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 mol...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.展开更多
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 com...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.展开更多
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...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.展开更多
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 erl...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.展开更多
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 salinit...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.展开更多
This editorial is a commentary on the article by Ni et al,which was published in the World Journal of Clinical Cases.The article discusses the diagnostic and therapeutic challenges of melioidosis caused by Burkholderi...This editorial is a commentary on the article by Ni et al,which was published in the World Journal of Clinical Cases.The article discusses the diagnostic and therapeutic challenges of melioidosis caused by Burkholderia pseudomallei.The case study highlights a rare instance of multisystemic melioidosis in a female patient who did not have a travel history,emphasizing the significance of recognizing this condition in non-endemic regions.Diagnostic complexities and therapeutic strategies are addressed,emphasizing the need for heightened clinical suspicion,comprehensive evaluation,and multidisciplinary collaboration.The editorial delves into the clinical presentation,diagnostic dilemmas,therapeutic approaches,and their implications for patient care in managing multi-systemic melioidosis.展开更多
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 amplitud...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.展开更多
Introduction: Resistance to antituberculosis drugs and adverse drug reactions remain the leading causes of tuberculosis therapeutic failure globally. Despite the increasing acceptance of medicinal plant use in combina...Introduction: Resistance to antituberculosis drugs and adverse drug reactions remain the leading causes of tuberculosis therapeutic failure globally. Despite the increasing acceptance of medicinal plant use in combination with conventional antituberculosis drugs in treatment of tuberculosis (TB) in Uganda, there is paucity of knowledge on their combination effect. Aim: This research aimed to determine combination activity of standard antituberculosis drugs with extracts of Zanthoxylum leprieurii Guill. & Perr. and Rubia cordifolia L., the two common antituberculosis medicinal plants in Uganda, against pansensitive (H37Rv) and multi-drug resistant (MDR) Mycobacterium tuberculosis strains. Materials and Methods: Two reference MTB strains (H37Rv and MDR strain) were inoculated on Middlebrook 7H11 medium containing a combination of standard antituberculosis drugs and methanol extracts of Z. leprieurii and R. cordifolia at varying concentrations. The number of colonies on the plates was observed and counted weekly for up to 8 weeks. In vitro combination activity was determined using proportion method. Mean percentage inhibition was calculated for the reduction of number of colonies on drug-extract combination medium in relation to drug-extract-free control medium. Results: Drug-extract combinations showed good combination activity against Mycobacterium tuberculosis strains when compared with individual standard anti-TB drugs. This was more exhibited against MDR strain. There was however a reduction in percentage inhibition when extracts were combined with ethambutol and streptomycin against H37Rv strain. Conclusions: Zanthoxylum leprieurii and Rubia cordifolia in combination with standard anti-TB drugs exhibited increased in vitro activity against Mycobacterium tuberculosis, especially MDR-TB strain. This justifies the local use of these plants in traditional treatment of tuberculosis especially in resistant cases in Uganda.展开更多
Background: This study evaluated the bioequivalence of empagliflozin 12.5 mg/metformin 1000 mg tablets compared to Synjardy® (Empagliflozin 12.5 mg/metformin 1000 mg) tablets in healthy male subjects under fastin...Background: This study evaluated the bioequivalence of empagliflozin 12.5 mg/metformin 1000 mg tablets compared to Synjardy® (Empagliflozin 12.5 mg/metformin 1000 mg) tablets in healthy male subjects under fasting conditions. Methods: This was a phase I, randomized, single-dose, two-period, two-sequence, crossover study to evaluate the bioequivalence (BE) profiles of two fixed-dose combinations (FDCs) of empagliflozin/metformin. Cmax, AUC0-t and AUC0-∞ from test and reference formulations were evaluated to access BE. The plasma concentrations were measured using a validated liquid chromatography-mass spectrometry (LC-MS/MS) method. Of the 24 subjects enrolled, 23 completed both periods of the study. The two formulations test and reference were considered bioequivalent if 90% confidence interval (CI) fell within 80.00% - 125.00% for Cmax, AUC0-t and AUC0-∞. Tolerability and safety were assessed throughout the study. Results: The pharmacokinetic (PK) parameters were similar between the test product (T) and reference product (R) Synjardy®. The 90% CI of the test/reference ratios of log-transformed PK parameters point estimates was Cmax: 89.87% (85.68% - 94.27%), AUC0-t: 87.91% (83.65% - 92.39%) and AUC0-∞: 87.16% (82.80% - 91.75%) to empagliflozin and Cmax: 92.19% (87.95% - 96.65%), AUC0-t: 91.38% (84.42% - 98.91%) and AUC0-∞: 93.78% (83.82% - 104.93%) to metformin respectively (90% CI for all PK parameters fell within 80.00% - 125.00%). Conclusion: Our results demonstrated BE between the test and reference formulations of oral tablets of empagliflozin 12.5 mg/metformin 1000 mg (FDC) in healthy male subjects under fasting conditions.展开更多
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 starvatio...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.展开更多
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 undergroun...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.展开更多
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 in...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.展开更多
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 effecti...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.展开更多
BACKGROUND Recently,combination therapy has shown a better trend towards improved tumour response and survival outcomes than monotherapy in patients with hepatocellular carcinoma(HCC).However,research on triple therap...BACKGROUND Recently,combination therapy has shown a better trend towards improved tumour response and survival outcomes than monotherapy in patients with hepatocellular carcinoma(HCC).However,research on triple therapy[lenvatinib+sintilimab+transarterial chemoembolization(TACE)]as a first-line treatment for advanced HCC is limited.AIM To evaluate the safety and efficacy of triple therapy as a first-line treatment for advanced HCC.METHODS HCC patients with Barcelona Clinic Liver Cancer stage C treated with triple therapy were enrolled.All patients were treated with lenvatinib every day and sintilimab once every 3 wk.Moreover,TACE was performed every 4-6 wk if necessary.The primary outcome of the study was overall survival(OS).The secondary outcomes were the objective response rate(ORR),disease control rate(DCR),and incidence of adverse events.RESULTS Forty HCC patients who underwent triple therapy were retrospectively analysed from January 2019 to January 2022.With a median follow-up of 8.5 months,the 3-,6-,and 12-mo OS rates were 100%,88.5%,and 22.5%,respectively.The ORR and DCR were 45%and 90%,respectively.The median progressive free survival and median OS were not reached.Common complications were observed in 76%of the patients(grade 3,15%;grade 4,2.5%).CONCLUSION Combination therapy comprising lenvatinib,sintilimab and TACE achieved promising outcomes in advanced HCC patients and had manageable effects.展开更多
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...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.展开更多
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 nanocarr...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.展开更多
Objective: To explore the clinical effectiveness of combined use of intravenous pain pump with Parecoxib injection in alleviating pain in patients during the early postoperative period after thoracoscopic surgery. Met...Objective: To explore the clinical effectiveness of combined use of intravenous pain pump with Parecoxib injection in alleviating pain in patients during the early postoperative period after thoracoscopic surgery. Methods: Eighty patients who underwent thoracoscopic surgery in a tertiary hospital were selected as the study subjects and randomly divided into two groups, with 40 patients in each group. The control group received routine postoperative treatment with intravenous pain pump, while the experimental group received Parecoxib in addition to the standard postoperative pain pump treatment. Visual Analog Scale (VAS) pain scores were used to evaluate postoperative pain relief in both groups, along with adverse reactions, postoperative complications, and patient satisfaction with pain relief. Results: Patients who received Parecoxib injection in addition to the routine use of intravenous pain pump had VAS pain scores lower than 3 points at 6 h, 12 h, 24 h, and 36 h postoperatively compared to those in the control group. The incidence of postoperative lung collapse, pleural effusion, and pulmonary infections was also significantly lower in the experimental group. The differences between the two groups were statistically significant (P Conclusion: Early combined use of Parecoxib injection in the early postoperative period after thoracoscopic surgery has shown good clinical efficacy. It can reduce the level of pain in patients, promote effective coughing and expectoration, facilitate early mobilization of patients, improve patient compliance, reduce complications, shorten hospital stay, and expedite patient recovery. Therefore, it is worth promoting the widespread clinical application of Parecoxib injection in this setting.展开更多
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...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.展开更多
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 not...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.展开更多
Molten aluminum is among the most common causes of burns in the metal industry.However,only few reports are available on molten aluminum injuries.Herein,we report an unusual case of molten aluminum burn.The patient ha...Molten aluminum is among the most common causes of burns in the metal industry.However,only few reports are available on molten aluminum injuries.Herein,we report an unusual case of molten aluminum burn.The patient had burns not only on the body surface but also in the respiratory tract and esophagus,adding to the difficulty of treatment.Multidisciplinary consultation and cooperation led to the development of a treatment plan for the patient,which included tracheotomy,respiratory management,endoscopic therapy,infection control,and psychological support.To our knowledge,this is the first report of molten aluminum-induced burns involving the face,neck,respiratory tract,esophagus,and eyes.We also describe our experience with multidisciplinary treatment for the management of molten aluminum burns.展开更多
基金This work was supported by the Chinese TMSR Strategic Pioneer Science and Technology Project(No.XDA02010300).
文摘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.
文摘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.
文摘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.
基金Supported by NIH/National Cancer Institute Grant,No.R01CA138441 and No.R01CA269452UW Madison Centene Pancreas Cancer Collaborative Award,No.21-8568.
文摘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.
基金financed by the National Key Research and Development Program,China(Grant Nos.2022YFE0113400 and 2022YFD1500402)National Natural Science Foundation of China(Grant No.32001466)+3 种基金Scientific and Technological Innovation Fund of Carbon Emissions Peak and Neutrality of Jiangsu Provincial Department of Science and Technology,China(Grant Nos.BE2022304 and BE2022305)Joints Funds of the National Natural Science Foundation of China(Grant No.U20A2022)Postdoctoral Research Foundation of China(Grant No.2020M671628)the Priority Academic Program Development of Jiangsu Higher Education Institutions,China.
文摘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.
文摘This editorial is a commentary on the article by Ni et al,which was published in the World Journal of Clinical Cases.The article discusses the diagnostic and therapeutic challenges of melioidosis caused by Burkholderia pseudomallei.The case study highlights a rare instance of multisystemic melioidosis in a female patient who did not have a travel history,emphasizing the significance of recognizing this condition in non-endemic regions.Diagnostic complexities and therapeutic strategies are addressed,emphasizing the need for heightened clinical suspicion,comprehensive evaluation,and multidisciplinary collaboration.The editorial delves into the clinical presentation,diagnostic dilemmas,therapeutic approaches,and their implications for patient care in managing multi-systemic melioidosis.
基金Project supported by Youth Innovation Promotion Association of the Chinese Academy of Sciences (Grant No.2020029)。
文摘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.
文摘Introduction: Resistance to antituberculosis drugs and adverse drug reactions remain the leading causes of tuberculosis therapeutic failure globally. Despite the increasing acceptance of medicinal plant use in combination with conventional antituberculosis drugs in treatment of tuberculosis (TB) in Uganda, there is paucity of knowledge on their combination effect. Aim: This research aimed to determine combination activity of standard antituberculosis drugs with extracts of Zanthoxylum leprieurii Guill. & Perr. and Rubia cordifolia L., the two common antituberculosis medicinal plants in Uganda, against pansensitive (H37Rv) and multi-drug resistant (MDR) Mycobacterium tuberculosis strains. Materials and Methods: Two reference MTB strains (H37Rv and MDR strain) were inoculated on Middlebrook 7H11 medium containing a combination of standard antituberculosis drugs and methanol extracts of Z. leprieurii and R. cordifolia at varying concentrations. The number of colonies on the plates was observed and counted weekly for up to 8 weeks. In vitro combination activity was determined using proportion method. Mean percentage inhibition was calculated for the reduction of number of colonies on drug-extract combination medium in relation to drug-extract-free control medium. Results: Drug-extract combinations showed good combination activity against Mycobacterium tuberculosis strains when compared with individual standard anti-TB drugs. This was more exhibited against MDR strain. There was however a reduction in percentage inhibition when extracts were combined with ethambutol and streptomycin against H37Rv strain. Conclusions: Zanthoxylum leprieurii and Rubia cordifolia in combination with standard anti-TB drugs exhibited increased in vitro activity against Mycobacterium tuberculosis, especially MDR-TB strain. This justifies the local use of these plants in traditional treatment of tuberculosis especially in resistant cases in Uganda.
文摘Background: This study evaluated the bioequivalence of empagliflozin 12.5 mg/metformin 1000 mg tablets compared to Synjardy® (Empagliflozin 12.5 mg/metformin 1000 mg) tablets in healthy male subjects under fasting conditions. Methods: This was a phase I, randomized, single-dose, two-period, two-sequence, crossover study to evaluate the bioequivalence (BE) profiles of two fixed-dose combinations (FDCs) of empagliflozin/metformin. Cmax, AUC0-t and AUC0-∞ from test and reference formulations were evaluated to access BE. The plasma concentrations were measured using a validated liquid chromatography-mass spectrometry (LC-MS/MS) method. Of the 24 subjects enrolled, 23 completed both periods of the study. The two formulations test and reference were considered bioequivalent if 90% confidence interval (CI) fell within 80.00% - 125.00% for Cmax, AUC0-t and AUC0-∞. Tolerability and safety were assessed throughout the study. Results: The pharmacokinetic (PK) parameters were similar between the test product (T) and reference product (R) Synjardy®. The 90% CI of the test/reference ratios of log-transformed PK parameters point estimates was Cmax: 89.87% (85.68% - 94.27%), AUC0-t: 87.91% (83.65% - 92.39%) and AUC0-∞: 87.16% (82.80% - 91.75%) to empagliflozin and Cmax: 92.19% (87.95% - 96.65%), AUC0-t: 91.38% (84.42% - 98.91%) and AUC0-∞: 93.78% (83.82% - 104.93%) to metformin respectively (90% CI for all PK parameters fell within 80.00% - 125.00%). Conclusion: Our results demonstrated BE between the test and reference formulations of oral tablets of empagliflozin 12.5 mg/metformin 1000 mg (FDC) in healthy male subjects under fasting conditions.
基金the National Natural Science Foundation of China(Grant Nos.:82102767 and 82002655)the 1·3·5 Project for Disciplines of Excellence-Clinical Research Incubation Project,West China Hospital,Sichuan University,China(Grant No.:2020HXFH036)+2 种基金the Knowledge Innovation Program of the Chinese Academy of Sciences,China(Grant No.:JH2022007)the Cultivation Project of Basic Medical College of Xinxiang Medical University,China(Grant No.:JCYXYKY202112)the Key Project of Science and Technology of Henan Province,China(Grant No.:222102310260).
文摘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.
基金supported by National Key R&D Program of China(No.2022YFC3004705)the National Natural Science Foundation of China(Nos.52074280,52227901 and 52204249)National Natural Science Foundation of China Youth Fund(No.52104230).
文摘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.
基金the National Natural Science Fund of China(61471080)Training Plan for Young Backbone Teachers in Colleges and Universities of Henan Province(2018GGJS171).
文摘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.
基金supported by the National Natural Science Foundation of China (Nos.52074334,51991365)the National Key R&D Program of China (2021YFC2800903),which are gratefully acknowledged.
文摘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.
基金Capital Health Development and Scientific Research Special Project,No.2022-2-2175.
文摘BACKGROUND Recently,combination therapy has shown a better trend towards improved tumour response and survival outcomes than monotherapy in patients with hepatocellular carcinoma(HCC).However,research on triple therapy[lenvatinib+sintilimab+transarterial chemoembolization(TACE)]as a first-line treatment for advanced HCC is limited.AIM To evaluate the safety and efficacy of triple therapy as a first-line treatment for advanced HCC.METHODS HCC patients with Barcelona Clinic Liver Cancer stage C treated with triple therapy were enrolled.All patients were treated with lenvatinib every day and sintilimab once every 3 wk.Moreover,TACE was performed every 4-6 wk if necessary.The primary outcome of the study was overall survival(OS).The secondary outcomes were the objective response rate(ORR),disease control rate(DCR),and incidence of adverse events.RESULTS Forty HCC patients who underwent triple therapy were retrospectively analysed from January 2019 to January 2022.With a median follow-up of 8.5 months,the 3-,6-,and 12-mo OS rates were 100%,88.5%,and 22.5%,respectively.The ORR and DCR were 45%and 90%,respectively.The median progressive free survival and median OS were not reached.Common complications were observed in 76%of the patients(grade 3,15%;grade 4,2.5%).CONCLUSION Combination therapy comprising lenvatinib,sintilimab and TACE achieved promising outcomes in advanced HCC patients and had manageable effects.
基金supported by the National Natural Science Foundation of China (NSFC)under Grant Nos.12172350,11772322 and 11702238。
文摘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.
基金supported by Zanjan University of Medical Sciences,Zanjan,Iran(Grant Number:A-12-1244-16&Ethical Code:IR.ZUMS.REC.1399.316).
文摘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.
文摘Objective: To explore the clinical effectiveness of combined use of intravenous pain pump with Parecoxib injection in alleviating pain in patients during the early postoperative period after thoracoscopic surgery. Methods: Eighty patients who underwent thoracoscopic surgery in a tertiary hospital were selected as the study subjects and randomly divided into two groups, with 40 patients in each group. The control group received routine postoperative treatment with intravenous pain pump, while the experimental group received Parecoxib in addition to the standard postoperative pain pump treatment. Visual Analog Scale (VAS) pain scores were used to evaluate postoperative pain relief in both groups, along with adverse reactions, postoperative complications, and patient satisfaction with pain relief. Results: Patients who received Parecoxib injection in addition to the routine use of intravenous pain pump had VAS pain scores lower than 3 points at 6 h, 12 h, 24 h, and 36 h postoperatively compared to those in the control group. The incidence of postoperative lung collapse, pleural effusion, and pulmonary infections was also significantly lower in the experimental group. The differences between the two groups were statistically significant (P Conclusion: Early combined use of Parecoxib injection in the early postoperative period after thoracoscopic surgery has shown good clinical efficacy. It can reduce the level of pain in patients, promote effective coughing and expectoration, facilitate early mobilization of patients, improve patient compliance, reduce complications, shorten hospital stay, and expedite patient recovery. Therefore, it is worth promoting the widespread clinical application of Parecoxib injection in this setting.
基金supported by National Major Science and Technology Projects of China 2017ZX10105015-001-002。
文摘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.
基金supported by the National Natural Science Foundation of China(42377354)the Natural Science Foundation of Hubei province(2024AFB951)the Chunhui Plan Cooperation Research Project of the Chinese Ministry of Education(202200199).
文摘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.
基金supported by the Biomaterials and Regenerative Medicine Institute Cooperative Research Project at Shanghai Jiao Tong University School of Medicine(grant no.2022LHA05)the Shanghai Clinical Research Center of Plastic and Reconstructive Surgery funded by the Science and Technology Commission of Shanghai Municipality(grant no.22Mc1940300).
文摘Molten aluminum is among the most common causes of burns in the metal industry.However,only few reports are available on molten aluminum injuries.Herein,we report an unusual case of molten aluminum burn.The patient had burns not only on the body surface but also in the respiratory tract and esophagus,adding to the difficulty of treatment.Multidisciplinary consultation and cooperation led to the development of a treatment plan for the patient,which included tracheotomy,respiratory management,endoscopic therapy,infection control,and psychological support.To our knowledge,this is the first report of molten aluminum-induced burns involving the face,neck,respiratory tract,esophagus,and eyes.We also describe our experience with multidisciplinary treatment for the management of molten aluminum burns.