Antidepressant effect of teriflunomide via oligodendrocyte protection in a mouse model.

Addressing the treatment of depression is crucial; nevertheless, the etiology and pathogenesis remain unelucidated. Therefore, this study investigated the effects of teriflunomide (TF) on corticosterone (CORT)-induced depression-like behaviors in mice. Notably, TF administration resulted in a substantial amelioration of anxiety and depression-like behaviors observed in CORT-treated mice. This was evidenced by behavioral assessments conducted via the sucrose preference test (SPT), open-field test (OFT), novelty-suppressed feeding test (NSFT), forced swimming test (FST), and tail suspension test (TST). The administration of CORT inflicts damage upon oligodendrocytes and neurons within the hippocampus. Our findings indicate that TF offers significant protective effects on oligodendrocytes, mitigating apoptosis both invivo and invitro. Additionally, TF was found to counteract the CORT-induced neuronal loss and synaptic damage, as demonstrated by an increase in Nissl-positive cells across hippocampal regions CA1, CA3, and the dentate gyrus (DG) alongside elevated levels of synapse-related proteins including PSD-95 and synaptophysin. Additionally, TF treatment facilitated a reduction in the levels of apoptosis-related proteins while simultaneously augmenting the levels of Bcl2. Our findings indicate that TF administration effectively mitigates CORT-induced depression-like behaviors and reverses damage to oligodendrocytes and neurons in the hippocampus, suggesting TF as a promising candidate for depression.

Pancreatitis affects gut microbiota via metabolites and inflammatory cytokines: an exploratory two-step Mendelian randomisation study.

Previous studies have observed relationships between pancreatitis and gut microbiota; however, specific changes in gut microbiota abundance and underlying mechanisms in pancreatitis remain unknown. Metabolites are important for gut microbiota to fulfil their biological functions, and changes in the metabolic and immune environments are closely linked to changes in microbiota abundance. We aimed to clarify the mechanisms of gut-pancreas interactions and explore the possible role of metabolites and the immune system. To this end, we conducted two-sample Mendelian randomisation (MR) analysis to evaluate the casual links between four different types of pancreatitis and gut microbiota, metabolites, and inflammatory cytokines. A two-step MR analysis was conducted to further evaluate the probable mediating pathways involving metabolites and inflammatory cytokines in the causal relationship between pancreatitis and gut microbiota. In total, six potential mediators were identified in the causal relationship between pancreatitis and gut microbiota. Nineteen species of gut microbiota and seven inflammatory cytokines were genetically associated with the four types of pancreatitis. Metabolites involved in glucose and amino acid metabolisms were genetically associated with chronic pancreatitis, and those involved in lipid metabolism were genetically associated with acute pancreatitis. Our study identified alterations in the gut microbiota, metabolites, and inflammatory cytokines in pancreatitis at the genetic level and found six potential mediators of the pancreas-gut axis, which may provide insights into the precise diagnosis of pancreatitis and treatment interventions for gut microbiota to prevent the exacerbation of pancreatitis. Future studies could elucidate the mechanism underlying the association between pancreatitis and the gut microbiota.

Effect of enrichment conditions of secondary feeding on the synthesis of polyhydroxyalkanoates (PHAs) by activated sludge.

Polyhydroxyalkanoates (PHAs) are biodegradable plastics with great performance and development prospects. However, their traditional anaerobic/aerobic enrichment process requires a high concentration of dissolved oxygen (DO), resulting in high energy consumption. In this study, an anaerobic/oxygen-limited with secondary feeding enrichment mode was used to enhance the synthesis of PHAs while reducing energy consumption. The enrichment process of PHAs-synthesizing bacteria lasted up to 100 days, and the experiment was conducted to investigate the change of the PHAs synthesizing ability of the system in this mode by detecting the PHAs content and community distribution of the activated sludge under different stages. Under these conditions, the system enriched two major genera of PHAs-synthesizing bacteria, Thauera (30.21%) and Thiothrix (21.30%). The content of PHAs in the sludge increased from 4.51% to 30.87% and was able to achieve a concomitant increase in poly(3-hydroxyvalerate) (PHV) monomer content. After nitrogen limitation (C/N = 150) treatment, the content of PHAs reached 63.05%. The results showed that the enrichment mode of anaerobic/oxygen-limited with secondary feeding could enrich more PHAs-synthesizing bacteria and significantly increase the synthesis amount of PHAs, which revealed the great potential of this mode in solid waste value-added and reduce the production cost of PHAs and could provide a theoretical basis for the production of PHAs from activated sludge.

Series-Biased Micro-LED Array for Lighting, Detection, and Optical Communication.

Micro-LED arrays exhibit high brightness, a long lifespan, low power consumption, and a fast response speed. In this paper, we have proposed a series-biased micro-LED array by using a nitride layer with multi-quantum wells epitaxial on sapphire substrate. The III-nitride multiple quantum wells serving as the micro-LED active material enable both luminescence and detection functionalities. The micro-LED array combines lighting, detection, and communication capabilities. We have conducted a thorough analysis of the micro-LED array's optoelectronic features in both lighting and detection modes. We also explore visible light communication performance across different arrangements of single micro-LED devices within the series-biased array. Our research achieves 720p video transmission via visible light communication using the micro-LED array, supporting a communication rate of up to 10 Mbps. Our contributions encompass the successful integration of lighting and detection functions and a comprehensive assessment of optoelectronic and communication performance. This study highlights the multifunctional micro-LED array's potential as a transceiver terminal in visible light communication systems, expanding its applications from smart lighting to visible light communication and photonic integrated chips. These innovations enhance our understanding of micro-LED technology and its versatile applications.

Periodontitis was associated with mesial concavity of the maxillary first premolar: a cross-sectional study.

The association between the anatomical features of teeth and the pathogenesis of periodontitis is well-documented. This study aimed to evaluate the influence of the mesial concavity of the maxillary first premolar on periodontal clinical indices and alveolar bone resorption rates. Employing a cross-sectional design, in 226 patients with periodontitis, we used cone beam computed tomography(CBCT) to examine the mesial concavity and alveolar bone resorption of 343 maxillary first premolar. Periodontal clinical indicators recorded by periodontal probing in the mesial of the maxillary first premolar in patients with periodontitis. Our findings indicate that the presence of mesial concavity at the cemento-enamel junction of the maxillary first premolar was not significantly influenced by either tooth position or patient sex (p > 0.05). Nonetheless, the mesial concavity at the cemento-enamel junction of the maxillary first premolar was found to exacerbate alveolar bone resorption and the inflammatory condition (p < 0.05). We infer that the mesial concavity at the cemento-enamel junction of the maxillary first premolar may contribute to localized alveolar bone loss and accelerate the progression of periodontal disease.

Coproduction with peer support groups: A new approach to culturally responsive social services.

The disparity of access to suitable social services for people from culturally diverse backgrounds is receiving increased attention. Coproduction between service users and providers has the potential as an approach to improve the cultural responsiveness of social services. What remains unknown is how social service organizations can facilitate and support coproduction with people from culturally diverse backgrounds. This article examines how three disability support organizations in Australia worked with peer support groups run by people with disability and their families from Chinese background to improve the organizations' service provision. We collected qualitative data through observations of activities in the groups and semistructured interviews with group members and organization staff. We found that organizing peer support groups facilitated knowledge exchange between people from culturally diverse backgrounds and organizations to inform practice development. Five contributors to the knowledge exchange were as follows: (1) assigning staff responsibility for exchange and trust with the group; (2) encouraging the group to challenge practice and cultural norms; (3) identifying and supporting the capacity of peer facilitators; (4) fostering trust within the group; and (5) collaborating with other organizations. Cultural responsiveness means incorporating people's cultural preferences in support provision and addressing the negative influences of cultural norms on people.

The impact of maxillary non-impacted third molars on the distal alveolar bone of adjacent teeth using CBCT: a retrospective study.

OBJECTIVE: The purpose of the study was to determine how the maxillary non-impacted third molars impact the distal region of alveolar bone of adjacent second molars. METHOD AND MATERIALS: The periodontal condition of maxillary second molars for which the neighboring third molars were missing (NM3- group) and those with intact non-impacted third molars (NM3+ group) was analyzed in a retrospective study. Using CBCT, the patients were categorized based on the presence or absence of periodontitis, and the alveolar bone resorption parameters in the distal area of the second molars were measured. RESULTS: A total of 135 patients with 200 maxillary second molars were enrolled in this retrospective study. Compared to the NM3- group, the second molars of the NM3+ group exhibited greater odds of increasing alveolar bone resorption in the distal region (health, OR = 3.60; periodontitis, OR = 7.68), regardless of the presence or absence of periodontitis. In healthy patients, factors such as female sex (OR = 1.48) and age above 25 years old (OR = 2.22) were linked to an elevated risk of alveolar bone resorption in the distal region of the second molars. In patients with periodontitis, male sex (OR = 3.63) and age above 45 years old (OR = 3.97) served as risk factors. CONCLUSIONS: Advanced age, sex, and the presence of non-impacted third molars are risk factors associated with alveolar bone resorption in individuals with adjacent second molars. In addition, the detrimental effects of non-impacted third molars in the population with periodontitis may be exacerbated. From a periodontal perspective, this serves as supportive evidence for the proactive removal of non-impacted third molars.

Identification of large yellow croakers (Larimichthys crocea) scavenger receptor genes: Involvement in immune response to Pseudomonas plecoglossicida infection and hypoxia-exposure experiments.

Scavenger receptors (SRs) are pattern recognition receptors involved in the innate immune defense against pathogen infection in fish. However, there has not been much research done on teleosts. In this study, 18 members of the SR gene family were found in large yellow croaker. The identification of the SR gene family showed that the protein length of SR members in large yellow croaker were quite different, and most SR genes were distributed in nuclear and endoplasmic. The evolutionary relationship, exon/intron structure and motif analysis revealed that members of the SR gene family were highly conserved. The results of the expression profiles after Pseudomonas plecoglossicida infection and hypoxia-exposure demonstrated that SR members were involved in inflammatory reactions. Especially, COLEC12 and SCARF1 exhibited substantial changes in response to both P. plecoglossicida and hypoxia stress, indicating their possible immunological functions. The result of this study revealed that SR genes played a vital part in the innate immune response of large yellow croaker, and would give important details for a deeper comprehension of the SR gene family's regulation mechanism under various conditions in large yellow croaker.

Increased FGFR3 is involved in T-2 toxin-induced lesions of hypertrophic cartilage associated with endemic osteoarthritis.

This study evaluated the effect of fibroblast growth factor receptor 3 (FGFR3) on damaged hypertrophic chondrocytes of Kashin-Beck disease (KBD). Immunohistochemical staining was used to evaluate FGFR3 expression in growth plates from KBD rat models and engineered cartilage. In vitro study, hypertrophic chondrocytes were pretreated by FGFR3 binding inhibitor (BGJ398) for 24 h before incubation at different T-2 toxin concentrations. Differentiation -related genes (Runx2, Sox9, and Col Ⅹ) and ECM degradation -related genes (MMP-13, Col Ⅱ) in the hypertrophic chondrocytes were analyzed using RT-PCR, and the corresponding proteins were analyzed using western blotting. Hypertrophic chondrocytes death was detected by the Annexin V/PI double staining assay. The integrated optical density of FGFR3 staining was increased in knee cartilage of rats and engineered cartilage treated with T-2 toxin. Both protein and mRNA levels of Runx2, Sox9, Col Ⅱ, and Col Ⅹ were decreased in a dose-dependent manner when exposed to the T-2 toxin and significantly upregulated by 1 µM BGJ398. The expression of MMP-1, MMP-9, and MMP-13 increased in a dose-dependent manner when exposed to T-2 toxin and significantly reduced by 1 µM BGJ398. 1 µM BGJ398 could prevent early apoptosis and necrosis induced by the T-2 toxin. Inhibiting the FGFR3 signal could alleviate extracellular matrix degradation, abnormal chondrocytes differentiation, and excessive cell death in T-2 toxin-induced hypertrophic chondrocytes.

High prevalence of subjective cognitive decline in older Chinese adults: a systematic review and meta-analysis.

Background: Subjective cognitive decline (SCD) is considered a preclinical stage of Alzheimer's disease. However, reliable prevalence estimates of SCD in the Chinese population are lacking, underscoring the importance of such metrics for policymakers to formulate appropriate healthcare strategies. Objective: To systematically evaluate SCD prevalence among older Chinese adults. Methods: PubMed, Web of Science, The Cochrane Library, Embase, CNKI, Wanfang, VIP, CBM, and Airiti Library databases were searched for studies on SCD in older Chinese individuals published before May 2023. Two investigators independently screened the literature, extracted the information, and assessed the bias risk of the included studies. A meta-analysis was then conducted using Stata 16.0 software via a random-effects model to analyze SCD prevalence in older Chinese adults. Results: A total of 17 studies were included (n = 31,782). The SCD prevalence in older Chinese adults was 46.4% (95% CI, 40.6-52.2%). Further, subgroup analyzes indicated that SCD prevalence was 50.8% in men and 58.9% among women. Additionally, SCD prevalence in individuals aged 60-69, 70-79, and ≥ 80 years was 38.0, 45.2, and 60.3%, respectively. Furthermore, SCD prevalence in older adults with BMI <18.5, 18.5-24.0, and > 24.0 was 59.3, 54.0, and 52.9%, respectively. Geographically, SCD prevalence among older Chinese individuals was 41.3% in North China and 50.0% in South China. In terms of residence, SCD prevalence was 47.1% in urban residents and 50.0% among rural residents. As for retired individuals, SCD prevalence was 44.2% in non-manual workers and 49.2% among manual workers. In the case of education, individuals with an education level of "elementary school and below" had an SCD prevalence rate of 62.8%; "middle school, "52.4%; "high school, "55.0%; and "college and above, "51.3%. Finally, SCD prevalence was lower among married individuals with surviving spouses than in single adults who were divorced, widowed, or unmarried. Conclusion: Our systematic review and meta-analysis identified significant and widespread SCD prevalence in the older population in China. Therefore, our review findings highlight the urgent requirement for medical institutions and policymakers across all levels to prioritize and rapidly develop and implement comprehensive preventive and therapeutic strategies for SCD.Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023406950, identifier: CRD42023406950.

Water extract of green tea attenuates alcohol-related hepatitis by inhibiting liver inflammation and gut microbiota disturbance in mice.

Green tea is one of the main types of tea in China, and it has been widely consumed in the world. This study aims to investigate the potential mechanism by which the water extract of green tea (GTWE) may be effective in the treatment of alcohol-related hepatitis (ARH), utilizing a combination of network pharmacology, molecular docking, and experimental validation. Through network pharmacology analysis, seven active components and 45 potential targets were identified, with TLR4 being confirmed as the central target. Experimental findings demonstrate that GTWE exhibits significant efficacy in mitigating alcohol-induced liver inflammation and steatosis. Furthermore, the administration of GTWE has demonstrated significant efficacy in mitigating alcohol-induced intestinal inflammation and microbiota disturbance while concurrently restoring intestinal barrier function. Consequently, GTWE exhibits considerable potential as a pharmacological intervention and warrants further research and development as a lead compound for the treatment of ARH. Moreover, the prospective utilization of green tea in prolonged intakes exhibits potential as a prophylactic nutritive regimen against ARH.

Highly Biocompatible Polyester-Based Piezoelectric Elastomer with Antitumor and Antibacterial Activity for Ultrasound-Enhanced Piezoelectric Therapy.

Currently, the use of piezoelectric materials to provide sustainable and noninvasive bioelectric stimulation to eradicate tumor cells and accelerate wound healing has raised wide attention. The development of a multifunctional piezoelectric elastomer with the ability to perform in situ tumor therapy as well as wound repair is of paramount importance. However, current piezoelectric materials have a large elastic modulus and limited stretchability, making it difficult to match with the dynamic curvature changes of the wound. Therefore, by copolymerizing lactic acid, butanediol, sebacic acid, and itaconic acid to develop a piezoelectric elastomer (PLBSIE), we construct a new ultrasound-activated PLBSIE-based tumor/wound unified therapeutic platform. Excitedly, it showed outstanding piezoelectric performance and high stretchability, and the separated carrier could react with water to generate highly cytotoxic reactive oxygen species (ROS), contributing to effectively killing tumor cells and eliminating bacteria through piezoelectric therapy. In addition, ultrasound-triggered piezoelectric effects could promote the migration and differentiation of wound-healing-related cells, thus accelerating wound healing. Herein, such a piezoelectric elastomer exerted a critical role in postoperative tumor-induced wound therapy and healing with the merits of possessing multifunctional abilities. Taken together, the developed ultrasound-activated PLBSIE will offer a comprehensive treatment for postoperative osteosarcoma therapy.

Optimization of activated sludge polyhydroxyalkanoates(PHAs) synthesis system by performing sludge activity recovery experiments and varying the initial sludge concentration.

Polyhydroxyalkanoates(PHAs) are considered a good alternative to petroleum-based plastics because of their good biodegradability and biocompatibility. The synthesis of PHAs using activated sludge can not only solve the problem of the high cost of pure cultures but also improve the utilization value of activated sludge. In this study, sludge activity recovery experiments were firstly conducted and the effects of different initial sludge concentrations on the activated sludge PHAs synthesis system were further investigated. the initial sludge concentrations were 1#SBR (2800 ± 50) mg/L, 2#SBR (4200 ± 50) mg/L, and 3#SBR (5500 ± 50) mg/L. The results showed that the activity, sedimentation performance and PHAs synthesis capacity of activated sludge were enhanced after the sludge activity recovery experiment. At the initial sludge concentration of 4200 mg/L, the activated sludge PHAs synthesis system was operated stably and the synthesis efficiency of PHAs was enhanced. In contrast, at the initial sludge concentration of 2800 and 5500 mg/L, the steady state of the activated sludge PHAs synthesis system was damaged to different degrees at different times, and the synthesis efficiency of PHAs was greatly reduced.

Rehabilitation effect of intelligent rehabilitation training system on hemiplegic limb spasms after stroke.

This article aimed to explore the rehabilitation efficacy of intelligent rehabilitation training systems in hemiplegic limb spasms after stroke and provided more theoretical basis for the application of intelligent rehabilitation systems in the rehabilitation of hemiplegic limb spasms after stroke. To explore the rehabilitation efficacy of intelligent rehabilitation training system (RTS for short here) in post-stroke hemiplegic limb spasms, this study selected 99 patients with post-stroke hemiplegic limb spasms admitted to a local tertiary hospital from March 2021 to March 2023 as the research subjects. This article used blind selection to randomly divide them into three groups: control group 1, control group 2, and study group, with 33 patients in each group. Control group 1 used a conventional RTS, group 2 used the brain-computer interface RTS from reference 9, and research group used the intelligent RTS from this article. This article compared the degree of spasticity, balance ability score, motor function score, and daily living activity score of three groups of patients after 10 weeks of treatment. After 10 weeks of treatment, the number of patients in the study group with no spasms at level 0 (24) was significantly higher than the number of patients in group 1 (7) and group 2 (10), with a statistically significant difference (P < 0.05); In the comparison of Barthel index scores, after ten weeks of treatment, the total number of people in the study group with scores starting at 71-80 and 81-100 was 23. The total number of people in the score range of 71-80 and 81-100 in group 1 was 5, while in group 2, the total number of people in this score range was 8. The study group scored considerably higher than the control group and the difference was found to be statistically relevant (P < 0.05). In the Berg balance assessment scale and motor function assessment scale, after 10 weeks of treatment, the scores of the study group patients on both scales were significantly higher than those of group 1 and group 2 (P < 0.05). The intelligent RTS is beneficial for promoting the improvement of spasticity in stroke patients with hemiplegic limb spasms, as well as improving their balance ability, motor ability, and daily life activities. Its rehabilitation effect is good.

Inhibition of IKKß via a DNA-Based In Situ Delivery System Improves Achilles Tendinopathy Healing in a Rat Model.

BACKGROUND: The inhibition of IKKß by the inhibitor 2-amino-6-[2-(cyclopropylmethoxy)-6-hydroxyphenyl]-4-(4-piperidinyl)-3-pyridine carbonitrile (ACHP) is a promising strategy for the treatment of Achilles tendinopathy. However, the poor water solubility of ACHP severely hinders its in vivo application. Moreover, the effective local delivery of ACHP to the tendon and its therapeutic effects have not been reported. PURPOSE: To investigate the therapeutic effects of IKKß inhibition via injection of ACHP incorporated into a DNA supramolecular hydrogel in a collagenase-induced tendinopathy rat model. STUDY DESIGN: Controlled laboratory study. METHODS: Dendritic DNA, a Y-shaped monomer, and a crosslinking monomer were mixed with ACHP and self-assembled into an ACHP-DNA supramolecular hydrogel (ACHP-Gel). The effects of ACHP-Gel in tendon stem/progenitor cells were investigated via RNA sequencing and validated using quantitative reverse transcription polymerase chain reaction (qRT-PCR). A total of 120 collagenase-induced rats were randomly assigned to 5 groups: blank, phosphate-buffered saline (PBS), DNA-Gel, ACHP, and ACHP-Gel. Healing outcomes were evaluated using biomechanic and histologic evaluations at 4 and 8 weeks. RESULTS: ACHP-Gel enhanced the solubility of ACHP and sustained its release for ≥21 days in vivo, which significantly increased the retention time of ACHP and markedly reduced the frequency of administration. RNA sequencing and qRT-PCR showed that ACHP effectively downregulated genes related to inflammation and extracellular matrix remodeling and upregulated genes related to tenogenic differentiation. The cross-sectional area (P = .024), load to failure (P = .002), stiffness (P = .039), and elastic modulus (P = .048) significantly differed between the ACHP-Gel and PBS groups at 8 weeks. The ACHP-Gel group had better histologic scores than the ACHP group at 4 (P = .042) and 8 weeks (P = .009). Type I collagen expression (COL-I; P = .034) and the COL-I/collagen type III ratio (P = .015) increased while interleukin 6 expression decreased (P < .001) in the ACHP-Gel group compared with the ACHP group at 8 weeks. CONCLUSION: DNA supramolecular hydrogel significantly enhanced the aqueous solubility of ACHP and increased its release-retention time. Injection frequency was markedly reduced. ACHP-Gel suppressed inflammation in Achilles tendinopathy and promoted tendon healing in a rat model. CLINICAL RELEVANCE: ACHP-Gel injection is a promising strategy for the treatment of Achilles tendinopathy in clinical practice.

Change in quality of life and return to work and sports after isolated closing-wedge distal femoral osteotomy.

PURPOSE: To analyze return to work and sports, and health-related quality of life (HRQoL) after closing-wedge distal femoral osteotomy (CWDFO) for valgus deformity and lateral compartmental osteoarthritis. METHODS: Thirty-three patients underwent isolated CWDFO in our center between January 2018 and June 2020 were enrolled, of whom 32 and 23 patients were included in the return-to-work and return-to-sports analyses, respectively. Short Form-36 (SF-36), Tegner score, Knee injury and Osteoarthritis Outcome Score (KOOS) and visual analog scale (VAS) pain score were compared preoperatively and postoperatively. And postoperative complications were recorded. RESULTS: Overall, 33 patients were contacted at a mean follow-up of 37.94 ± 6.68 months, with a median age of 35 years (range: 26-63 years) at the surgery time. The physical component summary of SF-36 (p < 0.001) increased significantly at 1 year postoperatively. All patients returned to work, including 96.86% who returned to the same level of work in 1.89 ± 0.98 months, and to sports, including 78.26% who returned to the same sport level in 6.50 ± 2.05 months. Rates of returning to work (p = 0.215) and sports (p = 0.165) did not differ with work/sports intensity. Tegner scores (p = 0.025) and VAS pain scores (p < 0.001) decreased, and KOOS (p < 0.001) increased at 1 year postoperatively. Revision/conversion surgery was not required. In all, 30.43% patients reported a subjective decrease in sports ability; 82.61% patients considered their sports ability acceptable. CONCLUSION: Patients returned to work/sports after isolated CWDFO, and had increased HRQoL. Patients playing high-impact sports had lower rates of returning to the same sport level, and may require preoperative counseling. LEVEL OF EVIDENCE: IV, Case series.

Melatonin Improves Mitochondrial Dysfunction and Attenuates Neuropathic Pain by Regulating SIRT1 in Dorsal Root Ganglions.

Neuropathic pain is a debilitating chronic pain condition and is refractory to the currently available treatments. Emerging evidence suggests that melatonin exerts analgesic effects in rodent models of neuropathic pain. Nevertheless, the exact underlying mechanisms of the analgesic effects of melatonin on neuropathic pain are largely unknown. Here, we observed that spinal nerve ligation (SNL) in rats L5 and L6 induced an obvious decrease in the 50% paw withdrawal threshold (PWT) and paw withdrawal latency (PWL), indicating the induction of mechanical allodynia and the hyperalgesia, and melatonin prevented the genesis and maintenance of mechanical allodynia and the hyperalgesia. Notably, the inhibitory action of melatonin on SNL-induced mechanical allodynia and heat hypersensitivity was inhibited by a SIRT1 inhibitor (EX527). Melatonin treatment increased the expression of neuronal sirtuin1 (SIRT1) in DRGs following nerve injury. Furthermore, melatonin treatment restored the injury-dependent decrease in mitochondrial membrane potential and peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) and reduced the injury-dependent increase in hydrogen peroxide and 8-hydroxy-2-deoxyguanosine (8-OHdG), which was inhibited by EX527. In addition, we found that EX527 impeded the inhibitory effects of melatonin on the SNL-induced increased expression of cytokines tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1ß). In conclusion, the above data demonstrated that melatonin alleviated mechanical allodynia and hyperalgesia induced by peripheral nerve injury via SIRT1 activation. Melatonin resolved mitochondrial dysfunction-oxidative stress-dependent and neuroinflammation mechanisms that were driven by SIRT1 after nerve injury.

A novel NET-related gene signature for predicting DLBCL prognosis.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is an aggressive malignancy. Neutrophil extracellular traps (NETs) are pathogen-trapping structures in the tumor microenvironment that affect DLBCL progression. However, the predictive function of NET-related genes (NRGs) in DLBCL has received little attention. This study aimed to investigate the interaction between NRGs and the prognosis of DLBCL as well as their possible association with the immunological microenvironment. METHODS: The gene expression and clinical data of patients with DLBCL were downloaded from the Gene Expression Omnibus database. We identified 148 NRGs through the manual collection of literature. GSE10846 (n = 400, GPL570) was used as the training dataset and divided into training and testing sets in a 7:3 ratio. Univariate Cox regression analysis was used to identify overall survival (OS)-related NETs, and the least absolute shrinkage and selection operator was used to evaluate the predictive efficacy of the NRGs. Kaplan-Meier plots were used to visualize survival functions. Receiver operating characteristic (ROC) curves were used to assess the prognostic predictive ability of NRG-based features. A nomogram containing the clinical information and prognostic scores of the patients was constructed using multivariate logistic regression and Cox proportional risk regression models. RESULTS: We identified 36 NRGs that significantly affected patient overall survival (OS). Eight NRGs (PARVB, LYZ, PPARGC1A, HIF1A, SPP1, CDH1, S100A9, and CXCL2) were found to have excellent predictive potential for patient survival. For the 1-, 3-, and 5-year survival rates, the obtained areas under the receiver operating characteristic curve values were 0.8, 0.82, and 0.79, respectively. In the training set, patients in the high NRG risk group presented a poorer prognosis (p < 0.0001), which was validated using two external datasets (GSE11318 and GSE34171). The calibration curves of the nomogram showed that it had excellent predictive ability. Moreover, in vitro quantitative real-time PCR (qPCR) results showed that the mRNA expression levels of CXCL2, LYZ, and PARVB were significantly higher in the DLBCL group. CONCLUSIONS: We developed a genetic risk model based on NRGs to predict the prognosis of patients with DLBCL, which may assist in the selection of treatment drugs for these patients.

The PFNA in treatment of intertrochanteric fractures with or without lateral wall fracture in elderly patients: a retrospective cohort study.

BACKGROUND: There is no consensus about intertrochanteric fractures with lateral wall treated with intramedullary nail-proximal femoral nail antirotation (PFNA). The aim of the present study was to compare function outcomes between lateral wall and no lateral wall fractures after surgery by PFNA. METHODS: This retrospective study evaluated patients with or without lateral wall fractures who underwent PFNA between January 2015 and June 2018. The operative time, intraoperative blood loss, time to fracture healing, complications and functional outcomes qualified by Harris hip score and Parker - Palmer mobility score (PPMS) were compared between the two groups. RESULTS: Two groups were comparable with regard to patient age, sexual distribution, mechanism of injury, fracture type, body mass index (BMI), Time to surgery, American Society of Anesthesiologists (ASA) score and quality of reduction. The incomplete group had a longer operation time (54.1 ± 8.74 min vs. 51.0 ± 9.86 min) and more intraoperative blood loss (228.4 ± 48.8 ml vs. 151.3 ± 43.5 ml) in comparison with the control group (P < 0.01). Regarding functional outcome, the HHSs of the two groups were 76.2 ± 11.6 vs 75.6 ± 12.5 at the 3 months (P = 0.603), 81.9 ± 9.4 vs 82.6 ± 8.7 at the six months (P = 0.224), 83.8 ± 6.6 vs 84.5 ± 6.0 at the twelve months 85.2 ± 5.5 vs 86.0 ± 5.8 at the twenty-four months (P > 0.05), respectively. Similar results were obtained about PPMS. We found no difference in Weight bearing time, Time of fracture healing, and Complications between incomplete group and intact group. CONCLUSIONS: There is no substantial difference in functional results or complication rates for intertrochanteric fractures with lateral wall fractures, except from increased blood loss and operation time. We believe that an intramedullary nail will be sufficient to repair an intertrochanteric fracture with or without a lateral wall fracture.

The relationship between dietary patterns derived from inflammation and cognitive impairment in patients undergoing hemodialysis.

Introduction: Dietary patterns were shown to be closely related to inflammation, which was independently associated with cognitive impairment (CI) in patients undergoing hemodialysis (HD). However, it remains unclear the influence of dietary patterns derived from inflammation on CI in this population. This study aimed to examine the association between dietary patterns derived from C-reactive protein (CRP) and interleukin-6 (IL-6) and CI in patients undergoing HD. Methods: Dietary intake was obtained from the simplified quantitative food frequency questionnaire. Reduced rank regression (RRR) was used to extract two dietary patterns, with IL-6 and CRP as response variables. Cognitive function was examined by the Montreal Cognitive Assessment (Beijing version). Venous blood was drawn for measuring IL-6 and CRP levels. Multivariable logistic regression was used to investigate the association between dietary patterns and CI. Results: Dietary pattern derived from IL-6 was not significantly associated with CI. The third quartile of dietary pattern, which used CRP as the response variable, significantly contributed to the increased risk of CI (AOR 8.62, 95% CI 1.47-50.67) after controlling age, sex, education level, marital status, and residential pattern (p-for-trend = 0.028). After considering hypertension and diabetes, physical activity level, anxiety and depression, smoking and drinking status, social support, energy intake, and the dietary pattern derived from IL-6 (p-for-trend = 0.026), the relationship between the dietary pattern derived from CRP and CI remained significant (AOR 14.54, 95% CI 1.40-151.13). Conclusion: Dietary pattern associated with high CRP level, including high intake of rice, liquor, fruit, tea and coffee and low intake of dark vegetables and juice, contributed to the increased risk of CI. The association between the consumption of seafood, sweet beverages, and alcohol and CI is yet to be established. However, they may be dietary contributing factors to inflammation in patients undergoing HD.