Lactobacillus reuteri mitigates hepatic ischemia/reperfusion injury by modulating gut microbiota and metabolism through the Nrf2/HO-1 signaling.

BACKGROUND: This study seeks to investigate the impacts of Lactobacillus reuteri (L. reuteri) on hepatic ischemia-reperfusion (I/R) injury and uncover the mechanisms involved. METHODS: Mice in the I/R groups were orally administered low and high doses of L.reuteri (L.reuteri-low and L. reuteri-hi; 1 × 1010 CFU/d and 1 × 1011 CFU/d), for 4 weeks prior to surgery. Following this, mice in the model group were treated with an Nrf2 inhibitor (ML-385), palmitoylcarnitine, or a combination of both. RESULTS: After treatment with L. reuteri, mice exhibited reduced levels of serum aminotransferase (ALT), aspartate aminotransferase (AST), and myeloperoxidase (MPO) activity, as well as a lower Suzuki score and apoptosis rate. L. reuteri effectively reversed the I/R-induced decrease in Bcl2 expression, and the significant increases in the levels of Bax, cleaved-Caspase3, p-p65/p65, p-IκB/IκB, p-p38/p38, p-JNK/JNK, and p-ERK/ERK. Furthermore, the administration of L. reuteri markedly reduced the inflammatory response and oxidative stress triggered by I/R. This treatment also facilitated the activation of the Nrf2/HO-1 pathway. L. reuteri effectively counteracted the decrease in levels of beneficial gut microbiota species (such as Blautia, Lachnospiraceae NK4A136, and Muribaculum) and metabolites (including palmitoylcarnitine) induced by I/R. Likewise, the introduction of exogenous palmitoylcarnitine demonstrated a beneficial impact in mitigating hepatic injury induced by I/R. However, when ML-385 was administered prior to palmitoylcarnitine treatment, the previously observed effects were reversed. CONCLUSION: L. reuteri exerts protective effects against I/R-induced hepatic injury, and its mechanism may be related to the promotion of probiotic enrichment, differential metabolite homeostasis, and the Nrf2/HO-1 pathway, laying the foundation for future clinical applications.

Efficacy and Safety of Ultrasound-Guided High-Intensity Focused Ultrasound Ablation in Women With Multiple Uterine Fibroids: An Exploratory Study.

OBJECTIVE: The aim of the work described here was to explore the clinical efficacy and safety of ultrasound-guided high-intensity focused ultrasound (USg-HIFU) treatment in women with multiple fibroids and identify the characteristic parameters predicting USg-HIFU efficacy in multiple fibroids. METHODS: From February 2021 to August 2022, 138 patients with multiple fibroids (group A comprising 125 patients with two to four fibroids and 13 patients with five or more fibroids) and 149 patients with solitary fibroids (group B) were included. HIFU treatment information, efficacy comparisons and adverse events were recorded. A nomogram model of the characteristic parameters used to predict the efficacy of USg-HIFU in multiple fibroids was established. RESULTS: After USg-HIFU treatment, the statistical comparison of pre-operative versus post-operative symptom scores and fibroid volume in the two groups indicated obvious symptom relief and substantial shrinkage of fibroid volume (all p values <0.001). Nevertheless, group A required more energy and longer treatment and sonication times to achieve a 70% non-perfused volume (NPV) ratio, and had a lower energy efficiency factor than group B (all p values <0.05). No severe complications were observed in either group. The nomogram model included fibroid volume, fibroid location and signal intensity on T2-weighted imaging (T2WI). The area under the receiver operating characteristic curve and the accuracy of the model were 0.698 and 0.686, respectively. CONCLUSION: USg-HIFU appears to be an effective and safe treatment option for multiple fibroids. Knowledge of the fibroid volume, location and signal intensity on T2WI may help determine the efficacy of USg-HIFU in multiple fibroids.

Multimodal predictive factors of metastasis in lymph nodes posterior to the right recurrent laryngeal nerve in papillary thyroid carcinoma.

Objective: The lymph node posterior to the right recurrent laryngeal nerve (LN-prRLN) is a crucial component of the central lymph nodes (LNs). We aimed to evaluate multimodal predictive factors of LN-prRLN metastasis in patients with papillary thyroid carcinomas (PTCs), including the clinical data, pathologic data, and preoperative sonographic characteristics of PTCs. Methods: A total of 403 diagnosed PTC patients who underwent unilateral, sub-total, or total thyroidectomy with central neck dissection were enrolled in this retrospective study. The clinical data, pathologic data, conventional ultrasound (US) and contrast-enhanced ultrasound (CEUS) characteristics of PTCs were collected and evaluated for predicting LN-prRLN metastasis. Results: In this study, 96 PTC patients with LN-prRLN metastasis and 307 PTC patients without LN-prRLN metastasis were included. Univariate analysis demonstrated that PTC patients with LN-prRLN metastasis more often had younger age, larger size, multifocal cancers, A/T < 1, well-margins, microcalcification, petal-like calcification, internal vascularity, centripetal perfusion pattern and surrounding ring enhancement. Multivariate logistic regression analysis revealed that the CEUS centripetal perfusion pattern, central LN detected by ultrasound and LN-arRLN metastasis were independent characteristics for predicting LN-prRLN metastasis in PTC patients. Conclusion: According to our research, it is essential for clinicians to thoroughly dissect central LNs, particularly LN-prRLNs.

Corroded iron stent increases fibrin deposition and promotes endothelialization after stenting.

Poststent restenosis is caused by insufficient endothelialization and is one of the most serious clinical complications of stenting. We observed a rapid endothelialization rate and increased fibrin deposition on the surfaces of the corroded iron stents. Thus, we hypothesized that corroded iron stents would promote endothelialization by increasing fibrin deposition on rough surfaces. To verify this hypothesis, we conducted an arteriovenous shunt experiment to analyze fibrin deposition in the corroded iron stents. We implanted a corroded iron stent in both the carotid and iliac artery bifurcations to elucidate the effects of fibrin deposition on endothelialization. Co-culture experiments were conducted under dynamic flow conditions to explore the relationship between fibrin deposition and rapid endothelialization. Our findings indicate that, from the generation of corrosion pits, the surface of the corroded iron stent was rough, and numerous fibrils were deposited in the corroded iron stent. Fibrin deposition in corroded iron stents facilitates endothelial cell adhesion and proliferation, which, in turn, promotes endothelialization after stenting. Our study is the first to elucidate the role of iron stent corrosion in endothelialization, pointing to a new direction for preventing clinical complications caused by insufficient endothelialization.

Contrast-enhanced ultrasound characteristics of preoperative central cervical lymph node metastasis in papillary thyroid carcinoma.

This study evaluated the preoperative diagnostic value of lymph node ultrasonography in distinguishing between benign and malignant central cervical lymph nodes (CCLNs) in patients with papillary thyroid carcinoma (PTC). A total of 176 patients who had PTC with 216 CCLNs (49 benign and 155 malignant) were enrolled in this study and preoperatively imaged by ultrasonography, including conventional ultrasound (US) and contrast-enhanced ultrasound (CEUS). We evaluated the ultrasonography parameters for each lymph node. Binary logistic regression analysis indicated that multifocality of PTC and the absence of Hashimoto's thyroiditis are independent clinical features related to patients with PTC who also have malignant CCLNs. For preoperative ultrasonography features, heterogeneous enhancement and centripetal perfusion are independent ultrasonographic features to identify malignant and benign CCLNs. This study demonstrated that preoperative CEUS characteristics help to distinguish malignant CCLNs from benign CCLNs.

Clinical Features Differ Between Patients With Vertigo Attack Only and Weakness Attack Accompanying Vertigo Before Vertebrobasilar Stroke: A Retrospective Study.

Objective: To determine the different clinical features of patients with vertigo attacks alone and of those with weakness accompanying vertigo attacks before the vertebrobasilar ischemic stroke. Methods: In this 4-year retrospective study, we manually screened the medical records of 209 patients, hospitalized with vertigo attack as the main complaint who were finally diagnosed with acute vertebrobasilar ischemic stroke. Patients were divided into two groups according to their symptoms: patients who only experienced vertigo attacks prior to the vertebrobasilar stroke (VO group) and patients who had both vertigo and weakness attacks (VW group) prior to the stroke. Clinical parameters, such as infarction site and volume, relative risk factors, ABCD2 score, and medical intervention, were compared between the two groups. Results: The prevalence of hypertension was higher in the Vertigo attacks only (VO) group (42.2 vs. 29.0%, p < 0.05). The total cerebral infarction volume in the VO group was larger than the Vertigo and weakness attacks (VW) group (4.44 vs. 2.12 cm3, p < 0.05). Additionally, the cerebellum was more likely to be affected in the VO group. In contrast, patients in the VW group had higher carotid stenosis (14.2 vs. 27.2%, p < 0.05) and ABCD2 score (2.1 ± 1.2 vs. 3.6 ± 1.5, p = 0.02). The percentage of patients with medullary infarctions also increased in the VW group. Vertigo attack events occurred more frequently in the VW group (median 2.4 vs. 4.3, p < 0.04). We also found that the patients in the VW group were more likely to seek medical intervention after vertigo. Conclusions: Clinical parameters, such as infarction location, relative risk factors, and ABCD2 score, differed between patients with vertigo symptoms with or without weakness attacks. These findings highlight the different clinical features of patients with vertigo attack only and those with weakness attacks accompanying vertigo prior to vertebrobasilar ischemic stroke.

Value of Contrast-Enhanced Ultrasound in Mummified Thyroid Nodules.

Mummified thyroid nodules (MTNs) are rarely reported and are usually misdiagnosed as malignant nodules. This article first reviewed the contrast-enhanced ultrasound (CEUS) enhancement features of 218 MTNs and classified them into three (A, B, C) patterns. The A pattern MTNs show linear hypo-enhancement, the B pattern MTNs show heterogeneous hypo-enhancement, and the C pattern MTNs show no enhancement in thyroid nodules. The A and C pattern enhancements of MTNs demonstrated a high specificity compared with the enhancement of previously reported typical papillary thyroid carcinomas (PTCs). To further study the B pattern MTNs, 24 B pattern MTNs and 42 PTCs were enrolled in this study, and CEUS parameters for each nodule were evaluated. Univariate analysis indicated that compared with PTCs, the B pattern MTNs more frequently exhibited heterogeneous hypo-enhancement and clear margins after clearance (p <0.05). A multivariate analysis revealed that heterogeneous hypo-enhancement and clear margins after clearance were independent characteristics related to the B pattern MTNs for differentiating them from PTCs (p <0.05). Thus, preoperative CEUS may provide more important information for distinguishing MTNs from malignant thyroid nodules to avoid surgical excisions or unnecessary fine-needle aspiration (FNA).

Mendelian Randomization Analysis Suggests No Associations of Herpes Simplex Virus Infections With Multiple Sclerosis.

Previous studies have suggested an association between infection with herpes simplex virus (HSV) and liability to multiple sclerosis (MS), but it remains largely unknown whether the effect is causal. We performed a two-sample Mendelian randomization (MR) study to explore the relationship between genetically predicted HSV infection and MS risk. Genetic instrumental variables for diagnosed infections with HSV (p < 5 × 10-6) were retrieved from the FinnGen study, and single nucleotide polymorphisms associated with circulating immunoglobulin G (IgG) levels of HSV-1 and HSV-2 and corresponding summary-level statistics of MS were obtained from genome-wide association studies of the European-ancestry. Inverse-variance weighted MR was employed as the primary method and multiple sensitivity analyses were performed. Genetically proxied infection with HSV was not associated with the risk of MS (odds ratio [OR], 0.96; 95% confidence interval [CI], 0.90-1.02; p = 0.22) per one-unit increase in log-OR of herpes viral infections. MR results provided no evidence for the relationship between circulating HSV-1 IgG levels and MS risks (OR = 0.91; 95% CI, 0.81-1.03; p = 0.37), and suggested no causal effect of HSV-2 IgG (OR = 1.04; 95% CI, 0.96-1.13; p = 0.32). Additional sensitivity analyses confirmed the robustness of these null findings. The MR study did not support the causal relationship between genetic susceptibly to HSV and MS in the European population. Further studies are still warranted to provide informative knowledge, and triangulating evidence across multiple lines of evidence are necessary to plan interventions for the treatment and prevention of MS.

Value of Contrast-Enhanced Ultrasound for Evaluation of Cervical Lymph Node Metastasis in Papillary Thyroid Carcinoma.

The aim of the study was to evaluate the diagnostic value of contrast-enhanced ultrasound (CEUS) in distinguishing between benign and malignant cervical lymph nodes (LNs) in patients with papillary thyroid carcinoma (PTC). Two hundred and one cervical LNs (157 metastatic from PTC and 44 benign) were evaluated using conventional ultrasonography (US) and CEUS before biopsy or surgery. Histopathology was used as the gold standard. We evaluated the size, long axis/short axis ratio (L/S), fatty hilum, hyper-echogenicity, calcification, cystic change, peripheral vascularity and CEUS parameters for each lymph nodule. The CEUS parameters included enhancement type, homogeneity, perfusion type, ring enhancement, peak intensity (PI) index and area under the curve (AUC) index. Univariate analysis demonstrated that compared with benign LNs, malignant LNs more frequently had L/S < 2, absence of a fatty hilum, presence of hyper-echogenicity, presence of calcification, peripheral vascularity, hyper-enhancement, heterogeneous enhancement, centripetal perfusion, ring enhancement, PI index > 1 and AUC index > 1 on preoperative US and CEUS. Binary logistic regression analysis demonstrated that hyper-enhancement, centripetal perfusion, and ring enhancement are independent CEUS characteristics related to malignant LNs for their differentiation from benign LNs (all p < 0.05). Our study indicated that preoperative CEUS characteristics may serve as a useful tool to identify malignant cervical LNs from benign cervical LNs.

Value of Contrast-Enhanced Ultrasound in Differentiating Clinically Atypical Subacute Thyroiditis from Papillary Thyroid Carcinomas.

Our objective was to provide the various sonographic characteristics of clinically atypical subacute thyroiditis (CAST) in distinguishing CAST from papillary thyroid carcinomas (PTCs) by using conventional ultrasound (US) and contrast-enhanced ultrasound (CEUS). Forty-six CAST patients and 50 PTC patients were enrolled in this study. We evaluated the size, shape, margin, echogenicity, calcification, vascularity and CEUS parameters for each nodule. The final diagnosis of CAST was confirmed via fine-needle aspiration (FNA) or surgery. Of the 46 CASTs, 13 (28.3%) were confirmed by surgery to be benign, and 33 (71.7%) were proven by FNA to be benign. Univariate analysis indicated that compared with PTCs, CAST lesions more frequently had wider-than-taller shapes, blurred margins, the absence of microcalcifications, peripheral high echogenicity, the absence of internal vascularity, hypo-enhancement, centrifugal perfusion and a peak intensity index <1 and area under the curve index <1 on pre-operative US and CEUS. A multivariate analysis revealed that clear margins, microcalcifications and centripetal perfusion were independent characteristics related to PTCs for their differentiation from CAST (all p values <0.05). Our study indicated that the pre-operative multiparameter US characteristics may serve as a useful tool for distinguishing CAST from malignant thyroid nodules to avoid surgical excisions or unnecessary FNAs.

New Insights Into Vertigo Attack Frequency as a Predictor of Ischemic Stroke.

Background: Recurrent attacks of vertigo account for 2.6 million emergency department visits per year in the USA, of which more than 4% are attributable to ischemic infarction. However, few studies have investigated the frequency of attacks of vertigo before an ischemic stroke. Methods: We conducted this retrospective analysis and manually screened the medical records of 231 patients who experienced recurrent attacks of vertigo prior to an ischemic stroke. Patients were divided into four different groups based on the frequency of vertigo attacks as well as the region of ischemic infarction. Those with ≤2 attacks of vertigo preceding the ischemic stroke were defined as the low-frequency group. Those with ≥3 attacks were defined as the high-frequency group. Clinical parameters, including vascular risk factors, average National Institutes of Health Stroke Scale (NIHSS) score, and infarction volume, were compared between the groups. Results: On analysis, we found that patients with posterior infarction in the high-frequency group exhibited a higher prevalence of vertebral artery stenosis. However, the incidence of diabetes mellitus (DM) was higher in the low-frequency group. In addition, patients with posterior infarction in the low-frequency group were more active in seeking medical intervention after an attack of vertigo. Notably, the brain stem, especially the lateral medullary region, had a higher probability of being involved in posterior infarction in the high-frequency group. However, the cerebellum was more commonly involved in posterior infarction in the low-frequency group. Conclusions: Our findings indicate that the clinical parameters, including arterial stenosis, DM, and magnetic resonance imaging (MRI) findings, differed between the low- and high-frequency groups. We also found that patients in the low-frequency group were more willing to seek medical intervention after the attacks of vertigo. These findings could be valuable for clinicians to focus on specific examination of the patients according to the frequency of vertigo attacks.

Detailed Echocardiographic Measurements of Individual Chamber in a Chinese Cohort of Hypoplastic Left Heart Syndrome and Comparison with Normal Fetuses via Z-score Modeling.

Hypoplastic left heart syndrome (HLHS) is a rare, but exceptionally serious, congenital heart defect. We aimed to explore the best-fitted Z-score models for individual chamber dimension and to draw a comparison between fetuses with HLHS and the normal Chinese cohort. We made measurements of 1674 healthy fetuses and 79 fetuses with HLHS, undertaking echocardiography. Normal fetal cardiovascular Z-score formulae were established by curve-fitting with 5 algorithmic functions and weighted regression of absolute residuals. Classic linear models were fitted for left ventricular diameter against gestational age, and log-transformed linear-power models-were statistically better for left ventricular length, diameter of left atrium and ascending aorta. Fetuses with HLHS manifested significantly lower Z-score means (≤3.5) for these 4 parameters and the vast majority (∼90%) lay beyond -2. Overall, cardiovascular Z-score equations were reliably constructed in a larger Chinese cohort, and their application should benefit evaluation and diagnosis of HLHS.

[Echocardiographic diagnosis for ventricular non-compaction cardiomyopathy in foetus and the pathologically comparative study].

OBJECTIVE: To evaluate the echocardiographic diagnosis for ventricular non-compaction cardiomyopathy (NCCM) in foetus and to analyze the pathologic features of NCCM.
 METHODS: A total of 9 patients with fetal NCCM were examined by prenatal echocardiography from 2004 to 2013, which was compared with postnatal echocardiography or autopsy to analyze the fetal characteristic of myocardial ultrastructure.
 RESULTS: The results of echocardiography displayed an excessive muscle trabecular meshwork and muscle trabecular crypt, and the ventricular myocardium and non-compaction/compaction ratio was ≥2.0. Among the 9 fetuses of NCCM, 6 fetuses were involved in left ventricle, 2 in both left and right ventricles and 1 in right ventricle. Two fetuses were confirmed by postnatal echocardiography, the remaining 7 patients were chosen to terminate their pregnancies, which were confirmed by autopsy later. Muscle biopsies revealed the abnormal myocardial mitochondria, sarcomeres and myocardial fibrosis.
 CONCLUSION: It is feasible to accurately diagnose NCCM by prenatal echocardiography. Fetal NCCM most often involves the left ventricle, but it can involve the right ventricle or both, too. The myocardial ultrastructure of fetal NCCM possesses certain unique characteristics, such as the low maturation of the mitochondria, sarcomeres and myocardial fibers.