Japanese encephalitis virus inhibits superinfection of Zika virus in cells by the NS2B protein.

Superinfection exclusion (SIE) is a phenomenon in which a preexisting infection prevents a secondary infection. SIE has been described for several flaviviruses, such as West Nile virus vs Nhumirim virus and Dengue virus vs yellow fever virus. Zika virus (ZIKV) is an emerging flavivirus posing threats to human health. The SIE between ZIKV and Japanese encephalitis virus (JEV) is investigated in this study. Our results demonstrate for the first time that JEV inhibits ZIKV infection in both mammalian and mosquito cells, whether co-infects or subsequently infects after ZIKV. The exclusion effect happens at the stage of ZIKV RNA replication. Further studies show that the expression of JEV NS2B protein is sufficient to inhibit the replication of ZIKV, and the outer membrane region of NS2B (46-103 aa) is responsible for this SIE. JEV infection and NS2B expression also inhibit the infection of the vesicular stomatitis virus. In summary, our study characterized a SIE caused by JEV NS2B. This may have potential applications in the prevention and treatment of ZIKV or other RNA viruses.IMPORTANCEThe reemerged Zika virus (ZIKV) has caused severe symptoms in humans and poses a continuous threat to public health. New vaccines or antiviral agents need to be developed to cope with possible future pandemics. In this study, we found that infection of Japanese encephalitis virus (JEV) or expression of NS2B protein well inhibited the replication of ZIKV. It is worth noting that both the P3 strain and vaccine strain SA14-14-2 of JEV exhibited significant inhibitory effects on ZIKV. Additionally, the JEV NS2B protein also had an inhibitory effect on vesicular stomatitis virus infection, suggesting that it may be a broad-spectrum antiviral factor. These findings provide a new way of thinking about the prevention and treatment of ZIKV.

Bile Acids Control Inflammation and Metabolic Disorder through Inhibition of NLRP3 Inflammasome.

Reciprocal interactions between the metabolic system and immune cells play pivotal roles in diverse inflammatory diseases, but the underlying mechanisms remain elusive. The activation of bile acid-mediated signaling has been linked to improvement in metabolic syndromes and enhanced control of inflammation. Here, we demonstrated that bile acids inhibited NLRP3 inflammasome activation via the TGR5-cAMP-PKA axis. TGR5 bile acid receptor-induced PKA kinase activation led to the ubiquitination of NLRP3, which was associated with the PKA-induced phosphorylation of NLRP3 on a single residue, Ser 291. Furthermore, this PKA-induced phosphorylation of NLRP3 served as a critical brake on NLRP3 inflammasome activation. In addition, in vivo results indicated that bile acids and TGR5 activation blocked NLRP3 inflammasome-dependent inflammation, including lipopolysaccharide-induced systemic inflammation, alum-induced peritoneal inflammation, and type-2 diabetes-related inflammation. Altogether, our study unveils the PKA-induced phosphorylation and ubiquitination of NLRP3 and suggests TGR5 as a potential target for the treatment of NLRP3 inflammasome-related diseases.

Oral administration of PEDV-dissolved Alg-CS gel induces high and sustained mucosal immunity in mice.

Porcine epidemic diarrhea (PED) is a serious disease in piglets that leads to high mortality. An effective measure that provides higher IgA levels in the intestine and milk is required to decrease losses. Porcine epidemic diarrhea virus (PEDV) was dissolved in calcium alginate (Alg) and combined with chitosan (CS) via electrostatic interactions between cationic chitosan and anionic alginate to create a porous gel (Alg-CS+PEDV). The gel was used to immunize mice orally or in combination with subcutaneous injections of inactivated PEDV vaccine. At 12 and 24 days after immunization, levels of IgA and IgG in Alg-CS+PEDV were higher than with normal PEDV oral administration. At 24 days after immunization, the concentration of IFN-γ in Alg-CS+PEDV was higher than with normal PEDV oral administration. Furthermore, oral administration combining subcutaneous immunization induced higher levels of IgG and IgA than oral administration alone. Our study provides a new method for the preparation and administration of oral vaccines to achieve enhanced mucosal immunity against PEDV.

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 score for predicting intracranial hemorrhage in patients using antiplatelet drugs.

Antiplatelet drugs in patients increase the risk of intracranial hemorrhage (ICH), which can seriously affect patients' quality of life and even endanger their lives. Currently, there is no specific score for predicting the risk of ICH caused by antiplatelet drugs. We aimed to identify factors associated with ICH in patients on antiplatelet drugs and to construct and validate a predictive model that would provide a validated tool for the clinic. Data were obtained from the patient medical records inpatient system. Prediction models were built by logistic regression, the area under the curve (AUC), and column line plots. Internal validation, analytical identification and calibration of the model using AUC, calibration curves and Hosmer-Lemeshow test. The registration number of this study is ChiCTR2000031909, and the ethical review number is 2020KY087. This single-center retrospective study enrolled 753 patients treated with antiplatelet drugs, including 527 in the development cohort. Multifactorial analysis showed that male, headache or vomiting, hypertension, cerebrovascular disease, CT-defined white matter hypodensity, abnormal GCS, fibrinogen and D-dimer were independent risk factors for ICH, and lipid-lowering drugs was a protective factor. The model was constructed using these nine factors with an AUC value of 0.949. In the validation cohort, the model showed good discriminatory power with an AUC value of 0.943 and good calibration (Hosmer-Lemeshow test P value of 0.818). Based on 9 factors, we derived and validated a predictive model for ICH with antiplatelet drugs in patients. The model has good predictive value and may be an effective tool to reduce the occurrence of ICH.

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.

Ru-Doped Ultrasmall Cu Nanoparticles Decorated with Carbon for Electroreduction of Nitrate to Ammonia.

Electrocatalytic nitrate reduction reaction offers a sustainable approach to treating wastewater and synthesizing high-value ammonia under ambient conditions. However, electrocatalysts with low faradaic efficiency and selectivity severely hinder the development of nitrate-to-ammonia conversion. Herein, Ru-doped ultrasmall copper nanoparticles loaded on a carbon substrate (Cu-Ru@C) were fabricated by the pyrolysis of Cu-BTC metal-organic frameworks (MOFs). The Cu-Ru@C-0.5 catalyst exhibits a high faradaic efficiency (FE) of 90.4% at -0.6 V (vs RHE) and an ammonia yield rate of 1700.36 µg h-1mgcat.-1 at -0.9 V (vs RHE). Moreover, the nitrate conversion rate is almost 100% over varied pHs (including acid, neutral, and alkaline electrolytes) and different nitrate concentrations. The remarkable performance is attributed to the synergistic effect between Cu and Ru and the excellent conductivity of the carbon substrate. This work will open an exciting avenue to exploring MOF derivatives for ambient ammonia synthesis via selective electrocatalytic nitrate reduction.

Ru-Doped NiFe-MIL-53 with Facilitated Reconstruction and Active Hydrogen Supplement for Enhanced Nitrate Reduction.

The Electrochemical reduction of nitrate to ammonia (NH3) is a process of great significance to energy utilization and environmental protection. However, it suffers from sluggish multielectron/proton-involved steps involving coupling reactions between different reaction intermediates and active hydrogen species (Hads) produced by water decomposition. In this study, a Ru-doped NiFe-MIL-53 (NiFeRu-MIL-53) supported on Ni foam (NF) has been designed for the nitrate reduction reaction (NO3RR). The NiFeRu-MIL-53 exhibits excellent NO3RR activity with a maximum Faradaic efficiency (FE) of 100% at -0.4 V vs. RHE for NH3 and a maximum NH3 yield of 62.39 mg h-1 cm-2 at -0.7 V vs. RHE in alkaline media. This excellent performance for the NO3RR is attributed to a strong synergistic effect between Ru and reconstructed NiFe(OH)2. Additionally, the doped Ru facilitates water dissociation, leading to an appropriate supply of Hads required for N species hydrogenation during NO3RR, thereby further enhancing its performance. Furthermore, in situ Raman analysis reveals that incorporating Ru facilitates the reconstruction of MOFs and promotes the formation of hydroxide active species during the NO3RR process. This work provides a valuable strategy for designing electrocatalysts to improve the efficiency of the reduction of electrochemical nitrate to ammonia.

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.

Comparison of the Correlation Between Coagulation Indices and Rivaroxaban Concentrations.

BACKGROUND: Rivaroxaban has predictable pharmacokinetics and pharmacodynamics. However, monitoring rivaroxaban concentrations should be provided for special patients with hepatic insufficiency, high bleeding risk, and high thrombotic risk. OBJECTIVE: This study aimed to correlate chromogenic anti-Xa assay, prothrombin time (PT), activated partial thromboplastin time (APTT), thromboelastogram reaction time (TEG R-time), and rivaroxaban concentration measured by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) (MS-Riva). METHODS: Peripheral venous blood was collected from recruited patients 30 minutes before and 2 to 4 hours after drug administration. High-performance liquid chromatography-tandem mass spectrometry and chromogenic anti-Xa assay measured rivaroxaban concentration. Different assays were compared by Pearson correlation coefficient and Bland-Altman analysis. RESULTS: A total of 104 patients with 191 plasma were included in the study. Overall analysis shows that chromogenic anti-Xa assay, PT, APTT, and TEG R-time strongly correlated with MS-Riva (r = 0.986; r = 0.884; r = 0.741; r = 0.739; P < 0.001). Rivaroxaban peak concentration detected by HPLC-MS/MS (MS-peak) showed a very strong correlation with the chromogenic anti-Xa assay (r = 0.977, P < 0.001) and moderate correlation with PT, APTT, and TEG R-time (r = 0.670; r = 0.571; r = 0.481, P < 0.001). Rivaroxaban trough concentration detected by HPLC-MS/MS (MS-trough) correlated strongly with the chromogenic anti-Xa assay (r = 0.884, P < 0.001), weakly with APTT (r = 0.313; P = 0.043), and not significantly with PT and TEG R-time (P = 0.140; P = 0.341). CONCLUSION AND RELEVANCE: High-performance liquid chromatography-tandem mass spectrometry/MS is the preferred choice for monitoring peak and tough concentrations, followed by anti-Xa, while PT is only suitable for peak concentrations. This study can help the clinicians to better adjust the medication regimen and reduce the risk of recurrence of thrombosis as well as the risk of bleeding.

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.

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 dabigatran and rivaroxaban in atrial fibrillation patients with impaired liver function: a multicenter retrospective cohort study.

BACKGROUND: The efficacy and safety of direct oral anticoagulants (DOACs) in atrial fibrillation (AF) patients with impaired liver function (ILF) have not been sufficiently studied. The aim of this study was to evaluate the efficacy and safety of DOACs for stroke prevention in patients with AF and ILF. METHOD: This study was based on data from 15 centers in China, including 4,982 AF patients. The patients were divided into 2 subgroups based on their liver function status: patients with normal liver function (NLF)(n = 4213) and patients with ILF (n = 769). Logistic regression analysis was used to investigate the risk of total bleeding, major bleeding, thromboembolism, and all-cause deaths in AF patients with NLF and ILF after taking dabigatran or rivaroxaban, respectively. RESULTS: Among AF patients treated with dabigatran or rivaroxaban, patients with ILF were associated with significantly higher major bleeding, compared with NLF patients (aOR: 4.797; 95% CI: 2.224-10.256; P < 0.001). In patients with NLF, dabigatran (n = 2011) had considerably lower risk of total bleeding than rivaroxaban (n = 2202) (aOR: 1.23; 95% CI: 1.002-1.513; P = 0.049). In patients with ILF, dabigatran (n = 321) significantly favored lower risks of major bleeding compared with rivaroxaban(n = 448) (aOR: 5.484; 95% CI: 1.508-35.269; P = 0.026). CONCLUSION: After using dabigatran or rivaroxaban, patients with ILF had remarkably increased risk of major bleeding compared with patients with NLF. In AF patients with NLF, dabigatran had the distinct strength of significantly reduced risk of total bleeding compared with rivaroxaban. In patients with AF and ILF, dabigatran use was associated with lower risk for major bleeding compared with rivaroxaban.

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.

The role of lncRNA HCG18 in human diseases.

A substantial number of long noncoding RNAs (lncRNAs) have been identified as potent regulators of human disease. Human leukocyte antigen complex group 18 (HCG18) is a new type of lncRNA that has recently been proven to play an important role in the occurrence and development of various diseases. Studies have found that abnormal expression of HCG18 is closely related to the clinicopathological characteristics of many diseases. More importantly, HCG18 was also found to promote disease progression by affecting a series of cell biological processes. This article mainly discusses the expression characteristics, clinical characteristics, biological effects and related regulatory mechanisms of HCG18 in different human diseases, providing a scientific theoretical basis for its early clinical application.

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.

Association between high-mobility group box 1 levels and preeclampsia: a systematic review and meta-analysis.

PURPOSE: Previous studies had demonstrated that high-mobility group box 1 (HMGB1) levels were elevated in preeclampsia (PE). However, the conclusion remains controversial. This study aimed to investigate the association between blood and placenta HMGB1 levels and PE in pregnant women. METHODS: After a systematic literature search, eligible literature was screened according to inclusion and exclusion criteria. Data extraction and quality assessment were performed independently by two reviewers. The extracted data were analyzed using Review Manager 5.4 and STATA 12.0 software. Subgroup analysis and meta-regression analysis were conducted to find potential sources of heterogeneity. RESULTS: Twelve studies were included, with a total of 1145 participants. Compared with normal pregnancies, pregnant women with PE had significantly higher blood HMGB1 levels (SMD = 1.34, 95% CI: 0.72-1.95, p < 0.0001). Similarly, the expression of placental HMGB1 in PE was higher than that in normal controls by using Western blot (MD = 0.37, 95% CI: 0.27-0.47, p < 0.00001) or immunohistochemistry (OR = 6.36, 95% CI: 1.48-27.25, p = 0.01). In addition, the blood HMGB1 levels were positively correlated with the severity of PE, with higher blood HMGB1 levels in severe PE than those in mild PE (SMD = 3.35, 95% CI: 0.63-6.06, p = 0.02). The subgroup analysis indicated a close association of blood HMGB1 with PE in the Asian group, but not in the European group. CONCLUSION: Both blood and placental HMGB1 levels in patients with PE were significantly elevated, and higher blood HMGB1 levels indicated a more serious disease condition, suggesting that higher levels of HMGB1 were associated with the risk of PE.

Separation and Detection of Catechins and Epicatechins in Shanxi Aged Vinegar Using Solid-Phase Extraction and Hydrophobic Deep Eutectic Solvents Combined with HPLC.

This research presents a new, eco-friendly, and swift method combining solid-phase extraction and hydrophobic deep eutectic solvents (DES) with high-performance liquid chromatography (SPE-DES-HPLC) for extracting and quantifying catechin and epicatechin in Shanxi aged vinegar (SAV). The parameters, such as the elution solvent type, the XAD-2 macroporous resin dosage, the DES ratio, the DES volume, the adsorption time, and the desorption time, were optimized via a one-way experiment. A central composite design using the Box-Behnken methodology was employed to investigate the effects of various factors, including 17 experimental runs and the construction of three-dimensional response surface plots to identify the optimal conditions. The results show that the optimal conditions were an HDES (tetraethylammonium chloride and octanoic acid) ratio of 1:3, an XAD-2 macroporous resin dosage of 188 mg, and an adsorption time of 11 min. Under these optimal conditions, the coefficients of determination of the method were greater than or equal to 0.9917, the precision was less than 5%, and the recoveries ranged from 98.8% to 118.8%. The environmentally friendly nature of the analytical process and sample preparation was assessed via the Analytical Eco-Scale and AGREE, demonstrating that this method is a practical and eco-friendly alternative to conventional determination techniques. In summary, this innovative approach offers a solid foundation for the assessment of flavanol compounds present in SAV samples.

Qualitative study on the perception of good death in patients with end-stage cancer in oncology nurses.

OBJECTIVE: To explore the perception of good death of patients with end-stage cancer by nurses in the oncology department. METHOD: In the study we used a phenomenological approach and semi-structured interviews. A total of 11 nurses from the oncology department of a Grade A hospital in Taizhou were interviewed on the cognition of good death from July 1 to September 30, 2022. Colaizzi's analysis method was used to analyse the interview data. This study followed the consolidated criteria for reporting qualitative research (COREQ). RESULT: Four themes were identified: a strong sense of responsibility and mission; To sustain hope and faith; The important role of family members; Improve patients' quality of life. CONCLUSION: The nurses in the department of oncology have a low level of knowledge about the "good death", and the correct understanding and view of the "good death" is the premise of the realization of " good death". The ability of nursing staff to improve the "good death", attention, and meet the needs and wishes of individuals and families, is the guarantee of the realization of "good death".