Reference values of carotid intima-media thickness and arterial stiffness in Chinese adults based on ultrasound radio frequency signal: A nationwide, multicenter study.

BACKGROUND: Carotid intima-media thickness (IMT) and diameter, stiffness, and wave reflections, are independent and important clinical biomarkers and risk predictors for cardiovascular diseases. The purpose of the present study was to establish nationwide reference values of carotid properties for healthy Chinese adults and to explore potential clinical determinants. METHODS: A total of 3053 healthy Han Chinese adults (1922 women) aged 18-79 years were enrolled at 28 collaborating tertiary centers throughout China between April 2021 and July 2022. The real-time tracking of common carotid artery walls was achieved by the radio frequency (RF) ultrasound system. The IMT, diameter, compliance coefficient, ß stiffness, local pulse wave velocity (PWV), local systolic blood pressure, augmented pressure (AP), and augmentation index (AIx) were then automatically measured and reported. Data were stratified by age groups and sex. The relationships between age and carotid property parameters were analyzed by Jonckheere-Terpstra test and simple linear regressions. The major clinical determinants of carotid properties were identified by Pearson's correlation, multiple linear regression, and analyses of covariance. RESULTS: All the parameters of carotid properties demonstrated significantly age-related trajectories. Women showed thinner IMT, smaller carotid diameter, larger AP, and AIx than men. The ß stiffness and PWV were significantly higher in men than women before forties, but the differences reversed after that. The increase rate of carotid IMT (5.5 µm/year in women and 5.8 µm/year in men) and diameter (0.03 mm/year in both men and women) were similar between men and women. For the stiffness and wave reflections, women showed significantly larger age-related variations than men as demonstrated by steeper regression slopes (all P for age by sex interaction <0.05). The blood pressures, body mass index (BMI), and triglyceride levels were identified as major clinical determinants of carotid properties with adjustment of age and sex. CONCLUSIONS: The age- and sex-specific reference values of carotid properties measured by RF ultrasound for healthy Chinese adults were established. The blood pressures, BMI, and triglyceride levels should be considered for clinical application of corresponding reference values.

The long-term effect of bariatric/metabolic surgery versus pharmacologic therapy in type 2 diabetes mellitus patients: A systematic review and meta-analysis.

Metabolic/bariatric surgery as a treatment for obesity and related diseases, such as type 2 diabetes mellitus (T2DM), has been increasingly recognised in recent years. However, compared with conventional pharmacologic therapy, the long-term effect (≥ 5 years) of metabolic surgery in T2DM patients is still unclear. This study aimed to evaluate the diabetes remission rate, incidence of diabetic microvascular complications, incidence of macrovascular complications, and mortality in T2DM patients who received metabolic surgery versus pharmacologic therapy more than 5 years after the surgery. Searching the database, including PubMed, Embase, Web of Science, and Cochrane Library from the inception to recent (2024), for randomised clinical trials (RCTs) or cohort studies comparing T2DM patients treated with metabolic surgery versus pharmacologic therapy reporting on the outcomes of the diabetes remission rate, diabetic microvascular complications, macrovascular complications, or mortality over 5 years or more. A total of 15 articles with a total of 85,473 patients with T2DM were eligible for review and meta-analysis in this study. There is a significant long-term increase in diabetes remission for metabolic surgery compared with conventional medical therapy in the overall pooled estimation and RCT studies or cohort studies separately (overall: OR = 4.58, 95% CI: 1.89-11.07, P < 0.001). Significant long-term decreases were found in the pooled results of microvascular complications incidence (HR = 0.57, 95% CI: 0.41-0.78, P < 0.001), macrovascular complications incidence (HR = 0.59, 95% CI: 0.50-0.70, P < 0.001) and mortality (HR = 0.53, 95% CI: 0.53-0.79, P = 0.0018). Metabolic surgery showed more significant long-term effects than pharmacologic therapy on diabetes remission, macrovascular complications, microvascular complications incidence, and all-cause mortality in patients with T2DM using currently available evidence. More high-quality evidence is needed to validate the long-term effects of metabolic surgery versus conventional treatment in diabetes management.

Advances in microneedles for transdermal diagnostics and sensing applications.

Microneedles, the miniaturized needles, which can pierce the skin with minimal invasiveness open up new possibilities for constructing personalized Point-of-Care (POC) diagnostic platforms. Recent advances in microneedle-based POC diagnostic systems, especially their successful implementation with wearable technologies, enable biochemical detection and physiological recordings in a user-friendly manner. This review presents an overview of the current advances in microneedle-based sensor devices, with emphasis on the biological basis of transdermal sensing, fabrication, and application of different types of microneedles, and a summary of microneedle devices based on various sensing strategies. It concludes with the challenges and future prospects of this swiftly growing field. The aim is to present a critical and thorough analysis of the state-of-the-art development of transdermal diagnostics and sensing devices based on microneedles, and to bridge the gap between microneedle technology and pragmatic applications.

Establishment of a RAA-CRISPR Cas12a based diagnostic method for peste des petits ruminants virus N gene and M gene.

Peste des petis ruminants (PPR) is an acute, highly contagious fatal disease affecting both domestic and wild small ruminants, caused by Morbillivirus caprinae (also known as peste des petis ruminants virus (PPRV)). Herein, a rapid method based on recombinase aided amplification-clustered regularly interspaced short palindromic repeats-Cas12a (RAA-CRISPR Cas12a) to detect PPRV was developed. CRISPR RNAs and RAA primers for PPRV-N (nucleocapsid) and PPRV-M (matrix) fragments were designed. The reaction system was constructed following screening and optimization. Detection could be completed within in 50 minutes at 37°C. Detection of gradient dilutions of plasmids carrying of PPRV N and M gene fragments indicated a minimum limit of detection of 10 copies/µL. There were no cross-reactions with related viruses and all tested lineages of PPRV were detected successfully. The method also showed good repeatability. The detection of clinical samples (previously detected using reverse transcription polymerase chain reaction (RT-PCR)) indicated good consistency between the RAA-CRISPR Cas12a method and RT-PCR. Thus, the RAA-CRISPR Cas12a method for rapid PPRV diagnosis has strong specificity, high sensitivity, and stable repeatability. Moreover, the results can be observed visually under blue or UV light or using lateral flow strips without complex instruments.

Non-Destructive Inspection of Physicochemical Indicators of Lettuce at Rosette Stage Based on Visible/Near-Infrared Spectroscopy.

Lettuce is a globally important cash crop, valued by consumers for its nutritional content and pleasant taste. However, there is limited research on the changes in the growth indicators of lettuce during its growth period in domestic settings. Quality assessment primarily relies on subjective evaluations, resulting in significant variability. This study focused on hydroponically grown lettuce during the rosette stage and investigated the patterns of changes in the indicators and spectral curves over time. By employing spectral preprocessing and selecting characteristic wavelengths, three models were developed to predict the indicators. The results showed that the optimal model structures were S_G-UVE-PLSR (SSC and vitamin C) and Nor-CARS-PLSR (moisture content). The PLSR models achieved prediction set correlation coefficients of 0.8648, 0.8578, and 0.8047, with residual prediction deviations of 1.9685, 1.9568, and 1.6689, respectively. The optimal models were integrated into a portable device, using real-time analysis software written in Matlab2021a, for the prediction of the physicochemical indicators of lettuce during the rosette stage. The results demonstrated prediction set correlation coefficients of 0.8215, 0.8472, and 0.7671, with root mean square errors of prediction of 0.5348, 1.5813, and 2.3347 for a sample size of 180. The small discrepancies between the predicted and actual values indicate that the developed device can meet the requirements for real-time detection.

Experimental and molecular dynamics simulation studies on the physical properties of three HBc-VLP derivatives as nanoparticle protein vaccine candidates.

Self-assembling virus-like particles (VLPs) are promising platforms for vaccine development. However, the unpredictability of the physical properties, such as self-assembly capability, hydrophobicity, and overall stability in engineered protein particles fused with antigens, presents substantial challenges in their downstream processing. We envision that these challenges can be addressed by combining more precise computer-aided molecular dynamics (MD) simulations with experimental studies on the modified products, with more to-date forcefield descriptions and larger models closely resembling real assemblies, realized by rapid advancement in computing technology. In this study, three chimeric designs based on the hepatitis B core (HBc) protein as model vaccine candidates were constructed to study and compare the influence of inserted epitopes as well as insertion strategy on HBc modifications. Large partial VLP models containing 17 chains for the HBc chimeric model vaccines were constructed based on the wild-type (wt) HBc assembly template. The findings from our simulation analysis have demonstrated good consistency with experimental results, pertaining to the surface hydrophobicity and overall stability of the chimeric vaccine candidates. Furthermore, the different impact of foreign antigen insertions on the HBc scaffold was investigated through simulations. It was found that separately inserting two epitopes into the HBc platform at the N-terminal and the major immunogenic regions (MIR) yields better results compared to a serial insertion at MIR in terms of protein structural stability. This study substantiates that an MD-guided design approach can facilitate vaccine development and improve its manufacturing efficiency by predicting products with extreme surface hydrophobicity or structural instability.

The mechanism of Xihuang pills' intervention in the tumour immune microenvironment for the treatment of liver cancer based on the STAT3-PDL1 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Xihuang pills, a time-honored Chinese compound formula with a history spanning thousands of years, have demonstrated remarkable efficacy in treating various cancers, such as breast cancer, colon cancer, and liver cancer. Clinical applications over the years have established their effectiveness. Several scholars conducting experimental studies have elucidated the potent tumor-suppressing effects of Xihuang pills. While the inhibition of tumor vascular development and prevention of tumor cell invasion and metastasis have been well-explored mechanisms, the impact on the tumor immune microenvironment has received less attention. This study focuses on investigating the immune microenvironment adjustments induced by Xihuang pills in hepatocellular carcinoma. AIM OF THE STUDY: Tumour cells will find an escape phenomenon during tumour immunotherapy, which will affect immunotherapy results. We will research the regulation of the tumour immune microenvironment, to provide a more complete and precise basis for the elucidation of the mechanism of Xihuang pills in treating cancers. It provides new research ideas for people to treat liver cancer. MATERIALS AND METHODS: Through in vivo and in vitro assessments confirming the intervention effects of Xihuang pills, we observed alterations in T cell typing, macrophage polarization, and tumor-associated cytokine levels. The primary active ingredients of Xihuang pills were identified using UPLC-MS/GC-MS, and relevant pathways in the treatment of hepatocellular carcinoma were predicted through network pharmacology. Combining the network pharmacology approach, we predicted the pathways relevant to Xihuang pills in treating hepatocellular carcinoma and experimentally validated the involvement of PD-1/PD-L1, a key immunity-related axis. RESULTS: Xihuang Pill has a regulatory effect on the tumor immune microenvironment. CONCLUSIONS: The results indicated that Xihuang pills could impact splenic lymphocyte phenotyping, macrophage polarization, and IL-6 cytokine expression in liver cancer mice. The mechanism of action was associated with the regulation of the PD-1/PD-L1 signaling pathway by the STAT3 protein.

Resilience provides mediating effect of resilience between fear of progression and sleep quality in patients with hematological malignancies.

BACKGROUND: Hematological tumors are common malignant tumors, with high morbidity and mortality rates. Most patients with hematological malignancies develop sleep disorders that seriously affect their life and health because of acute onset of disease, rapid progression, high recurrence rates, complex treatment methods, and treatment costs. AIM: To explore the mediating effect of resilience on fear of disease progression and sleep quality in patients with hematological malignancies. METHODS: A cross-sectional analysis of 100 patients with hematological malignancies, treated in the First Affiliated Hospital of Jinzhou Medical University between August 2022 and August 2023, was conducted. Patients were assessed using a general data survey, a simplified scale for the fear of progression (FoP) of disease, a resilience scale, and the Pittsburgh Sleep Quality Index. Statistical analysis was conducted to determine the relationship between various patient characteristics and FoP, resilience, and sleep quality. Spearman's correlation analysis was used to examine the correlations between mental resilience, FoP, and sleep quality. RESULTS: The total FoP score mean value in patients with hematological malignancies was 38.09 ± 5.16; the total resilience score mean value was 40.73 ± 7.04; and the Pittsburgh Sleep Quality Index score mean value was 10.72 ± 1.90. FoP, resilience, and sleep quality of the patients were associated with family per capita monthly income and patient education level (P < 0.05). Spearman correlation analysis revealed that FoP was negatively correlated with resilience and sleep quality scores (r = -0.560, -0.537, P < 0.01), respectively, and resilience was significantly associated with sleep quality scores (r = 0.688, P < 0.01). Mediation analysis showed that the mediating effect of resilience between FoP and sleep quality in patients with hematological malignancies was -0.100 and accounted for 50.51% of the total effect. This indicated that FoP directly and indirectly affected sleep quality through the mesomeric effect of resilience. CONCLUSION: Resilience is an intermediary variable between FoP and sleep quality in patients with hematological malignancies. Medical staff should evaluate and follow-up FoP and resilience to implement measures to improve sleep quality.

The therapeutic potential of Ziziphi Spinosae Semen and Polygalae Radix in insomnia management: Insights from gut microbiota and serum metabolomics techniques.

ETHNOPHARMACOLOGICAL RELEVANCE: Ziziphi Spinosae Semen and Polygalae Radix (ZSS-PR) constitute a traditional Chinese herbal combination with notable applications in clinical and experimental settings due to their evident sedative and calming effects. Aligned with traditional Chinese medicine principles, Ziziphi Spinosae Semen supports cardiovascular health, nourishes the liver, and induces mental tranquillity. Simultaneously, Polygalae Radix elicits calming effects, fosters clear thinking, and reinstates proper coordination between the heart and kidneys. ZSS-PR is commonly employed as a therapeutic intervention for various insomnia types, demonstrating distinct clinical efficacy. Our previous study findings provide evidence that ZSS-PR administration significantly reduces sleep onset latency, increases overall sleep duration, and improves abnormal neurotransmitter levels in a murine insomnia model. AIM OF STUDY: This investigation aimed to scrutinize the intrinsic regulatory mechanism of ZSS-PR in managing insomnia using gut microbiota and serum metabolomics techniques. MATERIALS AND METHODS: Mice were given DL-4-Chlorophenylalanine to induce insomnia and then treated with ZSS-PR. The open-field test assessed the animals' spontaneous activity. Concentrations of neurotransmitters, endocrine hormones, and cytokines in the duodenum were measured using enzyme linked immunosorbent assay, and brain histopathology was evaluated with H&E staining. The impact of ZSS-PR on the metabolic profile was examined by liquid chromatography couped to high resolution mass spectrometry, and 16S rDNA sequencing was used to study the influence of ZSS-PR on the gut microbiota. Additionally, the content of short-chain fatty acids (SCFAs) was analyzed by GC-MS. Finally, correlation analysis investigated relationships between biochemical markers, metabolites, SCFAs, and gut microbiota. RESULTS: ZSS-PR treatment significantly increased movement time and distance in mice with insomnia and improved pathological impairments in the cerebral cortex and hippocampus. It also restored abnormal levels of biochemical markers in the gut of insomnia-afflicted mice, including 5-hydroxytryptamine, dopamine, gastrin, melatonin, tumour necrosis factor-α, and interleukin-1ß. Metabolomics findings showed that ZSS-PR had a significant restorative effect on 15 endogenous metabolites in mice with insomnia. Furthermore, ZSS-PR primarily influenced five metabolic pathways, such as phenylalanine, tyrosine, and tryptophan biosynthesis, glutamine, and glutamate metabolism. Additionally, gut microbiota analysis revealed notable alterations in both diversity and microbial composition after ZSS-PR treatment. These changes were primarily attributed to the relative abundances of microbiota, including Firmicutes, Bacteroidota, Fusobacteriota, Muribaculaceae_unclassified, and Ligilactobacillus. The results of SCFAs analysis demonstrated that ZSS-PR effectively restored abnormal levels of acetic acid, propionic acid, isobutyric acid, butyric acid, isovaleric acid, and valeric acid in insomniac mice. Subsequent correlation analysis revealed that microbiota show obvious correlations with both biochemical markers and metabolites. CONCLUSIONS: The results provide compelling evidence that ZSS-PR effectively mitigates abnormal activity, reduces cerebral pathological changes, and restores abnormal levels of neurotransmitters, endocrine hormones, and cytokines in mice with insomnia. The underlying mechanism is intricately linked to the modulation of gut microbiota and endogenous metabolic pathways.

Glycosides constituents from Codonopsis pilosula.

A new glycoside (1) along with six known analogues (1-7) were isolated from Codonopsis pilosula collected at Shanxi in China. The structure of 1 was established based on comprehensive spectroscopic data and literature comparison. The anti-inflammatory effects of isolated compounds were further investigated in LPS-induced RAW264.7 macrophage.

Microenvironmental Enzyme-Responsive Methotrexate Modified Quercetin Micelles for the Treatment of Rheumatoid Arthritis.

Purpose: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease involving synovial inflammation and joint destruction. Although therapeutic drugs for RA have some efficacy, they usually cause severe side effects and are expensive. RA is characterized by synovial hyperplasia, intra-articular hypoxia, upregulated expression of matrix metalloproteinases, and excessive accumulation of reactive oxygen species. The adverse microenvironment further aggravates activated macrophage infiltration. Therefore, controlling the microenvironment of diseased tissues and targeting the activated macrophages have become new therapeutic targets in RA patients. Methods: Here, microenvironment-targeting micelles (PVGLIG-MTX-Que-Ms) were synthesized using the thin film hydration method. In the inflammatory microenvironment, PVGLIG was cleaved by the highly expressed MMP-2, PEG5000 was eliminated, MTX was exposed, macrophage activation was targeted, and Que enrichment was enhanced. The cytotoxicity, targeting, antioxidant, and anti-inflammatory properties of drug-loaded micelles were tested in vitro. The drug-loaded micelles were used to treat CIA rats. In vivo targeting, expression of serum inflammatory factors, immunohistochemistry of the articular cartilage, and changes in immunofluorescence staining were observed. Results: The developed micelles had a particle size of (89.62 ±1.33) nm and a zeta potential of (-4.9 ±0.53) mV. The IC50 value of PVGLIG-MTX-Que-Ms (185.90 ±6.98) µmol/L was significantly lower than that of free Que (141.10 ±6.39) µmol/L. The synthesized micelles exhibited slow-release properties, low cytotoxicity, strong targeting abilities, and significant anti-inflammatory effects in vitro. In vivo, the drug-loaded micelles accumulated at the joint site for a long time. PVGLIG-MTX-Que-Ms significantly reduced joint swelling, improved bone destruction, and decreased the expression of serum inflammatory factors in CIA rats. Conclusion: The smart-targeting micelles PVGLIG-MTX-Que-Ms with strong targeting, anti-inflammatory, cartilage-protective, and other multiple positive effects are a promising new tool for RA treatment.

Emerging non-antibody‒drug conjugates (non-ADCs) therapeutics of toxins for cancer treatment.

The non-selective cytotoxicity of toxins limits the clinical relevance of the toxins. In recent years, toxins have been widely used as warheads for antibody‒drug conjugates (ADCs) due to their efficient killing activity against various cancer cells. Although ADCs confer certain targeting properties to the toxins, low drug loading capacity, possible immunogenicity, and other drawbacks also limit the potential application of ADCs. Recently, non-ADC delivery strategies for toxins have been extensively investigated. To further understand the application of toxins in anti-tumor, this paper provided an overview of prodrugs, nanodrug delivery systems, and biomimetic drug delivery systems. In addition, toxins and their combination strategies with other therapies were discussed. Finally, the prospect and challenge of toxins in cancer treatment were also summarized.

Fe-MOF/AuNP-based ratiometric electrochemical immunosensor for the detection of deoxynivalenol in grain products.

A ratiometric assay was designed to improve the sensitivity and reliability of electrochemical immunosensors for deoxynivalenol (DON) detection. The indicator signal caused by the Fe-based metal-organic framework nanocomposites loaded with gold nanoparticles and the internal reference signal from the [Fe(CN)6]3-/4- in the electrolyte came together at the immunosensor. When immunoreactivity occurred, the indicator signals decreased as the concentration of DON increased, while the internal reference signals increased slightly. The ratio of the indicator signal to the internal reference signal was available for reproducible and sensitive monitoring of DON. The prepared immunosensor showed excellent performance in the range from 0.5 to 5000 pg mL-1, and the detection limit was 0.0166 pg mL-1. The immunosensor achieved satisfactory detection toward DON in spiked and actual samples and has a promising application in the control of DON in grain products.

Mechanistic insights into the interactions of TAX1BP1 with RB1CC1 and mammalian ATG8 family proteins.

TAX1BP1, a multifunctional autophagy adaptor, plays critical roles in different autophagy processes. As an autophagy receptor, TAX1BP1 can interact with RB1CC1, NAP1, and mammalian ATG8 family proteins to drive selective autophagy for relevant substrates. However, the mechanistic bases underpinning the specific interactions of TAX1BP1 with RB1CC1 and mammalian ATG8 family proteins remain elusive. Here, we find that there are two distinct binding sites between TAX1BP1 and RB1CC1. In addition to the previously reported TAX1BP1 SKICH (skeletal muscle and kidney enriched inositol phosphatase (SKIP) carboxyl homology)/RB1CC1 coiled-coil interaction, the first coiled-coil domain of TAX1BP1 can directly bind to the extreme C-terminal coiled-coil and Claw region of RB1CC1. We determine the crystal structure of the TAX1BP1 SKICH/RB1CC1 coiled-coil complex and unravel the detailed binding mechanism of TAX1BP1 SKICH with RB1CC1. Moreover, we demonstrate that RB1CC1 and NAP1 are competitive in binding to the TAX1BP1 SKICH domain, but the presence of NAP1's FIP200-interacting region (FIR) motif can stabilize the ternary TAX1BP1/NAP1/RB1CC1 complex formation. Finally, we elucidate the molecular mechanism governing the selective interactions of TAX1BP1 with ATG8 family members by solving the structure of GABARAP in complex with the non-canonical LIR (LC3-interacting region) motif of TAX1BP1, which unveils a unique binding mode between LIR and ATG8 family protein. Collectively, our findings provide mechanistic insights into the interactions of TAX1BP1 with RB1CC1 and mammalian ATG8 family proteins and are valuable for further understanding the working mode and function of TAX1BP1 in autophagy.

Integrating shear wave elastography and estimated glomerular filtration rate to enhance diagnostic strategy for renal fibrosis assessment in chronic kidney disease.

Background: Assessing renal fibrosis non-invasively in patients with chronic kidney disease (CKD) remains a considerable clinical challenge. This study aimed to investigate the diagnostic efficacy of different approaches that combine shear wave elastography (SWE) and estimated glomerular filtration rate (eGFR) in distinguishing between mild fibrosis and moderate-to-severe fibrosis in CKD patients. Methods: In this prospective study, 162 patients underwent renal SWE examinations and renal biopsies. Using SWE, the right renal cortex stiffness was measured, and the corresponding SWE value was recorded. Four diagnostic patterns were used to combine eGFR and SWE value: in isolation, in series, in parallel, and in integration. The receiver operating characteristic (ROC) curve was established, and the area under the ROC curve (AUC) was calculated to quantify diagnostic performance. Sensitivity, specificity, and accuracy were computed. Results: The eGFR demonstrated sensitivity of 68.2% and specificity of 83.8%, whereas the SWE value displayed sensitivity of 84.1% and specificity of 62.2%, yielding a similar AUC (78.2% and 77.8%, respectively). Combining in series improved specificity to 97.3%, superior to other diagnostic patterns (all P values <0.01), but compromised sensitivity to 58.0%. When combined in parallel, the sensitivity increased to 94.3%, exceeding any other strategies (all P values <0.05), but the specificity dropped to 48.7%. The integrated strategy, incorporating eGFR with SWE value via the logistic regression algorithm, exhibited an AUC of 85.8%, outperforming all existing approaches (all P values <0.01), with balanced sensitivity, specificity, and accuracy of 86.4%, 74.3%, and 80.9%, respectively. Conclusions: Using an integrated strategy to combine eGFR and SWE value could improve diagnostic performance in distinguishing between mild renal fibrosis and moderate-to-severe renal fibrosis in patients with CKD, thereby helping clinicians perform a more accurate clinical diagnosis.

Interpretable machine learning model integrating clinical and elastosonographic features to detect renal fibrosis in Asian patients with chronic kidney disease.

BACKGROUND: Non-invasive renal fibrosis assessment is critical for tailoring personalized decision-making and managing follow-up in patients with chronic kidney disease (CKD). We aimed to exploit machine learning algorithms using clinical and elastosonographic features to distinguish moderate-severe fibrosis from mild fibrosis among CKD patients. METHODS: A total of 162 patients with CKD who underwent shear wave elastography examinations and renal biopsies at our institution were prospectively enrolled. Four classifiers using machine learning algorithms, including eXtreme Gradient Boosting (XGBoost), Support Vector Machine (SVM), Light Gradient Boosting Machine (LightGBM), and K-Nearest Neighbor (KNN), which integrated elastosonographic features and clinical characteristics, were established to differentiate moderate-severe renal fibrosis from mild forms. The area under the receiver operating characteristic curve (AUC) and average precision were employed to compare the performance of constructed models, and the SHapley Additive exPlanations (SHAP) strategy was used to visualize and interpret the model output. RESULTS: The XGBoost model outperformed the other developed machine learning models, demonstrating optimal diagnostic performance in both the primary (AUC = 0.97, 95% confidence level (CI) 0.94-0.99; average precision = 0.97, 95% CI 0.97-0.98) and five-fold cross-validation (AUC = 0.85, 95% CI 0.73-0.98; average precision = 0.90, 95% CI 0.86-0.93) datasets. The SHAP approach provided visual interpretation for XGBoost, highlighting the features' impact on the diagnostic process, wherein the estimated glomerular filtration rate provided the largest contribution to the model output, followed by the elastic modulus, then renal length, renal resistive index, and hypertension. CONCLUSION: This study proposed an XGBoost model for distinguishing moderate-severe renal fibrosis from mild forms in CKD patients, which could be used to assist clinicians in decision-making and follow-up strategies. Moreover, the SHAP algorithm makes it feasible to visualize and interpret the feature processing and diagnostic processes of the model output.

Association of renal elasticity evaluated by real-time shear wave elastography with renal fibrosis in patients with chronic kidney disease.

OBJECTIVE: Renal fibrosis is a final common pathological hallmark in the progression of chronic kidney disease (CKD). Non-invasive evaluation of renal fibrosis by mapping renal stiffness obtained by shear wave elastography (SWE) may facilitate the clinical therapeutic regimen for CKD patients. METHODS: A cohort of 162 patients diagnosed with CKD, who underwent renal biopsy, was prospectively and consecutively recruited between April 2019 and December 2021. The assessment of renal cortex stiffness was performed using SWE imaging. The patients were classified into different groups based on pathological renal fibrosis (mild group: n = 74; moderate-to-severe group: n = 88). Binary logistic regression model and generalized additive model were conducted to investigate the association of renal elasticity with renal fibrosis. RESULTS: Compared with the mildly impaired group, the moderate-to-severe group showed a significant decline in renal elasticity (P < .001). In the fully adjusted model, each 10 kPa drop in renal elasticity was associated with a 3.5-fold increment in the risk of moderate-to-severe renal fibrosis (fully adjusted odds ratio, 4.54; 95% CI, 2.41-8.57). Particularly, participants in the lowest elasticity group (≤29.92 kPa) had a 20-fold increased chance of moderate-to-severe renal fibrosis than those in the group with highest elasticity (≥37.93 kPa). An inverse linear association was observed between renal elasticity increment and moderate-to-severe renal fibrosis risk. CONCLUSION: There is a negative linear association between increased renal elasticity and moderate-to-severe renal fibrosis risk among CKD patients. Patients with diminished renal stiffness have a higher risk of moderate-to-severe renal fibrosis. ADVANCES IN KNOWLEDGE: CKD patients with reduced renal stiffness have a higher likelihood of moderate-to-severe renal fibrosis.

Influencing factors of cancer-related fatigue in acute leukemia patients: A cross-sectional study.

Purpose: To investigate influencing factors of cancer-related fatigue (CRF) in adult patients with acute leukemia (AL). Methods: A total of 288 adult patients diagnosed with acute leukemia in West China Hospital were included in this study. A cross-sectional survey, including the Clinical Information Questionnaire, the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Pittsburgh Sleep Quality Index (PSQI), and Hospital Anxiety and Depression Scale (HAD), was provided to the patients. Hierarchical multiple linear regression analyses were conducted to evaluate the associations of the variable factors and the AL patients' CRF. Results: The CRF score of AL patients was 33.25 ± 10.35. Gender, age, albumin level, depression, anxiety status of the patients and treatment cycles were identified as influencing factors of CRF in AL patients (P < 0.05). The CRF level of acute leukemia patients in the complete remission group was lower than that of patients who were not achieving complete remission. Depression, anxiety, age, employment, albumin, and sleep disturbance were independent influencing factors for CRF in patients who were not achieving complete remission. Conclusions: Acute leukemia patients who are female, older, hypoalbuminemia，or in the induction therapy have a higher risk of developing a high degree of CRF. Clinical staff should pay more attention to the CRF of patients who were not achieving complete remission. Early screening and aggressive intervention could be adopted in caring for these patients.

Mechanistic insights into the homo-dimerization of HOIL-1L and SHARPIN.

HOIL-1L and SHARPIN are two essential regulatory subunits of the linear ubiquitin chain assembly complex (LUBAC), which is the only known E3 ligase complex generating linear ubiquitin chains. In addition to their LUBAC-dependent functions, HOIL-1L and SHARPIN alone play crucial roles in many LUBAC-independent cellular processes. Importantly, deficiency of HOIL-1L or SHARPIN leads to severe disorders in humans or mice. However, the mechanistic bases underlying the multi-functions of HOIL-1L and SHARPIN are still largely unknown. Here, we uncover that HOIL-1L and SHARPIN alone can form homo-dimers through their LTM motifs. We solve two crystal structures of the dimeric LTM motifs of HOIL-1L and SHARPIN, which not only elucidate the detailed molecular mechanism underpinning the dimer formations of HOIL-1L and SHARPIN, but also reveal a general mode shared by the LTM motifs of HOIL-1L and SHARPIN for forming homo-dimer or hetero-dimer. Furthermore, we elucidate that the polyglucosan body myopathy-associated HOIL-1L A18P mutation disturbs the structural folding of HOIL-1L LTM, and disrupts the dimer formation of HOIL-1L. In summary, our study provides mechanistic insights into the homo-dimerization of HOIL-1L and SHARPIN mediated by their LTM motifs, and expands our understandings of the multi-functions of HOIL-1L and SHARPIN as well as the etiology of relevant human disease caused by defective HOIL-1L.