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.

基于主客观环流分型的强降水数值预报MODE检验方法及其在2019年暖季东北地区的应用

本文构建了基于主客观环流分型的强降水数值预报空间检验(MODE)方法框架,并利用该框架对欧洲中期天气预报中心全球模式(ECMWF)和中国气象局区域中尺度数值天气预报模式(CMA_MESO)的2019年暖季东北地区强降水预报进行检验。结果表明,2019年暖季东北地区54个强降水日的环流型可分为:西风槽型(15个)、副热带高压影响型(13个)、急流型(5个)、西部(12个)和东部冷涡型(9个)。其中,西风槽型和急流型以区域性强降水为主,模式对其强降水发生与否的预报能力强,TS评分较高;西部、东部冷涡型强降水的局地性强,模式对其强降水发生与否的预报能力差,TS评分低;副热带高压影响型也以区域性强降水为主,模式对其强降水发生与否的预报能力也比较强,但是对其强降水质心位置、强度、面积等属性预报偏差较大,TS评分也相对较低。另外,从两种模式预报性能对比看,CMA_MESO强降水强度和面积预报较实况普遍偏强,虽然其预报的TS评分一般高于ECMWF,但其对强降水预报的空报率也都比ECMWF大,对强降水的属性预报偏差一致性一般也低于ECMWF,其预报的可订正性整体上不及ECMWF。

一种基于粗糙熵的改进K-modes聚类算法

K-modes聚类算法被广泛应用于人工智能、数据挖掘等领域。传统的K-modes聚类算法有不错的聚类效果,但是存在迭代次数多、计算量大、容易受到冗余属性的干扰等问题,且仅采用简单的0-1匹配的方法来定义2个样本属性值之间的距离,没有充分考虑每个属性对聚类结果的影响。针对上述问题,该文将粗糙熵引入K-modes算法。首先利用粗糙集属性约简算法消除冗余属性,确定各属性的重要程度;然后利用粗糙熵确定每个属性的权重,从而定义新的类内距离。将该文所提算法与传统的K-modes聚类算法分别在4组公开数据集上进行对比试验。试验结果表明,该文所提算法聚类准确率比传统的K-modes聚类算法更高。

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.

Transition from a filamentary mode to a diffuse one with varying distance from needle to stream of an argon plasma jet

Plasma jet has extensive application potentials in various fields, which normally operates in a diffuse mode when helium is used as the working gas. However, when less expensive argon is used, the plasma jet often operates in a filamentary mode. Compared to the filamentary mode, the diffuse mode is more desirable for applications. Hence, many efforts have been exerted to accomplish the diffuse mode of the argon plasma jet. In this paper, a novel single-needle argon plasma jet is developed to obtain the diffuse mode. It is found that the plasma jet operates in the filamentary mode when the distance from the needle tip to the central line of the argon stream(d) is short. It transits to the diffuse mode with increasing d. For the diffuse mode, there is always one discharge pulse per voltage cycle, which initiates at the rising edge of the positive voltage. For comparison, the number of discharge pulse increases with an increase in the peak voltage for the filamentary mode. Fast photography reveals that the plasma plume in the filamentary mode results from a guided positive streamer,which propagates in the argon stream. However, the plume in the diffuse mode originates from a branched streamer, which propagates in the interfacial layer between the argon stream and the surrounding air. By optical emission spectroscopy,plasma parameters are investigated for the two discharge modes, which show a similar trend with increasing d. The diffuse mode has lower electron temperature, electron density, vibrational temperature, and gas temperature compared to the filamentary mode.

MODE降水检验评价指标改进及卷积半径应用

基于对象的诊断检验方法(MODE)受降水临界值、卷积半径、属性权重等参数的影响,合理选取卷积半径并准确表征预报场与观测场之间的空间相似度决定了MODE的应用效果。本文基于2020年夏季贵州54个降水个例,以多源融合降水(CMPA)作为实况,使用MODE和FSS评分(Fractions Skill Score)对中国气象局广东快速更新同化数值预报系统(CMA-GD)24 h日降水预报进行空间检验。结果表明:卷积半径过小易造成MODE提取降水对象过多,而卷积半径过大则导致局部降水信息丢失,无法从降水场中提取到降水对象。不同卷积半径下计算的最大相似度中值(M_(MI))存在突变。在M_(MI)基础上引入面积权重构造面积平均最大相似度(A_(MMI))。A_(MMI)不受提取降水对象个数的影响,较M_(MI)更具有稳定性,用于表征降水场之间的整体空间相似程度更为合理。根据对象总面积随卷积半径的变化将降水分为大范围降水和局部降水2类。大范围降水平均总面积随着卷积半径的增加而增加,A_(MMI)随卷积半径变化不大。随着卷积半径的增加,局部降水平均总面积减小,平均A_(MMI)有所减小。局部降水对卷积半径选取较为敏感,以观测场对象面积变化不超过10%的最大半径作为卷积半径有助于保留降水场大部分信息。

Suppression of the m/n=2/1 tearing mode by electron cyclotron resonance heating on J-TEXT

Stabilization of tearing modes and neoclassical tearing modes is of great importance for tokamak operation.Electron cyclotron waves(ECWs)have been extensively used to stabilize the tearing modes with the virtue of highly localized power deposition.Complete suppression of the m/n=2/1 tearing mode(TM)by electron cyclotron resonance heating(ECRH)has been achieved successfully on the J-TEXT tokamak.The effects of ECW deposition location and power amplitude on the 2/1 TM suppression have been investigated.It is found that the suppression is more effective when the ECW power is deposited closer to the rational surface.As the ECW power increases to approximately 230 k W,the 2/1 TM can be completely suppressed.The island rotation frequency is increased when the island width is reduced.The experimental results show that the local heating inside the magnetic island and the resulting temperature perturbation increase at the O-point of the island play dominant roles in TM suppression.As the ECW power increases,the 2/1 island is suppressed to smaller island width,and the flow shear also plays a stabilizing effect on small magnetic islands.With the stabilizing contribution of heating and flow shear,the 2/1 TM can be completely suppressed.

Control of 2-D Semi-Markov Jump Systems:A View from Mode Generation Mechanism

Dear Editor,Two-dimensional(2-D) systems have wide applications in image data processing,gas absorption and fluid dynamics analysis [1]-[3].When there exist abrupt changes in 2-D systems,they are usually modeled by 2-D Markov jump systems(MJSs) or 2-D semi-Markov jump systems(SMJSs).This letter investigates the control of 2-D SMJSs based on a novel mode generation mechanism,which could avoid mode ambiguousness phenomenon caused by the evolution of system mode in two different directions.The criterion that guarantees the almost surely exponential stability of the system is obtained.A thermal process is studied to demonstrate the availability of the proposed method.

Influences of Co-Flow and Counter-Flow Modes of Reactant Flow Arrangement on a PEMFC at Start-Up

To investigate the influences of co-flowand counter-flowmodes of reactant flowarrangement on a proton exchange membrane fuel cell(PEMFC)during start-up,unsteady physical and mathematical models fully coupling the flow,heat,and electrochemical reactions in a PEMFC are established.The continuity equation and momentum equation are solved by handling pressure-velocity coupling using the SIMPLE algorithm.The electrochemical reaction rates in the catalyst layers(CLs)of the cathode and anode are calculated using the Butler-Volmer equation.The multiphase mixture model describes the multiphase transport process of gas mixtures and liquid water in the fuel cell.After validation,the influences of co-flow and counter-flow modes on the PEMFC performance are investigated,including the evolution of the current density,flow field,temperature field,and reactant concentration field during start-up,as well as the steady distribution of the current density,reactant concentration,andmembrane water content when the start-up stabilizes.Co-flow and counter-flow modes influence the current density distribution and temperature distribution.On the one hand,the co-flow mode accelerates the start-up process of the PEMFC and leads to a more evenly distributed current density than the counter-flow mode.On the other hand,the temperature difference between the inlet and outlet sections of the cell is up to 10.1℃ under the co-flow mode,much larger than the 5.0℃ observed in the counter-flow mode.Accordingly,the counter-flowmode results in a more evenly distributed temperature and a lower maximum temperature than the co-flow case.Therefore,in the flow field design of a PEMFC,the reactant flow arrangements can be considered to weigh between better heat management and higher current density distribution of the cell.

Investigation on the roles of equilibrium toroidal rotation during edge-localized mode mitigated by resonant magnetic perturbations

The effects of equilibrium toroidal rotation during edge-localized mode(ELM)mitigated by resonant magnetic perturbation(RMP)are studied with the experimental equilibria of the EAST tokamak based on the four-field model in the BOUT++code.As the two main parameters to determine the toroidal rotation profiles,the rotation shear and magnitudes were separately scanned to investigate their roles in the impact of RMPs on peeling-ballooning(P-B)modes.On one hand,the results show that strong toroidal rotation shear is favorable for the enhancement of the self-generated E×B shearing rate<ω_(E×B)>with RMPs,leading to significant ELM mitigation with RMP in the stronger toroidal rotation shear region.On the other hand,toroidal rotation magnitudes may affect ELM mitigation by changing the penetration of the RMPs,more precisely the resonant components.RMPs can lead to a reduction in the pedestal energy loss by enhancing the multimode coupling in the turbulence transport phase.The shielding effects on RMPs increase with the toroidal rotation magnitude,leading to the enhancement of the multimode coupling with RMPs to be significantly weakened.Hence,the reduction in pedestal energy loss by RMPs decreased with the rotation magnitude.In brief,the results show that toroidal rotation plays a dual role in ELM mitigation with RMP by changing the shielding effects of plasma by rotation magnitude and affecting<ω_(E×B)>by rotation shear.In the high toroidal rotation region,toroidal rotation shear is usually strong and hence plays a dominant role in the influence of RMP on P-B modes,whereas in the low rotation region,toroidal rotation shear is weak and has negligible impact on P-B modes,and the rotation magnitude plays a dominant role in the influence of RMPs on the P-B modes by changing the field penetration.Therefore,the dual role of toroidal rotation leads to stronger ELM mitigation with RMP,which may be achieved both in the low toroidal rotation region and the relatively high rotation region that has strong rotational shear.

Dissipative soliton resonance within different dispersion regimes in a single mode-locked laser

Dissipative soliton resonance(DSR) was previously studied in separated mode-locked fiber lasers within different dispersion regimes including anomalous, near-zero and normal dispersion. Here we propose a method to study DSR in a single mode-locked laser in these different dispersion regimes. This is achieved by virtue of a waveshaper which can control the laser dispersion readily using software, avoiding the usual tedious cutback method. We find that dispersion has a negligible effect on DSR since the pulse duration keeps constant while dispersion is varied. Moreover, we examine the dynamics of DSR on the parameters of the SA including modulation depth and saturation power, and find that the pulse duration can be changed in a large range when the saturation power is decreased. Our numerical simulations could be important to guide relative experimental studies.

On the generation of high-quality Nyquist pulses in mode-locked fiber lasers

Nyquist pulses have wide applications in many areas,from electronics to optics.Mode-locked lasers are ideal platforms to generate such pulses.However,how to generate high-quality Nyquist pulses in mode-locked lasers remains elusive.We address this problem by managing different physical effects in mode-locked fiber lasers through extensive numerical simulations.We find that net dispersion,linear loss,gain and filter shaping can affect the quality of Nyquist pulses significantly.We also demonstrate that Nyquist pulses experience similariton shaping due to the nonlinear attractor effect in the gain medium.Our work may contribute to the design of Nyquist pulse sources and enrich the understanding of pulse shaping dynamics in mode-locked lasers.

Effects of diamagnetic drift on nonlinear interaction between multi-helicity neoclassical tearing modes

A numerical study of the diamagnetic drift effect on the nonlinear interaction between multi-helicity neoclassical tearing modes(NTMs) is carried out using a set of four-field equations including two-fluid effects.The results show that,in contrast to the single-fluid case,5/3 NTM cannot be completely suppressed by 3/2 NTM with diamagnetic drift flow.Both modes exhibit oscillation and coexist in the saturated phase.To better understand the effect of the diamagnetic drift flow on multiple-helicity NTMs,the influence of typical relevant parameters is investigated.It is found that the average saturated magnetic island width increases with increasing bootstrap current fraction f_(b) but decreases with the ion skin depth δ.In addition,as the ratio of parallel to perpendicular transport coefficients χ_(‖)/χ_(⊥) increases,the average saturated magnetic island widths of the 3/2 and 5/3 NTMs increase.The underlying mechanisms behind these observations are discussed in detail.

Constraint on the focal mechanism of the 2011 Tohoku earthquake from the radial modes

Different from other normal modes of the Earth’s free oscillation that depend on all the six components(M_(rr),M_(tt),M_(pp),M_(rt),M_(rp),and M_(tp))of the centroid moment tensor,the amplitudes of the radial modes depend on the M_(rr)component(e.g.,scalar moment(M_(0)),dip(δ),and slip(λ))and hypocenter depth of the focal mechanism,and hence can be easily used to constrain these parameters of the focal mechanism.In this study,we use the superconducting gravimeter(SG)records after the 2011 Tohoku earthquake to analyze the radial modes_(0)S_(0)and_(1)S_(0).Based on the solutions of the focal mechanism provided by the GCMT and USGS,we can obtain the theoretical amplitudes of these two radial modes.Comparing the theoretical amplitudes with the observation amplitudes,it is found that there are obvious differences between the former and the latter,which means that the GCMT and USGS focal mechanisms cannot well represent the real focal mechanism of the 2011 event.Taking the GCMT solution as a reference and changing the depth and the three parameters of the M_(rr)moment,the scalar moment(M_(0))and the dip(δ)have significant influences,but the effects of the slip(λ)and the depth are minor.After comparisons,we provide a new constraint(M_(0)=5.8±0.09×10^(22)N·m,δ=10.1±0.08°,λ=88°,and depth=20 km)for the focal mechanism of the 2011 event.In addition,we further determine the center frequency(1.631567±2.6e^(-6)mHz)and quality factor(2046.4±50.1)of the_(1)S_(0)mode.

Observation of Doppler shift f_(D) modulated by the internal kink mode using conventional reflectometry in the EAST tokamak

In this paper we present a new experimental observation using a conventional reflectometry technique,poloidal correlation reflectometry(PCR),in the Experimental Advanced Superconducting Tokamak(EAST).The turbulence spectrum detected by the PCR system exhibits an asymmetry and induced Doppler shift f_(D)during the internal kink mode(IKM)rotation phase.This Doppler shift f_(D)is the target measurement of Doppler reflectometry,but captured by conventional reflectometry.Results show that the Doppler shift f_(D)is modulated by the periodic changes in the effective angle between the probing wave and cutoff layer normal,but not by plasma turbulence.The fishbone mode and saturated long-lived mode are typical IKMs,and this modulation phenomenon is observed in both cases.Moreover,the value of the Doppler shift f_(D)is positively correlated with the amplitude of the IKM,even when the latter is small.However,the positive and negative frequency components of the Doppler shift f_(D)can be asymmetric,which is related to the plasma configuration.A simulated analysis is performed by ray tracing to verify these observations.These results establish a clear link between f_(D)and IKM rotation,and are helpful for studying the characteristics of IKM and related physical phenomena.

Generation of lossy mode resonances(LMR)using perovskite nanofilms

The results presented here show for the first time the experimental demonstration of the fabrication of lossy mode resonance(LMR) devices based on perovskite coatings deposited on planar waveguides. Perovskite thin films have been obtained by means of the spin coating technique and their presence was confirmed by ellipsometry, scanning electron microscopy, and X-ray diffraction testing. The LMRs can be generated in a wide wavelength range and the experimental results agree with the theoretical simulations. Overall, this study highlights the potential of perovskite thin films for the development of novel LMR-based devices that can be used for environmental monitoring, industrial sensing, and gas detection, among other applications.

Extraction of Acoustic Normal Mode Depth Functions Using Range-Difference Method with Vertical Linear Array Data

Data-derived normal mode extraction is an effective method for extracting normal mode depth functions in the absence of marine environmental data.However,when the corresponding singular vectors become nonunique when two or more singular values obtained from the cross-spectral density matrix diagonalization are nearly equal,this results in unsatisfactory extraction outcomes for the normal mode depth functions.To address this issue,we introduced in this paper a range-difference singular value decomposition method for the extraction of normal mode depth functions.We performed the mode extraction by conducting singular value decomposition on the individual frequency components of the signal's cross-spectral density matrix.This was achieved by using pressure and its range-difference matrices constructed from vertical line array data.The proposed method was validated using simulated data.In addition,modes were successfully extracted from ambient noise.