Accurate genotyping and prognosis of glioma patients present significant clinical challenges,often dependent on subjective judgement and insufficient scientific evidence.This study aims to develop a robust,noninvasive...Accurate genotyping and prognosis of glioma patients present significant clinical challenges,often dependent on subjective judgement and insufficient scientific evidence.This study aims to develop a robust,noninvasive preoperative multi-modal MRIbased transformer learning model to predict IDH genotyping and glioma prognosis.This multi-centre study included 563 glioma patients to develop an interpretable classification model utilising various preoperative imaging sequences,including T1-weighted,T2-weighted,fluid-attenuated inversion recovery,contrast-enhanced T1-weighted,and diffusion-weighted imaging.The model employs a multi-task learning framework to extract and fuse radiomic,deep learning,and clinical features for IDH genotyping and glioma prognosis.Additionally,a multi-modal transformer strategy is integrated to analyse structural and functional MRI,thereby enhancing model performance.Experimental results indicate that the model demonstrates superior performance,surpassing previous research and other state-of-the-art methods.The model achieves an AUC of 91.40% in the IDH genotyping task and 93.37% in the glioma prognosis task.Group analysis reveals that the model exhibits higher sensitivity to IDH-mutant cases and more accurately identifies low-risk groups compared to medium-or high-risk groups.This study aims to achieve accurate IDH genotyping and glioma prognosis through effective classification method,offering valuable diagnostic insights for clinical practice and expediting treatment decisions.展开更多
Traumatic brain injury can be categorized into primary and secondary injuries.Secondary injuries are the main cause of disability following traumatic brain injury,which involves a complex multicellular cascade.Microgl...Traumatic brain injury can be categorized into primary and secondary injuries.Secondary injuries are the main cause of disability following traumatic brain injury,which involves a complex multicellular cascade.Microglia play an important role in secondary injury and can be activated in response to traumatic brain injury.In this article,we review the origin and classification of microglia as well as the dynamic changes of microglia in traumatic brain injury.We also clarify the microglial polarization pathways and the therapeutic drugs targeting activated microglia.We found that regulating the signaling pathways involved in pro-inflammatory and anti-inflammatory microglia,such as the Toll-like receptor 4/nuclear factor-kappa B,mitogen-activated protein kinase,Janus kinase/signal transducer and activator of transcription,phosphoinositide 3-kinase/protein kinase B,Notch,and high mobility group box 1 pathways,can alleviate the inflammatory response triggered by microglia in traumatic brain injury,thereby exerting neuroprotective effects.We also reviewed the strategies developed on the basis of these pathways,such as drug and cell replacement therapies.Drugs that modulate inflammatory factors,such as rosuvastatin,have been shown to promote the polarization of antiinflammatory microglia and reduce the inflammatory response caused by traumatic brain injury.Mesenchymal stem cells possess anti-inflammatory properties,and clinical studies have confirmed their significant efficacy and safety in patients with traumatic brain injury.Additionally,advancements in mesenchymal stem cell-delivery methods—such as combinations of novel biomaterials,genetic engineering,and mesenchymal stem cell exosome therapy—have greatly enhanced the efficiency and therapeutic effects of mesenchymal stem cells in animal models.However,numerous challenges in the application of drug and mesenchymal stem cell treatment strategies remain to be addressed.In the future,new technologies,such as single-cell RNA sequencing and transcriptome analysis,can facilitate further experimental studies.Moreover,research involving non-human primates can help translate these treatment strategies to clinical practice.展开更多
Neuroinflammation is a key process in the pathogenesis of various neurodegenerative diseases,such as multiple sclerosis(MS),Alzheimer's disease,and traumatic brain injury.Even for disorders historically unrelated ...Neuroinflammation is a key process in the pathogenesis of various neurodegenerative diseases,such as multiple sclerosis(MS),Alzheimer's disease,and traumatic brain injury.Even for disorders historically unrelated to neuroinflammation,such as Alzheimer's disease,it is now shown to precede pathological protein aggregations.展开更多
GNAO1-associated disorder is a rare disease and an example of developmental and epileptic encephalopathies.Caused by ca.150 different dominant missense mutations in the gene encoding the major neuronal G protein Gao,i...GNAO1-associated disorder is a rare disease and an example of developmental and epileptic encephalopathies.Caused by ca.150 different dominant missense mutations in the gene encoding the major neuronal G protein Gao,it spans a wide range of neurological clinical manifestations,that may include epileptic seizures,motor dysfunctions,developmental and intellectual delay,and other symptoms(Sáez González et al.,2023).展开更多
AIM:To build a functional generalized estimating equation(GEE)model to detect glaucomatous visual field progression and compare the performance of the proposed method with that of commonly employed algorithms.METHODS:...AIM:To build a functional generalized estimating equation(GEE)model to detect glaucomatous visual field progression and compare the performance of the proposed method with that of commonly employed algorithms.METHODS:Totally 716 eyes of 716 patients with primary open angle glaucoma(POAG)with at least 5 reliable 24-2 test results and 2y of follow-up were selected.The functional GEE model was used to detect perimetric progression in the training dataset(501 eyes).In the testing dataset(215 eyes),progression was evaluated the functional GEE model,mean deviation(MD)and visual field index(VFI)rates of change,Advanced Glaucoma Intervention Study(AGIS)and Collaborative Initial Glaucoma Treatment Study(CIGTS)scores,and pointwise linear regression(PLR).RESULTS:The proposed method showed the highest proportion of eyes detected as progression(54.4%),followed by the VFI rate(34.4%),PLR(23.3%),and MD rate(21.4%).The CIGTS and AGIS scores had a lower proportion of eyes detected as progression(7.9%and 5.1%,respectively).The time to detection of progression was significantly shorter for the proposed method than that of other algorithms(adjusted P≤0.019).The VFI rate displayed moderate pairwise agreement with the proposed method(k=0.47).CONCLUSION:The functional GEE model shows the highest proportion of eyes detected as perimetric progression and the shortest time to detect perimetric progression in patients with POAG.展开更多
Neuroserpin,a secreted protein that belongs to the serpin superfamily of serine protease inhibitors,is highly expressed in the central nervous system and plays multiple roles in brain development and pathology.As a na...Neuroserpin,a secreted protein that belongs to the serpin superfamily of serine protease inhibitors,is highly expressed in the central nervous system and plays multiple roles in brain development and pathology.As a natural inhibitor of recombinant tissue plasminogen activator,neuroserpin inhibits the increased activity of tissue plasminogen activator in ischemic conditions and extends the therapeutic windows of tissue plasminogen activator for brain ischemia.However,the neuroprotective mechanism of neuroserpin against ischemic stroke remains unclear.In this study,we used a mouse model of middle cerebral artery occlusion and oxygen-glucose deprivation/reperfusion-injured cortical neurons as in vivo and in vitro ischemia-reperfusion models,respectively.The models were used to investigate the neuroprotective effects of neuroserpin.Our findings revealed that endoplasmic reticulum stress was promptly triggered following ischemia,initially manifesting as the acute activation of endoplasmic reticulum stress transmembrane sensors and the suppression of protein synthesis,which was followed by a later apoptotic response.Notably,ischemic stroke markedly downregulated the expression of neuroserpin in cortical neurons.Exogenous neuroserpin reversed the activation of multiple endoplasmic reticulum stress signaling molecules,the reduction in protein synthesis,and the upregulation of apoptotic transcription factors.This led to a reduction in neuronal death induced by oxygen/glucose deprivation and reperfusion,as well as decreased cerebral infarction and neurological dysfunction in mice with middle cerebral artery occlusion.However,the neuroprotective effects of neuroserpin were markedly inhibited by endoplasmic reticulum stress activators thapsigargin and tunicamycin.Our findings demonstrate that neuroserpin exerts neuroprotective effects on ischemic stroke by suppressing endoplasmic reticulum stress.展开更多
Primary liver cancer(PLC) is one of the most common malignant tumors in China. PLC is characterized by insidious onset, rapid progress, poor quality of life, and short survival time. Notably, current treatment strateg...Primary liver cancer(PLC) is one of the most common malignant tumors in China. PLC is characterized by insidious onset, rapid progress, poor quality of life, and short survival time. Notably, current treatment strategies remain unsatisfactory. Traditional Chinese medicines(TCM) have been used to treat a variety of diseases, including liver diseases, for more than 2000 years. In this study, we performed a review of the use frequency and clinical efficacy of TCM in treating PLC. Relevant literature from January 1, 2009, to January 1, 2021 was retrieved from network databases of China National Knowledge Infrastructure(CNKI), Chongqing VIP, Wanfang, PubMed, and SinoMed. The most frequently used TCM and their efficacy in PLC treatment were summarized. Based on the inclusion and exclusion criteria, 33 articles were selected. Overall, the efficacy of the combination of TCM and Western medicines in the treatment of PLC was higher than that in the control groups(i.e. treatment with Western medicines alone)(65.11% vs.44.31%, P <.05). Among the 33 selected articles, 11 were investigated for TCM preparation(marketed drugs) and 22 for TCM formulas. In total, 102 types of TCM(single herbs) were used to treat PLC. The top five most frequently used TCM were Poria(14.71%), Astragali radix(13.73%), Atractylodis Macrocephalae Rhizoma(12.75%), Bupleuri radix(12.75%), and Glycyrrhizae radix et Rhizoma(11.76%). Of the 102 types of TCM, tonics were the most frequently used categories, followed by heat-clearing medicines, blood-invigorating medicines, and stasis-resolving medicines. Of 207 papers, 174(84.06%) could not be subjected to statistical analysis due to research quality. Further high-quality research on herb sources, formula components and dosage, toxicology, and ethics of TCM is necessary. In conclusion, TCM play a promising role in the treatment and management of PLC, although further investigations are warranted.展开更多
Epigenetics refers to herita ble and reversible processes regulating gene expression that do not involve a change to the DNA sequence.Epigenetic modifications include DNA modifications(e.g.DNA methylation a nd hydroxy...Epigenetics refers to herita ble and reversible processes regulating gene expression that do not involve a change to the DNA sequence.Epigenetic modifications include DNA modifications(e.g.DNA methylation a nd hydroxymethyl at ion),histone modifications,and non-coding RNAs such as micro RNAs and long-coding RNAs(Holtzman and Gersbach.展开更多
Historically,"big pharma"did most central nervous system drug discovery R&D in-house.Yet,in modern times their"management reductionism"resulted in disappointing pipelines and pharma resided to(...Historically,"big pharma"did most central nervous system drug discovery R&D in-house.Yet,in modern times their"management reductionism"resulted in disappointing pipelines and pharma resided to(late)development,regulatory approval,and marketing(Thong,2015).This had significant consequences for financing and executing research,resulting in a larger role for funding by governments and patient-organizations and a shift of research to academia(Mazzucato,2013).展开更多
Objective Junctophilin-2(JPH2)is an essential structural protein that maintains junctional membrane complexes(JMCs)in cardiomyocytes by tethering the plasma membrane to the sarcoplasmic reticulum,thereby facilitating ...Objective Junctophilin-2(JPH2)is an essential structural protein that maintains junctional membrane complexes(JMCs)in cardiomyocytes by tethering the plasma membrane to the sarcoplasmic reticulum,thereby facilitating excitationcontraction(E-C)coupling.Mutations in JPH2 have been associated with hypertrophic cardiomyopathy(HCM),but the molecular mechanisms governing its membrane-binding properties and the functional relevance of its membrane occupation and recognition nexus(MORN)repeat motifs remain incompletely understood.This study aimed to elucidate the structural basis of JPH2 membrane association and its implications for HCM pathogenesis.Methods A recombinant N-terminal fragment of mouse JPH2(residues 1-440),encompassing the MORN repeats and an adjacent helical region,was purified under near-physiological buffer conditions.X-ray crystallography was employed to determine the structure of the JPH2 MORN-Helix domain.Sequence conservation analysis across species and junctophilin isoforms was performed to assess the evolutionary conservation of key structural features.Functional membrane-binding assays were conducted using liposome co-sedimentation and cell-based localization studies in COS7 and HeLa cells.In addition,site-directed mutagenesis targeting positively charged residues and known HCM-associated mutations,including R347C,was used to evaluate their effects on membrane interaction and subcellular localization.Results The crystal structure of the mouse JPH2 MORN-Helix domain was resolved at 2.6Å,revealing a compact,elongated architecture consisting of multiple tandem MORN motifs arranged in a curved configuration,forming a continuous hydrophobic core stabilized by alternating aromatic residues.A C-terminalα-helix further reinforced structural integrity.Conservation analysis identified the inner groove of the MORN array as a highly conserved surface,suggesting its role as a protein-binding interface.A flexible linker segment enriched in positively charged residues,located adjacent to the MORN motifs,was found to mediate direct electrostatic interactions with negatively charged phospholipid membranes.Functional assays demonstrated that mutation of these basic residues impaired membrane association,while the HCM-linked R347C mutation completely abolished membrane localization in cellular assays,despite preserving the overall MORN-Helix fold in structural modeling.Conclusion This study provides structural insight into the membrane-binding mechanism of the cardiomyocyte-specific protein JPH2,highlighting the dual roles of its MORN-Helix domain in membrane anchoring and protein interactions.The findings clarify the structural basis for membrane targeting via a positively charged linker and demonstrate that disruption of this interaction—such as that caused by the R347C mutation—likely contributes to HCM pathogenesis.These results not only enhance current understanding of JPH2 function in cardiac E-C coupling but also offer a structural framework for future investigations into the assembly and regulation of JMCs in both physiological and disease contexts.展开更多
BACKGROUND Primary splenic lesions are rare and often detected incidentally through imaging,biopsy,or autopsy,typically without distinct clinical symptoms.Although imaging can help differentiate benign from malignant ...BACKGROUND Primary splenic lesions are rare and often detected incidentally through imaging,biopsy,or autopsy,typically without distinct clinical symptoms.Although imaging can help differentiate benign from malignant lesions,splenic hamartomas,and angiosarcomas may exhibit overlapping features,making diagnosis challenging.This report presents a case of splenic hamartoma suspected to be an angiosarcoma based on preoperative imaging.Splenic hamartomas that mimic angiosarcomas are exceedingly rare.CASE SUMMARY A 33-year-old male presented to the Department of Emergency with frank red blood hematemesis and a 1-week history of epigastric pain.On arrival,he was alert and hemodynamically stable.Contrast-enhanced abdominal computed tomography revealed splenomegaly with significant engorgement of the portal and splenic veins,along with a diffuse nodular splenic lesion measuring 8.2 cm×6.2 cm.Following esophageal varix ligation,abdominal magnetic resonance imaging demonstrated iso-to high-signal intensity within the splenic mass and multiple hypervascular lesions in the right hepatic lobe,raising suspicion for splenic an-giosarcoma with hepatic metastases.18F-fluorodeoxyglucose positron emission tomography-computed tomography showed diffusely mild increased metabolic activity in the spleen.The patient subsequently underwent splenectomy and liver biopsy.Histopathological examination revealed chronic inflammation in the liver,and the splenic lesion was confirmed to be a splenic hamartoma.The patient successfully returned to work and remains in good health.CONCLUSION This rare case of splenic hamartoma mimicking angiosarcoma highlights the importance of differential diagnosis in managing splenic tumors.展开更多
BACKGROUND Although obesity is a well-established contributor to surgical risks,evidence regarding the specific outcomes of laparoscopic cholecystectomy(LC)in obese patients remains scarce.AIM To assess clinicopatholo...BACKGROUND Although obesity is a well-established contributor to surgical risks,evidence regarding the specific outcomes of laparoscopic cholecystectomy(LC)in obese patients remains scarce.AIM To assess clinicopathologic differences and 1-year outcomes following elective LC in patients with obesity and gallstone disease.METHODS This retrospective study analyzed data from 65 patients who underwent elective LC for gallstone disease between January 2020 and May 2022,with outcomes assessed at the 1-year follow-up.Patients were categorized as obese(body mass index≥25 kg/m^(2))or non-obese(body mass index<25 kg/m^(2)),and comparisons were made across preoperative laboratory values,intraoperative parameters,and patient-reported outcomes.RESULTS The obese group had significantly higher American Society of Anesthesiologists scores,higher glycated hemoglobin levels,and lower vitamin D levels than the non-obese group.Elevated triglycerides were more frequent in the obese group,whereas higher high-density lipoprotein levels were more common in the nonobese group.Intraoperative and postoperative outcomes did not differ between the groups.At the 1-year follow-up,24.6%of patients reported post-cholecystectomy symptoms,with no group differences.CONCLUSION Obese patients had higher American Society of Anesthesiologists scores,lower vitamin D,and elevated triglycerides preoperatively,but these differences did not significantly affect intraoperative findings or 1-year postoperative outcomes compared to non-obese patients.展开更多
In this editorial,I discuss the article by Wang et al,published in the World Journal of Diabetes,which explores jejunoileal side-to-side anastomosis as a novel surgical intervention for type 2 diabetes mellitus(T2DM)....In this editorial,I discuss the article by Wang et al,published in the World Journal of Diabetes,which explores jejunoileal side-to-side anastomosis as a novel surgical intervention for type 2 diabetes mellitus(T2DM).T2DM,often associated with obesity,remains a global health challenge,as sustained remission is difficult to achieve with conventional pharmacological therapy.Jejunoileal anastomosis offers a promising alternative,particularly for patients with normal or relatively high body mass index,and addresses the unique challenges posed by diverse patient populations.This procedure preserves gastric anatomy while simultaneously improving metabolic parameters,such as glycemic control,lipid profiles,and pancreaticβ-cell function.Unlike traditional metabolic surgeries that involve permanent anatomical alterations,this approach provides advantages such as reversibility,shorter operative times,and minimal nutritional complications,making it appealing to patients for whom conventional bariatric surgery is unsuitable.Advances in gut hormone physiology and incretin modulation support these findings.This innovative approach represents a potential paradigm shift in T2DM treatment,offering insights into the evolving role of surgical interventions in metabolic regulation.While early findings show promising diabetes remission rates and metabolic improvements at six months post-surgery,further studies with longer follow-up periods and broader patient cohorts are required.展开更多
The treatment of prolonged inflammation and cartilage damage due to osteoarthritis(OA)is a major clinical challenge.We developed a comprehensive cartilage repair therapy using a dual drug-loaded nanocomposite hydrogel...The treatment of prolonged inflammation and cartilage damage due to osteoarthritis(OA)is a major clinical challenge.We developed a comprehensive cartilage repair therapy using a dual drug-loaded nanocomposite hydrogel that leveraged the spatiotemporal immunomodulatory effects of a naturally degradable protein-based nanocomposite hydrogel.The hydrogel acted as a scaffold that created a favorable microenvironment for cartilage regeneration.The hydrogel recruited macrophages and human mesenchymal stem cells(hMSCs),which supported the growth and adhesion of osteoblasts,and degraded to provide nutrition.Silk protein nanoparticles were chemically cross-linked with kartogenin,and humanlike collagen was physically cross-linked with dexamethasone through hydrogen bonding.In the early stages of cartilage repair,a large quantity of dexamethasone was released.The dexamethasone acted as an anti-inflammatory agent and a spatiotemporal modulator of the polarization of M1 macrophages into M2 macrophages.In the middle and late stages of cartilage repair,kartogenin underwent sustained release from the hydrogel,inducing the differentiation of hMSCs into chondrocytes and maintaining chondrocyte stability.Therefore,kartogenin and dexamethasone acted synergistically to induce cartilage repair.In conclusion,we developed an integrated therapeutic system by constructing a cartilage regeneration microenvironment and inducing synergistic drug-based cartilage regeneration.The therapeutic system demonstrated satisfactory efficacy for repairing cartilage damage in rabbits.展开更多
People living long-term in areas with UV will cause premature photoaging.An abnormal reduction in autophagy is a key feature of photoaging,and p38 MAPK has been regarded as a key regulator of autophagy.Isothiocyanate ...People living long-term in areas with UV will cause premature photoaging.An abnormal reduction in autophagy is a key feature of photoaging,and p38 MAPK has been regarded as a key regulator of autophagy.Isothiocyanate is one of the main active components of Moringa oleifera Lam.seeds.Studies have reported that M.oleifera Lam.seeds iso thiocyanate(MITC)has anticancer,anti-inflammatory,cardio metabolic repair,nervous system protection,blood lipid regulation and diabetes prevention properties.However,the molecular mechanisms of MITC with protective effects against skin photoaging have not been studied thus far.In this study,we aimed to evaluate the antiphotoaging activity of MITC and to investigate the effect of p38 MAPK-dependent autophagy in vivo and in vitro models of photoaging.In this research we found that MITC can reverse the intracellular reactive oxygen species(ROS)content and inhibit the activation of p38 MAPK to improve the autophagy level,reduce the expression of matrix metalloproteinases(MMPs),and finally protect against photoaging by UV.Our results will uncover the molecular mechanisms of MITC that play a role in the protective effects against skin photoaging,provide helpful information for developing MITC as an anti-photoaging plant material and improve the utilization of M.oleifera Lam.seeds.展开更多
BACKGROUND To treat flexor pollicis longus(FPL)muscle function loss,the 4th flexor digitorum superficialis(FDS)to the FPL tendon transfer is preferred as a reconstruction method.Various complications can occur during ...BACKGROUND To treat flexor pollicis longus(FPL)muscle function loss,the 4th flexor digitorum superficialis(FDS)to the FPL tendon transfer is preferred as a reconstruction method.Various complications can occur during transfer.However,median nerve neuropathy has not been reported yet.We present a case of median nerve neuropathy caused by irritation of suture knots of the 4th FDS to the FPL tendon transfer with a review of the literature.CASE SUMMARY A 52-year-old male patient presented with paresthesia along median nerve distribution of right hand after tendon transfer.He complained of right thumb flexion limitation due to FPL function loss so authors performed the 4th FDS to FPL transfer using Pulvertaft weave technique.FPL function loss was due to adhesion resulting from repeated surgery of radius shaft.He had a history of radius shaft open fracture 9 years ago and nonunion 7 years ago.During surgery,FPL muscle was severely adhered and indistinguishable.However,tendon continuity remained intact.After tendon transfer,he experienced paresthesia along median nerve distribution upon movement of thumb.He was diagnosed with median nerve neuropathy caused by irritation of tendon suture knots.Exploration was then performed.The median nerve was irritated by suture knots of transferred tendon.Thus,knots were removed.Twelve months later,he demonstrated thumb flexion of 80°.Additionally,median nerve neuropathy symptoms fully resolved.CONCLUSION Median nerve neuropathy can occur after tendon transfer from irritation of suture knots.Covering knots using surrounding tissue is recommended.展开更多
BACKGROUND Balloon-assisted enteroscopy with a specialized overtube has improved the success of endoscopic retrograde cholangiopancreatography(ERCP)in patients with surgically altered anatomy(SAA).However,direct compa...BACKGROUND Balloon-assisted enteroscopy with a specialized overtube has improved the success of endoscopic retrograde cholangiopancreatography(ERCP)in patients with surgically altered anatomy(SAA).However,direct comparative data between double-balloon enteroscopy(DBE)and single-balloon enteroscopy(SBE)remain limited.AIM To compare the ERCP-related outcomes between DBE and SBE in patients with SAA.METHODS We retrospectively reviewed the medical records of 1042 patients with SAA who underwent ERCP.After propensity score matching for age and sex,494 patients were included,with 247 patients in each of the SBE and DBE groups.RESULTS The success rates of intubation,cannulation,completion of intended ERCP,and adverse events were similar between the DBE and SBE groups(94.3%vs 96.4%,P=0.393;89.5%vs 93.5%,P=0.147;88.3%vs 92.7%,P=0.125;10.5%vs 14.6%,P=0.222,respectively).However,the SBE group had significantly longer intubation and procedure times than the DBE group(23.5±22.3 minutes vs 14.1±13.5 minutes,P<0.001;65.2±37.9 minutes vs 31.0±18.5 minutes,P<0.001).Preserved gastric anatomy and Roux-en-Y reconstruction were independently associated with intubation failure(odds ratio=3.18,95%confidence interval:1.30-8.31;odds ratio=8.65,95%confidence interval:1.71-157.60,respectively).CONCLUSION DBE and SBE showed comparable clinical success and safety profiles in ERCP for patients with SAA,although SBE required significantly longer procedure times.DBE could provide procedural efficiency benefits in cases where an extended procedure duration is expected.Furthermore,a preserved gastric anatomy and Roux-en-Y reconstruction were identified as independent risk factors for intubation failure.展开更多
Ferroptosis is a form of cell death that occurs when there is an excess of reactive oxygen species(ROS),lipid peroxidation,and iron accumulation.The precise regulation of metabolic pathways,including iron,lipid,and am...Ferroptosis is a form of cell death that occurs when there is an excess of reactive oxygen species(ROS),lipid peroxidation,and iron accumulation.The precise regulation of metabolic pathways,including iron,lipid,and amino acid metabolism,is crucial for cell survival.This type of cell death,which is associated with oxidative stress,is controlled by a complex network of signaling molecules and pathways.It is also implicated in various respiratory diseases such as asthma,chronic obstructive pulmonary disease(COPD),acute lung injury(ALI),lung cancer,pulmonary fibrosis(PF),and the coronavirus disease 2019(COVID-19).To combat drug resistance,it is important to identify appropriate biological markers and treatment targets,as well as intervene in respiratory disorders to either induce or prevent ferroptosis.The focus is on the role of ferroptosis in the development of respiratory diseases and the potential of targeting ferroptosis for prevention and treatment.The review also explores the interaction between immune cell ferroptosis and inflammatory mediators in respiratory diseases,aiming to provide more effective strategies for managing cellular ferroptosis and respiratory disorders.展开更多
The growth of Caenorhabditis elegans involves multiple molting processes,during which old cuticles are shed and new cuticles are rapidly formed.This process requires the regulated bulk secretion of cuticle components....The growth of Caenorhabditis elegans involves multiple molting processes,during which old cuticles are shed and new cuticles are rapidly formed.This process requires the regulated bulk secretion of cuticle components.The transmembrane protein-39(TMEM-39)mutant exhibits distinct dumpy and ruptured phenotypes characterized by notably thin cuticles.TMEM-39 primarily co-localizes with the coat protein II complex(COPII)in large vesicles rather than small COPII vesicles.These TMEM-39-associated large vesicles(TMEM-39-LVs)form robustly during the molting period and co-localize with various extracellular matrix components,including BLI-1 collagen,BLI-3 dual oxidase,and carboxypeptidases.Through immunoprecipitation using TMEM39A-FLAG and proteomics analysis in human sarcoma cells,we identify TMEM39A-associated proteins,including TMEM131.Knockdown of TMEM131 results in reduced TMEM39A-LV formation and collagen secretion in both C.elegans and human sarcoma cells,indicating a cooperative role between TMEM39A and TMEM131 in the secretion of extracellular components through the formation of large COPII vesicles.Given the conservation of TMEM39A and its associated proteins between C.elegans and humans,TMEM39A-LVs may represent a fundamental machinery for rapid and extensive secretion across metazoans.展开更多
A recent single-center retrospective study by Rao et al has offered valuable insights into the prognostic utility of ascitic fluid characteristics in acute pancreatitis.Their findings,which demonstrate associations be...A recent single-center retrospective study by Rao et al has offered valuable insights into the prognostic utility of ascitic fluid characteristics in acute pancreatitis.Their findings,which demonstrate associations between ascitic color,turbidity,and elevated lactate dehydrogenase levels with organ failure,infected pancreatic necrosis,and in-hospital mortality provide a valuable contribution to a relatively underexplored area in pancreatology.However,the reliance on subjective visual assessment and a single time-point evaluation raises concerns regarding reproducibility and dynamic disease monitoring.Furthermore,the lack of integration with objective indicators such as polymorphonuclear cell counts,microbiological cultures,and exudative vs transudative analysis limits the interpretability of the results.Despite these limitations,the study provides a clinically relevant framework that supports further investigation and refinement through prospective,multicenter validation.展开更多
基金supported by the National Natural Science Foundation of China(Grants 82441022,82371934)Medical Science and Technology Research Project of Henan Province(SBGJ202101002)+1 种基金Joint Fund of Henan Province Science and Technology R&D Programme(225200810062)Henan Provincial Medical Science and Technology Research Joint Construction Project(LHGJ20240053,LHGJ20240036).
文摘Accurate genotyping and prognosis of glioma patients present significant clinical challenges,often dependent on subjective judgement and insufficient scientific evidence.This study aims to develop a robust,noninvasive preoperative multi-modal MRIbased transformer learning model to predict IDH genotyping and glioma prognosis.This multi-centre study included 563 glioma patients to develop an interpretable classification model utilising various preoperative imaging sequences,including T1-weighted,T2-weighted,fluid-attenuated inversion recovery,contrast-enhanced T1-weighted,and diffusion-weighted imaging.The model employs a multi-task learning framework to extract and fuse radiomic,deep learning,and clinical features for IDH genotyping and glioma prognosis.Additionally,a multi-modal transformer strategy is integrated to analyse structural and functional MRI,thereby enhancing model performance.Experimental results indicate that the model demonstrates superior performance,surpassing previous research and other state-of-the-art methods.The model achieves an AUC of 91.40% in the IDH genotyping task and 93.37% in the glioma prognosis task.Group analysis reveals that the model exhibits higher sensitivity to IDH-mutant cases and more accurately identifies low-risk groups compared to medium-or high-risk groups.This study aims to achieve accurate IDH genotyping and glioma prognosis through effective classification method,offering valuable diagnostic insights for clinical practice and expediting treatment decisions.
基金supported by the Natural Science Foundation of Yunnan Province,No.202401AS070086(to ZW)the National Key Research and Development Program of China,No.2018YFA0801403(to ZW)+1 种基金Yunnan Science and Technology Talent and Platform Plan,No.202105AC160041(to ZW)the Natural Science Foundation of China,No.31960120(to ZW)。
文摘Traumatic brain injury can be categorized into primary and secondary injuries.Secondary injuries are the main cause of disability following traumatic brain injury,which involves a complex multicellular cascade.Microglia play an important role in secondary injury and can be activated in response to traumatic brain injury.In this article,we review the origin and classification of microglia as well as the dynamic changes of microglia in traumatic brain injury.We also clarify the microglial polarization pathways and the therapeutic drugs targeting activated microglia.We found that regulating the signaling pathways involved in pro-inflammatory and anti-inflammatory microglia,such as the Toll-like receptor 4/nuclear factor-kappa B,mitogen-activated protein kinase,Janus kinase/signal transducer and activator of transcription,phosphoinositide 3-kinase/protein kinase B,Notch,and high mobility group box 1 pathways,can alleviate the inflammatory response triggered by microglia in traumatic brain injury,thereby exerting neuroprotective effects.We also reviewed the strategies developed on the basis of these pathways,such as drug and cell replacement therapies.Drugs that modulate inflammatory factors,such as rosuvastatin,have been shown to promote the polarization of antiinflammatory microglia and reduce the inflammatory response caused by traumatic brain injury.Mesenchymal stem cells possess anti-inflammatory properties,and clinical studies have confirmed their significant efficacy and safety in patients with traumatic brain injury.Additionally,advancements in mesenchymal stem cell-delivery methods—such as combinations of novel biomaterials,genetic engineering,and mesenchymal stem cell exosome therapy—have greatly enhanced the efficiency and therapeutic effects of mesenchymal stem cells in animal models.However,numerous challenges in the application of drug and mesenchymal stem cell treatment strategies remain to be addressed.In the future,new technologies,such as single-cell RNA sequencing and transcriptome analysis,can facilitate further experimental studies.Moreover,research involving non-human primates can help translate these treatment strategies to clinical practice.
基金supported by FWO(Fonds voor Wetenschappelijk Onderzoek),grant number G07562NFWO(to BB)。
文摘Neuroinflammation is a key process in the pathogenesis of various neurodegenerative diseases,such as multiple sclerosis(MS),Alzheimer's disease,and traumatic brain injury.Even for disorders historically unrelated to neuroinflammation,such as Alzheimer's disease,it is now shown to precede pathological protein aggregations.
文摘GNAO1-associated disorder is a rare disease and an example of developmental and epileptic encephalopathies.Caused by ca.150 different dominant missense mutations in the gene encoding the major neuronal G protein Gao,it spans a wide range of neurological clinical manifestations,that may include epileptic seizures,motor dysfunctions,developmental and intellectual delay,and other symptoms(Sáez González et al.,2023).
基金Supported by the Korea Health Technology R&D Project through the Korea Health Industry Development Institute(KHIDI),funded by the Ministry of Health&Welfare,Republic of Korea(No.HR20C0026)the National Research Foundation of Korea(NRF)(No.RS-2023-00247504)the Patient-Centered Clinical Research Coordinating Center,funded by the Ministry of Health&Welfare,Republic of Korea(No.HC19C0276).
文摘AIM:To build a functional generalized estimating equation(GEE)model to detect glaucomatous visual field progression and compare the performance of the proposed method with that of commonly employed algorithms.METHODS:Totally 716 eyes of 716 patients with primary open angle glaucoma(POAG)with at least 5 reliable 24-2 test results and 2y of follow-up were selected.The functional GEE model was used to detect perimetric progression in the training dataset(501 eyes).In the testing dataset(215 eyes),progression was evaluated the functional GEE model,mean deviation(MD)and visual field index(VFI)rates of change,Advanced Glaucoma Intervention Study(AGIS)and Collaborative Initial Glaucoma Treatment Study(CIGTS)scores,and pointwise linear regression(PLR).RESULTS:The proposed method showed the highest proportion of eyes detected as progression(54.4%),followed by the VFI rate(34.4%),PLR(23.3%),and MD rate(21.4%).The CIGTS and AGIS scores had a lower proportion of eyes detected as progression(7.9%and 5.1%,respectively).The time to detection of progression was significantly shorter for the proposed method than that of other algorithms(adjusted P≤0.019).The VFI rate displayed moderate pairwise agreement with the proposed method(k=0.47).CONCLUSION:The functional GEE model shows the highest proportion of eyes detected as perimetric progression and the shortest time to detect perimetric progression in patients with POAG.
基金supported in part by the National Key Research&Development Program of China,No.2022YFA1104900(to LS)the National Natural Science Foundation of China,Nos.82371175,82071535(both to LS),82101614(to YP)+5 种基金the International Science and Technology Cooperation Projects of Guangdong Province,No.2023A0505050121(to LS)Guangdong Basic and Applied Basic Research Foundation,Nos.2022B1515130007(to LS),2023A1515030012(to SZ),2022A1515010666(to WL)the Science and Technology Program of Guangzhou,Nos.202102070001(to LS),202201010041(to YP)Shenzhen Basic Research Grant,Nos.JCYJ20200109140414636,JCYJ20230807145103007(both to WL)awarded a Royal Society Newton Advanced Fellowship,No.AOMS-NAF0051003in collaboration with Zoltán Molnár,Department of Physiology,Anatomy and Genetics,University of Oxford(2017–2021)。
文摘Neuroserpin,a secreted protein that belongs to the serpin superfamily of serine protease inhibitors,is highly expressed in the central nervous system and plays multiple roles in brain development and pathology.As a natural inhibitor of recombinant tissue plasminogen activator,neuroserpin inhibits the increased activity of tissue plasminogen activator in ischemic conditions and extends the therapeutic windows of tissue plasminogen activator for brain ischemia.However,the neuroprotective mechanism of neuroserpin against ischemic stroke remains unclear.In this study,we used a mouse model of middle cerebral artery occlusion and oxygen-glucose deprivation/reperfusion-injured cortical neurons as in vivo and in vitro ischemia-reperfusion models,respectively.The models were used to investigate the neuroprotective effects of neuroserpin.Our findings revealed that endoplasmic reticulum stress was promptly triggered following ischemia,initially manifesting as the acute activation of endoplasmic reticulum stress transmembrane sensors and the suppression of protein synthesis,which was followed by a later apoptotic response.Notably,ischemic stroke markedly downregulated the expression of neuroserpin in cortical neurons.Exogenous neuroserpin reversed the activation of multiple endoplasmic reticulum stress signaling molecules,the reduction in protein synthesis,and the upregulation of apoptotic transcription factors.This led to a reduction in neuronal death induced by oxygen/glucose deprivation and reperfusion,as well as decreased cerebral infarction and neurological dysfunction in mice with middle cerebral artery occlusion.However,the neuroprotective effects of neuroserpin were markedly inhibited by endoplasmic reticulum stress activators thapsigargin and tunicamycin.Our findings demonstrate that neuroserpin exerts neuroprotective effects on ischemic stroke by suppressing endoplasmic reticulum stress.
基金financially supported by the National Natural Science Foundation of China(81874356)the Open Project of Hubei Key Laboratory of Wudang Local Chinese Medicine Research from Hubei University of Medicine(WDCM2018002,WDCM201917,WDCM201918)+1 种基金the Chinese Medicine Project of Health Commission of Hubei Province(ZY2021010)the Foundation for Innovative Research Team of Hubei University of Medicine(2018YHKT01)。
文摘Primary liver cancer(PLC) is one of the most common malignant tumors in China. PLC is characterized by insidious onset, rapid progress, poor quality of life, and short survival time. Notably, current treatment strategies remain unsatisfactory. Traditional Chinese medicines(TCM) have been used to treat a variety of diseases, including liver diseases, for more than 2000 years. In this study, we performed a review of the use frequency and clinical efficacy of TCM in treating PLC. Relevant literature from January 1, 2009, to January 1, 2021 was retrieved from network databases of China National Knowledge Infrastructure(CNKI), Chongqing VIP, Wanfang, PubMed, and SinoMed. The most frequently used TCM and their efficacy in PLC treatment were summarized. Based on the inclusion and exclusion criteria, 33 articles were selected. Overall, the efficacy of the combination of TCM and Western medicines in the treatment of PLC was higher than that in the control groups(i.e. treatment with Western medicines alone)(65.11% vs.44.31%, P <.05). Among the 33 selected articles, 11 were investigated for TCM preparation(marketed drugs) and 22 for TCM formulas. In total, 102 types of TCM(single herbs) were used to treat PLC. The top five most frequently used TCM were Poria(14.71%), Astragali radix(13.73%), Atractylodis Macrocephalae Rhizoma(12.75%), Bupleuri radix(12.75%), and Glycyrrhizae radix et Rhizoma(11.76%). Of the 102 types of TCM, tonics were the most frequently used categories, followed by heat-clearing medicines, blood-invigorating medicines, and stasis-resolving medicines. Of 207 papers, 174(84.06%) could not be subjected to statistical analysis due to research quality. Further high-quality research on herb sources, formula components and dosage, toxicology, and ethics of TCM is necessary. In conclusion, TCM play a promising role in the treatment and management of PLC, although further investigations are warranted.
基金supported by FWO research project G042121 NFWO-SB project 1S25119N+1 种基金tUL PhD grantAlzheimer Netherlands(AN)Major Award(#NL-18026)。
文摘Epigenetics refers to herita ble and reversible processes regulating gene expression that do not involve a change to the DNA sequence.Epigenetic modifications include DNA modifications(e.g.DNA methylation a nd hydroxymethyl at ion),histone modifications,and non-coding RNAs such as micro RNAs and long-coding RNAs(Holtzman and Gersbach.
基金funded by the FWO(1S34321N)the Fondation Charcot Stichting(to TV and RS)。
文摘Historically,"big pharma"did most central nervous system drug discovery R&D in-house.Yet,in modern times their"management reductionism"resulted in disappointing pipelines and pharma resided to(late)development,regulatory approval,and marketing(Thong,2015).This had significant consequences for financing and executing research,resulting in a larger role for funding by governments and patient-organizations and a shift of research to academia(Mazzucato,2013).
文摘Objective Junctophilin-2(JPH2)is an essential structural protein that maintains junctional membrane complexes(JMCs)in cardiomyocytes by tethering the plasma membrane to the sarcoplasmic reticulum,thereby facilitating excitationcontraction(E-C)coupling.Mutations in JPH2 have been associated with hypertrophic cardiomyopathy(HCM),but the molecular mechanisms governing its membrane-binding properties and the functional relevance of its membrane occupation and recognition nexus(MORN)repeat motifs remain incompletely understood.This study aimed to elucidate the structural basis of JPH2 membrane association and its implications for HCM pathogenesis.Methods A recombinant N-terminal fragment of mouse JPH2(residues 1-440),encompassing the MORN repeats and an adjacent helical region,was purified under near-physiological buffer conditions.X-ray crystallography was employed to determine the structure of the JPH2 MORN-Helix domain.Sequence conservation analysis across species and junctophilin isoforms was performed to assess the evolutionary conservation of key structural features.Functional membrane-binding assays were conducted using liposome co-sedimentation and cell-based localization studies in COS7 and HeLa cells.In addition,site-directed mutagenesis targeting positively charged residues and known HCM-associated mutations,including R347C,was used to evaluate their effects on membrane interaction and subcellular localization.Results The crystal structure of the mouse JPH2 MORN-Helix domain was resolved at 2.6Å,revealing a compact,elongated architecture consisting of multiple tandem MORN motifs arranged in a curved configuration,forming a continuous hydrophobic core stabilized by alternating aromatic residues.A C-terminalα-helix further reinforced structural integrity.Conservation analysis identified the inner groove of the MORN array as a highly conserved surface,suggesting its role as a protein-binding interface.A flexible linker segment enriched in positively charged residues,located adjacent to the MORN motifs,was found to mediate direct electrostatic interactions with negatively charged phospholipid membranes.Functional assays demonstrated that mutation of these basic residues impaired membrane association,while the HCM-linked R347C mutation completely abolished membrane localization in cellular assays,despite preserving the overall MORN-Helix fold in structural modeling.Conclusion This study provides structural insight into the membrane-binding mechanism of the cardiomyocyte-specific protein JPH2,highlighting the dual roles of its MORN-Helix domain in membrane anchoring and protein interactions.The findings clarify the structural basis for membrane targeting via a positively charged linker and demonstrate that disruption of this interaction—such as that caused by the R347C mutation—likely contributes to HCM pathogenesis.These results not only enhance current understanding of JPH2 function in cardiac E-C coupling but also offer a structural framework for future investigations into the assembly and regulation of JMCs in both physiological and disease contexts.
基金Supported by Clinical Research Grant from Pusan National University Hospital in 2024.
文摘BACKGROUND Primary splenic lesions are rare and often detected incidentally through imaging,biopsy,or autopsy,typically without distinct clinical symptoms.Although imaging can help differentiate benign from malignant lesions,splenic hamartomas,and angiosarcomas may exhibit overlapping features,making diagnosis challenging.This report presents a case of splenic hamartoma suspected to be an angiosarcoma based on preoperative imaging.Splenic hamartomas that mimic angiosarcomas are exceedingly rare.CASE SUMMARY A 33-year-old male presented to the Department of Emergency with frank red blood hematemesis and a 1-week history of epigastric pain.On arrival,he was alert and hemodynamically stable.Contrast-enhanced abdominal computed tomography revealed splenomegaly with significant engorgement of the portal and splenic veins,along with a diffuse nodular splenic lesion measuring 8.2 cm×6.2 cm.Following esophageal varix ligation,abdominal magnetic resonance imaging demonstrated iso-to high-signal intensity within the splenic mass and multiple hypervascular lesions in the right hepatic lobe,raising suspicion for splenic an-giosarcoma with hepatic metastases.18F-fluorodeoxyglucose positron emission tomography-computed tomography showed diffusely mild increased metabolic activity in the spleen.The patient subsequently underwent splenectomy and liver biopsy.Histopathological examination revealed chronic inflammation in the liver,and the splenic lesion was confirmed to be a splenic hamartoma.The patient successfully returned to work and remains in good health.CONCLUSION This rare case of splenic hamartoma mimicking angiosarcoma highlights the importance of differential diagnosis in managing splenic tumors.
基金Supported by Biomedical Research Institute Grant from Pusan National University Hospital,No.202500360001.
文摘BACKGROUND Although obesity is a well-established contributor to surgical risks,evidence regarding the specific outcomes of laparoscopic cholecystectomy(LC)in obese patients remains scarce.AIM To assess clinicopathologic differences and 1-year outcomes following elective LC in patients with obesity and gallstone disease.METHODS This retrospective study analyzed data from 65 patients who underwent elective LC for gallstone disease between January 2020 and May 2022,with outcomes assessed at the 1-year follow-up.Patients were categorized as obese(body mass index≥25 kg/m^(2))or non-obese(body mass index<25 kg/m^(2)),and comparisons were made across preoperative laboratory values,intraoperative parameters,and patient-reported outcomes.RESULTS The obese group had significantly higher American Society of Anesthesiologists scores,higher glycated hemoglobin levels,and lower vitamin D levels than the non-obese group.Elevated triglycerides were more frequent in the obese group,whereas higher high-density lipoprotein levels were more common in the nonobese group.Intraoperative and postoperative outcomes did not differ between the groups.At the 1-year follow-up,24.6%of patients reported post-cholecystectomy symptoms,with no group differences.CONCLUSION Obese patients had higher American Society of Anesthesiologists scores,lower vitamin D,and elevated triglycerides preoperatively,but these differences did not significantly affect intraoperative findings or 1-year postoperative outcomes compared to non-obese patients.
文摘In this editorial,I discuss the article by Wang et al,published in the World Journal of Diabetes,which explores jejunoileal side-to-side anastomosis as a novel surgical intervention for type 2 diabetes mellitus(T2DM).T2DM,often associated with obesity,remains a global health challenge,as sustained remission is difficult to achieve with conventional pharmacological therapy.Jejunoileal anastomosis offers a promising alternative,particularly for patients with normal or relatively high body mass index,and addresses the unique challenges posed by diverse patient populations.This procedure preserves gastric anatomy while simultaneously improving metabolic parameters,such as glycemic control,lipid profiles,and pancreaticβ-cell function.Unlike traditional metabolic surgeries that involve permanent anatomical alterations,this approach provides advantages such as reversibility,shorter operative times,and minimal nutritional complications,making it appealing to patients for whom conventional bariatric surgery is unsuitable.Advances in gut hormone physiology and incretin modulation support these findings.This innovative approach represents a potential paradigm shift in T2DM treatment,offering insights into the evolving role of surgical interventions in metabolic regulation.While early findings show promising diabetes remission rates and metabolic improvements at six months post-surgery,further studies with longer follow-up periods and broader patient cohorts are required.
基金supported by the National Key Research and Development Program of China(2019YFA0905200).
文摘The treatment of prolonged inflammation and cartilage damage due to osteoarthritis(OA)is a major clinical challenge.We developed a comprehensive cartilage repair therapy using a dual drug-loaded nanocomposite hydrogel that leveraged the spatiotemporal immunomodulatory effects of a naturally degradable protein-based nanocomposite hydrogel.The hydrogel acted as a scaffold that created a favorable microenvironment for cartilage regeneration.The hydrogel recruited macrophages and human mesenchymal stem cells(hMSCs),which supported the growth and adhesion of osteoblasts,and degraded to provide nutrition.Silk protein nanoparticles were chemically cross-linked with kartogenin,and humanlike collagen was physically cross-linked with dexamethasone through hydrogen bonding.In the early stages of cartilage repair,a large quantity of dexamethasone was released.The dexamethasone acted as an anti-inflammatory agent and a spatiotemporal modulator of the polarization of M1 macrophages into M2 macrophages.In the middle and late stages of cartilage repair,kartogenin underwent sustained release from the hydrogel,inducing the differentiation of hMSCs into chondrocytes and maintaining chondrocyte stability.Therefore,kartogenin and dexamethasone acted synergistically to induce cartilage repair.In conclusion,we developed an integrated therapeutic system by constructing a cartilage regeneration microenvironment and inducing synergistic drug-based cartilage regeneration.The therapeutic system demonstrated satisfactory efficacy for repairing cartilage damage in rabbits.
基金supported by National Natural Science Foundation of China(82260703)。
文摘People living long-term in areas with UV will cause premature photoaging.An abnormal reduction in autophagy is a key feature of photoaging,and p38 MAPK has been regarded as a key regulator of autophagy.Isothiocyanate is one of the main active components of Moringa oleifera Lam.seeds.Studies have reported that M.oleifera Lam.seeds iso thiocyanate(MITC)has anticancer,anti-inflammatory,cardio metabolic repair,nervous system protection,blood lipid regulation and diabetes prevention properties.However,the molecular mechanisms of MITC with protective effects against skin photoaging have not been studied thus far.In this study,we aimed to evaluate the antiphotoaging activity of MITC and to investigate the effect of p38 MAPK-dependent autophagy in vivo and in vitro models of photoaging.In this research we found that MITC can reverse the intracellular reactive oxygen species(ROS)content and inhibit the activation of p38 MAPK to improve the autophagy level,reduce the expression of matrix metalloproteinases(MMPs),and finally protect against photoaging by UV.Our results will uncover the molecular mechanisms of MITC that play a role in the protective effects against skin photoaging,provide helpful information for developing MITC as an anti-photoaging plant material and improve the utilization of M.oleifera Lam.seeds.
文摘BACKGROUND To treat flexor pollicis longus(FPL)muscle function loss,the 4th flexor digitorum superficialis(FDS)to the FPL tendon transfer is preferred as a reconstruction method.Various complications can occur during transfer.However,median nerve neuropathy has not been reported yet.We present a case of median nerve neuropathy caused by irritation of suture knots of the 4th FDS to the FPL tendon transfer with a review of the literature.CASE SUMMARY A 52-year-old male patient presented with paresthesia along median nerve distribution of right hand after tendon transfer.He complained of right thumb flexion limitation due to FPL function loss so authors performed the 4th FDS to FPL transfer using Pulvertaft weave technique.FPL function loss was due to adhesion resulting from repeated surgery of radius shaft.He had a history of radius shaft open fracture 9 years ago and nonunion 7 years ago.During surgery,FPL muscle was severely adhered and indistinguishable.However,tendon continuity remained intact.After tendon transfer,he experienced paresthesia along median nerve distribution upon movement of thumb.He was diagnosed with median nerve neuropathy caused by irritation of tendon suture knots.Exploration was then performed.The median nerve was irritated by suture knots of transferred tendon.Thus,knots were removed.Twelve months later,he demonstrated thumb flexion of 80°.Additionally,median nerve neuropathy symptoms fully resolved.CONCLUSION Median nerve neuropathy can occur after tendon transfer from irritation of suture knots.Covering knots using surrounding tissue is recommended.
基金Supported by National Research Foundation of Korea,No.RS-2022-NRO71822Hallym University Medical Center Research Fund(Mighty Hallym,4.0).
文摘BACKGROUND Balloon-assisted enteroscopy with a specialized overtube has improved the success of endoscopic retrograde cholangiopancreatography(ERCP)in patients with surgically altered anatomy(SAA).However,direct comparative data between double-balloon enteroscopy(DBE)and single-balloon enteroscopy(SBE)remain limited.AIM To compare the ERCP-related outcomes between DBE and SBE in patients with SAA.METHODS We retrospectively reviewed the medical records of 1042 patients with SAA who underwent ERCP.After propensity score matching for age and sex,494 patients were included,with 247 patients in each of the SBE and DBE groups.RESULTS The success rates of intubation,cannulation,completion of intended ERCP,and adverse events were similar between the DBE and SBE groups(94.3%vs 96.4%,P=0.393;89.5%vs 93.5%,P=0.147;88.3%vs 92.7%,P=0.125;10.5%vs 14.6%,P=0.222,respectively).However,the SBE group had significantly longer intubation and procedure times than the DBE group(23.5±22.3 minutes vs 14.1±13.5 minutes,P<0.001;65.2±37.9 minutes vs 31.0±18.5 minutes,P<0.001).Preserved gastric anatomy and Roux-en-Y reconstruction were independently associated with intubation failure(odds ratio=3.18,95%confidence interval:1.30-8.31;odds ratio=8.65,95%confidence interval:1.71-157.60,respectively).CONCLUSION DBE and SBE showed comparable clinical success and safety profiles in ERCP for patients with SAA,although SBE required significantly longer procedure times.DBE could provide procedural efficiency benefits in cases where an extended procedure duration is expected.Furthermore,a preserved gastric anatomy and Roux-en-Y reconstruction were identified as independent risk factors for intubation failure.
基金funded by the Science and Technology Special Project of Zhanjiang,China(Grant No.:2022A01034)the Guangdong Provincial Department of Education Research Project,China(Grant No.:2022KTSCX)+2 种基金the Science and Technology Program of Guangdong Province,China(Grant No.:2023A1515010850)the Special Fund for Science and Technology Innovation Strategy of Guangdong Province,China(Grant No.:pdjh2023a0227)the National Undergraduate Training Program for Innovation and Entrepreneurship,China(Grant No.:202310571003).
文摘Ferroptosis is a form of cell death that occurs when there is an excess of reactive oxygen species(ROS),lipid peroxidation,and iron accumulation.The precise regulation of metabolic pathways,including iron,lipid,and amino acid metabolism,is crucial for cell survival.This type of cell death,which is associated with oxidative stress,is controlled by a complex network of signaling molecules and pathways.It is also implicated in various respiratory diseases such as asthma,chronic obstructive pulmonary disease(COPD),acute lung injury(ALI),lung cancer,pulmonary fibrosis(PF),and the coronavirus disease 2019(COVID-19).To combat drug resistance,it is important to identify appropriate biological markers and treatment targets,as well as intervene in respiratory disorders to either induce or prevent ferroptosis.The focus is on the role of ferroptosis in the development of respiratory diseases and the potential of targeting ferroptosis for prevention and treatment.The review also explores the interaction between immune cell ferroptosis and inflammatory mediators in respiratory diseases,aiming to provide more effective strategies for managing cellular ferroptosis and respiratory disorders.
基金supported by the National Institutes of Health-Office of Research Infrastructure Programs(P40 OD010440)supported in part by grants from the National Cancer Center of Korea(NCC-2110160,NCC-2110263,and NCC-2310750)supported by the Basic Science Research Program of the National Research Foundation of Korea,funded by the Ministry of Science,ICT,and Future Planning(NRF-2015R1C1A1A01053611).
文摘The growth of Caenorhabditis elegans involves multiple molting processes,during which old cuticles are shed and new cuticles are rapidly formed.This process requires the regulated bulk secretion of cuticle components.The transmembrane protein-39(TMEM-39)mutant exhibits distinct dumpy and ruptured phenotypes characterized by notably thin cuticles.TMEM-39 primarily co-localizes with the coat protein II complex(COPII)in large vesicles rather than small COPII vesicles.These TMEM-39-associated large vesicles(TMEM-39-LVs)form robustly during the molting period and co-localize with various extracellular matrix components,including BLI-1 collagen,BLI-3 dual oxidase,and carboxypeptidases.Through immunoprecipitation using TMEM39A-FLAG and proteomics analysis in human sarcoma cells,we identify TMEM39A-associated proteins,including TMEM131.Knockdown of TMEM131 results in reduced TMEM39A-LV formation and collagen secretion in both C.elegans and human sarcoma cells,indicating a cooperative role between TMEM39A and TMEM131 in the secretion of extracellular components through the formation of large COPII vesicles.Given the conservation of TMEM39A and its associated proteins between C.elegans and humans,TMEM39A-LVs may represent a fundamental machinery for rapid and extensive secretion across metazoans.
文摘A recent single-center retrospective study by Rao et al has offered valuable insights into the prognostic utility of ascitic fluid characteristics in acute pancreatitis.Their findings,which demonstrate associations between ascitic color,turbidity,and elevated lactate dehydrogenase levels with organ failure,infected pancreatic necrosis,and in-hospital mortality provide a valuable contribution to a relatively underexplored area in pancreatology.However,the reliance on subjective visual assessment and a single time-point evaluation raises concerns regarding reproducibility and dynamic disease monitoring.Furthermore,the lack of integration with objective indicators such as polymorphonuclear cell counts,microbiological cultures,and exudative vs transudative analysis limits the interpretability of the results.Despite these limitations,the study provides a clinically relevant framework that supports further investigation and refinement through prospective,multicenter validation.
