Development and status quo of digestive endoscopy in China: An analysis based on the national census in 2013 and 2020.

Background and Objectives: Technique and practice of digestive endoscopy are undergoing speedy development all over the world. This study aimed to evaluate its status quo and development in China. Methods: All hospitals performing digestive endoscopy in mainland China participated in the national census in 2013 and 2020. Retrospective data of hospitals, endoscopists, volumes, and qualities were collected via an online structured questionnaire, and its accuracy and rationality were verified by logical tests and manual reviews. Data from other countries were used to compare with that of China. Results: From 2012 to 2019, the number of hospitals performing digestive endoscopy increased from 6,128 to 7,470 (1.22-fold), in which primary healthcare played a minor role. The median hospitals per 100,000 inhabitants per provincial region increased from 0.49 (IQR, 0.39-0.57) to 0.55 (IQR, 0.49-0.63). The endoscopists increased from 26,203 to 39,638 (1.51-fold), but their average workload even expanded. Overall volume increased from 28.8 million to 44.5 million (1.55-fold), and most types of endoscopic procedures recorded a high growth rate. Contrastingly, the specific utilization rates were low and paled in comparison with some developed countries. Nationwide, regional utilization rates showed a significant correlation with GDP per capita (P <0.001). Overall qualities of digestive endoscopy were excellent, but certain results of quality indicators posed a huge challenge, such as the detection rates of adenoma and early cancers. Conclusions: Impressive progress has been made in digestive endoscopy with rapidly expanding economy in China. However, primary healthcare, utilization rates, and income-related inequality of regional services were needed to be improved to promote public health better.

Validation of an automated iron stain process for use with bone marrow aspirate smear slides.

The assessment of bone marrow iron stores is typically performed on an aspirate smear slide that has been manually stained by a technologist using a commercially available kit. This approach can contribute to inconsistent results and limit the broad use of iron staining in bone marrow specimens, particularly when laboratories have low staffing and/or high specimen volumes. Here, we describe the adaptation and validation of the Ventana Benchmark automated stainer and iron stain kit for routine clinical use of staining iron in bone marrow aspirate smear slides. We assessed accuracy and precision of the Ventana automated iron staining protocol compared to the Perls Prussian blue manual iron staining index method. Hematopathologists assigned Gale scores and enumerated the percentages of erythroid sideroblasts on paired patient bone marrow aspirate smear slides stained by the automated method and the manual iron staining method. We found a similar level of performance of the Ventana automated iron stain relative to the index manual method (as assessed by Pearson correlation and Bland-Altman analyses). In addition, there was low imprecision between replicates performed via the automated iron stain protocol. We also report superior qualitative findings of the automated method in ease of localization of iron storage, visualization of sideroblasts, and counterstain consistency. Automated iron staining of bone marrow aspirate smear slides performed similarly to the manual method and may allow for accurate routine evaluation of bone marrow iron stores as part of bone marrow analysis.

Boosting Formate Electrooxidation by Heterostructured PtPd Alloy and Oxides Nanowires.

Direct formate fuel cells (DFFCs) receive increasing attention as promising technologies for the future energy mix and environmental sustainability, as formate can be made from carbon dioxide utilization and is carbon neutral. Herein, heterostructured platinum-palladium alloy and oxides nanowires (PtPd-ox NWs) with abundant defect sites are synthesized through a facile self-template method and demonstrated high activity toward formate electrooxidation reaction (FOR). The electronic tuning arising from the heterojunction between alloy and oxides influence the work function of PtPd-ox NWs. The sample with optimal work function reveals the favorable adsorption behavior for intermediates and strong interaction in the d-p orbital hybridization between Pt site and oxygen in formate, favoring the FOR direct pathway with a low energy barrier. Besides the thermodynamic regulation, the heterostructure can also provide sufficient hydroxyl species to facilitate the formation of carbon dioxide due to the ability of combining absorbed hydrogen and carbon monoxide at adjacent active sites, which contributes to the improvement of FOR kinetics on PtPd-ox NWs. Thus, heterostructured PtPd-ox NWs achieve dual regulation of FOR thermodynamics and kinetics, exhibiting remarkable performance and demonstrating potential in practical systems.

Cellulose separation from ramie bone by one step process with green hydrogen peroxide-citric acid.

Ramie bone (RB), an agricultural waste generated in the textile industry, is a vastly productive renewable natural resource with the potential to be used as a source of cellulose. In this study, ramie bone cellulose (RB-CE) was obtained in one step using a simple and ecologically friendly hydrogen peroxide-citric acid (HPCA) treatment procedure that avoided the use of halogenated reagents and strong acids while also streamlining the treatment processes. Various analytical methods were used to investigate the chemical composition and structure, crystallinity, morphology, thermal properties, surface area and hydration properties of cellulose separated at different treatment temperatures. HPCA successfully removed lignin and hemicellulose from RB, according to chemical composition analysis and FTIR. RB-CE had a type I cellulose crystal structure, and the crystallinity improved with increasing treatment temperature, reaching 72.51 % for RB-CE90. The RB-CE showed good thermal stability with degradation temperatures ranging from 294.2 °C to 319.1 °C. Furthermore, RB-CE had a high water/oil binding capacity, with RB-CE90 having WHC and OBC of 9.68 g/g and 7.24 g/g, respectively. The current work serves as a model for the environmentally friendly and convenient extraction of cellulose from biomass, and the cellulose obtained can be employed in the field of food and composite materials.

A multi-omics study to monitor senescence-associated secretory phenotypes of Alzheimer's disease.

OBJECTIVE: Alzheimer's disease (AD) is characterized by the progressive degeneration and damage of neurons in the brain. However, developing an accurate diagnostic assay using blood samples remains a challenge in clinic practice. The aim of this study was to explore senescence-associated secretory phenotypes (SASPs) in peripheral blood using mass spectrometry based multi-omics approach and to establish diagnostic assays for AD. METHODS: This retrospective study included 88 participants, consisting of 29 AD patients and 59 cognitively normal (CN) individuals. Plasma and serum samples were examined using high-resolution mass spectrometry to identify proteomic and metabolomic profiles. Receiver operating characteristic (ROC) analysis was employed to screen biomarkers with diagnostic potential. K-nearest neighbors (KNN) algorithm was utilized to construct a multi-dimensional model for distinguishing AD from CN. RESULTS: Proteomics analysis revealed upregulation of five plasma proteins in AD, including RNA helicase aquarius (AQR), zinc finger protein 587B (ZNF587B), C-reactive protein (CRP), fibronectin (FN1), and serum amyloid A-1 protein (SAA1), indicating their potential for AD classification. Interestingly, KNN-based three-dimensional model, comprising AQR, ZNF587B, and CRP, demonstrated its high accuracy in AD recognition, with evaluation possibilities of 0.941, 1.000, and 1.000 for the training, testing, and validation datasets, respectively. Besides, metabolomics analysis suggested elevated levels of serum phenylacetylglutamine (PAGIn) in AD. INTERPRETATION: The multi-omics outcomes highlighted the significance of the SASPs, specifically AQR, ZNF587B, CRP, and PAGIn, in terms of their potential for diagnosing AD and suggested neuronal aging-associated pathophysiology.

Tracking Fat Grafts by Magnetic Resonance Imaging: A Comparative Study of Adolescent and Adult Patients with Stable Localized Scleroderma.

BACKGROUND: The optimal timing of reconstruction for patients with facial localized scleroderma is uncertain. The purpose of this study was to compare the outcomes of autologous fat transplantation in adolescent and adult patients with stable localized scleroderma. METHODS: Adolescent (age 10-19 years) and adult (age >19 years) patients with no previous surgery were enrolled (n = 10, each group). Preoperative magnetic resonance imaging (MRI), blood tests and dermatological assessments were used for disease activity assessment. All patients underwent autologous fat transplantation for anatomic facial fat restoration with preoperative MRI planning. Preoperative, immediate and one-year postoperative 3D Dixon MRI scans with image registration and fusion techniques were used for fat graft tracking. Patient satisfaction was assessed with a 5-point Likert scale. RESULTS: There was no significant difference in sex, body mass index, disease severity, or volume of injected fat between the two groups (p > 0.05), except for age (p < 0.05). The one-year postoperative fat graft retention rate was not significantly different, with 36.6 ± 2.4% (ranging from 25.3 to 49.3%) in the adolescent group and 32.9 ± 1.7% (ranging from 27.3 to 40.1%) in the adult group (p > 0.05). Surgical outcomes were favorable in all patients, with satisfaction scores of 3.8 ± 0.2 points in the adolescent group and 3.6 ± 0.2 points in the adult group (p > 0.05). CONCLUSION: In stable localized scleroderma, the initial autologous fat transplantation was equally effective for facial contour deformity improvement, with no significant difference in fat graft retention or satisfaction.

Selective hydrodeoxygenation of α, ß-unsaturated carbonyl compounds to alkenes.

Achieving selective hydrodeoxygenation of α, ß-unsaturated carbonyl groups to alkenes poses a substantial challenge due to the presence of multiple functional groups. In this study, we develop a ZnNC-X catalyst (X represents the calcination temperature) that incorporates both Lewis acidic-basic sites and Zn-Nx sites to address this challenge. Among the catalyst variants, ZnNC-900 catalyst exhibits impressive selectivity for alkenes in the hydrodeoxygenation of α, ß-unsaturated carbonyl compounds, achieving up to 94.8% selectivity. Through comprehensive mechanism investigations and catalyst characterization, we identify the Lewis acidic-basic sites as responsible for the selective hydrogenation of C=O bonds, while the Zn-Nx sites facilitate the subsequent selective hydrodeoxygenation step. Furthermore, ZnNC-900 catalyst displays broad applicability across a diverse range of unsaturated carbonyl compounds. These findings not only offer valuable insights into the design of effective catalysts for controlling alkene selectivity but also extend the scope of sustainable transformations in synthetic chemistry.

Afamitresgene autoleucel for advanced synovial sarcoma and myxoid round cell liposarcoma (SPEARHEAD-1): an international, open-label, phase 2 trial.

BACKGROUND: Afamitresgene autoleucel (afami-cel) showed acceptable safety and promising efficacy in a phase 1 trial (NCT03132922). The aim of this study was to further evaluate the efficacy of afami-cel for the treatment of patients with HLA-A*02 and MAGE-A4-expressing advanced synovial sarcoma or myxoid round cell liposarcoma. METHODS: SPEARHEAD-1 was an open-label, non-randomised, phase 2 trial done across 23 sites in Canada, the USA, and Europe. The trial included three cohorts, of which the main investigational cohort (cohort 1) is reported here. Cohort 1 included patients with HLA-A*02, aged 16-75 years, with metastatic or unresectable synovial sarcoma or myxoid round cell liposarcoma (confirmed by cytogenetics) expressing MAGE-A4, and who had received at least one previous line of anthracycline-containing or ifosfamide-containing chemotherapy. Patients received a single intravenous dose of afami-cel (transduced dose range 1·0 × 109-10·0 × 109 T cells) after lymphodepletion. The primary endpoint was overall response rate in cohort 1, assessed by a masked independent review committee using Response Evaluation Criteria in Solid Tumours (version 1.1) in the modified intention-to-treat population (all patients who received afami-cel). Adverse events, including those of special interest (cytokine release syndrome, prolonged cytopenia, and neurotoxicity), were monitored and are reported for the modified intention-to-treat population. This trial is registered at ClinicalTrials.gov, NCT04044768; recruitment is closed and follow-up is ongoing for cohorts 1 and 2, and recruitment is open for cohort 3. FINDINGS: Between Dec 17, 2019, and July 27, 2021, 52 patients with cytogenetically confirmed synovial sarcoma (n=44) and myxoid round cell liposarcoma (n=8) were enrolled and received afami-cel in cohort 1. Patients were heavily pre-treated (median three [IQR two to four] previous lines of systemic therapy). Median follow-up time was 32·6 months (IQR 29·4-36·1). Overall response rate was 37% (19 of 52; 95% CI 24-51) overall, 39% (17 of 44; 24-55) for patients with synovial sarcoma, and 25% (two of eight; 3-65) for patients with myxoid round cell liposarcoma. Cytokine release syndrome occurred in 37 (71%) of 52 of patients (one grade 3 event). Cytopenias were the most common grade 3 or worse adverse events (lymphopenia in 50 [96%], neutropenia 44 [85%], leukopenia 42 [81%] of 52 patients). No treatment-related deaths occurred. INTERPRETATION: Afami-cel treatment resulted in durable responses in heavily pre-treated patients with HLA-A*02 and MAGE-A4-expressing synovial sarcoma. This study shows that T-cell receptor therapy can be used to effectively target solid tumours and provides rationale to expand this approach to other solid malignancies. FUNDING: Adaptimmune.

KSHV vIL-6 promotes SIRT3-induced deacetylation of SERBP1 to inhibit ferroptosis and enhance cellular transformation by inducing lipoyltransferase 2 mRNA degradation.

Ferroptosis, a defensive strategy commonly employed by the host cells to restrict pathogenic infections, has been implicated in the development and therapeutic responses of various types of cancer. However, the role of ferroptosis in oncogenic Kaposi's sarcoma-associated herpesvirus (KSHV)-induced cancers remains elusive. While a growing number of non-histone proteins have been identified as acetylation targets, the functions of these modifications have yet to be revealed. Here, we show KSHV reprogramming of host acetylation proteomics following cellular transformation of rat primary mesenchymal precursor. Among them, SERPINE1 mRNA binding protein 1 (SERBP1) deacetylation is increased and required for KSHV-induced cellular transformation. Mechanistically, KSHV-encoded viral interleukin-6 (vIL-6) promotes SIRT3 deacetylation of SERBP1, preventing its binding to and protection of lipoyltransferase 2 (Lipt2) mRNA from mRNA degradation resulting in ferroptosis. Consequently, a SIRT3-specific inhibitor, 3-TYP, suppresses KSHV-induced cellular transformation by inducing ferroptosis. Our findings unveil novel roles of vIL-6 and SERBP1 deacetylation in regulating ferroptosis and KSHV-induced cellular transformation, and establish the vIL-6-SIRT3-SERBP1-ferroptosis pathways as a potential new therapeutic target for KSHV-associated cancers.

Evaluation of metabolomics-based urinary biomarker models for recognizing major depression disorder and bipolar disorder.

BACKGROUND: Major depressive disorder (MDD) and bipolar disorder (BD) are psychiatric disorders with overlapping symptoms, leading to high rates of misdiagnosis due to the lack of biomarkers for differentiation. This study aimed to identify metabolic biomarkers in urine samples for diagnosing MDD and BD, as well as to establish unbiased differential diagnostic models. METHODS: We utilized a metabolomics approach employing ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS) to analyze the metabolic profiles of urine samples from individuals with MDD (n = 50), BD (n = 12), and healthy controls (n = 50). The identification of urine metabolites was verified using MS data analysis tools and online metabolite databases. RESULTS: Two diagnostic panels consisting of a combination of metabolites and clinical indicators were identified-one for MDD and another for BD. The discriminative capacity of these panels was assessed using the area under the receiver operating characteristic (ROC) curve, yielding an area under the curve (AUC) of 0.9084 for MDD and an AUC value of 0.9017 for BD. CONCLUSIONS: High-resolution mass spectrometry-based assays show promise in identifying urinary biomarkers for depressive disorders. The combination of urine metabolites and clinical indicators is effective in differentiating healthy controls from individuals with MDD and BD. The metabolic pathway indicating oxidative stress is seen to significantly contribute to depressive disorders.

Modulating the Electronic Structure of Cobalt in Molecular Catalysts via Coordination Environment Regulation for Highly Efficient Heterogeneous Nitrate Reduction.

Ammonia (NH3) is pivotal in modern industry and represents a promising next-generation carbon-free energy carrier. Electrocatalytic nitrate reduction reaction (eNO3RR) presents viable solutions for NH3 production and removal of ambient nitrate pollutants. However, the development of eNO3RR is hindered by lacking the efficient electrocatalysts. To address this challenge, we synthesized a series of macrocyclic molecular catalysts for the heterogeneous eNO3RR. These materials possess different coordination environments around metal centers by surrounding subunits. Consequently, electronic structures of the active centers can be altered, enabling tunable activity towards eNO3RR. Our investigation reveals that metal center with an N2(pyrrole)-N2(pyridine) configuration demonstrates superior activity over the others and achieves a high NH3 Faradaic efficiency (FE) of over 90 % within the tested range, where the highest FE of approximately 94 % is obtained. Furthermore, it achieves a production rate of 11.28 mg mgcat -1 h-1, and a turnover frequency of up to 3.28 s-1. Further tests disclose that these molecular catalysts with diverse coordination environments showed different magnetic moments. Theoretical calculation results indicate that variated coordination environments can result in a d-band center variation which eventually affects rate-determining step energy and calculated magnetic moments, thus establishing a correlation between electronic structure, experimental activity, and computational parameters.

Damage evaluation of craniofacial localized scleroderma using magnetic resonance imaging.

Background: Localized scleroderma (LoS) is an autoimmune disease in which craniofacial lesions can cause severe facial deformities with brain involvement. Objective evaluation of craniofacial LoS is challenging. Magnetic resonance imaging (MRI) may be used as a damage assessment tool. This study aimed to analyze the tissue involvement of craniofacial LoS based on MRI and evaluate MRI for craniofacial LoS assessment. Methods: This cross-sectional study included patients with craniofacial LoS from September 2021 to August 2022 in Peking Union Medical College Hospital. Patients who were clinically assessed in a stable phase were enrolled; patients with previous surgical treatment or contraindications to MRI were excluded. Participants underwent clinical, MRI, and ultrasound assessments. MRI was compared with ultrasound by correlation analysis and Bland-Altman analysis. The involvement of different tissues and different facial subunits was compared. The accumulated soft tissue atrophy index (ASTAI) was compared with clinical scores by correlation analysis. Results: A total of 28 patients were included (13 female; mean age, 18 years). MRI showed a good correlation and agreement with ultrasound (r=0.916, P<0.001). In different facial subunits, a significant negative correlation between the forehead and chin was found (r=-0.593, P=0.001). The ASTAI correlated well with the facial LoS damage index (r=0.580, P=0.001) and the Peking Union Medical College LoS facial aesthetic index (PUMC LoSFAI) (r=0.921, P<0.001). A total of 38.6% of clinical scores were inaccurate based on MRI. Neurological changes were found in one patient. Conclusions: MRI can reliably quantify damage in craniofacial LoS, and may serve as a useful and objective tool for overall craniofacial LoS evaluation.

Acute effects of resistance-type and cycling-type high-intensity interval training on arterial stiffness, cardiac autonomic modulation and cardiac biomarkers.

BACKGROUND: High-intensity interval training (HIIT) has been shown to enhance cardiovascular health. However, there is a lack of research investigating the specific cardiovascular effects of different HIIT training modes. Therefore, this study aimed to compare the acute effects of cycling-type high intensity interval training (C-HIIT) and resistance-type high intensity interval training (R-HIIT) on arterial stiffness, cardiac autonomic modulation, and cardiac biomarkers in healthy young men. METHODS: This is a cross-over randomized trial. Eleven healthy active young men took part in both C-HIIT and R-HIIT. Cardio-ankle vascular index (CAVI), heart rate variability (HRV), and systolic blood pressure (SBP) were measured before, immediately and 30 min after the exercise in C-HIIT and R-HIIT. Meanwhile, blood samples for cardiac troponin-T (cTnT) and amino-terminal pro-B-type natriuretic peptide (NT-proBNP) were assessed using ELISA before, 5min and 35min after exercise. RESULTS: There was a significant time × group interaction effect (P = 0.019, ηp2 = 0.182) and time main effect for ⊿CAVI (P < 0.001, ηp2 = 0.729), and R-HIIT resulted in a more significant reduction in ⊿CAVI compared to C-HIIT (- 0.60 ± 0.30, P = 0.043, d = 0.924) immediately after exercise. There was a significant time main effect was observed for SBP (P = 0.001, ηp2 = 0.304). A significant time main effect for lnHF (P < 0.001, ηp2 = 0.782), lnRMSSD (P < 0.001, ηp2 = 0.693), and LF/HF (P = 0.001, ηp2 = 0.302) of HRV was observed. A significant time main effect was observed for cTnT (P = 0.023, ηp2 = 0.193) and NT-proBNP (P = 0.001, ηp2 = 0.334) of cardiac biomarkers. CONCLUSION: R-HIIT and C-HIIT elicited similar acute responses in cardiac autonomic modulation and cardiac biomarkers. However, R-HIIT was more effective in reducing arterial stiffness in healthy young men. Furthermore, the increase in cardiac biomarkers induced by both C-HIIT and R-HIIT was reversible. TRIAL REGISTRATION: The study was prospectively registered on 22 February 2022 at www.chictr.org.cn with identification number ChiCTR2200056897.

Etanercept Combined with Glucocorticoid and Gamma Globulin for Treating Children with Toxic Epidermal Necrolysis: A Case Report.

Toxic epidermal necrolysis (TEN) is a type of drug eruption in dermatology emergencies that is rare in clinical practice but has a high mortality rate. The main causes are drug and viral infections. Unfortunately, no expert consensus on treating this disease exists, and a standard therapy is absent. Up to now, glucocorticoids combined with gamma globulin are commonly used in clinical practice, but their efficacy is highly controversial. This study reports on a 7-year-old girl with TEN who did not respond to traditional therapy, such as methylprednisolone combined with gamma globulin, but was finally cured with an additional low-dose etanercept. The results showed that etanercept therapy in paediatric TEN is safe, reliable and worth recommending.

Changes of dry eye parameters after small incision lenticule extraction surgery in patients with different ocular surface disease index scores.

To evaluate the changes of dry eye parameters after small incision lenticule extraction (SMILE) surgery in patients with different ocular surface disease index (OSDI) scores. Prospective research. Participants were divided into two groups: Group A, OSDI < 13; and Group B, OSDI ≥ 13. The OSDI scores, tear meniscus height (TMH), first non-invasive tear film break-up time (NIBUT-First), and meibomian gland loss (MGL, %) were recorded at postoperative 1 -week and 1-month.113 eyes (57 patients) were enrolled, 70 eyes in Group A, and 43 eyes in Group B. In Group A, the OSDI scores significantly increased at 1-week and 1-month postoperative (all P < 0.001); the TMH, NIBUT-First and lipid layer grade significantly decreased at postoperative 1-week (P = 0.003, 0.005, 0.007, 0.004, respectively), but returned to preoperative level at 1-month postoperative. In Group B, only the lipid layer grade significantly decreased at postoperative 1-week (P < 0.05). Patients with different preoperative OSDI scores may experience different changes early after SMILE surgery. Patients with OSDI scores < 13 may experience more dramatic changes in dry eye symptoms which would resolve, while subjective complains could still exists at 1 month after surgery.

Effects of gene polymorphisms on delayed MTX clearance, toxicity, and metabolomic changes after HD-MTX treatment in children with acute lymphoblastic leukemia.

This study aims to assess the role of methotrexate-related gene polymorphisms in children with acute lymphoblastic leukemia (ALL) during high-dose methotrexate (HD-MTX) therapy and to explore their effects on serum metabolites before and after HD-MTX treatment. The MTHFR 677C>T, MTHFR 1298A>C, ABCB1 3435C>T, and GSTP1 313A>G genotypes of 189 children with ALL who received chemotherapy with the CCCG-ALL-2020 regimen from January 2020 to April 2023 were analyzed, and toxic effects were reported according to the Common Terminology Criteria for Adverse Events (CTCAE, version 5.0). Fasting peripheral blood serum samples were collected from 27 children before and after HD-MTX treatment, and plasma metabolites were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS). The results of univariate and multivariate analyses showed that MTHFR 677C>T and ABCB1 3435 C>T gene polymorphisms were associated with the delayed MTX clearance (P < 0.05) and lower platelet count after treatment in children with MTHFR 677 mutation compared with wild-type ones (P < 0.05), and pure mutations in ABCB1 3435 were associated with higher serum creatinine levels (P < 0.05). No significant association was identified between MTHFR 677C>T, MTHFR 1298A>C, ABCB1 3435 C>T, and GSTP1 313A>G genes and hepatotoxicity or nephrotoxicity (P > 0.05). However, the serum metabolomic analysis indicated that the presence of the MTHFR 677C > T gene polymorphism could potentially contribute to delayed MTX clearance by influencing L-phenylalanine metabolism, leading to the occurrence of related toxic side effects. CONCLUSION: MTHFR 677C>T and ABCB1 3435 C>T predicted the risk of delayed MTX clearance during HD-MTX treatment in children with ALL. Serum L-phenylalanine levels were significantly elevated after HD-MTX treatment in children with the MTHFR 677C>T mutation gene. TRIAL REGISTRATION: This study was registered at the Chinese Clinical Trial Registry (registration number: ChiCTR2000035264; registration: 2020/08/05; https://www.chictr.org.cn/ ). WHAT IS KNOWN: • MTX-related genes play an important role in MTX pharmacokinetics and toxicity, but results from different studies are inconsistent and the mechanisms involved are not clear. WHAT IS NEW: • Characteristics, prognosis, polymorphisms of MTX-related genes, and metabolite changes were comprehensively evaluated in children treated with HD-MTX chemotherapy. • Analysis revealed that both heterozygous and pure mutations in MTHFR 677C>T resulted in a significantly increased risk of delayed MTX clearance, and that L-phenylalanine has the potential to serve as a predictive marker for the metabolic effects of the MTHFR 677C>T polymorphism.

Autoimmune diseases exhibit shared alterations in the gut microbiota.

OBJECTIVE: Accumulating evidence from microbial studies have highlighted the modulatory roles of intestinal microbes in numerous human diseases, however, the shared microbial signatures across different diseases remain relatively unclear. METHODS: To consolidate existing knowledge across multiple studies, we performed meta-analyses of 17 disease types, covering 34 case-control datasets of 16S rRNA sequencing data, to identify shared alterations among different diseases. Furthermore, the impact of a microbial species, Lactobacillus salivarius, was established in a dextran sodium sulphate-induced colitis model and a collagen type II-induced arthritis mouse model. RESULTS: Microbial alterations among autoimmune diseases were substantially more consistent compared with that of other diseases (cancer, metabolic disease and nervous system disease), with microbial signatures exhibiting notable discriminative power for disease prediction. Autoimmune diseases were characterized by the enrichment of Enterococcus, Veillonella, Streptococcus and Lactobacillus and the depletion of Ruminococcus, Gemmiger, Oscillibacter, Faecalibacterium, Lachnospiracea incertae sedis, Anaerostipes, Coprococcus, Alistipes, Roseburia, Bilophila, Barnesiella, Dorea, Ruminococcus2, Butyricicoccus, Phascolarctobacterium, Parabacteroides and Odoribacter, among others. Functional investigation of L. salivarius, whose genus was commonly enriched in numerous autoimmune diseases, demonstrated protective roles in two separate inflammatory mouse models. CONCLUSION: Our study highlights a strong link between autoimmune diseases and the gut microbiota, with notably consistent microbial alterations compared with that of other diseases, indicating that therapeutic strategies that target the gut microbiome may be transferable across different autoimmune diseases. Functional validation of L. salivarius highlighted that bacterial genera associated with disease may not always be antagonistic, but may represent protective or adaptive responses to disease.

Extraction and characterization of nanocellulose from cattail leaves: Morphological, microstructural and thermal properties.

Hydrogen peroxide combined with acid treatment demonstrates its respective characteristics for the separation of lignocellulosic biomass. Herein, holocellulose was extracted from Cattail leaves (CL) by a two-step treatment with alkali and hydrogen peroxide-acetic acid (HPAA). Then carboxylated nanocellulose was hydrolyzed with a mixed organic/inorganic acid. The chemical composition of the holocellulose and the physicochemical properties of the separated carboxylated nanocellulose were comparable. Carboxyl groups were introduced on the nanocellulose as a result of the esterification process with citric acid (CA), which endows the nanocellulose with high thermal stability (315-318 °C) and good light transmission (>80 %). Furthermore, morphological analyses revealed that nanocellulose had a spider-web-like structure with diameter between 5 and 20 nm.

Deep learning reconstruction improves the image quality of low-dose temporal bone CT with otitis media and mastoiditis patients.

Objective: To evaluate the image quality of low-dose temporal bone computed tomography (CT) in otitis media and mastoiditis patients by using deep learning reconstruction (DLR). Materials and methods: A total of ninety-seven temporal bones from 53 consecutive adult patients who had suspected otitis media and mastoiditis and underwent temporal bone CT were prospectively enrolled. All patients underwent high resolution CT protocol (group A) and an additional low-dose protocol (group B). In group A, high resolution data were reconstructed by filter back projection (FBP). In group B, low-dose data were reconstructed by DLR mild (B1), DLR standard (B2) and DLR strong (B3). The objective image quality was analyzed by measuring the CT value and image noise on the transverse image and calculating the signal-to-noise ratio (SNR) on incudomallear joint, retroauricular muscle, vestibule and subcutaneous fat. Subjective image quality was analyzed by using a five-point scale to evaluate nine anatomical structures of middle and inner ear. The number of temporal bone lesions which involved in five structures of middle ear were assessed in group A, B1, B2 and B3 images. Results: There were no significant differences in the CT values of the four reconstruction methods at four structures (all p > 0.05). The DLR group B1, B2 and B3 had significantly less image noise and a significantly higher SNR than group A at four structures (all p < 0.001). The group B1 had comparable subjective image quality as group A in nine structures (all p > 0.05), however, the group B3 had lower subjective image quality than group A in modiolus, spiral osseous lamina and stapes (all p < 0.001), the group B2 had lower subjective image quality than group A in modiolus and spiral osseous lamina (both p < 0.05). The number of temporal bone lesions which involved in five structures for group A, B1 and B2 images were no significant difference (all p > 0.05), however, the number of temporal bone lesions which involved in mastoid for group B3 images were significantly more than group A (p < 0.05). The radiation dose of high resolution CT protocol and low-dose protocol were 0.55 mSv and 0.11 mSv, respectively. Conclusion: Compared with high resolution CT protocol, in the low-dose protocol of temporal bone CT, DLR mild and standard could improve the objective image quality, maintain good subjective image quality and satisfy clinical diagnosis of otitis media and mastoiditis patients.