Indirect influence of soil enzymes and their stoichiometry on soil organic carbon response to warming and nitrogen deposition in the Tibetan Plateau alpine meadow.

Despite extensive research on the impact of warming and nitrogen deposition on soil organic carbon components, the response mechanisms of microbial community composition and enzyme activity to soil organic carbon remain poorly understood. This study investigated the effects of warming and nitrogen deposition on soil organic carbon components in the Tibetan Plateau alpine meadow and elucidated the regulatory mechanisms of microbial characteristics, including soil microbial community, enzyme activity, and stoichiometry, on organic carbon components. Results indicated that both warming and nitrogen deposition significantly increased soil organic carbon, readily oxidizable carbon, dissolved organic carbon, and microbial biomass carbon. The interaction between warming and nitrogen deposition influenced soil carbon components, with soil organic carbon, readily oxidizable carbon, and dissolved organic carbon reaching maximum values in the W0N32 treatment, while microbial biomass carbon peaked in the W3N32 treatment. Warming and nitrogen deposition also significantly increased soil Cellobiohydrolase, ß-1,4-N-acetylglucosaminidase, leucine aminopeptidase, and alkaline phosphatase. Warming decreased the soil enzyme C: N ratio and C:P ratio but increased the soil enzyme N:P ratio, while nitrogen deposition had the opposite effect. The bacterial Chao1 index and Shannon index increased significantly under warming conditions, particularly in the N32 treatment, whereas there were no significant changes in the fungal Chao1 index and Shannon index with warming and nitrogen addition. Structural equation modeling revealed that soil organic carbon components were directly influenced by the negative impact of warming and the positive impact of nitrogen deposition. Furthermore, warming and nitrogen deposition altered soil bacterial community composition, specifically Gemmatimonadota and Nitrospirota, resulting in a positive impact on soil enzyme activity, particularly soil alkaline phosphatase and ß-xylosidase, and enzyme stoichiometry, including N:P and C:P ratios. In summary, changes in soil organic carbon components under warming and nitrogen deposition in the alpine meadows of the Tibetan Plateau primarily depend on the composition of soil bacterial communities, soil enzyme activity, and stoichiometric characteristics.

Effect of dissolved oxygen and ammonia nitrogen on Culter alburnus: Physiology, biochemistry, and molecular analyses.

Culter alburnus (topmouth culter)is an economically valuable freshwater fish. However, its insufficient tolerance to dissolved oxygen (DO) and ammonia nitrogen (AN) hinders its industrialisation. 360 experimental fish (4.87 ± 1.10 g) were placed in breathing chambers (oxygen level was 0.70-6.50 mg/L) or water tanks (control AN, 0 mg/L; low AN, 8 mg/L; high AN, 16 mg/L). This study analysed the effects of DO and AN on C. alburnus at physiological, biochemical, and molecular levels. (1) Physiology level: the floating point, coma critical point, and coma point at 20 °C group were significantly higher than those at 30 °C. The oxygen consumption rate of C. alburnus at 20 °C, 25 °C, and 30 °C was (256.65 ± 25.87), (470.47 ± 83.84), and (520.87 ± 55.40) mg/kg.h. The LC50 of AN after 96 h was 24.13 mg/L, and the safe concentration was 2.41 mg/L. The survival rate in the high AN group was significantly lower than that in the other two groups. (2) Biochemistry level: The change curves of antioxidant enzyme activity in the liver tissue under hypoxic stress reached a maximum at 12 h and then decreased. In addition, the increase and decrease in enzyme activity (except malondialdehyde) in the high AN group was lower than that in the low AN group. (3) Molecular level: the angiotensin-converting enzyme and carboxypeptidase genes were the major differentially expressed genes (DEGs) in hypoxic stress, and the DEGs were mainly enriched in the ABC transporter signal transduction pathway. In addition, the serum/glucocorticoid-regulated kinase, stearoyl-CoA desaturase, and 3-hydroxy-3-methylglutaryl-coenzyme A reductase genes were among the major DEGs under high AN stress. The DEGs were mainly enriched in steroid biosynthesis or glycine, serine, and threonine metabolism transporter signal transduction pathways. In summary, it is necessary to focus on the DO and AN during C. alburnus breeding.

Clinical evaluation of droplet digital pcr for suspected ascites infection in patients with liver cirrhosis.

BACKGROUND: Droplet digital PCR (ddPCR) is increasingly used in diagnosing clinical pathogens, but its effectiveness in cirrhosis patients with suspected ascites infection remains uncertain. METHODS: The diagnostic performance of ddPCR was assessed in 305 ascites samples, utilizing culture and clinical composite standards. The quantitative value and potential clinical impact of ddPCR were further analyzed in patients with spontaneous bacterial peritonitis. RESULTS: With culture standards, ddPCR demonstrated a sensitivity of 86.5% and specificity of 83.2% for bacterial or fungal detection. After adjustment of clinical composite criteria, specificity increased to 96.4%. Better diagnostic performance for all types of targeted pathogens, particularly fungi, was observed with ddPCR compared to culture, and more polymicrobial infections were detected (30.4% versus 5.7%, p < 0.001). Pathogen loads detected by ddPCR correlated with white blood cell count in ascites and blood, as well as polymorphonuclear cell (PMN) count in ascites, reflecting infection status rapidly. A positive clinical impact of 55.8% (43/77) was observed for ddPCR, which was more significant among patients with PMN count ≤ 250/mm3 in terms of medication adjustment and new diagnosis. ddPCR results for fungal detection were confirmed by clinical symptoms and other microbiological tests, which could guide antifungal therapy and reduce the risk of short-term mortality. CONCLUSIONS: ddPCR, with appropriate panel design, has advantages in pathogen detection and clinical management of ascites infection, especially for patients with fungal and polymicrobial infections. Patients with atypical spontaneous bacterial peritonitis benefited more from ddPCR.

REMIMAZOLAM IMPROVES THE MARKERS OF POSTRESUSCITATION CEREBRAL INJURY IN A SWINE MODEL OF CARDIAC ARREST.

ABSTRACT: Introduction: Previous studies have manifested that those sedatives acting on γ-aminobutyric acid A (GABAa) receptor could produce effective brain protection against regional and global ischemic stimulation. The present study was designed to investigate the effect of a novel GABAa receptor agonist, remimazolam postconditioning (RP) on cerebral outcome after global ischemic stimulation induced by cardiac arrest and resuscitation in swine. Methods: A total of 24 swine were used in this study, in which the animals were randomly divided into the following three groups: sham group (n = 6), cardiopulmonary resuscitation (CPR) group (n = 9), and CPR + RP group (n = 9). The experimental model was established by the procedure of 10 min of cardiac arrest and 5 min of CPR. Those resuscitated swine in the CPR + RP group received an intravenous infusion of 2.5 mg/kg of remimazolam within 60 min. Postresuscitation cerebral injury biomarkers and neurological function were evaluated for a total of 24 h. At 24 h after resuscitation, brain cortex was harvested to evaluate the severity of pathologic damage, including tissue inflammation, oxidative stress, apoptosis, and necroptosis. Results: Baseline characteristics and CPR outcomes were not significantly different between the CPR and CPR + RP groups. After resuscitation, significantly greater cerebral injury and neurological dysfunction were observed in the CPR and CPR + RP groups than in the sham group. However, remimazolam postconditioning significantly alleviated cerebral injury and improved neurological dysfunction after resuscitation when compared with the CPR group. At 24 h after resuscitation, tissue inflammation, oxidative stress, and cell apoptosis and necroptosis were significantly increased in the CPR and CPR + RP groups when compared with the sham group. Nevertheless, the severity of pathologic damage mentioned previously were significantly milder in those swine treated with the remimazolam when compared with the CPR group. Conclusions: In a swine model of cardiac arrest and resuscitation, the remimazolam administered after resuscitation significantly improved the markers of postresuscitation cerebral injury and therefore protected the brain against global ischemic stimulation.

Biologic Therapy in Rare Eosinophil-Associated Disorders: Remaining Questions and Translational Research Opportunities.

Rare eosinophil-associated disorders (EADs), including hypereosinophilic syndrome, eosinophilic granulomatosis with polyangiitis and eosinophilic gastrointestinal disorders, are a heterogeneous group of conditions characterized by blood and/or tissue hypereosinophilia and eosinophil-related clinical manifestations. Although the recent availability of biologic therapies that directly and indirectly target eosinophils has the potential to dramatically improve treatment options for all EADs, clinical trials addressing their safety and efficacy in rare EADs have been relatively few. Consequently, patient access to therapy is limited for many biologics, and the establishment of evidence-based treatment guidelines has been extremely difficult. In this regard, multicenter retrospective collaborative studies focusing on disease manifestations and treatment responses in rare EADs have provided invaluable data for physicians managing patients with these conditions and helped identify important questions for future translational research. During the Clinical Pre-Meeting Workshop held in association with the July 2023 biennial meeting of the International Eosinophil Society in Hamilton, Ontario, Canada, the successes and limitations of pivotal multicenter retrospective studies in EADs were summarized, and unmet needs regarding the establishment of guidelines for use of biologics in rare EADs were discussed. Key topics of interest included: 1) clinical outcome measures, 2) minimally invasive biomarkers of disease activity, 3) predictors of response to biologic agents, and 4) long-term safety of eosinophil depletion. Herein, we report a summary of these discussions, presenting a state-of-the-art overview of data currently available for each of these topics, the limitations of the data, and avenues for future data generation through implementation of multidisciplinary and multicenter studies.

Drivers of habitat availability for terrestrial mammals: Unravelling the role of livestock, land conversion and intrinsic traits in the past 50 years.

The global decline of terrestrial species is largely due to the degradation, loss and fragmentation of their habitats. The conversion of natural ecosystems for cropland, rangeland, forest products and human infrastructure are the primary causes of habitat deterioration. Due to the paucity of data on the past distribution of species and the scarcity of fine-scale habitat conversion maps, however, accurate assessment of the recent effects of habitat degradation, loss and fragmentation on the range of mammals has been near impossible. We aim to assess the proportions of available habitat within the lost and retained parts of mammals' distribution ranges, and to identify the drivers of habitat availability. We produced distribution maps for 475 terrestrial mammals for the range they occupied 50 years ago and compared them to current range maps. We then calculated the differences in the percentage of 'area of habitat' (habitat available to a species within its range) between the lost and retained range areas. Finally, we ran generalized linear mixed models to identify which variables were more influential in determining habitat availability in the lost and retained parts of the distribution ranges. We found that 59% of species had a lower proportion of available habitat in the lost range compared to the retained range, thus hypothesizing that habitat loss could have contributed to range declines. The most important factors negatively affecting habitat availability were the conversion of land to rangeland and high density of livestock. Significant intrinsic traits were those related to reproductive timing and output, habitat breadth and medium body size. Our findings emphasize the importance of implementing conservation strategies to mitigate the impacts caused by human activities on the habitats of mammals, and offer evidence indicating which species have the potential to reoccupy portions of their former range if other threats cease to occur.

Global research trends and prospects on the first-generation college students from 2002 to 2022: a bibliometric analysis via CiteSpace.

Objectives: To review literature related to first-generation college students, the paper aims to outline the research direction, identify prominent research topics and frontiers, report on current research trends, and offer valuable insights and fresh perspectives for future advancements in the field, utilizing CiteSpace. Methods: CiteSpace is a citation visualization software designed to analyze the scholarly literature and uncover potential knowledge within it. This study retrieved articles related to first-generation college students from 2002 to 2022 from Web of Science Core Collection database. After collecting the data, CiteSpace V.6.1.R3 (64-bit) was used to perform analyses on various aspects, including annual publication output, top cited journals, country and institutional affiliations, prominent authors, cited references, and keywords. The data was visualized using tools such as knowledge maps, collaborative network analysis, cluster analysis, and strongest citation burst analysis. Results: We obtained a total of 471 articles on first-generation college students. The number of publications annually is increasing, and the number of publications generally shows an upward trend, especially in 2017-2021 with a sharp growth. The United States has the most articles on this topic (395 articles), and it is also the most authoritative and influential country (with a centrality of 0.93). Followed by South Africa (14 articles) and Germany (14 articles), The top 10 cited journals and institutions are predominantly from the United States. When analyzing the top cited references and authors, the research consistently highlights the academic achievement and engagement of first-generation college students. Conclusion: This study analyzed the current situation of first-generation college students field via CiteSpace, then identify the research hotspots and frontiers on first-generation college students. Current global trends in first-generation college students researches and the growing public awareness of academic performance and equality suggest that first-generation college students researches will grow in popularity with further breakthroughs.

A Cell-Free Protein Synthesis Platform to Produce a Clinically Relevant Allergen Panel.

Allergens are used in the clinical diagnosis (e.g., skin tests) and treatment (e.g., immunotherapy) of allergic diseases. With growing interest in molecular allergy diagnostics and precision therapies, new tools are needed for producing allergen-based reagents. As a step to address this need, we demonstrate a cell-free protein synthesis approach for allergen production of a clinically relevant allergen panel composed of common allergens spanning a wide range of phylogenetic kingdoms. We show that allergens produced with this approach can be recognized by allergen-specific immunoglobulin E (IgE), either monoclonals or in patient sera. We also show that a cell-free expressed allergen can activate human cells such as peripheral blood basophils and CD34+ progenitor-derived mast cells in an IgE-dependent manner. We anticipate that this cell-free platform for allergen production will enable diagnostic and therapeutic technologies, providing useful tools and treatments for both the allergist and allergic patient.

Distinct CRTH2+CD161+ (peTh2) memory CD4+ T-cell cytokine profiles in food allergy and eosinophilic gastrointestinal disorders.

INTRODUCTION: Although IgE-mediated food allergy (FA) and eosinophilic gastrointestinal disorders (EGID) are clinically distinct and treated differently, pathogenic effector Th2 (peTh2) cells are implicated in the pathogenesis of both FA and EGID. The aim of this study was to better characterize peTh2 cells in the context of FA and EGID and the overlap between these two conditions. METHODS: Peripheral blood peTh2 cells (CD3+CD4+CD27-CD49d+CRTH2+CD161+) were profiled by intracellular cytokine flow cytometry in the following patient cohorts: patients with FA alone (n = 8), FA and food-triggered EGID (EGID+FA+FT, n = 7), food-triggered EGID alone (EGID+FT, n = 7), EGID without FA or specific food triggers (ONLY_EGID, n = 9), and healthy volunteers (HV, n = 7). Overnight peripheral blood mononuclear cell (PBMC) culture supernatants were assessed for cytokine production by multiplex analysis. RESULTS: CRTH2+CD161+ (peTh2) memory CD4+ T cells were significantly increased in both patients with FA and those with ALL_EGID (inclusive of EGID+FA+FT, EGID+FT and ONLY_EGID) when compared to HV. However, ALL_EGID patients, particularly those with EGID+FA+FT, had significantly elevated IL-5+IL-13+ peTh2 cells, whereas FA patients had significantly elevated IFN-γ or IL-17A-expressing peTh2 cells. This finding was supported by increased spontaneous IL-5 and IL-13 production in overnight cultures of PBMC from EGID+FA+FT patients compared to spontaneous IL-10 and IFN-γ production by PBMC from FA patients. FA patients had increased IL-9, IL-10, IL-17A, and IFN-γ production in overnight cultures of stimulated PBMC. CONCLUSIONS: EGID and IgE-mediated FA share a common cell subtype defined by specific surface markers and termed CRTH2+CD161+ (peTh2) memory CD4+ T cells. However, the cytokine profiles of these CRTH2+CD161+ (peTh2) memory CD4+ T cells are markedly different between the two disorders.

Biologics and Hypereosinophilic Syndromes: Knowledge Gaps and Controversies.

Hypereosinophilic syndromes (HES) are a heterogeneous group of disorders defined by blood and/or tissue hypereosinophilia and clinical manifestations attributable to the eosinophilia. Although various clinical subtypes of HES have been described, the general approach to therapy in all subtypes has focused on the reduction of blood and tissue eosinophilia to improve symptoms and halt disease progression. Until recently, this typically involved the use of corticosteroids and/or other immunosuppressive or cytotoxic drugs with significant toxicity. Whereas imatinib, the first targeted therapy approved for treatment of HES, has dramatically changed the prognosis of patients with primary (myeloid) forms of HES, it is ineffective in patients with other HES subtypes. For these nonmyeloid patients with HES, the development of eosinophil-targeting biologics (most notably, mepolizumab, the first biologic approved for the treatment of HES) has been transformative. Nevertheless, important issues remain with respect to the efficacy and safety of these biologics in the treatment of the varied subtypes of HES. Moreover, with the increasing number of commercially available biologics with direct or indirect effects on eosinophils, questions related to the choice of initial biologic, potential reasons for biologic failure, and treatment options in the setting of incomplete response are becoming increasingly common.

False-Negative Testing for FIP1L1::PDGFRA by Fluorescence in situ Hybridization Is a Frequent Cause of Diagnostic Delay.

The imatinib-sensitive fusion gene FIP1L1::PDGFRA is the most frequent molecular abnormality identified in patients with eosinophilic myeloid neoplasms. Rapid recognition of this mutation is essential given the poor prognosis of PDGFRA-associated myeloid neoplasms prior to the availability of imatinib therapy. We report a case of a patient in whom delayed diagnosis resulted in cardiac transplantation for eosinophilic endomyocardial fibrosis. The delay in diagnosis was due, in part, to a false-negative result in fluorescence in situ hybridization (FISH) testing for FIP1L1::PDGFRA. To explore this further, we examined our cohort of patients presenting with confirmed or suspected eosinophilic myeloid neoplasms and found 8 additional patients with negative FISH results despite a positive reverse-transcriptase polymerase chain reaction test for FIP1L1::PDGFRA. More importantly, false-negative FISH results delayed the median time to imatinib treatment by 257 days. These data emphasize the importance of empiric imatinib therapy in patients with clinical features suggestive of PDGFRA-associated disease.

Bulk T-cell receptor sequencing confirms clonality in pediatric eosinophilic esophagitis and identifies a food-specific repertoire.

BACKGROUND: Eosinophilic esophagitis (EoE) involves a chronic immune-mediated response to dietary antigens. Recent work identifies T-cell clonality in children with EoE, however, it is unknown whether this is true in adults or whether there is a restricted food-specific T-cell repertoire. We sought to confirm T-cell receptor (TCR) clonality in EoE and assess for differences with specific food triggers. METHODS: Bulk TCR sequencing was performed on mRNA isolated from esophageal biopsies obtained from adults and children with EoE (n = 15) who had food triggers confirmed by endoscopic evaluation. Non-EoE adult and pediatric controls (n = 10) were included. Differences in TCR clonality by disease and treatment status were assessed. Shared and similar V-J-CDR3s were assessed based on specific food triggers. RESULTS: Active EoE biopsies from children but not adults displayed decreased unique TCRα/ß clonotypes and increased relative abundance of TCRs comprising >1% of the total compared to non-EoE controls and paired inactive EoE samples. Among patients in which baseline, post diet elimination, and food trigger reintroduction samples (n = 6) were obtained, we observed ~1% of TCRs were shared only between pre-diet elimination and trigger reintroduction. Patients with a shared EoE trigger (milk) had a greater degree of shared and similar TCRs compared to patients with differing triggers (seafood, wheat, egg, soy). CONCLUSION: We confirmed relative clonality in children but not adults with active EoE and identified potential food-specific TCRs, particularly for milk-triggered EoE. Further studies are needed to better identify the broad TCR repertoire relevant to food triggers.

Patient Access to Orphan Drugs Covered by Medical Insurance in China: Real-World Evidence From Patient Survey.

BACKGROUND: After the inclusion of more high-cost orphan drugs in China's National Reimbursement Drugs List, this study investigated issues relating to patient access to the 7 medicines for 4 rare diseases after listing. METHODS: This study collected data from a national survey conducted in China. Three aspects associated with the accessibility of medicines, namely, approachability, availability, and affordability, were analyzed using descriptive statistics. In addition, multilevel logistic regression models were used to investigate the associations between patient characteristics and the accessibility of surveyed orphan drugs. RESULTS: Of the 999 completed responses included in the study, 15% of the patients (n = 150) did not use the medicines because of non-medicine-related issues. Among the 849 patients using the surveyed medications, 64.4% (n = 547) encountered the problem of unavailability, whereas 51.2% (n = 435) reported affordability as an issue, and 49.6% (n = 320) had health expenditure beyond the catastrophic threshold. The data also indicated that Commercial Medical Insurance helped patients to relieve the cost burden on orphan drugs, but the payout of Commercial Medical Insurance failed to influence patients' decisions to continue the treatments. CONCLUSION: Accessibility of orphan drugs has improved in China after their inclusion in the National Reimbursement Drugs List. Nevertheless, the availability and affordability of medicines remained the barriers for patients to access the desired treatments. It is recommended that further policy refinement in conjunction with the collaboration among healthcare stakeholders is required to deliver better care for patients with rare disease.

Clinical Evaluation of Metagenomic Next-Generation Sequencing Method for the Diagnosis of Suspected Ascitic Infection in Patients with Liver Cirrhosis in a Clinical Laboratory.

Metagenomic next-generation sequencing (mNGS), mostly carried out in independent clinical laboratories, has been increasingly applied in clinical pathogen diagnosis. We aimed to explore the feasibility of mNGS in clinical laboratories and analyze its potential in the diagnosis of infectious ascites. Two reference panels composed of 12 strains commonly appearing in peritonitis were constructed to evaluate the performance metrics based on in-house mNGS protocols. The mNGS clinical detection value was analyzed in 211 ascitic samples and compared with culture and composite standards. Finally, eight patients with cirrhosis were prospectively enrolled to verify the clinical value of mNGS in peritoneal infection diagnosis. The mNGS analytical performance showed that the assay had great linearity, specificity, stability, interference, and limits of detection of 33 to 828 CFU/mL. The sensitivity and specificity of mNGS for bacterial or fungal detection using culture standards were 84.2% and 82.0%, respectively. After adjustment using digital PCR and clinical judgment, the sensitivity and specificity increased to 87.2% and 90.1%, respectively. Compared with culture, mNGS detected a broad range of pathogens and more polymicrobial infections (49% versus 9%, P < 0.05). The pathogen results were obtained within 24 h using mNGS in eight prospective cases, which effectively guided antibiotics therapy. mNGS testing in clinical laboratories affiliated with a hospital has certain advantages. It has unique superiority in pathogens detection, particularly in patients with polymicrobial infections. However, considering spectrum characteristics and test cost, pertinent pathogen panels should be developed in clinical practice. IMPORTANCE This study established and evaluated a complete metagenomics next-generation sequencing assay to improve the diagnosis of suspected ascitic infection in a clinical laboratory affiliated with a hospital. The assay is superior to traditional culture testing and will aid in the early and accurate identification of pathogens, particularly in patients with polymicrobial infections. This assay is also essential for precision therapy and can reduce the incidence of drug resistance stemming from irrational use of antibiotics.

Effectiveness of microwave ablation for the treatment of hepatic hemangioma - meta-analysis and meta-regression.

BACKGROUND: The treatment of hepatic hemangioma includes surgical resection, radiofrequency ablation and Transarterial embolization. However, complications, mortality and compromised effectiveness limit their applications. Microwaves with effective heating generation and short ablation time become a promising treatment. The aim of this study is to conduct systematic review and meta-analyses to evaluate the effectiveness of Microwave Ablation (MWA) for the treatment of hepatic hemangioma. METHODS: A systematic literature review was conducted in PubMed. Main outcomes were defined as hemangioma decreases in diameters and volume changes post-MWA. Conventional random-effect meta-analysis technique was applied to analyze the pooled data, and meta-regression model was established to explore the association among factors. RESULTS: There were nine studies with a total of 501 patients retrieved. The pooled estimate of mean differences and 95% CI of hemangioma decreases after MWA treatment in diameter and in volume change (%) were 3.009 cm and (1.856, 4.161), and 53.169% and (51.274, 55.065), respectively. The pooled estimates of liver enzyme, ALT and AST, elevation were 219.905 with 95%CI (160.860, 278.949) and 315.679 with 95%CI (226.961, 404.397), respectively. Major complications were defined as acute kidney injury (AKI), pleural effusion, diaphragmatic hernia, and jaundice that needed to be treated, and the pooled incidence was 0.017 with 95% CI of (0.006, 0.029). No mortality related to MWA was reported. Meta-regression showed ablation time was associated with pre-operative lesion size (p = .001). CONCLUSION: MWA is effective and safe in treatment of hepatic hemangioma, and our study suggests that hemangioma size should be investigated in the future MWA pretreatment difficulty scoring system study.

Urine eosinophil-derived neurotoxin: A potential marker of activity in select eosinophilic disorders.

BACKGROUND: Biomarkers of eosinophilic disease activity, especially in the context of novel therapies that reduce blood eosinophil counts, are an unmet need. Absolute eosinophil count (AEC) does not accurately reflect tissue eosinophilia or eosinophil activation. Therefore, the aims of this study were to compare the reliability of plasma and urine eosinophil major basic protein 1, eosinophil cationic protein, eosinophil-derived neurotoxin (EDN), and eosinophil peroxidase measurement and to evaluate the usefulness of eosinophil granule protein (EGP) measurement for the assessment of disease activity in patients with eosinophil-associated diseases treated with mepolizumab, benralizumab, or dexpramipexole. METHODS: Eosinophil granule protein concentrations were measured in serum, plasma, and urine from healthy volunteers and patients with hypereosinophilic syndrome (HES), eosinophilic granulomatosis with polyangiitis (EGPA), and eosinophilic asthma using a multiplex assay. RESULTS: Urine EGP concentrations remained stable, whereas serum and plasma EGP concentrations increased significantly with delayed processing. Plasma (p) EDN, but not urine (u) EDN, concentration correlated with AEC and negatively correlated with prednisone dose. Both pEDN and uEDN decreased significantly following treatment of HES patients with benralizumab and EGPA patients with mepolizumab. uEDN appeared to increase with clinical relapse in both patient groups. CONCLUSIONS: Measurement of EGP in urine is noninvasive and unaffected by cellular lysis. Although plasma and urine EDN concentrations showed a similar pattern following benralizumab and mepolizumab treatment, the lack of correlation between AEC or prednisone dose and uEDN concentrations suggests that measurement of uEDN may provide a potential biomarker of disease activity in patients with HES and EGPA.

Influences of aerobic exercise associated with the pharmacological treatment of copd / Influências do exercício aeróbico associado ao tratamento farmacológico da dpoc / Influencias del ejercicio aeróbico asociado al tratamiento farmacológico de la epoc

ABSTRACT Introduction: Chronic obstructive pulmonary disease (COPD) is a type of inflammatory respiratory system disease characterized by chronic airflow limitation. Aerobic exercise training is believed to influence the drug treatment of this disease positively. Objective: Study the impact of complementary aerobic exercise intervention on pharmacological treatment in patients with COPD. Methods: In a controlled experiment, 40 volunteers under pharmacological treatment for COPD were selected and equally divided into two groups. The experimental group was treated with aerobic exercise training and drug treatment, while the control group was treated with regular drug treatment only. The exercise protocol lasted 60 minutes daily for a total period of eight weeks. Borg scale, oxygen saturation, and six-minute walk test among other markers were checked before and after the intervention. Results: According to the data obtained from the experiment, the peak oxygen consumption of aerobic exercise combined with the drug group was from 1,205.42±293.74ml/min to 1,301.84±293.91ml/min, peak ventilation started at 37.85±11.67L/min to 48.81±13.11L/min. However, the variations in the control group were not significant. Conclusion: Aerobic exercise associated with pharmacological intervention positively influenced the treatment of patients with COPD. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução: A doença pulmonar obstrutiva crônica (DPOC) é um tipo de doença inflamatória do sistema respiratório caracterizada pela limitação crônica do fluxo de ar. Acredita-se que o treinamento com exercícios aeróbicos possa influenciar positivamente no tratamento medicamentoso dessa enfermidade. Objetivo: Estudar os impactos da intervenção complementar com exercícios aeróbicos sobre o tratamento farmacológico em portadores de DPOC. Métodos: Através de um experimento controlado, 40 voluntários sob tratamento farmacológico para DPOC foram selecionados e igualmente divididos em dois grupos. O grupo experimental foi tratado com treinamento de exercício aeróbico combinado com o tratamento medicamentoso, enquanto o grupo controle foi tratado apenas com o tratamento medicamentoso regular. O protocolo de exercícios teve duração de 60 minutos diários, num período total de oito semanas. A escala de Borg, saturação de oxigênio, teste de caminhada de seis minutos entre outros marcadores foram verificados antes e após a intervenção. Resultados: De acordo com os dados obtidos do experimento, o pico de consumo de oxigênio do exercício aeróbico combinado com o grupo de fármacos foi de 1.205,42±293,74ml/min para 1.301,84±293,91ml/min, pico de ventilação iniciou em 37,85±11,67L/min para 48,81±13,11L/min. Porém as variações no grupo controle não foram significativas. Conclusão: O exercício aeróbico associado à intervenção farmacológica representou uma influência positiva no tratamento dos pacientes portadores de DPOC. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción: La enfermedad pulmonar obstructiva crónica (EPOC) es un tipo de enfermedad inflamatoria del sistema respiratorio caracterizada por la limitación crónica del flujo aéreo. Se cree que el entrenamiento con ejercicios aeróbicos puede influir positivamente en el tratamiento farmacológico de esta enfermedad. Objetivo: Estudiar el impacto de la intervención complementaria con ejercicios aeróbicos sobre el tratamiento farmacológico en pacientes con EPOC. Métodos: Mediante un experimento controlado, se seleccionaron 40 voluntarios bajo tratamiento farmacológico para la EPOC y se dividieron equitativamente en dos grupos. El grupo experimental fue tratado con entrenamiento de ejercicio aeróbico combinado con tratamiento farmacológico, mientras que el grupo de control fue tratado únicamente con tratamiento farmacológico regular. El protocolo de ejercicio duró 60 minutos diarios durante un período total de ocho semanas. Se comprobaron la escala de Borg, la saturación de oxígeno y la prueba de la marcha de seis minutos, entre otros marcadores, antes y después de la intervención. Resultados: Según los datos obtenidos del experimento, el consumo máximo de oxígeno del grupo de ejercicio aeróbico combinado con fármaco fue de 1.205,42±293,74ml/min a 1.301,84±293,91ml/min, la ventilación máxima comenzó en 37,85±11,67L/min a 48,81±13,11L/min. Sin embargo, las variaciones en el grupo de control no fueron significativas. Conclusión: El ejercicio aeróbico asociado a la intervención farmacológica tuvo una influencia positiva en el tratamiento de los pacientes con EPOC. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Second allogeneic hematopoietic stem cell transplantation with reduced-intensity conditioning and donor changes in relapsed hematological malignancies after the first allogeneic transplant / 中华血液学杂志

Objective: The purpose of this study was to assess the safety and efficacy of a second allogeneic hematopoietic stem cell transplantation (allo-HSCT) with reduced-intensity conditioning (RIC) in patients with hematological malignancies who had relapsed after the first allo-HSCT. Methods: Between April 2018 and June 2021, 44 patients with hematological malignancies (B-ALL 23, T-ALL/T-LBL 4, AML15, and MDS 2) were enrolled and retrospectively examined. Unrelated donors (n=12) or haploidentical donors (n=32) were used. Donors were replaced in all patients for the second allo-HSCT. Hematological and immunological germline predisposition genes and hematopoietic and immune function tests were used to select the best-related donor. Total body irradiation (TBI) /fludarabine (FLU) -based (n=38), busulfan (BU) /FLU-based (n=4), total marrow irradiation (TMI) /FLU-based (n=1), and BU/cladribine-based (n=1) were the RIC regimens used. For graft versus host disease (GVHD) prevention, cyclosporine, mycophenolate mofetil, short-term methotrexate, and ATG were used. Eighteen (40.9%) of 44 patients with gene variations for which targeted medications are available underwent post-transplant maintenance therapy. Results: The median age was 25 years old (range: 7-55). The median interval between the first and second HSCT was 19.5 months (range: 6-77). Before the second allo-HSCT, 33 (75%) of the patients were in complete remission (CR), whereas 11 (25%) were not. All patients had long-term engraftment. The grade Ⅱ-Ⅳ GVHD and severe acute GVHD rates were 20.5% and 9.1%, respectively. Chronic GVHD was found in 20.5% of limited patterns and 22.7% of severe patterns. CMV and EBV reactivation rates were 29.5% and 6.8%, respectively. Hemorrhage cystitis occurred in 15.9% of cases, grade Ⅰ or Ⅱ. The 1-yr disease-free survival (DFS), overall survival (OS), and cumulative recurrence incidence (RI) rates of all patients were 72.5% (95% CI, 54.5%-84.3%), 80.6% (95% CI, 63.4%-90.3%), and 25.1% (95% CI, 13.7%-43.2%), respectively, with a median follow-up of 14 (2-39) months. There were eight deaths (seven relapses and one infection). The rate of non-relapse mortality (NRM) was only 2.3%. The CR patients' 1-yr RI rate was significantly lower than the NR patients (16.8% vs 48.1%, P=0.026). The DFS rate in CR patients was greater than in NR patients, although there was no statistical difference (79.9% vs 51.9%, P=0.072). Univariate analysis revealed that CR before the second allo-HSCT was an important prognostic factor. Conclusion: With our RIC regimens, donor change, and post-transplant maintenance therapy, the second allo-HSCT in relapsed hematological malignancies after the first allo-HSCT is a safe and effective treatment with high OS and DFS and low NRM and relapse rate. The most important factor influencing the prognosis of the second allo-HSCT is the patient's illness condition before the transplant.