This study examines the pivotal findings of the network meta-analysis of Zhou et al,which evaluated the efficacy of hepatic arterial infusion chemotherapy and combination therapies for advanced hepatocellular carcinom...This study examines the pivotal findings of the network meta-analysis of Zhou et al,which evaluated the efficacy of hepatic arterial infusion chemotherapy and combination therapies for advanced hepatocellular carcinoma(HCC).This meta-analysis suggests that therapeutic combinations have greater efficacy than do standard treatments.The article highlights the key insights that have the potential to shift current clinical practice and enhance outcomes for patients with advanced HCC.Additionally,this article discusses further research that can be conducted to optimize these treatments and achieve personalized care for patients with HCC.展开更多
Pancreatic cancer is highly vulnerable to ferroptosis.Consequently,treatments that target pancreatic cancer through ferroptosis induction demonstrate immense potential for enhancing therapeutic outcomes in this condit...Pancreatic cancer is highly vulnerable to ferroptosis.Consequently,treatments that target pancreatic cancer through ferroptosis induction demonstrate immense potential for enhancing therapeutic outcomes in this condition.In the present study,we synthesized hollow mesoporous iron oxide nanoparticles(MHFe)using a hydrothermal method.These nanoparticles retained the superparamagnetic properties of iron oxide and its Fenton reaction-catalyzing ability.Meanwhile,they also showed superior drug-loading capacity compared to traditional ferric oxide nanoparticles due to their hollow and mesoporous structure.Under the guidance of a magnetic field,these nanoparticles could accumulate in tumor cells.Following the incorporation of Ce6,a sonosensitizer,the Ce6@MHFe system could generate singlet oxygen under ultrasound treatment to promote tumor cell apoptosis while simultaneously producing hydroxyl radicals through the enhanced Fenton effect of MHFe.This promoted ferroptosis in pancreatic cancer cells,achieving combined therapeutic effects.In vivo experiments confirmed the good biocompatibility of Ce6@MHFe and demonstrated that the nanoparticles could effectively kill tumor cells under magnetic targeting and ultrasound irradiation,thereby inhibiting tumor growth.The findings suggested that these hollow mesoporous iron oxide nanoparticles(Ce6@MHFe)with a high drug-loading capacity,tumor retention ability,and potential for combination therapy have potential for the treatment of various malignancies,including pancreatic cancer.展开更多
BACKGROUND Peripheral artery disease(PAD)affects millions globally,with a 5.6%prevalence in 2015 impacting 236 million adults,rising above 10%in those over 60 due to factors like diabetes and smoking.Post-revasculariz...BACKGROUND Peripheral artery disease(PAD)affects millions globally,with a 5.6%prevalence in 2015 impacting 236 million adults,rising above 10%in those over 60 due to factors like diabetes and smoking.Post-revascularization,single antiplatelet therapy(SAPT)is standard,but dual antiplatelet therapy(DAPT)may improve outcomes,though duration and bleeding risks are unclear.The 2024 American College of Cardiology/American Heart Association guidelines endorse short-term DAPT,yet evidence gaps remain in comparative efficacy and safety.We hypothesized that DAPT reduces cardiovascular events and reinterventions vs SAPT without significantly elevating bleeding in PAD patients’post-lower extremity revascularization.AIM To evaluate the efficacy and safety of DAPT vs SAPT in PAD patients’post-revascularization.METHODS This systematic review and meta-analysis followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines,searching PubMed,EMBASE,and ScienceDirect up to July 2025.Included were randomized controlled trials(RCTs)and cohort studies from various global settings(e.g.,hospitals,tertiary care)comparing DAPT(aspirin plus P2Y12 inhibitor for>1 month)to SAPT in symptomatic PAD patients undergoing endovascular or surgical revascularization(n up to 28244 participants selected via eligibility criteria).Data were pooled using random-effects models for risk ratio(RR)with 95%CI;heterogeneity was assessed via the I²statistic.Quality appraisal used Risk of Bias in Non-randomized Studies of Interventions for cohorts and Risk of Bias 2.0 for RCTs;certainty was evaluated via Grading of Recommendations Assessment,Development and Evaluation(GRADE).RESULTS Twelve studies(3 RCTs,9 cohorts,conducted 2010–2025 with follow-ups of 6 months to 5 years)were included.DAPT showed no significant difference but a trend toward reduced all-cause mortality(RR:0.52,95%CI:0.27–1.01,P=0.05,DAPT of 298/9545 events vs SAPT of 165/566 events)or stroke(RR:0.72,95%CI:0.30–1.72,P=0.46,DAPT of 16/3729 events vs SAPT of 41/7673 events)vs SAPT.DAPT significantly reduced cardiac mortality(RR:0.46,95%CI:0.27–0.80,P=0.006,DAPT of 78/2903 events vs SAPT of 171/1465 events,risk difference:-5.4%),myocardial infarction(RR:0.82,95%CI:0.71–0.94,P=0.004,DAPT of 233/7704 events vs SAPT of 262/9130 events,risk difference:-1.8%),and major reintervention(RR:0.58,95%CI:0.35–0.98,P=0.04,DAPT of 803/205 events vs SAPT of 1197/4 events,risk difference:-42%).Bleeding showed no difference(RR:1.12,95%CI:0.42–3.03,P=0.82,DAPT of 195/2775 events vs SAPT of 202/8234 events).Heterogeneity was high(I^(2)=59%–97%).Quality revealed moderate to serious bias in cohorts and some concerns in RCTs;GRADE certainty moderate for cardiac mortality,myocardial infarction,reintervention,low for others due to inconsistency and imprecision.CONCLUSION DAPT reduces cardiac mortality,myocardial infarction,and major reintervention risks compared to SAPT in PAD post-revascularization without apparent bleeding increase,though limited by heterogeneity and low certainty for some outcomes.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)is a leading cause of cancer-related deaths worldwide and currently lacks effective treatment options.This is particularly true for advanced HCC,for which conventional therapies...BACKGROUND Hepatocellular carcinoma(HCC)is a leading cause of cancer-related deaths worldwide and currently lacks effective treatment options.This is particularly true for advanced HCC,for which conventional therapies often lead to a poor prognosis.AIM To assess the safety and efficacy of transarterial chemoembolization(TACE)with donafenib and immune checkpoint inhibitors(ICIs)for unresectable HCC.METHODS We retrospectively assessed the data of patients with HCC who underwent TACE combined with donafenib and an ICI(tislelizumab or cedilimumab).Patients received oral donafenib daily for 2 weeks before TACE,followed by tislelizumab or cedilimumab 200 mg intravenously on day 1 of a 21-day therapeutic cycle.The primary endpoints were objective response rate,disease control rate,and duration of response according to the modified RECIST criteria.The secondary endpoint was presence of treatment-related adverse events(TRAEs).RESULTS The median follow-up was 7.8 months(95%CI:5.0-11.8 months).The objective response rate was 60.0%(18/30),while the disease control rate was 93.3%.The median duration of response in confirmed responders was 6.6 months(95%CI:1.3-12.9 months).The median progression-free survival was 11.8 months(95%CI:8.3-15.4 months).More than half of the patients survived until the end of the study.Grade>3 TRAEs occurred in 40%of the patients with no grade 5 TRAEs reported.The most common grade 3/4 TRAE was palmar-plantar erythrodysesthesia,a dermatologic condition characterized by painful redness and swelling of the palms and soles,with an incidence of 56.7%.No ICI-related adverse effects were observed.CONCLUSION TACE combined with donafenib and ICI is a promising and safe therapeutic regimen for unresectable HCC.展开更多
Autism spectrum disorder(ASD)is a complex neurodevelopmental disorder affecting over 2%of the global population,marked by social communication deficits and repetitive behaviors.Kabatas et al explored the efficacy and ...Autism spectrum disorder(ASD)is a complex neurodevelopmental disorder affecting over 2%of the global population,marked by social communication deficits and repetitive behaviors.Kabatas et al explored the efficacy and safety of Wharton’s jelly-derived mesenchymal stem cell(WJ-MSC)therapy in a 4-year-old child with ASD.Using the childhood autism rating scale and Denver II develop-mental screening test,significant improvements were seen after six WJ-MSC sessions,with no adverse events over 2 years.Despite promising results,the study’s single-case design limits generalizability.Larger,multi-center trials are needed to validate the findings and assess long-term effects of WJ-MSC therapy in ASD.展开更多
Efficient siRNA delivery is highly desirable for disease treatment.However,the application of conventional nanoparticles is limited by the inability to escape from endo-lysosomes.Herein,we report a strategy using smal...Efficient siRNA delivery is highly desirable for disease treatment.However,the application of conventional nanoparticles is limited by the inability to escape from endo-lysosomes.Herein,we report a strategy using small-molecule drugs to enhance siRNA endo-lysosomal release,addressing this challenge.We encapsulated gentamicin(GM)into the marketed Onpattro■ formulation to establish LNP-siRNA/GM nanoparticles that promote siRNA endo-lysosomal escape through endosomal disruption,mechanistically exhibiting unique functionality and synergistic effects of LNP-siRNA/GM to improve cancer therapy.Besides,GM induced reactive oxygen species(ROS)and phospholipids accumulation in endolysosomes,as well as the physical characteristics of lipid nanoparticles(LNPs)were preserved.We also revealed that GM causes endo-lysosomal swelling and disrupts the endosomal membrane to enable siRNA release,as confirmed by Galectin 3 recruitment and acridine orange release.This approach achieved∼81%mRNA-EGFR silencing,which is more than LNP-siEGFR(∼56.23%)by enhancing siRNA endo-lysosomal escape efficiency.Meanwhile,LNP-siEGFR/GM exhibited significant biological activities in HepG2 cells,driven by the synergistic effects of siEGFR and GM with the VEGF and CXCL12 downregulation of,and ROS and phospholipids upregulation.Furthermore,tumor growth was notably suppressed after intravenous injection of LNP-siEGFR/GM in tumor-bearing nude mice.The combination of EGFR-siRNA and GM could also greatly inhibit angiogenesis,be antiproliferative,and induce tumor cells apoptosis.Therefore,this GM and siRNA co-delivery system would provide an efficient strategy for siRNA endosomal escape,significantly improving knockdown in various LNPs based siRNA delivery systems and efficiently enhancing cancer therapy.展开更多
BACKGROUND Significant gaps in guideline-directed medical therapy(GDMT)for heart failure(HF)stem from shortages of cardiologists and advanced HF providers,as well as a lack of optimal HF management knowledge among hos...BACKGROUND Significant gaps in guideline-directed medical therapy(GDMT)for heart failure(HF)stem from shortages of cardiologists and advanced HF providers,as well as a lack of optimal HF management knowledge among hospitalists.This study compared the impact of optimal medical therapy in HF(OMT-HF)certification on GDMT implementation and patient outcomes between an intervention group(IG)of hospitalists and a standard-of-care comparison group(SOC-CG).METHODS This study was implemented from November 2022 to May 2023.Hospitalized car-diology patients with HF and left ventricular ejection fraction≤40%were rando-mized to IG or SOC-CG.Exclusion criteria included patients in cardiogenic shock,unable to consent,or at high risk.Follow-up was at 30 days post-discharge.Diffe-rences between groups were analyzed using Fisher’s exact test for categorical va-riables and Wilcoxon rank-sum or unpaired t-test for continuous variables.Chan-ges in Minnesota Living with Heart Failure Questionnaire(MLWHFQ)scores were evaluated using a paired t-test.RESULTS IG patients had lower readmission rates[9(42.85%)vs 11(17.46%),P=0.03]and a decreased trend in mortality 30-day post discharge.IG patients also showed greater mean improvements in total(-27.03±24.59 vs-5.85±23.52,P<0.001),physical(-13.8±12.3 vs-2.71±11.16,P<0.001)and emotional(-4.76±8.10 vs-1.42±5.98)dimensions on the MLWHFQ compared to SOC-CG,however,change in emotional dimension did not reach statistical significance.CONCLUSION Hospitalist OMT-HF certification may lead to better 30-day outcomes in hospitalized HF patients including quality of life,mortality and readmission rates.Larger prospective studies are warranted to validate these findings.展开更多
This study aimed to systematically evaluate the clinical efficacy of combining wax therapy with conventional drug therapy for rheumatoid arthritis(RA)and to provide evidence supporting its clinical application.A compr...This study aimed to systematically evaluate the clinical efficacy of combining wax therapy with conventional drug therapy for rheumatoid arthritis(RA)and to provide evidence supporting its clinical application.A comprehensive search was conducted across PubMed,Cochrane Library,China Biomedical Literature Database(CBM),China National Knowledge Infrastructure(CNKI),Wanfang,and VIP databases from their inception to May 2024.Randomized controlled trials(RCTs)investigating the combination of wax therapy and conventional drug therapy for RA were included in the analysis.Statistical analysis was performed using Review Manager 5.3 software.Nine studies,encompassing a total of 843 patients,were included.The results demonstrated that the combination therapy significantly improved clinical efficacy compared to conventional drug therapy alone[RR=1.22,95%CI(1.11,1.34)].Moreover,the combination therapy led to notable improvements in DAS 28 scores[MD=-0.90,95%CI(-1.23,-0.57),P<0.00001],VAS scores[MD=-0.90,95%CI(-1.13,-0.66),P<0.00001],reduction in joint tenderness[MD=-1.27,95%CI(-1.81,-0.72),P<0.00001],decreased duration of morning stiffness[MD=-25.47,95%CI(-34.33,-16.61),P<0.00001],and lowered C-reactive protein levels[MD=-6.29,95%CI(-12.02,-0.57),P<0.05].In conclusion,wax therapy combined with conventional anti-rheumatic drugs significantly enhanced the clinical outcomes for RA patients by alleviating symptoms,reducing joint pain and morning stiffness,and decreasing inflammatory markers more effectively than conventional drug therapy alone.展开更多
Publications of Soufan et al and Kristjánsson et al in the World Journal of Orthopedics on mesenchymal stem cell(MSC)therapy for osteoarthritis(OA)represent a significant exploration of regenerative medicine’s p...Publications of Soufan et al and Kristjánsson et al in the World Journal of Orthopedics on mesenchymal stem cell(MSC)therapy for osteoarthritis(OA)represent a significant exploration of regenerative medicine’s potential in OA treatment.In their research,it is highlighted that MSCs can alleviate OA symptoms and even regenerate cartilage,potentially reversing the disease.They also compared the efficacy of three MSC subtypes,emphasizing the therapeutic advantages of adipose-derived MSCs.MSC injections,a novel and less invasive alternative to traditional treatments such as chondrocyte transplantation or arthroplasty,have a low cost,low risks,and favorable outcomes,presenting a promising approach for OA patients.Additionally,we stressed that the efficacy evaluation criteria,heterogeneity,safety,and other factors must be carefully considered to further advance the clinical translation of MSC therapy for OA.展开更多
Photodynamic therapy(PDT)has been established as one of the most promising novel cancer therapies with fewer side-effects and enhanced efficacy compared to the currently available conventional treatments.However,its a...Photodynamic therapy(PDT)has been established as one of the most promising novel cancer therapies with fewer side-effects and enhanced efficacy compared to the currently available conventional treatments.However,its application has been hindered by the limitations that photosensitizers(PS)have.The combination of PS with metallic nanoparticles like platinum nanoparticles(PtNPs),can help to overcome these intrinsic drawbacks.In this work,the combination of PtNPs and the natural photosensitizer riboflavin(RF)is proposed.PtNPs are synthesized using RF(Pt@RF)as reducing and stabilizing agent in a one-step method,obtaining nanoparticles with mesoporous structure for UV triggered PDT.In view of possible future UV irradiation treatments,the degradation products of RF,ribitol(RB)and lumichrome(LC),this last being a photosensitizing byproduct,are also employed for the synthesis of porous PtNPs,obtaining Pt@LC and Pt@RB.When administered in vitro to lung cancer cells,all the samples elicit a strong decrease of cell viability and a decrease of intracellular ATP levels.The antitumoral effect of both Pt@RF and Pt@LC is triggered by UV-A irradiation.This antitumoral activity is caused by the induction of oxidative stress,shown in our study by the decrease in intracellular glutathione and increased expression of antioxidant enzymes.展开更多
Community-acquired pneumonia(CAP)in adults(≥18 years old)is the most common infectious disease encountered in emergency departments.Its clinical complexity and the need for prompt treatment decisions pose significant...Community-acquired pneumonia(CAP)in adults(≥18 years old)is the most common infectious disease encountered in emergency departments.Its clinical complexity and the need for prompt treatment decisions pose significant challenges for patient management.The physician-pharmacist collaborative management(PPCM)model,which optimizes drug therapy regimens through collaboration between physicians and clinical pharmacists,has demonstrated strong clinical value in practice.However,the lack of standardized national guidelines for the application of the PPCM model in emergency departments in China has hampered its widespread adoption.This guideline is developed based on evidence-based medicine and clinical practice experience,with a focus on the application of the PPCM model in the management of CAP in emergency settings.It outlines the significance of the PPCM model,its applicable scenarios,the respective roles of emergency physicians and clinical pharmacists,and its practical implementation in the antimicrobial treatment of CAP patients.In addition,the guideline proposes standardized implementation processes and clinical pathways.By promoting the PPCM model,the expert panel aims to standardize the use of antimicrobial agents in the emergency treatment of CAP,reduce the risk of antimicrobial resistance,and improve patient outcomes.展开更多
BACKGROUND Advanced esophageal squamous cell carcinoma(ESCC)has an extremely poor prognosis.Preoperative chemoradiotherapy(CRT)can significantly prolong survival,especially in those who achieve pathological complete r...BACKGROUND Advanced esophageal squamous cell carcinoma(ESCC)has an extremely poor prognosis.Preoperative chemoradiotherapy(CRT)can significantly prolong survival,especially in those who achieve pathological complete response(pCR).However,the pretherapeutic prediction of pCR remains challenging.AIM To predict pCR and survival in ESCC patients undergoing CRT using an artificial intelligence(AI)-based diffusion-weighted magnetic resonance imaging(DWI-MRI)radiomics model.METHODS We retrospectively analyzed 70 patients with ESCC who underwent curative surgery following CRT.For each patient,pre-treatment tumors were semi-automatically segmented in three dimensions from DWI-MRI images(b=0,1000 second/mm^(2)),and a total of 76 radiomics features were extracted from each segmented tumor.Using these features as explanatory variables and pCR as the objective variable,machine learning models for predicting pCR were developed using AutoGluon,an automated machine learning library,and validated by stratified double cross-validation.RESULTS pCR was achieved in 15 patients(21.4%).Apparent diffusion coefficient skewness demonstrated the highest predictive performance[area under the curve(AUC)=0.77].Gray-level co-occurrence matrix(GLCM)entropy(b=1000 second/mm²)was an independent prognostic factor for relapse-free survival(RFS)(hazard ratio=0.32,P=0.009).In Kaplan-Meier analysis,patients with high GLCM entropy showed significantly better RFS(P<0.001,log-rank).The best-performing machine learning model achieved an AUC of 0.85.The predicted pCR-positive group showed significantly better RFS than the predicted pCR-negative group(P=0.007,log-rank).CONCLUSION AI-based radiomics analysis of DWI-MRI images in ESCC has the potential to accurately predict the effect of CRT before treatment and contribute to constructing optimal treatment strategies.展开更多
Ischemic stroke is currently the second leading cause of death worldwide,and insufficient endogenous neurogenesis is the greatest cause of post-stroke disability.MicroRNAs have been proven to hold therapeutic potentia...Ischemic stroke is currently the second leading cause of death worldwide,and insufficient endogenous neurogenesis is the greatest cause of post-stroke disability.MicroRNAs have been proven to hold therapeutic potential,unfortunately,they have a low stability that hinders their clinical usage.Our earlier work revealed that Panax notoginseng derived exosome like nanoparticles,namely PDNs have potential to bypass BBB and reduce the cerebral ischemia/reperfusion(CI/R)damage.In this study,we employed microRNA-124 as a model therapeutic gene,utilizing its engineered variant Agomir-124(Ago124)to optimize loading efficiency.The therapeutic effects of Ago124@R-PDN were further assessed in several sets of experiments.Pharmacokinetic study showed that erythrocyte membrane extended the half-life of PDNs from 7 min to 11.3 h,and the loading efficiency of Ago124 reached 40%.In an in vitro oxygen-glucose deprivation/reperfusion(OGD/R)model,Ago124@R-PDN enhanced IL-10 production in microglia by 67%(vs 11.7%with free Ago124),and promoted Tuj1+neuronal differentiation by 2.23-fold compared with vehicle.Also,Ago124@R-PDN brought gene cargo into the brain,alleviated infarct volume,and improved functional behaviors in model mice.At last,we demonstrated that surface glycosyl of PDN facilitated its brain-entering ability by being recognized by sodium-glucose linked transporter-1 protein.In conclusion,our erythrocyte fused PDNs offer a promising strategy for delivering biomacromolecule to treat brain diseases.展开更多
Hepatic arterial infusion chemotherapy (HAIC) is an advanced targeted therapeuticapproach for hepatocellular carcinoma (HCC), the most common type ofprimary liver cancer. HAIC has demonstrated significant potential in...Hepatic arterial infusion chemotherapy (HAIC) is an advanced targeted therapeuticapproach for hepatocellular carcinoma (HCC), the most common type ofprimary liver cancer. HAIC has demonstrated significant potential in managingadvanced HCC, particularly in regions with high prevalence rates. Despite itspromise, several challenges and areas for future research remain. Clinical studieshave substantiated the efficacy of HAIC in enhancing survival outcomes forpatients with advanced hepatic carcinoma. Notably, combination therapiesinvolving immune checkpoint inhibitors, such as lenvatinib and programmeddeath-1 inhibitors, have shown substantial improvements in median overallsurvival and progression-free survival compared to systemic chemotherapy.These combination therapies have also exhibited superior response rates anddisease control, with manageable and often less severe adverse events relative tosystemic treatments. This article is based on the review by Zhou et al and aims todiscuss the current status and future directions in the treatment of HCC, emphasizingthe role of HAIC and its integration with novel therapeutic agents.展开更多
The hydrophobic sonosensitizer IR780 iodide(IR780)was loaded into liposomes to form Liposome@IR780 nanoparticles(NPs)for triple-negative breast cancer(TNBC)to enhance SDT via low-intensity ultrasound(LIU)irradiation.T...The hydrophobic sonosensitizer IR780 iodide(IR780)was loaded into liposomes to form Liposome@IR780 nanoparticles(NPs)for triple-negative breast cancer(TNBC)to enhance SDT via low-intensity ultrasound(LIU)irradiation.The NPs were characterized using various physicochemical methods including size distribution,zeta potential,and morphology.In vitro experiments show that the Liposome@IR780 NPs can generate more reactive oxygen species(ROS)upon LIU irradiation.The apoptosis experiment results further demonstrate that Liposome@IR780 NPs show better apoptosis rate against 4T1 cells.Our results indicate that Liposome@IR780 NPs will provide a promising approach for TNBC upon SDT treatment.展开更多
Colorectal cancer(CRC)with liver metastasis remains a significant therapeutic challenge,particularly in cases of postoperative recurrence.While transarterial chemoembolization(TACE)and targeted therapies have shown pr...Colorectal cancer(CRC)with liver metastasis remains a significant therapeutic challenge,particularly in cases of postoperative recurrence.While transarterial chemoembolization(TACE)and targeted therapies have shown promise individually,the efficacy combining these for treating postoperative recurrent CRC with liver metastasis requires further investigation.AIM To evaluate the efficacy and safety of TACE combined with targeted therapies for postoperative recurrent CRC with liver metastasis.METHODS This observational study enrolled 75 patients with postoperative recurrent CRC accompanied by liver metastasis between January 2020 and December 2023.All patients received combined treatment with TACE and targeted therapy:Bevacizumab(40 patients,53.3%),cetuximab(25 patients,33.3%),or panitumumab(10 patients,13.3%).Treatment response was evaluated using the Response Evaluation Criteria in Solid Tumors 1.1 criteria,with overall survival(OS)and progression-free survival as the primary endpoints.Quality of life was assessed using the European Organization for Research and Treatment of Cancer quality of life questionnaire at baseline and after six months of treatment.RESULTS The median OS was 28 months(95%confidence interval:24-32 months),and the median progression-free survival was 12 months(95%confidence interval:10-14 months).Patients treated with bevacizumab showed significantly better survival outcomes than those treated with cetuximab/panitumumab(median OS,30 vs 24 months,P=0.015).The overall response rate was 58.7%,with a disease control rate of 86.7%.Quality of life scores improved significantly across all domains,with greater improvements observed in the bevacizumab group.Treatment-related adverse events were manageable,with grade 3-4 events occurring in 13.3%of the patients and no treatment-related mortality.CONCLUSION The combination of TACE with targeted therapy,particularly bevacizumab,has demonstrated promising efficacy and acceptable safety for the treatment of postoperative recurrent CRC with liver metastasis.This multimodal approach not only improved survival outcomes but also enhanced the patients’quality of life,suggesting its potential as a valuable treatment strategy for this challenging condition.展开更多
Glioblastoma multiforme(GBM)is a highly aggressive and lethal brain tumor with limited treatment options.To improve therapeutic efficacy,we developed a novel multifunctional nanoplatform,GM@P(T/S),comprised of polymer...Glioblastoma multiforme(GBM)is a highly aggressive and lethal brain tumor with limited treatment options.To improve therapeutic efficacy,we developed a novel multifunctional nanoplatform,GM@P(T/S),comprised of polymeric nanoparticles coated with GBM cell membranes as well as co-loaded with temozolomide(TMZ)and superparamagnetic iron oxide(SPIO)nanoparticles.The successful preparation was confirmed in terms of particle size,morphology,stability,the in vitro drug release,and cellular uptake assays.We demonstrated that GM@P(T/S)exhibited the enhanced homotypic targeting,the prolonged blood circulation,and efficient bloodbrain barrier penetration in both in vitro and in vivo studies.The combination of TMZ and SPIO nanoparticles within GM@P(T/S)synergistically improved chemo-radiation therapy,leading to a reduced tumor growth,an increased survival,and minimal systemic toxicity in the orthotopic GBM mouse models.Our findings suggest that GM@P(T/S)holds a great promise as a targeted and efficient therapeutic strategy for GBM.展开更多
Stem cell therapy holds great promise for the regeneration and repair of damaged tissues and organs.Stem cell therapy has been successfully applied to treat diseases that cannot be cured with conventional medicine.A c...Stem cell therapy holds great promise for the regeneration and repair of damaged tissues and organs.Stem cell therapy has been successfully applied to treat diseases that cannot be cured with conventional medicine.A careful evaluation of the outcomes is required for successful implementation of stem cell therapy.Recently,artificial intelligence(AI)has opened new avenues for research in the stem cell therapy field.The integration of AI can assist in evaluating the quality,efficiency and safety of stem cells by analyzing available data.It has the potential to improve and accelerate progress in various aspects of stem cell research and therapeutic applications.AI is still in its infancy and has certain limitations,such as algorithm validation problems,inadequate data availability,poor data quality,and ethical considerations.Considering the potential of AI to improve stem cell research and therapeutics,this review aims to explore applications of AI in understanding stem cell behavior,identification and characterization,optimization of the delivery methods,stem cell modeling and prediction of mortality risk.In addition,this review highlights the role of AI,machine learning,deep learning,and other subtypes in advancing stem cell biology research.This review also discusses the current limitations,ethical considerations,and future prospective of use of AI in stem cell research and therapeutic applications.展开更多
Background:Drama therapy as a discipline in clinical and public health areas dates back to movements in the Netherlands,Great Britain and the United States of America in the 1960s.Today,drama therapy comprises a huge ...Background:Drama therapy as a discipline in clinical and public health areas dates back to movements in the Netherlands,Great Britain and the United States of America in the 1960s.Today,drama therapy comprises a huge variety of methods and is applied in numerous medical domains such as psychiatry,pediatrics and neurogeriatrics.Nonetheless,historical and philosophical considerations suggest that at all times dramatic arts have encompassed curative potential and helped to promote mental health.Regarding this perspective,the present article aims to explore the spirit of drama therapy in ancient Chinese and Greek cultures.Methods:Involving cross-cultural psychiatry and medical anthropology,comparative research centred around salutary momentums inhering in drama and dramatic practices in Ancient China and Greece.The entire research process consisted of three phases:(i)screening of ancient Chinese and Greek dramatic rituals and arts to select phenomena and genres with pathological,therapeutic and mental health relevance;(ii)medical ontological processing,in particular from a psychopathological,psychiatric,psychotherapeutic and mental health scientific point of view,to explore and elucidate their curative and preventative features;(iii)transdisciplinary considerations about the evolution of drama therapy,as well as their diverse modes of artistic and medical reasoning.Results:The research process resulted in the identification of five(functional)roots of drama therapy,as well as public health benefits of dramatic arts:(i)dramatic rituals,stage-trance settings and spiritual immersion,(ii)mise-en-scène of divine spheres and alternative worlds,as well as scenic imagination and creative fusion of reality and fantasy,desire and satisfaction,(iii)anthropologic ontology,search of meaning and self-actualisation‘beyond codes and conventions’,(iv)personality traits and differential psychological symbolism,aesthetic self-exploration and auxiliary egos,(v)introjection and role-identity,inventive ways to tackle life problems,‘working through’and catharsis.Conclusion:Interdisciplinary constructivist reasoning suggests that dramatic arts and drama therapy share similar health promoting potential and innate therapeutic power.This calls for further research(i)to explore the entire spectrum of curative factors inhering in dramatic entities,(ii)to explain how drama-based interventions may alleviate mental-health issues alongside culturally sensitive differential diagnostic guidelines,and(iii)to optimise beneficial effects through advanced drama therapeutic settings.The present study suggests that dramatic arts shall also be studied with regard to public health challenges,self-regulation and self-care,mental resilience,well-being and quality of life,and emphatically advocates intensified collaboration between drama theory and drama therapy.展开更多
In this manuscript,we comment on the article by Zhou et al,who assessed the efficacy of hepatic arterial infusion chemotherapy(HAIC)and its combination strategies for advanced hepatocellular carcinoma(HCC)using networ...In this manuscript,we comment on the article by Zhou et al,who assessed the efficacy of hepatic arterial infusion chemotherapy(HAIC)and its combination strategies for advanced hepatocellular carcinoma(HCC)using network metaanalysis methodology.We focus specifically on the potential advantages and role of HAIC in the treatment algorithm for advanced HCC.However,there remains numerous knowledge gaps before the role of HAIC can be established.There is significant heterogeneity of HAIC regimes with difficult interpretation of the clinical outcomes.Additionally,there is a lack of direct comparative data between HAIC,systemic chemotherapy,novel immunotherapies and targeted therapies.The underlying biochemical mechanisms that might explain the efficacy of HAIC and its effect on the HCC microenvironment requires further research.In the developing era of nanotechnology and targeted drug delivery systems,there is potential for integration of HAIC with novel technologies to effectively treat advanced HCC whilst minimising systemic complications.展开更多
文摘This study examines the pivotal findings of the network meta-analysis of Zhou et al,which evaluated the efficacy of hepatic arterial infusion chemotherapy and combination therapies for advanced hepatocellular carcinoma(HCC).This meta-analysis suggests that therapeutic combinations have greater efficacy than do standard treatments.The article highlights the key insights that have the potential to shift current clinical practice and enhance outcomes for patients with advanced HCC.Additionally,this article discusses further research that can be conducted to optimize these treatments and achieve personalized care for patients with HCC.
基金financially supported by the National Natural Science Foundation of China(Nos.32201138,No.82302193)the Natural Science Foundation of Zhejiang Province(No.LQ24H180004)
文摘Pancreatic cancer is highly vulnerable to ferroptosis.Consequently,treatments that target pancreatic cancer through ferroptosis induction demonstrate immense potential for enhancing therapeutic outcomes in this condition.In the present study,we synthesized hollow mesoporous iron oxide nanoparticles(MHFe)using a hydrothermal method.These nanoparticles retained the superparamagnetic properties of iron oxide and its Fenton reaction-catalyzing ability.Meanwhile,they also showed superior drug-loading capacity compared to traditional ferric oxide nanoparticles due to their hollow and mesoporous structure.Under the guidance of a magnetic field,these nanoparticles could accumulate in tumor cells.Following the incorporation of Ce6,a sonosensitizer,the Ce6@MHFe system could generate singlet oxygen under ultrasound treatment to promote tumor cell apoptosis while simultaneously producing hydroxyl radicals through the enhanced Fenton effect of MHFe.This promoted ferroptosis in pancreatic cancer cells,achieving combined therapeutic effects.In vivo experiments confirmed the good biocompatibility of Ce6@MHFe and demonstrated that the nanoparticles could effectively kill tumor cells under magnetic targeting and ultrasound irradiation,thereby inhibiting tumor growth.The findings suggested that these hollow mesoporous iron oxide nanoparticles(Ce6@MHFe)with a high drug-loading capacity,tumor retention ability,and potential for combination therapy have potential for the treatment of various malignancies,including pancreatic cancer.
文摘BACKGROUND Peripheral artery disease(PAD)affects millions globally,with a 5.6%prevalence in 2015 impacting 236 million adults,rising above 10%in those over 60 due to factors like diabetes and smoking.Post-revascularization,single antiplatelet therapy(SAPT)is standard,but dual antiplatelet therapy(DAPT)may improve outcomes,though duration and bleeding risks are unclear.The 2024 American College of Cardiology/American Heart Association guidelines endorse short-term DAPT,yet evidence gaps remain in comparative efficacy and safety.We hypothesized that DAPT reduces cardiovascular events and reinterventions vs SAPT without significantly elevating bleeding in PAD patients’post-lower extremity revascularization.AIM To evaluate the efficacy and safety of DAPT vs SAPT in PAD patients’post-revascularization.METHODS This systematic review and meta-analysis followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines,searching PubMed,EMBASE,and ScienceDirect up to July 2025.Included were randomized controlled trials(RCTs)and cohort studies from various global settings(e.g.,hospitals,tertiary care)comparing DAPT(aspirin plus P2Y12 inhibitor for>1 month)to SAPT in symptomatic PAD patients undergoing endovascular or surgical revascularization(n up to 28244 participants selected via eligibility criteria).Data were pooled using random-effects models for risk ratio(RR)with 95%CI;heterogeneity was assessed via the I²statistic.Quality appraisal used Risk of Bias in Non-randomized Studies of Interventions for cohorts and Risk of Bias 2.0 for RCTs;certainty was evaluated via Grading of Recommendations Assessment,Development and Evaluation(GRADE).RESULTS Twelve studies(3 RCTs,9 cohorts,conducted 2010–2025 with follow-ups of 6 months to 5 years)were included.DAPT showed no significant difference but a trend toward reduced all-cause mortality(RR:0.52,95%CI:0.27–1.01,P=0.05,DAPT of 298/9545 events vs SAPT of 165/566 events)or stroke(RR:0.72,95%CI:0.30–1.72,P=0.46,DAPT of 16/3729 events vs SAPT of 41/7673 events)vs SAPT.DAPT significantly reduced cardiac mortality(RR:0.46,95%CI:0.27–0.80,P=0.006,DAPT of 78/2903 events vs SAPT of 171/1465 events,risk difference:-5.4%),myocardial infarction(RR:0.82,95%CI:0.71–0.94,P=0.004,DAPT of 233/7704 events vs SAPT of 262/9130 events,risk difference:-1.8%),and major reintervention(RR:0.58,95%CI:0.35–0.98,P=0.04,DAPT of 803/205 events vs SAPT of 1197/4 events,risk difference:-42%).Bleeding showed no difference(RR:1.12,95%CI:0.42–3.03,P=0.82,DAPT of 195/2775 events vs SAPT of 202/8234 events).Heterogeneity was high(I^(2)=59%–97%).Quality revealed moderate to serious bias in cohorts and some concerns in RCTs;GRADE certainty moderate for cardiac mortality,myocardial infarction,reintervention,low for others due to inconsistency and imprecision.CONCLUSION DAPT reduces cardiac mortality,myocardial infarction,and major reintervention risks compared to SAPT in PAD post-revascularization without apparent bleeding increase,though limited by heterogeneity and low certainty for some outcomes.
文摘BACKGROUND Hepatocellular carcinoma(HCC)is a leading cause of cancer-related deaths worldwide and currently lacks effective treatment options.This is particularly true for advanced HCC,for which conventional therapies often lead to a poor prognosis.AIM To assess the safety and efficacy of transarterial chemoembolization(TACE)with donafenib and immune checkpoint inhibitors(ICIs)for unresectable HCC.METHODS We retrospectively assessed the data of patients with HCC who underwent TACE combined with donafenib and an ICI(tislelizumab or cedilimumab).Patients received oral donafenib daily for 2 weeks before TACE,followed by tislelizumab or cedilimumab 200 mg intravenously on day 1 of a 21-day therapeutic cycle.The primary endpoints were objective response rate,disease control rate,and duration of response according to the modified RECIST criteria.The secondary endpoint was presence of treatment-related adverse events(TRAEs).RESULTS The median follow-up was 7.8 months(95%CI:5.0-11.8 months).The objective response rate was 60.0%(18/30),while the disease control rate was 93.3%.The median duration of response in confirmed responders was 6.6 months(95%CI:1.3-12.9 months).The median progression-free survival was 11.8 months(95%CI:8.3-15.4 months).More than half of the patients survived until the end of the study.Grade>3 TRAEs occurred in 40%of the patients with no grade 5 TRAEs reported.The most common grade 3/4 TRAE was palmar-plantar erythrodysesthesia,a dermatologic condition characterized by painful redness and swelling of the palms and soles,with an incidence of 56.7%.No ICI-related adverse effects were observed.CONCLUSION TACE combined with donafenib and ICI is a promising and safe therapeutic regimen for unresectable HCC.
文摘Autism spectrum disorder(ASD)is a complex neurodevelopmental disorder affecting over 2%of the global population,marked by social communication deficits and repetitive behaviors.Kabatas et al explored the efficacy and safety of Wharton’s jelly-derived mesenchymal stem cell(WJ-MSC)therapy in a 4-year-old child with ASD.Using the childhood autism rating scale and Denver II develop-mental screening test,significant improvements were seen after six WJ-MSC sessions,with no adverse events over 2 years.Despite promising results,the study’s single-case design limits generalizability.Larger,multi-center trials are needed to validate the findings and assess long-term effects of WJ-MSC therapy in ASD.
基金supported by National Natural Science Foundation of China(81502688)Cooperation Research Funding of Capital Medical University(2020KJ000514)+1 种基金Cooperation Research Funding of Capital Medical University(2023KJ000814)R&D Program of Beijing Municipal Education Commission(KM202210025024).
文摘Efficient siRNA delivery is highly desirable for disease treatment.However,the application of conventional nanoparticles is limited by the inability to escape from endo-lysosomes.Herein,we report a strategy using small-molecule drugs to enhance siRNA endo-lysosomal release,addressing this challenge.We encapsulated gentamicin(GM)into the marketed Onpattro■ formulation to establish LNP-siRNA/GM nanoparticles that promote siRNA endo-lysosomal escape through endosomal disruption,mechanistically exhibiting unique functionality and synergistic effects of LNP-siRNA/GM to improve cancer therapy.Besides,GM induced reactive oxygen species(ROS)and phospholipids accumulation in endolysosomes,as well as the physical characteristics of lipid nanoparticles(LNPs)were preserved.We also revealed that GM causes endo-lysosomal swelling and disrupts the endosomal membrane to enable siRNA release,as confirmed by Galectin 3 recruitment and acridine orange release.This approach achieved∼81%mRNA-EGFR silencing,which is more than LNP-siEGFR(∼56.23%)by enhancing siRNA endo-lysosomal escape efficiency.Meanwhile,LNP-siEGFR/GM exhibited significant biological activities in HepG2 cells,driven by the synergistic effects of siEGFR and GM with the VEGF and CXCL12 downregulation of,and ROS and phospholipids upregulation.Furthermore,tumor growth was notably suppressed after intravenous injection of LNP-siEGFR/GM in tumor-bearing nude mice.The combination of EGFR-siRNA and GM could also greatly inhibit angiogenesis,be antiproliferative,and induce tumor cells apoptosis.Therefore,this GM and siRNA co-delivery system would provide an efficient strategy for siRNA endosomal escape,significantly improving knockdown in various LNPs based siRNA delivery systems and efficiently enhancing cancer therapy.
基金Supported by Houston Methodist DeBakey Heart and Vascular Center Grant.
文摘BACKGROUND Significant gaps in guideline-directed medical therapy(GDMT)for heart failure(HF)stem from shortages of cardiologists and advanced HF providers,as well as a lack of optimal HF management knowledge among hospitalists.This study compared the impact of optimal medical therapy in HF(OMT-HF)certification on GDMT implementation and patient outcomes between an intervention group(IG)of hospitalists and a standard-of-care comparison group(SOC-CG).METHODS This study was implemented from November 2022 to May 2023.Hospitalized car-diology patients with HF and left ventricular ejection fraction≤40%were rando-mized to IG or SOC-CG.Exclusion criteria included patients in cardiogenic shock,unable to consent,or at high risk.Follow-up was at 30 days post-discharge.Diffe-rences between groups were analyzed using Fisher’s exact test for categorical va-riables and Wilcoxon rank-sum or unpaired t-test for continuous variables.Chan-ges in Minnesota Living with Heart Failure Questionnaire(MLWHFQ)scores were evaluated using a paired t-test.RESULTS IG patients had lower readmission rates[9(42.85%)vs 11(17.46%),P=0.03]and a decreased trend in mortality 30-day post discharge.IG patients also showed greater mean improvements in total(-27.03±24.59 vs-5.85±23.52,P<0.001),physical(-13.8±12.3 vs-2.71±11.16,P<0.001)and emotional(-4.76±8.10 vs-1.42±5.98)dimensions on the MLWHFQ compared to SOC-CG,however,change in emotional dimension did not reach statistical significance.CONCLUSION Hospitalist OMT-HF certification may lead to better 30-day outcomes in hospitalized HF patients including quality of life,mortality and readmission rates.Larger prospective studies are warranted to validate these findings.
基金supported by the Key Research and Development Program of Yunnan Science and Technology Department(Grant No.202303AC100326)the National Natural Science Foundation of China(Grant No.81960863)the Education Department of Yunnan Province(Grant No.2023Y0463 and 2024Y380).
文摘This study aimed to systematically evaluate the clinical efficacy of combining wax therapy with conventional drug therapy for rheumatoid arthritis(RA)and to provide evidence supporting its clinical application.A comprehensive search was conducted across PubMed,Cochrane Library,China Biomedical Literature Database(CBM),China National Knowledge Infrastructure(CNKI),Wanfang,and VIP databases from their inception to May 2024.Randomized controlled trials(RCTs)investigating the combination of wax therapy and conventional drug therapy for RA were included in the analysis.Statistical analysis was performed using Review Manager 5.3 software.Nine studies,encompassing a total of 843 patients,were included.The results demonstrated that the combination therapy significantly improved clinical efficacy compared to conventional drug therapy alone[RR=1.22,95%CI(1.11,1.34)].Moreover,the combination therapy led to notable improvements in DAS 28 scores[MD=-0.90,95%CI(-1.23,-0.57),P<0.00001],VAS scores[MD=-0.90,95%CI(-1.13,-0.66),P<0.00001],reduction in joint tenderness[MD=-1.27,95%CI(-1.81,-0.72),P<0.00001],decreased duration of morning stiffness[MD=-25.47,95%CI(-34.33,-16.61),P<0.00001],and lowered C-reactive protein levels[MD=-6.29,95%CI(-12.02,-0.57),P<0.05].In conclusion,wax therapy combined with conventional anti-rheumatic drugs significantly enhanced the clinical outcomes for RA patients by alleviating symptoms,reducing joint pain and morning stiffness,and decreasing inflammatory markers more effectively than conventional drug therapy alone.
基金Supported by Capital Fund Project for Clinical Diagnosis and Treatment Technology Research and Translational Application,No.Z201100005520091.
文摘Publications of Soufan et al and Kristjánsson et al in the World Journal of Orthopedics on mesenchymal stem cell(MSC)therapy for osteoarthritis(OA)represent a significant exploration of regenerative medicine’s potential in OA treatment.In their research,it is highlighted that MSCs can alleviate OA symptoms and even regenerate cartilage,potentially reversing the disease.They also compared the efficacy of three MSC subtypes,emphasizing the therapeutic advantages of adipose-derived MSCs.MSC injections,a novel and less invasive alternative to traditional treatments such as chondrocyte transplantation or arthroplasty,have a low cost,low risks,and favorable outcomes,presenting a promising approach for OA patients.Additionally,we stressed that the efficacy evaluation criteria,heterogeneity,safety,and other factors must be carefully considered to further advance the clinical translation of MSC therapy for OA.
基金funded by the Horizon Europe Project"PERSEUS"(No.101099423)financed by the Ministry of Universities under application 33.50.460A.752by the European Union NextGenerationEU/PRTR through a contract Margarita Salas from Universidade de Vigo.
文摘Photodynamic therapy(PDT)has been established as one of the most promising novel cancer therapies with fewer side-effects and enhanced efficacy compared to the currently available conventional treatments.However,its application has been hindered by the limitations that photosensitizers(PS)have.The combination of PS with metallic nanoparticles like platinum nanoparticles(PtNPs),can help to overcome these intrinsic drawbacks.In this work,the combination of PtNPs and the natural photosensitizer riboflavin(RF)is proposed.PtNPs are synthesized using RF(Pt@RF)as reducing and stabilizing agent in a one-step method,obtaining nanoparticles with mesoporous structure for UV triggered PDT.In view of possible future UV irradiation treatments,the degradation products of RF,ribitol(RB)and lumichrome(LC),this last being a photosensitizing byproduct,are also employed for the synthesis of porous PtNPs,obtaining Pt@LC and Pt@RB.When administered in vitro to lung cancer cells,all the samples elicit a strong decrease of cell viability and a decrease of intracellular ATP levels.The antitumoral effect of both Pt@RF and Pt@LC is triggered by UV-A irradiation.This antitumoral activity is caused by the induction of oxidative stress,shown in our study by the decrease in intracellular glutathione and increased expression of antioxidant enzymes.
基金supported by Sanming Project of Medicine in Shenzhen(No.SZZYSM202411012)Beijing Clinical Key Specialty Project(2023).
文摘Community-acquired pneumonia(CAP)in adults(≥18 years old)is the most common infectious disease encountered in emergency departments.Its clinical complexity and the need for prompt treatment decisions pose significant challenges for patient management.The physician-pharmacist collaborative management(PPCM)model,which optimizes drug therapy regimens through collaboration between physicians and clinical pharmacists,has demonstrated strong clinical value in practice.However,the lack of standardized national guidelines for the application of the PPCM model in emergency departments in China has hampered its widespread adoption.This guideline is developed based on evidence-based medicine and clinical practice experience,with a focus on the application of the PPCM model in the management of CAP in emergency settings.It outlines the significance of the PPCM model,its applicable scenarios,the respective roles of emergency physicians and clinical pharmacists,and its practical implementation in the antimicrobial treatment of CAP patients.In addition,the guideline proposes standardized implementation processes and clinical pathways.By promoting the PPCM model,the expert panel aims to standardize the use of antimicrobial agents in the emergency treatment of CAP,reduce the risk of antimicrobial resistance,and improve patient outcomes.
文摘BACKGROUND Advanced esophageal squamous cell carcinoma(ESCC)has an extremely poor prognosis.Preoperative chemoradiotherapy(CRT)can significantly prolong survival,especially in those who achieve pathological complete response(pCR).However,the pretherapeutic prediction of pCR remains challenging.AIM To predict pCR and survival in ESCC patients undergoing CRT using an artificial intelligence(AI)-based diffusion-weighted magnetic resonance imaging(DWI-MRI)radiomics model.METHODS We retrospectively analyzed 70 patients with ESCC who underwent curative surgery following CRT.For each patient,pre-treatment tumors were semi-automatically segmented in three dimensions from DWI-MRI images(b=0,1000 second/mm^(2)),and a total of 76 radiomics features were extracted from each segmented tumor.Using these features as explanatory variables and pCR as the objective variable,machine learning models for predicting pCR were developed using AutoGluon,an automated machine learning library,and validated by stratified double cross-validation.RESULTS pCR was achieved in 15 patients(21.4%).Apparent diffusion coefficient skewness demonstrated the highest predictive performance[area under the curve(AUC)=0.77].Gray-level co-occurrence matrix(GLCM)entropy(b=1000 second/mm²)was an independent prognostic factor for relapse-free survival(RFS)(hazard ratio=0.32,P=0.009).In Kaplan-Meier analysis,patients with high GLCM entropy showed significantly better RFS(P<0.001,log-rank).The best-performing machine learning model achieved an AUC of 0.85.The predicted pCR-positive group showed significantly better RFS than the predicted pCR-negative group(P=0.007,log-rank).CONCLUSION AI-based radiomics analysis of DWI-MRI images in ESCC has the potential to accurately predict the effect of CRT before treatment and contribute to constructing optimal treatment strategies.
基金supported by National Natural Science Foundation of China(82374296,82271965,62331021)Development Project of Shanghai Peak Disciplines-Integrated Medicine(201801)+1 种基金Shanghai Municipal Science and Technology Major Project(2018SHZDZX01)Shanghai Municipal Science and Technology Explorer Project(23TS1400500).
文摘Ischemic stroke is currently the second leading cause of death worldwide,and insufficient endogenous neurogenesis is the greatest cause of post-stroke disability.MicroRNAs have been proven to hold therapeutic potential,unfortunately,they have a low stability that hinders their clinical usage.Our earlier work revealed that Panax notoginseng derived exosome like nanoparticles,namely PDNs have potential to bypass BBB and reduce the cerebral ischemia/reperfusion(CI/R)damage.In this study,we employed microRNA-124 as a model therapeutic gene,utilizing its engineered variant Agomir-124(Ago124)to optimize loading efficiency.The therapeutic effects of Ago124@R-PDN were further assessed in several sets of experiments.Pharmacokinetic study showed that erythrocyte membrane extended the half-life of PDNs from 7 min to 11.3 h,and the loading efficiency of Ago124 reached 40%.In an in vitro oxygen-glucose deprivation/reperfusion(OGD/R)model,Ago124@R-PDN enhanced IL-10 production in microglia by 67%(vs 11.7%with free Ago124),and promoted Tuj1+neuronal differentiation by 2.23-fold compared with vehicle.Also,Ago124@R-PDN brought gene cargo into the brain,alleviated infarct volume,and improved functional behaviors in model mice.At last,we demonstrated that surface glycosyl of PDN facilitated its brain-entering ability by being recognized by sodium-glucose linked transporter-1 protein.In conclusion,our erythrocyte fused PDNs offer a promising strategy for delivering biomacromolecule to treat brain diseases.
文摘Hepatic arterial infusion chemotherapy (HAIC) is an advanced targeted therapeuticapproach for hepatocellular carcinoma (HCC), the most common type ofprimary liver cancer. HAIC has demonstrated significant potential in managingadvanced HCC, particularly in regions with high prevalence rates. Despite itspromise, several challenges and areas for future research remain. Clinical studieshave substantiated the efficacy of HAIC in enhancing survival outcomes forpatients with advanced hepatic carcinoma. Notably, combination therapiesinvolving immune checkpoint inhibitors, such as lenvatinib and programmeddeath-1 inhibitors, have shown substantial improvements in median overallsurvival and progression-free survival compared to systemic chemotherapy.These combination therapies have also exhibited superior response rates anddisease control, with manageable and often less severe adverse events relative tosystemic treatments. This article is based on the review by Zhou et al and aims todiscuss the current status and future directions in the treatment of HCC, emphasizingthe role of HAIC and its integration with novel therapeutic agents.
文摘The hydrophobic sonosensitizer IR780 iodide(IR780)was loaded into liposomes to form Liposome@IR780 nanoparticles(NPs)for triple-negative breast cancer(TNBC)to enhance SDT via low-intensity ultrasound(LIU)irradiation.The NPs were characterized using various physicochemical methods including size distribution,zeta potential,and morphology.In vitro experiments show that the Liposome@IR780 NPs can generate more reactive oxygen species(ROS)upon LIU irradiation.The apoptosis experiment results further demonstrate that Liposome@IR780 NPs show better apoptosis rate against 4T1 cells.Our results indicate that Liposome@IR780 NPs will provide a promising approach for TNBC upon SDT treatment.
基金Supported by 2023 Hebei Provincial Medical Scientific Research Project Plan,No.20231304.
文摘Colorectal cancer(CRC)with liver metastasis remains a significant therapeutic challenge,particularly in cases of postoperative recurrence.While transarterial chemoembolization(TACE)and targeted therapies have shown promise individually,the efficacy combining these for treating postoperative recurrent CRC with liver metastasis requires further investigation.AIM To evaluate the efficacy and safety of TACE combined with targeted therapies for postoperative recurrent CRC with liver metastasis.METHODS This observational study enrolled 75 patients with postoperative recurrent CRC accompanied by liver metastasis between January 2020 and December 2023.All patients received combined treatment with TACE and targeted therapy:Bevacizumab(40 patients,53.3%),cetuximab(25 patients,33.3%),or panitumumab(10 patients,13.3%).Treatment response was evaluated using the Response Evaluation Criteria in Solid Tumors 1.1 criteria,with overall survival(OS)and progression-free survival as the primary endpoints.Quality of life was assessed using the European Organization for Research and Treatment of Cancer quality of life questionnaire at baseline and after six months of treatment.RESULTS The median OS was 28 months(95%confidence interval:24-32 months),and the median progression-free survival was 12 months(95%confidence interval:10-14 months).Patients treated with bevacizumab showed significantly better survival outcomes than those treated with cetuximab/panitumumab(median OS,30 vs 24 months,P=0.015).The overall response rate was 58.7%,with a disease control rate of 86.7%.Quality of life scores improved significantly across all domains,with greater improvements observed in the bevacizumab group.Treatment-related adverse events were manageable,with grade 3-4 events occurring in 13.3%of the patients and no treatment-related mortality.CONCLUSION The combination of TACE with targeted therapy,particularly bevacizumab,has demonstrated promising efficacy and acceptable safety for the treatment of postoperative recurrent CRC with liver metastasis.This multimodal approach not only improved survival outcomes but also enhanced the patients’quality of life,suggesting its potential as a valuable treatment strategy for this challenging condition.
基金supported by the National Natural Science Foundation of China(Grant Nos.82073308 and 82104089)。
文摘Glioblastoma multiforme(GBM)is a highly aggressive and lethal brain tumor with limited treatment options.To improve therapeutic efficacy,we developed a novel multifunctional nanoplatform,GM@P(T/S),comprised of polymeric nanoparticles coated with GBM cell membranes as well as co-loaded with temozolomide(TMZ)and superparamagnetic iron oxide(SPIO)nanoparticles.The successful preparation was confirmed in terms of particle size,morphology,stability,the in vitro drug release,and cellular uptake assays.We demonstrated that GM@P(T/S)exhibited the enhanced homotypic targeting,the prolonged blood circulation,and efficient bloodbrain barrier penetration in both in vitro and in vivo studies.The combination of TMZ and SPIO nanoparticles within GM@P(T/S)synergistically improved chemo-radiation therapy,leading to a reduced tumor growth,an increased survival,and minimal systemic toxicity in the orthotopic GBM mouse models.Our findings suggest that GM@P(T/S)holds a great promise as a targeted and efficient therapeutic strategy for GBM.
文摘Stem cell therapy holds great promise for the regeneration and repair of damaged tissues and organs.Stem cell therapy has been successfully applied to treat diseases that cannot be cured with conventional medicine.A careful evaluation of the outcomes is required for successful implementation of stem cell therapy.Recently,artificial intelligence(AI)has opened new avenues for research in the stem cell therapy field.The integration of AI can assist in evaluating the quality,efficiency and safety of stem cells by analyzing available data.It has the potential to improve and accelerate progress in various aspects of stem cell research and therapeutic applications.AI is still in its infancy and has certain limitations,such as algorithm validation problems,inadequate data availability,poor data quality,and ethical considerations.Considering the potential of AI to improve stem cell research and therapeutics,this review aims to explore applications of AI in understanding stem cell behavior,identification and characterization,optimization of the delivery methods,stem cell modeling and prediction of mortality risk.In addition,this review highlights the role of AI,machine learning,deep learning,and other subtypes in advancing stem cell biology research.This review also discusses the current limitations,ethical considerations,and future prospective of use of AI in stem cell research and therapeutic applications.
文摘Background:Drama therapy as a discipline in clinical and public health areas dates back to movements in the Netherlands,Great Britain and the United States of America in the 1960s.Today,drama therapy comprises a huge variety of methods and is applied in numerous medical domains such as psychiatry,pediatrics and neurogeriatrics.Nonetheless,historical and philosophical considerations suggest that at all times dramatic arts have encompassed curative potential and helped to promote mental health.Regarding this perspective,the present article aims to explore the spirit of drama therapy in ancient Chinese and Greek cultures.Methods:Involving cross-cultural psychiatry and medical anthropology,comparative research centred around salutary momentums inhering in drama and dramatic practices in Ancient China and Greece.The entire research process consisted of three phases:(i)screening of ancient Chinese and Greek dramatic rituals and arts to select phenomena and genres with pathological,therapeutic and mental health relevance;(ii)medical ontological processing,in particular from a psychopathological,psychiatric,psychotherapeutic and mental health scientific point of view,to explore and elucidate their curative and preventative features;(iii)transdisciplinary considerations about the evolution of drama therapy,as well as their diverse modes of artistic and medical reasoning.Results:The research process resulted in the identification of five(functional)roots of drama therapy,as well as public health benefits of dramatic arts:(i)dramatic rituals,stage-trance settings and spiritual immersion,(ii)mise-en-scène of divine spheres and alternative worlds,as well as scenic imagination and creative fusion of reality and fantasy,desire and satisfaction,(iii)anthropologic ontology,search of meaning and self-actualisation‘beyond codes and conventions’,(iv)personality traits and differential psychological symbolism,aesthetic self-exploration and auxiliary egos,(v)introjection and role-identity,inventive ways to tackle life problems,‘working through’and catharsis.Conclusion:Interdisciplinary constructivist reasoning suggests that dramatic arts and drama therapy share similar health promoting potential and innate therapeutic power.This calls for further research(i)to explore the entire spectrum of curative factors inhering in dramatic entities,(ii)to explain how drama-based interventions may alleviate mental-health issues alongside culturally sensitive differential diagnostic guidelines,and(iii)to optimise beneficial effects through advanced drama therapeutic settings.The present study suggests that dramatic arts shall also be studied with regard to public health challenges,self-regulation and self-care,mental resilience,well-being and quality of life,and emphatically advocates intensified collaboration between drama theory and drama therapy.
文摘In this manuscript,we comment on the article by Zhou et al,who assessed the efficacy of hepatic arterial infusion chemotherapy(HAIC)and its combination strategies for advanced hepatocellular carcinoma(HCC)using network metaanalysis methodology.We focus specifically on the potential advantages and role of HAIC in the treatment algorithm for advanced HCC.However,there remains numerous knowledge gaps before the role of HAIC can be established.There is significant heterogeneity of HAIC regimes with difficult interpretation of the clinical outcomes.Additionally,there is a lack of direct comparative data between HAIC,systemic chemotherapy,novel immunotherapies and targeted therapies.The underlying biochemical mechanisms that might explain the efficacy of HAIC and its effect on the HCC microenvironment requires further research.In the developing era of nanotechnology and targeted drug delivery systems,there is potential for integration of HAIC with novel technologies to effectively treat advanced HCC whilst minimising systemic complications.
