Facile fabrication of linezolid/strontium coated hydroxyapatite/graphene oxide nanocomposite for osteoporotic bone defect.

Hydroxyapatite (HAp) coatings currently have limited therapeutic applications because they lack anti-infection, osteoinductivity, and poor mechanical characteristics. On the titanium substrate, electrochemical deposition (ECD) was used to construct the strontium (Sr)-featuring hydroxyapatite (HAp)/graphene oxides (GO)/linezolid (LZ) nanomaterial coated with antibacterial and drug delivery properties. The newly fabricated nanomaterials were confirmed by X-ray diffraction analysis (XRD), Fourier-transform infrared spectroscopy (FTIR), and X-ray photoelectron spectroscopy (XPS) analysis and morphological features were examined by scanning electron microscope (SEM) analysis. The results reveal multiple nucleation sites for SrHAp/GO/LZ composite coatings due to oxygen-comprising moieties on the 2D surface of GO. It was shown to be favorable for osteoblast proliferation and differentiation. The elastic modulus and hardness of LZ nanocomposite with SrHAp/GO/LZ coatings were increased by 67 % and 121 %, respectively. An initial 5 h burst of LZ release from the SrHAp/GO/LZ coating was followed by 14 h of gradual release, owing to LZ's physical and chemical adsorption. The SrHAp/GO/LZ coating effectively inhibited both S. epidermidis and S. aureus, and the inhibition lasted for three days, as demonstrated by the inhibition zone and colony count assays. When MG-63 cells are coated with SrHAp/GO/LZ composite coating, their adhesion, proliferation, and differentiation greatly improve when coated with pure titanium. A novel surface engineering nanomaterial for treating and preventing osteoporotic bone defects, SrHAp/GO/LZ, was shown to have high mechanical characteristics, superior antibacterial abilities, and osteoinductivity.

A Case of Squamous Cell Carcinoma Arising in Disseminated Superficial Porokeratosis.

Porokeratosis (PK), characterized by keratotic lesions with an atrophic center and a prominent peripheral ridge, with a typical histological hallmark, namely, the cornoid lamella, has two forms: disseminated and localized. While PK often converts into squamous cell carcinoma (SCC), conversion from disseminated superficial porokeratosis (DSP) alone is rarely reported except for one case in which DSP and LP coexisted and converted to SCC. Here, we report the case of a patient with SCC converted from DSP alone, presenting with coin-sized macules on the bottom right of his waist that developed into an ulcer at the center. The patient underwent radiation therapy, which effectively treated the SCC but did not resolve the PK. This article highlights regular follow-up and undergo comprehensive diagnosis, both of which are beneficial to enable early detection and management of DSP that has converted to into SCC; in addition, standardized medical treatment may help improve the treatment therapeutic effect of in similar diseases.

Association between allergic diseases and both psoriasis and psoriatic arthritis: a bidirectional 2-sample Mendelian randomization study.

Background An increasing body of observational studies has indicated a potential link between allergic diseases, namely atopic dermatitis (AD), allergic rhinitis (AR), allergic asthma (AA), and psoriasis (PSO) as well as psoriatic arthritis (PSA). However, the presence and causal direction of this association remain uncertain. Methods We conducted two-sample Mendelian randomization (TSMR) analyses utilizing summary statistics derived from genome-wide association studies (GWAS) consortia. The summary statistics were obtained from a substantial participant cohort, consisting of 116,000 individuals (21,000 AD cases and 95,000 controls), 462,933 individuals (26,107 AR cases and 436,826 controls), and 140,308 individuals (4859 AA cases and 135,449 controls). The summary statistics for PSO (9267 cases and 360,471 controls) and PSA (3186 cases and 240,862 controls) were sourced from the FinnGen database. The primary analytical approach employed inverse variance weighting (IVW) as the main method within TSMR. We validated our findings through a series of sensitivity analyses. Furthermore, we performed reverse TSMR analyses to evaluate the potential presence of reverse causality. Results Our investigation revealed a potential protective effect of AD against both PSO (OR = 0.922, 95% CI = 0.863-0.984, p = 0.015)and PSA(OR = 0.915, 95% CI = 0.843-0.993, p = 0.033). Moreover, employing inverse MR analysis, we obtained compelling evidence supporting the protective role of PSO in preventing AD (OR = 0.891, 95% CI = 0.829-0.958, p = 0.002), as well as AR (OR = 0.998, 95% CI = 0.996-0.999, p = 0.008), these associations remained statistically significant even after Bonferroni correction was applied to account for multiple comparisons. Furthermore, our findings did not reveal any substantial causal relationship between AA and either PSO or PSA. Conclusion Our study provides compelling evidence that PSO significantly confers protection against both AD and AR, while AD is likely to act as a protective factor for both PSO and PSA. Despite previous studies suggesting an association between allergic diseases and the incidence of PSO and PSA, our findings do not support this claim. To obtain more accurate and reliable conclusions regarding the causal mechanisms involved, larger sample sizes in randomized controlled trials or MR studies are warranted.

Selective intrafascicular stimulation of myelinated and unmyelinated nerve fibers through a longitudinal electrode: A computational study.

Carbon nanotube (CNT) fiber electrodes have demonstrated exceptional spatial selectivity and sustained reliability in the context of intrafascicular electrical stimulation, as evidenced through rigorous animal experimentation. A significant presence of unmyelinated C fibers, known to induce uncomfortable somatosensory experiences, exists within peripheral nerves. This presence poses a considerable challenge to the excitation of myelinated Aß fibers, which are crucial for tactile sensation. To achieve nuanced tactile sensory feedback utilizing CNT fiber electrodes, the selective stimulation of Aß sensory afferents emerges as a critical factor. In confronting this challenge, the present investigation sought to refine and apply a rat sciatic-nerve model leveraging the capabilities of the COMSOL-NEURON framework. This approach enables a systematic evaluation of the influence exerted by stimulation parameters and electrode geometry on the activation dynamics of both myelinated Aß and unmyelinated C fibers. The findings advocate for the utilization of current pulses featuring a pulse width of 600 µs, alongside the deployment of CNT fibers characterized by a diminutive diameter of 10 µm, with an exclusively exposed cross-sectional area, to facilitate reduced activation current thresholds. Comparative analysis under monopolar and bipolar electrical stimulation conditions revealed proximate activation thresholds, albeit with bipolar stimulation exhibiting superior fiber selectivity relative to its monopolar counterpart. Concerning pulse waveform characteristics, the adoption of an anodic-first biphasic stimulation modality is favored, taking into account the dual criteria of activation threshold and fiber selectivity optimization. Consequently, this investigation furnishes an efficacious stimulation paradigm for the selective activation of touch-related nerve fibers, alongside provisioning a comprehensive theoretical foundation for the realization of natural tactile feedback within the domain of prosthetic hand applications.

Research progress on the role of macrophages in acne and regulation by natural plant products.

Acne vulgaris is one of the most common skin diseases. The current understanding of acne primarily revolves around inflammatory responses, sebum metabolism disorders, aberrant hormone and receptor expression, colonization by Cutibacterium acnes, and abnormal keratinization of follicular sebaceous glands. Although the precise mechanism of action remains incompletely understood, it is plausible that macrophages exert an influence on these pathological features. Macrophages, as a constituent of the human innate immune system, typically manifest distinct phenotypes across various diseases. It has been observed that the polarization of macrophages toward the M1 phenotype plays a pivotal role in the pathogenesis of acne. In recent years, extensive research on acne has revealed an increasing number of natural remedies exhibiting therapeutic efficacy through the modulation of macrophage polarization. This review investigates the role of cutaneous macrophages, elucidates their potential significance in the pathogenesis of acne, a prevalent chronic inflammatory skin disorder, and explores the therapeutic mechanisms of natural plant products targeting macrophages. Despite these insights, the precise role of macrophages in the pathogenesis of acne remains poorly elucidated. Subsequent investigations in this domain will further illuminate the pathogenesis of acne and potentially offer guidance for identifying novel therapeutic targets for this condition.

Modulation of immune responses in the central nervous system by Zika virus, West Nile virus, and dengue virus.

Arthropod-borne viruses (arboviruses) pose significant threats to global public health by causing a spectrum of diseases ranging from mild febrile illnesses to severe neurological complications. Understanding the intricate interplay between arboviruses and the immune system within the central nervous system is crucial for developing effective strategies to combat these infections and mitigate their neurological sequelae. This review comprehensively explores the mechanisms by which arboviruses such as Zika virus, West Nile virus, and Dengue virus manipulate immune responses within the CNS, leading to diverse clinical manifestations.

Host-microbiota interactions in collagen-induced arthritis rats treated with human umbilical cord mesenchymal stem cell exosome and ginsenoside Rh2.

Mesenchymal stem cell exosome (MSCs-exo) is a class of products secreted by mesenchymal stem cells (MSCs) that contain various biologically active substances. MSCs-exo is a promising alternative to MSCs due to their lower immunogenicity and lack of ethical constraints. Ginsenoside Rh2 (Rh2) is a hydrolyzed component of the primary active substance of ginsenosides. Rh2 has a variety of pharmacological functions, including anti-inflammatory, anti-tumor, and antioxidant. Studies have demonstrated that gut microbiota and metabolites are critical in developing rheumatoid arthritis (RA). In this study, we constructed a collagen-induced arthritis (CIA) model in rats. We used MSCs-exo combined with Rh2 to treat CIA rats. To observe the effect of MSCs-exo combined with Rh2 on joint inflammation, rat feces were collected for 16 rRNA amplicon sequencing and untargeted metabolomics analysis. The results showed that the arthritis index score and joint swelling of CIA rats treated with MSCs-exo in combination with Rh2 were significantly lower than those of the model and MSCs-exo alone groups. MSCs-exo and Rh2 significantly ameliorated the disturbed gut microbiota in CIA rats. The regulation of Candidatus_Saccharibacteria and Clostridium_XlVb regulation may be the most critical. Rh2 enhanced the therapeutic effect of MSCs-exo compared with the MSCs-exo -alone group. Furthermore, significant changes in gut metabolites were observed in the CIA rat group, and these differentially altered metabolites may act as messengers for host-microbiota interactions. These differential metabolites were enriched into relevant critical metabolic pathways, revealing possible pathways for host-microbiota interactions.

Post-sepsis psychiatric disorder: Pathophysiology, prevention, and treatment.

Post-sepsis psychiatric disorder, encompassing anxiety, depression, post-traumatic stress disorder and delirium, is a highly prevalent complication secondary to sepsis, resulting in a marked increase in long-term mortality among affected patients. Regrettably, psychiatric impairment associated with sepsis is frequently disregarded by clinicians. This review aims to summarize recent advancements in the understanding of the pathophysiology, prevention, and treatment of post-sepsis mental disorder, including coronavirus disease 2019-related psychiatric impairment. The pathophysiology of post-sepsis psychiatric disorder is complex and is known to involve blood-brain barrier disruption, overactivation of the hypothalamic-pituitary-adrenal axis, neuroinflammation, oxidative stress, neurotransmitter dysfunction, programmed cell death, and impaired neuroplasticity. No unified diagnostic criteria for this disorder are currently available; however, screening scales are often applied in its assessment. Modifiable risk factors for psychiatric impairment post-sepsis include the number of experienced traumatic memories, the length of ICU stay, level of albumin, the use of vasopressors or inotropes, daily activity function after sepsis, and the cumulative dose of dobutamine. To contribute to the prevention of post-sepsis psychiatric disorder, it may be beneficial to implement targeted interventions for these modifiable risk factors. Specific therapies for this condition remain scarce. Nevertheless, non-pharmacological approaches, such as comprehensive nursing care, may provide a promising avenue for treating psychiatric disorder following sepsis. In addition, although several therapeutic drugs have shown preliminary efficacy in animal models, further confirmation of their potential is required through follow-up clinical studies.

Revealing the Impact of Gut Microbiota on Acne Through Mendelian Randomization Analysis.

Background: The association between acne and gut microbiota has garnered considerable attention; nevertheless, given the substantial diversity within gut microbiota, the precise cause-and-effect relationship linking specific microbial species to acne remains elusive. To address this gap in knowledge, our study utilized Mendelian randomization analysis to elucidate a potential causal link between gut microbiota composition and acne development while also investigating underlying mechanisms involving microbial factors associated with metabolic disorders. Materials and Methods: The independent single nucleotide polymorphisms (SNPs) closely associated with 196 gut microbiota samples (N=18340) were selected as variable tools. The relationship between gut microbiota and acne (N=212438) was analyzed using the Twosample package in R4.3.1, employing various methods including inverse variance weighting (IVW), weighted median, MR-Egger, Simple-mode, and Weighted-mode. To ensure the stability of the estimates, a series of sensitivity analyses were conducted, such as Cochran's Q-test, MR-Egger intercept analysis, leave-one-out analysis, and funnel plots. Additionally, the impact of each instrumental variable was calculated. Results: In the Mendelian randomization analysis, we identified twelve microbial taxa potentially associated with acne: family.Bacteroidaceae, family.Clostridiaceae1, genus.Allisonella, genus.Bacteroides, genus.Butyricimonas, genus.Clostridiumsensustricto1, and genus.Coprococcus3. These seven bacterial groups were found to be potential risk factors for acne. Conversely, family.Lactobacillaceae and genus.Ruminococcustorquesgroup along with genus.CandidatusSoleaferrea, genus.Fusicatenibacter, family.Lactobacillaceae, and genus.Lactobacillus exhibited a protective effect against acne. Furthermore, our investigation revealed that some of these microbial taxa have been implicated in metabolic diseases through previous studies. Importantly though, no causal relationship was observed in the reverse Mendelian randomization analysis.

In situ vaccination caused by diverse irradiation-driven cell death programs.

Interest surrounding the effect of irradiation on immune activation has exponentially grown within the last decade. This includes work regarding mechanisms of the abscopal effect and the success achieved by combination of radiotherapy and immunotherapy. It is hypothesized that irradiation triggers the immune system to eliminate tumors by inducing tumor cells immunogenic cell death (ICD) in tumor cells. Activation of the ICD pathways can be exploited as an in situ vaccine. In this review, we provide fundamental knowledge of various forms of ICD caused by irradiation, describe the relationship between various cell death pathways and the immune activation effect driven by irradiation, and focus on the therapeutic value of exploiting these cell death programs in the context of irradiation. Furthermore, we summarize the immunomodulatory effect of different cell death programs on combinative radiotherapy and immunotherapy. In brief, differences in cell death programs significantly impact the irradiation-induced immune activation effect. Evaluating the transition between them will provide clues to develop new strategies for radiotherapy and its combination with immunotherapy.

Long non-coding RNA ACTA2-AS1 suppresses metastasis of papillary thyroid cancer via regulation of miR-4428/KLF9 axis.

BACKGROUND: Metastasis is the primary cause of recurrence and death in patients with papillary thyroid carcinoma (PTC). LncRNA ACTA2-AS1, a long non-coding RNA, acts as a tumor suppressor in multiple types of human malignancies, while the role of ACTA2-AS1 in PTC metastasis remains unclear. METHODS: The ACTA2-AS1 expression in PTC tissues was analyzed. The sponged roles of ACTA2-AS1 via miR-4428/KLF9 axis were identified using starBase tool. The function of ACTA2-AS1 in PTC was performed with in vitro and in vivo experiments. The correlation between DNA methylation and mRNA expressions of these gene in the TCGA dataset was explored. RESULTS: ACTA2-AS1 expression was downregulated in PTC tissues without metastasis and further decreased in PTC tissues with lymph node metastasis compared with that in normal tissues. Functionally, the overexpression of ACTA2-AS1 inhibited the growth, proliferation, and invasion of PTC cells, whereas its depletion exerted opposite effect. In vivo, ACTA2-AS1 expression inhibited PTC metastasis. Furthermore, ACTA2-AS1 acted as a competing endogenous RNA for miR-4428, thereby positively regulating the expression of miR-4428 target gene, KLF9. Finally, miR-4428 overexpression enhanced invasive potential of PTC cells and significantly weakened the effects of ACTA2-AS1 on promotion and inhibition of KLF9 expression as well as invasive ability of PTC cells, respectively. In the TCGA dataset, the methylation level of ACTA2-AS1 was significantly correlated with its mRNA expression (r = 0.21, p = 2.1 × e-6). CONCLUSIONS: Our findings demonstrate that ACTA2-AS1 functions as a tumor suppressor in PTC progression at least partly by regulating the miR-4428-dependent expression of KLF9.

Type 1 diabetes and the risk of epilepsy: A meta-analysis.

AIMS/INTRODUCTION: An overrepresentation of epilepsy has been suggested in patients with type 1 diabetes (T1D). This meta-analysis was conducted to evaluate if type 1 diabetes is associated with a higher incidence of epilepsy. MATERIALS AND METHODS: Longitudinal observational studies which are relevant to the purpose of the meta-analysis were screened and obtained by searching PubMed, Embase, and Web of Science databases. Random-effects models were used when significant heterogeneity was observed; otherwise, fixed-effects models were used. RESULTS: Six observational studies involving 10 datasets of 8,001,899 participants were included, with six datasets including children and only one dataset including older people. Among them, 100,414 (1.25%) had type 1 diabetes. During the follow-up duration of 5.4-15.2 years (mean: 9.5 years), 98,644 cases (1.23%) of epilepsy were observed. Compared with participants with normoglycemia, those with type 1 diabetes were shown to have a higher incidence of epilepsy (risk ratio [RR]: 2.41, 95% confidence interval 1.69-3.44, P < 0.001; I2 = 95%) after adjustment of potential confounding variables including age and sex. Subgroup analysis showed consistent results in nested case-control and retrospective cohort studies, and in studies of children, non-elderly adult, and older participants (P for subgroup difference = 0.42 and 0.07). In addition, a stronger association of type 1 diabetes and epilepsy was suggested in studies with follow-up duration <10 years compared with those ≥10 years (RR: 3.34 vs 1.61, P for subgroup difference < 0.001). CONCLUSION: Patients with type 1 diabetes may have a higher risk of epilepsy, which was mainly driven by datasets including children.

Engineering irradiated tumor-derived microparticles as personalized vaccines to enhance anti-tumor immunity.

The inadequate activation of antigen-presenting cells, the entanglement of T cells, and the highly immunosuppressive conditions in the tumor microenvironment (TME) are important factors that limit the effectiveness of cancer vaccines. Studies show that a personalized and broad antigen repertoire fully activates anti-tumor immunity and that inhibiting the function of transforming growth factor (TGF)-ß facilitates T cell migration. In our study, we introduce a vaccine strategy by engineering irradiated tumor cell-derived microparticles (RT-MPs), which have both personalized and broad antigen repertoire, to induce comprehensive anti-tumor effects. Encouraged by the proinflammatory effects of the spike protein from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the high affinity between TGF-ß receptor 2 (TGFBR2) and TGF-ß, we develop RT-MPs with the SARS-CoV-2 spike protein and TGFBR2. This spike protein and high TGFBR2 expression induce the innate immune response and ameliorate the immunosuppressive TME, thereby promoting T cell activation and infiltration and ultimately inhibiting tumor growth. Our study provides a strategy for producing an effective personalized anti-tumor vaccine.

Lysosomal-targeted doxorubicin delivery using RBC-derived vesicles to overcome drug-resistant cancer through mitochondrial-dependent cell death.

Multidrug resistance (MDR) is a major challenge in cancer chemotherapy. Nanoparticles as drug delivery systems (DDSs) show promise for MDR cancer therapy. However, current DDSs require sophisticated design and construction based on xenogeneic nanomaterials, evoking feasibility and biocompatibility concerns. Herein, a simple but versatile biological DDS (bDDS) composed of human red blood cell (RBC)-derived vesicles (RDVs) with excellent biocompatibility was surface-linked with doxorubicin (Dox) using glutaraldehyde (glu) to form Dox-gluRDVs that remarkably suppressed MDR in uterine sarcoma through a lysosomal-mitochondrial axis-dependent cell death mechanism. Dox-gluRDVs can efficiently deliver and accumulate Dox in lysosomes, bypassing drug efflux transporters and facilitating cellular uptake and retention of Dox in drug-resistant MES-SA/Dx5 cells. The transfer of lysosomal calcium to the mitochondria during mitochondria-lysosome contact due to lysosomal Dox accumulation may result in mitochondrial ROS overproduction, mitochondrial membrane potential loss, and activation of apoptotic signaling for the superior anti-MDR activity of Dox-gluRDVs in vitro and in vivo. This work highlights the great promise of RDVs to serve as a bDDS of Dox to overcome MDR cancers but also opens up a reliable strategy for lysosomal-mitochondrial axis-dependent cell death for fighting against other inoperable cancers.

AXL transcriptionally up-regulates TMEM14A expression to mediate cell proliferation in non-small-cell lung cancer cells.

In non-small cell lung cancer (NSCLC), the receptor tyrosine kinase AXL has been identified as a potent activator of tumor progression and resistance to therapies. However, the molecular mechanisms behind AXL-mediated oncogenesis remain elusive. Current study thus aimed to uncover potential downstream genes regulated by AXL in NSCLC. Through transcriptomic RNA sequencing of AXL-silenced NSCLC cells, TMEM14A was identified as a significantly up-regulated gene. Clinical evaluations using GEPIA2 revealed that TMEM14A mRNA expression was notably higher in lung adenocarcinoma (LUAD) tumor tissues compared to normal tissues. Further, significantly increased TMEM14A levels were associated with poorer overall survival in LUAD patients. Experimentally, silencing TMEM14A in NSCLC cells led to reduced cellular proliferation and ATP levels, highlighting a key role of TMEM14A in NSCLC progression. Moreover, our promoter analysis demonstrated that AXL-mediated regulation of TMEM14A transcription could involve binding of transcription factors STAT and NF-κB to 5'-promoter of TMEM14A. Collectively, current study unveils TMEM14A as a novel downstream target of AXL, suggesting its potential as a therapeutic target to counteract resistance in future NSCLC patients undergoing AXL-targeted therapies.

Lipid Metabolism Reprogramming of Immune Cells in Acne: An Update.

Acne vulgaris is one of the most widespread skin conditions and the main reason for visiting a dermatologist. Inflammatory response and abnormal infiltrations of immune cells are the main pathogenesis of acne. The increased lipid is the prerequisite for the acne, and the perturbation of lipid composition and content is consistent with the severity of acne. Furthermore, the increased lipid production not only contributes to the occurrence and development of acne, but also sensitizes the function of immune cells. The lipid metabolic dysfunction aggravates the severity of local tissue and provides pro-inflammatory-cytokine cues, which indicates the crucial roles of lipid metabolism on immune cells. Recent advances have demonstrated the lipid metabolism reprogramming of various immune cells in acne lesion. The abnormal lipid accumulation, lipolysis, and fatty acid oxidation lead to the activation and differentiation of immune cells, which promotes the pro-inflammatory cytokines production. Thus, this review discusses the emerging role of lipid metabolism reprogramming of immune cells in the progress of acne and aims to constitute food for others' projects involved in acne research.

Abnormal voxel-mirrored homotopic connectivity in first-episode major depressive disorder using fMRI: a machine learning approach.

Objective: To explore the interhemispheric information synergy ability of the brain in major depressive disorder (MDD) patients by applying the voxel-mirrored homotopic connectivity (VMHC) method and further explore the potential clinical diagnostic value of VMHC metric by a machine learning approach. Methods: 52 healthy controls and 48 first-episode MDD patients were recruited in the study. We performed neuropsychological tests and resting-state fMRI scanning on all subjects. The VMHC values of the symmetrical interhemispheric voxels in the whole brain were calculated. The VMHC alterations were compared between two groups, and the relationship between VMHC values and clinical variables was analyzed. Then, abnormal brain regions were selected as features to conduct the classification model by using the support vector machine (SVM) approach. Results: Compared to the healthy controls, MDD patients exhibited decreased VMHC values in the bilateral middle frontal gyrus, fusiform gyrus, medial superior frontal gyrus and precentral gyrus. Furthermore, the VMHC value of the bilateral fusiform gyrus was positively correlated with the total Hamilton Depression Scale (HAMD). Moreover, SVM analysis displayed that a combination of all clusters demonstrated the highest area under the curve (AUC) of 0.87 with accuracy, sensitivity, and specificity values of 86.17%, 76.74%, and 94.12%, respectively. Conclusion: MDD patients had reduced functional connectivity in the bilateral middle frontal gyrus, fusiform gyrus, medial superior frontal gyrus and precentral gyrus, which may be related to depressive symptoms. The abnormality in these brain regions could represent potential imaging markers to distinguish MDD patients from healthy controls.

Predictors of favorable outcome and mortality after endovascular thrombectomy in young Chinese patients with large vascular occlusions.

Background: Endovascular thrombectomy (EVT) has evolved into the standard treatment for patients with acute ischemic stroke (AIS) and large vessel occlusion (LVO). However, little information is available on the management of EVT in young patients with AIS-LVO in China. The purpose of this study was to assess the favorable outcomes and mortality rates after 90 days of EVT in young Chinese patients with AIS-LVO and their predictors. Methods: This retrospective study included young Chinese patients aged 18-50 years with AIS-LVO. The primary efficacy endpoint was the modified Rankin scale (mRS) score at day 90, and the primary safety endpoint was mortality within 90 days. Using univariate and multivariate logistic regression analyses, the associations between clinical, imaging, and procedure variables and favorable (mRS 0-2) outcomes or mortality at 90 days were analyzed. Results: A total of 113 patients were included in the study with a mean age of 43.1 ± 6.3 years. Symptomatic intracranial hemorrhage (sICH) occurred in 8 (7.1%) patients. Favorable functional outcomes (mRS 0-2) were recovered in 42.5% of patients at 3 months. After 90 days, the mortality rate was 32.3%. Multivariate analysis revealed that the increase in admission NIHSS score was associated with a lower probability of functional independence (aOR 1.08, 95% CI 1.02-1.15, p = 0.01 and aOR 1.01, 95% CI 1-1.01, p = 0.008, respectively) and a higher probability of death at 90 days (aOR 1.1, 95% CI 1.03-1.18, p = 0.007 and aOR 1.00, 95% CI 1-1.01, p = 0.021, respectively). Conclusion: This study demonstrate that EVT provides higher rates of arterial recanalization, rather than better favorable outcomes and lower risk of death at 3 months in young Chinese patients with AIS-LVO. Increased NIHSS scores on admission may be associated with poor patient prognosis.

Application of magnetic resonance imaging-related techniques in the diagnosis of sepsis-associated encephalopathy: present status and prospect.

Sepsis-associated encephalopathy (SAE) refers to diffuse brain dysfunction secondary to systemic infection without central nervous system infection. The early diagnosis of SAE remains a major clinical problem, and its diagnosis is still exclusionary. Magnetic resonance imaging (MRI) related techniques, such as magnetic resonance spectroscopy (MRS), molecular MRI (mMRI), arterial spin-labeling (ASL), fluid-attenuated inversion recovery (FLAIR), and diffusion-weighted imaging (DWI), currently provide new options for the early identification of SAE. This review collected clinical and basic research and case reports related to SAE and MRI-related techniques in recent years, summarized and analyzed the basic principles and applications of MRI technology in diagnosing SAE, and provided a basis for diagnosing SAE by MRI-related techniques.

Oxymatrine blocks the NLRP3 inflammasome pathway, partly downregulating the inflammatory responses of M1 macrophages differentiated from THP-1 monocytes.

Many chronic inflammatory diseases, such as autoimmune inflammation, are associated with M1 macrophages, and the key to their treatment is blocking inflammation. Oxymatrine (OMT), a traditional Chinese medicine, has a marked anti-inflammatory effect. However, its anti-inflammatory target and mechanism in M1 cells remain unclear, which limits its clinical application. In this study, we investigated the anti-inflammatory effects of oxymatrine (OMT) on the M1 inflammatory response. We also determined the relationship between OMT treatment and the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) pathway with OMT treatment. To this end, we induced the differentiation of human peripheral blood monocytes (THP-1) into M1 cells. THP-1 cells were induced with a phorbol ester (phorbol-12-myristate-13-acetate (PMA)) and differentiated into naïve M0 macrophages. M0 cells were induced into M1 cells using lipopolysaccharide (LPS). The experimental groups were divided into the M0 macrophage group (NC), M1 inflammatory response group (LPS group), and M1 group treated with different concentrations of OMT (LPS + OMT-L, LPS + OMT-M, LPS + OMT-H). The cells in the OMT-treated groups were treated with OMT for 6 h, followed by LPS for 24 h, and the LPS group was treated with LPS only. The resulting supernatants and cells were collected. The secretion levels of NO were detected by the Griess method and the secretion levels of TNF-α and IL-1ß in the supernatants were detected by the ELISA method. The secretion levels of these inflammatory factors were reduced in every OMT-treated group compared to the LPS group (P < 0.01), and the most significant reductions were found in the OMT-H group (P < 0.0001). By western blotting, the protein expression levels of TLR4, NF-κB, NLRP3, and Caspase-1 were all found to be downregulated in the cells of OMT-treated groups compared to the LPS group (P < 0.0001). In situ changes in NLRP3 expression were observed using immunofluorescence. The fluorescence intensity of NLRP3 in M1 cells was weaker in all OMT intervention groups than in the LPS group (P < 0.001). In conclusion, OMT has significant anti-inflammatory effects on the M1 inflammatory responses, and the TLR4/NF-κB/NLRP3 pathway was blocked proportional to the concentration of OMT.