[Objectives] To observe the clinical therapeutic efficacy of local hot-wet compress therapy of digestion ointment prescription on the patients with moderate and severe mastalgia. [Methods] Firstly,60 patients with mas...[Objectives] To observe the clinical therapeutic efficacy of local hot-wet compress therapy of digestion ointment prescription on the patients with moderate and severe mastalgia. [Methods] Firstly,60 patients with mastalgia were selected,and divided into the experimental group and control group( 30 cases for each group). The control group was treated with acupuncture at distal point,and the experimental group was treated with TCM local hot-wet compress therapy combined with acupuncture at distal point. Then,the clinical therapeutic efficacy of two groups was compared. [Results]The experimental group was superior to the control group in relieving the breast pain,improving emotional integral,reducing breast lumps,improving lump texture,and improving TCM syndrome integral( P < 0. 05). [Conclusions]The digestion ointment prescription local hot-wet compress therapy has a significant therapeutic effect on treatment of mastalgia and can significantly improve the breast pain symptom of patients.展开更多
Objective:To systematically evaluate TCM of Fuzheng and Kangai combined with chemotherapy in the treatment of Advanced NSCLC,including the efficacy and effect on the quality of life of patients.Methods:Two researchers...Objective:To systematically evaluate TCM of Fuzheng and Kangai combined with chemotherapy in the treatment of Advanced NSCLC,including the efficacy and effect on the quality of life of patients.Methods:Two researchers independently searched the literature of clinical trails from Jan.2010 until Jun.2020 in the Cochrane Library,Pubmed,Embase,CBM,CNKI,WanFang Data and VIP database.Also,they had been evaluated and extracted strictly by REVMAN 5.3.Results:A total of 1303 patients were included in 15 articles.The meta analysis shows that the TCM of Fuzheng and Kangai combined with chemotherapy can improve the objective response rate[OR=2.14,95%CI(1.67,2.74),P<0.00001],disease control rate[OR=2.54,95%CI(1.88,3.42),P<0.00001]and KPS score[OR=3.28,95%CI(1.92,5.60),P<0.0001],decrease the incidence rate of liver injury[OR=0.34,95%CI(0.21,0.54),P=0.003],hemoglobin reduction[OR=0.53,95%CI(0.28,1.01),P=0.05],leukopenia[OR=0.22,95%CI(0.13,0.39),P<0.00001],thrombocytopenia[OR=0.32,95%CI(0.21,0.50),P<0.00001],toxic effects on the digestive systems[OR=0.30,95%CI(0.19,0.46),P<0.00001].Conclusions:the experimental group was better than control one in short-term efficacy and KPS score.Furthermore,the experimental group can reduce the incidence rate of myelosuppression,toxicity of digestive system and liver.展开更多
Objective:To explore the effective prevention and treatment of portal hypertension(PH).Methods:A total of 220 patients who came to our hospital from March 2015 to October 2018 were treated.They were randomly divided i...Objective:To explore the effective prevention and treatment of portal hypertension(PH).Methods:A total of 220 patients who came to our hospital from March 2015 to October 2018 were treated.They were randomly divided into the treatment group and the control group,each with 110 cases.Before treatment,there was no significant differences in age,sex,clinical symptoms,signs,laboratory tests and color Doppler ultrasound related examinations between the 2 groups(P>0.05).Among them,the treatment group on the basis of traditional Chinese and Western medicine treatment in our hospital,the Qi-acupuncture therapy of TCM was added.The extra meridian acupoints along with acupoints were selected.The control group received conventional treatment with traditional Chinese and Western medicine in our hospital.Results:There were significant differences in clinical symptoms,signs and chemistry between groups after treatment(P<0.01).There were significant differences in test,color ultrasound related examination and so on(P<0.01).Those in the treatment group was significantly better than the control group(P<0.01).Conclusion:On the basis of the Qi-acupuncture therapy of TCM,selecting extra meridian acupoint and acupoints can effectively treat PH.展开更多
Objective:To dig deeper into the traditional Chinese medicine treatment rules of chemotherapy-induced diarrhea with traditional Chinese medicine(TCM)inheritance computing platform system.Methods:Taking“traditional Ch...Objective:To dig deeper into the traditional Chinese medicine treatment rules of chemotherapy-induced diarrhea with traditional Chinese medicine(TCM)inheritance computing platform system.Methods:Taking“traditional Chinese medicine”,“chemotherapy”and“diarrhea”as the theme words,comprehensive search of the database of CNKI,Wanfang and VIP from its inception to November 2020 was conduct-ed.The formulas of external treatment of traditional Chinese medicine for chemotherapy-induced diarrhea were included and the association rule,clustering and factor analysis were carried out.Results:A total of 145 papers,57 prescriptions meeting the inclusion criteria were collected,among which high-frequency drugs including Baizhu(Atractylodis macrocephalae rhizoma),Fuling(Poria),Dangshen(Codonopsisradix),Huanglian(Coptidis rhizoma),Zhigancao(Glycyrrhizae radix et rhizoma praeparata cum melle)were the most commonly used.The confidence level was set as 0.7 and the support level was set as 10,12 core compatibility groups were obtained,and 6 categories were cluster analyzed.Conclusion:The principle of external treatment of chemotherapy-induced diarrhea is mainly“restore deficiency and benefiting qi”,“benefiting water infiltration and dampness”,“clearing heat”and“inducing astringency”.Prescription combination and new prescription combination based on traditional Chinese medicine(TCM)inheritance computing platform system can be used as reference for clinicians and applied in primary hospitals.展开更多
Non-pharmacotogicat treatment is an important means to control hypertension, with many advantages such as tow cost, tess medication, stable btood pressure, tess compHcations, and improved prognosis. This article revie...Non-pharmacotogicat treatment is an important means to control hypertension, with many advantages such as tow cost, tess medication, stable btood pressure, tess compHcations, and improved prognosis. This article reviews the research progress of non-drug treatment of hypertension in Chinese medicine in the past five years, and evaluates traditional Chinese medicine such as TCM Qigong, Wuhuo opera, Ba Duanjin and Taijiquan, and Chinese medicine acupuncture, moxibustion, massage, apptication, acupoint embedding and other traditional Chinese medicine. The effect of external treatment in hypertension control provides guidance for non-drug therapy to control hypertension.展开更多
Objective: To study and evaluate the effect and influence of TCM physiotherapy nursing scheme on improving cervical pain in patients with cervical spondylosis.Methods: Taking March 2019 as the starting time for collec...Objective: To study and evaluate the effect and influence of TCM physiotherapy nursing scheme on improving cervical pain in patients with cervical spondylosis.Methods: Taking March 2019 as the starting time for collecting cases and March 2021 as the deadline for collecting cases, a total of 112 patients with cervical spondylosis were included. Clinical intervention was carried out through traditional Chinese medicine physiotherapy nursing, and the improvement effect of patients' condition before and after treatment and nursing was analyzed.Results: the scores of cervical pain and cervical dysfunction before treatment and nursing were higher than those after treatment and Nursing (P < 0.05);The score of quality of life before treatment and nursing was lower than that after treatment and Nursing (P < 0.05);According to the clinical nursing satisfaction and effective rate, the satisfaction was 100.00%, and the total effective rate was 98.21%.Conclusion: in the clinical treatment and nursing of patients with cervical spondylosis, the implementation of TCM physiotherapy nursing measures can significantly improve the patient's cervical condition, significantly alleviate the symptoms of cervical pain, improve the cervical function, improve the quality of life, and significantly promote the patient's evaluation of the nursing model.展开更多
47 senile non-parvicellular lung cancer patients at stage Ⅲ or Ⅳ were randomly divided into a treatment group (26 cases) treated by radiotherapy plus traditional Chinese medicine (TCM) and a control group (21 cases)...47 senile non-parvicellular lung cancer patients at stage Ⅲ or Ⅳ were randomly divided into a treatment group (26 cases) treated by radiotherapy plus traditional Chinese medicine (TCM) and a control group (21 cases) treated only by radiotherapy for observation of the therapeutic effects.The patients in the treatment group orally took Chinese medicine during and after the radiotherapy.There was no obvious difference in short-term therapeutic effects between the two groups,but the long-term curative effects in the treatment group was obviously superior to that in the control group (P<0.05 or P<0.01).Conclusion:radiotherapy plus TCM can prolong the survival period for senile non-parvicellular lung cancer patients.展开更多
Objective:To systematically evaluate the therapeutic effect of TCM on cardiotoxicity induced by anthracycline chemotherapy to provide clinical guidance.Methods:China hownet database(CNKI),Chinese biomedical literature...Objective:To systematically evaluate the therapeutic effect of TCM on cardiotoxicity induced by anthracycline chemotherapy to provide clinical guidance.Methods:China hownet database(CNKI),Chinese biomedical literature retrieval(SinoMed),ten thousand Data knowledge service system(WanFang Data),VIP full-text database(VIP),PubMed,MedLine and the cochrane library were searched from inception to 1st,December,2020.Relevant combined TCM and Western medicine on cardiotoxicity randomized controlled trials(RCTs)were collected.The risk of bias in included RCTs were evaluated according to the Cochrane Handbook.The required indicators were extracted and included in RevMan5.4 analysis.Results:A total of 2844 patients were included in 37 RCTs.The results of meta-analysis showed that compared with the control group,TCM treatment group could alleviate the effect of anthracycline on ventricular ejection function,reduce the effect of anthracycline chemotherapy drugs in lowering left ventricular ejection fraction(WMD=6.44,95%CI 0.38 to 12.50,P=0.04),reduce the effect of anthracycline chemotherapy in increasing left ventricular end diastolic diameter(WMD=-0.59,95%CI-0.74 to-0.44,P<0.00001),reduce the effect of anthracycline chemotherapy drugs in increasing left ventricular end systolic diameter(WMD=-0.47,95%CI-0.60 to-0.34,P<0.00001),and reduce the effect of anthracyclines on troponin I(WMD=-0.19,95%CI-0.23 to-0.16,P<0.00001),troponin T(WMD=-0.02,95%CI-0.03 to-0.01,P<0.00001)and brain natriuretic peptide(WMD=-32.21,95%CI-58.21 to-6.22,P=0.02).Conclusion:The existing evidence can prove that TCM has a protective effect on cardiotoxicity caused by anthracycline chemotherapy,maintaining left ventricular ejection fraction and ventricular diameter,controlling the level of myocardial injury markers,and alleviating cardiac injury.展开更多
An upconversion nanoparticle(NaErF_(4)∶Yb/Tm@NaLuF_(4)∶Yb@NaLuF_(4)∶Nd/Yb@NaLuF_(4),noted as UC)was designed,emitting strong red light by 808 nm laser.The mesoporous silica(mSiO_(2))shell co‑doped with chlorin e6(C...An upconversion nanoparticle(NaErF_(4)∶Yb/Tm@NaLuF_(4)∶Yb@NaLuF_(4)∶Nd/Yb@NaLuF_(4),noted as UC)was designed,emitting strong red light by 808 nm laser.The mesoporous silica(mSiO_(2))shell co‑doped with chlorin e6(Ce6)and triethoxy(1H,1H,2H,2H‑nonafluorohexyl)silane(TFS)was coated on the outer layer of UC,and then a layer of HKUST‑1 shell was coated.The obtained nanocomposite UC@Ce6/TFS@mSiO_(2)@HKUST‑1(noted as UCTSH)was used for the synergistic treatment of chemodynamic therapy(CDT)and photodynamic therapy(PDT).Interestingly,the nanostructures can specifically re lease Cu^(2+)in the acidic tumor microenvironment.Cu^(2+)reacts with excess hydrogen peroxide(H_(2)O_(2))in the tumor microenvironment to form cytotoxic hydroxyl radical.Secondly,Ce6,with the action of oxygen‑carrying TFS,selectively produces a large amount of singlet oxygen by 808 nm laser irradiation.UCTSH can enhance the anti‑tumor effects of PDT and CDT by increasing the production level of reactive oxygen species,without causing damage to normal cells.展开更多
Objective:This study aimed to observe the efficacy and safety of traditional Chinese medicine therapy in patients with positive antibody responses to severe acute respiratory syndrome coronavirus 2.Methods:A retrospec...Objective:This study aimed to observe the efficacy and safety of traditional Chinese medicine therapy in patients with positive antibody responses to severe acute respiratory syndrome coronavirus 2.Methods:A retrospective observation was conducted on 25 patients with positive antibody responses but negative nucleic acid testing results who received Anshouxinshen therapy.The changes in symptoms,infective indicators,and safety were recorded.Results:Following treatment,the positive IgM responses of 18 patients became negative within one week,with an average time for antibody to become negative being 2 days.Of the seven patients with positive IgG responses,six became IgG-negative with an average time for antibody to become negative being 6.8 days.All symptoms of anxiety,insomnia,cough,fever,fatigue,and other symptoms improved 100%for all patients.After treatment,the lymphocyte count and lymphocyte ratio of patients significantly increased.No adverse reactions to Anshouxinshen therapy were reported.Conclusion:Anshouxinshen therapy is an effective treatment for patients with positive antibody responses to syndrome coronavirus 2,safely improving their immune functions.Early traditional Chinese medicine intervention can reduce the incidence of coronavirus disease 2019 and improve its cure rate,thereby promoting the prevention and control of coronavirus disease 2019.展开更多
BACKGROUND The liver represents a common site of distant metastasis in patients with esophageal cancer(EC).Conventional chemotherapy(CMT)presents limited efficacy for EC,and EC patients with liver metastases typically...BACKGROUND The liver represents a common site of distant metastasis in patients with esophageal cancer(EC).Conventional chemotherapy(CMT)presents limited efficacy for EC,and EC patients with liver metastases typically experience a poor prognosis,highlighting an urgent need to explore novel treatment approaches.This study evaluated the overall efficacy and safety of CMT vs CMT combined with immune checkpoint inhibitors(ICIs)in the treatment of EC patients with liver metastases.Furthermore,prognostic factors influencing outcomes in this patient population were identified.AIM To evaluate the efficacy and safety of first-line chemoimmunotherapy for EC patients with liver metastases and to analyze prognostic factors.METHODS This retrospective study included 126 EC patients with liver metastases at Zhejiang Cancer Hospital between 2014 and 2024.Patients receiving CMT were compared with those receiving CMT+ICI.Analyzed variables included clinicopathological features,treatment history,characteristics of metastasis,systemic and local treatments,overall survival(OS),and treatment-related adverse events(TRAEs).Prognostic factors were evaluated using univariate and multivariate Cox proportional-hazards regression models.Finally,efficacy outcomes and TRAE profiles were compared between the two groups.RESULTS A significant difference in median OS was identified between the two groups(10.8 months in the CMT group vs 20.8 months in the CMT+ICI group,P=0.004).The CMT+ICI group also demonstrated a significantly longer median progression-free survival of 11.7 months(P<0.001).Patients receiving combination therapy exhibited significantly improved systemic objective response rate and disease control rate.Multivariate analysis identified key factors significantly influencing OS in EC patients with liver metastases:Karnofsky Performance Status score≥70,receipt of local therapy for liver metastases,and the number of cycles of CMT and immunotherapy received.Furthermore,the incidence of TRAEs did not significantly differ between the CMT+ICI and CMT groups.CONCLUSION For EC patients with liver metastases,the combination of CMT and ICIs demonstrates significantly superior efficacy compared with CMT alone,while maintaining manageable TRAEs.展开更多
Malignant pleural effusion(MPE) is a serious disease caused by malignant tumors with high morbidity and mortality.Chemotherapy,immunotherapy,and antiangiogenic therapy are common treatments for MPE at present.However,...Malignant pleural effusion(MPE) is a serious disease caused by malignant tumors with high morbidity and mortality.Chemotherapy,immunotherapy,and antiangiogenic therapy are common treatments for MPE at present.However,traditional chemotherapeutic drugs have many side effects and can easily lead to drug resistance in patients.The complex tumor microenvironment(TME) of MPE directly reduces the antitumor efficacy of immunotherapy.Fortunately,drug delivery systems(DDSs) based on biomaterials have the ability to overcome some of the drawbacks of conventional treatments by improving drug stability,increasing the accuracy of tumor cell targeting,reducing toxic side effects,and remodeling TME,ultimately improving drug efficacy.Therefore,the purpose of this review is to provide an overview and discussion of the latest progress in biomaterial-based DDSs for the treatment of MPE.We discuss the application of biomaterials in the treatment of MPE from multiple perspectives,including chemotherapy,immunotherapy,combination therapy,and pleurodesis,where microspheres,cell membrane-derived microparticles(MPs),micelles,nanoparticles,and liposomes,are involved.The application of these biomaterials has been proven to have great potential in the treatment of MPE,providing a new idea for follow-up research.展开更多
Regenerative medicine is a promising therapeutic avenue for previously incurable diseases.As the risk of chronic and degenerative diseases significantly increases with age,the elderly population represents a major coh...Regenerative medicine is a promising therapeutic avenue for previously incurable diseases.As the risk of chronic and degenerative diseases significantly increases with age,the elderly population represents a major cohort for stem cell-based therapies.However,the regenerative potential of stem cells significantly decreases with advanced age and deteriorating health status of the donor.Therefore,the efficacy of autologous stem cell therapy is significantly compromised in older patients.To overcome these limitations,alternative strategies have been used to restore the age-and disease-depleted function of stem cells.These methods aim to restore the therapeutic efficacy of aged stem cells for autologous use.This article explores the effect of donor age and health status on the regenerative potential of stem cells.It further highlights the limitations of stem cell-based therapy for autologous treatment in the elderly.A comprehensive insight into the potential strategies to address the“age”and“disease”compromised regenerative potential of autologous stem cells is also presented.The information provided here serves as a valuable resource for physicians and patients for optimization of stem cellbased autologous therapy for aged patients.展开更多
Therapy discontinuation in inflammatory bowel disease,particularly involving immunomodulators,biologics,and small molecules,remains a controversial and evolving topic.This letter reflects on developments following the...Therapy discontinuation in inflammatory bowel disease,particularly involving immunomodulators,biologics,and small molecules,remains a controversial and evolving topic.This letter reflects on developments following the publication by Meštrovićet al,emphasizing the complex balance between risks of relapse,antidrug antibody formation,and potential complications of long-term immunosuppression.Recent evidence underscores high relapse rates following withdrawal-especially of anti-tumor necrosis factor agents-and highlights the lack of robust data for newer biologics.Updated guidelines from European Crohn’s and Colitis Organization,British Society of Gastroenterology,and American College of Gastroenterology all support cautious and individualized approaches,with strict criteria and close follow-up,particularly in Crohn’s disease.For ulcerative colitis,therapeutic cycling remains insufficiently addressed.We proposed a flowchart to support clinical decision-making and stress the importance of shared decisionmaking in the era of personalized medicine since,despite new drug classes and evolving strategies,the therapeutic ceiling in inflammatory bowel disease has yet to be fully overcome.展开更多
Serbisütherapy(ST)is a distinctive external treatment modality within traditional Mongolian medicine(TMM),historically developed within a nomadic cultural framework.This study presents a comprehensive philologica...Serbisütherapy(ST)is a distinctive external treatment modality within traditional Mongolian medicine(TMM),historically developed within a nomadic cultural framework.This study presents a comprehensive philological and historical analysis of ST,tracing its evolution from early battlefield applications to contemporary clinical use.By critically examining classical Mongolian medical texts alongside modern case studies,we aim to systematize ST’s therapeutic methods,indications,and limitations,while exploring its mechanisms of action through both traditional theory and modern biomedical perspectives.ST has undergone significant transformation,shifting from whole-body cavity immersion in the 13th century to targeted,organ-specific applications in modern practice.Its four primary methods–Covering,Mounted,Organ Placement,and Suction–demonstrate efficacy in treating cold-natured diseases,musculoskeletal disorders,gynecological conditions,and certain emergencies.ST embodies the core principles of TMM,particularly the balance of the“Three Roots”and the correction of cold-induced pathologies through heat.Despite challenges related to standardization,cultural translation,and regulatory acceptance,ST holds translational potential for integrative medicine.Future research should prioritize mechanistic validation,clinical standardization,and the development of biocompatible thermal technologies to bridge traditional practice with modern healthcare systems.展开更多
The rising prevalence of antibiotic resistance has created a need to reassess the established Helicobacter pylori(H.pylori)eradication protocols,and to develop new ones.Various bacterial and host factors are evaluated...The rising prevalence of antibiotic resistance has created a need to reassess the established Helicobacter pylori(H.pylori)eradication protocols,and to develop new ones.Various bacterial and host factors are evaluated,and their contribution to eradication failure is estimated.For a long time being considered the cornerstone eradication scheme,the standard triple therapy has been replaced with novel,more efficient regimens,namely sequential and concomitant,along with the emergence of a new design of bismuth quadruple therapy.A rescue levofloxacin based regimen has overcome the fear of therapy failure due to higher prevalence of dual resistant(clarithromycin and metronidazole)H.pylori.Culture-free and efficient susceptibility test are reestablishing the concept of tailored therapy,making eradication success close to originally desirable rates.Alleviating therapy side effects and improving patient compliance are as important as choosing appropriate eradication schemes,so various probiotic compound supplements are taken into consideration.Finally,we summarize the emerging efforts and obstacles in creating efficientH.pylori vaccine.展开更多
The development of highly effective therapeutics is a priority in addressing the escalating threat that cancer poses to human health.Cyclodextrins(CDs) with exceptional biocompatibility and devisable structural hierar...The development of highly effective therapeutics is a priority in addressing the escalating threat that cancer poses to human health.Cyclodextrins(CDs) with exceptional biocompatibility and devisable structural hierarchy are emerging as versatile building blocks for engineered drug delivery systems,showing a promising prospect in cancer therapy.CDs enable precise synthesis of functionalized polymers with tailored architectures,endowing their excellent stability and large surface area to prolong drug circulation,enhance solubility,and increase targeting efficiency.Recently,CD-based nanotherapeutics has shown transformative potential in chemotherapy,phototherapy,immunotherapy,gene therapy and other codelivery systems of combination therapy.This review will introduce the types of CD-based nanotherapeutics,systematically summarize their design methods and anticancer application,and further discuss the prospects and challenges,providing a roadmap for advancing CD nanotechnology toward cancer therapeutics.展开更多
Gastric cancer,a prevalent malignancy worldwide,ranks sixth in terms of frequency and third in fatality,causing over a million new cases and 769000 annual deaths.Predominant in Eastern Europe and Eastern Asia,risk fac...Gastric cancer,a prevalent malignancy worldwide,ranks sixth in terms of frequency and third in fatality,causing over a million new cases and 769000 annual deaths.Predominant in Eastern Europe and Eastern Asia,risk factors include family medical history,dietary habits,tobacco use,Helicobacter pylori,and Epstein-Barr virus infections.Unfortunately,gastric cancer is often diagnosed at an advanced stage,leading to a grim prognosis,with a 5-year overall survival rate below 5%.Surgical intervention,particularly with D2 Lymphadenectomy,is the mainstay for early-stage cases but offers limited success.For advanced cases,the National Comprehensive Cancer Network recommends chemotherapy,radiation,and targeted therapy.Emerging immunotherapy presents promise,especially for unresectable or metastatic cases,with strategies like immune checkpoint inhibitors,tumor vaccines,adoptive immunotherapy,and nonspecific immunomodulators.In this Editorial,with regards to the article“Advances and key focus areas in gastric cancer immunotherapy:A comprehensive scientometric and clinical trial review”,we address the advances in the field of immunotherapy in gastric cancer and its future prospects.展开更多
Despite demonstrating significant anti-tumor potential as an artemisinin derivative,artesunate faces delivery efficiency challenges due to low water solubility and insufficient targeting specificity.To improve the del...Despite demonstrating significant anti-tumor potential as an artemisinin derivative,artesunate faces delivery efficiency challenges due to low water solubility and insufficient targeting specificity.To improve the delivery efficiency,we engineered three artesunate(ART) derivatives,AC_(15)-L(linear),AC_(15)-B(branched),and AC_(15)-C(cyclic) with distinct aliphatic chain architectures.Unexpectedly,we observed that AC_(15)-C exhibited superior cytotoxicity against 4T1 breast cancer cells,and had the highest binding affinity for Lon protease 1(LONP1)(-72.6 kcal/mol).Subsequently,disulfide bond-containing lipid-PEG(DSPESS-PEG2K) modified chain architecture-engineered ART derivatives nanoassemblies(NAs) were developed to mitigate solubility-related limitations while enhancing targeting precision.Molecular docking and experimental validation demonstrated that ART derivatives inhibited LONP1 through hydrophobic interactions while preserved Fe^(2+)-mediated Fenton-like reaction activity.In vitro and in vivo evaluations demonstrated that AC_(15)-C NAs outperformed free ART and other NAs,suppressing 4T1 tumor growth via dual action:LONP1-directed mitochondrial proteostasis collapse and reactive oxygen species(ROS) amplification through Fe^(2+)-ART interactions.This study elucidated a novel anti-tumor mechanism of ART through the rational design of derivatives with spatially configured aliphatic chains,and developed reductionresponsive NAs to provide an advanced delivery strategy.展开更多
Thermally activated delayed fluorescence(TADF) emitters show great potential in photodynamic therapy(PDT) and bioimaging,leveraging their structural adaptability,efficient reverse intersystem crossing(RISC),robust pho...Thermally activated delayed fluorescence(TADF) emitters show great potential in photodynamic therapy(PDT) and bioimaging,leveraging their structural adaptability,efficient reverse intersystem crossing(RISC),robust photosensitizing capability,and high photoluminescence quantum yields(PLQYs).Herein,we developed a new class of donor-acceptor-donor(D-A-D)-type TADF materials by connecting the highly twisted indolizine-benzophenone electron acceptors with a series of electron donors including phenoxazine,phenothiazine and 9,9-dimethyl-9,10-dihydroacridine.These materials exhibit enhanced TADF properties,aggregation-induced emission(AIE),alongside high reactive oxygen species(ROS) generation efficiency,effectively mitigating aggregation-caused quenching observed in traditional fluorophores.Among them,IDP-p-PXZ,incorporating the phenoxazine donor,stands out with the smallest singlet-triplet splitting energy(ΔE_(ST)) and the highest spin-orbit coupling matrix elements(SOCMEs).Upon encapsulation into 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000](DSPE-PEG2000) nanoparticles(NPs),IDP-p-PXZ demonstrates extended delayed fluorescence lifetimes in air,an exceptionally fast intersystem crossing(ISC) rate constant(k_(ISC)) of 3.4×10^(7)s^(-1),and a radiative rate constant(k_(r)) of 5.05×10^(6)s^(-1).These NPs exhibit superior biocompatibility,efficient cellular internalization,and potent ROS production,enabling effective simultaneous PDT and confocal fluorescence imaging in HeLa cells.展开更多
基金Supported by Basic Scientific Research Project of Beijing University of Chinese Medicine(2015-JYB-XS166)Project of National Natural Science Foundation(3157397)+2 种基金Project of Beijing Natural Science Foundation(7162082)Beijing TCM Science and Technology Development Fund Project(JJ2015-13)Beijing Municipal Health System High-level Health Technology Talents Training Program(2015-3-113)
文摘[Objectives] To observe the clinical therapeutic efficacy of local hot-wet compress therapy of digestion ointment prescription on the patients with moderate and severe mastalgia. [Methods] Firstly,60 patients with mastalgia were selected,and divided into the experimental group and control group( 30 cases for each group). The control group was treated with acupuncture at distal point,and the experimental group was treated with TCM local hot-wet compress therapy combined with acupuncture at distal point. Then,the clinical therapeutic efficacy of two groups was compared. [Results]The experimental group was superior to the control group in relieving the breast pain,improving emotional integral,reducing breast lumps,improving lump texture,and improving TCM syndrome integral( P < 0. 05). [Conclusions]The digestion ointment prescription local hot-wet compress therapy has a significant therapeutic effect on treatment of mastalgia and can significantly improve the breast pain symptom of patients.
基金National Natural Science Foundation of China(No.81974543)。
文摘Objective:To systematically evaluate TCM of Fuzheng and Kangai combined with chemotherapy in the treatment of Advanced NSCLC,including the efficacy and effect on the quality of life of patients.Methods:Two researchers independently searched the literature of clinical trails from Jan.2010 until Jun.2020 in the Cochrane Library,Pubmed,Embase,CBM,CNKI,WanFang Data and VIP database.Also,they had been evaluated and extracted strictly by REVMAN 5.3.Results:A total of 1303 patients were included in 15 articles.The meta analysis shows that the TCM of Fuzheng and Kangai combined with chemotherapy can improve the objective response rate[OR=2.14,95%CI(1.67,2.74),P<0.00001],disease control rate[OR=2.54,95%CI(1.88,3.42),P<0.00001]and KPS score[OR=3.28,95%CI(1.92,5.60),P<0.0001],decrease the incidence rate of liver injury[OR=0.34,95%CI(0.21,0.54),P=0.003],hemoglobin reduction[OR=0.53,95%CI(0.28,1.01),P=0.05],leukopenia[OR=0.22,95%CI(0.13,0.39),P<0.00001],thrombocytopenia[OR=0.32,95%CI(0.21,0.50),P<0.00001],toxic effects on the digestive systems[OR=0.30,95%CI(0.19,0.46),P<0.00001].Conclusions:the experimental group was better than control one in short-term efficacy and KPS score.Furthermore,the experimental group can reduce the incidence rate of myelosuppression,toxicity of digestive system and liver.
基金Project of Research Plan of Traditional Chinese Medicine of Hebei Administration of Traditional Chinese Medicine(No.2019490)。
文摘Objective:To explore the effective prevention and treatment of portal hypertension(PH).Methods:A total of 220 patients who came to our hospital from March 2015 to October 2018 were treated.They were randomly divided into the treatment group and the control group,each with 110 cases.Before treatment,there was no significant differences in age,sex,clinical symptoms,signs,laboratory tests and color Doppler ultrasound related examinations between the 2 groups(P>0.05).Among them,the treatment group on the basis of traditional Chinese and Western medicine treatment in our hospital,the Qi-acupuncture therapy of TCM was added.The extra meridian acupoints along with acupoints were selected.The control group received conventional treatment with traditional Chinese and Western medicine in our hospital.Results:There were significant differences in clinical symptoms,signs and chemistry between groups after treatment(P<0.01).There were significant differences in test,color ultrasound related examination and so on(P<0.01).Those in the treatment group was significantly better than the control group(P<0.01).Conclusion:On the basis of the Qi-acupuncture therapy of TCM,selecting extra meridian acupoint and acupoints can effectively treat PH.
基金National Natural Science Foundation of China Youth Science Foundation Project(No.81904001)Capital Health Development Scientific Research Project(No.first issue 2018-1-4061)+1 种基金State Administration of Traditional Chinese Medicine Clinical Collaboration Project of TCM and Western Medicine for Major and Intractable Diseases(No.2019-ZX-005)In-Hospital Project of China-Japan Friendship Hospital(No.2019-1-QN-56)。
文摘Objective:To dig deeper into the traditional Chinese medicine treatment rules of chemotherapy-induced diarrhea with traditional Chinese medicine(TCM)inheritance computing platform system.Methods:Taking“traditional Chinese medicine”,“chemotherapy”and“diarrhea”as the theme words,comprehensive search of the database of CNKI,Wanfang and VIP from its inception to November 2020 was conduct-ed.The formulas of external treatment of traditional Chinese medicine for chemotherapy-induced diarrhea were included and the association rule,clustering and factor analysis were carried out.Results:A total of 145 papers,57 prescriptions meeting the inclusion criteria were collected,among which high-frequency drugs including Baizhu(Atractylodis macrocephalae rhizoma),Fuling(Poria),Dangshen(Codonopsisradix),Huanglian(Coptidis rhizoma),Zhigancao(Glycyrrhizae radix et rhizoma praeparata cum melle)were the most commonly used.The confidence level was set as 0.7 and the support level was set as 10,12 core compatibility groups were obtained,and 6 categories were cluster analyzed.Conclusion:The principle of external treatment of chemotherapy-induced diarrhea is mainly“restore deficiency and benefiting qi”,“benefiting water infiltration and dampness”,“clearing heat”and“inducing astringency”.Prescription combination and new prescription combination based on traditional Chinese medicine(TCM)inheritance computing platform system can be used as reference for clinicians and applied in primary hospitals.
文摘Non-pharmacotogicat treatment is an important means to control hypertension, with many advantages such as tow cost, tess medication, stable btood pressure, tess compHcations, and improved prognosis. This article reviews the research progress of non-drug treatment of hypertension in Chinese medicine in the past five years, and evaluates traditional Chinese medicine such as TCM Qigong, Wuhuo opera, Ba Duanjin and Taijiquan, and Chinese medicine acupuncture, moxibustion, massage, apptication, acupoint embedding and other traditional Chinese medicine. The effect of external treatment in hypertension control provides guidance for non-drug therapy to control hypertension.
文摘Objective: To study and evaluate the effect and influence of TCM physiotherapy nursing scheme on improving cervical pain in patients with cervical spondylosis.Methods: Taking March 2019 as the starting time for collecting cases and March 2021 as the deadline for collecting cases, a total of 112 patients with cervical spondylosis were included. Clinical intervention was carried out through traditional Chinese medicine physiotherapy nursing, and the improvement effect of patients' condition before and after treatment and nursing was analyzed.Results: the scores of cervical pain and cervical dysfunction before treatment and nursing were higher than those after treatment and Nursing (P < 0.05);The score of quality of life before treatment and nursing was lower than that after treatment and Nursing (P < 0.05);According to the clinical nursing satisfaction and effective rate, the satisfaction was 100.00%, and the total effective rate was 98.21%.Conclusion: in the clinical treatment and nursing of patients with cervical spondylosis, the implementation of TCM physiotherapy nursing measures can significantly improve the patient's cervical condition, significantly alleviate the symptoms of cervical pain, improve the cervical function, improve the quality of life, and significantly promote the patient's evaluation of the nursing model.
文摘47 senile non-parvicellular lung cancer patients at stage Ⅲ or Ⅳ were randomly divided into a treatment group (26 cases) treated by radiotherapy plus traditional Chinese medicine (TCM) and a control group (21 cases) treated only by radiotherapy for observation of the therapeutic effects.The patients in the treatment group orally took Chinese medicine during and after the radiotherapy.There was no obvious difference in short-term therapeutic effects between the two groups,but the long-term curative effects in the treatment group was obviously superior to that in the control group (P<0.05 or P<0.01).Conclusion:radiotherapy plus TCM can prolong the survival period for senile non-parvicellular lung cancer patients.
基金National Key Research and Development Program(No.2018YFC1704901)。
文摘Objective:To systematically evaluate the therapeutic effect of TCM on cardiotoxicity induced by anthracycline chemotherapy to provide clinical guidance.Methods:China hownet database(CNKI),Chinese biomedical literature retrieval(SinoMed),ten thousand Data knowledge service system(WanFang Data),VIP full-text database(VIP),PubMed,MedLine and the cochrane library were searched from inception to 1st,December,2020.Relevant combined TCM and Western medicine on cardiotoxicity randomized controlled trials(RCTs)were collected.The risk of bias in included RCTs were evaluated according to the Cochrane Handbook.The required indicators were extracted and included in RevMan5.4 analysis.Results:A total of 2844 patients were included in 37 RCTs.The results of meta-analysis showed that compared with the control group,TCM treatment group could alleviate the effect of anthracycline on ventricular ejection function,reduce the effect of anthracycline chemotherapy drugs in lowering left ventricular ejection fraction(WMD=6.44,95%CI 0.38 to 12.50,P=0.04),reduce the effect of anthracycline chemotherapy in increasing left ventricular end diastolic diameter(WMD=-0.59,95%CI-0.74 to-0.44,P<0.00001),reduce the effect of anthracycline chemotherapy drugs in increasing left ventricular end systolic diameter(WMD=-0.47,95%CI-0.60 to-0.34,P<0.00001),and reduce the effect of anthracyclines on troponin I(WMD=-0.19,95%CI-0.23 to-0.16,P<0.00001),troponin T(WMD=-0.02,95%CI-0.03 to-0.01,P<0.00001)and brain natriuretic peptide(WMD=-32.21,95%CI-58.21 to-6.22,P=0.02).Conclusion:The existing evidence can prove that TCM has a protective effect on cardiotoxicity caused by anthracycline chemotherapy,maintaining left ventricular ejection fraction and ventricular diameter,controlling the level of myocardial injury markers,and alleviating cardiac injury.
文摘An upconversion nanoparticle(NaErF_(4)∶Yb/Tm@NaLuF_(4)∶Yb@NaLuF_(4)∶Nd/Yb@NaLuF_(4),noted as UC)was designed,emitting strong red light by 808 nm laser.The mesoporous silica(mSiO_(2))shell co‑doped with chlorin e6(Ce6)and triethoxy(1H,1H,2H,2H‑nonafluorohexyl)silane(TFS)was coated on the outer layer of UC,and then a layer of HKUST‑1 shell was coated.The obtained nanocomposite UC@Ce6/TFS@mSiO_(2)@HKUST‑1(noted as UCTSH)was used for the synergistic treatment of chemodynamic therapy(CDT)and photodynamic therapy(PDT).Interestingly,the nanostructures can specifically re lease Cu^(2+)in the acidic tumor microenvironment.Cu^(2+)reacts with excess hydrogen peroxide(H_(2)O_(2))in the tumor microenvironment to form cytotoxic hydroxyl radical.Secondly,Ce6,with the action of oxygen‑carrying TFS,selectively produces a large amount of singlet oxygen by 808 nm laser irradiation.UCTSH can enhance the anti‑tumor effects of PDT and CDT by increasing the production level of reactive oxygen species,without causing damage to normal cells.
文摘Objective:This study aimed to observe the efficacy and safety of traditional Chinese medicine therapy in patients with positive antibody responses to severe acute respiratory syndrome coronavirus 2.Methods:A retrospective observation was conducted on 25 patients with positive antibody responses but negative nucleic acid testing results who received Anshouxinshen therapy.The changes in symptoms,infective indicators,and safety were recorded.Results:Following treatment,the positive IgM responses of 18 patients became negative within one week,with an average time for antibody to become negative being 2 days.Of the seven patients with positive IgG responses,six became IgG-negative with an average time for antibody to become negative being 6.8 days.All symptoms of anxiety,insomnia,cough,fever,fatigue,and other symptoms improved 100%for all patients.After treatment,the lymphocyte count and lymphocyte ratio of patients significantly increased.No adverse reactions to Anshouxinshen therapy were reported.Conclusion:Anshouxinshen therapy is an effective treatment for patients with positive antibody responses to syndrome coronavirus 2,safely improving their immune functions.Early traditional Chinese medicine intervention can reduce the incidence of coronavirus disease 2019 and improve its cure rate,thereby promoting the prevention and control of coronavirus disease 2019.
基金Supported by National Natural Science Foundation of China,No.82303672Zhejiang Provincial Health Commission and Zhejiang Provincial Administration of Traditional Chinese Medicine through the Targeted Project for Medical and Health Research,No.2025ZL017and China Primary Health Care Foundation,No.ZLMY20240311001ZJ.
文摘BACKGROUND The liver represents a common site of distant metastasis in patients with esophageal cancer(EC).Conventional chemotherapy(CMT)presents limited efficacy for EC,and EC patients with liver metastases typically experience a poor prognosis,highlighting an urgent need to explore novel treatment approaches.This study evaluated the overall efficacy and safety of CMT vs CMT combined with immune checkpoint inhibitors(ICIs)in the treatment of EC patients with liver metastases.Furthermore,prognostic factors influencing outcomes in this patient population were identified.AIM To evaluate the efficacy and safety of first-line chemoimmunotherapy for EC patients with liver metastases and to analyze prognostic factors.METHODS This retrospective study included 126 EC patients with liver metastases at Zhejiang Cancer Hospital between 2014 and 2024.Patients receiving CMT were compared with those receiving CMT+ICI.Analyzed variables included clinicopathological features,treatment history,characteristics of metastasis,systemic and local treatments,overall survival(OS),and treatment-related adverse events(TRAEs).Prognostic factors were evaluated using univariate and multivariate Cox proportional-hazards regression models.Finally,efficacy outcomes and TRAE profiles were compared between the two groups.RESULTS A significant difference in median OS was identified between the two groups(10.8 months in the CMT group vs 20.8 months in the CMT+ICI group,P=0.004).The CMT+ICI group also demonstrated a significantly longer median progression-free survival of 11.7 months(P<0.001).Patients receiving combination therapy exhibited significantly improved systemic objective response rate and disease control rate.Multivariate analysis identified key factors significantly influencing OS in EC patients with liver metastases:Karnofsky Performance Status score≥70,receipt of local therapy for liver metastases,and the number of cycles of CMT and immunotherapy received.Furthermore,the incidence of TRAEs did not significantly differ between the CMT+ICI and CMT groups.CONCLUSION For EC patients with liver metastases,the combination of CMT and ICIs demonstrates significantly superior efficacy compared with CMT alone,while maintaining manageable TRAEs.
基金financial support from the Noncommunicable Chronic Diseases-National Science and Technology Major Project (Nos.2024ZD0522800,2024ZD0522803)the National Natural Science Foundation of China (Nos.U21A20417,31930067,31800797)+2 种基金the Natural Science Foundation of Sichuan Province (No.2024NSFSC0046)the Sichuan Science and Technology Program (No.2022YFS0333)the 1·3·5 Project for Disciplines of Excellence,West China Hospital,Sichuan University (No.ZYGD24003)。
文摘Malignant pleural effusion(MPE) is a serious disease caused by malignant tumors with high morbidity and mortality.Chemotherapy,immunotherapy,and antiangiogenic therapy are common treatments for MPE at present.However,traditional chemotherapeutic drugs have many side effects and can easily lead to drug resistance in patients.The complex tumor microenvironment(TME) of MPE directly reduces the antitumor efficacy of immunotherapy.Fortunately,drug delivery systems(DDSs) based on biomaterials have the ability to overcome some of the drawbacks of conventional treatments by improving drug stability,increasing the accuracy of tumor cell targeting,reducing toxic side effects,and remodeling TME,ultimately improving drug efficacy.Therefore,the purpose of this review is to provide an overview and discussion of the latest progress in biomaterial-based DDSs for the treatment of MPE.We discuss the application of biomaterials in the treatment of MPE from multiple perspectives,including chemotherapy,immunotherapy,combination therapy,and pleurodesis,where microspheres,cell membrane-derived microparticles(MPs),micelles,nanoparticles,and liposomes,are involved.The application of these biomaterials has been proven to have great potential in the treatment of MPE,providing a new idea for follow-up research.
文摘Regenerative medicine is a promising therapeutic avenue for previously incurable diseases.As the risk of chronic and degenerative diseases significantly increases with age,the elderly population represents a major cohort for stem cell-based therapies.However,the regenerative potential of stem cells significantly decreases with advanced age and deteriorating health status of the donor.Therefore,the efficacy of autologous stem cell therapy is significantly compromised in older patients.To overcome these limitations,alternative strategies have been used to restore the age-and disease-depleted function of stem cells.These methods aim to restore the therapeutic efficacy of aged stem cells for autologous use.This article explores the effect of donor age and health status on the regenerative potential of stem cells.It further highlights the limitations of stem cell-based therapy for autologous treatment in the elderly.A comprehensive insight into the potential strategies to address the“age”and“disease”compromised regenerative potential of autologous stem cells is also presented.The information provided here serves as a valuable resource for physicians and patients for optimization of stem cellbased autologous therapy for aged patients.
文摘Therapy discontinuation in inflammatory bowel disease,particularly involving immunomodulators,biologics,and small molecules,remains a controversial and evolving topic.This letter reflects on developments following the publication by Meštrovićet al,emphasizing the complex balance between risks of relapse,antidrug antibody formation,and potential complications of long-term immunosuppression.Recent evidence underscores high relapse rates following withdrawal-especially of anti-tumor necrosis factor agents-and highlights the lack of robust data for newer biologics.Updated guidelines from European Crohn’s and Colitis Organization,British Society of Gastroenterology,and American College of Gastroenterology all support cautious and individualized approaches,with strict criteria and close follow-up,particularly in Crohn’s disease.For ulcerative colitis,therapeutic cycling remains insufficiently addressed.We proposed a flowchart to support clinical decision-making and stress the importance of shared decisionmaking in the era of personalized medicine since,despite new drug classes and evolving strategies,the therapeutic ceiling in inflammatory bowel disease has yet to be fully overcome.
基金supported by The China Ethnic Medicine Association Research Grant(No.2023MY055-81)Science and Technology Program of the Joint Fund of Scientific Research for the Public Hospitals of Inner Mongolia Academy of Medical Sciences(2023GLLHD177,2023GLLH0174)Inner Mongolia Autonomous Region Regional Medical Center for Specialized Care(2025).
文摘Serbisütherapy(ST)is a distinctive external treatment modality within traditional Mongolian medicine(TMM),historically developed within a nomadic cultural framework.This study presents a comprehensive philological and historical analysis of ST,tracing its evolution from early battlefield applications to contemporary clinical use.By critically examining classical Mongolian medical texts alongside modern case studies,we aim to systematize ST’s therapeutic methods,indications,and limitations,while exploring its mechanisms of action through both traditional theory and modern biomedical perspectives.ST has undergone significant transformation,shifting from whole-body cavity immersion in the 13th century to targeted,organ-specific applications in modern practice.Its four primary methods–Covering,Mounted,Organ Placement,and Suction–demonstrate efficacy in treating cold-natured diseases,musculoskeletal disorders,gynecological conditions,and certain emergencies.ST embodies the core principles of TMM,particularly the balance of the“Three Roots”and the correction of cold-induced pathologies through heat.Despite challenges related to standardization,cultural translation,and regulatory acceptance,ST holds translational potential for integrative medicine.Future research should prioritize mechanistic validation,clinical standardization,and the development of biocompatible thermal technologies to bridge traditional practice with modern healthcare systems.
文摘The rising prevalence of antibiotic resistance has created a need to reassess the established Helicobacter pylori(H.pylori)eradication protocols,and to develop new ones.Various bacterial and host factors are evaluated,and their contribution to eradication failure is estimated.For a long time being considered the cornerstone eradication scheme,the standard triple therapy has been replaced with novel,more efficient regimens,namely sequential and concomitant,along with the emergence of a new design of bismuth quadruple therapy.A rescue levofloxacin based regimen has overcome the fear of therapy failure due to higher prevalence of dual resistant(clarithromycin and metronidazole)H.pylori.Culture-free and efficient susceptibility test are reestablishing the concept of tailored therapy,making eradication success close to originally desirable rates.Alleviating therapy side effects and improving patient compliance are as important as choosing appropriate eradication schemes,so various probiotic compound supplements are taken into consideration.Finally,we summarize the emerging efforts and obstacles in creating efficientH.pylori vaccine.
基金financially supported by National Natural Science Foundation of China (No.3240117,X.S)Sichuan Science and Technology Program (No.2024YFFK0345,Z.X)+3 种基金Natural Science Foundation of Chongqing (No.CSTB2024NSCQ-MSX0046,F.R)Startup Fund of Chongqing Normal University (No.23XLB036,F.R)National College Student Innovation and Entrepreneurship Program of Southwest University (No.202410635109,Y.Z)Guangdong High-level Hospital Construction Fund。
文摘The development of highly effective therapeutics is a priority in addressing the escalating threat that cancer poses to human health.Cyclodextrins(CDs) with exceptional biocompatibility and devisable structural hierarchy are emerging as versatile building blocks for engineered drug delivery systems,showing a promising prospect in cancer therapy.CDs enable precise synthesis of functionalized polymers with tailored architectures,endowing their excellent stability and large surface area to prolong drug circulation,enhance solubility,and increase targeting efficiency.Recently,CD-based nanotherapeutics has shown transformative potential in chemotherapy,phototherapy,immunotherapy,gene therapy and other codelivery systems of combination therapy.This review will introduce the types of CD-based nanotherapeutics,systematically summarize their design methods and anticancer application,and further discuss the prospects and challenges,providing a roadmap for advancing CD nanotechnology toward cancer therapeutics.
文摘Gastric cancer,a prevalent malignancy worldwide,ranks sixth in terms of frequency and third in fatality,causing over a million new cases and 769000 annual deaths.Predominant in Eastern Europe and Eastern Asia,risk factors include family medical history,dietary habits,tobacco use,Helicobacter pylori,and Epstein-Barr virus infections.Unfortunately,gastric cancer is often diagnosed at an advanced stage,leading to a grim prognosis,with a 5-year overall survival rate below 5%.Surgical intervention,particularly with D2 Lymphadenectomy,is the mainstay for early-stage cases but offers limited success.For advanced cases,the National Comprehensive Cancer Network recommends chemotherapy,radiation,and targeted therapy.Emerging immunotherapy presents promise,especially for unresectable or metastatic cases,with strategies like immune checkpoint inhibitors,tumor vaccines,adoptive immunotherapy,and nonspecific immunomodulators.In this Editorial,with regards to the article“Advances and key focus areas in gastric cancer immunotherapy:A comprehensive scientometric and clinical trial review”,we address the advances in the field of immunotherapy in gastric cancer and its future prospects.
基金financially supported by the Liaoning Revitalization Talents Program (No.XLYC2403107)the Excellent Youth Science Foundation of Liaoning Province (No.2024JH3/10200046)the Basic Scientific Research Project of Liaoning Provincial Department of Education (No.LJ212410163015)。
文摘Despite demonstrating significant anti-tumor potential as an artemisinin derivative,artesunate faces delivery efficiency challenges due to low water solubility and insufficient targeting specificity.To improve the delivery efficiency,we engineered three artesunate(ART) derivatives,AC_(15)-L(linear),AC_(15)-B(branched),and AC_(15)-C(cyclic) with distinct aliphatic chain architectures.Unexpectedly,we observed that AC_(15)-C exhibited superior cytotoxicity against 4T1 breast cancer cells,and had the highest binding affinity for Lon protease 1(LONP1)(-72.6 kcal/mol).Subsequently,disulfide bond-containing lipid-PEG(DSPESS-PEG2K) modified chain architecture-engineered ART derivatives nanoassemblies(NAs) were developed to mitigate solubility-related limitations while enhancing targeting precision.Molecular docking and experimental validation demonstrated that ART derivatives inhibited LONP1 through hydrophobic interactions while preserved Fe^(2+)-mediated Fenton-like reaction activity.In vitro and in vivo evaluations demonstrated that AC_(15)-C NAs outperformed free ART and other NAs,suppressing 4T1 tumor growth via dual action:LONP1-directed mitochondrial proteostasis collapse and reactive oxygen species(ROS) amplification through Fe^(2+)-ART interactions.This study elucidated a novel anti-tumor mechanism of ART through the rational design of derivatives with spatially configured aliphatic chains,and developed reductionresponsive NAs to provide an advanced delivery strategy.
基金supported by the National Natural Science Foundation of China (No.22405062)the Guangdong Basic and Applied Basic Research Foundation (No.2021A1515110869)+2 种基金the Shenzhen Science and Technology Program (No.ZDSYS20210623091813040)Innovation Program of Zhanjiang (No.2020LHJH005)Funds for Ph.D.researchers of Guangdong Medical University in 2025 (No.4SG25007G)。
文摘Thermally activated delayed fluorescence(TADF) emitters show great potential in photodynamic therapy(PDT) and bioimaging,leveraging their structural adaptability,efficient reverse intersystem crossing(RISC),robust photosensitizing capability,and high photoluminescence quantum yields(PLQYs).Herein,we developed a new class of donor-acceptor-donor(D-A-D)-type TADF materials by connecting the highly twisted indolizine-benzophenone electron acceptors with a series of electron donors including phenoxazine,phenothiazine and 9,9-dimethyl-9,10-dihydroacridine.These materials exhibit enhanced TADF properties,aggregation-induced emission(AIE),alongside high reactive oxygen species(ROS) generation efficiency,effectively mitigating aggregation-caused quenching observed in traditional fluorophores.Among them,IDP-p-PXZ,incorporating the phenoxazine donor,stands out with the smallest singlet-triplet splitting energy(ΔE_(ST)) and the highest spin-orbit coupling matrix elements(SOCMEs).Upon encapsulation into 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000](DSPE-PEG2000) nanoparticles(NPs),IDP-p-PXZ demonstrates extended delayed fluorescence lifetimes in air,an exceptionally fast intersystem crossing(ISC) rate constant(k_(ISC)) of 3.4×10^(7)s^(-1),and a radiative rate constant(k_(r)) of 5.05×10^(6)s^(-1).These NPs exhibit superior biocompatibility,efficient cellular internalization,and potent ROS production,enabling effective simultaneous PDT and confocal fluorescence imaging in HeLa cells.