Echocardiography-guided percutaneous intramyocardial alginate hydrogel implants for heart failure: canine models with 6-month outcomes.

Background: Echocardiography-guided percutaneous intramyocardial alginate-hydrogel implantation (PIMAHI) is a novel treatment approach for heart failure (HF). We validated PIMAHI safety and efficacy in canine HF models. Methods: Fourteen canines with HF [produced by coronary artery ligation, left ventricular ejection fraction (LVEF) < 35%] were randomised to PIMAHI treatment (n = 8) or controls (n = 6). Echocardiography, two-dimensional speckle tracking echocardiography, and pathological examinations after a 6-month follow-up were performed. Repeated-measures analysis of variance was used for within-group comparisons. Results: At 6-month follow-up, PIMAHI treatment reversed LV dilation and remodelling, increasing LV free wall thickness (LVFW, p = 0.002) and interventricular septum thickness (IVS, p < 0.001) and reducing LV end-diastolic volume (EDV, p = 0.008) and end-systolic volume (ESV, p = 0.004). PIMAHI significantly improved LV systolic function, increasing LVEF (EF, p = 0.004); enhanced LV myocardial contractility, including increased LV global longitudinal strain (GLS, p < 0.001), global circumferential strain (GCS, p = 0.006), and mitral annulus displacement (MAD, p = 0.001). Compared with controls at 6-month, PIMAHI group significantly increased LVFW thickness (8.5 ± 0.3 vs. 6.8 ± 0.2 mm, p = 0.002) and IVS (7.9 ± 0.1 vs. 6.1 ± 0.2 mm, p < 0.001); decreased LVEDV (30.1 ± 1.6 vs. 38.9 ± 4.5 ml, p = 0.049) and ESV (17.3 ± 1.2 vs. 28.7 ± 3.6 ml, p = 0.004); increased LV systolic function (42.7 ± 1.5 vs. 26.7 ± 1.1% in EF, p = 0.001); and enhanced LV myocardial contractility including GLS (13.5 ± 0.8 vs. 8.4 ± 0.6%, p = 0.002), GCS (16.5 ± 1.4 vs. 9.2 ± 0.6%, p = 0.001), and MAD (11.4 ± 3.5vs 4.6 ± 2.5 mm, p = 0.003). During PIMAHI treatment, no sustained arrhythmia, pericardial, or pleural effusion occurred. Conclusions: PIMAHI in canine HF models was safe and effective. It reversed LV dilation and improved LV function.

Diagnosis of obstetric brachial plexus injury in a 2-year-old girl using high­frequency ultrasonography.

We describe an unusual case of infant obstetric brachial plexus injury located in the cervical (C)5-C6 brachial plexus nerve, which was preoperatively diagnosed using high-frequency ultrasonography (US) at 2 years of age. The girl was diagnosed with a right clavicular fracture because of shoulder dystocia. She had been showing movement limitations of her entire right upper limb after fracture healing and was then referred to our hospital at 2 years of age. High-frequency US showed that the roots of the right brachial plexus ran continuously, but the diameter of C6 was thinner on the affected side than on the contralateral side (right 0.12 cm vs. left 0.20 cm). A traumatic neuroma had formed at the upper trunk, which was thicker (diameter: right 0.35 cm vs. left 0.23 cm; cross-sectional area: right 0.65 cm2 vs. left 0.31 cm2) at the level of the supraclavicular fossa. Intraoperative findings were consistent with ultrasound findings. Postoperative pathology confirmed brachial plexus traumatic neuroma.

Diagnosis of thoracic outlet syndrome with the lower trunk compression of brachial plexus by high-frequency ultrasonography.

BACKGROUND: Thoracic outlet syndrome (TOS) with the lower trunk compression of brachial plexus (BP) is difficult to diagnosis. This study aimed to summarize the features of thoracic outlet syndrome (TOS) with the lower trunk compression of brachial plexus observed on high-frequency ultrasonography (HFUS). METHODS: The ultrasound data of 27 patients who had TOS with the lower trunk compression of brachial plexus were collected and eventually confirmed by surgery. The imaging data were compared, and the pathogenesis of TOS was analyzed on the basis of surgical data. RESULTS: TOS occurred predominantly in females (70.4%). Most cases had unilateral involvement (92.6%), mainly on the right side (66.7%). The HFUS features of TOS can be summarized as follows: (1) Lower trunk compression. HFUS revealed focal thinning that reflected compression at the level of the lower trunk; furthermore, the distal part of the nerve was thickened for edema (Affected side: 0.49 ± 0.12 cm vs. Healthy side: 0.38 ± 0.06, P = 0.009), and the cross-sectional area of brachial plexus cords was markedly greater on the injured side than on the healthy side (0.95 ± 0.08 cm² vs. 0.65 ± 0.11 cm², P = 0.004). (2) Hyperechoic fibromuscular bands behind the compressed nerve (mostly the scalenus minimus muscle). (3) Abnormal bony structures: cervical ribs or elongated transverse processes of the 7th cervical vertebra (C7). Surgical results showed that the etiological factors contributing to TOS were (1) muscle hypertrophy and/or fibrosis (100%) and (2) cervical ribs/elongated C7 transverse processes (20.7%). CONCLUSION: TOS with the lower trunk compression of brachial plexus can be diagnosed accurately and reliably by high-frequency ultrasound.

Contrast-enhanced echocardiographic diagnosis of benign and malignant cardiac tumors and its correlation with pathology.

Background: This study aimed to explore the diagnostic value of contrast-enhanced echocardiography (CEE) in benign and malignant cardiac tumors and detect the correlation of CEE parameters and immunohistochemistry (IHC) markers. Methods: The data of 44 patients with cardiac tumors confirmed by pathology were reviewed. Lesions were examined before surgery using transthoracic echocardiography (TTE) and CEE with time-intensity curve analysis. The expression of CD31, VEGF and Ki67 was measured by IHC staining. Microvessel density (MVD) was quantified via IHC for CD31. The clinical variables, TTE, CEE and IHC parameters were compared between benign and malignant cardiac tumors. Receiver operating characteristic curve were used to analyze the value of factors in predicting malignant cardiac tumors. The correlation between CEE and IHC parameters was analyzed. Results: Among 44 cardiac tumors, 34 were benign and 10 were malignant. There were significant differences in the TTE parameters (pericardial effusion, tumor boundary, diameter, basal width), CEE parameters (tumor peak intensity (TPI), peak intensity ratio of tumor to myocardium (TPI/MPI), area under time-intensity curve (AUTIC)) and IHC parameters (Ki67, MVD, CD31, VEGF) between the benign and malignant tumor groups (all P < 0.05). Receiver operating characteristic curve analysis showed that the CEE and IHC parameters had diagnostic value in malignant cardiac tumors. There was a correlation between TPI/MPI and Ki67 (r = 0.62), AUTIC and Ki67 (r = 0.50), and AUTIC and CD31 (r = 0.56). Conclusion: TTE and CEE parameters were different between benign and malignant cardiac tumors. CEE is helpful to differentiate the properties of cardiac tumors. There is a correlation between CEE parameters and IHC markers. AUTIC and TPI/MPI can reflect the proliferation and invasion of tumors.

Cerebral infarction and risk factors in acute type A aortic dissection with arch branch extension.

OBJECTIVE: Stanford type A aortic dissection (AAD) may affect the supra-aortic arteries, which are associated with acute ischemic stroke (AIS) or transient ischemic attack (TIA). This study aimed to investigate cerebral perfusion, the infarction incidence and risk factors in AAD patients. METHODS: A total of 156 consecutive AAD patients were enrolled and divided into two groups according to whether the aortic arch branches were involved: the affected group (n = 90) and the unaffected group (n = 66). Clinical, echocardiographic/carotid Doppler data and cerebral infarction morbidity were compared between the groups. Independent predictors of 30-day AAD mortality were identified through multivariable Cox regression, and perioperative risk factors were analyzed. RESULTS: In total, 57.7% of AAD patients had aortic arch branch involvement. Abnormal Doppler waveforms were more common in the affected group (p < 0.05). Regarding intracranial perfusion, the blood flow volumes (BFVs) of the bilateral internal carotid arteries (ICAs) and right vertebral artery (RVA) in the affected group were significantly reduced (p < 0.05). The incidence of cerebral infarction in the affected group was significantly higher than that in the unaffected group (35.6% vs. 19.7%, p = 0.031). Multivariable analysis revealed that age >45 years old, right internal carotid artery (RICA) involvement and reduced left ventricular ejection fraction (LVEF) were significant predictors of perioperative death. CONCLUSIONS: Aortic arch branch involvement is common in patients with AAD and is associated with reduced cerebral blood flow (especially on the right side) and a higher incidence of cerebral infarction. Age, extension of the RICA dissection and LVEF impairment are independent risk factors for AAD-related death.

Rare malignant melanotic nerve sheath tumors of the upper limb nerves: utility of high-frequency ultrasonography in preoperative imaging.

Melanotic nerve sheath tumor (MNST) is a rare variant of schwannoma. Here, we report an unusual case of multiple MNST lesions located in the upper limb nerves. The patient presented with a mass on the left wrist in 2016 and another mass on the left thumb in 2017. In both instances, magnetic resonance imaging scans confirmed multiple giant-cell tumors of the tendon sheath. Persistent pain in the left upper limb and numbness in the ring finger and little finger recurred in 2021. High-frequency ultrasound (HFUS) showed that the left brachial plexus nerves (C5-8) were widened compared with those on the contralateral side; the neuroma formed at the lateral cord, and the median nerve was markedly thickened. The surgical findings were consistent with the ultrasound results. Pathology confirmed that the tumors were malignant MNSTs. HFUS is important for preoperative diagnosis and lesion localization, even identifying some lesions that are unrecognized on magnetic resonance imaging; thus, HFUS is crucial for improving surgical strategy and decision-making.

A study of 399 cardiac tumors: Characteristics of echocardiography and pathological features.

AIMS: This study aimed to summarize the transthoracic echocardiography (TTE) characteristics of cardiac tumors with different pathologies. METHODS: The data of 399 patients with cardiac tumors confirmed by pathology, who had undergone surgical resection were consecutively collected in our hospital between January 1, 2011 and December 31, 2019. The TTE characteristics were summarized and compared with the pathology. RESULTS: Mean patient age was 49.8±15.7 years (22 children and 377 adults), and 62.2% were female. Of the tumors, 90.5% (361) were primary and 9.5% (38) were secondary. Further, 88.7% (354) were benign and 11.3% (45) were malignant. Of the primary tumors (96.1% benign and 3.9% malignant), 84.2% were myxomas, followed by 3.5% lipomas and 1.5% fibromas in adults, while in children, 31.8% were rhabdomyomas and 22.7% were fibromas. The most common type of secondary cardiac tumor was malignant liver carcinoma metastasis (39.5%) and benign intravenous leiomyomatosis with cardiac extension from the uterus (18.4%). TTE features of myxoma showed four variation types among 8.9% of myxomas: liquefaction (anechoic region mostly), calcification (hyperechoic range with a shadow), multiple nodules, and high proliferative activity (a large irregular mass with a wide base and a high Ki67 index). The TTE characteristics of some common benign non-myxoma tumors had specific findings. The TTE features of malignant tumors mostly showed hypoechogenicity, an unclear boundary, a wide basement, and multi-chambers or tissue invasion. CONCLUSIONS: Most cardiac tumors have typical ultrasonic manifestations. Preoperative echocardiography could roughly judge cardiac tumor type and may be helpful for guiding clinical treatment decisions.

Diagnosis of cervical plexus tumours by high-frequency ultrasonography.

BACKGROUND: Cervical plexus (CP) tumours are difficult to diagnose because of atypical symptoms. This study aimed to summarize the features of a normal CP and CP tumours observed on high-frequency ultrasonography. METHODS: The ultrasound data of 11 CP tumour patients and 22 normal volunteers were collected. All 11 patients underwent magnetic resonance imaging (MRI), and 4 patients also underwent computed tomography (CT). The imaging data were compared with surgery and pathology data. RESULTS: The C7 vertebra and bifurcation of the carotid common artery (CCA) were useful anatomic markers for identifying the CP. In contrast to the C1 nerve (22.7%), the C2-4 nerves were well displayed and thinner than the brachial plexus (P < 0.05). CP tumours were more common in females (72.7%) and generally located at C4 (72.7%) on the right side (81.8%). Additionally, the nerve trunk in tumour patients was obviously wider than that in normal controls (7.49 ± 1.03 mm vs 2.67 ± 0.36 mm, P < 0.01). Compared with pathology, the diagnostic rates of CP tumours by MRI, CT and high-frequency ultrasound were 72.7% (8/11), 25% (1/4) and 90.9% (10/11), respectively. CONCLUSIONS: The diagnosis of CP neuropathy is accurate and reliable by high-frequency ultrasound, and the C7 vertebra and bifurcation of the CCA are useful anatomic markers in CP ultrasonography.

Pentahydroxy flavonoid isolated from Madhuca indica ameliorated adjuvant-induced arthritis via modulation of inflammatory pathways.

Rheumatoid arthritis (RA) is an autoimmune disease associated with advanced joint dysfunction. Madhuca indica J. F. Gmel, from the family Sapotaceae, is an Indian medicinal plant reported to have an array of pharmacological properties. The aim of present investigation was to determine the anti-arthritic potential of an isolated phytoconstituent from methanolic leaf extract of Madhuca indica (MI-ALC) against FCA-induced experimental arthritis. Polyarthritis was induced in female rats (strain: Wistar) via an intradermal injection of FCA (0.1 mL) into the tail. Polyarthritis developed after 32 days of FCA administration. Then rats were treated orally with an isolated phytoconstituent from MI-ALC at doses of 5, 10, and 20 mg/kg. Findings suggested that High-Performance Thin-Layer Chromatography, Fourier-Transform Infrared Spectroscopy, and Liquid Chromatography-Mass Spectrometry spectral analyses of the phytoconstituent isolated from MI-ALC confirmed the structure as 3,5,7,3',4'-Pentahydroxy flavone (i.e., QTN). Treatment with QTN (10 and 20 mg/kg) showed significant (p < 0.05) inhibition of increased joint diameter, paw volume, paw withdrawal threshold, and latency. The elevated synovial oxidative stress (Superoxide dismutase, reduced glutathione, and malondialdehyde) and protein levels of Tumor necrosis factor-α (TNF-α) and Interleukin (ILs) were markedly (p < 0.05) reduced by QTN. It also effectively (p < 0.05) ameliorated cyclooxygenase-2 (COX-2), Nuclear factor of kappa light polypeptide gene enhancer in B cells (NF-kß) and its inhibitor-α (Ikßα), and ATP-activated P2 purinergic receptors (P2X7) protein expressions as determined by western blot analysis. In conclusion, QTN ameliorates FCA-induced hyperalgesia through modulation of elevated inflammatory release (NF-kß, Ikßα, P2X7, and COX-2), oxido-nitrosative stress, and pro-inflammatory cytokines (ILs and TNF-α) in experimental rats.

Corrigendum: Müller Cell Regulated Microglial Activation and Migration in Rats With N-Methyl-N-Nitrosourea-Induced Retinal Degeneration.

[This corrects the article DOI: 10.3389/fnins.2018.00890.].

Ultrasonic Characteristics of Cardiovascular Changes in Children with Hutchinson-Gilford Progeria Syndrome: A Comparative Study with Normal Children and Aging People.

BACKGROUND: The cardiovascular characteristics of children with Hutchinson-Gilford progeria syndrome (HGPS) remain unclear. The present study is aimed at evaluating the cardiovascular changes with ultrasound examination in children with HGPS and compared these with those in normal children and older people. METHODS: Seven HGPS children, 21 age-matched healthy children, and 14 older healthy volunteers were evaluated by three-dimensional echocardiography (including strain analysis) and carotid elasticity examination with the echo-tracking technique. RESULTS: Children with HGPS had higher left ventricular ejection fraction (LVEF) and global longitudinal strain, when compared to older healthy volunteers (P < 0.05). However, these parameters were not significantly different, when compared to those in healthy children. Furthermore, children with HGPS had lower average peak times in the left ventricle, when compared with the other two groups. For the structure of the carotid artery detected by ultrasound, the abnormality rates were similar between children with HGPS and older healthy volunteers (83.3% vs. 71.4%). The elastic parameters, elastic modulus, stiffness parameter, and pulsed wave transmittal velocity of children with HGPS were lower, when compared to those in older healthy volunteers (P < 0.05), while they were higher with arterial compliance (P > 0.05). Furthermore, no significant difference existed among the vascular elastic parameters between HGPS and normal children. CONCLUSION: HGPS children had impaired left ventricular (LV) synchrony, when compared to normal children, although the difference in LVEF was not statistically significant. Furthermore, the structural abnormality of the carotid artery in HGPS children was similar to that in older people, although the index of elasticity appears to be more favorable. These results suggest that the cardiovascular system in HGPS children differs from natural aging.

Anti-inflammatory effects of eriocitrin against the dextran sulfate sodium-induced experimental colitis in murine model.

Inflammatory bowel disease (IBD) is a continual ailment condition which engrosses the entire alimentary canal. The IBD can be primarily distinguished into two forms, ulcerative colitis, and Crohn's disease. The major symptoms of IBD include pustules or abscesses, severe abdominal pain, diarrhea, fistula, and stenosis, which may directly affect the patient's quality of life. A variety of mediators can stimulate the circumstances of IBD, some examples include infections by microbes such as bacteria, perturbation of the immune system and the surrounding environment of the intestines. Severe colitis was stimulated in the experimental animals through administering 4% dextran sulfate sodium (DSS) which is mixed in water ad libitum for 6 days. Eriocitrin (30 mg/kg) was then administered to the experimental animals followed by the induction of severe colitis to evaluate the therapeutic prospective of eriocitrin against the colon inflammation stimulated by DSS. In this study, eriocitrin (30 mg/kg) demonstrated significant (P < .05) attenuation activity against the DSS-stimulated severe colitis in experimental animals. Eriocitrin counteracted all of the clinical deleterious effects induced by DSS, such as body-weight loss, colon shortening, histopathological injury, accretion of infiltrated inflammatory cells at the inflamed region and the secretion of inflammatory cytokines. The results clearly showed that eriocitrin effectively attenuated DSS-induced acute colitis in experimental animals.

Involvement of the microglial NLRP3 inflammasome in the anti-inflammatory effect of the antidepressant clomipramine.

BACKGROUND: Depression has recently been referred to as a neuroimmune disease because it is characterized by inflammatory changes in the cerebral cortex and hippocampus. Studies have demonstrated that microglial activation plays a crucial role in releasing inflammatory cytokines in the central nervous system (CNS), thereby contributing to depression, the mechanism underlying which remains unclear. METHODS: First, we examined microglial activation and inflammatory changes in C57BL/6 male mice injected with lipopolysaccharide (LPS; 1 mg/kg), which leads to depressive behaviors in mice that were attenuated by the antidepressant clomipramine. Second, we utilized a BV2 cell line and primary microglial cultures to determine the inflammatory response in vitro, and the effects of clomipramine exerted on the inflammatory response using real-time polymerase chain reaction and ELISA. Third, we utilized NLRP3 (NOD-like receptor protein 3) knock-out (KO) mice to prove that NLRP3 is involved in the effects of clomipramine. RESULTS: The results showed that LPS injection induced depressive-like behaviors in mice, as assessed using several behavioral tests including body weight, and forced swimming and tail suspension tests. The LPS-induced expression of interleukin-1beta (IL-1ß), IL-6, and tumor necrosis factor alpha could be downregulated by clomipramine pre-treatment both in vivo and in vitro. The inhibitory effect of clomipramine on the LPS-induced increase in cytokines was found at both the protein and gene levels. Clomipramine significantly reduced the LPS-induced increase in NLRP3 gene expression in BV2 cells. Furthermore, we utilized NLRP3 KO mice to explore whether NLPP3 was involved in this process and found that clomipramine treatment inhibits the LPS-induced increased expression of IL-1ß. CONCLUSION: These results imply that clomipramine could attenuate depressive behaviors and neuroinflammation induced by LPS via partial regulation of NLRP3.

Müller Cell Regulated Microglial Activation and Migration in Rats With N-Methyl-N-Nitrosourea-Induced Retinal Degeneration.

During the pathogenesis of retinitis pigmentosa (RP), the roles of retinal microglial cells after activation have not been fully elucidated. Herein, experimental RP was induced in Sprague Dawley rats by intraperitoneal injection of N-methyl-N-nitrosourea (MNU) at 50 mg/kg, and the effects of MNU on the retinas were evaluated, respectively, by retinal histology and electroretinography recordings at serial time points. Time-dependent and gradual loss of photoreceptor cells, disrupted arrangement of the outer nuclear layer (ONL), and significant reductions in both a-wave and b-wave amplitudes were observed. Morphology changes were observed in retinal microglial cells; meanwhile, with time, the number of Iba1-positive microglia and their infiltration into the ONL gradually increased. Furthermore, physical interaction of microglial-Müller cell processes following microglial activation was observed after MNU injection. In addition, Müller cells increased CX3CL1 secretion, enhanced microglial cell migration, and upregulated the CX3CR1 expression of the latter. Our observations implied that, during the pathogenesis of RP by MNU, microglial cells exhibit a prominent morphology change and Müller cells can induce activated microglia infiltration by increasing secretion of the chemotaxis factor, CX3CL1, and promoting the migration of retinal microglial cells. This novel finding highlights a potential therapeutic target aimed at regulating the microglial response.

Microglial activation mediates chronic mild stress-induced depressive- and anxiety-like behavior in adult rats.

BACKGROUND: Depression is a heterogeneous disorder, with the exact neuronal mechanisms causing the disease yet to be discovered. Recent work suggests it is accompanied by neuro-inflammation, characterized, in particular, by microglial activation. However, microglial activation and its involvement in neuro-inflammation and stress-related depressive disorders are far from understood. METHODS: We utilized multiple detection methods to detect the neuro-inflammation in the hippocampus of rats after exposure to chronic mild stress (CMS). Male Sprague Dawley (SD) rats were subjected to chronic mild stressors for 12 weeks. Microglial activation and hippocampal neuro-inflammation were detected by using a combinatory approach of in vivo [18F] DPA-714 positron emission computed tomography (PET) imaging, ionized calcium-binding adapter molecule 1 and translocator protein (TSPO) immunohistochemistry, and detection of NOD-like receptor protein 3 (NLRP3) inflammasome and some inflammatory mediators. Then, the rats were treated with minocycline during the last 4 weeks to observe its effect on hippocampal neuro-inflammation and depressive-like behavior induced by chronic mild stress. RESULTS: The results show that 12 weeks of chronic mild stress induced remarkable depressive- and anxiety-like behavior, simultaneously causing hippocampal microglial activation detected by PET, immunofluorescence staining, and western blotting. Likewise, activation of NLRP3 inflammasome and upregulation of inflammatory mediators, such as interleukin-1ß (IL-1ß), IL-6, and IL-18, were also observed in the hippocampus after exposure to chronic stress. Interestingly, the anti-inflammatory mediators, such as IL-4 and IL-10, were also increased in the hippocampus following chronic mild stress, which may hint that chronic stress activates different types of microglia, which produce pro-inflammatory cytokines or anti-inflammatory cytokines. Furthermore, chronic minocycline treatment alleviated the depressive-like behavior induced by chronic stress and significantly inhibited microglial activation. Similarly, the activation of NLRP3 inflammasome and the increase of inflammatory mediators were not exhibited or significantly less marked in the minocycline treatment group. CONCLUSION: These results together indicate that microglial activation mediates the chronic mild stress-induced depressive- and anxiety-like behavior and hippocampal neuro-inflammation.