Time-restricted feeding ameliorates non-alcoholic fatty liver disease through modulating hepatic nicotinamide metabolism via gut microbiota remodeling.

Non-alcoholic fatty liver disease (NAFLD) has emerged as a global health concern, lacking specific therapeutic strategies. Time-restricted feeding (TRF) regimen demonstrated beneficial effects in NAFLD; however, the underlying mechanisms remain unclear. In this study, we established a NAFLD mouse model through a high-fat diet (HFD) and implemented the 16:8 TRF regimen for a duration of 6 weeks. We demonstrated that TRF remarkably alleviated hepatic steatosis in HFD mice. Of note, aldehyde oxidase 1 (AOX1), a key enzyme in hepatic nicotinamide (NAM) catabolism, exhibited apparent upregulation in response to HFD, leading to abnormal accumulation of N-Methyl-6-pyridone-3-carboxamide (N-Me-6-PY, also known as 2PY) and N-Methyl-4-pyridone-5-carboxamide (N-Me-4-PY, also known as 4PY), whereas it was almost restored by TRF. Both N-Me-6-PY and N-Me-4-PY promoted de novo lipogenesis and fatty acid uptake capacities in hepatocyte, and aggravated hepatic steatosis in mice either fed chow diet or HFD. In contrast, pharmacological inhibition of AOX1 was sufficient to ameliorate the hepatic steatosis and lipid metabolic dysregulation induced by HFD. Moreover, transplantation of fecal microbiota efficiently mimicked the modulatory effect of TRF on NAM metabolism, thus mitigating hepatic steatosis and lipid metabolic disturbance, suggesting a gut microbiota-dependent manner. In conclusion, our study reveals the intricate relationship between host NAM metabolic modification and gut microbiota remodeling during the amelioration of NAFLD by TRF, providing promising insights into the prevention and treatment of NAFLD.

MiR-199a-5p Deficiency Promotes Artery Restenosis in Peripheral Artery Disease by Regulating ASMCs Function via Targeting HIF-1α and E2F3.

BACKGROUND: Restenosis (RS) poses a significant concern, leading to recurrent ischemia and the potential for amputation following intraluminal angioplasty in the treatment of Peripheral Artery Disease (PAD). Through microRNA microarray analysis, the study detected a significant downregulation of miR-199a-5p within arterial smooth muscle cells (ASMCs) associated with RS. OBJECTIVE: This research aims to explore the possible function and the underlying mechanisms of miR-199a-5p in the context of RS. METHODS: Primary ASMCs were extracted from the femoral arteries of both healthy individuals and patients with PAD or RS. The expression levels of miR-199a-5p were assessed using both qRT-PCR and in situ hybridization techniques. To examine the impacts of miR-199a-5p, a series of experiments were performed, including flow cytometry, TUNEL assay, EdU assay, CCK8 assay, Transwell assay, and wound closure assay. A rat carotid balloon injury model was employed to elucidate the mechanism through which miR-199a-5p mitigated neointimal hyperplasia. RESULTS: MiR-199a-5p exhibited downregulation in RS patients and was predominantly expressed within ASMCs. Elevated the expression of miR-199a-5p resulted in an inhibitory effect of proliferation and migration in ASMCs. Immunohistochemistry and a dual-luciferase reporter assay uncovered that RS exhibited elevated expression levels of both HIF-1α and E2F3, and they were identified as target genes regulated by miR-199a-5p. The co-transfection of lentiviruses carrying HIF-1α and E2F3 alongside miR-199a-5p further elucidated their role in the cellular responses mediated by miR-199a-5p. In vivo, the delivery of miR-199a-5p via lentivirus led to the mitigation of neointimal formation following angioplasty, achieved by targeting HIF-1α and E2F3. CONCLUSION: MiR-199a-5p exhibits promise as a prospective therapeutic target for RS since it alleviates the condition by inhibiting the proliferation and migration of ASMCs via its regulation of HIF-1α and E2F3.

Introducing and Validating the Cranial-Dorsal-Hip Angle (∠CDH): A Method for Accurate Fetal Position Assessment in the First Trimester and Future AI Applications.

Purpose To introduce the cranial-dorsal-hip angle (∠CDH) as a novel quantitative tool for assessing fetal position in the first trimester and to validate its feasibility for future AI applications. Materials and Methods 2520 first-trimester fetal NT exams with 2582 CRL images (January-August 2022) were analyzed at a tertiary hospital as the pilot group. Additionally, 1418 cases with 1450 fetal CRL images (September-December 2022) were examined for validation. Three expert sonographers defined a standard for fetal positions. ∠CDH measurements, conducted by two ultrasound technicians, were validated for consistency using Bland-Altman plots and the intra-class correlation coefficient (ICC). This method allowed for categorizing fetal positions as hyperflexion, neutral, and hyperextension based on ∠CDH. Comparative accuracy was assessed against Ioannou, Wanyonyi, and Roux methods using the weighted Kappa coefficient (k value). Results The pilot group comprised 2186 fetal CRL images, and the validation group included 1193 images. Measurement consistency was high (ICCs of 0.993; P<0.001). The established 95% reference range for ∠CDH in the neutral fetal position was 118.3° to 137.8°. The ∠CDH method demonstrated superior accuracy over the Ioannou, Wanyonyi, and Roux methods in both groups, with accuracy rates of 94.5% (k values: 0.874, 95%CI: 0.852-0.896) in the pilot group, and 92.6% (k values: 0.838, 95%CI: 0.806-0.871) in the validation group. Conclusion The ∠CDH method has been validated as a highly reproducible and accurate technique for first-trimester fetal position assessment. This sets the stage for its potential future integration into intelligent assessment models.

Glycoursodeoxycholic Acid Alleviates Arterial Thrombosis via Suppressing Diacylglycerol Kinases Activity in Platelet.

BACKGROUND: Glycoursodeoxycholic acid (GUDCA) has been acknowledged for its ability to regulate lipid homeostasis and provide benefits for various metabolic disorders. However, the impact of GUDCA on arterial thrombotic events remains unexplored. The objective of this study is to examine the effects of GUDCA on thrombogenesis and elucidate its underlying mechanisms. METHODS: Plasma samples from patients with arterial thrombotic events and diet-induced obese mice were collected to determine the GUDCA concentrations using mass spectrometry. Multiple in vivo murine thrombosis models and in vitro platelet functional assays were conducted to comprehensively evaluate the antithrombotic effects of GUDCA. Moreover, lipidomic analysis was performed to identify the alterations of intraplatelet lipid components following GUDCA treatment. RESULTS: Plasma GUDCA level was significantly decreased in patients with arterial thrombotic events and negatively correlated with thrombotic propensity in diet-induced obese mice. GUDCA exhibited prominent suppressing effects on platelet reactivity as evidenced by the attenuation of platelet activation, secretion, aggregation, spreading, and retraction (P<0.05). In vivo, GUDCA administration robustly alleviated thrombogenesis (P<0.05) without affecting hemostasis. Mechanistically, GUDCA inhibited DGK (diacylglycerol kinase) activity, leading to the downregulation of the phosphatidic acid-mediated signaling pathway. Conversely, phosphatidic acid supplementation was sufficient to abolish the antithrombotic effects of GUDCA. More importantly, long-term oral administration of GUDCA normalized the enhanced DGK activity, thereby remarkably alleviating the platelet hyperreactivity as well as the heightened thrombotic tendency in diet-induced obese mice (P<0.05). CONCLUSIONS: Our study implicated that GUDCA reduces platelet hyperreactivity and improves thrombotic propensity by inhibiting DGKs activity, which is a potentially effective prophylactic approach and promising therapeutic agent for arterial thrombotic events.

Endovascular Treatment of Ruptured or Symptomatic Thoracoabdominal and Pararenal Aortic Aneurysms Using Octopus Endograft Technique: Mid-Term Clinical Outcomes.

OBJECTIVE: To evaluate the effectiveness and safety of using off-the-shelf "Octopus" technique to treat ruptured or symptomatic thoracoabdominal aortic aneurysm (TAAA) and pararenal abdominal aortic aneurysm (PRAAA). METHODS AND RESULTS: All cases who underwent "Octopus" technique from May 2016 to May 2019 at our center were retrospectively analyzed. A total of 10 cases (8 males) were included. The mean age was 54.5±14.2 years (range: 31-80 years). Eight cases presented as aneurysm rupture or impending rupture accepted emergency repair. Technical success, defined by placement of all endografts as planned, was achieved in all cases. A total of 30 target visceral branches were successfully cannulated, 9 celiac arteries were covered intentionally. Intraoperative endoleak was observed in 6 patients, all of them were gutter leak. During hospital stay, there was no death, no side branch occlusion or spinal cord ischemia. Median follow-up was 30 months (range: 12-50 months). One patient died of lung cancer at 14-month follow-up. There was no secondary endoleak. The primary endoleak were found spontaneously resolved in 3 cases at 7 days, 3-month, and 1-year imaging. One persistent endoleak totally resolved after sealing of gutter spaces at 4-month follow-up. The other 2 persistent endoleak decreased during follow-up, which are still under observation. The branch patency rate was 90.3% (28/31). All the 3 occluded branches were renal arteries. Branch occlusion occurred in 2 cases at 1-month follow-up and 1 case at 2-year follow-up, but renal insufficiency was not observed in these cases. Obvious aneurysm sac shrinkage (≥5 mm) was observed in all cases. The aneurysm size shrunk from 7.6±1.9 to 5.5±1.4 cm. No spinal cord ischemia occurred during follow-up. CONCLUSION: Treatment of ruptured TAAA and PRAAA with "Octopus" technique is feasible and safe for high surgical risk patients in the absence of fenestrated and branched devices. The long-term clinical outcomes needed to be investigated.

A Prenatal Ultrasound Scanning Approach: One-Touch Technique in Second and Third Trimesters.

This study was aimed at evaluating the performance of the innovative technique Smart Fetus (SF) developed to recognize the planes and obtain the basic biometric measurements of fetuses automatically. This prospective study included 1005 uncomplicated singleton pregnancies undergoing routine examinations. For every pregnancy, planes, including the transverse section of the thalami, transverse section of the abdomen and longitudinal section of the femur, were acquired, and standard biometric measurements, including biparietal diameter, head circumference, abdominal circumference and femur length, were obtained using SF and traditional ultrasound technique (TUT). The accuracy, reproducibility and time required for the analysis of SF were compared with those of TUT. In 998 of 1005 cases (99.30%), SF successfully acquired the sections and made all measurements. The agreement between the techniques was high for all measurements. The time to obtain sections and measure biometric parameters or solely measure biometric parameters was significantly shorter with SF than with TUT. No significant differences were found in SF repeated measurements obtained by two independent observers. The SF technique helped in the acquisition of reliable standard sections and biometric measurements and saved time. It might serve as a novel ultrasound scanning approach and improve workflow efficiency.

Treatment strategies for inferior vena cava aneurysms.

OBJECTIVE: An inferior vena cava (IVC) aneurysm is a rare but potentially life-threatening entity. We successfully embolized an IVC aneurysm in a patient with history of blue rubber bleb nevus syndrome, a rare syndrome with multiple venous malformations. This new case was added to a literature review of previously reported cases, to analyze the management algorithm. METHODS: A PubMed search for all English-language articles and abstracts of IVC aneurysm were conducted. A comprehensive descriptive analysis, including etiology, presentation, classification, comorbidities, and treatment options of our case joining all previously published cases, is presented and discussed. RESULTS: Including our new case, a total of 74 (44 males) IVC aneurysms were analyzed. The average age was 39.0 ± 21.1 years (range, 0.4-89 years). Forty-nine (66.2%) were symptomatic; common symptoms include abdominal or back pain (24/74, 32.4%) and leg swelling or heaviness (20/74, 27.0%). Nineteen (19/59, 33.2%) were complicated with vena cava thrombosis, and 14 (14/59, 23.7%) were complicated with deep venous thrombosis of lower extremities. Thirty-two (43.2%) accepted surgical or endovascular intervention. There were 26 type I, 13 type II, 31 type III, and 4 type IV aneurysms. In type I group, 25 of 26 were treated conservatively, 2 deaths were reported. In type II group, 5 of 13 accepted conservative treatment. In type III group, 9 of 31 accepted conservative treatment, and 1 death was reported. In type IV group, 3 of 4 accepted conservative treatment, and 1 death was reported. CONCLUSIONS: Conservative management can be conducted in type I and type IV groups with close surveillance. For type II and III groups, considering the high incidence of vena cava thrombosis and risk of rupture, more active treatment should be considered.