Efficacy and safety of low-dose cyclophosphamide combined with lenvatinib, pembrolizumab and TACE for unresectable hepatocellular carcinoma:A single-center, prospective,single-arm clinical trial

Objective: Unresectable hepatocellular carcinoma(uHCC) continues to pose effective treatment options. The objective of this study was to assess the efficacy and safety of combining low-dose cyclophosphamide with lenvatinib, pembrolizumab and transarterial chemoembolization(TACE) for the treatment of uHCC.Methods: From February 2022 to November 2023, a total of 40 patients diagnosed with uHCC were enrolled in this small-dose, single-center, single-arm, prospective study. They received a combined treatment of low-dose cyclophosphamide with lenvatinib, pembrolizumab, and TACE. Study endpoints included progression-free survival(PFS), objective response rate(ORR), and safety assessment. Tumor response was assessed using the modified Response Evaluation Criteria in Solid Tumors(mRECIST), while survival analysis was conducted through KaplanMeier curve analysis for overall survival(OS) and PFS. Adverse events(AEs) were evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events(version 5.0).Results: A total of 34 patients were included in the study. The median follow-up duration was 11.2 [95% confidence interval(95% CI), 5.3-14.6] months, and the median PFS(mPFS) was 15.5(95% CI, 5.4-NA) months.Median OS(mOS) was not attained during the study period. The ORR was 55.9%, and the disease control rate(DCR) was 70.6%. AEs were reported in 27(79.4%) patients. The most frequently reported AEs(with an incidence rate >10%) included abnormal liver function(52.9%), abdominal pain(44.1%), abdominal distension and constipation(29.4%), hypertension(20.6%), leukopenia(17.6%), constipation(17.6%), ascites(14.7%), and insomnia(14.7%). Abnormal liver function(14.7%) had the most common grade 3 or higher AEs.Conclusions: A combination of low-dose cyclophosphamide with lenvatinib, pembrolizumab, and TACE is safe and effective for u HCC, showcasing a promising therapeutic strategy for managing uHCC.

Malignant glaucoma treated by low-dose laser cycloplasty: a 1-year multicenter prospective noncomparative study

AIM:To report a one-year clinical outcomes of low-dose laser cycloplasty(LCP)among malignant glaucoma patients.METHODS:In this prospective,multicenter,noncomparative clinical study,participants with malignant glaucoma were recruited and underwent LCP at eight ophthalmic centers in China.Patients were followed up at 1wk,1,3,6,and 12mo.Intraocular pressure(IOP),number of glaucoma medications,anterior chamber depth(ACD),and complications were recorded.Anatomical success was defined as the reformation of the anterior chamber based on slit-lamp biomicroscopy.Recurrence was defined by the presence of a shallow orflat anterior chamber after initial recovery from treatment.RESULTS:A total of 34 eyes received LCP.Mean IOP and medications decreased from 36.1±11.5 mm Hg with 3.3±1.5 glaucoma medications pre-treatment to 20.9±9.8 mm Hg(P<0.001)with 2.9±1.6 medications(P=0.046)at 1d,and 17.4±6.7 mm Hg(P<0.001)with 1.3±1.7 medications(P<0.001)at 12mo.The ACD increased from 1.1±0.8 mm at baseline to 1.7±1.0 mm and to 2.0±0.5 mm at 1d and 12mo,respectively.A total of 32(94.1%)eyes achieved initial anatomical success.During follow-up,2(5.9%)eyes failed and 8(23.5%)eyes relapsed,yielding a 12-month anatomical success rate of 64.3%.Complications including anterior synechia(8.82%),choroidal/ciliary detachment(5.88%)and hypopyon(2.94%)were observed within 1wk.CONCLUSION:LCP is simple,safe,and effective in reforming the anterior chamber in malignant glaucoma.

Analysis of the Efficacy of Low-Dose Betaloc Combined with Amiodarone in Treating Ventricular Arrhythmia

Objective:To explore and analyze the clinical effect of low-dose Betaloc combined with amiodarone in treating ventricular arrhythmia.Methods:70 patients with ventricular arrhythmia who were admitted to the Department of Cardiology of our hospital between August 2022 and August 2023 were selected as research subjects.They were divided into two groups using the coin-tossing method:the combination group(n=35)and the reference group(n=35).The combination group was treated with low-dose Betaloc and amiodarone,and the control group was treated with low-dose Betaloc alone.The treatment efficacy,cardiac function indicators,and related tested indicators of the two groups were compared.Results:The total efficacy of the treatment received by the combination group was much higher than that of the control group(P<0.05).Besides,after treatment,the cardiac function indicators such as left ventricular ejection fraction(LVEF),left ventricular end-systolic volume(LVESV),and cardiac index(CI)of the patients in the combination group were significantly better than those of the reference group(P<0.05).Furthermore,the high-sensitivity C-reactive protein(Hs-CRP),N-terminal prohormone of brain natriuretic peptide(NT-proBNP),adiponectin(APN),and other related test indicators of the patients in the combination group were significantly better than those of the reference group(P<0.05).Conclusion:Low-dose Betaloc combined with amiodarone has a noticeable effect in treating ventricular arrhythmia and deserves to be widely promoted.

Successful treatment of patients with refractory idiopathic membranous nephropathy with low-dose Rituximab:A single-center experience

BACKGROUND The recognition of idiopathic membranous nephropathy(IMN)as an autoimmune disease has paved the way for the use of B-cell-depleting agents,such as Rituximab(RTX),which is now a first-line drug for treating IMN with proven safety and efficacy.Nevertheless,the usage of RTX for the treatment of refractory IMN remains controversial and challenging.AIM To evaluate the efficacy and safety of a new low-dose RTX regimen for the treatment of patients with refractory IMN.METHODS A retrospective study was performed on refractory IMN patients that accepted a low-dose RTX regimen(RTX,200 mg,once a month for five months)in the Xiyuan Hospital of Chinese Academy of Chinese Medical Sciences’Department of Nephrology from October 2019 to December 2021.To assess the clinical and immune remission data,we performed a 24 h urinary protein quantification(UTP)test and measured the serum albumin(ALB)and serum creatinine(SCr)levels,phospholipase A2 receptor(PLA2R)antibody titer,and CD19+B-cell count every three months.RESULTS A total of nine refractory IMN patients were analyzed.During follow-up conducted twelve months later,the results from the 24 h UTP decreased from baseline[8.14±6.05 g/d to 1.24±1.34 g/d(P<0.05)]and the ALB levels increased from baseline[28.06±8.42 g/L to 40.93±5.85 g/L(P<0.01)].Notably,after administering RTX for six months,the SCr decreased from 78.13±16.49μmol/L to 109.67±40.87μmol/L(P<0.05).All of the nine patients were positive for serum anti-PLA2R at the beginning,and four patients had normal anti-PLA2R titer levels at six months.The level of CD19+B-cells decreased to 0 at three months,and CD19+B-cell count remained at 0 up until six months of follow-up.CONCLUSION Our low-dose RTX regimen appears to be a promising treatment strategy for refractory IMN.

Hformer:highly efficient vision transformer for low-dose CT denoising

In this paper,we propose Hformer,a novel supervised learning model for low-dose computer tomography(LDCT)denoising.Hformer combines the strengths of convolutional neural networks for local feature extraction and transformer models for global feature capture.The performance of Hformer was verified and evaluated based on the AAPM-Mayo Clinic LDCT Grand Challenge Dataset.Compared with the former representative state-of-the-art(SOTA)model designs under different architectures,Hformer achieved optimal metrics without requiring a large number of learning parameters,with metrics of33.4405 PSNR,8.6956 RMSE,and 0.9163 SSIM.The experiments demonstrated designed Hformer is a SOTA model for noise suppression,structure preservation,and lesion detection.

Design and implementation of the monochromator shielding for the cold neutron spectrometers XINGZHI and BOYA

An innovative monochromator shielding is designed and implemented for the cold neutron spectrometers XINGZHI and BOYA operated by Renmin University of China at China Advanced Research Reactor.Via Monte Carlo simulations and careful mechanical designs,a shielding configuration has been successfully developed to satisfy safety requirements of below 3μSv/h dose rate at its exterior,meanwhile fulfilling space,floor load and nonmagnetic requirements.Composite materials are utilized to form the sandwich-type shielding walls:the inner layer of boron carbide rubber,the middle layer of steel-encased lead and the outer layer of borated polyethylene.Special-shaped liftable shielding blocks are incorporated to facilitate a continuous adjustment of the neutron energy while preventing radiation leakage.Our work has demonstrated that by utilizing composite shielding materials,along with the sandwich structure and liftable shielding blocks,a compact and lightweight shielding solution can be achieved.This enables the realization of advanced neutron scattering instruments that provide expanded space of measurement,larger energy and momentum coverage,and higher flux on the sample.This shielding represents the first of its kind in neutron scattering instruments in China.Following its successful operation,it has been subsequently employed by other neutron instruments across the country.

Benchmark experiment on slab^(238)U with D-T neutrons for validation of evaluated nuclear data

A benchmark experiment on^(238)U slab samples was conducted using a deuterium-tritium neutron source at the China Institute of Atomic Energy.The leakage neutron spectra within energy levels of 0.8-16 MeV at 60°and 120°were measured using the time-of-flight method.The samples were prepared as rectangular slabs with a 30 cm square base and thicknesses of 3,6,and 9 cm.The leakage neutron spectra were also calculated using the MCNP-4C program based on the latest evaluated files of^(238)U evaluated neutron data from CENDL-3.2,ENDF/B-Ⅷ.0,JENDL-5.0,and JEFF-3.3.Based on the comparison,the deficiencies and improvements in^(238)U evaluated nuclear data were analyzed.The results showed the following.(1)The calculated results for CENDL-3.2 significantly overestimated the measurements in the energy interval of elastic scattering at 60°and 120°.(2)The calculated results of CENDL-3.2 overestimated the measurements in the energy interval of inelastic scattering at 120°.(3)The calculated results for CENDL-3.2 significantly overestimated the measurements in the 3-8.5 MeV energy interval at 60°and 120°.(4)The calculated results with JENDL-5.0 were generally consistent with the measurement results.

Neutron irradiation influence on high-power thyristor device under fusion environment

Because of their economy and applicability,high-power thyristor devices are widely used in the power supply systems for large fusion devices.When high-dose neutrons produced by deuterium–tritium(D–T)fusion reactions are irradiated on a thyristor device for a long time,the electrical characteristics of the device change,which may eventually cause irreversible damage.In this study,with the thyristor switch of the commutation circuit in the quench protection system(QPS)of a fusion device as the study object,the relationship between the internal physical structure and external electrical parameters of the irradiated thyristor is established.Subsequently,a series of targeted thyristor physical simulations and neutron irradiation experiments are conducted to verify the accuracy of the theoretical analysis.In addition,the effect of irradiated thyristor electrical characteristic changes on the entire QPS is studied by accurate simulation,providing valuable guidelines for the maintenance and renovation of the QPS.

Nondestructive technique for identifying nuclides using neutron resonance transmission analysis at CSNS Back-n

Nondestructive and noninvasive neutron assays are essential applications of neutron techniques.Neutron resonance transmission analysis(NRTA)is a powerful nondestructive method for investigating the elemental composition of an object.The back-streaming neutron line(Back-n)is a newly built time-of-flight facility at the China Spallation Neutron Source(CSNS)that provides neutrons in the eV to 300 MeV range.A feasibility study of the NRTA method for nuclide identification was conducted at the CSNS Back-n via two test experiments.The results demonstrate that it is feasible to identify different elements and isotopes in samples using the NRTA method at Back-n.This study reveals its potential future applications.

An efficient parallel algorithm of variational nodal method for heterogeneous neutron transport problems

The heterogeneous variational nodal method(HVNM)has emerged as a potential approach for solving high-fidelity neutron transport problems.However,achieving accurate results with HVNM in large-scale problems using high-fidelity models has been challenging due to the prohibitive computational costs.This paper presents an efficient parallel algorithm tailored for HVNM based on the Message Passing Interface standard.The algorithm evenly distributes the response matrix sets among processors during the matrix formation process,thus enabling independent construction without communication.Once the formation tasks are completed,a collective operation merges and shares the matrix sets among the processors.For the solution process,the problem domain is decomposed into subdomains assigned to specific processors,and the red-black Gauss-Seidel iteration is employed within each subdomain to solve the response matrix equation.Point-to-point communication is conducted between adjacent subdomains to exchange data along the boundaries.The accuracy and efficiency of the parallel algorithm are verified using the KAIST and JRR-3 test cases.Numerical results obtained with multiple processors agree well with those obtained from Monte Carlo calculations.The parallelization of HVNM results in eigenvalue errors of 31 pcm/-90 pcm and fission rate RMS errors of 1.22%/0.66%,respectively,for the 3D KAIST problem and the 3D JRR-3 problem.In addition,the parallel algorithm significantly reduces computation time,with an efficiency of 68.51% using 36 processors in the KAIST problem and 77.14% using 144 processors in the JRR-3 problem.

Isotopic dependence of the yield ratios of light fragments from different projectiles and their unified neutron skin thicknesses

The yield ratios of neutron-proton(R(n/p))and^(3)H-^(3)He(R(^(3)H∕^(3)He))with reduced rapidity from 0 to 0.5 were simulated at 50 MeV/u even-even ^(36−56)Ca+^(40)Ca,even-even ^(48−78)Ni+^(58)Ni,and ^(100−139)Sn(every third isotopes)+112 Sn for full reduced impact parameters using the isospin-dependent quantum molecular dynamics(IQMD)model.The neutron and proton density distributions and root-mean-square radii of the reaction systems were obtained using the Skyrme-Hartree-Fock model,which was used for the phase space initialization of the projectile and target in IQMD.We defined the unified neutron skin thickness asΔRnp=<r^(2)>^(1∕2) n−<r^(2)>^(1∕2)p,which was negative for neutron-deficient nuclei.The unifiedΔRnp values for nuclei with the same relative neutron excess from different isotopic chains were nearly equal,except for extreme neutron-rich isotopes,which is a type of scaling behavior.The yield ratios of the three isotopic chain-induced reactions,which depended on the reduced impact parameter and unified neutron skin thickness,were studied.The results showed that both R(n/p)and R(^(3)H∕^(3)He)decreased with a reduced impact parameter for extreme neutron-deficient isotopes;however,they increased with reduced impact parameters for extreme neutron-rich isotopes,and increased with theΔRnp of the projectiles for all reduced impact parameters.In addition,a scaling phenomenon was observed betweenΔR np and the yield ratios in peripheral colli-sions from different isotopic chain projectiles(except for extreme neutron-rich isotopes).Thus,R(n/p)and R(^(3)H∕^(3)He)from peripheral collisions were suggested as experimental probes for extracting the neutron or proton skin thicknesses of non-extreme neutron-rich nuclei from different isotopic chains.

FPGA-based position reconstruction method for neutron beam flux spatial distribution measurement in BNCT

A new measurement method for the spatial distribution of neutron beam flux in boron neutron capture therapy(BNCT)is being developed based on the two-dimensional Micromegas detector.To address the issue of long processing times in traditional offline position reconstruction methods,this paper proposes a field programmable gate array based online position reconstruction method utilizing the micro-time projection chamber principle.This method encapsulates key technical aspects:a self-adaptive serial link technique built upon the dynamical adjustment of the delay chain length,fast sorting,a coordinate-matching technique based on the mapping between signal timestamps and random access memory(RAM)addresses,and a precise start point-merging technique utilizing a circular combined RAM.The performance test of the selfadaptive serial link shows that the bit error rate of the link is better than 10-12 at a confidence level of 99%,ensuring reliable data transmission.The experiment utilizing the readout electronics and Micromegas detector shows a spatial resolution of approximately 1.4 mm,surpassing the current method’s resolution level of 5 mm.The beam experiment confirms that the readout electronics system can obtain the flux spatial distribution of neutron beams online,thus validating the feasibility of the position reconstruction method.The online position reconstruction method avoids traditional methods,such as bubble sorting and traversal searching,simplifies the design of the logic firmware,and reduces the time complexity from O(n2)to O(n).This study contributes to the advancement in measuring neutron beam flux for BNCT.

Microstructures and micromechanical behaviors of high -entropy alloys investigated by synchrotron X-ray and neutron diffraction techniques: A review

High-entropy alloys(HEAs)possess outstanding features such as corrosion resistance,irradiation resistance,and good mechan-ical properties.A few HEAs have found applications in the fields of aerospace and defense.Extensive studies on the deformation mech-anisms of HEAs can guide microstructure control and toughness design,which is vital for understanding and studying state-of-the-art structural materials.Synchrotron X-ray and neutron diffraction are necessary techniques for materials science research,especially for in situ coupling of physical/chemical fields and for resolving macro/microcrystallographic information on materials.Recently,several re-searchers have applied synchrotron X-ray and neutron diffraction methods to study the deformation mechanisms,phase transformations,stress behaviors,and in situ processes of HEAs,such as variable-temperature,high-pressure,and hydrogenation processes.In this review,the principles and development of synchrotron X-ray and neutron diffraction are presented,and their applications in the deformation mechanisms of HEAs are discussed.The factors that influence the deformation mechanisms of HEAs are also outlined.This review fo-cuses on the microstructures and micromechanical behaviors during tension/compression or creep/fatigue deformation and the application of synchrotron X-ray and neutron diffraction methods to the characterization of dislocations,stacking faults,twins,phases,and intergrain/interphase stress changes.Perspectives on future developments of synchrotron X-ray and neutron diffraction and on research directions on the deformation mechanisms of novel metals are discussed.

Study on the optimal incident proton energy of ^(7)Li(p,n)^(7)Be neutron source for boron neutron capture therapy

Boron neutron capture therapy(BNCT)is recognized as a precise binary targeted radiotherapy technique that effectively eliminates tumors through the^(10)B(n,α)^(7)Li nuclear reaction.Among various neutron sources,accelerator-based sources have emerged as particularly promising for BNCT applications.The^(7)Li(p,n)^(7)Be reaction is highly regarded as a potential neutron source for BNCT,owing to its low threshold energy for the reaction,significant neutron yield,appropriate average neutron energy,and additional benefits.This study utilized Monte Carlo simulations to model the physical interactions within a lithium target subjected to proton bombardment,including neutron moderation by an MgF_(2)moderator and subsequent BNCT dose analysis using a Snyder head phantom.The study focused on calculating the yields of epithermal neutrons for various incident proton energies,finding an optimal energy at 2.7 MeV.Furthermore,the Snyder head phantom was employed in dose simulations to validate the effectiveness of this specific incident energy when utilizing a^(7)Li(p,n)^(7)Be neutron source for BNCT purposes.

Multi-distortion suppression for neutron radiographic images based on generative adversarial network

Neutron radiography is a crucial nondestructive testing technology widely used in the aerospace,military,and nuclear industries.However,because of the physical limitations of neutron sources and collimators,the resulting neutron radiographic images inevitably exhibit multiple distortions,including noise,geometric unsharpness,and white spots.Furthermore,these distortions are particularly significant in compact neutron radiography systems with low neutron fluxes.Therefore,in this study,we devised a multi-distortion suppression network that employs a modified generative adversarial network to improve the quality of degraded neutron radiographic images.Real neutron radiographic image datasets with various types and levels of distortion were built for the first time as multi-distortion suppression datasets.Thereafter,the coordinate attention mechanism was incorporated into the backbone network to augment the capability of the proposed network to learn the abstract relationship between ideally clear and degraded images.Extensive experiments were performed;the results show that the proposed method can effectively suppress multiple distortions in real neutron radiographic images and achieve state-of-theart perceptual visual quality,thus demonstrating its application potential in neutron radiography.

High-resolution neutronics model for ^(238)Pu production in high-flux reactors

We proposed and compared three methods(filter burnup,single energy burnup,and burnup extremum analysis)to build a high-resolution neutronics model for 238Pu production in high-flux reactors.The filter burnup and single energy burnup methods have no theoretical approximation and can achieve a spectrum resolution of up to~1 eV,thereby constructing the importance curve and yield curve of the full energy range.The burnup extreme analysis method combines the importance and yield curves to consider the influence of irradiation time on production efficiency,thereby constructing extreme curves.The three curves,which quantify the transmutation rate of the nuclei in each energy region,are of physical significance because they have similar distributions.A high-resolution neutronics model for ^(238)Pu production was established based on these three curves,and its universality and feasibility were proven.The neutronics model can guide the neutron spectrum optimization and improve the yield of ^(238)Pu by up to 18.81%.The neutronics model revealed the law of nuclei transmutation in all energy regions with high spectrum resolution,thus providing theoretical support for high-flux reactor design and irradiation production of ^(238)Pu.

Measurement of the neutron-induced total cross sections of ^(nat)Pb from 0.3 eV to 20 MeV on the Back-n at CSNS

The neutron-induced total cross sections of natural lead have been measured in a wide energy range(0.3 eV-20 MeV)on the back-streaming white neutron beamline(Back-n)at the China Spallation Neutron Source.Neutron energy was determined by the neutron total cross-section spectrometer using the time-of-flight technique.A fast multi-cell fission chamber was used as the neutron detector,and a 10-mm-thick high-purity natural lead sample was employed for the neutron transmission measurements.The on-beam background was determined using Co,In,Ag,and Cd filters.The excitation function of ^(nat)Pb(n,tot)reaction below 20 MeV was calculated using the TALYS-1.96 nuclear-reaction modeling program.The present results were compared with previous results,the evaluated data available in the five major evaluated nuclear data libraries(i.e.,ENDF/B-VIII.0,JEFF-3.3,JENDL-5,CENDL-3.2,and BROND-3.1),and the theoretical calculation curve.Good agreement was found between the new results and those of previous experiments and with the theoretical curves in the corresponding region.This measurement obtained the neutron total cross section of natural lead with good accuracy over a wide energy range and added experimental data in the resonance energy range.This provides more reliable experimental data for nuclear engineering design and nuclear data evaluation of lead.

Nucleation of Supercooled Water by Neutrons: Latitude Dependence and Implications for Cloud Modelling

It has recently been shown that incident particles, neutrons, can initiate the freezing in a supercooled water volume. This new finding may have ramifications for the interpretation of both experimental data on the nucleation of laboratory samples of supercooled water and perhaps more importantly on the interpretation of ice nucleation involved in cloud physics. For example, if some fraction of the cloud nucleation previously attributed to dust, soot, or aerosols has been caused by cosmogenic neutrons, fresh consideration is required in the context of climate models. Moreover, as cosmogenic neutrons, most being muon-induced, have much greater flux at high latitudes, estimates of ice nucleates in these regions may be larger than required to accurately model cloud and condensation properties. This discrepancy has been pointed out in IPCC reports. Our paper discusses the connection between the new concept of neutrons nucleating supercooled water and the need for a new source of nucleation in high latitude clouds, ideally causing others to review current data, or to analyse future data with this idea in mind. .

The Crystal Structure Study of CaSrFe0.75Co0.75Mn0.5O6−δ by Neutron Diffraction

The crystal structure of CaSrFe0.75Co0.75Mn0.5O6−δ is investigated through neutron diffraction techniques in this study. The material is synthesized using a solid-state synthesis method at a temperature of 1200˚C. Neutron diffraction data is subjected to Rietveld refinement, and a comparative analysis with X-ray diffraction (XRD) data is performed to unravel the structural details of the material. The findings reveal that the synthesized material exhibits a cubic crystal structure with a Pm-3m phase. The neutron diffraction results offer valuable insights into the arrangement of atoms within the lattice, contributing to a comprehensive understanding of the material’s structural properties. This research enhances our knowledge of CaSrFe0.75Co0.75Mn0.5O6−δ, with potential implications for its applications in various technological and scientific domains.

Clinical features of gastroduodenal injury associated with long-term low-dose aspirin therapy

Low-dose aspirin(LDA) is clinically used for the prevention of cardiovascular and cerebrovascular events with the advent of an aging society.On the other hand,a very low dose of aspirin(10 mg daily) decreases the gastric mucosal prostaglandin levels and causes significant gastric mucosal damage.The incidence of LDAinduced gastrointestinal mucosal injury and bleeding has increased.It has been noticed that the incidence of LDA-induced gastrointestinal hemorrhage has increased more than that of non-aspirin non-steroidal anti-inflammatory drug(NSAID)-induced lesions.The pathogenesis related to inhibition of cyclooxygenase(COX)-1 includes reduced mucosal flow,reduced mucus and bicarbonate secretion,and impaired platelet aggregation.The pathogenesis related to inhibition of COX-2 involves reduced angiogenesis and increased leukocyte adherence.The pathogenic mechanisms related to direct epithelial damage are acid back diffusion and impaired platelet aggregation.The factors associated with an increased risk of upper gastrointestinal(GI) complications in subjects taking LDA are aspirin dose,history of ulcer or upper GI bleeding,age > 70 years,concomitant use of non-aspirin NSAIDs including COX-2-selective NSAIDs,and Helicobacter pylori(H.pylori) infection.Moreover,no significant differences have been found between ulcer and non-ulcer groups in the frequency and severity of symptoms such as nausea,acid regurgitation,heartburn,and bloating.It has been shown that the ratios of ulcers located in the body,fundus and cardia are significantly higher in bleeding patients than the ratio of gastroduodenal ulcers in patients taking LDA.Proton pump inhibitors reduce the risk of developing gastric and duodenal ulcers.In contrast to NSAIDinduced gastrointestinal ulcers,a well-tolerated histamine H2-receptor antagonist is reportedly effective in prevention of LDA-induced gastrointestinal ulcers.The eradication of H.pylori is equivalent to treatment with omeprazole in preventing recurrent bleeding.Continuous aspirin therapy for patients with gastrointestinal bleeding may increase the risk of recurrent bleeding but potentially reduces the mortality rates,as stopping aspirin therapy is associated with higher mortality rates.It is very important to prevent LDA-induced gastroduodenal ulcer complications including bleeding,and every effort should be exercised to prevent the bleeding complications.