-coding RNAs(lncRNAs)associated with protein palmitoylation to the progression of hepatocellular carcinoma(HCC)remains largely unclear.This study sought to establish a prognostic ...Objective:The contribution of long non-coding RNAs(lncRNAs)associated with protein palmitoylation to the progression of hepatocellular carcinoma(HCC)remains largely unclear.This study sought to establish a prognostic signature based on palmitoylation-related lncRNAs and explore their functional implications in HCC.Methods:RNA sequencing and clinical data for HCC and normal tissues were sourced from the Cancer Genome Atlas(TCGA).Pearson correlation analysis was used to identify lncRNAs that were co-expressed with palmitoylation-related genes.Univariate Cox regression was applied to select lncRNAs with prognostic value,followed by the construction of a predictive model using the least absolute shrinkage and selection operator(LASSO)regression.A focused analysis was performed on one key lncRNA,AC009403.1.Expression levels of the final nine lncRNAs included in the model were further validated by reverse transcription quantitative polymerase chain reaction(RT-qPCR).Results:A prognostic model for HCC was developed using nine palmitoylation-associated lncRNAs:AC009403.1,AC010789.1,AC026402.2,AC107021.2,AC135050.6,AL353572.4,MKLN1-AS,PRRT3-AS1,and ZNF582-AS1.This model effectively stratified patients into high-and low-risk groups exhibiting significantly different overall survival(OS)and progression-free survival(PFS),with the low-risk group showing more favorable outcomes.The high-risk group was associated with an immunosuppressive microenvironment,higher tumor mutation burden(TMB),and increased sensitivity to certain chemotherapeutic drugs(e.g.,Sorafenib).Finally,RT-qPCR validation revealed that all nine lncRNAs were significantly upregulated in HCC tissues.Conclusion:The nine-lncRNA signature exhibits robust predictive power for HCC prognosis and provides novel insights into the mechanisms of lncRNA-regulated palmitoylation in HCC development.展开更多
Background:Aberrant expression of transcription factors(TFs)is a key mechanism mediating tumor immune escape and therapeutic resistance.The involvement of E26 transformation-specific(ETS)family of TFs in immune regula...Background:Aberrant expression of transcription factors(TFs)is a key mechanism mediating tumor immune escape and therapeutic resistance.The involvement of E26 transformation-specific(ETS)family of TFs in immune regulation is not fully understood.The study aimed to elucidate the function of E-twenty-six variant 4(ETV4)in tumor immune evasion and its potential as a predictive biomarker for immunotherapy in melanoma.Methods:The expression patterns of ETS family TFs were analyzed in melanoma and hepatocellular carcinoma(HCC).Single-cell RNA sequencing(scRNA-seq)was used to dissect the cellular expression and function of ETV4 in the tumor microenvironment.Functional studies and murine models were employed to investigate the role of ETV4 in T cell-mediated tumor killing and tumor growth.The correlation between ETV4 expression level and patient responsiveness to programmed cell death protein 1(PD-1)blockade therapy was evaluated.Results:TFs in the ETS family were found to effectively stratify melanoma and HCC patients into prognostic subgroups.In melanoma,the polyoma enhancer activator 3(PEA3)subfamily,particularly ETV4 and ETV5,showed a negative correlation with immune infiltration.scRNA-seq analysis showed that ETV4 is preferentially expressed in melanoma cells and involves in mediating tumor-immunocyte interactions.Functional studies demonstrated that ETV4 impairs T cell-mediated tumor killing by transcriptionally upregulating programmed death-ligand 1(PD-L1).In immunocompetent murine models,ETV4 downregulation significantly suppressed tumor growth.Furthermore,high ETV4 expression correlated with poor responses to anti-PD-1 therapy.Conclusion:Our findings identify ETV4 as a key transcriptional regulator of immune evasion in melanoma by controlling PD-L1 expression.ETV4 may act as a predictive biomarker for immunotherapy outcomes.展开更多
基金supported by the National Natural Science Foundation of China,Nos.82371310(to YJ),82271306(to JP)the Sichuan Science and Technology Support Program,Nos.2023YFH0069(to JP),2023NSFSC0028(to YJ),2023NSFSC1559(to YJ),2022YFS0615(to JP),2022NSFSC1421(to JP)+1 种基金Scientific Research Project of Sichuan Provincial Health Commission,No.23LCYJ040(to YJ)Youth Foundation of Southwestern Medical University and Southwest Medical University Project,Nos.2020ZRQNA038(to JP),2021ZKZD013(to JP),2021LZXNYD-P01(to YJ),2023QN014(to JP).
文摘Neuronal cell death is a common outcome of multiple pathophysiological processes and a key factor in neurological dysfunction after subarachnoid hemorrhage.Neuronal ferroptosis in particular plays an important role in early brain injury.Bromodomain-containing protein 4,a member of the bromo and extraterminal domain family of proteins,participated in multiple cell death pathways,but the mechanisms by which it regulates ferroptosis remain unclear.The primary aim of this study was to investigate how bromodomain-containing protein 4 affects neuronal ferroptosis following subarachnoid hemorrhage in vivo and in vitro.Our findings revealed that endogenous bromodomain-containing protein 4 co-localized with neurons,and its expression was decreased 48 hours after subarachnoid hemorrhage of the cerebral cortex in vivo.In addition,ferroptosis-related pathways were activated in vivo and in vitro after subarachnoid hemorrhage.Targeted inhibition of bromodomain-containing protein 4 in neurons increased lipid peroxidation and intracellular ferrous iron accumulation via ferritinophagy and ultimately led to neuronal ferroptosis.Using cleavage under targets and tagmentation analysis,we found that bromodomain-containing protein 4 enrichment in the Raf-1 promoter region decreased following oxyhemoglobin stimulation in vitro.Furthermore,treating bromodomain-containing protein 4-knockdown HT-22 cell lines with GW5074,a Raf-1 inhibitor,exacerbated neuronal ferroptosis by suppressing the Raf-1/ERK1/2 signaling pathway.Moreover,targeted inhibition of neuronal bromodomain-containing protein 4 exacerbated early and long-term neurological function deficits after subarachnoid hemorrhage.Our findings suggest that bromodomain-containing protein 4 may have neuroprotective effects after subarachnoid hemorrhage,and that inhibiting ferroptosis could help treat subarachnoid hemorrhage.
文摘A recently published study(Xin et al.,Prog Biochem Biophys,2026,53(2):431-441.DOI:10.3724/j.pibb.2025.0508)addresses the therapeutic challenges of pancreatic ductal adenocarcinoma(PDAC)by innovatively developing an orally administered nanogene delivery system.Designed to achieve in situ,efficient delivery of chimeric antigen receptor(CAR)genes to tumor sites,this approach offers a novel strategy for CAR-macrophage(CAR-M)based immunotherapy.Its key highlights are as follows.
基金supported by the National Natural Science Foundation of China,Nos.82172196(to KX),82372507(to KX)the Natural Science Foundation of Hunan Province,China,No.2023JJ40804(to QZ)the Key Laboratory of Emergency and Trauma(Hainan Medical University)of the Ministry of Education,China,No.KLET-202210(to QZ)。
文摘Ischemia–reperfusion injury is a common pathophysiological mechanism in retinal degeneration.PANoptosis is a newly defined integral form of regulated cell death that combines the key features of pyroptosis,apoptosis,and necroptosis.Oligomerization of mitochondrial voltage-dependent anion channel 1 is an important pathological event in regulating cell death in retinal ischemia–reperfusion injury.However,its role in PANoptosis remains largely unknown.In this study,we demonstrated that voltage-dependent anion channel 1 oligomerization-mediated mitochondrial dysfunction was associated with PANoptosis in retinal ischemia–reperfusion injury.Inhibition of voltage-dependent anion channel 1 oligomerization suppressed mitochondrial dysfunction and PANoptosis in retinal cells subjected to ischemia–reperfusion injury.Mechanistically,mitochondria-derived reactive oxygen species played a central role in the voltagedependent anion channel 1-mediated regulation of PANoptosis by promoting PANoptosome assembly.Moreover,inhibiting voltage-dependent anion channel 1 oligomerization protected against PANoptosis in the retinas of rats subjected to ischemia–reperfusion injury.Overall,our findings reveal the critical role of voltage-dependent anion channel 1 oligomerization in regulating PANoptosis in retinal ischemia–reperfusion injury,highlighting voltage-dependent anion channel 1 as a promising therapeutic target.
基金supported by the National Natural Science Foundation of China,No.81870927(to ZH)the Natural Science Foundation Project ofChongqing Science and Technology Commission,No.CSTB2023NSCQ-MSX0112(to ZH).
文摘Phosphodiesterase 4 is a key enzyme involved in the regulation of cell signal transduction,but its role in subarachnoid hemorrhage remains unclear.Neuronal pyroptosis has been reported to be involved in early brain injury after subarachnoid hemorrhage.This study aimed to investigate whether phosphodiesterase 4 contributes to early brain injury after subarachnoid hemorrhage by mediating neuronal pyroptosis and its related mechanisms.Endovascular perforation of male C57BL/6J mice was performed to model subarachnoid hemorrhage in vivo,and oxyhemoglobin was added to the culture medium of primary neurons to model subarachnoid hemorrhage in vitro.A phosphodiesterase 4-specific inhibitor,etazolate,was intraperitoneally injected 30 minutes after subarachnoid hemorrhage induction.Small interfering RNA(siRNA)was administered intracerebroventricularly 72 hours before subarachnoid hemorrhage to achieve genetic knockdown of phosphodiesterase 4.To investigate the mechanism,a nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3(NLRP3)-specific agonist,nigericin,was intracerebroventricularly injected 60 minutes before subarachnoid hemorrhage.Neuronal phosphodiesterase 4 expression increased after subarachnoid hemorrhage and reached the highest point at 24 hours.Etazolate treatment reduced neurological deficits and brain edema in mice,alleviated neuronal pyroptosis and inflammatory response,and improved neuronal injury.Treatment with phosphodiesterase 4 siRNA had the same neuroprotective effects as etazolate.Mechanistically,phosphodiesterase 4 triggered the nuclear factor kappa-B pathway,and simultaneously caused lysosomal and mitochondrial dysfunction after subarachnoid hemorrhage,which promoted NLRP3 inflammasome activation and induced neuronal pyroptosis.Blocking of phosphodiesterase 4 inhibited the nuclear factor kappa-B pathway,and improved lysosome and mitochondrial function.Activation of NLRP3 reversed the neuroprotective effects of etazolate without affecting phosphodiesterase 4 expression.Together,the results indicate that phosphodiesterase 4 regulates NLRP3-mediated neuronal pyroptosis in early brain injury after subarachnoid hemorrhage.Phosphodiesterase 4 may be a potential therapeutic molecular target for subarachnoid hemorrhage.
基金supported by a grant from the Beijing Union Medical College Foundation-Rui E Emergency Medicine Research Fund in 2025。
文摘Central venous catheterization(CVC)is a fundamental clinical procedure widely performed across medical specialties.However,the complication rate of subclavian vein catheterization ranges from 6%to 11%.[1]Common complications include hemothorax,pneumothorax,air embolism,arterial puncture,and aortic perforation.[2]Herein,we report a rare case of accidental puncture of the aorta during subclavian CVC,which was successfully managed with a ventricular septal defect(VSD)occluder.
基金supported by the Nature Science Foundation of Liaoning Province,Nos.2022-MS-211,2021-MS-064,and 2024-MS-048(all to YC).
文摘Alzheimer’s disease,a devastating neurodegenerative disorder,is characterized by progressive cognitive decline,primarily due to amyloid-beta protein deposition and tau protein phosphorylation.Effectively reducing the cytotoxicity of amyloid-beta42 aggregates and tau oligomers may help slow the progression of Alzheimer’s disease.Conventional drugs,such as donepezil,can only alleviate symptoms and are not able to prevent the underlying pathological processes or cognitive decline.Currently,active and passive immunotherapies targeting amyloid-beta and tau have shown some efficacy in mice with asymptomatic Alzheimer’s disease and other transgenic animal models,attracting considerable attention.However,the clinical application of these immunotherapies demonstrated only limited efficacy before the discovery of lecanemab and donanemab.This review first discusses the advancements in the pathogenesis of Alzheimer’s disease and active and passive immunotherapies targeting amyloid-beta and tau proteins.Furthermore,it reviews the advantages and disadvantages of various immunotherapies and considers their future prospects.Although some antibodies have shown promise in patients with mild Alzheimer’s disease,substantial clinical data are still lacking to validate their effectiveness in individuals with moderate Alzheimer’s disease.
基金supported by grants from the Major Projects of Health Science Research Foundation for Middle-Aged and Young Scientist of Fujian Province,China,No.2022ZQNZD01010010the National Natural Science Foundation of China,No.82371390Fujian Province Scientific Foundation,No.2023J01725(all to XC).
文摘The neuroinflammatory response mediated by microglial activation plays an important role in the secondary nerve injury of traumatic brain injury.The post-transcriptional modification of N^(6)-methyladenosine is ubiquitous in the immune response of the central nervous system.The fat mass and obesity-related protein catalyzes the demethylation of N^(6)-methyladenosine modifications on mRNA and is widely expressed in various tissues,participating in the regulation of multiple diseases’biological processes.However,the role of fat mass and obesity in microglial activation and the subsequent neuroinflammatory response after traumatic brain injury is unclear.In this study,we found that the expression of fat mass and obesity was significantly down-regulated in both lipopolysaccharide-treated BV2 cells and a traumatic brain injury mouse model.After fat mass and obesity interference,BV2 cells exhibited a pro-inflammatory phenotype as shown by the increased proportion of CD11b^(+)/CD86^(+)cells and the secretion of pro-inflammatory cytokines.Fat mass and obesity-mediated N^(6)-methyladenosine demethylation accelerated the degradation of ADAM17 mRNA,while silencing of fat mass and obesity enhanced the stability of ADAM17 mRNA.Therefore,down-regulation of fat mass and obesity expression leads to the abnormally high expression of ADAM17 in microglia.These results indicate that the activation of microglia and neuroinflammatory response regulated by fat mass and obesity-related N^(6)-methyladenosine modification plays an important role in the pro-inflammatory process of secondary injury following traumatic brain injury.
文摘Objectives Dysregulated osteoclast function contributes to skeletal diseases.However,the specific ubiquitination regulators of the osteoclastogenesis repressor MafB,particularly at the post-translational level,remain undefined.This study aims to identify ubiquitin-specific proteases(USPs)that deubiquitinate MafB and enhance its stability.Methods We constructed a MafB-conjugated luciferase and overexpressed 40 individual USPs,measuring changes in luciferase activity.The identified USP was overexpressed in human CD14^(+) peripheral blood mononuclear cells(PBMCs)to evaluate its effect.Osteoclast differentiation was assessed through osteoclast marker Integrin alpha-V(CD51)staining and Western blot analysis.Co-immunoprecipitation(co-IP)was performed to assess the interplay.The influence on MafB ubiquitination and degradation was evaluated via immunoprecipitation and Western blot.Finally,MafB was knocked down in the USP-overexpressing PBMCs to analyze its effect on osteoclast differentiation.Results Overexpression of ubiquitin-specific protease 29(USP29)significantly increased MafB expression by approximately 75%(p<0.0001).Elevated USP29 levels strongly inhibited osteoclastic differentiation in CD14^(+) PBMCs(p<0.0001).USP29 was found to interact with MafB,markedly reducing its ubiquitination and subsequent degradation in PBMCs(p<0.001).Knocking down MafB in USP29-overexpressing PBMCs alleviated the inhibitory effect of USP29 on osteoclastogenesis.Conclusion USP29 acts as a potent stabilizer of MafB,inhibiting osteoclastogenesis in human CD14^(+) PBMCs,at least in part,by enhancing MafB stability.These findings expand our understanding of USP29’s role and the post-translational regulation of MafB.Furthermore,USP29 serves as a vital factor that controls osteoclast differentiation,and its regulatory function is at least partially mediated by deubiquitinating and stabilizing MafB.
基金supported by National Natural Science Foundation of China(Grant No.81900873 to A.Q.)the Jiangsu Provincial Key Research and Development Programme-social development(Grant No.BE2023777 to W.Z.)+1 种基金the Key Medical Research Project of Jiangsu Commission of Health(Grant No.H2022185 to W.Z.)the Clinical Capacity Enhancement Project of Jiangsu Province Hospital(Grant No.JSPH-MB-2023-18 to W.Z.)。
文摘Diabetic retinopathy(DR),a common complication of diabetes,is characterized by retinal angiogenesis and inflammation.The role of hepatoma-derived growth factor(HDGF)in mediating inflammation during DR remains unclear.We measured HDGF levels in the aqueous humor and found that HDGF was increased in DR but decreased after anti-angiogenesis treatment.Using public single-cell RNA sequencing datasets,we found that elevated HDGF in DR was mainly produced by Müller cells and targeted microglia.Additionally,integrin beta 2(Itgb2),a target gene of HDGF that induces microglial activation,was significantly upregulated in DR.To verify these results,we performed enzyme-linked immunosorbent assays,quantitative reverse transcription-PCR,Western blotting,and fluorescence immunostaining in cultured Müller and microglial cells treated with HDGF or anti-HDGF,as well as in DR mice receiving intravitreal injections of HDGF or its antibody.Exogenous HDGF further promoted microglial activation,migration,and secretion of pro-inflammatory cytokines,while neutralization of HDGF suppressed these effects caused by high glucose.Furthermore,the HDGF receptor nucleolin was overexpressed in microglia under high glucose stimulation.Therefore,blocking HDGF from Müller cells in DR reduced the excessive inflammatory response in microglia,highlighting HDGF as a potential therapeutic target.
文摘Based on the Bismuth-Corlette classification of hilar cholangiocarcinoma,the patients with types I,II,and III can undergo radical resection in the absence of extensive intrahepatic metastasis and vascular invasion[1].Depending on the scope of tumor invasion in bile duct,a combined resection of parts of the liver,hepatic ducts,common bile ducts,regional lymph nodes,and even parts of the duodenum and pancreas is necessary,along with biliary and gastrointestinal reconstructions[2].The surgical plan is complex,involving a large resection area and significant trauma.In recent years,laparoscopic or robot assisted radical resection of hilar cholangiocarcinoma has been applied clinically[3,4].With the advanced laparoscopic equipment,many patients undergo hepatopancreatoduodenectomy successfully[5].The limitations of traditional laparoscopic techniques restrict their wide application in clinical practice.However,the Da Vinci robot has been widely applied due to its clear field of vision and flexible manipulation.However,its utilization in hepato-pancreatoduodenectomy for hilar cholangiocarcinoma is still relatively rare.Here,we report a case with hilar cholangiocarcinoma at clinical stage IIIb who underwent robot-assisted hepato-pancreatoduodenectomy.
文摘Background:Sarcomatoid carcinoma of the ureter(SCU)is a highly aggressive and relatively uncommon malignant tumor of the urinary tract.Its frequency is quite low,and its prognosis is very bad when compared to other cancers of the urinary system.SCU clinical reports are still hard to come by.MRI and PEI/CT imaging of ureteral sarcomatoid cancer is presented in this case to promote diagnostic awareness and comprehension of the imaging characteristics of this uncommon illness.Method:The patient had ureteral sarcomatoid cancer,which was verified by pathological investigation after ureteroscopic biopsy.The patient’s clinical information,imaging results,surgical outcomes,and pathological findings were gathered.A retrospective study was carried out in combinationwith pertinent national and international literature.Results:An 84-year-old female patient was admitted for“left flank discomfort lasting over one month.”MRI revealed an irregular soft tissue mass in the middle-lower segment of the left ureter.T2-weighted imaging showed an unevenly slightly hyperintense signal.Diffusion-weighted imaging demonstrated restricted diffusion.Contrastenhanced imaging exhibited heterogeneous enhancement.PET/CT demonstrated significantly increased fluorodeoxyglucose metabolism in the mass with secondary left upper urinary tract obstruction.Concurrent findings included a solitary metastatic lesion in hepatic segment S6 and multiple lymph node metastases along the left common iliac and external iliac arteries.Preoperative diagnosis suggested a malignant tumor of the ureter.The patient underwent left nephroureteroscopy with biopsy,and the postoperative pathological diagnosis was ureteral sarcomatoid carcinoma.Conclusion:Ureteral sarcomatoid carcinoma is a rare,highly malignant,and aggressive tumor with nonspecific imaging features,typically presenting as an invasively growing mass.Diagnosis relies on postoperative pathology and immunohistochemical examination.MRI and PET/CT scans are valuable for preoperative localization and characterization,tumor staging,treatment planning,and postoperative follow-up.The prognosis is extremely negative.The main treatment option is radical surgery,although constant monitoring is necessary since early recurrence and metastases are frequent after surgery.
文摘Organophosphate pesticide poisoning is an acute form of poisoning primarily found in underdeveloped regions.Its main clinical manifestations include muscarinic symptoms,nicotinic symptoms,and central nervous system disturbances.This report presents a case of a middleaged female who developed extremely rare symptoms of optic nerve damage after ingesting a large amount of an organophosphate pesticide.
基金Supported by the Guangdong Provincial Natural Science Foundation(No.2114050001527).
文摘Micro/nanoplastics(M/NPs)have become pervasive environmental pollutants,posing significant risks to human health through various exposure routes,including ingestion,inhalation,and direct contact.This review systematically examined the potential impacts of M/NPs on ocular health,focusing on exposure pathways,toxicological mechanisms,and resultant damage to the eye.Ocular exposure to M/NPs can occur via direct contact and oral ingestion,with the latter potentially leading to the penetration of particles through ocular biological barriers into ocular tissues.The review highlighted that M/NPs can induce adverse effects on the ocular surface,elevate intraocular pressure,and cause abnormalities in the vitreous and retina.Mechanistically,oxidative stress and inflammation are central to M/NP-induced ocular damage,with smaller particles often exhibiting greater toxicity.Overall,this review underscored the potential risks of M/NPs to ocular health and emphasized the need for further research to elucidate exposure mechanisms,toxicological pathways,and mitigation strategies.
基金supported by Shenzhen Science and Technology Program, No. JCYJ20230807110259002 (to JL)The Seventh Affiliated Hospital of Sun Yat-sen University, No. ZSQYRSFPD0050 (to JL)The Postdoctoral Fellowship Program of CPSF, No. GZC20242074 (to KT)
文摘Oxidative stress significantly contributes to secondary damage after spinal cord injury.Despite its importance,research on oxidative stress in spinal cord injury remains limited.Investigating the expression and regulation of oxidative stress-related genes could enhance the diagnosis and treatment of spinal cord injury.In this study,we analyzed the sequencing data of human blood samples and injured mouse spinal cord tissue that were sourced from GEO databases and identified diagnostic biomarkers associated with the severity of spinal cord injury.We also explored the expression patterns of oxidative stress-related genes,potential regulatory mechanisms,and therapeutic drugs.To validate our findings,we performed immunofluorescence and quantitative polymerase chain reaction to assess gene expression in the injured spinal cord.Our results revealed biomarkers associated with oxidative stress and immune responses across different levels of spinal cord injury in humans.We identified differentially expressed oxidative stress-related genes and key hub genes in injured mouse spinal cord tissue and revealed their temporal expression patterns at both the tissue and single-cell levels.We also clarified the signaling pathways associated with oxidative stress and identified ligand-receptor pairs among various cell types at different time points after injury.Furthermore,we discovered microRNAs,long non-coding RNAs,and transcription factors that regulate these hub genes and revealed their roles in modulating gene expression at various stages after spinal cord injury.We also identified drugs targeting these hub genes.The findings from this study not only aid in identifying diagnostic biomarkers that reflect the severity of spinal cord injury,but also provide insights into the expression dynamics of oxidative stress-related genes.In addition,the study reveals potential regulatory mechanisms and identifies potential drugs to treat patients with spinal cord injury.
基金supported by a grant from General Scientific Research Project of Zhejiang Provincial Department of Education(No.Y202455614).
文摘Diabetes mellitus is an escalating global health issue,with 463 million adults affected in 2019.Without intervention,this number is projected to increase to 578 million by 2030 and 700 million by 2045[1].Diabetic wound,a significant complication,is characterized by delayed healing,high disability rates,and elevated mortality[2].The challenges of wound healing in diabetic patients,compounded by their high morbidity and mortality rates,have drawn growing attention in biomedical research.
基金supported by the National Natural Science Foundation of China(No.82274474)。
文摘Despite effective antiretroviral therapy(ART),many individuals with human immunodeficiency virus(HIV)/acquired immune deficiency syndrome(AIDS)achieve viral suppression but fail to fully restore cluster of differentiation 4(CD4)^(+)T lymphocyte(CD4 cell)counts—a condition known as immunological non-response(INRs).INRs are associated with elevated health risks,including increased susceptibility to AIDS-related and non-AIDS-related complications.The pathogenesis of INRs remains incompletely understood,and no established therapeutic interventions exist,posing a major challenge in contemporary HIV/AIDS management.Emerging evidence indicates that INRs exhibit significant alterations in gut microbiota composition.Dysbiosis of the gut microbiota may contribute to persistent immune activation,cytokine imbalance,and cellular pyroptosis,all of which could impair immune reconstitution in people living with HIV/AIDS.Traditional Chinese medicine(TCM)has demonstrated potential immunomodulatory effects and is increasingly utilized in the management of INRs.Targeting the gut microbiota and elucidating the mechanisms by which TCM modulates this microbial ecosystem may offer new avenues for preventing and treating INRs.This review explores the interplay between gut microbiota and TCM,examines the association between gut dysbiosis and INRs,discusses the mechanistic pathways through which microbiota imbalance contributes to INRs development,and highlights how TCM interventions regulate gut microbiota to promote immune recovery.By focusing on the gut microbiota as a therapeutic interface,this article provides novel insights into TCM-based strategies for improving outcomes in INRs and supports the development of innovative treatment approaches.
文摘BACKGROUND Perimenopausal women are prone to anxiety and depression due to fluctuating hormone levels,which significantly impair their quality of life.The current treatments have certain limitations.In traditional Chinese medicine,liver-soothing formulas are commonly prescribed for mood-related disorders,but their overall efficacy in perimenopausal anxiety and depression remains uncertain and requires verification through meta-analysis.AIM To provide evidence-based support for clinical decision-making and research,a meta-analysis was conducted to evaluate the effectiveness of liver-soothing formulas in treating perimenopausal anxiety and depression.METHODS Relevant studies published up to April 2025 were retrieved from ClinicalTrials.gov,PubMed,Web of Science,EMBASE,and the Cochrane Library.Eligible studies were screened according to predefined inclusion and exclusion criteria.Data were extracted and analyzed using the Stata 12.0 software.RESULTS After searching and screening,12 articles involving 1798 patients(922 in the treatment group and 876 in the control group)were included in the analysis.Meta-analysis showed that the standardized scores for anxiety[standardized mean difference(SMD)=-0.71,95%confidence interval(95%CI):-1.06 to-0.36]and depression(SMD=-0.67,95%CI:-1.06 to-0.27)of the treatment group were lower than those of the control group.Subgroup analysis results revealed that for anxiety,liver-soothing formulas used alone(SMD=-0.34,95%CI:-0.50 to-0.18)or in combination(SMD=-0.88,95%CI:-1.43 to-0.34)both significantly reduced scores compared with the control group.For depression,monotherapy of liversoothing formulas showed no significant statistical difference between the treatment and control groups(SMD=-0.47,95%CI:-1.11 to 0.17),whereas combination therapy produced significantly lower standardized scale scores in the treatment group than in the control group,with a statistically significant difference(SMD=-0.83,95%CI:-1.39 to-0.28).Regarding Greene scores,no statistically significant difference was observed with monotherapy(SMD=0.87,95%CI:-0.32 to 2.06),whereas combination therapy had significantly lower Greene scores(SMD=-0.24,95%CI:-0.44 to-0.04).No statistically significant difference was found between the groups in the occurrence of adverse reactions(odds ratio=0.90,95%CI:0.57-1.43).However,liver-soothing formulas did not affect estrogen levels in perimenopausal women.CONCLUSION Compared with placebo,conventional Western medicine,or other interventions,the monotherapy of liver-soothing formulas demonstrates superior efficacy in treating perimenopausal anxiety.When used as an adjuvant,they exert a synergistic effect in alleviating negative emotions and improving overall perimenopausal symptoms.
基金supported by the National Key R&D Program of China,Nos.2017YFA0104302(to NG and XM)and 2017YFA0104304(to BW and ZZ)
文摘Mesenchymal stromal cell transplantation is an effective and promising approach for treating various systemic and diffuse diseases.However,the biological characteristics of transplanted mesenchymal stromal cells in humans remain unclear,including cell viability,distribution,migration,and fate.Conventional cell tracing methods cannot be used in the clinic.The use of superparamagnetic iron oxide nanoparticles as contrast agents allows for the observation of transplanted cells using magnetic resonance imaging.In 2016,the National Medical Products Administration of China approved a new superparamagnetic iron oxide nanoparticle,Ruicun,for use as a contrast agent in clinical trials.In the present study,an acute hemi-transection spinal cord injury model was established in beagle dogs.The injury was then treated by transplantation of Ruicun-labeled mesenchymal stromal cells.The results indicated that Ruicunlabeled mesenchymal stromal cells repaired damaged spinal cord fibers and partially restored neurological function in animals with acute spinal cord injury.T2*-weighted imaging revealed low signal areas on both sides of the injured spinal cord.The results of quantitative susceptibility mapping with ultrashort echo time sequences indicated that Ruicun-labeled mesenchymal stromal cells persisted stably within the injured spinal cord for over 4 weeks.These findings suggest that magnetic resonance imaging has the potential to effectively track the migration of Ruicun-labeled mesenchymal stromal cells and assess their ability to repair spinal cord injury.
基金supported by the Science and Technology Program in Guangxi Province(2023JJD140004).
文摘Objective:The contribution of long non-coding RNAs(lncRNAs)associated with protein palmitoylation to the progression of hepatocellular carcinoma(HCC)remains largely unclear.This study sought to establish a prognostic signature based on palmitoylation-related lncRNAs and explore their functional implications in HCC.Methods:RNA sequencing and clinical data for HCC and normal tissues were sourced from the Cancer Genome Atlas(TCGA).Pearson correlation analysis was used to identify lncRNAs that were co-expressed with palmitoylation-related genes.Univariate Cox regression was applied to select lncRNAs with prognostic value,followed by the construction of a predictive model using the least absolute shrinkage and selection operator(LASSO)regression.A focused analysis was performed on one key lncRNA,AC009403.1.Expression levels of the final nine lncRNAs included in the model were further validated by reverse transcription quantitative polymerase chain reaction(RT-qPCR).Results:A prognostic model for HCC was developed using nine palmitoylation-associated lncRNAs:AC009403.1,AC010789.1,AC026402.2,AC107021.2,AC135050.6,AL353572.4,MKLN1-AS,PRRT3-AS1,and ZNF582-AS1.This model effectively stratified patients into high-and low-risk groups exhibiting significantly different overall survival(OS)and progression-free survival(PFS),with the low-risk group showing more favorable outcomes.The high-risk group was associated with an immunosuppressive microenvironment,higher tumor mutation burden(TMB),and increased sensitivity to certain chemotherapeutic drugs(e.g.,Sorafenib).Finally,RT-qPCR validation revealed that all nine lncRNAs were significantly upregulated in HCC tissues.Conclusion:The nine-lncRNA signature exhibits robust predictive power for HCC prognosis and provides novel insights into the mechanisms of lncRNA-regulated palmitoylation in HCC development.
基金funded by the National Natural Science Foundation of China(Grant Nos.82204517 to T.Z.and 82404756 to J.Z.)the Science and Technology Program in Medicine and Health of Zhejiang Province(Grant No.2023KY726 to T.Z.).
文摘Background:Aberrant expression of transcription factors(TFs)is a key mechanism mediating tumor immune escape and therapeutic resistance.The involvement of E26 transformation-specific(ETS)family of TFs in immune regulation is not fully understood.The study aimed to elucidate the function of E-twenty-six variant 4(ETV4)in tumor immune evasion and its potential as a predictive biomarker for immunotherapy in melanoma.Methods:The expression patterns of ETS family TFs were analyzed in melanoma and hepatocellular carcinoma(HCC).Single-cell RNA sequencing(scRNA-seq)was used to dissect the cellular expression and function of ETV4 in the tumor microenvironment.Functional studies and murine models were employed to investigate the role of ETV4 in T cell-mediated tumor killing and tumor growth.The correlation between ETV4 expression level and patient responsiveness to programmed cell death protein 1(PD-1)blockade therapy was evaluated.Results:TFs in the ETS family were found to effectively stratify melanoma and HCC patients into prognostic subgroups.In melanoma,the polyoma enhancer activator 3(PEA3)subfamily,particularly ETV4 and ETV5,showed a negative correlation with immune infiltration.scRNA-seq analysis showed that ETV4 is preferentially expressed in melanoma cells and involves in mediating tumor-immunocyte interactions.Functional studies demonstrated that ETV4 impairs T cell-mediated tumor killing by transcriptionally upregulating programmed death-ligand 1(PD-L1).In immunocompetent murine models,ETV4 downregulation significantly suppressed tumor growth.Furthermore,high ETV4 expression correlated with poor responses to anti-PD-1 therapy.Conclusion:Our findings identify ETV4 as a key transcriptional regulator of immune evasion in melanoma by controlling PD-L1 expression.ETV4 may act as a predictive biomarker for immunotherapy outcomes.
