Arecoline induces dual modulation of blood pressure in rat, including an initial downregulation and a subsequent upregulation

Purpose: To determine the role of arecoline in cardiovascular modulation in rats.Methods: After rats were anaesthetized with intraperitoneal urethane (1.4 g/kg body weight), saline or arecoline (at doses of 1.0, 3.0 and 10.0 mg/kg) was intraperitoneally administered, and blood pressure (BP) was continuously recorded using a physiological apparatus. Mean arterial pressure (MAP), maximum changes in MAP and reaction time due to arecoline stimulations were calculated and analyzed.Results: Arecoline induced biphasic modulation in BP, including an initial downregulation followed by a subsequent upregulation. The MAP and maximum change in MAP exhibited a concentration-dependent effect in the downregulation phase (p < 0.001 within each group), but not in the upregulation phase (p > 0.05 within each group), while BP reaction time showed a dose-dependent prolongation in both downregulation and upregulation phases (ps < 0.01 within each group). Remarkably, arecoline-induced BP downregulation more rapidly and drastically than upregulation in each arecoline group.Conclusion: These results indicate that arecoline exerts a complex effect in cardiovascular modulation that should be considered as side effects in the clinical use of arecoline and/or with the habitual chewing of areca nuts. Keywords: Arecoline, Blood pressure, Downregulation, Upregulatio

Ultrafast and Ultralight Network-Based Intelligent System for Real-time Diagnosis of Ear diseases in Any Devices

Traditional ear disease diagnosis heavily depends on experienced specialists and specialized equipment, frequently resulting in misdiagnoses, treatment delays, and financial burdens for some patients. Utilizing deep learning models for efficient ear disease diagnosis has proven effective and affordable. However, existing research overlooked model inference speed and parameter size required for deployment. To tackle these challenges, we constructed a large-scale dataset comprising eight ear disease categories and normal ear canal samples from two hospitals. Inspired by ShuffleNetV2, we developed Best-EarNet, an ultrafast and ultralight network enabling real-time ear disease diagnosis. Best-EarNet incorporates the novel Local-Global Spatial Feature Fusion Module which can capture global and local spatial information simultaneously and guide the network to focus on crucial regions within feature maps at various levels, mitigating low accuracy issues. Moreover, our network uses multiple auxiliary classification heads for efficient parameter optimization. With 0.77M parameters, Best-EarNet achieves an average frames per second of 80 on CPU. Employing transfer learning and five-fold cross-validation with 22,581 images from Hospital-1, the model achieves an impressive 95.23% accuracy. External testing on 1,652 images from Hospital-2 validates its performance, yielding 92.14% accuracy. Compared to state-of-the-art networks, Best-EarNet establishes a new state-of-the-art (SOTA) in practical applications. Most importantly, we developed an intelligent diagnosis system called Ear Keeper, which can be deployed on common electronic devices. By manipulating a compact electronic otoscope, users can perform comprehensive scanning and diagnosis of the ear canal using real-time video. This study provides a novel paradigm for ear endoscopy and other medical endoscopic image recognition applications.Comment: This manuscript has been submitted to Neural Network

Central Nervous System Involvement in ANCA-Associated Vasculitis: What Neurologists Need to Know

Objective: To provide a comprehensive review of the central nervous system (CNS) involvement in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), including the pathogenesis, clinical manifestations, ancillary investigations, differential diagnosis, and treatment. Particular emphasis is placed on the clinical spectrum and diagnostic testing of AAV.Recent Findings: AAV is a pauci-immune small-vessel vasculitis characterized by neutrophil-mediated vasculitis and granulomatousis. Hypertrophic pachymeninges is the most frequent CNS presentation. Cerebrovascular events, hypophysitis, posterior reversible encephalopathy syndrome (PRES) or isolated mass lesions may occur as well. Spinal cord is rarely involved. In addition, ear, nose and throat (ENT), kidney and lung involvement often accompany or precede the CNS manifestations. Positive ANCA testing is highly suggestive of the diagnosis, with each ANCA serotype representing different groups of AAV patients. Pathological evidence is the gold standard but not necessary. Once diagnosed, prompt initiation of induction therapy, including steroid and other immunosuppressants, can greatly mitigate the disease progression.Conclusions and Relevance: Early recognition of AAV as the underlying cause for various CNS disorders is important for neurologists. Ancillary investigations especially the ANCA testing can provide useful information for diagnosis. Future studies are needed to better delineate the clinical spectrum of CNS involvement in AAV and the utility of ANCA serotype to classify those patients.Evidence Review: We searched Pubmed for relevant case reports, case series, original research and reviews in English published between Sep 1st, 2001 and Sep 1st, 2018. The following search terms were used alone or in various combinations: “ANCA,” “proteinase 3/PR3-ANCA,” “myeloperoxidase/MPO-ANCA,” “ANCA-associated vasculitis,” “Wegener's granulomatosis,” “microscopic polyangiitis,” “Central nervous system,” “brain” and “spinal cord”. All articles identified were full-text papers

Coexistence of Histologically Confirmed Hashimoto's Thyroiditis with Different Stages of Papillary Thyroid Carcinoma in a Consecutive Chinese Cohort

Purpose. To determine the relationship between Hashimoto's thyroiditis (HT) and all stages of papillary thyroid carcinoma (PTC) with or without local lymph node metastasis (LNM). Methods:. We conducted a retrospective study of thyroidectomies from 2008–2013 in First Affiliated Hospital of Nanjing Medical University. We categorized patients according to the presence of histopathologically proven HT. The prevalence of mPTC (maximum diameter ≤ 10 mm) and crPTC (clinical relevant PTC) and local LNM rates were compared. Results:. We evaluated 6,432 consecutive thyroidectomies. In total, 1,328 specimens were confirmed as HT. The prevalence of PTC in this HT cohort was 43.8%, significantly higher than non-HT group. After adjustment of gender and age, the prevalence of PTC was still higher in HT group. HT was a risk factor for PTC in multivariate analysis with odds ratio 2.725 (95% CI, 2.390–3.109) (P < 0.001). However, no correlation was found between HT and LNM of PTC. Conclusion:. HT was associated with an increased prevalence of all stages of PTC, independent of tumor size, gender, and age. In contrast, locally advanced disease defined by LNM was unrelated to HT. These data suggest an association of HT with low risk PTC and a potential protective immunologic effect from further disease progression

Angiopoietin-2 impairs collateral artery growth associated with the suppression of the infiltration of macrophages in mouse hindlimb ischaemia

Abstract Background Angiopoietin-2 (Ang-2), a ligand of the Tie-2 receptor, plays an important role in maintaining endothelial cells and in destabilizing blood vessels. Collateral artery growth (arteriogenesis) is a key adaptive response to arterial occlusion. It is unknown whether the destabilization of blood vessels by Ang-2 can affect arteriogenesis and modulate mononuclear cell function. This study aimed to investigate the effects of Ang-2 on collateral artery growth. Methods Hindlimb ischaemia model was produced in C57BL/6 mice by femoral artery ligation. Blood flow perfusion was measured using a laser Doppler perfusion imager quantitative RT-PCR analysis was applied to identify the level of angiogenic factors. Results After the induction of hindlimb ischaemia, blood flow recovery was impaired in mice treated with recombinant Ang-2 protein; this was accompanied by a reduction of peri-collateral macrophage infiltration. In addition, quantitative RT-PCR analysis revealed that Ang-2 treatment decreased monocyte chemotactic protein-1 (MCP-1), platelet-derived growth factor-BB (PDGF-BB) mRNA levels in ischaemic adductor muscles. Ang-2 can lead to macrophage M1/M2 polarization shift inhibition in the ischaemic muscles. Furthermore, Ang-2 reduced the in vitro inflammatory response in macrophages and vascular cells involved in arteriogenesis. Conclusions Our results demonstrate that Ang-2 is essential for efficient arteriogenesis, which controls macrophage infiltration

Clinical features and therapeutic outcomes of GH/TSH cosecreting pituitary adenomas: experience of a single pituitary center

BackgroundGrowth hormone (GH)/thyroid stimulating hormone (TSH) cosecreting pituitary adenoma (PA) is an exceedingly rare kind of bihormonal pituitary neuroendocrine tumors (PitNETs). Its clinical characteristics have rarely been reported.ObjectivesThis study aimed to summarize the clinical characteristics and experience of diagnosis and treatment among patients with mixed GH/TSH PAs from a single center.MethodsWe retrospectively reviewed GH/TSH cosecreting PAs from 2063 patients diagnosed with GH-secreting PAs admitted to Peking Union Medical College Hospital between January 1st, 2010, and August 30th, 2022, to investigate the clinical characteristics, hormone detection, imaging findings, treatment patterns and outcomes of follow-up. We further compared these mixed adenomas with age- and sex-matched cases of GH mono-secreting PAs (GHPAs). The data of the included subjects were collected using electronic records from the hospital’s information system.ResultsBased on the inclusion and exclusion criteria, 21 GH/TSH cosecreting PAs were included. The average age of symptom onset was 41.6 ± 14.9 years old, and delayed diagnosis occurred in 57.1% (12/21) of patients. Thyrotoxicosis was the most common complaint (10/21, 47.6%). The median inhibition rates of GH and TSH in octreotide suppression tests were 79.1% [68.8%, 82.0%] and 94.7% [88.2%, 97.0%], respectively. All these mixed PAs were macroadenomas, and 23.8% (5/21) of them were giant adenomas. Comprehensive treatment strategies comprised of two or more therapy methods were applied in 66.7% (14/21) of patients. Complete remission of both GH and TSH was accomplished in one-third of cases. In the comparison with the matched GHPA subjects, the mixed GH/TSH group presented with a higher maximum diameter of the tumor (24.0 [15.0, 36.0] mm vs. 14.7 [10.8, 23.0] mm, P = 0.005), a greater incidence of cavernous sinus invasion (57.1% vs. 23.8%, P = 0.009) and a greater difficulty of long-term remission (28.6% vs. 71.4%, P &lt;0.001). In addition, higher occurrence rates of arrhythmia (28.6% vs. 2.4%, P = 0.004), heart enlargement (33.3% vs. 4.8%, P = 0.005) and osteopenia/osteoporosis (33.3% vs. 2.4%, P = 0.001) were observed in the mixed PA group.ConclusionThere are great challenges in the treatment and management of GH/TSH cosecreting PA. Early diagnosis, multidisciplinary therapy and careful follow-up are required to improve the prognosis of this bihormonal PA

Vitronectin Increases Vascular Permeability by Promoting VE-Cadherin Internalization at Cell Junctions

Cross-talk between integrins and cadherins regulates cell function. We tested the hypothesis that vitronectin (VN), a multi-functional adhesion molecule present in the extracellular matrix and plasma, regulates vascular permeability via effects on VE-cadherin, a critical regulator of endothelial cell (EC) adhesion.Addition of multimeric VN (mult VN) significantly increased VE-cadherin internalization in human umbilical vein EC (HUVEC) monolayers. This effect was blocked by the anti-α(V)β(3) antibody, pharmacological inhibition and knockdown of Src kinase. In contrast to mult VN, monomeric VN did not trigger VE-cadherin internalization. In a modified Miles assay, VN deficiency impaired vascular endothelial growth factor-induced permeability. Furthermore, ischemia-induced enhancement of vascular permeability, expressed as the ratio of FITC-dextran leakage from the circulation into the ischemic and non-ischemic hindlimb muscle, was significantly greater in the WT mice than in the Vn(-/-) mice. Similarly, ischemia-mediated macrophage infiltration was significantly reduced in the Vn(-/-) mice vs. the WT controls. We evaluated changes in the multimerization of VN in ischemic tissue in a mouse hindlimb ischemia model. VN plays a previously unrecognized role in regulating endothelial permeability via conformational- and integrin-dependent effects on VE-cadherin trafficking.These results have important implications for the regulation of endothelial function and angiogenesis by VN under normal and pathological conditions