Association of urinary chlorpyrifos, paraquat, and cyproconazole levels with the severity of fatty liver based on MRI.

BACKGROUND: The objective of this study was to detect the urinary levels of chlorpyrifos, paraquat, and cyproconazole in residents living in Fuyang City and to analyze the correlation between these urinary pesticides levels and the severity of fatty liver disease (FLD). METHODS: All participants' fat fraction (FF) values were recorded by MRI (Magnetic resonance imaging). First-morning urine samples were collected from 53 participants from Fuyang Peoples'Hospital. The levels of three urinary pesticides were measured using ß-glucuronidase hydrolysis followed by a. The results were analyzed by using Pearson correlation analysis and binary logistic regression analysis to reveal the correlation between three urinary pesticides and the severity of fatty liver. RESULTS: 53 individuals were divided into 3 groups based on the results from MRI, with 20 cases in the normal control group, 16 cases in the mild fatty liver group, and 17 cases in the moderate and severe fatty liver group. Urinary chlorpyrifos level was increased along with the increase of the severity of fatty liver. Urinary paraquat level was significantly higher both in the low-grade fatty liver group and moderate & serve grade fatty liver group compared with the control group. No significant differences in urinary cyproconazole levels were observed among the three groups. Furthermore, urinary chlorpyrifos and paraquat levels were positively correlated with FF value. And chlorpyrifos was the risk factor that may be involved in the development of FLD and Receiver Operating Characteristic curve (ROC curve) analysis showed that chlorpyrifos and paraquat may serve as potential predictors of FLD. CONCLUSION: The present findings indicate urinary chlorpyrifos and paraquat were positively correlated with the severity of fatty liver. Moreover, urinary chlorpyrifos and paraquat have the potential to be considered as the predictors for development of FLD. Thus, this study may provide a new perspective from the environmental factors for the diagnosis, prevention, and treatment of FLD.

Clinical manifestations and MRI features of Danon disease: a case series.

BACKGROUND: Danon disease (DD) is an exceptionally uncommon X-linked dominant lysosomal glycogen storage disorder characterized by pronounced ventricular hypertrophy and cardiac insufficiency. The timely identification of cardiac impairment in individuals with DD holds significant clinical importance. CASE PRESENTATION: We present a case of Danon Disease in a three-generation pedigree from Anhui Province, China. Clinical features and laboratory data were collected and analyzed for a 16-year-old male proband (III-1) and two affected female family members (II-2 and II-3). The proband exhibited Wolf-Parkinson-White syndrome, hypertrophic cardiomyopathy, abnormal cognitive function, and muscle weakness. Gene sequencing confirmed a mutation (c.963G > A) in the LAMP-2 gene. CONCLUSION: Patients with DD may present both dilated and hypertrophic cardiomyopathy. Comprehensive myocardial tissue characterization by MRI plays a key role in the diagnosis of the disease.

[Clinical Value of Cystatin C-Based Estimated Glomerular Filtration Rate in Assessing Short-Term Mortality in Patients with Hepatitis B Virus-Related Acute-on-Chronic Liver Failure Treated with Artificial Liver Support System].

OBJECTIVE: To evaluate the predictive value of using cystatin c-based estimated glomerular filtration rate (eGFR-CysC) in assessing the prognosis of hepatitis B virus-associated acute-on-chronic liver failure (HBV-ACLF) patients treated with artificial liver support system (ALSS). METHODS: A total of 364 HBV-ACLF inpatients treated with ALSS at our hospital were enrolled retrospectively in the study. The patients were divided into the survival group ( n=269) and non-survival group ( n=95) according to mortality within 28 d, and their clinical information and laboratory data were analyzed for assessing short-term prognostic values. RESULTS: Multivariate Cox regression analysis identified eGFR-CysC as one of the independent risk factors associated with mortality within 28 days in HBV-ACLF patients (the hazard ratio=0.987; 95% confidence interval, 0.979-0.996, P=0.003). In addition, baseline eGFR-CysC was negatively correlated with the model for end-stage liver disease (MELD) score ( r=-0.439, P<0.001), MELD plus sodium (MELD-Na) score ( r=-0.481, P<0.001) and Chronic Liver Failure Consortium ACLF (CLIF-C ACLF) score ( r=-0.340, P<0.001). Receiver operating characteristic (ROC) curve analysis showed area under the curve ( AUC) of eGFR-CysC were 0.639, 0.697, 0.716, 0.749 and the best cut-off value were 70.620, 67.525, 61.725, 64.685 mL/(min·1.73 m 2), respectively, for baseline value and the first, second, and third treatment with ALSS. CONCLUSION: eGFR-CysC could be used to assist clinical assessment of short-term mortality in HBV-ACLF patients treated with ALSS, and has better clinical application value for dynamic monitoring.

Breast Edema of Early-stage Invasive Ductal Carcinoma: Correlation with Axillary Lymph Node Metastasis and Clinical-pathological Characteristics.

OBJECTIVE: This study aimed to evaluate the association of different patterns of breast edema and clinical-pathological features and axillary lymph node (ALN) status in early invasive ductal carcinoma (IDC) for simple and readily available assessment and to guide surgeons to perform sentinel lymph node biopsy for selected patients. MATERIALS AND METHODS: This retrospective analysis involved 207 individuals with clinical T1-T2 stage IDC. The clinical-pathological features of the patients were compared with different breast edema and ALN statuses. Independent risk factors for ALN metastasis were verified using multivariate logistic regression analysis. RESULTS: ALN metastasis was confirmed in 100 of 207 patients (48.3%) with early-stage IDC. Significant differences were found between different ALN states for tumour size, clinical T stage, and breast edema (P <0.05). The clinical T2 stage (odds ratio-1.882, p=0.043) and moderate to severe edema (odds ratio-10.869, p=0.004) were independent risk factors for ALN metastasis. Moreover, better prognostic factors, including smaller tumour size, lower Ki-67 index and histologic grade, luminal A subtype, and lower incidence of lymph node metastasis, were more frequently found in patients with no breast edema (p<0.05). CONCLUSION: Breast edema can be considered a promising feature to improve the predictive performance of pathological ALN status in patients with early-stage breast cancer and thus may contribute to preoperative treatment planning.

Changes in antibiotic residues and the gut microbiota during ciprofloxacin administration throughout Silkie chicken development.

The use of antibiotics leads to antibiotic residues in livestock and poultry products, adversely affecting human health. Ciprofloxacin (CFX) is a broad-spectrum antibiotic shared between animals and humans that is useful in treatments besides infections. However, changes in the gut microbiota caused by CFX and the possible link with the elimination of CFX residues have not been investigated. Herein, we used the Silkie chicken model to study the changes in the gut microbiota during the entire CFX-metabolic repertoire. We detected CFX residues in different tissues and showed that the elimination time of CFX from different tissues was dissimilar (liver > kidney > chest muscle > skin). Analysis of liver and kidney injury biomarkers and plasma antioxidant indices indicated slight hepatotoxicity and nephrotoxicity in the Silkie chickens. Importantly, the changes in the gut microbial community predominantly occurred early in the metabolic process. Correlation analysis revealed that the particular bacterial microbiota were associated with the pharmacokinetics of CFX in different Silkie chicken tissues (e.g., aerobic bacteria, including Escherichia and Coprococcus, and anaerobic bacteria, including Fusobacterium, Ruminococcus, Bifidobacterium, and Eubacterium). Collectively, certain microbiota may boost antibiotic metabolism and participate in restoring the microbial consortia after CFX is metabolized. Therefore, regulating the core intestinal microbiota may reduce foodborne antibiotics and accelerate the development of drug resistance.

Disruption of protein geranylgeranylation in the cerebellum causes cerebellar hypoplasia and ataxia via blocking granule cell progenitor proliferation.

The prenylation of proteins is involved in a variety of biological functions. However, it remains unknown whether it plays an important role in the morphogenesis of the cerebellum. To address this question, we generated a mouse model, in which the geranylgeranyl pyrophosphate synthase (Ggps1) gene is inactivated in neural progenitor cells in the developing cerebellum. We report that conditional knockout (cKO) of Ggps1 leads to severe ataxia and deficient locomotion. To identify the underlying mechanisms, we completed a series of cellular and molecular experiments. First, our morphological analysis revealed significantly decreased population of granule cell progenitors (GCPs) and impaired proliferation of GCPs in the developing cerebellum of Ggps1 cKO mice. Second, our molecular analysis showed increased expression of p21, an important cell cycle regulator in Ggps1 cKO mice. Together, this study highlights a critical role of Ggpps-dependent protein prenylation in the proliferation of cerebellar GCPs during cerebellar development.

3D whole-heart noncontrast coronary MR angiography based on compressed SENSE technology: a comparative study of conventional SENSE sequence and coronary computed tomography angiography.

OBJECTIVE: The relatively long scan time has hampered the clinical use of whole-heart noncontrast coronary magnetic resonance angiography (NCMRA). The compressed sensitivity encoding (SENSE) technique, also known as the CS technique, has been found to improve scan times. This study aimed to identify the optimal CS acceleration factor for NCMRA. METHODS: Thirty-six participants underwent four NCMRA sequences: three sequences using the CS technique with acceleration factors of 4, 5, and 6, and one sequence using the conventional SENSE technique with the acceleration factor of 2. Coronary computed tomography angiography (CCTA) was considered as a reference sequence. The acquisition times of the four NCMRA sequences were assessed. The correlation and agreement between the visible vessel lengths obtained via CCTA and NCMRA were also assessed. The image quality scores and contrast ratio (CR) of eight coronary artery segments from the four NCMRA sequences were quantitatively evaluated. RESULTS: The mean acquisition time of the conventional SENSE was 343 s, while that of CS4, CS5, and CS6 was 269, 215, and 190 s, respectively. The visible vessel length from the CS4 sequence showed good correlation and agreement with CCTA. The image quality score and CR from the CS4 sequence were not statistically significantly different from those in the other groups (p > 0.05). Moreover, the image score and CR showed a decreasing trend with the increase in the CS factor. CONCLUSIONS: The CS technique could significantly shorten the acquisition time of NCMRA. The CS sequence with an acceleration factor of 4 was generally acceptable for NCMRA in clinical settings to balance the image quality and acquisition time.

B Lymphocyte Development in the Bursa of Fabricius of Young Broilers is Influenced by the Gut Microbiota.

Chickens have been used as a valuable and traditional model for studies on basic immunology. B lymphocytes were first identified in the bursa of Fabricius (BF) of broilers. The microbiota is important for immune system development and function. However, the effect of the microbiota on mediating B cell development and its regulatory mechanism is poorly elucidated. Here, we show that the gut microbiota is associated with the development of bursal B cells in young chickens. Changing patterns of both the alpha diversity and the expression of the B cell marker Bu-1α in the gut microbiota were related to the ages of chickens at different growth phases. Further correlation analysis revealed the marked correlation between the relative abundances of Intestinimonas, Bilophila, Parasutterella, Bacteroides, Helicobacter, Campylobacter, and Mucispirillum and the expression of Bu-1α. In antibiotic-treated chickens, BF and B cell development had aberrations as the relative abundance of the microbiota in early life decreased. These findings were consistent with Spearman's correlation results. Single-cell transcriptome analysis indicated that the heterogeneity in the cellular composition and developmental trajectory of bursal B cells from antibiotic-treated chickens was large. We found a novel subpopulation of unnamed B cells and identified Taf1 as a new pivotal regulator of B cell lineage differentiation. Therefore, we provide novel insights into the regulatory role of the gut microbiota in B cell development in early life and the maturation of host humoral immunity. IMPORTANCE In this study, we used young broilers to investigate the relationship between their gut microbiota and bursal B cell development. We characterized the important variables, microbes, B cells, and immunoglobulins during the posthatch development of birds. We also identified several candidate taxa in the cecal contents associated with B cells. Our study provides a rich resource and cell-cell cross talk model supporting B cell differentiation from the bursa in vitro at single-cell resolution. Furthermore, we determined a new pivotal regulator (Taf1) of B cell differentiation. We believe that our study makes a significant contribution to the literature because our findings may elucidate the role of the gut microbiota in B cell differentiation. This study also serves as a basis for developing new strategies that modulate B cell differentiation to prevent diseases.

Thymic T-Cell Production Is Associated With Changes in the Gut Microbiota in Young Chicks.

Increasing studies show that gut microbiota play a central role in immunity, although the impact of the microbiota on mediation of thymic T cells throughout life is not well understood. Chickens have been shown to be a valuable model for studying basic immunology. Here, we show that changes in the gut microbiota are associated with the development of thymic T cells in young chickens. Our results showed that T-cell numbers in newborn chicks sharply increased from day 0 and peaked at day 49. Interestingly, the α-diversity score pattern of change in gut microbiota also increased after day 0 and continued to increase until day 49. We found that early antibiotic treatment resulted in a dramatic reduction in gut alpha diversity: principal component analysis (PCA) showed that antibiotic treatment resulted in a different cluster from the controls on days 9 and 49. In the antibiotic-treated chickens, we identified eight significantly different (p < 0.05) microbes at the phylum level and 14 significantly different (p < 0.05) microbes at the genus level, compared with the controls. Importantly, we found that antibiotic treatment led to a decreased percentage and number of T cells in the thymus when measured at days 9 and 49, as evaluated by flow cytometry. Collectively, our data suggest that intestinal microbiota may be involved in the regulation of T cells in birds, presenting the possibility that interventions that actively modify the gut microbiota in early life may accelerate the maturation of humoral immunity, with resulting anti-inflammatory effects against different pathogens.