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Preoperative prognostic nutritional index value as a predictive factor for postoperative delirium in older adult patients with hip fractures: a secondary analysis.
Mi, X, Jia, Y, Song, Y, Liu, K, Liu, T, Han, D, Yang, N, Wang, G, Guo, X, Yuan, Y, et al
BMC geriatrics. 2024;(1):21
Abstract
BACKGROUND Malnutrition is a common geriatric syndrome and can be targeted preoperatively to decrease the risk of postoperative delirium (POD) in older adult patients. To analyze the value of the prognostic nutritional index (PNI) to predict the incidence of POD in older adult patients with hip fractures. METHODS This was a prospective, observational, cohort study of older adult patients with hip fractures. Preoperative PNI was calculated as 10 × serum albumin (g/dL) + 0.005 × total lymphocyte count (/μL) using preoperative laboratory results. Patients were divided into POD and non-POD groups using the Confusion Assessment Method (CAM). The risk factors associated with POD as well as the relationship between PNI values and the incidence of POD were analyzed using univariate and multivariate logistic regression analyses. The predictive value of PNI for POD was assessed using receiver operating characteristic curve analysis. RESULTS In this cohort of 369 patients who underwent hip fracture surgery, 67 patients (18.2%) were diagnosed with POD by the CAM results. Low PNI increased the risk of POD (odds ratio (OR) = 0.928, 95% confidence interval (CI): 0.864-0.997). General anesthesia (OR = 2.307, 95% CI: 1.279-4.162) and Mini-Mental State Examination (MMSE) score (OR = 0.956, 95% CI: 0.920-0.994) were also identified as risk factors for POD. Receiver operating characteristic curve analysis suggested that PNI combined with the anesthetic method and MMSE score may be used as a potential predictive indicator of POD after hip fracture surgery. CONCLUSION Preoperative PNI value is related to POD in older adult patients with hip fractures. TRIAL REGISTRATION This secondary analysis study was approved by the Peking University Third Hospital Medical Science Research Ethics Committee (approval No. M2022578) and registered in the Chinese Clinical Trial Registry (ChiCTR2300070569).
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Recent advances in the treatment and delivery system of diabetic retinopathy.
Wang, Z, Zhang, N, Lin, P, Xing, Y, Yang, N
Frontiers in endocrinology. 2024;:1347864
Abstract
Diabetic retinopathy (DR) is a highly tissue-specific neurovascular complication of type 1 and type 2 diabetes mellitus and is among the leading causes of blindness worldwide. Pathophysiological changes in DR encompass neurodegeneration, inflammation, and oxidative stress. Current treatments for DR, including anti-vascular endothelial growth factor, steroids, laser photocoagulation, and vitrectomy have limitations and adverse reactions, necessitating the exploration of novel treatment strategies. This review aims to summarize the current pathophysiology, therapeutic approaches, and available drug-delivery methods for treating DR, and discuss their respective development potentials. Recent research indicates the efficacy of novel receptor inhibitors and agonists, such as aldose reductase inhibitors, angiotensin-converting enzyme inhibitors, peroxisome proliferator-activated receptor alpha agonists, and novel drugs in delaying DR. Furthermore, with continuous advancements in nanotechnology, a new form of drug delivery has been developed that can address certain limitations of clinical drug therapy, such as low solubility and poor penetration. This review serves as a theoretical foundation for future research on DR treatment. While highlighting promising therapeutic targets, it underscores the need for continuous exploration to enhance our understanding of DR pathogenesis. The limitations of current treatments and the potential for future advancements emphasize the importance of ongoing research in this field.
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Mushroom consumption and cardiometabolic health outcomes in the general population: a systematic review.
Hong, JY, Kim, MK, Yang, N
Nutrition research and practice. 2024;(2):165-179
Abstract
BACKGROUND/OBJECTIVES Mushroom consumption, rich in diverse nutrients and bioactive compounds, is suggested as a potential significant contributor to preventing cardiometabolic diseases (CMDs). This systematic review aimed to explore the association between mushrooms and cardiometabolic health outcomes, utilizing data from prospective cohort studies and clinical trials focusing on the general population, with mushrooms themselves as a major exposure. SUBJECTS/METHODS All original articles, published in English until July 2023, were identified through searches on PubMed, Ovid-Embase, and google scholar. Of 1,328 studies, we finally selected 5 prospective cohort studies and 4 clinical trials. RESULTS Existing research is limited, typically consisting of 1 to 2 studies for each CMD and cardiometabolic condition. Examination of articles revealed suggestive associations in some cardiometabolic conditions including blood glucose (both fasting and postprandial), high-density lipoprotein cholesterol related indices, high-sensitivity C-reactive protein, and obesity indices (body weight, body mass index, and waist circumference). However, mushroom consumption showed no association with the mortality and morbidity of cardiovascular diseases, stroke, and type 2 diabetes, although there was a potentially beneficial connection with all cause-mortality, hyperuricemia, and metabolic syndrome. CONCLUSION Due to the scarcity of available studies, drawing definitive conclusions is premature. Further comprehensive investigations are needed to clarify the precise nature and extent of this relationship before making conclusive recommendations for the general population.
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Novel NARS2 variants in a patient with early-onset status epilepticus: case study and literature review.
Yang, N, Chen, L, Zhang, Y, Wu, X, Hao, Y, Yang, F, Yang, Z, Liang, J
BMC pediatrics. 2024;(1):96
Abstract
BACKGROUND NARS2 as a member of aminoacyl-tRNA synthetases was necessary to covalently join a specific tRNA to its cognate amino acid. Biallelic variants in NARS2 were reported with disorders such as Leigh syndrome, deafness, epilepsy, and severe myopathy. CASE PRESENTATION Detailed clinical phenotypes were collected and the NARS2 variants were discovered by whole exome sequencing and verified by Sanger sequencing. Additionally, 3D protein structure visualization was performed by UCSF Chimera. The proband in our study had early-onset status epilepticus with abnormal EEG and MRI results. She also performed global developmental delay (GDD) and myocardial dysfunction. Next-generation sequencing (NGS) and Sanger sequencing revealed compound heterozygous missense variants [NM_024678.6:exon14: c.1352G > A(p.Arg451His); c.707T > C(p.Phe236Ser)] of the NARS2 gene. The proband develops refractory epilepsy with GDD and hyperlactatemia. Unfortunately, she finally died for status seizures two months later. CONCLUSION We discovered two novel missense variants of NARS2 in a patient with early-onset status epilepticus and myocardial dysfunction. The NGS enables the patient to be clearly diagnosed as combined oxidative phosphorylation deficiency 24 (COXPD24, OMIM616,239), and our findings expands the spectrum of gene variants in COXPD24.
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Manganese molybdate nanodots with dual amplification of STING activation for "cycle" treatment of metalloimmunotherapy.
Lei, H, Li, Q, Li, G, Wang, T, Lv, X, Pei, Z, Gao, X, Yang, N, Gong, F, Yang, Y, et al
Bioactive materials. 2024;:53-62
Abstract
Certain types of cationic metal ions, such as Mn2+ are able to activate immune functions via the stimulator of interferon genes (STING) pathway, showing potential applications in eliciting antitumor immunity. How anionic ions interact with immune cells remains largely unknown. Herein, selecting from a range of cationic and anionic ions, we were excited to discover that MoO42- could act as a cGAS-STING agonist and further confirmed the capability of Mn2+ to activate the cGAS-STING pathway. Inspired by such findings, we synthesized manganese molybdate nanoparticles with polyethylene glycol modification (MMP NDs) for cancer metalloimmunotherapy. Meanwhile, MMP NDs could consume glutathione (GSH) over-expressed in tumors and induce ferroptosis owing to high-valence Mo and Mn to elicit tumor-specific immune responses, which was further amplified by MMP-triggered the cGAS-STING activation. In turn, activated CD8+ T cells to secrete high levels of interferon γ (IFN-γ) and reduced GPX4 expression in tumor cells to trigger ferroptosis-specific lipid peroxidation, which constituted a "cycle" of therapy. As a result, the metalloimmunotherapy with systemic administration of MMP NDs offered a remarkable tumor inhibition effect for a variety of tumor models. Our work for the first time discovered the ability of anionic metal ions to activate the immune system and rationally designed bimetallic oxide nanostructures as a multifunctional therapeutic nanoplatform for tumor immunotherapy.
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PCDH8 is a novel prognostic biomarker in thyroid cancer and promotes cell proliferation and viability.
Yang, R, Yang, N, Yin, P, Xue, Z, Sun, F, Fan, R, Liang, J, Lv, X, Wu, S, Sun, L
Functional & integrative genomics. 2024;(2):35
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Abstract
Protocadherin 8 (PCDH8), a calcium-dependent transmembrane protein in the protocadherin family, regulates cell adhesion and signal transduction. While some studies have provided indirect evidence that PCDH8 has cancer-promoting properties, this association is controversial. In particular, its involvement in thyroid cancer (THCA) remains unclear. We aimed to elucidate the role of PCDH8 in THCA using bioinformatic analysis. Subsequently, the results were experimentally validated. The analysis conducted using the R programming language and online web tools explored PCDH8 expression levels, prognostic, and clinical implications, and its relationship with the tumor immune microenvironment in THCA. Furthermore, we examined the association between PCDH8 and co-expressed genes, highlighting their involvement in several biological processes relevant to THCA. The potential of PCDH8 as a therapeutic target for this pathology was also explored. Immunohistochemical (IHC) staining was performed on samples from 98 patients with THCA, and experimental validation was carried out. PCDH8 was significantly elevated in cancer tissues and associated with poor prognosis, several clinical factors, and immune cell and checkpoint abundance. Cox regression and survival analyses, together with Receiver Operating Curves (ROC) indicated that PCDH8 was an independent prognostic factor for THCA. Furthermore, PCDH8 impacts cell viability and proliferation, promoting tumorigenesis. Also, it influences tumor cell sensitivity to various drugs. Thus, PCDH8 might be a potential therapeutic target for THCA. IHC, cell culture, MTT, and colony formation experiments further confirmed our findings. This analysis provided insights into the potential carcinogenic role of PCDH8 in THCA, as it impacts cell viability and proliferation. Thus, PCDH8 might play an important role in its prognosis, immune infiltration, and diagnosis.
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High hydrostatic pressure stimulates microbial nitrate reduction in hadal trench sediments under oxic conditions.
Yang, N, Lv, Y, Ji, M, Wu, S, Zhang, Y
Nature communications. 2024;(1):2473
Abstract
Hadal trenches are extreme environments situated over 6000 m below sea surface, where enormous hydrostatic pressure affects the biochemical cycling of elements. Recent studies have indicated that hadal trenches may represent a previously overlooked source of fixed nitrogen loss; however, the mechanisms and role of hydrostatic pressure in this process are still being debated. To this end, we investigate the effects of hydrostatic pressure (0.1 to 115 MPa) on the chemical profile, microbial community structure and functions of surface sediments from the Mariana Trench using a Deep Ocean Experimental Simulator supplied with nitrate and oxygen. We observe enhanced denitrification activity at high hydrostatic pressure under oxic conditions, while the anaerobic ammonium oxidation - a previously recognized dominant nitrogen loss pathway - is not detected. Additionally, we further confirm the simultaneous occurrence of nitrate reduction and aerobic respiration using a metatranscriptomic dataset from in situ RNA-fixed sediments in the Mariana Trench. Taken together, our findings demonstrate that hydrostatic pressure can influence microbial contributions to nitrogen cycling and that the hadal trenches are a potential nitrogen loss hotspot. Knowledge of the influence of hydrostatic pressure on anaerobic processes in oxygenated surface sediments can greatly broaden our understanding of element cycling in hadal trenches.
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In vitro and in vivo evaluation of iRoot BP Plus as a coronal sealing material for regenerative endodontic procedures.
Yang, N, Yang, W, Shen, R, Zhang, S, Ma, T, Liu, Y
Clinical oral investigations. 2024;(1):70
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Abstract
OBJECTIVES To investigate in vitro effects of a nanoparticle bioceramic material, iRoot BP Plus, on stem cells from apical papilla (SCAP) and in vivo capacity to induce pulp-dentin complex formation. MATERIALS AND METHODS The sealing ability of iRoot BP Plus was measured via scanning electron microscopy (SEM). SCAP were isolated and treated in vitro by iRoot BP Plus conditioned medium, with mineral trioxide aggregate (MTA) conditioned medium and regular medium used as controls, respectively. Cell proliferation was assessed by BrdU labeling and MTT assay and cell migration was evaluated with wound healing and transwell assays. Osteo/odontogenic potential was evaluated by Alizarin red S staining and qPCR. Pulp-dentin complex formation in vivo was assessed by a tooth slice subcutaneous implantation model. RESULTS iRoot BP Plus was more tightly bonded with the dentin. There was no difference in SCAP proliferation between iRoot BP Plus and control groups (P > 0.05). iRoot BP Plus had a greater capacity to elevated cell migration (P < 0.05) and osteo/odontogenic marker expression and mineralization nodule formation of SCAP compared with MTA groups (P < 0.05). Furthermore, the new continuous dentine layer and pulp-like tissue was observed in the iRoot BP Plus group in vivo. CONCLUSIONS iRoot BP Plus showed excellent sealing ability, promoted the migration and osteo/odontogenesis of SCAP and induced pulp-dentin complex formation without affecting the cell proliferation, which indicated iRoot BP Plus was a promising coronal sealing material in REPs. CLINICAL RELEVANCE The coronal sealing materials play crucial roles for the outcomes of REPs. This study showed that iRoot BP Plus has good coronal sealing and promote pulp-dentin complex formation compared with MTA, providing experimental evidences for the clinical application of iRoot BP Plus as a promising coronal seal material in REPs.
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Uremic toxins mediate kidney diseases: the role of aryl hydrocarbon receptor.
Xie, H, Yang, N, Yu, C, Lu, L
Cellular & molecular biology letters. 2024;(1):38
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Aryl hydrocarbon receptor (AhR) was originally identified as an environmental sensor that responds to pollutants. Subsequent research has revealed that AhR recognizes multiple exogenous and endogenous molecules, including uremic toxins retained in the body due to the decline in renal function. Therefore, AhR is also considered to be a uremic toxin receptor. As a ligand-activated transcriptional factor, the activation of AhR is involved in cell differentiation and senescence, lipid metabolism and fibrogenesis. The accumulation of uremic toxins in the body is hazardous to all tissues and organs. The identification of the endogenous uremic toxin receptor opens the door to investigating the precise role and molecular mechanism of tissue and organ damage induced by uremic toxins. This review focuses on summarizing recent findings on the role of AhR activation induced by uremic toxins in chronic kidney disease, diabetic nephropathy and acute kidney injury. Furthermore, potential clinical approaches to mitigate the effects of uremic toxins are explored herein, such as enhancing uremic toxin clearance through dialysis, reducing uremic toxin production through dietary interventions or microbial manipulation, and manipulating metabolic pathways induced by uremic toxins through controlling AhR signaling. This information may also shed light on the mechanism of uremic toxin-induced injury to other organs, and provide insights into clinical approaches to manipulate the accumulated uremic toxins.
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Comprehensive Investigation on Associations between Dietary Intake and Blood Levels of Fatty Acids and Colorectal Cancer Risk.
Lu, Y, Li, D, Wang, L, Zhang, H, Jiang, F, Zhang, R, Xu, L, Yang, N, Dai, S, Xu, X, et al
Nutrients. 2023;(3)
Abstract
BACKGROUND Increasingly, studies have discovered that different fatty acids (Fas) are linked to colorectal cancer (CRC) risk. METHODS We systematically searched Embase and Medline databases to identify eligible studies that examined the associations of different types of Fas with CRC risk. The effect estimates and their 95% confidence intervals (Cis) were pooled using a random-effects model. Subgroup and sensitivity analyses were performed to examine the robustness of the study findings. RESULTS This study evaluated the associations of 28 dietary and 18 blood Fas with CRC risk by summarizing the most updated evidence from 54 observational and four Mendelian Randomization (MR) studies. The present findings suggested that high dietary intake of eicosapentaenoic acid (EPA), docosahexanoic acid (DHA), and docosapentaenoic acid (DPA) are related to low risk of CRC, while the n-6/n-3 PUFA ratio and trans-FA are related to high risk of CRC. The summary of all cohort studies found that a high intake of SFA and DHA was a protective factor for CRC, and a high intake of the n-6/n-3 PUFA ratio was a risk factor for CRC. In the subgroup analysis of cancer subsites, we found that the dietary intake of linoleic acid (LA) and trans-FA are risk factors, while DPA is a protective factor for colon cancer. High dietary DHA intake was associated with a lower risk of rectal cancer, while the dietary n-6/n-3 PUFA ratio was associated with a higher risk of rectal cancer. Meta-analysis of blood FA levels showed a significant reverse association between blood pentadecanoic acid and CRC risk, whilst other blood Fas showed no significant association with CRC risk. All included MR studies showed that high plasma arachidonic acid (AA) is associated with increased CRC risk. CONCLUSIONS Current evidence on the dietary intake and blood levels of Fas in relation to CRC risk is less consistent. Future studies are needed to investigate how the metabolism of Fas contributes to CRC development.