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
Accumulating evidence has highlighted the functional role of the endogenous nociceptin/orphanin FQ peptide(N/OFQ)and its nociceptin opioid receptor(NOP)in alcohol and cocaine reward.However,the effects of NOP agonists...Accumulating evidence has highlighted the functional role of the endogenous nociceptin/orphanin FQ peptide(N/OFQ)and its nociceptin opioid receptor(NOP)in alcohol and cocaine reward.However,the effects of NOP agonists on methamphetamine(MAP)reinforcement,motivation,and relapse remain uncertain.In this study,we evaluated the effects of Ro 64-6198,a selective NOP agonist,on MAP reinforcement,motivation,and relapse in rats.Rats underwent a fixed-ratio 1(FR1)training to establish stable MAP intravenous self-administration(0.05 mg/kg/infusion)for 12 days,and the motivation for MAP was quantified using a progressive-ratio(PR)schedule,while the relapse was assessed through cue-and MAP-primed reinstatement after abstinence.Western blot analysis was employed to measure the relative expression of phosphorylated CREB,ERK,and Akt in the nucleus accumbens(NAc)following drug priming.Acute treatment of Ro 64-6198(1 mg/kg)significantly reduced the motivated behavior for MAP under PR testing(P<0.05 vs.vehicle).Ro 64-6198 at doses of 0.3 and 1 mg/kg could suppress the drug-seeking behavior induced by extinction or cues,respectively(P<0.05),whereas only the higher dose(1 mg/kg)could attenuate MAP primed drug-seeking(P<0.05).These behavioral effects were related to the upregulated phosphorylation of CREB and Akt in the NAc.Our results provide preclinical evidence that NOP activation disrupts multiple addiction-relevant behaviors,positioning Ro 64-6198 as a potential therapeutic candidate for treating MAP use disorders.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
Cyclopropenones have been extensively utilized in catalytic ring-opening and ring-expansion reactions for the synthesis of unsaturated carbonyl compounds.The first rhodium-catalyzed ring-opening reaction of aryl-/alky...Cyclopropenones have been extensively utilized in catalytic ring-opening and ring-expansion reactions for the synthesis of unsaturated carbonyl compounds.The first rhodium-catalyzed ring-opening reaction of aryl-/alkyl-substituted cyclopropenones is accomplished,successfully affording acyloin derivatives.This transformation represents a novel reaction pattern involving cyclopropenones.The resulting acyloin products constitute important building blocks in organic synthesis and serve as fundamental structural frameworks in numerous natural products.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
This study investigated the neuroprotective effects of lactate in subarachnoid hemorrhage,a severe cerebrovascular disease that is commonly caused by arterial aneurysm rupture and has limited early treatment options.L...This study investigated the neuroprotective effects of lactate in subarachnoid hemorrhage,a severe cerebrovascular disease that is commonly caused by arterial aneurysm rupture and has limited early treatment options.Lactate,a metabolic byproduct,has been shown to have neuroprotective properties,including enhancing cerebral microcirculation and reducing intracranial pressure in acute brain injury patients.However,the protective mechanisms of lactate in subarachnoid hemorrhage remain unknown.In this study,we showed that lactate alleviates early brain damage in subarachnoid hemorrhage by promoting neuronal lipid synthesis and the formation of lipid droplets in astrocytes.In vivo experiments using a subarachnoid hemorrhage mouse model showed that lactate treatment significantly improved neurological scores,reduced brain inflammation,and promoted lipid droplet formation in astrocytes within 24 hours.Lactate treatment increased free fatty acids levels in the brain.The results suggest that astrocytes absorbed these free fatty acids and converted them into lipid droplets,thus reducing cellular lipotoxicity.Moreover,lactate enhanced the antiapoptotic capacity of astrocytes by upregulating the expression of PLIN5,a protein crucial for lipid droplet formation.The inhibition of lipid synthesis or lipid droplet formation counteracted the neuroprotective effects of lactate,indicating that lactate’s protective role is closely linked to lipid metabolism and lipid droplet formation.In vitro experiments on HT22 neuronal cells exposed to hemin-an agent used to simulate subarachnoid hemorrhage injury-demonstrated that lactate mitigated cellular damage by reducing lipid peroxidation and preserving mitochondrial membrane potential.Lactate treatment in HT22 cells and astrocytes also showed that inhibition of lipid synthesis or lipid droplet formation reversed its protective effects,further emphasizing the importance of lipid metabolism in the neuroprotective action of lactate.This study provides insights into the neuroprotective mechanisms of lactate in subarachnoid hemorrhage.It indicates that lactate plays a role in promoting lipid synthesis in neurons and enhancing lipid droplet formation in astrocytes,thus mitigating brain damage and improving cell survival.These findings suggest that lactate,through its regulation of lipid metabolism,could be a potential therapeutic agent for subarachnoid hemorrhage.展开更多
Mosquito-borne diseases pose a significant global health threat,necessitating the development of innovative vector control strategies.In this study,we investigated the potential of harnessing host immunity against mos...Mosquito-borne diseases pose a significant global health threat,necessitating the development of innovative vector control strategies.In this study,we investigated the potential of harnessing host immunity against mosquitoes through vaccination.Using Culex pipiens(C.pipiens)as a model,we demonstrated that polyclonal antibodies against C.pipiens abdominal protein extracts significantly impaired oviposition and increased mosquito mortality,primarily through the classical complement activation pathways.However,repeated exposure led to resistance,indicating potential adaptation.Proteomic analysis identified metabolic proteins as key targets,with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses highlighting their roles in carboxylic acid metabolism,tyrosine degradation,and the proteasome pathways.Notably,cross-species reactivity was revealed by Western blotting,showing strong binding of Culex-specific antibodies to Anopheles and Aedes abdominal proteins.This study provides mechanistic insights into antibody-based mosquito suppression,highlighting its potential as an innovative vector control strategy while underscoring the need for further research on resistance management and ecological impacts.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
Subarachnoid hemorrhage is a subtype of stroke that causes severe neurological damage and is associated with poor long-term prognosis.Cognitive impairment is a major manifestation of long-term neurological dysfunction...Subarachnoid hemorrhage is a subtype of stroke that causes severe neurological damage and is associated with poor long-term prognosis.Cognitive impairment is a major manifestation of long-term neurological dysfunction in patients with subarachnoid hemorrhage.However,there is notable absence of biological markers to predict long-term prognosis in this patient population.Given the aging-like neurocognitive phenomena associated with subarachnoid hemorrhage,this study postulates that telomere length,a recognized biomarker for aging,could be used as a prognostic indicator for subarachnoid hemorrhage.A left internal carotid artery intravascular puncture mouse model was used to simulate subarachnoid hemorrhage.Comprehensive neurological test scores were obtained through neurobehavioral assessments conducted at one-month intervals.Concurrently,the relative telomere length was analyzed by quantitative polymerase chain reaction,which was performed using DNA extracted from ear notch and brain tissue after each assessment.Furthermore,proteomic analysis was employed to investigate differential protein expression in hippocampal tissue.Subarachnoid hemorrhage mice exhibited persistent neurocognitive impairment over a prolonged period of time.There was a significant positive correlation between telomere length and neurological test scores,confirming the usefulness of telomere length as a prognostic indicator in subarachnoid hemorrhage.Hippocampal tissue from subarachnoid hemorrhage mice showed reduced expression of acetyl-coenzyme A synthetase-2 and abnormalities in the expression of proteins related to ribosomes,energy metabolism,and cellular signal transduction.This study confirmed telomere shortening in the brain and metabolic disturbances in the hippocampi of subarachnoid hemorrhage mice.Thus,telomere length is a predictive marker for long-term impairment of cognitive function in mice following experimental subarachnoid hemorrhage.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
Objective:To investigate the effect of pectic polysaccharides isolated from Rauvolfia verticillata on ulcerative colitis and its underlying mechanisms.Methods:Pectic polysaccharides were characterized using high-perfo...Objective:To investigate the effect of pectic polysaccharides isolated from Rauvolfia verticillata on ulcerative colitis and its underlying mechanisms.Methods:Pectic polysaccharides were characterized using high-performance liquid chromatography with 1-phenyl-3-methyl-5-pyrazolone pre-column derivatization,phenol-sulfuric acid assay,and gel permeation chromatography.HT-29 cells were stimulated with lipopolysaccharide and then treated with pectic polysaccharides;conditioned medium was applied to THP-1-derived macrophages to assess cell viability and polarization,while tight junction protein expression was analyzed in HT-29 cells.Furthermore,a mouse model of dextran sulfate sodium-induced colitis was treated with oral pectic polysaccharides or NOS2 overexpression.Body weight,disease activity index,colon length,histopathology,and the protein expression related to the JAK2/STAT3-NOS2 signaling were evaluated.Results:The pectic polysaccharide was characterized as an acidic pectic polysaccharide,primarily composed of galacturonic acid and various neutral sugars,with a narrow molecular weight distribution and high purity.Pectic polysaccharides significantly enhanced THP-1 macrophage viability,promoted M1 to M2 polarization,and upregulated the expression of epithelial tight junction proteins.In addition,pectic polysaccharide treatment attenuated body weight loss,lowered disease activity index scores and improved colon histology in mice with dextran sulfate sodium-induced colitis.It also reduced JAK2/STAT3 phosphorylation and NOS2 expression,and increased the expression of tight junction proteins(ZO-1,occludin,and claudin-1).Conclusions:Pectic polysaccharides attenuate ulcerative colitis by increasing M2-related macrophage markers,inhibiting the JAK2/STAT3-NOS2 signaling,and enhancing epithelial barrier-related protein expression.These findings support pectic polysaccharides as a natural candidate for the treatment of ulcerative colitis.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
This study investigated the expression characteristics and clinical significance of gamma-aminobutyric acid A(GABAA)receptor subunit gamma1(GABRG1)in glioma by integrating cancer and normal tissue data from multiple d...This study investigated the expression characteristics and clinical significance of gamma-aminobutyric acid A(GABAA)receptor subunit gamma1(GABRG1)in glioma by integrating cancer and normal tissue data from multiple databases and combining them with experimental evidence.The research revealed that GABRG1 exhibited low expression levels in glioma,and its low expression was closely associated with unfavorable clinical outcomes.Furthermore,a prognostic model with strong decision-making ability was constructed using multivariate Cox regression analysis,incorporating age,isocitric dehydrogenase(IDH)mutation status,O6-methylguanine-DNA methyltransferase(MGMT)methylation status,World Health Organization(WHO)grade,and GABRG1 expression.Additionally,GABRG1 might be associated with the expression of tumor-associated macrophages and was significantly linked to immune regulatory processes.This study provided a new target for immunotherapy in glioma and offered a novel indicator for predicting and evaluating the clinical prognosis of patients.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
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.
基金supported by Ningbo Top Medical and Health Research Program(No.2022030410)National Key Research and Development Program of China(No.2022YFC3300905,2023YFC3304202).
文摘Accumulating evidence has highlighted the functional role of the endogenous nociceptin/orphanin FQ peptide(N/OFQ)and its nociceptin opioid receptor(NOP)in alcohol and cocaine reward.However,the effects of NOP agonists on methamphetamine(MAP)reinforcement,motivation,and relapse remain uncertain.In this study,we evaluated the effects of Ro 64-6198,a selective NOP agonist,on MAP reinforcement,motivation,and relapse in rats.Rats underwent a fixed-ratio 1(FR1)training to establish stable MAP intravenous self-administration(0.05 mg/kg/infusion)for 12 days,and the motivation for MAP was quantified using a progressive-ratio(PR)schedule,while the relapse was assessed through cue-and MAP-primed reinstatement after abstinence.Western blot analysis was employed to measure the relative expression of phosphorylated CREB,ERK,and Akt in the nucleus accumbens(NAc)following drug priming.Acute treatment of Ro 64-6198(1 mg/kg)significantly reduced the motivated behavior for MAP under PR testing(P<0.05 vs.vehicle).Ro 64-6198 at doses of 0.3 and 1 mg/kg could suppress the drug-seeking behavior induced by extinction or cues,respectively(P<0.05),whereas only the higher dose(1 mg/kg)could attenuate MAP primed drug-seeking(P<0.05).These behavioral effects were related to the upregulated phosphorylation of CREB and Akt in the NAc.Our results provide preclinical evidence that NOP activation disrupts multiple addiction-relevant behaviors,positioning Ro 64-6198 as a potential therapeutic candidate for treating MAP use disorders.
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Project supported by the National Natural Science Foundation of China(Nos.22071242,21871260)。
文摘Cyclopropenones have been extensively utilized in catalytic ring-opening and ring-expansion reactions for the synthesis of unsaturated carbonyl compounds.The first rhodium-catalyzed ring-opening reaction of aryl-/alkyl-substituted cyclopropenones is accomplished,successfully affording acyloin derivatives.This transformation represents a novel reaction pattern involving cyclopropenones.The resulting acyloin products constitute important building blocks in organic synthesis and serve as fundamental structural frameworks in numerous natural products.
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National Nature Science Foundation of China,No.81870944(to FL).
文摘This study investigated the neuroprotective effects of lactate in subarachnoid hemorrhage,a severe cerebrovascular disease that is commonly caused by arterial aneurysm rupture and has limited early treatment options.Lactate,a metabolic byproduct,has been shown to have neuroprotective properties,including enhancing cerebral microcirculation and reducing intracranial pressure in acute brain injury patients.However,the protective mechanisms of lactate in subarachnoid hemorrhage remain unknown.In this study,we showed that lactate alleviates early brain damage in subarachnoid hemorrhage by promoting neuronal lipid synthesis and the formation of lipid droplets in astrocytes.In vivo experiments using a subarachnoid hemorrhage mouse model showed that lactate treatment significantly improved neurological scores,reduced brain inflammation,and promoted lipid droplet formation in astrocytes within 24 hours.Lactate treatment increased free fatty acids levels in the brain.The results suggest that astrocytes absorbed these free fatty acids and converted them into lipid droplets,thus reducing cellular lipotoxicity.Moreover,lactate enhanced the antiapoptotic capacity of astrocytes by upregulating the expression of PLIN5,a protein crucial for lipid droplet formation.The inhibition of lipid synthesis or lipid droplet formation counteracted the neuroprotective effects of lactate,indicating that lactate’s protective role is closely linked to lipid metabolism and lipid droplet formation.In vitro experiments on HT22 neuronal cells exposed to hemin-an agent used to simulate subarachnoid hemorrhage injury-demonstrated that lactate mitigated cellular damage by reducing lipid peroxidation and preserving mitochondrial membrane potential.Lactate treatment in HT22 cells and astrocytes also showed that inhibition of lipid synthesis or lipid droplet formation reversed its protective effects,further emphasizing the importance of lipid metabolism in the neuroprotective action of lactate.This study provides insights into the neuroprotective mechanisms of lactate in subarachnoid hemorrhage.It indicates that lactate plays a role in promoting lipid synthesis in neurons and enhancing lipid droplet formation in astrocytes,thus mitigating brain damage and improving cell survival.These findings suggest that lactate,through its regulation of lipid metabolism,could be a potential therapeutic agent for subarachnoid hemorrhage.
基金supported by the National Natural Science Foundation of China(Grant No.82472312).
文摘Mosquito-borne diseases pose a significant global health threat,necessitating the development of innovative vector control strategies.In this study,we investigated the potential of harnessing host immunity against mosquitoes through vaccination.Using Culex pipiens(C.pipiens)as a model,we demonstrated that polyclonal antibodies against C.pipiens abdominal protein extracts significantly impaired oviposition and increased mosquito mortality,primarily through the classical complement activation pathways.However,repeated exposure led to resistance,indicating potential adaptation.Proteomic analysis identified metabolic proteins as key targets,with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses highlighting their roles in carboxylic acid metabolism,tyrosine degradation,and the proteasome pathways.Notably,cross-species reactivity was revealed by Western blotting,showing strong binding of Culex-specific antibodies to Anopheles and Aedes abdominal proteins.This study provides mechanistic insights into antibody-based mosquito suppression,highlighting its potential as an innovative vector control strategy while underscoring the need for further research on resistance management and ecological impacts.
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.
基金National Natural Science Foundation of China,No.81901336(to JM).
文摘Subarachnoid hemorrhage is a subtype of stroke that causes severe neurological damage and is associated with poor long-term prognosis.Cognitive impairment is a major manifestation of long-term neurological dysfunction in patients with subarachnoid hemorrhage.However,there is notable absence of biological markers to predict long-term prognosis in this patient population.Given the aging-like neurocognitive phenomena associated with subarachnoid hemorrhage,this study postulates that telomere length,a recognized biomarker for aging,could be used as a prognostic indicator for subarachnoid hemorrhage.A left internal carotid artery intravascular puncture mouse model was used to simulate subarachnoid hemorrhage.Comprehensive neurological test scores were obtained through neurobehavioral assessments conducted at one-month intervals.Concurrently,the relative telomere length was analyzed by quantitative polymerase chain reaction,which was performed using DNA extracted from ear notch and brain tissue after each assessment.Furthermore,proteomic analysis was employed to investigate differential protein expression in hippocampal tissue.Subarachnoid hemorrhage mice exhibited persistent neurocognitive impairment over a prolonged period of time.There was a significant positive correlation between telomere length and neurological test scores,confirming the usefulness of telomere length as a prognostic indicator in subarachnoid hemorrhage.Hippocampal tissue from subarachnoid hemorrhage mice showed reduced expression of acetyl-coenzyme A synthetase-2 and abnormalities in the expression of proteins related to ribosomes,energy metabolism,and cellular signal transduction.This study confirmed telomere shortening in the brain and metabolic disturbances in the hippocampi of subarachnoid hemorrhage mice.Thus,telomere length is a predictive marker for long-term impairment of cognitive function in mice following experimental subarachnoid hemorrhage.
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.
基金supported by the Key Research and Development Project of Hainan Province(ZDYF2022SHFZ099)the Academic Enhancement Support Program of Hainan Medical University(XSTS2025040 and XSTS2025063).
文摘Objective:To investigate the effect of pectic polysaccharides isolated from Rauvolfia verticillata on ulcerative colitis and its underlying mechanisms.Methods:Pectic polysaccharides were characterized using high-performance liquid chromatography with 1-phenyl-3-methyl-5-pyrazolone pre-column derivatization,phenol-sulfuric acid assay,and gel permeation chromatography.HT-29 cells were stimulated with lipopolysaccharide and then treated with pectic polysaccharides;conditioned medium was applied to THP-1-derived macrophages to assess cell viability and polarization,while tight junction protein expression was analyzed in HT-29 cells.Furthermore,a mouse model of dextran sulfate sodium-induced colitis was treated with oral pectic polysaccharides or NOS2 overexpression.Body weight,disease activity index,colon length,histopathology,and the protein expression related to the JAK2/STAT3-NOS2 signaling were evaluated.Results:The pectic polysaccharide was characterized as an acidic pectic polysaccharide,primarily composed of galacturonic acid and various neutral sugars,with a narrow molecular weight distribution and high purity.Pectic polysaccharides significantly enhanced THP-1 macrophage viability,promoted M1 to M2 polarization,and upregulated the expression of epithelial tight junction proteins.In addition,pectic polysaccharide treatment attenuated body weight loss,lowered disease activity index scores and improved colon histology in mice with dextran sulfate sodium-induced colitis.It also reduced JAK2/STAT3 phosphorylation and NOS2 expression,and increased the expression of tight junction proteins(ZO-1,occludin,and claudin-1).Conclusions:Pectic polysaccharides attenuate ulcerative colitis by increasing M2-related macrophage markers,inhibiting the JAK2/STAT3-NOS2 signaling,and enhancing epithelial barrier-related protein expression.These findings support pectic polysaccharides as a natural candidate for the treatment of ulcerative colitis.
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 National Natural Science Foundation of China(82271340,82071368)the Outstanding Youth Funding of Harbin Medical University(HYD2020JQ0016)the Horizontal Subject(86010900)。
文摘This study investigated the expression characteristics and clinical significance of gamma-aminobutyric acid A(GABAA)receptor subunit gamma1(GABRG1)in glioma by integrating cancer and normal tissue data from multiple databases and combining them with experimental evidence.The research revealed that GABRG1 exhibited low expression levels in glioma,and its low expression was closely associated with unfavorable clinical outcomes.Furthermore,a prognostic model with strong decision-making ability was constructed using multivariate Cox regression analysis,incorporating age,isocitric dehydrogenase(IDH)mutation status,O6-methylguanine-DNA methyltransferase(MGMT)methylation status,World Health Organization(WHO)grade,and GABRG1 expression.Additionally,GABRG1 might be associated with the expression of tumor-associated macrophages and was significantly linked to immune regulatory processes.This study provided a new target for immunotherapy in glioma and offered a novel indicator for predicting and evaluating the clinical prognosis of patients.
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.
