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Cu/Cu 2 O with controllable ratios were prepared via thermal decomposition of copper nitrate on hydrothermal carbon (HTC) for effective electrocatalytic nitrate reduction to ammonia. [Display omitted] • A series of Cu/Cu 2 O with different ratios were prepared on hydrothermal carbon. • The effect of the ratio of Cu/Cu 2 O on NRA was investigated. • Low energetic barrier for supplying electrons promotes nitrate electroreduction. Considering the background of low carbon emission and environmental protection, the development of electrocatalysts for efficient nitrate reduction to ammonia (NRA) has recently attracted increasing attention. Cu/Cu 2 O has been widely adopted as an efficient catalyst for the NRA reaction. However, the preparation of Cu/Cu 2 O with controllable ratios remains a challenge. Herein, a series of Cu/Cu 2 O were prepared through thermal decomposition of copper nitrate on the surface of hydrothermal carbon (HTC) under different temperatures. The ratios of Cu to Cu 2 O gradually increased with increasing calcination temperature. The effect of the Cu/Cu 2 O ratio on the NRA activity was investigated. The Cu/Cu 2 O/HTC-350 catalyst achieved the optimum NRA performance (Faradaic efficiency: 89.5%, ammonia selectivity: 81.7%). Further research demonstrated that the low energetic barrier for supplying electrons from the catalyst surface to the adsorbed reactant and the fastest electron transfer rate were beneficial for the nitrate electroreduction to ammonia. The electrochemical quasi in situ electron spin resonance (ESR) experiments proved the positive effect of active hydrogen (*H) during NRA process. This study provides a new avenue for the preparation of efficient Cu/Cu 2 O with controllable ratio catalysts for NRA reaction. [ABSTRACT FROM AUTHOR]

Objective: IgA nephropathy (IgAN) and IgA vasculitis with nephritis (IgAV-N) are related diseases. Galactose-deficient IgA1 (Gd-IgA1) plays an important role in the pathology of IgAV-N and IgAN, so we aim to compare the serum levels of Gd-IgA1 in Chinese pediatric patients with IgAN, IgAV-N, and IgAV. Methods: We retrospectively enrolled 52 patients with IgAN, 57 patients with IgAV-N, 26 patients with IgAV, and 40 healthy children. The serum levels of Gd-IgA1 were measured at the time of biopsy using a lectin-based ELISA method. Results: Gd-IgA1 levels in IgAV-N patients and IgAN patients were higher than in healthy controls (303.94 ± 39.37 U/ml, 314.91 ± 47.79 U/ml vs. 273.57 ± 48.29 U/ml, P < 0.001), and Gd-IgA1 levels in IgAV-N patients were higher than in IgAV patients (303.94 ± 39/ml vs. 286. 21 ± 38.81 U/ml, P = 0.059), but the latter result is not statistically significant. The Gd-IgA1 levels in IgAV patients were comparable with those in healthy controls (286.21 ± 38.81 U/ml vs. 273.57 ± 48.29 U/ml, P = 0.267). Among the four groups, we did not observe significant correlations of Gd-IgA1 levels with eGFR, proteinuria, or the MEST-C score. Conclusion: Serum Gd-IgA1 maybe involved in the pathogenesis of the IgAV-N and IgAN. However, we found no statistically significant correlation between Gd-IgA1 levels and clinical and pathological features. [ABSTRACT FROM AUTHOR]

[Display omitted] • Ag@AgPd x nanotriangulars were obtained by immobilizing Pd atoms onto Ag nanotriangulars. • Ag@AgPd 0.8 nanotriangulars has a regular triangular shape. • Ag@AgPd 0.8 shown the highest performance in H 2 production with 1980 mmol·g−1·h−1. • The mechanism of FA dehydrogenation has been confirmed by in-situ DRIFT analysis. Hydrogen with advantages of high energy density, zero pollution and zero carbon dioxide emissions is regarded as a carrier of clean energy for replacing fossil fuels. Therefore, the development of a high activity, selectivity and stability catalyst for H 2 production remains a great challenge. Herein, we report a new Ag@AgPd x nanotriangulars catalysts via immobilizing Pd atoms onto the surface of Ag nanotriangulars, for H 2 production from formic acid (FA) at room temperature, with superior catalytic activity and stability over commercial Pd/C and Pt/C. The in-situ DRIFT results shown the FA dehydrogenation process over Ag@AgPd 0.8 nanotriangulars, first the HCOOH* was rapidly converted to HCOO*, and finally to CO 2 *, which explained the fact that Ag@AgPd 0.8 nanotriangulars have high activity and selectivity for FA dehydrogenation. This strategy opens up a new way to design effective catalysts for efficient H 2 production from FA dehydrogenation to meet the requirement and applications of fuel cell. [ABSTRACT FROM AUTHOR]

Background and objective: Calcaneal Sanders type II or III fractures are highly disabling with significant burden. Surgical treatment modalities include open reduction and internal fixation (ORIF) techniques and a variety of minimally invasive surgical (MIS) approaches. ORIF techniques are associated with complications and traditional MIS techniques need extensive intraoperative fluoroscopic procedures. The present study aims to investigate the effects of three different minimally invasive internal fixation (MIIF) techniques used to treat Sanders type II intra-articular calcaneal fractures using finite element analyses. Methods: A 64-row spiral computed tomography scan was used to observe the calcaneus of a healthy adult. The scanning data were imported into Mimics in a DICOM format. Using a new model of a Sanders type II-B intra-articular calcaneal fracture, three minimally invasive techniques were simulated. Technique A involved fixation using an isolated minimally invasive locking plate; Technique B used a minimally invasive locking plate with one medial support screw; and Technique C simulated a screw fixation technique using four 4.0-mm screws. After simulating a 640-N load on the subtalar facet, the maximum displacement and von Mises stress of fragments and implants were recorded to evaluate the biomechanical stability of different fixation techniques using finite element analyses. Results: After stress loading, the maximum displacements of the fragments and implants were located at the sustentaculum tali and the tip of sustentaculum tali screw, respectively, in the three techniques; however, among the three techniques, Technique B had better results for displacement of both. The maximum von Mises stress on the fragments was < 56 Mpa, and stress on the implants using the three techniques was less than the yield strength, with Technique C having the least stress. Conclusion: All three techniques were successful in providing a stable fixation for Sanders type II intra-articular calcaneal fractures, while the minimally invasive calcaneal locking plate with medial support screw fixation approach exhibited greater stability, leading to improved enhancement for the facet fragment; however, screw fixation dispersed the stress more effectively than the other two techniques. [ABSTRACT FROM AUTHOR]

• Functionalized graphene/SiC nanowires hybrid skeletons were constructed. • Incorporating skeletons significantly improved the thermal conductivity of epoxy. • Functionalized hybrid skeleton revealed an enhanced synergistic reinforcing effect. Functionalized graphene nanoplatelets/SiC nanowires (f-GnP/SiCnw) and unmodified (u-GnP/SiCnw) hybrid skeletons with different amounts of SiCnw were successfully constructed through a vacuum-assisted self-assembly technique. Subsequently, the hybrid skeletons were incorporated into an epoxy resin to fabricate nanocomposites with excellent thermal and thermomechanical properties. The study revealed that the f-GnP/SiCnw hybrid skeletons exhibit a more pronounced reinforcing effect than the f-GnP-only skeleton without SiCnw and the unmodified (u-GnP/SiCnw) counterparts at the same filler loading. Incorporating the f-GnP/SiCnw hybrid skeleton with 5 wt% SiCnw resulted in through-plane and in-plane thermal conductivity of the epoxy composites as high as 1.58 W/m·K and 6.20 W/m·K, which is 690 and 3000% higher than that of the neat epoxy, respectively. Meanwhile, the storage modulus and glass transition temperature of the epoxy composites were also evidently enhanced after the introduction of the hybrid skeletons. This work provides an insight into the fabrication of high-performance thermally conductive composites. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] • A facile and lyophilization-free method to fabricate anisotropic cellulose aerogels. • Directional stabilization of cellulose nanofibrils induced by electrostatic complexation. • Ambient-dried cellulose aerogels have porous structure and aligned channels. • NCA@PPy achieves excellent photothermal property and efficient solar evaporation. Anisotropic aerogels, mimicking natural porous materials such as wood and bone, always exhibit distinctive properties due to their aligned channels, which, however, generally require complicated ice templating configuration and costly freeze-drying. In this work, we develop a novel, facile, low-cost, and scalable method combining directional stabilization and ambient drying to prepare anisotropic aerogels. The frozen aqueous TEMPO-oxidized cellulose nanofibrils (TOCNFs) monolith embedded in a mold is directly immersed in ethanol/Fe3+ bath. The ice crystals directionally dissolve in ethanol, and simultaneously the TOCNFs are directionally stabilized due to the electrostatic complexation between their carboxyl groups and Fe3+ ions. The obtained anisotropic nanocellulose aerogel (NCA) after ambient drying exhibits an ordered porous structure, which is tunable by adjusting the contents of carboxyl groups on TOCNFs. The NCAs reveal distinct anisotropy, excellent mechanical compressibility in the radial direction, and high water-stability. To demonstrate their promising potentials for application in various advanced fields such as solar steam generation, the NCA is coated with polypyrrole (PPy) by in-situ polymerization to achieve excellent photothermal property but well maintain the original aligned channels of NCA, which endow the NCA@PPy with an efficient solar evaporation performance. [ABSTRACT FROM AUTHOR]

Background: DNA methylation is a form of epigenetic modification that regulates gene expression. However, there are limited data on the comprehensive analysis of DNA methylation regulated gene mutations (DMRGM) in acute myeloid leukemia (AML) mainly referring to DNA methyltransferase 3α (DNMT3A), isocitrate dehydrogenase 1 (IDH1), isocitrate dehydrogenase 2 (IDH2), and Tet methylcytidine dioxygenase 2 (TET2). Results: A retrospective study of the clinical characteristics and gene mutations in 843 newly diagnosed non-M3 AML patients was conducted between January 2016 and August 2019. 29.7% (250/843) of patients presented with DMRGM. It was characterized by older age, higher white blood cell count, and higher platelet count (P < 0.05). DMRGM frequently coexisted with FLT3-ITD, NPM1, FLT3-TKD, and RUNX1 mutations (P < 0.05). The CR/CRi rate was only 60.3% in DMRGM patients, significantly lower than in non-DMRGM patients (71.0%, P = 0.014). In addition to being associated with poor overall survival (OS), DMRGM was also an independent risk factor for relapse-free survival (RFS) (HR: 1.467, 95% CI: 1.030–2.090, P = 0.034). Furthermore, OS worsened with an increasing burden of DMRGM. Patients with DMRGM may be benefit from hypomethylating drugs, and the unfavorable prognosis of DMRGM can be overcome by hematopoietic stem cell transplantation (HSCT). For external validation, the BeatAML database was downloaded, and a significant association between DMRGM and OS was confirmed (P < 0.05). Conclusion: Our study provides an overview of DMRGM in AML patients, which was identified as a risk factor for poor prognosis. [ABSTRACT FROM AUTHOR]

Hematopoietic stem cell transplantation-associated thrombotic microangiopathy (TA-TMA) is a fatal post-transplant complication. It has a high mortality rate and worse prognosis, but treatment strategies remain controversial. We screened 6 out of 3453 studies on the treatment of TA-TMA. These investigations compared 5 treatment strategies with a network meta-analysis approach. The final outcome was the proportion of patients who responded to these therapies. There were significant differences in response rates for each treatment. Achieving analysis through direct and indirect evidence in the rank probabilities shows that rTM (recombinant human soluble thrombomodulin) is most likely to be rank 1 (64.98%), Eculizumab intervention rank 2 (48.66%), ISM (immunosuppression manipulation) rank 3 (32.24%), TPE (therapeutic plasma exchange) intervention rank 4 (69.56%), and supportive care intervention rank 5 (70.20%). Eculizumab and ISM have significantly higher efficacy than supportive care (odds ratio (OR): 18.04, 18.21 respectively); and TPE having lower efficacy than all other TA-TMA therapies exception to supportive care. In our study, rTM and Eculizumab may be the best choice when treating TA-TMA. [ABSTRACT FROM AUTHOR]

Bacterial cellulose (BC) hydrogel is renowned in the field of tissue engineering for its high biocompatibility, excellent mechanical strength, and eco-friendliness. Herein, we present a biomimetic mineralization method for preparing BC/hydroxyapatite (HAP) composite hydrogel scaffolds with different mineralization time and ion concentration of the mineralized solution. Spherical HAP reinforcement enhanced bone mineralization, thereby imparting increased bioactivity to BC matrix materials. Subsequently, platelet-rich plasma (PRP) was introduced into the scaffold. The PRP-loaded hydrogel enhanced the release of growth factors, which promoted cell adhesion, growth, and bone healing. After 3 weeks of MC3T3-E1 cell-induced osteogenesis, PRP positively affected cell differentiation in BC/HAP@PRP scaffolds. Overall, these scaffolds exhibited excellent biocompatibility, mineralized nodule formation, and controlled release in vitro , demonstrating great potential for application in bone tissue repair. [ABSTRACT FROM AUTHOR]

[Display omitted] • The porous PdPtNi nanosheets with adjustable compositions were designed. • The PdPtNi nanosheets have ultrathin thickness, abundant step atoms and optimized electronic structure. • The Pd 45 Pt 42 Ni 13 /C exhibits the excellent mass and specific activities of 16.2 A mg PGM −1 and 12.7 mA cm−2, respectively. • The porous PdPtNi nanosheets can serve as high-efficiency electrocatalysts towards EOR and AORs. The development of ultrathin porous nanostructures contributes a new opportunity to optimize the activity and stability of electrocatalysts, especially for those complicated alcohol oxidation reactions (AORs). Herein, a series of porous PdPtNi nanosheets with adjustable compositions were designed and synthesized to achieve highly active and stable electrocatalysis towards methanol and ethanol oxidation reactions (MOR and EOR) in alkaline electrolyte containing the corresponding alcohol molecules. Benefited from the ultrathin structures, abundant step atoms and optimized electronic structures, the optimized Pd 45 Pt 42 Ni 13 /C exhibits the mass and specific activities of 16.2 A mg PGM −1 and 12.7 mA cm−2, respectively, much higher than those of commercial Pt/C and PdPt-based catalysts. In addition, the Pd 45 Pt 42 Ni 13 /C also displays desirable stability with the highest retained current density after long-term durability tests. We also demonstrate that the porous PdPtNi nanosheets can serve as high-efficiency electrocatalysts towards EOR, confirming the versatility of improved electrocatalytic performance of AORs with multi-electron transfer. By maximizing the number of electrocatalytically active sites and enhancing the intrinsic catalytic activity of single sites, this work provides a class of high-performance Pt-based anodic catalyst for DAFCs via introducing porosity into ultrathin Pt- or Pd-based nanostructures. [ABSTRACT FROM AUTHOR]

The damage or degeneration of spiral ganglion neurons (SGNs) can impair the auditory signals transduction from hair cells to the central auditory system, and cause significant hearing loss. Herein, a new form of bioactive hydrogel incorporating topological graphene oxide (GO) and TEMPO-oxidized bacterial cellulose (GO/TOBC hydrogel) was developed to provide a favorable microenvironment for SGN neurite outgrowth. As the network structure of lamellar interspersed fiber cross-linked by GO/TOBC hydrogels well simulated the structure and morphology of ECM, with the controllable hydrophilic property and appropriate Young's modulus well met those requirements of SGNs microenvironment, the GO/TOBC hybrid matrix exhibited great potential to promote the growth of SGNs. The quantitative real-time PCR result confirmed that the GO/TOBC hydrogel can significantly accelerate the development of growth cones and filopodia, by increasing the mRNA expression levels of diap3 , fscn2 , and integrin β1. These results suggest that GO/TOBC hydrogel scaffolds have the potential to be used to construct biomimetic nerve grafts for repairing or replacing nerve defects. [Display omitted] [ABSTRACT FROM AUTHOR]

This study innovatively utilized kelp-derived nanocellulose and sodium caseinate (SC) to prepare fucoxanthin (Fx)-loaded nanoparticles, exploring their efficacy in reducing oxidative stress and inhibiting lipid accumulation. 2, 2, 6, 6-Tetramethylpiperidine-1-oxyl (TEMPO)-mediated oxidation produced well-dispersed, kelp-derived nanocellulose. When these celluloses were mixed with SC at varying mass ratios, the composite nanoparticles showed excellent stability. Specifically, at a TEMPO-oxidized kelp nanocellulose (TKNC) to SC mass ratio of 1:3, the encapsulation efficiency for Fx reached 82.2 %, with a retention of 56.12 % after 14 days of storage. In vitro, the nanoparticles demonstrated good biocompatibility and were efficiently absorbed by cells, significantly enhancing Fx bioavailability. This enhanced delivery efficiency alleviates oxidative stress by activating the Nrf2/HO-1/NQO1 signaling pathways and effectively inhibits lipid droplet formation induced by excessive free fatty acids (FFAs). Moreover, distribution studies in mice revealed effective accumulation of nanoparticles in the intestines and liver, indicating their potential for targeted drug delivery. These findings provide strong experimental support for the use of TKNC and SC as biocompatible materials in nanoparticles for drug delivery and treatment applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

In this study, we used the whole-exome sequencing (WES) approach to obtain genomic profiles from 92 marrow samples of myelodysplastic syndrome (MDS) patients before haematopoietic stem cell transplantation. We identified 129 mutations in 45 driver genes. Fifty-five patients (59.8%) carried at least 1 driver mutation. The splicing factor U2AF1 was the most frequently mutated in the cohort (21 cases, 23%), followed by BCOR (9 cases, 10%), ASXL1 (8 cases, 9%), TET2 (6 cases, 7%), NPM1 (5 cases, 5%), RUNX1 (5 cases, 5%), and SETBP1 (5 cases, 5%). WES also identified 49 possible oncogenic variants in six genes (PIEZO1, LOXHD1, MYH13, DNAH5, DPH1, and USH2A) that were associated with overall survival (OS) or relapse-free survival (RFS) in MDS after transplantation. Multivariate analysis showed mutations in DNAH5 and USH2A to be independent risk factors for OS. Mutations in DNAH5 and LOXHD1 were risk factors for worse RFS. The Molecular International Prognostic Scoring System retained its independent prognostic significance for RFS after multivariate analysis., (© 2024 British Society for Haematology and John Wiley & Sons Ltd.)

Cordyceps cicadae is recognized for its medicinal properties, attributed to bioactive constituents like polysaccharides and adenosine, which have been shown to improve kidney and liver functions and possess anti-tumor properties. Rho GTPase activating proteins (Rho GAPs) serve as inhibitory regulators of Rho GTPases in eukaryotic cells by accelerating the GTP hydrolysis of Rho GTPases, leading to their inactivation. In this study, we explored the function of the CcRga8 gene in C. cicadae, which encodes a Rho-type GTPase activating protein. Our study found that the knockout of CcRga8 resulted in a decrease in polysaccharide levels and an increase in adenosine concentration. Furthermore, the mutants exhibited altered spore yield and morphology, fruiting body development, decreased infectivity, reduced resistance to hyperosmotic stress, oxidative conditions, and cell wall inhibitors. These findings suggest that CcRga8 plays a crucial role in the development, stress response, and bioactive compound production of C. cicadae., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Platelet transfusion refractoriness (PTR) is an intractable issue in hematological patients, which increases bleeding risks and hospitalization costs to a great extent. We reviewed 108 patients with hematological diseases including acute leukemia, myelodysplastic syndrome, aplastic anemia, and others who received allogeneic hematopoietic stem cell transplantation (HSCT) from January 2019 through December 2020. After multivariable logistic regression, we found that splenomegaly (odds ratio [OR] = 26.98, p  < .001) and JAK mutation (OR = 17.32, p  = .024) were independent risk factors for PTR. During the period of transplantation, patients in the PTR group had a significantly higher platelet transfusion demand, which was reflected in the increased number of platelet transfusions (10.23 ± 6.696 vs. 5.06 ± 1.904, p  < .001). After multivariate adjustment, PTR turned out to be independently associated with worse overall survival (hazard ratio = 2.794, 95% confidence interval = 1.083-7.207, p  = .034). In conclusion, we found that splenomegaly and JAK gene mutation were independent risk factors for PTR in patients with hematological diseases. A history of PTR prior to allo-HSCT indicates a poor prognosis.

Hepatitis B virus (HBV) infection is a noteworthy cause of liver diseases, especially cirrhosis and hepatocellular carcinomas. However, the interaction between the host and HBV has not been fully elucidated. Peptide YY (PYY) is a 36-amino-acid gastrointestinal hormone that is mainly involved in the regulation of the human digestive system. This study found that PYY expression was reduced in HBV-expressing hepatocytes and HBV patients. Overexpression of PYY could significantly inhibit HBV RNA, DNA levels, and the secretion of HBsAg. In addition, PYY inhibits HBV RNA dependent on transcription through reducing the activities of CP/Enh I/II, SP1 and SP2. Meanwhile, PYY blocks HBV replication independent on core, polymerase protein and ε structure of pregenomic RNA. These results suggest that PYY can impair HBV replication by suppressing viral promoters/enhancers in hepatocytes. Our data shed light on a novel role for PYY as anti-HBV restriction factor., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Chronic ankle instability (CAI) is a common sequela following an acute lateral ankle sprain (LAS). To treat an acute LAS more effectively and efficiently, it is important to identify patients at substantial risk for developing CAI. This study identifies magnetic resonance imaging (MRI) manifestations for predicting CAI development after a first episode of LAS and explores appropriate clinical indications for ordering MRI scans for these patients., Methods: All patients with a first-episode LAS who received plain radiograph and MRI scanning within the first 2 weeks after LAS from December 1, 2017 to December 1, 2019 were identified. Data were collected using the Cumberland Ankle Instability Tool at final follow-up. Demographic and other related clinical variables, including age, sex, body mass index, and treatment were also recorded. Univariable and multivariable analyses were performed successively to identify risk factors for CAI after first-episode LAS., Results: A total 131 out of 362 patients with a mean follow-up of 3.0 ± 0.6 years (mean ± SD; 2.0-4.1 years) developed CAI after first-episode LAS. According to multivariable regression, development of CAI after first-episode LAS was associated with 5 prognostic factors: age (odds ratio (OR) = 0.96, 95% confidence interval (95%CI): 0.93-1.00, p = 0.032); body mass index (OR = 1.09, 95%CI: 1.02-1.17, p = 0.009); posterior talofibular ligament injury (OR = 2.17, 95%CI: 1.05-4.48, p = 0.035); large bone marrow lesion of the talus (OR = 2.69, 95%CI: 1.30-5.58, p = 0.008), and Grade 2 effusion of the tibiotalar joint (OR = 2.61, 95%CI: 1.39-4.89, p = 0.003). When patients had at least 1 positive clinical finding in the 10-m walk test, anterior drawer test, or inversion tilt test, they had a 90.2% sensitivity and 77.4% specificity in terms of detecting at least 1 prognostic factor by MRI., Conclusion: MRI scanning is valuable in predicting CAI after first-episode LAS for those patients with at least 1 positive clinical finding in the 10-m walk test, anterior drawer test, and inversion tilt test. Further prospective and large-scale studies are necessary for validation., (Copyright © 2023. Production and hosting by Elsevier B.V.)

In this work, the effects of konjac glucomannan (KGM) concentrations on microstructure, gel properties, stability and digestibility of water-in-oil-in-water emulsion gels stabilized by polyglycerol polyricinoleate and whey protein isolate were investigated. Visual appearance indicated that a non-layered double emulsion gel was formed when KGM increased to 0.75%. Emulsion gels with 1.5% KGM showed the highest encapsulation, freeze-thaw and photochemical stability due to the formation of the smallest droplets, which were supported by microscopic observations. Moreover, the addition of KGM improved water holding capacity, rheological and texture properties of emulsion gels. Particularly, at 1.5% or 1.75% KGM, color and potential of hydrogen showed the most stable level after 14 days of storage. During in vitro digestion, KGM delayed the hydrolysis of protein and oil droplets, and then improved the bioavailability of grape seed proanthocyanidin. These results promoted the application of KGM in emulsion gels and the encapsulation of nutraceuticals., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Platelet transfusion refractoriness (PTR) remains an intractable issue in clinical practice, and is common in hematological patients. At present, it is believed that both immune and non-immune factors play a role. We conducted a meta-analysis of various risk factors which may contribute to PTR., Methods: PubMed, Embase, Cochrane library, and Web of Science were selected as research database platforms. Citations included were further assessed for quality and bias using the Newcastle-Ottawa Scale. All analyses were performed using Review Manager Version 5.4 and STATA 16.0., Results: The preliminary search revealed 1069 publications, and 17 (5929 patients in total) were ultimately included in the quantitative analysis. The following variables were associated with the occurrence of PTR: fever (OR = 2.26, 95%CI 2.00-2.55, p < 0.00001), bleeding (OR = 2.10, 95%CI 1.36-3.24, p = 0.0008), female sex (OR = 2.06, 95%CI 1.13-3.75, p = 0.02), antibiotic use (OR = 2.94, 95%CI 1.54-5.59, p = 0.001), and infection (OR = 2.19, 95%CI 1.20-4.03, p = 0.01). Antibodies involved in immune activation were a higher risk factor (OR = 4.17, 95%CI 2.36-7.36, p < 0.00001), and splenomegaly was nearly significant (OR = 1.73, 95%CI 0.97-3.07, p = 0.06)., Conclusions: We identified some important risk factors for PTR, but further research is needed to identify the many other possible elements that may contribute to or mediate PTR., (© 2023. Japanese Society of Hematology.)

Background: Thrombotic thrombocytopenic purpura (TTP) is a rare and life-threatening thrombotic microangiopathy. Several studies have demonstrated the efficacy of caplacizumab in iTTP. However, the effect on different populations remains controversial. Therefore, we performed a systematic review and meta-analysis to assess the effectiveness and safety of caplacizumab for treating iTTP., Materials and Methods: We searched PubMed, Embase, and the Cochrane Library for studies until 24 March 2023. Participants were hospitalized patients with iTTP. Interventions included caplacizumab versus placebo or standard of care (SOC). Outcomes assessed included all-cause mortality, exacerbation, relapse, refractory, time-to-platelet-count-recovery, length of TPE and hospital stay, bleeding, and thrombosis., Results: A total of 1119 patients from eight studies were subjected to meta-analysis. The results of the meta-analysis showed that iTTP patients treated with caplacizumab achieved a reduction in mortality (RR 0.38, 95% CI: 0.19-0.75), exacerbation (RR 0.29, 95% CI: 0.14-0.61) and refractory (RR 0.50, 95% CI: 0.31-0.81). Besides, adding caplacizumab to SOC was associated with a shorten time-to-platelet-count-recovery (MD - 2.31, 95% CI: -3.86 to -0.77) and length of TPE (MD - 4.61, 95% CI: -6.20 to -3.02). In terms of safety, the bleeding rate was higher in the caplacizumab group (RR 1.57, 95% CI: 1.21-2.02), while there was no significant difference in hospital stay and thrombosis between the two groups., Conclusions: Caplacizumab is an effective treatment for patients with iTTP, especially in reducing all-cause mortality, exacerbations, refractoriness, and the time-to-platelet-count-recovery. Although the risk of bleeding may be increased, it is generally modest and manageable.

Introduction: Transplant-associated thrombotic microangiopathy (TA-TMA) is a severe hematopoietic stem cell transplantation complication with high mortality and a poor patient prognosis. The pathogenesis of TA-TMA is not yet clear. In previous studies, the conclusions of different centers remain controversial. We conducted a systematic review and meta-analysis of nine selected risk factors that might be associated with the onset of TA-TMA., Materials and Methods: PubMed databases were searched from their inception up to 15 September 2021, for relevant studies. The articles included unprocessed data related to one or more of the risk factors discussed in this meta-analysis, including recipient gender, donor type, graft source, pretreatment, infection, aGVHD, diagnosis, total body irradiation (TBI), and CMV infection. The outcome is the incidence rate (IR) of TA-TMA., Results and Conclusions: According to the sixteen articles included, risk factors included in this Meta-analysis included gender, unrelated donor source (95% CI: 1.29-2.01), graft source from peripheral blood stem cell (PBSC)(95% CI: 0.48-0.97), RIC/NMA, class II-IV aGVHD (95% CI: 2.22-4.78), nonmalignant disease, TBI. However, inconsistent diagnostic criteria for TA-TMA and the limited number of studies have an impact on the results of the study. More prospective cohort studies and More accurate diagnostic criteria are needed.

Purpose: The aim of this study was to evaluate the relation between anteromedial ankle osteophytes (AMAO) and anteromedial ankle impingement (AMAI) in chronic lateral ankle instability (CLAI) through visualization and quantification., Methods: Forty-three patients with unilateral CLAI between September 2018 and March 2020 accepted arthroscopic repair of an anterior talofibular ligament (ATFL) and were split into two groups: AMAI (AMAI including intraoperative AMAO resection) and pure CLAI (with AMAO but without AMAI, no AMAO resection). The AMAO protrusion lengths in each direction were measured and compared after all of the ankles were reconstructed. All patients were assessed preoperatively and at 2-year follow-up with ankle dorsiflexion, the American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot score, and visual analog scale (VAS) score., Results: Intelligent analysis showed that a large extent of osteophytes was found at the dorsomedial surface of the talar neck in AMAI group. The upper and inner bound protrusion distances of AMAO in AMAI group were greater than in the pure CLAI group. There was no significant difference in anterior bound protrusion distance of AMAO between the two groups. Preoperatively, the ankle dorsiflexion of AMAI group (7.6 ± 1.4°) was considerably lower than that of pure CLAI group (22.4 ± 1.9°) (p < 0.001). When compared to the pure CLAI group, the AMAI group had a substantially worse AOFAS score (62.2 ± 6.7 vs 71.1 ± 9.1; p < 0.001) and VAS score (6.0 ± 1.0 vs 4.9 ± 0.8; p < 0.05). However, there was no significant difference in postoperative ankle dorsiflexion, AOFAS score, or VAS score between the two groups., Conclusion: AMAO is formed mostly on the dorsomedial surface of the talar neck in CLAI with AMAI, and the upper and inner bound protrusion lengths of AMAO were shown to be significantly correlated with the existence of AMAI in CLAI., (© 2023. The Author(s).)

Purpose: Appropriate pre-transplant strategies in patients with myelodysplastic syndromes (MDS) remain challenging. We sought to assess the effect of different pre-transplant therapies and transplantation interval times on patient prognosis., Methods: We retrospectively analysed clinical data for 371 consecutive MDS patients after myeloablative transplantation between 2007 and 2019., Results: The median age of the patients was 38 years (range, 12-64 years). A total of 114 patients (31%) received supportive care (SC), 108 (29%) hypomethylating agents (HMAs), and 149 (40%) chemotherapy-based therapy before transplantation. In patients who received HMA or SC, there was no significant difference in overall survival (OS; P=0.151) or relapse-free survival (RFS; P=0.330), except that HMA-treated patients had a lower rate of non-relapse mortality (5-year NRM: 18% vs. 32%, P=0.035). However, compared with patients who received HMA, those who received chemotherapy-based therapy had a lower 5-year OS rate (56% vs. 69%, P=0.020) and a slightly higher 5-year NRM rate (28% vs. 18%, P=0.067). Compared to the delayed transplant group (transplant interval ≥6 months), the early transplant group (transplant interval <6 months) had a superior 5-year OS (66% vs. 51%, P=0.001) and a lower 5-year cumulative incidence of NRM (22% vs. 36%, P=0.001)., Conclusion: The findings of the study indicate that receiving an appropriate pre-transplant strategy (SC/HMA + <6 months) significantly improves OS and decreases NRM in MDS patients after myeloablative transplantation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wang, Wang, Qi, Li, Chu, Qiu, Fu, Tang, Ruan, Wu and Han.)

The NLR family CARD domain containing 3 (NLRC3) gene has been reported to have a crucial effect on immunity, inflammation, and tumorigenesis. However, the clinical relevance of NLRC3 in lung adenocarcinoma (LUAD) remains unclear. This study analyzed both RNA sequencing data and corresponding clinical outcomes obtained from public databases to identify (i) NLRC3 as a tumor suppressor in LUAD and (ii) its predictive value for the likelihood of patient responsiveness to immunotherapy. The results showed that NLRC3 expression was reduced in LUAD and was lower in advanced-stage tumors. Additionally, reduced NLRC3 expression was correlated with worse patient prognosis. The protein level of NLRC3 was also observed to have prognostic significance. Moreover, downregulation of NLRC3 was found to suppress the chemotaxis and infiltration of antitumor lymphocyte subpopulations as well as natural killer cells. Mechanistic analysis indicated that NLRC3 may be involved in immune infiltration by regulating chemokines and their receptors in LUAD. Furthermore, NLRC3 functions as a molecular switch in macrophages, whereby it mediates the polarization of M1 macrophages. Patients with high NLRC3 expression were also found to exhibit a more promising response to immunotherapy. In conclusion, NLRC3 could serve as a potential prognostic biomarker for LUAD, help predict the immunotherapeutic response of patients, and guide personalized strategies for the treatment of LUAD., (© 2023. The Author(s).)

Objectives: With positive outcomes recorded, the mixed reality (MR) technology has lately become popular in orthopedic surgery. However, there are few studies that specifically address the utility of MR in talocalcaneal coalitions (TCC) resection. Our goal in this retrospective study is to assess certain data while examining the viability of using MR to treat TCC resection., Methods: Six consecutive patients with TCC diagnosed by computed tomography (CT) for which nonoperative therapy had failed and MR system assisted TCC resection were included in this study from March 2021 to December 2021. The feasibility and accuracy of TCC resection were assessed by post-operation radiography. The American Orthopaedic Foot & Ankle Society (AOFAS) hindfoot score and visual analog scale (VAS) score were used to assess the recovery condition and pain level pre- and post-operation., Results: The surgeon can accurately resect the TCC according to the preoperatively determined range by superimposing the holographic model with the actual anatomy of the TCC using an MR system. Additionally, no additional x-ray was necessary while operating. Mean follow-up was 10.3 months, with a minimum of 6 months. There is a significant difference between the preoperative AOFAS score of 53.4 ± 3.8 and the 6-month follow-up AOFAS score of 97.3 ± 2.2 ( p  < 0.05). There is also a significant difference between the preoperative VAS score of 8.1 ± 0.7 and the 6-month follow-up VAS score of 1.7 ± 0.4 ( p  < 0.05). All individuals had clinical subtalar mobility without stiffness following surgery., Conclusion: While the TCC resection operation is being performed, the application of MR technology is practicable, effective, and radiation-free, giving surgeons satisfactory support., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Zhang, Wang, Li, Fu, Gu and Shi.)

Purpose: The common disease hallux valgus results in foot discomfort and dysfunction. Less soft tissue damage and faster wound healing have made minimally invasive surgery (MIS) more popular. However, little research has compared the fixation results of minimally invasive chevron-akin (MICA) osteotomy thus far. In this study, the clinical and radiographic results of MICA with first metatarsal single- or dual-screw fixation are being examined., Methods: A total of 107 feet of 103 patients with mild to moderate symptomatic hallux valgus treated MICA from January 2018 to June 2020 were retrospective evaluated, with at least 12-months follow-up. 51 patients underwent single-screw fixation procedures and 52 patients received dual-screw fixation procedures. Patients were assessed preoperatively and at the final follow-up with radiographic measurements [hallux valgus angle (HVA), intermetatarsal angle (IMA) and distal metatarsal articular angle (DMAA)] and clinical scores (american orthopaedic foot and ankle society (AOFAS) forefoot score, visual analog scale (VAS) and Manchester-Oxford Foot Questionnaire (MOxFQ) scores). The coughlin satisfaction scores were also obtained., Results: Both groups showed significantly improved HVA, IMA and DMAA at the final follow-up ( P  < 0.001). Regarding clinical outcomes, the AOFAS, VAS and MOxFQ in two categories also significantly improved postoperatively ( P  < 0.001). There was no obvious difference in the clinical and radiographic outcomes between the two groups (HVA, P  = 0.833; IMA, P  = 0.073; DMAA, P  = 0.35; AOFAS, P  = 0.48; VAS, P  = 0.86; MOxFQ, P  = 0.87). However, the single-screw fixation group showed significantly lower operation time and less number of intraoperative fluoroscopy ( P  < 0.001). No serious complications were observed in either group. The single-screw fixation technique saves at least $1,086 compared with the dual-screw group., Conclusion: At the final follow-up, both the single- and dual-screw fixation groups had comparable good to excellent clinical and radiographic outcomes, as well as a similar incidence of complications. Additionally, the single-screw fixation group reduces overall surgical costs, number of intraoperative fluoroscopy and operational time., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer CG declared a shared parent affiliation with the authors to the handling editor at the time of review., (© 2023 Li, Zhang, Fu, Wang, Yang and Shi.)

Background: Because of the rising prevalence of anterior talofibular ligament (ATFL) damage, there is a considerable interest in developing innovative techniques to improve the biological healing response of ATFL. Platelet-rich plasma (PRP) includes several growth factors linked to a favorable healing response, however none of the studies involved both quality evaluation and clinical results to evaluate this treatment. Purpose: To determine the clinical results of PRP injections into the ATFL in lateral ankle sprain (LAS) patients, as well as the quality of the ATFL based on radiographic outcomes. Methods: Patients with clinically confirmed grade II LAS for the first time ( n = 83) were examined. The clinical outcomes of three types of injection methods were evaluated: none, once within 48 h after the sprain, and once more 4 weeks later after first injection. PRP was injected into the tear site of the ATFL using ultrasound guidance, and all ankles were immobilized for 2 weeks. The American Orthopedic Foot and Ankle Score (AOFAS) ankle-hindfoot scale and the Visual Analogue Scale (VAS) were used to assess the results at 2, 6, 8, 24, and 48 weeks of follow-up. The signal/noise ratio (SNR) value of Magnetic Resonance Imaging (MRI)-based ATFL signal intensity can disclose ATFL quality. The ATFL SNR results were then assessed 8, 24 and 48 weeks following the first injection to compare ATFL quality. Results: The PRP injection groups outperformed the control group in terms of clinical outcomes, and the two injections group outperformed other groups in terms of pain reduction and functional outcome at 8 weeks. The clinical results of all groups were comparable at 6 and 12 months follow-up. ATFL SNR findings improved significantly across all groups over time. At the same follow-up time, the PRP injection groups outperformed the control group, and the best SNR result showed in the two injections group at the final follow-up. Conclusion: PRP injection helped relieve early symptoms of LAS, although all patients saw a similar development after 6 months. The two PRP injections group produced considerably better clinical results and quality of the ATFL in short-term follow-up., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Wang, Li, Fu, Gu and Shi.)

Background and Objectives: Platelets are affected by many factors, such as infectious or aseptic inflammation, and different inflammatory states may induce either thrombocytopenia or thrombocytosis. Tumor necrosis factor α (TNFα) is an important inflammatory cytokine that has been shown to affect the activity of hematopoietic stem cells. However, its role in megakaryocyte (MK) development and platelet production remains largely unknown. This study aimed to investigate the effects of TNFα on MK and platelet generation., Methods and Results: The ex vivo study with human CD34 + cells demonstrated that TNFα differentially modulated commitment toward the MK lineage. Specifically, a low concentration of 0.5 ng/ml TNFα promoted MK maturation, proplatelet formation, and platelet production, whereas a high concentration of 10 ng/ml or more TNFα exhibited a substantial inhibitory effect on MK and platelet production. The distinct effect of TNFα on MKs was mainly dependent on TNFα receptor 1. TNFα differentially regulated the MAPK-ERK1/2 signaling pathway and the cytoskeletal proteins cofilin and MLC2. The in vivo study with Balb/c mice indicated that low-dose or high-dose TNFα administration differentially affected short-term platelet recovery after bone marrow transplantation., Conclusions: Our study revealed distinct roles for TNFα in megakaryopoiesis and thrombopoiesis and may provide new insights regarding the treatment for platelet disorders., (© 2022 International Society on Thrombosis and Haemostasis.)

Background: Arthroscopic microfracture for osteochondral lesion of the talus (OLT) has shown good functional outcomes in the short and long term., Purpose: To investigate 5-year radiographic and clinical outcomes after arthroscopic microfracture in treatment of OLT and the effectiveness of adjunct therapies including platelet-rich plasma (PRP) and hyaluronic acid (HA)., Study Design: Cohort study; Level of evidence, 2., Methods: We prospectively enrolled 432 patients who underwent arthroscopic microfracture for OLT from May 1, 2011, to May 31, 2015. Magnetic resonance imaging (MRI) and weightbearing radiographs were performed annually after the initial surgery. The MOCART (magnetic resonance observation of cartilage repair tissue) score was used to evaluate the structure of the repaired cartilage on MRI, and patient-reported outcomes (American Orthopaedic Foot and Ankle Society ankle-hindfoot scale [AOFAS] and the Foot and Ankle Outcome Score) were collected annually. The primary outcome measure was 5-year AOFAS score. We recorded baseline characteristics including age, body mass index (BMI), and lesion size, and other potentially related factors including number of PRP/HA injection and change in BMI from baseline., Results: Included were 355 patients, all with minimum 5-year follow-up data. The overall reoperation rate was 9.0% (32 of 355). According to multivariable analysis, 5-year AOFAS scores were associated with number of PRP injections (correlation coefficient, 3.12 [95% CI, 2.36 to 3.89]; P < .001), BMI at baseline (correlation coefficient, -0.222 [95% CI, -0.363 to -0.082]; P = .002), and mean BMI change from baseline (correlation coefficient, -1.15 [95% CI, -1.32 to -0.98]; P < .001). When comparing number of PRP injections (0, 1-2, or ≥3), we found that patients who had serial PRP injection (≥3 with at least a 3-month interval between injections) had diminished functional and radiographic deterioration over time., Conclusion: Arthroscopic microfracture improved patient-reported and structural outcomes for patients with OLT at 5 years after surgery. Serial PRP injections and reduction in BMI from baseline were able to slow radiographic and functional deterioration. Future trials regarding the combination of microfracture and PRP in treatment of OLT should focus on the efficacy of longer term, intra-articular, serial injections of PRP instead of single injections., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: This study was funded by Ningxia Hui Autonomous Region Key R&D Program (2020BCH01001), Shanghai Science and Technology Innovation Action Plan (20025800200), and Shanghai Municipal Technical and Scientific Commission (19441902400). AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2022.)

Hepatitis B virus (HBV) infection remains a major health problem worldwide, and the current antiviral therapy, including nucleoside analogs, cannot achieve life-long cure, and clarification of antiviral host immunity is necessary for eradication. Here, we found that a clathrin-binding membrane protein epsin3 (EPN3) negatively regulates the expression of HBV RNA. EPN3 expression was induced by transfection of an HBV replicon plasmid, and reduced HBV-RNA level in hepatic cell lines and murine livers hydrodynamically injected with the HBV replicon plasmid. Viral RNA reduction by EPN3 was dependent on transcription, and independent from epsilon structure of viral RNA. Viral RNA reduction by overexpression of p53 or IFN-α treatment, was attenuated by knockdown of EPN3, suggesting its role downstream of IFN-α and p53. Taken together, this study demonstrates the anti-HBV role of EPN3. The mechanism how it decreases HBV transcription is discussed., (Copyright © 2022 Li, Wang, Zhou, Fu, Zhang, Sun, Yang, Bai, Dai, Xu, Cui, Zhao, Zhang, Wang, Li, Muramatsu, Wakae and Liu.)

Prolonged isolated thrombocytopenia (PT) is a common complication affecting the outcome of stem cell transplantation. In this study, we undertook a real-world study of 303 myelodysplastic syndrome (MDS) patients who received allogeneic hematopoietic stem cell transplantation (HSCT) between December 2007 and June 2018. 28.4% of MDS patients suffered from PT after HSCT. Survival analysis indicated that PT was associated with worse overall survival (OS) in MDS patients. The 2-year and 5-year OS in MDS patients with PT after HSCT were 49% and 47%, significantly worse than that of 68% and 60% in patients without PT (P=0.005). For RFS, patients with PT did not have an increased risk of disease relapse (P=0.964). After multivariate adjustment, PT was proved to be the independent risk factor associated with the worse OS (HR 1.49, 95% CI 1.00-2.21, P =0.048). We further analyzed risk factors associated with the occurrence of PT in MDS patients. Multiple logistic regression identified grade II-IV aGVHD, extensive chronic GVHD, hemorrhagic cystitis, and CMV activation as significant risk factors for developing PT. Among these variables, the Odds Ratio (OR) of grade II-IV aGVHD was the highest (P =0.001, OR: 2.65, 95% CI: 1.51-4.64). These data indicated the prognostic value of PT in MDS after HSCT. The identification of risk factors for PT may help improve patient management and lead to the design of effective treatment strategies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Qi, Li, Chu, Qiu, Fu, Tang, Ruan, Wu and Han.)

ITP is a common autoimmune bleeding disorder with elusive pathogenesis. Our study was implemented to profile the plasma metabolic alterations of patients diagnosed with ITP, aiming at exploring the potential novel biomarkers and partial mechanism of ITP. The metabolomic analysis of plasma samples was conducted using GC-MS on 98 ITP patients and 30 healthy controls (HCs). Age and gender matched samples were selected to enter the training set or test set respectively. OPLS-DA, t-test with FDR correction and ROC analyses were employed to screen out and evaluate the differential metabolites. Possible pathways were enriched based on metabolomics pathway analysis (MetPA). A total of 85 metabolites were investigated in our study and 17 differential metabolites with diagnostic potential were identified between ITP patients and HCs. MetPA showed that the metabolic disorders of ITP patients were mainly related to phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism and glyoxylate and dicarboxylate metabolism. Additionally, we discriminated 6 differential metabolites and 5 enriched pathways in predicting the resistance to glucocorticoids in chronic ITP patients. The distinct metabolites discovered in our study could become novel biomarkers for the auxiliary diagnosis and prognosis prediction of ITP. Besides, the dysregulated pathways might contribute to the development of ITP., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Wu, Zhou, Qi, Zhang, Li, Wang, Ruan and Han.)