Microneedles(MNs)have been extensively investigated for transdermal delivery of large-sized drugs,including proteins,nucleic acids,and even extracellular vesicles(EVs).However,for their sufficient skin penetration,con...Microneedles(MNs)have been extensively investigated for transdermal delivery of large-sized drugs,including proteins,nucleic acids,and even extracellular vesicles(EVs).However,for their sufficient skin penetration,conventional MNs employ long needles(≥600μm),leading to pain and skin irritation.Moreover,it is critical to stably apply MNs against complex skin surfaces for uniform nanoscale drug delivery.Herein,a dually amplified transdermal patch(MN@EV/SC)is developed as the stem cell-derived EV delivery platform by hierarchically integrating an octopusinspired suction cup(SC)with short MNs(≤300μm).While leveraging the suction effect to induce nanoscale deformation of the stratum corneum,MN@EV/SC minimizes skin damage and enhances the adhesion of MNs,allowing EV to penetrate deeper into the dermis.When MNs of various lengths are applied to mouse skin,the short MNs can elicit comparable corticosterone release to chemical adhesives,whereas long MNs induce a prompt stress response.MN@EV/SC can achieve a remarkable penetration depth(290μm)for EV,compared to that of MN alone(111μm).Consequently,MN@EV/SC facilitates the revitalization of fibroblasts and enhances collagen synthesis in middle-aged mice.Overall,MN@EV/SC exhibits the potential for skin regeneration by modulating the dermal microenvironment and ensuring patient comfort.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
With people living longer,the societal impact of age-related cognitive decline is becoming more pronounced(Crimmins,2015).Thus,it is increasingly important to comprehend the cognitive shifts linked to aging-whether th...With people living longer,the societal impact of age-related cognitive decline is becoming more pronounced(Crimmins,2015).Thus,it is increasingly important to comprehend the cognitive shifts linked to aging-whether they are physiological or pathological.展开更多
Lifestyle and demographics of the world's population are causing serious health problems impacting the brain,increasing the incidence of Alzheimer's disease(AD)and other types of dementia.Although we have gain...Lifestyle and demographics of the world's population are causing serious health problems impacting the brain,increasing the incidence of Alzheimer's disease(AD)and other types of dementia.Although we have gained important insights into the pathogenic mechanisms of AD,only palliative care is available to patients.AD is characterized by the abnormal deposition of protein aggregates in the brain formed by amyloidβand hyper-phosphorylated,Tau in addition to neuroinflammation.展开更多
Spinal cord injury results in the loss of sensory,motor,and autonomic functions,which almost always produces permanent physical disability.Thus,in the search for more effective treatments than those already applied fo...Spinal cord injury results in the loss of sensory,motor,and autonomic functions,which almost always produces permanent physical disability.Thus,in the search for more effective treatments than those already applied for years,which are not entirely efficient,researches have been able to demonstrate the potential of biological strategies using biomaterials to tissue manufacturing through bioengineering and stem cell therapy as a neuroregenerative approach,seeking to promote neuronal recovery after spinal cord injury.Each of these strategies has been developed and meticulously evaluated in several animal models with the aim of analyzing the potential of interventions for neuronal repair and,consequently,boosting functional recovery.Although the majority of experimental research has been conducted in rodents,there is increasing recognition of the importance,and need,of evaluating the safety and efficacy of these interventions in non-human primates before moving to clinical trials involving therapies potentially promising in humans.This article is a literature review from databases(PubMed,Science Direct,Elsevier,Scielo,Redalyc,Cochrane,and NCBI)from 10 years ago to date,using keywords(spinal cord injury,cell therapy,non-human primates,humans,and bioengineering in spinal cord injury).From 110 retrieved articles,after two selection rounds based on inclusion and exclusion criteria,21 articles were analyzed.Thus,this review arises from the need to recognize the experimental therapeutic advances applied in non-human primates and even humans,aimed at deepening these strategies and identifying the advantages and influence of the results on extrapolation for clinical applicability in humans.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
Biomedical scaffold fabrication has seen advancements in mimicking the native extracellular matrix through intricate three-dimensional(3D)structures conducive to tissue regeneration.Coiled fibrous scaffolds have emerg...Biomedical scaffold fabrication has seen advancements in mimicking the native extracellular matrix through intricate three-dimensional(3D)structures conducive to tissue regeneration.Coiled fibrous scaffolds have emerged as promising substrates owing to their ability to provide unique topographical cues.In this study,coiled poly(ε-caprolactone)(PCL)fibrous bundles were fabricated using an alginate-based composite system,and processed with 3D printing.The unique structure was obtained through the die-swell phenomenon related to the release of residual stresses from the printed strut,thereby transforming aligned PCL fibers into coiled structures.The effects of printing parameters,such as pneumatic pressure and nozzle moving speed,on fiber morphology were investigated to ensure a consistent formation of coiled PCL fibers.The resulting coiled PCL fibrous scaffold demonstrated higher activation of mechanotransduction signaling as well as upregulation of osteogenic-related genes in human adipose stem cells(hASCs),supporting its potential in bone tissue engineering.展开更多
Bioprinting is a widely used technique for creating three-dimensional,complex,and heterogeneous artificial tissue constructs that are biologically and biophysically similar to natural tissues.The skin is composed of s...Bioprinting is a widely used technique for creating three-dimensional,complex,and heterogeneous artificial tissue constructs that are biologically and biophysically similar to natural tissues.The skin is composed of several layers including the epidermis,basement membrane(BM),and dermis.However,the unique undulating structure of basement membranes(i.e.rete ridges)and the function of BM have not been extensively studied in the fabrication of engineered skin substitutes.In this study,a novel engineered skin substitute incorporating an artificially designed rete ridge(i.e.mogul-shape)was developed using bioprinting and bioinks prepared using collagen and fibrinogen.To mimic the structure of the rete ridges of skin tissue,we developed a modified bioprinting technique,controlling rheological property of bioink to create a mogul-shaped layer.In vitro cellular activities,including the expression of specific genes(those encoding vimentin,laminin-5,collagen IV,and cytokeratins),demonstrated that the engineered skin substitute exhibited more potent cellular responses than the normally bioprinted control owing to the favorable biophysical BM structure and the bioink microenvironment.Additionally,the feasibility of utilizing the bioprinted skin-structure was evaluated in a mouse model,and in vivo results demonstrated that the bioprinted skin substitutes effectively promoted wound healing capabilities.Based on these results,we suggest that bioprinted skin tissues and the bioprinting technique for mimicking rete ridges can be used not only as potential lab-chip models for testing cosmetic materials and drugs,but also as complex physiological models for understanding human skin.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
The potential of induced pluripotent stem cells(iPSCs)for modeling and treating metabolic associated fatty liver disease(MAFLD)and metabolic associated steatohepatitis(MASH)is emerging.MAFLD is a growing global health...The potential of induced pluripotent stem cells(iPSCs)for modeling and treating metabolic associated fatty liver disease(MAFLD)and metabolic associated steatohepatitis(MASH)is emerging.MAFLD is a growing global health concern,currently with limited treatment options.While primary mesenchymal stem cells hold promise,iPSCs offer a versatile alternative due to their ability to differentiate into various cell types,including iPSC-derived mesenchymal stem cells.However,challenges remain,including optimizing differentiation protocols,ensuring cell safety,and addressing potential tumorigenicity risks.In addition,iPSCs offer the possibility to generate complex cellular models,including three-dimensional organoid models,which are closer representations of the human disease than animal models.Those models would also be valuable for drug discovery and personalized medicine approaches.Overall,iPSCs and their derivatives offer new perspectives for advancing MAFLD/MASH research and developing novel therapeutic strategies.Further research is needed to overcome current limitations and translate this potential into effective clinical applications.展开更多
基金supported by National Research Foundation of Korea(NRF)grants funded by the Korean government(MSIT)(No.RS-2023-00256265,RS-2024-00352352,RS-2024-00405818)the Korean Fund for Regenerative Medicine(KFRM)grant funded by the Korea government(the Ministry of Science and ICT,the Ministry of Health&Welfare).(No.25A0102L1)support from the Market-led K-sensor technology program(RS-2022-00154781,Development of large-area wafer-level flexible/stretchable hybrid sensor platform technology for form factor-free highly integrated convergence sensor),funded By the Ministry of Trade,Industry&Energy(MOTIE,Korea).
文摘Microneedles(MNs)have been extensively investigated for transdermal delivery of large-sized drugs,including proteins,nucleic acids,and even extracellular vesicles(EVs).However,for their sufficient skin penetration,conventional MNs employ long needles(≥600μm),leading to pain and skin irritation.Moreover,it is critical to stably apply MNs against complex skin surfaces for uniform nanoscale drug delivery.Herein,a dually amplified transdermal patch(MN@EV/SC)is developed as the stem cell-derived EV delivery platform by hierarchically integrating an octopusinspired suction cup(SC)with short MNs(≤300μm).While leveraging the suction effect to induce nanoscale deformation of the stratum corneum,MN@EV/SC minimizes skin damage and enhances the adhesion of MNs,allowing EV to penetrate deeper into the dermis.When MNs of various lengths are applied to mouse skin,the short MNs can elicit comparable corticosterone release to chemical adhesives,whereas long MNs induce a prompt stress response.MN@EV/SC can achieve a remarkable penetration depth(290μm)for EV,compared to that of MN alone(111μm).Consequently,MN@EV/SC facilitates the revitalization of fibroblasts and enhances collagen synthesis in middle-aged mice.Overall,MN@EV/SC exhibits the potential for skin regeneration by modulating the dermal microenvironment and ensuring patient comfort.
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Clévio Nóbrega’s laboratory is funded by the Cure CSB projectthe Viljem Julijan Association for Children with Rare Diseases(Slovenia)+1 种基金the Algarve Biomedical Center Research Institute(ABC-Ri)funded by CRESC Algarve 2020(Operation Code:ALG-01-0145-FEDER-072586)(to CN)。
文摘With people living longer,the societal impact of age-related cognitive decline is becoming more pronounced(Crimmins,2015).Thus,it is increasingly important to comprehend the cognitive shifts linked to aging-whether they are physiological or pathological.
基金funded by U.S.Air Force Office of Scientific Research FA9550-21-1-0096,FONDAP program 15150012,ANID/FONDEF ID1ID22I10120,FONDECY/ANID 1220573the US Army Medical Research Acquisition Activity(USAMRAA)project number AL2201415DoD Award HT9425-23-1-0990,AL220141(to CH)。
文摘Lifestyle and demographics of the world's population are causing serious health problems impacting the brain,increasing the incidence of Alzheimer's disease(AD)and other types of dementia.Although we have gained important insights into the pathogenic mechanisms of AD,only palliative care is available to patients.AD is characterized by the abnormal deposition of protein aggregates in the brain formed by amyloidβand hyper-phosphorylated,Tau in addition to neuroinflammation.
文摘Spinal cord injury results in the loss of sensory,motor,and autonomic functions,which almost always produces permanent physical disability.Thus,in the search for more effective treatments than those already applied for years,which are not entirely efficient,researches have been able to demonstrate the potential of biological strategies using biomaterials to tissue manufacturing through bioengineering and stem cell therapy as a neuroregenerative approach,seeking to promote neuronal recovery after spinal cord injury.Each of these strategies has been developed and meticulously evaluated in several animal models with the aim of analyzing the potential of interventions for neuronal repair and,consequently,boosting functional recovery.Although the majority of experimental research has been conducted in rodents,there is increasing recognition of the importance,and need,of evaluating the safety and efficacy of these interventions in non-human primates before moving to clinical trials involving therapies potentially promising in humans.This article is a literature review from databases(PubMed,Science Direct,Elsevier,Scielo,Redalyc,Cochrane,and NCBI)from 10 years ago to date,using keywords(spinal cord injury,cell therapy,non-human primates,humans,and bioengineering in spinal cord injury).From 110 retrieved articles,after two selection rounds based on inclusion and exclusion criteria,21 articles were analyzed.Thus,this review arises from the need to recognize the experimental therapeutic advances applied in non-human primates and even humans,aimed at deepening these strategies and identifying the advantages and influence of the results on extrapolation for clinical applicability in humans.
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.
基金supported by the‘Korea National Institute of Health’research project(2022ER130502)a grant from by SMC-SKKU Future Convergence Academic Research Program,2024supported by the National Research Foundation of Korea(NRF)grant funded by the Korea government(MSIT)(RS-2024-00336758)。
文摘Biomedical scaffold fabrication has seen advancements in mimicking the native extracellular matrix through intricate three-dimensional(3D)structures conducive to tissue regeneration.Coiled fibrous scaffolds have emerged as promising substrates owing to their ability to provide unique topographical cues.In this study,coiled poly(ε-caprolactone)(PCL)fibrous bundles were fabricated using an alginate-based composite system,and processed with 3D printing.The unique structure was obtained through the die-swell phenomenon related to the release of residual stresses from the printed strut,thereby transforming aligned PCL fibers into coiled structures.The effects of printing parameters,such as pneumatic pressure and nozzle moving speed,on fiber morphology were investigated to ensure a consistent formation of coiled PCL fibers.The resulting coiled PCL fibrous scaffold demonstrated higher activation of mechanotransduction signaling as well as upregulation of osteogenic-related genes in human adipose stem cells(hASCs),supporting its potential in bone tissue engineering.
基金supported by the‘Korea National Institute of Health’(KNIH)research project(Project No.2022ER130502)the National Research Foundation of Korea(NRF)Grant funded by the Korea Government(MSIT)(No.2021R1A2C20060331222182102840102)。
文摘Bioprinting is a widely used technique for creating three-dimensional,complex,and heterogeneous artificial tissue constructs that are biologically and biophysically similar to natural tissues.The skin is composed of several layers including the epidermis,basement membrane(BM),and dermis.However,the unique undulating structure of basement membranes(i.e.rete ridges)and the function of BM have not been extensively studied in the fabrication of engineered skin substitutes.In this study,a novel engineered skin substitute incorporating an artificially designed rete ridge(i.e.mogul-shape)was developed using bioprinting and bioinks prepared using collagen and fibrinogen.To mimic the structure of the rete ridges of skin tissue,we developed a modified bioprinting technique,controlling rheological property of bioink to create a mogul-shaped layer.In vitro cellular activities,including the expression of specific genes(those encoding vimentin,laminin-5,collagen IV,and cytokeratins),demonstrated that the engineered skin substitute exhibited more potent cellular responses than the normally bioprinted control owing to the favorable biophysical BM structure and the bioink microenvironment.Additionally,the feasibility of utilizing the bioprinted skin-structure was evaluated in a mouse model,and in vivo results demonstrated that the bioprinted skin substitutes effectively promoted wound healing capabilities.Based on these results,we suggest that bioprinted skin tissues and the bioprinting technique for mimicking rete ridges can be used not only as potential lab-chip models for testing cosmetic materials and drugs,but also as complex physiological models for understanding human skin.
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American Heart Association Award,No.24IVPHA1288417and FCT Fellowships,No.2022.13253.BDANA.
文摘The potential of induced pluripotent stem cells(iPSCs)for modeling and treating metabolic associated fatty liver disease(MAFLD)and metabolic associated steatohepatitis(MASH)is emerging.MAFLD is a growing global health concern,currently with limited treatment options.While primary mesenchymal stem cells hold promise,iPSCs offer a versatile alternative due to their ability to differentiate into various cell types,including iPSC-derived mesenchymal stem cells.However,challenges remain,including optimizing differentiation protocols,ensuring cell safety,and addressing potential tumorigenicity risks.In addition,iPSCs offer the possibility to generate complex cellular models,including three-dimensional organoid models,which are closer representations of the human disease than animal models.Those models would also be valuable for drug discovery and personalized medicine approaches.Overall,iPSCs and their derivatives offer new perspectives for advancing MAFLD/MASH research and developing novel therapeutic strategies.Further research is needed to overcome current limitations and translate this potential into effective clinical applications.
