A four-in-one first-in-human study to assess safety, tolerability, pharmacokinetics, pharmacodynamics, and concentration-QTc relationship of HRS-1780, a selective non-steroidal mineralocorticoid receptor antagonist, in healthy men.

BACKGROUND: This first-in-human study evaluated HRS-1780, an oral selective non-steroidal mineralocorticoid receptor antagonist, in healthy men. RESEARCH DESIGN AND METHODS: In single ascending dose (SAD) part, ten participants for each dose cohort (5, 10, 20, 40, 60, and 80 mg) were randomized (8:2) to HRS-1780 or placebo. In multiple ascending dose part, 12 participants for each dose (10, 20, and 40 mg) were randomized (9:3) to HRS-1780 or placebo once daily for 7 days. Primary endpoint was safety and tolerability. RESULTS: HRS-1780 was well-tolerated with all adverse events being mild. At steady state, median time to maximum concentration (Tmax) was 0.750 h and mean half-life was 1.76-1.96 h. High-fat/high-calorie meal prolonged Tmax but did not affect exposure. Multiple dosing of HRS-1780 at 40 mg showed a decreasing trend in systolic blood pressure compared with placebo. Changes in plasma aldosterone and norepinephrine with HRS-1780 were higher compared to placebo. Upper bounds of two-sided 90% confidence interval of placebo-adjusted change-from-baseline QTcF were below 10 msec at the maximum concentration in SAD. The trial had limited sample size and short study duration. CONCLUSIONS: HRS-1780 had favorable safety and pharmacokinetics profiles and did not cause clinically meaningful QTcF prolongation. TRIAL REGISTRATION: : ClinicalTrials.gov (NCT05638126).

Network pharmacology and molecular docking analysis predict the mechanisms of Huangbai liniment in treating oral lichen planus.

This study explored the mechanism of Huangbai liniment (HB) for the treatment of oral lichen planus (OLP) through network pharmacology and molecular docking techniques. The study identified HB' active ingredients, therapeutic targets for OLP, and associated signaling pathways. The chemical composition of HB was screened using the HERB database. The disease targets of OLP were obtained through the GeneCards and OMIM databases. A protein-protein interactions network was constructed with the String platform. Topological analysis was performed using Cytoscape software to identify core targets. Gene ontology and Kyoto encyclopedia of genes and genomes pathway enrichment analysis were performed using the Hiplot database, and the active ingredients and core targets were verified by molecular docking. Date analysis showed that the active composition of HB in the treatment of OLP were quercetin, wogonin, kaempferol, and luteolin. This survey identified 10 potential therapeutic targets, including TNF, CXCL8, IL-6, IL1B, PIK3R1, ESR1, JUN, AKT1, PIK3CA, and CTNNB1. Molecular docking revealed stable interactions between OLP' key targets and HB. These key targets were predominantly involved in the PI3K-Akt signaling pathway, AGE-RAGE signaling pathway, TNF signaling pathway, and HIF-1 signaling pathway. HB plays a crucial role in the treatment of OLP, acting on multiple targets and pathways, particularly the PI3K-Akt signaling pathway. It regulated biological processes like the proliferation of epithelial cells and lymphocytes and mediates the expression of transcription factors, cytokines, and chemokines. Therefore, this study provides a theoretical basis for the clinical trial and application of HB in the therapy of OLP.

Long noncoding RNA H19 knockdown promotes angiogenesis via IMP2 after ischemic stroke.

AIMS: This study aimed to explore the effects of long noncoding RNA (lncRNA) H19 knockdown on angiogenesis and blood-brain barrier (BBB) integrity following cerebral ischemia/reperfusion (I/R) and elucidate their underlying regulatory mechanisms. METHODS: A middle cerebral artery occlusion/reperfusion model was used to induce cerebral I/R injury. The cerebral infarct volume and neurological impairment were assessed using 2,3,5-triphenyl-tetrazolium chloride staining and neurobehavioral tests, respectively. Relevant proteins were evaluated using western blotting and immunofluorescence staining. Additionally, a bioinformatics website was used to predict the potential target genes of lncRNA H19. Finally, a rescue experiment was conducted to confirm the potential mechanism. RESULTS: Silencing of H19 significantly decreased the cerebral infarct volume, enhanced the recovery of neurological function, mitigated BBB damage, and stimulated endothelial cell proliferation following ischemic stroke. Insulin-like growth factor 2 mRNA-binding protein 2 (IMP2) is predicted to be a potential target gene for lncRNA H19. H19 knockdown increased IMP2 protein expression and IMP2 inhibition reversed the protective effects of H19 inhibition. CONCLUSION: Downregulation of H19 enhances angiogenesis and mitigates BBB damage by regulating IMP2, thereby alleviating cerebral I/R injury.

N-terminal truncated trehalose-6-phosphate synthase 1 gene (△NIbTPS1) enhances the tolerance of sweet potato to abiotic stress.

Sweet potato [Ipomoea batatas (L.) Lam], the crop with the seventh highest annual production globally, is susceptible to various adverse environmental influences, and the study of stress-resistant genes is important for improving its tolerance to abiotic stress. The enzyme trehalose-6-phosphate synthase (TPS) is indispensable in the one pathway for synthesizing trehalose in plants. TPS is known to participate in stress response in plants, but information on TPS in sweet potato is limited. This study produced the N-terminal truncated IbTPS1 gene (△NIbTPS1) overexpression lines of Arabidopsis thaliana and sweet potato. Following salt and mannitol-induced drought treatment, the germination rate, root elongation, and fresh weight of the transgenic A. thaliana were significantly higher than that in the wild type. Overexpression of △NIbTPS1 elevated the photosynthetic efficiency (Fv/Fm) and the activity of superoxide dismutase, peroxidase, catalase, and ascorbate peroxidase in sweet potato during drought and salt treatments, while reducing malondialdehyde and O2∙- contents, although expression of the trehalose-6-phosphate phosphatase gene IbTPP and trehalose concentrations were not affected. Thus, overexpressing the △NIbTPS1 gene can improve the stress tolerance of sweet potato to drought and salt by enhancing the photosynthetic efficiency and antioxidative enzyme system. These results will contribute to understand the functions of the △NIbTPS1 gene and trehalose in the response mechanism of higher plants to abiotic stress.

Chromodomain Y-like (CDYL) inhibition ameliorates acute kidney injury in mice by regulating tubular pyroptosis.

Acute kidney injury (AKI) is a common disease, but lacking effective drug treatments. Chromodomain Y-like (CDYL) is a kind of chromodomain protein that has been implicated in transcription regulation of autosomal dominant polycystic kidney disease. Benzo[d]oxazol-2(3H)-one derivative (compound D03) is the first potent and selective small-molecule inhibitor of CDYL (KD = 0.5 µM). In this study, we investigated the expression of CDYL in three different models of cisplatin (Cis)-, lipopolysaccharide (LPS)- and ischemia/reperfusion injury (IRI)-induced AKI mice. By conducting RNA sequencing and difference analysis of kidney samples, we found that tubular CDYL was abnormally and highly expressed in injured kidneys of AKI patients and mice. Overexpression of CDYL in cisplatin-induced AKI mice aggravated tubular injury and pyroptosis via regulating fatty acid binding protein 4 (FABP4)-mediated reactive oxygen species production. Treatment of cisplatin-induced AKI mice with compound D03 (2.5 mg·kg-1·d-1, i.p.) effectively attenuated the kidney dysfunction, pathological damages and tubular pyroptosis without side effects on liver or kidney function and other tissue injuries. Collectively, this study has, for the first time, explored a novel aspect of CDYL for tubular epithelial cell pyroptosis in kidney injury, and confirmed that inhibition of CDYL might be a promising therapeutic strategy against AKI.

Linear-Array Endoscopic Ultrasound and Narrow-Band Imaging Measure the Invasion Depth of Nonpedunculated Rectal Lesions With Comparable Accuracy Based on a Randomized Controlled Trial.

INTRODUCTION: Linear-array endoscopic ultrasound (EUS) and narrow-band imaging (NBI) are both used to estimate the invasion depth of nonpedunculated rectal lesions (NPRLs). However, it is unclear which procedure is more accurate. This randomized controlled trial aimed to compare the diagnostic accuracy of linear EUS and NBI for estimating the invasion depth of NPRLs. METHODS: This study is a single-center, randomized, tandem trial. Eligible patients with NPRLs were randomly assigned to A group (assessment with EUS followed by NBI) or B group (assessment with NBI followed by EUS). The invasion depth of each lesion was independently measured by each procedure and categorized as mucosal to slight submucosal (M-SM s , invasion depth <1,000 µm) or deep submucosal (SM d , invasion depth ≥1,000 µm) invasion, with postoperative pathology as the standard of measurement. The primary outcome was diagnostic accuracy, and secondary outcomes included sensitivity, specificity, and procedure time. RESULTS: Eighty-six patients with NPRLs were enrolled, and 79 patients were finally analyzed, including 39 cases in the A group and 40 cases in the B group. Comparable diagnostic accuracies were observed between EUS and NBI (96.2% vs 93.7%, P = 0.625). EUS identified lesions with deep submucosal invasion with 81.8% sensitivity while that of NBI was 63.6% ( P = 0.500). The specificity of both EUS and NBI was 98.5%. The procedure time was also similar between EUS and NBI (5.90 ± 3.44 vs 6.4 ± 3.94 minutes, P = 0.450). Furthermore, the combined use of EUS and NBI did not improve diagnostic accuracy compared with EUS or NBI alone (94.9% vs 96.2% vs 93.7%, P = 0.333). DISCUSSION: Linear EUS and NBI measure the invasion depth of NPRLs with comparable accuracy. The combination of the 2 methods does not improve the diagnostic accuracy. Single NBI should be preferred, considering its simplicity and convenience in clinical practice.

Alteration of N6-methyladenosine modification profiles in the neutrophilic RNAs following ischemic stroke.

BACKGROUND: N6-methyladenosine (m6A) is one of the most extensive RNA methylation modifications in eukaryotes and participates in the pathogenesis of numerous diseases including ischemic stroke. Peripheral blood neutrophils are forerunners after ischemic brain injury and exert crucial functions. This study aims to explore the transcriptional profiles of m6A modification in neutrophils of patients with ischemic stroke. RESULTS: We found that the expression levels of m6A regulators FTO and YTHDC1 were notably decreased in the neutrophils following ischemic stroke, and FTO expression was negatively correlated with neutrophil counts and neutrophil-to-lymphocyte ratio (NLR). The m6A mRNA&lncRNA epigenetic transcriptome microarray identified 416 significantly upregulated and 500 significantly downregulated mRNA peaks in neutrophils of ischemic stroke patients. Moreover, 48 mRNAs and 18 lncRNAs were hypermethylated, and 115 mRNAs and 29 lncRNAs were hypomethylated after cerebral ischemia. Gene ontology (GO) analysis identified that these m6A-modified mRNAs were primarily enriched in calcium ion transport, long-term synaptic potentiation, and base-excision repair. The signaling pathways involved were EGFR tyrosine kinase inhibitor resistance, ErbB, and base excision repair signaling pathway. MeRIP-qPCR validation results showed that NRG1 and GDPD1 were significantly hypermethylated, and LIG1, CHRND, lncRNA RP11-442J17.2, and lncRNA RP11-600P1.2 were significantly hypomethylated after cerebral ischemia. Moreover, the expression levels of major m6A regulators Mettl3, Fto, Ythdf1, and Ythdf3 were obviously declined in the brain and leukocytes of post-stroke mouse models. CONCLUSION: This study explored the RNA m6A methylation pattern in the neutrophils of ischemic stroke patients, indicating that it is an intervention target of epigenetic regulation in ischemic stroke.

Cysteine-induced growth of jagged gold bipyramids from penta-twinned nanorod seeds.

The understanding on the growth mechanism of complex gold nanostructures both experimentally and theoretically can guide their design and fabrication toward various applications. In this work, we report a cysteine-directed overgrowth of penta-twinned nanorod seeds into jagged gold bipyramids with discontinuous stepped {hhk} facets. By monitoring the growth process, we find that {hhk} facets with large k/h values (∼7) are formed first at two ends of the nanorods, followed by the protrusion of the middle section exposing {hhk} facets with smaller indices (k/h ∼ 2-3). Molecular dynamics simulations indicate that the strong adsorption of cysteine molecules on {110} facets is likely responsible for the formation of stepped {hhk} facets, and the stronger adsorption of cysteine molecules on {hhk} facets with smaller k/h compared to that on {hhk} facets with larger k/h is a possible cause of the discontinuity of {hhk} facets at the middle of gold bipyramids. The obtained jagged gold bipyramids display large field enhancement under illumination due to their sharp nanostructures, demonstrating their application potentials in surface-enhanced spectroscopy and catalysis.

Overexpression of sweetpotato glutamylcysteine synthetase (IbGCS) in Arabidopsis confers tolerance to drought and salt stresses.

Various environmental stresses induce the production of reactive oxygen species (ROS), which have deleterious effects on plant cells. Glutathione (GSH) is an antioxidant used to counteract reactive oxygen species. Glutathione is produced by glutamylcysteine synthetase (GCS) and glutathione synthetase (GS). However, evidence for the GCS gene in sweetpotato remains scarce. In this study, the full-length cDNA sequence of IbGCS isolated from sweetpotato cultivar Xu18 was 1566 bp in length, which encodes 521 amino acids. The qRT-PCR analysis revealed a significantly higher expression of the IbGCS in sweetpotato flowers, and the gene was induced by salinity, abscisic acid (ABA), drought, extreme temperature and heavy metal stresses. The seed germination rate, root elongation and fresh weight were promoted in T3 Arabidopsis IbGCS-overexpressing lines (OEs) in contrast to wild type (WT) plants under mannitol and salt stresses. In addition, the soil drought and salt stress experiment results indicated that IbGCS overexpression in Arabidopsis reduced the malondialdehyde (MDA) content, enhanced the levels of GCS activity, GSH and AsA content, and antioxidant enzyme activity. In summary, overexpressing IbGCS in Arabidopsis showed improved salt and drought tolerance.

Inhibition of ACSS2-mediated histone crotonylation alleviates kidney fibrosis via IL-1ß-dependent macrophage activation and tubular cell senescence.

Histone lysine crotonylation (Kcr), as a posttranslational modification, is widespread as acetylation (Kac); however, its roles are largely unknown in kidney fibrosis. In this study, we report that histone Kcr of tubular epithelial cells is abnormally elevated in fibrotic kidneys. By screening these crotonylated/acetylated factors, a crotonyl-CoA-producing enzyme ACSS2 (acyl-CoA synthetase short chain family member 2) is found to remarkably increase histone 3 lysine 9 crotonylation (H3K9cr) level without influencing H3K9ac in kidneys and tubular epithelial cells. The integrated analysis of ChIP-seq and RNA-seq of fibrotic kidneys reveal that the hub proinflammatory cytokine IL-1ß, which is regulated by H3K9cr, play crucial roles in fibrogenesis. Furthermore, genetic and pharmacologic inhibition of ACSS2 both suppress H3K9cr-mediated IL-1ß expression, which thereby alleviate IL-1ß-dependent macrophage activation and tubular cell senescence to delay renal fibrosis. Collectively, our findings uncover that H3K9cr exerts a critical, previously unrecognized role in kidney fibrosis, where ACSS2 represents an attractive drug target to slow fibrotic kidney disease progression.

Anticyanobacterial effect of p-coumaric acid on Limnothrix sp. determined by proteomic and metabolomic analysis.

Regulating photosynthetic machinery is a powerful but challenging strategy for selectively inhibiting bloom-forming cyanobacteria, in which photosynthesis mainly occurs in thylakoids. P-coumaric acid (p-CA) has several biological properties, including free radical scavenging and antibacterial effects, and studies have shown that it can damage bacterial cell membranes, reduce chlorophyll a in cyanobacteria, and effectively inhibit algal growth at concentrations exceeding 0.127 g/L. Allelochemicals typically inhibit cyanobacteria by inhibiting photosynthesis; however, research on inhibiting harmful algae using phenolic acids has focused mainly on their inhibitory and toxic effects and metabolite levels, and the molecular mechanism by which p-CA inhibits photosynthesis remains unclear. Thus, we examined the effect of p-CA on the photosynthesis of Limnothrix sp. in detail. We found that p-CA inhibits algal growth and damages photosynthesis-related proteins in Limnothrix sp., reduces carotenoid and allophycocyanin levels, and diminishes the actual quantum yield of Photosystem II (PSII). Moreover, p-CA significantly altered algal cell membrane protein systems, and PSII loss resulting from p-CA exposure promoted reactive oxygen species production. It significantly altered algae cell membrane protein systems. Finally, p-CA was found to be environmentally nontoxic; 80 % of 48-h-old Daphnia magna larvae survived when exposed to 0.15 g/L p-CA. These findings provide insight into the mechanism of cyanobacterial inhibition by p-CA, providing a more practical approach to controlling harmful algal blooms.

The development of variable system-based internet of things for the solar greenhouse and its application in lettuce.

The east-west ridge orientation has recently become an important agronomic method to improve mechanization in solar greenhouses. However, these ridge orientation changes shape differences between different ridges in crop water consumption, and there is a lack of research on the regulation and adaptation of water consumption. Therefore, this study introduces a variable irrigation decision-making method based on the Internet of Things management and control system for an east-west ridge orientation. To replenish water on demand, this study seting the variable irrigation decision-making (VRI) methods and traditional average irrigation decision-making (URI) methods in the system, and lettuce cultivation experiments were conducted to verify the effectiveness of the model and system. The results show that the difference of accumulated photosynthetically active radiation is the most significant between different ridges of the east-west ridge orientation, and the coefficient of variation is 43.77 %, which can be used as an activating factor for VRI methods. The irrigation water consumption, yield, water-use efficiencies, and irrigation water utilization of lettuce at different levels of irrigation were 307.12 L/m2, 5854.07 kg·ha-1, 1391.47 kg·ha-1·mm-1, and 7.63 kg·cm-3, respectively. Compared with the URI methods, the VRI method saved 10.02 % of water, increased yield by 9 %, and enhanced water use efficiency and irrigation water use efficiency by 12 % and 21.32 %, respectively. This study provides a new approach for improving crop production efficiency under an east-west ridge orientation.

Transformer guided self-adaptive network for multi-scale skin lesion image segmentation.

BACKGROUND: In recent years, skin lesion has become a major public health concern, and the diagnosis and management of skin lesions depend heavily on the correct segmentation of the lesions. Traditional convolutional neural networks (CNNs) have demonstrated promising results in skin lesion segmentation, but they are limited in their ability to capture distant connections and intricate features. In addition, current medical image segmentation algorithms rarely consider the distribution of different categories in different regions of the image and do not consider the spatial relationship between pixels. OBJECTIVES: This study proposes a self-adaptive position-aware skin lesion segmentation model SapFormer to capture global context and fine-grained detail, better capture spatial relationships, and adapt to different positional characteristics. The SapFormer is a multi-scale dynamic position-aware structure designed to provide a more flexible representation of the relationships between skin lesion characteristics and lesion distribution. Additionally, it increases skin lesion segmentation accuracy and decreases incorrect segmentation of non-lesion areas. INNOVATIONS: SapFormer designs multiple hybrid transformers for multi-scale feature encoding of skin images and multi-scale positional feature sensing of the encoded features using a transformer decoder to obtain fine-grained features of the lesion area and optimize the regional feature distribution. The self-adaptive feature framework, built upon the transformer decoder module, dynamically and automatically generates parameterizations with learnable properties at different positions. These parameterizations are derived from the multi-scale encoding characteristics of the input image. Simultaneously, this paper utilizes the cross-attention network to optimize the features of the current region according to the features of other regions, aiming to increase skin lesion segmentation accuracy. MAIN RESULTS: The ISIC-2016, ISIC-2017, and ISIC-2018 datasets for skin lesions are used as the basis for the experiment. On these datasets, the proposed model has accuracy values of 97.9 %, 94.3 %, and 95.7 %, respectively. The proposed model's IOU values are, in order, 93.2 %, 86.4 %, and 89.4 %. The proposed model's DSC values are 96.4 %, 92.6 %, and 94.3 %, respectively. All three metrics surpass the performance of the majority of state-of-the-art (SOTA) models. SapFormer's metrics on these datasets demonstrate that it can precisely segment skin lesions. Notably, our approach exhibits remarkable noise resistance in non-lesion areas, while simultaneously conducting finer-grained regional feature extraction on the skin lesion image. CONCLUSIONS: In conclusion, the integration of a transformer-guided position-aware network into semantic skin lesion segmentation results in a notable performance boost. The ability of our proposed network to capture spatial relationships and fine-grained details proves beneficial for effective skin lesion segmentation. By enhancing lesion localization, feature extraction, quantitative analysis, and classification accuracy, the proposed segmentation model improves the diagnostic efficiency of skin lesion analysis on dermoscopic images. It assists dermatologists in making more accurate and efficient diagnoses, ultimately leading to better patient care and outcomes. This research paves the way for advances in diagnosing and treating skin lesions, promoting better understanding and decision-making in the clinical setting.

Application of Kirschner wire placement guided technology in paediatric supracondylar humerus fractures.

BACKGROUND: To analyze the clinical efficacy of K-wire placement guided technology in paediatric supracondylar humerus fractures. METHODS: A retrospective study was conducted in 105 patients who underwent closed reduction and percutaneous pinning surgeries in our hospital from June 2019 to August 2022. 54 patients treated with a assisted reduction fixation device to assist in closed reduction and percutaneous K-wire cross-fixation were allocated into the Non-guided group, and 51 patients with K-wire placement guided technology to guide K-wire placement were assigned into the Guided group. The operation duration, number of disposable K-wire placement, intraoperative fluoroscopy frequency, Baumann angle, carrying angle, fracture healing time and Flynn score of elbow joint function at the final follow-up were compared between two groups. The postoperative complications of two groups were recorded. RESULTS: There were significant differences between two groups in terms of operation duration, intraoperative fluoroscopy frequency, and disposable K-wire placement rate (p < 0. 05), while no significant differences of Baumann angle, carrying angle and the fracture healing time between two groups were observed (p > 0. 05). In the control group, ulnar nerve injury in 2 case, pin site infection in 4 cases, mild cubitus varus in 2 cases and loss of reduction in 4 cases were detected. In the study group, ulnar nerve injury in 1 case, pin site infection in 2 cases and loss of reduction in 1 case was observed. There was no significant difference in Flynn scores between two groups. CONCLUSION: K-wire placement guided technology is simple and convenient. The application of K-wire placement guided technology could relatively improved disposable K-wire placement rate, shorten the intraoperative fluoroscopy frequencies and reduce complication rates.

Metal-based nanoparticles in antibacterial application in biomedical field: Current development and potential mechanisms.

The rise in drug resistance in pathogenic bacteria greatly endangers public health in the post-antibiotic era, and drug-resistant bacteria currently pose a great challenge not only to the community but also to clinical procedures, including surgery, stent implantation, organ transplantation, and other medical procedures involving any open wound and compromised human immunity. Biofilm-associated drug failure, as well as rapid resistance to last-resort antibiotics, necessitates the search for novel treatments against bacterial infection. In recent years, the flourishing development of nanotechnology has provided new insights for exploiting promising alternative therapeutics for drug-resistant bacteria. Metallic agents have been applied in antibacterial usage for several centuries, and the functional modification of metal-based biomaterials using nanotechnology has now attracted great interest in the antibacterial field, not only for their intrinsic antibacterial nature but also for their ready on-demand functionalization and enhanced interaction with bacteria, rendering them with good potential in further translation. However, the possible toxicity of MNPs to the host cells and tissue still hinders its application, and current knowledge on their interaction with cellular pathways is not enough. This review will focus on recent advances in developing metallic nanoparticles (MNPs), including silver, gold, copper, and other metallic nanoparticles, for antibacterial applications, and their potential mechanisms of interaction with pathogenic bacteria as well as hosts.

Caffeoylquinic acids protect against alcoholic liver injury and rare C10 acetylenic acids from Erigeron breviscapus.

Three new compounds (1-2, 4) along with ten known ones (3, 5-13), were isolated from the whole plant of Erigeron breviscapus. Compounds 1 and 2, two novel C10 acetylenic acids and compound 4, a jasmone glucoside were elucidated by the detailed analysis of 1D and 2D NMR, HRESIMS spectra, and experimental and calculated electronic circular dichroism (ECD). Compounds 1-3 represent the first example of acetylenic acids incorporating C10 skeleton from E. breviscapus. In addition, the antioxidant effects of all compounds were evaluated by ferric reducing power, 2,2'-Azinobis-(3-ethylbenzthiazoline-6-sulphonate acid) (ABTS) and 2.2-Diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assays. Our results indicated the significant antioxidant activity of caffeoylquinic acids. Additionally, compounds 10-11 and 13 played protective role on alcoholic liver injury cells in a dose-dependent manner.

All-Arthroscopic Glenoid Bone Augmentation Using Iliac Crest Autograft Procedure for Recurrent Anterior Shoulder Instability: Button Fixation Is a Feasible and Satisfactory Alternative to Screw Fixation.

PURPOSE: To investigate the efficacy of all-arthroscopic glenoid bone augmentation surgery using the iliac crest autograft procedure. Furthermore, we sought to compare the clinical and radiographic outcomes of using screw versus button fixation, in patients with recurrent anterior shoulder instability. METHODS: Between 2015 and 2019, 134 shoulders with persistent instability were surgically treated with an arthroscopically placed autologous iliac crest bone graft transfer procedure. Preoperative and postoperative clinical follow-up data were evaluated using the range of motion, and the Walch-Duplay, American Shoulder and Elbow Society, and Rowe scores. Radiologic assessment on 3-dimensional computed tomography scans was performed preoperatively, immediately after surgery, as well as postoperatively, at 3 months, 6 months, 1 year, and at the final follow-up stage. Graft positions, healing, and resorption were evaluated from postoperative images. RESULTS: This study included 102 patients who underwent arthroscopic iliac crest bone grafting procedure with 2 screws fixation (n = 37; group 1) and 2 button fixation (n = 65; group 2). The mean follow-up period was 37 months. There were no significant differences between groups in terms of clinical scores, shoulder motion range, graft healing, or graft positions on computed tomography scans (P>.05). In group 1, 1 patient showed mechanical irritation and persistent pain around the screw insertion site, being treated through the arthroscopic removal of the screws. The average postoperative bony resorption percentages were 20.3% and 11.2% at 6 months, and 32.4% and 19.3% at 12 months, in group 1 and group 2, respectively. A statistically significant difference was detected between the two groups (P<.05). CONCLUSIONS: In the arthroscopic iliac crest bone grafting procedure for the treatment of chronic osseous anterior shoulder instability, excellent functional results were obtained after both button fixation and screw fixation techniques. In addition, less graft resorption and no hardware-related complications were detected with suture button fixation technique. LEVEL OF EVIDENCE: Level III, retrospective comparative therapeutic trial.

Knockdown of JMJD3 ameliorates cigarette smoke extract-triggered bronchial epithelial cell injury via ACSL4-dependent ferroptosis.

Chronic obstructive pulmonary disease (COPD), a heterogeneity of chronic respiratory disease pattern, presents considerable prevalence and mortality. We aimed to explore the role and mechanisms of Jumonji domain-containing protein-3 (JMJD3) in COPD. The viability and JMJD3 expression in human bronchial epithelial cell line BEAS-2B were respectively assayed by CCK-8 assay and Western blot following stepwise exposure to increasing concentrations of cigarette smoke extract (CSE). After JMJD3 was silenced and acyl-CoA synthetase long-chain family member 4 (ACSL4) was overexpressed in CSE-treated BEAS-2B cells, cell viability, cytotoxicity, oxidative stress and total iron level were estimated using kits. ELISA estimated inflammatory levels. DCFH-DA probe and BODIPY 581/591 C11 probe were exposed to assess ROS production and lipid peroxidation. Western blot tested the expressions of ferroptosis-associated proteins. Besides, H3K27me3 and ACSL4 expressions were tested by Western blot and immunofluorescence staining. In CSE-induced BEAS-2B cells, JMJD3 expression was increased and deletion of JMJD3 improved cell viability, reduced LDH release, mitigated inflammation, oxidative stress and inhibited ferroptosis. Moreover, JMJD3 interference raised H3K27me3 expression whereas lessened ACSL4 expression in CSE-treated BEAS-2B cells. CSE exposure reduced the abundance of ACSL4 in H3K27me3 antibody. Further ACSL4 elevation reversed the impacts of JMJD3 silencing on the damage of CSE-induced BEAS-2B cells. Collectively, JMJD3 depletion might suppress ferroptosis mediated by ACSL4 to alleviate CSE-triggered inflammation and oxidative stress in BEAS-2B cells.