Targeting FTO induces colorectal cancer ferroptotic cell death by decreasing SLC7A11/GPX4 expression.

Ferroptosis is a newly identified iron-dependent form of death that is becoming increasingly recognized as a promising avenue for cancer therapy. N6-methyladenosine (m6A) is the most abundant reversible methylation modification in mRNA contributing to tumorigenesis. However, the crucial role of m6A modification in regulating ferroptosis during colorectal cancer (CRC) tumorigenesis remains elusive. Herein, we find that m6A modification is increased during ferroptotic cell death and correlates with the decreased m6A demethylase fat mass and obesity-associated protein (FTO) expression. Functionally, we demonstrate that suppressing FTO significantly induces CRC ferroptotic cell death, as well as enhancing CRC cell sensitivity to ferroptosis inducer (Erastin and RSL3) treatment. Mechanistically, high FTO expression increased solute carrier family 7 member 11 (SLC7A11) or glutathione peroxidase 4 (GPX4) expressions in an m6A-YTHDF2 dependent manner, thereby counteracting ferroptotic cell death stress. In addition, we identify Mupirocin as a novel inhibitor of FTO, and Mupirocin induces CRC ferroptosis and inhibits tumor growth. Clinically, the levels of FTO, SLC7A11, and GPX4, are highly correlated expression in CRC tissues. Our findings reveal that FTO protects CRC from ferroptotic cell death in promoting CRC tumorigenesis through triggering SLC7A11/GPX4 expression.

The safety and tolerability of a one strength dose-escalation scheme for subcutaneous immunotherapy with a native house dust mite extract in Chinese children: A multicenter, randomized, open label clinical trial.

Background: Allergen immunotherapy (AIT) is still the only treatment that may affect the natural cause of allergic disease. This study is to investigate whether an accelerated up-dosing scheme for subcutaneous allergen immunotherapy (SCIT) using a native house dust mite (HDM) allergen extract is as safe as the standard 3-strengths dose-escalation scheme in children with moderate to severe allergic rhinitis or rhinoconjunctivitis with or without asthma in China. Methods: In this multicenter, open label, randomized controlled trial, the children aged 5-14 years were randomized 1:1 either to One Strength group or the Standard group. The dose escalation scheme for patients in the One Strength group included 6 injections of strength 3, whereas the Standard group comprised 14 injections using strength 1, 2, and 3. All treatment-emergent adverse events (TEAEs) were recorded and analyzed. The 5-point Likert scale was used to assess tolerability (ChiCTR2100050311). Results: Overall, 101 children were included in the Safety Set (One Strength group: 50 vs. Standard group: 51). A total of 26 TEAEs were reported for 15 children. TEAEs related to AIT occurred in 10 % of the children in the One Strength group and 11.8 % of the Standard group. The number of systemic adverse reactions was comparable in both groups (One Strength: 5 vs. Standard: 4). No serious TEAEs was recorded for either group. 90.0 % of patients in the One Strength group reached the maintenance dose without an interventional dose adjustment due to adverse events, compared to 78.4 % in the Standard group. All patients who completed the dose-escalation phase reached the recommended maintenance dose of 1.0 ml of strength 3.Investigators and patients rated the tolerability of the One Strength regimen slightly better than the Standard scheme. Conclusions: This exploratory study suggests that the accelerated One Strength dose-escalation scheme is comparable in safety and tolerability to the Standard regimen. However, due to the preliminary nature and small sample size, further research with larger sample sizes and robust study designs is necessary for confirmation.

Dissimilarity in radial growth and response to drought of Korshinsk peashrub (Caragana korshinskii Kom.) under different management practices in the western Loess Plateau.

Quantitative assessment of tree responses to the local environment can help provide scientific guidance for planted forest management. However, research on the climate-growth relationship of Korshinsk peashrub (Caragana korshinskii Kom.) under different land preparation and post-management (irrigation) conditions is still insufficient. In this study, we collected 223 tree-ring samples from Korshinsk peashrubs using dendroecological methods and systematically quantified the relationships between shrub growth and climatic factors under different management practices in the western Loess Plateau of China. Our findings demonstrated that drought stress caused by scarce precipitation from April to August was the primary factor limiting the growth of Korshinsk peashrubs in the northern and southern mountains of Lanzhou. The "climwin" climate model results showed a weak correlation between natural Korshinsk peashrub growth and drought stress, whereas planted Korshinsk peashrub under rain-fed conditions in the southern mountain was significantly (p<0.05) limited by drought stress from April to August. Moreover, planted Korshinsk peashrub growth under irrigated conditions in the northern mountain was limited only by drought stress in January. Drought model explained 28.9%, 38.3%, and 9.80% of the radial growth variation in Xiguoyuan (XGY), Shuibaozhan (SBZ), and Zhichagou (ZCG) sites, respectively. Artificial supplementary irrigation alleviated the limitation of drought on planted forest growth, which may be implemented for Korshinsk peashrubs planted on sunny slopes, while planted Korshinsk peashrubs under natural rain-fed conditions can be planted on shady slopes through rainwater harvesting and conservation measures such as horizontal ditches and planting holes.

Symptom profiles in patients receiving maintenance hemodialysis and their association with quality of life: a longitudinal study.

PURPOSE: Many patients receiving maintenance hemodialysis experience one or multiple symptoms. Using a latent profile analysis to identify symptom profiles may provide insights for person-centered symptom management strategies. METHODS: This is a longitudinal study based on data from patients receiving maintenance hemodialysis at three hospitals in Shanghai, China. Of the 448 patients who completed the surveys at baseline (T1), 309 completed the 12-month follow-up survey (T2). Symptoms and quality of life were measured by the Chinese version of Kidney Disease Quality of Life 36 Short Form. The optimal classification of symptoms was identified using latent profile analysis. RESULTS: Five symptom profiles were identified: High (9.2%), Fatigue and Gastrointestinal (7.1%), Fatigue and Skin (10.7%), Skin (23.2%), and Low (49.8%). The high-symptom profile and the-fatigue-and-skin-symptom profile were associated with a lower level of physical functioning, a higher burden of kidney disease, and more negative effects of kidney disease than the low symptom profile at T1 and T2. Multivariate regression analysis showed that the high-symptom profile predicted a poorer physical functioning at T2, and the-fatigue-and-skin-symptom profile predicted a poorer physical functioning and higher burden of kidney disease at T2. CONCLUSION: Patients receiving maintenance hemodialysis reported unique symptom experiences which could be classified into different profiles. Patients reporting an overall high level of symptoms or a high level of fatigue and skin symptoms were more likely to have a poorer quality of life.

Conditional c-MYC activation in catecholaminergic cells drives distinct neuroendocrine tumors: neuroblastoma vs somatostatinoma.

The MYC proto-oncogenes (c-MYC, MYCN , MYCL ) are among the most deregulated oncogenic drivers in human malignancies including high-risk neuroblastoma, 50% of which are MYCN -amplified. Genetically engineered mouse models (GEMMs) based on the MYCN transgene have greatly expanded the understanding of neuroblastoma biology and are powerful tools for testing new therapies. However, a lack of c-MYC-driven GEMMs has hampered the ability to better understand mechanisms of neuroblastoma oncogenesis and therapy development given that c-MYC is also an important driver of many high-risk neuroblastomas. In this study, we report two transgenic murine neuroendocrine models driven by conditional c-MYC induction in tyrosine hydroxylase (Th) and dopamine ß-hydroxylase (Dbh)-expressing cells. c-MYC induction in Th-expressing cells leads to a preponderance of Pdx1 + somatostatinomas, a type of pancreatic neuroendocrine tumor (PNET), resembling human somatostatinoma with highly expressed gene signatures of δ cells and potassium channels. In contrast, c-MYC induction in Dbh-expressing cells leads to onset of neuroblastomas, showing a better transforming capacity than MYCN in a comparable C57BL/6 genetic background. The c-MYC murine neuroblastoma tumors recapitulate the pathologic and genetic features of human neuroblastoma, express GD2, and respond to anti-GD2 immunotherapy. This model also responds to DFMO, an FDA-approved inhibitor targeting ODC1, which is a known MYC transcriptional target. Thus, establishing c-MYC-overexpressing GEMMs resulted in different but related tumor types depending on the targeted cell and provide useful tools for testing immunotherapies and targeted therapies for these diseases.

Rituximab potentially improves clinical outcomes of CAR-T therapy for r/r B-ALL via sensitizing leukemia cells to CAR-T-mediated cytotoxicity and reducing CAR-T exhaustion.

PURPOSE: Despite chimeric antigen receptor (CAR) T-cell therapy has achieved great advances in recent year, approximately 50% of relapsed/refractory B cell acute lymphoblastic leukemia (r/r B-ALL) patients treated with CAR-T experience relapse 6 months post CAR-T treatment. CD20 express on 30 to 50% of B-ALL, which makes CD20 Monoclonal Antibody as one of the potential therapy strategies to decrease the tumor burden and improve the efficacy of CAR-T therapy. Adding Rituximab to chemotherapy protocol had been demonstrated to improve the outcome for CD20-positive ALL. However, rare study explored the influence of Rituximab combined with CAR-T therapy. METHODS: We retrospectively analyzed 20 r/r B-ALL patients who received CAR-T therapy, all of whom had failed multiple lines of therapy. Before CAR-T infusion, we administered Rituximab to 10 patients with high CD20 expression at a dose of 375 mg/m2 for 1 day. Meanwhile, we selected 10 patients with the comparable features who underwent CAR-T treatment without Rituximab in the same period as the control group. In vitro, the surface molecule expression and killing of CAR-T post Rituximab-treated B-ALL cells co-incubated with CAR-T cells were detected by flow cytometry. RESULTS: The median follow-up of Rituximab and Control groups were 29.27 and 9.83 months. We found that adding Rituximab may confer a favorable prognosis compared with Control group. The 2-year overall survival (OS) and leukemia-free survival (LFS) rates both were longer in the Rituximab group (90% vs. 26.7%, p = 0.0342; 41.7% vs. 25%, p = 0.308). In vitro, we observed that Rituximab-treated tumour cells are more sensitive to CAR-T killing and a broad range of cytokines and chemokines were produced when Rituximab-treated Nalm-6 cells co-cultured with 19-22CAR-T cells, such as interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α) and interleukin-2 (IL-2). To investigate whether Rituximab has an effect on CAR-T persistence, we stimulated CAR-T cells repeatedly in vitro with Rituximab-treated Nalm-6 to evaluate the changes in CAR-T surface exhaustion molecules at different times. We found that the expression of exhaustion molecules (LAG-3, PD-1, TIM-3) on CAR-T cells were significantly lower in the Rituximab group than in the Control group. CONCLUSION: Rituximab combined with CAR-T therapy is effective for improving the long-term prognosis of B-ALL patients who have failed multiple lines of therapy. In vitro, we observed that rituximab potentially improves CAR-T efficacy by sensitizing ALL to CART-mediated cytotoxicity and reducing CAR-T exhaustion.

Tumor-associated macrophage subtypes on cancer immunity along with prognostic analysis and SPP1-mediated interactions between tumor cells and macrophages.

Tumor-associated macrophages (TAM) subtypes have been shown to impact cancer prognosis and resistance to immunotherapy. However, there is still a lack of systematic investigation into their molecular characteristics and clinical relevance in different cancer types. Single-cell RNA sequencing data from three different tumor types were used to cluster and type macrophages. Functional analysis and communication of TAM subpopulations were performed by Gene Ontology-Biological Process and CellChat respectively. Differential expression of characteristic genes in subpopulations was calculated using zscore as well as edgeR and Wilcoxon rank sum tests, and subsequently gene enrichment analysis of characteristic genes and anti-PD-1 resistance was performed by the REACTOME database. We revealed the heterogeneity of TAM, and identified eleven subtypes and their impact on prognosis. These subtypes expressed different molecular functions respectively, such as being involved in T cell activation, apoptosis and differentiation, or regulating viral bioprocesses or responses to viruses. The SPP1 pathway was identified as a critical mediator of communication between TAM subpopulations, as well as between TAM and epithelial cells. Macrophages with high expression of SPP1 resulted in poorer survival. By in vitro study, we showed SPP1 mediated the interactions between TAM clusters and between TAM and tumor cells. SPP1 promoted the tumor-promoting ability of TAM, and increased PDL1 expression and stemness of tumor cells. Inhibition of SPP1 attenuated N-cadherin and ß-catenin expression and the activation of AKT and STAT3 pathway in tumor cells. Additionally, we found that several subpopulations could decrease the sensitivity of anti-PD-1 therapy in melanoma. SPP1 signal was a critical pathway of communication between macrophage subtypes. Some specific macrophage subtypes were associated with immunotherapy resistance and prognosis in some cancer types.

The pore-rhizosheath shapes maize root architecture by enhancing root distribution in macropores.

Pores and old root-channels are preferentially used by roots to allow them to penetrate hard soils. However, there are few studies that have accounted for the effects of pore-rhizosheath on root growth. In this study, we developed an approach by adding the synthetic root exudates using a porous stainless tube with 0.1-mm micropores through a peristaltic pump to reproduce the rhizosheath around the artificial pore, and investigated the effects of pores with and without rhizosheaths on maize root growth in a dense soil. The results indicated that the artificial rhizosheath was about 2.69 mm wide in the region surrounding the pores. The rhizosheath had a higher content of organic carbon, total nitrogen, and abundance of Actinobacteria than that of the bulk soil. Compared with the artificial macropores, the artificial root-pores with a rhizosheath increased the opportunities for root utilisation of the pores space, promoting steeper and deeper root growth. It is concluded that the pore-rhizosheath has a significant impact on root architecture by enhancing root distribution in macropores.

Prognostic effect of masked morning hypertension in Chinese inpatients with non-dialysis chronic kidney disease: A multi-center retrospective study.

OBJECTIVE: This study aimed to elucidate the prognostic role of Masked Morning Hypertension (MMH) in non-dialysis-dependent chronic kidney disease (NDD-CKD). METHODS: 2,130 NDD-CKD patients of inpatient department were categorized into four blood pressure groups: clinical normotension (CH-), clinical hypertension (CH+) with morning hypertension (MH+), and without MH+ (MH-) respectively. The correlation between these four blood pressure types and the primary (all-cause mortality) and secondary endpoints (cardio-cerebrovascular disease [CVD] and end-stage kidney disease [ESKD]) was analyzed. RESULTS: The prevalences of morning hypertension and masked morning hypertension were 47.4% and 14.98%, respectively. Morning hypertension independently increased the risk of all-cause mortality (P=0.004) and CVD (P<0.001) but not ESKD (P=0.092). Masked morning hypertension was associated with heightened all-cause mortality (HR = 4.22, 95% CI = 1.31-13.59; P=0.02) and CVD events (HR = 5.14, 95% CI = 1.37-19.23; P=0.02), with no significant association with ESKD (HR = 1.18, 95% CI = 0.65-2.15; P=0.60). When considering non-CVD deaths as a competing risk factor, a high cumulative incidence of CVD events was observed in the masked morning hypertension group (HR = 5.16, 95% CI = 1.39-19.08). CONCLUSIONS: MMH is an independent risk factor for all-cause mortality and combined cardiovascular and cerebrovascular events in NDD-CKD patients, underscoring its prognostic significance. This highlights the need for comprehensive management of morning hypertension in this population.

The efficacy and safety of Chinese herbal medicine for mild cognitive impairment: a systematic review and meta-analysis of randomized placebo-controlled trials.

Objective: Effective and safe treatments for mild cognitive impairment (MCI) are limited. Chinese herbal medicine (CHM) is commonly used in China to manage MCI. However, its efficacy and safety remain uncertain. This review aims to evaluate the efficacy and safety of CHM for MCI. Methods: Nine databases were searched from their inceptions to January 2023. Randomized, placebo-controlled trials of oral CHM for MCI were included. Study quality was assessed using the Cochrane risk-of-bias tool 2.0, and the certainty of evidence was evaluated via the GRADE approach. Results: Thirteen studies, involving 1,043 participants, were analyzed. Most of the studies (10 out of 13) were associated with "some concerns" regarding the overall risk of bias. Meta-analyses results indicated that CHM significantly improved cognitive function compared to placebo in terms of Mini-Mental State Examination (MMSE) (MD: 1.90 [1.22, 2.58], I2 = 87%, 11 studies, 823 participants) and Montreal Cognitive Assessment (MoCA) (MD: 2.88 [1.69, 4.06], I2 = 81%, 3 studies, 241 participants). The certainty of evidence for MMSE was assessed as "moderate", while it was "low" for MoCA. One study did not report adverse events (AEs), one study reported no statistical difference between the groups in terms of AEs, and 11 studies provided detailed numbers of AE cases where gastrointestinal symptoms were the most commonly reported AEs. Two studies reported no SAEs among participants and one study found no significant difference in SAEs proportions between groups. The meta-analysis revealed no significant difference in AEs between the two groups (RR: 1.31 [0.92, 1.87), I2 = 0%, 11 studies, 839 participants). The cognitive-enhancing function of commonly used herbs (Panax ginseng C.A.Mey., Acorus calamus var. angustatus Besser, and Polygala tenuifolia Willd.) may be attributed to mechanisms including antioxidant, anti-apoptotic, anti-neurotoxic, anti-cytotoxic, and anti-inflammatory actions. Conclusion: Chinese herbal medicine holds potential as an effective intervention to improve cognitive function in MCI patients, supported by meta-analyses evidence of low to moderate certainty. Although current data suggests CHM is generally safe, caution is advised due to the lack of AE reporting or detailed information in some instances. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=400292, identifier [CRD42023400292].

Achieving widely distributed feature matches using flattened-affine-SIFT algorithm for fisheye images.

Performing correction first is the most common methods to address feature matching issues for fisheye images, but corrections often result in significant loss of scene details or stretching of images, leaving peripheral regions without matches. In this paper, we propose a novel approach, named flattened-affine-SIFT, to find widely distributed feature matches between stereo fisheye images. Firstly, we establish a new imaging model that integrates a scalable model and a hemisphere model. Utilizing the extensibility of the imaging model, we design a flattened array model to reduce the distortion of fisheye images. Additionally, the affine transformation is performed on the flattened simulation images, which are computed using the differential expansion and the optimal rigidity transformation. Then feature matches are extracted and matched from the simulated images. Experiments on indoor and outdoor fisheye images show that the proposed algorithm can find a large number of reliable feature matches. Moreover, these matches tend to be dispersed over the entire effective image, including peripheral regions with dramatic distortion.

Impact of iodinated oil in proton therapy on relative stopping power of liver post-cTACE.

Objective. Conventional transarterial chemoembolization (cTACE) is a common treatment for hepatocellular carcinoma (HCC), often with unsatisfactory local controls. Combining cTACE with radiotherapy shows a promise for unresectable large HCC, with proton therapy preserving healthy liver tissue. However, the proton therapy benefits are subject to the accuracy of tissue relative stopping power (RSP) prediction. The RSP values are typically derived from computed tomography (CT) images using stoichiometric calibration. Lipiodol deposition significantly increases CT numbers in liver regions of post-cTACE. Hence, it is necessary to evaluate the accuracy of RSP in liver regions of post-cTACE.Approach. Liver, water, and iodinated oil samples were prepared. Some liver samples contained iodinated oil. The water equivalent path length (WEPL) of sample was measured through the pullbacks of spread-out Bragg peak (SOBP) depth-dose profiles scanned in a water tank with and without sample in the beam path. Measured RSP values were compared to estimated RSP values derived from the CT number based on the stoichiometric calibration method.Main results. The measured RSP of water was 0.991, confirming measurement system calibration. After removing the RSP contribution from container walls, the pure iodinated oil and liver samples had RSP values of 1.12 and 1.06, while the liver samples mixed with varying oil volumes (5 ml, 10 ml, 15 ml) showed RSP values of 1.05, 1.05 and 1.06. Using the stoichiometric calibration method, pure iodinated oil and liver samples had RSP values of 2.79 and 1.06. Liver samples mixed with iodinated oil (5 ml, 10 ml, 15 ml) had calculated RSP values of 1.21, 1.34, and 1.46. The RSP discrepancy reached 149.1% for pure iodinated oil.Significance.Iodinated oil notably raises CT numbers in liver tissue. However, there is almost no effect on its RSP value. Proton treatment of post-cTACE HCC patients can therefore be overshooting if no proper measures are taken against this specific effect.

24-h central pressure is a valuable predictor for left ventricular hypertrophy in non-dialysis patients with chronic kidney disease.

The current research on the relationship between 24-h central pressure and 24-h brachial pressure with left ventricular hypertrophy (LVH) is characterised by limited sample size and inconsistent findings. Furthermore, the association has never been explored in chronic kidney disease (CKD). A multicentre, cross-sectional study among non-dialysis patients with CKD was conducted. All participants underwent brachial and central ambulatory blood pressure monitoring using MobilO-Graph PWA, while trained cardiologists performed echocardiography. In this study, 2117 non-dialysis patients with CKD were examined. 24-h central systolic blood pressure with c2 calibration (24-h c2SBP) demonstrated a stronger association with left ventricular mass index and LVH compared with 24-h brachial systolic blood pressure (24-h bSBP) in the univariate and multivariate regression analyses. The multivariate net reclassification index (NRI) analysis revealed that 24-h c2SBP exhibited greater discriminatory power over 24-h bSBP (NRI = 0.310, 95% CI [0.192-0.429], P < 0.001). Applying 130/135 mmHg as the threshold for 24-h bSBP/c2SBP to cross-classify, the patients were divided into concordant normotension (1509 individuals), isolated brachial hypertension (155 individuals), isolated central hypertension (11 individuals), and concordant hypertension (442 individuals). With concordant normotension as the reference, the multivariable-adjusted ORs were 0.954 (95% CI, 0.534-1.640; P = 0.870) for isolated brachial hypertension and 2.585 (95%CI, 1.841-3.633; P < 0.001) for concordant hypertension. Among non-dialysis patients with CKD, 24-h c2SBP exhibits greater efficacy in identifying the presence of LVH compared with 24-h bSBP. The presence of LVH was greater in cases of concordant hypertension compared with cases of isolated brachial hypertension and concordant normotension.

Structurally diverse macrocycle co-crystals for solid-state luminescence modulation.

Organic co-crystals offer an opportunity to fabricate organic functional materials. Traditional co-crystals are generally packed following the segregated or mixed stacking mode, leading to the lack of structural and functional diversity. Herein, we report three sets of macrocycle co-crystals with identical co-constitutions. The macrocycle co-crystals differ in the stoichiometric ratios (2:1, 1:1, and 2:3) of the constituents and molecular packing modes. The co-crystals are constructed using triangular pyrene-macrocycle and 1,2,4,5-tetracyanobenzene exploiting exo-wall charge-transfer interactions. Interestingly, the three co-crystals exhibit distinct, tunable emission properties. The corresponding emission peaks appear at 575, 602, and 635 nm, covering yellow via orange to red. The X-ray diffraction analyses and the density functional theory calculations reveal the superstructure-property relationships that is attributed to the formation of different ratios of charge-transfer transition states between the donor and acceptor motifs, resulting in red-shifted luminescence.

Benefit finding in individuals undergoing maintenance hemodialysis in Shanghai: a latent profile analysis.

Objective: This multi-center cross-sectional study aimed to delineate latent profiles of benefit finding (BF) in individuals undergoing maintenance hemodialysis (MHD) in Shanghai and examine associations between these BF profiles, social support, and coping style. Methods: A total of 384 individuals undergoing MHD (mean age = 57.90, SD = 13.36) were assessed using the Benefit Finding Scale, Simplified Coping Style Questionnaire, and Perceived Social Support Scale. Latent profile analysis (LPA) identified distinct BF categories. Analysis of variance (ANOVA) evaluated the correlation between BF groups and demographic variables, while the relationship between BF, social support, and coping style was tested through correlation and multiple regression analyses. Results: LPA identified three BF groups: rich BF (54.17%), moderate BF (41.14%), and poor BF (4.69%). Regression analyses indicated that positive coping and social support are protective factors for BF. Additionally, older age and heightened understanding of MHD correlated with higher BF levels. Conclusion: The findings highlighted the importance of recognizing different BF profiles in individuals on MHD and working toward promoting BF levels in the rich BF and moderate BF groups, while helping the poor BF group to identify and address their challenges. Medical professionals should consider interventions tailored to individual psychological profiles to improve mental health and quality of life outcomes in this population.

Prevalence and risk factors of MAFLD and its metabolic comorbidities in community-based adults in China: A cross-sectional study.

AIMS: There is a growing interest in the co-management of metabolic dysfunction-associated fatty liver disease (MAFLD) and its metabolic comorbidities. However, there is insufficient epidemiological data regarding MAFLD and its metabolic comorbidities in China. This study aims to investigate the prevalence and risk factors of MAFLD and its metabolic comorbidities. METHODS: 9171 participants were recruited in this cross-sectional study, utilizing a multistage, stratified sampling method. All participants underwent a comprehensive assessment. The diagnosis of MAFLD was based on vibration-controlled transient elastography (VCTE). The prevalence of MAFLD and its metabolic comorbidities was calculated. Binary and ordinary logistic regressions were conducted. RESULTS: The overall weighted prevalence of MAFLD was 21.18%. Of the 2081 adults with MAFLD, 1866 (89.67%) had more than one metabolic comorbidity, and only 215 (10.33%) did not have comorbidity. Among the population with MAFLD, the prevalence of dyslipidemia, hypertension, hyperuricemia, and diabetes was 67.47%, 43.73%, 39.10%, and 33.88%, respectively. Advanced age, male gender, overweight/obesity, excessive alcohol consumption, and elevated HOMA-IR levels were positively correlated with the number of MAFLD-related metabolic comorbidities. CONCLUSIONS: A significant proportion of individuals diagnosed with MAFLD presented with metabolic comorbidities. Therefore, engaging in the co-management of MAFLD and its metabolic comorbidities is imperative.

Associations of demographics, aggravating factors, comorbidities, and treatments with atopic dermatitis severity in China: A national cross-sectional study.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disorder impacting populations worldwide, although its clinical characteristics and patient demographics remain uncharacterized in China. The aim of this study was to investigate the demographics, comorbidities, aggravating factors, and treatments in AD patients across different age groups in China. METHODS: This cross-sectional study included Chinese AD patients from 205 hospitals spanning 30 provinces. Patients completed dermatologist-led surveys of general medical history, comorbidities, AD-related aggravating factors, and medications. Two-level mixed-ordered logistic regression was used to evaluate aggravating factors. RESULTS: Overall, 16,838 respondents were included in the final analysis (age 30.9 ± 24.1 years). The proportion of severe AD was the highest in patients with AD onset at ≥60 years (26.73%). Allergic rhinitis and hypertension were the most common atopic and metabolism-related non-atopic comorbidities, respectively. AD severity was significantly associated with chronic urticaria, food allergies, and diabetes. Aggravating factors including foods, seasonal changes, and psychological factors were also linked to AD severity. The cross-sectional survey implied that severe AD may be related to the undertreatment of effective systemic or topical interventions. CONCLUSION: To enhance the management of AD, it is crucial to consider both aggravating factors and the increased utilization of systemic immunotherapy. REGISTRATION: ClinicalTrials.gov Identifier: NCT05316805, CORNERSTONE.

Higher Nocturnal Blood Pressure and Blunted Nocturnal Dipping Are Associated With Decreased Daytime Urinary Sodium and Potassium Excretion in Patients With CKD.

Introduction: Sodium homeostasis is intimately associated with blood pressure (BP) rhythm, and potassium excretion is closely associated with sodium excretion in the general population. However, the association between circadian sodium and potassium pattern excretion and nocturnal BP in patients with chronic kidney disease (CKD) is not elucidated. Methods: We evaluated the correlation between the day-to-night ratio of urinary sodium and potassium excretion rate, nocturnal blood pressure, and nocturnal BP dipping in a CKD cohort. Results: A total of 3152 (56.76% males, mean age 47.63 years) individuals with CKD were included in the study. Patients in quartile 1 (with the lowest ratio) exhibited a 12 mmHg or 9 mmHg higher nocturnal systolic blood pressure (SBP) and blunted SBP dipping than those in quartile 4 when urinary sodium or potassium excretion rate was divided into day-to-night ratios (both P < 0.001). In multivariate analyses, lower day-to-night ratio of urinary sodium was independently linked to higher nocturnal SBP and blunted SBP dipping (linear regression coefficient (95% confidence interval [CI]): -6.89 (-9.48 to -4.31), and -3.64 (-5.48 to -1.80), respectively; both P < 0.001). Similarly, compared with the highest quartile of day-to-night ratio of urinary potassium excretion rate, linear regression coefficient (95% CI) for the lowest quartile was -5.60 (-8.13 to -3.07) for nocturnal SBP, and -2.47 (-4.28 to -0.67) for SBP dipping (both P < 0.001). Moreover, urine flow rate and concentrates of sodium or potassium in the urine were positively associated with urinary sodium or potassium excretion during daytime (P < 0.001). Conclusion: A higher nocturnal BP and a blunted nocturnal BP dipping were both independently linked to a lower excretion of sodium or potassium during the day in patients with CKD. Furthermore, a decreased urine flow rate and a diminished capacity to concentrate sodium or potassium in the urine appear to be the key contributors to a low day-to-night ratio of urinary sodium excretion or potassium rate.

Research on the morphological structure of partial fracture healing process in diabetic mice based on synchrotron radiation phase-contrast imaging computed tomography and deep learning.

The prevalence of diabetes mellitus has exhibited a notable surge in recent years, thereby augmenting the susceptibility to fractures and impeding the process of fracture healing. The primary objective of this investigation is to employ synchrotron radiation phase-contrast imaging computed tomography (SR-PCI-CT) to examine the morphological and structural attributes of different types of callus in a murine model of diabetic partial fractures. Additionally, a deep learning image segmentation model was utilized to facilitate both qualitative and quantitative analysis of callus during various time intervals. A total of forty male Kunming mice, aged five weeks, were randomly allocated into two groups, each consisting of twenty mice, namely, simple fracture group (SF) and diabetic fracture group (DF). Mice in DF group were intraperitoneally injected 60 mg/kg 1 % streptozotocin(STZ) solution for 5 consecutive days, and the standard for modeling was that the fasting blood glucose level was ≥11.1 mmol /l one week after the last injection of STZ. The right tibias of all mice were observed to have oblique fractures that did not traverse the entire bone. At three, seven, ten and fourteen days after the fracture occurred, the fractured tibias were extracted for SR-PCI-CT imaging and histological analysis. Furthermore, a deep learning image segmentation model was devised to automatically detect, categorize and quantitatively examine different types of callus. Image J software was utilized to measure the grayscale values of different types of callus and perform quantitative analysis. The findings demonstrated that:1)SR-PCI-CT imaging effectively depicted the morphological attributes of different types of callus of fracture healing. The grayscale values of different types of callus were significantly different(P < 0.01).2)In comparison to the SF group, the DF group exhibited a significant reduction in the total amount of callus during the same period (P < 0.01). Additionally, the peak of cartilage callus in the hypertrophic phase was delayed.3)Histology provides the basis for training algorithms for deep learning image segmentation models. The deep-learning image segmentation models achieved accuracies of 0.69, 0.81 and 0.733 for reserve/proliferative cartilage, hypertrophic cartilage and mineralized cartilage, respectively, in the test set. The corresponding Dice values were 0.72, 0.83 and 0.76, respectively. In summary, SR-PCI-CT images are close to the histological level, and a variety of cartilage can be identified on synchrotron radiation CT images compared with histological examination, while artificial intelligence image segmentation model can realize automatic analysis and data generation through deep learning, and further determine the objectivity and accuracy of SR-PCI-CT in identifying various cartilage tissues. Therefore, this imaging technique combined with deep learning image segmentation model can effectively evaluate the effect of diabetes on the morphological and structural changes of callus during fracture healing in mice.