5S-Heudelotinone alleviates experimental colitis by shaping the immune system and enhancing the intestinal barrier in a gut microbiota-dependent manner.

Aberrant changes in the gut microbiota are implicated in many diseases, including inflammatory bowel disease (IBD). Gut microbes produce diverse metabolites that can shape the immune system and impact the intestinal barrier integrity, indicating that microbe-mediated modulation may be a promising strategy for preventing and treating IBD. Although fecal microbiota transplantation and probiotic supplementation are well-established IBD therapies, novel chemical agents that are safe and exert strong effects on the gut microbiota are urgently needed. Herein, we report the total synthesis of heudelotinone and the discovery of 5S-heudelotinone (an enantiomer) as a potent agent against experimental colitis that acts by modulating the gut microbiota. 5S-Heudelotinone alters the diversity and composition of the gut microbiota and increases the concentration of short-chain fatty acids (SCFAs); thus, it regulates the intestinal immune system by reducing proinflammatory immune cell numbers, and maintains intestinal mucosal integrity by modulating tight junctions (TJs). Moreover, 5S-heudelotinone (2) ameliorates colitis-associated colorectal cancer (CAC) in an azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced in situ carcinoma model. Together, these findings reveal the potential of a novel natural product, namely, 5S-heudelotinone, to control intestinal inflammation and highlight that this product is a safe and effective candidate for the treatment of IBD and CAC.

Synthesis and Anti-Inflammatory Activity of Ferulic Acid-Sesquiterpene Lactone Hybrids.

Acute lung injury (ALI) is a respiratory failure disease associated with high mortality rates in patients. The primary pathological damage is attributed to the excessive release of pro-inflammatory mediators in pulmonary tissue. However, specific therapy for ALI has not been developed. In this study, a series of novel ferulic acid-parthenolide (FA-PTL) and ferulic acid-micheliolide (FA-MCL) hybrid derivatives were designed, synthesized, and evaluated for their anti-inflammatory activities in vitro. Compounds 2, 4, and 6 showed pronounced anti-inflammatory activity against LPS-induced expression of pro-inflammatory cytokines in vitro. Importantly, compound 6 displayed good water solubility, and treatment of mice with compound 6 (10 mg/kg) significantly prevented weight loss and ameliorated inflammatory cell infiltration and edema in lung tissue, as well as improving the alveolar structure. These results suggest that compound 6 (((1aR,7aS,8R,10aS,10bS,E)-8-((dimethylamino)methyl)-1a-methyl-9-oxo-1a,2,3,6,7,7a,8,9,10a,10b-decahydrooxireno[2',3':9,10]cyclodeca[1,2-b]furan-5-yl)methyl (E)-3-(4-hydroxy-3-methoxyphenyl)acrylate 2-hydroxypropane-1,2,3-tricarboxylate) might be considered as a lead compound for further evaluation as a potential anti-ALI agent.

Contrast-enhanced Ultrasonography for Diagnosis of Small Intestinal Leiomyosarcoma with Hepatic Metastasis: A Clinical Report of One Case and Review of the Literature.

BACKGROUND: Small intestinal leiomyosarcoma is a rare malignant tumor of the gastrointestinal tract. Clinical symptoms are atypical and can be complicated by gastrointestinal bleeding and intestinal obstruction. CASE PRESENTATION: We report a case of a 73-year-old patient with small intestinal smooth muscle sarcoma with hepatic metastasis. No significant abnormalities were seen on examination of the abdomen. We performed abdominal enhancement CT, contrast-enhanced ultrasonography (CEUS), and ultrasoundguided pelvic mass puncture biopsy, and we found a heterogeneous density and echogenicity of the pelvic mass, and the enhancement was progressive with sustained hyperenhancement. The postoperative pathology was smooth muscle sarcoma of the small intestine. The typical fast-in, fast-out bull's-eye sign of metastases, characterized the liver presented with multiple hypodense and echogenic nodules and the enhancement. The clinical presentation, imaging, histologic features, and treatment are also discussed in this article. CONCLUSION: This article briefly reviews the literature on small intestinal leiomyosarcoma. The purpose of this case report is to emphasize the specificity of the case and evaluate the imaging presentation of ultrasound (US) and CEUS and the main differential diagnosis of this rare gastrointestinal tumor.

A Review about C-TIRADS, ACR-TIRADS, and K-TIRADS Combined with Real-Time Tissue Elastography to Diagnose Thyroid Nodules.

PURPOSE: This study aimed to evaluate the diagnostic efficiency of the Chinese version of thyroid imaging reporting and data system (C-TIRADS), American College of Radiology (ACR)-TIRADS, and Korean (K)-TIRADS combined with real-time tissue elastography to diagnose thyroid nodules. METHODS: A total of 574 thyroid nodule ultrasonographic images were retrospectively analyzed and classified based on the three TIRADS methods. The MedCale statistical software was used to construct the receiver operating characteristic (ROC) curve based on the pathological results of surgery. The diagnostic efficiency before and after assessing elastographies from the three TIRADS was compared between C-TIRADS, ACR-TIRADS, and K-TIRADS groups and within before and after TIRADS combined with elastic imaging. Furthermore, the unnecessary biopsy rates were also compared. Comparing area under ROC curve (AUC) with MEDCALC software (20.0.15, MedCalc Software Ltd., Ostend, Belgium), Delong test was used. The sensitivity and specificity were compared by STATA software (15.1, StataCorp LP, College Station, TX, USA) and Chi-square test. The rate of unnecessary biopsy was compared by SPSS software (23.0, IBM, Armonk, NY, USA) and Chi-square test. RESULTS: C-TIRADS, ACR-TIRADS, K-TIRADS cut-off values, and real-time tissue elastography (RTE) were 4b, 5, 5, and 3, respectively, and the areas under the ROC curve were 0.932, 0.914, 0.904, and 0.883, respectively. C-TIRADS had the highest AUC (p < 0.05) and sensitivity (p < 0.001), while ACR-TIRADS had the highest specificity (p < 0.001). After conducting a combined elastography with the three TIRADS, AUC showed increases of different degrees. Comparing TIRADS with TIRADS+RTE, the difference of C-TIRADS had statistical significance (p < 0.001), but the difference of ACR-TIRADS and K-TIRADS had no statistical significance (p > 0.05). The unnecessary biopsy rate showed decreases of different degrees. Differences between C-TIRADS and K-TIRADS were significant (p < 0.05), but in the case of ACR-TIRADS were not significant (p > 0.05). CONCLUSIONS: C-TIRADS, ACR-TIRADS, K-TIRA and RTE showed high diagnostic efficiency, with C-TIRADS having the highest. Real-time tissue elastography can improve TIRADS diagnostic efficiency and reduce its unnecessary biopsy rate. In this case C-TIRADS showed again the highest efficiency.

Fibrolipomatous Hamartoma of the Median Nerve: A Clinical Report of One Case and Review of the Literature.

BACKGROUND: The ultrasound imaging findings and clinical treatment procedure of a case of fibrolipomatous hamartoma of the median nerve are reported in this paper. The disease diagnosis was mainly dependent on magnetic resonance, and rarely described by ultrasound. This paper introduces the imaging manifestations of median neurofibromatoid hamartoma under ultrasound. CASE PRESENTATION: This case is a middle-aged female with pituitary adenoma. Fibrolipomatous hamartoma, as a rare benign fibrofatty tumor, is characterized by the slow proliferation of mature adipocytes and fibrous tissue around and inside the peripheral nerves, eventually leading to the fusiform enlargement of nerve fiber bundles. DISSCUSSION: This paper discusses the value and application of color doppler ultrasound in the diagnosis of FLH to provide a reference for the clinical diagnosis and treatment of this disease in the future and reviews the literature on this disease. CONCLUSION: Because fibrolipomatous hamartoma is very rare, it is very important to improve the understanding and diagnosis of this disease.

Ultrasonography in the assessment of primary myxofibrosarcoma in the left atrium: a case report.

BACKGROUND: Cardiac myxofibrosarcoma is a rare cardiac malignant tumor, whose diagnosis is challenging due to its rare and non-specific manifestations. Ultrasound is the most important tool for detecting cardiac tumors. Yet, its diagnostic value in cardiac myxoidfibrosarcoma is rarely reported. Herein, we summarized the ultrasonic manifestations of myxofibrosarcoma in a 72-year-old Han woman. CASE PRESENTATION: The patient presented with crushing chest pain without obvious inducement, lasting 3-5 min each time, which would be relieved after rest, accompanied by palpitation, chest tightness, shortness of breath, dizziness, and syncope. The electrocardiogram (ECG) suggested atrial fibrillation. Ultrasound found two moderate echogenic masses in the left atrium; one was about 48 × 31 mm in size, and the other was about 25 × 24 mm in size. The clinical diagnosis was atrial mass and atrial fibrillation. The patient underwent the operation of left atrial tumor resection + mitral valvuloplasty + atrial fibrillation radiofrequency ablation + left atrial appendectomy. The tumor was completely removed, and the patient did not receive radiotherapy or chemotherapy after surgery. The patient was reexamined by ultrasound at 6, 42, and 91 days after surgery, and no obvious abnormalities were found. On day 115, moderate echoic mass was detected on the posterior wall of the left atrium, nearing the mitral valve ring, with a size of about 28 × 23 mm. Currently, the patient is under follow-up care. CONCLUSION: As the most important examination method for cardiac tumors, cardiac ultrasound has good diagnostic and differential diagnosis value and can be used regularly due to its simplicity and safety. The diagnosis rate of cardiac myxofibrosarcoma can be greatly improved by summarizing the ultrasonographic manifestations of cardiac myxofibrosarcoma and differentiating them from other lesions.

Synthetic role of miR-200b-3p, ABCD2 score, and carotid ultrasound in the prediction of cerebral infarction in patients with transient ischemic attack.

BACKGROUND: Transient ischemic attack (TIA) is a major risk factor for the occurrence of cerebral infarction (CI). This study aimed to evaluate the predictive value of the synthetic role of miR-200b-3p, ABCD2 score, and carotid ultrasound for CI onset in patients with TIA. METHODS: Expression of miR-200b-3p was detected by reverse transcription quantitative PCR and carotid stenosis degree was evaluated using carotid ultrasound examination. Association of miR-200b-3p with ABCD2 scores and carotid stenosis degree was assessed using t-test and chi-square test. Logistic regression analysis was used to judge the ability of miR-200b-3p, ABCD2 score, and carotid ultrasound to predict the occurrence of CI. Receiver operating characteristic curve was used to analyze the diagnostic value of miR-200b-3p and the accuracy of miR-200b-3p, ABCD2 score, and carotid ultrasound in predicting CI development. RESULTS: Expression of serum miR-200b-3p was significantly increased in TIA patients compared with healthy controls, and had diagnostic value in TIA patients. Serum miR-200b-3p was significantly associated with dyslipidemia, ABCD2 score, and carotid stenosis degree in TIA patients. ABCD2 score, carotid stenosis degree, and serum miR-200b-3p were independently associated with CI onset, and the synthetic role of these three indicators had the best accuracy in the prediction of CI onset in TIA patients. CONCLUSION: Serum miR-200b-3p expression was increased in TIA patients with considerable diagnostic value to screen TIA cases from healthy controls. Moreover, we speculated that the combination of miR-200b-3p, ABCD2 score, and carotid stenosis degree by ultrasound may propose as an efficient predictive strategy for the prediction of CI in TIA patients.

Effect of evolocumab on the progression of intraplaque neovascularization of the carotid based on contrast-enhanced ultrasonography (EPIC study): A prospective single-arm, open-label study.

Background and Purpose: The aim of this study was to explore the effect of half a year of evolocumab plus moderate-intensity statin treatment on carotid intraplaque neovascularization (IPN) and blood lipid levels. Methods: A total of 31 patients with 33 carotid plaques who received evolocumab plus statin treatment were included. Blood lipid levels, B-mode ultrasound and contrast-enhanced ultrasonography (CEUS) at baseline and after half a year of evolocumab plus statin therapy were collected. The area under the curve (AUC) reflected the total amount of acoustic developer entering the plaque or lumen within the 180 s measurement period. The enhanced intensity reflected the peak blood flow intensity during the monitoring period, and the contrast agent area reflected the area of vessels in the plaques. Results: Except for high-density lipoprotein cholesterol (HDL-c), all other lipid indices decreased. Compared with baseline, low-density lipoprotein cholesterol (LDL-c) decreased by approximately 57% (p < 0.001); total cholesterol (TC) decreased by approximately 34% (p < 0.001); small dense low-density lipoprotein (sd-LDL) decreased by approximately 52% (p < 0.001); and HDL-c increased by approximately 20% (p < 0.001). B-mode ultrasonography showed that the length and thickness of the plaque and the hypoechoic area ratio were reduced (p < 0.05). The plaque area, calcified area ratio, and lumen cross-sectional area changed little (p > 0.05). CEUS revealed that the area under the curve of plaque/lumen [AUC (P/L)] decreased from 0.27 ± 0.13 to 0.19 ± 0.11 (p < 0.001). The enhanced intensity ratio of plaque/lumen [intensity ratio (P/L)] decreased from 0.37 ± 0.16 to 0.31 ± 0.14 (p = 0.009). The contrast agent area in plaque/area of plaque decreased from 19.20 ± 13.23 to 12.66 ± 9.59 (p = 0.003). The neovascularization score decreased from 2.64 ± 0.54 to 2.06 ± 0.86 (p < 0.001). Subgroup analysis based on statin duration (<6 months and ≥6 months) showed that there was no significant difference in the AUC (P/L) or intensity ratio (P/L) at baseline or after half a year of evolocumab treatment. Conclusion: This study found that evolocumab combined with moderate-intensity statins significantly improved the blood lipid profile and reduced carotid IPN. Clinical Trial Registration: https://www.clinicaltrials.gov; identifier: NCT04423406.

Association between circulating full-length angiopoietin-like protein 8 and non-high-density lipoprotein cholesterol levels in Chinese non-diabetic individuals: a cross-sectional study.

BACKGROUND: Angiopoietin-like protein 8 (ANGPTL8) is a novel hormone involved in the regulation of lipid metabolism and glucose homeostasis. There are inconsistent results regarding the association between ANGPTL8 and lipids in humans. We aimed to investigate the associations between ANGPTL8 and lipids in people without diabetes. METHODS: This was a cross-sectional study of 107 patients with dyslipidemia and 141 patients without. Dyslipidemia diagnosis was based on Chinese guidelines for the prevention and treatment of dyslipidemia in adults. Total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol (HDL-C) were examined. Non-HDL-C was calculated by subtracting HDL-C from TC. Circulating full-length ANGPTL8 concentrations were measured using enzyme-linked immunosorbent assay. Associations between log-transformed circulating full-length ANGPTL8 and serum lipids were examined using multivariate linear regression analysis. RESULTS: Circulating ANGPTL8 concentrations were significantly elevated in patients with dyslipidemia compared with patients without dyslipidemia. Circulating full-length ANGPTL8 concentrations were positively associated with non-HDL-C, TG and TC levels after adjusting for age, gender, body mass index, high-sensitivity C-reactive protein, alanine aminotransferase, and creatinine. CONCLUSION: In people without diabetes, circulating full-length ANGPTL8 concentrations in patients with dyslipidemia were significantly elevated compared with non-dyslipidemia, and ANGPTL8 was positively associated with serum non-HDL-C levels.

Identification of absorbed constituents and in vivo metabolites in rats after oral administration of Physalis alkekengi var. franchetii by ultra-high-pressure liquid chromatography quadrupole time-of-flight mass spectrometry.

The calyces of Physalis alkekengi var. franchetii (Chinese Lantern, JDL) are well-known as traditional Chinese medicine owing to its various therapeutic effects. However, the bioactive constituents responsible for the pharmacological effects of JDL and their metabolites in vivo are still unclear to date. In this paper, an ultra-high-pressure liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC/Q-TOF-MS/MS) method was established to identify absorbed constituents and in vivo metabolites in rat biological fluids after oral administration of JDL. Based on the proposed strategy, 33 compounds were observed in dosed rat biosamples. Twelve of 33 compounds were indicated as prototype components of JDL, and 21 compounds were predicted to be metabolites of JDL. Finally, the metabolic pathways were proposed, which were glucuronidation, sulfation, methylation and dehydroxylation for flavonoid constituents and sulfonation and hydroxylation for physalin consitituents. This is the first systematic study on the absorbed constituents and metabolic profiling of JDL and will provide a useful template for screening and characterizing the ingredients and metabolites of traditional Chinese medicine.

Risk-aware multi-armed bandit problem with application to portfolio selection.

Sequential portfolio selection has attracted increasing interest in the machine learning and quantitative finance communities in recent years. As a mathematical framework for reinforcement learning policies, the stochastic multi-armed bandit problem addresses the primary difficulty in sequential decision-making under uncertainty, namely the exploration versus exploitation dilemma, and therefore provides a natural connection to portfolio selection. In this paper, we incorporate risk awareness into the classic multi-armed bandit setting and introduce an algorithm to construct portfolio. Through filtering assets based on the topological structure of the financial market and combining the optimal multi-armed bandit policy with the minimization of a coherent risk measure, we achieve a balance between risk and return.