Acute respiratory distress syndrome(ARDS)is a life-threatening condition that is characterized by high mortality rates and limited therapeutic options.Notably,Zhang et al demonstrated that CD146+mesenchymal stromal ce...Acute respiratory distress syndrome(ARDS)is a life-threatening condition that is characterized by high mortality rates and limited therapeutic options.Notably,Zhang et al demonstrated that CD146+mesenchymal stromal cells(MSCs)exhibited greater therapeutic efficacy than CD146-MSCs.These cells enhance epithelial repair through nuclear factor kappa B/cyclooxygenase-2-associated paracrine signaling and secretion of pro-angiogenic factors.We concur that MSCs hold significant promise for ARDS treatment;however,the heterogeneity of cell products is a translational barrier.Phenotype-aware strategies,such as CD146 enrichment,standardized potency assays,and extracellular vesicle profiling,are essential for improving the consistency of these studies.Further-more,advanced preclinical models,such as lung-on-a-chip systems,may provide more predictive insights into the therapeutic mechanisms.This article underscores the importance of CD146+MSCs in ARDS,emphasizes the need for precision in defining cell products,and discusses how integrating subset selection into translational pipelines could enhance the clinical impact of MSC-based therapies.展开更多
Penicine A(1),a meroterpenoid featuring a novel 3/5/6/6/11/6/6 polycyclic backbone,together with two new metabolites,penicines B(2)and C(4),and six known compounds,were isolated from the mangrove rhizosphere soil-deri...Penicine A(1),a meroterpenoid featuring a novel 3/5/6/6/11/6/6 polycyclic backbone,together with two new metabolites,penicines B(2)and C(4),and six known compounds,were isolated from the mangrove rhizosphere soil-derived fungus Penicillium brefeldianum SMU03.The structures of these metabolites were elucidated through extensive spectroscopic analysis combined with quantum chemical calculations.Notably,1 exhibits a highly unusual molecular architecture,incorporating a dioxaspiro[4.5]decane motif and a rare bridgehead double bond(anti-Bredt system).A plausible biosynthetic pathway,involving sequential intermolecular[4+2]cycloaddition reactions,is proposed.Additionally,meroterpenoids 1 and 3 demonstrate significant antifibrotic activity in transforming growth factorβ1(TGF-β1)-induced human renal proximal tubular epithelial cells.展开更多
Conventional ultrasound(US)evaluation of enthesitis in psoriatic arthritis(PsA)is limited by its inability to quantify metabolic alterations such as hypoxia,a key driver of disease activity.We introduce an oxygenation...Conventional ultrasound(US)evaluation of enthesitis in psoriatic arthritis(PsA)is limited by its inability to quantify metabolic alterations such as hypoxia,a key driver of disease activity.We introduce an oxygenation-integrated multimodal photoacoustic/ultrasound(PA/US)imaging framework designed to quantify entheseal oxygen saturation(SO_(2))for assessing entheseal disease activity in PsA.In this cross-sectional study,25 PsA patients underwent bilateral PA/US imaging of 12 entheses,where ultrasound lesions were scored using the Outcome Measures in Rheumatology scoring system,and PA-derived SO_(2) levels,quantified via dual-wavelength PA imaging,were classified into hyperoxia or hypoxia groups using k-means clustering.This approach provides metabolic insights complementary to conventional ultrasonic assessment.A composite score integrating hypoxia with US parameters was validated against clinical disease activity indices(Disease Activity Score 28-C-reactive protein,DAS28-CRP;Disease Activity Index for Psoriatic Arthritis,DAPSA).Among 300 entheses,103(34.3%)exhibited PA positivity,with 40(38.8%)classified as hypoxia.Hypoxia scores independently predicted DAS28-CRP(β=0.618,p=0.001)and DAPSA(β=0.612,p<0:001).The hypoxia-optimized PAUS score demonstrated superior correlation with disease activity indices compared to conventional US(DAS28-CRP:r=0.615,p=0.001 versus r=0.474,p=0.017;DAPSA:r=0.743,p<0:001 versus r=0.567,p=0.003),alongside superior diagnostic accuracy for minimal disease activity(area under the curve,AUC 0.776 versus 0.614,p=0.008)and low disease activity(AUC 0.853 versus 0.772,p=0.009).This multimodal scoring system enhances the stratification of PsA disease activity by providing unique metabolic insights,offering a potential tool for therapeutic monitoring and guiding treat-to-target strategies.展开更多
Background:Prostate cancer(PCa)is the most prevalent malignancy in men and often correlates with distant metastasis in its advanced stages.The study aimed to investigate the effects of Ugonin J,a natural compound isol...Background:Prostate cancer(PCa)is the most prevalent malignancy in men and often correlates with distant metastasis in its advanced stages.The study aimed to investigate the effects of Ugonin J,a natural compound isolated from Helminthostachys zeylanica,on PCa metastasis.Methods:The effects of Ugonin J on cell motility were assessed using migration and invasion assays.Reverse Transcription Quantitative PCR(RT-qPCR)and Western blotting were used to evaluate the impact of Ugonin J on mRNA and protein expression.RNA sequencing(RNA-seq)analysis was performed to investigate candidate mechanisms.Differential gene expression analysis in PCa patients was conducted using multiple databases.Results:Here,we reveal that Ugonin J blocks migration and invasion in PCa cells without affecting cell viability.RNA-seq analysis suggests that epithelial-mesenchymal transition(EMT)is potentially involved in Ugonin J’s anti-motility effects.Ugonin J also suppresses the expression of mesenchymal markers N-cadherin,β-catenin,Snail,and Slug while upregulating the expression of the epithelial marker E-cadherin.Furthermore,among 13 A disintegrin and metalloproteinase(ADAM)proteins,A disintegrin and metalloproteinase domain-containing protein 9(ADAM9)is the most downregulated following Ugonin J treatment,according to our RNA-seq data.Importantly,clinical data revealed that ADAM9 expression are higher in PCa patients than in healthy controls and are associated with distant metastasis.Transfection with ADAM9 cDNA reverses Ugonin J-regulated downregulation of EMT,migration,and invasion in PCa cells.Ugonin J inhibits ADAM9-dependent motility by downregulating the phosphoinositide 3-kinase(PI3K),protein kinase B(Akt)and nuclear factor-κB(NF-κB)pathways.Conclusions:Our evidence suggests that Ugonin J is a novel therapeutic candidate for further development as a treatment for metastatic PCa.展开更多
The functional regeneration of the dentin-pulp complex is pivotal for tooth preservation,yet the molecular mechanisms governing odontoblast differentiation remain poorly understood.In the current study,we revealed a d...The functional regeneration of the dentin-pulp complex is pivotal for tooth preservation,yet the molecular mechanisms governing odontoblast differentiation remain poorly understood.In the current study,we revealed a distinct NKD1^(+) subpopulation exhibiting secretory odontoblast characteristics,which was specifically induced in dental pulp stem cells(DPSCs) by Wnt3a,but not by Wnt5a or Wnt10a through single-cell transcriptomic profiling.We then found that the NKD1^(+) subpopulation was functional conservation,which were consistently identified in the odontoblast layers of developing tooth germs in both murine and miniature pig models,as well as within the apical open area in human molars.This conserved spatial distribution and co-localization with DSPP strongly indicates that NKD1^(+) cells were active dentin-secreting odontoblasts.Analysis of gene regulatory networks using SCENIC identified MSX1 as a key transcription factor regulating the specification of NKD1^(+) lineage.Mechanistically,Wnt3a orchestrates a tripartite cascade:upregulating NKD1/MSX1 expression,triggering NKD1 membrane detachment,and facilitating direct NKD1-MSX1interaction to promote MSX1 nuclear translocation.CUT&Tag analysis demonstrated MSX1 occupancy at promoters of odontogenic regulato rs,esta blishing its necessity for odontogenic gene activation.Murine pulp exposure models validated that Wnt3a-activated NKD1-MSX1 signaling significantly enhances reparative dentin formation.This study delineates an evolutionarily conserved Wnt3aNKD1-MSX1 axis that resolves stem cell heterogeneity into functional odontoblast commitment,providing both mechanistic insights into dentin-pulp regeneration and a foundation for targeted regenerative therapies.展开更多
Stroke is classified as ischemic or hemorrhagic,and there are few effective treatments for either type.Immunologic mechanisms play a critical role in secondary brain injury following a stroke,which manifests as cytoki...Stroke is classified as ischemic or hemorrhagic,and there are few effective treatments for either type.Immunologic mechanisms play a critical role in secondary brain injury following a stroke,which manifests as cytokine release,blood–brain barrier disruption,neuronal cell death,and ultimately behavioral impairment.Suppressing the inflammatory response has been shown to mitigate this cascade of events in experimental stroke models.However,in clinical trials of anti-inflammatory agents,longterm immunosuppression has not demonstrated significant clinical benefits for patients.This may be attributable to the dichotomous roles of inflammation in both tissue injury and repair,as well as the complex pathophysiologic inflammatory processes in stroke.Inhibiting acute harmful inflammatory responses or inducing a phenotypic shift from a pro-inflammatory to an anti-inflammatory state at specific time points after a stroke are alternative and promising therapeutic strategies.Identifying agents that can modulate inflammation requires a detailed understanding of the inflammatory processes of stroke.Furthermore,epigenetic reprogramming plays a crucial role in modulating post-stroke inflammation and can potentially be exploited for stroke management.In this review,we summarize current findings on the epigenetic regulation of the inflammatory response in stroke,focusing on key signaling pathways including nuclear factor-kappa B,Janus kinase/signal transducer and activator of transcription,and mitogen-activated protein kinase as well as inflammasome activation.We also discuss promising molecular targets for stroke treatment.The evidence to date indicates that therapeutic targeting of the epigenetic regulation of inflammation can shift the balance from inflammation-induced tissue injury to repair following stroke,leading to improved post-stroke outcomes.展开更多
Scar formation resulting from burns or severe trauma can significantly compromise the structural integrity of skin and lead to permanent loss of skin appendages,ultimately impairing its normal physiological function.A...Scar formation resulting from burns or severe trauma can significantly compromise the structural integrity of skin and lead to permanent loss of skin appendages,ultimately impairing its normal physiological function.Accumulating evidence underscores the potential of targeted modulation of mechanical cues to enhance skin regeneration,promoting scarless repair by influencing the extracellular microenvironment and driving the phenotypic transitions.The field of skin repair and skin appendage regeneration has witnessed remarkable advancements in the utilization of biomaterials with distinct physical properties.However,a comprehensive understanding of the underlying mechanisms remains somewhat elusive,limiting the broader application of these innovations.In this review,we present two promising biomaterial-based mechanical approaches aimed at bolstering the regenerative capacity of compromised skin.The first approach involves leveraging biomaterials with specific biophysical properties to create an optimal scarless environment that supports cellular activities essential for regeneration.The second approach centers on harnessing mechanical forces exerted by biomaterials to enhance cellular plasticity,facilitating efficient cellular reprogramming and,consequently,promoting the regeneration of skin appendages.In summary,the manipulation of mechanical cues using biomaterial-based strategies holds significant promise as a supplementary approach for achieving scarless wound healing,coupled with the restoration of multiple skin appendage functions.展开更多
As a new type of production factor in healthcare,healthcare data elements have been rapidly integrated into various health production processes,such as clinical assistance,health management,biological testing,and oper...As a new type of production factor in healthcare,healthcare data elements have been rapidly integrated into various health production processes,such as clinical assistance,health management,biological testing,and operation and supervision[1,2].Healthcare data elements include biolog.ical and clinical data that are related to disease,environ-mental health data that are associated with life,and operational and healthcare management data that are related to healthcare activities(Figure 1).Activities such as the construction of a data value assessment system,the devel-opment of a data circulation and sharing platform,and the authorization of data compliance and operation products support the strong growth momentum of the market for health care data elements in China[3].展开更多
BACKGROUND Coronavirus disease 2019(COVID-19)is strongly associated with an increased risk of thrombotic events,including severe outcomes such as pulmonary embolism.Elevated D-dimer levels are a critical biomarker for...BACKGROUND Coronavirus disease 2019(COVID-19)is strongly associated with an increased risk of thrombotic events,including severe outcomes such as pulmonary embolism.Elevated D-dimer levels are a critical biomarker for assessing this risk.In Gabon,early implementation of anticoagulation therapy and D-dimer testing has been crucial in managing COVID-19.This study hypothesizes that elevated Ddimer levels are linked to increased COVID-19 severity.AIM To determine the impact of D-dimer levels on COVID-19 severity and their role in guiding clinical decisions.METHODS This retrospective study analyzed COVID-19 patients admitted to two hospitals in Gabon between March 2020 and December 2023.The study included patients with confirmed COVID-19 diagnoses and available D-dimer measurements at admission.Data on demographics,clinical outcomes,D-dimer levels,and healthcare costs were collected.COVID-19 severity was classified as non-severe(outpatients)or severe(inpatients).A multivariable logistic regression model was used to assess the relationship between D-dimer levels and disease severity,with adjusted odds ratios(OR)and 95%CI.RESULTS A total of 3004 patients were included,with a mean age of 50.17 years,and the majority were female(53.43%).Elevated D-dimer levels were found in 65.81%of patients,and 57.21%of these experienced severe COVID-19.Univariate analysis showed that patients with elevated D-dimer levels had 3.33 times higher odds of severe COVID-19(OR=3.33,95%CI:2.84-3.92,P<0.001),and this association remained significant in the multivariable analysis,adjusted for age,sex,and year of collection.The financial analysis revealed a substantial burden,particularly for uninsured patients.CONCLUSION D-dimer predicts COVID-19 severity and guides treatment,but the high cost of anticoagulant therapy highlights the need for policies ensuring affordable access in resource-limited settings like Gabon.展开更多
Atrial fibrillation(AF)is a prevalent cardiac arrhythmia with a multifactorial pathophysiology involving electrical,structural,and autonomic remodeling of the atria.AF is closely associated with elevated interleukin-6...Atrial fibrillation(AF)is a prevalent cardiac arrhythmia with a multifactorial pathophysiology involving electrical,structural,and autonomic remodeling of the atria.AF is closely associated with elevated interleukin-6(IL-6)levels,which contribute to atrial remodeling and the progression of AF.This review summarizes the mechanisms by which IL-6 promotes AF through inflammatory pathways,atrial fibrosis,electrical remodeling,and calcium mishandling.Experimental models have demonstrated that IL-6 neutralization reduces the incidence of AF,highlighting its potential as a therapeutic target.Future studies should focus on IL-6 blockade strategies to manage AF,aiming to improve patient outcomes.展开更多
Dear Editor,Post-traumatic stress disorder(PTSD)is a major issue for military personnel,with prevalence rates between 1%and 35%in veterans^([1]),significantly higher than in the general population^([2]).Psychological ...Dear Editor,Post-traumatic stress disorder(PTSD)is a major issue for military personnel,with prevalence rates between 1%and 35%in veterans^([1]),significantly higher than in the general population^([2]).Psychological resources,particularly hope,can protect against PTSD and promote post-traumatic growth^([3]).Hope,conceptualized as both a trait and a state,contributes to well-being and resilience and is negatively associated with PTSD symptoms,representing a psychological factor while mitigating the impact of trauma by fostering resilience and adaptive coping mechanisms.展开更多
GaN diodes for high energy(64.8 MeV)proton detection were fabricated and investigated.A comparison of the performance of GaN diodes with different structures is presented,with a focus on sapphire and on GaN substrates...GaN diodes for high energy(64.8 MeV)proton detection were fabricated and investigated.A comparison of the performance of GaN diodes with different structures is presented,with a focus on sapphire and on GaN substrates,Schottky and pin diodes,and different active layer thicknesses.Pin diodes fabricated on a sapphire substrate are the best choice for a GaN proton detector working at 0 V bias.They are sensitive(minimum detectable proton beam<1 pA/cm^(2)),linear as a function of proton current and fast(<1 s).High proton current sensitivity and high spatial resolution of GaN diodes can be exploited in the future for proton imaging of patients in proton therapy.展开更多
BACKGROUND Second-line treatment of Crohn’s disease(CD)commonly involves immunosuppressants such as azathioprine,mercaptopurine,or methotrexate(MTX),used either alone or in combination.AIM To investigate the current ...BACKGROUND Second-line treatment of Crohn’s disease(CD)commonly involves immunosuppressants such as azathioprine,mercaptopurine,or methotrexate(MTX),used either alone or in combination.AIM To investigate the current use of MTX among French gastroenterologists.METHODS An online questionnaire was distributed between March and August 2023 to 116 French gastroenterologists managing CD.A total of 87 respondents completed the survey and were included in the analysis.RESULTS Respondents reported a mean annual caseload of 140 CD patients(median:50).Overall,71%prescribed MTX,predominantly in injectable form(92%),either as monotherapy or in combination with biologics or cyclosporin.MTX was prescribed for mild-to-moderate CD by 64%of respondents,and for severe CD by 58%,often in combination with an anti-tumor necrosis factor agent(89%and 94%,respectively).Injectable MTX was favored(84%)in specific clinical scenarios:Patients with articular manifestations(77%),Epstein-Barr virus-negative status(65%),or aged over 65 years(58%).Among the 29%of non-prescribers,the primary reason cited was lack of familiarity with MTX use(60%).Both prescribers and non-prescribers expressed the need for clearer guidelines and real-world data to support MTX use.CONCLUSION Regardless of prescribing habits,most respondents had a favorable opinion of MTX and recognized its good longterm safety profile.French learned societies and medical associations should provide consensus guidelines on MTX use,supported by validated real-world safety and effectiveness data.展开更多
This study aimed(1)to describe the experience of adolescents and adults using FitSpirit asynchronous virtual(V)exercise videos that target adolescent girls,(2)to compare physical activity(PA)levels and exercise-relate...This study aimed(1)to describe the experience of adolescents and adults using FitSpirit asynchronous virtual(V)exercise videos that target adolescent girls,(2)to compare physical activity(PA)levels and exercise-related selfperception variables among groups(2019 in-person[IP],2021 IP,and 2021 V)of adolescent girls,and(3)to assess the association between the adolescents’PA levels and their exercise-related self-perception in response to IP(pre-pandemic and during pandemic)and V(during pandemic)FitSpirit exercise modes.Regarding the first aim,28 adolescent girls([15.5±0.8]years old)and 29 adult women([33.0±10.3]years old)experienced the V exercise mode.For the second and third aims,376 girls([15.3±1.7]years old)participated IP in 2019(prepandemic),339 girls([14.9±1.6]years old)participated IP in 2021(during the pandemic),and 27 girls([15.5±0.8]years old)watched V FitSpirit exercise videos in 2021(during the pandemic).Data was collected using online questionnaires.Chi-square(χ^(2))and Pearson tests were performed.Adults(76%)had a significantly higher intention to use FitSpirit exercise videos again than adolescents(14%)(p<0.001).For IP exercise mode,we observed significant correlations between PA levels and being proud(r?0.08,p?0.046),feeling good(r=0.14,p<0.001),and being disappointed(r=-0.12,p<0.001).For the V exercise mode,there were no significant correlations.In conclusion,better exercise-related self-perception was only correlated to PA levels when IP training was offered.These first findings support IP training for adolescent girls when the pandemic situation allows it.展开更多
This letter comments on the recently published article in the World Journal of Gastroenterology,in which the authors demonstrated a strong link between lymphangiogenesis and the process of platelet adherence,aggregati...This letter comments on the recently published article in the World Journal of Gastroenterology,in which the authors demonstrated a strong link between lymphangiogenesis and the process of platelet adherence,aggregation,and activation by employing a rat model of liver cirrhosis caused by bile duct ligation(BDL).The authors applied both gain and loss of function approach by using platelet-rich plasma and vascular endothelial growth factor 3 receptor inhibitor MAZ-51 to activate and inhibit angiogenetic signaling in BDL rat model,respectively,to verify the crucial function of lymphangiogenesis in the development of liver cirrhosis and portal hypertension(PHT).In clinical practice,platelet transfusion has been applied to improve liver function in patients suffering from chronic liver disease and cirrhosis.Therefore,this study provides support for the application of platelet transfusion or pharmacological intervention of lymphangiogenesis as novel therapeutic approaches for liver cirrhosis and PHT.展开更多
Background:The prediction of postoperative pancreatic fistula(POPF)is important.This study aimed to investigate the role of postoperative serum lipase level in predicting POPF.Methods:Data from 234 consecutive patient...Background:The prediction of postoperative pancreatic fistula(POPF)is important.This study aimed to investigate the role of postoperative serum lipase level in predicting POPF.Methods:Data from 234 consecutive patients who underwent pancreaticoduodenectomy(PD)were collected.The predictive values of serum amylase and serum lipase during postoperative days(PODs)1 to 3 for POPF were compared.Subgroup analyses were performed to determine the prognostic value of different levels and durations of elevated serum lipase.Results:Fifty-six patients developed POPF.The POPF group exhibited increased levels of serum amylase and lipase from PODs 1 to 3(all P<0.001).Compared with serum amylase,serum lipase has greater predictive value for POPF.Specifically,serum lipase had the highest area under the receiver operating characteristic curve(AUC)at POD 1(0.791).Body mass index>24 kg/m2[odds ratio(OR)=2.431,95%confidence interval(CI):1.094–5.404,P=0.029],soft pancreatic texture(OR=3.189,95%CI:1.263–8.056,P=0.014),serum lipase>60 U/L at POD 1(OR=5.135,95%CI:1.257–20.982,P=0.023),and C-reactive protein>167 mg/dL at POD 3(OR=3.607,95%CI:1.431–9.090,P=0.007)were identified as independent risk factors for POPF.Patients with serum lipase≤60 U/L at POD 1(n=104)exhibited lower rates of POPF(3.8%vs.40.0%,P<0.001)and severe complications(Clavien-Dindo≥IIIa)(4.8%vs.25.4%,P<0.001)than those with serum lipase>60 U/L at POD 1.Moreover,no additional elevation or duration of serum lipase offered any further prognostic value.Conclusions:Postoperative serum lipase outperformed serum amylase in the prediction of POPF,and patients with normal serum lipase level at POD 1 had favorable outcomes.A sustained increase in the serum lipase level offers no additional prognostic value.展开更多
BACKGROUND The full implementation of the national two-child policy has presented significant challenges in ensuring the safety of pregnant women.AIM To investigate the effect of cervical balloon fluid volume on mater...BACKGROUND The full implementation of the national two-child policy has presented significant challenges in ensuring the safety of pregnant women.AIM To investigate the effect of cervical balloon fluid volume on maternal processes,maternal and infant outcomes,and anxiety during pregnancy.METHODS A total of 100 singleton term pregnancies with cervical maturity induction and anxiety were selected using a lottery method;50 women were included.Cervical balloons were used for all participants.In the control group,80 mL of fluid was injected into both balloons;in the observation group,80 and 100 mL were injected into the vaginal and cervical balloons,respectively.The two groups were compared for cervical maturity,labor duration,anxiety,maternal and infant outcomes,and effects on cervical ripening.RESULTS After treatment,the cervical maturity test(Bishop)score was significantly higher in the observation group(9.76±1.19)than in the control group(7.62±0.83),and the Hamilton Anxiety Scale score was lower in the observation group(7.32±0.85)than in the control group(13.05±1.12).The observation group showed higher rates of natural delivery and lower rates of cesarean section than the control group.The first and total stages of labor were shorter in the observation than in the control group;no significant differences were found in the second and third stages.The incidence of complications was lower in the observation group[1(2.00%)vs 9(18.00%)for complications;49(98.00%)vs 41(82.00%)for non-complications].CONCLUSION The selected fluid volumes to promote cervical maturity and induce labor stabilize maternal mood,increase the natural delivery rate,shorten labor,and improve maternal and infant outcomes.展开更多
Given the critical shortage of antibody-drug conjugates(ADCs)for bladder cancer(BCa),we developed a novel FGFR3-targeted ADC,LZU-WZLYFG001,composed of a humanized anti-FGFR3 IgG1 monoclonal antibody,a cleavable GGFG l...Given the critical shortage of antibody-drug conjugates(ADCs)for bladder cancer(BCa),we developed a novel FGFR3-targeted ADC,LZU-WZLYFG001,composed of a humanized anti-FGFR3 IgG1 monoclonal antibody,a cleavable GGFG linker,and the payload DXD.The antibody was engineered in 293 cells and conjugated via thiol-based chemistry,achieving a drug-to-antibody ratio(DAR)of eight.Comprehensive preclinical assessments,including in vitro and in vivo studies using BCa cells,organoids,cell-derived xenograft and patient-derived xenograft(PDX)models,were conducted to evaluate efficacy,targeting ability,mechanism,safety and tissue distribution.LZU-WZLYFG001 demonstrated high purity,targeting specificity and low endotoxin levels,and it significantly inhibited BCa cell proliferation,migration and invasion at nanomolar concentrations,with efficacy strongly associated with FGFR3 expression levels.Mechanistic studies showed binding to FGFR3,internalization and lysosomal release of LZU-WZLYFG001.In organoid and xenograft models,LZU-WZLYFG001 exhibited superior efficacy compared with the gemcitabine+cisplatin(GC)regimen,particularly in GC-resistant PDX tumors,while also showing robust 3D penetration,a bystander effect,and no significant short-term toxicity.展开更多
Sepsis,characterized as life-threatening organ dysfunction resulting from dysregulated host responses to infection,remains a significant challenge in clinical practice.Despite advancements in understanding host-bacter...Sepsis,characterized as life-threatening organ dysfunction resulting from dysregulated host responses to infection,remains a significant challenge in clinical practice.Despite advancements in understanding host-bacterial interactions,molecular responses,and therapeutic approaches,the mortality rate associated with sepsis has consistently ranged between 10%and 16%.This elevated mortality highlights critical gaps in our comprehension of sepsis etiology.Traditionally linked to bacterial and fungal pathogens,recent outbreaks of acute viral infections,including Middle East respiratory syndrome coronavirus(MERS-CoV),influenza virus,and severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),among other regional epidemics,have underscored the role of viral pathogenesis in sepsis,particularly when critically ill patients exhibit classic symptoms indicative of sepsis.However,many cases of viral-induced sepsis are frequently underdiagnosed because standard evaluations typically exclude viral panels.Moreover,these viruses not only activate conventional pattern recognition receptors(PRRs)and retinoic acid-inducible gene-I(RIG-I)-like receptors(RLRs)but also initiate primary antiviral pathways such as cyclic guanosine monophosphate adenosine monophosphate(GMP-AMP)synthase(cGAS)-stimulator of interferon genes(STING)signaling and interferon response mechanisms.Such activations lead to cellular stress,metabolic disturbances,and extensive cell damage that exacerbate tissue injury while leading to a spectrum of clinical manifestations.This complexity poses substantial challenges for the clinical management of affected cases.In this review,we elucidate the definition and diagnosis criteria for viral sepsis while synthesizing current knowledge regarding its etiology,epidemiology,and pathophysiology,molecular mechanisms involved therein as well as their impact on immune-mediated organ damage.Additionally,we discuss clinical considerations related to both existing therapies and advanced treatment interventions,aiming to enhance the comprehensive understanding surrounding viral sepsis.展开更多
BACKGROUND Childhood intestinal lymphoma is characterized by its insidious onset and the absence of specific clinical symptoms.The thinner abdominal wall in children significantly aids in the ultrasound visualization ...BACKGROUND Childhood intestinal lymphoma is characterized by its insidious onset and the absence of specific clinical symptoms.The thinner abdominal wall in children significantly aids in the ultrasound visualization of the abdominal cavity and intestines.Although many typical cases of intestinal lymphoma can be diagnosed through ultrasound,physicians often either overlook these values or assume that ultrasound has limited diagnostic value for intestinal lymphoma.AIM To clarify the diagnosis of intestinal lymphoma and classify its severity using ultrasound,as well as to correlate this with prognosis.METHODS The correlation between ultrasound diagnostic outcomes,laboratory indicators,and clinical prognosis was analyzed to demonstrate the effectiveness of ultrasound in assessing the severity of intestinal lymphoma and to provide new evidence for the diagnosis and treatment of the disease in children.A retro-spective analysis was conducted on the sonographic images and case data of 28 children diagnosed with intestinal lymphoma and confirmed by surgical pathology.Additionally,we sought to determine the correlation between ultrasonic classification of lymphoma,lactate dehydrogenase(LDH)values,pathological classification,and prognosis.RESULTS Ultrasound was utilized to categorize 28 cases of intestinal lymphoma into focal segmental(15 cases)and extensive(13 cases)types.Ultrasound classification and LDH levels were significantly correlated with prognosis(P<0.05),while pathological type,age,gender,and treatment modality showed no significant correlation(P>0.05).Among ultrasound manifestations,there was a significant difference in LDH levels between the segmental and extensive groups(P<0.05).The prognosis for children with extensive intestinal lymphoma was poorer than that for children with localized segmental intestinal lymphoma(P<0.05).CONCLUSION Ultrasound can be used in the diagnosis and classification of intestinal lymphoma in children.Extensive intestinal lymphoma is associated with significantly elevated LDH and poor prognosis.展开更多
基金the Scientific and Technological Research Council of Türkiye(TÜBİTAK)Under the International Postdoctoral Research Fellowship Program(2219),No.1059B192400980the National Postdoctoral Research Fellowship Program(2218),No.122C158.
文摘Acute respiratory distress syndrome(ARDS)is a life-threatening condition that is characterized by high mortality rates and limited therapeutic options.Notably,Zhang et al demonstrated that CD146+mesenchymal stromal cells(MSCs)exhibited greater therapeutic efficacy than CD146-MSCs.These cells enhance epithelial repair through nuclear factor kappa B/cyclooxygenase-2-associated paracrine signaling and secretion of pro-angiogenic factors.We concur that MSCs hold significant promise for ARDS treatment;however,the heterogeneity of cell products is a translational barrier.Phenotype-aware strategies,such as CD146 enrichment,standardized potency assays,and extracellular vesicle profiling,are essential for improving the consistency of these studies.Further-more,advanced preclinical models,such as lung-on-a-chip systems,may provide more predictive insights into the therapeutic mechanisms.This article underscores the importance of CD146+MSCs in ARDS,emphasizes the need for precision in defining cell products,and discusses how integrating subset selection into translational pipelines could enhance the clinical impact of MSC-based therapies.
基金supported by the National Natural Science Foundation of China(Nos.82104039 and 82404471)Guangdong Science Foundation for Young Top-Notch Talent of Zhu-Jiang Talent Plan(No.0920220225)+1 种基金Guangdong Basic and Applied Basic Research Foundation(Nos.2023B1515120053 and 2022A1515111026)Guangzhou Municipal Science and Technology Bureau Foundation(No.2024A04J2704).
文摘Penicine A(1),a meroterpenoid featuring a novel 3/5/6/6/11/6/6 polycyclic backbone,together with two new metabolites,penicines B(2)and C(4),and six known compounds,were isolated from the mangrove rhizosphere soil-derived fungus Penicillium brefeldianum SMU03.The structures of these metabolites were elucidated through extensive spectroscopic analysis combined with quantum chemical calculations.Notably,1 exhibits a highly unusual molecular architecture,incorporating a dioxaspiro[4.5]decane motif and a rare bridgehead double bond(anti-Bredt system).A plausible biosynthetic pathway,involving sequential intermolecular[4+2]cycloaddition reactions,is proposed.Additionally,meroterpenoids 1 and 3 demonstrate significant antifibrotic activity in transforming growth factorβ1(TGF-β1)-induced human renal proximal tubular epithelial cells.
基金supported by the National Natural Science Foundation of China(62325112)the National Key Research and Development Program of China(2023YFC2411700,2023YFC2411705)+2 种基金the National Natural Science Foundation of China(U22A2023)the National High-Level Hospital Clinical Research Funding(2022-PUMCH-C-009,2022-PUMCH-B-064,2022-PUMCH-D-002)the National Basic Research Program of China(973 Program,2014CB541801).
文摘Conventional ultrasound(US)evaluation of enthesitis in psoriatic arthritis(PsA)is limited by its inability to quantify metabolic alterations such as hypoxia,a key driver of disease activity.We introduce an oxygenation-integrated multimodal photoacoustic/ultrasound(PA/US)imaging framework designed to quantify entheseal oxygen saturation(SO_(2))for assessing entheseal disease activity in PsA.In this cross-sectional study,25 PsA patients underwent bilateral PA/US imaging of 12 entheses,where ultrasound lesions were scored using the Outcome Measures in Rheumatology scoring system,and PA-derived SO_(2) levels,quantified via dual-wavelength PA imaging,were classified into hyperoxia or hypoxia groups using k-means clustering.This approach provides metabolic insights complementary to conventional ultrasonic assessment.A composite score integrating hypoxia with US parameters was validated against clinical disease activity indices(Disease Activity Score 28-C-reactive protein,DAS28-CRP;Disease Activity Index for Psoriatic Arthritis,DAPSA).Among 300 entheses,103(34.3%)exhibited PA positivity,with 40(38.8%)classified as hypoxia.Hypoxia scores independently predicted DAS28-CRP(β=0.618,p=0.001)and DAPSA(β=0.612,p<0:001).The hypoxia-optimized PAUS score demonstrated superior correlation with disease activity indices compared to conventional US(DAS28-CRP:r=0.615,p=0.001 versus r=0.474,p=0.017;DAPSA:r=0.743,p<0:001 versus r=0.567,p=0.003),alongside superior diagnostic accuracy for minimal disease activity(area under the curve,AUC 0.776 versus 0.614,p=0.008)and low disease activity(AUC 0.853 versus 0.772,p=0.009).This multimodal scoring system enhances the stratification of PsA disease activity by providing unique metabolic insights,offering a potential tool for therapeutic monitoring and guiding treat-to-target strategies.
基金supported by the National Science and Technology Council(NSTC 113-2320-B-039-049-MY3 and NSTC 114-2314-B-039-051-MY3)China Medical University(CMU113-ASIA-05,CMU-114-ASIA-01).
文摘Background:Prostate cancer(PCa)is the most prevalent malignancy in men and often correlates with distant metastasis in its advanced stages.The study aimed to investigate the effects of Ugonin J,a natural compound isolated from Helminthostachys zeylanica,on PCa metastasis.Methods:The effects of Ugonin J on cell motility were assessed using migration and invasion assays.Reverse Transcription Quantitative PCR(RT-qPCR)and Western blotting were used to evaluate the impact of Ugonin J on mRNA and protein expression.RNA sequencing(RNA-seq)analysis was performed to investigate candidate mechanisms.Differential gene expression analysis in PCa patients was conducted using multiple databases.Results:Here,we reveal that Ugonin J blocks migration and invasion in PCa cells without affecting cell viability.RNA-seq analysis suggests that epithelial-mesenchymal transition(EMT)is potentially involved in Ugonin J’s anti-motility effects.Ugonin J also suppresses the expression of mesenchymal markers N-cadherin,β-catenin,Snail,and Slug while upregulating the expression of the epithelial marker E-cadherin.Furthermore,among 13 A disintegrin and metalloproteinase(ADAM)proteins,A disintegrin and metalloproteinase domain-containing protein 9(ADAM9)is the most downregulated following Ugonin J treatment,according to our RNA-seq data.Importantly,clinical data revealed that ADAM9 expression are higher in PCa patients than in healthy controls and are associated with distant metastasis.Transfection with ADAM9 cDNA reverses Ugonin J-regulated downregulation of EMT,migration,and invasion in PCa cells.Ugonin J inhibits ADAM9-dependent motility by downregulating the phosphoinositide 3-kinase(PI3K),protein kinase B(Akt)and nuclear factor-κB(NF-κB)pathways.Conclusions:Our evidence suggests that Ugonin J is a novel therapeutic candidate for further development as a treatment for metastatic PCa.
基金supported by the National Natural Science Foundation of China(82170951,82470961)the Beijing Natural Science Foundation (7222079)+4 种基金the Beijing Hospital Authority"Dengfeng"Talent Training Plan (DFL 20221301)the Beijing Stomatological HospitalCapital Medical University Young Scientist Program (No.YSP202401)the Laboratory for Clinical Medicine and the Central Laboratory of Capital Medical University for their technical support and fundingthe Japan China Sasakawa Medical Fellowship for their generous support and funding。
文摘The functional regeneration of the dentin-pulp complex is pivotal for tooth preservation,yet the molecular mechanisms governing odontoblast differentiation remain poorly understood.In the current study,we revealed a distinct NKD1^(+) subpopulation exhibiting secretory odontoblast characteristics,which was specifically induced in dental pulp stem cells(DPSCs) by Wnt3a,but not by Wnt5a or Wnt10a through single-cell transcriptomic profiling.We then found that the NKD1^(+) subpopulation was functional conservation,which were consistently identified in the odontoblast layers of developing tooth germs in both murine and miniature pig models,as well as within the apical open area in human molars.This conserved spatial distribution and co-localization with DSPP strongly indicates that NKD1^(+) cells were active dentin-secreting odontoblasts.Analysis of gene regulatory networks using SCENIC identified MSX1 as a key transcription factor regulating the specification of NKD1^(+) lineage.Mechanistically,Wnt3a orchestrates a tripartite cascade:upregulating NKD1/MSX1 expression,triggering NKD1 membrane detachment,and facilitating direct NKD1-MSX1interaction to promote MSX1 nuclear translocation.CUT&Tag analysis demonstrated MSX1 occupancy at promoters of odontogenic regulato rs,esta blishing its necessity for odontogenic gene activation.Murine pulp exposure models validated that Wnt3a-activated NKD1-MSX1 signaling significantly enhances reparative dentin formation.This study delineates an evolutionarily conserved Wnt3aNKD1-MSX1 axis that resolves stem cell heterogeneity into functional odontoblast commitment,providing both mechanistic insights into dentin-pulp regeneration and a foundation for targeted regenerative therapies.
基金supported by the National Natural Science Foundation of China,Nos.32070735(to QL),82371321(to QL),82171270(to ZL)Public Service Platform for Artificial Intelligence Screening and Auxiliary Diagnosis for the Medical and Health Industry,Ministry of Industry and Information Technology of the People's Republic of China,No.2020-0103-3-1(to ZL)+2 种基金the Natural Science Foundation of Beijing,No.Z200016(to ZL)Beijing Talents Project,No.2018000021223ZK03(to ZL)Beijing Municipal Committee of Science and Technology,No.Z201100005620010(to ZL)。
文摘Stroke is classified as ischemic or hemorrhagic,and there are few effective treatments for either type.Immunologic mechanisms play a critical role in secondary brain injury following a stroke,which manifests as cytokine release,blood–brain barrier disruption,neuronal cell death,and ultimately behavioral impairment.Suppressing the inflammatory response has been shown to mitigate this cascade of events in experimental stroke models.However,in clinical trials of anti-inflammatory agents,longterm immunosuppression has not demonstrated significant clinical benefits for patients.This may be attributable to the dichotomous roles of inflammation in both tissue injury and repair,as well as the complex pathophysiologic inflammatory processes in stroke.Inhibiting acute harmful inflammatory responses or inducing a phenotypic shift from a pro-inflammatory to an anti-inflammatory state at specific time points after a stroke are alternative and promising therapeutic strategies.Identifying agents that can modulate inflammation requires a detailed understanding of the inflammatory processes of stroke.Furthermore,epigenetic reprogramming plays a crucial role in modulating post-stroke inflammation and can potentially be exploited for stroke management.In this review,we summarize current findings on the epigenetic regulation of the inflammatory response in stroke,focusing on key signaling pathways including nuclear factor-kappa B,Janus kinase/signal transducer and activator of transcription,and mitogen-activated protein kinase as well as inflammasome activation.We also discuss promising molecular targets for stroke treatment.The evidence to date indicates that therapeutic targeting of the epigenetic regulation of inflammation can shift the balance from inflammation-induced tissue injury to repair following stroke,leading to improved post-stroke outcomes.
基金supported in part by the National Nature Science Foundation of China(92268206,81830064)the CAMS Innovation Fund for Medical Sciences(CIFMS,2019-I2M-5-059)+4 种基金the Military Medical Research Projects(145AKJ260015000X,2022-JCJQ-ZB-09600)the Military Key Basic Research of Foundational Strengthening Program(2020-JCJQ-ZD-256-021)the Science Foundation of National Defense Science and Technology for Excellent Young(2022-JCJQ-ZQ-017)the Military Medical Research and Development Projects(AWS17J005,2019-126)the Specific Research Fund of The Innovation Platform for Academicians of Hainan Province(YSPTZX202317).
文摘Scar formation resulting from burns or severe trauma can significantly compromise the structural integrity of skin and lead to permanent loss of skin appendages,ultimately impairing its normal physiological function.Accumulating evidence underscores the potential of targeted modulation of mechanical cues to enhance skin regeneration,promoting scarless repair by influencing the extracellular microenvironment and driving the phenotypic transitions.The field of skin repair and skin appendage regeneration has witnessed remarkable advancements in the utilization of biomaterials with distinct physical properties.However,a comprehensive understanding of the underlying mechanisms remains somewhat elusive,limiting the broader application of these innovations.In this review,we present two promising biomaterial-based mechanical approaches aimed at bolstering the regenerative capacity of compromised skin.The first approach involves leveraging biomaterials with specific biophysical properties to create an optimal scarless environment that supports cellular activities essential for regeneration.The second approach centers on harnessing mechanical forces exerted by biomaterials to enhance cellular plasticity,facilitating efficient cellular reprogramming and,consequently,promoting the regeneration of skin appendages.In summary,the manipulation of mechanical cues using biomaterial-based strategies holds significant promise as a supplementary approach for achieving scarless wound healing,coupled with the restoration of multiple skin appendage functions.
基金supported by National Natural Science Foundation of China(Grants 72474022,71974011,72174022,71972012,71874009)"BIT think tank"Promotion Plan of Science and Technology Innovation Program of Beijing Institute of Technology(Grants 2024CX14017,2023CX13029).
文摘As a new type of production factor in healthcare,healthcare data elements have been rapidly integrated into various health production processes,such as clinical assistance,health management,biological testing,and operation and supervision[1,2].Healthcare data elements include biolog.ical and clinical data that are related to disease,environ-mental health data that are associated with life,and operational and healthcare management data that are related to healthcare activities(Figure 1).Activities such as the construction of a data value assessment system,the devel-opment of a data circulation and sharing platform,and the authorization of data compliance and operation products support the strong growth momentum of the market for health care data elements in China[3].
文摘BACKGROUND Coronavirus disease 2019(COVID-19)is strongly associated with an increased risk of thrombotic events,including severe outcomes such as pulmonary embolism.Elevated D-dimer levels are a critical biomarker for assessing this risk.In Gabon,early implementation of anticoagulation therapy and D-dimer testing has been crucial in managing COVID-19.This study hypothesizes that elevated Ddimer levels are linked to increased COVID-19 severity.AIM To determine the impact of D-dimer levels on COVID-19 severity and their role in guiding clinical decisions.METHODS This retrospective study analyzed COVID-19 patients admitted to two hospitals in Gabon between March 2020 and December 2023.The study included patients with confirmed COVID-19 diagnoses and available D-dimer measurements at admission.Data on demographics,clinical outcomes,D-dimer levels,and healthcare costs were collected.COVID-19 severity was classified as non-severe(outpatients)or severe(inpatients).A multivariable logistic regression model was used to assess the relationship between D-dimer levels and disease severity,with adjusted odds ratios(OR)and 95%CI.RESULTS A total of 3004 patients were included,with a mean age of 50.17 years,and the majority were female(53.43%).Elevated D-dimer levels were found in 65.81%of patients,and 57.21%of these experienced severe COVID-19.Univariate analysis showed that patients with elevated D-dimer levels had 3.33 times higher odds of severe COVID-19(OR=3.33,95%CI:2.84-3.92,P<0.001),and this association remained significant in the multivariable analysis,adjusted for age,sex,and year of collection.The financial analysis revealed a substantial burden,particularly for uninsured patients.CONCLUSION D-dimer predicts COVID-19 severity and guides treatment,but the high cost of anticoagulant therapy highlights the need for policies ensuring affordable access in resource-limited settings like Gabon.
基金supported by the National Natural Science Foundation of China(No.82170326 and No.82470328 to Y.D.,No.82100339 to Q.D.).
文摘Atrial fibrillation(AF)is a prevalent cardiac arrhythmia with a multifactorial pathophysiology involving electrical,structural,and autonomic remodeling of the atria.AF is closely associated with elevated interleukin-6(IL-6)levels,which contribute to atrial remodeling and the progression of AF.This review summarizes the mechanisms by which IL-6 promotes AF through inflammatory pathways,atrial fibrosis,electrical remodeling,and calcium mishandling.Experimental models have demonstrated that IL-6 neutralization reduces the incidence of AF,highlighting its potential as a therapeutic target.Future studies should focus on IL-6 blockade strategies to manage AF,aiming to improve patient outcomes.
基金supported by the Institut de Recherche Biomédicale des Armées(Brétigny-sur-Orge,France).
文摘Dear Editor,Post-traumatic stress disorder(PTSD)is a major issue for military personnel,with prevalence rates between 1%and 35%in veterans^([1]),significantly higher than in the general population^([2]).Psychological resources,particularly hope,can protect against PTSD and promote post-traumatic growth^([3]).Hope,conceptualized as both a trait and a state,contributes to well-being and resilience and is negatively associated with PTSD symptoms,representing a psychological factor while mitigating the impact of trauma by fostering resilience and adaptive coping mechanisms.
基金support from MATRIX(ANR-22-CE92-0047)with financial support from ITMI Cancer of Aviesan within the framework of the 2021−2030 Cancer Control Strategy,on funds administrated by INSERM through the project NECTAR.Matilde Siviero acknowledges funding from the French−German University/Saarbrücken(contract CDOC-06-2022).
文摘GaN diodes for high energy(64.8 MeV)proton detection were fabricated and investigated.A comparison of the performance of GaN diodes with different structures is presented,with a focus on sapphire and on GaN substrates,Schottky and pin diodes,and different active layer thicknesses.Pin diodes fabricated on a sapphire substrate are the best choice for a GaN proton detector working at 0 V bias.They are sensitive(minimum detectable proton beam<1 pA/cm^(2)),linear as a function of proton current and fast(<1 s).High proton current sensitivity and high spatial resolution of GaN diodes can be exploited in the future for proton imaging of patients in proton therapy.
文摘BACKGROUND Second-line treatment of Crohn’s disease(CD)commonly involves immunosuppressants such as azathioprine,mercaptopurine,or methotrexate(MTX),used either alone or in combination.AIM To investigate the current use of MTX among French gastroenterologists.METHODS An online questionnaire was distributed between March and August 2023 to 116 French gastroenterologists managing CD.A total of 87 respondents completed the survey and were included in the analysis.RESULTS Respondents reported a mean annual caseload of 140 CD patients(median:50).Overall,71%prescribed MTX,predominantly in injectable form(92%),either as monotherapy or in combination with biologics or cyclosporin.MTX was prescribed for mild-to-moderate CD by 64%of respondents,and for severe CD by 58%,often in combination with an anti-tumor necrosis factor agent(89%and 94%,respectively).Injectable MTX was favored(84%)in specific clinical scenarios:Patients with articular manifestations(77%),Epstein-Barr virus-negative status(65%),or aged over 65 years(58%).Among the 29%of non-prescribers,the primary reason cited was lack of familiarity with MTX use(60%).Both prescribers and non-prescribers expressed the need for clearer guidelines and real-world data to support MTX use.CONCLUSION Regardless of prescribing habits,most respondents had a favorable opinion of MTX and recognized its good longterm safety profile.French learned societies and medical associations should provide consensus guidelines on MTX use,supported by validated real-world safety and effectiveness data.
基金co-funded by the Public Health Agency of Canada and the FitSpirit organization.
文摘This study aimed(1)to describe the experience of adolescents and adults using FitSpirit asynchronous virtual(V)exercise videos that target adolescent girls,(2)to compare physical activity(PA)levels and exercise-related selfperception variables among groups(2019 in-person[IP],2021 IP,and 2021 V)of adolescent girls,and(3)to assess the association between the adolescents’PA levels and their exercise-related self-perception in response to IP(pre-pandemic and during pandemic)and V(during pandemic)FitSpirit exercise modes.Regarding the first aim,28 adolescent girls([15.5±0.8]years old)and 29 adult women([33.0±10.3]years old)experienced the V exercise mode.For the second and third aims,376 girls([15.3±1.7]years old)participated IP in 2019(prepandemic),339 girls([14.9±1.6]years old)participated IP in 2021(during the pandemic),and 27 girls([15.5±0.8]years old)watched V FitSpirit exercise videos in 2021(during the pandemic).Data was collected using online questionnaires.Chi-square(χ^(2))and Pearson tests were performed.Adults(76%)had a significantly higher intention to use FitSpirit exercise videos again than adolescents(14%)(p<0.001).For IP exercise mode,we observed significant correlations between PA levels and being proud(r?0.08,p?0.046),feeling good(r=0.14,p<0.001),and being disappointed(r=-0.12,p<0.001).For the V exercise mode,there were no significant correlations.In conclusion,better exercise-related self-perception was only correlated to PA levels when IP training was offered.These first findings support IP training for adolescent girls when the pandemic situation allows it.
基金Supported by National Natural Science Foundation of China,No.82460461Medical Subject Leader of Yunnan Province(General Surgery),No.D-2024029+2 种基金Yunnan Fundamental Research Project for Excellent Young Scholars,No.202401AW070003The Young and Mid-aged Academic and Technical Leader Reserve Talent Program of Yunnan Province,No.202205AC160063Beijing Bethune Charitable Foundation,No.STLKY0089.
文摘This letter comments on the recently published article in the World Journal of Gastroenterology,in which the authors demonstrated a strong link between lymphangiogenesis and the process of platelet adherence,aggregation,and activation by employing a rat model of liver cirrhosis caused by bile duct ligation(BDL).The authors applied both gain and loss of function approach by using platelet-rich plasma and vascular endothelial growth factor 3 receptor inhibitor MAZ-51 to activate and inhibit angiogenetic signaling in BDL rat model,respectively,to verify the crucial function of lymphangiogenesis in the development of liver cirrhosis and portal hypertension(PHT).In clinical practice,platelet transfusion has been applied to improve liver function in patients suffering from chronic liver disease and cirrhosis.Therefore,this study provides support for the application of platelet transfusion or pharmacological intervention of lymphangiogenesis as novel therapeutic approaches for liver cirrhosis and PHT.
基金supported by grants from the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2019-I2M-5–056)the National Natural Science Foundation of China(81930119,82090050,and 82090053)。
文摘Background:The prediction of postoperative pancreatic fistula(POPF)is important.This study aimed to investigate the role of postoperative serum lipase level in predicting POPF.Methods:Data from 234 consecutive patients who underwent pancreaticoduodenectomy(PD)were collected.The predictive values of serum amylase and serum lipase during postoperative days(PODs)1 to 3 for POPF were compared.Subgroup analyses were performed to determine the prognostic value of different levels and durations of elevated serum lipase.Results:Fifty-six patients developed POPF.The POPF group exhibited increased levels of serum amylase and lipase from PODs 1 to 3(all P<0.001).Compared with serum amylase,serum lipase has greater predictive value for POPF.Specifically,serum lipase had the highest area under the receiver operating characteristic curve(AUC)at POD 1(0.791).Body mass index>24 kg/m2[odds ratio(OR)=2.431,95%confidence interval(CI):1.094–5.404,P=0.029],soft pancreatic texture(OR=3.189,95%CI:1.263–8.056,P=0.014),serum lipase>60 U/L at POD 1(OR=5.135,95%CI:1.257–20.982,P=0.023),and C-reactive protein>167 mg/dL at POD 3(OR=3.607,95%CI:1.431–9.090,P=0.007)were identified as independent risk factors for POPF.Patients with serum lipase≤60 U/L at POD 1(n=104)exhibited lower rates of POPF(3.8%vs.40.0%,P<0.001)and severe complications(Clavien-Dindo≥IIIa)(4.8%vs.25.4%,P<0.001)than those with serum lipase>60 U/L at POD 1.Moreover,no additional elevation or duration of serum lipase offered any further prognostic value.Conclusions:Postoperative serum lipase outperformed serum amylase in the prediction of POPF,and patients with normal serum lipase level at POD 1 had favorable outcomes.A sustained increase in the serum lipase level offers no additional prognostic value.
基金Supported by the Wuxi Municipal Health Commission Maternal and Child Health Research Project,No.FYKY202202.
文摘BACKGROUND The full implementation of the national two-child policy has presented significant challenges in ensuring the safety of pregnant women.AIM To investigate the effect of cervical balloon fluid volume on maternal processes,maternal and infant outcomes,and anxiety during pregnancy.METHODS A total of 100 singleton term pregnancies with cervical maturity induction and anxiety were selected using a lottery method;50 women were included.Cervical balloons were used for all participants.In the control group,80 mL of fluid was injected into both balloons;in the observation group,80 and 100 mL were injected into the vaginal and cervical balloons,respectively.The two groups were compared for cervical maturity,labor duration,anxiety,maternal and infant outcomes,and effects on cervical ripening.RESULTS After treatment,the cervical maturity test(Bishop)score was significantly higher in the observation group(9.76±1.19)than in the control group(7.62±0.83),and the Hamilton Anxiety Scale score was lower in the observation group(7.32±0.85)than in the control group(13.05±1.12).The observation group showed higher rates of natural delivery and lower rates of cesarean section than the control group.The first and total stages of labor were shorter in the observation than in the control group;no significant differences were found in the second and third stages.The incidence of complications was lower in the observation group[1(2.00%)vs 9(18.00%)for complications;49(98.00%)vs 41(82.00%)for non-complications].CONCLUSION The selected fluid volumes to promote cervical maturity and induce labor stabilize maternal mood,increase the natural delivery rate,shorten labor,and improve maternal and infant outcomes.
基金supported by the Major Science and Technology Special Project of Gansu Province(24ZDFA002)the National Natural Science Foundation of China(82060459)+1 种基金the Key Research and Development Program of Gansu Province(23YFFA0007)the Joint Research Fund of Gansu Province(23JRRA1511)。
文摘Given the critical shortage of antibody-drug conjugates(ADCs)for bladder cancer(BCa),we developed a novel FGFR3-targeted ADC,LZU-WZLYFG001,composed of a humanized anti-FGFR3 IgG1 monoclonal antibody,a cleavable GGFG linker,and the payload DXD.The antibody was engineered in 293 cells and conjugated via thiol-based chemistry,achieving a drug-to-antibody ratio(DAR)of eight.Comprehensive preclinical assessments,including in vitro and in vivo studies using BCa cells,organoids,cell-derived xenograft and patient-derived xenograft(PDX)models,were conducted to evaluate efficacy,targeting ability,mechanism,safety and tissue distribution.LZU-WZLYFG001 demonstrated high purity,targeting specificity and low endotoxin levels,and it significantly inhibited BCa cell proliferation,migration and invasion at nanomolar concentrations,with efficacy strongly associated with FGFR3 expression levels.Mechanistic studies showed binding to FGFR3,internalization and lysosomal release of LZU-WZLYFG001.In organoid and xenograft models,LZU-WZLYFG001 exhibited superior efficacy compared with the gemcitabine+cisplatin(GC)regimen,particularly in GC-resistant PDX tumors,while also showing robust 3D penetration,a bystander effect,and no significant short-term toxicity.
基金supported by the National Natural Science Foundation of China(82372176,82272217,82002026,81971818)the Hubei Provincial Key Research and Development Program of China(2023BCB091)the National Key Research and Development Program of China(2021YFC2500802,2021YFC2300200).
文摘Sepsis,characterized as life-threatening organ dysfunction resulting from dysregulated host responses to infection,remains a significant challenge in clinical practice.Despite advancements in understanding host-bacterial interactions,molecular responses,and therapeutic approaches,the mortality rate associated with sepsis has consistently ranged between 10%and 16%.This elevated mortality highlights critical gaps in our comprehension of sepsis etiology.Traditionally linked to bacterial and fungal pathogens,recent outbreaks of acute viral infections,including Middle East respiratory syndrome coronavirus(MERS-CoV),influenza virus,and severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),among other regional epidemics,have underscored the role of viral pathogenesis in sepsis,particularly when critically ill patients exhibit classic symptoms indicative of sepsis.However,many cases of viral-induced sepsis are frequently underdiagnosed because standard evaluations typically exclude viral panels.Moreover,these viruses not only activate conventional pattern recognition receptors(PRRs)and retinoic acid-inducible gene-I(RIG-I)-like receptors(RLRs)but also initiate primary antiviral pathways such as cyclic guanosine monophosphate adenosine monophosphate(GMP-AMP)synthase(cGAS)-stimulator of interferon genes(STING)signaling and interferon response mechanisms.Such activations lead to cellular stress,metabolic disturbances,and extensive cell damage that exacerbate tissue injury while leading to a spectrum of clinical manifestations.This complexity poses substantial challenges for the clinical management of affected cases.In this review,we elucidate the definition and diagnosis criteria for viral sepsis while synthesizing current knowledge regarding its etiology,epidemiology,and pathophysiology,molecular mechanisms involved therein as well as their impact on immune-mediated organ damage.Additionally,we discuss clinical considerations related to both existing therapies and advanced treatment interventions,aiming to enhance the comprehensive understanding surrounding viral sepsis.
基金Supported by the Fujian Province Science and Technology Innovation Joint Fund Project,No.2021Y9188。
文摘BACKGROUND Childhood intestinal lymphoma is characterized by its insidious onset and the absence of specific clinical symptoms.The thinner abdominal wall in children significantly aids in the ultrasound visualization of the abdominal cavity and intestines.Although many typical cases of intestinal lymphoma can be diagnosed through ultrasound,physicians often either overlook these values or assume that ultrasound has limited diagnostic value for intestinal lymphoma.AIM To clarify the diagnosis of intestinal lymphoma and classify its severity using ultrasound,as well as to correlate this with prognosis.METHODS The correlation between ultrasound diagnostic outcomes,laboratory indicators,and clinical prognosis was analyzed to demonstrate the effectiveness of ultrasound in assessing the severity of intestinal lymphoma and to provide new evidence for the diagnosis and treatment of the disease in children.A retro-spective analysis was conducted on the sonographic images and case data of 28 children diagnosed with intestinal lymphoma and confirmed by surgical pathology.Additionally,we sought to determine the correlation between ultrasonic classification of lymphoma,lactate dehydrogenase(LDH)values,pathological classification,and prognosis.RESULTS Ultrasound was utilized to categorize 28 cases of intestinal lymphoma into focal segmental(15 cases)and extensive(13 cases)types.Ultrasound classification and LDH levels were significantly correlated with prognosis(P<0.05),while pathological type,age,gender,and treatment modality showed no significant correlation(P>0.05).Among ultrasound manifestations,there was a significant difference in LDH levels between the segmental and extensive groups(P<0.05).The prognosis for children with extensive intestinal lymphoma was poorer than that for children with localized segmental intestinal lymphoma(P<0.05).CONCLUSION Ultrasound can be used in the diagnosis and classification of intestinal lymphoma in children.Extensive intestinal lymphoma is associated with significantly elevated LDH and poor prognosis.
