Association of serum 25-hydroxyvitamin D with cardiovascular mortality and kidney outcome in patients with early stages of CKD.

PURPOSE: While serum 25-hydroxyvitamin D (25[OH]D) deficiency is prevalent in chronic kidney disease (CKD), the effects of 25(OH)D deficiency on cardiovascular mortality and kidney outcomes in patients with early-stage CKD remain incompletely understood. METHODS: This multicenter retrospective cohort study included adult patients with stages 1-3 CKD from 19 medical centers across China between January 2000 and May 2021. The primary outcome was cardiovascular mortality. The secondary study outcome included CKD progression (defined as a sustained > 40% eGFR decrease from baseline or progress to end-stage kidney disease), and annual percentage change of eGFR. RESULTS: Of 9229 adults with stages 1-3 CKD, 27.0% and 38.9% had severe (< 10 ng/mL) and moderate (10 to < 20 ng/mL) serum 25(OH)D deficiency, respectively. Compared with patients having 25(OH)D ≥ 20 ng/mL, a significantly higher risk of cardiovascular mortality (hazard ratio [HR] 1.90, 95% CI 1.37-2.63), CKD progression (HR 2.20, 95% CI 1.68-2.88), and a steeper annual decline in eGFR (estimate - 7.87%; 95% CI - 10.24% to - 5.51% per year) was found in those with serum 25(OH)D < 10 ng/mL. Similar results were obtained in subgroups and by sensitivity analyses. CONCLUSIONS: 25(OH)D deficiency is associated with increased risks of cardiovascular mortality and CKD progression in patients with early-stage CKD. Studies are needed to determine whether early intervention for 25(OH)D deficiency could improve the prognosis of patients with early-stage CKD.

Fine mapping and analysis of a candidate gene controlling Phytophthora blight resistance in cucumber.

Cucumber blight is a destructive disease. The best way to control this disease is resistance breeding. This study focuses on disease resistance gene mapping and molecular marker development. We used the resistant cucumber, JSH, and susceptible cucumber, B80, as parents to construct F2 populations. Bulked segregant analysis (BSA) combined with specific length amplified fragment sequencing (SLAF-seq) were used, from which we developed cleaved amplified polymorphic sequence (CAPs) markers to map the resistance gene. Resistance in F2 individuals showed a segregation ratio of resistance:susceptibility close to 3:1. The gene in JSH resistant cucumber was mapped to an interval of 9.25 kb, and sequencing results for the three genes in the mapped region revealed three mutations at base sites 225, 302, and 591 in the coding region of Csa5G139130 between JSH and B80, but no mutations in coding regions of Csa5G139140 and Csa5G139150. The mutations caused changes in amino acids 75 and 101 of the protein encoded by Csa5G139130, suggesting that Csa5G139130 is the most likely resistance candidate gene. We developed a molecular marker, CAPs-4, as a closely linked marker for the cucumber blight resistance gene. This is the first report on mapping of a cucumber blight resistance gene and will provideg a useful marker for molecular breeding of cucumber resistance to Phytophthora blight.

High MCM6 expression promotes proliferation and correlates with poor prognosis in triple-negative breast cancer.

OBJECTIVE: Triple-negative breast cancer (TNBC) is an aggressive subtype with a poor prognosis. Minichromosome maintenance genes (MCM2-7) crucial for DNA replication are significant biomarkers for various tumor types; however, their roles in TNBC remain underexplored. MATERIALS AND METHODS: We utilized four TNBC-related GEO databases to examine MCM2-7 gene expression and predict its prognosis in TNBC, performing single-cell analysis and GSEA to discover MCM6's potential function. The Cancer Dependency Map gene effect scores and CCK8 assay were used to assess MCM6's impact on TNBC cell proliferation. The correlations between MCM6 expression, immune infiltrates, and immune cells were also analyzed. WGCNA and LASSO Cox regression built a risk score model predicting TNBC patient survival based on MCM6-related gene expression. RESULTS: MCM2-7 gene expression was higher in TNBC tissues compared to adjacent normal tissues. High MCM6 expression correlated with shorter TNBC patient survival time. GSEA and single-cell analysis revealed a relationship between elevated MCM6 expression and the cell cycle pathway. MCM6 knockdown inhibited TNBC cell proliferation. A risk model featuring MCM6, CDC23, and CCNB1 effectively predicts TNBC patient survival. CONCLUSIONS: MCM6 overexpression in TNBC links to a worse prognosis and reduced cell proliferation upon MCM6 knockdown. We developed a risk score model based on MCM6-related genes predicting TNBC patient prognosis, potentially assisting future treatment strategies.

Quantification of left atrial strain in patients with idiopathic inflammatory myopathy using cardiovascular magnetic resonance feature tracking.

BACKGROUND: Left atrial (LA) dysfunction is involved in idiopathic inflammatory myopathy (IIM). Multiparametric cardiovascular magnetic resonance (CMR) strain imaging is a feasible and reproducible tool for examining global and regional LA functions, as well as left ventricular (LV) function in IIM patients. AIM: The aim of this study was to evaluate the feasibility and reproducibility of LA strain occurrence and strain rate for LA function assessment using CMR in IIM cases. MATERIALS AND METHODS: A total of 36 IIM and 42 healthy control cases were included. Baseline ventricular function was comparatively assessed in both groups. LA strain occurrence and strain rate were examined by cine cardiac magnetic resonance imaging [MRI] utilizing an in-house semiautomated technique. LA global function indexes were quantitated, including reservoir, conduit, and booster-pump functions. RESULTS: A total of 78 participants were enrolled in this study. There was no significant difference in left/right ventricular routine functions between IIM patients and control individuals (p>0.05); the same results (p>0.05) was also observed between patients with high hs-cTnI and normal. However, LV mass index had significant difference (p1=0.003, p2<0.01). Compared with IIM patients and control individuals, only total strain (εs) (p4=0.046) and passive strain (εe) (p4=0.002) showed significant difference, and in cases with high hs-cTnI and normal hs-cTnI, there are differences for εs (p3=0.012) and εe (p4=0.047). The strongest association was found between εe and LV ejection fraction (LVEF) (r=0.581, p<0.01). CONCLUSION: IIM cases have altered LA reservoir and conduit functions, and LA strain could reflect LA function.

Effect of Esketamine on perioperative anxiety and depression in women with systemic tumors based on big data medical background.

OBJECTIVE: Perioperative anxiety and depression syndrome (PADS) is a common clinical concern among women with systemic tumors. Esketamine has been considered for its potential to alleviate anxiety and depressive symptoms. However, its specific application and effectiveness in PADS among women with systemic tumors remain unclear. This study aimed to analyze the utility of Machine Learning (ML) algorithms based on electroencephalogram (EEG) signals in evaluating perioperative anxiety and depression in women with systemic tumors treated with Esketamine, utilizing a large-scale medical data background. PATIENTS AND METHODS: A single-center, randomized, placebo-controlled (SC-RPC) trial design was adopted. A total of 112 female patients with systemic tumors and PADS who received Esketamine treatment were included as study participants. A moderate dose (0.7 mg/kg) of Esketamine was administered through intravenous infusion over a duration of 60 minutes. EEG signals were collected from all patients, and the EEG signal features of individuals with depression were compared to those without depression. In this study, a Support Vector Machine (SVM)-K-Nearest Neighbour (KNN) hybrid classifier was constructed based on SVM and KNN algorithms. Using the EEG signals, the classifier was utilized to assess the anxiety and depression status of the patients. The predictive performance of the classifier was evaluated using accuracy, sensitivity, and specificity measures. RESULTS: The C2 correntropy feature of the delta rhythm in the left-brain EEG signal was significantly higher in individuals with depression compared to those without depression (p<0.05). Moreover, the C2 correntropy feature of the Alpha, Beta, and Gamma rhythms in the left-brain EEG signal was significantly lower in individuals with depression compared to those without depression (p<0.05). In the right brain EEG signal, the C2 correntropy feature of the delta rhythm was significantly higher in individuals with depression (p<0.05), while the C2 correntropy feature of the alpha and gamma rhythms was significantly lower in individuals with depression compared to those without depression (p<0.05). Additionally, the C1 correntropy feature of the Gamma rhythm in the right brain EEG signal was significantly higher in individuals with depression compared to those without depression (p<0.05). The SVM classifier achieved accuracy, sensitivity, and specificity of 98.23%, 98.10%, and 98.56%, respectively, in recognizing the left-brain EEG signals, with a correlation coefficient of 0.95. In recognizing the right brain EEG signals, the SVM classifier achieved accuracy, sensitivity, and specificity of 98.74%, 98.43%, and 99.03%, respectively, with a correlation coefficient of 0.96. The improved SVM-KNN approach yielded an accuracy, recall, precision, F-score, area over the curve (AOC), and Receiver Operation Characteristics (ROC) of 0.829, 0.811, 0.791, 0.853, 0.787, and 0.877, respectively, in predicting anxiety. For predicting depression, the accuracy, recall, precision, F-score, AOC, and ROC were 0.869, 0.842, 0.831, 0.893, 0.827, and 0.917, respectively. CONCLUSIONS: Significant differences were observed in the brain EEG signals between individuals with depression and those without depression. The improved SVM-KNN algorithm developed in this study demonstrates good predictive capability for anxiety and depression.

[A real-world study on the features of postpartum hepatitis flares in pregnant women with chronic HBV infection].

Objective: To analyze the clinical features of postpartum hepatitis flares in pregnant women with hepatitis B virus (HBV) infection. Methods: A retrospective study was conducted. Patients who met the enrollment criteria were included. Liver function and HBV virology tests were collected from pregnant women with chronic HBV infection at delivery, 6, 24, 36, and 48 weeks after delivery through the hospital information and test system. Additionally, antiviral therapy types and drug withdrawal times were collected. Statistical analysis was performed on all the resulting data. Results: A total of 533 pregnant women who met the inclusion criteria were included, with all patients aged (29.5±3.7) years old. A total of 408 cases received antiviral drugs during pregnancy to interrupt mother-to-child transmission. There was no significant difference in the levels of alanine aminotransferase (ALT, z = -1.981, P = 0.048), aspartate aminotransferase (AST, z = -3.956, P < 0.001), HBV load (z = -15.292, P < 0.001), and HBeAg (z = -4.77, P < 0.001) at delivery in patients who received medication and those who did not. All patients ALT, AST, total bilirubin, direct bilirubin, and albumin showed an upward trend within six weeks after delivery. A total of 231 cases developed hepatitis within 48 weeks after delivery. Among them, 173 cases first showed ALT abnormalities within six weeks postpartum. Conclusion: Hepatitis flare incidence peaked six weeks after delivery or six weeks after drug withdrawal in pregnant women with chronic HBV infection.

Monkeypox virus infection of human astrocytes causes gasdermin B cleavage and pyroptosis.

Monkeypox virus (MPXV) infections in humans cause neurological disorders while studies of MPXV-infected animals indicate that the virus penetrates the brain. Pyroptosis is an inflammatory type of regulated cell death, resulting from plasma membrane rupture (PMR) due to oligomerization of cleaved gasdermins to cause membrane pore formation. Herein, we investigated the human neural cell tropism of MPXV compared to another orthopoxvirus, vaccinia virus (VACV), as well as its effects on immune responses and cell death. Astrocytes were most permissive to MPXV (and VACV) infections, followed by microglia and oligodendrocytes, with minimal infection of neurons based on plaque assays. Aberrant morphological changes were evident in MPXV-infected astrocytes that were accompanied with viral protein (I3) immunolabelling and detection of over 125 MPXV-encoded proteins in cell lysates by mass spectrometry. MPXV- and VACV-infected astrocytes showed increased expression of immune gene transcripts (IL12, IRF3, IL1B, TNFA, CASP1, and GSDMB). However, MPXV infection of astrocytes specifically induced proteolytic cleavage of gasdermin B (GSDMB) (50 kDa), evident by the appearance of cleaved N-terminal-GSDMB (30 kDa) and C-terminal- GSDMB (18 kDa) fragments. GSDMB cleavage was associated with release of lactate dehydrogenase and increased cellular nucleic acid staining, indicative of PMR. Pre-treatment with dimethyl fumarate reduced cleavage of GSDMB and associated PMR in MPXV-infected astrocytes. Human astrocytes support productive MPXV infection, resulting in inflammatory gene induction with accompanying GSDMB-mediated pyroptosis. These findings clarify the recently recognized neuropathogenic effects of MPXV in humans while also offering potential therapeutic options.

[Diagnostic value of high frequency oscillation in localization of type â ¡ focal cortical dysplasia epilepsy].

Retrospective analysis was conducted on 9 patients with type Ⅱ focal cortical dysplasia (FCD) who underwent stereo-electroencephalography (SEEG) implantation in the Department of Neurosurgery of the First Affiliated Hospital of Fujian Medical University from November 2020 to February 2023. The onset area, onset time, and frequency of high-frequency oscillations (HFO) were analyzed and the correlation of HFOs with interictal, preictal, and ictal periods. SEEG recordings of 80-500 Hz HFOs were observed in both interictal and ictal periods in 9 patients, with 6 patients exhibiting fast ripples (FR) in the range of 250-500 Hz. Surgical resection of the seizure onset area and FR-generating electrodes was performed, and postoperative follow-up for over 2 years indicated Engel I in 5 cases. 6 patients showed continuous discharge during the preictal period, and the distribution index of continuous discharge was positively correlated with seizure frequency. HFOs in the range of 80-500 Hz were present in all four seizure onset patterns during the ictal period. The onset area and FR-emitting electrode were surgically removed in 6 patients with continuous discharge and overlapping HFOs during the preictal period, with 5 cases of Engel I. Type Ⅱ FCD discharges exhibited complexity, high discharge indices, and a close association with HFOs. Compared with the spike wave, the electrode range of HF is more limited, and the incidence of HF before attack is significantly increased, which is closely correlated with the onset area. The simultaneous occurrence of HFO and the spike waves has higher diagnostic value than the individual occurrence, effectively enhancing surgical efficacy.

Treponema pallidum-induced prostaglandin E2 secretion in skin fibroblasts leads to neuronal hyperpolarization: A cause of painless ulcers.

BACKGROUND: Primary syphilis is characterized by painless ulcerative lesions in the genitalia, the aetiology of painless remains elusive. OBJECTIVES: To investigate the role of Treponema pallidum in painless ulcer of primary syphilis, and the mechanisms underlying painless ulcers caused by T. pallidum. METHODS: An experimental rabbit model of primary syphilis was established to investigate its effects on peripheral nerve tissues. Human skin fibroblasts were used to examine the role of T. pallidum in modulating neurotransmitters associated with pain and to explore the signalling pathways related to neurotransmitter secretion by T. pallidum in vitro. RESULTS: Treponema pallidum infection did not directly lead to neuronal damage or interfere with the neuronal resting potential. Instead, it facilitated the secretion of prostaglandin E2 (PGE2) through endoplasmic reticulum stress in both rabbit and human skin fibroblasts, and upregulation of PGE2 induced the hyperpolarization of neurones. Moreover, the IRE1α/COX-2 signalling pathway was identified as the underlying mechanism by which T. pallidum induced the production of PGE2 in human skin fibroblasts. CONCLUSION: Treponema pallidum promotes PGE2 secretion in skin fibroblasts, leading to the excitation of neuronal hyperpolarization and potentially contributing to the pathogenesis of painless ulcers in syphilis.

Development of a clinical prediction model for diabetic kidney disease with glucose and lipid metabolism disorders based on machine learning and bioinformatics technology.

OBJECTIVE: In this study, we investigated the internal relationship between the pathogenesis of diabetic kidney disease (DKD) and abnormal glucose and lipid metabolism to identify potential biomarkers for diagnosis and treatment and investigated the role of the immune microenvironment of glucose and lipid metabolism disorders in the occurrence and progression of DKD. MATERIALS AND METHODS: The chip datasets GSE104948 and GSE96804 from the Gene Expression Common Database (GEO) were merged using the "lima" and "sva" software packages in R Software (4.2.3), and the merged dataset was used as the validation set. The intersection between the differential genes of DKD and the glucose and lipid metabolism genes in the MSigDB database was identified, and a nomogram of the incidence risk of DKD was built using three machine learning methods, namely LASSO regression, support vector machine (SVM), and random forest (RF), to validate the accuracy of the prediction model. Immune scores were conducted using the unsupervised clustering method, and patients were divided into two subgroups. The two subgroups were screened for differential genes for enrichment analysis. The differential genes of patients diagnosed with DKD were clustered into two gene subgroups for co-expression analysis. In this study, we utilized the Cytoscape software to construct a network of interactions among key genes. RESULTS: Using machine learning, a diagnostic model was developed with G6PC and HSD17B14 as key factors. Enrichment analysis and immune scoring demonstrated that the development of DKD was related to the imbalance in the microenvironment brought about by glucose lipid metabolism disorders. CONCLUSIONS: G6PC and HSD17B14 may be potential biomarkers for DKD, and the established predictive model is more helpful in predicting the incidence of DKD.

[Analysis of clinical epidemiological characteristics of respiratory syncytial virus in children in a hospital of pediatric in Hubei Province from 2020 to 2023].

Objective: To explore the clinical epidemiological characteristics of respiratory syncytial virus in children in Hubei Province from 2020 to 2023. Method: A single-center and cross-sectional study was used to analyze the clinical data of 3 271 children with respiratory syncytial virus infection in Wuhan Children's Hospital affiliated to Huazhong University of Science and Technology from July 1, 2020 to June 30, 2023. Nonparametric rank sum test and χ2 test were used for comparative analysis. Results: From July 1, 2020 to June 30, 2023, a total of 25 583 children were included in the analysis, of which 3 271(12.8%) children infected RSV. The detection rate was 16.3% in 2020-2021, 14.7% in 2021-2022 and 9.1% in 2022-2023. The detection rate decreased year by year (χ2=222.054, P<0.05). From 2020 to 2023, there was an anti-seasonal epidemic of RSV in spring and autumn. The detection rate of RSV in infants under 1 year old was the highest, but the median ages of RSV positive children increased (H=140.575, P<0.05). Pneumonia was the main clinical manifestation of RSV respiratory tract infection. Conclusion: The epidemiological characteristics of RSV in children in Hubei Province were different from those before. From 2020 to 2023, the detection rate of RSV decreased year by year. Besides winter, the prevalence of RSV could also be seen in spring and autumn. The median age of children infected with RSV increased after the epidemic. Pneumonia was the main clinical manifestation after RSV infection.

Unveiling attenuation structures in the northern Taiwan volcanic zone.

This cutting-edge study delves into regional magmatism in northern Taiwan through advanced 3-D P- and S-wave frequency-dependent attenuation tomography. Positioned at the dynamic convergence boundary between the Philippine Sea Plate and the Eurasian Plate, Taiwan experiences moderate earthquakes and intriguing volcanic activity, with a focus on the Tatun volcano group. Employing the Formosa seismic array for high-resolution results, our research identifies high-attenuation anomalies (low Q) beneath the northern Taiwan volcanic zone (NTVZ) and offshore submarine volcanoes, indicative of potential hydrothermal activities and magma reservoirs at varying depths. Additionally, we explore low-attenuation anomalies (high Q) in the forearc region of the Ryukyu subduction zone, suggestive of partial saturation linked to serpentinization processes resulting from seawater infiltration or forearc mantle hydration. These findings shed light on the complex geological features and provide essential insights into the crustal properties of northern Taiwan, contributing to a deeper understanding of its magmatic evolution and tectonic processes.

Treponema pallidum protein Tp47 induced prostaglandin E2 to inhibit the phagocytosis in human macrophages.

BACKGROUND: During Treponema pallidum (T. pallidum) infection, the host's immune system actively engages in pursuit and elimination of T. pallidum, while T. pallidum skillfully employs various mechanisms to evade immune recognition. Macrophages exhibit incomplete clearance of T. pallidum in vitro and the underlying mechanism of how T. pallidum resists the attack of macrophage remains unclear. OBJECTIVES: To investigate the effect of T. pallidum membrane protein Tp47 on the phagocytosis of macrophages. METHODS: THP-1-derived macrophages were used to investigate the role of Tp47 in the secretion of Prostaglandin E2 (PGE2) in macrophages and the mechanism by which Tp47 induced the production of PGE2, as well as the impact of PGE2 on the macrophage's phagocytosis. RESULTS: Tp47 (1-10 µg/mL) significantly inhibited the phagocytosis of latex beads and T. pallidum in macrophages (p ≤ 0.05). PGE2 production by macrophages could be induced by Tp47, and the phagocytic function of macrophages could be restored using PGE2 antibody. Tp47 produced PGE2 by activating the PERK/NF-κB/COX-2 pathway in macrophages. Inhibitors targeting PERK, NF-κB and COX-2, respectively, reduced the level of PGE2 and restored the phagocytic function of macrophages. CONCLUSION: Tp47-induced PGE2 production via the PERK/NF-κB/COX-2 pathway contributed to macrophage phagocytosis inhibition, which potentially contributes to immune evasion during the T. pallidum infection.

Dietary supplementation of proteases on growth performance, nutrient digestibility, blood characteristics and gut microbiota of growing pigs fed sorghum-based diets.

Low-tannin sorghum is an excellent energy source in pig diets. However, sorghum contains several anti-nutritional factors that may have negative effects on nutrient digestibility. The impacts of proteases on growth performance, nutrient digestibility, blood parameters, and gut microbiota of growing pigs fed sorghum-based diets were studied in this study. Ninety-six pigs (20.66 ± 0.65 kg BW) were allocated into three groups (eight pens/group, four pigs/pen): (1) CON (control diet, sorghum-based diet included 66.98% sorghum), (2) PRO1 (CON + 200 mg/kg proteases), (3) PRO2 (CON + 400 mg/kg proteases) for 28 d. No differences were observed in growth performance and apparent total tract digestibility (ATTD) of nutrients between CON and PRO1 groups. Pigs fed PRO2 diet had increased (P < 0.05) BW on d 21 and 28, and increased (P < 0.05) average daily gain during d 14-21 and the overall period compared with pigs fed CON diet. In addition, pigs fed PRO2 diet had improved (P < 0.05) ATTD of gross energy, CP, and DM compared with pigs fed CON and PRO1 diets. Pigs fed PRO2 diet had lower (P < 0.05) plasma globulin (GLB) level and higher (P < 0.05) plasma glucose, albumin (ALB) and immunoglobulin G levels, and ALB/GLB ratio than pigs fed CON and PRO1 diets. Furthermore, pigs fed PRO2 diet had decreased (P < 0.05) the relative abundance of Acidobacteriota at the phylum level and increased (P < 0.05) the relative abundance of Prevotella_9 at the genus level. The linear discriminant analysis effect size analysis also showed that pigs fed PRO2 diet had significantly enriched short-chain fatty acid-producing bacteria, such as Subdoligranulum and Parabacteroides. In conclusion, protease supplementation at 400 mg/kg improved the growth performance of growing pigs fed sorghum-based diets, which may be attributed to the improvement of nutrient digestibility, host metabolism, immune status and associated with the altered gut microbiota profiles.

Notch signaling regulates Th17 cells differentiation through PI3K/AKT/mTORC1 pathway and involves in the thyroid injury of autoimmune thyroiditis.

PURPOSE: Autoimmune Thyroiditis (AIT) is the most common thyroid disease; however, there were no measures to prevent the progression of the disease. The present study attempts to identify that Notch signaling regulates the differentiation of T helper 17 (Th17) cells by activating downstream Phosphatidylinositol-3 kinase/protein kinase/mechanistic target of rapamycin complex 1 (PI3K/AKT/mTORC1) pathway participating in the thyroid injury of the experimental autoimmune thyroiditis (EAT). METHODS: In vivo experiments, mice were randomly divided into 4 groups: a control group, an EAT group, and two groups with LY294002 treatment (pTg plus 25 mg/kg or 50 mg/kg LY294002, respectively). The degrees of thyroiditis were evaluated, and the percentage of Th17 cells, expression of interleukin-17A (IL-17A), and the main components of the Notch-PI3K signaling pathway were detected in different groups. In vitro experiments, two different dosages of LY294002 (25 and 50 µM) were used to intervene splenic mononuclear cells (SMCs) from EAT mice to further evaluate the regulatory effect of Notch-PI3K pathway on Th17 cells. RESULTS: Our data demonstrate that the infiltration of Th17 cells and the expressions of IL-17A, Notch, hairy and split 1 (Hes1), p­AKT (Ser473), p­AKT (Thr308), p­mTOR (Ser2448), S6K1, and S6K2 increased remarkably in EAT mice. After PI3K pathway was blocked, the degrees of thyroiditis were significantly alleviated, and the proportion of Th17 cells, the expression of IL-17A, and the above Notch-PI3K pathway-related molecules decreased in a dose-dependent manner. Additionally, the proportion of Th17 cells was positively correlated with the concentration of serum thyroglobulin antibody (TgAb), IL-17A, and Notch-PI3K pathway-related molecules mRNA levels. CONCLUSIONS: Notch signal promotes the secretion of IL-17A from Th17 cells by regulating the downstream PI3K/AKT/mTORC1 pathway through Hes-Phosphatase and tensin homolog (PTEN) and participates in thyroid autoimmune damage, and the PI3K pathway inhibitor may play important effects on AIT by affecting Th17 cells differentiation.

Comparison of contrast-enhanced ultrasonography and MRI results obtained by expert and novice radiologists indicating short-term response after transarterial chemoembolisation for hepatocellular carcinoma.

AIM: To evaluate inter-reader agreement between novice and expert radiologists in assessing contrast-enhanced ultrasonography (CEUS) and magnetic resonance imaging (MRI) images for detecting viable tumours with different sizes after conventional transarterial chemoembolisation (cTACE). MATERIALS AND METHODS: This prospective study included patients who had less than five hepatomas and who underwent cTACE. Hepatomas with one or two feeding arteries were selected as target lesions. CEUS and MRI were performed within 1 week after cTACE to evaluate viable tumours. RESULTS: The expert group had higher kappa values in evaluating all tumour sizes via CEUS compared with MRI. The novice group had similar kappa values. In patients with tumours measuring ≤3 cm, the expert group had higher kappa values in reading CEUS compared with MRI images; however, in the novice group, the kappa value was lower in evaluating CEUS compared with MRI images. In patients with tumours measuring >3 cm, the expert and novice groups had good to excellent kappa values. The confidence level of the two groups in reading MRI images was high; however, the novice group had a lower confidence level. CONCLUSION: CEUS is a convenient, cost-effective, and easy to apply imaging tool that can help interventionists perform early detection of viable hepatocellular carcinoma post-TACE. It has a higher inter-rater agreement in interpreting CEUS images compared with MRI images among expert radiologists even when they are extremely familiar with post-cTACE MRI images. In novice radiologists, there may be a learning curve to achieve good consistency in CEUS interpretation.

Blood lipid profile, HbA1c, fasting glucose, and diabetes: a cohort study and a two-sample Mendelian randomization analysis.

PURPOSE: The prevalence of diabetes is increasing worldwide. The associations between the lipid profile and glycated hemoglobin (HbA1c), fasting glucose, and diabetes remain unclear, so we aimed to perform a cohort study and a two-sample Mendelian randomization (MR) study to investigate the causality between blood lipid profile and HbA1c, fasting glucose, and diabetes. METHODS: A total of 25,171 participants from the Taiwan Biobank were enrolled. We applied a cohort study and an MR study to assess the association between blood lipid profile and HbA1c, fasting glucose, and diabetes. The summary statistics were obtained from the Asian Genetic Epidemiology Network (AGEN), and the estimates between the instrumental variables (IVs) and outcomes were calculated using the inverse-variance weighted (IVW) method. A series of sensitivity analyses were performed. RESULTS: In the cohort study, high-density lipoprotein cholesterol (HDL-C) was negatively associated with HbA1c, fasting glucose, and diabetes, while the causal associations between HDL-C and HbA1c (ßIVW = - 0.098, p = 0.003) and diabetes (ßIVW = - 0.594, p < 0.001) were also observed. Furthermore, there was no pleiotropy effect in this study using the MR-Egger intercept test and MR-PRESSO global test. CONCLUSIONS: Our results support the hypothesis that a genetically determined increase in HDL-C is causally related to a reduction in HbA1c and a lower risk of diabetes.

Growth, not digestibility, in chickens receiving reduced-protein diets is independent of non-specific amino-nitrogen sources when the essential-to-total-nitrogen ratio is constant and lower than 50.

1. A 21 d experiment was conducted to investigate whether growth performance and coefficients of amino acids digestibility (cAID) in broilers receiving reduced-protein diets supplemented with different non-essential amino acids (NEAA) were dependent on supplemented NEAA in diets with the same essential-to-total N (eN-to-tN) ratio kept at <50%.2. The experiment used 240 male broiler chicks, allocated to eight treatments with six replicate pens per treatment, and five chicks per replicate. The diets were either adequate in protein diet (PC), reduced protein (NC) diet or the NC diet supplemented with Gly, Gln, Ser, Ala, Gly + Ser or Ala + Ser. Digesta from the distal half of the ileum were collected on d 21. Tissue samples were collected for analysis for gene expression of protein synthesis and degradation (pectoralis major and liver) and peptide and AA transporters (jejunum).3. The treatments had no effects on growth performance. Generally, cAID was greater (P < 0.05) in NC compared to the PC diet. Individual supplementation of the NC diet with Gly, Gln, Ser, Ala or Ala+Ser increased (P < 0.01) cAID of Cys compared to the PC diet. There were no treatment effects on mRNA levels for the AA or peptide transporters in the jejunum. Supplementation of the NC diet with Gln, Ser, Ala, or Gly + Ser produced an upward expression (P < 0.05) of S6 kinase in the liver compared to PC and NC. In addition, there was greater (P < 0.05) expression of TRIM36 in the pectoralis major of broiler chickens receiving the NC diet supplemented with Gly.4. When reduced-protein diets have an eN-to-tN ratio of <50% and the ratio is kept constant in all the diets, growth performance response was independent of the source of non-specific amino-N, but the treatments may influence ileal digestibility of individual AA.