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1.
Sci Rep ; 14(1): 16860, 2024 Jul 23.
Article in English | MEDLINE | ID: mdl-39043754

ABSTRACT

HRB500E rebar is a low-alloy high-strength steel with excellent mechanical properties and good plasticity but suffers from deficient corrosion resistance. This can be solved by adding trace elements, including rare earth elements. Herein, the corrosion-resistant behavior of rebar was evaluated by weightlessness testing and electrochemical measurements, and the effects of Ce on the structural evolution of the corrosion product layer were investigated by scanning electron microscopy (SEM), Electron Probe X-ray Micro-Analyzer (EPMA), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS). The results showed that adding Ce to the rebar improved the densification of the reinforcing surface corrosion products, as well as reduced the corrosion rate of the experimental rebar. Compared to C0 sample without Ce, the rebar sample containing 0.044 wt.% Ce displayed increased Ecorr by 0.051 V, decreased Icorr by 15.573 mA cm-2, enhanced Rc of the corrosion product layer by 112.71 Ω cm2, incremented α-FeOOH content in the corrosion product layer, and boosted ratio of α/γ* in the corrosion product layer by 10.11%. Furthermore, the oxide (CeO2) formed by Ce in the corrosion layer of the rebar bar surface existed in the rust layer, resulting in a stable corrosion product layer with improved blocking ability of the corrosive medium. Overall, the addition of Ce at certain ratios looks promising to produce HRB500E rebar with excellent corrosion resistance and extended service life under harsh conditions.

2.
Am J Transl Res ; 16(6): 2525-2532, 2024.
Article in English | MEDLINE | ID: mdl-39006285

ABSTRACT

PURPOSE: To investigate the prevalence of occupational lower back pain (OLBP) among medical workers and identify the contributing factors. METHODS: An electronic questionnaire was distributed to medical workers at Yuebei People's Hospital to gather information on various factors, including gender, age, body mass index (BMI), length of employment, job role, education level, professional title, marital status, fertility status, frequency of night shift, weight lifting daily, duration of daily standing at work, frequency of bending, work-related stress, experience with low back protection training, and frequency of waist exercises. Univariate and multivariate logistic regression analyses were conducted to identify the factors associated with OLBP in medical workers. RESULTS: Out of the 98 medical workers surveyed, 67 experienced OLBP (68.37%). The results of multivariate logistic regression analysis revealed that working for more than 5 years, holding a nursing position, and lacking training in low back protection were significant risk factors for developing OLBP in medical workers (all P<0.05). CONCLUSION: OLBP is a prevalent issue among medical workers, and various factors such as length of employment, job role, and training in low back protection can influence its occurrence.

3.
Sci Rep ; 14(1): 15578, 2024 07 06.
Article in English | MEDLINE | ID: mdl-38971817

ABSTRACT

There is a growing body of evidence suggesting that Hashimoto's thyroiditis (HT) may contribute to an increased risk of papillary thyroid carcinoma (PTC). However, the exact relationship between HT and PTC is still not fully understood. The objective of this study was to identify potential common biomarkers that may be associated with both PTC and HT. Three microarray datasets from the GEO database and RNA-seq dataset from TCGA database were collected to identify shared differentially expressed genes (DEGs) between HT and PTC. A total of 101 genes was identified as common DEGs, primarily enriched inflammation- and immune-related pathways through GO and KEGG analysis. We performed protein-protein interaction analysis and identified six significant modules comprising a total of 29 genes. Subsequently, tree hub genes (CD53, FCER1G, TYROBP) were selected using random forest (RF) algorithms for the development of three diagnostic models. The artificial neural network (ANN) model demonstrates superior performance. Notably, CD53 exerted the greatest influence on the ANN model output. We analyzed the protein expressions of the three genes using the Human Protein Atlas database. Moreover, we observed various dysregulated immune cells that were significantly associated with the hub genes through immune infiltration analysis. Immunofluorescence staining confirmed the differential expression of CD53, FCER1G, and TYROBP, as well as the results of immune infiltration analysis. Lastly, we hypothesise that benzylpenicilloyl polylysine and aspirinmay be effective in the treatment of HT and PTC and may prevent HT carcinogenesis. This study indicates that CD53, FCER1G, and TYROBP play a role in the development of HT and PTC, and may contribute to the progression of HT to PTC. These hub genes could potentially serve as diagnostic markers and therapeutic targets for PTC and HT.


Subject(s)
Biomarkers, Tumor , Computational Biology , Hashimoto Disease , Machine Learning , Thyroid Cancer, Papillary , Thyroid Neoplasms , Humans , Hashimoto Disease/genetics , Thyroid Cancer, Papillary/genetics , Thyroid Cancer, Papillary/diagnosis , Computational Biology/methods , Biomarkers, Tumor/genetics , Thyroid Neoplasms/genetics , Thyroid Neoplasms/diagnosis , Protein Interaction Maps/genetics , Gene Expression Regulation, Neoplastic , Gene Expression Profiling , Gene Regulatory Networks , Neural Networks, Computer
4.
J Hepatocell Carcinoma ; 11: 1403-1414, 2024.
Article in English | MEDLINE | ID: mdl-39005968

ABSTRACT

Objective: To develop a simple and effective prognostic scoring system to predict the efficacy of drug-eluting bead-transcatheter arterial chemoembolization (DEB-TACE) in the treatment of hepatocellular carcinoma (HCC). Methods: Data were retrospectively collected from 230 patients with HCC who received DEB-TACE treatment at six medical centers between January 2019 and December 2022. We developed a predictive score based on independent risk factors for overall survival (OS), validated the model using a validation cohort, and compared its prognostic accuracy with commonly used HCC staging systems. Results: The number of tumors, albumin-bilirubin levels, alpha-fetoprotein levels, and portal vein thrombus grade were identified as independent factors influencing OS. Based on these factors, we established the DEB-TACE treatment of HCC (DTH) scoring system. The DTH score correlated well with OS, which decreased as the DTH score increased. According to the DTH score, patients were categorized into three risk groups: low-risk (DTH-A, 0-4 points), medium-risk (DTH-B, 5-6 points), and high-risk (DTH-A, 7 points). The OS of each risk group was 18.73±0.62 months, 12.73±0.10 months, and 6.93±0.19 months, respectively (p<0.001). The external cohort validation confirmed the accuracy of the DTH score, demonstrating superior predictive performance compared to other commonly used HCC scoring systems. Conclusion: The DTH-HCC scoring system effectively predicts the outcomes of HCC patients undergoing DEB-TACE as initial treatment. This model can aid in the initial planning and decision-making process for DEB-TACE treatment in HCC patients.

5.
World J Clin Cases ; 12(21): 4661-4672, 2024 Jul 26.
Article in English | MEDLINE | ID: mdl-39070824

ABSTRACT

BACKGROUND: There is a lack of literature discussing the utilization of the stacking ensemble algorithm for predicting depression in patients with heart failure (HF). AIM: To create a stacking model for predicting depression in patients with HF. METHODS: This study analyzed data on 1084 HF patients from the National Health and Nutrition Examination Survey database spanning from 2005 to 2018. Through univariate analysis and the use of an artificial neural network algorithm, predictors significantly linked to depression were identified. These predictors were utilized to create a stacking model employing tree-based learners. The performances of both the individual models and the stacking model were assessed by using the test dataset. Furthermore, the SHapley additive exPlanations (SHAP) model was applied to interpret the stacking model. RESULTS: The models included five predictors. Among these models, the stacking model demonstrated the highest performance, achieving an area under the curve of 0.77 (95%CI: 0.71-0.84), a sensitivity of 0.71, and a specificity of 0.68. The calibration curve supported the reliability of the models, and decision curve analysis confirmed their clinical value. The SHAP plot demonstrated that age had the most significant impact on the stacking model's output. CONCLUSION: The stacking model demonstrated strong predictive performance. Clinicians can utilize this model to identify high-risk depression patients with HF, thus enabling early provision of psychological interventions.

6.
Rev Cardiovasc Med ; 25(4): 111, 2024 Apr.
Article in English | MEDLINE | ID: mdl-39076545

ABSTRACT

Background: The C-reactive protein-albumin-lymphocyte (CALLY) index is a novel inflammatory biomarker, and its association with the prognosis of coronary artery disease (CAD) after percutaneous coronary intervention (PCI) has not previously been studied. Therefore, this study aimed to investigate the effect of using the CALLY index on adverse outcomes in CAD patients undergoing PCI. Methods: From December 2016 to October 2021, we consecutively enrolled 15,250 CAD patients and performed follow-ups for primary endpoints consisting of all-cause mortality (ACM) and cardiac mortality (CM). The CALLY index was computed using the following formula: (albumin × lymphocyte)/(C-reactive protein (CRP) × 10 4 ). The average duration of the follow-up was 24 months. Results: A total of 3799 CAD patients who had undergone PCI were ultimately enrolled in the present study. The patients were divided into four groups according to the CALLY index quartiles: Q1 ( ≤ 0.69, n = 950), Q2 (0.69-2.44, n = 950), Q3 (2.44-9.52, n = 950), and Q4 ( > 9.52, n = 949). The low-Q1 group had a significantly higher prevalence of ACM (p < 0.001), CM (p < 0.001), major adverse cardiac events (MACEs) (p = 0.002), and major adverse cardiac and cerebrovascular events (MACCEs) (p = 0.002). Kaplan-Meier analysis revealed that a low CALLY index was significantly linked with adverse outcomes. After univariate and multivariate Cox regression analysis, the risk of ACM, CM, MACEs, and MACCEs decreased by 73.7% (adjust hazard risk [HR] = 0.263, 95% CI: 0.147-0.468, p < 0.001), 70.6% (adjust HR = 0.294, 95% CI: 0.150-0.579, p < 0. 001), 37.4% (adjust HR = 0.626, 95% CI: 0.422-0.929, p = 0.010), and 41.5% (adjust HR = 0.585, 95% CI: 0.401-0.856, p = 0.006), respectively, in the Q4 quartiles compared with the Q1 quartiles. Conclusions: This study revealed that a decreased CALLY index was associated with worse prognoses for CAD patients after PCI. The categorization of patients with a decreased CALLY index could provide valuable evidence for the risk stratification of adverse outcomes in CAD patients after PCI. Clinical Trial Registration: The details are available at http://www.chictr.org.cn (Identifier: NCT05174143).

7.
Rev Cardiovasc Med ; 25(1): 17, 2024 Jan.
Article in English | MEDLINE | ID: mdl-39077643

ABSTRACT

Background: The correlation between 5 ' -Nucleotidase ( 5 ' -NT) and the clinical outcomes in coronary artery disease (CAD) patients following percutaneous coronary intervention (PCI) is not clear. This study aims to clarify this relationship. Methods: The PRACTICE study enrolled 15,250 patients between December 2016 and October 2021. After filtering out those without 5 ' -NT data, a total of 6555 patients were analyzed with a median follow-up of 24 months. Based on the receiver operating characteristic (ROC) curve analysis, a 5 ' -NT level of 5.57 U/L was selected as the optimal cutoff value. All research samples were divided into high-value ( ≥ 5.57 U/L, n = 2346) and low-value groups ( < 5.57 U/L, n = 4209). Key clinical outcomes included all-cause death (ACD), cardiovascular death (CD), major adverse cardiovascular events (MACE), and major adverse cardiovascular and cerebrovascular events (MACCE). After separating patients into high and low value groups, multivariate Cox regression analysis was used to correct for potential confounding variables. Finally, risk ratios and their 95% confidence intervals (CIs) were calculated. Results: During the follow-up period, 129 instances of ACD were recorded-49 cases (1.2%) in the low-value group and 80 cases (3.4%) in the high-value group. Similarly, 102 CDs occurred, including 42 low-value group cases (1.0%) and 60 high-value group cases (2.6%). A total of 363 MACE occurred, including 198 low-value group cases (4.7%) and 165 high-value group cases (7%). A total of 397 cases of MACCE occurred, including 227 low-value group cases (5.4%) and 170 high-value group cases (7.2%). As serum 5 ' -NT increased, the incidence of ACD, CD, MACE and MACCE increased. After multivariate Cox regression, high 5 ' -NT levels were linked with a 1.63-fold increase in ACD risk (hazard ratio [HR] = 2.630, 95% CI: [1.770-3.908], p < 0.001) when compared to low 5 ' -NT patients. Similarly, the risk of CD, MACE, and MACCE increased by 1.298-fold (HR = 2.298, 95% CI: [1.477-3.573], p < 0.001), 41% (HR = 1.410, 95% CI: [1.124-1.768], p = 0.003) and 30.5% (HR = 1.305, 95% CI: [1.049-1.623], p = 0.017), respectively. Conclusions: high serum 5 ' -NT levels were independently correlated with adverse clinical outcomes in CAD patients following PCI, affirming its potential as a prognostic indicator.

8.
Life Sci ; 352: 122866, 2024 Sep 01.
Article in English | MEDLINE | ID: mdl-38936605

ABSTRACT

Chronic kidney disease (CKD) represents a significant and escalating global health challenge, with morbidity and mortality rates rising steadily. Evidence increasingly implicates perirenal adipose tissue (PRAT) deposition as a contributing factor in the pathogenesis of CKD. This review explores how PRAT deposition may exert deleterious effects on renal structure and function. The anatomical proximity of PRAT to the kidneys not only potentially causes mechanical compression but also leads to the dysregulated secretion of adipokines and inflammatory mediators, such as adiponectin, leptin, visfatin, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and exosomes. Additionally, PRAT deposition may contribute to renal lipotoxicity through elevated levels of free fatty acids (FFA), triglycerides (TAG), diacylglycerol (DAG), and ceramides (Cer). PRAT deposition is also linked to the hyperactivation of the renin-angiotensin-aldosterone system (RAAS), which further exacerbates CKD progression. Recognizing PRAT deposition as an independent risk factor for CKD underscores the potential of targeting PRAT as a novel strategy for the prevention and management of CKD. This review further discusses interventions that could include measuring PRAT thickness to establish a baseline, managing metabolic risk factors that promote its deposition, and inhibiting key PRAT-induced signaling pathways.


Subject(s)
Adipose Tissue , Disease Progression , Renal Insufficiency, Chronic , Renin-Angiotensin System , Humans , Renal Insufficiency, Chronic/metabolism , Renal Insufficiency, Chronic/pathology , Adipose Tissue/metabolism , Adipose Tissue/pathology , Renin-Angiotensin System/physiology , Kidney/metabolism , Kidney/pathology , Animals , Adipokines/metabolism
9.
BMJ Open ; 14(6): e079954, 2024 Jun 16.
Article in English | MEDLINE | ID: mdl-38885991

ABSTRACT

OBJECTIVES: Decreased prognostic nutritional index (PNI) was associated with adverse outcomes in many clinical diseases. This study aimed to evaluate the relationship between baseline PNI value and adverse clinical outcomes in patients with coronary artery disease (CAD). DESIGN: The Personalized Antiplatelet Therapy According to CYP2C19 Genotype in Coronary Artery Disease (PRACTICE) study, a prospective cohort study of 15 250 patients with CAD, was performed from December 2016 to October 2021. The longest follow-up period was 5 years. This study was a secondary analysis of the PRACTICE study. SETTING: The study setting was Xinjiang Medical University Affiliated First Hospital in China. PARTICIPANTS: Using the 50th and 90th percentiles of the PNI in the total cohort as two cut-off limits, we divided all participants into three groups: Q1 (PNI <51.35, n = 7515), Q2 (51.35 ≤ PNI < 59.80, n = 5958) and Q3 (PNI ≥ 59.80, n = 1510). The PNI value was calculated as 10 × serum albumin (g/dL) + 0.005 × total lymphocyte count (per mm3). PRIMARY OUTCOME: The primary outcome measure was mortality, including all-cause mortality (ACM) and cardiac mortality (CM). RESULTS: In 14 983 participants followed for a median of 24 months, a total of 448 ACM, 333 CM, 1162 major adverse cardiovascular events (MACE) and 1276 major adverse cardiovascular and cerebrovascular events (MACCE) were recorded. The incidence of adverse outcomes was significantly different among the three groups (p <0.001). There were 338 (4.5%), 77 (1.3%) and 33 (2.2%) ACM events in the three groups, respectively. A restricted cubic spline displayed a J-shaped relationship between the PNI and worse 5-year outcomes, including ACM, CM, MACE and MACCE. After adjusting for traditional cardiovascular risk factors, we found that only patients with extremely high PNI values in the Q3 subgroup or low PNI values in the Q1 subgroup had a greater risk of ACM (Q3 vs Q2, HR: 1.617, 95% CI 1.012 to 2.585, p=0.045; Q1 vs Q2, HR=1.995, 95% CI 1.532 to 2.598, p <0.001). CONCLUSION: This study revealed a J-shaped relationship between the baseline PNI and ACM in patients with CAD, with a greater risk of ACM at extremely high PNI values. TRIAL REGISTRATION NUMBER: NCT05174143.


Subject(s)
Coronary Artery Disease , Nutrition Assessment , Humans , Coronary Artery Disease/mortality , Female , Male , China/epidemiology , Prospective Studies , Middle Aged , Prognosis , Aged , Risk Factors , Cause of Death
10.
J Pharm Biomed Anal ; 246: 116213, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-38754155

ABSTRACT

Triterpenoid saponins, a major bioactive component of liquorice, possess high hydrophilicity and often co-occur with other impurities of similar polarity. Additionally, subtle structural differences of some triterpenoid saponins bring challenges to comprehensive characterisation. In this study, triterpenoid saponins of three Glycyrrhiza species were systematically analysed using rapid resolution liquid chromatography quadrupole time-of-flight mass spectrometry (RRLC-Q-TOF-MS) coupled with mass defect filtering (MDF). Firstly, comprehensive date acquisition was achieved using RRLC-Q-TOF-MS. Secondly, a polygonal MDF method was established by summarizing known and speculated substituents and modifications based on the core structure to rapidly screen potential triterpenoid saponins. Thirdly, based on the fragmentation patterns of reference compounds, an identification strategy for characterisation of triterpenoid saponins was proposed. The strategy divided triterpenoid saponins into three distinct classes. By this strategy, 98 triterpenoid saponins including 10 potential new ones were tentatively characterised. Finally, triterpenoid saponins of three Glycyrrhiza species were further analysed using principle component analysis (PCA) and orthogonality partial least squares discriminant analysis (OPLS-DA). Among these, 18 compounds with variable importance in projections (VIP) > 1.0 and P values < 0.05 were selected to distinguish three Glycyrrhiza species. Overall, our study provided a reference for quality control and rational use of the three species.


Subject(s)
Glycyrrhiza , Saponins , Triterpenes , Saponins/chemistry , Saponins/analysis , Glycyrrhiza/chemistry , Triterpenes/chemistry , Triterpenes/analysis , Mass Spectrometry/methods , Chromatography, High Pressure Liquid/methods , Chromatography, Liquid/methods , Plant Extracts/chemistry
11.
Drug Discov Today ; 29(6): 103984, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38642702

ABSTRACT

Given their high affinity and specificity for a range of macromolecules, antibodies are widely used in the treatment of autoimmune diseases, cancers, inflammatory diseases, and Alzheimer's disease (AD). Traditional experimental methods are time-consuming, expensive, and labor-intensive. Recent advances in artificial intelligence (AI) technologies provide complementary methods that can reduce the time and costs required for antibody design by minimizing failures and increasing the success rate of experimental tests. In this review, we scrutinize the plethora of AI-driven methodologies that have been deployed over the past 4 years for modeling antibody structures, predicting antibody-antigen interactions, optimizing antibody affinity, and generating novel antibody candidates. We also briefly address the challenges faced in integrating AI-based models with traditional antibody discovery pipelines and highlight the potential future directions in this burgeoning field.


Subject(s)
Antibodies , Artificial Intelligence , Drug Discovery , Humans , Drug Discovery/methods , Antibodies/immunology , Animals
12.
Int J Surg ; 110(7): 4240-4248, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38597399

ABSTRACT

BACKGROUND: Thermal ablation is routinely used for solitary colorectal liver metastases (SCLM), but the added value of adjuvant systemic therapy in SCLM remains unclear. This study aimed to compare the long-term outcomes for SCLM treated by ablation alone (AB) versus ablation plus systemic therapy (AS). METHODS: This multicenter retrospective study using nationwide data from fourteen institutions between October 2010 and May 2023, 369 patients with initial SCLM smaller than 5 cm, no extrahepatic metastases, and colorectal cancer R0 resection treated by thermal ablation were included. The crude analysis was used to analyze eligible cases between the two groups. The propensity score matching to control for potential confounders in each matched group. Subgroup analyses were performed to identify specific survival benefits. RESULTS: 61.2% (226/369) of eligible patients were treated with AS and 38.8% (143/369) with AB. During the median follow-up period of 8.8 years, 1-/3-/5-year DFS/OS rates did not differ between the two groups, when analyzed via propensity score matching ( P =0.52/0.08). Subgroup analysis revealed that AS was significantly associated with better OS than AB in patients with plasma CEA >5 ug/l ( P =0.036), T (III-IV) category of primary cancer ( P =0.034), or clinical risk score (1-2) ( P =0.041). In each matched group, the authors did find a significant difference in drug-related adverse events ( P <0.001) between AS group (24.1%, 28/116) and AB group (0.0%, 0/116). CONCLUSIONS: For patients with plasma CEA >5 ug/l, T (III-IV) category of primary cancer, or clinical risk score (1-2), thermal ablation plus systemic therapy appeared to be associated with improved overall survival. Thermal ablation was equally effective in disease-free survival for treating SCLM, whether with or without adjuvant systemic therapy.


Subject(s)
Colorectal Neoplasms , Liver Neoplasms , Humans , Colorectal Neoplasms/pathology , Male , Female , Liver Neoplasms/secondary , Liver Neoplasms/surgery , Liver Neoplasms/mortality , Retrospective Studies , Middle Aged , Aged , Propensity Score , Chemotherapy, Adjuvant , Treatment Outcome , Adult , Combined Modality Therapy
13.
ACS Appl Mater Interfaces ; 16(15): 19175-19183, 2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38573052

ABSTRACT

Inorganic lead-free perovskite nanocrystals (NCs) with broadband self-trapped exciton (STEs) emission and low toxicity have shown enormous application prospects in the field of display and lighting. However, white light-emitting diodes (WLEDs) based on a single-component material with high photoluminescence quantum yield (PLQY) remain challenging. Here, we demonstrate a novel codoping strategy by introducing Sb3+/Mn2+ ions to achieve the tuneable dual emission in lead-free perovskite Cs3InCl6 NCs. The PLQY increases to 59.64% after doping with Sb3+. The codoped Cs3InCl6 NCs exhibit efficient white light emission due to the energy transfer channel from STEs to Mn2+ ions with PLQY of 51.38%. Density functional theory (DFT) calculations have been used to verify deeply the effects of Sb3+/Mn2+ doping. WLEDs based on Sb3+/Mn2+-codoped Cs3InCl6 NCs are explored with color rendering index of 85.5 and color coordinate of (0.398, 0.445), which have been successfully applied as photodetector lighting sources. This work provides a new perspective for designing novel lead-free perovskites to achieve single-component WLEDs.

14.
Elife ; 132024 Apr 04.
Article in English | MEDLINE | ID: mdl-38573820

ABSTRACT

Thrombocytopenia caused by long-term radiotherapy and chemotherapy exists in cancer treatment. Previous research demonstrates that 5-Hydroxtrayptamine (5-HT) and its receptors induce the formation of megakaryocytes (MKs) and platelets. However, the relationships between 5-HT1A receptor (5-HTR1A) and MKs is unclear so far. We screened and investigated the mechanism of vilazodone as a 5-HTR1A partial agonist in promoting MK differentiation and evaluated its therapeutic effect in thrombocytopenia. We employed a drug screening model based on machine learning (ML) to screen the megakaryocytopoiesis activity of Vilazodone (VLZ). The effects of VLZ on megakaryocytopoiesis were verified in HEL and Meg-01 cells. Tg (itga2b: eGFP) zebrafish was performed to analyze the alterations in thrombopoiesis. Moreover, we established a thrombocytopenia mice model to investigate how VLZ administration accelerates platelet recovery and function. We carried out network pharmacology, Western blot, and immunofluorescence to demonstrate the potential targets and pathway of VLZ. VLZ has been predicted to have a potential biological action. Meanwhile, VLZ administration promotes MK differentiation and thrombopoiesis in cells and zebrafish models. Progressive experiments showed that VLZ has a potential therapeutic effect on radiation-induced thrombocytopenia in vivo. The network pharmacology and associated mechanism study indicated that SRC and MAPK signaling are both involved in the processes of megakaryopoiesis facilitated by VLZ. Furthermore, the expression of 5-HTR1A during megakaryocyte differentiation is closely related to the activation of SRC and MAPK. Our findings demonstrated that the expression of 5-HTR1A on MK, VLZ could bind to the 5-HTR1A receptor and further regulate the SRC/MAPK signaling pathway to facilitate megakaryocyte differentiation and platelet production, which provides new insights into the alternative therapeutic options for thrombocytopenia.


Subject(s)
Thrombocytopenia , Vilazodone Hydrochloride , Mice , Animals , Vilazodone Hydrochloride/adverse effects , Vilazodone Hydrochloride/metabolism , Zebrafish , Receptor, Serotonin, 5-HT1A/metabolism , Blood Platelets/metabolism , Thrombocytopenia/drug therapy , Thrombocytopenia/metabolism , Megakaryocytes/metabolism , Thrombopoiesis
15.
Eur J Pharmacol ; 971: 176548, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38570080

ABSTRACT

OBJECTIVES: Thrombocytopenia is a disease in which the number of platelets in the peripheral blood decreases. It can be caused by multiple genetic factors, and numerous challenges are associated with its treatment. In this study, the effects of alnustone on megakaryocytes and platelets were investigated, with the aim of developing a new therapeutic approach for thrombocytopenia. METHODS: Random forest algorithm was used to establish a drug screening model, and alnustone was identified as a natural active compound that could promote megakaryocyte differentiation. The effect of alnustone on megakaryocyte activity was determined using cell counting kit-8. The effect of alnustone on megakaryocyte differentiation was determined using flow cytometry, Giemsa staining, and phalloidin staining. A mouse model of thrombocytopenia was established by exposing mice to X-rays at 4 Gy and was used to test the bioactivity of alnustone in vivo. The effect of alnustone on platelet production was determined using zebrafish. Network pharmacology was used to predict targets and signaling pathways. Western blotting and immunofluorescence staining determined the expression levels of proteins. RESULTS: Alnustone promoted the differentiation and maturation of megakaryocytes in vitro and restored platelet production in thrombocytopenic mice and zebrafish. Network pharmacology and western blotting showed that alnustone promoted the expression of interleukin-17A and enhanced its interaction with its receptor, and thereby regulated downstream MEK/ERK signaling and promoted megakaryocyte differentiation. CONCLUSIONS: Alnustone can promote megakaryocyte differentiation and platelet production via the interleukin-17A/interleukin-17A receptor/Src/RAC1/MEK/ERK signaling pathway and thus provides a new therapeutic strategy for the treatment of thrombocytopenia.


Subject(s)
Megakaryocytes , Thrombocytopenia , Mice , Animals , Megakaryocytes/metabolism , Zebrafish/metabolism , Interleukin-17/metabolism , Blood Platelets , Thrombocytopenia/drug therapy , Thrombocytopenia/metabolism , Signal Transduction , Mitogen-Activated Protein Kinase Kinases/metabolism , Mitogen-Activated Protein Kinase Kinases/pharmacology
16.
Medicine (Baltimore) ; 103(16): e37792, 2024 Apr 19.
Article in English | MEDLINE | ID: mdl-38640281

ABSTRACT

Currently, few studies have demonstrated the relationship between total serum IgE (T-IgE) and acute exacerbation chronic obstructive pulmonary disease (AECOPD). In this study, T-IgE in AECOPD patients were investigated and jointly analyzed with the clinical characteristics. AECOPD patients hospitalized from July 2018 to July 2019 were included in this study. In this patient cohort, clinical information was investigated. Routine blood tests, C-reactive protein and T-IgE levels of patients were determined along with blood gas analysis. The length of hospital stays, mechanical ventilation during hospitalization, ICU admission, glucocorticoid related clinical information were recorded. A total of 285 AECOPD patients were included in this study, which consisted of a high proportion of males. Of all patients, 49.82% patients exhibited higher T-IgE levels. Based on the reference T-IgE value 60 kU/L, patients were divided into high T-IgE group with T-IgE > 60 kU/L, and low T-IgE group with T-IgE ≤ 60 kU/L. There was no significant difference in the dosage of glucocorticoid between the two groups. Patients in the high T-IgE group had shorter hospital stays and lower probability of mechanical ventilation compared to the low T-IgE group. After adjustment for confounding factors, T-IgE was negatively correlated with the length of hospital stays. AECOPD patients with elevated T-IgE had shorter hospital stays and lower risks of mechanical ventilation and ICU admission. Our results showed that T-IgE might play an important role on evaluating the condition and guiding for treatment decisions in AECOPD patients.


Subject(s)
Glucocorticoids , Pulmonary Disease, Chronic Obstructive , Male , Humans , Retrospective Studies , Glucocorticoids/therapeutic use , Hospitalization , Pulmonary Disease, Chronic Obstructive/therapy , Immunoglobulin E , Disease Progression
17.
Clin Cardiol ; 47(3): e24214, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38472152

ABSTRACT

BACKGROUND: This is a sub-analysis of the Personalized Antithrombotic Therapy for Coronary Heart Disease after PCI (PATH-PCI) trial in China to explore the relationship between smoking and outcomes following personalized antiplatelet therapy (PAT) in chronic coronary syndrome (CCS) patients undergoing percutaneous coronary intervention (PCI). METHODS: As a single-center, prospective, randomized controlled and open-label trial, the PATH-PCI trial randomized CCS patients undergoing PCI into standard group or personalized group guided by a novel platelet function test (PFT), from December 2016 to February 2018. All patients were divided into smokers and nonsmokers according to their smoking status. Subsequently, we underwent a 180-day follow-up evaluation. The primary endpoint was the net adverse clinical events (NACE). RESULTS: Regardless of smoking status, in the incidence of NACE, there was a reduction with PAT but that the reductions are not statistically significant. In the incidence of bleeding events, we found no statistically significant difference between two groups (smokers: 2.0% vs. 1.4%, HR = 1.455, 95% confidence interval [CI]: 0.595-3.559, p = .412; nonsmokers: 2.2% vs. 1.8%, HR = 1.228, 95% CI: 0.530-2.842, p = .632). In smokers, PAT reduced major adverse cardiac and cerebrovascular events (MACCE) by 48.7% (3.0% vs. 5.9%, HR = 0.513, 95% CI: 0.290-0.908, p = .022), compared with standard antiplatelet therapy (SAT). PAT also reduced the major adverse cardiovascular events (MACE) but there was no statistically difference in the reductions (p > .05). In nonsmokers, PAT reduced MACCE and MACE by 51.5% (3.3% vs. 6.7%, HR = 0.485, 95% CI: 0.277-0.849, p = .011) and 63.5% (1.8% vs. 4.9%, HR = 0.365, 95% CI: 0.178-0.752, p = .006), respectively. When testing p-values for interaction, we found there was no significant interaction of smoking status with treatment effects of PAT (pint-NACE = .184, pint-bleeding = .660). CONCLUSION: Regardless of smoking, PAT reduced the MACE and MACCE, with no significant difference in bleeding. This suggests that PAT was an recommendable regimen to CCS patients after PCI, taking into consideration both ischemic and bleeding risk.


Subject(s)
Acute Coronary Syndrome , Percutaneous Coronary Intervention , Humans , Acute Coronary Syndrome/therapy , Hemorrhage/chemically induced , Percutaneous Coronary Intervention/adverse effects , Platelet Aggregation Inhibitors/adverse effects , Prospective Studies , Smoking , Treatment Outcome
18.
Biol Methods Protoc ; 9(1): bpae005, 2024.
Article in English | MEDLINE | ID: mdl-38414648

ABSTRACT

Transurethral catheterization in mice is multifaceted, serving essential functions such as perfusion and drug delivery, and is critical in the development of various urological animal disease models. The complex anatomy of the male mouse urethra presents significant challenges in transurethral catheterization, leading to a predominance of research focused on female specimens. This bias limits the utilization of male mice in lower urinary tract disease studies. Our research aims to develop new reliable methods for transurethral catheterization in adult male mice, thereby expanding their use in relevant disease research. Experiments were conducted on adult male C57BL/6J mice. Utilizing a PE10 catheter measuring 4.5-5 cm in length, the catheter was inserted into the bladder via the mouse's urethra under anesthesia. The intubation technique entailed regulating the insertion force, ensuring the catheter's lubrication, using a trocar catheter, modifying the catheter's trajectory, and accommodating the curvature of the bladder neck. Post-catheter insertion, ultrasound imaging was employed to confirm the catheter's accurate positioning within the bladder. Subsequent to catheterization, the bladder was perfused using trypan blue. This method was further validated through its successful application in establishing an acute urinary retention (AUR) model, where the mouse bladder was infused with saline to a pressure of 50 or 80 cm H2O, maintained steadily for 30 min. A thorough morphological assessment of the mouse bladder was conducted after the infusion. Our study successfully pioneered methods for transurethral catheterization in male mice. This technique not only facilitates precise transurethral catheterization but also proves applicable to male mouse models for lower urinary tract diseases, such as AUR.

19.
Chem Commun (Camb) ; 60(11): 1448-1451, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38213273

ABSTRACT

We present an iridium and Brønsted acid co-catalyzed enantioselective formal [4+2] cycloaddition reaction of cyclic enamides with 2-(1-hydroxyallyl)phenols. This method yields a wide range of N-unsubstituted spiro-N,O-ketals, with good efficiency (up to 94%) and excellent enantioselectivities (most >95% ee). The protocol features easy scale-up and facile product derivatization.

20.
Cell Commun Signal ; 22(1): 54, 2024 01 19.
Article in English | MEDLINE | ID: mdl-38243314

ABSTRACT

BACKGROUND: The gut microbiota plays a crucial role in coronary artery disease (CAD) development, but limited attention has been given to the role of the microbiota in preventing this disease. This study aimed to identify key biomarkers using metagenomics and untargeted metabolomics and verify their associations with atherosclerosis. METHODS: A total of 371 participants, including individuals with various CAD types and CAD-free controls, were enrolled. Subsequently, significant markers were identified in the stool samples through gut metagenomic sequencing and untargeted metabolomics. In vivo and in vitro experiments were performed to investigate the mechanisms underlying the association between these markers and atherosclerosis. RESULTS: Faecal omics sequencing revealed that individuals with a substantial presence of Faecalibacterium prausnitzii had the lowest incidence of CAD across diverse CAD groups and control subjects. A random forest model confirmed the significant relationship between F. prausnitzii and CAD incidence. Notably, F. prausnitzii emerged as a robust, independent CAD predictor. Furthermore, our findings indicated the potential of the gut microbiota and gut metabolites to predict CAD occurrence and progression, potentially impacting amino acid and vitamin metabolism. F. prausnitzii mitigated inflammation and exhibited an antiatherosclerotic effect on ApoE-/- mice after gavage. This effect was attributed to reduced intestinal LPS synthesis and reinforced mechanical and mucosal barriers, leading to decreased plasma LPS levels and an antiatherosclerotic outcome. CONCLUSIONS: Sequencing of the samples revealed a previously unknown link between specific gut microbiota and atherosclerosis. Treatment with F. prausnitzii may help prevent CAD by inhibiting atherosclerosis.


Subject(s)
Atherosclerosis , Gastrointestinal Microbiome , Humans , Animals , Mice , Faecalibacterium prausnitzii/metabolism , Lipopolysaccharides
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