Background: Erythrodermic psoriasis (EP) is a rare, severe variant of psoriasis characterized by widespread erythema, scaling, and systemic complications. Despite advances in systemic treatments, the management of EP ...Background: Erythrodermic psoriasis (EP) is a rare, severe variant of psoriasis characterized by widespread erythema, scaling, and systemic complications. Despite advances in systemic treatments, the management of EP remains challenging, particularly in patients with comorbidities or contraindications to standard therapies. Objectives: To evaluate the effectiveness of ozonated water as an adjunctive treatment for EP, delivered using a patented robotic therapy system designed for hygiene and infection prevention in non-self-sufficient patients. Methods: We report the case of a 90-year-old male patient with acute EP who received daily skin treatments with ozonated water in conjunction with supportive care, including rehydration and antibiotics. The intervention was facilitated by the robotic system “COPERNICO Surveillance & Prevention,” which ensured standardized hygiene practices and clinical documentation. Results: Within one week of treatment, the patient showed complete desquamation of necrotic skin, resolution of erythema, and significant metabolic recovery. Fever subsided, renal function improved, and the patient was discharged in stable condition. Follow-up confirmed sustained clinical improvement, and no adverse events were reported. Conclusions: Ozonated water demonstrated efficacy in alleviating the dermatological and systemic manifestations of EP in a high-risk elderly patient. This case highlights the potential of ozone therapy as a safe, cost-effective adjunctive treatment for EP and underscores the utility of robotic systems in managing complex dermatological conditions. Further research is warranted to validate these findings in larger cohorts.展开更多
Objective： To construct Bifidobacterium Infantis/CD targeting gene therapy system. Methods： CD gene was amplified from E. Coli K12λ using PCR method, pGEX-1LamdaT plasmid and CD gene were digested with dual restric...Objective： To construct Bifidobacterium Infantis/CD targeting gene therapy system. Methods： CD gene was amplified from E. Coli K12λ using PCR method, pGEX-1LamdaT plasmid and CD gene were digested with dual restriction endonucleas of EcoR Ⅰ and BamH Ⅰ and two segments of 4.9 kb and 1.3 kb were obtained. T4 DNA ligase was added to these two segments to make a recombinant CD/pGEX-1LamdaT plasmid. Then the recombinant plasmid was transfected into Bifidobacterium Infantis by electroporation. The recombinant plasmid was extracted from the positively transfected Bifidobacterium Infantis and digested with dual restriction endonucleases. Then the size of digested fragments was detected and sequencing of the gene segment inserted in extracted recombinant plasmid was performed according to the method of Sanger dideoxynucleotide triphosphate chain termination. Results： 6.2 kb recombinant plasmid was obtained from the positively transfected bacterial colony of Bifidobacterium Infantis. After being digested with dual restriction endonucleases, two segments of approximate 4.9 kb and 1.3 kb were gained from the extracted recombinant plasmid, which were equal to the size of pGEX-1LamdaT plasmid and CD gene, respectively. The full length and sequence of nucleotide acid of the inserted gene in extracted recombinant plasmid was completely identical to the CD gene. Conclusion： The foreign gene, CD gene was correctly inserted into pGEX-1LambdaT plasmid and transferred into Bifidobacterium Infantis. Bifidobacterium Infantis/CD targeting gene therapy system was successfully constructed.展开更多
A proton therapy(PT)facility with multiple treatment rooms based on the superconducting cyclotron scheme is under development at Huazhong University of Science and Technology(HUST).This paper attempts to describe the ...A proton therapy(PT)facility with multiple treatment rooms based on the superconducting cyclotron scheme is under development at Huazhong University of Science and Technology(HUST).This paper attempts to describe the design considerations and implementation of the PT beamline from a systematic viewpoint.Design considerations covering beam optics and the influence of high-order aberrations,beam energy/intensity modulation,and beam orbit correction are described.In addition to the technical implementation of the main beamline components and subsystems,including the energy degrader,fast kicker,beamline magnets,beam diagnostic system,and beamline control system are introduced.展开更多
Background: At-home phototherapy devices for the treatment of acne have emerged as an appealing treatment option and as an effective adjunct treatment to existing modalities. The principal goal of the study was to det...Background: At-home phototherapy devices for the treatment of acne have emerged as an appealing treatment option and as an effective adjunct treatment to existing modalities. The principal goal of the study was to determine the changes in the number of inflammatory lesions in acne patients. Methods: Patients received instruction for daily at-home use of Silk’n Blue device for 12 weeks. Follow-up visits were conducted at 1 and 3 months to collect data. Results: Fifteen subjects with mild to severe cases experienced improvement over the course of the trial. The decrease in mean inflammatory acne counts (from 41.26 to 24.46) and mean percent reduction (41.8%) were statistically significant (p < 0.001). Some participants experienced percent reductions as great as 67%. No adverse events were recorded. Conclusions: The Silk’n Blue device is a safe and effective modality for at-home treatment of mild, moderate, and severe inflammatory acne vulgaris with proper use.展开更多
The human retina,a complex and highly specialized structure,includes multiple cell types that work synergistically to generate and transmit visual signals.However,genetic predisposition or age-related degeneration can...The human retina,a complex and highly specialized structure,includes multiple cell types that work synergistically to generate and transmit visual signals.However,genetic predisposition or age-related degeneration can lead to retinal damage that severely impairs vision or causes blindness.Treatment options for retinal diseases are limited,and there is an urgent need for innovative therapeutic strategies.Cell and gene therapies are promising because of the efficacy of delivery systems that transport therapeutic genes to targeted retinal cells.Gene delivery systems hold great promise for treating retinal diseases by enabling the targeted delivery of therapeutic genes to affected cells or by converting endogenous cells into functional ones to facilitate nerve regeneration,potentially restoring vision.This review focuses on two principal categories of gene delivery vectors used in the treatment of retinal diseases:viral and non-viral systems.Viral vectors,including lentiviruses and adeno-associated viruses,exploit the innate ability of viruses to infiltrate cells,which is followed by the introduction of therapeutic genetic material into target cells for gene correction.Lentiviruses can accommodate exogenous genes up to 8 kb in length,but their mechanism of integration into the host genome presents insertion mutation risks.Conversely,adeno-associated viruses are safer,as they exist as episomes in the nucleus,yet their limited packaging capacity constrains their application to a narrower spectrum of diseases,which necessitates the exploration of alternative delivery methods.In parallel,progress has also occurred in the development of novel non-viral delivery systems,particularly those based on liposomal technology.Manipulation of the ratios of hydrophilic and hydrophobic molecules within liposomes and the development of new lipid formulations have led to the creation of advanced non-viral vectors.These innovative systems include solid lipid nanoparticles,polymer nanoparticles,dendrimers,polymeric micelles,and polymeric nanoparticles.Compared with their viral counterparts,non-viral delivery systems offer markedly enhanced loading capacities that enable the direct delivery of nucleic acids,mRNA,or protein molecules into cells.This bypasses the need for DNA transcription and processing,which significantly enhances therapeutic efficiency.Nevertheless,the immunogenic potential and accumulation toxicity associated with non-viral particulate systems necessitates continued optimization to reduce adverse effects in vivo.This review explores the various delivery systems for retinal therapies and retinal nerve regeneration,and details the characteristics,advantages,limitations,and clinical applications of each vector type.By systematically outlining these factors,our goal is to guide the selection of the optimal delivery tool for a specific retinal disease,which will enhance treatment efficacy and improve patient outcomes while paving the way for more effective and targeted therapeutic interventions.展开更多
Background:Isotonic crystalloids are recommended as the first choice for fluid therapy in acute pan-creatitis(AP),with normal saline(NS)and lactate Ringer’s(LR)used most often.Evidence based recom-mendations on the t...Background:Isotonic crystalloids are recommended as the first choice for fluid therapy in acute pan-creatitis(AP),with normal saline(NS)and lactate Ringer’s(LR)used most often.Evidence based recom-mendations on the type of fluid are conflicting and generally come from small single-center randomized controlled trials(RCTs).We therefore conducted a systematic review and meta-analysis to compare the effect of balanced solutions(BS)versus NS on patient-centered clinical outcomes in AP.Methods:From four databases searched up to October 2024,we included only RCTs of adult patients with AP that compared the use of BS(including LR,acetate Ringer’s,etc.)with NS.The primary out-come was the disease advances from AP to moderately severe and severe AP(MSAP/SAP).Trial sequential analyses(TSA)were conducted to control for type-I and type-II errors and Grading of Recommendations Assessment,Development,and Evaluation(GRADE)was used to assess the quality of evidence.Results:Six RCTs were identified and included,involving 260 patients treated with BS and 298 patients with NS.Patients who received the BS had less MSAP/SAP[odds ratio(OR)=0.50,95%confidence in-terval(CI):0.29 to 0.85,P=0.01,I^(2)=0%;5 studies,299 patients],reduced the need of ICU admission(OR=0.60,95%CI:0.39 to 0.93,P=0.02,I^(2)=0%;5 studies,507 patients)and shorter length of hospital stay[mean difference(MD)=-0.88,95%CI:-1.48 to-0.28,P=0.004,I^(2)=0%;6 studies,558 patients;confirmed by TSA with high certainty]compared with those who received NS.The evidence for most of the clinical outcomes was rated as moderate to low due to the risk of bias,imprecision and inconsistency.Conclusions:BS,compared with NS,was associated with improved clinical outcomes in patients with AP.However,given the moderate to low quality of evidence for most of the outcomes assessed,further trials are warranted.展开更多
Gastric cancer(GC)and gastroesophageal junction cancer(GEJC)represent a significant burden globally,with complications such as overt bleeding(OB)further exacerbating patient outcomes.A recent study by Yao et al evalua...Gastric cancer(GC)and gastroesophageal junction cancer(GEJC)represent a significant burden globally,with complications such as overt bleeding(OB)further exacerbating patient outcomes.A recent study by Yao et al evaluated the effectiveness and safety of systematic treatment in GC/GEJC patients presenting with OB.Using propensity score matching,the study balanced the comparison groups to investigate overall survival and treatment-related adverse events.The study's findings emphasize that systematic therapy can be safe and effective and contribute to the ongoing debate about the management of advanced GC/GEJC with OB,highlighting the complexities of treatment decisions in these high-risk patients.展开更多
Hepatocellular carcinoma(HCC)is a lethalmalignancy.Formany years,chemotherapeutic regimens have served as the foundation of sys-temic therapies for advanced HCCdespite their limited efficacy and significant adverse ef...Hepatocellular carcinoma(HCC)is a lethalmalignancy.Formany years,chemotherapeutic regimens have served as the foundation of sys-temic therapies for advanced HCCdespite their limited efficacy and significant adverse effects.In recent decades,novel systemic therapies such as immunotherapy and targeted therapy have profoundly transformed HCC management.Although some patients with advanced HCC exhibit dramatically improved outcomes,the efficacy of immunotherapy and targeted therapy,either asmonotherapy or in combina-tion,remains limited.Numerous trials have indicated that locoregional therapies,including transarterial chemoembolization(TACE),hepatic arterial infusion chemotherapy(HAIC),and transarterial radioembolization(TARE),may synergize with systemic therapies to enhance ad-vanced HCC treatment.However,further studies are required to optimize these combination regimens.In contrast,curative treatments,such as surgical resection,liver transplantation,or local ablation,are typically recommended for patients with early-stage HCC.Although these treatments have achieved an impressivemedian overall survival(OS)exceeding 60months,more than half of the patients experience recurrence within 5 years.Consequently,the development of effective perioperative neoadjuvant or adjuvant therapies is urgently needed to reduce the incidence of recurrence and metastasis.It provides a comprehensive overview of recent advances in systemic therapies for advanced HCC,as well as adjuvant or neoadjuvant immunotherapies for early HCC.Additionally,emerging clinical trials and trial designs for future investigations into systemic therapies for HCC management are critically analyzed.展开更多
BACKGROUND Acceptance and commitment therapy(ACT)is a third-generation therapy that appears to be a promising psychological intervention for psychotic disorders.While several systematic reviews and meta-analyses that ...BACKGROUND Acceptance and commitment therapy(ACT)is a third-generation therapy that appears to be a promising psychological intervention for psychotic disorders.While several systematic reviews and meta-analyses that address the efficacy of ACT for psychosis have been conducted,no systematic review has specifically focused on the application of ACT to the early stages of psychosis.AIM To review the state of the art regarding the feasibility and efficacy of treating early psychosis(EP)with ACT-based interventions.METHODS First,we describe the foundations of the ACT model to provide the background required to contextualize the main objective of this review.Second,we searched the PubMed and PsycINFO databases for studies published up to January 2025 and identified eight studies that met our selection criteria.The systematic review was conducted in accordance with the PRISMA guidelines and the critical appraisal checklist provided by the Joanna Briggs Institute for randomized controlled trials(RCTs).RESULTS All studies were published after 2019.Among the reviewed studies,five were RCTs with a total combined sample of 399 nonoverlapping participants.The methodological quality was moderate for RCTs.The results showed that ACTbased treatments are feasible and improve psychotic symptoms,medication adherence,and global functioning in patients with EP.Furthermore,preliminary evidence exists for the benefits of group-based and online-delivered programs and those that combine face-to-face therapy with novel real-time digital interventions,such as“ecological momentary intervention”,to apply therapeutic con cepts to real life.CONCLUSION ACT-based treatments in the early stages of psychosis are feasible and improve symptoms,treatment adherence,and self-care skills.Although promising,these results are inconclusive.Further research is required.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
Dear Editor,Rosacea is characterized by persistent or transient erythema,papules,pustules,telangiectasia,and/or phymatous lesions[1].Although multiple treatments are available for rosacea,the advent of biological agen...Dear Editor,Rosacea is characterized by persistent or transient erythema,papules,pustules,telangiectasia,and/or phymatous lesions[1].Although multiple treatments are available for rosacea,the advent of biological agents and small-molecule agents has significantly advanced our ability to target the disease more effectively[2].In the current review,we summarize the outcomes of targeted therapies in rosacea,mainly focusing on interleukin(IL)-17 inhibitors and Janus kinase(JAK)inhibitors.展开更多
BACKGROUND Cardiac resynchronization therapy(CRT)has been a major therapeutic advancement for patients with heart failure and electrical dyssynchrony.While CRT improves symptoms,reduces hospitalizations,and enhances s...BACKGROUND Cardiac resynchronization therapy(CRT)has been a major therapeutic advancement for patients with heart failure and electrical dyssynchrony.While CRT improves symptoms,reduces hospitalizations,and enhances survival,the role of implantable cardioverter-defibrillators(ICDs)alongside CRT in patients with non-ischemic cardiomyopathy(NICM)remains controversial.To evaluate and compare the outcomes of CRT with ICD(CRT-D)versus CRT with pacemaker-only(CRT-P)in individuals diagnosed with NICM,with a specific focus on the elderly.METHODS A comprehensive search of PubMed,Embase,and the Cochrane Central Register of Controlled Trials was conducted in January 2024.Studies comparing CRT-D and CRT-P in patients with NICM were included,with subgroup analyses focusing on patients aged 75 years and older.RESULTS Twelve studies,including two randomized clinical trials,with a total of 62,145 patients and 16,754 pooled death events(9,171 in CRT-D and 7,583 in CRT-P),were analyzed.CRT-D was associated with a significantly lower risk of all-cause mortality compared to CRT-P(pooled OR=0.72;95%CI:0.61-0.85;P<0.01),with significant heterogeneity(I2=83%).RCT subgroup analysis,was not statistically significant(pooled OR=0.82;95%CI:0.64-1.06;P=0.41;I2=0%).In patients older than 75 years,no significant difference in mortality risk was observed(pooled OR 0.96;95%CI:0.81-1.15;I2=39%).CONCLUSION Our meta-analysis suggests that the addition of ICD therapy to CRT in patients with NICM significantly reduces all-cause mortality.However,this benefit does not extend to cardiovascular mortality,likely due to the primary role of ICDs in preventing sudden cardiac death rather than other causes such as progressive heart failure.The survival advantage of CRT-D is most pronounced in younger patients,with those over 75 years of age deriving less benefit.This highlights the importance of careful patient selection,considering age and comorbidities,when deciding on ICD implantation in NICM patients.展开更多
BACKGROUND Eosinophilic esophagitis(EoE)is a chronic inflammatory disorder presenting as symptoms of dysphagia,esophageal food impaction,chest pain,and heartburn.After an initial trial of proton pump inhibitor(PPI)the...BACKGROUND Eosinophilic esophagitis(EoE)is a chronic inflammatory disorder presenting as symptoms of dysphagia,esophageal food impaction,chest pain,and heartburn.After an initial trial of proton pump inhibitor(PPI)therapy,swallowed topical corticosteroids(STC)are effective as induction therapy for EoE.However,out-come data for STC as a maintenance strategy is limited.RESULTS Three randomized control trials and one observational study were included,involving 303 patients(189 in the STC group,114 in the placebo-controlled group).Analysis showed that histologic recurrence was significantly lower with STC(OR:0.04,95%CI:0.01-0.28,P<0.00001,I^(2)=78%).Overall symptom recurrence was similar between groups(OR:0.23,95%CI:0.02-3.54,P=0.29,I^(2)=92%).On sensitivity analysis,symptom recurrence was significantly lower in the STC group(OR:0.05,95%CI:0.02-0.17,P=0.00001,I^(2)=39%).Odds of repeat dilation were significantly lower in the STC group(OR:0.14,95%CI:0.02-0.91,P=0.04,I^(2)=0%).Candida infection rates were similar between groups(OR:6.13,95%CI:0.85-44.26,P=0.07,I^(2)=24%).Proportion of concomitant PPI use was similar between groups(OR:1.64,95%CI:0.83-3.21,P=0.15,I^(2)=0%).CONCLUSION For patients who successfully achieved remission of EoE with STC induction therapy,maintaining treatment is effective in sustaining histologic remission,while newer regimens may be effective in preventing symptom recurrence compared to placebo.We found no significant difference for oropharyngeal/esophageal candidiasis with STC maintenance therapy.Future studies with longer follow-up periods are needed.展开更多
Hepatocellular carcinoma(HCC)is a leading cause of cancer-related mortality,and resistance to systemic therapies remains a significant clinical challenge.This study investigated the mechanisms by which metabolic repro...Hepatocellular carcinoma(HCC)is a leading cause of cancer-related mortality,and resistance to systemic therapies remains a significant clinical challenge.This study investigated the mechanisms by which metabolic reprogramming contributes to systemic treatment resistance in HCC.We established HCC cell lines with multidrug resistance characteristics and observed enhanced metabolic activity in these cells.Integrated multiomics analyses revealed hyperactive glucose‒lipid and glutathione metabolic pathways that play critical roles in supporting tumor cell proliferation and survival.We constructed a metabolic reprogramming atlas for HCC-resistant cells and identified aldo-keto reductase(Aldo-keto reductase family 1 Member B1,AKR1B1)as a key regulator of this reprogramming,which sustains drug resistance by regulating energy metabolism and enhancing stress tolerance.Importantly,AKR1B1 expression levels are closely associated with drug resistance and poor prognosis in HCC patients.The secretory nature of AKR1B1 not only underscores its predictive value but also facilitates the intercellular transmission of drug resistance.In terms of overcoming resistance,the AKR1B1 inhibitor epalrestat significantly mitigated drug resistance when it was used in combination with standard therapies.These findings underscore the importance of metabolic reprogramming in the development of HCC resistance.AKR1B1,a key enzyme that regulates metabolic reprogramming,has been identified as a potential biomarker and therapeutic target,providing new insights into overcoming resistance in HCC treatment.展开更多
Background:Gastric Cancer(GC)is the 5th most prevalent and 4th most deadly neoplasm globally.Immunotherapy has emerged as a promising treatment approach in GC,potentially improving positive clinical outcomes while add...Background:Gastric Cancer(GC)is the 5th most prevalent and 4th most deadly neoplasm globally.Immunotherapy has emerged as a promising treatment approach in GC,potentially improving positive clinical outcomes while addressing the limitations of conventional therapies.GC immunotherapy modalities consist of adoptive cell therapy(ACT),cancer vaccines,and immune checkpoint inhibitors(ICI).Objectives:This systematic review aims to provide an overview of the advances in immune-based therapeutic approaches in GC,highlighting the potential of this therapy as a strategy for GC treatment.Methods:Key studies investigating several immunotherapeutic agents and combination therapies were searched in PUBMED and included in this study.Specific cancer outcomes related to disease progression or survival were analyzed.Results:After screening 236 studies,the results revealed that immunotherapy,particularly the ICI pembrolizumab,demonstrated promising efficacy in the treatment of GC,as several studies reported improved OS,PFS,and objective response rate with the use of pembrolizumab alone or in combination with other treatment modalities.Conclusion:Safety analysis showed that immunotherapy was mostly well-tolerated,with manageable adverse events and relatively good safety profiles.Nonetheless,further research is required to understand the mechanisms of tumor resistance better and identify predictive biomarkers that can direct treatment optimization.展开更多
In this article,we revisit an article,which specifically focuses on the utilization of exosomes derived from human bone marrow mesenchymal stem cells(MSCs)for targeted delivery of gemcitabine in pancreatic cancer trea...In this article,we revisit an article,which specifically focuses on the utilization of exosomes derived from human bone marrow mesenchymal stem cells(MSCs)for targeted delivery of gemcitabine in pancreatic cancer treatment.The experimental results demonstrated that the exosome-based drug delivery system derived from MSCs significantly augmented apoptosis in pancreatic cancer cells.The biocompatibility,targeting specificity,and low immunogenicity of exosomes render them as optimal carriers for drug delivery,enabling precise administration of therapeutics to diseased tissues while mitigating adverse effects,thereby achieving targeted treatment of cancer cells and significantly enhancing anti-tumor efficacy.However,the clinical application of exosome drug delivery platforms in oncology still presents challenges,necessitating further optimization to ensure their stability and efficacy.This study focuses on elucidating the advantages of exosomes as a drug delivery platform,exploring the utilization of MSC-derived exosomes in oncology therapy,and discussing their potential and future directions in cancer treatment.展开更多
Liver cancer presents unique challenges due to its systemic impact and complex treatment modalities.Patients often experience a range of complications,including cardiovascular,renal,hematological,and metabolic abnorma...Liver cancer presents unique challenges due to its systemic impact and complex treatment modalities.Patients often experience a range of complications,including cardiovascular,renal,hematological,and metabolic abnormalities,which can significantly affect treatment outcomes and quality of life.This article emphasizes the integration of multidisciplinary strategies and artificial intelligence-driven diagnostics,which have the potential to improve patient outcomes by optimizing early detection and targeted management of these complications.A recent study on 60 liver cancer patients undergoing interventional therapy highlighted the importance of recognizing and managing these complications.This article offers an overview of systemic complications in liver cancer,focusing on pathophysiological mechanisms,risk factors,and strategies to improve care.By addressing gaps in the existing literature and proposing future research directions,it underscores the importance of comprehensive,patient-centered approaches to refine therapeutic strategies.展开更多
OBJECTIVE:To update the current best evidence on the effectiveness and safety of cupping therapy in pain management.METHODS:The protocol of this systematic review was registered at PROSPERO(CRD42021261308).An updated ...OBJECTIVE:To update the current best evidence on the effectiveness and safety of cupping therapy in pain management.METHODS:The protocol of this systematic review was registered at PROSPERO(CRD42021261308).An updated literature searching in 7 databases was conducted from January 2014 to January 2023.Two authors extracted data and assessed the risk of bias independently.Statistical analysis was performed using RevMan 5.4.1 software(Cochrane Collaboration,London,UK).Meta-analysis with a random effect model was conducted when there was no serious statistical heterogeneity among trials(I^(2) ≤ 75%).Grading of Recommendations Assessment,Development,and Evaluation was also conducted to assess the quality of evidence.RESULTS:Seventy-two trials with 5720 participants were included.All included trials were assessed as having high risk of bias.The majority of the included trials reported the benefit of cupping plus other therapy or cupping alone on improving cure rate(average risk ratio more than 1.15) and reducing visual analogue scale [average mean difference(MD) reduction 0.16 to 7.0 cm],improving quality of life,quality of sleep or other symptoms related to pain condition.And there was low/very low quality evidence that the incidence of adverse events in the cupping groups were lower than that in the control groups.Although the heterogeneity between studies and the methodological quality of the study itself lead to the low evidence strength of the current conclusions,the results of this study are a valuable supplement to the founding of previous review.CONCLUSION:Cupping therapy alone or combined with other therapy was considered benefit in relieving pain,improving the quality of life,and increasing the cure rate of patients with pain conditions,though supported by the low quality of evidence.According to the limited evidence,cupping therapy seems to have less harm than drugs when treating pain conditions.展开更多
The diversity,complexity,heterogeneity,and drug resistance of tumors make it challenging to meet the clinical needs of a single apoptosis-inducing chemotherapy.The combination of apoptosis and ferroptosis is expected ...The diversity,complexity,heterogeneity,and drug resistance of tumors make it challenging to meet the clinical needs of a single apoptosis-inducing chemotherapy.The combination of apoptosis and ferroptosis is expected to address the side effects of chemotherapy and enhance therapeutic efficacy.Here,an amphiphilic pH-responsive doxorubicin(DOX)and ferrocene(Fc)-containing copolyprodrug(P(ADH-DOXFc)-PEG)was designed with high DOX and Fc content of 66.5%and 0.58 mmol/g by a facile polycondensation for combining chemotherapy with ferroptosis in cancer treatment.A drug self-delivery system(DSDS)with an average hydrodynamic diameter(D_(h))of 135 nm can be easily obtained via self-assembly with the polyprodrug blocks as the hydrophobic core and PEG as the hydrophilic brush.The cumulative DOX release reached 72.7%in the simulated tumor intracellular acidic microenvironment within 56 h,whereas the premature drug leakage was only 6.2%in the simulated normal physiological medium.The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)assay results indicated an IC_(50)of 8.2μg/mL,exhibiting enhanced anti-tumor efficacy and a successful combination of apoptosis and ferroptosis,with a combination index(CI)of 0.88.展开更多
Cancer therapy continues to face major challenges,including drug resistance,toxicity,and tumor heterogeneity,which highlight the need for multitarget strategies.This review examines the molecular compatibility theory ...Cancer therapy continues to face major challenges,including drug resistance,toxicity,and tumor heterogeneity,which highlight the need for multitarget strategies.This review examines the molecular compatibility theory in integrative oncology,which combines traditional Chinese medicine(TCM)with systems biology to address these limitations.TCM formulas,such as Banxia Xiexin decoction and Qiqin Huchang formula,contain bioactive compounds(e.g.,quercetin and berberine)that modulate interconnected pathways(phosphoinositide 3-kinase/protein kinase B and mitogen-activated protein kinase)and the tumor microenvironment,thereby promoting apoptosis,inhibiting angiogenesis,and regulating immune responses.The theory modernizes TCM’s“Jun-Chen-Zuo-Shi”principle by optimizing herb combinations through network pharmacology and omics technologies.For instance,Astragalus membranaceus(Fisch.)Bge.var.mongholicus(Bge.)Hsiao(Huang Qi)-Curcuma phaeocaulis Val.(E Zhu)pairs co-target hypoxia-inducible factor 1-alpha to suppress metastasis,while artificial intelligence-driven models predict synergistic interactions such as quercetin-cyclin-dependent kinase 1 inhibition.Clinical studies have shown improved outcomes;for instance,modified Banxia Xiexin decoction reduces chemotherapy-induced toxicity in gastric cancer,and Xihuang pill enhances immunotherapy via signal transducer and activator of transcription 3-programmed death-ligand 1 modulation.Despite these advances,challenges remain in standardization and mechanistic validation.Future research should prioritize single-cell sequencing,organoid models,and international collaboration to refine personalized therapies and translate TCM into evidence-based oncology.By integrating empirical knowledge with modern science,molecular compatibility theory provides a robust framework for multitarget drug development and the advancement of integrative cancer therapies.展开更多
文摘Background: Erythrodermic psoriasis (EP) is a rare, severe variant of psoriasis characterized by widespread erythema, scaling, and systemic complications. Despite advances in systemic treatments, the management of EP remains challenging, particularly in patients with comorbidities or contraindications to standard therapies. Objectives: To evaluate the effectiveness of ozonated water as an adjunctive treatment for EP, delivered using a patented robotic therapy system designed for hygiene and infection prevention in non-self-sufficient patients. Methods: We report the case of a 90-year-old male patient with acute EP who received daily skin treatments with ozonated water in conjunction with supportive care, including rehydration and antibiotics. The intervention was facilitated by the robotic system “COPERNICO Surveillance & Prevention,” which ensured standardized hygiene practices and clinical documentation. Results: Within one week of treatment, the patient showed complete desquamation of necrotic skin, resolution of erythema, and significant metabolic recovery. Fever subsided, renal function improved, and the patient was discharged in stable condition. Follow-up confirmed sustained clinical improvement, and no adverse events were reported. Conclusions: Ozonated water demonstrated efficacy in alleviating the dermatological and systemic manifestations of EP in a high-risk elderly patient. This case highlights the potential of ozone therapy as a safe, cost-effective adjunctive treatment for EP and underscores the utility of robotic systems in managing complex dermatological conditions. Further research is warranted to validate these findings in larger cohorts.
文摘Objective： To construct Bifidobacterium Infantis/CD targeting gene therapy system. Methods： CD gene was amplified from E. Coli K12λ using PCR method, pGEX-1LamdaT plasmid and CD gene were digested with dual restriction endonucleas of EcoR Ⅰ and BamH Ⅰ and two segments of 4.9 kb and 1.3 kb were obtained. T4 DNA ligase was added to these two segments to make a recombinant CD/pGEX-1LamdaT plasmid. Then the recombinant plasmid was transfected into Bifidobacterium Infantis by electroporation. The recombinant plasmid was extracted from the positively transfected Bifidobacterium Infantis and digested with dual restriction endonucleases. Then the size of digested fragments was detected and sequencing of the gene segment inserted in extracted recombinant plasmid was performed according to the method of Sanger dideoxynucleotide triphosphate chain termination. Results： 6.2 kb recombinant plasmid was obtained from the positively transfected bacterial colony of Bifidobacterium Infantis. After being digested with dual restriction endonucleases, two segments of approximate 4.9 kb and 1.3 kb were gained from the extracted recombinant plasmid, which were equal to the size of pGEX-1LamdaT plasmid and CD gene, respectively. The full length and sequence of nucleotide acid of the inserted gene in extracted recombinant plasmid was completely identical to the CD gene. Conclusion： The foreign gene, CD gene was correctly inserted into pGEX-1LambdaT plasmid and transferred into Bifidobacterium Infantis. Bifidobacterium Infantis/CD targeting gene therapy system was successfully constructed.
基金the National Key Research and Development Program of China(No.2016YFC0105305)the National Natural Science Foundation of China(11975107)the Program for HUST Academic Frontier Youth Team.
文摘A proton therapy(PT)facility with multiple treatment rooms based on the superconducting cyclotron scheme is under development at Huazhong University of Science and Technology(HUST).This paper attempts to describe the design considerations and implementation of the PT beamline from a systematic viewpoint.Design considerations covering beam optics and the influence of high-order aberrations,beam energy/intensity modulation,and beam orbit correction are described.In addition to the technical implementation of the main beamline components and subsystems,including the energy degrader,fast kicker,beamline magnets,beam diagnostic system,and beamline control system are introduced.
文摘Background: At-home phototherapy devices for the treatment of acne have emerged as an appealing treatment option and as an effective adjunct treatment to existing modalities. The principal goal of the study was to determine the changes in the number of inflammatory lesions in acne patients. Methods: Patients received instruction for daily at-home use of Silk’n Blue device for 12 weeks. Follow-up visits were conducted at 1 and 3 months to collect data. Results: Fifteen subjects with mild to severe cases experienced improvement over the course of the trial. The decrease in mean inflammatory acne counts (from 41.26 to 24.46) and mean percent reduction (41.8%) were statistically significant (p < 0.001). Some participants experienced percent reductions as great as 67%. No adverse events were recorded. Conclusions: The Silk’n Blue device is a safe and effective modality for at-home treatment of mild, moderate, and severe inflammatory acne vulgaris with proper use.
基金Hongguang Wu,Both authors contributed equally to this work and share first authorshipLing Dong,Both authors contributed equally to this work and share first authorship。
文摘The human retina,a complex and highly specialized structure,includes multiple cell types that work synergistically to generate and transmit visual signals.However,genetic predisposition or age-related degeneration can lead to retinal damage that severely impairs vision or causes blindness.Treatment options for retinal diseases are limited,and there is an urgent need for innovative therapeutic strategies.Cell and gene therapies are promising because of the efficacy of delivery systems that transport therapeutic genes to targeted retinal cells.Gene delivery systems hold great promise for treating retinal diseases by enabling the targeted delivery of therapeutic genes to affected cells or by converting endogenous cells into functional ones to facilitate nerve regeneration,potentially restoring vision.This review focuses on two principal categories of gene delivery vectors used in the treatment of retinal diseases:viral and non-viral systems.Viral vectors,including lentiviruses and adeno-associated viruses,exploit the innate ability of viruses to infiltrate cells,which is followed by the introduction of therapeutic genetic material into target cells for gene correction.Lentiviruses can accommodate exogenous genes up to 8 kb in length,but their mechanism of integration into the host genome presents insertion mutation risks.Conversely,adeno-associated viruses are safer,as they exist as episomes in the nucleus,yet their limited packaging capacity constrains their application to a narrower spectrum of diseases,which necessitates the exploration of alternative delivery methods.In parallel,progress has also occurred in the development of novel non-viral delivery systems,particularly those based on liposomal technology.Manipulation of the ratios of hydrophilic and hydrophobic molecules within liposomes and the development of new lipid formulations have led to the creation of advanced non-viral vectors.These innovative systems include solid lipid nanoparticles,polymer nanoparticles,dendrimers,polymeric micelles,and polymeric nanoparticles.Compared with their viral counterparts,non-viral delivery systems offer markedly enhanced loading capacities that enable the direct delivery of nucleic acids,mRNA,or protein molecules into cells.This bypasses the need for DNA transcription and processing,which significantly enhances therapeutic efficiency.Nevertheless,the immunogenic potential and accumulation toxicity associated with non-viral particulate systems necessitates continued optimization to reduce adverse effects in vivo.This review explores the various delivery systems for retinal therapies and retinal nerve regeneration,and details the characteristics,advantages,limitations,and clinical applications of each vector type.By systematically outlining these factors,our goal is to guide the selection of the optimal delivery tool for a specific retinal disease,which will enhance treatment efficacy and improve patient outcomes while paving the way for more effective and targeted therapeutic interventions.
文摘Background:Isotonic crystalloids are recommended as the first choice for fluid therapy in acute pan-creatitis(AP),with normal saline(NS)and lactate Ringer’s(LR)used most often.Evidence based recom-mendations on the type of fluid are conflicting and generally come from small single-center randomized controlled trials(RCTs).We therefore conducted a systematic review and meta-analysis to compare the effect of balanced solutions(BS)versus NS on patient-centered clinical outcomes in AP.Methods:From four databases searched up to October 2024,we included only RCTs of adult patients with AP that compared the use of BS(including LR,acetate Ringer’s,etc.)with NS.The primary out-come was the disease advances from AP to moderately severe and severe AP(MSAP/SAP).Trial sequential analyses(TSA)were conducted to control for type-I and type-II errors and Grading of Recommendations Assessment,Development,and Evaluation(GRADE)was used to assess the quality of evidence.Results:Six RCTs were identified and included,involving 260 patients treated with BS and 298 patients with NS.Patients who received the BS had less MSAP/SAP[odds ratio(OR)=0.50,95%confidence in-terval(CI):0.29 to 0.85,P=0.01,I^(2)=0%;5 studies,299 patients],reduced the need of ICU admission(OR=0.60,95%CI:0.39 to 0.93,P=0.02,I^(2)=0%;5 studies,507 patients)and shorter length of hospital stay[mean difference(MD)=-0.88,95%CI:-1.48 to-0.28,P=0.004,I^(2)=0%;6 studies,558 patients;confirmed by TSA with high certainty]compared with those who received NS.The evidence for most of the clinical outcomes was rated as moderate to low due to the risk of bias,imprecision and inconsistency.Conclusions:BS,compared with NS,was associated with improved clinical outcomes in patients with AP.However,given the moderate to low quality of evidence for most of the outcomes assessed,further trials are warranted.
文摘Gastric cancer(GC)and gastroesophageal junction cancer(GEJC)represent a significant burden globally,with complications such as overt bleeding(OB)further exacerbating patient outcomes.A recent study by Yao et al evaluated the effectiveness and safety of systematic treatment in GC/GEJC patients presenting with OB.Using propensity score matching,the study balanced the comparison groups to investigate overall survival and treatment-related adverse events.The study's findings emphasize that systematic therapy can be safe and effective and contribute to the ongoing debate about the management of advanced GC/GEJC with OB,highlighting the complexities of treatment decisions in these high-risk patients.
基金work was supported by grants from the National Natural Science Foundation of China(No.82073346)Doctoral Through Train Scien-tific Research Project of Chongqing(No.CSTB2022BSXM-JCX0004)+1 种基金Famous Teachers section of the Chongqing Talents Program(No.4246ZP112)Special Projects of Army Medical University for Improving Scientific and Technological Innovation Capabilities(No.2019XLC1009).
文摘Hepatocellular carcinoma(HCC)is a lethalmalignancy.Formany years,chemotherapeutic regimens have served as the foundation of sys-temic therapies for advanced HCCdespite their limited efficacy and significant adverse effects.In recent decades,novel systemic therapies such as immunotherapy and targeted therapy have profoundly transformed HCC management.Although some patients with advanced HCC exhibit dramatically improved outcomes,the efficacy of immunotherapy and targeted therapy,either asmonotherapy or in combina-tion,remains limited.Numerous trials have indicated that locoregional therapies,including transarterial chemoembolization(TACE),hepatic arterial infusion chemotherapy(HAIC),and transarterial radioembolization(TARE),may synergize with systemic therapies to enhance ad-vanced HCC treatment.However,further studies are required to optimize these combination regimens.In contrast,curative treatments,such as surgical resection,liver transplantation,or local ablation,are typically recommended for patients with early-stage HCC.Although these treatments have achieved an impressivemedian overall survival(OS)exceeding 60months,more than half of the patients experience recurrence within 5 years.Consequently,the development of effective perioperative neoadjuvant or adjuvant therapies is urgently needed to reduce the incidence of recurrence and metastasis.It provides a comprehensive overview of recent advances in systemic therapies for advanced HCC,as well as adjuvant or neoadjuvant immunotherapies for early HCC.Additionally,emerging clinical trials and trial designs for future investigations into systemic therapies for HCC management are critically analyzed.
文摘BACKGROUND Acceptance and commitment therapy(ACT)is a third-generation therapy that appears to be a promising psychological intervention for psychotic disorders.While several systematic reviews and meta-analyses that address the efficacy of ACT for psychosis have been conducted,no systematic review has specifically focused on the application of ACT to the early stages of psychosis.AIM To review the state of the art regarding the feasibility and efficacy of treating early psychosis(EP)with ACT-based interventions.METHODS First,we describe the foundations of the ACT model to provide the background required to contextualize the main objective of this review.Second,we searched the PubMed and PsycINFO databases for studies published up to January 2025 and identified eight studies that met our selection criteria.The systematic review was conducted in accordance with the PRISMA guidelines and the critical appraisal checklist provided by the Joanna Briggs Institute for randomized controlled trials(RCTs).RESULTS All studies were published after 2019.Among the reviewed studies,five were RCTs with a total combined sample of 399 nonoverlapping participants.The methodological quality was moderate for RCTs.The results showed that ACTbased treatments are feasible and improve psychotic symptoms,medication adherence,and global functioning in patients with EP.Furthermore,preliminary evidence exists for the benefits of group-based and online-delivered programs and those that combine face-to-face therapy with novel real-time digital interventions,such as“ecological momentary intervention”,to apply therapeutic con cepts to real life.CONCLUSION ACT-based treatments in the early stages of psychosis are feasible and improve symptoms,treatment adherence,and self-care skills.Although promising,these results are inconclusive.Further research is required.
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Dear Editor,Rosacea is characterized by persistent or transient erythema,papules,pustules,telangiectasia,and/or phymatous lesions[1].Although multiple treatments are available for rosacea,the advent of biological agents and small-molecule agents has significantly advanced our ability to target the disease more effectively[2].In the current review,we summarize the outcomes of targeted therapies in rosacea,mainly focusing on interleukin(IL)-17 inhibitors and Janus kinase(JAK)inhibitors.
文摘BACKGROUND Cardiac resynchronization therapy(CRT)has been a major therapeutic advancement for patients with heart failure and electrical dyssynchrony.While CRT improves symptoms,reduces hospitalizations,and enhances survival,the role of implantable cardioverter-defibrillators(ICDs)alongside CRT in patients with non-ischemic cardiomyopathy(NICM)remains controversial.To evaluate and compare the outcomes of CRT with ICD(CRT-D)versus CRT with pacemaker-only(CRT-P)in individuals diagnosed with NICM,with a specific focus on the elderly.METHODS A comprehensive search of PubMed,Embase,and the Cochrane Central Register of Controlled Trials was conducted in January 2024.Studies comparing CRT-D and CRT-P in patients with NICM were included,with subgroup analyses focusing on patients aged 75 years and older.RESULTS Twelve studies,including two randomized clinical trials,with a total of 62,145 patients and 16,754 pooled death events(9,171 in CRT-D and 7,583 in CRT-P),were analyzed.CRT-D was associated with a significantly lower risk of all-cause mortality compared to CRT-P(pooled OR=0.72;95%CI:0.61-0.85;P<0.01),with significant heterogeneity(I2=83%).RCT subgroup analysis,was not statistically significant(pooled OR=0.82;95%CI:0.64-1.06;P=0.41;I2=0%).In patients older than 75 years,no significant difference in mortality risk was observed(pooled OR 0.96;95%CI:0.81-1.15;I2=39%).CONCLUSION Our meta-analysis suggests that the addition of ICD therapy to CRT in patients with NICM significantly reduces all-cause mortality.However,this benefit does not extend to cardiovascular mortality,likely due to the primary role of ICDs in preventing sudden cardiac death rather than other causes such as progressive heart failure.The survival advantage of CRT-D is most pronounced in younger patients,with those over 75 years of age deriving less benefit.This highlights the importance of careful patient selection,considering age and comorbidities,when deciding on ICD implantation in NICM patients.
文摘BACKGROUND Eosinophilic esophagitis(EoE)is a chronic inflammatory disorder presenting as symptoms of dysphagia,esophageal food impaction,chest pain,and heartburn.After an initial trial of proton pump inhibitor(PPI)therapy,swallowed topical corticosteroids(STC)are effective as induction therapy for EoE.However,out-come data for STC as a maintenance strategy is limited.RESULTS Three randomized control trials and one observational study were included,involving 303 patients(189 in the STC group,114 in the placebo-controlled group).Analysis showed that histologic recurrence was significantly lower with STC(OR:0.04,95%CI:0.01-0.28,P<0.00001,I^(2)=78%).Overall symptom recurrence was similar between groups(OR:0.23,95%CI:0.02-3.54,P=0.29,I^(2)=92%).On sensitivity analysis,symptom recurrence was significantly lower in the STC group(OR:0.05,95%CI:0.02-0.17,P=0.00001,I^(2)=39%).Odds of repeat dilation were significantly lower in the STC group(OR:0.14,95%CI:0.02-0.91,P=0.04,I^(2)=0%).Candida infection rates were similar between groups(OR:6.13,95%CI:0.85-44.26,P=0.07,I^(2)=24%).Proportion of concomitant PPI use was similar between groups(OR:1.64,95%CI:0.83-3.21,P=0.15,I^(2)=0%).CONCLUSION For patients who successfully achieved remission of EoE with STC induction therapy,maintaining treatment is effective in sustaining histologic remission,while newer regimens may be effective in preventing symptom recurrence compared to placebo.We found no significant difference for oropharyngeal/esophageal candidiasis with STC maintenance therapy.Future studies with longer follow-up periods are needed.
基金supported in part by grants from the following sources:the National Natural Science Foundation of China(No.82090051,32371477,92168207)the National Key Research and Development Program of China(No.2022YFA1103400,2022YFC2406704)+1 种基金the Chief Scientist Research Project of Hubei Shizhen Laboratory(HSL2024SX0001)the Beijing Tsinghua Changgung Hospital Foundation(No.12025C01011).
文摘Hepatocellular carcinoma(HCC)is a leading cause of cancer-related mortality,and resistance to systemic therapies remains a significant clinical challenge.This study investigated the mechanisms by which metabolic reprogramming contributes to systemic treatment resistance in HCC.We established HCC cell lines with multidrug resistance characteristics and observed enhanced metabolic activity in these cells.Integrated multiomics analyses revealed hyperactive glucose‒lipid and glutathione metabolic pathways that play critical roles in supporting tumor cell proliferation and survival.We constructed a metabolic reprogramming atlas for HCC-resistant cells and identified aldo-keto reductase(Aldo-keto reductase family 1 Member B1,AKR1B1)as a key regulator of this reprogramming,which sustains drug resistance by regulating energy metabolism and enhancing stress tolerance.Importantly,AKR1B1 expression levels are closely associated with drug resistance and poor prognosis in HCC patients.The secretory nature of AKR1B1 not only underscores its predictive value but also facilitates the intercellular transmission of drug resistance.In terms of overcoming resistance,the AKR1B1 inhibitor epalrestat significantly mitigated drug resistance when it was used in combination with standard therapies.These findings underscore the importance of metabolic reprogramming in the development of HCC resistance.AKR1B1,a key enzyme that regulates metabolic reprogramming,has been identified as a potential biomarker and therapeutic target,providing new insights into overcoming resistance in HCC treatment.
文摘Background:Gastric Cancer(GC)is the 5th most prevalent and 4th most deadly neoplasm globally.Immunotherapy has emerged as a promising treatment approach in GC,potentially improving positive clinical outcomes while addressing the limitations of conventional therapies.GC immunotherapy modalities consist of adoptive cell therapy(ACT),cancer vaccines,and immune checkpoint inhibitors(ICI).Objectives:This systematic review aims to provide an overview of the advances in immune-based therapeutic approaches in GC,highlighting the potential of this therapy as a strategy for GC treatment.Methods:Key studies investigating several immunotherapeutic agents and combination therapies were searched in PUBMED and included in this study.Specific cancer outcomes related to disease progression or survival were analyzed.Results:After screening 236 studies,the results revealed that immunotherapy,particularly the ICI pembrolizumab,demonstrated promising efficacy in the treatment of GC,as several studies reported improved OS,PFS,and objective response rate with the use of pembrolizumab alone or in combination with other treatment modalities.Conclusion:Safety analysis showed that immunotherapy was mostly well-tolerated,with manageable adverse events and relatively good safety profiles.Nonetheless,further research is required to understand the mechanisms of tumor resistance better and identify predictive biomarkers that can direct treatment optimization.
基金Natural Science Foundation of Zhejiang Province,No.LQ23H050005Zhejiang Medical and Health Science and Technology Project,No.2023KY615+2 种基金Scientific Research Project of Zhejiang Provincial Education Department,No.Y202250731 and No.Y202353130the China Students’Innovation and Entrepreneurship Training Program,No.202310338044China Postdoctoral Science Foundation,No.2022M721720.
文摘In this article,we revisit an article,which specifically focuses on the utilization of exosomes derived from human bone marrow mesenchymal stem cells(MSCs)for targeted delivery of gemcitabine in pancreatic cancer treatment.The experimental results demonstrated that the exosome-based drug delivery system derived from MSCs significantly augmented apoptosis in pancreatic cancer cells.The biocompatibility,targeting specificity,and low immunogenicity of exosomes render them as optimal carriers for drug delivery,enabling precise administration of therapeutics to diseased tissues while mitigating adverse effects,thereby achieving targeted treatment of cancer cells and significantly enhancing anti-tumor efficacy.However,the clinical application of exosome drug delivery platforms in oncology still presents challenges,necessitating further optimization to ensure their stability and efficacy.This study focuses on elucidating the advantages of exosomes as a drug delivery platform,exploring the utilization of MSC-derived exosomes in oncology therapy,and discussing their potential and future directions in cancer treatment.
文摘Liver cancer presents unique challenges due to its systemic impact and complex treatment modalities.Patients often experience a range of complications,including cardiovascular,renal,hematological,and metabolic abnormalities,which can significantly affect treatment outcomes and quality of life.This article emphasizes the integration of multidisciplinary strategies and artificial intelligence-driven diagnostics,which have the potential to improve patient outcomes by optimizing early detection and targeted management of these complications.A recent study on 60 liver cancer patients undergoing interventional therapy highlighted the importance of recognizing and managing these complications.This article offers an overview of systemic complications in liver cancer,focusing on pathophysiological mechanisms,risk factors,and strategies to improve care.By addressing gaps in the existing literature and proposing future research directions,it underscores the importance of comprehensive,patient-centered approaches to refine therapeutic strategies.
基金National Natural Science Foundation of China Project:Research on the Correlation between Traditional Chinese Medicine Constitution,Cupping Marks Color,and Clinical Efficacy Based on Regression Models (No.81804000)。
文摘OBJECTIVE:To update the current best evidence on the effectiveness and safety of cupping therapy in pain management.METHODS:The protocol of this systematic review was registered at PROSPERO(CRD42021261308).An updated literature searching in 7 databases was conducted from January 2014 to January 2023.Two authors extracted data and assessed the risk of bias independently.Statistical analysis was performed using RevMan 5.4.1 software(Cochrane Collaboration,London,UK).Meta-analysis with a random effect model was conducted when there was no serious statistical heterogeneity among trials(I^(2) ≤ 75%).Grading of Recommendations Assessment,Development,and Evaluation was also conducted to assess the quality of evidence.RESULTS:Seventy-two trials with 5720 participants were included.All included trials were assessed as having high risk of bias.The majority of the included trials reported the benefit of cupping plus other therapy or cupping alone on improving cure rate(average risk ratio more than 1.15) and reducing visual analogue scale [average mean difference(MD) reduction 0.16 to 7.0 cm],improving quality of life,quality of sleep or other symptoms related to pain condition.And there was low/very low quality evidence that the incidence of adverse events in the cupping groups were lower than that in the control groups.Although the heterogeneity between studies and the methodological quality of the study itself lead to the low evidence strength of the current conclusions,the results of this study are a valuable supplement to the founding of previous review.CONCLUSION:Cupping therapy alone or combined with other therapy was considered benefit in relieving pain,improving the quality of life,and increasing the cure rate of patients with pain conditions,though supported by the low quality of evidence.According to the limited evidence,cupping therapy seems to have less harm than drugs when treating pain conditions.
文摘The diversity,complexity,heterogeneity,and drug resistance of tumors make it challenging to meet the clinical needs of a single apoptosis-inducing chemotherapy.The combination of apoptosis and ferroptosis is expected to address the side effects of chemotherapy and enhance therapeutic efficacy.Here,an amphiphilic pH-responsive doxorubicin(DOX)and ferrocene(Fc)-containing copolyprodrug(P(ADH-DOXFc)-PEG)was designed with high DOX and Fc content of 66.5%and 0.58 mmol/g by a facile polycondensation for combining chemotherapy with ferroptosis in cancer treatment.A drug self-delivery system(DSDS)with an average hydrodynamic diameter(D_(h))of 135 nm can be easily obtained via self-assembly with the polyprodrug blocks as the hydrophobic core and PEG as the hydrophilic brush.The cumulative DOX release reached 72.7%in the simulated tumor intracellular acidic microenvironment within 56 h,whereas the premature drug leakage was only 6.2%in the simulated normal physiological medium.The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)assay results indicated an IC_(50)of 8.2μg/mL,exhibiting enhanced anti-tumor efficacy and a successful combination of apoptosis and ferroptosis,with a combination index(CI)of 0.88.
基金supported from the Key R&D Program of Zhejiang(2025C02198)Zhejiang Provincial Administration of Traditional Chinese Medicine Co-construction Science and Technology Plan Project(GZY-ZJ-KJ-24083).
文摘Cancer therapy continues to face major challenges,including drug resistance,toxicity,and tumor heterogeneity,which highlight the need for multitarget strategies.This review examines the molecular compatibility theory in integrative oncology,which combines traditional Chinese medicine(TCM)with systems biology to address these limitations.TCM formulas,such as Banxia Xiexin decoction and Qiqin Huchang formula,contain bioactive compounds(e.g.,quercetin and berberine)that modulate interconnected pathways(phosphoinositide 3-kinase/protein kinase B and mitogen-activated protein kinase)and the tumor microenvironment,thereby promoting apoptosis,inhibiting angiogenesis,and regulating immune responses.The theory modernizes TCM’s“Jun-Chen-Zuo-Shi”principle by optimizing herb combinations through network pharmacology and omics technologies.For instance,Astragalus membranaceus(Fisch.)Bge.var.mongholicus(Bge.)Hsiao(Huang Qi)-Curcuma phaeocaulis Val.(E Zhu)pairs co-target hypoxia-inducible factor 1-alpha to suppress metastasis,while artificial intelligence-driven models predict synergistic interactions such as quercetin-cyclin-dependent kinase 1 inhibition.Clinical studies have shown improved outcomes;for instance,modified Banxia Xiexin decoction reduces chemotherapy-induced toxicity in gastric cancer,and Xihuang pill enhances immunotherapy via signal transducer and activator of transcription 3-programmed death-ligand 1 modulation.Despite these advances,challenges remain in standardization and mechanistic validation.Future research should prioritize single-cell sequencing,organoid models,and international collaboration to refine personalized therapies and translate TCM into evidence-based oncology.By integrating empirical knowledge with modern science,molecular compatibility theory provides a robust framework for multitarget drug development and the advancement of integrative cancer therapies.
