Seismogenic model of the 2023 M_(W)5.5 Pingyuan earthquake in North China Plain and its tectonic implications

The 6 August 2023 M_(W)5.5 Pingyuan earthquake is the largest earthquake in the central North China Plain(NCP)over the past two decades.Due to the thick sedimentary cover,no corresponding active faults have been reported yet in the epicenter area.Thus,this earthquake presents a unique opportunity to delve into the buried active faults beneath the NCP.By integrating strong ground motion records,high-precision aftershock sequence relocation,and focal mechanism solutions,we gain insights into the seismotectonics of the Pingyuan earthquake.The aftershocks are clustered at depths ranging from 15 to 20 km and delineate a NE-SW trend,consistent with the distribution of ground motion records.A NE-SW nodal plane(226°)of the focal mechanism solutions is also derived from regional waveform inversion,suggesting that the mainshock was dominated by strike-slip motion with minor normal faulting component.Integrating regional geological data,we propose that an unrecognized fault between the NE-SW trending Gaotang and Lingxian-Yangxin faults is the seismogenic fault of this event.Based on the S-wave velocity structure beneath the NCP,this fault probably extends into the lower crust with a high angle.Considering the tectonic regime and stress state,we speculate that the interplay of shear strain between the Amurian and South China blocks and the hot upwelling magma from the subducted paleo Pacific flat slab significantly contributed to the generation of the Pingyuan earthquake.

Meta-Auto-Decoder:a Meta-Learning-Based Reduced Order Model for Solving Parametric Partial Differential Equations

Many important problems in science and engineering require solving the so-called parametric partial differential equations(PDEs),i.e.,PDEs with different physical parameters,boundary conditions,shapes of computational domains,etc.Typical reduced order modeling techniques accelerate the solution of the parametric PDEs by projecting them onto a linear trial manifold constructed in the ofline stage.These methods often need a predefined mesh as well as a series of precomputed solution snapshots,and may struggle to balance between the efficiency and accuracy due to the limitation of the linear ansatz.Utilizing the nonlinear representation of neural networks(NNs),we propose the Meta-Auto-Decoder(MAD)to construct a nonlinear trial manifold,whose best possible performance is measured theoretically by the decoder width.Based on the meta-learning concept,the trial manifold can be learned in a mesh-free and unsupervised way during the pre-training stage.Fast adaptation to new(possibly heterogeneous)PDE parameters is enabled by searching on this trial manifold,and optionally fine-tuning the trial manifold at the same time.Extensive numerical experiments show that the MAD method exhibits a faster convergence speed without losing the accuracy than other deep learning-based methods.

Laser speckle contrast imaging to predict the effect of temporary spinal cord stimulation in postherpetic neuralgia patients: A prospective observational study

Temporary spinal cord stimulation(tSCS)can effectively reduce the pain and severity of postherpetic neuralgia(PHN).However,there are no effective and objective methods for predicting the effects of tSCS on PHN.Laser speckle contrast imaging(LSCI)is frequently used in neurology to evaluate the effectiveness of treatment.To assess the accuracy of LSCI in predicting the impact of tSCS on PHN,14 adult patients receiving tSCS treatments for spinal nerve-innervated(C6-T2)PHN participated in this observational study.Visual analog scale(VAS)assessments and LSCI bloodflow images of the-ngers were recorded after the tSCS procedure.The results showed that the VAS scores of all patients decreased signi-cantly.Moreover,the bloodflow index(BFI)values were signi-cantly higher than they were before the procedure.Increased bloodflow and pain alleviation were positively correlated.The-ndings indicated that spinal nerve PHN(C6-T2)was signi-cantly reduced by tSCS.Pain alleviation by tSCS was positively correlated with increased bloodflow in the hand.The effect of tSCS on PHN may thus be predicted using an independent and consistent indicator such as LSCI.

过渡金属元素与氧对钴晶界能与晶界强度作用的第一性原理研究

以Co的Σ5(210)[001]晶界为模型,基于第一性原理研究过渡金属元素与氧对钴晶界能与晶界强度的影响。定量分析过渡金属在晶界处的偏析,揭示晶界能与原子半径之间的负相关关系。结果表明,溶质和晶界处基体原子之间的相互作用影响晶界强度。其中,Re、W、Os、Cr、Tc、Mo、Ir、Ta、Zr、Ru、Nb、V、Rh、Pt、Pd和Ni能显著强化晶界,而其他过渡金属会弱化晶界。特别地,Cr、Hf、Ta、W、Re、Os、Ir和Pt能有效缓解O原子引起的晶界弱化。

Evaporative Cooling Applied in Thermal Power Plants:A Review of the State-ofthe-Art and Typical Case Studies

A review is conducted about the application of the evaporative cooling technology in thermal power plants.Different case studies are considered,namely,evaporative air conditioners,evaporative cooling in direct air-cooled systems,gas turbine inlet cooling,wet cooling towers,and hybrid cooling towers with a crosswind effect.Some effort is provided to describe the advantages related to direct evaporative cooling when it is applied in thermal power plants and illustrate the research gaps,which have not been filled yet.In particular,typical case studies are intentionally used to compare the cooling performances when direct evaporative cooling is implemented in different types of cooling towers,including the natural draft wet cooling tower(NDWCT)and the pre-cooled natural draft dry cooling tower(NDDCT).It is shown that the NDWCT provides the best cooling performance in terms of power station cooling,followed by the pre-cooled NDDCT,and the NDDCT;moreover,the evaporative pre-cooling is able to enhance the cooling performance of NDDCT.Besides,on a yearly basis,better NDDCT cooling performances can be obtained by means of a spray-based pre-cooling approach with respect to wet media pre-cooling.Therefore,the use of nozzle spray is suggested for improvement in the performance of indirect/direct air-cooling systems with controlled water consumption.

电子态调控促进氢气无损耗纯化中CO的光致富集和氧化

随着选择性氧化(PROX)的快速发展,将氢气中残留的微量CO去除以达到质子交换膜燃料电池的使用氢要求,成为氢气纯化中迫切需要解决的问题.光催化氧化可将氢气流中的CO浓度降低至1×10^(-6)以下.本质上,该反应是光生·OH与痕量CO在氢气中反应.在该过程中,虽然·OH会不可避免地与H2发生碰撞而形成氢自由基(·H),但是环境中的H2会与之结合并通过氢交换促进自由基间的有效碰撞而结合成H2,避免氢气损耗.相比于现有的氢气纯化方案,光催化CO氧化可发展成为一种不损耗氢气的纯化技术.该技术虽然具有应用前景,但·OH的非选择性碰撞严重降低了其利用率以及整个氢气无损耗纯化反应过程中的光子利用率,因此,提出可行方案来促进·OH的产生及其与CO的碰撞成为研究重点.本文采用密度泛函理论结会Climbing image-nudged elastic band方法研究水分子在TiO_(2)上的反应过程.在普通TiO_(2)(101)晶面上形成*OH的势垒为0.57eV;而采用Mg来取代TiO_(2)的5c-或者6c-Ti位点后,势垒分别降至0.25和0.2 eV,并且*OH吸附在相邻Ti位点上的自由能比·OH高.除了促进光致·OH的产生,Mg掺杂所形成的位点还能促进发生在半导体-助催化剂界面秒级别的电子转移,进一步提高光子利用率.而且,Mg掺杂降低了TiO_(2)中Ti4+的电子云密度,促进了CO分子中碳5σ轨道上的负电荷转移至半导体阳离子,同时增强了半导体中阴离子向CO分子转移负电荷的能力,由此可以增强所形成的Mg掺杂TiO_(2)(Mg-TiO_(2))与CO的静电作用,实现该气体在半导体附近的富集.因此,Mg掺杂不仅可以促进羟基自由基的产生,还可以通过静电作用促进CO在Mg-TiO_(2)表面的富集,提高自由基对目标反应的碰撞概率.在光催化CO氧化反应中,Mg-TiO_(2)展现出比普通TiO_(2)更优的性能;并且随着CO浓度降低,Mg掺杂带来的CO富集效应愈加显著,进而表现出更好的催化性能.在光催化氢气无损耗纯化反应中,基于Mg-TiO_(2)催化剂的光催化固定床反应可将流速为1 L/min的H2气流中CO/H2的比浓度降低至<1×10^(-6),并展现出高效的光子利用.与其它将CO/H2比浓度降低至10-6的方法相比,本文催化剂气时空速可达600000 h^(-1),远高于PROX的5000 h^(-1)以及CO甲烷化的7500 h^(-1).综上,本工作揭示了电子态调控对CO光致富集和氧化的促进作用,对氢气无损耗纯化的光子利用效率提升和商业化具有借鉴意义.

Long-term efficacy and predictors of pembrolizumab-based regimens in patients with advanced esophageal cancer in the real world

BACKGROUND Pembrolizumab combined with chemotherapy has been proven effective as firstline therapy in patients with advanced esophageal cancer.Few trials have assessed the safety and efficacy of this treatment in patients with locally advanced disease.AIM To analyze long-term outcomes of pembrolizumab in locally advanced or metastatic esophageal squamous cell carcinoma(ESCC)in the real world.METHODS Patients with advanced ESCC admitted to our center from October 2019 to October 2021 were enrolled in this study.Clinical staging of the patients was based on the 8th edition of the American Joint Committee on Cancer TNM staging system.The patients received different treatments based on clinical stage.In brief,patients with locally advanced and resectable ESCC received neoadjuvant therapy combined with surgery.For those who were not candidates for resection,radical concurrent chemoradiotherapy plus pembrolizumab was more preferable.Patients with metastatic ESCC or who were unsuitable for radiotherapy underwent chemotherapy in combination with pembrolizumab.Long-term survival outcomes such as overall survival(OS),progression-free survival,disease-free survival,long-term adverse effects(AEs),immune maintenance therapy and predictors of immune checkpoint inhibitors(ICIs)efficacy were evaluated.RESULTS A total of 55 patients with advanced ESCC were enrolled in this retrospective,observational study.The median age was 61 years(range 44-74),with 47.3%(26/55)of the patients in stage IV and 45.5%of the patients had the tumor(25/55)located in the middle third of the esophagus.The median OS in all patients was not reached.The 12-mo OS rate among all patients was 78.8%and the 18-mo OS rate was 72.7%.9 patients died due to tumor progression and 7 patients died due to treatment-related complications.The therapeutic effect evaluated at the interim evaluation was significantly reflected in the long-term outcome.Patients with complete response or partial response in all patients(P=0.005)and in the chemoradiotherapy plus pembrolizumab group(P=0.007)obtained a better prognosis than non-responders.A total of 20 patients(20/55,36%)received immune maintenance therapy.Baseline peripheral blood biomarkers of the neutrophil-to-lymphocyte ratio,platelet-to-lymphocyte ratio,and neutrophil-to-(leukocyte-neutrophil)ratio did not predict the efficacy of ICIs.CONCLUSION Pembrolizumab combined with chemotherapy or radiotherapy resulted in favorable long-term survival in patients with locally advanced or metastatic ESCC,with safe and manageable long-term AEs.

Jujube witches’ broom phytoplasmas inhibit ZjBRC1-mediated abscisic acid metabolism to induce shoot proliferation

Jujube witches’broom(JWB)phytoplasmas parasitize the sieve tubes of diseased phloem and cause an excessive proliferation of axillary shoots from dormant lateral buds to favour their transmission.In previous research,two JWB effectors,SJP1 and SJP2,were identified to induce lateral bud outgrowth by disrupting ZjBRC1-mediated auxin flux.However,the pathogenesis of JWB disease remains largely unknown.Here,tissue-specific transcriptional reprogramming was examined to gain insight into the genetic mechanisms acting inside jujube lateral buds under JWB phytoplasma infection.JWB phytoplasmas modulated a series of plant signalling networks involved in lateral bud development and defence,including auxin,abscisic acid(ABA),ethylene,jasmonic acid,and salicylic acid.JWB-induced bud outgrowth was accompanied by downregulation of ABA synthesis within lateral buds.ABA application rescued the bushy appearances of transgenic Arabidopsis overexpressing SJP1 and SJP2 in Col-0 and ZjBRC1 in the brc1-2 mutant.Furthermore,the expression of ZjBRC1 and ABA-related genes ZjHB40 and ZjNCED3 was negatively correlated with lateral main bud outgrowth in decapitated healthy jujube.Molecular evidence showed that ZjBRC1 interacted with ZjBRC2 via its N-terminus to activate ZjHB40 and ZjNCED3 expression and ABA accumulation in transgenic jujube calli.In addition,ZjBRC1 widely regulated differentially expressed genes related to ABA homeostasis and ABA signalling,especially by binding to and suppressing ABA receptors.Therefore,these results suggest that JWB phytoplasmas hijack the ZjBRC1-mediated ABA pathways to stimulate lateral bud outgrowth and expansion,providing a strategy to engineer plants resistant to JWB phytoplasma disease and regulate woody plant architecture to promote crop yield and quality.

Probabilistic analysis of tunnel displacements based on correlative recognition of rock mass parameters

Displacement is vital in the evaluations of tunnel excavation processes,as well as in determining the postexcavation stability of surrounding rock masses.The prediction of tunnel displacement is a complex problem because of the uncertainties of rock mass properties.Meanwhile,the variation and the correlation relationship of geotechnical material properties have been gradually recognized by researchers in recent years.In this paper,a novel probabilistic method is proposed to estimate the uncertainties of rock mass properties and tunnel displacement,which integrated multivariate distribution function and a relevance vector machine(RVM).The multivariate distribution function is used to establish the probability model of related random variables.RVM is coupled with the numerical simulation methods to construct the nonlinear relationship between tunnel displacements and rock mass parameters,which avoided a large number of numerical simulations.Also,the residual rock mass parameters are taken into account to reflect the brittleness of deeply buried rock mass.Then,based on the proposed method,the uncertainty of displacement in a deep tunnel of CJPL-II laboratory are analyzed and compared with the in-situ measurements.It is found that the predicted tunnel displacements by the RVM model closely match with the measured ones.The correlations of parameters have significant impacts on the uncertainty results.The uncertainty of tunnel displacement decreases while the reliability of the tunnel increases with the increases of the negative correlations among rock mass parameters.When compared to the deterministic method,the proposed approach is more rational and scientific,and also conformed to rock engineering practices.

Estimation of the three-dimensional in situ stress field around a large deep underground cavern group near a valley

Understanding three-dimensional(3D)in situ stress field is of key importance for estimating the stability of large deep underground cavern groups near valleys.However,the complete 3D in situ stress fields around large deep underground cavern groups are difficult to determine based on in situ stress data from a limited number of measuring points due to the insufficient representativeness and unreliability of such measurements.In this study,an integrated approach for estimating the 3D in situ stress field around a large deep underground cavern group near a valley is developed based on incomplete in situ stress measurements and the stress-induced failures of tunnels excavated prior to the step excavation of the cavern group.This integrated approach is implemented via four interrelated and progressive basic steps,i.e.inference of the regional tectonic stress field direction,analyses of in situ stress characteristics and measurement reliability,regression-based in situ stress field analysis and reliability assessment,and modified in situ stress field analysis and reliability verification.The orientations and magnitudes of the 3D in situ stress field can be analyzed and obtained at a strategic level following these four basic steps.First,the tectonic stress field direction around the cavern group is deduced in accordance with the regional tectonic framework and verified using a regional crustal deformation velocity map.Second,the reliability of the in situ stress measurements is verified based on the locations and depths of stressinduced brittle failures in small tunnels(such as exploratory tunnels and pilot tunnels)within the excavation range of the cavern group.Third,considering the influences of the valley topography and major geological structures,the 3D in situ stress field is regressed using numerical simulation and multiple linear regression techniques based on the in situ stress measurements.Finally,the regressed in situ stress field is further modified and reverified based on the stress-induced brittle failures of small tunnels and the initial excavation of the cavern group.A case study of the Shuangjiangkou underground cavern group demonstrates that the proposed approach is reliable for estimating the 3D in situ stress fields of large deep underground cavern groups near valleys,thus contributing to the optimization of practical excavation and design of mitigating the instability of the surrounding rock masses during step excavations.

A local homogenization approach for simulating the reinforcement effect of the fully grouted bolt in deep underground openings

Fully grouted bolts are a key component of the support system for underground openings.Although considerable effort has been made in the simulation of the reinforcement effect of the fully grouted bolts on the rock masses surrounding underground openings,most of the work has limited significance since the structural element approach is used.This study proposes a local homogenization approach(L-H approach)that integrates elastoplastic mechanics,composite mechanics,and analytical approaches with numerical simulation to effectively simulate the reinforcement effect of the fully grouted bolt on deep surrounding rock masses.In the L-H approach,the representative volume of bolted rock mass(RVBRM)with a fully grouted bolt is established based on the original mesh model utilized in the rockbolt element approach.The RVBRM is a regular quadrangular prism with a cross-sectional size equal to the bolt spacing and a length equal to the bolt length.The RVBRM is homogenized by the L-H approach from a unidirectional bolt-reinforced composite into a homogeneous transversely isotropic medium whose mechanical properties are described by a new transversely isotropic elastoplastic model.The L-H parameters for the RVBRM are obtained using analytical approaches,composite mechanics,and known parameters of the rock mass and bolt.Using the L-H approach,the reinforcement effect of the fully grouted bolt on the bolted rock specimen and the surrounding rock mass in Jinping II Diversion Tunnel#2 with a depth greater than 2000 m is simulated.The results show that the predictions of the L-H approach are more in agreement with the physical model results of bolted rock specimen and provide a more realistic response of the bolted surrounding rock mass.The L-H approach demonstrates that fully grouted bolts with common bolt spacings and diameters substantially enhance the elastic modulus,shear strength,and tensile strength of the rock mass in the direction of the bolt axis.

Synthesis and Characterization of Co-Doped Brookite Titania Photocatalysts with High Photocatalytic Activity

Transition metal-doping could effectively extend the light response range of TiO _2 photocatalysts from the ultraviolet(UV)to the visible region.Co-doped brookite titanium dioxide(Co–TiO_2)photocatalysts were synthesized via the hydrothermal method with titanium tetrachloride as the raw material and cobalt chloride hexahydrate as the dopant.The prepared Co–TiO_2 photocatalysts were characterized by X-ray diffraction(XRD),scanning electron microscopy(SEM),transmission electron microscopy(TEM),Raman spectroscopy,X-ray photoelectron spectroscopy(XPS)and UV–Vis diffuse reflectance spectroscopy(UV–Vis DRS).The photocatalytic activities of Co–TiO _2 photocatalysts were evaluated by photocatalytic degradation of isopropanol alcohol(IPA),a typical volatile organic compound(VOC),under visible light.The influences ofdifferent Co doping rates,initial concentrations of IPA gas and the amounts of photocatalyst addition were also studied.At the same time,the enhancement mechanism ofcobalt ions as a trap for photogenerated holes was discussed.Thus,we found the optimum doping rate,initial concentration of IPA gas and amount of photocatalyst to add.The results show that the mesoporous Co–TiO _2 photocatalysts possess smaller size particles,larger specific surface area,lower forbidden bandgap energy(Eg)and better photocatalytic activity than pure brookite TiO _2.When the doping of Co was 7% by mass,the initial concentration ofIPA gas was 1.0×10^(-6 )mol/L and the addition of Co–TiO_2 photocatalysts was 50 mg,the best photocatalytic activity was achieved.Furthermore,the degradation rate ofIPA was up to 91%,which shows great potential for waste water treatment.

Skeleton-vasculature chain reaction: a novel insight into the mystery of homeostasis

Angiogenesis and osteogenesis are coupled.However,the cellular and molecular regulation of these processes remains to be further investigated.Both tissues have recently been recognized as endocrine organs,which has stimulated research interest in the screening and functional identification of novel paracrine factors from both tissues.This review aims to elaborate on the novelty and significance of endocrine regulatory loops between bone and the vasculature.In addition,research progress related to the bone vasculature,vessel-related skeletal diseases,pathological conditions,and angiogenesis-targeted therapeutic strategies are also summarized.With respect to future perspectives,new techniques such as single-cell sequencing,which can be used to show the cellular diversity and plasticity of both tissues,are facilitating progress in this field.Moreover,extracellular vesicle-mediated nuclear acid communication deserves further investigation.In conclusion,a deeper understanding of the cellular and molecular regulation of angiogenesis and osteogenesis coupling may offer an opportunity to identify new therapeutic targets.

Predicting the excavation damaged zone within brittle surrounding rock masses of deep underground caverns using a comprehensive approach integrating in situ measurements and numerical analysis

Excavation Damaged Zone(EDZ)scope is important for optimizing excavation and support schemes in deep underground caverns.However,accurately predicting the full EDZ scope within the surrounding rock masses of deep underground caverns during excavation remains a pressing problem.This study presents a comprehensive EDZ scope prediction approach(CESPA)for the brittle surrounding rock masses of deep underground caverns by coupling numerical simulation with quantitative analysis of borehole wall images and ultrasonic test results.First,the changes in both P-velocity(V_(p))and joint distribution of the surrounding rock masses before and after excavation damage are captured using ultrasonic tests and borehole digital cameras.Second,the quality Q-parameters of the surrounding rock mass before and after excavation damage are preliminarily rated with the rock mass descriptions provided by borehole wall images,and the rock mass V_(p)-parameter values are determined according to the V_(p)-borehole depth curves.Third,the Q-parameter ratings are further finely adjusted by updating the related Q-values to be similar with the Q-values estimated by V_(p)-parameter values.Fourth,the initial and residual mechanical parameters for the rock mass deterioration model(RDM)are estimated by the adjusted Q-parameter ratings based on the modified Q-based relations,and the elastic modulus deterioration index(EDI)threshold to describe the EDZ boundary is determined with the V_(p)-parameter values.Finally,EDZ scope is predicted using the elastoplastic numerical simulation with RDM and EDI based on the mechanical parameter estimates and EDI threshold.Analyses of applications in Sub-lab D1 in Jinping II project show that CESPA can provide a reliable and operable solution for predicting full EDZ scopes within the brittle surrounding rock masses of deep underground caverns.

Novel Stereoselective Synthesis of 1,3-Dienyl Tellurides by Palladium Catalyzed Cross-coupling Reaction of (E)-β--Bromovinyl Tellurides

β-Bromovinyl tellurides are new difuctional reagents which undergo palladium-catalyzed cross-coupling reaction with alkenes to give conjugated dienyl tellurides.

Reaction of Arylselenium Titanocene Complexes with Diaryl Iodonium Salts——a Convenient Synthesis of Unsymmetrical Diarylselenides

The diaryldiselenides reacted with titanocene hydried （Cp2TiH） generted from Cp2TiCl2/i-BuMgBr to give arylselenium complexes of titanocene. They reacted readily with diaryliodoiums salt to give unsymmetical diarylselenides.

Probing time delay of strong-field resonant above-threshold ionization

The high-resolution three-dimensional photoelectron momentum distributions via above-threshold ionization(ATI)of Xe atoms are measured in an intense near circularly polarized laser field using velocity map imaging and tomography reconstruction. Compared to the linearly polarized laser field, the employed near circularly polarized laser field imposes a more strict selection rule for the transition via resonant excitation, and therefore we can selectively enhance the resonant ATI through certain atomic Rydberg states. Our results show the self-reference ionization delay, which is determined from the difference between the measured streaking angles for nonadiabatic ATI via the 4 f and 5 f Rydberg states, is 45.6 as. Our method provides an accessible route to highlight the role of resonant transition between selected states, which will pave the way for fully understanding the ionization dynamics toward manipulating electron motion as well as reaction in an ultrafast time scale.

Ablation of apoptosis-stimulating of p53 protein 1 protects mice from acute hepatic injury and dysfunction via NF-κB pathway in CCl4-induced hepatotoxicity

Acute liver injury(ALI)is characterized by apoptosis,inflammation,and oxidative stress,and pathogenic mechanism of ALI is poorly understood.Apoptosis-stimulating of p53 protein 1(ASPP1)is involved in environmental responses,tumor growth,and NF-κB activity,which is of critical importance to ALI.However,the role of ASPP1 in ALI remains largely unexplored.The current study aimed to determine the role of ASPP1 in ALI induced by CCl4 and the underlying mechanism.ASPP1 expression was detected in wild type(WT)mice with ALI induced by CCl4.The function of ASPP1 in ALI induced by CCl4 was investigated using conventional knockout ASPP1 mice.ASPP1 expression significantly increased in ALI mice at 24 hours after CCl4 injection.Deletion of ASSP1 ameliorated apoptosis,inflammation,and necrosis in ALI relative to WT mice.In addition,deficiency of ASPP1 improved liver flood flow as well as ALT and AST levels.The levels of phosphorylated p65 and phosphorylated IκBαwere lower in ASPP1-/-mice than in WT mice with ALI.These results implicate that deletion of ASPP1 may act via inhibition of the NF-кB pathway and protect mice from ALI,which may be a new potential therapeutic target for the treatment of ALI.

Inetetamab combined with pyrotinib and oral vinorelbine for patients with human epidermal growth factor receptor 2 positive advanced breast cancer:A single-arm phase 2 clinical trial

Background Human epidermal growth factor receptor 2(HER2)-targeted agents have significantly improved the outcomes of patients with HER2-positive breast cancer;however,a large proportion of patients still develop resistance to trastuzumab.In this study,we investigated the efficacy and safety of inetetamab,another anti-HER2 antibody,combined with pyrotinib and oral vinorelbine in patients with HER2-positive advanced breast cancer so as to provide new ideas for the treatment.Methods In this prospective,single-arm,phase 2 trial,patients with HER2-positive advanced breast cancer with disease progression after trastuzumab were recruited.Patients received a combination of inetetamab(loading dose of 8 mg/kg and subsequent doses of 6 mg/kg intravenously once every 3 weeks),pyrotinib(400 mg orally once daily),and vinorelbine(60 mg/m^(2)orally once weekly)until disease progression or intolerable toxicity.The primary endpoint was progression-free survival(PFS).The secondary endpoints included objective response rate(ORR),overall survival(OS),disease control rate(DCR),and safety.Results Between February 13,2022 and December 25,2022,30 patients were screened and enrolled in this study.The median age of the patients at enrollment was 54 years,12 patients(40.0%)had hormone-receptor-positive disease and 23 patients(76.7%)had visceral metastasis.The median PFS was 8.63 months(95%confidence interval[CI]4.15-13.12 months).The median OS was not reached.The ORR was 53.3%(16/30)and the DCR was 96.7%(29/30).The most common Grade III/IV adverse events were leukopenia(n=5,16.7%),neutropenia(n=4,13.3%),and diarrhea(n=3,10%).No treatment-related serious adverse events or deaths occurred.Conclusions The combination regimen of inetetamab,pyrotinib,and oral vinorelbine showed encouraging efficacy and favorable safety in patients with HER2-positive advanced breast cancer and could be considered as an alternative treatment option for the patients.