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
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
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
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 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
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
Triple-negative breast cancer (TNBC) is an aggressive and often fatal disease, especially since the brain metastasis of TNBC has been a particularly severe manifestation. However, brain metastasis in TNBC at early sta...Triple-negative breast cancer (TNBC) is an aggressive and often fatal disease, especially since the brain metastasis of TNBC has been a particularly severe manifestation. However, brain metastasis in TNBC at early stages often lacks noticeable symptoms, making it challenging to detect. Near-infrared II (NIR-II) fluorescence microscopic imaging obtains long wavelength, which enables reduced scattering, high spatial resolution and minimal autofluorescence, it is also a favorable imaging method for tumor diagnosis. PbS@CdS quantum dots (QDs) are one of the popular NIR-II fluorescence nanoprobes for well brightness. In this study, NIR-II emissive PbS@CdS QDs were utilized and further encapsulated with thiol-terminated poly(ethylene oxide) (SH-PEG, MW = 5000) to form PbS@CdS@PEG QDs nanoparticles (NPs). The obtained PbS@CdS@PEG QDs NPs were then characterized and further studied in detail. The PbS@CdS@PEG QDs NPs had large absorption spectra, exhibited strong NIR-II fluorescence emission at approximately 1300nm, and possessed good NIR-II fluorescence properties. Then, the mice model of early-stage brain metastases of TNBC was established, and the PbS@CdS@PEG QDs NPs were injected into the tumor-bearing mice for NIR-II fluorescence microscopic bioimaging. The brain vessels and tumors of the living mice were detected with high spatial resolution under the NIR-II fluorescence microscopic imaging system with irradiation of 808nm laser. The tumor tissues were further restricted and prepared as thin slices. The NIR-II fluorescence signals were collected from the tumor slices with high spatial resolution and signal-to-background ratio (SBR). Thus, the PbS@CdS@PEG QDs NPs-assisted NIR-II fluorescence microscopic system can effectively achieve targeting brain metastases of TNBC imaging, offering a novel and promising approach for TNBC-specific diagnosis.展开更多
In recent years,the rapid evolution of cancer therapies has markedly increased patient survival rates.However,the incidence of adverse events caused by anticancer treatments remains high,leading to significant clinica...In recent years,the rapid evolution of cancer therapies has markedly increased patient survival rates.However,the incidence of adverse events caused by anticancer treatments remains high,leading to significant clinical challenges.As the central hub of drug metabolism and detoxification,the liver is susceptible to therapeutic insults.The specific mechanisms of liver injury caused by different types of antineoplastic treatments vary.Chemotherapy induces hepatic damage via oxidative stress and mitochondrial dysfunction,whereas targeted therapy disrupts signaling pathways in hepatic cells.Immunotherapy triggers immunemediated hepatitis through cytokine storms and immune cell infiltration,and radiation therapy causes hepatic microvascular injury.Additionally,patients with preexisting chronic liver diseases(such as cirrhosis,hepatitis B/C,or nonalcoholic fatty liver disease)are more likely to face increased risks of hepatic injury during cancer treatment.Therefore,early detection and timely treatment are crucial for these high-risk populations.This review introduces the emerging field of“oncohepatology”,which illuminates the mechanisms underlying hepatic injury due to cancer treatments,summarizes the influence and management of preexisting liver disease during cancer treatment,analyzes diagnostic and therapeutic strategies for cancer treatment-associated liver function damage,and discusses potential future research directions to provide valuable insights for liver injury management in clinical oncology.展开更多
Background:Effective inhibition of pathological cardiac hypertrophy is critical for managing various cardiovascular diseases,especially in cold environments.The communication between cardiomyocytes and fibroblasts,med...Background:Effective inhibition of pathological cardiac hypertrophy is critical for managing various cardiovascular diseases,especially in cold environments.The communication between cardiomyocytes and fibroblasts,mediated by secreted proteins,plays a significant role in the development and progression of pathological cardiac hypertrophy.Serpin Family E Member 2(serpinE2),secreted by fibroblasts into the extracellular space,has been implicated in this process.However,whether serpinE2 can be internalized by cardiomyocytes and whether cold exposure influences this process remains unclear.Materials and methods:Mice were subjected to cold exposure(4°C,12 h/day for 8 weeks),and cardiac hypertrophy was induced by transverse aortic constriction(TAC).SerpinE2 expression was silenced by short interfering RNA(siRNA).Cardiac fibroblasts were stimulated with angiotensin II(Ang II)to induce serpinE2 secretion.Exogenous recombinant serpinE2,labeled with DyLight 488 or His-tag,was used to evaluate its internalization and functional role in cardiomyocytes.Internalization was inhibited by using antibodies against serpinE2,heparin,or endocytosis inhibitors(β-cyclodextrin,nystatin,dynasore,and chlorpromazine).Chromatin immunoprecipitation followed by quantitative polymerase chain reaction(PCR)was used to assess the binding of the transcription factor CDX1 to the serpinE2 promoter.Results:Cold exposure significantly increased serpinE2 mRNA and protein expression in mouse hearts.SerpinE2 levels were also upregulated in plasma and cardiac tissue following TAC.Knockdown of serpinE2 attenuated TAC-induced hypertrophy,restored left ventricular function,and reduced atrial natriuretic peptide,brain natriuretic peptide,andβ-myosin heavy chain fragment levels.Exogenous serpinE2 promoted cardiomyocyte hypertrophy,an effect that was reversed by serpinE2 knockdown.Co-culture with conditioned medium from Ang II-stimulated fibroblasts increased serpinE2 expression in cardiomyocytes.Exogenous serpinE2 was internalized via endocytosis,which was inhibited by antibodies,heparin,and endocytosis blockers.Internalized serpinE2 activated the protein kinase B(AKT)/β-catenin pathway in cardiomyocytes.CDX1 bound to the serpinE2 promoter and promoted its transcription in fibroblasts.CDX1 overexpression increased serpinE2 and collagen expression,while its suppression had the opposite effect.Administration of exogenous fibroblast growth factor 4(FGF4)or overexpression of FGF4 plasmid upregulated CDX1,serpinE2,and collagen expression in fibroblasts.Conclusions:SerpinE2 expression is responsive to cold stress and mediates intercellular communication between fibroblasts and cardiomyocytes.Fibroblast-secreted serpinE2 is internalized by cardiomyocytes via endocytosis,promoting hypertrophy through activation of the phosphatidylinositol 3-kinase(PI3K)-AKT/β-catenin pathway.The FGF4-CDX1 axis regulates serpinE2 expression and secretion in cardiac fibroblasts.展开更多
Drug resistance poses a significant challenge to effective long-term treatment across various medical fields.This study proposed a feasible strategy to enhance lysosomal alkalinization by transporting mitochondria-tar...Drug resistance poses a significant challenge to effective long-term treatment across various medical fields.This study proposed a feasible strategy to enhance lysosomal alkalinization by transporting mitochondria-targeting quaternary ammonium salts into lysosomes,creating a deprotonated environment.This environment allows drugs to bypass protonation issues in lysosomes,thereby reversing drug resistance and improving therapeutic efficacy.As a proof of concept,a quaternary ammonium salt-based pH indicator was developed,berberrubine(BRB),enhancing the action of the anticancer drug hydroxycamptothecin(HCPT)in resistant cells.BRB-induced alkalinization increased lysosomal pH and deactivated lysosomal activity,enabling HCPT to bypass protonation constraints.This enhancement markedly improved the anticancer efficacy of HCPT in resistant cells,providing an innovative approach to address drug resistance and advancing therapeutic technologies.展开更多
BACKGROUND Children with autism spectrum disorder(ASD)face unique challenges in maintaining oral health due to sensory sensitivities,communication difficulties,and behavioral barriers.These factors,along with limited ...BACKGROUND Children with autism spectrum disorder(ASD)face unique challenges in maintaining oral health due to sensory sensitivities,communication difficulties,and behavioral barriers.These factors,along with limited access to ASD-trained dental professionals,increase their risk of dental caries,periodontal disease,bruxism,and other oral health issues.Despite growing awareness of these challenges,a comprehensive synthesis of evidence-based solutions remains lacking.AIM To review synthesizes existing research on dental problems in ASD,barriers to care,management strategies,and future directions for improved oral health outcomes.METHODS A systematic search of PubMed,Cochrane Library,and Scopus was conducted using predefined search terms.Related to ASD,dental health,and management strategies.Inclusion criteria encompassed studies focusing on children with ASD,dental health issues,and interventions.Data extraction included study design,participant characteristics,key findings,and intervention outcomes.The quality of studies was assessed using appropriate tools such as the Cochrane Risk of Bias Tool and the Newcastle-Ottawa Scale.A narrative synthesis approach,incorporating thematic analysis,was utilized to evaluate the findings.RESULTS A total of 165 studies met the inclusion criteria.Children with ASD exhibited a higher prevalence of dental caries,gingivitis,bruxism,and malocclusion compared to neurotypical peers.Barriers to dental care included sensory sensitivities,communication difficulties,financial constraints,and a shortage of ASD-trained dental professionals.Effective interventions included desensitization programs,behavioral therapy,digital applications,and interdiscip-linary collaboration.Parental education and professional training were crucial for improving oral health outcomes.CONCLUSION Tailored dental care strategies,including sensory adaptations,behavioral interventions,and interdisciplinary collaboration,are essential for children with ASD.Standardized guidelines and long-term studies are needed to refine evidence-based protocols.Future research should explore digital interventions and probiotic applications in ASD dental care.展开更多
BACKGROUND Although chronic-phase chronic myeloid leukemia(CP-CML)is treatable and nearly curable in about 50%of patients,accelerated-phase chronic myeloid leukemia(AP-CML)shows concerning drug resistance,while blast ...BACKGROUND Although chronic-phase chronic myeloid leukemia(CP-CML)is treatable and nearly curable in about 50%of patients,accelerated-phase chronic myeloid leukemia(AP-CML)shows concerning drug resistance,while blast crisis chronic myeloid leukemia(BC-CML)is highly lethal.Advances in whole exome sequencing(WES)reveal pan-cancer mutations in BC-CML,supporting mutation-guided therapies beyond Breakpoint cluster region-Abelson.Artificial intelligence(AI)and machine learning(ML)enable genomic stratification and drug repurposing,addressing overlooked actionable mutations.AIM To stratify BC-CML into molecular subtypes using WES,ML,and AI for precision drug repurposing.METHODS Included 123 CML patients(111 CP-CML,5 AP-CML,7 BC-CML).WES identified pan-cancer mutations.Variants annotated via Ensembl Variant Effect Predictor and Catalogue of Somatic Mutations in Cancer(COSMIC).ML(principal component analysis,K-means)stratified BC-CML.COSMIC signatures and PanDrugs prioritized drugs.Analysis of variance/Kruskal-Wallis validated differences(P<0.05).RESULTS In this exploratory,hypothesis-generating study of BC-CML patients(n=7),we detected over 2500 somatic mutations.ML identified three BC-CML clusters:(1)Cluster 1[breast cancer susceptibility gene 2(BRCA2),TP53];(2)Cluster 2[isocitrate dehydrogenase(IDH)1/2,ten-eleven translocation 2];and(3)Cluster 3[Janus kinase(JAK)2,colony-stimulating factor 3 receptor],with distinct COSMIC signatures.Therapies:(1)Polyadenosinediphosphate-ribose polymerase inhibitors(olaparib);(2)IDH inhibitors(ivosidenib);and(3)JAK inhibitors(ruxolitinib).Mutational burden,signatures,and targets varied significantly across clusters,supporting precision stratification.CONCLUSION This WES-AI-ML framework provides mutation-guided therapies for BC-CML,enabling real-time stratification and Food and Drug Administration-approved drug repurposing.While this exploratory study is limited by its small sample size(n=7),it establishes a methodological framework for precision oncology stratification that warrants validation in larger,multi-center cohorts.展开更多
1.Introduction Cancer continues to be a major cause of global mortality rates,with conventional treatments such as chemotherapy and radiotherapy exhibiting inconsistent efficacy,high costs,and considerable side effect...1.Introduction Cancer continues to be a major cause of global mortality rates,with conventional treatments such as chemotherapy and radiotherapy exhibiting inconsistent efficacy,high costs,and considerable side effects.Over the past decade,a promising alternative has emerged:cancer immunotherapy,which leverages the body's immune system to identify and eradicate cancer cells[1].展开更多
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 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 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.
基金supported by the National Natural Science Foundation of China(NSFC)under Grant Nos.62035011,82202220 and 82060326State Key Laboratory of Pathogenesis,Prevention and treat ment of High Incident Diseases in central Asia(Nos.SKL-HIDCA-2022-3 and SKL-HIDCA-2022-GJ1)+3 种基金the Xinjiang Uygur Autonomous Region Regional Collaborative Innovation Special Science and Technology Assistance Program(No.2022E02130)Xinjiang Uygur Autonomous Region Natural Sci ence Foundation Key Project(No.2022D01D40)Outstanding Youth Project(2023D01E06)Y.Gao and C.Zhang authors contributed equally to this work.
文摘Triple-negative breast cancer (TNBC) is an aggressive and often fatal disease, especially since the brain metastasis of TNBC has been a particularly severe manifestation. However, brain metastasis in TNBC at early stages often lacks noticeable symptoms, making it challenging to detect. Near-infrared II (NIR-II) fluorescence microscopic imaging obtains long wavelength, which enables reduced scattering, high spatial resolution and minimal autofluorescence, it is also a favorable imaging method for tumor diagnosis. PbS@CdS quantum dots (QDs) are one of the popular NIR-II fluorescence nanoprobes for well brightness. In this study, NIR-II emissive PbS@CdS QDs were utilized and further encapsulated with thiol-terminated poly(ethylene oxide) (SH-PEG, MW = 5000) to form PbS@CdS@PEG QDs nanoparticles (NPs). The obtained PbS@CdS@PEG QDs NPs were then characterized and further studied in detail. The PbS@CdS@PEG QDs NPs had large absorption spectra, exhibited strong NIR-II fluorescence emission at approximately 1300nm, and possessed good NIR-II fluorescence properties. Then, the mice model of early-stage brain metastases of TNBC was established, and the PbS@CdS@PEG QDs NPs were injected into the tumor-bearing mice for NIR-II fluorescence microscopic bioimaging. The brain vessels and tumors of the living mice were detected with high spatial resolution under the NIR-II fluorescence microscopic imaging system with irradiation of 808nm laser. The tumor tissues were further restricted and prepared as thin slices. The NIR-II fluorescence signals were collected from the tumor slices with high spatial resolution and signal-to-background ratio (SBR). Thus, the PbS@CdS@PEG QDs NPs-assisted NIR-II fluorescence microscopic system can effectively achieve targeting brain metastases of TNBC imaging, offering a novel and promising approach for TNBC-specific diagnosis.
文摘In recent years,the rapid evolution of cancer therapies has markedly increased patient survival rates.However,the incidence of adverse events caused by anticancer treatments remains high,leading to significant clinical challenges.As the central hub of drug metabolism and detoxification,the liver is susceptible to therapeutic insults.The specific mechanisms of liver injury caused by different types of antineoplastic treatments vary.Chemotherapy induces hepatic damage via oxidative stress and mitochondrial dysfunction,whereas targeted therapy disrupts signaling pathways in hepatic cells.Immunotherapy triggers immunemediated hepatitis through cytokine storms and immune cell infiltration,and radiation therapy causes hepatic microvascular injury.Additionally,patients with preexisting chronic liver diseases(such as cirrhosis,hepatitis B/C,or nonalcoholic fatty liver disease)are more likely to face increased risks of hepatic injury during cancer treatment.Therefore,early detection and timely treatment are crucial for these high-risk populations.This review introduces the emerging field of“oncohepatology”,which illuminates the mechanisms underlying hepatic injury due to cancer treatments,summarizes the influence and management of preexisting liver disease during cancer treatment,analyzes diagnostic and therapeutic strategies for cancer treatment-associated liver function damage,and discusses potential future research directions to provide valuable insights for liver injury management in clinical oncology.
基金supported by the National Natural Science Foundation of China(82370279,82170299,82330011,82003757).
文摘Background:Effective inhibition of pathological cardiac hypertrophy is critical for managing various cardiovascular diseases,especially in cold environments.The communication between cardiomyocytes and fibroblasts,mediated by secreted proteins,plays a significant role in the development and progression of pathological cardiac hypertrophy.Serpin Family E Member 2(serpinE2),secreted by fibroblasts into the extracellular space,has been implicated in this process.However,whether serpinE2 can be internalized by cardiomyocytes and whether cold exposure influences this process remains unclear.Materials and methods:Mice were subjected to cold exposure(4°C,12 h/day for 8 weeks),and cardiac hypertrophy was induced by transverse aortic constriction(TAC).SerpinE2 expression was silenced by short interfering RNA(siRNA).Cardiac fibroblasts were stimulated with angiotensin II(Ang II)to induce serpinE2 secretion.Exogenous recombinant serpinE2,labeled with DyLight 488 or His-tag,was used to evaluate its internalization and functional role in cardiomyocytes.Internalization was inhibited by using antibodies against serpinE2,heparin,or endocytosis inhibitors(β-cyclodextrin,nystatin,dynasore,and chlorpromazine).Chromatin immunoprecipitation followed by quantitative polymerase chain reaction(PCR)was used to assess the binding of the transcription factor CDX1 to the serpinE2 promoter.Results:Cold exposure significantly increased serpinE2 mRNA and protein expression in mouse hearts.SerpinE2 levels were also upregulated in plasma and cardiac tissue following TAC.Knockdown of serpinE2 attenuated TAC-induced hypertrophy,restored left ventricular function,and reduced atrial natriuretic peptide,brain natriuretic peptide,andβ-myosin heavy chain fragment levels.Exogenous serpinE2 promoted cardiomyocyte hypertrophy,an effect that was reversed by serpinE2 knockdown.Co-culture with conditioned medium from Ang II-stimulated fibroblasts increased serpinE2 expression in cardiomyocytes.Exogenous serpinE2 was internalized via endocytosis,which was inhibited by antibodies,heparin,and endocytosis blockers.Internalized serpinE2 activated the protein kinase B(AKT)/β-catenin pathway in cardiomyocytes.CDX1 bound to the serpinE2 promoter and promoted its transcription in fibroblasts.CDX1 overexpression increased serpinE2 and collagen expression,while its suppression had the opposite effect.Administration of exogenous fibroblast growth factor 4(FGF4)or overexpression of FGF4 plasmid upregulated CDX1,serpinE2,and collagen expression in fibroblasts.Conclusions:SerpinE2 expression is responsive to cold stress and mediates intercellular communication between fibroblasts and cardiomyocytes.Fibroblast-secreted serpinE2 is internalized by cardiomyocytes via endocytosis,promoting hypertrophy through activation of the phosphatidylinositol 3-kinase(PI3K)-AKT/β-catenin pathway.The FGF4-CDX1 axis regulates serpinE2 expression and secretion in cardiac fibroblasts.
基金supported by Young Elite Scientists Sponsorship Program by China Association for Science and Technology(No.CACM-2023-QNRC1–02)Shandong Province Key R&D Program(Major Technological Innovation Project)(No.2021CXGC010501)+6 种基金National Natural Science Foundation of China(No.22107059)Natural Science Foundation of Shandong Province(No.ZR2021QH057)Program for Youth Innovation Technology in Colleges and Universities of Shandong Province of China(No.2021KJ035)Taishan Scholars Program(No.TSQN202211221)Shandong Science Fund for Excellent Young Scholars(No.ZR2022YQ66)Funded by Shandong Postdoctoral Science Foundation(No.SDCX-ZG-202400084)the National Administration of Traditional Chinese Medicine Young Qihuang Scholar Project。
文摘Drug resistance poses a significant challenge to effective long-term treatment across various medical fields.This study proposed a feasible strategy to enhance lysosomal alkalinization by transporting mitochondria-targeting quaternary ammonium salts into lysosomes,creating a deprotonated environment.This environment allows drugs to bypass protonation issues in lysosomes,thereby reversing drug resistance and improving therapeutic efficacy.As a proof of concept,a quaternary ammonium salt-based pH indicator was developed,berberrubine(BRB),enhancing the action of the anticancer drug hydroxycamptothecin(HCPT)in resistant cells.BRB-induced alkalinization increased lysosomal pH and deactivated lysosomal activity,enabling HCPT to bypass protonation constraints.This enhancement markedly improved the anticancer efficacy of HCPT in resistant cells,providing an innovative approach to address drug resistance and advancing therapeutic technologies.
文摘BACKGROUND Children with autism spectrum disorder(ASD)face unique challenges in maintaining oral health due to sensory sensitivities,communication difficulties,and behavioral barriers.These factors,along with limited access to ASD-trained dental professionals,increase their risk of dental caries,periodontal disease,bruxism,and other oral health issues.Despite growing awareness of these challenges,a comprehensive synthesis of evidence-based solutions remains lacking.AIM To review synthesizes existing research on dental problems in ASD,barriers to care,management strategies,and future directions for improved oral health outcomes.METHODS A systematic search of PubMed,Cochrane Library,and Scopus was conducted using predefined search terms.Related to ASD,dental health,and management strategies.Inclusion criteria encompassed studies focusing on children with ASD,dental health issues,and interventions.Data extraction included study design,participant characteristics,key findings,and intervention outcomes.The quality of studies was assessed using appropriate tools such as the Cochrane Risk of Bias Tool and the Newcastle-Ottawa Scale.A narrative synthesis approach,incorporating thematic analysis,was utilized to evaluate the findings.RESULTS A total of 165 studies met the inclusion criteria.Children with ASD exhibited a higher prevalence of dental caries,gingivitis,bruxism,and malocclusion compared to neurotypical peers.Barriers to dental care included sensory sensitivities,communication difficulties,financial constraints,and a shortage of ASD-trained dental professionals.Effective interventions included desensitization programs,behavioral therapy,digital applications,and interdiscip-linary collaboration.Parental education and professional training were crucial for improving oral health outcomes.CONCLUSION Tailored dental care strategies,including sensory adaptations,behavioral interventions,and interdisciplinary collaboration,are essential for children with ASD.Standardized guidelines and long-term studies are needed to refine evidence-based protocols.Future research should explore digital interventions and probiotic applications in ASD dental care.
文摘BACKGROUND Although chronic-phase chronic myeloid leukemia(CP-CML)is treatable and nearly curable in about 50%of patients,accelerated-phase chronic myeloid leukemia(AP-CML)shows concerning drug resistance,while blast crisis chronic myeloid leukemia(BC-CML)is highly lethal.Advances in whole exome sequencing(WES)reveal pan-cancer mutations in BC-CML,supporting mutation-guided therapies beyond Breakpoint cluster region-Abelson.Artificial intelligence(AI)and machine learning(ML)enable genomic stratification and drug repurposing,addressing overlooked actionable mutations.AIM To stratify BC-CML into molecular subtypes using WES,ML,and AI for precision drug repurposing.METHODS Included 123 CML patients(111 CP-CML,5 AP-CML,7 BC-CML).WES identified pan-cancer mutations.Variants annotated via Ensembl Variant Effect Predictor and Catalogue of Somatic Mutations in Cancer(COSMIC).ML(principal component analysis,K-means)stratified BC-CML.COSMIC signatures and PanDrugs prioritized drugs.Analysis of variance/Kruskal-Wallis validated differences(P<0.05).RESULTS In this exploratory,hypothesis-generating study of BC-CML patients(n=7),we detected over 2500 somatic mutations.ML identified three BC-CML clusters:(1)Cluster 1[breast cancer susceptibility gene 2(BRCA2),TP53];(2)Cluster 2[isocitrate dehydrogenase(IDH)1/2,ten-eleven translocation 2];and(3)Cluster 3[Janus kinase(JAK)2,colony-stimulating factor 3 receptor],with distinct COSMIC signatures.Therapies:(1)Polyadenosinediphosphate-ribose polymerase inhibitors(olaparib);(2)IDH inhibitors(ivosidenib);and(3)JAK inhibitors(ruxolitinib).Mutational burden,signatures,and targets varied significantly across clusters,supporting precision stratification.CONCLUSION This WES-AI-ML framework provides mutation-guided therapies for BC-CML,enabling real-time stratification and Food and Drug Administration-approved drug repurposing.While this exploratory study is limited by its small sample size(n=7),it establishes a methodological framework for precision oncology stratification that warrants validation in larger,multi-center cohorts.
基金supported by Australian Centre for AI in Medical Innovation(ACAMI)funded by the Victoria State Government,National University of Singapore(NUHSRO/2020/133/Startup/08,NUHSRO/2023/008/NUSMed/TCE/LOA,NUHSRO/2021/034/TRP/09/Nanomedicine,NUHSRO/2021/044/Kickstart/09/LOA,and 230173-A0001)National Medical Research Council(MOH-001388-00,CG21APR1005,MOH-001500-00,and MOH-001609-00)+1 种基金Singapore Ministry of Education(MOE-000387-00 and MOET32023-0005)National Research Foundation(NRF-000352-00)。
文摘1.Introduction Cancer continues to be a major cause of global mortality rates,with conventional treatments such as chemotherapy and radiotherapy exhibiting inconsistent efficacy,high costs,and considerable side effects.Over the past decade,a promising alternative has emerged:cancer immunotherapy,which leverages the body's immune system to identify and eradicate cancer cells[1].
