In this paper, based on the experience and practice of school-enterprise cooperation in developed countries, the current situation ofschool-enterprise cooperation in China was studied. Through analysis and comparison,...In this paper, based on the experience and practice of school-enterprise cooperation in developed countries, the current situation ofschool-enterprise cooperation in China was studied. Through analysis and comparison, the mode of school-enterprise cooperationsuitable for higher vocational education in China was explored to promote the development of higher vocational education inChina. The current situation and existing problems of work-study integration in higher vocational education in China wereanalyzed, and different modes of work-study combination in foreign higher vocational education were compared. Under thecurrent situation, earnestly studying and drawing lessons from the experience of foreign developed countries is of greatsignificance to the continuing development of school-enterprise cooperation and the talent training mode of work-studycombination in national model colleges and key universities.展开更多
Coherent polarization beam combination （CPBC） is a new kind of coherent beam combination configuration with high combining efficiency and excellent beam quality. In order to extend the CPBC system to a large scale, ...Coherent polarization beam combination （CPBC） is a new kind of coherent beam combination configuration with high combining efficiency and excellent beam quality. In order to extend the CPBC system to a large scale, we provide a comparative study on the power scaling performance of three different coherent polarization beam combination system structures. It is found that the pairwise structure has high tolerance to aberrations and has the potential to extend to a large scale with high combining efficiency. In consideration of all the aberrations, the combining efficiency of the pairwise structure can be attained as high as 90% when the combined beams are more than 200. Some instructive suggestions are given to extend the CPBC system to a large scale.展开更多
With the development of Global Navigation Satellite Systems(GNSS),geodetic GNSS receivers have been utilized to monitor sea levels using GNSS-Interferometry Reflectometry(GNSS-IR)technology.The multi-mode,multi-freque...With the development of Global Navigation Satellite Systems(GNSS),geodetic GNSS receivers have been utilized to monitor sea levels using GNSS-Interferometry Reflectometry(GNSS-IR)technology.The multi-mode,multi-frequency signals of GPS,GLONASS,Galileo,and Beidou can be used for GNSS-IR sea level retrieval,but combining these retrievals remains problematic.To address this issue,a GNSS-IR sea level retrieval combination system has been developed,which begins by analyzing error sources in GNSS-IR sea level retrieval and establishing and solving the GNSS-IR retrieval equation.This paper focuses on two key points:time window selection and equation stability.The stability of the retrieval combination equations is determined by the condition number of the coefficient matrix within the time window.The impact of ill-conditioned coefficient matrices on the retrieval results is demonstrated using an extreme case of SNR data with only ascending or descending trajectories.After determining the time window and removing ill-conditioned equations,the multi-mode,multi-frequency GNSS-IR retrieval is performed.Results from three International GNSS Service(IGS)stations show that the combination method produces high-precision,high-resolution,and high-reliability sea level retrieval combination sequences.展开更多
In this paper, based on the experience and practice of school-enterprise cooperation in developed countries, the current situation of school-enterprise cooperation in China was studied. Through analysis and comparison...In this paper, based on the experience and practice of school-enterprise cooperation in developed countries, the current situation of school-enterprise cooperation in China was studied. Through analysis and comparison, the mode of school-enterprise cooperation suitable for higher vocational education in China was explored to promote the development of higher vocational education in China. The current situation and existing problems of work-study integration in higher vocational education in China were analyzed, and different modes of work-study combination in foreign higher vocational education were compared. Under the current situation, earnestly studying and drawing lessons from the experience of foreign developed countries is of great significance to the continuing development of school-enterprise cooperation and the talent training mode of work-study combination in national model colleges and key universities.展开更多
BACKGROUND Thiocolchicoside(TCC),a muscle relaxant with anti-inflammatory properties,is often used alongside nonsteroidal anti-inflammatory drugs(NSAIDs)to treat musculoskeletal pain.This synergistic approach leverage...BACKGROUND Thiocolchicoside(TCC),a muscle relaxant with anti-inflammatory properties,is often used alongside nonsteroidal anti-inflammatory drugs(NSAIDs)to treat musculoskeletal pain.This synergistic approach leverages the complementary mechanisms of action,providing more effective relief for conditions such as arthritis,muscle spasms,and soft tissue injuries.AIM To evaluate the comparative efficacy of the combination therapy of TCC and NSAIDs vs NSAID monotherapy in pain management.METHODS A systematic search of PubMed and Google Scholar databases through October 2024 was performed to evaluate the effectiveness of combined TCC and NSAID therapy vs NSAIDs alone.A retrospective analysis of electronic medical records from India spanning 3 years(2020-2023)examined treatment patterns and focused on clinical outcomes including pain relief,functional improvement,and adverse effects.Key metrics for assessment included visual analog scale scores and hand-to-floor distance,with secondary outcomes assessing patient satisfaction and adverse event(AE)incidence.RESULTS A systematic literature search revealed seven studies,involving 1137 subjects,aligning with the eligibility criteria from a total of 833 hits.Combination therapy using parenteral TCC with NSAIDs significantly reduced pain intensity[standardised mean difference(SMD):-1.33,P<0.001]and enhanced functional improvement(SMD:-1.08,P<0.001)compared to NSAIDs alone.Patients on combination therapy are 6.7 times more likely to experience over 30%pain relief and 5.2 times more likely to achieve over 50%pain relief.Post surgery pain reduction and patient satisfaction were notably higher in the combination group[odds ratio(OR)=10.14,P<0.001].There were no significant differences in mild/moderate AE rates between the groups(OR=1.30,P=0.378).CONCLUSION Evidence indicates that multimodal therapy,including parenteral TCC with NSAIDs,provides quicker and effective pain relief,reduces muscle spasms,and improves hand-to-floor distance compared to using NSAIDs or TCC alone.展开更多
The vibration response and noise caused by subway trains can affect the safety and comfort of superstructures.To study the dynamic response characteristics of subway stations and superstructures under train loads with...The vibration response and noise caused by subway trains can affect the safety and comfort of superstructures.To study the dynamic response characteristics of subway stations and superstructures under train loads with a hard combination,a numerical model is developed in this study.The indoor model test verified the accuracy of the numerical model.The influence laws of different hard combinations,train operating speeds and modes were studied and evaluated accordingly.The results show that the frequency corresponding to the peak vibration acceleration level of each floor of the superstructure property is concentrated at 10–20 Hz.The vibration response decreases in the high-frequency parts and increases in the lowfrequency parts with increasing distance from the source.Furthermore,the factors,such as train operating speed,operating mode,and hard combination type,will affect the vibration of the superstructure.The vibration response under the reversible operation of the train is greater than that of the unidirectional operation.The operating speed of the train is proportional to its vibration response.The vibration amplification area appears between the middle and the top of the superstructure at a higher train speed.Its vibration acceleration level will exceed the limit value of relevant regulations,and vibration-damping measures are required.Within the scope of application,this study provides some suggestions for constructing subway stations and superstructures.展开更多
Nanotechnology in cancer therapy has significantly advanced treatment precision,effectiveness,and safety,improving patient outcomes and personalized care.Engineered smart nanoparticles and cell-based therapies are des...Nanotechnology in cancer therapy has significantly advanced treatment precision,effectiveness,and safety,improving patient outcomes and personalized care.Engineered smart nanoparticles and cell-based therapies are designed to target tumor cells,precisely sensing the tumor microenvironment(TME)and sparing normal cells.These nanoparticles enhance drug accumulation in tumors by solubilizing insoluble compounds or preventing their degradation,and they can also overcome therapy resistance and deliver multiple drugs simultaneously.Despite these benefits,challenges remain in patient-specific responses and regulatory approvals for cell-based or nanoparticle therapies.Cell-based drug delivery systems(DDSs)that primarily utilize the immune-recognition principle between ligands and receptors have shown promise in selectively targeting and destroying cancer cells.This review aims to provide a comprehensive overview of various nanoparticle and cell-based drug delivery system types used in cancer research.It covers approved and experimental nanoparticle therapies,including liposomes,micelles,protein-based and polymeric nanoparticles,as well as cell-based DDSs like macrophages,T-lymphocytes,dendritic cells,viruses,bacterial ghosts,minicells,SimCells,and outer membrane vesicles(OMVs).The review also explains the role of TME and its impact on developing smart DDSs in combination therapies and integrating nanoparticles with cell-based systems for targeting cancer cells.By detailing DDSs at different stages of development,from laboratory research to clinical trials and approved treatments,this review provides the latest insights and a collection of valuable citations of the innovative strategies that can be improved for the precise treatment of cancer.展开更多
BACKGROUND Precision medicine is an emerging field that includes tumor-targeted delivery and tumor microenvironment.This review explores the synergistic potential of combining nano-drug delivery systems with low radia...BACKGROUND Precision medicine is an emerging field that includes tumor-targeted delivery and tumor microenvironment.This review explores the synergistic potential of combining nano-drug delivery systems with low radiation doses to achieve optimized therapeutic outcomes,particularly in the context of cancer treatment.Nanoparticle-based drug carriers offer precise and targeted delivery,enhancing the therapeutic index of anticancer agents.The use of lower radiation doses has become a focus in radiation oncology to minimize off-target effects on healthy tissues in palliation treatment with high-target volume lesions.AIM To conduct a bibliometric review of nanomedicine and glioblastoma(GBM),all relevant studies from the last two decades were included.METHODS The search strategy comprised the keywords“nanomedicine”and“glioblastoma”in the title and/or abstract.All English-language documents from 1 January 2000 to 31 December 2023 were considered for the analysis.R code(version 4.2.0)with R Studio(version 2022.12.0-353)and the Bibliometrix package(version 4.0.1)were used for the analysis.A total of 680 documents were collected.RESULTS We analyzed the bibliometric features of nanomedicine in glioma.With the limitations of the research,our analysis aims to highlight the increasing interest of researchers in the precision medicine field in GBM treatment and lead us to suggest further studies focusing on the association between nanomedicine and radiotherapy.CONCLUSION Due to the poor prognosis associated with GBM,new therapeutic approaches are necessary.There is an increasing interest in precision medicine,which includes nanomedicine and radiotherapy,for GBM treatment.This integration enhances the efficacy of targeted treatments and provides a promising avenue for reducing adverse effects,signifying a notable advancement in precision oncology.展开更多
To tackle the difficulties of the point prediction in quantifying the reliability of landslide displacement prediction,a data-driven combination-interval prediction method(CIPM)based on copula and variational-mode-dec...To tackle the difficulties of the point prediction in quantifying the reliability of landslide displacement prediction,a data-driven combination-interval prediction method(CIPM)based on copula and variational-mode-decomposition associated with kernel-based-extreme-learningmachine optimized by the whale optimization algorithm(VMD-WOA-KELM)is proposed in this paper.Firstly,the displacement is decomposed by VMD to three IMF components and a residual component of different fluctuation characteristics.The key impact factors of each IMF component are selected according to Copula model,and the corresponding WOA-KELM is established to conduct point prediction.Subsequently,the parametric method(PM)and non-parametric method(NPM)are used to estimate the prediction error probability density distribution(PDF)of each component,whose prediction interval(PI)under the 95%confidence level is also obtained.By means of the differential evolution algorithm(DE),a weighted combination model based on the PIs is built to construct the combination-interval(CI).Finally,the CIs of each component are added to generate the total PI.A comparative case study shows that the CIPM performs better in constructing landslide displacement PI with high performance.展开更多
Diabetes mellitus is a substantial global health threat due to its high prevalence and its serious complications.The hyperglycemic state causes damage to vascular endothelial cells and disturbance of lipid metabolism,...Diabetes mellitus is a substantial global health threat due to its high prevalence and its serious complications.The hyperglycemic state causes damage to vascular endothelial cells and disturbance of lipid metabolism,thus contributing to the development of vascular disorders,especially atherosclerotic diseases.Aggressive glycemic control combined with vascular intervention is critical to the prevention and treatment of diabetes-associated atherosclerosis.It is suggested that metformin should be combined with hypoglycemic agents with proven vascular benefits for treating type 2 diabetes(T2DM)complicated with atherosclerotic diseases.Clinical studies indicates that the preferred combination is metformin with either glucagon-like peptide-1 receptor agonist or sodium/glucose cotransporter-2 inhibitor,which could offer additional vascular benefits and reduce the risk of atherosclerotic complications.Likewise,combination therapy with metformin and hypolipidemic agents has also shown additive effects on glucose control and lipid-lowering in patients with both diabetes and dyslipidemia,whereas extensive clinical trials using atherosclerotic-associated outcomes are required to support the vascular benefits.Moreover,co-administration of metformin with systemic antioxidant or anti-inflammatory therapy may also provide additional vascular benefits as indicated by several animal studies.For instance,a recent study found that additional supplementation of cholecalciferol and taurine enhanced metformin efficacy in controlling diabetes while reducing the risk of associated atherosclerotic complications.However,these potential benefits remain need validation by the evidence from clinical studies.Despite the limitations,such as heterogeneity across different patient populations,and deficiency in long-term outcomes,such efforts can contribute to finding optimal drug combinations to improve the management of T2DM and reduce its atherosclerotic complications.展开更多
Astragali Radix(AR), a traditional Chinese medicine(TCM), has demonstrated therapeutic efficacy against various diseases, including cardiovascular conditions, over centuries of use.While doxorubicin serves as an effec...Astragali Radix(AR), a traditional Chinese medicine(TCM), has demonstrated therapeutic efficacy against various diseases, including cardiovascular conditions, over centuries of use.While doxorubicin serves as an effective chemotherapeutic agent against multiple cancers, its clinical application remains constrained by significant cardiotoxicity. Research has indicated that AR exhibits protective properties against doxorubicin-induced cardiomyopathy(DIC);however, the specific bioactive components and underlying mechanisms responsible for this therapeutic effect remain incompletely understood. This investigation seeks to identify the protective bioactive components in AR against DIC and elucidate their mechanisms of action.Through network medicine analysis, astragaloside Ⅳ(AsⅣ) and formononetin(FMT) were identified as potential cardioprotective agents from 129 AR components. In vitro experiments using H9c2 rat cardiomyocytes revealed that the AsⅣ-FMT combination(AFC) effectively reduced doxorubicin-induced cell death in a dose-dependent manner, with optimal efficacy at a 1∶2 ratio. In vivo, AFC enhanced survival rates and improved cardiac function in both acute and chronic DIC mouse models. Additionally, AFC demonstrated cardiac protection while maintaining doxorubicin's anti-cancer efficacy in a breast cancer mouse model. Lipidomic and metabolomics analyses revealed that AFC normalized doxorubicin-induced lipid profile alterations, particularly by reducing fatty acid accumulation. Gene knockdown studies and inhibitor experiments in H9c2 cells demonstrated that AsⅣ and FMT upregulated peroxisome proliferator activated receptor γ coactivator 1α(PGC-1α) and PPARα, respectively, two key proteins involved in fatty acid metabolism. This research establishes AFC as a promising therapeutic approach for DIC, highlighting the significance of multi-target therapies derived from natural herbals in contemporary medicine.展开更多
Objective:To explore the potential mechanisms of a baicalin-geniposide combination against cerebral ischemia using a network pharmacology strategy.Method:We used network pharmacology integrating drug-target-disease in...Objective:To explore the potential mechanisms of a baicalin-geniposide combination against cerebral ischemia using a network pharmacology strategy.Method:We used network pharmacology integrating drug-target-disease interactions to identify key pathways which were validated in a rat middle cerebral artery occlusion model treated with baicalin(55 mg/kg),geniposide(5 mg/kg),or their 11:1 combination.Therapeutic efficacy and mechanistic insights were evaluated using triphenyltetrazolium chloride staining,Evans blue assay,enzyme-linked immunosorbent assay,and Western blot.Results:The results revealed that the nuclear factor-kappa B(NF-κB)signaling pathway is inhibited in combination treatment of cerebral ischemia.Ten targets were identified as key nodes in the protein-protein interaction network:interleukin 6(IL-6),interleukin-1β,interleukin 18,C-C motif ligand 2,C-C motif ligand 4,interleukin 10,interferon-γ-inducible protein 10,C-C motif ligand 3,tumor necrosis factor-α(TNF-α),interleukin-1α.The baicalin-geniposide combination significantly reduced infarct volume,improved neurological deficits,and alleviated brain edema/blood-brain barrier leakage compared with monotherapy.Additionally,it significantly inhibited toll-like receptor 4(TLR4)/NF-κB signaling and downregulated pro-inflammatory cytokines TNF-αand IL-6 levels.Conclusion:The baicalin-geniposide combination alleviated cerebral ischemia-reperfusion injury by synergistically suppressing the TLR4/NF-κB pathway and its downstream inflammatory factors.展开更多
Background:Human skin is affected by ultraviolet rays on a daily basis,and excessive ultraviolet radiation(UVR)can lead to sunburn erythema,tanning,photoaging,and skin tumors.The combination of Astragali Radix(AR)and ...Background:Human skin is affected by ultraviolet rays on a daily basis,and excessive ultraviolet radiation(UVR)can lead to sunburn erythema,tanning,photoaging,and skin tumors.The combination of Astragali Radix(AR)and Anemarrhenae Rhizoma(AAR)is a common pairing in traditional Chinese medicine(TCM).According to earlier studies,they possess properties capable of alleviating the adverse impacts of UVR on the skin.However,the specific actions and underlying mechanisms require further investigation.The study aims to analyze the efficacy of AR-AAR in preventing UVR-induced skin damage and to clarify the associated molecular mechanisms.Methods:Potential signaling pathways by which AR and AAR may protect against UVR-induced skin damage were identified with network pharmacology,molecular docking techniques and molecular dynamics(MD)simulation.Except the normal group,the back skin of SD rats was exposed to 1.1 mW/cm^(2) UVA combined with 0.1 mW/cm^(2) UVB daily,and the UVR skin damage model was established.Morphological features of skin tissues of different groups were discovered through Hematoxylin and Eosin(HE)staining,Masson staining,Weigert staining.ELISA was utilized to measure the levels of reactive oxygen species(ROS),Interleukin 6(IL-6),Interleukin 1β(IL-1β)and Tumor necrosis factos-α(TNF-α)in skin tissues.RT-PCR and Western blot were employed to quantify the mRNA and protein contents of PI3K,AKT,and MMP-9.Results:Network pharmacology analysis predicts that AR-AAR may improve skin damage induced by UVR through the PI3K/AKT signaling pathway.Histological staining shows that AR-AAR can significantly reduce inflammatory infiltration and fibrosis in damaged skin.Treatment with AR-AAR(2:1)significantly reduced the expression levels of IL-1β,IL-6,TNF-αand ROS in UVR-damaged rat skin.After treatment with AR-AAR(2:1),not only did the relative mRNA expression levels of PI3K and AKT and the protein expression levels of PI3K,AKT,P-PI3K,and P-AKT increase,but the mRNA and protein expression levels of MMP-9 decreased.Conclusion:The study indicate that the AR-AAR combination and its active components may mitigate UVR skin damage by modulating the PI3K/AKT signaling pathway.展开更多
Cancer remains one of the major threats to public health.Traditional chemotherapy,radiotherapy,and other anti-tumor therapies have numerous limitations in clinical treatment.Notwithstanding the considerable advances m...Cancer remains one of the major threats to public health.Traditional chemotherapy,radiotherapy,and other anti-tumor therapies have numerous limitations in clinical treatment.Notwithstanding the considerable advances made in recent years with regard to immunotherapy in both basic research and clinical practice,there remains scope for further improvement,particularly with respect to its efficacy against solid tumors.With advancements in nanotechnology,tumor nanovaccines hold immense potential for preventing tumor recurrence and treating metastatic tumors.Nevertheless,the considerable heterogeneity of tumor immunogenicity presents a number of significant challenges in the development of nanometrescale vaccines targeting solid tumors.Recent findings indicate that immune checkpoint inhibitor(ICI)therapy can improve the immunosuppressive microenvironment within tumors,while nanovaccines can also augment tumor sensitivity toward ICIs.Consequently,combining tumor nanovaccine with ICI therapy holds promise for effectively eradicating tumors or controlling their recurrence and metastasis during cancer treatment.This review delves into the mechanism behind combining tumor nanovaccine with ICI while focusing on factors influencing this combined therapy approach.Moreover,it offers an overview of the current research status regarding the combination of tumor nanovaccines with chemotherapy,radiotherapy,photothermal therapy,and sonodynamic therapy,as well as prospects for future developments in this field.展开更多
BACKGROUND Chemotherapy combined with anti-angiogenic therapy has become an important strategy for the treatment of advanced gastric cancer(AGC);however,the regimen needs optimization.AIM To evaluate the efficacy of a...BACKGROUND Chemotherapy combined with anti-angiogenic therapy has become an important strategy for the treatment of advanced gastric cancer(AGC);however,the regimen needs optimization.AIM To evaluate the efficacy of albumin-bound paclitaxel(nab-ptx)combined with the small molecule vascular endothelial growth factor inhibitor anlotinib in secondline and beyond treatment of AGC.METHODS We collected data from AGC patients at our hospital who experienced disease progression after first-line chemotherapy and received anlotinib combined with nab-ptx.The primary endpoints included overall survival(OS)and progressionfree survival(PFS),while the secondary endpoints were objective response rate(ORR),disease control rate(DCR),and adverse events(AEs).RESULTS Preliminary results indicated that anlotinib combined with nab-ptx can provide significant efficacy in second-line or above treatment for AGC(median PFS=6.0 months,median OS=12.0 months),with an ORR of 42%and a DCR of 78%.Further analysis revealed that patients who experienced hypertension,proteinuria,and hand-foot syndrome during treatment had better efficacy compared to those who did not experience these AEs.Mechanistic studies suggest that this regimen likely exerts synergistic anti-tumor effects by activating the immune response through the reduction of regulatory T-cell proportions.Common adverse reactions included bone marrow suppression,peripheral neuropathy,hypertension,proteinuria,and hand-foot syndrome,which were manageable and resolved with appropriate interventions,indicating the promising application of this regimen in second-line or above treatment for AGC.CONCLUSION The combination of anlotinib and nab-ptx shows promising efficacy with fewer toxicities in AGC treatment.The regimen holds promise as a second-line treatment of AGC;however,its specific clinical value requires further research.展开更多
Histone deacetylase inhibitors(HDACis),such as trichostatin A(TSA),have been recognized as promising anti-cancer agents due to their capacity to restore epigenetic regulation and reactivate tumor suppressor genes.Howe...Histone deacetylase inhibitors(HDACis),such as trichostatin A(TSA),have been recognized as promising anti-cancer agents due to their capacity to restore epigenetic regulation and reactivate tumor suppressor genes.However,emerging evidence indicates that unintended pro-metastatic effects may offset the therapeutic benefits of HDACis.Chen et al elucidate this paradox,demonstrating that TSA-induced hyperacetylation activates the BRD4/c-Myc/ER-stress axis,thereby promoting epithelial-mesenchymal transition and metastasis in esophageal squamous cell carcinoma(ESCC).Furthermore,they clarify the clinical significance of histone acetylation in the prognostic evaluation of ESCC.Their findings underscore the complexity of epigenetic therapies and highlight the necessity of reevaluating the associated risks and combinatorial therapeutic strategies with HDACi-based treatments.Here,we summarize the potential risks of HDACis therapy and discuss feasible combination therapeutic strategies.展开更多
The diversity,complexity,heterogeneity,and drug resistance of tumors make it challenging to meet the clinical needs of a single apoptosis-inducing chemotherapy.The combination of apoptosis and ferroptosis is expected ...The diversity,complexity,heterogeneity,and drug resistance of tumors make it challenging to meet the clinical needs of a single apoptosis-inducing chemotherapy.The combination of apoptosis and ferroptosis is expected to address the side effects of chemotherapy and enhance therapeutic efficacy.Here,an amphiphilic pH-responsive doxorubicin(DOX)and ferrocene(Fc)-containing copolyprodrug(P(ADH-DOXFc)-PEG)was designed with high DOX and Fc content of 66.5%and 0.58 mmol/g by a facile polycondensation for combining chemotherapy with ferroptosis in cancer treatment.A drug self-delivery system(DSDS)with an average hydrodynamic diameter(D_(h))of 135 nm can be easily obtained via self-assembly with the polyprodrug blocks as the hydrophobic core and PEG as the hydrophilic brush.The cumulative DOX release reached 72.7%in the simulated tumor intracellular acidic microenvironment within 56 h,whereas the premature drug leakage was only 6.2%in the simulated normal physiological medium.The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)assay results indicated an IC_(50)of 8.2μg/mL,exhibiting enhanced anti-tumor efficacy and a successful combination of apoptosis and ferroptosis,with a combination index(CI)of 0.88.展开更多
BACKGROUND Endoscopy allows for the direct observation of primary tumor characteristics and responses after neoadjuvant treatment.However,reports on endoscopic evaluation following neoadjuvant immunotherapy remain lim...BACKGROUND Endoscopy allows for the direct observation of primary tumor characteristics and responses after neoadjuvant treatment.However,reports on endoscopic evaluation following neoadjuvant immunotherapy remain limited.AIM To examine the predictive value of endoscopic findings of primary tumors for responses to neoadjuvant immunotherapy.METHODS This retrospective study,conducted at a tertiary center in China,evaluated 74 patients with colorectal cancer,including 17 with deficient mismatch repair(dMMR)and 15 with proficient mismatch repair(pMMR)tumors.Patients underwent neoadjuvant immunotherapy followed by surgery.Endoscopic findings before and after neoadjuvant immunotherapy were reviewed and compared with the pathology of the resected specimens.RESULTS In the pMMR group(n=57 evaluable patients),endoscopy identified 11/17 patients who achieved a complete response(CR),while misidentifying 1/40 patients with residual disease as CR(64.7%vs 2.5%,P<0.01).Conversely,22/40 patients with residual disease were accurately identified as achieving a partial response(PR),with 1/17 patients who achieved CR misclassified as PR(55.0%vs 5.9%,P<0.01).The sensitivity,specificity,and accuracy of endoscopic diagnosis for pathological CR were 64.7%,97.5%,and 87.7%,respectively.In the dMMR cohort,endoscopy classified 9/17 patients as CR and 2 of the remaining patients with residual tumors as PR(64.3%vs 66.7%,P=0.73).The method demonstrated 100%sensitivity and 82.4%accuracy in diagnosing pathological CR.CONCLUSION Endoscopic evidence of CR or PR was well correlated with postoperative pathological outcomes in the pMMR cohort.Despite endoscopic indications of tumor residue,a complete pathological response post-surgery was possible in the dMMR cohort.展开更多
Recently,Choe-Koo-Wang(J Funct Anal,2020,278)demonstrated the rigid phenomenon:The compact linear combination of composition operators under the Coefficient Non-cancellation Condition(CNC),implies that each difference...Recently,Choe-Koo-Wang(J Funct Anal,2020,278)demonstrated the rigid phenomenon:The compact linear combination of composition operators under the Coefficient Non-cancellation Condition(CNC),implies that each difference is compact on the weighted Bergman space in the unit disk.Motivated by the subtle connection of composition operator theory on the weighted Bergman spaces,Korenblum spaces and bounded holomorphic function spaces,we first explore the rigid phenomenon which also holds on the Korenblum space over the unit ball.Furthermore,we discuss which difference of composition operators is compact when the compact combination of composition operators does not satisfy the condition(CNC)on Korenblum spaces and bounded holomorphic function spaces over the unit ball setting.展开更多
Agricultural land development is a pivotal strategy for addressing the global food security crisis.Barren grassland,especially those in mountainous regions,constitutes critical areas where cultivation can substantiall...Agricultural land development is a pivotal strategy for addressing the global food security crisis.Barren grassland,especially those in mountainous regions,constitutes critical areas where cultivation can substantially enhance land resources.This study highlights the necessity for a precise correlation between land development initiatives and constraints in order to optimize efficiency and enhance the effectiveness of such projects,with the core being the seamless integration of land development engineering and techniques to eliminate agricultural constraints.This study employs a systems engineering approach to classify improvement factors into mobile and fixed categories,elucidating the integration methods of constraint factors.Adhering to the Wooden Barrel Principle,these constraints were rigorously analyzed based on soil quality,land topography,water availability,and agricultural infrastructure.An innovative method of engineering type combination is proposed,which effectively explains the correlation between natural factors combination,project type combination,and target factors combination.It provides a convenient way for the selection of barren grassland development projects and lays a foundation for land planning,development project establishment,program selection,engineering design,and budget preparation.Taking Tang County of China as an example,it is divided into 19 factor improvement areas,a quick reference table of engineering types is established,and 14 main types of engineering combinations are obtained,which lays a foundation for the application of theoretical framework in practice.展开更多
文摘In this paper, based on the experience and practice of school-enterprise cooperation in developed countries, the current situation ofschool-enterprise cooperation in China was studied. Through analysis and comparison, the mode of school-enterprise cooperationsuitable for higher vocational education in China was explored to promote the development of higher vocational education inChina. The current situation and existing problems of work-study integration in higher vocational education in China wereanalyzed, and different modes of work-study combination in foreign higher vocational education were compared. Under thecurrent situation, earnestly studying and drawing lessons from the experience of foreign developed countries is of greatsignificance to the continuing development of school-enterprise cooperation and the talent training mode of work-studycombination in national model colleges and key universities.
文摘Coherent polarization beam combination （CPBC） is a new kind of coherent beam combination configuration with high combining efficiency and excellent beam quality. In order to extend the CPBC system to a large scale, we provide a comparative study on the power scaling performance of three different coherent polarization beam combination system structures. It is found that the pairwise structure has high tolerance to aberrations and has the potential to extend to a large scale with high combining efficiency. In consideration of all the aberrations, the combining efficiency of the pairwise structure can be attained as high as 90% when the combined beams are more than 200. Some instructive suggestions are given to extend the CPBC system to a large scale.
基金National Natural Science Foundation of China(No.42004018)。
文摘With the development of Global Navigation Satellite Systems(GNSS),geodetic GNSS receivers have been utilized to monitor sea levels using GNSS-Interferometry Reflectometry(GNSS-IR)technology.The multi-mode,multi-frequency signals of GPS,GLONASS,Galileo,and Beidou can be used for GNSS-IR sea level retrieval,but combining these retrievals remains problematic.To address this issue,a GNSS-IR sea level retrieval combination system has been developed,which begins by analyzing error sources in GNSS-IR sea level retrieval and establishing and solving the GNSS-IR retrieval equation.This paper focuses on two key points:time window selection and equation stability.The stability of the retrieval combination equations is determined by the condition number of the coefficient matrix within the time window.The impact of ill-conditioned coefficient matrices on the retrieval results is demonstrated using an extreme case of SNR data with only ascending or descending trajectories.After determining the time window and removing ill-conditioned equations,the multi-mode,multi-frequency GNSS-IR retrieval is performed.Results from three International GNSS Service(IGS)stations show that the combination method produces high-precision,high-resolution,and high-reliability sea level retrieval combination sequences.
文摘In this paper, based on the experience and practice of school-enterprise cooperation in developed countries, the current situation of school-enterprise cooperation in China was studied. Through analysis and comparison, the mode of school-enterprise cooperation suitable for higher vocational education in China was explored to promote the development of higher vocational education in China. The current situation and existing problems of work-study integration in higher vocational education in China were analyzed, and different modes of work-study combination in foreign higher vocational education were compared. Under the current situation, earnestly studying and drawing lessons from the experience of foreign developed countries is of great significance to the continuing development of school-enterprise cooperation and the talent training mode of work-study combination in national model colleges and key universities.
文摘BACKGROUND Thiocolchicoside(TCC),a muscle relaxant with anti-inflammatory properties,is often used alongside nonsteroidal anti-inflammatory drugs(NSAIDs)to treat musculoskeletal pain.This synergistic approach leverages the complementary mechanisms of action,providing more effective relief for conditions such as arthritis,muscle spasms,and soft tissue injuries.AIM To evaluate the comparative efficacy of the combination therapy of TCC and NSAIDs vs NSAID monotherapy in pain management.METHODS A systematic search of PubMed and Google Scholar databases through October 2024 was performed to evaluate the effectiveness of combined TCC and NSAID therapy vs NSAIDs alone.A retrospective analysis of electronic medical records from India spanning 3 years(2020-2023)examined treatment patterns and focused on clinical outcomes including pain relief,functional improvement,and adverse effects.Key metrics for assessment included visual analog scale scores and hand-to-floor distance,with secondary outcomes assessing patient satisfaction and adverse event(AE)incidence.RESULTS A systematic literature search revealed seven studies,involving 1137 subjects,aligning with the eligibility criteria from a total of 833 hits.Combination therapy using parenteral TCC with NSAIDs significantly reduced pain intensity[standardised mean difference(SMD):-1.33,P<0.001]and enhanced functional improvement(SMD:-1.08,P<0.001)compared to NSAIDs alone.Patients on combination therapy are 6.7 times more likely to experience over 30%pain relief and 5.2 times more likely to achieve over 50%pain relief.Post surgery pain reduction and patient satisfaction were notably higher in the combination group[odds ratio(OR)=10.14,P<0.001].There were no significant differences in mild/moderate AE rates between the groups(OR=1.30,P=0.378).CONCLUSION Evidence indicates that multimodal therapy,including parenteral TCC with NSAIDs,provides quicker and effective pain relief,reduces muscle spasms,and improves hand-to-floor distance compared to using NSAIDs or TCC alone.
基金National Natural Science Foundation of China under Grant No.51578463。
文摘The vibration response and noise caused by subway trains can affect the safety and comfort of superstructures.To study the dynamic response characteristics of subway stations and superstructures under train loads with a hard combination,a numerical model is developed in this study.The indoor model test verified the accuracy of the numerical model.The influence laws of different hard combinations,train operating speeds and modes were studied and evaluated accordingly.The results show that the frequency corresponding to the peak vibration acceleration level of each floor of the superstructure property is concentrated at 10–20 Hz.The vibration response decreases in the high-frequency parts and increases in the lowfrequency parts with increasing distance from the source.Furthermore,the factors,such as train operating speed,operating mode,and hard combination type,will affect the vibration of the superstructure.The vibration response under the reversible operation of the train is greater than that of the unidirectional operation.The operating speed of the train is proportional to its vibration response.The vibration amplification area appears between the middle and the top of the superstructure at a higher train speed.Its vibration acceleration level will exceed the limit value of relevant regulations,and vibration-damping measures are required.Within the scope of application,this study provides some suggestions for constructing subway stations and superstructures.
文摘Nanotechnology in cancer therapy has significantly advanced treatment precision,effectiveness,and safety,improving patient outcomes and personalized care.Engineered smart nanoparticles and cell-based therapies are designed to target tumor cells,precisely sensing the tumor microenvironment(TME)and sparing normal cells.These nanoparticles enhance drug accumulation in tumors by solubilizing insoluble compounds or preventing their degradation,and they can also overcome therapy resistance and deliver multiple drugs simultaneously.Despite these benefits,challenges remain in patient-specific responses and regulatory approvals for cell-based or nanoparticle therapies.Cell-based drug delivery systems(DDSs)that primarily utilize the immune-recognition principle between ligands and receptors have shown promise in selectively targeting and destroying cancer cells.This review aims to provide a comprehensive overview of various nanoparticle and cell-based drug delivery system types used in cancer research.It covers approved and experimental nanoparticle therapies,including liposomes,micelles,protein-based and polymeric nanoparticles,as well as cell-based DDSs like macrophages,T-lymphocytes,dendritic cells,viruses,bacterial ghosts,minicells,SimCells,and outer membrane vesicles(OMVs).The review also explains the role of TME and its impact on developing smart DDSs in combination therapies and integrating nanoparticles with cell-based systems for targeting cancer cells.By detailing DDSs at different stages of development,from laboratory research to clinical trials and approved treatments,this review provides the latest insights and a collection of valuable citations of the innovative strategies that can be improved for the precise treatment of cancer.
文摘BACKGROUND Precision medicine is an emerging field that includes tumor-targeted delivery and tumor microenvironment.This review explores the synergistic potential of combining nano-drug delivery systems with low radiation doses to achieve optimized therapeutic outcomes,particularly in the context of cancer treatment.Nanoparticle-based drug carriers offer precise and targeted delivery,enhancing the therapeutic index of anticancer agents.The use of lower radiation doses has become a focus in radiation oncology to minimize off-target effects on healthy tissues in palliation treatment with high-target volume lesions.AIM To conduct a bibliometric review of nanomedicine and glioblastoma(GBM),all relevant studies from the last two decades were included.METHODS The search strategy comprised the keywords“nanomedicine”and“glioblastoma”in the title and/or abstract.All English-language documents from 1 January 2000 to 31 December 2023 were considered for the analysis.R code(version 4.2.0)with R Studio(version 2022.12.0-353)and the Bibliometrix package(version 4.0.1)were used for the analysis.A total of 680 documents were collected.RESULTS We analyzed the bibliometric features of nanomedicine in glioma.With the limitations of the research,our analysis aims to highlight the increasing interest of researchers in the precision medicine field in GBM treatment and lead us to suggest further studies focusing on the association between nanomedicine and radiotherapy.CONCLUSION Due to the poor prognosis associated with GBM,new therapeutic approaches are necessary.There is an increasing interest in precision medicine,which includes nanomedicine and radiotherapy,for GBM treatment.This integration enhances the efficacy of targeted treatments and provides a promising avenue for reducing adverse effects,signifying a notable advancement in precision oncology.
基金financially supported by the National Natural Science Foundation of China(Nos.42277149,41502299,41372306)the Research Planning of Sichuan Education Department,China(No.16ZB0105)+3 种基金the State Key Laboratory of Geohazard Prevention and Geoenvironment Protection Independent Research Project(Nos.SKLGP2016Z007,SKLGP2018Z017,SKLGP2020Z009)Chengdu University of Technology Young and Middle Aged Backbone Program(No.KYGG201720)Sichuan Provincial Science and Technology Department Program(No.19YYJC2087)China Scholarship Council。
文摘To tackle the difficulties of the point prediction in quantifying the reliability of landslide displacement prediction,a data-driven combination-interval prediction method(CIPM)based on copula and variational-mode-decomposition associated with kernel-based-extreme-learningmachine optimized by the whale optimization algorithm(VMD-WOA-KELM)is proposed in this paper.Firstly,the displacement is decomposed by VMD to three IMF components and a residual component of different fluctuation characteristics.The key impact factors of each IMF component are selected according to Copula model,and the corresponding WOA-KELM is established to conduct point prediction.Subsequently,the parametric method(PM)and non-parametric method(NPM)are used to estimate the prediction error probability density distribution(PDF)of each component,whose prediction interval(PI)under the 95%confidence level is also obtained.By means of the differential evolution algorithm(DE),a weighted combination model based on the PIs is built to construct the combination-interval(CI).Finally,the CIs of each component are added to generate the total PI.A comparative case study shows that the CIPM performs better in constructing landslide displacement PI with high performance.
基金Supported by the Natural Science Research Project of Anhui Province,No.2023AH053172National Natural Science Foundation of Anhui Province,No.2408085QH260+1 种基金Projects of Administration of Traditional Chinese Medicine of Anhui Province,No.2024CCCX082National Natural Science Foundation Incubation Program of The Second Hospital of Anhui Medical University,No.2022GMFY08.
文摘Diabetes mellitus is a substantial global health threat due to its high prevalence and its serious complications.The hyperglycemic state causes damage to vascular endothelial cells and disturbance of lipid metabolism,thus contributing to the development of vascular disorders,especially atherosclerotic diseases.Aggressive glycemic control combined with vascular intervention is critical to the prevention and treatment of diabetes-associated atherosclerosis.It is suggested that metformin should be combined with hypoglycemic agents with proven vascular benefits for treating type 2 diabetes(T2DM)complicated with atherosclerotic diseases.Clinical studies indicates that the preferred combination is metformin with either glucagon-like peptide-1 receptor agonist or sodium/glucose cotransporter-2 inhibitor,which could offer additional vascular benefits and reduce the risk of atherosclerotic complications.Likewise,combination therapy with metformin and hypolipidemic agents has also shown additive effects on glucose control and lipid-lowering in patients with both diabetes and dyslipidemia,whereas extensive clinical trials using atherosclerotic-associated outcomes are required to support the vascular benefits.Moreover,co-administration of metformin with systemic antioxidant or anti-inflammatory therapy may also provide additional vascular benefits as indicated by several animal studies.For instance,a recent study found that additional supplementation of cholecalciferol and taurine enhanced metformin efficacy in controlling diabetes while reducing the risk of associated atherosclerotic complications.However,these potential benefits remain need validation by the evidence from clinical studies.Despite the limitations,such as heterogeneity across different patient populations,and deficiency in long-term outcomes,such efforts can contribute to finding optimal drug combinations to improve the management of T2DM and reduce its atherosclerotic complications.
基金supported by the National Natural Science Foundation of China(No.82173947).
文摘Astragali Radix(AR), a traditional Chinese medicine(TCM), has demonstrated therapeutic efficacy against various diseases, including cardiovascular conditions, over centuries of use.While doxorubicin serves as an effective chemotherapeutic agent against multiple cancers, its clinical application remains constrained by significant cardiotoxicity. Research has indicated that AR exhibits protective properties against doxorubicin-induced cardiomyopathy(DIC);however, the specific bioactive components and underlying mechanisms responsible for this therapeutic effect remain incompletely understood. This investigation seeks to identify the protective bioactive components in AR against DIC and elucidate their mechanisms of action.Through network medicine analysis, astragaloside Ⅳ(AsⅣ) and formononetin(FMT) were identified as potential cardioprotective agents from 129 AR components. In vitro experiments using H9c2 rat cardiomyocytes revealed that the AsⅣ-FMT combination(AFC) effectively reduced doxorubicin-induced cell death in a dose-dependent manner, with optimal efficacy at a 1∶2 ratio. In vivo, AFC enhanced survival rates and improved cardiac function in both acute and chronic DIC mouse models. Additionally, AFC demonstrated cardiac protection while maintaining doxorubicin's anti-cancer efficacy in a breast cancer mouse model. Lipidomic and metabolomics analyses revealed that AFC normalized doxorubicin-induced lipid profile alterations, particularly by reducing fatty acid accumulation. Gene knockdown studies and inhibitor experiments in H9c2 cells demonstrated that AsⅣ and FMT upregulated peroxisome proliferator activated receptor γ coactivator 1α(PGC-1α) and PPARα, respectively, two key proteins involved in fatty acid metabolism. This research establishes AFC as a promising therapeutic approach for DIC, highlighting the significance of multi-target therapies derived from natural herbals in contemporary medicine.
基金supported by grants from the National Natural Science Foundation of China(U21A20400,81973789,82004327).
文摘Objective:To explore the potential mechanisms of a baicalin-geniposide combination against cerebral ischemia using a network pharmacology strategy.Method:We used network pharmacology integrating drug-target-disease interactions to identify key pathways which were validated in a rat middle cerebral artery occlusion model treated with baicalin(55 mg/kg),geniposide(5 mg/kg),or their 11:1 combination.Therapeutic efficacy and mechanistic insights were evaluated using triphenyltetrazolium chloride staining,Evans blue assay,enzyme-linked immunosorbent assay,and Western blot.Results:The results revealed that the nuclear factor-kappa B(NF-κB)signaling pathway is inhibited in combination treatment of cerebral ischemia.Ten targets were identified as key nodes in the protein-protein interaction network:interleukin 6(IL-6),interleukin-1β,interleukin 18,C-C motif ligand 2,C-C motif ligand 4,interleukin 10,interferon-γ-inducible protein 10,C-C motif ligand 3,tumor necrosis factor-α(TNF-α),interleukin-1α.The baicalin-geniposide combination significantly reduced infarct volume,improved neurological deficits,and alleviated brain edema/blood-brain barrier leakage compared with monotherapy.Additionally,it significantly inhibited toll-like receptor 4(TLR4)/NF-κB signaling and downregulated pro-inflammatory cytokines TNF-αand IL-6 levels.Conclusion:The baicalin-geniposide combination alleviated cerebral ischemia-reperfusion injury by synergistically suppressing the TLR4/NF-κB pathway and its downstream inflammatory factors.
基金supported by the Shaanxi Qinchuang Yuan“scientist+engineer”team construction(No.2023KXJ-080)Shaanxi Chiral Drug Engineering Technology Research Center(Department of Science and Technology of Shaanxi Province.No.[2011]-251).
文摘Background:Human skin is affected by ultraviolet rays on a daily basis,and excessive ultraviolet radiation(UVR)can lead to sunburn erythema,tanning,photoaging,and skin tumors.The combination of Astragali Radix(AR)and Anemarrhenae Rhizoma(AAR)is a common pairing in traditional Chinese medicine(TCM).According to earlier studies,they possess properties capable of alleviating the adverse impacts of UVR on the skin.However,the specific actions and underlying mechanisms require further investigation.The study aims to analyze the efficacy of AR-AAR in preventing UVR-induced skin damage and to clarify the associated molecular mechanisms.Methods:Potential signaling pathways by which AR and AAR may protect against UVR-induced skin damage were identified with network pharmacology,molecular docking techniques and molecular dynamics(MD)simulation.Except the normal group,the back skin of SD rats was exposed to 1.1 mW/cm^(2) UVA combined with 0.1 mW/cm^(2) UVB daily,and the UVR skin damage model was established.Morphological features of skin tissues of different groups were discovered through Hematoxylin and Eosin(HE)staining,Masson staining,Weigert staining.ELISA was utilized to measure the levels of reactive oxygen species(ROS),Interleukin 6(IL-6),Interleukin 1β(IL-1β)and Tumor necrosis factos-α(TNF-α)in skin tissues.RT-PCR and Western blot were employed to quantify the mRNA and protein contents of PI3K,AKT,and MMP-9.Results:Network pharmacology analysis predicts that AR-AAR may improve skin damage induced by UVR through the PI3K/AKT signaling pathway.Histological staining shows that AR-AAR can significantly reduce inflammatory infiltration and fibrosis in damaged skin.Treatment with AR-AAR(2:1)significantly reduced the expression levels of IL-1β,IL-6,TNF-αand ROS in UVR-damaged rat skin.After treatment with AR-AAR(2:1),not only did the relative mRNA expression levels of PI3K and AKT and the protein expression levels of PI3K,AKT,P-PI3K,and P-AKT increase,but the mRNA and protein expression levels of MMP-9 decreased.Conclusion:The study indicate that the AR-AAR combination and its active components may mitigate UVR skin damage by modulating the PI3K/AKT signaling pathway.
基金financially supported by the Key Scientific Research Project of Henan Provincial Universities in 2024(No.24A350013)the Project of Basic Research Fund of Henan Institute of Medical and Pharmaceutical Sciences(No.2024BP0202)+1 种基金the Key Scientific and Technological Project of Henan Province(No.242102311213)the Henan Province Postdoctoral Program(No.343915)。
文摘Cancer remains one of the major threats to public health.Traditional chemotherapy,radiotherapy,and other anti-tumor therapies have numerous limitations in clinical treatment.Notwithstanding the considerable advances made in recent years with regard to immunotherapy in both basic research and clinical practice,there remains scope for further improvement,particularly with respect to its efficacy against solid tumors.With advancements in nanotechnology,tumor nanovaccines hold immense potential for preventing tumor recurrence and treating metastatic tumors.Nevertheless,the considerable heterogeneity of tumor immunogenicity presents a number of significant challenges in the development of nanometrescale vaccines targeting solid tumors.Recent findings indicate that immune checkpoint inhibitor(ICI)therapy can improve the immunosuppressive microenvironment within tumors,while nanovaccines can also augment tumor sensitivity toward ICIs.Consequently,combining tumor nanovaccine with ICI therapy holds promise for effectively eradicating tumors or controlling their recurrence and metastasis during cancer treatment.This review delves into the mechanism behind combining tumor nanovaccine with ICI while focusing on factors influencing this combined therapy approach.Moreover,it offers an overview of the current research status regarding the combination of tumor nanovaccines with chemotherapy,radiotherapy,photothermal therapy,and sonodynamic therapy,as well as prospects for future developments in this field.
基金Supported by Natural Science Foundation of Hubei Province,No.2019CFC929.
文摘BACKGROUND Chemotherapy combined with anti-angiogenic therapy has become an important strategy for the treatment of advanced gastric cancer(AGC);however,the regimen needs optimization.AIM To evaluate the efficacy of albumin-bound paclitaxel(nab-ptx)combined with the small molecule vascular endothelial growth factor inhibitor anlotinib in secondline and beyond treatment of AGC.METHODS We collected data from AGC patients at our hospital who experienced disease progression after first-line chemotherapy and received anlotinib combined with nab-ptx.The primary endpoints included overall survival(OS)and progressionfree survival(PFS),while the secondary endpoints were objective response rate(ORR),disease control rate(DCR),and adverse events(AEs).RESULTS Preliminary results indicated that anlotinib combined with nab-ptx can provide significant efficacy in second-line or above treatment for AGC(median PFS=6.0 months,median OS=12.0 months),with an ORR of 42%and a DCR of 78%.Further analysis revealed that patients who experienced hypertension,proteinuria,and hand-foot syndrome during treatment had better efficacy compared to those who did not experience these AEs.Mechanistic studies suggest that this regimen likely exerts synergistic anti-tumor effects by activating the immune response through the reduction of regulatory T-cell proportions.Common adverse reactions included bone marrow suppression,peripheral neuropathy,hypertension,proteinuria,and hand-foot syndrome,which were manageable and resolved with appropriate interventions,indicating the promising application of this regimen in second-line or above treatment for AGC.CONCLUSION The combination of anlotinib and nab-ptx shows promising efficacy with fewer toxicities in AGC treatment.The regimen holds promise as a second-line treatment of AGC;however,its specific clinical value requires further research.
基金Supported by National Natural Science Foundation of China,No.32270768,No.82273970,No.32070726 and No.82370715Hubei Natural Science Foundation of China,No.2024AFB218+1 种基金National Key R&D Program of China,No.2023YFC2507904Doctoral Startup Foundation of Hubei University of Technology,No.XJ2022003901.
文摘Histone deacetylase inhibitors(HDACis),such as trichostatin A(TSA),have been recognized as promising anti-cancer agents due to their capacity to restore epigenetic regulation and reactivate tumor suppressor genes.However,emerging evidence indicates that unintended pro-metastatic effects may offset the therapeutic benefits of HDACis.Chen et al elucidate this paradox,demonstrating that TSA-induced hyperacetylation activates the BRD4/c-Myc/ER-stress axis,thereby promoting epithelial-mesenchymal transition and metastasis in esophageal squamous cell carcinoma(ESCC).Furthermore,they clarify the clinical significance of histone acetylation in the prognostic evaluation of ESCC.Their findings underscore the complexity of epigenetic therapies and highlight the necessity of reevaluating the associated risks and combinatorial therapeutic strategies with HDACi-based treatments.Here,we summarize the potential risks of HDACis therapy and discuss feasible combination therapeutic strategies.
文摘The diversity,complexity,heterogeneity,and drug resistance of tumors make it challenging to meet the clinical needs of a single apoptosis-inducing chemotherapy.The combination of apoptosis and ferroptosis is expected to address the side effects of chemotherapy and enhance therapeutic efficacy.Here,an amphiphilic pH-responsive doxorubicin(DOX)and ferrocene(Fc)-containing copolyprodrug(P(ADH-DOXFc)-PEG)was designed with high DOX and Fc content of 66.5%and 0.58 mmol/g by a facile polycondensation for combining chemotherapy with ferroptosis in cancer treatment.A drug self-delivery system(DSDS)with an average hydrodynamic diameter(D_(h))of 135 nm can be easily obtained via self-assembly with the polyprodrug blocks as the hydrophobic core and PEG as the hydrophilic brush.The cumulative DOX release reached 72.7%in the simulated tumor intracellular acidic microenvironment within 56 h,whereas the premature drug leakage was only 6.2%in the simulated normal physiological medium.The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)assay results indicated an IC_(50)of 8.2μg/mL,exhibiting enhanced anti-tumor efficacy and a successful combination of apoptosis and ferroptosis,with a combination index(CI)of 0.88.
基金Supported by the National Natural Science Foundation of China,No.82072732.
文摘BACKGROUND Endoscopy allows for the direct observation of primary tumor characteristics and responses after neoadjuvant treatment.However,reports on endoscopic evaluation following neoadjuvant immunotherapy remain limited.AIM To examine the predictive value of endoscopic findings of primary tumors for responses to neoadjuvant immunotherapy.METHODS This retrospective study,conducted at a tertiary center in China,evaluated 74 patients with colorectal cancer,including 17 with deficient mismatch repair(dMMR)and 15 with proficient mismatch repair(pMMR)tumors.Patients underwent neoadjuvant immunotherapy followed by surgery.Endoscopic findings before and after neoadjuvant immunotherapy were reviewed and compared with the pathology of the resected specimens.RESULTS In the pMMR group(n=57 evaluable patients),endoscopy identified 11/17 patients who achieved a complete response(CR),while misidentifying 1/40 patients with residual disease as CR(64.7%vs 2.5%,P<0.01).Conversely,22/40 patients with residual disease were accurately identified as achieving a partial response(PR),with 1/17 patients who achieved CR misclassified as PR(55.0%vs 5.9%,P<0.01).The sensitivity,specificity,and accuracy of endoscopic diagnosis for pathological CR were 64.7%,97.5%,and 87.7%,respectively.In the dMMR cohort,endoscopy classified 9/17 patients as CR and 2 of the remaining patients with residual tumors as PR(64.3%vs 66.7%,P=0.73).The method demonstrated 100%sensitivity and 82.4%accuracy in diagnosing pathological CR.CONCLUSION Endoscopic evidence of CR or PR was well correlated with postoperative pathological outcomes in the pMMR cohort.Despite endoscopic indications of tumor residue,a complete pathological response post-surgery was possible in the dMMR cohort.
基金supported by National Science Foundations of China(Grant No.11771340,12171373).
文摘Recently,Choe-Koo-Wang(J Funct Anal,2020,278)demonstrated the rigid phenomenon:The compact linear combination of composition operators under the Coefficient Non-cancellation Condition(CNC),implies that each difference is compact on the weighted Bergman space in the unit disk.Motivated by the subtle connection of composition operator theory on the weighted Bergman spaces,Korenblum spaces and bounded holomorphic function spaces,we first explore the rigid phenomenon which also holds on the Korenblum space over the unit ball.Furthermore,we discuss which difference of composition operators is compact when the compact combination of composition operators does not satisfy the condition(CNC)on Korenblum spaces and bounded holomorphic function spaces over the unit ball setting.
基金funded by Science and Technology Project of Hebei Education Department[QN2023085].
文摘Agricultural land development is a pivotal strategy for addressing the global food security crisis.Barren grassland,especially those in mountainous regions,constitutes critical areas where cultivation can substantially enhance land resources.This study highlights the necessity for a precise correlation between land development initiatives and constraints in order to optimize efficiency and enhance the effectiveness of such projects,with the core being the seamless integration of land development engineering and techniques to eliminate agricultural constraints.This study employs a systems engineering approach to classify improvement factors into mobile and fixed categories,elucidating the integration methods of constraint factors.Adhering to the Wooden Barrel Principle,these constraints were rigorously analyzed based on soil quality,land topography,water availability,and agricultural infrastructure.An innovative method of engineering type combination is proposed,which effectively explains the correlation between natural factors combination,project type combination,and target factors combination.It provides a convenient way for the selection of barren grassland development projects and lays a foundation for land planning,development project establishment,program selection,engineering design,and budget preparation.Taking Tang County of China as an example,it is divided into 19 factor improvement areas,a quick reference table of engineering types is established,and 14 main types of engineering combinations are obtained,which lays a foundation for the application of theoretical framework in practice.
