Combination treatment of inflammatory bowel disease:Present status and future perspectives

The treatment of patients with inflammatory bowel disease(IBD),especially those with severe or refractory disease,represents an important challenge for the clinical gastroenterologist.It seems to be no exaggeration to say that in these patients,not only the scientific background of the gastroenterologist is tested,but also the abundance of“gifts”that he should possess(insight,intuition,determ-ination,ability to take initiative,etc.)for the successful outcome of the treatment.In daily clinical practice,depending on the severity of the attack,IBD is treated with one or a combination of two or more pharmaceutical agents.These combin-ations include not only the first-line drugs(e.g.,mesalazine,corticosteroids,antibiotics,etc)but also second-and third-line drugs(immunosuppressants and biologic agents).It is a fact that despite the significant therapeutic advances there is still a significant percentage of patients who do not satisfactorily respond to the treatment applied.Therefore,a part of these patients are going to surgery.In recent years,several small-size clinical studies,reviews,and case reports have been published combining not only biological agents with other drugs(e.g.,immunosuppressants or corticosteroids)but also the combination of two biologi-cal agents simultaneously,especially in severe cases.In our opinion,it is at least a strange(and largely unexplained)fact that we often use combinations of drugs in a given patient although studies comparing the simultaneous administration of two or more drugs with monotherapy are very few.As mentioned above,there is a timid tendency in the literature to combine two biological agents in severe cases unresponsive to the applied treatment or patients with severe extraintestinal manifestations.The appropriate dosage,the duration of the administration,the suitable timing for checking the clinical and laboratory outcome,as well as the treatment side-effects,should be the subject of intense clinical research shortly.In this editorial,we attempt to summarize the existing data regarding the already applied combination therapies and to humbly formulate thoughts and suggestions for the future application of the combination treatment of biological agents in a well-defined category of patients.We suggest that the application of biomarkers and artificial intelligence could help in establishing new forms of treatment using the available modern drugs in patients with IBD resistant to treatment.

Dynamic simulation analysis of molten salt reactor-coupled air-steam combined cycle power generation system

A nonlinear dynamic simulation model based on coordinated control of speed and flow rate for the molten salt reactor and combined cycle systems is proposed here to ensure the coordination and stability between the molten salt reactor and power system.This model considers the impact of thermal properties of fluid variation on accuracy and has been validated with Simulink.This study reveals the capability of the control system to compensate for anomalous situations and maintain shaft stability in the event of perturbations occurring in high-temperature molten salt tank outlet parameters.Meanwhile,the control system’s impact on the system’s dynamic characteristics under molten salt disturbance is also analyzed.The results reveal that after the disturbance occurs,the controlled system benefits from the action of the control,and the overshoot and disturbance amplitude are positively correlated,while the system power and frequency eventually return to the initial values.This simulation model provides a basis for utilizing molten salt reactors for power generation and maintaining grid stability.

Back to the drawing board:Overview of the next generation of combination therapy for inflammatory bowel disease

Inflammatory bowel disease(IBD)is entering a potentially new era of combined therapeutics.Triantafillidis et al provide an insightful review of the current state of combination therapy,with a focus on the use of a combined biologic and immunomodulator,as well as emerging data on the future potential of dual-biologic therapy(DBT).While current evidence for DBT is limited,encouraging safety profiles and ongoing trials suggest a brighter future for this approach.The importance of controlled trials should be stressed in establishing new treatment paradigms.Ongoing prospective randomized trials of DBT and perhaps future combinations of biologics and small molecule therapies will hopefully guide the next generation of IBD care.

Grain Yield,Biomass Accumulation,and Leaf Photosynthetic Characteristics of Rice under Combined Salinity-Drought Stress

Simultaneous stresses of salinity and drought often coincide during rice-growing seasons in saline lands,primarily due to insufficient water resources and inadequate irrigation facilities.Consequently,combined salinity-drought stress poses a major threat to rice production.In this study,two salinity levels(NS,non-salinity;HS,high salinity)along with three drought treatments(CC,control condition;DJ,drought stress imposed at jointing;DH,drought stress imposed at heading)were performed to investigate their combined influences on leaf photosynthetic characteristics,biomass accumulation,and rice yield formation.Salinity,drought,and their combination led to a shortened growth period from heading to maturity,resulting in a reduced overall growth duration.Grain yield was reduced under both salinity and drought stress,with a more substantial reduction under the combined salinity-drought stress.The combined stress imposed at heading caused greater yield losses in rice compared with the stress imposed at jointing.Additionally,the combined salinity-drought stress induced greater decreases in shoot biomass accumulation from heading to maturity,as well as in shoot biomass and nonstructural carbohydrate(NSC)content in the stem at heading and maturity.However,it increased the harvest index and NSC remobilization reserve.Salinity and drought reduced the leaf area index and SPAD value of flag leaves and weakened the leaf photosynthetic characteristics as indicated by lower photosynthetic rates,transpiration rates,and stomatal conductance.These reductions were more pronounced under the combined stress.Salinity,drought,and especially their combination,decreased the activities of ascorbate peroxidase,catalase,and superoxide dismutase,while increasing the contents of malondialdehyde,hydrogen peroxide,and superoxide radical.Our results indicated a more significant yield loss in rice when subjected to combined salinity-drought stress.The individual and combined stresses of salinity and drought diminished antioxidant enzyme activities,inhibited leaf photosynthetic functions,accelerated leaf senescence,and subsequently lowered assimilate accumulation and grain yield.

Erlotinib combination with a mitochondria-targeted ubiquinone effectively suppresses pancreatic cancer cell survival

BACKGROUND Pancreatic cancer is a leading cause of cancer-related deaths.Increased activity of the epidermal growth factor receptor(EGFR)is often observed in pancreatic cancer,and the small molecule EGFR inhibitor erlotinib has been approved for pancreatic cancer therapy by the food and drug administration.Nevertheless,erlotinib alone is ineffective and should be combined with other drugs to improve therapeutic outcomes.We previously showed that certain receptor tyrosine kinase inhibitors can increase mitochondrial membrane potential(Δψm),facilitate tumor cell uptake ofΔψm-sensitive agents,disrupt mitochondrial homeostasis,and subsequently trigger tumor cell death.Erlotinib has not been tested for this effect.AIM To determine whether erlotinib can elevateΔψm and increase tumor cell uptake ofΔψm-sensitive agents,subsequently triggering tumor cell death.METHODSΔψm-sensitive fluorescent dye was used to determine how erlotinib affectsΔψm in pancreatic adenocarcinoma(PDAC)cell lines.The viability of conventional and patient-derived primary PDAC cell lines in 2D-and 3D cultures was measured after treating cells sequentially with erlotinib and mitochondria-targeted ubiquinone(MitoQ),aΔψm-sensitive MitoQ.The synergy between erlotinib and MitoQ was then analyzed using SynergyFinder 2.0.The preclinical efficacy of the twodrug combination was determined using immune-compromised nude mice bearing PDAC cell line xenografts.RESULTS Erlotinib elevatedΔψm in PDAC cells,facilitating tumor cell uptake and mitochondrial enrichment ofΔψm-sensitive agents.MitoQ triggered caspase-dependent apoptosis in PDAC cells in culture if used at high doses,while erlotinib pretreatment potentiated low doses of MitoQ.SynergyFinder suggested that these drugs synergistically induced tumor cell lethality.Consistent with in vitro data,erlotinib and MitoQ combination suppressed human PDAC cell line xenografts in mice more effectively than single treatments of each agent.CONCLUSION Our findings suggest that a combination of erlotinib and MitoQ has the potential to suppress pancreatic tumor cell viability effectively.

Pressure stimulated current in progressive failure process of combined coal-rock under uniaxial compression:Response and mechanism

Effective monitoring of the structural health of combined coal-rock under complex geological conditions by pressure stimulated currents(PSCs)has great potential for the understanding of dynamic disasters in underground engineering.To reveal the effect of this way,the uniaxial compression experiments with PSC monitoring were conducted on three types of coal-rock combination samples with different strength combinations.The mechanism explanation of PSCs are investigated by resistivity test,atomic force microscopy(AFM)and computed tomography(CT)methods,and a PSC flow model based on progressive failure process is proposed.The influence of strength combinations on PSCs in the progressive failure process are emphasized.The results show the PSC responses between rock part,coal part and the two components are different,which are affected by multi-scale fracture characteristics and electrical properties.As the rock strength decreases,the progressive failure process changes obviously with the influence range of interface constraint effect decreasing,resulting in the different responses of PSC strength and direction in different parts to fracture behaviors.The PSC flow model is initially validated by the relationship between the accumulated charges of different parts.The results are expected to provide a new reference and method for mining design and roadway quality assessment.

Enhancing metformin-induced tumor metabolism destruction by glucose oxidase for triple-combination therapy

Despite decades of laboratory and clinical trials,breast cancer remains the main cause of cancer-related disease burden in women.Considering the metabolism destruction effect of metformin(Met)and cancer cell starvation induced by glucose oxidase(GOx),after their efficient delivery to tumor sites,GOx and Met may consume a large amount of glucose and produce sufficient hydrogen peroxide in situ.Herein,a pH-responsive epigallocatechin gallate(EGCG)-conjugated low-molecular-weight chitosan(LC-EGCG,LE)nanoparticle(Met–GOx/Fe@LE NPs)was constructed.The coordination between iron ions(Fe3+)and EGCG in this nanoplatform can enhance the efficacy of chemodynamic therapy via the Fenton reaction.Met–GOx/Fe@LE NPs allow GOx to retain its enzymatic activity while simultaneously improving its stability.Moreover,this pH-responsive nanoplatform presents controllable drug release behavior.An in vivo biodistribution study showed that the intracranial accumulation of GOx delivered by this nanoplatform was 3.6-fold higher than that of the free drug.The in vivo anticancer results indicated that this metabolism destruction/starvation/chemodynamic triple-combination therapy could induce increased apoptosis/death of tumor cells and reduce their proliferation.This triple-combination therapy approach is promising for efficient and targeted cancer treatment.

Using harmonic beam combining to generate pulse-burst in nonlinear optical laser

The ultrashort lasers working in pulse-burst mode reveal great machining performance in recent years. The number of pulses in bursts effects greatly on the removal rate and roughness. To generate a more equal amplitude of pulses in burst with linear polarization output and time gap adjustable, we propose a new method by the harmonic beam combining(HBC).The beam combining is commonly used in adding pulses into the output beam while maintaining the pulse waveform and beam quality. In the HBC, dichroic mirrors are used to combine laser pulses of fundamental wave(FW) into harmonic wave(HW), and nonlinear crystals are used to convert the FW into HW. Therefore, HBC can add arbitrarily more HW pulses to generate pulse-burst in linear polarization with simple structure. The amplitude of each pulse in bursts can be adjusted the same to increase the stability of the burst, the time gap of each pulse can be adjusted precisely by proper time delay. Because HBC adds pulses sequentially, the peak power density of the burst is the same as each pulse, pulses can be combined without concern of back-conversion which often occurs in high peak power density. In the demonstration, the extendibility of HBC was verified by combining two beams with a third beam. The combined efficiency rates were larger than 99%, and the beam quality of each beam was maintained at M^(2)≈1.4.

Advances in extracellular vesicle-based combination therapies for spinal cord injury

Spinal cord injury is a severe insult to the central nervous system that causes persisting neurological deficits.The currently available treatments involve surgical,medical,and rehabilitative strategies.However,none of these techniques can markedly reverse neurological deficits.Recently,extracellular vesicles from various cell sources have been applied to different models of spinal cord injury,thereby generating new cell-free therapies for the treatment of spinal cord injury.However,the use of extracellular vesicles alone is still associated with some notable shortcomings,such as their uncertainty in targeting damaged spinal cord tissues and inability to provide structural support to damaged axons.Therefore,this paper reviews the latest combined strategies for the use of extracellular vesicle-based technology for spinal cord injury,including the combination of extracellular vesicles with nanoparticles,exogenous drugs and/or biological scaffold materials,which facilitate the targeting ability of extracellular vesicles and the combinatorial effects with extracellular vesicles.We also highlight issues relating to the clinical transformation of these extracellular vesicle-based combination strategies for the treatment of spinal cord injury.

Evaluation of soil erosion vulnerability in Hubei Province of China using RUSLE model and combination weighting method

Soil erosion has been recognized as a critical environmental issue worldwide.While previous studies have primarily focused on watershed-scale soil erosion vulnerability from a natural factor perspective,there is a notable gap in understanding the intricate interplay between natural and socio-economic factors,especially in the context of spatial heterogeneity and nonlinear impacts of human-land interactions.To address this,our study evaluates the soil erosion vulnerability at a provincial scale,taking Hubei Province as a case study to explore the combined effects of natural and socio-economic factors.We developed an evaluation index system based on 15 indicators of soil erosion vulnerability:exposure,sensitivity,and adaptability.In addition,the combination weighting method was applied to determine index weights,and the spatial interaction was analyzed using spatial autocorrelation,geographical temporally weighted regression and geographical detector.The results showed an overall decreasing soil erosion intensity in Hubei Province during 2000 and 2020.The soil erosion vulnerability increased before 2000 and then.The areas with high soil erosion vulnerability were mainly confined in the central and southern regions of Hubei Province(Xiantao,Tianmen,Qianjiang and Ezhou)with obvious spatial aggregation that intensified over time.Natural factors(habitat quality index)had negative impacts on soil erosion vulnerability,whereas socio-economic factors(population density)showed substantial spatial variability in their influences.There was a positive correlation between soil erosion vulnerability and erosion intensity,with the correlation coefficients ranging from-0.41 and 0.93.The increase of slope was found to enhance the positive correlation between soil erosion vulnerability and intensity.

A Subdivision-Based Combined Shape and Topology Optimization in Acoustics

We propose a combined shape and topology optimization approach in this research for 3D acoustics by using the isogeometric boundary element method with subdivision surfaces.The existing structural optimization methods mainly contain shape and topology schemes,with the former changing the surface geometric profile of the structure and the latter changing thematerial distribution topology or hole topology of the structure.In the present acoustic performance optimization,the coordinates of the control points in the subdivision surfaces fine mesh are selected as the shape design parameters of the structure,the artificial density of the sound absorbing material covered on the structure surface is set as the topology design parameter,and the combined topology and shape optimization approach is established through the sound field analysis of the subdivision surfaces boundary element method as a bridge.The topology and shape sensitivities of the approach are calculated using the adjoint variable method,which ensures the efficiency of the optimization.The geometric jaggedness and material distribution discontinuities that appear in the optimization process are overcome to a certain degree by the multiresolution method and solid isotropic material with penalization.Numerical examples are given to validate the effectiveness of the presented optimization approach.

Anti-OX40 Antibody Combined with HBc VLPs Delays Tumor Growth in a Mouse Colon Cancer Model

Objective Combination immunotherapy strategies targeting OX40,a co-stimulatory molecule that can enhance antitumor immunity by modulating the proliferation,differentiation,and effector function of tumor-infiltrating T cells,have attracted much attention for their excellent therapeutic effects.In this study,we aimed to evaluate the antitumor efficacy of combined anti-OX40 and hepatitis B core viruslike particles(HBc VLPs)therapy using a mouse colon cancer model.Methods Humanized B-h OX40 mice were injected subcutaneously with MC38 colon tumor cells and treated with HBc VLPs+anti-h OX40 antibody.Tumor growth was monitored.Flow cytometric analysis was performed to evaluate the populations of T cell subsets in the tumors.Results The combination of anti-OX40 with HBc VLPs resulted in a significant delay in tumor growth,suggesting that a potent antitumor immunity was induced by the combination therapy.Further studies revealed that HBc VLPs+anti-OX40 treatment induced a significant increase in effector T cells(Teffs)and a significant decrease in regulatory T cells(Tregs)in the tumor microenvironment(TME),which accounted for the synergistic antitumor effect of anti-OX40 in combination with HBc VLPs.Conclusion Combination therapy of anti-h OX40 and HBc VLPs provides synergistic antitumor activity in colon cancer-bearing mice,which may represent a potential design strategy for cancer immunotherapy.

Combinational therapy with Myc decoy oligodeoxynucleotides encapsulated in nanocarrier and X-irradiation on breast cancer cells

The Myc gene is the essential oncogene in triple-negative breast cancer(TNBC).This study investigates the synergistic effects of combining Myc decoy oligodeoxynucleotides-encapsulated niosomes-selenium hybrid nanocarriers with X-irradiation exposure on the MDA-MB-468 cell line.Decoy and scramble ODNs for Myc transcription factor were designed and synthesized based on promoter sequences of the Bcl2 gene.The nanocarriers were synthesized by loading Myc ODNs and selenium into chitosan(Chi-Se-DEC),which was then encapsulated in niosome-nanocarriers(NISM@Chi-Se-DEC).FT-IR,DLS,FESEM,and hemolysis tests were applied to confirm its characterization and physicochemical properties.Moreover,cellular uptake,cellular toxicity,apoptosis,cell cycle,and scratch repair assays were performed to evaluate its anticancer effects on cancer cells.All anticancer assessments were repeated under X-ray irradiation conditions(fractionated 2Gy).Physicochemical characteristics of niosomes containing SeNPs and ODNs showed that it is synthesized appropriately.It revealed that the anticancer effect of NISM@Chi-Se-DEC can be significantly improved in combination with X-ray irradiation treatment.It can be concluded that NISM@Chi-Se-DEC nanocarriers have the potential as a therapeutic agent for cancer treatment,particularly in combination with radiation therapy and in-vivo experiments are necessary to confirm the efficacy of this nano-drug.

Numerical Investigation of Combined Production of Natural Gas Hydrate and Conventional Gas

Natural gas hydrate(NGH)is generally produced and accumulated together with the underlying conventional gas.Therefore,optimizing the production technology of these two gases should be seen as a relevant way to effectively reduce the exploitation cost of the gas hydrate.In this study,three types of models accounting for the coexistence of these gases are considered.Type A considers the upper hydrate-bearing layer(HBL)adjacent to the lower conventional gas layer(CGL);with the Type B a permeable interlayer exists between the upper HBL and the lower CGL;with the type C there is an impermeable interlayer between the upper HBL and the lower CGL.The production performances associated with the above three models are calculated under different conditions,including only a depressurized HBL(only HBL DP);only a depressurized CGL(only CGL DP);and both the HBL and the CGL being depressurized(HBL+CGL DP).The results show that for Type A and Type B coexistence accumulation models,when only HBL or CGL is depressurized,the gas from the other layer will flow into the production layer due to the pressure difference between the two layers.In the coexistence accumulation model of type C,the cumulative gas production is much lower than that of Type A and Type B,regardless of whether only HBL DP,only CGL DP,or HBL+CGL DP are considered.This indicates that the impermeable interlayer restricts the cross-flow of gas between HBL and CGL.For three different coexistence accumulation models,CGL DP has the largest gas-to-water ratio.

LociScan,a tool for screening genetic marker combinations for plant variety discrimination

To reduce the cost and increase the efficiency of plant genetic marker fingerprinting for variety discrimination,it is desirable to identify the optimal marker combinations.We describe a marker combination screening model based on the genetic algorithm(GA)and implemented in a software tool,Loci Scan.Ratio-based variety discrimination power provided the largest optimization space among multiple fitness functions.Among GA parameters,an increase in population size and generation number enlarged optimization depth but also calculation workload.Exhaustive algorithm afforded the same optimization depth as GA but vastly increased calculation time.In comparison with two other software tools,Loci Scan accommodated missing data,reduced calculation time,and offered more fitness functions.In large datasets,the sample size of training data exerted the strongest influence on calculation time,whereas the marker size of training data showed no effect,and target marker number had limited effect on analysis speed.

Targeted anti-tumor synergistic effects of Myc decoy oligodeoxynucleotides-loaded selenium nanostructure combined with chemoradiotherapy on LNCaP prostate cancer cells

In the present study,we investigated the synergistic effects of targeted methotrexate-selenium nanostructure containing Myc decoy oligodeoxynucleotides along with X-irradiation exposure as a combination therapy on LNCaP prostate cancer cells.Myc decoy ODNs were designed based on the promoter of Bcl-2 gene and analyzed by molecular docking and molecular dynamics assays.ODNs were loaded on the synthesized Se@BSA@Chi-MTX nanostructure.The physicochemical characteristics of nanostructures were determined by FTIR,DLS,UV-vis,TEM,EDX,in vitro release,and hemolysis tests.Subsequently,the cytotoxicity properties of them with and without X-irradiation were investigated by uptake,MTT,cell cycle,apoptosis,and scratch assays on the LNCaP cell line.The results of DLS and TEM showed negative charge(−9 mV)and nanometer size(40 nm)for Se@BSA@Chi-DEC-MTX NPs,respectively.The results of FTIR,UV-vis,and EDX showed the proper interaction of different parts and the correct synthesis of nanoparticles.The results of hemolysis showed the hemocompatibility of this nanoparticle in concentrations less than 6 mg/mL.The ODNs release from the nanostructures showed a pH-dependent manner,and the release rate was 15%higher in acidic pH.The targeted Se@BSA@Chi-labeled ODN-MTX NPs were efficiently taken up by LNCaP cells by targeting the prostate-specific membrane antigen(PSMA).The significant synergistic effects of nanostructure(containing MTX drug)treatment along with X-irradiation showed cell growth inhibition,apoptosis induction(~57%),cell cycle arrest(G2/M phase),and migration inhibition(up to 90%)compared to the control.The results suggested that the Se@BSA@Chi-DEC-MTX NPs can potentially suppress the cell growth of LNCaP cells.This nanostructure system can be a promising approach for targeted drug delivery and chemoradiotherapy in prostate cancer treatment.

Combined blasting for protection of gob-side roadway with thick and hard roof

The deformation control of surrounding rock in gobside roadway with thick and hard roof poses a significant challenge to the safety and efficiency of coal mining.To address this issue,a novel approach combining directional and non-directional blasting techniques,known as combined blasting,was proposed.This study focuses on the experimental investigation of the proposed method in the 122108 working face in Caojiatan Coal Mine as the engineering background.The initial phase of the study involves physical model experiments to reveal the underlying mechanisms of combined blasting for protecting gob-side roadway with thick and hard roof.The results demonstrate that this approach effectively accelerates the collapse of thick and hard roofs,enhances the fragmentation and expansion coefficient of gangue,facilitates the filling of the goaf with gangue,and provides support to the overlying strata,thus reducing the subsidence of the overlying strata above the goaf.Additionally,the method involves cutting the main roof into shorter beams to decrease the stress and disrupt stress transmission pathways.Subsequent numerical simulations were conducted to corroborate the findings of the physical model experiments,thus validating the accuracy of the experimental results.Furthermore,field engineering experiments were performed,affirming the efficacy of the combined blasting method in mitigating the deformation of surrounding rock and achieving the desired protection of the gob-side roadway.

Heterogeneous information phase space reconstruction and stability prediction of filling body–surrounding rock combination

Traditional research believes that the filling body can effectively control stress concentration while ignoring the problems of unknown stability and the complex and changeable stress distribution of the filling body–surrounding rock combination under high-stress conditions.Current monitoring data processing methods cannot fully consider the complexity of monitoring objects,the diversity of monitoring methods,and the dynamics of monitoring data.To solve this problem,this paper proposes a phase space reconstruction and stability prediction method to process heterogeneous information of backfill–surrounding rock combinations.The three-dimensional monitoring system of a large-area filling body–surrounding rock combination in Longshou Mine was constructed by using drilling stress,multipoint displacement meter,and inclinometer.Varied information,such as the stress and displacement of the filling body–surrounding rock combination,was continuously obtained.Combined with the average mutual information method and the false nearest neighbor point method,the phase space of the heterogeneous information of the filling body–surrounding rock combination was then constructed.In this paper,the distance between the phase point and its nearest point was used as the index evaluation distance to evaluate the stability of the filling body–surrounding rock combination.The evaluated distances(ED)revealed a high sensitivity to the stability of the filling body–surrounding rock combination.The new method was then applied to calculate the time series of historically ED for 12 measuring points located at Longshou Mine.The moments of mutation in these time series were at least 3 months ahead of the roadway return dates.In the ED prediction experiments,the autoregressive integrated moving average model showed a higher prediction accuracy than the deep learning models(long short-term memory and Transformer).Furthermore,the root-mean-square error distribution of the prediction results peaked at 0.26,thus outperforming the no-prediction method in 70%of the cases.

A technique for enhancing tight oil recovery by multi-field reconstruction and combined displacement and imbibition

A seepage-geomechanical coupled embedded fracture flow model has been established for multi-field coupled simulation in tight oil reservoirs,revealing the patterns of change in pressure field,seepage field,and stress field after long-term water injection in tight oil reservoirs.Based on this,a technique for enhanced oil recovery(EOR)combining multi-field reconstruction and combination of displacement and imbibition in tight oil reservoirs has been proposed.The study shows that after long-term water flooding for tight oil development,the pressure diffusion range is limited,making it difficult to establish an effective displacement system.The variation in geostress exhibits diversity,with the change in horizontal minimum principal stress being greater than that in horizontal maximum principal stress,and the variation around the injection wells being more significant than that around the production wells.The deflection of geostress direction around injection wells is also large.The technology for EOR through multi-field reconstruction and combination of displacement and imbibition employs water injection wells converted to production and large-scale fracturing techniques to restructure the artificial fracture network system.Through a full lifecycle energy replenishment method of pre-fracturing energy supplementation,energy increase during fracturing,well soaking for energy storage,and combination of displacement and imbibition,it effectively addresses the issue of easy channeling of the injection medium and difficult energy replenishment after large-scale fracturing.By intensifying the imbibition effect through the coordination of multiple wells,it reconstructs the combined system of displacement and imbibition under a complex fracture network,transitioning from avoiding fractures to utilizing them,thereby improving microscopic sweep and oil displacement efficiencies.Field application in Block Yuan 284 of the Huaqing Oilfield in the Ordos Basin has demonstrated that this technology increases the recovery factor by 12 percentage points,enabling large scale and efficient development of tight oil.

Adaptive H_(∞)Filtering Algorithm for Train Positioning Based on Prior Combination Constraints

To solve the problem of data fusion for prior information such as track information and train status in train positioning,an adaptive H∞filtering algorithm with combination constraint is proposed,which fuses prior information with other sensor information in the form of constraints.Firstly,the train precise track constraint method of the train is proposed,and the plane position constraint and train motion state constraints are analysed.A model for combining prior information with constraints is established.Then an adaptive H∞filter with combination constraints is derived based on the adaptive adjustment method of the robustness factor.Finally,the positioning effect of the proposed algorithm is simulated and analysed under the conditions of a straight track and a curved track.The results show that the positioning accuracy of the algorithm with constrained filtering is significantly better than that of the algorithm without constrained filtering and that the algorithm with constrained filtering can achieve better performance when combined with track and condition information,which can significantly reduce the train positioning error.The effectiveness of the proposed algorithm is verified.