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Biliary atresia (BA) is the leading cause of liver cirrhosis and chronic liver insufficiency in children in the world. Gastroesophageal varices bleeding is an ominous complication of cirrhosis in BA patients and is associated with high morbidity and mortality. In this study, we aimed to investigate the utility of noninvasive Baveno VI and Baveno VII criteria for the screening of varices need treatment (VNT) and the need for liver transplantation in BA patients. This study enrolled 48 BA patients (23 females and 25 males) who underwent an esophagogastroduodenoscopy (EGD) and transient elastography at a mean age of 11.18 ± 1.48 years; the clinical data were surveyed in a retrospective design. The sensitivity and negative predictive value of Baveno VI and Baveno VII criteria for the prediction of VNT in BA patients are both 100% and 100%, respectively. The VNT missing rate of Baveno VI and Baveno VII criteria are both 0% in our cohort. The Baveno VI, expanded Baveno VI, and Baveno VII criteria are also predictive of the need for liver transplantation in our cohort (OR = 10.33, 4.24, and 21.33; p= 0.009, 0.03, and 0.007, respectively). The Baveno VI and Baveno VII criteria are useful for the screening of VNT and minimize non‐necessary invasive EGD in BA patients with low VNT missing rates. The Baveno VI, expanded Baveno VI, and Baveno VII criteria are associated with the need for liver transplantation. Non‐invasive Baveno criteria for BA patients Biliary atresia (BA) is one of the leading causes of pediatric chronic active liver diseases and is usually complicated with varices bleeding.Baveno VI, expanded Baveno VI, and Baveno VII criteria are widely used for the prediction of clinical outcomes in adults with chronic active liver diseases. Biliary atresia (BA) is one of the leading causes of pediatric chronic active liver diseases and is usually complicated with varices bleeding. Baveno VI, expanded Baveno VI, and Baveno VII criteria are widely used for the prediction of clinical outcomes in adults with chronic active liver diseases. In this study, we demonstrated that the noninvasive Baveno VI and Baveno VII criteria are useful for screening varices that need treatment in BA patients.The Baveno VI expanded Baveno VI, and Baveno VII criteria correlate with the need for liver transplantation in BA patients. In this study, we demonstrated that the noninvasive Baveno VI and Baveno VII criteria are useful for screening varices that need treatment in BA patients. The Baveno VI expanded Baveno VI, and Baveno VII criteria correlate with the need for liver transplantation in BA patients.

Particle erosion induced by foreign object damage (FOD) is an important factor that restricts the working life of thermal barrier coatings (TBCs). A dense α-Al2O3overlay was prepared by magnetron sputtering and vacuum treatment on the surface of 7YSZ TBCs sprayed by plasma spray-physical vapor deposition (PS-PVD) to improve the erosion resistance of the TBCs. The FOD behavior of the TBCs was systematically studied and the interface of α-Al2O3/c-ZrO2was investigated by first principles calculations. The experimental results show that the erosion rates of the PS-PVD, atmospheric plasma spraying (APS), and electron beam-physical vapor deposition (EB-PVD) TBCs were 324, 248, and 139 μg/g, respectively, while the erosion rate of the Al2O3-modified PS-PVD TBCs was reduced to 199 μg/g. In addition, the highest interface adhesive energy of 3.88 J/m2observed in the top configuration model of Al2O3/ZrO2−O is much higher than that of ZrO2/Ni (2.011 J/m 2), which results in improved interface bonding performance.

Genome editing tools based on SpCas9 and FnCpf1 have facilitated strain improvements for natural product production and novel drug discovery in Streptomyces. However, due to high toxicity, their editing requires high DNA transformation efficiency, which is unavailable in most streptomycetes. The transformation efficiency of an all-in-one editing tool based on miniature Cas nuclease AsCas12f1 was significantly higher than those of SpCas9 and FnCpf1 in tested streptomycetes, which is due to its small size and weak DNA cleavage activity. Using this tool, in Streptomyces coelicolor, we achieved 100% efficiency for single gene or gene cluster deletion and 46.7 and 40% efficiency for simultaneous deletion of two genes and two gene clusters, respectively. AsCas12f1 was successfully extended to Streptomyces hygroscopicusSIPI-054 for efficient genome editing, in which SpCas9/FnCpf1 does not work well. Collectively, this work offers a low-toxicity, high-efficiency genome editing tool for streptomycetes, particularly those with low DNA transformation efficiency.

Due to the limited accessibility of wind turbines (WTs) and the complexity of operation and maintenance (O&M), it is increasingly important to early warn the component faults of WTs, and the difficulties lie in balancing the comprehensiveness and delicacy of early warning. In this paper, a two-stage cascaded high-precision fault early warning method based on machine learning (ML) and data graphization is proposed. The first stage copes with the early warning of the main components, in which the supervisory control and data acquisition (SCADA) data are converted into Gramian Angular Field (GAF) images to establish the potential relationship of fault features at different time points, and the fault characteristics are extracted by convolutional neural network (CNN) to realize fault early warning for multiple main components simultaneously. The second stage focus on the fault subcomponents inside the main components further, in which the time generative adversarial network (TimeGAN) is adopted to enhance the fault code data samples, then the enhanced data in the form of grayscale images is input into the Vision Transformer (ViT) to train the subcomponent early warning model. The proposed method is validated with real SCADA data, the results show the effectiveness of the proposed method.

The contributions of early potassic and later phyllic alteration stages to Cu endowment of the giant Dexing porphyry Cu–Mo–Au system in South China are determined using changes in the Cu isotope composition of hypogene chalcopyrite from three vein stages. The δ65Cu values of chalcopyrite (δ65Cucpyvalues) from the potassic (stage 1: -0.05‰ to 0.21‰) to the phyllic alteration stages (stage 2: -0.03‰ to 0.24‰) are relatively invariable, but chalcopyrite in the propylitic alteration stage (stage 3) has notably lower isotopic values (-0.35‰ to 0.02‰). The sharp decrease in δ65Cucpyvalues in the latest vein stage is likely a result of precipitation of significant amounts of isotopically heavy chalcopyrite in the phyllic alteration environment. The overall isotopic evolution can be simulated, using a Rayleigh fractionation model, with the majority of Cu having precipitated during the phyllic alteration stage. By comparing our data with published Cu isotope results from other porphyry deposits, we demonstrate that the systematics of δ65Cucpyvalues during different hydrothermal alteration stages could convincingly trace the relative timing and mechanism(s) of Cu precipitation in porphyry Cu systems. Spatial mapping of Cu isotopes at Dexing suggest that sharp decreases of δ65Cucpyvalues in hypogene zones may be used to delineate the boundary of high-grade ore zones.

Glioblastoma multiforme (GBM) is characterized by highly invasive growth, which leads to extensive infiltration and makes complete tumor excision difficult. Since cytoskeleton proteins are related to leading processes and cell motility, and through analysis of public GBM databases, we determined that an actin-interacting protein, zyxin (ZYX), may involved in GBM invasion. Our own glioma cohort as well as the cancer genome atlas (TCGA), Rembrandt, and Gravendeel databases consistently showed that increased ZYXexpression was related to tumor progression and poor prognosis of glioma patients. In vitro and in vivo experiments further confirmed the oncogenic roles of ZYXand demonstrated the role of ZYXin GBM invasive growth. Moreover, RNA-seq and mass-spectrum data from GBM cells with or without ZYXrevealed that stathmin 1 (STMN1) was a potential target of ZYX. Subsequently, we found that both mRNA and protein levels of STMN1were positively regulated by ZYX. Functionally, STMN1not only promoted invasion of GBM cells but also rescued the invasion repression caused by ZYXloss. Taken together, our results indicate that high ZYXexpression was associated with worse prognosis and highlighted that the ZYX-STMN1axis might be a potential therapeutic target for GBM.

In this paper, we study the existence of positive solutions for the following Quasilinear Schrödinger-Poisson systems, -Δpu+|u|p-2u+ϕ|u|p-2u=|u|q-2u+λuγ,x∈RN,-Δϕ=|u|p,x∈RN;where N20, γ∈(0,1). The existence of multiple positive solutions of this kind of system is established on positive cone by using the variational method and the critical point theory of nonsmooth functional.

Gastroesophageal reflux disease (GERD) is a prevalent chronic ailment, and present therapeutic approaches are not always effective. This study aimed to find new drug targets for GERD and Barrett’s esophagus (BE). We obtained genetic instruments for GERD, BE, and 2004 plasma proteins from recently published genome-wide association studies (GWAS), and Mendelian randomization (MR) was employed to explore potential drug targets. We further winnowed down MR-prioritized proteins through replication, reverse causality testing, colocalization analysis, phenotype scanning, and Phenome-wide MR. Furthermore, we constructed a protein-protein interaction network, unveiling potential associations among candidate proteins. Simultaneously, we acquired mRNA expression quantitative trait loci (eQTL) data from another GWAS encompassing four different tissues to identify additional drug targets. Meanwhile, we searched drug databases to evaluate these targets. Under Bonferroni correction (P< 4.8 × 10−5), we identified 11 plasma proteins significantly associated with GERD. Among these, 7 are protective proteins (MSP, GPX1, ERBB3, BT3A3, ANTR2, CCM2, and DECR2), while 4 are detrimental proteins (TMEM106B, DUSP13, C1-INH, and LINGO1). Ultimately, C1-INH and DECR2 successfully passed the screening process and exhibited similar directional causal effects on BE. Further analysis of eQTLs highlighted 4 potential drug targets, including EDEM3, PBX3, MEIS1-AS3, and NME7. The search of drug databases further supported our conclusions. Our study indicated that the plasma proteins C1-INH and DECR2, along with 4 genes (EDEM3, PBX3, MEIS1-AS3, and NME7), may represent potential drug targets for GERD and BE, warranting further investigation.

The anisotropy of tensile properties and fracture toughness of Ti−6Al−4V (Ti64) alloy fabricated by βforging was investigated. In order to evaluate anisotropic mechanical properties, the microstructure and crystallographic texture of billets with different orientations were characterized, and the influence of sampling direction on tensile properties and fracture toughness was studied. The results reveal that the prior βgrains of Ti64 billet display pan-cake-type characteristics. At room temperature, the alloy is mainly composed of αphase, and several αphase variants produced by β→αphase transformation decrease the αtexture intensity. The anisotropy of mechanical properties is affected by prior βgrain morphology and the slip activation related to αtexture. The initiation toughness was obtained by the J-integral resistance curve method. The initiation toughness was divided into intrinsic and extrinsic toughness by calculation. The anisotropy of intrinsic toughness is mainly attributed to the size of crack tip plastic zone, which is affected by prior βgrain morphology. In contrast, the extrinsic toughness is affected by zigzag degree of crack, which is mainly influenced by αlamellae and colonies.

The phase transition of titanium alloys is sensitive to the heat-treatment procedure, accompanied with the latent heat induced by phase transition. However, the latent heat during phase transition of titanium alloy has not been systematically studied, which may result in the gap between designed and actual temperature of the sample and affect the final mechanical properties. In this work, DSC (differential scanning calorimetry) and first-principles simulate methods were used to study the β → α phase transition process of TB18 (Ti–Al-Mo-V-Cr-Nb-Fe system) metastable β titanium alloy, especially to reveal the influence of the heating rate on latent heat. The ratio of latent heat to endothermic heat of the sample during temperature rising was introduced to interpret the effect of latent heat to actual temperature. The ratio of latent heat to endothermic heat at 1 ℃/min is about 15 to 20 times higher than that at 10 ℃/min. The higher ratio indicates that the latent heat of phase transition has a more significant effect on the temperature, which is related to the temperature range of phase transition and the α volume fraction. Compared with the heating rate of 1 ℃/min, the β → α phase transition takes place at higher temperature and the volume fraction of α is smaller at 10 ℃/min. Meanwhile, there is a precipitation free zone between grain boundary α and intragranular α and the distribution of α lamellae is heterogeneous when the heating rate is 10 ℃/min. Both of the experimental and theoretical results suggest that the latent heat of phase transition is the main cause of the temperature fluctuation during heat-treatment process. This work has guiding significance for microstructure optimization affected by temperature, to achieve the desired mechanical properties.

Timely diagnosis is a critical challenge and is associated with improved survival of biliary atresia (BA) patients. We aimed to measure matrix metalloproteinase-7 (MMP-7) levels in BA patients within 3 days of birth using the dried blood spot (DBS) method and evaluate its potential as a screening tool. The study enrolled 132 patients, including 25 patients diagnosed with BA and 107 non-BA patients with other congenital or perinatal conditions from the National Taiwan University Children Hospital. The stored DBS samples collected from 48 to 72 hours of life were retrieved from newborn screening centers. MMP-7 on the DBS was quantified using a sensitive sandwich enzyme-linked immunosorbent assay (ELISA). The MMP-7 levels of BA patients on the DBS were significantly higher than those of non-BA patients (19.2?±?10.4 vs 5.6?±?2.7?ng/mL, Pvalue < 0.0001). MMP-7 levels in non-BA patients, including 5 patients with hepatobiliary structural anomaly, 9 patients with intrahepatic cholestasis, and 93 patients with other perinatal diseases, were 11.6?±?4.2?ng/mL, 6.9?±?3.0?ng/mL, and 5.2?±?2.1?ng/mL, respectively. The DBS MMP-7 level showed good accuracy for identifying BA, with an area under the curve of 93.7% [95% confidence interval (CI): 87.7%–99.7%]. The MMP-7 cutoff at 8.0?ng/mL showed a sensitivity of 92.0% (95% CI: 75.0%–98.6%) and specificity of 92.5% (95% CI: 85.9%–96.1%) for detecting BA from other congenital or perinatal diseases. MMP-7 DBS analysis can be used to distinguish BA from other conditions as early as 3 days of age.

Although mesoporous silica nanoparticles (MSNs) have been intensively investigated, their mesostructure and formation mechanism are still a topic of debate. Here, we show that MSNS are generated at the interface of the biphasic water–surfactant–triethanolamine–tetraalkoxysilane (TAOS) quaternary system. The spontaneous microemulsification of the hydrophobic TAOS generates microdroplets and direct micelles that both determine the particle size and the pore size. We confirmed also that the dendritic morphology with conical pores is an intermediate species, which readily transforms into regular MSNs concomitantly with the collapse of the microemulsion due to the continuous consumption of TAOS. The prominent effect of the microemulsion on the mechanism growth as a primary template is thoroughly investigated and named here tetraalkoxysilane-assisted self-emulsification templating.

Phenotypic modulation of vascular smooth muscle cells (VSMCs) plays critical roles in the pathogenesis of aortic aneurysm (AA). The function of nuclear receptor corepressor1 (NCOR1) in regulation of VSMC phenotype and AA is unclear. Herein, using smooth muscle NCOR1 knockout mice, we demonstrated that smooth muscle NCOR1 deficiency decreased both mRNA and protein levels of contractile genes, impaired stress fibers formation and RhoA pathway activation, reduced synthesis of elastin and collagens, and induced the expression and activity of MMPs, manifesting a switch from contractile to degradative phenotype of VSMCs. NCOR1 modulated VSMC phenotype through 3 different mechanisms. First, NCOR1 deficiency increased acetylated FOXO3a to inhibit the expression of Myocd, which downregulated contractile genes. Second, deletion of NCOR1 derepressed NFAT5 to induce the expression of Rgs1, thus impeding RhoA activation. Third, NCOR1 deficiency increased the expression of Mmp12 and Mmp13 by derepressing ATF3. Finally, a mouse model combined apoE knockout mice with angiotensin II was used to study the role of smooth muscle NCOR1 in the development of AA. The results showed that smooth muscle NCOR1 deficiency increased the incidence of aortic aneurysms and exacerbated medial degeneration in angiotensin II-induced AA mouse model. Collectively, our data illustrated that NCOR1 interacts with FOXO3a, NFAT5, and ATF3 to maintain contractile phenotype of VSMCs and suppress AA development. Manipulation of smooth muscle NCOR1 may be a potential approach for AA treatment.

The design methods for gradient coils are mostly based on discrete extrinsic methods (e.g., the Biot–Savartintegration calculation), for which the surface normal vector strongly influences any numerical calculation of the discretized surface. Previous studies are mostly based on regular or analytical surfaces, which allow normal vectors to be expressed analytically. For certain applications, design methods for extending current-carrying surfaces from developable or analytic geometries to arbitrary surfaces generated from a scanned point cloud are required. The key task is to correctly express the discretized normal vectors to ensure geometrical accuracy of the designed coils. Mathematically, it has been proven that applying a Delaunay triangulation to approximate a smooth surface can result in the discrete elemental normal vectors converging to those of the original surface. Accordingly, this article uses Delaunay triangulation to expand upon previous design methods so that they encompass arbitrary piecewise continuous surfaces. Two design methods, the stream function and the so-called solid isotropic material with penalization (SIMP) method, are used to design circumvolute and noncircumvolute gradient coils on general surfaces.

In confined nanospaces and/or at confined nanoscale interfaces, the catalytic nature of active sites on the molecule level remains elusive. Herein, with the catalytic hydride reduction of 4-nitrophenol (4-NP) over a gold nanoparticle (NP) catalyst as a prototype reaction, the influence of a delicate change of the microenvironment of the catalytically active site on the kinetics of the reaction of 4-NP to 4-aminophenol (4-AP) with the introduction of various alkali-metal ion (AM+) salts has been investigated in detail. We demonstrate that structural water (SW) adsorbed on Au NPs in the form of {OH−·H2O@Au NPs} is the real catalytically active site (not Au NPs alone), and in the presence of lithium chloride (LiCl) it shows the best catalytic performance. In addition, isotope labeling and kinetic isotope effect (KIE) experiments show that the reduction of 4-NP does not follow the classical Langmuir–Hinshelwood (L–H) bimolecular mechanism, but an interfacial SW dominated electron and proton transfer mechanism. The proposed mechanism explains why the dissociation of the O–H bond of water is the rate-determining step (RDS) of 4-NP reduction, and, counter-intuitively, the solvent water is the hydrogen source of final product 4-AP, instead of sodium borohydride (NaBH4) reducer. Importantly, the co-existence of Li+and Cl−ions synergistically stabilizes the transition state of the reaction and accelerates the interfacial electron and proton transfer, consequently enhancing the reaction kinetics. The model of structural water as a bridge to transfer electrons and protons at the nanoscale interface is reminiscent of the working mechanism of photosystem two (PSII) for water splitting on Mn4CaO5clusters.

To determine the outcomes of patients with cystic biliary atresia by correlating the anatomy of the hepatic ducts with the choice of biliary reconstruction surgery. The Kasai hepatoportoenterostomy (Kasai) is the initial surgical procedure offered to most patients with biliary atresia. In contrast, a hepatic‐cyst‐jejunostomy has been reported to be effective in patients with the cystic form of biliary atresia. We performed an international multicenter retrospective review. Two hundred eighty‐seven patients were included, and 33 cases of cystic biliary atresia were identified. Outcomes were the serum total bilirubin level 3 months post‐surgery and native liver survival at 2 years of age and were compared between cases who received the Kasai versus hepatic‐cyst‐jejunostomy in correlation to the anatomy of proximal hepatic ducts. The patients were categorized into 3 anatomical groups: patent intact hepatic ducts (n = 10), patent hypoplastic hepatic ducts (n = 13), and obliterated hepatic ducts (n = 10). All 10 patients with patent intact hepatic duct group underwent hepatic‐cyst‐jejunostomy, and 9 experienced bile drainage and native liver survival. Among the 13 patients with hypoplastic hepatic ducts, 11 underwent the Kasai procedure, and 9 had bile drainage, whereas 2 underwent hepatic‐cyst‐jejunostomy, and one survived with the native liver. All of the patients with obliterated hepatic ducts underwent the Kasai procedure; 5 established biliary drainage and survived with the native liver. Of 5 who did not drain, 3 underwent liver transplantation. In patients with cystic biliary atresia, the subset with a connection between cyst and intrahepatic bile ducts via intact proximal hepatic ducts had favorable clinical outcomes following hepatic‐cyst‐jejunostomy.

We consider a Kirchhoff-type equation with critical and supercritical nonlinear terms in a ball. By providing a method of decomposition of energy functional and subtle analysis, we show that every Palais–Smale sequence at a level below a certain energy threshold admits a subsequence that converges strongly to a nontrivial critical point of the variational functional.

Vitamin C (VC) can greatly enhance the quality properties of dough and steamed bread in the food field. However, there are few studies on the interaction between VC and gluten, and the mechanism of VC influencing the foaming capacity, emulsifiablity, and dynamic viscosity of gluten is not clear. In this study, different content of VC (0, 1%, 2%, 3%, 4% and 5%) was added to gluten to obtain VC-gluten dough samples (CK, GV1, GV2, GV3, GV4 and GV5), and the properties of the VC-gluten dough were determined. Results showed that the increasing VC content lead to increase in the content of high-, medium- and low-molecular weight gluten, suggesting that VC improved the protein solubility of gluten. The G' and G" values of dough containing VC were higher than those of the control with the increase of scanning frequency. The foaming ability of gluten increased with the increase of VC content. Emulsibility of the dough of GV1 to GV 5 were significantly lower than that of the CK. Furthermore, VC could reduce the number of bubbles in gluten protein, when the VC content was less than 3%. In conclusion, VC might reduce the emulsifying characteristic and emulsifying stability of gluten, increase the solubility of gluten, and improve the dynamic viscosity of gluten dough by changing the content of disulfide bond in gluten. This study hopes to not only improve the functional characteristics of gluten protein, but also provide the basis for future development and improvement of VC-enriched health foods.

•Performed analyses using multiple large genome-wide association study databases.•Provided evidence for the causal association between primary biliary cholangitis with diabetes and cardiovascular diseases.•Offered novel insights into the therapeutic strategies for primary biliary cholangitis.

This article proposes a variable voltage variable frequency modular multilevel ac/ac converter (VVVF-MMC) with a high-frequency isolation link, which can realize voltage and frequency conversion simultaneously with insulated-gate bipolar transistors (IGBTs) of the same rated voltage and current level. The parallel connection of multiple modules is realized by coupling reactors, which can realize large-scale voltage and current transformation and save volume. It combines parallel multiplexing and serial multiplexing technology of submodules (SMs) to increase the equivalent switching frequency, thereby canceling nonzero sequence high-frequency voltage and current harmonics, so it has good power quality in the steady-state. Under the improved carrier phase-shifted pulsewidth modulation (CPS-PWM) strategy, the pulse flip circuit can realize soft switching operation, thereby improving energy conversion efficiency. Furthermore, dc capacitor voltage balancing and parallel SM current balancing control strategies are designed. With the strong filtering ability, the proposed ac/ac converter can be used as the onshore converter station of fractional frequency offshore wind power system. Due to the advantages of small size and high efficiency, it also has broad application prospects in distribution networks and electric drive. Simulation and experimental results validate the effectiveness of the proposed converter topology.

The study aimed to compare the efficacy and safety of all-transretinoic acid (ATRA) plus low-dose rituximab (LD-RTX) with LD-RTX monotherapy in corticosteroid-resistant or relapsed immune thrombocytopenia (ITP) patients. Recruited patients were randomized at a ratio of 2:1 into 2 groups: 112 patients received LD-RTX plus ATRA, and 56 patients received LD-RTX monotherapy. Overall response (OR), defined as achieving a platelet count of ≥30 × 109/L confirmed on ≥2 separate occasions (≥7 days apart), at least a doubling of the baseline platelet count without any other ITP-specific treatment, and the absence of bleeding within 1 year after enrollment, was observed in more patients in the LD-RTX plus ATRA group (80%) than in the LD-RTX monotherapy group (59%) (between-group difference, 0.22; 95% CI, 0.07-0.36). Sustained response (SR), defined as maintenance of a platelet count >30 × 109/L, an absence of bleeding, and no requirement for any other ITP-specific treatment for 6 consecutive months after achievement of OR during 1 year following enrollment, was achieved by 68 (61%) patients in the combination group and 23 (41%) patients in the monotherapy group (between-group difference, 0.20; 95% CI, 0.04-0.35). The 2 most common adverse events (AEs) for the combination group were dry skin and headache or dizziness. Our findings demonstrated that ATRA plus LD-RTX significantly increased the overall and sustained response, indicating a promising treatment option for corticosteroid-resistant or relapsed adult ITP. This study is registered at www.clinicaltrials.govas #NCT03304288.

The study aimed to compare the efficacy and safety of all-trans retinoic acid (ATRA) plus low-dose rituximab (LD-RTX) with LD-RTX monotherapy in corticosteroid-resistant or relapsed immune thrombocytopenia (ITP) patients. Recruited patients were randomized at a ratio of 2:1 into 2 groups: 112 patients received LD-RTX plus ATRA, and 56 patients received LD-RTX monotherapy. Overall response (OR), defined as achieving a platelet count of ≥30 × 109/L confirmed on ≥2 separate occasions (≥7 days apart), at least a doubling of the baseline platelet count without any other ITP-specific treatment, and the absence of bleeding within 1 year after enrollment, was observed in more patients in the LD-RTX plus ATRA group (80%) than in the LD-RTX monotherapy group (59%) (between-group difference, 0.22; 95% CI, 0.07-0.36). Sustained response (SR), defined as maintenance of a platelet count >30 × 109/L, an absence of bleeding, and no requirement for any other ITP-specific treatment for 6 consecutive months after achievement of OR during 1 year following enrollment, was achieved by 68 (61%) patients in the combination group and 23 (41%) patients in the monotherapy group (between-group difference, 0.20; 95% CI, 0.04-0.35). The 2 most common adverse events (AEs) for the combination group were dry skin and headache or dizziness. Our findings demonstrated that ATRA plus LD-RTX significantly increased the overall and sustained response, indicating a promising treatment option for corticosteroid-resistant or relapsed adult ITP. This study is registered at www.clinicaltrials.gov as #NCT03304288.

Halogens are elements in soil and water that occur as organic and inorganic species. Studies have shown that inorganic halogens are closely related to animal and plant life. Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) can achieve high-throughput and rapid analysis, which is also an essential characteristic in some environmental studies. However, there is currently no report on MALDI-MS analysis for water-soluble inorganic halogen compounds. In this study, we aimed to develop a reliable and reproductive method to detect inorganic halogens in soil and water by MALDI-MS. Based on sinapic acid (SA) and silver trifluoromethanesulfonate (SA/AgOTf) as the matrix in negative-ion mode, MALDI-MS showed excellent MS signals related to halogens. Under the optimum conditions, the method achieved satisfactory linearity (R2> 0.99) and repeatability (RSD < 18%). The LODs for Cl−, Br−and I−were 0.76, 0.11 and 0.10 μg/mL, respectively. The concentration of inorganic halogens from 24 samples was successfully determined by MALDI-MS. In summary, an innovative method was developed for the analysis of inorganic halogens by MALDI-MS using a novel SA/AgOTf matrix, extending the application of MALDI-MS in inorganic compounds.

Background: Anti-reflux mucosal intervention (ARMI), including anti-reflux mucosectomy (ARMS) and anti-reflux mucosal ablation (ARMA), is a promising endoscopic treatment for gastroesophageal reflux disease (GERD). Few studies reported a detailed analysis of the objective reflux parameters. Methods: Patients with chronic PPI-dependent GERD and receiving ARMI were prospectively enrolled. Comprehensive clinical symptom profiles, endoscopy results, and 24-h multichannel intraluminal impedance-pH (MII-pH) monitoring were collected and analyzed before and 3 months after ARMI. Results: Twenty-three patients undergoing ARMI (11 ARMS and 12 ARMA) were enrolled. The median (IQR) operative time and post-procedure stays were 50 (46–56) min and 2 (2–2) days without major complications. 73.9% of patients reported subjective global improvement. A significant decrease in the total reflux symptom index score was noted from 12 (5–19) to 8 (4–12) (P= 0.010). The esophageal acid exposure time (AET) significantly decreased from 4.6 (2.8–6.9) to 2.1 (1.1–5.6) (P= 0.013), and the number of acid refluxes and DeMeester score were significantly reduced. Three patients (13%) had increased AET (3.4% to 6.1%, 6.3% to 15.4%, and 3.2% to 5.6%); however, all reported global improvement and two patients could discontinue PPI subjectively. One patient (4.3%) had worsened erosive esophagitis and reflux symptoms. 56.5% of patients stopped PPI. Conclusions: ARMI is generally effective and safe in PPI-dependent patients. However, possible negative effects of ARMI exist in some patients; further application of MII-pH is necessitated to evaluate the treatment response after ARMI and avoid the detrimental effect of PPI discontinuation. Graphical abstract: