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1.
Br J Pharmacol ; 2024 May 02.
Article in English | MEDLINE | ID: mdl-38698493

ABSTRACT

BACKGROUND AND PURPOSE: Traumatic brain injury (TBI) causes lifelong physical and psychological dysfunction in affected individuals. The current study investigated the effects of chronic nicotine exposure via E-cigarettes (E-cig) (vaping) on TBI-associated behavioural and biochemical changes. EXPERIMENTAL APPROACH: Adult C57/BL6J male mice were subjected to controlled cortical impact (CCI) followed by daily exposure to E-cig vapour for 6 weeks. Sensorimotor functions, locomotion, and sociability were subsequently evaluated by nesting, open field, and social approach tests, respectively. Immunoblots were conducted to examine the expression of mature brain-derived neurotrophic factor (mBDNF) and associated downstream proteins (p-Erk, p-Akt). Histological analyses were performed to evaluate neuronal survival and neuroinflammation. KEY RESULTS: Post-injury chronic nicotine exposure significantly improved nesting performance in CCI mice. Histological analysis revealed increased survival of cortical neurons in the perilesion cortex with chronic nicotine exposure. Immunoblots revealed that chronic nicotine exposure significantly up-regulated mBDNF, p-Erk and p-Akt expression in the perilesion cortex of CCI mice. Immunofluorescence microscopy indicated that elevated mBDNF and p-Akt expression were mainly localized within cortical neurons. Immunolabelling of Iba1 demonstrated that chronic nicotine exposure attenuated microglia-mediated neuroinflammation. CONCLUSIONS AND IMPLICATIONS: Post-injury chronic nicotine exposure via vaping facilitates recovery of sensorimotor function by upregulating neuroprotective mBDNF/TrkB/Akt/Erk signalling. These findings suggest potential neuroprotective properties of nicotine despite its highly addictive nature. Thus, understanding the multifaceted effects of chronic nicotine exposure on TBI-associated symptoms is crucial for paving the way for informed and properly managed therapeutic interventions.

2.
IEEE Trans Image Process ; 33: 3470-3485, 2024.
Article in English | MEDLINE | ID: mdl-38809731

ABSTRACT

Recent years have witnessed the incredible performance boost of data-driven deep visual object trackers. Despite the success, these trackers require millions of sequential manual labels on videos for supervised training, implying the heavy burden of human annotating. This raises a crucial question: how to train a powerful tracker from abundant videos using limited manual annotations? In this paper, we challenge the conventional belief that frame-by-frame labeling is indispensable, and show that providing a small number of annotated bounding boxes in each video is sufficient for training a strong tracker. To facilitate that, we design a novel SParsely-supervised Object Tracking (SPOT) framework. It regards the sparsely annotated boxes as anchors and progressively explores in the temporal span to discover unlabeled target snapshots. Under the teacher-student paradigm, SPOT leverages the unique transitive consistency inherent in the tracking task as supervision, extracting knowledge from both anchor snapshots and unlabeled target snapshots. We also utilize several effective training strategies, i.e., IoU filtering, asymmetric augmentation, and temporal calibration to further improve the training robustness of SPOT. The experimental results demonstrate that, given less than 5 labels for each video, trackers trained via SPOT perform on par with their fully-supervised counterparts. Moreover, our SPOT exhibits two desirable properties: 1) SPOT enables us to fully exploit large-scale video datasets by efficiently allocating sparse labels to more videos even under a limited labeling budget; 2) when equipped with a target discovery module, SPOT can even learn from purely unlabeled videos for performance gain. We hope this work could inspire the community to rethink the current annotation principles and make a step towards practical label-efficient deep tracking.

3.
RSC Adv ; 14(20): 13944-13945, 2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38686303

ABSTRACT

[This corrects the article DOI: 10.1039/D0RA05640E.].

4.
Bioorg Chem ; 147: 107369, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38640721

ABSTRACT

Non-alcoholic fatty liver disease (NAFLD) is a complex pathogenic metabolic syndrome characterized by increased inflammation and endoplasmic reticulum stress. In recent years, natural polysaccharides derived from traditional Chinese medicine have shown significant anti-inflammatory effects, making them an attractive therapeutic option. However, little research has been conducted on the therapeutic potential of dried tangerine peel polysaccharide (DTPP) - one of the most important medicinal resources in China. The results of the present study showed that DTPP substantially reduced macrophage infiltration in vivo and suppressed the expression of pro-inflammatory factors and endoplasmic reticulum stress-related genes. Additionally, surface plasmon resonance analysis revealed that DTPP had a specific affinity to myeloid differentiation factor 2, which consequently suppressed lipopolysaccharide-induced inflammation via interaction with the toll-like receptor 4 signaling pathway. This study provides a potential molecular mechanism underlying the anti-inflammatory effects of DTPP on NAFLD and suggests DTPP as a promising therapeutic strategy for NAFLD treatment.


Subject(s)
Endoplasmic Reticulum Stress , Inflammation , Polysaccharides , Toll-Like Receptor 4 , Toll-Like Receptor 4/metabolism , Toll-Like Receptor 4/antagonists & inhibitors , Polysaccharides/pharmacology , Polysaccharides/chemistry , Animals , Endoplasmic Reticulum Stress/drug effects , Mice , Inflammation/drug therapy , Inflammation/metabolism , Lymphocyte Antigen 96/antagonists & inhibitors , Lymphocyte Antigen 96/metabolism , Carthamus tinctorius/chemistry , Mice, Inbred C57BL , Molecular Structure , Dose-Response Relationship, Drug , Structure-Activity Relationship , Non-alcoholic Fatty Liver Disease/drug therapy , Non-alcoholic Fatty Liver Disease/pathology , Non-alcoholic Fatty Liver Disease/metabolism , Humans , Lipopolysaccharides/antagonists & inhibitors , Lipopolysaccharides/pharmacology , Male , RAW 264.7 Cells , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry
5.
Biomaterials ; 307: 122512, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38430646

ABSTRACT

Proteotoxic stress, caused by the accumulation of abnormal unfolded or misfolded cellular proteins, can efficiently activate inflammatory innate immune response. Initiating the mitochondrial proteotoxic stress might go forward to enable the cytosolic release of intramitochondrial DNA (mtDNA) for the immune-related mtDNA-cGAS-STING activation, which however is easily eliminated by a cell self-protection, i.e., mitophagy. In light of this, a nanoinducer (PCM) is reported to trigger mitophagy-inhibited cuproptotic proteotoxicity. Through a simple metal-phenolic coordination, PCMs reduce the original Cu2+ with the phenolic group of PEG-polyphenol-chlorin e6 (Ce6) into Cu+. Cu+ thereby performs its high binding affinity to dihydrolipoamide S-acetyltransferase (DLAT) and aggregates DLAT for cuproptotic proteotoxic stress and mitochondrial respiratory inhibition. Meanwhile, intracellular oxygen saved from the respiratory failure can be utilized by PCM-conjugated Ce6 to boost the proteotoxic stress. Next, PCM-loaded mitophagy inhibitor (Mdivi-1) protects proteotoxic products from being mitophagy-eliminated, which allows more mtDNA to be released in the cytosol and successfully stimulate the cGAS-STING signaling. In vitro and in vivo studies reveal that PCMs can upregulate the tumor-infiltrated NK cells by 24% and enhance the cytotoxic killing of effector T cells. This study proposes an anti-tumor immunotherapy through mitochondrial proteotoxicity.


Subject(s)
DNA, Mitochondrial , Neoplasms , Proteotoxic Stress , Mitochondria , Nucleotidyltransferases , Immunotherapy , Dihydrolipoyllysine-Residue Acetyltransferase , Neoplasms/therapy
6.
Heliyon ; 10(5): e27270, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38463766

ABSTRACT

The genus Bifidobacterium widely exists in human gut and has been increasingly used as the adjuvant probiotics for the prevention and treatment of diseases. However, the functional differences of Bifidobacterium genomes from different regions of the world remain unclear. We here describe an extensive study on the genomic characteristics and function annotations of 1512 genomes (clustered to 849 non-redundant genomes) of Bifidobacterium cultured from human gut. The distribution of some carbohydrate-active enzymes varied among different Bifidobacterium species and continents. More than 36% of the genomes of B. pseudocatenulatum harbored biosynthetic gene clusters of lanthipeptide-class-iv. 99.76% of the cultivated genomes of Bifidobacterium harbored genes of bile salt hydrolase. Most genomes of B. adolescentis, and all genomes of B. dentium harbored genes involved in gamma-aminobutyric acid synthesis. B. longum subsp. infantis were characterized harboring most genes related to human milk oligosaccharide utilization. Significant differences between the distribution of antibiotic resistance genes among different species and continents revealed the importance to use antibiotics precisely in the clinical treatment. Phages infecting Bifidobacterium and horizontal gene transfers occurring in genomes of Bifidobacterium were dependent on species and region sources, and might help Bifidobacterium adapt to the environment. In addition, the distribution of Bifidobacterium in human gut was found varied from different regions of the world. This study represents a comprehensive view of characteristics and functions of genomes of cultivated Bifidobacterium from human gut, and enables clinical advances in the future.

7.
Int J Biol Macromol ; 262(Pt 1): 129998, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38336326

ABSTRACT

How to effectively improve the poor interfacial adhesion between polylactic acid/poly(butylene adipate-co-terephthalate) (PLA/PBAT) matrix and thermoplastic starch (TPS) is still a challenge. Therefore, this work aims to introduce a convenient method to enhance the performance of PLA/PBAT/TPS blend by melt reactive extrusion. Here, using 4,4'-methylene-bis(N,N-diglycidyl-aniline) (MBDG) containing four epoxy groups as a reactive compatibilizer, and respectively using 1-methylimidazole (MI) or triethylenediamine (TD) as a catalyzer, serial PLA/PBAT/TPS ternary bio-composites are successfully prepared via melt reactive extrusion. The results showed that, under the catalysis of organic base, especially MI, the epoxy groups of MBDG can effectively react with hydroxyl and carboxyl groups of PLA/PBAT and hydroxyl groups in TPS to form chain-expanded and cross-linked structures. The tensile strength of the composites is increased by 20.0 % from 21.1 MPa, and the elongation at break is increased by 182.4 % from 17.6 % owing to the chain extension and the forming of cross-linked structures. The molecular weight, thermal stability, crystallinity, and surface hydrophobicity of the materials are gradually improved with the increase of MBDG content. The melt fluidity of the composites is also improved due to the enhancement of compatibility. The obtained PLA/PBAT/TPS materials have the potential to be green plastic products with good properties.


Subject(s)
Alkenes , Epoxy Resins , Phthalic Acids , Polyesters , Adipates , Starch
8.
Adv Mater ; 36(19): e2312588, 2024 May.
Article in English | MEDLINE | ID: mdl-38316447

ABSTRACT

Cancer cells can upregulate the MYC expression to repair the radiotherapy-triggered DNA damage, aggravating therapeutic resistance and tumor immunosuppression. Epigenetic treatment targeting the MYC-transcriptional abnormality may intensively solve this clinical problem. Herein, 5-Aza (a DNA methyltransferase inhibitor) and ITF-2357 (a histone deacetylase inhibitor) are engineered into a tungsten-based nano-radiosensitizer (PWAI), to suppress MYC rising and awaken robust radiotherapeutic antitumor immunity. Individual 5-Aza depletes MYC expression but cannot efficiently awaken radiotherapeutic immunity. This drawback can be overcome by the addition of ITF-2357, which triggers cancer cellular type I interferon (IFN-I) signaling. Coupling 5-Aza with ITF-2357 ensures that PWAI does not evoke the treated model with high MYC-related immune resistance while amplifying the radiotherapeutic tumor killing, and more importantly promotes the generation of IFN-I signal-related proteins involving IFN-α and IFN-ß. Unlike the radiation treatment alone, PWAI-triggered immuno-radiotherapy remarkably enhances antitumor immune responses involving the tumor antigen presentation by dendritic cells, and improves intratumoral recruitment of cytotoxic T lymphocytes and their memory-phenotype formation in 4T1 tumor-bearing mice. Downgrading the radiotherapy-induced MYC overexpression via the dual-epigenetic reprogramming strategy may elicit a robust immuno-radiotherapy.


Subject(s)
Epigenesis, Genetic , Immunotherapy , Proto-Oncogene Proteins c-myc , Radiation-Sensitizing Agents , Animals , Mice , Proto-Oncogene Proteins c-myc/metabolism , Proto-Oncogene Proteins c-myc/genetics , Epigenesis, Genetic/drug effects , Cell Line, Tumor , Radiation-Sensitizing Agents/pharmacology , Radiation-Sensitizing Agents/chemistry , Radiation-Sensitizing Agents/therapeutic use , Nanoparticles/chemistry , Humans , Dendritic Cells/immunology , Dendritic Cells/metabolism , Neoplasms/therapy , Neoplasms/immunology , Immunosuppression Therapy , Interferon Type I/metabolism
9.
Tissue Cell ; 87: 102324, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38354685

ABSTRACT

Lactate serves not merely as an energy substrate for skeletal muscle but also regulates myogenic differentiation, leading to an elevation of reactive oxygen species (ROS) levels. The present study was focused on exploring the effects of lactate and ROS/p38 MAPK in promoting C2C12 myoblasts differentiation. Our results demonstrated that lactate increased C2C12 myoblasts differentiation at a range of physiological concentrations, accompanied by enhanced ROS contents. We used n-acetylcysteine (NAC, a ROS scavenger) pretreatment and found that it delayed lactate-induced C2C12 myoblast differentiation by upregulating Myf5 expression on days 5 and 7 and lowering MyoD and MyoG expression. The finding implies that lactate accompanies ROS-dependent manner to promote C2C12 myoblast differentiation. Additionally, lactate significantly increased p38 MAPK phosphorylation to promote C2C12 cell differentiation, but pretreatment with SB203580 (p38 MAPK inhibitor) reduced lactate-induced C2C12 myoblasts differentiation. whereas lactate pretreatment with NAC inhibited p38 MAPK phosphorylation in C2C12 cells, demonstrating that lactate mediated ROS and regulated the p38 MAPK signalling pathway to promote C2C12 cell differentiation. In conclusion, our results suggest that the promotion of C2C12 myoblasts differentiation by lactate is dependent on ROS and the p38 MAPK signalling pathway. These observations reveal a beneficial role for lactate in increasing myogenesis through ROS-sensitive mechanisms as well as providing new ideas regarding the positive impact of ROS in improving the function of skeletal muscle.


Subject(s)
Lactic Acid , p38 Mitogen-Activated Protein Kinases , Reactive Oxygen Species/metabolism , Lactic Acid/metabolism , Lactic Acid/pharmacology , Cell Differentiation , p38 Mitogen-Activated Protein Kinases/metabolism , Myoblasts/metabolism
10.
Heliyon ; 10(4): e26270, 2024 Feb 29.
Article in English | MEDLINE | ID: mdl-38375243

ABSTRACT

The principle of acupoint stimulation efficacy is based on traditional meridian theory. However, the molecular mechanisms underlying the therapeutic effects of acupoints in treating diseases remain unclear in modern scientific understanding. In this study, we selected the ST36 acupoint for investigation and summarized all relevant literature from the PubMed database over the past 10 years. The results indicate that stimulation of ST36 single acupoints has therapeutic effects mainly in models of respiratory, neurological, digestive, endocrine and immune system diseases. And it can affect the inflammatory state, oxidative stress, respiratory mucus secretion, intestinal flora, immune cell function, neurotransmitter transmission, hormone secretion, the network of Interstitial Cells of Cajal (ICC) and glucose metabolism of the organism in these pathological states. Among them, acupuncture at the ST36 single point has the most prominent function in regulating the inflammatory state, which can mainly affect the activation of MAPK signaling pathway and drive the "molecular-cellular" mode involving macrophages, T-lymphocytes, mast cells (MCs) and neuroglial cells as the core to trigger the molecular level changes of the acupuncture point locally or in the target organ tissues, thereby establishing a multi-system, multi-target, multi-level molecular regulating mechanism. This article provides a comprehensive summary and discussion of the molecular mechanisms and effects of acupuncture at the ST36 acupoint, laying the groundwork for future in-depth research on acupuncture point theory.

11.
Sci Rep ; 14(1): 1292, 2024 01 14.
Article in English | MEDLINE | ID: mdl-38221534

ABSTRACT

The Illumina HiSeq platform has been a commonly used option for bacterial genome sequencing. Now the BGI DNA nanoball (DNB) nanoarrays platform may provide an alternative platform for sequencing of bacterial genomes. To explore the impact of sequencing platforms on bacterial genome assembly, quality assessment, sequence alignment, functional annotation, mutation detection, and metagenome mapping, we compared genome assemblies based on sequencing of cultured bacterial species using the HiSeq 2000 and BGISEQ-500 platforms. In addition, simulated reads were used to evaluate the impact of insert size on genome assembly. Genome assemblies based on BGISEQ-500 sequencing exhibited higher completeness and fewer N bases in high GC genomes, whereas HiSeq 2000 assemblies exhibited higher N50. The majority of assembly assessment parameters, sequences of 16S rRNA genes and genomes, numbers of single nucleotide variants (SNV), and mapping to metagenome data did not differ significantly between platforms. More insertions were detected in HiSeq 2000 genome assemblies, whereas more deletions were detected in BGISEQ-500 genome assemblies. Insert size had no significant impact on genome assembly. Taken together, our results suggest that DNBSEQ platforms would be a valid substitute for HiSeq 2000 for bacterial genome sequencing.


Subject(s)
DNA , Genome, Bacterial , RNA, Ribosomal, 16S/genetics , Sequence Analysis, DNA/methods , High-Throughput Nucleotide Sequencing/methods , Bacteria/genetics
13.
Adv Healthc Mater ; 13(6): e2302811, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37909376

ABSTRACT

Malignant melanoma is an aggressive skin cancer with a high metastatic and mortality rate. Owing to genetic alterations, melanoma cells are resistant to apoptosis induction, which reduces the efficacy of most adjuvant systemic anticancer treatments in clinical. Here, a noninvasive strategy for anti-melanoma immunotherapy based on a manganese-coordinated nanomedicine is provided. Supplemented with photoirradiation, photon-mediated reactive oxygen species generation by photosensitizer chlorin e6 initiates photon-controlled pyroptosis activation (PhotoPyro) and promotes antitumor immunity. Simultaneously, photoirradiation-triggered double-stranded DNA generation in the cytosol would activate the Mn2+ -sensitized cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway, which further augment the PhotoPyro-induced immune response. The syngeneic effect of these immunostimulatory pathways significantly benefits dendritic cell maturation by damage-associated molecular patterns and proinflammatory cytokines secretion, thereby activating T cells and remarkably eliciting a systemic antitumor immune response to inhibiting both primary and distant tumor growth. Collaboratively, the photoirradiation-triggered PhotoPyro and cGAS-STING pathway activation by nanomedicine administration could enhance the antitumor capacity of immunotherapy and serve as a promising strategy for melanoma treatment.


Subject(s)
Melanoma , Skin Neoplasms , Humans , Melanoma/therapy , Manganese/pharmacology , Nanomedicine , Immunotherapy
14.
Lett Appl Microbiol ; 77(1)2024 Jan 02.
Article in English | MEDLINE | ID: mdl-38126115

ABSTRACT

An important risk factor for cardiovascular disease is dyslipidemia, especially abnormal cholesterol levels. The relation between probiotics and cholesterol-lowering capability has been extensively studied. Lactobacillus acidophilus plays a significant role in affecting host health, and produces multitudinous metabolites, which have prohibitory functions against pathogenic microorganisms. In this study, we identified a cholesterol-lowering strain AM13-1, isolated from a fecal sample obtained from a healthy adult male, and performed comprehensive function analysis by whole-genome analysis and in vitro experiments. Genome analyses of L. acidophilus AM13-1 revealed that carbohydrate and amino acid transport, metabolism, translation, ribosomal structure, and biogenesis are abundant categories of functional genes. No virulence factors or toxin genes with experimentally verified were found in the genome of strain AM13-1. Besides, plenty of probiotic-related genes were predicted from the L. acidophilus AM13-1 genome, such as cbh, atpA-D, and dltD, with functions related to cholesterol-lowering and acid resistance. And strain AM13-1 showed high-efficiency of bile salt hydrolase activity and the capacity for removing cholesterol with efficiency rates of 70%. These function properties indicate that strain AM13-1 can be considered as a probiotic candidate for use in food and health care products.


Subject(s)
Lactobacillus acidophilus , Probiotics , Humans , Male , Lactobacillus acidophilus/genetics , Lactobacillus acidophilus/metabolism , Probiotics/metabolism , Cholesterol/metabolism , Feces
15.
J Appl Microbiol ; 134(12)2023 Dec 01.
Article in English | MEDLINE | ID: mdl-38040628

ABSTRACT

AIMS: Lactobacillus acidophilus has been extensively applied in plentiful probiotic products. Although several studies have been performed to investigate the beneficial characteristics and genome function of L. acidophilus, comparative genomic analysis remains scarce. In this study, we collected 74 L. acidophilus genomes from our gut bacterial genome collection and the public database and conducted a comprehensive comparative genomic analysis. METHODS AND RESULTS: This study revealed the potential correlation of the genomic diversity and niche adaptation of L. acidophilus from different perspectives. The pan-genome of L. acidophilus was found to be open, with metabolism, information storage, and processing genes mainly distributed in the core genome. Phage- and peptidase-associated genes were found in the genome of the specificity of animal-derived strains, which were related to the adaptation of the animal gut. SNP analysis showed the differences of the utilization of vitamin B12 in cellular of L. acidophilus strains from animal gut and others. CONCLUSIONS: This work provides new insights for the genomic diversity analysis of L. acidophilus and uncovers the ecological adaptation of the specific strains.


Subject(s)
Lactobacillus acidophilus , Probiotics , Animals , Lactobacillus acidophilus/genetics , Genome, Bacterial , Genomics
16.
Zhen Ci Yan Jiu ; 48(10): 1048-1054, 2023 Oct 25.
Article in English, Chinese | MEDLINE | ID: mdl-37879956

ABSTRACT

Gastrointestinal dysfunction is manifested as digestive symptoms. Clinically, Zusanli (ST36) is crucial in the acupoint prescriptions of acupuncture no matter which type of the disease is differentiated in traditional Chinese medicine, but the underlying mechanism remains to be explored. Aiming to summarize the current status of the researches in terms of ameliorating gastrointestinal mucosal damage and regulating gastrointestinal motility disorders, we systematically reviewed the basic researches on the intervention with electroacupuncture (EA) at "ST36" in treatment of the diseases related to gastrointestinal dysfunction in the past 5 years, after searching the articles from Chinese and English databases. The results suggest that EA at ST36 may regulate the local gastrointestinal inflammation, oxidative stress and immune microenvironment to relieve gastrointestinal mucosal damage and adjust gastrointestinal motility disorders by means of modulating the central and peripheral nerve signaling as well as the function of mast cells and Cajal interstitial cells.


Subject(s)
Acupuncture Therapy , Electroacupuncture , Gastrointestinal Diseases , Rats , Animals , Humans , Electroacupuncture/methods , Rats, Sprague-Dawley , Acupuncture Points , Gastrointestinal Diseases/genetics , Gastrointestinal Diseases/therapy
17.
Research (Wash D C) ; 6: 0243, 2023.
Article in English | MEDLINE | ID: mdl-37795336

ABSTRACT

Organic mechanophores have been widely adopted for polymer mechanotransduction. However, most examples of polymer mechanotransduction inevitably experience macromolecular chain rupture, and few of them mimic mussel's mechanochemical regeneration, a mechanically mediated process from functional units to functional materials in a controlled manner. In this paper, inorganic mechanoluminescent (ML) materials composed of CaZnOS-ZnS-SrZnOS: Mn2+ were used as a mechanotransducer since it features both piezoelectricity and mechanolunimescence. The utilization of ML materials in polymerization enables both mechanochemically controlled radical polymerization and the synthesis of ML polymer composites. This procedure features a mechanochemically controlled manner for the design and synthesis of diverse mechanoresponsive polymer composites.

18.
Infect Drug Resist ; 16: 6209-6216, 2023.
Article in English | MEDLINE | ID: mdl-37727274

ABSTRACT

Purpose: Ceftazidime-avibactam (C-A) is a treatment option for carbapenem-resistant gram-negative bacterial (CR-GNB) infections, but little is known regarding its suitability for the intensive care unit (ICU). The current study aimed to analyze use of C-A for critically ill patients, determine independent predictors of clinical outcome and mortality and explore routine dosages for patients in continuous renal replacement therapy (CRRT). Patients and Methods: A single-center, retrospective and observational study was conducted in critically ill patients receiving different C-A-based therapies for CR-GNB infections in a tertiary teaching hospital in Beijing, China. Demographic data, severity of infection, clinical outcomes and mortality were assessed. The primary and secondary outcome of this study was 90-day all-cause mortality and 14-day clinical response, respectively. Results: A total of 43 patients with CR-GNB infection were enrolled, including 14 (32.6%) patients received C-A monotherapy. C-A monotherapy and combination with other agents did not affect 14-day clinical response or 90-day survival. All-cause mortality at 90-days was 39.5% (17/43). Multivariate Cox analysis showed that concomitant with bloodstream infection was independent risk factors for 90-day mortality and that the time to initiation of C-A and Acute Physiology and Chronic Health Evaluation (APACHE) score was independent predictors of 14-day clinical response. Five CRRT patients who received high-dose C-A therapy (>3.75 g/d) had prolonged survival compared with 5 who received low-dose C-A (<3.75 g/d, p = 0.03). Conclusion: C-A was an effective therapy for severe CR-GNB infections and clinical response correlated with the time of C-A initiation. A dosage >3.75g/d C-A was associated with prolonged survival of CRRT patients. Randomized controlled trials or multicenter studies are needed to confirm these findings.

20.
Front Neurol ; 14: 1200741, 2023.
Article in English | MEDLINE | ID: mdl-37396764

ABSTRACT

Background: Stroke survivors often exhibit low motivation for rehabilitation, hindering their ability to effectively complete rehabilitation training task effectively and participate in daily activities actively. Reward strategies have been identified as an effective method for boosting rehabilitation motivation, but their long-term efficacy remains uncertain. Transcranial direct current stimulation (tDCS) has been recognized as a technique that facilitates plastic changes and functional reorganization of cortical areas. Particularly, tDCS can improve the functional connectivity between brain regions associated with goal-directed behavior when applied to the left dorsolateral prefrontal cortex (dlPFC). Combing reward strategies with tDCS (RStDCS) has been shown to motivate healthy individuals to exert more effort in task performance. However, research exploring the combined and sustained effects of these strategies on rehabilitation motivation in stroke survivors is lacking. Methods and design: Eighty-seven stroke survivors with low motivation and upper extremity dysfunction will be randomized to receive either conventional treatment, RS treatment, or RStDCS treatment. The RStDCS group will receive reward strategies combined with anodal tDCS stimulation of the left dlPFC. The RS group will receive reward strategies combined with sham stimulation. The conventional group will receive conventional treatment combined with sham stimulation. tDCS stimulation is performed over 3 weeks of hospitalization, 20 min/time, five times a week. Reward strategies refers to personalized active exercise programs for patients during hospitalization and at home. Patients can voluntarily choose tasks for active exercise and self-report to the therapist so as to punch a card for points and exchange gifts. The conventional group will receive home rehabilitation instructions prior to discharge. Rehabilitation motivation, measured using RMS. RMS, FMA, FIM, and ICF activity and social engagement scale will be compared at baseline, 3 weeks, 6 weeks, and 3 months post-enrollment to evaluate patients' multifaceted health condition based on the ICF framework. Discussion: This study integrates knowledge from social cognitive science, economic behavioral science, and other relevant fields. We utilize straightforward and feasible reward strategies, combined with neuromodulation technology, to jointly improve patients' rehabilitation motivation. Behavioral observations and various assessment tools will be used to monitor patients' rehabilitation motivation and multifaceted health condition according to the ICF framework. The aim is to provide a preliminary exploration path for professionals to develop comprehensive strategies for improving patient rehabilitation motivation and facilitating a complete "hospital-home-society" rehabilitation process. Clinical trial registration: https://www.chictr.org.cn/showproj.aspx?proj=182589, ChiCTR2300069068.

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