In this work,iron-doped carbon dots(Fe-CDs)with strong peroxidase-mimicking activity were synthesized for tumor-specific therapy.Their intrinsic red fluorescence enabled high-contrast cellular imaging,revealing prefer...In this work,iron-doped carbon dots(Fe-CDs)with strong peroxidase-mimicking activity were synthesized for tumor-specific therapy.Their intrinsic red fluorescence enabled high-contrast cellular imaging,revealing preferen⁃tial mitochondrial accumulation.In the acidic and hydrogen peroxide(H_(2)O_(2))-rich tumor microenvironment,Fe-CDs catalyzed hydroxyl radical(·OH)generation,inducing oxidative stress and lipid peroxidation,ultimately triggering ferroptosis.In vitro and in vivo studies demonstrated potent tumor inhibition.Furthermore,Fe-CDs exhibited excel⁃lent biocompatibility with no significant systemic toxicity.By integrating fluorescence imaging and catalytic therapy,this study presents a promising nanoplatform for tumor treatment and ferroptosis research.展开更多
A nanomicelle(denoted as TPGS/Ppa)was fabricated via the coassembly of the amphiphilic D-α-tocopheryl polyethylene glycol 1000 succinate(TPGS)and the hydrophobic photosensitizer pyropheophorbide a(Ppa)for photodynami...A nanomicelle(denoted as TPGS/Ppa)was fabricated via the coassembly of the amphiphilic D-α-tocopheryl polyethylene glycol 1000 succinate(TPGS)and the hydrophobic photosensitizer pyropheophorbide a(Ppa)for photodynamic therapy(PDT).The obtained nanomicelle possessed a spherical structure with a diameter of(18.0±2.2)nm and a zeta potential of approximately -18 mV.Besides,the nanomicelle exhibited excellent photostability,biocompatibility,and phototoxicity,and could effectively reach the tumor region via the enhanced permeability and retention effect.Additionally,it could be found that the TPGS/Ppa nanomicelle exhibited higher phototoxicity against 4T1 murine mammary cancer cells than free Ppa.In the 4T1 tumor-bearing mouse model,the nanomicelle showed an excellent antitumor therapeutic effect.This study develops a new type of photodynamic nanomicelle TPGS/Ppa,which can increase the accumulation of drugs and prolong their tumor retention time,providing a feasible strategy for realizing the delivery of small-molecule hydrophobic drugs and tumor PDT.展开更多
Background and objective:Epidermal growth factor receptor(EGFR)mutations are often associated with non-EGFR genetic alterations,which maybe a reason for the poor efficacy of EGFR tyrosine kinase inhibitors(TKIs).Here ...Background and objective:Epidermal growth factor receptor(EGFR)mutations are often associated with non-EGFR genetic alterations,which maybe a reason for the poor efficacy of EGFR tyrosine kinase inhibitors(TKIs).Here we conducted this study to explore whether EGFR-TKIs combined with chemotherapy would benefit advanced lung adenocarcinoma patients with both sensitive EGFR mutation and concomitant non-EGFR genetic alterations.Materials and methods:Cases of advanced lung adenocarcinoma with EGFR mutation combined with concomitant nonEGFR genetic alterations were retrospectively collected.And the patients were required to receive first-line EGFR-TKIs and chemotherapy combination or EGFR-TKIs monotherapy.Demographic,clinical and pathological data were collected,and the electronic imaging data were retrieved to evaluate the efficacy and time of disease progression.Survival data were obtained through face-to-face or telephone follow-up.The differences between the two groups in objective response rate(ORR),disease control rate(DCR),progression-free survival(PFS)and overall survival(OS)were investigated.Results:107 patients were included,including 63 cases in the combination group and 44 cases in the monotherapy group.The ORR were 78%and 50%(P=0.003),and DCR were 97%and 77%(P=0.002),respectively.At a median follow-up of 13.7 mon,a PFS event occurred in 38.1%and 81.8%of patients in the two groups,with median PFS of18.8 mon and 5.3 mon,respectively(P<0.000,1).Median OS was unreached in the combination group,and 27.8 mon in the monotherapy group(P=0.31).According to the Cox multivariate regression analysis,combination therapy was an independent prognostic factor of PFS.Conclusion:In patients with EGFR-mutant advanced lung adenocarcinoma with concomitant non-EGFR genetic alterations,combination of TKIs and chemotherapy was significantly superior to EGFR-TKIs monotherapy,which should be the preferred treatment option.展开更多
Objective The aim of this study was to assess quality of results of elderly patients with coronary disease after medical or revascularisation therapy. Methods In this study, we enrolled 103 patients aged 75 years or o...Objective The aim of this study was to assess quality of results of elderly patients with coronary disease after medical or revascularisation therapy. Methods In this study, we enrolled 103 patients aged 75 years or older with chronic angina in which 47 patients were assigned coronary angiography and revascularisation and 56 patients with optimised medical therapy. The primary endpoint was quality of life after 6 months, as assessed by questionnaire and the presence of major adverse cardiac events (death, non fatal myocardial infarction, or hospital admission for acute coronary syndrome with or without the need for revascularisation). Results After 6 months follow up, angina severity decreased and measures of quality of life increased in both treatment groups( P <0.05 ); however, these improvements were significantly greater after revascularisation( P <0.01 ). Major adverse cardiac events occurred in 30 ( 53.6% ) of patients in the medical group and 9 ( 19.1% ) in the invasive group ( P <0.01 ).Conclusions Patients aged 75 years or older with angina benefit more from revascularisation than from optimised medical therapy in terms of symptom relief and quality of life. Therefore, these patients should be offered invasive assessment despite their high risk profile followed by revascularisation if feasible.展开更多
The realization of real-time thermal feedback for monitoring photothermal therapy(PTT)under near-infrared(NIR)light irradiation is of great interest and challenge for antitumor therapy.Herein,by assembling highly effi...The realization of real-time thermal feedback for monitoring photothermal therapy(PTT)under near-infrared(NIR)light irradiation is of great interest and challenge for antitumor therapy.Herein,by assembling highly efficient photothermal conversion gold nanorods and a temperature-responsive probe((E)-4-(4-(diethylamino)styryl)-1-methylpyridin-1-ium,PyS)within MOF-199,an intelligent nanoplatform(AMPP)was fabricated for simultaneous chemodynamic therapy and NIR light-induced temperature-feedback PTT.The fluorescence intensity and temperature of the PyS probe are linearly related due to the restriction of the rotation of the characteristic monomethine bridge.Moreover,the copper ions resulting from the degradation of MOF-199 in an acidic microenvironment can convert H_(2)O_(2)into•OH,resulting in tumor ablation through a Fenton-like reaction,and this process can be accelerated by increasing the temperature.This study establishes a feasible platform for fabricating highly sensitive temperature sensors for efficient temperature-feedback PTT.展开更多
OBJECTIVE Plasmonic nanostructures act as a type of promising candidate for cancer photothermal therapy.These photothermal agents with good biocompatibility and high photothermal conversion efficiency are highly desir...OBJECTIVE Plasmonic nanostructures act as a type of promising candidate for cancer photothermal therapy.These photothermal agents with good biocompatibility and high photothermal conversion efficiency are highly desirable.In the present study,we synthesized poly(diallyldimethylammonium chloride)(PDDAC)coated porous platinum(Pt)nanoparticles for photothermal therapy.METHODS Biocompatibility and cellular uptake of Pt nanoparticles were studied in human glioblastoma U-87 MG cells.Cell viability was evaluated by ATP assay and calcein AM staining.The photothermal therapeutic effect of the Pt nanoparticles was studied under 808-nm laser irradiation.In addition,the synergistic anti-cancer effect of the Pt nanoparticle-based photothermal therapy and doxorubicinwas investigated.RESULTS The as-prepared Pt nanoparticles exhibited considerable photothermal conversion efficiency under 809 nm and 980 nm laser irradiation.In vitro study indicated that the Pt nanoparticles displayed good biocompatibility and high cellular uptake efficiency.In the presence of the Pt nanoparticles,808-nm laser irradiation at 8.4 W·cm-2for3 min induces significant cytotoxicity,and cell necrosis is involved in the photothermal injury.Furthermore,simultaneousapplication of photothermal therapy synergistically enhances the cytotoxicity of anticancer drug doxorubicin.CONCLUSION Therefore,PDADMAC-coated Pt nanoparticles will have great potential in cancer photothermal therapy.展开更多
Resistance to cancer therapy continues to be a major limitation for the successful treatment of cancer. There are many published studies on therapy resistance in breast and prostate cancers; however, there are current...Resistance to cancer therapy continues to be a major limitation for the successful treatment of cancer. There are many published studies on therapy resistance in breast and prostate cancers; however, there are currently no data on molecular markers associated with resistance. The conflicting data were reported regarding the AKT/m-TOR signaling pathway components as markers predicting resistance. The AKT/m-TOR signaling pathway is involved in the development of many human cancers; its activation is related to cell proliferation, angiogenesis, apoptosis, as well as to therapy resistance. Molecular alterations in the AKT/m-TOR signaling pathway provide a platform to identify universal markers associated with the development of resistance to cancer therapy.展开更多
OBJECTIVE To explain the high inter-individual variability and the frequency of exceeding the therapeutic reference range and the laboratory alert level of amisulpride,a popula⁃tion pharmacokinetic model in Chinese pa...OBJECTIVE To explain the high inter-individual variability and the frequency of exceeding the therapeutic reference range and the laboratory alert level of amisulpride,a popula⁃tion pharmacokinetic model in Chinese patients with schizophrenia was built based on therapeu⁃tic drug monitoring data to guide individualized therapy.METHODS Plasma concentration data(330 measurements from 121 patients)were ana⁃lyzed using a nonlinear mixed-effects model⁃ing approach with first-order conditional estima⁃tion with interaction(FOCE I).The concentra⁃tions of amisulpride were detected by HPLC-MS/MS.Age,weight,sex,combination medication history and renal function status were evaluated as main covariates.The model was internally val⁃idated using goodness-of-fit,bootstrap and nor⁃malized prediction distribution error.Recom⁃mended dosage regimens for patients with key covariates were estimated on the basis of Monte Carlo simulations and the established model.RESULTS A one-compartment model with first-order absorption and elimination was found to adequately characterize amisulpride concentra⁃tion in Chinese patients with schizophrenia.The population estimates of the apparent volume of distribution(V/F)and apparent clearance(CL/F)were 12.7 L and 1.12 L·h-1,respectively.Age sig⁃nificantly affected the clearance of amisulpride and the final model was as follow:CL/F=1.04×(AGE/32)-0.624(L·h-1).To avoid exceeding the lab⁃oratory alert level(640μg·L-1),the model-based simulation results showed that the recommended dose of amisulpride was no more than 600 mg per day for patients aged 60 years,800 mg per day for those aged 40 years and 1200 mg per day for those aged 20 years,respectively.CON⁃CLUSION Dosage optimization of amisulpride can be carried out according to age to reduce the risk of adverse reactions.The model can be used as a suitable tool for designing individual⁃ized therapy for Chinese patients with schizo⁃phrenia.展开更多
In order to study the epidemiological characteristics of cytomegalovirus(CMV)infection in allogeneichematopoietic stem cell transplantation(allo-HSCT)recipients by means of plasma real time quantitative polymerasechai...In order to study the epidemiological characteristics of cytomegalovirus(CMV)infection in allogeneichematopoietic stem cell transplantation(allo-HSCT)recipients by means of plasma real time quantitative polymerasechain reaction(RQ-PCR),141 adult patients undergoing allo-HSCT between January 2008 and June 2010 were seriallymonitored by RQ-PCR for detecting CMV and guiding the preemptive therapy followed up to 180 days post-HSCT.Theresults showed that the incidence of CMV infection and CMV pneumonia was 81.5%and 2.9%respectively,whichmainly occurred within 2 months post-HSCT.Single-therapy with ganciclovir(GCV)for 63 patients or foscarnet 6patients was performed for preemptive therapy.The total efficacy was 87.8%,and the response patterns were different.CMV infection was more frequent in female patients(P=0.044),and those with aGVHD(P=0.043),using ATG orbasiliximab in conditioning regimens(P=0.049),as well as earlier in patients using ATG or basiliximab or those withaGVHD(P=0.007;P=0.000).The aGVHD,maximum load,positive times of CMV-DNA detection and therapyduration all correlated with the efficacy(P<0.05).It is concluded that the incidence of CMV infection is still high afterHSCT.Plasma RQ-PCR assay for CMV-DNA shows a strong correlation with the clinical outcome of CMV infection,which is useful and suitable for management of CMV infection in HSCT.展开更多
An essential prerequisite of any genetherapy technique is the efficient and stable de-livery of transferred DNA into the target cell.Avariety of techniques are available for directly in-troducing DNA into eukaryotic c...An essential prerequisite of any genetherapy technique is the efficient and stable de-livery of transferred DNA into the target cell.Avariety of techniques are available for directly in-troducing DNA into eukaryotic cells,includingcoprecipitation with calcium phosphate,electroporation and microinjection. The efficien-cy of most of these physical transfection tech-niques is less than one in ten thousand, and展开更多
Mechanical forces produced from cells regulate cell functions and fate for tissue development and regeneration.Knowledge in mechanobiology thus provides new strategy for diagnosis and prosthetics.In our work,we develo...Mechanical forces produced from cells regulate cell functions and fate for tissue development and regeneration.Knowledge in mechanobiology thus provides new strategy for diagnosis and prosthetics.In our work,we develop a platform which could precisely detect cellular traction force with resolution of 100 pN,enabling quantification of chemotherapy at early stage,re-epithelialization and cell collision.Additionally,a better solution for antimicrobial dressing managing infection has been provided by modifying the surface to enable both the disruption on biofilm and the elimination of engaged planktonic bacteria.Mechanobiological study demonstrated our dual-function surface remains harmless to host mammalian cells during thermalablation.Our design could pave the way further for creating soft miniaturized medical robots that defend our living system via safe interaction down to cellular level.展开更多
OBJECTIVE To prepare hypocrellin B-loaded apoferritin nanoparticles(HB-AFT NPs)for photodynamic therapy on tumor.METHODS HB-AFT NPs were prepared by taking advantage of the reversibleunfolding and refolding character ...OBJECTIVE To prepare hypocrellin B-loaded apoferritin nanoparticles(HB-AFT NPs)for photodynamic therapy on tumor.METHODS HB-AFT NPs were prepared by taking advantage of the reversibleunfolding and refolding character of apoferritin in different pH environments.The photophysical and photobiological properties of hypocrellin B-loaded apoferritin were measured.RESULETS HB molecules were successfully encapsulated within apoferritincavity.HB-AFT-NPs exhibited higher ROS productionthan free HB.Additionally,phototoxicity of HB-AFT NPs to MDA-MB-231 cells was significantly improved as compared to free HB.CONCLUSION Together these results demonstrate that hypocrellin B-loaded apoferritin might be a potential nanoscale photosensitizer.展开更多
Objective Recent evidence has indicated that hypertension is associated with impaired cognitive function. However, the prevention of cognitive disorders with antihypertensive therapy remains controversial.The trial pr...Objective Recent evidence has indicated that hypertension is associated with impaired cognitive function. However, the prevention of cognitive disorders with antihypertensive therapy remains controversial.The trial provided evidence to compare the efficacy on cognitive function with the combination of amlodipine with diuretics or angiotensin II receptor blocker.展开更多
Objective To analyze the clinical features and effects of target therapy of post splenectomy pulmonary hypertension, and improve the diagnosis and treatment of the disease.Methods Clinical data of 18 patients with pos...Objective To analyze the clinical features and effects of target therapy of post splenectomy pulmonary hypertension, and improve the diagnosis and treatment of the disease.Methods Clinical data of 18 patients with post splenectomy pulmonary hypertension admitted to our hospital from October 2006 to March 2017 were systematically reviewed.展开更多
Objective To explore the application of evidence-based nursing intervention in patients with congenital heart diseases treated by transcatheter interventional therapy.Methods A total of 64 patients with congenital hea...Objective To explore the application of evidence-based nursing intervention in patients with congenital heart diseases treated by transcatheter interventional therapy.Methods A total of 64 patients with congenital heart diseases who were administered in our hospital from June 2011 to July 2013 were recruited in our research.展开更多
Background It’s essential to prevent from thrombosis on device without increasing the risk of bleeding complications after successfully implanted left atrial appendage device.At present,no guidelines recommend about ...Background It’s essential to prevent from thrombosis on device without increasing the risk of bleeding complications after successfully implanted left atrial appendage device.At present,no guidelines recommend about postoperative antithrombotic therapy of left atrial appendage closure(LAAC).The purpose of this study is to investigate the safety and efficacy of different antithrombotic therapies after LAAC.展开更多
Corrole,a representative branch of porphyrin,has recently gained popularity.These molecules,viewed as ring‑contracted porphyrinoids containing direct pyrrole‑pyrrole linkages due to the absence of a meso‑carbon atom,e...Corrole,a representative branch of porphyrin,has recently gained popularity.These molecules,viewed as ring‑contracted porphyrinoids containing direct pyrrole‑pyrrole linkages due to the absence of a meso‑carbon atom,exhibit significant photo‑physicochemical properties that make them attractive for various applications.Herein,this review comprehensively discusses the remarkable properties of corrole complexes,as well as related structures and chelation properties.It further explores the biological applications of corrole complexes for in vivo imaging and anticancer therapy.Additionally,it addresses common research bottlenecks and challenges,providing insights into future potential applications in disease diagnosis and treatment.Generally,this review aims to illuminate the significance of corrole complexes and their promising biological applications.展开更多
Osteoarthritis(OA)is a most common form of degenerative joint disease,primarily characterized by the degradation of articular cartilage,subchondral sclerosis and inflammation of the synovial membrane.Mesenchymal stem ...Osteoarthritis(OA)is a most common form of degenerative joint disease,primarily characterized by the degradation of articular cartilage,subchondral sclerosis and inflammation of the synovial membrane.Mesenchymal stem cells(MSCs),a multipotent adult stem cell population,can be isolated from many connective tissue lineages,including those of the diarthrodial joint.Joint-resident MSCs or MSC-like progenitor cells contribute to the maintenance of healthy microenvironment or to the response to trauma.The onset of degenerative changes in the joint related to abnormal condition or depletion of these endogenous MSCs and native host hyaline cartilage cells,leading to limited selfrepair potential of the joint and advance of the degradation.To date,no acknowledged medical treatment strategies,including non-operative and classical surgical techniques,are efficient in restoring normal anatomy and function of hyaline cartilage in OA.This highlights an urgent need for better celled-based therapeutic strategies that supplement these functional cel s exogenously to recover the tissue homeostasis and repair in joint cavity via chondrogenic and anti-in fl ammatory functions.In this review we focus on the role of native MSCs in healthy or OA joint and recent progress in cel-based researches utilizing culture-expanded chondrocytes,pluripotent stem cel s,or MSCs from different sources for treating OA.展开更多
OBJECTIVE To explore the effect of connexin(Cx)40-formed gap junctional intercellular communication(GJIC)on Photofrin-photodynamic therapy(PDT)phototoxicity in Cx40-transfected He La cells and its potential mechanisms...OBJECTIVE To explore the effect of connexin(Cx)40-formed gap junctional intercellular communication(GJIC)on Photofrin-photodynamic therapy(PDT)phototoxicity in Cx40-transfected He La cells and its potential mechanisms.METHODS He La cell line stably transfected to express Cx40 was seeded at high and low cell density,respectively,to assess in vitro photosensitivity using CCK8 assay.Western blot assay was performed to detect the expression of Cx40.The intracellular ROS and Ca^(2+) concentrations were determined using flow cytometer.4-HNE and ceramide were measured using ELISA assay.RESULTS Cx40-composed GJ formation at high density enhances the phototoxicity of PhotofrinPDT.When the Cx40 is not expressed or Cx40 channels are blocked,the phototoxicity in high-density cultures substantially reduces,indicating that the enhanced PDT phototoxicity at high density is mediated by Cx40-composed GJIC.The GJIC-mediated increase in PDT phototoxicity was associated with ROS and calcium-mediated stress signaling pathways.CONCLUSION The work uniquely presents the ability of Cx40-composed GJIC to enhance the sensitivity of malignant cells to PDT,and indicates that maintenance or increase of Cx40-formed GJIC may be a profitable strategy towards the enhancement of PDT therapeutic efficiency.展开更多
Redacted by Specialty Committee of Heat-sensitive Moxibustion of WFCMS,Standardized Manipulations of Heat-sensitive Moxibustion(HSM).Therapy states the scope,normative references,terms and definitions,preoperative pre...Redacted by Specialty Committee of Heat-sensitive Moxibustion of WFCMS,Standardized Manipulations of Heat-sensitive Moxibustion(HSM).Therapy states the scope,normative references,terms and definitions,preoperative preparations,operation methods and procedure,indications and notice of HSM Therapy.展开更多
文摘In this work,iron-doped carbon dots(Fe-CDs)with strong peroxidase-mimicking activity were synthesized for tumor-specific therapy.Their intrinsic red fluorescence enabled high-contrast cellular imaging,revealing preferen⁃tial mitochondrial accumulation.In the acidic and hydrogen peroxide(H_(2)O_(2))-rich tumor microenvironment,Fe-CDs catalyzed hydroxyl radical(·OH)generation,inducing oxidative stress and lipid peroxidation,ultimately triggering ferroptosis.In vitro and in vivo studies demonstrated potent tumor inhibition.Furthermore,Fe-CDs exhibited excel⁃lent biocompatibility with no significant systemic toxicity.By integrating fluorescence imaging and catalytic therapy,this study presents a promising nanoplatform for tumor treatment and ferroptosis research.
文摘A nanomicelle(denoted as TPGS/Ppa)was fabricated via the coassembly of the amphiphilic D-α-tocopheryl polyethylene glycol 1000 succinate(TPGS)and the hydrophobic photosensitizer pyropheophorbide a(Ppa)for photodynamic therapy(PDT).The obtained nanomicelle possessed a spherical structure with a diameter of(18.0±2.2)nm and a zeta potential of approximately -18 mV.Besides,the nanomicelle exhibited excellent photostability,biocompatibility,and phototoxicity,and could effectively reach the tumor region via the enhanced permeability and retention effect.Additionally,it could be found that the TPGS/Ppa nanomicelle exhibited higher phototoxicity against 4T1 murine mammary cancer cells than free Ppa.In the 4T1 tumor-bearing mouse model,the nanomicelle showed an excellent antitumor therapeutic effect.This study develops a new type of photodynamic nanomicelle TPGS/Ppa,which can increase the accumulation of drugs and prolong their tumor retention time,providing a feasible strategy for realizing the delivery of small-molecule hydrophobic drugs and tumor PDT.
文摘Background and objective:Epidermal growth factor receptor(EGFR)mutations are often associated with non-EGFR genetic alterations,which maybe a reason for the poor efficacy of EGFR tyrosine kinase inhibitors(TKIs).Here we conducted this study to explore whether EGFR-TKIs combined with chemotherapy would benefit advanced lung adenocarcinoma patients with both sensitive EGFR mutation and concomitant non-EGFR genetic alterations.Materials and methods:Cases of advanced lung adenocarcinoma with EGFR mutation combined with concomitant nonEGFR genetic alterations were retrospectively collected.And the patients were required to receive first-line EGFR-TKIs and chemotherapy combination or EGFR-TKIs monotherapy.Demographic,clinical and pathological data were collected,and the electronic imaging data were retrieved to evaluate the efficacy and time of disease progression.Survival data were obtained through face-to-face or telephone follow-up.The differences between the two groups in objective response rate(ORR),disease control rate(DCR),progression-free survival(PFS)and overall survival(OS)were investigated.Results:107 patients were included,including 63 cases in the combination group and 44 cases in the monotherapy group.The ORR were 78%and 50%(P=0.003),and DCR were 97%and 77%(P=0.002),respectively.At a median follow-up of 13.7 mon,a PFS event occurred in 38.1%and 81.8%of patients in the two groups,with median PFS of18.8 mon and 5.3 mon,respectively(P<0.000,1).Median OS was unreached in the combination group,and 27.8 mon in the monotherapy group(P=0.31).According to the Cox multivariate regression analysis,combination therapy was an independent prognostic factor of PFS.Conclusion:In patients with EGFR-mutant advanced lung adenocarcinoma with concomitant non-EGFR genetic alterations,combination of TKIs and chemotherapy was significantly superior to EGFR-TKIs monotherapy,which should be the preferred treatment option.
文摘Objective The aim of this study was to assess quality of results of elderly patients with coronary disease after medical or revascularisation therapy. Methods In this study, we enrolled 103 patients aged 75 years or older with chronic angina in which 47 patients were assigned coronary angiography and revascularisation and 56 patients with optimised medical therapy. The primary endpoint was quality of life after 6 months, as assessed by questionnaire and the presence of major adverse cardiac events (death, non fatal myocardial infarction, or hospital admission for acute coronary syndrome with or without the need for revascularisation). Results After 6 months follow up, angina severity decreased and measures of quality of life increased in both treatment groups( P <0.05 ); however, these improvements were significantly greater after revascularisation( P <0.01 ). Major adverse cardiac events occurred in 30 ( 53.6% ) of patients in the medical group and 9 ( 19.1% ) in the invasive group ( P <0.01 ).Conclusions Patients aged 75 years or older with angina benefit more from revascularisation than from optimised medical therapy in terms of symptom relief and quality of life. Therefore, these patients should be offered invasive assessment despite their high risk profile followed by revascularisation if feasible.
基金supported by the National Natural Science Foundation of China(22171001,22305001,51972001,52372073)the Natural Science Foundation of Anhui Province of China(2108085MB49).
文摘The realization of real-time thermal feedback for monitoring photothermal therapy(PTT)under near-infrared(NIR)light irradiation is of great interest and challenge for antitumor therapy.Herein,by assembling highly efficient photothermal conversion gold nanorods and a temperature-responsive probe((E)-4-(4-(diethylamino)styryl)-1-methylpyridin-1-ium,PyS)within MOF-199,an intelligent nanoplatform(AMPP)was fabricated for simultaneous chemodynamic therapy and NIR light-induced temperature-feedback PTT.The fluorescence intensity and temperature of the PyS probe are linearly related due to the restriction of the rotation of the characteristic monomethine bridge.Moreover,the copper ions resulting from the degradation of MOF-199 in an acidic microenvironment can convert H_(2)O_(2)into•OH,resulting in tumor ablation through a Fenton-like reaction,and this process can be accelerated by increasing the temperature.This study establishes a feasible platform for fabricating highly sensitive temperature sensors for efficient temperature-feedback PTT.
基金The project supported by the Macao Science and Technology Development Fund(FDCT)(014/2014/A1)
文摘OBJECTIVE Plasmonic nanostructures act as a type of promising candidate for cancer photothermal therapy.These photothermal agents with good biocompatibility and high photothermal conversion efficiency are highly desirable.In the present study,we synthesized poly(diallyldimethylammonium chloride)(PDDAC)coated porous platinum(Pt)nanoparticles for photothermal therapy.METHODS Biocompatibility and cellular uptake of Pt nanoparticles were studied in human glioblastoma U-87 MG cells.Cell viability was evaluated by ATP assay and calcein AM staining.The photothermal therapeutic effect of the Pt nanoparticles was studied under 808-nm laser irradiation.In addition,the synergistic anti-cancer effect of the Pt nanoparticle-based photothermal therapy and doxorubicinwas investigated.RESULTS The as-prepared Pt nanoparticles exhibited considerable photothermal conversion efficiency under 809 nm and 980 nm laser irradiation.In vitro study indicated that the Pt nanoparticles displayed good biocompatibility and high cellular uptake efficiency.In the presence of the Pt nanoparticles,808-nm laser irradiation at 8.4 W·cm-2for3 min induces significant cytotoxicity,and cell necrosis is involved in the photothermal injury.Furthermore,simultaneousapplication of photothermal therapy synergistically enhances the cytotoxicity of anticancer drug doxorubicin.CONCLUSION Therefore,PDADMAC-coated Pt nanoparticles will have great potential in cancer photothermal therapy.
文摘Resistance to cancer therapy continues to be a major limitation for the successful treatment of cancer. There are many published studies on therapy resistance in breast and prostate cancers; however, there are currently no data on molecular markers associated with resistance. The conflicting data were reported regarding the AKT/m-TOR signaling pathway components as markers predicting resistance. The AKT/m-TOR signaling pathway is involved in the development of many human cancers; its activation is related to cell proliferation, angiogenesis, apoptosis, as well as to therapy resistance. Molecular alterations in the AKT/m-TOR signaling pathway provide a platform to identify universal markers associated with the development of resistance to cancer therapy.
文摘OBJECTIVE To explain the high inter-individual variability and the frequency of exceeding the therapeutic reference range and the laboratory alert level of amisulpride,a popula⁃tion pharmacokinetic model in Chinese patients with schizophrenia was built based on therapeu⁃tic drug monitoring data to guide individualized therapy.METHODS Plasma concentration data(330 measurements from 121 patients)were ana⁃lyzed using a nonlinear mixed-effects model⁃ing approach with first-order conditional estima⁃tion with interaction(FOCE I).The concentra⁃tions of amisulpride were detected by HPLC-MS/MS.Age,weight,sex,combination medication history and renal function status were evaluated as main covariates.The model was internally val⁃idated using goodness-of-fit,bootstrap and nor⁃malized prediction distribution error.Recom⁃mended dosage regimens for patients with key covariates were estimated on the basis of Monte Carlo simulations and the established model.RESULTS A one-compartment model with first-order absorption and elimination was found to adequately characterize amisulpride concentra⁃tion in Chinese patients with schizophrenia.The population estimates of the apparent volume of distribution(V/F)and apparent clearance(CL/F)were 12.7 L and 1.12 L·h-1,respectively.Age sig⁃nificantly affected the clearance of amisulpride and the final model was as follow:CL/F=1.04×(AGE/32)-0.624(L·h-1).To avoid exceeding the lab⁃oratory alert level(640μg·L-1),the model-based simulation results showed that the recommended dose of amisulpride was no more than 600 mg per day for patients aged 60 years,800 mg per day for those aged 40 years and 1200 mg per day for those aged 20 years,respectively.CON⁃CLUSION Dosage optimization of amisulpride can be carried out according to age to reduce the risk of adverse reactions.The model can be used as a suitable tool for designing individual⁃ized therapy for Chinese patients with schizo⁃phrenia.
基金Key Program of Capital Development Foundation(编号2007-2040)
文摘In order to study the epidemiological characteristics of cytomegalovirus(CMV)infection in allogeneichematopoietic stem cell transplantation(allo-HSCT)recipients by means of plasma real time quantitative polymerasechain reaction(RQ-PCR),141 adult patients undergoing allo-HSCT between January 2008 and June 2010 were seriallymonitored by RQ-PCR for detecting CMV and guiding the preemptive therapy followed up to 180 days post-HSCT.Theresults showed that the incidence of CMV infection and CMV pneumonia was 81.5%and 2.9%respectively,whichmainly occurred within 2 months post-HSCT.Single-therapy with ganciclovir(GCV)for 63 patients or foscarnet 6patients was performed for preemptive therapy.The total efficacy was 87.8%,and the response patterns were different.CMV infection was more frequent in female patients(P=0.044),and those with aGVHD(P=0.043),using ATG orbasiliximab in conditioning regimens(P=0.049),as well as earlier in patients using ATG or basiliximab or those withaGVHD(P=0.007;P=0.000).The aGVHD,maximum load,positive times of CMV-DNA detection and therapyduration all correlated with the efficacy(P<0.05).It is concluded that the incidence of CMV infection is still high afterHSCT.Plasma RQ-PCR assay for CMV-DNA shows a strong correlation with the clinical outcome of CMV infection,which is useful and suitable for management of CMV infection in HSCT.
文摘An essential prerequisite of any genetherapy technique is the efficient and stable de-livery of transferred DNA into the target cell.Avariety of techniques are available for directly in-troducing DNA into eukaryotic cells,includingcoprecipitation with calcium phosphate,electroporation and microinjection. The efficien-cy of most of these physical transfection tech-niques is less than one in ten thousand, and
基金financially supported by the NTU-Northwestern Institute for Nanomedicine ( NRF-NRFI2017-07)Startup Foundation of Nanjing Medical University
文摘Mechanical forces produced from cells regulate cell functions and fate for tissue development and regeneration.Knowledge in mechanobiology thus provides new strategy for diagnosis and prosthetics.In our work,we develop a platform which could precisely detect cellular traction force with resolution of 100 pN,enabling quantification of chemotherapy at early stage,re-epithelialization and cell collision.Additionally,a better solution for antimicrobial dressing managing infection has been provided by modifying the surface to enable both the disruption on biofilm and the elimination of engaged planktonic bacteria.Mechanobiological study demonstrated our dual-function surface remains harmless to host mammalian cells during thermalablation.Our design could pave the way further for creating soft miniaturized medical robots that defend our living system via safe interaction down to cellular level.
基金The project supported by the general grant fund from Hong Kong Research Grant Committee(476912)Health and Medical Research Fund(13120442)Innovation and Technology Fund of Shenzhen(CXZZ20120619150627260)
文摘OBJECTIVE To prepare hypocrellin B-loaded apoferritin nanoparticles(HB-AFT NPs)for photodynamic therapy on tumor.METHODS HB-AFT NPs were prepared by taking advantage of the reversibleunfolding and refolding character of apoferritin in different pH environments.The photophysical and photobiological properties of hypocrellin B-loaded apoferritin were measured.RESULETS HB molecules were successfully encapsulated within apoferritincavity.HB-AFT-NPs exhibited higher ROS productionthan free HB.Additionally,phototoxicity of HB-AFT NPs to MDA-MB-231 cells was significantly improved as compared to free HB.CONCLUSION Together these results demonstrate that hypocrellin B-loaded apoferritin might be a potential nanoscale photosensitizer.
文摘Objective Recent evidence has indicated that hypertension is associated with impaired cognitive function. However, the prevention of cognitive disorders with antihypertensive therapy remains controversial.The trial provided evidence to compare the efficacy on cognitive function with the combination of amlodipine with diuretics or angiotensin II receptor blocker.
文摘Objective To analyze the clinical features and effects of target therapy of post splenectomy pulmonary hypertension, and improve the diagnosis and treatment of the disease.Methods Clinical data of 18 patients with post splenectomy pulmonary hypertension admitted to our hospital from October 2006 to March 2017 were systematically reviewed.
文摘Objective To explore the application of evidence-based nursing intervention in patients with congenital heart diseases treated by transcatheter interventional therapy.Methods A total of 64 patients with congenital heart diseases who were administered in our hospital from June 2011 to July 2013 were recruited in our research.
文摘Background It’s essential to prevent from thrombosis on device without increasing the risk of bleeding complications after successfully implanted left atrial appendage device.At present,no guidelines recommend about postoperative antithrombotic therapy of left atrial appendage closure(LAAC).The purpose of this study is to investigate the safety and efficacy of different antithrombotic therapies after LAAC.
文摘Corrole,a representative branch of porphyrin,has recently gained popularity.These molecules,viewed as ring‑contracted porphyrinoids containing direct pyrrole‑pyrrole linkages due to the absence of a meso‑carbon atom,exhibit significant photo‑physicochemical properties that make them attractive for various applications.Herein,this review comprehensively discusses the remarkable properties of corrole complexes,as well as related structures and chelation properties.It further explores the biological applications of corrole complexes for in vivo imaging and anticancer therapy.Additionally,it addresses common research bottlenecks and challenges,providing insights into future potential applications in disease diagnosis and treatment.Generally,this review aims to illuminate the significance of corrole complexes and their promising biological applications.
基金supported by National Natural Science Foundation of China(81573443,81330081 and 81673444)
文摘Osteoarthritis(OA)is a most common form of degenerative joint disease,primarily characterized by the degradation of articular cartilage,subchondral sclerosis and inflammation of the synovial membrane.Mesenchymal stem cells(MSCs),a multipotent adult stem cell population,can be isolated from many connective tissue lineages,including those of the diarthrodial joint.Joint-resident MSCs or MSC-like progenitor cells contribute to the maintenance of healthy microenvironment or to the response to trauma.The onset of degenerative changes in the joint related to abnormal condition or depletion of these endogenous MSCs and native host hyaline cartilage cells,leading to limited selfrepair potential of the joint and advance of the degradation.To date,no acknowledged medical treatment strategies,including non-operative and classical surgical techniques,are efficient in restoring normal anatomy and function of hyaline cartilage in OA.This highlights an urgent need for better celled-based therapeutic strategies that supplement these functional cel s exogenously to recover the tissue homeostasis and repair in joint cavity via chondrogenic and anti-in fl ammatory functions.In this review we focus on the role of native MSCs in healthy or OA joint and recent progress in cel-based researches utilizing culture-expanded chondrocytes,pluripotent stem cel s,or MSCs from different sources for treating OA.
基金supported by National Natural Science Foundation of China(81402946)Initializing Fund of Xuzhou Medical University of China(D2014017 and D2014010)Natural Science Research Grant of Higher Education of Jiangsu Province of China(14KJD310002)
文摘OBJECTIVE To explore the effect of connexin(Cx)40-formed gap junctional intercellular communication(GJIC)on Photofrin-photodynamic therapy(PDT)phototoxicity in Cx40-transfected He La cells and its potential mechanisms.METHODS He La cell line stably transfected to express Cx40 was seeded at high and low cell density,respectively,to assess in vitro photosensitivity using CCK8 assay.Western blot assay was performed to detect the expression of Cx40.The intracellular ROS and Ca^(2+) concentrations were determined using flow cytometer.4-HNE and ceramide were measured using ELISA assay.RESULTS Cx40-composed GJ formation at high density enhances the phototoxicity of PhotofrinPDT.When the Cx40 is not expressed or Cx40 channels are blocked,the phototoxicity in high-density cultures substantially reduces,indicating that the enhanced PDT phototoxicity at high density is mediated by Cx40-composed GJIC.The GJIC-mediated increase in PDT phototoxicity was associated with ROS and calcium-mediated stress signaling pathways.CONCLUSION The work uniquely presents the ability of Cx40-composed GJIC to enhance the sensitivity of malignant cells to PDT,and indicates that maintenance or increase of Cx40-formed GJIC may be a profitable strategy towards the enhancement of PDT therapeutic efficiency.
文摘Redacted by Specialty Committee of Heat-sensitive Moxibustion of WFCMS,Standardized Manipulations of Heat-sensitive Moxibustion(HSM).Therapy states the scope,normative references,terms and definitions,preoperative preparations,operation methods and procedure,indications and notice of HSM Therapy.
