Nonalcoholic Fatty Liver Disease: Changes in Gut Microbiota and Blood Lipids.

Background and Aims: The global prevalence of nonalcoholic fatty liver disease (NAFLD) is 25%. This study aimed to explore differences in the gut microbial community and blood lipids between normal livers and those affected by NAFLD using 16S ribosomal deoxyribonucleic acid sequencing. Methods: Gut microbiome profiles of 40 NAFLD and 20 non-NAFLD controls were analyzed. Information about four blood lipids and 13 other clinical features was collected. Patients were divided into three groups by ultrasound and FibroScan, those with a normal liver, mild FL (FL1), and moderate-to-severe FL (FL2). FL1 and FL2 patients were divided into two groups, those with either hyperlipidemia or non-hyperlipidemia based on their blood lipids. Potential keystone species within the groups were identified using univariate analysis and a specificity-occupancy plot. Significant difference in biochemical parameters ion NAFLD patients and healthy individuals were identified by detrended correspondence analysis and canonical correspondence analysis. Results: Decreased gut bacterial diversity was found in patients with NAFLD. Firmicutes/Bacteroidetes decreased as NAFLD progressed. Faecalibacterium and Ruminococcus 2 were the most representative fatty-related bacteria. Glutamate pyruvic transaminase, aspartate aminotransferase, and white blood cell count were selected as the most significant biochemical indexes. Calculation of areas under the curve identified two microbiomes combined with the three biochemical indexes that identified normal liver and FL2 very well but performed poorly in diagnosing FL1. Conclusions: Faecalibacterium and Ruminococcus 2, combined with glutamate pyruvic transaminase, aspartate aminotransferase, and white blood cell count distinguished NAFLD. We speculate that regulating the health of gut microbiota may release NAFLD, in addition to providing new targets for clinicians to treat NAFLD.

Single-cell transcriptomic profiling reveals immune cell heterogeneity in acute myeloid leukaemia peripheral blood mononuclear cells after chemotherapy.

PURPOSE: Acute myeloid leukaemia (AML) is a heterogeneous disease characterised by the rapid clonal expansion of abnormally differentiated myeloid progenitor cells residing in a complex microenvironment. However, the immune cell types, status, and genome profile of the peripheral blood mononuclear cell (PBMC) microenvironment in AML patients after chemotherapy are poorly understood. In order to explore the immune microenvironment of AML patients after chemotherapy, we conducted this study for providing insights into precision medicine and immunotherapy of AML. METHODS: In this study, we used single-cell RNA sequencing (scRNA-seq) to analyse the PBMC microenvironment from five AML patients treated with different chemotherapy regimens and six healthy donors. We compared the cell compositions in AML patients and healthy donors, and performed gene set enrichment analysis (GSEA), CellPhoneDB, and copy number variation (CNV) analysis. RESULTS: Using scRNA-seq technology, 91,772 high quality cells of 44,950 PBMCs from AML patients and 46,822 PBMCs from healthy donors were classified as 14 major cell clusters. Our study revealed the sub-cluster diversity of T cells, natural killer (NK) cells, monocytes, dendritic cells (DCs), and haematopoietic stem cell progenitors (HSC-Prog) in AML patients under chemotherapy. NK cells and monocyte-DCs showed significant changes in transcription factor expression and chromosome copy number variation (CNV). We also observed significant heterogeneity in CNV and intercellular interaction networks in HSC-Prog cells. CONCLUSION: Our results elucidated the PBMC single-cell landscape and provided insights into precision medicine and immunotherapy for treating AML.

Knockdown of TXNDC5 alleviates CCL4-induced hepatic fibrosis in mice by enhancing endoplasmic reticulum stress.

BACKGROUND: Hepatic fibrosis is a common pathological process in many chronic liver diseases. TXNDC5 has been shown to be involved in the progression of renal and pulmonary fibrosis. However, the role of TXNDC5 in hepatic fibrosis is unknown. The purpose of this study is to explore the role and mechanism of TXNDC5 in hepatic fibrosis. METHODS: We used TGF-ß1 to activate LX-2 cells and reduced TXNDC5 expression by short hairpin RNA. Cell viability was assessed by CCK-8 assay. Cell apoptosis was analyzed by flow cytometry or Tunel assay. The fibrosis-related proteins and endoplasmic reticulum stress (ERs)-related proteins were measured by western blot. ELISA was performed to detect COL1AL levels and MMP2/9 activities in cell medium. A mouse model of hepatic fibrosis was constructed by intraperitoneal injection of CCL4. HE and Masson staining were performed to assess fibrosis in mouse liver tissue. RESULTS: The results show that TXNDC5 was up-regulated in activated LX-2 cells and CCL4-induced hepatic fibrosis mice. Knockdown of TXNDC5 inhibited the viability of activated LX-2 cells and the production of collagen COL1A1. Knockdown of TXNDC5 promoted apoptosis of activated LX-2 cells. Mechanically, inhibition of TXNDC5 enhanced ERs, and the ERs inhibitor 4-Phenylbutyric acid (4-PBA) reversed the effect of TXNDC5 on activated LX-2 cells. More importantly, knockdown of TXNDC5 alleviated CCl4-induced hepatic fibrosis in mice. CONCLUSIONS: Knockdown of TXNDC5 may reduce hepatic fibrosis by regulating ERs, and targeting TXNDC5 seems to be a candidate treatment for hepatic fibrosis.

Knockdown of ARL5B Induces Mitochondrial-mediated Apoptosis and Inhibits Glycolysis in Breast Cancer Cells by Activating MDA5 Signaling.

AIM: Mitochondria are essential for energy metabolism in the tumor microenvironment and the survival of cancer cells. BACKGROUND: ADP-ribosylation factor-like GTPase 5b (ARL5B) has been found to be associated with mitochondrial dysfunction and breast cancer (BC) progression, but the underlying mechanism needs to be further understood. OBJECTIVE: We investigated the effects of ARL5B on the apoptosis and glycolysis of breast cancer cells and its underlying mechanisms. METHODS: Quantitative reverse transcription-PCR (qRT-PCR) and western blot assays were used to detect the expression of ARL5B in breast cancer tissues and cells. An ARL5B loss-of-function assay was performed to verify its role in BC development. RESULTS: ARL5B was upregulated in breast cancer tissues and cell lines. ARL5B knockdown induced apoptosis and activated the mitochondrial pathway in breast cancer cells. Interestingly, the inhibition of ARL5B repressed the aerobic glycolysis of breast cancer cells. The role of ARL5B in breast cancer cells was exerted by mediating the activation of viral RNA sensor MDA5-evoked signaling. Silencing ARL5B triggered MDA5 signaling by upregulating the key proteins involved in the MDA5 pathway. Importantly, MDA5 silencing reversed the effects of ARL5B knockdown on mitochondrial-mediated apoptosis and glycolysis, whereas poly (I:C), as a ligand for MDA5, further enhanced ARL5B knockdown- facilitated mitochondrial apoptosis and the inhibition of glycolysis. CONCLUSION: The knockdown of ARL5B activated MDA5 signaling and thus led to the enhanced mitochondrial- mediated apoptosis and glycolysis inhibition in breast cancer cells. Our study suggested that ARL5B might be a potential therapy target for BC.

Elastography for the differential diagnosis of malignant versus benign testicular lesions: a meta-analysis.

PURPOSE: The aim of this study was to evaluate the value of elastography in the differential diagnosis of benign versus malignant testicular lesions. METHODS: The PubMed, Cochrane Library, and Embase databases were searched for relevant studies. The diagnostic accuracy of elastography was evaluated using pooled sensitivity, specificity, likelihood ratio, post-test probability, diagnostic odds ratio, and by summarizing the area under the hierarchical summary receiver operating characteristic (HSROC) curve. RESULTS: Seven studies with 568 lesions were included. The pooled sensitivity and specificity were 87% (95% confidence interval [CI], 81% to 92%) and 81% (95% CI, 65% to 90%), respectively. The pooled estimates of the positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 4.48 (95% CI, 2.37 to 8.47), 0.16 (95% CI, 0.10 to 0.25), and 28.11 (95% CI, 11.39 to 69.36), respectively. The area under the HSROC curve was 90% (95% CI, 88% to 93%). CONCLUSION: Elastography is useful for assessing the stiffness of testicular lesions and for differentiating benign from malignant lesions. Elastography can be an effective supplement to conventional ultrasonography.

One step further into the blackbox: a pilot study of how to build more confidence around an AI-based decision system of breast nodule assessment in 2D ultrasound.

OBJECTIVES: To investigate how a DL model makes decisions in lesion classification with a newly defined region of evidence (ROE) by incorporating "explainable AI" (xAI) techniques. METHODS: A data set of 785 2D breast ultrasound images acquired from 367 females. The DenseNet-121 was used to classify whether the lesion is benign or malignant. For performance assessment, classification results are evaluated by calculating accuracy, sensitivity, specificity, and receiver operating characteristic for experiments of both coarse and fine regions of interest (ROIs). The area under the curve (AUC) was evaluated, and the true-positive, false-positive, true-negative, and false-negative results with breakdown in high, medium, and low resemblance on test sets were also reported. RESULTS: The two models with coarse and fine ROIs of ultrasound images as input achieve an AUC of 0.899 and 0.869, respectively. The accuracy, sensitivity, and specificity of the model with coarse ROIs are 88.4%, 87.9%, and 89.2%, and with fine ROIs are 86.1%, 87.9%, and 83.8%, respectively. The DL model captures ROE with high resemblance of physicians' consideration as they assess the image. CONCLUSIONS: We have demonstrated the effectiveness of using DenseNet to classify breast lesions with limited quantity of 2D grayscale ultrasound image data. We have also proposed a new ROE-based metric system that can help physicians and patients better understand how AI makes decisions in reading images, which can potentially be integrated as a part of evidence in early screening or triaging of patients undergoing breast ultrasound examinations. KEY POINTS: • The two models with coarse and fine ROIs of ultrasound images as input achieve an AUC of 0.899 and 0.869, respectively. The accuracy, sensitivity, and specificity of the model with coarse ROIs are 88.4%, 87.9%, and 89.2%, and with fine ROIs are 86.1%, 87.9%, and 83.8%, respectively. • The first model with coarse ROIs is slightly better than the second model with fine ROIs according to these evaluation metrics. • The results from coarse ROI and fine ROI are consistent and the peripheral tissue is also an impact factor in breast lesion classification.

The role of grey-scale ultrasound in the diagnosis of adhesive capsulitis of the shoulder: a systematic review and meta-analysis.

AIMS: In this systematic review and meta-analysis, we discuss the value of grey-scale ultrasonography (US) in diagnosing adhesive capsulitis of the shoulder (ACS). MATERIAL AND METHODS: We retrieved relevant studies from PubMed, Cochrane Library, and Embase before 8 April 2019. We selected 7 studies concerning 446 patients (490 shoulders) that used grey-scale US to diagnose ACS and magnetic resonance imaging (MRI) or arthroscopy as the reference standard. We assessed the diagnostic accuracy of US on the basis of combined sensitivity, specificity, likelihood ratio (LR), and the area under the summary receiver operating characteristic (SROC) curve (AUC). RESULTS: The combined sensitivity, specificity, positive LR and negative LR were found to be 88% (95%CI: 74-95), 96% (95%CI: 88-99), 23.89 (95%CI: 6.31-90.51) and 0.12 (95%CI: 0.05-0.29), respectively. The AUC was 0.97 (95%CI: 0.96-0.98). ACS was diagnosed on the basis of four US features: coracohumeral ligament thickening, inferior capsule/axillary recess capsule thickening, rotator interval abnormality, and restriction of the range of motion. The corresponding sensitivities were 64.4 (95%CI: 48.8-78.1), 82.1 (95%CI: 73.8-88.7), 82.6 (95%CI: 74.1-89.2) and 94.3 (95%CI: 84.3-98.8), respectively, and specificities were 88.9 (95%CI: 76.0-96.3), 95.7 (95%CI: 90.3-98.6), 93.9 (95%CI: 89.8-96.7), and 90.9 (95%CI: 75.7-98.1), respectively. CONCLUSIONS: Our meta-analysis showed that grey-scale US plays a significant role in the diagnosis of ACS. Because of its high sensitivity and specificity, US can be added to the existing clinical diagnosis program.

Short-term numerosity training promotes symbolic arithmetic in children with developmental dyscalculia: The mediating role of visual form perception.

Studies have shown that numerosity-based arithmetic training can promote arithmetic learning in typically developing children as well as children with developmental dyscalculia (DD), but the cognitive mechanism underlying this training effect remains unclear. The main aim of the current study was to examine the role of visual form perception in arithmetic improvement through an 8-day numerosity training for DD children. Eighty DD children were selected from four Chinese primary schools. They were randomly divided into the intervention and control groups. The intervention group received training on an apple-collecting game, whereas the control group received an English dictation task. Children's cognitive and arithmetic performances were assessed before and after training. The results showed that the intervention group showed a significant improvement in arithmetic performance, approximate number system (ANS) acuity, and visual form perception, but not in spatial processing and sentence comprehension. The control group showed no significant improvement in any cognitive ability. Mediation analysis further showed that training-related improvement in arithmetic performance was fully mediated by the improvement in visual form perception. The results suggest that short-term numerosity training enhances the arithmetic performance of DD children by improving their visual form perception.

Visual form perception is fundamental for both reading comprehension and arithmetic computation.

Visual perception has been found to be a critical factor for reading comprehension and arithmetic computation in separate lines of research with different measures of visual form perception. The current study of 1099 Chinese elementary school students investigated whether the same visual form perception (assessed by a geometric figure matching task) underlies both reading comprehension and arithmetic computation. The results showed that visual form perception had close relations with both reading comprehension and arithmetic computation, even after controlling for age, gender, and cognitive factors such as processing speed, attention, working memory, visuo-spatial processing, and general intelligence. Results also showed that numerosity comparison's relations with reading comprehension and arithmetic computation were fully accounted for by visual form perception. These results suggest that reading comprehension and arithmetic computation might share a similar visual form processing mechanism.

Diffusion Kurtosis Imaging Detects Microstructural Changes in the Brain after Acute Alcohol Intoxication in Rats.

The aim of this study was to test the technical feasibility of diffusion kurtosis imaging (DKI) in the brain after acute alcohol intoxication. Diffusion tensor imaging (DTI) and DKI during 7.0 T MRI were performed in the frontal lobe and thalamus before and 30 min, 2 h, and 6 h after ethyl alcohol administration. Compared with controls, mean kurtosis values of the frontal lobe and thalamus first decreased by 44% and 38% within 30 min (p < 0.01 all) and then increased by 14% and 46% at 2 h (frontal lobe, p > 0.05; thalamus, p < 0.01) and by 29% and 68% at 6 h (frontal lobe, p < 0.05; thalamus, p < 0.01) after acute intake. Mean diffusivity decreased significantly in both the frontal lobe and the thalamus at various stages. However, fractional anisotropy decreased only in the frontal lobe, with no detectable change in the thalamus. This demonstrates that DKI possesses sufficient sensitivity for tracking pathophysiological changes at various stages associated with acute alcohol intoxication and may provide additional information that may be missed by conventional DTI parameters.