Radiomics-based model for prediction of TGF-ß1 expression in head and neck squamous cell carcinoma.

OBJECTIVE: To explore the connection between TGF-ß1 expression and the survival of patients with head and neck squamous cell carcinoma (HNSCC), as well as whether non-invasive CT-based Radiomics can predict TGF-ß1 expression in HNSCC patients. METHODS: Data on transcriptional profiling and clinical information were acquired from the TCGA database and subsequently categorized based on the TGF-ß1 expression cutoff value. Based on the completeness of enhanced arterial phase CT scans, 139 HNSCC patients were selected. The PyRadiomics package was used to extract radiomic features, and the 3D Slicer software was used for image segmentation. Using the mRMR_RFE and Repeat LASSO algorithms, the optimal features for establishing the corresponding gradient enhancement prediction models were identified. RESULTS: A survival analysis was performed on 483 patients, who were divided into two groups based on the TGF-ß1 expression cut-off. The Kaplan-Meier curve indicated that TGF-ß1 was a significant independent risk factor that reduced patient survival. To construct gradient enhancement prediction models, we used the mRMR_RFE algorithm and the Repeat_LASSO algorithm to obtain two features (glrlm and ngtdm) and three radiation features (glrlm, first order_10percentile, and gldm). In both the training and validation cohorts, the two established models demonstrated strong predictive potential. Furthermore, there was no statistically significant difference in the calibration curve, DCA diagram, or AUC values between the mRMR_RFE_GBM model and the LASSO_GBM model, suggesting that both models fit well. CONCLUSION: Based on these findings, TGF-ß1 was shown to be significantly associated with a poor prognosis and to be a potential risk factor for HNSCC. Furthermore, by employing the mRMR_RFE_GBM and Repeat_LASSO_GBM models, we were able to effectively predict TGF-ß1 expression levels in HNSCC through non-invasive CT-based Radiomics.

CircPOLA2 sensitizes non-small cell lung cancer cells to ferroptosis and suppresses tumorigenesis via the Merlin-YAP signaling pathway.

Circular RNAs (circRNAs) have been implicated in the tumorigenesis of non-small cell lung cancer (NSCLC). Ferroptosis is considered a mechanism to suppress tumorigenesis. Herein, we identified a downregulated circRNA, circPOLA2 (hsa_circ_0004291), in NSCLC tissues and found that it was correlated with advanced clinical stage in patients. Nuclear-cytoplasmic fractionation assays and FISH assays confirmed that circPOLA2 was predominantly localized in the cytoplasm. Overexpression of circPOLA2 promoted lipid peroxidation and ferroptosis in NSCLC cells, thereby inhibiting cell proliferation and migration, while knockdown of circPOLA2 exerted the opposite effects. Mechanistically, circPOLA2 interacted with Merlin, a critical regulator of the Hippo pathway, and restricted Merlin phosphorylation at S518, leading to the activation of the Hippo pathway. In addition, circPOLA2 enhanced ferroptosis in NSCLC cells by activating the Hippo pathway. Together, circPOLA2 sensitizes cells to ferroptosis and suppresses tumorigenesis in NSCLC by facilitating Merlin-mediated activation of the Hippo signaling pathway.

[Constructing an indexing template for ancient acupuncture medical cases based on knowledge element theory].

Ancient acupuncture medical cases not only possess historical literary value but also hold significant clinical importance. To enhance the utilization of ancient acupuncture medical cases and to guide the excavation of acupuncture theory and its clinical application, this study constructs an indexing template for "Ancient Acupuncture Medical Cases" based on the knowledge element theory and the fine-grained indexing requirements of ancient acupuncture texts. This template includes two levels, 7 categories, 28 knowledge element data, 31 semantic types, and 15 semantic relationships. These element data construct the interconnections of knowledge in ancient acupuncture medical cases, serving as a basis for fine-grained indexing of acupuncture medical case literature.

Characterization and structure-functionality analysis of starch in different layers of Lycoris chinensis bulb scales.

According to literature, the size distribution of starch granules varies significantly in different layers of Lycoris chinensis bulb scales, however its effect on structural and physicochemical properties of starch still remains unclear. In this study, outer, middle and inner layers of bulb scales of L. chinensis were compared for starch characteristics. Also, the structure-functionality association was investigated based on correlation analysis and hierarchical cluster analysis, using 37 starch quality traits. Compared to commonly consumed starches with similar amylose content, L. chinensis starch gel had lower hardness and viscosities. Among layers, starches varied significantly in particle size, physicochemical and structural properties. As compared to middle and inner scales, the starch in outer scales had higher amylose content, hardness and viscosities, but lower gelatinization temperature, weight-average molar mass and degree of polymorphism. Correlation analysis revealed significant correlations among traits, and interestingly, gelatinization temperature (Tp) was found positively correlated to traits of molecular weight (p < 0.05). The 37 traits of starch characteristics can be divided into three subgroups, as supported by the results of Pearson correlation analysis and hierarchical cluster analysis. In general, the information presented in the current study are useful for Lycoris bulb starch utilization and insightful for a better understanding of structure-functionality association of starch.

Xantolisweimingii (Sapotaceae), a new species from the Yuanjiang River basin, Yunnan, southwest China.

Xantolisweimingii sp. nov. (Sapotaceae) is described and illustrated from Yunnan, southwest China. The new species is morphologically most similar to X.tomentosa (Roxb.) Raf., but differs from the latter in the ovate or obovate leaves, entirely glabrous corollas, lanceolate, ca. 5 mm long staminodes, fringed at the base. We provided a distribution map and a preliminary conservation assessment for the new species. Additionally, an updated dichotomous key to all known species of Xantolis is presented.

Developing a Palladium(II) Agent to Overcome Multidrug Resistance and Metastasis of Liver Tumor by Targeted Multiacting on Tumor Cell, Inactivating Cancer-Associated Fibroblast and Activating Immune Response.

To targeted overcome the multidrug resistance (MDR) and metastasis of liver tumors, we proposed to develop a palladium (Pd) agent based on a specific residue of human serum albumin (HSA) for multiacting on tumor cell and other components in the tumor microenvironment. To this end, a series of Pd(II) 2-acetylpyridine thiosemicarbazone compounds were optimized to obtain a Pd(II) compound (5b) with significant cytotoxicity against HepG2/ADM cells. Subsequently, we constructed a HSA-5b complex delivery system and revealed the structural mechanism of HSA delivering 5b. Importantly, 5b/HSA-5b effectively inhibited the growth and metastasis of multidrug resistant liver tumors, and HSA enhanced the targeting ability of 5b and reduced its side effects in vivo. Furthermore, we confirmed the mechanisms of 5b/HSA-5b integrating to overcome MDR and metastasis of liver tumors: multiacting on cancer cell, activating immune response, and inactivating cancer-associated fibroblasts.

Object and spatial discrimination makes weakly supervised local feature better.

Local feature extraction plays a crucial role in numerous critical visual tasks. However, there remains room for improvement in both descriptors and keypoints, particularly regarding the discriminative power of descriptors and the localization precision of keypoints. To address these challenges, this study introduces a novel local feature extraction pipeline named OSDFeat (Object and Spatial Discrimination Feature). OSDFeat employs a decoupling strategy, training descriptor and detection networks independently. Inspired by semantic correspondence, we propose an Object and Spatial Discrimination ResUNet (OSD-ResUNet). OSD-ResUNet captures features from the feature map that differentiate object appearance and spatial context, thus enhancing descriptor performance. To further improve the discriminative capability of descriptors, we propose a Discrimination Information Retained Normalization module (DIRN). DIRN complementarily integrates spatial-wise normalization and channel-wise normalization, yielding descriptors that are more distinguishable and informative. In the detection network, we propose a Cross Saliency Pooling module (CSP). CSP employs a cross-shaped kernel to aggregate long-range context in both vertical and horizontal dimensions. By enhancing the saliency of keypoints, CSP enables the detection network to effectively utilize descriptor information and achieve more precise localization of keypoints. Compared to the previous best local feature extraction methods, OSDFeat achieves Mean Matching Accuracy of 79.4% in local feature matching task, improving by 1.9% and achieving state-of-the-art results. Additionally, OSDFeat achieves competitive results in Visual Localization and 3D Reconstruction. The results of this study indicate that object and spatial discrimination can improve the accuracy and robustness of local feature, even in challenging environments. The code is available at https://github.com/pandaandyy/OSDFeat.

The impact of high-altitude migration on cardiac structure and function: a 1-year prospective study.

Introduction: The trend of human migration to terrestrial high altitudes (HA) has been increasing over the years. However, no published prospective studies exist with follow-up periods exceeding 1 month to investigate the cardiac change. This prospective study aimed to investigate the changes in cardiac structure and function in healthy young male lowlanders following long-term migration to HA. Methods: A total of 122 Chinese healthy young males were divided into 2 groups: those migrating to altitudes between 3600 m and 4000 m (low HA group, n = 65) and those migrating to altitudes between 4000 m and 4700 m (high HA group, n = 57). Traditional echocardiographic parameters were measured at sea level, 1 month and 1 year after migration to HA. Results: All 4 cardiac chamber dimensions, areas, and volumes decreased after both 1 month and 1 year of HA exposure. This reduction was more pronounced in the high HA group than in the low HA group. Bi-ventricular diastolic function decreased after 1 month of HA exposure, while systolic function decreased after 1 year. Notably, these functional changes were not significantly influenced by altitude differences. Dilation of the pulmonary artery and a progressive increase in pulmonary artery systolic pressure were observed with both increasing exposure time and altitude. Additionally, a decreased diameter of the inferior vena cava and reduced bicuspid and tricuspid blood flow velocity indicated reduced blood flow following migration to the HA. Discussion: 1 year of migration to HA is associated with decreased blood volume and enhanced hypoxic pulmonary vasoconstriction. These factors contribute to reduced cardiac chamber size and slight declines in bi-ventricular function.

Whole-Genome Analyses Reveal the Distinct Taxonomic Status of the Hainan Population of Endangered Rucervus eldii and Its Conservation Implications.

Eld's deer Rucervus eldii (McClelland, 1842) is an ungulate that lives in tropical lowland forests in several countries of Indochina and Hainan Island of China. Its remaining population is small and scattered, and the species is listed as an Endangered species on the IUCN Red List. The debate over the taxonomic status of the Hainan population has persisted for over a century-as an island-endemic subspecies R. e. hainanus, or an insular population of the subspecies R. e. siamensis, would have significant conservation implications. And, given the Hainan population had experienced both population bottleneck and multiple translocations in the past, conservation genomics would be a powerful tool to evaluate the genetic impacts of these events. In this study, we used conservation genomics assessment to study population differentiation and genetic diversity of R. e. siamensis in Cambodia and three Eld's deer subpopulations on Hainan Island. Based on the unique genetic profile and demographic analysis, this study corroborated previous studies using genetic markers that the Hainan Eld's deer warrants the taxonomic status of a distinct subspecies. The Hainan population exhibits a reduction in genetic diversity and an increase in the level of inbreeding when compared to the population of Cambodia. The signs of purifying selection were found against homozygous loss-of-function mutations to decrease the deleterious burden in the Hainan population. However, there was an accumulation of more deleterious missense mutations. Furthermore, significant differences in genetic diversity and level of inbreeding found among the three Hainan subpopulations indicated population isolation and suboptimal translocation strategies, which calls for urgent, coordinated, and science-based genetic management to ensure the long-term viability of the endemic subspecies hainanus. This study provides guidance for the conservation and management of Eld's deer.

Advances in Liquid-Phase Assembly of Clusters into Single-Walled Carbon Nanotubes.

Insight into the behaviors of molecules in confined space is highly desired for the deep understanding of the mechanism of chemical reactions in a microenvironment. Yet the direct access of molecular evolutions at atomic resolution in nanoconfinements is still challenging. Among various guests, atomically precise clusters with well-defined structures are better suited for monitoring the chemical and physical processes in nanochannels because of their visibility under electron microscopy and identical structures that ensure homogeneous interactions. Developing an efficient method for assembling clusters into a confined space is essential for advancing mechanisms of these processes. In this Perspective, we provide an overview of the assembly of clusters into single-walled carbon nanotubes (SWCNTs) in the liquid phase. We begin with the introduction of assembling methodologies, followed by a discussion of mechanisms of confined assembly in liquids. The host-guest interactions between clusters and nanotubes and the molecular reactions in nanochannels revealed by transmission electron microscopy are unveiled, and the cluster@SWCNT heterostructure-based emerging applications are highlighted. At the end, we discuss the challenges and opportunities and expound our outlook in this field.

Anticancer Tetranuclear Cu(I) Complex Catalyzes a Click Reaction to Synthesize a Chemotherapeutic Agent in situ to Achieve Targeted Dual-Agent Combination Therapy for Cancer.

To develop next-generation metal-based drugs and dual-drug combination therapy for cancer, we proposed to develop a copper (Cu) complex that exerts anticancer function by integrating chemotherapy, immunotherapy and catalyzes a click reaction for the in situ synthesis of a chemotherapeutic agent, thereby achieving targeted dual-agent combination therapy. We designed and synthesized a tetranuclear Cu(I) complex (Cu4) with remarkable cytotoxicity and notable catalytic ability for the in situ synthesis of a chemotherapeutic agent via Cu(I)-catalyzed azide-alkyne 1,3-cycloaddition (CuAAC). We also constructed an apoferritin (AFt)-Cu4 nanoparticles (NPs) delivery system. AFt-Cu4 NPs not only showed an enhanced performance of tumor growth inhibition, but also improved the targeting ability and reduced the systemic toxicity of Cu4 in vivo. Importantly, the anticancer effect was enhanced by combining the AFt-Cu4 NPs with the resveratrol analogue obtained from the CuAAC reaction in situ. Finally, we revealed the anticancer mechanism of the Cu4/AFt-Cu4 NPs, which involves both cuproptosis and cuproptosis-induced systemic immune response.

Developing a Rhodium(III) Complex to Reprogram the Tumor Immune and Metabolic Microenvironments: Overcoming Multidrug Resistance and Metastasis in Non-Small Cell Lung Cancer.

To effectively inhibit the growth and metastasis of non-small cell lung cancer (NSCLC) and overcome its multidrug resistance (MDR), we designed and synthesized a series of rhodium (Rh, III) 2-benzoylpyridine thiosemicarbazone complexes. Through studying their structure-activity relationships, we identified the Rh(III) complex (Rh4) with excellent cytotoxicity against multidrug-resistant lung cancer cells (A549/ADR cells). Additionally, we successfully constructed an apoferritin (AFt) nanoparticle (NP) delivery system (AFt-Rh4 NPs). Importantly, AFt-Rh4 NPs not only exhibited excellent antitumor and antimetastatic capabilities against multidrug-resistant NSCLC in vivo but also demonstrated enhanced targeting ability and reduced systemic toxicity and adverse effects. Furthermore, we confirmed and elucidated the mechanisms by which Rh4/AFt-Rh4 NPs inhibit tumor metastasis and reverse MDR in NSCLC. This was achieved by reprogramming the immune and metabolic tumor microenvironments through induction of immunogenic cell death and inhibition of dual-energy metabolism.

Air-microwave simultaneously induced carbon fiber surface oxidation and magnetism adjustment by CoOx nanoparticles rapid assembly for interface enhancement and electromagnetic wave absorption of its composites.

It is a significant challenge to develop a fast carbon fiber (CF) surface modification method, especially for the high strength electromagnetic wave (EMW) absorption materials. Herein, magnetic CoOx nanoparticles are successfully synthesized and uniformly assembled on CF surface with high oxygen-containing groups by rapid ambient microwave carbon thermal shock (MCTS). The presence of oxygen defect sites on CF surface promotes CoOx nanoparticles nucleation. The number of oxygen defects and the types of magnetic nanoparticles on the CF surface effectively adjust the surface chemical activity and the electromagnetic properties of CF, which is conducive to improving the EMW absorption performance and interface compatibility of the CoOx nanoparticles modified CF reinforced polyamide 6 (CO@CF/PA6) composites. Compared with CO@CF-0 s/PA6, the tensile strength and modulus of CO@CF-3.5 s/PA6 composite are increased by 18.1 % and 18.6 %, respectively. It also displays a minimum reflection loss value (-59.9 dB) at a thinner thickness of 1.9 mm while the maximum effective absorption bandwidth reaches 5.02 GHz with a thickness of 1.8 mm. Its radar cross-section values exhibit less than -10 dBm2 at all tested detection angles. This rapid MCTS shows great potential for large-scale production of CF modification with low-cost, efficient and environmentally friendly process.

Polycaprolactone/gelatin/ZIF-8 nanofiber membrane for advanced guided tissue regeneration in periodontal therapy.

The periodontal tissue regeneration strategy based on guided tissue regeneration (GTR) membranes is an effective therapy for periodontal defects. Traditional GTR membranes, however, primarily serve as physical barriers and lack antimicrobial and osteogenic functions. Herein, we developed a multifunctional nanofiber membrane with zeolitic imidazolate framework-8 nanoparticles (ZIF-8 NPs) loaded in a hydrophilic gelatin layer. The release of Zn2+ from the ZIF-8 NPs effectively promoted bone tissue repair and simultaneously enabled GTR membranes with >99 % antibacterial efficacies against Escherichia coli and Staphylococcus aureus. Additionally, the incorporation of gelatin enhances cellular adhesion and growth. Furthermore, in vivo studies revealed significant bone regeneration, with increased trabecular number and reduced separation. Owing to its multiple functions, excellent biocompatibility and desirable mechanical properties, this membrane has considerable potential in the field of periodontal therapy.

Directional growth and reconstruction of ultrafine uranium oxide nanorods within single-walled carbon nanotubes.

Understanding the atomic structures and dynamic evolution of uranium oxides is crucial for the reliable operation of fission reactors. Among them, U4O9-as an important intermediate in the oxidation of UO2 to UO2+x -plays an important role in the nucleation and conversion of uranium oxides. Herein, we realize the confined assembly of uranyl within SWCNTs in liquid phase and reveal the directional growth and reconstruction of U4O9 nanorods in nanochannels, enabled by in situ scanning transmission electron microscopy (STEM) e-beam stimulation. The nucleation and crystallization of U4O9 nanorods in nanochannels obey the "non-classical nucleation" mechanism and exhibit remarkably higher growth rate compared to those grown outside. The rapid growth process is found to be accompanied by the formation and elimination of U atom vacancies and strain, aiming to achieve the minimum interfacial energy. Eventually, the segments of U4O9 nanorods in SWCNTs merge into single-crystal U4O9 nanorods via structural reconstruction at the interfaces, and 79% of them exhibit anisotropic growth along the specific 〈11̄0〉 direction. These findings pave the way for tailoring the atomic structures and interfaces of uranium oxides during the synthesis process to help improve the mechanical properties and stability of fission reactors.

Systemic immunoinflammatory index and prognostic nutrition index for predicting pathologic responses of patients with advanced gastric cancer after neoadjuvant therapy for advanced gastric cancer.

To investigate the value of prognostic nutrition index (PNI) and systemic immunoinflammatory index (SII) for predicting pathological responses of patients with advanced gastric cancer (GC) after neo-adjuvant chemotherapy (NACT). The clinicopathological data of 326 patients with advanced GC who received NACT in Xiangya School of Medicine, Central South University (The First People's Hospital of Changde City) from January 2017 to December 2021 were retrospectively collected. The SII and PNI of patients were calculated. The receiver operating characteristics (ROC) curve was leveraged for getting the optimal cutoff values of SII and PNI. The pathological response of patients after NACT, as obtained from their postoperative pathological examinations, was evaluated based on the tumor regression grade (TRG) criteria. Multivariate regression analysis was employed for identifying factors that led to various pathological responses after NACT in advanced GC patients. The log-rank test was utilized for between-group comparison of patients' survival curves. The SII and PNI were 507.45 and 48.48 respectively, and their levels were divided into high and low groups. Pathological response (TRG 0-1) was observed in 66 cases (20.25%), while non-pathological response (TRG 2-3) was observed in 260 cases (79.75%). The results of multivariate logistic regression analysis showed that tumor diameter < 5 cm, ypT T0-T2, ypN N0, chemotherapy regimen XELOX (capecitabine combined with oxaliplatin), SII < 507.45 (P=0.002), PNI > 48.48 were all independent factors affecting the pathological responses of advanced GC patients after NACT (all P < 0.05). With SII and PNI being included, the AUC was 0.821 (95% CI: 0.765-0.876), and the specificity was 87.90% and the sensitivity was 64.20%. The Kaplan-Meier survival curve analysis showed that NACT patients with tumor diameter < 5 cm, ypT T0-T2, ypN N0, XELOX chemotherapy regimen, SII < 507.45 and SII ≥ 507.45 had a higher survival rate. (P < 0.001). Before treatment, tumor diameter < 5 cm, ypT T0-T2, ypN N0, chemotherapy regimen XELOX, SII < 507.45, PNI > 48.48 were all independent factors affecting the pathological response of advanced GC patients after NACT. Moreover, the inclusion of SII and PNI increased the accuracy of predicting the pathological response of patients after NACT.

Hyperbaric oxygen treatment promotes tendon-bone interface healing in a rabbit model of rotator cuff tears.

Due to the high-intensity pressure that the shoulder cuff endures, it is prone to traumas and tears. The main critical function of the shoulder cuff muscles is to effectively facilitate shoulder movement and securely maintain the humeral head in the precise center of the joint cavity to prevent superior migration during abduction processes. Shoulder cuff injuries typically involve the muscle-tendon-bone interface, but existing repair techniques do not always guarantee complete and secure healing, leading to retears. Hyperbaric oxygen therapy, as an auxiliary treatment, can significantly promote the muscle-tendon-bone healing process. To explore the impact of hyperbaric oxygen therapy on the bone-tendon interface healing process in a rabbit model specifically designed for shoulder cuff tears, an experiment was conducted on New Zealand white rabbits by performing a full-thickness tear of the supraspinatus tendon in the left shoulder, followed by 2 hours per day of 100% oxygen treatment at 2 absolute atmospheres for 5 days. The results indicate that hyperbaric oxygen therapy significantly enhances vascularization at the interface between the shoulder cuff and tendon-bone, promotes collagen fiber regeneration in the tendon, improves the tensile strength of the tendon-bone complex, and does not have a significant effect on biomechanical stability. This suggests that hyperbaric oxygen therapy has a significant positive impact on the histological and biomechanical healing of shoulder cuff tears in rabbits, expediting the healing process of the tendon-bone interface.

Modulations in gastrointestinal microbiota during postpartum period fulfill energy requirements and maintain health of lactating Tibetan cattle.

Introduction: Postpartum period of dairy cattle is an important phase of their life mainly associated with the changes in physiology, rumen function, and energy metabolism. Studies have shown that gut microbial composition undergoes drastic changes during the postpartum period. However, little is known about the temporal variations in digestive tract microbiota in postpartum Tibetan cattle. The aim of this study was to investigate the temporal variations in blood metabolites, ruminal fermentation, and microbial community of oral, rumen, and gut in lactating Tibetan cattle during postpartum. Methods: We collected blood, saliva, rumen fluid, and fecal samples from lactating Tibetan cattle during 1st week (1 W), the 2nd week (2 W), the 1st month (1 M), and the 2nd month (2 M) of the postpartum period. The microbiota of saliva, rumen fluid, and fecal samples were assessed using 16S rRNA sequencing. The rumen volatile fatty acid and blood parameters were also quantified. Results: The content of volatile fatty acids (VFAs) and blood parameters showed opposite tendency to each other and reached to stability at 2 M. Rumen microbiota showed the highest alpha diversity compared to other two sites. At phylum level, the oral cavity was dominated by Proteobacteria, while most dominant phylum in rumen and feces were Firmicutes and Bacteroidetes, respectively. The dominant genera in oral cavity were Moraxella and Bibersteinia, while genera Prevotella 1 and Ruminococcaceae UCG-005 were dominant in rumen and fecal samples, respectively. Discussion: Microbial network analysis revealed that most of the active genera in all networks belonged to phylum Firmicutes, indicating the importance of this phyla during postpartum period of lactating cattle. The functional analysis revealed distinct division of labor among three gastrointestinal sites associated with defense, fatty acid synthesis, and maintaining health of host. All in all, our findings provide insights into the metabolic and microbial changes of lactating Tibetan cattle and help to the improvement of the management strategies.

Phenotyping Refractory Cardiogenic Shock Patients Receiving Venous-Arterial Extracorporeal Membrane Oxygenation Using Machine Learning Algorithms.

Background: This study used machine learning to categorize cardiogenic shock (CS) patients treated with venous-arterial extracorporeal membrane oxygenation (VA-ECMO) into distinct phenotypes. Subsequently, it aimed to clarify the wide mortality variance observed in refractory CS, attributing it to the condition's inherent heterogeneity. Methods: This study enrolled a cohort of CS patients who received VA-ECMO support. By employing rigorous machine learning (ML) techniques, we generated and validated clusters based on determinants identified through algorithmic analysis. These clusters, characterized by distinct clinical outcomes, facilitated the examination of clinical and laboratory profiles to enhance the understanding of patient responses to VA-ECMO treatment. Results: In a study of 210 CS patients undergoing VA-ECMO treatment, 70.5% were male with a median age of 62, ranging from 53 to 67 years. Survival rates were 67.6% during VA-ECMO and 49.5% post-discharge. Patients were classified into three phenotypes based on the clinical and laboratory findings: "platelet preserved (I)", those with stable platelet counts, "hyperinflammatory (II)", those indicating significant inflammation, and "hepatic-renal (III)", those showing compromised liver and kidney functions. Mortality rates (25.0%, 52.8%, and 55.9% for phenotypes I, Ⅱ, and Ⅲ, respectively (p = 0.005)) varied significantly among these groups, highlighting the importance of phenotype identification in patient management. Conclusions: This study identified three distinct phenotypes among refractory CS patients treated using VA-ECMO, each with unique clinical characteristics and mortality risks. Thus, highlighting the importance of early detection and targeted intervention, these findings suggest that proactive management could improve outcomes for those showing critical signs.

Impacts of the COVID-19 pandemic on pediatric and adult patients with hemophilia.

BACKGROUND: The coronavirus disease 2019 (COVID-19)-associated mortality rate of hemophilia patients is similar to that of the general population, but the risk of hospitalization and bleeding is higher. However, the specific impact of this infection on hemophilia patients remains unknown. We aimed to investigate the impact of the pandemic on the infection susceptibility, symptoms, drug use, and social intercourse of patients with hemophilia. METHODS: A survey was distributed to 265 patients with hemophilia (185 adults and 80 children) in the Fujian hemophilia therapeutic center (Fuzhou City, China) during the COVID-19 pandemic, and data were collected between January 2022 and January 2023. The impacts of SARS-CoV-2 infection on hemophilia symptoms, drug use, and social intercourse of these patients were investigated, and the association between the recovery time and disease conditions was explored in infected patients. RESULTS: During the pandemic, compared with adult patients, pediatric patients had significantly reduced social intercourse and outdoor activities because of the fear of contracting COVID-19 (85.0% vs. 66.5%). Bleeding events were also significantly fewer in children than in adults (61.2% vs. 81.1%). The SARS-CoV-2 infection rate was significantly higher in patients living in urban areas than in those living in rural areas (74.3% vs. 53.6%). The duration of symptomatic recovery from COVID-19 was not significantly associated with hemorrhage, type and classification of hemophilia, presence of inhibitors, complications, and vaccination status. CONCLUSION: Having COVID-19 infection did not significantly influence the symptoms and treatments in patients with hemophilia. Pediatric patients had significantly fewer bleeding events than adults.