Peripheral Structure Research Articles

Lymphocytes Change Their Phenotype and Function in Systemic Lupus Erythematosus and Lupus Nephritis.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease, characterized by considerable changes in peripheral lymphocyte structure and function, that plays a critical role in commencing and reviving the inflammatory and immune signaling pathways. In healthy individuals, B lymphocytes have a major role in guiding and directing defense mechanisms against pathogens. Certain changes in B lymphocyte phenotype, including alterations in surface and endosomal receptors, occur in the presence of SLE and lead to dysregulation of peripheral B lymphocyte subpopulations. Functional changes are characterized by loss of self-tolerance, intra- and extrafollicular activation, and increased cytokine and autoantibody production. T lymphocytes seem to have a supporting, rather than a leading, role in the disease pathogenesis. Substantial aberrations in peripheral T lymphocyte subsets are evident, and include a reduction of cytotoxic, regulatory, and advanced differentiated subtypes, together with an increase of activated and autoreactive forms and abnormalities in follicular T cells. Up-regulated subpopulations, such as central and effector memory T cells, produce pre-inflammatory cytokines, activate B lymphocytes, and stimulate cell signaling pathways. This review explores the pivotal roles of B and T lymphocytes in the pathogenesis of SLE and Lupus Nephritis, emphasizing the multifaceted mechanisms and interactions and their phenotypic and functional dysregulations.

Airway management for right thoracoscopic tracheal tumour resection after left pneumonectomy assisted by cardiopulmonary bypass: a case report

BackgroundThe incidence of secondary tracheal tumours following lung cancer surgery is notably low. Patients with tracheal tumours typically present with symptoms such as coughing, sputum production, haemoptysis, wheezing, stridor, and dyspnoea. In cases of peripheral structure invasion, symptoms may further extend to hoarseness and dysphagia. Initial symptoms may be notably non-distinct. However, the development of pronounced airway symptoms often signifies a critical condition.Case presentationA 70-year-old male with severe chest tightness and asthma was transferred to our hospital for emergency treatment. He had undergone left pneumonectomy for non-small cell carcinoma of the left upper lobe of the lung 3 years prior. The examination confirmed that a secondary tumour originated from the left main bronchus and extended to the carina, occupying 90% of the diameter of the tracheal lumen. To relieve the patient’s emergency airway, we chose right thoracoscopic resection of the tracheal tumour assisted by cardiopulmonary bypass (CPB), which provides extracorporeal lung support and a good surgical field.ConclusionIn patients with secondary tracheal tumours after left pneumonectomy for lung cancer, perioperative airway management is challenging for anaesthesiologists, and patients’ oxygenation should receive close attention. This article describes the airway management process of this patient for reference.

Influence of process parameters on the organization and properties of 316L-SCBCC bracket formed by selective zone laser melting

Abstract 316L porous skeletal scaffolds prepared by selective laser melting (SLM) technology are currently widely used in bone injuries. Its successful implantation is predicated on having properties that match those of natural bone. The process parameters significantly influence the performance of SLM-316L porous scaffold. In this study, the nine-group shaping process parameters were determined by orthogonal method. The 316L porous scaffolds were tested in compression, electrochemistry, XRD and microstructure. The influence of process parameters on the performance of body-centered cubic peripheral square structure bracket was investigated. The influence laws of process parameters on microstructure, mechanical properties and corrosion resistance were obtained. The results show that process parameters have a significant effect on the microstructure, properties and defect distribution. The reduction of defects and grain refinement in the stent is conducive to the improvement of compressive properties and hardness of the stent. The magnitude of the hardness is inversely related to the grain size. The corrosion current density of porous scaffolds are also affected by their microscopic defects and grain size. At an energy density of 78.70 J mm−3 presents the least defects and obtains smaller grains, resulting in the best mechanical properties and corrosion resistance.

Multivariate Alexander quandles, V. Constructing the medial quandle of a link

In this paper, we explain how the medial quandle of a classical or virtual link can be built from the peripheral structure of the reduced Alexander module.

Endothelial Dysfunction in Youth-Onset Type 2 Diabetes: A Clinical Translational Study.

Youth-onset type 2 diabetes (Y-T2D) is associated with increased risk for coronary atherosclerotic disease, but the timing of the earliest pathological features and evidence of cardiac endothelial dysfunction have not been evaluated in this population. Endothelial function magnetic resonance imaging may detect early and direct endothelial dysfunction in the absence of classical risk factors (severe hyperglycemia, hypertension, and hyperlipidemia). Using endothelial function magnetic resonance imaging, we evaluated peripheral and coronary artery structure and endothelial function in young adults with Y-T2D diagnosed ≤5 years compared with age-matched healthy peers. We isolated and characterized plasma-derived small extracellular vesicles and evaluated their effects on inflammatory and signaling biomarkers in healthy human coronary artery endothelial cells to validate the imaging findings. Right coronary wall thickness, coronary artery flow-mediated dilation, and brachial artery flow-mediated dilation were measured at baseline and during isometric handgrip exercise using a 3.0T magnetic resonance imaging. Human coronary artery endothelial cells were treated with Y-T2D plasma-derived small extracellular vesicles. Protein expression was measured by Western blot analysis, oxidative stress was measured using the redox-sensitive probe dihydroethidium, and nitric oxide levels were measured by 4-amino-5-methylamino-2',7'-difluororescein diacetate. Y-T2D (n=20) had higher hemoglobin A1c and high-sensitivity C-reactive protein, but similar total and LDL (low-density lipoprotein)-cholesterol compared with healthy peers (n=16). Y-T2D had greater coronary wall thickness (1.33±0.13 versus 1.22±0.13 mm; P=0.04) and impaired endothelial function: lower coronary artery flow-mediated dilation (-3.1±15.5 versus 15.9±17.3%; P<0.01) and brachial artery flow-mediated dilation (6.7±14.7 versus 26.4±15.2%; P=0.001). Y-T2D plasma-derived small extracellular vesicles reduced phosphorylated endothelial nitric oxide synthase expression and nitric oxide levels, increased reactive oxygen species production, and elevated ICAM (intercellular adhesion molecule)-mediated inflammatory pathways in human coronary artery endothelial cells. Coronary and brachial endothelial dysfunction was evident in Y-T2D who were within 5 years of diagnosis and did not have severe hyperglycemia or dyslipidemia. Plasma-derived small extracellular vesicles induced markers of endothelial dysfunction, which corroborated accelerated subclinical coronary atherosclerosis as an early feature in Y-T2D. URL: https://www.clinicaltrials.gov; Unique identifier: NCT02830308 and NCT01399385.

Local clustering coefficient-based iterative peeling strategy to extract the core and peripheral layers of a network

We propose a novel local clustering coefficient (LCC)-based strategy to extract the peripheral layers of a complex network and identify the nodes that be part of one of these layers as well as those that would form the core of the network. The LCC of a node is the probability that any two neighbors of the node are connected. Our hypothesis is that for any given network topology, nodes with a LCC of 1.0 ideally suit to the role of peripheral nodes. We propose an iterative peeling strategy wherein we remove the nodes with a LCC of 1.0 (the LCC values of the residual nodes are recalculated after each iteration) to extract the peripheral nodes at a particular layer (starting from the outermost peripheral layer to the innermost peripheral layer) and penetrate towards the inner core. We stop the iterative peeling when all the residual nodes (left over nodes in the network after the removal of the nodes at the peripheral layers) have a degree of 0 or the LCC values of all the non-zero degree residual nodes are less than 1.0. We show that the proposed LCC-based iterative peeling strategy has the potential to envision an inner most single-layer core and a hierarchical (one or more peripheral layers) peripheral structure for scale-free networks and a single layer of peer nodes (all nodes have a LCC of less than 1.0) for random networks.

Intestinal Ultrasound in Diagnosis and Follow up of Patients with Crohn’s Disease

Abstract Background Crohn's disease (CD) causes transmural ulceration of any section of the gastrointestinal tract (GI), with the terminal ileum and colon being the most commonly affected. Aim of the Work The aim of this study is to assess the sensitivity &amp; specificity of Intestinal ultrasound In diagnosis and follow up of patients with Crohn’s Disease, and related possible complications. Patients and Methods A Cross sectional study in Gastroenterology Department of Ain Shams University Hospitals for 30 Patients with Crohn’s disease and The Patients were selected from inpatient and outpatient clinic of gastroenterology department of Ain Shams University Hospitals, in the period from July to December 2021. Results The present study revealed that the mean age of our patients was 54.3± 7.69 years with range from 38-68 years. Male cases were more than females ones, as (70%) were males while (30%) were females, with male to female ratio was 2.33: 1. The present study revealed that the mean hemoglobin level was 11.66 ± 1.46 mg/dl, and the mean RBC, 4.18±0.48. The mean platelets was 267.73±61.94 (K/UL), mean WBCs was 9.94 ± 1.83 (K/UL), neutrophils was 7648.57 ± 1460.02 (/UL), and lymphocytic count was 1356.50 ±469.30 (UL) and neutrophil/ lymphocyte ratio (NLR) was 5.93 ±1.35. Regarding the renal function tests and electrolyte profile, the mean serum urea, creatinine and uric acid were 46.43-±10.18, 1.10-±0.25 and 5.30-±0.68 mg/dl respectively. The mean levels of Na and K were 140.43 ±3.50 and 3.82±0.26 mEq/L respectively, the mean AST was 37.63 ±8.27 U/L, the mean ALT was 26.30 ±8.36 U/L, the mean total bilirubin was 1.01±0.17 mg/dl and the mean direct bilirubin was 0.60 ±0.27 mg/dl. We found that the mean PT was 14.17±2.65 sec. and the mean Serum Albumin was 4.16 ± 0.29 g/dl. In this study the mean CRP was 4.91 ±4.55, the mean ESR at first was 21.67 ±4.22 and 2nd hour was 47.43±10.94. Conclusion Crohn's disease (CD) is a progressive, inflammatory disease that occurs in genetically predisposed individuals and necessitates continuous monitoring and development of various methods for diagnostic and therapeutic treatment options, as well as the discovery of new medications. While colonoscopy is the gold standard in CD, US, CT and MRI, can provide information not only about the luminal side of the bowel but also about the serous side and the peripheral structure; additionally, US is repeatable, safe, and well-accepted, but unlike CT is radiation-free, and unlike MRI is inexpensive, virtually hazard-free, and available to all patients without contraindications.

Optimization of Blasting Parameters Considering Both Vibration Reduction and Profile Control: A Case Study in a Mountain Hard Rock Tunnel

The number of excavated tunnels is increasing day by day, and the corresponding engineering scale is also getting increasing. Safe, efficient, and economically beneficial tunnel construction methods are indispensable in the process of crossing mountains and steep ridges in the southwest region. However, behind the improvement of transportation infrastructure in Southwest China is the support provided by the rapid development of blasting industry engineering technology in China. In the process of tunnel construction using the drilling and blasting method, in addition to blasting vibration disasters the phenomenon of overbreak and underbreak caused by blasting construction is a prominent problem. This phenomenon not only affects the safety and stability of the tunnel excavation but also seriously increases the construction cost. Based on a short mountain hard rock tunnel project in southwest China, this paper studies the effect of blasting construction on the blasting vibration of adjacent structures and the influence of tunnel contour forming quality. Through the monitoring and analysis of in situ blasting vibration, the Sadowski formula is used to study the attenuation law of blasting vibration velocity in different tunnel sites, which provides a theoretical basis for tunnel blasting vibration control. This article compares the use of overbreak and underbreak value with the traditional method to determine the degree of overbreak and underbreak. It introduces the analysis of contour section fractal dimension value and uses fractal theory in the Python image processing module to accurately and quantitatively describe the problems of tunnel overbreak and underbreak. The feasibility and accuracy of this method have been verified, by combining the total station and 3D laser scanner results of overbreak and underbreak measurements of the Brenner Base Tunnel and a short hard rock tunnel in a mountainous area of southwestern China. The blasting scheme was optimized from the aspects of cut hole form, detonator interval time, and peripheral hole charge structure, and the rationality of the optimized scheme was verified according to the on-site blasting experiments. It has a profound influence on strengthening the protection of adjacent tunnel structures and improving the economic benefit of mountain highway projects.

Analysis and Reflection on the Green, Low-Carbon, and Energy-Saving Design of the Super High-Rise Building

Shanghai Tower has become a new landmark of Shanghai. In the current trend advocating green building and energy efficiency, considerations of wind loads and thermal characteristics of the perimeter structure of Shanghai Tower are crucial. This paper conducts comparative simulation studies on the wind environment of Shanghai Tower using Ecotect software, and stress analyses and thermal simulations of the perimeter structure using ANSYS software. The study compared three buildings’ surface wind pressure distributions using models with equal-volume and circular cross-sections. We found that the unique exterior design of the Shanghai Tower results in a more regular and uniform distribution of wind pressure on its surface compared to both circular and square planar models, with a lower average wind pressure value. In addition, the stress analysis results indicate significant differences in deformation and stress distribution between the windward and leeward sides. Enhancing the bending moment detection of the peripheral structure and optimizing the layout of detection points are recommended. Thermal simulation results show excessive heat conduction flux in winter conditions, suggesting optimization using passive energy-saving methods such as light-sensitive thermal insulation materials during winter. This research is a reference for designing other super-tall buildings prioritizing low-carbon energy efficiency and structural safety.

Application of friction stir surface treatment for modification of peripheral coarse grain structure and mechanical properties of AZ31 Mg alloy

The presence of peripheral coarse grains (PCG) in the microstructure of extruded products is considered one of the causes of decreased mechanical properties. Such microstructure has been observed at the periphery of extruded AZ31 Mg alloy. This research aims to achieve a refined and homogeneous microstructure at the structure of extruded bars of AZ31 alloy using pinless friction stir processing (FSP). Up to six passes of FSP using pinless tools with different shoulder surface geometries were conducted. Tools with varying diameters of 12, 15, and 22 mm were used to investigate the effect of shoulder geometry. The rotational speed and traverse speed of the tool were set at 900 rpm and 70 mm/min, respectively. The tool tilt angle was also set to 3°. The effect of the tool geometry on the metallurgical and mechanical properties was investigated using metallography tests, microhardness testing, tensile testing, and fracture testing. According to the results, it was found that reducing the diameter of the tool and using featured tool can lead to homogenization and reduction of the average grain size in the processed samples, increasing the microhardness compared to the primary sample. It was also observed that mechanical properties were improved with the increase in the tool diameter due to the improved quality of the processing area. For samples processed with a 22 mm diameter tool, the final strength reached 242.7 and 248.81 MPa, respectively, for the simple and featured tools.

FK506 contributes to peripheral nerve regeneration by inhibiting neuroinflammatory responses and promoting neuron survival.

JOURNAL/nrgr/04.03/01300535-202507000-00031/figure1/v/2024-09-09T124005Z/r/image-tiff FK506 (Tacrolimus) is a systemic immunosuppressant approved by the U.S. Food and Drug Administration. FK506 has been shown to promote peripheral nerve regeneration, however, its precise mechanism of action and its pathways remain unclear. In this study, we established a rat model of sciatic nerve injury and found that FK506 improved the morphology of the injured sciatic nerve, increased the numbers of motor and sensory neurons, reduced inflammatory responses, markedly improved the conduction function of the injured nerve, and promoted motor function recovery. These findings suggest that FK506 promotes peripheral nerve structure recovery and functional regeneration by reducing the intensity of inflammation after neuronal injury and increasing the number of surviving neurons.

Evolution of Project-Based Collaborative Networks for Implementing Prefabricated Construction Technology: Case Study in Shanghai

Prefabricated construction (PC) is considered to be a low-carbon construction method. Implementing prefabricated construction projects (PCPs) requires multiple industry organizations to participate and collaborate. As different PCPs are initiated and implemented, industry organizations will gradually gather into a complex and evolving collaborative network at the industry level based on specific collaboration relationships with different project backgrounds. The evolution of the collaborative network is related to how industry organizations interact with each other, and how PC-related knowledge and innovation has spread among organizations in the long term. However, the laws of network evolution and the micro effects that drive network evolution are still unknown. This study analyzes 236 prefabricated construction projects (PCPs) in Shanghai during 2015–2023, using the stochastic actor-oriented models (SAOM) method to explore how the macro structure of project-based inter-organizational collaborative networks for prefabricated construction (PC) technology implementation evolves over time, and how micro effects jointly support the evolution of the networks. The macro-level descriptive analysis of the network indicates that the collaborative network has become increasingly dense over time and continues to show a core–peripheral structure, with a small number of super-connected organizations. The micro-level SAOM analysis further reveals that the evolution of the collaborative network structure is driven by structure-based preferential attachment and geographic proximity effects, as well as attribute-based ownership similarity effect. This exploratory effort applies a network dynamics model to investigate the micro mechanism of the evolution of inter-organizational collaboration. The research results provide theoretical guidance and decision-making references for PC industry organizations to develop efficient network action strategies. In addition, it can help industry managers to formulate appropriate network management strategies.

Preparation of bilayer tissue-engineered polyurethane/poly-L-lactic acid nerve conduits and their in vitro characterization for use in peripheral nerve regeneration

BackgroundDue to loss of peripheral nerve structure and/or function resulting from trauma, accidents, and other causes, peripheral nerve injuries continue to be a major clinical problem. These injuries can cause partial or total loss of sensory, motor, and autonomic capabilities as well as neuropathic pain. PNI affects between 13 and 23 out of every 100,000 people annually in developed countries. Regeneration of damaged nerves and restoration of function after peripheral nerve injury remain significant therapeutic challenges. Although autologous nerve graft transplantation is a viable therapy option in several clinical conditions, donor site morbidity and a lack of donor tissue often hinder full functional recovery. Biomimetic conduits used in tissue engineering to encourage and direct peripheral nerve regeneration by providing a suitable microenvironment for nerve ingrowth are only one example of the cutting-edge methods made possible by this field. Many innate extracellular matrix (ECM) structures of different tissues can be successfully mimicked by nanofibrous scaffolds. Nanofibrous scaffolds can closely mimic the surface structure and morphology of native ECMs of many tissues.MethodsIn this study, we have produced bilayer nanofibrous nerve conduit based on poly-lactic acid/polyurethane/multiwall carbon nanotube (PLA/PU/MWCNT), for application as composite scaffolds for static nerve tissue engineering. The contact angle was indicated to show the hydrophilicity properties of electrospun nanofibers. The SEM images were analyzed to determine the fiber’s diameters, scaffold morphology, and endometrial stem cell adhesion. Moreover, MTT assay and DAPI staining were used to show the viability and proliferation of endometrial stem cells.ResultsThe constructed bilayer PLA/PU/MWCNT scaffolds demonstrated the capacity to support cell attachment, and the vitality of samples was assessed using SEM, MTT assay, and DAPI staining technique.ConclusionsAccording to an in vitro study, electrospun bilayer PLA/PU/MWCNT scaffolds can encourage the adhesion and proliferation of human endometrial stem cells (hEnSCs) and create the ideal environment for increasing cell survival.

Expert consensus on management strategies for locally advanced differentiated thyroid cancer involving the laryngeal nerve

The laryngeal nerve is the most commonly involved peripheral structure of locally advanced differentiated thyroid carcinoma, which often requires larger resection range and corresponding reconstruction, resulting in a series of complications and sequelae. Therefore, treatment strategies must not only guarantee survival benefits, but also take into account functional protection or reconstruction. Comprehensive and detailed evaluation should be conducted before surgery, and a thorough treatment plan should be made according to scientific stratification in different situations. This consensus aims at thyroid surgeons, voice physicians, anesthesiologists, rehabilitators, nurses and other groups, and standardizes the diagnosis, treatment and rehabilitation technical standards and procedures of advanced differentiated thyroid cancer involving laryngeal nerve, so as to benefit the majority of thyroid cancer patients.

Rhenium(I) and technetium(I) complexes with megazol derivatives: towards the development of a theranostic platform for Chagas disease.

The diagnosis and treatment of Chagas disease (CD) in the chronic phase remains a challenge. With that in mind, a potential theranostic device based on the trypanocidal agent known as megazol and the fac-M(CO)3+ (M = Re or 99mTc) fragment is proposed in the present work. The peripheral structure of megazol (LH,H) was modified to obtain the compounds LR1,R2 (R1 = H, R2 = Me and R1 = R2 = Me), which were used in the syntheses of complexes of composition [ReBr(CO)3LR1,R2]. These compounds were studied by elemental analysis, FTIR, UV-vis, NMR (1H and 13C), HR-ESI-MS, HPLC/UPLC and single-crystal XRD. The trypanocidal activity of the rhenium complexes was evaluated in vitro against the intracellular form of Trypanosoma cruzi. With exception of the [ReBr(CO)3LMe,Me] complex, all compounds are more active than the standard drug, benznidazole (Bzn), while [ReBr(CO)3LH,H] also exhibited a much higher selectivity index. In addition, the interaction of megazol and its ReI complex was evaluated with the T. cruzi Old Yellow Enzyme (TcOYE) by both experimental and computational methods. The data showed that megazol as well as its metal complex exhibited a higher affinity for TcOYE compared to Bzn. Finally, the labelling of megazol with 99mTc was successfully carried out. However, the results indicated that the Re complexes used as standards were not homologous with the 99mTc complexes. Despite this discrepancy, this research suggests that the investigation into Re and 99mTc complexes with megazol could lead to the development of a theranostic device for CD in a near future.

Motor fiber function in spinal muscular atrophy-analysis of conduction velocity distribution.

The motor neuron survival protein, which is deficient in spinal muscular atrophy (SMA), performs numerous cellular functions. Currently, SMA is believed to be a multi-organ disease, including lesion of various structures of the central and peripheral nervous systems. Motor nerve damage, especially in milder SMA types, is controversial. This prompted the conduct of the electrophysiological studies in adults with SMA types 2 and 3 presented in this paper. The study group consisted of 44 adult patients with SMA types 2 and 3. All patients underwent neurological examination with Hammersmith Functional Motor Scale-Expanded (HFMSE) assessment. Standard electrophysiological studies in the ulnar nerve and conduction velocity distribution (CVD) tests were performed in all patients and controls. A prolongation of the distal latency and lowering of the motor potential amplitude with no changes in CVD were found in the whole patient group. There were no dependencies on the number of gene copies. Patients with low HFSME value had slower standard conduction velocity, CVD in upper and median quartiles, and narrower CVD spread; in milder SMA, CVD spread was greater than in controls. The significant reduction in motor response amplitude in SMA seems to be primarily related to motor neuron loss and directly proportional to its severity. The coexisting rearrangement in the peripheral nerve structure is present in SMA, and this could be partially caused by a coexisting demyelinating process. Nerve remodeling mainly affects large fibers and occurs in more severe SMA types with significant disability.

Multifractal Characteristics of Smooth Blasting Overbreak in Extra-Long Hard Rock Tunnel

With the development of infrastructure construction in mountainous areas, the number of new extra-long tunnels is increasing. However, these tunnels often face the challenge of complex and variable surrounding rock grades, resulting in a large number of overbreak and underbreak due to the untimely adjustment of smooth blasting parameters. This study focuses on the optimization of the peripheral hole charging structure and blasting parameters for extra-long hard rock tunnels, aiming to improve the effectiveness of smooth blasting technology. The results of this study demonstrate a significant improvement in the effect of smooth blasting after implementing bidirectional polymerization blasting in the tunnel. A comparison between the bidirectional shaped charge and spaced decoupled charge blasting reveals that the former yields better results. To obtain accurate data on the tunnel section profile during excavation, a laser cross-section meter is used for measurement. Furthermore, this study quantitatively compares the optimization effect of smooth blasting parameters. The multifractal characteristics of the tunnel profile overbreak point sequences are analyzed under different smooth blasting schemes using the multifractal detrended fluctuation analysis (MF-DFA) method. It is found that both the spaced decoupled charge and the bidirectional shaped charge blasting exhibit multifractal features in the overbreak measurement point sequences. The calculation results of the multifractal features of the tunnel profile under different smooth blasting plans are in line with the actual situation.

From Peripheral Structure to Discourse Operator: No Veas

This work describes the cooptation/grammaticalization process developed by the expression no veas. The hypothesis it defends, endorsed by previous research, considers that in this process, this expression appears in different constructions, originally integrated in the clause or peripheral, and is involved in a process of fixation towards pragmatic markers. The parenthetical distribution is fundamental to this subjectification and constructionalizationss. In some cases, the cooptation process has not ended, and constructions can act as semi-fixed patterns. These constructions provide procedural content but, at the same time, allow lexical choice in part of their structure. In other cases, we are already dealing with fixed markers. The Spanish structure no veas can appear as a free verbal construction (“No veas tanto la televisión” (don’t watch television so much)), as a semi-free intensification construction (“no veas lo enfadado que está” (you wouldn’t believe how angry he is), “está gritando que no veas” (he’s shouting like you wouldn’t believe)), or as a discourse operator (“El campo está lleno, no veas” (the stadium’s full, unbelievable)). In the latter case, the structure appears peripheral and displays a high degree of mobility (it could be inserted at the beginning of the utterance or appear in an intermediate position, not just at the end) and functions as a modal operator of surprise (a mirative) or a comment with intensifying meaning.

Integrating plasma metabolomics and gut microbiome to reveal the mechanisms of Huangqi Guizhi Wuwu Decoction intervene diabetic peripheral neuropathy

Ethnopharmacological relevanceHuangqi Guizhi Wuwu Decoction (HGWD) is a classic traditional Chinese herbal formula from “Synopsis of Golden Chamber,” which is used to treat blood stagnation and has been used for alleviating diabetic peripheral neuropathy (DPN) in the clinic. However, the mechanisms of HGWD intervention DPN are still to be discovered. Aim of the studyThis study aims to explore the mechanism of HGWD intervention DPN by integrating plasma metabolomics and gut microbiome. Materials and methodsBKS Cg-m+/+Leprdb/J (db/db) mice with DPN were at 16 weeks of age. The indices of DPN phenotypes in db/db mice, pathomorphology of the sciatic nerve, intraepithelial nerve fibers (IENF) of the foot pad, levels of blood lipids and oxidative stress, and inflammatory reaction were used to appraise the HGWD efficacy. Finally, the pharmacological mechanisms of HGWD intervening DPN were explored by metabolomics and 16S rRNA gene sequencing. ResultsHGWD reversed DPN phenotypes in db/db mice, improved peripheral nerve structure, ameliorated the level of blood lipids and nerve growth factor in plasma, enhanced antioxidant capacity, and alleviated inflammatory responses. Plasma metabolomics disclosed that HGWD remarkably regulated the unusual levels of thirty-seven metabolites involved in sphingolipid metabolism, biosynthesis of unsaturated fatty acids, arachidonic acid metabolism, and amino acid biosynthesis pathways. The gut microbiome showed that nine bacteria were highly correlated with the efficacy of HGWD in DPN. Integrating analysis of microbiome and metabolomics demonstrated that the interaction of four bacteria with four metabolic pathways might be the significant mechanism of HGWD intervention in DPN. ConclusionsThe mediation of gut microbiota and plasma metabolism may be the potential mechanism of HGWD ameliorating DPN in db/db mice. The interaction of Lactobacillus, Alloprevotella, Bacteroides, and Desulfovibio with four metabolic pathways might be the critical mechanism for HGWD treating DPN.

Impact of inner ear malformation and cochlear nerve deficiency on the development of auditory-language network in children with profound sensorineural hearing loss.

Profound congenital sensorineural hearing loss (SNHL) prevents children from developing spoken language. Cochlear implantation and auditory brainstem implantation can provide partial hearing sensation, but language development outcomes can vary, particularly for patients with inner ear malformations and/or cochlear nerve deficiency (IEM&CND). Currently, the peripheral auditory structure is evaluated through visual inspection of clinical imaging, but this method is insufficient for surgical planning and prognosis. The central auditory pathway is also challenging to examine in vivo due to its delicate subcortical structures. Previous attempts to locate subcortical auditory nuclei using fMRI responses to sounds are not applicable to patients with profound hearing loss as no auditory brainstem responses can be detected in these individuals, making it impossible to capture corresponding blood oxygen signals in fMRI. In this study, we developed a new pipeline for mapping the auditory pathway using structural and diffusional MRI. We used a fixel-based approach to investigate the structural development of the auditory-language network for profound SNHL children with normal peripheral structure and those with IEM&CND under 6 years old. Our findings indicate that the language pathway is more sensitive to peripheral auditory condition than the central auditory pathway, highlighting the importance of early intervention for profound SNHL children to provide timely speech inputs. We also propose a comprehensive pre-surgical evaluation extending from the cochlea to the auditory-language network, showing significant correlations between age, gender, Cn.VIII median contrast value, and the language network with post-implant qualitative outcomes.