Surgical Treatment of Multiple Large Tuberous and Tendinous Xanthoma Secondary to Familial Hypercholesterolaemia: A Case Report.

Xanthomas are well-circumscribed skin lesions that are commonly seen in patients with familial hypercholesterolemia (FH). The aim of this report is to present a rare case of multiple large tuberous and tendinous xanthomas. A 17-year-old female patient in this report presented with multiple asymptomatic and papulo-nodular masses in both sides of palms, elbows, buttocks, knees, and Achilles tendons. Surgical removal of the masses was carried out in combination with lipid-lowering therapy. A following up of 3 months showed all wounds were healing well, and no recurrence of masses was observed. Therefore, for patients with xanthomas related with familial hypercholesterolaemia, lipid-lowering therapy has reportedly reduced the size of masses, but surgical treatment may be essential for large xanthomas caused pain or limitation of daily activities.

Case report: acute isolated cilioretinal artery occlusion secondary to percutaneous coronary intervention.

INTRODUCTION: This case report aims to describe in detail the acute isolated cilioretinal artery occlusion (CLRAO) secondary to complicated therapeutic percutaneous coronary intervention (PCI). CASE DESCRIPTION: A 68-year-old Chinese man with coronary artery disease (CAD) complained of sudden, sharp chest pain. Coronary angiography revealed severe stenoses of the coronary arteries. The patient was then treated with PCI. One hour after the procedure, the patient presented with a sudden reduction in vision in the right eye. The patient was diagnosed with acute isolated CLRAO and treated with Salvia miltiorrhiza injections. CONCLUSIONS: This is the report to provide a detailed description of acute isolated CLRAO secondary to therapeutic PCI treated with Salvia miltiorrhiza. The visual prognosis of the untreated patients is poor. Suitable management and prevention are essential for interventional cardiologists to prevent these complications.

Nrf2 regulates iron-dependent hippocampal synapses and functional connectivity damage in depression.

Neuronal iron overload contributes to synaptic damage and neuropsychiatric disorders. However, the molecular mechanisms underlying iron deposition in depression remain largely unexplored. Our study aims to investigate how nuclear factor-erythroid 2 (NF-E2)-related factor 2 (Nrf2) ameliorates hippocampal synaptic dysfunction and reduces brain functional connectivity (FC) associated with excessive iron in depression. We treated mice with chronic unpredictable mild stress (CUMS) with the iron chelator deferoxamine mesylate (DFOM) and a high-iron diet (2.5% carbonyl iron) to examine the role of iron overload in synaptic plasticity. The involvement of Nrf2 in iron metabolism and brain function was assessed using molecular biological techniques and in vivo resting-state functional magnetic resonance imaging (rs-fMRI) through genetic deletion or pharmacologic activation of Nrf2. The results demonstrated a significant correlation between elevated serum iron levels and impaired hippocampal functional connectivity (FC), which contributed to the development of depression-induced CUMS. Iron overload plays a crucial role in CUMS-induced depression and synaptic dysfunction, as evidenced by the therapeutic effects of a high-iron diet and DFOM. The observed iron overload in this study was associated with decreased Nrf2 levels and increased expression of transferrin receptors (TfR). Notably, inhibition of iron accumulation effectively attenuated CUMS-induced synaptic damage mediated by downregulation of brain-derived neurotrophic factor (BDNF). Nrf2-/- mice exhibited compromised FC within the limbic system and the basal ganglia, particularly in the hippocampus, and inhibition of iron accumulation effectively attenuated CUMS-induced synaptic damage mediated by downregulation of brain-derived neurotrophic factor (BDNF). Activation of Nrf2 restored iron homeostasis and reversed vulnerability to depression. Mechanistically, we further identified that Nrf2 deletion promoted iron overload via upregulation of TfR and downregulation of ferritin light chain (FtL), leading to BDNF-mediated synapse damage in the hippocampus. Therefore, our findings unveil a novel role for Nrf2 in regulating iron homeostasis while providing mechanistic insights into poststress susceptibility to depression. Targeting Nrf2-mediated iron metabolism may offer promising strategies for developing more effective antidepressant therapies.

Direct observation of topological magnon polarons in a multiferroic material.

Magnon polarons are novel elementary excitations possessing hybrid magnonic and phononic signatures, and are responsible for many exotic spintronic and magnonic phenomena. Despite long-term sustained experimental efforts in chasing for magnon polarons, direct spectroscopic evidence of their existence is hardly observed. Here, we report the direct observation of magnon polarons using neutron spectroscopy on a multiferroic Fe2Mo3O8 possessing strong magnon-phonon coupling. Specifically, below the magnetic ordering temperature, a gap opens at the nominal intersection of the original magnon and phonon bands, leading to two separated magnon-polaron bands. Each of the bands undergoes mixing, interconverting and reversing between its magnonic and phononic components. We attribute the formation of magnon polarons to the strong magnon-phonon coupling induced by Dzyaloshinskii-Moriya interaction. Intriguingly, we find that the band-inverted magnon polarons are topologically nontrivial. These results uncover exotic elementary excitations arising from the magnon-phonon coupling, and offer a new route to topological states by considering hybridizations between different types of fundamental excitations.

Inducing itinerant ferromagnetism by manipulating van Hove singularity in epitaxial monolayer 1T-VSe2.

The itinerant ferromagnetism can be induced by a van Hove singularity (VHS) with a divergent density of states at Fermi level. Utilizing the giant magnified dielectric constant εr of SrTiO3(111) substrate with cooling, here we successfully manipulated the VHS in the epitaxial monolayer (ML) 1T-VSe2 film approaching to Fermi level via the large interfacial charge transfer, and thus induced a two-dimensional (2D) itinerant ferromagnetic state below 3.3 K. Combining the direct characterization of the VHS structure via angle-resolved photoemission spectroscopy (ARPES), together with the theoretical analysis, we ascribe the manipulation of VHS to the physical origin of the itinerant ferromagnetic state in ML 1T-VSe2. Therefore, we further demonstrated that the ferromagnetic state in the 2D system can be controlled through manipulating the VHS by engineering the film thickness or replacing the substrate. Our findings clearly evidence that the VHS can serve as an effective manipulating degree of freedom for the itinerant ferromagnetic state, expanding the application potentials of 2D magnets for the next-generation information technology.

Experiences of nurses working in nurse-led clinics in Traditional Chinese Medicine hospitals: A focused ethnographic study.

BACKGROUND: Traditional Chinese Medicine (TCM) nurse-led clinics (NLC) is an innovative working model in China, representing the specialization and extension of nurses' role. However, as a pioneer in TCM nursing, this new model of working is facing both opportunities and challenges because it is known little about the operational status of NLCs. AIMS: To explore the experiences of nurses who work in NLC in TCM hospitals. MATERIALS & METHODS: A focused ethnographic study was conducted in three TCM hospitals affiliated with Guangzhou University of Chinese Medicine. We interviewed eleven nurses in those hospitals and observed seven of them working with patients. We used snowball sampling for data collection including interview, non-participant observation and documents from medical records. All the data were processed as following steps: (a) coding for descriptive labels; (b) sorting for patterns; (c) identifying outliers or negative cases; (d) generalizing with construction and theories and (e) noting reflective remarks. RESULTS: Nurse-led clinics help nurses develop their skills and knowledge that are highly recognized by public since they meet the growing needs of patients and also relieve the workload of physicians in the hospitals. However, lack of specialization is still a major challenge in NLCs due to insufficiency of full-time staff with specialized education, nurse-led practice without standardized guidelines, restrictions on prescription right of nurses, and also inadequate support from hospitals. DISCUSSIONS: As a revolutionary innovation of working model for nurses in TCM hospitals, NLCs could improve quality of care and lead to a comprehensive promotion of nursing career. However, there are several challenges on providing high quality care for patients whilst improving educational development of nurses. This study suggests that nurses, hospital administration and the government should cooperate with each other to develop standard nursing programs for NLCs. CONCLUSIONS: It is imperative to identify nursing roles, collect available resources, and develop supportive policies and training programs to enhance the quality of NLCs.

Corrigendum: Xiaoyaosan exerts antidepressant effect by downregulating RAGE expression in cingulate gyrus of depressive-like mice.

[This corrects the article DOI: 10.3389/fphar.2021.703965.].

Rapid Sensor Fault Diagnosis for a Class of Nonlinear Systems via Deterministic Learning.

In this article, a rapid sensor fault diagnosis (SFD) method is presented for a class of nonlinear systems. First, by exploiting the linear adaptive observer technology and the deterministic learning method (DLM), an adaptive neural network (NN) observer is constructed to capture the information of the unknown sensor fault function. Second, when the NN input orbit is a period or recurrent one, the partial persistent excitation (PE) condition of the NNs can be guaranteed through the DLM. Based on the partial PE condition and the uniformly completely observable property of a linear time-varying system, the accurate state estimation and the sensor fault identification can be achieved by properly choosing the observer gain. Third, a bank of dynamical observers utilizing the experiential knowledge is constructed to achieve rapid SFD and data recovery. The attractions of the proposed approach are that accurate approximations of sensor faults can be achieved through the DLM, and the data that are destroyed by the sensor faults can be recovered by using the learning results. Simulation studies of a robot system are utilized to show the effectiveness of the proposed method.

Combined rs-fMRI study on brain functional imaging and mechanism of RAGE-DAMPs of depression: Evidence from MDD patients to chronic stress-induced depression models in cynomolgus monkeys and mice.

More and more evidence show that major depressive disorder (MDD) is closely related to inflammation caused by chronic stress, which seriously affects human physical and mental health. However, the inflammatory mechanism of depression and its effect on brain function have not been clarified. Based on resting-state functional magnetic resonance imaging (rs-fMRI), we investigated change of brain functional imaging and the inflammatory mechanism of damage-related molecular patterns (DAMPs)-receptor of advanced glycation protein end product (RAGE) in MDD patients and depressive-like cynomolgus monkeys and mice models induced by chronic stress. The regional homogeneity (ReHo) and functional connectivity (FC) were analyzed using MATLAB and SPM12 software. We detected the expression of DAMPs-RAGE pathway-related proteins and mRNA in MDD peripheral blood and in serum and brain tissue of cynomolgus monkeys and mice. Meanwhile, RAGE gene knockout mice, RAGE inhibitor, and overexpression of AVV9RAGE adeno-associated virus were used to verify that RAGE is a reliable potential biomarker of depression. The results showed that the ReHo value of prefrontal cortex (PFC) in MDD patients and depressive-like cynomolgus monkeys was decreased. Then, the PFC was used as a seed point, the FC of ipsilateral and contralateral PFC were weakened in depressive-like mice. At the same time, qPCR showed that RAGE and HMGB1 mRNA were upregulated and S100ß mRNA was downregulated. The expression of RAGE-related inflammatory protein in PFC of depressive-like monkeys and mice were consistent with that in peripheral blood of MDD patients. Moreover, the results were confirmed in RAGE-/- mice, injection of FPS-ZM1, and overexpression of AAV9RAGE in mice. To sum up, our findings enhance the evidence that chronic stress-PFC-RAGE are associated with depression. These results attempt to establish the links between brain functional imaging, and molecular targets among different species will help to reveal the pathophysiological mechanism of depression from multiple perspectives.

Xiaoyaosan Exerts Antidepressant Effect by Downregulating RAGE Expression in Cingulate Gyrus of Depressive-Like Mice.

Xiaoyaosan (XYS), as a classic Chinese medicine compound, has been proven to have antidepressant effect in many studies, but its mechanism has not been clarified. In our previous studies, we found that chronic stress can induce depressive-like behavior and lead to emotion-related cingulate gyrus (Cg) dysfunction, as well as the decrease of neurotrophic factors and the increase of inflammatory-related proteins. Therefore, we speculated that XYS may play an antidepressant role by regulating the inflammation-related receptor of advanced glycation protein end product (RAGE) to affect the functional connectivity (FC) signal of the Cg and improve the depressive-like behavior. In order to verify this hypothesis, we analyzed the FC and RAGE expression in the Cg of depressive-like mice induced by chronic unpredictable mild stress (CUMS) and verified it with RAGE knockout mice. At the same time, we detected the effect of XYS on the depressive-like behavior, expression of RAGE, and the FC of the Cg of mice. The results showed that the FC of the Cg of depressive-like mice induced by CUMS was weakened, and the expression of RAGE was upregulated. The antidepressant effect of XYS is similar to that of fluoxetine hydrochloride, which can significantly reduce the depressive-like behavior of mice and inhibit the expression of the RAGE protein and mRNA in the Cg, and increase the FC of the Cg in mice. In conclusion, XYS may play an antidepressant role by downregulating the expression of RAGE in the Cg of depressive-like mice induced by CUMS, thereby affecting the functional signal and improving the depressive-like behavior.

Blockade of Indoleamine 2, 3-dioxygenase 1 ameliorates hippocampal neurogenesis and BOLD-fMRI signals in chronic stress precipitated depression.

Indoleamine 2, 3-dioxygenase 1 (IDO1) has been implicated in the pathogenesis of depression, though its molecular mechanism is still poorly understood. We investigated the molecular mechanism of IDO1 in depression by using the chronic unpredictable mild stress (CUMS) model in Ido1-/- mice and WT mice. The brain blood oxygen level dependent (BOLD) signals in mice were collected by functional magnetic resonance imaging (fMRI) technology. IDO1 inhibitor INCB024360 was intervened in dorsal raphe nucleus (DRN) through stereotactic injection. We found an elevation of serum IDO1 activity and decreased 5-HT in CUMS mice, and the serum IDO1 activity was negatively correlated with 5-HT level. Consistently, IDO1 was increased in hippocampus and DRN regions, accompanied by a reduction of hippocampal BDNF levels in mice with CUMS. Specifically, pharmacological inhibition of IDO1 activity in the DRN alleviated depressive-like behaviour with improving hippocampal BDNF expression and neurogenesis in CUMS mice. Furthermore, ablation of Ido1 exerted stress resistance and decreased the sensitivity of depression in CUMS mice with the stable BOLD signals, BDNF expression and neurogenesis in hippocampus. Thus, IDO1 hyperactivity played crucial roles in modulating 5-HT metabolism and BDNF function thereby impacting outcomes of hippocampal neurogenesis and BOLD signals in depressive disorder.

Expert Consensus on Clinical Practice of Burn Units in Shanghai During the COVID-19 Epidemic.

In response to coronavirus disease 2019 (COVID-19), the Shanghai Burn Clinical Quality Control Center organized experts to formulate and implement a set of rapid, simple, and effective prevention and control measures, and there have not been any cases of health care professionals or inpatients in burn units suspected or confirmed with COVID-19. This article elaborates on the specific measures in burn units in response to the epidemic, including the implementation of standardized procedures, remote consultations, strengthened follow-up, exchange of experience, and popular science, among others. We share experience from Shanghai to benefit related disciplines in other countries and regions.

Pathophysiological regulation of lung function by the free fatty acid receptor FFA4.

Increased prevalence of inflammatory airway diseases including asthma and chronic obstructive pulmonary disease (COPD) together with inadequate disease control by current frontline treatments means that there is a need to define therapeutic targets for these conditions. Here, we investigate a member of the G protein-coupled receptor family, FFA4, that responds to free circulating fatty acids including dietary omega-3 fatty acids found in fish oils. We show that FFA4, although usually associated with metabolic responses linked with food intake, is expressed in the lung where it is coupled to Gq/11 signaling. Activation of FFA4 by drug-like agonists produced relaxation of murine airway smooth muscle mediated at least in part by the release of the prostaglandin E2 (PGE2) that subsequently acts on EP2 prostanoid receptors. In normal mice, activation of FFA4 resulted in a decrease in lung resistance. In acute and chronic ozone models of pollution-mediated inflammation and house dust mite and cigarette smoke-induced inflammatory disease, FFA4 agonists acted to reduce airway resistance, a response that was absent in mice lacking expression of FFA4. The expression profile of FFA4 in human lung was similar to that observed in mice, and the response to FFA4/FFA1 agonists similarly mediated human airway smooth muscle relaxation ex vivo. Our study provides evidence that pharmacological targeting of lung FFA4, and possibly combined activation of FFA4 and FFA1, has in vivo efficacy and might have therapeutic value in the treatment of bronchoconstriction associated with inflammatory airway diseases such as asthma and COPD.

Early-Life Stress Induces Depression-Like Behavior and Synaptic-Plasticity Changes in a Maternal Separation Rat Model: Gender Difference and Metabolomics Study.

More than 300 million people suffer from depressive disorders globally. People under early-life stress (ELS) are reportedly vulnerable to depression in their adulthood, and synaptic plasticity can be the molecular mechanism underlying such depression. Herein, we simulated ELS by using a maternal separation (MS) model and evaluated the behavior of Sprague-Dawley (SD) rats in adulthood through behavioral examination, including sucrose preference, forced swimming, and open-field tests. The behavior tests showed that SD rats in the MS group were more susceptible to depression- and anxiety-like behaviors than did the non-MS (NMS) group. Nissl staining analysis indicated a significant reduction in the number of neurons at the prefrontal cortex and hippocampus, including the CA1, CA2, CA3, and DG regions of SD rats in the MS group. Immunohistochemistry results showed that the percentages of synaptophysin-positive area in the prefrontal cortex and hippocampus (including the CA1, CA2, CA3, and DG regions) slice of the MS group significantly decreased compared with those of the NMS group. Western blot analysis was used to assess synaptic-plasticity protein markers, including postsynaptic density 95, synaptophysin, and growth-associated binding protein 43 protein expression in the cortex and hippocampus. Results showed that the expression levels of these three proteins in the MS group were significantly lower than those in the NMS group. LC-MS/MS analysis revealed no significant differences in the peak areas of sex hormones and their metabolites, including estradiol, testosterone, androstenedione, estrone, estriol, and 5ß-dihydrotestosterone. Through the application of nontargeted metabolomics to the overall analysis of differential metabolites, pathway-enrichment results showed the importance of arginine and proline metabolism; pantothenate and CoA biosyntheses; glutathione metabolism; and the phenylalanine, tyrosine, and tryptophan biosynthesis pathways. In summary, the MS model caused adult SD rats to be susceptible to depression, which may regulate synaptic plasticity through arginine and proline metabolism; pantothenate and CoA biosyntheses; glutathione metabolism; and phenylalanine, tyrosine, and tryptophan biosyntheses.

Physical exercise rectifies CUMS-induced aberrant regional homogeneity in mice accompanied by the adjustment of skeletal muscle PGC-1a/IDO1 signals and hippocampal function.

BACKGROUND: Depression is a debilitating condition with a profound influence on quality of life for millions of people globally. Physical exercise has been broadly recognized for its therapeutic effects on depression, but the mechanisms that underlie its benefits remain unknown. In the study, we investigated whether the physical exercise of could be a protection from stress-induced depression and its impact on the brain activity of Regional Homogeneity (ReHo) in mice. METHODS: Adult male C57BL/6 mice were assigned to one of the following groups: control group; exercise group, 2 h/day in a running wheel apparatus; chronic unpredictable mild stress (CUMS) group; CUMS + exercise group. rs-fMRI was applied to detect the changes of regional spontaneous activity. RESULTS: Firstly, CUMS-induced depressive behavior was significantly reduced by exercise. Base on the ReHo analysis, disorders of the regional spontaneous activity in the brain of CUMS mice, primarily in the limbic system, especially in the hippocampus and PFC, motor cortex, sensory cortex, visual cortex were found. While exercise remarkably prevented the CUMS-induced chaos of brain activity in parts of the above regions, such as cortex, hippocampus and corpus callosum. These results suggested physical exercise could prevent the dysfunction of mood-regulating circuit in CUMS model. Furthermore, exercise improved skeletal muscle PGC-1a and hippocampal BDNF levels in stress mice, and reduced IDO1 in skeletal muscle. CONCLUSIONS: These results suggested that exercise prevented CUMS induced depressive behaviors and brain regional spontaneous activity in mice, accompanied with the adjustment of skeletal muscle PGC-1a/IDO1 signals and hippocampal function.

SiNiSan ameliorates depression-like behavior in rats by enhancing synaptic plasticity via the CaSR-PKC-ERK signaling pathway.

BACKGROUND: Adverse stress in early life negatively influences psychiatric health by increasing the risk of developing depression and suicide in adulthood. Clinical antidepressants, such as fluoxetine, exhibit unsatisfactory results due to their low efficacy or intolerable side effects. SiNiSan (SNS), a traditional Chinese herbal formula, has been proven to have affirmatory antidepressive effects. However, the underlying mechanism remains poorly understood. Therefore, this study aimed to explore the impact and molecular mechanism of SNS treatment in rats exposed to neonatal maternal separation (MS)-combined young-adult chronic unpredictable mild stress (CUMS). METHOD: Seventy-two neonatal male Sprague-Dawley rats were randomly divided into six groups of 12 rats each: control + ddH2O, model + ddH2O, positive (fluoxetine: 5 mg/kg), SNS-low dose (2.5 g/kg), SNS-medium dose (5 g/kg), and SNS-high dose (10 g/kg). Behavioral tests included sucrose preference test, open-field test, and forced swimming test. Calcium sensitive receptor (CaSR), protein kinase C (PKC), ERK1/2, and synapse-associated proteins (PSD-95, GAP-43, and synaptophysin [Syn]) in the hippocampus (HIP) and prefrontal cortex (PFC) were assayed using Western blot. CaSR and Syn protein expression was measured by immunohistochemistry. RESULTS: MS-combined CUMS rats exhibited depression-like behavior. SNS exerted antidepressant effects on stress-induced depression-like behavior. The levels of CaSR, PKC, and p-ERK1/2 in the HIP and PFC decreased in stressed rats. SNS treatment significantly upregulated the expression of CaSR, PKC, and p-ERK1/2 in the HIP and PFC of adult stressed rats. CONCLUSION: MS-combined CUMS could develop depression-like behavior in adult. SNS exhibited antidepressive effects accompanied by improving synaptic plasticity by activation of the CaSR-PKC-ERK signaling pathway.

Guide Subspace Learning for Unsupervised Domain Adaptation.

A prevailing problem in many machine learning tasks is that the training (i.e., source domain) and test data (i.e., target domain) have different distribution [i.e., non-independent identical distribution (i.i.d.)]. Unsupervised domain adaptation (UDA) was proposed to learn the unlabeled target data by leveraging the labeled source data. In this article, we propose a guide subspace learning (GSL) method for UDA, in which an invariant, discriminative, and domain-agnostic subspace is learned by three guidance terms through a two-stage progressive training strategy. First, the subspace-guided term reduces the discrepancy between the domains by moving the source closer to the target subspace. Second, the data-guided term uses the coupled projections to map both domains to a unified subspace, where each target sample can be represented by the source samples with a low-rank coefficient matrix that can preserve the global structure of data. In this way, the data from both domains can be well interlaced and the domain-invariant features can be obtained. Third, for improving the discrimination of the subspaces, the label-guided term is constructed for prediction based on source labels and pseudo-target labels. To further improve the model tolerance to label noise, a label relaxation matrix is introduced. For the solver, a two-stage learning strategy with teacher teaches and student feedbacks mode is proposed to obtain the discriminative domain-agnostic subspace. In addition, for handling nonlinear domain shift, a nonlinear GSL (NGSL) framework is formulated with kernel embedding, such that the unified subspace is imposed with nonlinearity. Experiments on various cross-domain visual benchmark databases show that our methods outperform many state-of-the-art UDA methods. The source code is available at https://github.com/Fjr9516/GSL.