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
Cells of the central nervous system(CNS)are privileged in lying behind the blood-brain barrier(BBB).Unlike blood vessels in other organs,CNS blood vessels are unique in displaying high electrical resistance and low pe...Cells of the central nervous system(CNS)are privileged in lying behind the blood-brain barrier(BBB).Unlike blood vessels in other organs,CNS blood vessels are unique in displaying high electrical resistance and low permeability.With this unique structure and function,the BBB prevents potentially harmful blood components such as serum proteins,inflammatory cytokines,and inflammatory leukocytes from entering the hallowed space of the CNS and wreaking havoc.In addition to these“tightness”properties,the BBB has an array of specialized transporters designed to import essential nutrients.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
Background Exercise is an effective intervention for obesity and type 2 diabetes,with significant physiological benefits over pharmacological interventions.However,there is limited preclinical data available comparing...Background Exercise is an effective intervention for obesity and type 2 diabetes,with significant physiological benefits over pharmacological interventions.However,there is limited preclinical data available comparing endurance and resistance exercise for the impacts on obesogenic pathology and glycemic control.Methods Male mice were subjected to 8 weeks of diet-induced obesity(DIO)by high-fat diet(HFD)feeding concurrent with voluntary wheel running(endurance exercise(E_(EX)))or weightlifting(resistance exercise(R_(EX))).Sedentary(SED)mice fed on normal chow(NC)or HFD were used as controls.Results E_(EX) and R_(EX) interventions significantly attenuated weight gain vs.HFD-SED due to reduction of fat mass,not changes in lean mass,as assessed by EchoMRI.While REX suppressed visceral and subcutaneous fat accumulation significantly,only E_(EX) enlarged brown fat mass.Exercise tolerance testing(i.e.,run-to-fatigue)revealed significantly improved exercise capacity in E_(EX) group vs.NC-SED.Interestingly,although HFD led to trends of increased skeletal muscle mass,only E_(EX) with HFD led to significant muscle weight gain.Neither exercise modality resulted in significant changes of hindlimb skeletal muscle contractile properties and cardiac function compared to SED mice on HFD.Importantly,REX showed significantly enhanced benefits over EEX in improving homeostatic model assessment of insulin resistance(HOMA-IR),glucose tolerance,and insulin tolerance.Conclusion These results provide a direct and translatable comparison of endurance and resistance exercise training in a preclinical context of obesity and hyperglycemia.The current data set demonstrates an advantage of resistance exercise over endurance exercise in improving glucose and insulin tolerance under the condition of obesity,and that these improvements are independent of significant alterations of muscle weight gain and exercise performance.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
The temporal pole(TP),one of the most expanded cortical regions in humans relative to other primates,plays a crucial role in human language processing.It is also one of the most structurally and functionally asymmetri...The temporal pole(TP),one of the most expanded cortical regions in humans relative to other primates,plays a crucial role in human language processing.It is also one of the most structurally and functionally asymmetric regions.However,whether the functional architecture of the TP is shared by humans and macaques is an open question.We used spectral clustering algorithms to define a cross-species fine-grained TP atlas with different anatomical connectivity patterns.We identified three similar subregions,two ventral and one dorsal,within the TP in both humans and macaques.The parcellation scheme for the TP was validated using functional gradient mapping,anatomical connectivity and resting-state functional connectivity pattern analysis,and functional characterization.Furthermore,in conjunction with the Allen Human Brain Atlas,we revealed the molecular basis for the functional connectivity patterns of each human TP subregion.In addition,we compared the hemispheric asymmetry in mean gray matter volume,anatomical connectivity fingerprints,and whole brain functional connectivity patterns to reveal the evolutionary differences in the TP and found different asymmetric patterns between humans and macaques.In conclusion,our findings reveal that the asymmetry in structure and connectivity may underpin the hemispheric functional specialization of the brain and provide a novel insight into understanding the evolutionary origin of the TP.展开更多
The mammalian cochlea relies on outer and inner hair cells(OHCs/IHCs)for sound amplification and signal transmission.Rab3-interacting molecular binding protein 2(RIMBP2),expressed in receptor cells and neurons at syna...The mammalian cochlea relies on outer and inner hair cells(OHCs/IHCs)for sound amplification and signal transmission.Rab3-interacting molecular binding protein 2(RIMBP2),expressed in receptor cells and neurons at synaptic active zones,remains poorly characterized in hearing.We therefore generated a Rimbp2 knockout(KO)mouse model(Rimbp^(2-/-)),which exhibited severe hearing loss with elevated thresholds,prolonged latencies,and reduced amplitudes in auditory brainstem response Wave I.OHC loss via apoptosis was correlated with threshold elevation.In IHCs,patch-clamp recordings revealed reduced exocytosis,including a diminished readily-releasable pool,impaired sustained release,and blocked fast endocytosis.Immunostaining showed unchanged ribbon synapse numbers but positional shifts in the basal pole of KO IHCs.These findings demonstrated RIMBP2’s essential role in OHC survival and its broader regulatory functions in IHC synaptic transmission than previously recognized.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
AIM:To report the demographic and systemic characteristics of patients,clinical progression of endophthalmitis,and the efficacy of various treatment strategies,with a focus on identifying key factors for preserving vi...AIM:To report the demographic and systemic characteristics of patients,clinical progression of endophthalmitis,and the efficacy of various treatment strategies,with a focus on identifying key factors for preserving vision in eyes with endogenous endophthalmitis due to Klebsiella pneumoniae(K.pneumoniae)liver abscess.METHODS:In this single-center,retrospective case series of 18 patients with endogenous endophthalmitis due to K.pneumoniae liver abscess were analyzed.Ophthalmologic features of endophthalmitis at early,intermediate and advanced stages were obtained from eyes with endophthalmitis of different severities.Prompt vitrectomy was considered primarily for all eyes except for very early endophthalmitis.Intravitreal injections of antibiotics were performed in eyes with endophthalmitis in the very early stages and in eyes where vitrectomy was not available,and additional control of infection was needed after vitrectomy.Evisceration was performed in eyes with corneoscleral perforation,advanced endophthalmitis,perforation with preseptal or orbital cellulitis,uncontrolled infection,or severe pain with no vision.RESULTS:Mean(±standard deviation)age of the 18 patients with endophthalmitis was 64.5±12.2(range:32-84)y,and 14 patients(77.8%)were males.Endophthalmitis tended to involve the retinal parenchyma first and then progressed into the vitreous cavity and anterior segments.However,it presented a tendency to cause massive subretinal abscesses even after vitrectomy with silicone oil tamponade.Very high intraocular pressure with new vessels on the iris(41.7%)were also commonly observed.Although all but three patients had systemic disease such as diabetes or hypertension,visual prognosis after treatment did not appear to depend significantly on underlying comorbidities.A final best-corrected visual acuity better than 20/60 was achieved only when lesions were detected very early,with relatively good initial visual acuity,likely reflecting lower bacterial inoculation in the eye.CONCLUSION:Detection of early endophthalmitis lesions appears to be the only way to preserve good vision in patients with K.pneumoniae liver abscesses.Therefore,proper guidelines for ophthalmologic screening remain to be established for subjects at a high risk of endophthalmitis.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
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 the NIH RF1 grant NS119477 jointly funded by NINDS and NIA(to RM).
文摘Cells of the central nervous system(CNS)are privileged in lying behind the blood-brain barrier(BBB).Unlike blood vessels in other organs,CNS blood vessels are unique in displaying high electrical resistance and low permeability.With this unique structure and function,the BBB prevents potentially harmful blood components such as serum proteins,inflammatory cytokines,and inflammatory leukocytes from entering the hallowed space of the CNS and wreaking havoc.In addition to these“tightness”properties,the BBB has an array of specialized transporters designed to import essential nutrients.
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 National Institutes of Health(No.NIH-R01AR050429 and No.NIH-R01AR077440)a grant by Red Gates Foundation to ZY.
文摘Background Exercise is an effective intervention for obesity and type 2 diabetes,with significant physiological benefits over pharmacological interventions.However,there is limited preclinical data available comparing endurance and resistance exercise for the impacts on obesogenic pathology and glycemic control.Methods Male mice were subjected to 8 weeks of diet-induced obesity(DIO)by high-fat diet(HFD)feeding concurrent with voluntary wheel running(endurance exercise(E_(EX)))or weightlifting(resistance exercise(R_(EX))).Sedentary(SED)mice fed on normal chow(NC)or HFD were used as controls.Results E_(EX) and R_(EX) interventions significantly attenuated weight gain vs.HFD-SED due to reduction of fat mass,not changes in lean mass,as assessed by EchoMRI.While REX suppressed visceral and subcutaneous fat accumulation significantly,only E_(EX) enlarged brown fat mass.Exercise tolerance testing(i.e.,run-to-fatigue)revealed significantly improved exercise capacity in E_(EX) group vs.NC-SED.Interestingly,although HFD led to trends of increased skeletal muscle mass,only E_(EX) with HFD led to significant muscle weight gain.Neither exercise modality resulted in significant changes of hindlimb skeletal muscle contractile properties and cardiac function compared to SED mice on HFD.Importantly,REX showed significantly enhanced benefits over EEX in improving homeostatic model assessment of insulin resistance(HOMA-IR),glucose tolerance,and insulin tolerance.Conclusion These results provide a direct and translatable comparison of endurance and resistance exercise training in a preclinical context of obesity and hyperglycemia.The current data set demonstrates an advantage of resistance exercise over endurance exercise in improving glucose and insulin tolerance under the condition of obesity,and that these improvements are independent of significant alterations of muscle weight gain and exercise performance.
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supported by the Yunnan Fundamental Research Projects(202501AV070005 and 202201BE070001-004).
文摘The temporal pole(TP),one of the most expanded cortical regions in humans relative to other primates,plays a crucial role in human language processing.It is also one of the most structurally and functionally asymmetric regions.However,whether the functional architecture of the TP is shared by humans and macaques is an open question.We used spectral clustering algorithms to define a cross-species fine-grained TP atlas with different anatomical connectivity patterns.We identified three similar subregions,two ventral and one dorsal,within the TP in both humans and macaques.The parcellation scheme for the TP was validated using functional gradient mapping,anatomical connectivity and resting-state functional connectivity pattern analysis,and functional characterization.Furthermore,in conjunction with the Allen Human Brain Atlas,we revealed the molecular basis for the functional connectivity patterns of each human TP subregion.In addition,we compared the hemispheric asymmetry in mean gray matter volume,anatomical connectivity fingerprints,and whole brain functional connectivity patterns to reveal the evolutionary differences in the TP and found different asymmetric patterns between humans and macaques.In conclusion,our findings reveal that the asymmetry in structure and connectivity may underpin the hemispheric functional specialization of the brain and provide a novel insight into understanding the evolutionary origin of the TP.
基金supported by grants from the National Key R&D Program of China(2021YFA1101300,2021YFA1101800,2020YFA0112503,and 2024YFC2511103)the National Natural Science Foundation of China(82330033,82030029,82401375,81970882,92149304,and 81970883)+7 种基金the Natural Science Foundation of Jiangsu Province(BK20232007)the Science and Technology Department of Sichuan Province(2021YFS0371)Shenzhen Fundamental Research Program(JCYJ20210324125608022)the Open Project Fund of Guangdong Academy of Medical Sciences(YKY-KF202201)Beijing Natural Science Foundation(Z200019)the Jiangsu Provincial Scientific Research Center of Applied Mathematics(BK20233002)the China Postdoctoral Science Foundation(2023TQ0056,2023M730575,and GZC20230435)Jiangsu Funding Program for Excellent Postdoctoral Talent(2023ZB822).
文摘The mammalian cochlea relies on outer and inner hair cells(OHCs/IHCs)for sound amplification and signal transmission.Rab3-interacting molecular binding protein 2(RIMBP2),expressed in receptor cells and neurons at synaptic active zones,remains poorly characterized in hearing.We therefore generated a Rimbp2 knockout(KO)mouse model(Rimbp^(2-/-)),which exhibited severe hearing loss with elevated thresholds,prolonged latencies,and reduced amplitudes in auditory brainstem response Wave I.OHC loss via apoptosis was correlated with threshold elevation.In IHCs,patch-clamp recordings revealed reduced exocytosis,including a diminished readily-releasable pool,impaired sustained release,and blocked fast endocytosis.Immunostaining showed unchanged ribbon synapse numbers but positional shifts in the basal pole of KO IHCs.These findings demonstrated RIMBP2’s essential role in OHC survival and its broader regulatory functions in IHC synaptic transmission than previously recognized.
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.
文摘AIM:To report the demographic and systemic characteristics of patients,clinical progression of endophthalmitis,and the efficacy of various treatment strategies,with a focus on identifying key factors for preserving vision in eyes with endogenous endophthalmitis due to Klebsiella pneumoniae(K.pneumoniae)liver abscess.METHODS:In this single-center,retrospective case series of 18 patients with endogenous endophthalmitis due to K.pneumoniae liver abscess were analyzed.Ophthalmologic features of endophthalmitis at early,intermediate and advanced stages were obtained from eyes with endophthalmitis of different severities.Prompt vitrectomy was considered primarily for all eyes except for very early endophthalmitis.Intravitreal injections of antibiotics were performed in eyes with endophthalmitis in the very early stages and in eyes where vitrectomy was not available,and additional control of infection was needed after vitrectomy.Evisceration was performed in eyes with corneoscleral perforation,advanced endophthalmitis,perforation with preseptal or orbital cellulitis,uncontrolled infection,or severe pain with no vision.RESULTS:Mean(±standard deviation)age of the 18 patients with endophthalmitis was 64.5±12.2(range:32-84)y,and 14 patients(77.8%)were males.Endophthalmitis tended to involve the retinal parenchyma first and then progressed into the vitreous cavity and anterior segments.However,it presented a tendency to cause massive subretinal abscesses even after vitrectomy with silicone oil tamponade.Very high intraocular pressure with new vessels on the iris(41.7%)were also commonly observed.Although all but three patients had systemic disease such as diabetes or hypertension,visual prognosis after treatment did not appear to depend significantly on underlying comorbidities.A final best-corrected visual acuity better than 20/60 was achieved only when lesions were detected very early,with relatively good initial visual acuity,likely reflecting lower bacterial inoculation in the eye.CONCLUSION:Detection of early endophthalmitis lesions appears to be the only way to preserve good vision in patients with K.pneumoniae liver abscesses.Therefore,proper guidelines for ophthalmologic screening remain to be established for subjects at a high risk of endophthalmitis.
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.
