Enhancing sustainability in medical product supply chains: The role of remanufacturing and government subsidies.

This study explores the impact of government subsidies on the production dynamics within the medical product supply chain, particularly focusing on the remanufacturing of medical goods. Amidst the backdrop of the COVID-19 pandemic, which has underscored the critical shortages in medical supplies, our research delves into the adoption of remanufacturing practices by medical product manufacturers as a strategic response to these shortages and environmental concerns. We investigate how government subsidies influence the production volumes of original manufacturers and remanufacturers and examine the competitive interplay between newly manufactured and remanufactured medical products. Through the development of three production game models-Scenario B (manufacturers produce both new and refurbished products), Scenario N (separate production of new and refurbished products by manufacturers and remanufacturers, respectively), and Scenario C (similar to Scenario N but includes a certification fee paid by remanufacturers to original manufacturers)-we analyze the strategies that could mitigate supply deficiencies during medical crises. Our findings indicate that the certification strategy (Scenario C) not only yields the highest total production of medical products but also offers a viable solution to enhance the sustainability of the entire medical production system by alleviating supply chain disruptions. Furthermore, we discuss the managerial implications of our results, emphasizing the potential of a joint remanufacturing strategy to stabilize the supply chain and foster environmental conservation. Lastly, we highlight our study's limitations and suggest future research directions, particularly concerning the variability in product quality and the reliance on government subsidies. This research contributes to a nuanced understanding of green remanufacturing within the pharmaceutical supply chain, offering insights for manufacturers, remanufacturers, and policymakers aiming for sustainable industry practices.

MutaPT: A Multi-Task Pre-Trained Transformer for Classifying State of Disorders of Consciousness Using EEG Signal.

Deep learning (DL) has been demonstrated to be a valuable tool for classifying state of disorders of consciousness (DOC) using EEG signals. However, the performance of the DL-based DOC state classification is often challenged by the limited size of EEG datasets. To overcome this issue, we introduce multiple open-source EEG datasets to increase data volume and train a novel multi-task pre-training Transformer model named MutaPT. Furthermore, we propose a cross-distribution self-supervised (CDS) pre-training strategy to enhance the model's generalization ability, addressing data distribution shifts across multiple datasets. An EEG dataset of DOC patients is used to validate the effectiveness of our methods for the task of classifying DOC states. Experimental results show the superiority of our MutaPT over several DL models for EEG classification.

Identify the seasonal differences in water quality and pollution sources between river-connected and gate-controlled lakes in the Yangtze River basin.

The river-connected Dongting Lake (DT) and Poyang Lake (PY), and the gate-controlled Taihu Lake (TH) and Chaohu Lake (CH) are the four important lakes in the Yangtze River Basin. The comprehensive Water Quality Index (WQI), the Eutrophication Integrated Index (TLI(Σ)), and the Positive Matrix Factorization (PMF) model were employed to evaluate water quality and the contribution of pollution sources for these lakes. The results show that WQI for all lakes indicated generally good water quality, with DT scoring 73.52-86.18, the highest among them. During the wet season, the eutrophication degree of river-connected lake was medium, and that of gate-controlled lakes was high. The surface runoff and agricultural non-point sources are the main pollution sources for both types of lakes, but their impact is more pronounced in gate-controlled lakes during the wet season. The study provides evidence support for scientific understanding of water quality problems and management strategies in these areas.

NIR-Remote Selectively Triggered Buprenorphine Hydrochloride Release from Microneedle Patches for the Treatment of Neuropathic Pain.

Neuropathic pain is a prevalent form of intermittent chronic pain, affecting approximately 7-10% of the global population. However, the current clinical administration methods, such as injection and oral administration, are mostly one-time administration, which cannot achieve accurate control of pain degree and drug dose. Herein, we developed near-infrared (NIR) light-responsive microneedle patches (MNPs) to spatiotemporally control the drug dose released to treat neuropathic pain according to the onset state. The mechanism of action utilizes upconversion nanoparticles to convert NIR light into visible and ultraviolet light. This conversion triggers the rapid rotation of the azobenzene molecular motor in the mesoporous material, enabling the on-demand controlled release of a drug dose. Additionally, MNs are used to overcome the barrier of the stratum corneum in a minimally invasive and painless manner, effectively promoting the transdermal penetration of drug molecules. The effectiveness of these patches has been demonstrated through significant results. Upon exposure to NIR light for five consecutive cycles, with each cycle lasting 30 s, the patches achieved a precise release of 318 µg of medication. In a mouse model, maximum pain relief was observed within 1 h of one cycle of NIR light exposure, with the effects lasting up to 6 h. The same level of precise treatment efficacy was maintained for subsequent pain episodes with similar light exposure. The NIR-controlled drugs precision-released MNPs provide a novel paradigm for the treatment of intermittent neuropathic pain.

Culture and Awe: Understanding Awe as a Mixed Emotion.

Recent work is establishing awe as an important positive emotion that offers physical and psychological benefits. However, early theorizing suggests that awe's experience is often tinged with fear. How then, do we reconcile emergent positive conceptualizations of awe with its more fearful elements? We suggest that positive conceptualizations of awe may partially reflect modern Western experiences of this emotion, which make up the majority of participant samples when studying awe. To test whether awe contains more fearful qualities outside of Western cultures, we compared participants' experiences of this emotion in China to those in the United States. In a two-week daily diary study (Study 1), Chinese participants reported greater fear than American participants during experiences of awe, but not a comparison positive emotion. In response to a standardized awe induction (Study 2), Chinese participants reported more fear, whereas American participants reported more positive emotions. Physiological changes in autonomic activity differed by culture only for heart rate, but not skin conductance or respiratory sinus arrhythmia. These findings reveal that awe may be experienced as a more fearful, mixed emotion in China than in the United States and suggest that current positive conceptualizations of awe may reflect a disproportionate reliance on modern Western samples. Supplementary Information: The online version contains supplementary material available at 10.1007/s42761-024-00243-3.

Self-assembling gelatin based delivery of multienzyme activity nanozyme and photosensitizer for ROS storm based cancer therapy.

Nanozymes with multienzyme activity for reactive oxygen species (ROS) generation and intracellular redox imbalance are attractive strategy for cancer therapy. However, it is severely limited by low biocompatibility and catalytic efficiency, hypoxic and high levels of GSH in the tumor microenvironment. To address these issues, a copper doping carbon nanozyme (CC) with multienzyme activity was designed and integrated with photosensitizer Ce6 and gelatin to fabricate ROS amplifier (CCC). Gelatin endowed CCC with good biocompatibility, low hemolysis, and enzyme responsive degradation. CCC with high CAT-like, POD-like, OXD-like, and GSHox-like activities can induce the intracellular ROS storm formation to eliminate the cancer cells. The OXD-like activity and PDT performance mediated 1O2 generation was markedly potentiated by the CAT-like activity of CCC via catalyzing high expression of H2O2 to generate O2. At the same time, a large amount of ·OH were produced through POD-like activity of CCC and GSH was depleted by the GSHox-like activities of CCC, resulting in a destructive ROS storm formation and cellular redox homeostasis disruption. Both in vivo and in vitro experiments showed that CCC displayed satisfactory anti-tumor activity and biocompatibility. Our work provides a novel strategy for the development of nanozyne enhanced photodynamic therapy of cancer.

Embolization coils in treating postoperative bronchopleural fistula: a systematic review.

Objective: This study aims to comprehensively evaluate embolization coils in treating postoperative bronchopleural fistula (BPF). Methods: A systematic review based on PubMed, Embase, and The Cochrane Library studies was conducted. All cases receiving embolization coils in treating postoperative BPF were included. The primary outcome was the efficacy of embolization coils in achieving closure of postoperative BPF. Results: 20 patients from 9 studies were included in this systematic review. A median number of 3 (range: 1-10) embolization coils with sealants obtained a complete closure rate of 80% in patients with postoperative BPF with sizes ranging from 2 to 3.1 mm. Three patients with BPF over 3 mm and one with multiple organ failure failed this treatment. Two cases of coil migration were reported without causing respiratory failure or fistula recurrence. Conclusion: Embolization coils might be considered a safe and effective bronchoscopic treatment for small postoperative BPF of less than 3 mm in size. More extensive and rigorous studies are needed to further evaluate and confirm the optimal use of embolization coils in the context of an alternative to surgical repair.

Plugging performance and mechanism of an OBDF oil-absorbing resin (MMA-SMA-St) plugging agent.

To treat the issue of increased resource wastage due to the higher plugging tendencies of oil-based drilling fluids (OBDF) relative to water-based drilling fluids, this study synthesized a ternary composite oil-absorbing resin and optimized its synthesis parameters. The influence of temperature variations on the resin's oil absorption capacity was assessed. Techniques such as infrared spectroscopy, scanning electron microscopy, TGA-DSC measurements, crosslinking degree analysis, contact angle analysis, X-ray photoelectron spectrometry analysis and examination of the resin's plugging mechanism were employed to investigate its molecular structure, oil absorption properties, and plugging efficiency. Additionally, the impact of various synthesis conditions on the oil absorption expansion rate of the oil-absorbing resin was examined. The findings indicate that the resin developed in this research maintains robust oil absorption capabilities at 160 °C, exhibiting an oil absorption expansion rate of 12.5 g g-1. At this temperature, the composite resin particles effectively sealed leaks of widths 0.25, 0.5, and 0.75 µm. Comparative analysis revealed that adding 3% of these resin particles to OBDF significantly enhanced the sealing of fractures. Remarkably, at 160 °C, OBDF amended with resin particles managed to completely seal fractures measuring 0.25 µm. The novelty of this study is attributed to the utilization of styrene for enhancing the resin's rigidity, coupled with the application of octadecyl methacrylate, which contains long-chain alkyl groups, to optimize the oil absorption and expansion characteristics of the oil-absorbing resin.

Optimized Adsorption-Catalytic Conversion for Lithium Polysulfides by Constructing Bimetallic Compounds for Lithium-Sulfur Batteries.

Although lithium-sulfur batteries possess the advantage of high theoretical specific capacity, the inevitable shuttle effect of lithium polysulfides is still a difficult problem restricting its application. The design of highly active catalysts to promote the redox reaction during charge-discharge and thus reduce the existence time of lithium polysulfides in the electrolyte is the mainstream solution at present. In particular, bimetallic compounds can provide more active sites and exhibit better catalytic properties than single-component metal compounds by regulating the electronic structure of the catalysts. In this work, bimetallic compounds-nitrogen-doped carbon nanotubes (NiCo)Se2-NCNT and (CuCo)Se2-NCNT are designed by introducing Ni and Cu into CoSe2, respectively. The (CuCo)Se2-NCNT delivers an optimized adsorption-catalytic conversion for lithium polysulfide, benefitting from adjusted electron structure with downshifted d-band center and increased electron fill number of Co in (CuCo)Se2 compared with that of (NiCo)Se2. This endows (CuCo)Se2 moderate adsorption strength for lithium polysulfides and better catalytic properties for their conversion. As a result, the lithium-sulfur batteries with (CuCo)Se2-NCNT achieve a high specific capacity of 1051.06 mAh g-1 at 1C and an enhanced rate property with a specific capacity of 838.27 mAh g-1 at 4C. The work provides meaningful insights into the design of bimetallic compounds as catalysts for lithium-sulfur batteries.

Response of water quality in major tributaries to the difference of multi-scale landscape indicators in Dongting Lake basin, China.

River water quality has been increasingly deteriorated because of the influence of natural process and anthropogenic activities. Quantifying the influence of landscape metrics, namely topography and land use pattern, which encompass land use composition and landscape configuration, across different spatial and seasonal scales that reflect natural process and anthropogenic activities, is highly beneficial for water quality protection. In this study, we focused on investigating the effects of topography, landscape configuration and land use composition on water quality at different spatial scales, including 1-km buffer and sub-watershed, and seasonal scales, including wet and dry season, based on the monthly water quality data in 2016 of Dongting Lake in China. Multivariate statistical analysis of redundancy analysis and partial redundancy analysis was used to quantify the contributions of these factors under different scales. Our results showed that among the three environmental groups, topography made the greatest pure contribution to water quality, accounting for 11.4 to 30.9% of the variation. This was followed by landscape configuration, which accounted for 9.4 to 23.0%, and land use composition, which accounted for 5.9 to 15.7%. More specifically, water body made the greatest contribution to the water quality variation during dry season at both spatial scales, contributing 16.6 to 17.2% of the variation. In contrast, edge density was the primary interpreter of the variability in water quality during wet season at both spatial scales, accounting for 9.9 to 11.1% of the variation. The spatial variability in the influence of landscape metrics on water quality was not markedly distinct. However, these metrics have a minimal impact difference on water quality at the buffer scale and the sub-watershed scale. Moreover, the contribution of landscape configuration varied the most from the buffer to sub-watershed scales, indicating its importance for the spatial scale difference in water quality. The findings of this study offer useful insights into enhancing water quality through improved handling of landscape metrics.

Profibrotic role of the SOX9-MMP10-ECM biosynthesis axis in the tracheal fibrosis after injury and repair.

Fibroblast activation and extracellular matrix (ECM) deposition play an important role in the tracheal abnormal repair process and fibrosis. As a transcription factor, SOX9 is involved in fibroblast activation and ECM deposition. However, the mechanism of how SOX9 regulates fibrosis after tracheal injury remains unclear. We investigated the role of SOX9 in TGF-ß1-induced fibroblast activation and ECM deposition in rat tracheal fibroblast (RTF) cells. SOX9 overexpression adenovirus (Ad-SOX9) and siRNA were transfected into RTF cells. We found that SOX9 expression was up-regulated in RTF cells treated with TGF-ß1. SOX9 overexpression activated fibroblasts and promoted ECM deposition. Silencing SOX9 inhibited cell proliferation, migration, and ECM deposition, induced G2 arrest, and increased apoptosis in RTF cells. RNA-seq and chromatin immunoprecipitation sequencing (ChIP-seq) assays identified MMP10, a matrix metalloproteinase involved in ECM deposition, as a direct target of SOX9, which promotes ECM degradation by increasing MMP10 expression through the Wnt/ß-catenin signaling pathway. Furthermore, in vivo, SOX9 knockdown ameliorated granulation proliferation and tracheal fibrosis, as manifested by reduced tracheal stenosis. In conclusion, our findings indicate that SOX9 can drive fibroblast activation, cell proliferation, and apoptosis resistance in tracheal fibrosis via the Wnt/ß-catenin signaling pathway. The SOX9-MMP10-ECM biosynthesis axis plays an important role in tracheal injury and repair. Targeting SOX9 and its downstream target MMP10 may represent a promising therapeutic approach for tracheal fibrosis.

Transition-Metal-Oxide-Based Nanozymes for Antitumor Applications.

Transition metal oxide (TMO)-based nanozymes have appeared as hopeful tools for antitumor applications due to their unique catalytic properties and ability to modulate the tumor microenvironment (TME). The purpose of this review is to provide an overview of the latest progress made in the field of TMO-based nanozymes, focusing on their enzymatic activities and participating metal ions. These nanozymes exhibit catalase (CAT)-, peroxidase (POD)-, superoxide dismutase (SOD)-, oxidase (OXD)-, and glutathione oxidase (GSH-OXD)-like activities, enabling them to regulate reactive oxygen species (ROS) levels and glutathione (GSH) concentrations within the TME. Widely studied transition metals in TMO-based nanozymes include Fe, Mn, Cu, Ce, and the hybrid multimetallic oxides, which are also summarized. The review highlights several innovative nanozyme designs and their multifunctional capabilities. Despite the significant progress in TMO-based nanozymes, challenges such as long-term biosafety, targeting precision, catalytic mechanisms, and theoretical supports remain to be addressed, and these are also discussed. This review contributes to the summary and understanding of the rapid development of TMO-based nanozymes, which holds great promise for advancing nanomedicine and improving cancer treatment.

Revisiting the thermal decomposition mechanism of MAPbI3.

The thermal stability of MAPbI3 poses a challenge for the industry. To overcome this limitation, a thorough investigation of MAPbI3 is necessary. In this work, thermal gravimetric analysis (TGA) and Fourier transform infrared (FTIR) spectroscopy were conducted to identify the thermal decomposition products of MAPbI3, which were found to be CH3I, NH3, and PbI2. In situ X-ray diffraction (XRD) measurements were then performed in the temperature range from 300 to 700 K, which revealed the significant decomposition of the (110), (220), and (310) surfaces of MAPbI3 between 550 and 600 K. Density functional theory (DFT) calculations demonstrated that the (220) surface exhibited the highest stability. Additionally, the transition states of thermal decomposition showed that the energy barrier for the decomposition of the (110) surface was 2.07 eV. Our combined experimental and theoretical results provide a better understanding of the thermal decomposition mechanism of MAPbI3, providing valuable theoretical support for the design of long-term stable devices.

[Effect of Tiaojing Cuyun acupuncture therapy on pregnancy outcomes in women with diminished ovarian reserve undergoing IVF-ET: a cohort study].

OBJECTIVE: To assess the effect of Tiaojing Cuyun acupuncture therapy (acupuncture for regulating menstruation and promoting pregnancy) on pregnancy outcomes in patients with diminished ovarian reserve (DOR) undergoing in vitro fertilization-embryo transfer (IVF-ET). METHODS: Eighty women with DOR were divided into an observation group (40 cases, 1 case dropped out) and a control group (40 cases, 1 case dropped out) according to whether Tiaojing Cuyun acupuncture therapy was given or not. In the control group, IVF-ET was delivered. In the observation group, before IVF-ET, Tiaojing Cuyun acupuncture therapy was given. Two groups of acupoints were used alternatively, including Baihui (GV 20), Shenting (GV 24), Benshen (GB 13), Zhongwan (CV 12), Guanyuan (CV 4), and bilateral Tianshu (ST 25), Shenshu (BL 23), Ciliao (BL 32), etc. Acupuncture was operated once every other day, three interventions a week, for 12 weeks. The primary outcome was clinical pregnancy rate (CPR). Secondary outcomes included the total days and amount of gonadotropin (Gn) used, the number of oocytes retrieved, the number of oocytes in metaphase of second meiosis (MⅡ), the number of transferable embryos, the number of high-quality embryos, the cycle cancellation rate, the positive rate of human choriogonadotropin (HCG), the embryo implantation rate, live birth rate (LBR), the basal serum levels of sex hormones (follicular stimulating hormone [FSH], estradiol (E2), FSH/luteinizing hormone [LH]) and antral follicle count (AFC). RESULTS: CPR in the observation group was higher than that in the control group (53.8% [21/39] vs. 17.9% [7/39], P<0.05). The results of the number of oocytes retrieved, the number of oocytes in MⅡ, the number of transferable embryos, the number of high-quality embryos, the positive rate of HCG, the embryo implantation rate, and LBR in the observation group were higher than those in the control group (P<0.05). The serum level of FSH and FSH/LH in the observation group were lower thau those in the control group (P<0.05). The differences were not significant statistically in the total days and amount of Gn used, the cycle cancellation rate, serum level of E2 and AFC between the two groups (P>0.05). Logic regression analysis showed that CPR increased in the observation group when compared with that of the control group (OR = 5.33, 95%CI: 1.90-14.97, P = 0.001). CONCLUSION: Acupuncture can improve the pregnancy outcomes of DOR women undergoing IVF-ET.

Divergent impacts of fertilization regimes on below-ground prokaryotic and eukaryotic communities in the Tibetan Plateau.

Chemical nutrient amendment by human activities can lead to environmental impacts contributing to global biodiversity loss. However, the comprehensive understanding of how below- and above-ground biodiversity shifts under fertilization regimes in natural ecosystems remains elusive. Here, we conducted a seven-year field experiment (2011-2017) and examined the effects of different fertilization on plant biodiversity and soil belowground (prokaryotic and eukaryotic) communities in the alpine meadow of the Tibetan Plateau, based on data collected in 2017. Our results indicate that nitrogen addition promoted total plant biomass but reduced the plant species richness. Conversely, phosphorus enrichment did not promote plant biomass and exhibited an unimodal pattern with plant richness. In the belowground realm, distinct responses of soil prokaryotic and eukaryotic communities were observed under fertilizer application. Specifically, soil prokaryotic diversity decreased with nitrogen enrichment, correlating with shifts in soil pH. Similarly, soil eukaryotic diversity decreased with increased phosphorous inputs, aligning with the equilibrium between soil available and total phosphorus. We also established connections between these soil organism communities with above-ground plant richness and biomass. Overall, our study contributes to a better understanding of the sustainable impacts of human-induced nutrient enrichment on the natural environment. Future research should delve deeper into the long-term effects of fertilization on soil health and ecosystem functioning, aiming to achieve a balance between agricultural productivity and environmental conservation.

Preliminary study on AI-assisted diagnosis of bone remodeling in chronic maxillary sinusitis.

OBJECTIVE: To construct the deep learning convolution neural network (CNN) model and machine learning support vector machine (SVM) model of bone remodeling of chronic maxillary sinusitis (CMS) based on CT image data to improve the accuracy of image diagnosis. METHODS: Maxillary sinus CT data of 1000 samples in 500 patients from January 2018 to December 2021 in our hospital was collected. The first part is the establishment and testing of chronic maxillary sinusitis detection model by 461 images. The second part is the establishment and testing of the detection model of chronic maxillary sinusitis with bone remodeling by 802 images. The sensitivity, specificity and accuracy and area under the curve (AUC) value of the test set were recorded, respectively. RESULTS: Preliminary application results of CT based AI in the diagnosis of chronic maxillary sinusitis and bone remodeling. The sensitivity, specificity and accuracy of the test set of 93 samples of CMS, were 0.9796, 0.8636 and 0.9247, respectively. Simultaneously, the value of AUC was 0.94. And the sensitivity, specificity and accuracy of the test set of 161 samples of CMS with bone remodeling were 0.7353, 0.9685 and 0.9193, respectively. Simultaneously, the value of AUC was 0.89. CONCLUSION: It is feasible to use artificial intelligence research methods such as deep learning and machine learning to automatically identify CMS and bone remodeling in MSCT images of paranasal sinuses, which is helpful to standardize imaging diagnosis and meet the needs of clinical application.

miR-181c-5p/DERL1 pathway controls breast cancer progression mediated by TRAF6-linked K63 ubiquitination of AKT.

BACKGROUND: Aberrant Derlin-1 (DERL1) expression is associated with an overactivation of p-AKT, whose involvement in breast cancer (BRCA) development has been widely speculated. However, the precise mechanism that links DERL1 expression and AKT activation is less well-studied. METHODS: Bioinformatic analyses hold a promising approach by which to detect genes' expression levels and their association with disease prognoses in patients. In the present work, a dual-luciferase assay was employed to investigate the relationship between DERL1 expression and the candidate miRNA by both in vitro and in vivo methods. Further in-depth studies involving immunoprecipitation-mass spectrum (IP-MS), co-immunoprecipitation (Co-IP), as well as Zdock prediction were performed. RESULTS: Overexpression of DERL1 was detected in all phenotypes of BRCA, and its knockdown showed an inhibitory effect on BRCA cells both in vitro and in vivo. The Cancer Genome Atlas (TCGA) database reported that DERL1 overexpression was correlated with poor overall survival in BRCA cases, and so the quantification of DERL1 expression could be a potential marker for the clinical diagnosis of BRCA. On the other hand, miR-181c-5p was downregulated in BRCA, suggesting that its overexpression could be a potent therapeutic route to improve the overall survival of BRCA cases. Prior bioinformatic analyses indicated a somewhat positive correlation between DERL1 and TRAF6 as well as between TRAF6 and AKT, but not between miR-181c-5p and DERL1. In retrospect, DERL1 overexpression promoted p-AKT activation through K63 ubiquitination. DERL1 was believed to directly interact with the E3 ligase TRAF6. As Tyr77Ala or Tyr77Ala/Gln81Ala/Arg85Ala/Val158Ala attempts to prevent the interaction between DERL1 and TRAF domain of TRAF6, resulted in a significant reduction in K63-ubiquitinated p-AKT production. However, mutations in Gln81Ala, Arg85Ala, or Val158Ala could possibly interrupt with these processes. CONCLUSIONS: Our data confirm that mediation of the miR-181c-5p/DERL1 pathway by TRAF6-linked AKT K63 ubiquitination holds one of the clues to set our focus on toward meeting the therapeutic goals of BRCA.

The efficacy and safety of bilateral synchronous transcutaneous auricular vagus nerve stimulation for prolonged disorders of consciousness: a multicenter, double-blind, stratified, randomized controlled trial protocol.

Background: Treatment of disorders of consciousness (DOC) poses a huge challenge for clinical medicine. Transcutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive neuromodulation method, which shows potential in improving recovery of DOC. However, the evidence came from single-center, small-sample randomized controlled trial, which is insufficient to form a conclusion. Thereby, we propose a prospective, multicenter, double-blind, stratified, two-arm randomized controlled trial protocol to investigate the efficacy and safety of bilateral synchronous taVNS for treatment of DOC. Methods: We aim to recruit 382 patients with prolonged DOC, and divide them into an active stimulation group and a sham stimulation group. The patients in the active stimulation group will receive bilateral synchronous taVNS with a 200 µs pulse width, 20 Hz frequency, and personal adjusted intensity. The sham stimulation group will wear the same stimulator but without current output. Both groups will receive treatment for 30 min per session, twice per day, 6 days per week lasting for 4 weeks. The clinical assessment including Coma Recovery Scale-Revised (CRS-R), Full Outline of Unresponsiveness (FOUR), Glasgow Coma Scale (GCS), and Extended Glasgow Outcome Scale (GOS-E) will be conducted to evaluate its efficacy. Heart rate variability (HRV), blood pressure, and adverse events will be recorded to evaluate its safety. Discussion: These results will enable us to investigate the efficacy and safety of taVNS for DOC. This protocol will provide multicenter, large-sample, high-quality Class II evidence to support bilateral synchronous taVNS for DOC, and will advance the field of treatment options for DOC.Clinical trial registration:https://www.chictr.org.cn/showproj.html?proj=221851, ChiCTR2400081978.

Epigenetic modifications in abdominal aortic aneurysms: from basic to clinical.

Abdominal Aortic Aneurysm (AAA) is a disease characterized by localized dilation of the abdominal aorta, involving multiple factors in its occurrence and development, ultimately leading to vessel rupture and severe bleeding. AAA has a high mortality rate, and there is a lack of targeted therapeutic drugs. Epigenetic regulation plays a crucial role in AAA, and the treatment of AAA in the epigenetic field may involve a series of related genes and pathways. Abnormal expression of these genes may be a key factor in the occurrence of the disease and could potentially serve as promising therapeutic targets. Understanding the epigenetic regulation of AAA is of significant importance in revealing the mechanisms underlying the disease and identifying new therapeutic targets. This knowledge can contribute to offering AAA patients better clinical treatment options beyond surgery. This review systematically explores various aspects of epigenetic regulation in AAA, including DNA methylation, histone modification, non-coding RNA, and RNA modification. The analysis of the roles of these regulatory mechanisms, along with the identification of relevant genes and pathways associated with AAA, is discussed comprehensively. Additionally, a comprehensive discussion is provided on existing treatment strategies and prospects for epigenetics-based treatments, offering insights for future clinical interventions.