Second-line therapy for patients with steroid-refractory aGVHD: systematic review and meta-analysis of randomized controlled trials

ObjectiveSteroids-refractory (SR) acute graft-versus-host disease (aGVHD) is a life-threatening condition in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT), but the optimal second-line therapy still has not been established. We aimed to perform a systematic review and meta-analysis of randomized controlled trials (RCTs) to compare the efficacy and safety of different second-line therapy regimens.MethodsLiterature search in MEDLINE, Embase, Cochrane Library and China Biology Medicine databases were performed to retrieve RCTs comparing the efficacy and safety of different therapy regimens for patients with SR aGVHD. Meta-analysis was conducted with Review Manager version 5.3. The primary outcome is the overall response rate (ORR) at day 28. Pooled relative risk (RR) and 95% confidence interval (CI) were calculated with the Mantel-Haenszel method.ResultsEight eligible RCTs were included, involving 1127 patients with SR aGVHD and a broad range of second-line therapy regimens. Meta-analysis of 3 trials investigating the effects of adding mesenchymal stroma cells (MSCs) to other second-line therapy regimens suggested that the addition of MSCs is associated with significantly improvement in ORR at day 28 (RR = 1.15, 95% CI = 1.01–1.32, P = 0.04), especially in patients with severe (grade III–IV or grade C–D) aGVHD (RR = 1.26, 95% CI = 1.04–1.52, P = 0.02) and patients with multiorgan involved (RR = 1.27, 95% CI = 1.05–1.55, P = 0.01). No significant difference was observed betwwen the MSCs group and control group in consideration of overall survival and serious adverse events. Treatment outcomes of the other trials were comprehensively reviewed, ruxolitinib showed significantly higher ORR and complete response rate at day 28, higher durable overall response at day 56 and longer failure-free survival in comparison with other regimens; inolimomab shows similar 1-year therapy success rate but superior long-term overall survial in comparison with anti-thymocyte globulin, other comparisons did not show significant differences in efficacy.ConclusionsAdding MSCs to other second-line therapy regimens is associated with significantly improved ORR, ruxolitinib showed significantly better efficacy outcomes in comparison with other regimens in patients with SR aGVHD. Further well-designed RCTs and integrated studies are required to determine the optimal treatment.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022342487

Identification of important extracellular vesicle RNA molecules related to sperm motility and prostate cancer

Aim: Many male diseases are associated with sperm quality, such as prostate cancer (PCa), oligospermia, and asthenospermia. Seminal plasma extracellular vesicles (SPEVs) play important roles in sperm function. In this study, we explored the specific RNA molecules in SPEVs that play an important role in sperm motility and found promising biomarkers of PCa in SPEVs.Methods: Pigs have become an ideal model for human biomedical research. In this study, the whole transcriptome profiles of SPEVs of boars with high or low sperm motility were studied for the first time. Important long non-coding RNAs, microRNAs, and genes were identified through differentially expressed analysis and weighted correlation network analysis (WGCNA). In addition, we established a diagnosis model of PCa by differentially expressed miRNAs homologous with human.Results: In total, 27 differentially expressed miRNAs, 106 differentially expressed lncRNAs, and 503 differentially expressed genes were detected between the groups. The results of WGCNA show one module was significantly associated with sperm motility (r = 0.98, FDR = 2 × 10-6). The value of highly homologous miRNAs for the diagnosis of PCa was assessed and the combination of hsa-miR-27a-3p, hsa-miR-27b-3p, hsa-miR-155-5p, and hsa-miR-378a-3p exhibited the highest sensitivity (AUC = 0.914). Interestingly, mRNA expression of SPEVs was mainly enriched in resting memory CD4 T cells and monocytes, and 33 cell marker genes of monocytes overlapped with the differentially expressed genes.Conclusion: These data demonstrate that SPEVs of individuals with high and low sperm motility exhibit distinct transcriptional profiles, which provide valuable information for further research on diagnosis and molecular mechanism of diseases

Changes in cecal microbiota community of suckling piglets infected with porcine epidemic diarrhea virus.

Diarrhea, caused by porcine epidemic diarrhea virus (PEDV), is a catastrophic gastrointestinal disease among suckling piglets, with high infectivity, morbidity, and mortality, causing huge economic losses to the pig industry. In the present study, we investigated the different microbiota from the cecal mucosa and cecal contents between healthy and PEDV-infected piglets. High-throughput 16S rRNA gene sequencing was performed to explore differences. The results revealed that microbial dysbiosis by PEDV infection occurred in the cecal mucosa and contents of suckling piglets at each microbial taxonomic level. The abundance of pathogenic bacteria associated with diseases, including diarrhea, was increased. The abundance of Fusobacterium was 26.71% and 33.91% in cecal mucosa and contents of PEDV-infected group, respectively, whereas that in the healthy groups was 17.85% and 9.88%. The proportion of Proteobacteria in the infected groups was relatively high (24.67% and 22.79%, respectively), whereas that in the healthy group was 13.13% and 11.34% in the cecal mucosa and contents, respectively. Additionally, the proportion of Bacteroidetes in the healthy group (29.89%, 37.32%) was approximately twice that of the PEDV-infected group (15.50%, 15.39%). "Nitrate reduction", "Human pathogens diarrhea", "Human pathogens gastroenteritis", "Nitrite respiration", and "Nitrite ammonification" were the enriched functional annotation terms in the PEDV-infected groups. Porcine epidemic diarrhea virus infection increased the proportion of harmful bacteria and decreased the proportion of beneficial bacteria in the cecal mucosa and contents of suckling piglets. Our findings suggest that determining the intestinal microbiota might provide a promising method to prevent PEDV and open a new avenue for future research

Cross-Cultural Adaptation and Validation of the Simplified Chinese Version of the Lower Extremity Functional Scale

Purpose. The purpose of this study was to cross-culturally adapt and validate the Simplified Chinese version of the Lower Extremity Functional Scale (SC-LEFS). Methods. The original English version of the Lower Extremity Functional Scale was translated and cross-culturally adapted into Simplified Chinese according to international guidelines. The SC-LEFS and 36-Item Short-Form Health Survey were administered to 213 patients with lower extremity musculoskeletal disorders. Psychometric properties including internal consistency, test-retest reliability, content validity, and construct validity were tested. Results. There were no floor or ceiling effects for the SC-LEFS. The scale had high values for internal consistency (Cronbach α=0.97) and test-retest reliability (intraclass correlation coefficient=0.97). Corrected item-total correlations for every item ranged from 0.67 to 0.89. And the item-level content validity index (I-CVI) for each item ranged from 0.78 to 1.00. Principal component analysis revealed a one-factor structure. Nine of ten prior hypotheses were confirmed, which further supports good construct validity within the SC-LEFS. Conclusion. The SC-LEFS has high internal consistency, good test-retest reliability and content validity, convergent construct validity, and a one-factor structure. Thus, it could be regarded as a reliable and valid tool to assess activity limitations in Chinese patients with lower extremity musculoskeletal disorders

Understanding the Size-Dependent Sodium Storage Properties of Na₂C₆O₆‑Based Organic Electrodes for Sodium-Ion Batteries

Organic electroactive materials represent a new generation of sustainable energy storage technology due to their unique features including environmental benignity, material sustainability, and highly tailorable properties. Here a carbonyl-based organic salt Na₂C₆O₆, sodium rhodizonate (SR) dibasic, is systematically investigated for high-performance sodium-ion batteries. A combination of structural control, electrochemical analysis, and computational simulation show that rational morphological control can lead to significantly improved sodium storage performance. A facile antisolvent method was developed to synthesize microbulk, microrod, and nanorod structured SRs, which exhibit strong size-dependent sodium ion storage properties. The SR nanorod exhibited the best performance to deliver a reversible capacity of ∼190 mA h g^–1 at 0.1 C with over 90% retention after 100 cycles. At a high rate of 10 C, 50% of the capacity can be obtained due to enhanced reaction kinetics, and such high electrochemical activity maintains even at 80 °C. These results demonstrate a generic design route toward high-performance organic-based electrode materials for beyond Li-ion batteries. Using such a biomass-derived organic electrode material enables access to sustainable energy storage devices with low cost, high electrochemical performance and thermal stability

Dopant-Enabled Supramolecular Approach for Controlled Synthesis of Nanostructured Conductive Polymer Hydrogels

Conducting polymer hydrogels emerge as a novel class of polymeric materials that show great potential in many energy, environmental, and biomedical devices. We describe here for the first time a general supramolecular approach toward controlled in situ synthesis of one-dimensional nanostructured conductive hydrogels (polypyrrole (PPy) as a model system) using a rational dopant counterion, which is a disc-shaped liquid crystal molecular copper phthalocyanine-3,4′,4″,4‴-tetrasulfonic acid tetrasodium salt (CuPcTs). The dopant molecule CuPcTs cross-linked the PPy chains to form a three-dimensional network that gelated into a hydrogel. The PPy hydrogel could be synthesized in bulk quantities with uniform morphology of self-assembled interconnected nanofibers. The tetra-functional dopant favors a supramolecular self-assembly mechanism to form one-dimensional PPy nanostructures. Furthermore, the enhanced interchain charge transport of CuPcTs doped PPy resulted in greatly enhanced conductivity and pseudocapacitance compared with pristine PPy