Expression of NMU and NMUR1 in tryptase-positive mast cells and PBLs in allergic rhinitis patients' nasal mucosa.

BACKGROUND: The neuropeptide U (NMU) has been proven to elicit the release of mediators from mast cells (MCs) through its receptor NMUR1 in allergic inflammatory models. However, little is known about the correlations between NMU and MCs in human allergic rhinitis (AR). OBJECTIVE: The objective of this study is to investigate the expressions of NMU and NMUR1 in the tryptase + MCs and the peripheral blood leukocytes (PBLs) in human nasal mucosa with AR. METHODS: Specimens of nasal mucosa from patients with AR (n = 10) and control patients without AR (n = 8) were collected and soaked in frozen tissue liquid solution (OCT) in tum. Cryostat sections were prepared for immunofluorescence staining. Tryptase was used as a marker to detect mast cells and other tryptase + immune cells. The expression of NMU and NMUR1 was respectively determined by double staining using a confocal microscope. RESULTS: Neither NMU nor NMUR1 were detected in the tryptase + mast cells in the human nasal mucosa. To our surprise, both NMU and NMUR1 were co-expressed with tryptase in the PBLs within peripheral blood vessels in AR and controls. CONCLUSION: Our findings showed that NMU could not influence human nasal tryptase + mast cells directly through NMUR1 in AR. The co-expression of both NMU and NMUR1 with tryptase in the PBLs provided new insight into the potential roles of NMU and tryptase in the circulation PBLs, and the infiltrated PBLs may promote nasal allergic inflammation by producing tryptase and NMU.

Explainable Learning-Based Timeout Optimization for Accurate and Efficient Elephant Flow Prediction in SDNs.

Accurately and efficiently predicting elephant flows (elephants) is crucial for optimizing network performance and resource utilization. Current prediction approaches for software-defined networks (SDNs) typically rely on complete traffic and statistics moving from switches to controllers. This leads to an extra control channel bandwidth occupation and network delay. To address this issue, this paper proposes a prediction strategy based on incomplete traffic that is sampled by the timeouts for the installation or reactivation of flow entries. The strategy involves assigning a very short hard timeout (Tinitial) to flow entries and then increasing it at a rate of r until flows are identified as elephants or out of their lifespans. Predicted elephants are switched to an idle timeout of 5 s. Logistic regression is used to model elephants based on a complete dataset. Bayesian optimization is then used to tune the trained model Tinitial and r over the incomplete dataset. The process of feature selection, model learning, and optimization is explained. An extensive evaluation shows that the proposed approach can achieve over 90% generalization accuracy over 7 different datasets, including campus, backbone, and the Internet of Things (IoT). Elephants can be correctly predicted for about half of their lifetime. The proposed approach can significantly reduce the controller-switch interaction in campus and IoT networks, although packet completion approaches may need to be applied in networks with a short mean packet inter-arrival time.

Favorable cervical extension capacity preventing loss of cervical lordosis after laminoplasty due to spontaneous restoration of initial lordosis.

BACKGROUND CONTEXT: Cervical laminoplasty is a common approach for the treatment of multilevel cervical spondylotic myelopathy (CSM). Postoperative loss of cervical lordosis (LCL) was associated with lower extension motion of the cervical spine before laminoplasty. PURPOSE: To analyze the possible causes of preoperative cervical extension capacity affecting LCL after laminoplasty by evaluating the changes in cervical lordosis (CL) at different stages. STUDY DESIGN/SETTING: Retrospective study. PATIENT SAMPLE: Seventy-two patients undergoing laminoplasty due to multilevel CSM. OUTCOME MEASURES: Radiographic parameters included CL, extension CL (eCL), flexion CL (fCL), range of motion (ROM), extension ROM (eROM), flexion ROM (fROM) and LCL. Clinical outcomes were assessed using the Japanese Orthopedic Association (JOA) and neck disability index (NDI) score. METHODS: The data were recorded before surgery and at 3- and 24-month follow-up. All patients completed a cervical extension test preoperatively. A receiver operating characteristic (ROC) curve of eROM was constructed to discriminate the patients with and without postoperative kyphotic deformity. RESULTS: According to the optimal cut-off value of eROM, the patients were divided into two groups: extension group (eROM≥9.3°) and control group (eROM<9.3°). The radiographic outcomes demonstrated no significant differences in CL, eCL, fCL and ROM between the two groups. Both eROM and fROM were significantly different in the two groups. There was a significant change in CL in the extension group at 3-month follow-up and in the control group at 24-month follow-up. The extension group exhibited significantly lower LCL compared with the control group at follow-up. No significant difference between the two groups was noted in the JOA recovery rate, while the NDI score was significantly different at 24-month follow-up. The positivity ratio of the extension test was significantly greater in the extension group than that in the control group. CONCLUSIONS: eROM in patients with favorable preoperative cervical extension capacity (eROM≥9.3°) consisted of the actual extension capacity and compensatory flexion. The cervical alignment would be spontaneously restored to its initial lordosis in the short term after laminoplasty. These patients had no substantial LCL at 24-month follow-up and would be good candidates for laminoplasty.

[CGRP inhibits proliferation, activation and cytokine secretion of group 2 innate lymphoid cells (ILC2) in peripheral blood from patients with allergic rhinitis].

Objective To investigate the effect of calcitonin gene-related peptide (CGRP) on the regulation of group 2 innate lymphoid cells (ILC2) in the peripheral blood of patients with allergic rhinitis (AR). Methods Peripheral blood mononuclear cells (PBMCs) were extracted from normal healthy individuals and AR patients, then stimulated with CGRP, interleukin 33 (IL-33) and CGRP combined with IL-33 for 3 days, with blank stimulus as control. The percentage of ILC2 in the four groups was measured by flow cytometry. After being sorted, ILC2 was given to CGRP, IL-33 and CGRP combined with IL-33 stimulation for 3 days, with blank stimulus as control. The percentage of IL-5 and IL-13 positive cells in ILC2 was detected by flow cytometry, and the levels of IL-5 and IL-13 in ILC2 supernatant were measured by ELISA. Results The percentage of ILC2 in the peripheral blood of AR patients was significantly higher than that of the control group. The levels of IL-5+ILC2 and IL-13+ILC2 were significantly increased by IL-33 single stimulation after culturing PBMCs. After adding IL-33 combined with CGRP stimulation, the levels of IL-5+ILC2 and IL-13+ILC2 in PBMCs were significantly reduced; after CGRP single stimulation, the levels of IL-5+ILC2 and IL-13+ILC2 in PBMCs were further decreased. After ILC2 was sorted and cultured, the levels of IL-5+ILC2 and IL-13+ILC2 showed significant increase after IL-33 single stimulation. The levels of IL-5+ILC2 and IL-13+ILC2 were decreased by IL-33 and CGRP co-stimulation, and they were further reduced after CGRP single stimulation. Compared to IL-33 single stimulation, IL-5 and IL-13 levels dropped significantly due to the IL-33 and CGRP co-stimulation. The levels of IL-5 and IL-13 were further reduced by CGRP single stimulation. Conclusion CGRP inhibits the proliferation and activation of peripheral blood ILC2 in AR and exert anti-inflammatory effects in AR.

The effect of different sterilization methods on the shelf life and physicochemical indicators of fermented pork jerky.

Background: To determine the effect of different sterilization methods on shelf life and physicochemical parameters of fermented pork jerky. Methods: Various sterilization techniques, including boiling, pasteurization, medium-temperature steam sterilization, high-temperature steam sterilization, ultrasonic sterilization, and ultraviolet sterilization, were employed in this study to treat vacuum-sealed fermented pork jerky. Changes in microbial populations, physicochemical parameters, and sensory evaluations were monitored throughout the storage period. Results: The results indicated the presence of Staphylococcus aureus on the 24th, 21st, 33rd, 24th, 18th, and 15th days in pork jerky subjected to boiling (100°C, 20 min), pasteurization (85°C, 15 min), medium-temperature steam sterilization (105°C, 0.5 Pa, 30 min), high-temperature steam sterilization (121°C, 1.0 Pa, 20 min), ultrasonic sterilization (480 W, 30 kHz, 30 min), and ultraviolet sterilization (254 nm, 100 W/m2, 60 min), respectively. Coliforms, salmonella, and Shigella were not detected in any group during storage. The medium-temperature steam sterilization method yielded the most favorable microbiological results, with an aerobic plate count of less than 1.0 lg CFU/g. However, other physicochemical parameters and sensory evaluations were moderate, with total volatile basic nitrogen (TVB-N) and thiobarbituric acid reactive substances (TBARS) measuring 14.023 mg N/100 g and 0.427 mg MDA/kg, respectively, remaining within acceptable limits. Conclusion: Therefore, considering microbiological indicators as the primary determinant of shelf life and taking into account other physicochemical parameters, the medium-temperature steam sterilization method was identified as the most suitable approach for extending the shelf life of fermented pork jerky while preserving its flavor.

Repair of Oroantral Fistulas Using Free Bone and Mucoperiosteal Flaps After Endoscopic Removal of the Medial Wall of the Maxillary Sinus.

INTRODUCTION: Oroantral fistula (OAF) refers to a pathological connection between the oral cavity and maxillary sinus. It may lead to symptoms that include purulent mucus, nasal congestion, facial swelling, bad breath, and nasal regurgitation of food, all of which negatively impact patients' quality of life. OBJECTIVE: This study presents a novel approach for OAF repair using a 2-layered structure composed of free bone and a mucoperiosteal flap obtained from the medial wall of maxillary sinus. MATERIALS AND METHODS: Ten OAF patients who underwent repair using this method were retrospectively reviewed between August 2015 and June 2022. RESULTS: The extraction of maxillary molars was the most common cause of OAF. The size of the fistulas ranged from 1×2 mm to 5×8 mm. Nine of the 10 patients achieved successful OAF closure following the initial operation using the 2-layer structure composed of free bone and mucoperiosteal flag. One patient was lost to follow-up. The 9 patients were observed for 6 months to 1 year, and they exhibited no obvious complications or recurrence. CONCLUSION: The use of free bone and mucoperiosteal flag from the medial wall of maxillary sinus through an endoscope was effective for OAF repair.

Phosphatidylserine promotes immunotherapy for airway allergy.

Type 1 regulatory T cells (Tr1 cells) play an important role in the maintenance of the immune homeostasis in the body. The induction of Tr1 cell is to be further investigated. The interaction of phosphatidylserine (PS) with TIM3 has immune regulation functions. The objective of this study is to elucidate the role of PS-TIM3 signals in inducing Tr1 cells. In this study, mice were treated using PS or specific immunotherapy by nasal instillation. A murine model of allergic rhinitis was developed using ovalbumin as a specific antigen. We found that PS-containing nasal instillation induced Tr1 cells in the airway tissues. PS promoted gene activities associated with IL-10 through activation of TIM3 in CD4+ T cells. TIM3 mediated the effects of PS on inducing Tr1 cells, in which the TIM3- PI3K-AKT pathway played a critical role. PS boosted allergen-specific immunotherapy by inducing specific antigen Tr1 cell generation. Concomitant administration of PS and SIT resulted in better therapeutic effects on AR. In conclusion, the data demonstrate that PS can promote the specific immunotherapy for AR through inducing antigen specific Tr1 cells in the airway tissues.

Verapamil attenuates intervertebral disc degeneration by suppressing ROS overproduction and pyroptosis via targeting the Nrf2/TXNIP/NLRP3 axis in four-week puncture-induced rat models both in vivo and in vitro.

Low back pain is usually caused by intervertebral disc degeneration (IVDD), during which the involvement of oxidation system imbalance and inflammasome activation cannot be neglected. In this study, we aimed to validate the expression level of TXNIP in IVDD and investigate the function and potential mechanism of action of verapamil. TXNIP is upregulated in the degenerate nucleus pulposus in both humans and rats, as well as in tert-butyl hydroperoxide (TBHP)-stimulated nucleus pulposus cells. Administration of verapamil, a classic clinical drug, mitigated the TBHP-induced overproduction of reactive oxygen species and activation of the NLRP3 inflammasome, thus protecting cells from pyroptosis, apoptosis, and extracellular matrix degradation. The Nrf2/TXNIP/NLRP3 axis plays a major role in verapamail-mediated protection. In vivo, a puncture-induced IVDD rat model was constructed, and we found that verapamil delayed the development of IVDD at both the imaging and histological levels. In summary, our results indicate the potential therapeutic effects and mechanisms of action of verapamil in the treatment of IVDD.

A Clinical Study to Assess the Efficacy and Safety of MP-AzeFlu Nasal Spray in Comparison to Commercially Available Azelastine Hydrochloride and Fluticasone Propionate Nasal Sprays in Chinese Volunteers with Allergic Rhinitis.

INTRODUCTION: The objective of the present study was to evaluate the efficacy and safety of MP-AzeFlu nasal spray in comparison to commercially available azelastine hydrochloride and fluticasone propionate sprays in Chinese patients with moderate-to-severe allergic rhinitis (AR). METHODS: We conducted a 14-day multicenter, randomized, double-blind, active controlled prospective clinical study in adult and adolescent patients with AR, who had moderate-to-severe symptoms. The primary efficacy endpoint was the change from baseline in combined 12-h reflective total nasal symptom score (rTNSS) (morning [AM] + afternoon [PM]). The safety profile of the study medications was assessed through the recording, reporting, and analysis of baseline medical conditions, adverse events (AEs), vital signs, and focused nasal examination. Three hundred patients per treatment group were randomized, which led to a total sample size estimation of 900 patients. RESULTS: MP-AzeFlu group showed significantly higher symptom reduction for the entire 2-week treatment period in rTNSS when compared with the AZE group (LS mean difference: - 1.96; 95% CI: - 2.53, - 1.39; p < 0.0001), or the FLU group (LS mean difference: - 0.98; 95% CI: - 1.55, - 0.41; p = 0.0007). The results of adult RQLQ showed improvement in QoL in all treatment groups. Except for dysgeusia (bitter taste) that was reported by more patients (13 [4.3%]) in the MP-AzeFlu group, the incidence of all other TEAEs in the MP-AzeFlu group was comparable or even lower than in other treatment groups. CONCLUSIONS: MP-AzeFlu, when administered as one spray per nostril twice daily for 14 days, alleviated AR symptoms in Chinese patients with moderate-to-severe AR. TRIAL REGISTRATION: Clinicaltrials.gov; NCT03599791, Registered June 29, 2018, retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03599791 .

Efficacy and safety of CM310 in severe eosinophilic chronic rhinosinusitis with nasal polyps (CROWNS-1): a multicentre, randomised, double-blind, placebo-controlled phase 2 clinical trial.

Background: Severe eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP) remains the most relapsed subtype of uncontrolled CRSwNP. CM310, a humanised anti-interleukin (IL)-4 receptor alpha monoclonal antibody, inhibits IL-4 and IL-13 signaling which underlying eosinophilic inflammation. This study aims to evaluate the efficacy and safety of CM310 in patients with severe ECRSwNP. Methods: A multicentre, randomised, double-blind, and placebo-controlled phase 2 clinical trial was conducted. 56 eligible adult patients with severe ECRSwNP were randomised 1:1 to receive subcutaneously either CM310 (300 mg) or placebo every 2 weeks under the background therapy of mometasone furoate nasal spray (MFNS) for 16 weeks, with 8 weeks of follow-up. Coprimary endpoints included the changes from baseline in nasal polyp score (NPS) and nasal congestion score (NCS) at week 16. Key secondary endpoints included sinus Lund-Mackay CT score, change in sinus volume occupied by disease, University of Pennsylvania Smell Identification Test score, 22-item Sino-nasal Outcome Test score, and total symptom score. Safety, pharmacodynamics, and changes in type 2 inflammation biomarkers were assessed. This study is registered with ClinicalTrials.gov, NCT04805398. Findings: Between April 6, 2021, and March 18, 2022, 27 patients respectively in both the CM310 and placebo groups completed the study. Findings suggested that CM310 improved the coprimary efficacy endpoints of decreasing nasal polyp size and alleviating nasal congestion compared with the placebo. Least squares (LS) mean differences (CM310 vs placebo) of change from baseline in NPS and NCS at week 16 were -2.1 (95% CI -2.9, -1.4; p < 0.0001) and -0.9 (95% CI -1.4, -0.5; p < 0.0001), respectively. Sinus CT scan revealed that Lund-Mackay CT score (LS mean difference [95% CI] -7.6, [-9.4, -5.8]; p < 0.0001) and sinus volume occupied by disease (LS mean difference [95% CI] -37%, [-47%, -28%]; p < 0.0001) were significantly improved with CM310 compared with placebo. In addition, CM310 significantly relieved the daily symptoms of patients with CRSwNP and improved their quality of life reflected by the improvements in the TSS (-2.6 [95% CI -3.5, -1.6]), UPSIT (10.4 [95% CI 6.8, 14.0]) and SNOT-22 score (-19.1 [95% CI -29.8, -8.5]). Compared with placebo, CM310 administration significantly reduced type 2-related biomarkers including the serum TARC and total IgE, and tissue eosinophils. The most common adverse events were upper respiratory tract infection, blood cholesterol increased, and tinnitus, but none were considered drug-related. Interpretation: These findings support CM310 as an effective additional treatment option to the standard of care in patients with severe ECRSwNP. Funding: KeyMed Biosciences (Chengdu) Limited.

Circular RNA PDK1 targets miR-4731-5p to enhance TNXB expression in ligamentum flavum hypertrophy.

Hypertrophic ligamentum flavum (LF) is a main factor responsible for lumbar spinal stenosis (LSS); however, the exact mechanisms of the pathogenesis of these processes remain unknown. This study aimed to elucidate whether circular RNAs and microRNAs regulate the pathogenesis of LF and LSS, especially focusing on circPDK1 (hsa_circ_0057105), a circRNA targeting pyruvate dehydrogenase kinase 1 and differentially expressed in LF tissues between lumbar disk herniation and LSS patients. The circPDK1/miR-4731 and miR-4731/TNXB (Tenascin XB) interactions were predicted and validated by luciferase reporter assay. Colony formation, wound-healing, and MTT assays were used for estimating cell proliferation and migration. Protein expression levels were evaluated using Western blotting. TNXB expression was verified using immunohistochemistry (IHC). Overexpressing circPDK1 promoted the proliferation, migration, and expression of fibrosis-related protein (alpha smooth muscle actin (α-SMA), lysyl oxidase like 2 (LOXL2), Collagen I, matrix metalloproteinase-2 (MMP-2) and TNXB) in LF whereas miR-4731-5p showed opposite effects. The expression of TNXB was promoted by circPDK1; contrary results were observed with miR-4731-5p. Co-overexpression of miR-4731-5p partially reversed the proliferative and fibrosis-prompting effects of circPDK1 or TNXB. The circPDK1-miR-4731-TNXB pathway may be proposed as a regulatory axis in LF hypertrophy, which might shed light on in-depth research of LSS, as well as providing a novel therapeutic target for LF hypertrophy-induced LSS.

Axial superior facet slope may determine anterior or posterior atlantoaxial displacement secondary to os odontoideum and compensatory mechanisms of the atlantooccipital joint and subaxial cervical spine.

OBJECTIVE: To introduce novel parameters in determining directions of os odontoideum (OO) with atlantoaxial displacement (AAD) and compensations of cervical sagittal alignment after displacement. METHODS: Analysis was performed on 96 cases receiving surgeries for upper cervical myelopathy caused by OO with AAD from 2011 to 2021. Twenty-four patients were included in the OO group and divided into the OO-anterior displacement (AD) group and the OO-posterior displacement (PD) group by displacement. Seventy-two patients were included as the control (Ctrl) group and divided into Ctrl-positive (Ctrl-P) group and Ctrl-negative (Ctrl-N) group by axial superior facet slope (ASFS) in a neutral position. ASFS, the sum of C2 slope (C2S) and axial superior facet endplate angle (ASFEA), was measured and calculated by combining cervical supine CT with standing X-ray. Cervical sagittal parameters were measured to analyse the atlantoaxial facet and compensations after AAD. RESULTS: Atlas inferior facet angle (AIFA), ASFS, and ASFEA in Ctrl-P significantly differed from OO-AD.C0-C1, C1-C2, C0-C2, C2-C7, C2-C7 SVA, and C2S in Ctrl-P significant differed from the OO-AD group. C2-C7 SVA and C2S in Ctrl-N significantly were smaller than the OO-PD group. C1-C2 correlated with C0-C1 and C2-C7 negatively in the OO group. Slight kyphosis of C1-C2 in OO-AD was compared with lordosis of C1-C2 in Ctrl-P, inducing increased extension of C0-C1 and C2-C7. Mildly increased lordosis of C1-C2 in OO-PD was compared with C1-C2 in Ctrl-N, triggering augmented flexion of C0-C1 and C2-C7. CONCLUSION: ASFS was vital in determining directions of OO with AAD and explaining compensations. ASFS and ASFEA could provide pre- and intraoperative guidelines. KEY POINTS: • ASFS may determine the directions and compensatory mechanisms of AAD secondary to OO. • ASFS could be achieved by the sum of ASFEA and C2S.

Sal003 alleviated intervertebral disc degeneration by inhibiting apoptosis and extracellular matrix degradation through suppressing endoplasmic reticulum stress pathway in rats.

Apoptosis and extracellular matrix degradation of the nucleus pulposus are the main initiators of intervertebral disc degeneration (IVDD) and can be explained by endoplasmic reticulum (ER) stress. Thus, pharmacological therapy aimed at suppressing this pathway may be a promising approach for the management of intervertebral disc degeneration. In this study, we aimed to explore the protective effects of Sal003 against intervertebral disc degeneration and its underlying mechanisms. Thapsigargin (Tg)-stimulated rat nucleus pulposus cells and a needle puncture-induced intervertebral disc degeneration rat model were used to explore the protective effects of Sal003. Our results showed that Sal003 inhibited apoptosis and extracellular matrix degradation by suppressing the endoplasmic reticulum stress pathway. The therapeutic effects of Sal003 were also observed in the intervertebral disc degeneration rat model, as evidenced by improved degeneration along with decreased apoptosis and extracellular matrix degradation in intervertebral discs. Our results demonstrated Sal003 as a potential treatment for intervertebral disc degeneration.

Neuromedin U Induces Activation of Peripheral Group 2 Innate Lymphoid Cells through the ERK Pathway in Allergic Rhinitis Patients.

INTRODUCTION: In allergic diseases, group 2 innate lymphoid cells (ILC2s) play critical roles. Neuromedin U (NMU), a highly conserved multifunctional neuropeptide, is secreted by cholinergic neurons and involved in asthma pathogenesis by amplifying lung inflammation driven by ILC2s. However, the precise effects of NMU on ILC2s in allergic rhinitis (AR) and related diseases remain unclear. METHODS: A total of 15 patients with persistent AR and 8 healthy controls (HCs) were enrolled in the study. Visual analog scale (VAS) scores are used to assess the severity of clinical symptoms in AR patients. The percentages of ILC2s in peripheral blood mononuclear cells (PBMCs) were enumerated using flow cytometry. The soluble or intracellular cytokines (IL-5 and IL-13) in PBMCs or sorted ILC2s were assessed in response to various stimuli with IL-33, NMU, IL-33 combined with extracellular signal-related kinase (ERK) inhibitor or NMU combined with ERK inhibitor in the presence of IL-2. RESULTS: We confirmed the proportion of circulating ILC2s was significantly higher in AR patients than in HCs. ILC2s levels were found to be positively related to VAS scores. We also discovered that the release of IL-5 and IL-13 in AR patients' PBMCs stimulated by NMU (p < 0.0001 and p < 0.0001, respectively) or IL-33 (p = 0.002; p = 0.044, respectively) was significantly higher than in HCs. In AR patients, NMU stimulated PBMCs or ILC2s to generate greater inflammatory factors IL-5 and IL-13 compared to IL-33. Furthermore, we observed that NMU-promoted ILC2s activation and proliferation functions were restricted when the ERK pathway was inhibited. CONCLUSION: NMU effectively activated ILC2s in AR patients to produce Th2-type cytokines, and this activation can be prevented by ERK pathway inhibitors. Our findings shed new light on the neuro-immune mechanism of AR and offer new insights into its prevention and treatment.

Two polyphenols isolated from Corallodiscus flabellata B. L. Burtt ameliorate amyloid ß-protein induced Alzheimer's disease neuronal injury by improving mitochondrial homeostasis.

Corallodiscus flabellata B. L. Burtt (CF) is a Chinese folk herb with reported potential for the treatment of Alzheimer's disease (AD). 3,4-Dihydroxyphenylethanol-8-O-[4-O-trans-caffeoyl-ß-D-apiofuranosyl-(1→3)-ß-D-glucopyranosyl (1→6)][1]-ß-D-glucopyranoside (SDC-1-8) and hydroxytyrosol (HT) are two polyphenolic compounds isolated from CF. The aim of this study was to investigate the protective effects of SDC-1-8 and HT on an Aß25-35-induced AD model and to study the underlying mechanism. The AD mouse model was established using a brain injection of amyloid ß-protein 25-35 (Aß25-35, 200 µM), followed by continuous administration of SDC-1-8 and HT for 4 weeks, and found that they improved cognitive dysfunction; ameliorated neuronal damage and apoptosis; decreased oxidative stress, and mitochondrial fission protein levels; and increased mitochondrial fusion protein levels in AD mice. Moreover, SDC-1-8 and HT inhibited mitochondrial membrane depolarization, reduced intracellular stored Ca2+ levels, enhanced mitochondrial respiration, increased mitochondrial fusion, and decreased mitochondrial division in Aß25-35-induced PC12 cells even in the presence of mdivi-1. Furthermore, molecular docking simulations showed that SDC-1-8 and HT interacted with dynamin-related protein 1 with higher affinity than mitofusin 1. Thus, it is summarized that SDC-1-8 and HT may have neuroprotective effects by balancing the abnormalities of mitochondrial fission and fusion, and SDC-1-8 and HT are the components providing the therapeutic basis of CF.

ANGPTL4 May Regulate the Crosstalk Between Intervertebral Disc Degeneration and Type 2 Diabetes Mellitus: A Combined Analysis of Bioinformatics and Rat Models.

Introduction: The crosstalk between intervertebral disc degeneration (IVDD) and type 2 diabetes mellitus (T2DM) has been investigated. However, the common mechanism underlying this phenomenon has not been clearly elucidated. This study aimed to explore the shared gene signatures of IVDD and T2DM. Methods: The expression profiles of IVDD (GSE27494) and T2DM (GSE20966) were acquired from the Gene Expression Omnibus database. Five hub genes including ANGPTL4, CCL2, CCN3, THBS2, and INHBA were preliminarily screened. GO (Gene Ontology) enrichment analysis, functional correlation analysis, immune filtration, Transcription factors (TFs)-mRNA-miRNA coregulatory network, and potential drugs prediction were performed following the identification of hub genes. RNA sequencing, in vivo and in vitro experiments on rats were further performed to validate the expression and function of the target gene. Results: Five hub genes (ANGPTL4, CCL2, CCN3, THBS2, and INHBA) were identified. GO analysis demonstrated the regulation of the immune system, extracellular matrix (ECM), and SMAD protein signal transduction. There was a strong correlation between hub genes and different functions, including lipid metabolism, mitochondrial function, and ECM degradation. The immune filtration pattern grouped by disease and the expression of hub genes showed significant changes in the immune cell composition. TFs-mRNA-miRNA co-expression networks were constructed. In addition, pepstatin showed great drug-targeting relevance based on potential drugs prediction of hub genes. ANGPTL4, a gene that mediates the inhibition of lipoprotein lipase activity, was eventually determined after hub gene screening, validation by different datasets, RNA sequencing, and experiments. Discussion: This study screened five hub genes and ANGPTL4 was eventually determined as a potential target for the regulation of the crosstalk in patients with IVDD and T2DM.

Reliability and Validity Analysis of Pelvic Sagittal Inclination Calculated by Inverse Cosine Function Method on Pelvic Anteroposterior Radiographs.

OBJECTIVE: Evaluation of sagittal pelvic tilt is significant for hip surgeons. However, the accurate measurement of pelvic sagittal inclination (PSI) is still a challenge. The objective of this study is to propose a new method for measurement of PSI from pelvic anteroposterior radiograph based on the inverse cosine function obtained from individualized pelvic model. METHODS: Collecting the imaging data of 30 patients with both pelvic CT and full-length spine radiographs. Establishing pelvic model by customized 3D reconstruction software. The length of three groups of longitudinal and transverse line segments (A'p and B') were measured from full-length spine anteroposterior radiographs. The corresponding anatomical parameters, including A, B, b, ∠α, ∠γ, were measured and calculated on the same patient's pelvic model. The estimated PSI (ePSI) based on three groups of anatomical landmarks, including ePSI-1, ePSI-2, and ePSI-3, were calculated by equation, ePSI = arccos A ' p b * B ' - ∠ α , and compared with the actual PSI (aPSI) measured by Surgamap software. For the reliability and validation evaluation, three observers measured these parameters in two rounds. Intra-class correlation and inter-class correlation were both calculated. Bland-Altman method was used to evaluate the consistency between the estimated PSI (ePSI) and the actual PSI (aPSI). RESULTS: ePSI-1 and ePSI-2 showed excellent intra-observer reliability (0.921-0.997, p < 0.001) and inter-observer reliability (0.801-0.977, p < 0.001). ePSI-3 had a fair inter-observer reliability (0.239-0.823, p < 0.001). ePSI-1 showed the strongest correlation with aPSI (r = 0.917, p < 0.001). Mean (maximum) absolute difference of ePSI-1, ePSI-2, and ePSI-3 is 2.62° (7.42°), 4.23° (13.78°), and 7.74° (31.47°), respectively. The proportion of cases with absolute difference less than 5° in three groups were 86.7% (ePSI-1), 66.7% (ePSI-2), 56.7% (ePSI-3). CONCLUSION: This new method based on inverse cosine function has good reliability and validity when used in the evaluation of PSI on pelvic anteroposterior radiographs.

Unilateral versus bilateral pedicle screw fixation with transforaminal lumbar interbody fusion for treatment of lumbar foraminal stenosis.

BACKGROUND CONTEXT: Transforaminal lumbar interbody fusion (TLIF) with bilateral pedicle screw fixation (BPSF) is an effective treatment for lumbar foraminal stenosis (LFS). However, the effects of TLIF with unilateral pedicle screw fixation (UPSF) on LFS treatment have not been clearly elucidated. PURPOSE: We conducted this study to compare clinical outcomes and radiographic results of TLIF with UPSF and BPSF 2 years after the surgical treatment. DESIGN: Prospective randomized study. PATIENT SAMPLE: This study included 23 patients undergoing TLIF with UPSF and 25 patients undergoing TLIF with BPSF. OUTCOME MEASURES: Clinical outcomes were evaluated by visual analog scale (VAS) for low back pain and leg pain and Oswestry Disability Index (ODI) score. Radiographic outcomes included foraminal height, disc space height, segmental lordosis, and final fusion rates. METHODS: The clinical and radiographic outcomes were compared between the UPSF and BPSF group. The postoperative improvements were evaluated in either group. Intraoperative data such as duration of operation and estimated blood loss were collected. This study was registered at clinicaltrials.gov. RESULTS: Analysis of the VAS and ODI scores showed significant improvements in clinical outcomes within each group. No significant differences between the 2 groups were noted in the improvements of the VAS and ODI scores. The mean operative duration and blood loss were significantly greater in the BPSF group than in the UPSF group. There were significant improvements in the height of the foramen and intervertebral space and segmental lordosis in both groups, while there was no significant difference between the groups in amount of the improvements. No significant difference was found in the final fusion rates. CONCLUSIONS: TLIF is an appropriate procedure for LFS treatment. With balanced intervertebral support using a cage, UPSF could achieve similar and satisfactory effects on lumbar segmental stability and fusion compared to BPSF. The unilateral approach appears to be associated with slightly shorter operative time and less blood loss.