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
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
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
A later heading date generally leads to higher grain yield in favorable ecological regions;however,grain yield reaches a limit as the heading date exceeds a certain threshold.Ghd7 is the first cloned major gene that r...A later heading date generally leads to higher grain yield in favorable ecological regions;however,grain yield reaches a limit as the heading date exceeds a certain threshold.Ghd7 is the first cloned major gene that regulates heading date,plant height and grain number.Here,we investigated the relationship between Ghd7 and florigen genes Hd3a and RFT1,to determine their roles in regulating heading date and grain number under different photoperiods.Our results revealed that under long-day(LD)conditions,Hd3a acts prior to RFT1 to promote heading while negatively regulating plant height and grain number.In contrast,Ghd7 positively regulates heading date,plant height,and grain number by inhibiting both Hd3a and RFT1.Under short-day(SD)conditions,the functions of Hd3a and RFT1 remain consistent with those under LD conditions,but Ghd7 does not inhibit their expression,resulting in a weaker phenotypic effect compared to Hd3a.Additionally,under both LD and SD conditions,increased Ghd7 expression enhances its inhibitory effect on Hd3a and RFT1,leading to later heading and increased grain number;however,once the heading date exceeds 94 d,grain number no longer increases.Moreover,the gn1a allele increased grain number by 16.5%to 42.5%,while combinations of the elite alleles from Ghd7,Hd3a,RFT1,and Gn1a significantly increased grain number by up to 240.9%.Therefore,we propose a new breeding strategy to optimize the heading date and grain number using the Ghd7Hd3aRFT1gn1a combination of Ghd7,Hd3a,RFT1,and Gn1a under LD conditions,and the Ghd7hd3aRFT1gn1a combination under SD conditions.This strategy improved the yield of the high-quality Northeast variety Kongyu 131(KY131)by 69.1%in Beijing and 93.7%in Hainan.This strategy will greatly improve the efficiency of north-to-south adaptation in rice,providing theoretical guidance for expanding the geographical adaptability of rice varieties.展开更多
Natural product-based drug combinations(NPDCs)present distinctive advantages in treating complex diseases.While high-throughput screening(HTS)and conventional computational methods have partially accelerated synergist...Natural product-based drug combinations(NPDCs)present distinctive advantages in treating complex diseases.While high-throughput screening(HTS)and conventional computational methods have partially accelerated synergistic drug combination discovery,their applications remain constrained by experimental data fragmentation,high costs,and extensive combinatorial space.Recent developments in artificial intelligence(AI),encompassing traditional machine learning and deep learning algorithms,have been extensively applied in NPDC identification.Through the integration of multi-source heterogeneous data and autonomous feature extraction,prediction accuracy has markedly improved,offering a robust technical approach for novel NPDC discovery.This review comprehensively examines recent advances in AI-driven NPDC prediction,presents relevant data resources and algorithmic frameworks,and evaluates current limitations and future prospects.AI methodologies are anticipated to substantially expedite NPDC discovery and inform experimental validation.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
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
Effective isolation between the cement sheath and the sandstone is crucial for the development and production of oil and gas wells in sandstone formations.In this study,a cement-sandstone composite(CSC)was prepared,an...Effective isolation between the cement sheath and the sandstone is crucial for the development and production of oil and gas wells in sandstone formations.In this study,a cement-sandstone composite(CSC)was prepared,and based onμ-CT three-dimensional reconstruction imaging and finite element analysis(FEA)techniques,the stress distribution and potential failure mechanism at the cement-sandstone bonding interface under axial loading were analyzed.The key findings are as follows:(1)stress concentrations are highly likely to form at the gap between the cement and sandstone interface and around interfacial voids,with Von Mises stress reaching critical levels of 18.0-20.0 MPa at these locations,significantly exceeding the stress magnitudes in well-bonded regions;(2)the phenomenon of local stress concentration driven by interfacial defects can be identified as the main basis for predicting damage location in interfacial debonding and continuous shear under axial load;(3)ensuring tight cementation at the cement-sandstone interface and minimizing interfacial voids are paramount for preventing stress-induced failure;(4)the critical Von Mises stress value of 20 MPa at the interface defect can be used as a benchmark for material selection and designed to ensure long-term integrity in oil and gas well applications subjected to similar axial loads.These findings contribute to a more accurate understanding of the failure mechanism of the cement-sandstone interface and to the precise design of material properties,thereby ensuring the long-term integrity of oil and gas well applications subjected to similar axial loads.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
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
Purpose–To systematically characterize and objectively evaluate basic railway safety management capability,creating a closed-loop management approach which allows continuous improvement and optimization.Design/method...Purpose–To systematically characterize and objectively evaluate basic railway safety management capability,creating a closed-loop management approach which allows continuous improvement and optimization.Design/methodology/approach–A basic railway safety management capability evaluation index system based on a comprehensive analysis of national safety management standards,railway safety rules and regulations and existing safety data from railway transport enterprises is presented.The system comprises a guideline layer including safety committee formation,work safety responsibility,safety management organization and safety rules and regulations as its components,along with an index layer consisting of 12 quantifiable indexes.Game theory combination weighting is utilized to integrate subjective and objective weight values derived using AHP and CRITIC methods and further combined using the TOPSIS method in order to construct a comprehensive basic railway safety management capability evaluation model.Findings–The case study presented demonstrates that this evaluation index system and comprehensive evaluation model are capable of effectively characterizing and evaluating basic railway safety management capability and providing directional guidance for its sustained improvement.Originality/value–Construction of an evaluation index system that is quantifiable,generalizable and accessible,accurately reflects the main aspects of railway transportation enterprises’basic safety management capability and provides interoperability across various railway transportation enterprises.The application of the game theoretic combination weighting method to derive composite weights which combine experts’subjective evaluations with the objectivity of data.展开更多
BACKGROUND Early symptoms of hepatocellular carcinoma(HCC)are not obvious,and more than 70%of which does not receive radical hepatectomy,when first diagnosed.In recent years,molecular-targeted drugs combined with immu...BACKGROUND Early symptoms of hepatocellular carcinoma(HCC)are not obvious,and more than 70%of which does not receive radical hepatectomy,when first diagnosed.In recent years,molecular-targeted drugs combined with immunotherapy and other therapeutic methods have provided new treatment options for middle and advanced HCC(aHCC).Predicting the effect of targeted combined immunotherapy has become a hot topic in current research.AIM To explore the relationship between nodule enhancement in hepatobiliary phase and the efficacy of combined targeted immunotherapy for aHCC.METHODS Data from 56 patients with aHCC for magnetic resonance imaging with gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid were retrospectively collected.Signal intensity of intrahepatic nodules was measured,and the hepatobiliary relative enhancement ratio(RER)was calculated.Progression-free survival(PFS)of patients with high and low reinforcement of HCC nodules was compared.The model was validated using receiver operating characteristic curves.Univariate and multivariate logistic regression and Kaplan-Meier analysis were performed to explore factors influencing the efficacy of targeted immunization and PFS.RESULTS Univariate and multivariate analyses revealed that the RER,neutrophil-to-lymphocyte ratio,platelet-to-lymphocyte ratio,and prognostic nutritional index were significantly associated with the efficacy of tyrosine kinase inhibitors combined with immunotherapy(P<0.05).The area under the curve of the RER for predicting the efficacy of tyrosine kinase inhibitors combined with anti-programmed death 1 antibody in patients with aHCC was 0.876(95%confidence interval:0.781-0.971,P<0.05),the optimal cutoff value was 0.904,diagnostic sensitivity was 87.5%,and specificity was 79.2%.Kaplan-Meier analysis showed that neutrophil-to-lymphocyte ratio<5,plateletto-lymphocyte ratio<300,prognostic nutritional index<45,and RER<0.9 significantly improved PFS.CONCLUSION AHCC nodules enhancement in the hepatobiliary stage was significantly correlated with PFS.Imaging information and immunological indicators had high predictive efficacy for targeted combined immunotherapy and were associated with PFS.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
This article comments on the letter by Lowell et al,which addresses the next generation of combination therapy for inflammatory bowel disease(IBD).As the understanding of the pathogenesis of IBD continues to improve,t...This article comments on the letter by Lowell et al,which addresses the next generation of combination therapy for inflammatory bowel disease(IBD).As the understanding of the pathogenesis of IBD continues to improve,treatment strategies are evolving rapidly.The letter examines the current status and future directions of combination therapy for IBD,focusing on approaches that combine biologics with immunomodulators and the emerging dual-biologic therapy(DBT).The traditional combination of biologics and immunomodulators has demonstra-ted preliminary efficacy by enhancing the effects of biologics through immunomo-dulation.However,concerns regarding long-term safety warrant careful evalua-tion.Recent trials,including DUET-Crohn's disease and DUET-ulcerative colitis,have shown promising potential for the broader adoption of DBT.Nevertheless,comprehensive data on efficacy and safety,as well as the effective integration of supportive treatments,remain essential to establish new paradigms for the next generation of IBD care.展开更多
Breast cancer is a severe problem for women worldwide.Among them,estrogen receptor(ER)positive breast cancer accounted for 70%of total breast cancer cases,which is the most common subtype.Currently,the main therapy th...Breast cancer is a severe problem for women worldwide.Among them,estrogen receptor(ER)positive breast cancer accounted for 70%of total breast cancer cases,which is the most common subtype.Currently,the main therapy that targeted ER positive breast cancer is endocrine therapy.Herein,we summarized the latest research advances in combination therapies for ER positive breast cancer,focusing on ER as the main therapeutic target.The therapeutic approaches,therapeutic mechanism and resistance will be reviewed and discussed.The combinatorial targets and synergistic effects such as cell cycle-dependent kinase 4/6,phosphatidylinositol-3 kinase,histone deacetylase,bromodomain and extraterminal domain were summarized.In addition,the chemical structures of the inhibitors were also illustrated,along with a brief structure-activity relationship study.Finally,perspective and future directions on breast cancer were proposed and discussed.展开更多
In this paper,we develop an inexact symmetric proximal alternating direction method of multipliers(ISPADMM)with two convex combinations(ISPADMM-tcc)for solving two-block separable convex optimization problems with lin...In this paper,we develop an inexact symmetric proximal alternating direction method of multipliers(ISPADMM)with two convex combinations(ISPADMM-tcc)for solving two-block separable convex optimization problems with linear equality constraints.Specifically,the convex combination technique is incorporated into the proximal centers of both subproblems.We then approximately solve these two subproblems based on relative error criteria.The global convergence,and O(1/N)ergodic sublinear convergence rate measured by the function value residual and constraint violation are established under some mild conditions,where N denotes the number of iterations.Finally,numerical experiments on solving the l1-regularized analysis sparse recovery and the elastic net regularization regression problems illustrate the feasibility and effectiveness of the proposed method.展开更多
Alzheimer’s disease(AD)has become an important public health issue worldwide.p-Coumaric acid(CA)and lactoferrin(Lf)possessed antioxidant,anti-inflammatory,and anti-AD activities.Herein,we hypothesized that a combinat...Alzheimer’s disease(AD)has become an important public health issue worldwide.p-Coumaric acid(CA)and lactoferrin(Lf)possessed antioxidant,anti-inflammatory,and anti-AD activities.Herein,we hypothesized that a combination treatment of CA and Lf would synergistically improve AD symptoms and studied its mechanisms.Twelve-week-old amyloid precursor protein(APP)/presenilin 1(PS1)mice were treated with CA,Lf,or both CA and Lf for 8 weeks.Results showed that individual and combined treatments could ameliorate cognitive deficits to varying degrees,with stronger effects for combined intervention than for CA or Lf alone.Specifically,combined treatment was most effective in improving nesting ability and reducing amyloidββ_(1-42)(Aβ_(1-42))deposition in mice.Moreover,combined treatment was more effective in suppressing APP,β-site APP cleavage enzyme 1,and inflammation;it inhibited the CCAAT-enhancer-binding protein(C/EBPβ)/asparagine endopeptidase(AEP)signaling pathway in the hippocampus and colon and upregulated the expression of tight junction protein zonula occludens-1 in the colon;it also decreased the Firmicutes/Bacteroidetes ratio at the phylum level and increased the relative abundance of Prevotellaceae,Lachnospira,and Eubacterium at the genus level.Overall,the combination of CA and Lf may ameliorate cognitive deficits in APP/PS1 mice by improving inflammation and inhibiting the C/EBPβ/AEP signaling pathway via modulating gut microbiome.展开更多
The lamina(combination)types,reservoir characteristics and shale oil occurrence states of organic-rich shale in the Triassic Yanchang Formation Chang 73 sub-member in the Ordos Basin were systematically investigated t...The lamina(combination)types,reservoir characteristics and shale oil occurrence states of organic-rich shale in the Triassic Yanchang Formation Chang 73 sub-member in the Ordos Basin were systematically investigated to reveal the main controlling factors of shale oil occurrence under different lamina combinations.The differential enrichment mechanisms and patterns of shale oil were discussed using the shale oil micro-migration characterization and evaluation methods from the perspectives of relay hydrocarbon supply,stepwise migration,and multi-stage differentiation.The results are obtained in five aspects.First,Chang 73 shale mainly develops five types of lamina combination,i.e.non-laminated shale,sandy laminated shale,tuffaceous laminated shale,mixed laminated shale,and organic-rich laminated shale.Second,shales with different lamina combinations are obviously different in the reservoir space.Specifically,shales with sandy laminae and tuffaceous laminae have a large number of intergranular pores,dissolution pores and hydrocarbon generation-induced fractures.The multi-scale pore and fracture system constitutes the main place for liquid hydrocarbon occurrence.Third,the occurrence and distribution of shale oil in shale with different lamina combinations are jointly controlled by organic matter abundance,reservoir property,thermal evolution degree,mineral composition and laminae scale.The micro-nano-scale pore-fracture networks within shales containing rigid laminae,particularly sandy and tuffaceous laminations,primarily contain free-state light hydrocarbon components.In contrast,adsorption-phase heavy hydrocarbon components predominantly occupy surfaces of organic matter assemblages,clay mineral matrices,and framework mineral particulates.Fourth,there is obvious shale oil micro-migration between shales with different lamina combinations in Chang 73.Generally,such micro-migration is stepwise in a sequence of organic-rich laminated shale→tuffaceous laminated shale→mixed laminated shale→sandy lamiated shale→non-laminated shale.Fifth,the relay hydrocarbon supply of organic matter under the control of the spatial superposition of shales with various laminae,the stepwise migration via multi-scale pore and fracture network,and the multi-differentiation in shales with different lamina combinations under the control of organic-inorganic interactions fundamentally decide the differences of shale oil components between shales with different lamina combinations.展开更多
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.
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 grants from the Chinese Academy of Sciences(XDA24010101)the Biological Breeding-National Science and Technology Major Project(2024ZD04077)+2 种基金the National Key Research and Development Program of China(2023YFF1001200)Natural Science Foundation of Zhejiang Province(LD24C130001)the Agricultural Science and Technology Innovation Program(ASTIP)of CAAS。
文摘A later heading date generally leads to higher grain yield in favorable ecological regions;however,grain yield reaches a limit as the heading date exceeds a certain threshold.Ghd7 is the first cloned major gene that regulates heading date,plant height and grain number.Here,we investigated the relationship between Ghd7 and florigen genes Hd3a and RFT1,to determine their roles in regulating heading date and grain number under different photoperiods.Our results revealed that under long-day(LD)conditions,Hd3a acts prior to RFT1 to promote heading while negatively regulating plant height and grain number.In contrast,Ghd7 positively regulates heading date,plant height,and grain number by inhibiting both Hd3a and RFT1.Under short-day(SD)conditions,the functions of Hd3a and RFT1 remain consistent with those under LD conditions,but Ghd7 does not inhibit their expression,resulting in a weaker phenotypic effect compared to Hd3a.Additionally,under both LD and SD conditions,increased Ghd7 expression enhances its inhibitory effect on Hd3a and RFT1,leading to later heading and increased grain number;however,once the heading date exceeds 94 d,grain number no longer increases.Moreover,the gn1a allele increased grain number by 16.5%to 42.5%,while combinations of the elite alleles from Ghd7,Hd3a,RFT1,and Gn1a significantly increased grain number by up to 240.9%.Therefore,we propose a new breeding strategy to optimize the heading date and grain number using the Ghd7Hd3aRFT1gn1a combination of Ghd7,Hd3a,RFT1,and Gn1a under LD conditions,and the Ghd7hd3aRFT1gn1a combination under SD conditions.This strategy improved the yield of the high-quality Northeast variety Kongyu 131(KY131)by 69.1%in Beijing and 93.7%in Hainan.This strategy will greatly improve the efficiency of north-to-south adaptation in rice,providing theoretical guidance for expanding the geographical adaptability of rice varieties.
基金supported by National Natural Science Foundation of China(Nos.82404511,82373790)Central Guidance on Local Science and Technology Development Fund of Hebei Province(No.226Z2605G)Program for Young Scientists in the Field of Natural Science of Hebei Medical University(No.CYCZ2023011).
文摘Natural product-based drug combinations(NPDCs)present distinctive advantages in treating complex diseases.While high-throughput screening(HTS)and conventional computational methods have partially accelerated synergistic drug combination discovery,their applications remain constrained by experimental data fragmentation,high costs,and extensive combinatorial space.Recent developments in artificial intelligence(AI),encompassing traditional machine learning and deep learning algorithms,have been extensively applied in NPDC identification.Through the integration of multi-source heterogeneous data and autonomous feature extraction,prediction accuracy has markedly improved,offering a robust technical approach for novel NPDC discovery.This review comprehensively examines recent advances in AI-driven NPDC prediction,presents relevant data resources and algorithmic frameworks,and evaluates current limitations and future prospects.AI methodologies are anticipated to substantially expedite NPDC discovery and inform experimental validation.
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.
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 the National Natural Science Foundation of China(No.52274026)the National Key Research and Development Program(No.2022YFC2806504)the CNOOC Research Project(No.KJGG-2022-17-04 and NO.KJGG-2022-17-05).
文摘Effective isolation between the cement sheath and the sandstone is crucial for the development and production of oil and gas wells in sandstone formations.In this study,a cement-sandstone composite(CSC)was prepared,and based onμ-CT three-dimensional reconstruction imaging and finite element analysis(FEA)techniques,the stress distribution and potential failure mechanism at the cement-sandstone bonding interface under axial loading were analyzed.The key findings are as follows:(1)stress concentrations are highly likely to form at the gap between the cement and sandstone interface and around interfacial voids,with Von Mises stress reaching critical levels of 18.0-20.0 MPa at these locations,significantly exceeding the stress magnitudes in well-bonded regions;(2)the phenomenon of local stress concentration driven by interfacial defects can be identified as the main basis for predicting damage location in interfacial debonding and continuous shear under axial load;(3)ensuring tight cementation at the cement-sandstone interface and minimizing interfacial voids are paramount for preventing stress-induced failure;(4)the critical Von Mises stress value of 20 MPa at the interface defect can be used as a benchmark for material selection and designed to ensure long-term integrity in oil and gas well applications subjected to similar axial loads.These findings contribute to a more accurate understanding of the failure mechanism of the cement-sandstone interface and to the precise design of material properties,thereby ensuring the long-term integrity of oil and gas well applications subjected to similar axial loads.
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 China National Railway Group Co.,Ltd.Research and Development Project(P2023T002).
文摘Purpose–To systematically characterize and objectively evaluate basic railway safety management capability,creating a closed-loop management approach which allows continuous improvement and optimization.Design/methodology/approach–A basic railway safety management capability evaluation index system based on a comprehensive analysis of national safety management standards,railway safety rules and regulations and existing safety data from railway transport enterprises is presented.The system comprises a guideline layer including safety committee formation,work safety responsibility,safety management organization and safety rules and regulations as its components,along with an index layer consisting of 12 quantifiable indexes.Game theory combination weighting is utilized to integrate subjective and objective weight values derived using AHP and CRITIC methods and further combined using the TOPSIS method in order to construct a comprehensive basic railway safety management capability evaluation model.Findings–The case study presented demonstrates that this evaluation index system and comprehensive evaluation model are capable of effectively characterizing and evaluating basic railway safety management capability and providing directional guidance for its sustained improvement.Originality/value–Construction of an evaluation index system that is quantifiable,generalizable and accessible,accurately reflects the main aspects of railway transportation enterprises’basic safety management capability and provides interoperability across various railway transportation enterprises.The application of the game theoretic combination weighting method to derive composite weights which combine experts’subjective evaluations with the objectivity of data.
基金Supported by Natural Science Foundation of Henan Province,No.242300421286the research and practice project of higher education reform in Henan Province,No.2023SJGLX124Ythe research and practice project of higher education reform of Zhengzhou University,No.2023ZZUJGXM114.
文摘BACKGROUND Early symptoms of hepatocellular carcinoma(HCC)are not obvious,and more than 70%of which does not receive radical hepatectomy,when first diagnosed.In recent years,molecular-targeted drugs combined with immunotherapy and other therapeutic methods have provided new treatment options for middle and advanced HCC(aHCC).Predicting the effect of targeted combined immunotherapy has become a hot topic in current research.AIM To explore the relationship between nodule enhancement in hepatobiliary phase and the efficacy of combined targeted immunotherapy for aHCC.METHODS Data from 56 patients with aHCC for magnetic resonance imaging with gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid were retrospectively collected.Signal intensity of intrahepatic nodules was measured,and the hepatobiliary relative enhancement ratio(RER)was calculated.Progression-free survival(PFS)of patients with high and low reinforcement of HCC nodules was compared.The model was validated using receiver operating characteristic curves.Univariate and multivariate logistic regression and Kaplan-Meier analysis were performed to explore factors influencing the efficacy of targeted immunization and PFS.RESULTS Univariate and multivariate analyses revealed that the RER,neutrophil-to-lymphocyte ratio,platelet-to-lymphocyte ratio,and prognostic nutritional index were significantly associated with the efficacy of tyrosine kinase inhibitors combined with immunotherapy(P<0.05).The area under the curve of the RER for predicting the efficacy of tyrosine kinase inhibitors combined with anti-programmed death 1 antibody in patients with aHCC was 0.876(95%confidence interval:0.781-0.971,P<0.05),the optimal cutoff value was 0.904,diagnostic sensitivity was 87.5%,and specificity was 79.2%.Kaplan-Meier analysis showed that neutrophil-to-lymphocyte ratio<5,plateletto-lymphocyte ratio<300,prognostic nutritional index<45,and RER<0.9 significantly improved PFS.CONCLUSION AHCC nodules enhancement in the hepatobiliary stage was significantly correlated with PFS.Imaging information and immunological indicators had high predictive efficacy for targeted combined immunotherapy and were associated with PFS.
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Supported by the National Natural Science Foundation of China,No.82400591(to Wu FF).
文摘This article comments on the letter by Lowell et al,which addresses the next generation of combination therapy for inflammatory bowel disease(IBD).As the understanding of the pathogenesis of IBD continues to improve,treatment strategies are evolving rapidly.The letter examines the current status and future directions of combination therapy for IBD,focusing on approaches that combine biologics with immunomodulators and the emerging dual-biologic therapy(DBT).The traditional combination of biologics and immunomodulators has demonstra-ted preliminary efficacy by enhancing the effects of biologics through immunomo-dulation.However,concerns regarding long-term safety warrant careful evalua-tion.Recent trials,including DUET-Crohn's disease and DUET-ulcerative colitis,have shown promising potential for the broader adoption of DBT.Nevertheless,comprehensive data on efficacy and safety,as well as the effective integration of supportive treatments,remain essential to establish new paradigms for the next generation of IBD care.
基金the financial supports of the National Natural Science Foundation of China(No.82204181)Nanjing University of Chinese Medicine National Natural Science Foundation of China Counterpart Funding(No.XPT82204181)+3 种基金Jiangsu Provincial Health Commission(No.Z2021057)the Priority Academic Program Development of Jiangsu Higher Education Institutions(Integration of Chinese and Western Medicine)High level key discipline construction project of the National Administration of Traditional Chinese Medicine-Resource Chemistry of Chinese Medicinal Materials(No.zyyzdxk-2023083)the Key R&D Program of Jiangsu Province(No.BE2023840)。
文摘Breast cancer is a severe problem for women worldwide.Among them,estrogen receptor(ER)positive breast cancer accounted for 70%of total breast cancer cases,which is the most common subtype.Currently,the main therapy that targeted ER positive breast cancer is endocrine therapy.Herein,we summarized the latest research advances in combination therapies for ER positive breast cancer,focusing on ER as the main therapeutic target.The therapeutic approaches,therapeutic mechanism and resistance will be reviewed and discussed.The combinatorial targets and synergistic effects such as cell cycle-dependent kinase 4/6,phosphatidylinositol-3 kinase,histone deacetylase,bromodomain and extraterminal domain were summarized.In addition,the chemical structures of the inhibitors were also illustrated,along with a brief structure-activity relationship study.Finally,perspective and future directions on breast cancer were proposed and discussed.
基金supported by the National Natural Science Foundation of China(12171106)the Guangxi Science and Technology Program(AD23023001)+4 种基金the Natural Science Foundation of Guangxi Province(2023GXNSFBA026029)the National Natural Science Foundation of China(12401403,12361063)the Research Project of Guangxi Minzu University(2022KJQD03)the Middle-aged and Young Teachers’Basic Ability Promotion Project of Guangxi Province(2023KY0168)the Xiangsihu Young Scholars Innovative Research Team of Guangxi Minzu University(2022GXUNXSHQN04).
文摘In this paper,we develop an inexact symmetric proximal alternating direction method of multipliers(ISPADMM)with two convex combinations(ISPADMM-tcc)for solving two-block separable convex optimization problems with linear equality constraints.Specifically,the convex combination technique is incorporated into the proximal centers of both subproblems.We then approximately solve these two subproblems based on relative error criteria.The global convergence,and O(1/N)ergodic sublinear convergence rate measured by the function value residual and constraint violation are established under some mild conditions,where N denotes the number of iterations.Finally,numerical experiments on solving the l1-regularized analysis sparse recovery and the elastic net regularization regression problems illustrate the feasibility and effectiveness of the proposed method.
基金funded by the National Natural Science Foundation of China(82103818)the Suzhou Applied Basic Research(Medical and Health)Science and Technology Innovation Project(SYW2024179)+1 种基金Jiangsu Key Laboratory of Preventive and Translational Medicine for Major Chronic Non-communicable Diseases,Soochow University(KJS2437)the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD).
文摘Alzheimer’s disease(AD)has become an important public health issue worldwide.p-Coumaric acid(CA)and lactoferrin(Lf)possessed antioxidant,anti-inflammatory,and anti-AD activities.Herein,we hypothesized that a combination treatment of CA and Lf would synergistically improve AD symptoms and studied its mechanisms.Twelve-week-old amyloid precursor protein(APP)/presenilin 1(PS1)mice were treated with CA,Lf,or both CA and Lf for 8 weeks.Results showed that individual and combined treatments could ameliorate cognitive deficits to varying degrees,with stronger effects for combined intervention than for CA or Lf alone.Specifically,combined treatment was most effective in improving nesting ability and reducing amyloidββ_(1-42)(Aβ_(1-42))deposition in mice.Moreover,combined treatment was more effective in suppressing APP,β-site APP cleavage enzyme 1,and inflammation;it inhibited the CCAAT-enhancer-binding protein(C/EBPβ)/asparagine endopeptidase(AEP)signaling pathway in the hippocampus and colon and upregulated the expression of tight junction protein zonula occludens-1 in the colon;it also decreased the Firmicutes/Bacteroidetes ratio at the phylum level and increased the relative abundance of Prevotellaceae,Lachnospira,and Eubacterium at the genus level.Overall,the combination of CA and Lf may ameliorate cognitive deficits in APP/PS1 mice by improving inflammation and inhibiting the C/EBPβ/AEP signaling pathway via modulating gut microbiome.
基金Supported by the National Natural Science Foundation of China(42302184)Innovation Group Project of Basic Research in Gansu Province,China(22JR5RA045)。
文摘The lamina(combination)types,reservoir characteristics and shale oil occurrence states of organic-rich shale in the Triassic Yanchang Formation Chang 73 sub-member in the Ordos Basin were systematically investigated to reveal the main controlling factors of shale oil occurrence under different lamina combinations.The differential enrichment mechanisms and patterns of shale oil were discussed using the shale oil micro-migration characterization and evaluation methods from the perspectives of relay hydrocarbon supply,stepwise migration,and multi-stage differentiation.The results are obtained in five aspects.First,Chang 73 shale mainly develops five types of lamina combination,i.e.non-laminated shale,sandy laminated shale,tuffaceous laminated shale,mixed laminated shale,and organic-rich laminated shale.Second,shales with different lamina combinations are obviously different in the reservoir space.Specifically,shales with sandy laminae and tuffaceous laminae have a large number of intergranular pores,dissolution pores and hydrocarbon generation-induced fractures.The multi-scale pore and fracture system constitutes the main place for liquid hydrocarbon occurrence.Third,the occurrence and distribution of shale oil in shale with different lamina combinations are jointly controlled by organic matter abundance,reservoir property,thermal evolution degree,mineral composition and laminae scale.The micro-nano-scale pore-fracture networks within shales containing rigid laminae,particularly sandy and tuffaceous laminations,primarily contain free-state light hydrocarbon components.In contrast,adsorption-phase heavy hydrocarbon components predominantly occupy surfaces of organic matter assemblages,clay mineral matrices,and framework mineral particulates.Fourth,there is obvious shale oil micro-migration between shales with different lamina combinations in Chang 73.Generally,such micro-migration is stepwise in a sequence of organic-rich laminated shale→tuffaceous laminated shale→mixed laminated shale→sandy lamiated shale→non-laminated shale.Fifth,the relay hydrocarbon supply of organic matter under the control of the spatial superposition of shales with various laminae,the stepwise migration via multi-scale pore and fracture network,and the multi-differentiation in shales with different lamina combinations under the control of organic-inorganic interactions fundamentally decide the differences of shale oil components between shales with different lamina combinations.
