Suppressed Renin Status is a Risk Factor for Cardiocerebrovascular Events in Bilateral Primary Aldosteronism Treated with Mineralocorticoid Receptor Antagonists.

BACKGROUND: Mineralocorticoid receptor antagonists (MRAs) are the recommended medical therapy for bilateral primary aldosteronism (BPA). Compared with essential hypertension (EH), patients with BPA have higher cardiocerebrovascular disease (CCVD). There is no consensus on the criteria to assess the effectiveness of medical therapy for BPA. OBJECTIVE: To investigate the incidence and the risk factors for CCVD after medical therapy of BPA. METHODS: We conducted a retrospective cohort study including 240 BPA patients treated with MRA. The post-treatment plasma renin activity (PRA) was defined as unsuppressed (PRA≥1ng/ml/h) otherwise, it was defined as suppressed. We analyzed the association of post-treatment PRA status with CCVD outcomes. RESULTS: 7.1% (17/240) of patients with BPA developed CCVD at a median follow-up of 5.0 (2.96,7.66) years. 57.1% of patients had PRA ≥ 1ng/ml/h after treatment. Patients with PRA <1ng/ml/h have a higher incidence of CCVD (12.6% vs. 2.9%, P < 0.05) and they are at greater risk than those with PRA ≥1ng/ml/h (HR=4.50, 95% CI: 1.47-13.83, P<0.05; adjusted HR=3.98, 95% CI: 1.22-13.02, P<0.05). CONCLUSION: Patients with BPA treated with pharmacological have a high incidence of CCVD. PRA may be an indicator that mineralocorticoids are being adequately antagonized.

Integrating carbon and water footprint into nature-based solution (NBS) for urban planning in a highly built-up area in Guangzhou, China.

Stormwater management problems have been deteriorated with the high frequency and intensity of precipitation owing to rapid urbanization and climate variability, especially in urban highly built-up area. Nature-based solutions (NBS) have emerged as a powerful measure for rising these challenges due to their ability to mitigate urban waterlogging and increase carbon sequestration. Identifying optimal locations for NBS implementation remains a critical research focus. This study integrates carbon and water footprint accounting into NBS-based planning for sustainable urban development in central Guangzhou, China, to enhance urban flooding mitigation and carbon sequestration. Through carbon-water footprint analysis and weighting, we prioritized NBS planning. To achieve the objectives of increasing sequestered carbon and reducing urban runoff, three types of NBS-green roofs, permeable pavements, and bioretention systems-were optimized for a high-priority town street. The results showed that the implementation of green roof and permeable pavement reduced the surface runoff by 3.58 %, while the biological retention system reduced the runoff gray water by 27 %. Moreover, the application of green roof and biological retention increased the carbon sequestration by 2.57 million kg CO2-eq (life cycle). The findings of this study provide comprehensive insights into optimization of NBS planning based on carbon-water footprint accounting, facilitating to enhance mitigation of urban flooding vulnerability and carbon sequestration.

Prediction of pathological complete response and prognosis in locally advanced rectal cancer.

BACKGROUND: Colorectal cancer is currently the third most common malignant tumor and the second leading cause of cancer-related death worldwide. Neoadjuvant chemoradiotherapy (nCRT) is standard for locally advanced rectal cancer (LARC). Except for pathological examination after resection, it is not known exactly whether LARC patients have achieved pathological complete response (pCR) before surgery. To date, there are no clear clinical indicators that can predict the efficacy of nCRT and patient outcomes. AIM: To investigate the indicators that can predict pCR and long-term outcomes following nCRT in patients with LARC. METHODS: Clinical data of 128 LARC patients admitted to our hospital between September 2013 and November 2022 were retrospectively analyzed. Patients were categorized into pCR and non-pCR groups. Univariate analysis (using the χ 2 test or Fisher's exact test) and logistic multivariate regression analysis were used to study clinical predictors affecting pCR. The 5-year disease-free survival (DFS) and overall survival (OS) rates were calculated using Kaplan-Meier analysis, and differences in survival curves were assessed with the log-rank test. RESULTS: Univariate analysis showed that pretreatment carcinoembryonic antigen (CEA) level, lymphocyte-monocyte ratio (LMR), time interval between neoadjuvant therapy completion and total mesorectal excision, and tumor size were correlated with pCR. Multivariate results showed that CEA ≤ 5 ng/mL (P = 0.039), LMR > 2.73 (P = 0.023), and time interval > 10 wk (P = 0.039) were independent predictors for pCR. Survival analysis demonstrated that patients in the pCR group had significantly higher 5-year DFS rates (94.7% vs 59.7%, P = 0.002) and 5-year OS rates (95.8% vs 80.1%, P = 0.019) compared to the non-pCR group. Tumor deposits (TDs) were significantly correlated with shorter DFS (P = 0.002) and OS (P < 0.001). CONCLUSION: Pretreatment CEA, LMR, and time interval contribute to predicting nCRT efficacy in LARC patients. Achieving pCR demonstrates longer DFS and OS. TDs correlate with poor prognosis.

The influence of cortisol co-secretion on clinical characteristics and postoperative outcomes in unilateral primary aldosteronism.

Context: The prevalence of unilateral primary aldosteronism (UPA) with cortisol co-secretion varies geographically. Objective: To investigate the prevalence and clinical characteristics of UPA with cortisol co-secretion in a Chinese population. Design: Retrospective cohort study. Methods: We recruited 580 patients with UPA who underwent cosyntropin stimulation test (CST) after the 1-mg dexamethasone suppression test (DST) and retrospectively analyzed the clinical characteristics and postoperative outcomes of UPA with and without cortisol co-secretion. Results: UPA with cortisol co-secretion (1 mg DST>1.8 ug/dL) was identified in 65 of 580 (11.2%) patients. These patients were characterized by older age, longer duration of hypertension, higher concentration of plasma aldosterone and midnight cortisol, lower adrenocorticotropic hormone (ACTH) and dehydroepiandrosterone sulfate (DHEAS), larger tumor diameter, and more history of diabetes mellitus. Cortisol and aldosterone levels were higher and DHEAS level was lower in UPA with cortisol co-secretion at 0-120 min after CST. Among 342 UPA patients with KCNJ5 gene sequencing and follow-up results, the complete clinical success rate was lower in UPA with cortisol co-secretion (33.3% vs. 56.4%, P<0.05); the complete biochemical success rate and KCNJ5 mutation did not differ between the two groups. Age, tumor size, and ACTH were independent predictors of UPA with cortisol co-secretion. Sex, BMI, duration of hypertension, KCNJ5 mutation, and cortisol co-secretion were independent predictors for complete clinical success in UPA after surgery. Conclusions: UPA with cortisol co-secretion is not uncommon in China, but the clinical features were distinctly different from those without co-secretion. Cortisol co-secretion is an independent risk factor for incomplete clinical success after surgery in UPA.

Protection effect of lutein-loaded Pickering emulsion prepared via ultrasound-assisted Maillard reaction conjugates on dry age-related macular degeneration.

Age-related macular degeneration (AMD) is a prominent cause of vision loss among the elderly, and the treatment options for dry AMD (dAMD) are severely limited. Lutein has a favorable effect on the treatment of dAMD. Algae oil, rich in docosahexaenoic acid (DHA), is considered an effective intervention for eye diseases. In this study, casein-mannose conjugates were prepared to form algal oil-in-water Pickering emulsions by ultrasound-assisted Maillard reaction. As the ultrasound time increased from 0 to 25 min, the droplet size decreased to 648.2 ± 21.18 nm, which substantially improved the stability of the Pickering emulsions. The retention of lutein in the Pickering emulsions under ultrasonic treatment for 20 min was significantly improved under different conditions. The simulated gastrointestinal digestion revealed that ultrasound-assisted Pickering emulsions are an effective method for improving the bioaccessibility of lutein (19.76%-53.34%). In vivo studies elucidated that the lutein-loaded Pickering emulsions could effectively alleviate retinal thinning induced by sodium iodate (NaIO3) in mice with dAMD. Mechanistically, lutein-loaded Pickering emulsions significantly reduced oxidative stress by decreasing the MDA level, increasing the SOD production, and reducing the retinal ROS production. These findings explored the protective effects of lutein-loaded Pickering emulsions on dAMD and offered promising prospects for the nutritional intervention of dAMD.

Prevalence of prediabetes by the fasting plasma glucose and HbA1c screening criteria among the children and adolescents of Shenzhen, China.

Background: Prediabetes is associated with an increased risk of cardiovascular diseases and all-cause mortality. Rare research in China has evaluated the prevalence of prediabetes among children and adolescents using the HbA1c criterion or the combined FPG-or-HbA1c diagnostic criterion, and researchers paid no attention to the distributions of blood glucose in Shenzhen, especially for juveniles. Methods: We conducted a school-based cross-sectional study based on the first-year students from 17 primary, middle, and high schools. Prediabetes was defined as FPG of 5.6-6.9 mmol/L or HbA1c of 5.7%-6.4%. The crude and standardized prevalence of prediabetes with 95% confidence interval (95% CI) was estimated. Results: A total of 7519 participants, aged 6 to 17 years, were included. For all subjects, the crude prevalence (95% CI) of prediabetes was 1.49% (1.21-1.77), 8.72% (8.08-9.36), and 9.80% (9.13-10.47) by the FPG-only, HbA1c-only, and FPG-or-HbA1c criteria, respectively. Based on the 2010 Shenzhen census population, the standardized prevalence was 1.56% (males 1.85%, females 1.19%), 11.05% (males 11.47%, females 10.53%), and 12.19% (males 13.01%, females 11.15%) by the corresponding criteria. The proportion of prediabetes was higher for males than females, and the prevalence decreased with grade for males but increased for females. The association of BMI and prediabetes was U-shaped curve, indicating higher rates of prediabetes for underweight and obesity people. Conclusion: The blood glucose status of children and adolescents in Shenzhen is worrisome, and the early detection and management of prediabetes are imperative.

Adaptive control for shape memory alloy actuated systems with applications to human-robot interaction.

Introduction: Shape memory alloy (SMA) actuators are attractive options for robotic applications due to their salient features. So far, achieving precise control of SMA actuators and applying them to human-robot interaction scenarios remains a challenge. Methods: This paper proposes a novel approach to deal with the control problem of a SMA actuator. Departing from conventional mechanism models, we attempt to describe this nonlinear plant using a gray-box model, in which only the input current and the output displacement are measured. The control scheme consists of the model parameters updating and the control law calculation. The adaptation algorithm is founded on the multi-innovation concept and incorporates a dead-zone weighted factor, aiming to concurrently reduce computational complexities and enhance robustness properties. The control law is based on a PI controller, the gains of which are designed by the pole assignment technique. Theoretical analysis proves that the closed-loop performance can be ensured under mild conditions. Results: The experiments are first conducted through the Beckhoff controller. The comparative results suggest that the proposed adaptive PI control strategy exhibits broad applicability, particularly under load variations. Subsequently, the SMA actuator is designed and incorporated into the hand rehabilitation robot. System position tracking experiments and passive rehabilitation training experiments for various gestures are then conducted. The experimental outcomes demonstrate that the hand rehabilitation robot, utilizing the SMA actuator, achieves higher position tracking accuracy and a more stable system under the adaptive control strategy proposed in this paper. Simultaneously, it successfully accommodates hand rehabilitation movements for multiple gestures. Discussion: The adaptive controller proposed in this paper takes into account both the computational complexity of the model and the accuracy of the control results, Experimental results not only demonstrate the practicality and reliability of the controller but also attest to its potential application in human-machine interaction within the field of neural rehabilitation.

Physicochemical properties of esterified/crosslinked quinoa starches and their influence on bread quality.

BACKGROUND: Starch is the main component of quinoa seeds. However, quinoa starch has poor solubility in cold water and poor mechanical resistance and is easily aged, which limit its application. Therefore, modification of its structure to improve its functional properties is necessary. RESULTS: This research used acetic anhydride and sodium trimetaphosphate to modify the structure of starch molecules and investigated their influence on bread quality. The results showed that both esterification and crosslinking prevented the aggregation behavior of starch molecules. Moreover, they both decreased the gelatinization enthalpy change and relative crystallinity of the starch. Compared with native starch, modification significantly decreased the gelatinization temperature from 57.01 to 52.01 °C and the esterified starch exhibited the lowest enthalpy change with a 44.2% decrease. Modified starch increased the specific volume and decreased the hardness and chewiness of bread. Modification did not influence the moisture content in bread but impacted the water retention capacity, depending on the degree of modification. Low and medium degrees of modification improved the water retention capacity during storage. By contrast, a high degree of modification (10 g kg-1 crosslinking agent) decreased the water retention capacity. The dually modified quinoa starch (esterified and crosslinked) showed no influence on the textural properties of bread. CONCLUSION: This study demonstrated that both esterification and crosslinking significantly improved the functional properties of quinoa starch. Crosslinked or esterified quinoa starches have the potential to improve the textural properties of bakery products. © 2024 Society of Chemical Industry.

Incorporation of fucoxanthin into 3D printed Pickering emulsion gels stabilized by salmon by-product protein/pectin complexes.

The remarkable performance of fucoxanthin (FX) in antioxidant and weight loss applications has generated considerable interest. However, the application of fucoxanthin in the food and pharmaceutical industries is limited due to its highly unsaturated structure. This research aimed to investigate the synergistic mechanism of a unique Pickering emulsion gel stabilized by salmon byproduct protein (SP)-pectin (PE) aggregates and evaluate its ability to enhance the stability and bioavailability of FX. Various analytical techniques, including fluorescence spectroscopy, contact angle testing, turbidity analysis, and cryo-field scanning electron microscopy, were used to demonstrate that electrostatic and hydrophobic interactions between SP and PE contribute to the exceptional stability and wettability of the Pickering emulsion gels. Rheological analysis revealed that increasing the concentration of SP-PEs resulted in shear-thinning behavior, excellent thixotropic recovery performance, higher viscoelasticity, and good thermal stability of the Pickering emulsion gels stabilized by SP-PEs(SEGs). Furthermore, encapsulation of FX in the gels showed protected release under simulated oral and gastric conditions, with the subsequent controlled release in the intestine. Compared to free FX and the control group without PE (SEG-0), SEG-4 exhibited a 1.92-fold and 1.37-fold increase in the total bioavailable fraction of FX, respectively. Notably, during the study, it was observed that SEGs have the potential to serve as cake decoration for 3D printing to replace traditional cream under lower oil phase conditions (50%). These findings suggest that SP-PEs-stabilized Pickering emulsion gels hold promise as carriers for delivering bioactive compounds, offering the potential for various innovative food applications.

Working Memory Precision and Associative Binding in Mild Cognitive Impairment.

To better understand working memory (WM) deficits in Mild Cognitive Impairment (MCI), we examined information precision and associative binding in WM in 21 participants with MCI, compared to 16 healthy controls, using an item-location delayed reproduction task. WM, along with other executive functions (i.e. Trail Making Task (TMT) and Stroop task), were measured before and after a 2-h nap. The napping manipulation was intended as an exploratory element to this study exploring potential impacts of napping on executive functions.Compared to healthy participants, participants with MCI exhibited inferior performance not only in identifying encoded WM items but also on item-location associative binding and location precision even when only one item was involved. We also found changes on TMT and Stroop tasks in MCI, reflecting inferior attention and inhibitory control. Post-napping performance improved in most of these WM and other executive measures, both in MCI and their healthy peers.Our study shows that associative binding and WM precision can reliably differentiate MCIs from their healthy peers. Additionally, most measures showed no differential effect of group pre- and post-napping. These findings may contribute to better understanding cognitive deficits in MCI therefore improving the diagnosis of MCI.

Cushing Syndrome Is Associated With Gut Microbial Dysbiosis and Cortisol-Degrading Bacteria.

CONTEXT: Cushing syndrome (CS) is a severe endocrine disease characterized by excessive secretion of cortisol with multiple metabolic disorders. While gut microbial dysbiosis plays a vital role in metabolic disorders, the role of gut microbiota in CS remains unclear. OBJECTIVE: The objective of this work is to examine the alteration of gut microbiota in patients with CS. METHODS: We performed shotgun metagenomic sequencing of fecal samples from 78 patients with CS and 78 healthy controls matched for age and body mass index. Furthermore, we verify the cortisol degradation capacity of Ruminococcus gnavus in vitro and identify the potential metabolite by LC-MC/MS. RESULTS: We observed significant differences in microbial composition between CS and controls in both sexes, with CS showing reduced Bacteroidetes (Bacteroides vulgatus) and elevated Firmicutes (Erysipelotrichaceae_bacterium_6_1_45) and Proteobacteria (Enterobacter cloacae). Despite distinct causes of hypercortisolism in ACTH-dependent and ACTH-independent CS, we found no significant differences in metabolic profiles or gut microbiota between the 2 subgroups. Furthermore, we identified a group of gut species, including R. gnavus, that were positively correlated with cortisol levels in CS. These bacteria were found to harbor cortisol-degrading desAB genes and were consistently enriched in CS. Moreover, we demonstrated the efficient capacity of R. gnavus to degrade cortisol to 11-oxygenated androgens in vitro. CONCLUSION: This study provides evidence of gut microbial dysbiosis in patients with CS and identifies a group of CS-enriched bacteria capable of degrading cortisol. These findings highlight the potential role of gut microbiota in regulating host steroid hormone levels, and consequently host health.

(-)-Epigallocatechin-3-Gallate Reduces Perfluorodecanoic Acid-Exacerbated Adiposity and Hepatic Lipid Accumulation in High-Fat Diet-Fed Male C57BL/6J Mice.

Perfluorodecanoic acid (PFDA), an enduring and harmful organic pollutant, is widely employed in diverse food-related sectors. Our previous studies have provided evidence that PFDA has the potential to facilitate obesity and hepatic fat accumulation induced by high-fat diet (HFD) intake. Epigallocatechin-3-gallate (EGCG), a polyphenol found in green tea, has been suggested to possess potential preventive effects against metabolic abnormalities and fatty liver. The purpose of this research was to investigate the effects of EGCG on PFDA-exacerbated adiposity and hepatic lipid accumulation in HFD-fed mice. The results showed that EGCG reduced body weight gain; tissue and organ weights; blood glucose, serum insulin, HOMA-IR, leptin, and lipid parameters; serum inflammatory cytokines (IL-1ß, IL-18, IL-6, and TNF-α); and hepatic lipid accumulation in PFDA-exposed mice fed an HFD. Further work showed that EGCG improved liver function and glucose homeostasis in mice fed an HFD and co-exposed to PFDA. The elevated hepatic mRNA levels of SREBP-1 and associated lipogenic genes, NLRP3, and caspase-1 in PFDA-exposed mice fed an HFD were significantly decreased by EGCG. Our work provides evidence for the potential anti-obesity effect of EGCG on co-exposure to HFD and PFDA and may call for further research on the bioactivity of EGCG to attenuate the endocrine disruption effects of long-term exposure to pollutants.

Multiple-microarray analysis for identification of key genes involved in diabetic nephropathy.

The purpose of our study was to discover genes with significantly aberrant expression in diabetic nephropathy (DN) and to determine their potential mechanism. We acquired renal tubules, glomerulus and blood samples data from DN patients and controls from the GEO database. The differentially expressed genes (DEGs) in renal tubules, glomerulus and blood samples between DN patients and controls were studied. Based on these DEGs, we carried out the functional annotation and constructed protein-protein interaction (PPI) network. By comparing DN patients and controls of DEGs, we acquired the shared DGEs in renal tubules, glomerulus and blood samples of DN patients and controls. DN patients compared to controls, we obtained 3000 DEGs, 3064 DEGs, and 2296 DEGs in renal tubules, glomerulus and blood samples, respectively. The PPI networks of top 40 DEGs in renal tubules, glomerulus and blood samples was consisted of 229 nodes and 229 edges, 540 nodes and 606 edges, and 132 nodes and 124 edges, respectively. In total, 21 shared genes were finally found, including CASP3, DHCR24, CXCL1, GYPC, INHBA, LTF, MT1G, MUC1, NINJ1, PFKFB3, PPP1R3C, CCL5, SRSF7, PHLDA2, RBM39, WTAP, BASP1, PLK2, PDK2, PNPLA4, and SNED1. These genes may be associated with the DN process. Our study provides a basis to explore the potential mechanism and identify novel therapeutic targets for DN.

On-Chip Precisely Controlled Preparation of Uniform Core-Shell Salmon Byproduct Protein/Polysaccharide Microcapsules for Enhancing Probiotic Survivability in Fruit Juice.

The increasing demand for probiotic-fortified fruit juices stems from the dietary requirements of individuals with dairy allergies, lactose intolerance, and vegetarian diets. However, a notable obstacle arises from the degradation of probiotics in fruit juices due to their low pH levels and harsh gastrointestinal conditions. In response, this study proposes an innovative approach utilizing a microfluidic chip to create core-shell microcapsules that contain Lactobacillus plantarum Lp90. This method, based on internal-external gelation, forms highly uniform microcapsules that fully enclose the core, which consists of oil-in-water Pickering emulsions stabilized by salmon byproduct protein and sodium alginate. These emulsions remain stable for up to 72 h at a 1% sodium alginate concentration. The shell layer incorporates kelp nanocellulose and sodium alginate, thus improving the thermal properties. Furthermore, compared to free probiotics, the multilayer structure of the core-shell microcapsules provides a robust barrier, resulting in significantly enhanced probiotic stability. These findings introduce a novel strategy for augmenting probiotic delivery in functional fruit juice beverages, promising solutions to the challenges encountered during their development.

Synthesis and evaluation of imidazo[1,2-a]quinoxaline derivatives as potential antifungal agents against phytopathogenic fungi.

To discover novel and effective potential agricultural antifungal agents, various kinds of imidazo[1,2-a]quinoxaline derivatives were designed, and synthesized from available and inexpensive reagents. Their antifungal activities were first evaluated against ten typical phytopathogenic fungi. The in vitro antifungal activity showed that some compounds exhibited more obvious broad-spectrum fungicidal activity than the two commercially-available fungicides chlorothalonil and hymexazol. Valsa mali and Botrytis cinerea strains exhibited the highest susceptibility with EC50 values of 1.4-27.0 µg/mL to more than ten compounds. Compounds 5c and 5f showed the most promising inhibitory effects against Valsa mali (EC50 = 5.6 µg/mL) and Fusarium solani (EC50 = 5.1 µg/mL), respectively. Preliminary studies on the mechanism of action indicated that the imidazo[1,2-a]quinoxaline skeleton likely exerted its antifungal effects by disrupting hyphal differentiation, spore germination, and germ tube growth. Moreover, the cell experiment results indicated that these target compounds possessed good safety to BV2 cells. Overall, compounds 5c and 5f can be considered candidate compounds against specific fungi for further detailed research. This study can provide a theoretical basis for the application of imidazo[1,2-a]quinoxaline scaffolds as novel fungicides in agriculture.

[Multi-modal synergistic quantitative analysis and rehabilitation assessment of lower limbs for exoskeleton].

In response to the problem that the traditional lower limb rehabilitation scale assessment method is time-consuming and difficult to use in exoskeleton rehabilitation training, this paper proposes a quantitative assessment method for lower limb walking ability based on lower limb exoskeleton robot training with multimodal synergistic information fusion. The method significantly improves the efficiency and reliability of the rehabilitation assessment process by introducing quantitative synergistic indicators fusing electrophysiological and kinematic level information. First, electromyographic and kinematic data of the lower extremity were collected from subjects trained to walk wearing an exoskeleton. Then, based on muscle synergy theory, a synergistic quantification algorithm was used to construct synergistic index features of electromyography and kinematics. Finally, the electrophysiological and kinematic level information was fused to build a modal feature fusion model and output the lower limb motor function score. The experimental results showed that the correlation coefficients of the constructed synergistic features of electromyography and kinematics with the clinical scale were 0.799 and 0.825, respectively. The results of the fused synergistic features in the K-nearest neighbor (KNN) model yielded higher correlation coefficients ( r = 0.921, P < 0.01). This method can modify the rehabilitation training mode of the exoskeleton robot according to the assessment results, which provides a basis for the synchronized assessment-training mode of "human in the loop" and provides a potential method for remote rehabilitation training and assessment of the lower extremity.

Association between contralateral adrenal and hypothalamus-pituitary-adrenal axis in benign adrenocortical tumors.

Context: Adrenal incidentaloma (AI) is commonly discovered on cross-sectional imaging. Mild autonomous cortisol secretion is the most common functional disorder detected in AI. Objective: To delineate the association between radiological characteristics of benign adrenocortical tumors and hypothalamus-pituitary-adrenal (HPA) axis. Methods: In the study, 494 patients diagnosed with benign unilateral adrenocortical tumors were included. Mild autonomous cortisol secretion (MACS) was diagnosed when cortisol after 1mg-dexamethasone suppression test (1-mg DST) was in the range of 1.8-5ug/dl. Non-functional adrenocortical tumor (NFAT) was diagnosed as cortisol following 1-mg DST less than 1.8ug/dL. We performed Logistics regression and causal mediation analyses, looking for associations between radiological characteristics and the HPA axis. Results: Of 494 patients, 352 (71.3%) with NFAT and 142 (28.7%) with MACS were included. Patients with MACS had a higher tumor diameter, thinner contralateral adrenal gland, and lower plasma ACTH and serum DHEAS than those with NFAT. ACTH (OR 0.978, 0.962-0.993) and tumor diameter (OR 1.857, 95%CI, 1.357-2.540) were independent factors associated with decreased serum DHEAS (all P<0.05). ACTH was also associated with decreased contralateral adrenal diameter significantly (OR 0.973, 95%CI, 0.957-0.988, P=0.001). Causal mediation analysis showed ACTH mediated the effect significantly for the association between 1-mg DST results and DHEAS level (Pmediation<0.001, proportion=22.3%). Meanwhile, we found ACTH mediated 39.7% of the effects of 1-mg DST on contralateral adrenal diameter (Pmediation=0.012). Conclusions: Patients with MACS had thinner contralateral adrenal glands and disturbed HPA axes compared with NFAT. ACTH may partially be involved in mediating the mild autonomous cortisol secretion to DHEAS and the contralateral adrenal gland.

Machine learning in predicting T-score in the Oxford classification system of IgA nephropathy.

Background: Immunoglobulin A nephropathy (IgAN) is one of the leading causes of end-stage kidney disease (ESKD). Many studies have shown the significance of pathological manifestations in predicting the outcome of patients with IgAN, especially T-score of Oxford classification. Evaluating prognosis may be hampered in patients without renal biopsy. Methods: A baseline dataset of 690 patients with IgAN and an independent follow-up dataset of 1,168 patients were used as training and testing sets to develop the pathology T-score prediction (T pre) model based on the stacking algorithm, respectively. The 5-year ESKD prediction models using clinical variables (base model), clinical variables and real pathological T-score (base model plus T bio), and clinical variables and T pre (base model plus T pre) were developed separately in 1,168 patients with regular follow-up to evaluate whether T pre could assist in predicting ESKD. In addition, an external validation set consisting of 355 patients was used to evaluate the performance of the 5-year ESKD prediction model using T pre. Results: The features selected by AUCRF for the T pre model included age, systolic arterial pressure, diastolic arterial pressure, proteinuria, eGFR, serum IgA, and uric acid. The AUC of the T pre was 0.82 (95% CI: 0.80-0.85) in an independent testing set. For the 5-year ESKD prediction model, the AUC of the base model was 0.86 (95% CI: 0.75-0.97). When the T bio was added to the base model, there was an increase in AUC [from 0.86 (95% CI: 0.75-0.97) to 0.92 (95% CI: 0.85-0.98); P = 0.03]. There was no difference in AUC between the base model plus T pre and the base model plus T bio [0.90 (95% CI: 0.82-0.99) vs. 0.92 (95% CI: 0.85-0.98), P = 0.52]. The AUC of the 5-year ESKD prediction model using T pre was 0.93 (95% CI: 0.87-0.99) in the external validation set. Conclusion: A pathology T-score prediction (T pre) model using routine clinical characteristics was constructed, which could predict the pathological severity and assist clinicians to predict the prognosis of IgAN patients lacking kidney pathology scores.