Objective:Little progress has been made in recent years using first-line chemotherapy,including gemcitabine combined with nab-paclitaxel,FOLFIRINOX,and NALIRIFOX,for advanced pancreatic adenocarcinoma(APC).In addition...Objective:Little progress has been made in recent years using first-line chemotherapy,including gemcitabine combined with nab-paclitaxel,FOLFIRINOX,and NALIRIFOX,for advanced pancreatic adenocarcinoma(APC).In addition,the optimal second-line chemotherapy regimen has not been determined.This study aimed to compare the effectiveness of different types of second-line chemotherapy for APC.Methods:Patients with APC who received first-line treatment from January 2008 to January 2021 were considered eligible for this retrospective analysis.The primary and secondary endpoints were overall survival(OS)and progression-free survival(PFS),respectively.Results:Four hundred and thirty-seven and 617 patients were treated with 5-fluorouracil-and gemcitabine-based chemotherapy as first-line treatment,respectively.Demographic and clinical features,except age and liver metastasis,were comparable between the two groups(P<0.05).The median OS was 8.8 and 7.8 months in patients who received a 5-fluorouracil-and gemcitabine-based combined regimen for first-line therapy,respectively(HR=1.244,95%CI=1.090–1.419;P<0.001).The median OS was 5.6 and 1.9 months in patients who received second-line chemotherapy and supportive care,respectively(HR=0.766,95%CI=0.677–0.867;P<0.001).The median PFS was not significantly differently between gemcitabine or 5-fluorouracil monotherapy and combination therapy.Conclusions:A 5-fluorouracil-or gemcitabine-based combined regimen was shown to be as effective as a single 5-fluorouracil or gemcitabine regimen as second-line therapy for patients with APC.展开更多
In this paper, we have demonstrated an Er-doped ultrafast laser with a single mode fiber-gradient index multimode fiber-single mode fiber(SMF-GIMF-SMF, SMS) structure as saturable absorber(SA), which can generate not ...In this paper, we have demonstrated an Er-doped ultrafast laser with a single mode fiber-gradient index multimode fiber-single mode fiber(SMF-GIMF-SMF, SMS) structure as saturable absorber(SA), which can generate not only stable single-pulse state, but also special mode-locked pulses with the characteristics of high energy and noisy behaviors at proper pump power and cavity polarization state. In addition, we have deeply investigated the real-time spectral evolutions of the mode-locked pulses through the dispersive Fourier transformation(DFT) technique. It can be found that the pulse regime can actually consist of a lot of small noise pulses with randomly varying intensities. We believe that these results will further enrich the nonlinear dynamical processes in the ultrafast lasers.展开更多
Synchronized dual-wavelength mode-locked laser is investigated numerically and experimentally in the normal dispersion regime.A programmable optical processor is introduced to shape the spectral profile and adjust the...Synchronized dual-wavelength mode-locked laser is investigated numerically and experimentally in the normal dispersion regime.A programmable optical processor is introduced to shape the spectral profile and adjust the net dispersion,which is demonstrated be a convenient and reliable approach to generate dual-color solitons.The time-stretch dispersive Fourier transform and frequency-resolved optical grating techniques are utilized to measure the spectral and temporal characteristics of dual-color solitons,respectively.The numerical results are consistent with experimental results.This work may facilitate the development of filter-based mode-locked laser and the understanding of multi-wavelength soliton dynamics.展开更多
The spatial constraints of aircraft have accelerated the development of multi-wing deployable mechanisms.These systems enable the rapid,sub-second deployment of multiple folding wings,which generate high-energy impact...The spatial constraints of aircraft have accelerated the development of multi-wing deployable mechanisms.These systems enable the rapid,sub-second deployment of multiple folding wings,which generate high-energy impacts upon locking-resulting in oscillations that can adversely affect aerodynamic performance.Despite their importance,the transient dynamic characteristics during deployment and locking remain insufficiently explored.This study presents an integrated dynamic model for a single-actuator,multi-wing deployable mechanism that accounts for joint clearances,component elasticity,and locking collisions.This model is used to analyze the influence of transient driving on the motion errors of multiple folding wings,the locking oscillation amplitude,and the complete stabilization time.Results indicate that as the driving force and transient deployment speed increase,all dynamic performance characteristics are notably affected.Specifically,raising the transient driving force from 3000 to 7000 N leads to a maximum increase of 60.8%in oscillation amplitude and 78.4%in stabilization time.By comparing the results of the prototype experiment with the theoretical model,it is found that the errors of the maximum locking oscillation amplitude and the complete stabilization time for the three groups of folding wings are all within the acceptable range,which verifies the theoretical model.These findings advance the theoretical understanding of transient deployment dynamics and locking oscillations in high-speed deployable mechanisms.展开更多
A cavity magnonic oscillator uses the coupling of a planar transmission line oscillator(cavity) and spin excitations(magnons) in a ferrimagnetic material to achieve superior frequency stability and reduced phase noise...A cavity magnonic oscillator uses the coupling of a planar transmission line oscillator(cavity) and spin excitations(magnons) in a ferrimagnetic material to achieve superior frequency stability and reduced phase noise. Like many low phase noise oscillators, a cavity magnonic oscillator faces the challenge that its narrow resonance profile is not well suited for injection locking amplification. This work presents an improved design for such an oscillator configured as an injection locking amplifier(ILA) with an extended lock range. The proposed design features a two-stage architecture, consisting of a pre-amplification oscillator and a cavity magnonic oscillator, separated by an isolator to prevent backward locking.By optimizing the circuit parameters of each stage, the proposed design achieved an order of magnitude increase in lock range, when compared to its predecessors, all while preserving the phase noise quality of the input, making it well-suited for narrowband, sensitive signal amplification. Furthermore, this work provides a method for using oscillators with high spectral purity as injection locking amplifiers.展开更多
As a major fault in the northeastern Qinghai-Xizang Plateau,the Haiyuan fault zone is important for understanding the regional deformation.Aiming at the differences in the slip rate and locking degree obtained from di...As a major fault in the northeastern Qinghai-Xizang Plateau,the Haiyuan fault zone is important for understanding the regional deformation.Aiming at the differences in the slip rate and locking degree obtained from different studies,this study constructs a refined block model(including Qilian,Alxa,Ordos,Xining,Haiyuan,and Lanzhou blocks)and uses the grid search and simulated annealing methods to invert GPS data for slip rate and locking degree of the Haiyuan fault zone.The results are as follows:(1)The sinistral slip rates in the western,middle,and eastern segments are 4.93-5.22 mm/a,1.52-4.94 mm/a,and 0.43-1.18 mm/a,decreasing eastward on the whole,while the compression rates are 0.45-1.26 mm/a,0.58-2.62 mm/a,and3.52-4.48 mm/a,increasing eastward on the whole.(2)The locking depth of the western segment increases from about 5 km to about 20 km eastward;the middle segment decreases and then increases eastward;the eastern segment concentrates at about 20 km(PHI is about 0.86).(3)The slip deficit is relatively higher in the Lenglongling,Jinqianghe,Maomaoshan,and Liupanshan faults(averaging about 3.42 mm/a,4.16 mm/a,4.23 mm/a,and 3.43 mm/a within 20 km).(4)The Qilian,Alxa,Xining,Lanzhou,and Haiyuan blocks rotate clockwise,while the Ordos block rotates counterclockwise.Additionally,by comparing different block models,the Haiyuan block should be considered independently.The Haiyuan fault zone adjusts surrounding block movements and uplifts Liupanshan mountain tectonically.The results can provide important references for understanding the regional earthquake risk and deformation mechanism.展开更多
BACKGROUND Proximal humerus fractures(PHFs)are common,especially in the elderly,and optimal surgical management remains debated.This study compares clinical,functional,and radiographic outcomes of deltoid split(DS)vs ...BACKGROUND Proximal humerus fractures(PHFs)are common,especially in the elderly,and optimal surgical management remains debated.This study compares clinical,functional,and radiographic outcomes of deltoid split(DS)vs deltopectoral(DP)approaches in PHFs treated with locking plates.AIM To evaluate and compare the clinical,functional,and radiographic outcomes-as well as postoperative complication rates-associated with the DS vs the DP surgical approach in the open reduction and internal fixation(ORIF)of PHFs using locking plate constructs.METHODS A multicenter retrospective study of 120 patients undergoing ORIF for closed Neer type II-IV PHFs between January 2023 and December 2023.Patients were grouped by surgical approach[DS(n=70),DP(n=50)].Outcome measures included Numeric Rating Scale(NRS)for pain,Quick-Disabilities in Arm,Shoulder,and Hand questionnaire(QuickDASH),Constant-Murley score,Short Form Health Survey-12v2,and radiographic alignment.Complication rates were recorded.Statistical significance was defined as P<0.05.RESULTS Early outcomes favored the DS group:(1)Lower NRS(3.1 vs 5.9);(2)Higher Constant-Murley(68.2 vs 50.5);and(3)Better QuickDASH(25.4 vs 37.1).Complication rate was lower in the DS group(1.66%vs 5.81%).Radiographic outcomes were comparable.Long-term results were similar between groups.CONCLUSION While both approaches yield satisfactory long-term outcomes,the DS approach is associated with faster early recovery and fewer complications,supporting its use in selected cases.展开更多
Biology is governed by macromolecular interactions,perturbation of which often lies at the heart of disease.Most therapeutic drugs,whether they are small molecules or biologics,exert their effects through impeding suc...Biology is governed by macromolecular interactions,perturbation of which often lies at the heart of disease.Most therapeutic drugs,whether they are small molecules or biologics,exert their effects through impeding such interactions,whether they are of an enzyme with its substrate or a ligand with its receptor.Conversely,a handful of approved drugs and a larger number of candidates in development have the opposite effect:They either activate or inhibit a biological output by stabilizing a preexisting complex through reducing the rate at which its components dissociate(koff).展开更多
This study presents an achievement of laser cooling of alkaline-earth atoms in the Chinese Space Station’s strontium(Sr)atomic space optical clock.The system’s core components,physical unit,optical unit,and electric...This study presents an achievement of laser cooling of alkaline-earth atoms in the Chinese Space Station’s strontium(Sr)atomic space optical clock.The system’s core components,physical unit,optical unit,and electrical unit,have a total volume of 306 L and a total mass of 163.8 kg.These compact and robust units can overcome mechanical vibrations and temperature fluctuations during space launch.The laser sources of the optical unit are composed of diode lasers,and the injection locking of slave lasers is automatically performed by a program.In the experiment,a blue magneto-optical trap of cold atoms was achieved,with the atom numbers estimated to be approximately(1.50±0.13)×10^(6) for 87Sr and(8.00±0.56)×10^(6) for 88Sr.This work establishes a foundation for atomic confinement and high-precision interrogation in space-based optical clocks and expands the frontiers of cold atom physics in microgravity.展开更多
Fiber optic sensing technology,with its low transmission loss,wide bandwidth,and broad dynamic range,offers significant advantages for high-sensitivity measurements.In this study,a multi-band soliton modulation system...Fiber optic sensing technology,with its low transmission loss,wide bandwidth,and broad dynamic range,offers significant advantages for high-sensitivity measurements.In this study,a multi-band soliton modulation system for stress sensing is proposed,utilizing Ti_(3)C_(2)T_(x)to generate ultrashort pulses.By applying stress to microfibers,dichromatic periodic multisoliton mode-locking at 1530 nm and 1555.2 nm is achieved.Vibrational mechanical stress further modulates cross-phase interactions between solitons,inducing higher-order bound solitons with small-amplitude oscillations.These dynamic processes reveal complex nonlinear optical behaviors and enhance sensing capabilities.Additionally,the feasibility of stable mode-locking of Ti_(3)C_(2)T_(x)in a 1µm multimode cavity is analyzed using the multimode nonlinear Schrodinger equation,and multisoliton states are experimentally demonstrated by integrating a 1µm narrow-linewidth ultrafast multimode laser with a stressed microfiber.展开更多
In 2018,Baige,Xizang,witnessed two consecutive large-scale landslides,causing significant damage and drawing widespread attention.From March 2011 to February 2018,the Baige landslide exhibited a 50-m displacement with...In 2018,Baige,Xizang,witnessed two consecutive large-scale landslides,causing significant damage and drawing widespread attention.From March 2011 to February 2018,the Baige landslide exhibited a 50-m displacement without complete failure,culminating in a collapse in October 2018.The mechanisms behind its resistance to failure despite substantial deformation and the influence of the complex geo-structure within the tectonic mélange belt remain unclear.To address these questions,this study utilized a multidisciplinary approach,integrating on-site geological field mapping,surface deformation monitoring,multielectrode resistivity method,and deep displacement analysis.The aim was to evaluate the impact of the intricate geo-structure within the tectonic mélange belt on the Baige landslide events.Findings reveal that the landslide's geo-structure consists of structurally fractured,mesh-like rock masses,including heterogeneous lenticular rock masses and intermittent brittle shear zones distributed around the lens-shaped rock masses.The study underscores that the inhomogeneous and weakly deformed lenticular rock masses function as natural locked segments,governing the stability of the Baige landslide.Specifically,the relatively intact and hard granodiorite porphyry play a crucial role in locking the landslide's deformation.Deep displacement analysis indicates that the brittle shear zones act as the sliding surfaces.The progressive destruction of the locked segments and the gradual penetration of brittle shear zones,driven by gravitational potential energy,contribute to the landslide occurrence.This research provides critical insights into the formation mechanisms of large-scale landslides within tectonic mélange belts.展开更多
Spin-momentum locking is widely regarded as an inherent property of evanescent waves,where the transverse spin angular momentum is intrinsically tied to the wave's polarization.This principle is well established i...Spin-momentum locking is widely regarded as an inherent property of evanescent waves,where the transverse spin angular momentum is intrinsically tied to the wave's polarization.This principle is well established in systems such as surface plasmon polaritons,surface elastic waves,and other evanescent modes.Here,we theoretically unveil an anomalous breakdown of spin-momentum locking in evanescent electromagnetic waves at a metalgyromagnetic interface.We show that the hybrid polarization of the field induces two successive reversals of transverse spin near the interface—directly violating the conventional locking between spin and momentum.As a result,identical chiral sources placed at different heights above the interface excite evanescent waves propagating in opposite directions,defying standard expectations.This discovery challenges the presumed universality of spin-momentum locking and opens new degrees of freedom for controlling wave propagation in photonic and plasmonic systems.展开更多
Gastric cancer remains one among the leading causes of cancer-related deaths, regardless of its decreasing incidence and newly available treatment options. Most patients present at an advanced stage and are treated wi...Gastric cancer remains one among the leading causes of cancer-related deaths, regardless of its decreasing incidence and newly available treatment options. Most patients present at an advanced stage and are treated with upfront systemic chemotherapy. Those patients receiving first-line therapy may initially respond to treatment, but many of them relapse over time. In such condition, second-line treatment for disease progression remains the only available option. Although there exists no standard approach in the second-line setting, several phase Ⅲ trials have shown modest survival benefit in patients receiving irinotecan, taxane and ramucirumab over the best supportive care or active agents. This review analyzes the currently available treatment regimens and future directions of research in the second-line setting for metastatic gastric cancer with the best available evidence. Additionally, the prognostic factors that influence patient survival in those receiving second-line therapy are discussed.展开更多
Worldwide prevalence of Helicobacter pylori(H.pylori) infection is approximately 50%,with the highest being in developing countries.We compared cure rates and tolerability(SE) of second-line anti-H.pylori levofloxacin...Worldwide prevalence of Helicobacter pylori(H.pylori) infection is approximately 50%,with the highest being in developing countries.We compared cure rates and tolerability(SE) of second-line anti-H.pylori levofloxacin/amoxicillin(LA)-based triple regimens vs standard quadruple therapy(QT).An English language literature search was performed up to October 2010.A meta-analysis was performed including randomized clinical trials comparing 7-or 10-d LA with 7-d QT.In total,10 articles and four abstracts were identified.Overall eradication rate in LA was 76.5%(95% CI:64.4%-97.6%).When only 7-d regimens were included,cure rate was 70.6%(95% CI:40.2%-99.1%),whereas for 10-d combinations,cure rate was significantly higher(88.7%;95% CI:56.1%-109.9%;P < 0.05).Main eradication rate for QT was 67.4%(95% CI:49.7%-67.9%).The 7-d LA and QT showed comparable efficacy [odds ratio(OR):1.09;95% CI:0.63-1.87],whereas the 10-d LA regimen was significantly more effective than QT(OR:5.05;95% CI:2.74-9.31;P < 0.001;I 2 = 75%).No differences were reported in QT eradication rates among Asian and European studies,whereas LA regimens were more effective in European populations(78.3% vs 67.7%;P = 0.05).Incidence of SE was lower in LA therapy than QT(OR:0.39;95% CI:0.18-0.85;P = 0.02).A higher rate of side effects was reported in Asian patients who received QT.Our findings support the use of 10-d LA as a simple second-line treatment for H.pylori eradication with an excellent eradication rate and tolerability.The optimal second-line alternative scheme might differ among countries depending on quinolone resistance.展开更多
Gastric cancer and cancer of the gastro-oesophageal junction(GOJ) are the 4th most common cancer diagnoses worldwide with regional differences in incidence rates.The treatment of gastric and GOJ cancers is complex and...Gastric cancer and cancer of the gastro-oesophageal junction(GOJ) are the 4th most common cancer diagnoses worldwide with regional differences in incidence rates.The treatment of gastric and GOJ cancers is complex and requires multimodality treatment including chemotherapy treatment,surgery,and radiotherapy.During the past decade considerable improvements were achieved by advanced surgical techniques,tailored chemotherapies/radiotherapy and technical innovations in clinical diagnostics.In patients with advanced or metastatic gastric/GOJ cancer systemic chemotherapy with fluoropyrimidine/platinum-based regimens(+/-human epidermal growth factor receptor-2 antibody) is the mainstay of treatment.Despite these improvements,the clinical outcome for patients with advanced or metastatic disease is generally poor with 5-year survival rates ranging between 5%-15%.These poor survival rates may to some extent be related that standard therapies beyond first-line therapies have never been defined.Considering that this patient population is often not fit enough to receive further treatments there is an increasing body of evidence from phase-2 studies that in fact second-line therapies may have a positive impact in terms of overall survival.Moreover two recently published phase-3 studies support the use of second-line chemotherapy.A South Korean study compared either,irinotecan or docetaxel with best supportive care and a German study compared irinotecan with best supportive care-both studies met their primary endpoint overall survival.In this "Field of Vision" article,we review these recently published phase-3 studies and put them into the context of clinical prognostic factors helping to guide treatment decisions in patients who most likely benefit.展开更多
AIM: To compare the efficacy of 14- and 7-d bismuthbased quadruple therapies as second-line eradication treatment for Helicobacter pylori(H.pylori) infection.METHODS: Between 2004 and 2014,the medical records of 790 p...AIM: To compare the efficacy of 14- and 7-d bismuthbased quadruple therapies as second-line eradication treatment for Helicobacter pylori(H.pylori) infection.METHODS: Between 2004 and 2014,the medical records of 790 patients who had experienced failure of first-line proton pump inhibitor(PPI)-based eradication therapy and were then treated with bismuth-based quadruple therapy were retrospectively reviewed.Those who received bismuth-based quadruple therapy [PPI,bismuth,metronidazole,and tetracycline(PBMT)] for either 7 d or 14 d were assigned to a PBMT-7 group(n = 543) or a PBMT-14 group(n = 247),respectively.The eradication rates for both groups were determined by intention-to-treat(ITT) and per-protocol(PP) analyses.ITT analysis compared the treatment groups as originally allocated while the PP analysis including only those patients who had completed the treatment as originally allocated.Successful eradication therapy for H.pylori infection was defined as a negative 13C-urea breath test 4 wk after the end of eradication treatment.RESULTS: The overall ITT eradication rate was 69.1%(546/790).Final ITT eradication rates were 67.4%(366/543; 95%CI: 63.1%-71.7%) in the PBMT-7 group and 72.8%(180/247; 95%CI: 67.4%-78.2%) in the PBMT-14 group(P = 0.028).The overall PP eradication rate was 80.0%(546/682),and the final PP eradication rates were 78.2%(366/468; 95%CI: 72.1%-84.0%) in the PBMT-7 group and 84.1%(180/214; 95%CI: 76.8%-90.8%) in the PBMT-14 group(P = 0.009).The H.pylori eradication rates in the PBMT-14 group weresignificantly higher than in the PBMT-7 group according to both ITT(P = 0.028) and PP analysis(P = 0.009).Compliance was similar in both groups(PBMT-7 group: 97.9%; PBMT-14 group: 96.4%).Adverse event rates were 10.7%(51/478) and 17.1%(38/222) in the PBMT-7 and PBMT-14 groups,respectively(P = 0.487).CONCLUSION: The 14-d bismuth-based quadruple therapy is a significantly more effective second-line eradication treatment for H.pylori infection than the 7-d alternative.展开更多
Dasatinib is a second-generation tyrosine kinase inhibitor (TKI)and it could be used as a second-line treatment for patients with chronic myeloid leukemia (CML).Yinishu,a generic dasatinib made in China,was approved b...Dasatinib is a second-generation tyrosine kinase inhibitor (TKI)and it could be used as a second-line treatment for patients with chronic myeloid leukemia (CML).Yinishu,a generic dasatinib made in China,was approved by the China Food and Drug Administration in 2013 and it costs much less than the patented dasatinib SPRYCEL.The present study aimed to examine the efficacy and safety of Yinishu as a second-line treatment for CML by comparing the baseline clinical characteristics,rates of adverse events and efficacy between Yinishu and SPRYCEL groups. The results showed that there were no significant differences in the rates of optimal response between Yinishu and SPRYCEL for patients who started second-line treatment because of treatment failure.For patients who started second-line treatment because of intolerance of first-line treatment, their levels of BCR-ABL1/ABL1 on the international scale (BCR-ABL^IS)was maintained very low throughout the course of Yinishu treatment.Drug-related adverse events occurred with the same frequency in these two groups.It was confirmed that Yinishu was effective and safe as a second- line treatment for CML patients.Yinishu may be more suitable for patients who are economically unable to pay for the patented dasatinib SPRYCEL.展开更多
BACKGROUND The standard management of autoimmune hepatitis(AIH)is based on corticosteroids,alone or in combination with azathioprine.Second-line treatments are needed for patients who have refractory disease.However,h...BACKGROUND The standard management of autoimmune hepatitis(AIH)is based on corticosteroids,alone or in combination with azathioprine.Second-line treatments are needed for patients who have refractory disease.However,high-quality data on the alternative management of AIH are scarce.AIM To evaluate the efficacy and safety of tacrolimus and mycophenolate mofetil(MMF)and the quality of evidence by using the Grading of Recommendations Assessment,Development and Evaluation approach(GRADE).METHODS A systematic review and meta-analysis of the available data were performed.We calculated pooled event rates for three outcome measures:Biochemical remission,adverse events,and mortality,with their corresponding 95%confidence intervals(CI).RESULTS The pooled biochemical remission rate was 68.9%(95%CI:60.4-76.2)for tacrolimus,and 59.6%(95%CI:54.8-64.2)for MMF,and rates of adverse events were 25.5%(95%CI:12.4-45.3)for tacrolimus and 24.1%(95%CI:15.4-35.7)for MMF.The pooled mortality rate was estimated at 11.5%(95%CI:7.1-18.1)for tacrolimus and 9.01%(95%CI:6.2-12.8)for MMF.Pooled biochemical remission rates for tacrolimus and MMF in patients with intolerance to standard therapy were 56.6%(CI:43.4-56.6)vs 73.5%(CI:58.1-84.7),and among non-responders were 59.1%(CI:48.7-68.8)vs 40.8%(CI:32.3-50.0),respectively.Moreover,the overall quality assessments using GRADE proved to be very low for all our outcomes in both treatment groups.CONCLUSION Tacrolimus and MMF are in practice considered effective for patients with AIH who are non-responders or intolerant to first-line treatment,but we found no high-quality evidence to support this statement.展开更多
Background: Capecitabine and irinotecan combination therapy(XELIRI) has been examined at various dose levels to treat metastatic colorectal cancer(m CRC). Recently, in the Association of Medical Oncology of the German...Background: Capecitabine and irinotecan combination therapy(XELIRI) has been examined at various dose levels to treat metastatic colorectal cancer(m CRC). Recently, in the Association of Medical Oncology of the German Cancer Society(AIO) 0604 trial, tri?weekly XELIRI plus bevacizumab, with reduced doses of irinotecan(200 mg/m^2 on day 1) and capecitabine(1600 mg/m^2 on days 1–14), repeated every 3 weeks, has shown favorable tolerability and eicacy which were comparable to those of capecitabine and oxaliplatin(XELOX) plus bevacizumab. The doses of capecit?abine and irinotecan in the AIO trial are considered optimal. In a phase I/II study, XELIRI plus bevacizumab(BIX) as second?line chemotherapy was well tolerated and had promising eicacy in Japanese patients.Methods: The Asian XELIRI Projec T(AXEPT) is an East Asian collaborative, open?labelled, randomized, phase Ⅲ clinical trial which was designed to demonstrate the non?inferiority of XELIRI with or without bevacizumab versus standard FOLFIRI(5?fluorouracil, leucovorin, and irinotecan combination) with or without bevacizumab as second?line chemo?therapy for patients with m CRC. Patients with 20 years of age or older, histologically conirmed m CRC, Eastern Coop?erative Oncology Group performance status 0–2, adequate organ function, and disease progression or intolerance of the irst?line regimen will be eligible. Patients will be randomized(1:1) to receive standard FOLFIRI with or with?out bevacizumab(5 mg/kg on day 1), repeated every 2 weeks(FOLIRI arm) or XELIRI with or without bevacizumab(7.5 mg/kg on day 1), repeated every 3 weeks(XELIRI arm). A total of 464 events were estimated as necessary to show non?inferiority with a power of 80% at a one?sided α of 0.025, requiring a target sample size of 600 patients. The 95% conidence interval(CI) upper limit of the hazard ratio was pre?speciied as less than 1.3.Conclusion: The Asian XELIRI Projec T is a multinational phase III trial being conducted to provide evidence for XELIRI with or without bevacizumab as a second?line treatment option of mCRC.展开更多
基金This work was supported by the National Key Research and Development Program of China(Grant No.2021YFA1201100)the National Natural Science Foundation of China(Grant No.82072657).
文摘Objective:Little progress has been made in recent years using first-line chemotherapy,including gemcitabine combined with nab-paclitaxel,FOLFIRINOX,and NALIRIFOX,for advanced pancreatic adenocarcinoma(APC).In addition,the optimal second-line chemotherapy regimen has not been determined.This study aimed to compare the effectiveness of different types of second-line chemotherapy for APC.Methods:Patients with APC who received first-line treatment from January 2008 to January 2021 were considered eligible for this retrospective analysis.The primary and secondary endpoints were overall survival(OS)and progression-free survival(PFS),respectively.Results:Four hundred and thirty-seven and 617 patients were treated with 5-fluorouracil-and gemcitabine-based chemotherapy as first-line treatment,respectively.Demographic and clinical features,except age and liver metastasis,were comparable between the two groups(P<0.05).The median OS was 8.8 and 7.8 months in patients who received a 5-fluorouracil-and gemcitabine-based combined regimen for first-line therapy,respectively(HR=1.244,95%CI=1.090–1.419;P<0.001).The median OS was 5.6 and 1.9 months in patients who received second-line chemotherapy and supportive care,respectively(HR=0.766,95%CI=0.677–0.867;P<0.001).The median PFS was not significantly differently between gemcitabine or 5-fluorouracil monotherapy and combination therapy.Conclusions:A 5-fluorouracil-or gemcitabine-based combined regimen was shown to be as effective as a single 5-fluorouracil or gemcitabine regimen as second-line therapy for patients with APC.
基金supported by the Guangdong Basic and Applied Basic Research Foundation (No.2023A1515010093)the Shenzhen Fundamental Research Program (Stable Support Plan Program)(Nos.JCYJ20220809170611004, 20231121110828001 and 20231121113641002)the National Taipei University of Technology-Shenzhen University Joint Research Program (No.2024001)。
文摘In this paper, we have demonstrated an Er-doped ultrafast laser with a single mode fiber-gradient index multimode fiber-single mode fiber(SMF-GIMF-SMF, SMS) structure as saturable absorber(SA), which can generate not only stable single-pulse state, but also special mode-locked pulses with the characteristics of high energy and noisy behaviors at proper pump power and cavity polarization state. In addition, we have deeply investigated the real-time spectral evolutions of the mode-locked pulses through the dispersive Fourier transformation(DFT) technique. It can be found that the pulse regime can actually consist of a lot of small noise pulses with randomly varying intensities. We believe that these results will further enrich the nonlinear dynamical processes in the ultrafast lasers.
基金Project supported by the Innovation Program for Quantum Science and Technology(Grant No.2023ZD0301000)the National Natural Science Foundation of China(Grant Nos.12434018,62475073,1243000542,11621404,11561121003,11727812,61775059,12074122,62405090,62035005,and 11704123)+1 种基金the Natural Science Foundation of Shanghai(Grant No.23ZR1419000)China Postdoctoral Science Foundation(Grant Nos.2023M741188 and 2024T170275)。
文摘Synchronized dual-wavelength mode-locked laser is investigated numerically and experimentally in the normal dispersion regime.A programmable optical processor is introduced to shape the spectral profile and adjust the net dispersion,which is demonstrated be a convenient and reliable approach to generate dual-color solitons.The time-stretch dispersive Fourier transform and frequency-resolved optical grating techniques are utilized to measure the spectral and temporal characteristics of dual-color solitons,respectively.The numerical results are consistent with experimental results.This work may facilitate the development of filter-based mode-locked laser and the understanding of multi-wavelength soliton dynamics.
基金Supported by National Natural Science Foundation of China(Grant Nos.52192634,92471202,52105013,U2341237,T2388101).
文摘The spatial constraints of aircraft have accelerated the development of multi-wing deployable mechanisms.These systems enable the rapid,sub-second deployment of multiple folding wings,which generate high-energy impacts upon locking-resulting in oscillations that can adversely affect aerodynamic performance.Despite their importance,the transient dynamic characteristics during deployment and locking remain insufficiently explored.This study presents an integrated dynamic model for a single-actuator,multi-wing deployable mechanism that accounts for joint clearances,component elasticity,and locking collisions.This model is used to analyze the influence of transient driving on the motion errors of multiple folding wings,the locking oscillation amplitude,and the complete stabilization time.Results indicate that as the driving force and transient deployment speed increase,all dynamic performance characteristics are notably affected.Specifically,raising the transient driving force from 3000 to 7000 N leads to a maximum increase of 60.8%in oscillation amplitude and 78.4%in stabilization time.By comparing the results of the prototype experiment with the theoretical model,it is found that the errors of the maximum locking oscillation amplitude and the complete stabilization time for the three groups of folding wings are all within the acceptable range,which verifies the theoretical model.These findings advance the theoretical understanding of transient deployment dynamics and locking oscillations in high-speed deployable mechanisms.
基金funded by NSERC Discovery Grants, NSERC Discovery Accelerator Supplements, Innovation Proof-of-Concept Grant of Research Manitoba, and Faculty of Science Research Innovation and Commercialization Grant of University of Manitoba (C.-M.H.)。
文摘A cavity magnonic oscillator uses the coupling of a planar transmission line oscillator(cavity) and spin excitations(magnons) in a ferrimagnetic material to achieve superior frequency stability and reduced phase noise. Like many low phase noise oscillators, a cavity magnonic oscillator faces the challenge that its narrow resonance profile is not well suited for injection locking amplification. This work presents an improved design for such an oscillator configured as an injection locking amplifier(ILA) with an extended lock range. The proposed design features a two-stage architecture, consisting of a pre-amplification oscillator and a cavity magnonic oscillator, separated by an isolator to prevent backward locking.By optimizing the circuit parameters of each stage, the proposed design achieved an order of magnitude increase in lock range, when compared to its predecessors, all while preserving the phase noise quality of the input, making it well-suited for narrowband, sensitive signal amplification. Furthermore, this work provides a method for using oscillators with high spectral purity as injection locking amplifiers.
基金supported by the National Natural Science Foundation of China(42474003,42074007)the Fundamental Research Funds for the Central Universities(2042023kfyq01)。
文摘As a major fault in the northeastern Qinghai-Xizang Plateau,the Haiyuan fault zone is important for understanding the regional deformation.Aiming at the differences in the slip rate and locking degree obtained from different studies,this study constructs a refined block model(including Qilian,Alxa,Ordos,Xining,Haiyuan,and Lanzhou blocks)and uses the grid search and simulated annealing methods to invert GPS data for slip rate and locking degree of the Haiyuan fault zone.The results are as follows:(1)The sinistral slip rates in the western,middle,and eastern segments are 4.93-5.22 mm/a,1.52-4.94 mm/a,and 0.43-1.18 mm/a,decreasing eastward on the whole,while the compression rates are 0.45-1.26 mm/a,0.58-2.62 mm/a,and3.52-4.48 mm/a,increasing eastward on the whole.(2)The locking depth of the western segment increases from about 5 km to about 20 km eastward;the middle segment decreases and then increases eastward;the eastern segment concentrates at about 20 km(PHI is about 0.86).(3)The slip deficit is relatively higher in the Lenglongling,Jinqianghe,Maomaoshan,and Liupanshan faults(averaging about 3.42 mm/a,4.16 mm/a,4.23 mm/a,and 3.43 mm/a within 20 km).(4)The Qilian,Alxa,Xining,Lanzhou,and Haiyuan blocks rotate clockwise,while the Ordos block rotates counterclockwise.Additionally,by comparing different block models,the Haiyuan block should be considered independently.The Haiyuan fault zone adjusts surrounding block movements and uplifts Liupanshan mountain tectonically.The results can provide important references for understanding the regional earthquake risk and deformation mechanism.
文摘BACKGROUND Proximal humerus fractures(PHFs)are common,especially in the elderly,and optimal surgical management remains debated.This study compares clinical,functional,and radiographic outcomes of deltoid split(DS)vs deltopectoral(DP)approaches in PHFs treated with locking plates.AIM To evaluate and compare the clinical,functional,and radiographic outcomes-as well as postoperative complication rates-associated with the DS vs the DP surgical approach in the open reduction and internal fixation(ORIF)of PHFs using locking plate constructs.METHODS A multicenter retrospective study of 120 patients undergoing ORIF for closed Neer type II-IV PHFs between January 2023 and December 2023.Patients were grouped by surgical approach[DS(n=70),DP(n=50)].Outcome measures included Numeric Rating Scale(NRS)for pain,Quick-Disabilities in Arm,Shoulder,and Hand questionnaire(QuickDASH),Constant-Murley score,Short Form Health Survey-12v2,and radiographic alignment.Complication rates were recorded.Statistical significance was defined as P<0.05.RESULTS Early outcomes favored the DS group:(1)Lower NRS(3.1 vs 5.9);(2)Higher Constant-Murley(68.2 vs 50.5);and(3)Better QuickDASH(25.4 vs 37.1).Complication rate was lower in the DS group(1.66%vs 5.81%).Radiographic outcomes were comparable.Long-term results were similar between groups.CONCLUSION While both approaches yield satisfactory long-term outcomes,the DS approach is associated with faster early recovery and fewer complications,supporting its use in selected cases.
文摘Biology is governed by macromolecular interactions,perturbation of which often lies at the heart of disease.Most therapeutic drugs,whether they are small molecules or biologics,exert their effects through impeding such interactions,whether they are of an enzyme with its substrate or a ligand with its receptor.Conversely,a handful of approved drugs and a larger number of candidates in development have the opposite effect:They either activate or inhibit a biological output by stabilizing a preexisting complex through reducing the rate at which its components dissociate(koff).
基金supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(Grant No.XDB35010202)the National Natural Science Foundation of China(Grants No.62275268)。
文摘This study presents an achievement of laser cooling of alkaline-earth atoms in the Chinese Space Station’s strontium(Sr)atomic space optical clock.The system’s core components,physical unit,optical unit,and electrical unit,have a total volume of 306 L and a total mass of 163.8 kg.These compact and robust units can overcome mechanical vibrations and temperature fluctuations during space launch.The laser sources of the optical unit are composed of diode lasers,and the injection locking of slave lasers is automatically performed by a program.In the experiment,a blue magneto-optical trap of cold atoms was achieved,with the atom numbers estimated to be approximately(1.50±0.13)×10^(6) for 87Sr and(8.00±0.56)×10^(6) for 88Sr.This work establishes a foundation for atomic confinement and high-precision interrogation in space-based optical clocks and expands the frontiers of cold atom physics in microgravity.
基金supported by the National Natural Science Foundation of China(Grant Nos.12275240,12261131495,and 12475008)the Natural Science Foundation of Zhejiang Province(Grant No.LY24A050002).
文摘Fiber optic sensing technology,with its low transmission loss,wide bandwidth,and broad dynamic range,offers significant advantages for high-sensitivity measurements.In this study,a multi-band soliton modulation system for stress sensing is proposed,utilizing Ti_(3)C_(2)T_(x)to generate ultrashort pulses.By applying stress to microfibers,dichromatic periodic multisoliton mode-locking at 1530 nm and 1555.2 nm is achieved.Vibrational mechanical stress further modulates cross-phase interactions between solitons,inducing higher-order bound solitons with small-amplitude oscillations.These dynamic processes reveal complex nonlinear optical behaviors and enhance sensing capabilities.Additionally,the feasibility of stable mode-locking of Ti_(3)C_(2)T_(x)in a 1µm multimode cavity is analyzed using the multimode nonlinear Schrodinger equation,and multisoliton states are experimentally demonstrated by integrating a 1µm narrow-linewidth ultrafast multimode laser with a stressed microfiber.
基金supported by the National Major Scientific Instruments and Equipment Development Projects of China(No.41827808)the Major Program of the National Natural Science Foundation of China(No.42090055)Supported by Science and Technology Projects of Xizang Autonomous Region,China(No.XZ202402ZD0001)。
文摘In 2018,Baige,Xizang,witnessed two consecutive large-scale landslides,causing significant damage and drawing widespread attention.From March 2011 to February 2018,the Baige landslide exhibited a 50-m displacement without complete failure,culminating in a collapse in October 2018.The mechanisms behind its resistance to failure despite substantial deformation and the influence of the complex geo-structure within the tectonic mélange belt remain unclear.To address these questions,this study utilized a multidisciplinary approach,integrating on-site geological field mapping,surface deformation monitoring,multielectrode resistivity method,and deep displacement analysis.The aim was to evaluate the impact of the intricate geo-structure within the tectonic mélange belt on the Baige landslide events.Findings reveal that the landslide's geo-structure consists of structurally fractured,mesh-like rock masses,including heterogeneous lenticular rock masses and intermittent brittle shear zones distributed around the lens-shaped rock masses.The study underscores that the inhomogeneous and weakly deformed lenticular rock masses function as natural locked segments,governing the stability of the Baige landslide.Specifically,the relatively intact and hard granodiorite porphyry play a crucial role in locking the landslide's deformation.Deep displacement analysis indicates that the brittle shear zones act as the sliding surfaces.The progressive destruction of the locked segments and the gradual penetration of brittle shear zones,driven by gravitational potential energy,contribute to the landslide occurrence.This research provides critical insights into the formation mechanisms of large-scale landslides within tectonic mélange belts.
基金supported by the National Natural Science Foundation of China(Grant Nos.12434016 and 12474380)Science and Technology Project of Guangdong Province(Grant No.2020B0101-90001)+1 种基金the National Key Research and Development Program of China(Grant No.2023YFA1406900)the Natural Science Foundation of Guangdong Province(Grant No.2025A1515010714)。
文摘Spin-momentum locking is widely regarded as an inherent property of evanescent waves,where the transverse spin angular momentum is intrinsically tied to the wave's polarization.This principle is well established in systems such as surface plasmon polaritons,surface elastic waves,and other evanescent modes.Here,we theoretically unveil an anomalous breakdown of spin-momentum locking in evanescent electromagnetic waves at a metalgyromagnetic interface.We show that the hybrid polarization of the field induces two successive reversals of transverse spin near the interface—directly violating the conventional locking between spin and momentum.As a result,identical chiral sources placed at different heights above the interface excite evanescent waves propagating in opposite directions,defying standard expectations.This discovery challenges the presumed universality of spin-momentum locking and opens new degrees of freedom for controlling wave propagation in photonic and plasmonic systems.
文摘Gastric cancer remains one among the leading causes of cancer-related deaths, regardless of its decreasing incidence and newly available treatment options. Most patients present at an advanced stage and are treated with upfront systemic chemotherapy. Those patients receiving first-line therapy may initially respond to treatment, but many of them relapse over time. In such condition, second-line treatment for disease progression remains the only available option. Although there exists no standard approach in the second-line setting, several phase Ⅲ trials have shown modest survival benefit in patients receiving irinotecan, taxane and ramucirumab over the best supportive care or active agents. This review analyzes the currently available treatment regimens and future directions of research in the second-line setting for metastatic gastric cancer with the best available evidence. Additionally, the prognostic factors that influence patient survival in those receiving second-line therapy are discussed.
文摘Worldwide prevalence of Helicobacter pylori(H.pylori) infection is approximately 50%,with the highest being in developing countries.We compared cure rates and tolerability(SE) of second-line anti-H.pylori levofloxacin/amoxicillin(LA)-based triple regimens vs standard quadruple therapy(QT).An English language literature search was performed up to October 2010.A meta-analysis was performed including randomized clinical trials comparing 7-or 10-d LA with 7-d QT.In total,10 articles and four abstracts were identified.Overall eradication rate in LA was 76.5%(95% CI:64.4%-97.6%).When only 7-d regimens were included,cure rate was 70.6%(95% CI:40.2%-99.1%),whereas for 10-d combinations,cure rate was significantly higher(88.7%;95% CI:56.1%-109.9%;P < 0.05).Main eradication rate for QT was 67.4%(95% CI:49.7%-67.9%).The 7-d LA and QT showed comparable efficacy [odds ratio(OR):1.09;95% CI:0.63-1.87],whereas the 10-d LA regimen was significantly more effective than QT(OR:5.05;95% CI:2.74-9.31;P < 0.001;I 2 = 75%).No differences were reported in QT eradication rates among Asian and European studies,whereas LA regimens were more effective in European populations(78.3% vs 67.7%;P = 0.05).Incidence of SE was lower in LA therapy than QT(OR:0.39;95% CI:0.18-0.85;P = 0.02).A higher rate of side effects was reported in Asian patients who received QT.Our findings support the use of 10-d LA as a simple second-line treatment for H.pylori eradication with an excellent eradication rate and tolerability.The optimal second-line alternative scheme might differ among countries depending on quinolone resistance.
文摘Gastric cancer and cancer of the gastro-oesophageal junction(GOJ) are the 4th most common cancer diagnoses worldwide with regional differences in incidence rates.The treatment of gastric and GOJ cancers is complex and requires multimodality treatment including chemotherapy treatment,surgery,and radiotherapy.During the past decade considerable improvements were achieved by advanced surgical techniques,tailored chemotherapies/radiotherapy and technical innovations in clinical diagnostics.In patients with advanced or metastatic gastric/GOJ cancer systemic chemotherapy with fluoropyrimidine/platinum-based regimens(+/-human epidermal growth factor receptor-2 antibody) is the mainstay of treatment.Despite these improvements,the clinical outcome for patients with advanced or metastatic disease is generally poor with 5-year survival rates ranging between 5%-15%.These poor survival rates may to some extent be related that standard therapies beyond first-line therapies have never been defined.Considering that this patient population is often not fit enough to receive further treatments there is an increasing body of evidence from phase-2 studies that in fact second-line therapies may have a positive impact in terms of overall survival.Moreover two recently published phase-3 studies support the use of second-line chemotherapy.A South Korean study compared either,irinotecan or docetaxel with best supportive care and a German study compared irinotecan with best supportive care-both studies met their primary endpoint overall survival.In this "Field of Vision" article,we review these recently published phase-3 studies and put them into the context of clinical prognostic factors helping to guide treatment decisions in patients who most likely benefit.
文摘AIM: To compare the efficacy of 14- and 7-d bismuthbased quadruple therapies as second-line eradication treatment for Helicobacter pylori(H.pylori) infection.METHODS: Between 2004 and 2014,the medical records of 790 patients who had experienced failure of first-line proton pump inhibitor(PPI)-based eradication therapy and were then treated with bismuth-based quadruple therapy were retrospectively reviewed.Those who received bismuth-based quadruple therapy [PPI,bismuth,metronidazole,and tetracycline(PBMT)] for either 7 d or 14 d were assigned to a PBMT-7 group(n = 543) or a PBMT-14 group(n = 247),respectively.The eradication rates for both groups were determined by intention-to-treat(ITT) and per-protocol(PP) analyses.ITT analysis compared the treatment groups as originally allocated while the PP analysis including only those patients who had completed the treatment as originally allocated.Successful eradication therapy for H.pylori infection was defined as a negative 13C-urea breath test 4 wk after the end of eradication treatment.RESULTS: The overall ITT eradication rate was 69.1%(546/790).Final ITT eradication rates were 67.4%(366/543; 95%CI: 63.1%-71.7%) in the PBMT-7 group and 72.8%(180/247; 95%CI: 67.4%-78.2%) in the PBMT-14 group(P = 0.028).The overall PP eradication rate was 80.0%(546/682),and the final PP eradication rates were 78.2%(366/468; 95%CI: 72.1%-84.0%) in the PBMT-7 group and 84.1%(180/214; 95%CI: 76.8%-90.8%) in the PBMT-14 group(P = 0.009).The H.pylori eradication rates in the PBMT-14 group weresignificantly higher than in the PBMT-7 group according to both ITT(P = 0.028) and PP analysis(P = 0.009).Compliance was similar in both groups(PBMT-7 group: 97.9%; PBMT-14 group: 96.4%).Adverse event rates were 10.7%(51/478) and 17.1%(38/222) in the PBMT-7 and PBMT-14 groups,respectively(P = 0.487).CONCLUSION: The 14-d bismuth-based quadruple therapy is a significantly more effective second-line eradication treatment for H.pylori infection than the 7-d alternative.
文摘Dasatinib is a second-generation tyrosine kinase inhibitor (TKI)and it could be used as a second-line treatment for patients with chronic myeloid leukemia (CML).Yinishu,a generic dasatinib made in China,was approved by the China Food and Drug Administration in 2013 and it costs much less than the patented dasatinib SPRYCEL.The present study aimed to examine the efficacy and safety of Yinishu as a second-line treatment for CML by comparing the baseline clinical characteristics,rates of adverse events and efficacy between Yinishu and SPRYCEL groups. The results showed that there were no significant differences in the rates of optimal response between Yinishu and SPRYCEL for patients who started second-line treatment because of treatment failure.For patients who started second-line treatment because of intolerance of first-line treatment, their levels of BCR-ABL1/ABL1 on the international scale (BCR-ABL^IS)was maintained very low throughout the course of Yinishu treatment.Drug-related adverse events occurred with the same frequency in these two groups.It was confirmed that Yinishu was effective and safe as a second- line treatment for CML patients.Yinishu may be more suitable for patients who are economically unable to pay for the patented dasatinib SPRYCEL.
文摘BACKGROUND The standard management of autoimmune hepatitis(AIH)is based on corticosteroids,alone or in combination with azathioprine.Second-line treatments are needed for patients who have refractory disease.However,high-quality data on the alternative management of AIH are scarce.AIM To evaluate the efficacy and safety of tacrolimus and mycophenolate mofetil(MMF)and the quality of evidence by using the Grading of Recommendations Assessment,Development and Evaluation approach(GRADE).METHODS A systematic review and meta-analysis of the available data were performed.We calculated pooled event rates for three outcome measures:Biochemical remission,adverse events,and mortality,with their corresponding 95%confidence intervals(CI).RESULTS The pooled biochemical remission rate was 68.9%(95%CI:60.4-76.2)for tacrolimus,and 59.6%(95%CI:54.8-64.2)for MMF,and rates of adverse events were 25.5%(95%CI:12.4-45.3)for tacrolimus and 24.1%(95%CI:15.4-35.7)for MMF.The pooled mortality rate was estimated at 11.5%(95%CI:7.1-18.1)for tacrolimus and 9.01%(95%CI:6.2-12.8)for MMF.Pooled biochemical remission rates for tacrolimus and MMF in patients with intolerance to standard therapy were 56.6%(CI:43.4-56.6)vs 73.5%(CI:58.1-84.7),and among non-responders were 59.1%(CI:48.7-68.8)vs 40.8%(CI:32.3-50.0),respectively.Moreover,the overall quality assessments using GRADE proved to be very low for all our outcomes in both treatment groups.CONCLUSION Tacrolimus and MMF are in practice considered effective for patients with AIH who are non-responders or intolerant to first-line treatment,but we found no high-quality evidence to support this statement.
基金funding from Chugai Pharmaceutical Co.Ltd.Roche Korea Co.Ltd.Roche Shanghai.Co.Ltd
文摘Background: Capecitabine and irinotecan combination therapy(XELIRI) has been examined at various dose levels to treat metastatic colorectal cancer(m CRC). Recently, in the Association of Medical Oncology of the German Cancer Society(AIO) 0604 trial, tri?weekly XELIRI plus bevacizumab, with reduced doses of irinotecan(200 mg/m^2 on day 1) and capecitabine(1600 mg/m^2 on days 1–14), repeated every 3 weeks, has shown favorable tolerability and eicacy which were comparable to those of capecitabine and oxaliplatin(XELOX) plus bevacizumab. The doses of capecit?abine and irinotecan in the AIO trial are considered optimal. In a phase I/II study, XELIRI plus bevacizumab(BIX) as second?line chemotherapy was well tolerated and had promising eicacy in Japanese patients.Methods: The Asian XELIRI Projec T(AXEPT) is an East Asian collaborative, open?labelled, randomized, phase Ⅲ clinical trial which was designed to demonstrate the non?inferiority of XELIRI with or without bevacizumab versus standard FOLFIRI(5?fluorouracil, leucovorin, and irinotecan combination) with or without bevacizumab as second?line chemo?therapy for patients with m CRC. Patients with 20 years of age or older, histologically conirmed m CRC, Eastern Coop?erative Oncology Group performance status 0–2, adequate organ function, and disease progression or intolerance of the irst?line regimen will be eligible. Patients will be randomized(1:1) to receive standard FOLFIRI with or with?out bevacizumab(5 mg/kg on day 1), repeated every 2 weeks(FOLIRI arm) or XELIRI with or without bevacizumab(7.5 mg/kg on day 1), repeated every 3 weeks(XELIRI arm). A total of 464 events were estimated as necessary to show non?inferiority with a power of 80% at a one?sided α of 0.025, requiring a target sample size of 600 patients. The 95% conidence interval(CI) upper limit of the hazard ratio was pre?speciied as less than 1.3.Conclusion: The Asian XELIRI Projec T is a multinational phase III trial being conducted to provide evidence for XELIRI with or without bevacizumab as a second?line treatment option of mCRC.
