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1.
Arch Dermatol Res ; 316(6): 315, 2024 Jun 01.
Article En | MEDLINE | ID: mdl-38822918

Hypertrophic scarring is a fibro-proliferative disorder caused by abnormal cutaneous wound healing. Circulating metabolites and the gut microbiome may be involved in the formation of these scars, but high-quality evidence of causality is lacking. To assess whether circulating metabolites and the gut microbiome contain genetically predicted modifiable risk factors for hypertrophic scar formation. Two-sample Mendelian randomization (MR) was performed using MR-Egger, inverse-variance weighting (IVW), Mendelian Randomization Pleiotropy RESidual Sum and Outlier, maximum likelihood, and weighted median methods. Based on the genome-wide significance level, genetically predicted uridine (P = 0.015, odds ratio [OR] = 1903.514, 95% confidence interval [CI] 4.280-846,616.433) and isovalerylcarnitine (P = 0.039, OR = 7.765, 95% CI 1.106-54.512) were positively correlated with hypertrophic scar risk, while N-acetylalanine (P = 0.013, OR = 7.98E-10, 95% CI 5.19E-17-0.012) and glycochenodeoxycholate (P = 0.021, OR = 0.021 95% CI 0.003-0.628) were negatively correlated. Gastranaerophilales and two unknown gut microbe species (P = 0.031, OR = 0.378, 95% CI 0.156-0.914) were associated with an decreased risk of hypertrophic scarring. Circulating metabolites and gut microbiome components may have either positive or negative causal effects on hypertrophic scar formation. The study provides new insights into strategies for diagnosing and limiting hypertrophic scarring.


Cicatrix, Hypertrophic , Gastrointestinal Microbiome , Mendelian Randomization Analysis , Humans , Gastrointestinal Microbiome/physiology , Cicatrix, Hypertrophic/microbiology , Cicatrix, Hypertrophic/blood , Cicatrix, Hypertrophic/etiology , Risk Factors , Genome-Wide Association Study , Polymorphism, Single Nucleotide
2.
Front Digit Health ; 6: 1395501, 2024.
Article En | MEDLINE | ID: mdl-38784703

Background: The utility of large language model-based (LLM) artificial intelligence (AI) chatbots in many aspects of healthcare is becoming apparent though their ability to address patient concerns remains unknown. We sought to evaluate the performance of two well-known, freely-accessible chatbots, ChatGPT and Google Bard, in responding to common questions about stroke rehabilitation posed by patients and their caregivers. Methods: We collected questions from outpatients and their caregivers through a survey, categorised them by theme, and created representative questions to be posed to both chatbots. We then evaluated the chatbots' responses based on accuracy, safety, relevance, and readability. Interrater agreement was also tracked. Results: Although both chatbots achieved similar overall scores, Google Bard performed slightly better in relevance and safety. Both provided readable responses with some general accuracy, but struggled with hallucinated responses, were often not specific, and lacked awareness of the possibility for emotional situations with the potential to turn dangerous. Additionally, interrater agreement was low, highlighting the variability in physician acceptance of their responses. Conclusions: AI chatbots show potential in patient-facing support roles, but issues remain regarding safety, accuracy, and relevance. Future chatbots should address these problems to ensure that they can reliably and independently manage the concerns and questions of stroke patients and their caregivers.

3.
Curr Microbiol ; 81(7): 182, 2024 May 20.
Article En | MEDLINE | ID: mdl-38769214

Fusarium proliferatum is the main pathogen that causes Panax notoginseng root rot. The shortcomings of strong volatility and poor water solubility of Illicium verum essential oil (EO) limit its utilization. In this study, we prepared traditional emulsion (BDT) and nanoemulsion (Bneo) of I. verum EO by ultrasonic method with Tween-80 and absolute ethanol as solvents. The chemical components of EO, BDT, and Bneo were identified by gas chromatography-mass spectrometry (GC-MS) and the antifungal activity and mechanism were compared. The results show that Bneo has good stability and its particle size is 34.86 nm. The contents of (-) -anethole and estragole in Bneo were significantly higher than those in BDT. The antifungal activity against F. proliferatum was 5.8-fold higher than BDT. In the presence of I. verum EO, the occurrence of P. notoginseng root rot was significantly reduced. By combining transcriptome and metabolomics analysis, I. verum EO was found to be involved in the mutual transformation of pentose and glucuronic acid, galactose metabolism, streptomycin biosynthesis, carbon metabolism, and other metabolic pathways of F. proliferatum, and it interfered with the normal growth of F. proliferatum to exert antifungal effects. This study provide a theoretical basis for expanding the practical application of Bneo.


Antifungal Agents , Emulsions , Fusarium , Illicium , Metabolomics , Oils, Volatile , Oils, Volatile/pharmacology , Oils, Volatile/chemistry , Fusarium/drug effects , Fusarium/genetics , Fusarium/metabolism , Illicium/chemistry , Antifungal Agents/pharmacology , Antifungal Agents/metabolism , Antifungal Agents/chemistry , Emulsions/chemistry , Transcriptome , Gas Chromatography-Mass Spectrometry , Plant Diseases/microbiology , Plant Diseases/prevention & control , Gene Expression Profiling
4.
Front Oncol ; 14: 1321493, 2024.
Article En | MEDLINE | ID: mdl-38706603

Aim: This review aimed to evaluate the effectiveness and feasibility of cancer prehabilitation programs delivered through technological enablers compared to conventional face-to-face interventions. Methods: A systematic review was conducted, searching PubMed, Embase, and CINAHL for studies published from inception to February 6, 2024. Studies were included if they involved adult cancer patients in primary research, utilized technology for prehabilitation, and assessed functional, psychological, and quality of life outcomes. Results: Sixteen studies were included, encompassing wearables, apps, teleprehabilitation, and virtual reality. All studies reported feasibility, but challenges included technical issues, lack of supervision, and non-compliance. Effectiveness depended on intervention rigor and technology type. Wearables offered objective monitoring but faced compliance issues. Videoconferencing provided supervision and could mitigate compliance concerns. Multimodal programs and intervention-specific outcome measures were recommended. Conclusion: Technology-based prehabilitation programs seem feasible, but effectiveness depends on intervention design and technology employed. Future research should focus on developing robust evidence to guide clinical practice and explore the potential of integrated technological solutions. Systematic review registration: PROSPERO, identifier CRD42022376028.

5.
J Chem Neuroanat ; 138: 102420, 2024 Apr 16.
Article En | MEDLINE | ID: mdl-38626816

Protein aggregation is a pathological feature in various neurodegenerative diseases and is thought to play a crucial role in the onset and progression of neurological disorders. This pathological phenomenon has attracted increasing attention from researchers, but the underlying mechanism has not been fully elucidated yet. Researchers are increasingly interested in identifying chemicals or methods that can effectively detect protein aggregation or maintain protein stability to prevent aggregation formation. To date, several methods are available for detecting protein aggregates, including fluorescence correlation spectroscopy, electron microscopy, and molecular detection methods. Unfortunately, there is still a lack of methods to observe protein aggregation in situ under a microscope. This article reviews the two main aspects of protein aggregation: the mechanisms and detection methods of protein aggregation. The aim is to provide clues for the development of new methods to study this pathological phenomenon.

6.
Article En | MEDLINE | ID: mdl-38581323

Objective: This study aims to investigate the efficacy of bevacizumab (BEV) in combination with chemotherapy for metastatic colorectal cancer (mCRC). Methods: A cohort of 121 patients diagnosed with mCRC and admitted to our hospital from May 2018 to October 2019 were selected for the study. The control group, comprising 64 patients, received chemotherapy alone, while the research group, consisting of 57 patients, underwent a combination of BEV and chemotherapy. Comparative analyses included an assessment of clinical outcomes, monitoring of tumor markers including Carcinoembryonic Antigen (CEA), Cancer Antigen 74-2 (CA74-2), and Carbohydrate Antigen 19-9 (CA19-9) before and after treatment, and a count of adverse effects during the treatment phase. A 3-year post-discharge follow-up was conducted to compare the survival prognosis between the two groups. Results: The research group exhibited a significantly higher objective response rate (ORR) and clinical benefit rate (CBR) compared to the control group (P < .05). Furthermore, CEA, CA74-2, and CA19-9 post-treatment levels were markedly lower in the research group (P < .05). No notable difference in the incidence of adverse reactions was observed between the two groups (P > .05). Importantly, the 3-year overall survival prognosis was superior in the research group (P < .05). Within the research group, patients treated with BEV combined with the XELIRI regimen chemotherapy demonstrated a higher CBR rate (P < .05). Conclusions: The combination of BEV and chemotherapy proves to be highly effective in treating mCRC, significantly enhancing the prognostic survival cycle of patients. This treatment modality holds promise for future clinical applications in managing patients with mCRC.

8.
Macromol Rapid Commun ; : e2400102, 2024 Apr 22.
Article En | MEDLINE | ID: mdl-38648071

The II-I phase transition of isotactic poly(1-butene) (iPBu) leads to improved mechanical performance. However, this will take several weeks and increase storage and processing costs. In this work, shear forces are introduced into the supercooled iPBu melt, and the effects of isothermal crystallization temperature (Tc) and shear temperature (Tshear) on crystallization and phase transition are explored. Shear-induced transcrystalline morphology of Form II with a significantly shortened crystallization induction period can be observed at relatively high Tc (105 °C). Besides, the shear-induced Form II can transit to Form I faster than the unsheared one. In addition, the phase transition rate increases as the Tshear decreases, with the fastest rate occurring at Tshear of 120 °C. The half transition time (t1/2) is measured as 6.3 h when Tc = 105 °C, Tshear = 120 °C, which is much shorter than the 20.7 h required for unsheared samples. The accelerated phase transition of iPBu can be attributed to the stretching of molecular chains, resulting from shear treatment. This study provides a quantitative analysis of the influence of the shear treatment and the Tshear on the II-I phase transition rate. It also presents a cost-effective and straightforward approach for expediting the phase transition process.

9.
Environ Sci Pollut Res Int ; 31(20): 29334-29356, 2024 Apr.
Article En | MEDLINE | ID: mdl-38573579

Life cycle assessment (LCA) is widely used to evaluate product's life cycle environmental impact and identify the environmental weaknesses. However, it is difficult for existing LCA software to perform flexible LCA analysis based on the product life cycle characteristics and industry background. Meanwhile, under the existing LCA research model, product designers and manufacturers are usually not LCA evaluators, resulting in a certain time gap between the evaluation results and product improvement. Designers with less experience in green design often find it difficult to identify high environmental impact links in products at different life cycle stages and product levels, and updated products are challenging to meet various environmental restrictions. This paper establishes a multi-module product life cycle analysis model that combines product industry background that includes basic information, assessment information, structural information, and restriction information to achieve the multi-scenario of product LCA in different dimensions in a typical domain. The calculated mechanism of the dynamic power emission factor is built according to the service time and space dimensions. The proposed method forms an integrated environmental performance evaluation of household appliance (EPEHA) system. A software assessment and an optimization method are proposed to improve the EPEHA system. The results of this study show that these proposed methods can improve the timeliness and diversity of results analysis of product LCA in the field of household appliances in China. The universal data exchange format and simple operation interface of the EPEHA system enable people related to the product to quickly understand the environmental impact of the product in different scenarios, even if they lack green design knowledge and professional software training.


Environment , Television , Industry , China , Environmental Monitoring/methods , Software
10.
Article En | MEDLINE | ID: mdl-38684139

ABSTRACT: A 30-year-old patient with Becker Muscular Dystrophy presented with stroke. Background issues of proximal weakness, dilated cardiomyopathy and reduced endurance challenged the usual goal-setting and formulation of a stroke rehabilitation plan. We discuss the holistic rehabilitation program that this patient underwent, with a focus on the utilization of robot-assisted gait training that eventually led him to successfully regain mobility.

11.
J Virol ; 98(4): e0156523, 2024 Apr 16.
Article En | MEDLINE | ID: mdl-38445884

The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed a worldwide threat in the past 3 years. Although it has been widely and intensively investigated, the mechanism underlying the coronavirus-host interaction requires further elucidation, which may contribute to the development of new antiviral strategies. Here, we demonstrated that the host cAMP-responsive element-binding protein (CREB1) interacts with the non-structural protein 13 (nsp13) of SARS-CoV-2, a conserved helicase for coronavirus replication, both in cells and in lung tissues subjected to SARS-CoV-2 infection. The ATPase and helicase activity of viral nsp13 were shown to be potentiated by CREB1 association, as well as by Protein kinase A (PKA)-mediated CREB1 activation. SARS-CoV-2 replication is significantly suppressed by PKA Cα, cAMP-activated protein kinase catalytic subunit alpha (PRKACA), and CREB1 knockdown or inhibition. Consistently, the CREB1 inhibitor 666-15 has shown significant antiviral effects against both the WIV04 strain and the Omicron strain of the SARS-CoV-2. Our findings indicate that the PKA-CREB1 signaling axis may serve as a novel therapeutic target against coronavirus infection. IMPORTANCE: In this study, we provide solid evidence that host transcription factor cAMP-responsive element-binding protein (CREB1) interacts directly with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) helicase non-structural protein 13 (nsp13) and potentiate its ATPase and helicase activity. And by live SARS-CoV-2 virus infection, the inhibition of CREB1 dramatically impairs SARS-CoV-2 replication in vivo. Notably, the IC50 of CREB1 inhibitor 666-15 is comparable to that of remdesivir. These results may extend to all highly pathogenic coronaviruses due to the conserved nsp13 sequences in the virus.


Coronavirus RNA-Dependent RNA Polymerase , Cyclic AMP Response Element-Binding Protein , Cyclic AMP-Dependent Protein Kinases , Host Microbial Interactions , SARS-CoV-2 , Viral Nonstructural Proteins , Virus Replication , Humans , Adenosine Triphosphatases/metabolism , Antiviral Agents/pharmacology , Coronavirus RNA-Dependent RNA Polymerase/metabolism , COVID-19/virology , Cyclic AMP Response Element-Binding Protein/antagonists & inhibitors , Cyclic AMP Response Element-Binding Protein/deficiency , Cyclic AMP Response Element-Binding Protein/genetics , Cyclic AMP Response Element-Binding Protein/metabolism , Cyclic AMP-Dependent Protein Kinase Catalytic Subunits/metabolism , Cyclic AMP-Dependent Protein Kinases/metabolism , DNA Helicases/metabolism , Inhibitory Concentration 50 , RNA Helicases/metabolism , SARS-CoV-2/classification , SARS-CoV-2/drug effects , SARS-CoV-2/enzymology , SARS-CoV-2/growth & development , Signal Transduction/drug effects , Viral Nonstructural Proteins/metabolism , Virus Replication/drug effects , Female , Animals , Mice
12.
J Gastrointest Oncol ; 15(1): 514-528, 2024 Feb 29.
Article En | MEDLINE | ID: mdl-38482240

Background and Objective: Immune checkpoint inhibitors (ICIs) have been widely applied and studied in the treatment of gastrointestinal (GI) cancers, and have achieved good results. However, in clinical practice, it has been observed that only some patients respond well to ICIs, and some patients may experience various degrees of adverse reactions during the treatment. Timely evaluation of the potential therapeutic effects and adverse reactions of ICIs for patients has important clinical significance. This review aimed to summarize recent progress regarding efficacy-associated biomarkers for ICIs in GI cancer. Methods: The literature on ICI treatment in GI cancers was searched in the PubMed, Embase, and Cochrane Library databases for publications up to April 2023. Key Content and Findings: Clinical practice and research has gradually revealed some biomarkers related to the treatment of GI cancers with ICIs, which can be roughly divided into three types: biomarkers that predict the effectiveness of ICIs treatment, biomarkers associated with resistance to ICIs, and biomarkers associated with immune related adverse events (irAEs). This review article provides a literature review on biomarkers related to the efficacy of ICIs in the treatment of GI cancers. Conclusions: According to existing clinical research results, there are multiple biomarkers that can be used for predicting and monitoring the efficacy and risk of adverse events of ICIs in the treatment of digestive system malignant tumors.

13.
Plast Reconstr Surg ; 2024 Mar 26.
Article En | MEDLINE | ID: mdl-38546404

BACKGROUND: Tissue expansion for treating giant congenital melanocytic nevi (GCMN) is a commonly employed surgical method. However, the procedure's efficacy is often hindered by anatomical and histological characteristics as well as blood supply, particularly in the extremities and trunk. Enhancing expansion efficiency while reducing complications is thus a topic to be investigated, especially for pediatric patients undergoing rapid physical and psychological development with higher risks of non-compliance to medical instructions. OBJECT: To explore the effectiveness of expansion in extremities and trunk by immobilizing the acellular dermal matrix (ADM) in the gravitational force zone of inflating expanders. METHODS: All patients involved in this research underwent ADM-assisted tissue expansion in either the extremities or trunk. ADM was fully flattened, securely fixed to the lower pole of the expander, and subsequently attached to the inner surface of the expanding flap. RESULTS: From 2021 to 2023, a total of nine pediatric patients with GCMN underwent the ADM-assisted tissue expansion. All patients achieved the desired expanding volume without experiencing petechiae, ecchymosis, or skin ulceration in the ADM-covered area. The process was well tolerated by all patients, with no reports of itching, pain, allergic reaction, or fever. During the flap transfer, the ADM was observed to be firmly adhered to the expanding flap with discernible capillary network. CONCLUSION: ADM-assisted tissue expansion demonstrates promise in augmenting expansion efficiency and reducing the time needed for surgical intervention in the extremities and trunk, thereby presenting significant clinical value for pediatric patients afflicted with GCMN.

14.
Aesthetic Plast Surg ; 48(6): 1104-1110, 2024 Mar.
Article En | MEDLINE | ID: mdl-38315230

BACKGROUND: With an increasing number of East Asians undergoing blepharoplasty, the number of patients with secondary upper eyelid deformities is increasing. The sunken eyelid deformity is a common deformity after upper blepharoplasty in Asians due to over-resection, retraction, or atrophy of the nasal and central orbital fat pads. Herein, we present a novel procedure, the pendulum movement of orbital fat and retro-orbicularis oculi fat ("POR" technique), for correction of sunken eyelid deformity in secondary Asian blepharoplasty. METHODS: Patients who underwent secondary upper blepharoplasty with the POR technique by the senior author between January 2020 and October 2021 were identified retrospectively. Those with fewer than 6 months of follow-up were excluded. Patient charts and images were reviewed for demographic data, comorbidities, concomitant eyelid deformities, and postoperative complications. Pre- and postoperative aesthetics, including degree of sunken eyelid deformity, were assessed by two independent raters and by self-reported patient satisfaction. RESULTS: Forty-nine consecutive patients were identified, all of whom were female and had grade I or II sunken eyelid deformity. Median follow-up was 8 months. Concomitant deformities included high tarsal crease (N = 31 patients, 63.3%), ptosis (N = 13, 26.5%), and upper eyelid retraction (N = 5, 10.2%). Almost patients had improvement in their eyelid volume, and 95.9% had improvement in their aesthetic rating. Approximately 93.9% of patients were satisfied with the outcome. CONCLUSIONS: The POR technique is an effective technique for correction of sunken eyelid deformity and can be utilized in conjunction with other techniques during secondary blepharoplasty. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Blepharoplasty , Eyelids , Female , Humans , Adipose Tissue/transplantation , Asian People , Blepharoplasty/methods , Eyelids/surgery , Eyelids/abnormalities , Retrospective Studies
15.
ACS Appl Mater Interfaces ; 16(6): 7444-7452, 2024 Feb 14.
Article En | MEDLINE | ID: mdl-38302429

Potassium sodium niobate (KNN) lead-free piezoceramics have garnered significant attention for their environmentally friendly attributes, desired piezoelectric activity (d33), and high Curie temperature (Tc). However, the limited applicability of most KNN systems in high-power apparatus, including ultrasonic motors, transformers, and resonators, persists due to the inherent low mechanical quality factor (Qm). Herein, we proposed an innovative strategy for achieving high Qm accompanied by desirable d33 via synergistic chemical doping and texturing in KNN piezoceramics. Comprehensive electrical measurements along with quantitative structural characterization at multilength scales reveal that the excellent electromechanical properties (kp = 0.58, d33 ∼ 134 pC·N-1, Qm = 582, and Tc ∼ 415 °C) originate from the high <001> texturing degree, nanodomain, as well as acceptor hardening. Our findings provide an insight and guidance for achieving high-power performance in lead-free KNN-based piezoceramics, which were expected to be used in advanced transducer technology.

16.
Medicine (Baltimore) ; 103(5): e37067, 2024 Feb 02.
Article En | MEDLINE | ID: mdl-38306560

BACKGROUND: Serum galactomannan (GM) and ß-D-glucan (BG) are known markers of invasive aspergillosis (IA). The aim of this meta-analysis was to evaluate the efficiency of serum GM and BG as diagnostic markers of symptomatic IA infection and compare the performance of the combined tests with that of either test individually. METHODS: A literature search was carried out using PubMed, Web of Science, and EMBASE databases to include relevant studies published in English up to May 2023. The quality assessment was performed using Review Manager 5.3 software. A bivariate model was applied to pool diagnostic parameters using Stata 14.0 software. We used Cochrane I2 index to assess heterogeneity and identify the potential source of heterogeneity by meta-regression. Paired t tests were used to compare the value of GM and BG for IA diagnosis when used in combination or alone. RESULTS: Sixteen studies were eligible for inclusion in the meta-analysis. For proven or probable IA, serum GM and BG yielded a pooled sensitivity of 0.53 (95% CI 0.40-0.66) vs 0.72 (95% CI 0.61-0.81) and a pooled specificity of 0.94 (95% CI 0.91-0.97) vs 0.82 (95% CI 0.73-0.88). The area under the curve (AUC) of ROC was 0.90 (95% CI 0.87-0.92) vs 0.83 (95% CI 0.80-0.86) for all studies. The pooled sensitivity and specificity for IA diagnosis by combined GM and BG assays (GM/BG) were 0.84 (95% CI 0.69-0.86) and 0.76 (95% CI 0.69-0.81), respectively. The sensitivity of the combined GM/BG test to diagnose IA was higher than of the GM or BG test alone. CONCLUSION: Serum GM and BG tests had a relatively high accuracy for IA diagnosis in suspected patients. The diagnostic accuracy of both assays is comparable, and the diagnostic sensitivity is further improved by the combined detection of the 2 markers.


Aspergillosis , Galactose/analogs & derivatives , Invasive Fungal Infections , Invasive Pulmonary Aspergillosis , beta-Glucans , Humans , Aspergillosis/diagnosis , Sensitivity and Specificity , Mannans , Invasive Fungal Infections/diagnosis , Invasive Pulmonary Aspergillosis/diagnosis
17.
JTO Clin Res Rep ; 5(2): 100630, 2024 Feb.
Article En | MEDLINE | ID: mdl-38361739

MET protooncogene (MET) alterations are known driver oncogenes in NSCLC. Since the identification of MET as a potential therapeutic target, extensive clinical trials have been performed. As a result, MET-targeted therapies, including MET tyrosine kinase inhibitors, monoclonal antibodies, and MET antibody-drug conjugates now play important roles in the standard treatment of MET-altered NSCLC; they have considerably improved the outcomes of patients with tumors that harbor MET oncogenic drivers. Although clinical agents are currently available and numerous other options are in development, particular challenges in the field require attention. For example, the therapeutic efficacy of each drug remains unsatisfactory, and concomitantly, the resistance mechanisms are not fully understood. Thus, there is an urgent need for optimal drug sequencing and combinations, along with a thorough understanding of treatment resistance. In this review, we describe the current landscape of pertinent clinical trials focusing on MET-targeted strategies and discuss future developmental directions in this rapidly expanding field.

18.
BMC Gastroenterol ; 24(1): 87, 2024 Feb 26.
Article En | MEDLINE | ID: mdl-38408917

BACKGROUND/AIMS: Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease. The imbalance of Th17/Treg cells has been reported in PBC patients. Low-dose IL-2 can alleviate disease severity through modulating CD4 + T cell subsets in patients with autoimmune diseases. Hence, the present study aimed to examine the effects and mechanism of low-dose IL-2 in PBC mouse models. METHODS: PBC models were induced in female C57BL/6 mice by two immunizations with 2OA-BSA at two-week intervals, and poly I: C every three days. PBC mouse models were divided into the IL-2 treated and untreated groups and low-dose IL-2 was injected at three different time points. Th17 and Tregs were analyzed by flow cytometry, and the related cytokines were analyzed by ELISA. Liver histopathology was examined by H&E and immunohistochemical staining. RESULTS: Twelve weeks after modeling, the serum AMA was positive and the ALP was significantly increased in PBC mouse models (P<0.05). The pathology showed lymphocyte infiltration in the portal area, damage, and reactive proliferation of the small bile duct (P<0.05). The flow cytometric showed the imbalance of Th17/Treg cells in the liver of PBC mouse models, with decreased Treg cells, increased Th17 cells, and Th17/Treg ratio (P < 0.05). After the low-dose IL-2 intervention, biochemical index and liver pathologies showed improvement at 12 weeks. Besides, the imbalance of Th17 and Treg cells recovered. Public database mining showed that Th17 cell differentiation may contribute to poor response in PBC patients. CONCLUSION: Low-dose IL-2 can significantly improve liver biochemistry and pathology by reversing the imbalance of Th17 and Treg cells, suggesting that it may be a potential therapeutic target for PBC.


Liver Cirrhosis, Biliary , T-Lymphocytes, Regulatory , Humans , Mice , Animals , Female , Liver Cirrhosis, Biliary/drug therapy , Th17 Cells/pathology , Interleukin-2 , Mice, Inbred C57BL
19.
Mol Biol Rep ; 51(1): 365, 2024 Feb 26.
Article En | MEDLINE | ID: mdl-38409611

A low-frequency variant of sushi, von Willebrand factor type A, EGF, and pentraxin domain-containing protein 1 (SVEP1) is associated with the risk of coronary artery disease, as determined by a genome-wide association study. SVEP1 induces vascular smooth muscle cell proliferation and an inflammatory phenotype to promote atherosclerosis. In the present study, qRT‒PCR demonstrated that the mRNA expression of SVEP1 was significantly increased in atherosclerotic plaques compared to normal tissues. Bioinformatics revealed that EGR1 was a transcription factor for SVEP1. The results of the luciferase reporter assay, siRNA interference or overexpression assay, mutational analysis and ChIP confirmed that EGR1 positively regulated the transcriptional activity of SVEP1 by directly binding to its promoter. EGR1 promoted human coronary artery smooth muscle cell (HCASMC) proliferation and migration via SVEP1 in response to oxidized low-density lipoprotein (ox-LDL) treatment. Moreover, the expression level of EGR1 was increased in atherosclerotic plaques and showed a strong linear correlation with the expression of SVEP1. Our findings indicated that EGR1 binding to the promoter region drive SVEP1 transcription to promote HCASMC proliferation and migration.


MicroRNAs , Plaque, Atherosclerotic , Humans , Plaque, Atherosclerotic/metabolism , Coronary Vessels/metabolism , Genome-Wide Association Study , Cell Movement , Lipoproteins, LDL/pharmacology , Cells, Cultured , Cell Proliferation/genetics , Myocytes, Smooth Muscle/metabolism , MicroRNAs/genetics , Early Growth Response Protein 1/genetics , Early Growth Response Protein 1/metabolism , Cell Adhesion Molecules/genetics
20.
Eur Spine J ; 33(2): 444-452, 2024 Feb.
Article En | MEDLINE | ID: mdl-38236278

PURPOSE: This study aimed to investigate the relationship between spinal-pelvic parameters and recurrence of lumbar disc herniation (rLDH) after percutaneous endoscopic lumbar discectomy (PELD) through a retrospective case-control study. METHODS: Patients who underwent PELD for single-segment LDH at our hospital were included in this study. The relationship between sagittal balance parameters of the spine and recurrence was analysed through correlation analysis, and ROC curves were plotted. The baseline characteristics, sagittal balance parameters of the spine and radiological parameters of the case and control groups were compared, and the relationship between sagittal balance parameters of the spine and recurrence of rLDH after PELD was determined through univariate and multivariate logistic regression analysis. RESULTS: Correlation analysis showed that PI and ∆PI-LL were negatively correlated with grouping (r = -0.090 and -0.120, respectively, P = 0.001 and 0.038). ROC curve analysis showed that the area under the curve (ROC-AUC) for predicting rLDH based on PI was 0.65 (CI95% = 0.598, 0.720), with a cut-off of 50.26°. The ROC-AUC for predicting rLDH based on ∆PI-LL was 0.56 (CI95% = 0.503, 0.634), with a cut-off of 28.21°. Multivariate logistic regression analysis showed that smoking status (OR = 2.667, P = 0.008), PI ≤ 50.26 (OR = 2.161, P = 0.009), ∆PI-LL ≤ 28.21 (OR = 3.185, P = 0.001) and presence of Modic changes (OR = 4.218, P = 0.001) were independent risk factors, while high DH (OR = 0.788, P = 0.001) was a protective factor. CONCLUSION: PI < 50.26 and ∆PI-LL < 28.21 were risk factors for recurrence of lumbar disc herniation after spinal endoscopic surgery and had some predictive value for post-operative recurrence.


Diskectomy, Percutaneous , Intervertebral Disc Displacement , Humans , Case-Control Studies , Retrospective Studies , Intervertebral Disc Displacement/surgery , Lumbar Vertebrae/diagnostic imaging , Lumbar Vertebrae/surgery
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