Efficacy and safety of direct oral anticoagulants in patients with atrial fibrillation combined with chronic kidney disease: a systematic review and meta-analysis.

BACKGROUND: Currently published studies have not observed consistent results on the efficacy and safety of direct oral anticoagulants (DOACs) use in patients with chronic kidney disease (CKD) combined with atrial fibrillation (AF). Therefore, this study conducted a meta-analysis of the efficacy and safety of DOACs for patients with AF complicated with CKD. METHODS: Database literature was searched up to May 30, 2023, to include randomized controlled trials (RCT) involving patients with AF complicated with CKD DOACs and vitamin K antagonists (VKAs). Stroke, systemic embolism (SE), and all-cause mortality were used as effectiveness indicators, and major bleeding, intracranial hemorrhage (ICH), fatal bleeding, gastrointestinal bleeding (GIB), and clinically relevant non-major bleeding (CRNMB) were used as safety outcomes. RESULTS: Nine RCT studies were included for analysis according to the inclusion criteria. Results of the efficacy analysis showed that compared with VKAs, DOACs reduced the incidence of stroke/SE (OR = 0.75, 95% CI 0.67-0.84) and all-cause deaths (OR = 0.84, 95% CI 0.75-0.93) in patients with AF who had comorbid CKD. Safety analyses showed that compared with VKAs, DOACs improved safety by reducing the risk of major bleeding (OR = 0.76, 95%CI 0.65-0.90), ICH (OR = 0.46, 95%CI 0.38-0.56), and fatal bleeding (OR = 0.75, 95%CI 0.65-0.87), but did not reduce the incidence of GIB and CRNMB. CONCLUSION: Compared with VKAs, DOACs may increase efficacy and improve safety in AF patients with CKD (90 ml/min> Crcl≥15 ml/min), and shows at least similar efficacy and safety in AF patients with Kidney failure (Crcl<15 ml/min).

Risk factors for venous thromboembolism in a single pediatric intensive care unit in China.

BACKGROUND: Analyses of extensive, nationally representative databases indicate a rising prevalence of venous thromboembolism (VTE) among critically ill children. However, the majority of studies on childhood VTE have primarily concentrated on Caucasian populations in the United States and European countries. There is a lack of epidemiological studies on VTE in Chinese children. METHODS: We conducted a retrospective cohort study of data from the Pediatric Intensive Care (PIC) database. Data were obtained and extracted by using Structured Query Language (SQL) and the administrative platform pgAdmin4 for PostgreSQL. Bivariate analyses were conducted in which categorical variables were analyzed by a chi-square test and continuous variables were analyzed by a Student's t-test. Separate multivariable logistic regressions were employed to investigate the associations between VTE and sociodemographic factors as well as clinical factors. RESULTS: Our study included 12,881 pediatric patients from the PIC database, spanning the years 2010 to 2018. The incidence rate of pediatric VTE was 0.19% (24/12,881). The venous thrombotic locations were deep venous thrombosis extremities (n = 18), superior vena cava (n = 1), cerebral sinovenous (n = 1), and other deep venous thrombosis (n = 4). Univariate analysis showed that age, weight, shock, sepsis, cancer and vasopressor receipt were statistically significant risk factors for pediatric VTE (all p ≤ 0.05). After multivariable logistic regression analysis, only shock (aOR: 6.77, 95%CI: 1.33-34.73, p = 0.019) and admission for sepsis (aOR: 6.09, 95%CI: 1.76-21.09, p = 0.004) were statistically significant associated with pediatric VTE. CONCLUSIONS: In conclusion, data obtained from the Pediatric Intensive Care (PIC) database revealed a prevalence of VTE in pediatric patients of 0.19%. The most common location for venous thrombi was deep venous thrombosis (DVT) in the extremities. We identified that shock and sepsis were statistically significant factors associated with pediatric VTE.

Efficacy and safety of direct oral anticoagulants versus low-molecular-weight heparin for thromboprophylaxis after cancer surgery: a systematic review and meta-analysis.

BACKGROUND: Direct oral anticoagulants (DOACs) used as an alternative to low-molecular-weight heparin (LMWH) for thromboprophylaxis after cancer surgery for venous thromboembolic events (VTE) remains unclear. This study aimed to investigate the efficacy and safety of DOACs versus LMWH in these patients. MATERIALS AND METHODS: A search of EMBASE, MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science was carried out and included all randomized controlled trials (RCTs) and observational studies that directly compared DOACs with LMWH for thromboprophylaxis in patients after cancer surgery through July 25, 2023. The primary efficacy and safety outcomes were VTE, major bleeding, and clinically relevant non-major bleeding (CRNMB) within 30 days of surgery. The risk of bias was assessed using the Cochrane Risk of Bias 2 (RoB2) tool for RCTs and ROBINS-I tool for non-randomized studies. This study was registered in PROSPERO (CRD42023445386). RESULTS: We retrieved 5149articles, selected 27 for eligibility, and included 10 studies (three RCTs and seven observational studies) encompassing 3054 patients who underwent postoperative thromboprophylaxis with DOACs (41%) or LMWH (59%). Compared to LMWH thromboprophylaxis, DOACs had a comparable risk of VTE (RR:0.69[95% CI:0.46-1.02], I2 = 0%), major bleeding (RR:1.55 [95% CI:0.82-2.93], I2 = 2%), and CRNMB (RR, 0.89 [95% CI, 0.4-1.98], I2 = 31%) during the 30-day postoperative period. Subgroup analysis of VTE and major bleeding suggested no differences according to study type, extended thromboprophylaxis, tumor types, or different types of DOAC. CONCLUSION: DOACs are potentially effective alternatives to LMWH for thromboprophylaxis in patients undergoing cancer surgery, without increasing the risk of major bleeding events.

Ferritin-mediated mitochondrial iron homeostasis is essential for the survival of hematopoietic stem cells and leukemic stem cells.

Iron metabolism plays a crucial role in cell viability, but its relationship with adult stem cells and cancer stem cells is not fully understood. The ferritin complex, responsible for intracellular iron storage, is important in this process. We report that conditional deletion of ferritin heavy chain 1 (Fth1) in the hematopoietic system reduced the number and repopulation capacity of hematopoietic stem cells (HSCs). These effects were associated with a decrease in cellular iron level, leading to impaired mitochondrial function and the initiation of apoptosis. Iron supplementation, antioxidant, and apoptosis inhibitors reversed the reduced cell viability of Fth1-deleted hematopoietic stem and progenitor cells (HSPCs). Importantly, leukemic stem cells (LSCs) derived from MLL-AF9-induced acute myeloid leukemia (AML) mice exhibited reduced Fth1 expression, rendering them more susceptible to apoptosis induced by the iron chelation compared to normal HSPCs. Modulating FTH1 expression using mono-methyl fumarate increased LSCs resistance to iron chelator-induced apoptosis. Additionally, iron supplementation, antioxidant, and apoptosis inhibitors protected LSCs from iron chelator-induced cell death. Fth1 deletion also extended the survival of AML mice. These findings unveil a novel mechanism by which ferritin-mediated iron homeostasis regulates the survival of both HSCs and LSCs, suggesting potential therapeutic strategies for blood cancer with iron dysregulation.

Design of a novel long-acting dual GLP-1/GIP receptor agonist.

Tirzepatide, the first approved dual GLP-1/GIP receptor agonist (RA), has achieved better clinical outcomes than other GLP-1RAs. However, it is an imbalanced dual GIP/GLP-1 RA, and it remains unclear whether the degree of imbalance is optimal. Here, we present a novel long-acting dual GLP-1/GIP RA that exhibits better activity than tirzepatide toward GLP-1R. A candidate conjugate, D314, identified via peptide design, synthesis, conjugation, and experimentation, was evaluated using chronic studies in db/db and diet induced obese (DIO) mice. D314 achieved favorable blood glucose and body weight-lowering effects, equal to those of tirzepatide. Its half-life in dogs (T1/2: 78.3 ± 14.01 h) reveals its suitability for once-weekly administration in humans. This preclinical study suggests the potential role of D314 as an effective agent for treating T2DM and obesity.

MyD88 in myofibroblasts enhances nonalcoholic fatty liver disease-related hepatocarcinogenesis via promoting macrophage M2 polarization.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic liver diseases and has emerged as the leading factor in the pathogenesis of hepatocellular carcinoma (HCC). MyD88 contributes to the development of HCC. However, the underlying mechanism by which MyD88 in myofibroblasts regulates NAFLD-associated liver cancer development remains unknown. RESULTS: Myofibroblast MyD88-deficient (SMAMyD88-/-) mice were protected from diet-induced obesity and developed fewer and smaller liver tumors. MyD88 deficiency in myofibroblasts attenuated macrophage M2 polarization and fat accumulation in HCC tissues. Mechanistically, MyD88 signaling in myofibroblasts enhanced CCL9 secretion, thereby promoting macrophage M2 polarization. This process may depend on the CCR1 receptor and STAT6/ PPARß pathway. Furthermore, liver tumor growth was attenuated in mice treated with a CCR1 inhibitor. CCLl5 (homologous protein CCL9 in humans) expression was increased in myofibroblasts of HCC and was associated with shorter survival of patients with HCC. Thus, our results indicate that MyD88 in myofibroblasts promotes NAFLD-related HCC progression and may be a promising therapeutic target for HCC treatment. CONCLUSION: This study demonstrates that MyD88 in myofibroblasts can promote nonalcoholic fatty liver disease-related hepatocarcinogenesis by enhancing macrophage M2 polarization, which might provide a potential molecular therapeutic target for HCC.

Self-powered molecularly imprinted photoelectrochemical sensor based on Ppy/QD/HOF heterojunction for the detection of bisphenol A.

As an emerging porous material, hydrogen-bonded organic framework materials (HOFs) still pose application challenges. In this work, the designed type "I + II" heterojunction extracted hot electrons from HOFs using quantum dots (QDs) and polypyrrole (Ppy), improving the stability and photoelectrochemical performance of materials. In addition to serving as a potential well, electropolymerized Ppy was used as a recognition element for bisphenol A (BPA), and a novel self-powered molecularly imprinted photoelectrochemical (MIP-PEC) sensor was designed. The sensing platform showed a linear relationship from 1 × 10-10 to 1 × 10-7 mol∙L-1 and from 1 × 10-7 to 1 mol∙L-1 with an acceptable detection limit of 4.2 × 10-11 mol∙L-1. This is the first application of HOFs in constructing MIP-PEC sensors and a new attempt to improve the stability of HOFs for the application of porous crystal materials in the sensing field.

Radiosensitization of Osteosarcoma Cells Using the PARP Inhibitor Olaparib Combined with X-rays or Carbon Ions.

Objective: Osteosarcomas are derived from bone-forming mesenchymal cells that are insensitive to radiation. This study aimed to investigate the radiosensitization of osteosarcoma cells (U2OS and K7M2) using the PARP inhibitor olaparib combined with X-rays or carbon ions (C-ions). Methods: The effect of olaparib on the proliferation of osteosarcoma cells after irradiation was assessed using CCK-8 and clone formation assays. Cells were treated with olaparib and/or radiation and the effects of olaparib on the cell cycle and apoptosis were analysed by flow cytometry after 48h. Immunofluorescence was used to stain the nuclei, γ-H2AX, 53BP1, and Rad51 proteins, and the number of γ-H2AX, 53BP1, and Rad51 foci was observed under a fluorescence microscope. The effect of olaparib combined with radiation on double-stranded DNA breaks in osteosarcoma cells was evaluated. Results: At the same radiation dose, olaparib reduced the proliferation and colony formation ability of irradiated osteosarcoma cells (P < 0.05). Olaparib monotherapy induced minimal apoptotic effects and G2/M phase arrest in osteosarcoma cells and irradiation alone induced moderate apoptosis and G2/M phase arrest. However, radiation combined with olaparib significantly increased the percentage of apoptotic cells and G2/M phase arrest in osteosarcoma cells (P < 0.05). Immunofluorescence experiments showed that compared to the radiation group, the formation of γ-H2AX and 53BP1 foci was significantly increased in the combined group (P < 0.05). The expression levels of Rad51 foci in the irradiated group were higher than those in the control group (P < 0.05). However, the number of Rad51 foci in the combined group was significantly decreased (P < 0.05). Conclusion: The PARP inhibitor olaparib combined with irradiation (X-rays or C-ions) enhanced the radiosensitivity of osteosarcoma cell lines (U2OS and K7M2). Our findings provide a potential theoretical basis for the clinical application of olaparib in overcoming radiation resistance in osteosarcoma.

Direct oral anticoagulants (DOACs) versus low-molecular-weight heparin (LMWH) for extended thromboprophylaxis following major abdominal/pelvic cancer-related surgery: a systematic review and meta-analysis.

BACKGROUND: The use of direct oral anticoagulants (DOACs) as an alternative to low-molecular-weight heparin (LMWH) for extended thromboprophylaxis of abdominal/pelvic cancer-related postoperative thromboembolism (VTE) is unclear. We aim to investigate the efficacy and safety of DOACs vs. LMWH in these patients. METHODS: A systematic review was conducted using EMBASE, MEDLINE, CENTRAL, and Web of science through May 19th, 2023 for all randomized controlled trials (RCTs) and observational studies that compared the outcomes with DOACs vs. LMWH for extended thromboprophylaxis among patients undergoing abdominal/pelvic cancer surgery. Primary efficacy outcome was clinical VTE, and safety outcome was clinically relevant bleeding complications reported within the 30-day postoperative period. This study was registered in PROSPERO (CRD42023413175). RESULTS: We identified 5078 articles and selected 29 full-text articles for eligibility. A total of 9 studies (2 RCTs and 7 observational studies) encompassing 2651 patients were included for systematic review and 7 for meta-analysis. When compared with LMWH extended thromboprophylaxis, DOACs had a similar incidence of VTE (RR: 0.65 [95% CI: 0.32-1.33], I2 = 0%), major bleeding (RR: 1.68 [95% CI: 0.36-7.9], I2 = 26%), and clinically relevant non-major bleeding (RR: 0.68 [95% CI: 0.39-1.19], I2 = 0%). Subgroup analysis suggested no difference according to the study type (RCTs versus observational studies) regarding clinical VTE or major bleeding (Pinteraction = 0.43 and Pinteraction = 0.71, respectively). CONCLUSION: Our results suggest that DOACs for extended thromboprophylaxis were an effective and safe alternative to LMWH after major abdominal/pelvic cancer-related surgery.

Risk factors for anticoagulant-associated gastrointestinal hemorrhage: a systematic review and meta-analysis.

BACKGROUND/AIMS: There may be many predictors of anticoagulation-related gastrointestinal bleeding (GIB), but until now, systematic reviews and assessments of the certainty of the evidence have not been published. We conducted a systematic review to identify all risk factors for anticoagulant-associated GIB to inform risk prediction in the management of anticoagulation- related GIB. METHODS: A systematic review and meta-analysis were conducted to search PubMed, EMBASE, Web of Science, and Cochrane Library databases (from inception through January 21, 2022) using the following search terms: anticoagulants, heparin, warfarin, dabigatran, rivaroxaban, apixaban, DOACs, gastrointestinal hemorrhage, risk factors. According to inclusion and exclusion criteria, studies of risk factors for anticoagulation-related GIB were identified. Risk factors for anticoagulant-associated GIB were used as the outcome index of this review. RESULTS: We included 34 studies in our analysis. For anticoagulant-associated GIB, moderate-certainty evidence showed a probable association with older age, kidney disease, concomitant use of aspirin, concomitant use of the antiplatelet agent, heart failure, myocardial infarction, hematochezia, renal failure, coronary artery disease, helicobacter pylori infection, social risk factors, alcohol use, smoking, anemia, history of sleep apnea, chronic obstructive pulmonary disease, international normalized ratio (INR), obesity et al. Some of these factors are not included in current GIB risk prediction models. such as anemia, co-administration of gemfibrozil, co-administration of verapamil or diltiazem, INR, heart failure, myocardial infarction, etc. CONCLUSION: The study found that anemia, co-administration of gemfibrozil, co-administration of verapamil or diltiazem, INR, heart failure, myocardial infarction et al. were associated with anticoagulation-related GIB, and these factors were not in the existing prediction models. This study informs risk prediction for anticoagulant-associated GIB, it also informs guidelines for GIB prevention and future research.

Comparison of the Efficacy and Safety of Rivaroxaban and Low Molecular Heparin in Preventing Venous Thromboembolism in Inpatient Cancer Patients.

BACKGROUND: There are few studies on using rivaroxaban and low molecular heparin (LMWH) to prevent venous thromboembolism (VTE) in hospitalized cancer patients. OBJECTIVE: We conducted a retrospective study to evaluate the efficacy and safety of rivaroxaban versus LMWH for the primary prevention of VTE in inpatient cancer patients. METHODS: Information on patients was collected through 6-month follow-up and medical record inquiries. Clinical outcomes included VTE, total bleeding, thrombosis, major bleeding, minor bleeding, all-cause death, and a composite endpoint of bleeding, thrombosis, and death. RESULTS: A total of 602 hospitalized cancer patients were included in this study. During 6 months of follow-up, there were 26 VTE events (8.6%), 42 total bleeding events (7.0%), 62 all-cause deaths (10.3%), and 140 composite endpoints (23.3%). After adjusting for various confounding factors, there were no significant differences between the rivaroxaban and LMWH for VTE events (OR = 0.851, 95% CI [0.387-1.872], P=0.688), total bleeding (OR = 1.690, 95% CI [0.768-3.719], P = 0.192], thrombosis events (OR = 0.919, 95% CI [0.520-1.624], P = 0.772], major bleeding (OR = 0.276, 95% CI [0.037-2.059], P = 0.209), all-cause death (OR = 0.994, 95% CI [0.492-2.009], P = 0.987), and composite endpoints (OR = 0.994, 95% CI [0.492-2.009], P = 0.987), while minor bleeding (OR = 3.661 95% CI [1.000-7.083], P = 0.050) was significantly higher in the rivaroxaban than in the LMWH. CONCLUSIONS AND RELEVANCE: In thromboprophylaxis in inpatient cancer patients, rivaroxaban has a similar rate of VTE and bleeding events as LMWH. Our results may provide a reference for the clinical use of rivaroxaban to prevent VTE in hospitalized cancer patients.

An Erythrocyte-Templated Iron Single-Atom Nanozyme for Wound Healing.

Iron single-atom nanozymes represent a promising artificial enzyme with superior activity owing to uniform active sites that can precisely mimic active center of nature enzymes. However, current synthetic strategies are hard to guarantee each active site at single-atom state. In this work, an erythrocyte-templated strategy by utilizing intrinsic hemin active center of hemoglobin as sing-atom source for nanozyme formation is developed. By combining cell fixation, porous salinization, and high-temperature carbonization, erythrocytes are successfully served as uniform templates to synthesize nanozymes with fully single-atom FeN4 active sites which derived from hemin of hemoglobin, resulting in an enhanced peroxidase (POD)-like activity. Interestingly, the catalytic activity of erythrocyte-templated nanozyme (ETN) shows dependence on animal species, among which murine ETN performed superior catalytic efficiency. In addition, the as-prepared ETNs display a honeycomb-like network structure, serving as a sponge to accelerate hemostasis based on the interactions with prothrombin and fibrinogen. These features enable ETN to effectively kill methicillin-resistant Staphylococcus aureus (MRSA) by combining POD-like catalysis with near-infrared (NIR) induced photothermal effect, and subsequently suitable to promote wound healing. This study provides a proof-of-concept for facile fabrication of multifunctional nanozymes with uniform single-atom active sites by utilizing intrinsic iron structure characteristics of biogenic source like erythrocytes.

N-nitrosodimethylamine exposure to zebrafish embryos/larvae causes cardiac and spinal developmental toxicity.

N-nitrosodimethylamine (NDMA), one of the new nitrogen-containing disinfection by-products, is potentially cytotoxic, genotoxic, and carcinogenic. Its potential toxicological effects have attracted a wide range of attention, but the mechanism is still not sufficiently understood. To better understand the toxicological mechanisms of NDMA, zebrafish embryos were exposed to NDMA from 3 h post-fertilization (hpf) to 120hpf. Mortality and malformation were significantly increased, and hatching rate, heart rate, and swimming behavior were decreased in the exposure groups. The result indicated that NDMA exposure causes cardiac and spinal developmental toxicity. mRNA levels of genes involved in the apoptotic pathway, including p53, bax, and bcl-2 were significantly affected by NDMA exposure. Moreover, the genes associated with spinal and cardiac development (myh6, myh7, nkx2.5, eph, bmp2b, bmp4, bmp9, run2a, and run2b) were significantly downregulated after treatment with NDMA. Wnt and TGF-ß signaling pathways, crucial for the development of diverse tissues and organs in the embryo and the establishment of the larval spine, were also significantly disturbed by NDMA treatment. In summary, the disinfection by-product, NDMA, exhibits spinal and cardiac developmental toxicity in zebrafish embryos, providing helpful information for comprehensive analyses and a better understanding the mechanism of its toxicity.

Long-Term Strategies for Poorly Water-Soluble Peptides: Combining Fatty Acid Modification with PAS Fusion.

Bulevirtide, an entry inhibitor for the hepatitis B virus (HBV) and hepatitis D virus (HDV), is currently available on the European market. However, its clinical application is constrained by its short half-life and poor water solubility, rendering it unsuitable for fatty acid modification, aimed at achieving long-term effects. To address this limitation, we integrated a polypeptide chain consisting of Pro, Ala, and Ser at the C-terminus, which increased its hydrophilicity. To obtain the fusion sequence of A1 and A2, encompassing amino acids 1-47 of Bulevirtide and PAS, we used Escherichia coli fermentation expression. Subsequently, the N-terminal myristoyl groups of A1 and A2 were modified to yield Myr-A1 and Myr-A2, respectively. Five fatty acid moieties with the same hydrophilic spacers and different fatty acids were conjugated to analogs, generating 10 bioconjugations. The bioconjugates were then evaluated for their anti-HBV activity. Among them, HB-10 was selected for pharmacokinetic analysis and demonstrated a significantly prolonged half-life, with 5.88- and 13.18-fold increases in beagle dogs and rats, respectively. Additionally, higher drug doses resulted in substantially elevated liver concentrations. In conclusion, via fatty acid incorporation and PASylation, we successfully developed a novel Bulevirtide bioconjugate, HB-10, that exhibits an extended action duration. This compound holds substantial promise as a prospective long-acting entry inhibitor, warranting further investigation.

A Study on the Effect of Precise Rehabilitation Therapy Guided by Three-dimensional-computed Tomography Reconstruction Technology in Hip Fracture Surgery Patients.

OBJECTIVE: To evaluate the effectiveness of precise rehabilitation therapy guided by three-dimensional computed tomography (3D-CT) reconstruction technology in hip fracture patients through a retrospective cohort study. METHOD: Data were retrospectively collected from 60 patients aged over 60 who had undergone hip fracture surgery. They were divided into two groups based on their chosen rehabilitation method: a control group and a test group. The study collected demographic data, fracture characteristics, and quality of life indicators to assess the impact of rehabilitation on economic indicators and daily living activities (ADL). Additionally, it included assessments of muscle strength, joint mobility, hip function, postoperative complications, and records of hospitalization information and costs. Cognitive function was also assessed postoperatively. RESULTS: There were no significant differences in demographic data, fracture characteristics, ADL, or Fugl-Meyer assessment (FMA) between the two groups. However, the test group exhibited significantly higher post-surgery muscle strength recovery and hip mobility compared to the control group (P<0.05). Additionally, the test group had significantly fewer hospitalization days and lower hospitalization costs than the control group (P<0.05). CONCLUSION: Precise rehabilitation therapy guided by 3D-CT reconstruction technology for hip fracture surgery patients can enhance early muscle strength recovery, improve mobility of the affected limb, reduce hospitalization duration and costs, and enhance overall patient recovery outcomes.

The Immune Regulatory Role of Adenosine in the Tumor Microenvironment.

Adenosine, an immunosuppressive metabolite, is produced by adenosine triphosphate (ATP) released from dying or stressed cells and is found at high levels in the tumor microenvironment of most solid tumors. It mediates pro-tumor activities by inducing tumor cell proliferation, migration or invasion, tumor tissue angiogenesis, and chemoresistance. In addition, adenosine plays an important role in regulating anti-tumor immune responses and facilitating tumor immune escape. Adenosine receptors are broadly expressed by tumor-infiltrated immune cells, including suppressive tumor-associated macrophages and CD4+ regulatory T cells, as well as effector CD4+ T cells and CD8+ cytotoxic T lymphocytes. Therefore, adenosine is indispensable in down-regulating anti-tumor immune responses in the tumor microenvironment and contributes to tumor progression. This review describes the current progress on the role of adenosine/adenosine receptor pathway in regulating the tumor-infiltrating immune cells that contribute to tumor immune evasion and aims to provide insights into adenosine-targeted tumor immunotherapy.

The Separation, Purification, Structure Identification, and Antioxidant Activity of Elaeagnus umbellata Polysaccharides.

In order to investigate the antioxidant activity of Elaeagnus umbellata polysaccharides, the physicochemical characteristics of purified Elaeagnus umbellata polysaccharides (EUP, consisting of two fractions, EUP1 and EUP2) were investigated using UV spectrophotometry, high-performance liquid chromatography (HPLC), high-performance gel permeation chromatography (HPGPC), and Fourier transform infrared spectroscopy (FT-IR). This revealed that EUP1 and EUP2 were acidic polysaccharides with an average molecular weight (MW) of 63 and 38 kDa, respectively. EUP1 mainly consisted of L-rhamnose and D-galactose in a molar ratio of 2.05:1, and EUP2 consisted of D-mannose, L-rhamnose, D-galactose, and D-arabinose in a molar ratio of 2.06:1:2.78:1. Furthermore, EUP exhibited considerable antioxidant potential for scavenging hydroxyl, superoxide anion, DPPH, and ABTS radicals. Therefore, EUP can be developed as a potential antioxidant for the functional food or pharmaceutical field.

Clinical analysis of 908 patients with aortic dissection under different Stanford types: A cross-sectional study.

This study aims to investigate the difference of clinical characteristics and risk factors in aortic dissection (AD) of patients with 2 Stanford subtypes. A retrospective analysis was conducted on 908 patients admitted to Tongji Hospital from July 2019 to January 2021, and the aortic computed tomography angiography was used to clearly diagnose the artery dissection. Patient basic information as well as blood test indicators containing leukocytes, neutrophils, lymphocytes, hemoglobin, myoglobin, hypersensitive cardiac troponin, γ-glutamyl transferase, total cholesterol, triglyceride, high density lipoprotein, low density lipoprotein, ultrasensitive C-reactive protein, glucose were recorded and analyzed. There was no significant difference in gender, heart rate, smoking history, hypertension history and diabetes history between the 2 groups (P > .05), however, compared with type A patients, type B patients were older, and had a significantly higher frequency of alcohol consumption (P < .05); On laboratory tests, type A patients had significantly higher mean leukocytes and neutrophils (P < .05), and significantly lower frequency of reduced hemoglobin than type B patients (P < .05), although there was no statistical difference in lymphocyte, γ-glutamyl transferase, total cholesterol, triglyceride, high density lipoprotein, low density lipoprotein and glucose counts between the 2 groups. Additionally, type A patients had a significantly higher number of abnormal myoglobin, hypersensitive cardiac troponin and ultrasensitive C-reactive protein test results than type B patients (P < .05). The receiver operating characteristic curve analysis showed that the area under the curve for each parameter was 0.605 (0.538-0.673) for hemoglobin, 0.610 (0.543-0.677) for leukocytes and 0.627 (0.561-0.693) for neutrophils. Understanding the relevant clinical indicators and risk factors of patients with different types of AD can provide a new perspective to assist the classification and diagnosis of AD and a basis for effective and rational treatment.

The impact of ABCB1, CYP3A4/5 and ABCG2 gene polymorphisms on rivaroxaban trough concentrations and bleeding events in patients with non-valvular atrial fibrillation.

BACKGROUND: The influence of genetic factors on the pharmacokinetics and clinical outcomes of rivaroxaban in patients with non-valvular atrial fibrillation (NVAF) is poorly understood. This study aimed to explore the effects of CYP3A4/5, ABCB1, and ABCG2 gene polymorphisms on the trough concentrations and the bleeding risk of rivaroxaban in NVAF patients. PATIENTS AND METHODS: This study is a prospective multicenter study. The patient's blood samples were collected to detect the steady-state trough concentrations of rivaroxaban and gene polymorphisms. We visited the patients regularly at month 1, 3, 6, and 12 to record bleeding events and medications. RESULTS: A total of 95 patients were enrolled in this study, and 9 gene loci were detected. For the dose-adjusted trough concentration ratio (Ctrough/D) of rivaroxaban, the homozygous mutant type was significantly lower than wild type at ABCB1 rs4148738 locus (TT vs. CC, P = 0.033), and the mutant type was significantly lower than the wild type at ABCB1 rs4728709 locus (AA + GA vs. GG, P = 0.008). ABCB1 (rs1045642, rs1128503), CYP3A4 (rs2242480, rs4646437), CYP3A5 (rs776746), and ABCG2 (rs2231137, rs2231142) gene polymorphisms had no significant effect on the Ctrough/D of rivaroxaban. For the bleeding events, we found that there were no significant differences among genotypes of all gene loci. CONCLUSION: This study found for the first time that ABCB1 rs4148738 and rs4728709 gene polymorphisms had a significant impact on the Ctrough/D of rivaroxaban in NVAF patients. CYP3A4/5, ABCB1, and ABCG2 gene polymorphisms were not associated with the bleeding risk of rivaroxaban.

A new model (Alfalfa-Warfarin-GIB) for predicting the risk of major gastrointestinal bleeding in warfarin patients.

BACKGROUND: This study aimed to analyze the factors influencing warfarin-related major gastrointestinal bleeding (GIB) and to develop a score that would provide a reference for assessing the risk of major GIB associated with warfarin treatment. METHODS: This was a retrospective analysis of clinical and follow-up data from warfarin-treated patients. Scores were analyzed using logistic regression. The area under the subject working characteristic curve (AUC), sensitivity, specificity, and Hosmer-Lemeshow test were used to evaluate the scoring performance. RESULTS: A total of 1591 patients who met the requirements for warfarin use were included in this study, and 46 developed major GIB. After univariate analysis as well as multivariate logistic regression analysis, nine factors were found to be associated with increased risk of major GIB, namely age ≥ 65 years, history of peptic ulcer, history of major bleeding, abnormal liver function, abnormal renal function, cancer, anemia, labile international normalized ratio, and combination of antiplatelet agents/non-steroidal anti-inflammatory drugs. The Alfalfa-Warfarin-GIB score was constructed using these nine factors. The AUC and Bootstrap method-corrected AUC of the Alfalfa-Warfarin-GIB score were 0.916 (95% CI: 0.862-0.970, P < 0.001) and 0.919 (95% CI: 0.860-0.967, P < 0.001), respectively, which were higher than those of the HAS-BLED score (AUC = 0.868, 95% CI: 0.812-0.924, P < 0.001). CONCLUSION: Based on nine risk factors, the Alfalfa-Warfarin-GIB score was constructed to predict the risk of warfarin-related major GIB. The newly developed Alfalfa-Warfarin-GIB score has a better predictive value than the HAS-BLED score and may be an effective tool to help reduce the occurrence of major GIB in patients on warfarin.