Comparison of the efficacy and safety between rivaroxaban and dabigatran in the treatment of acute portal vein thrombosis in cirrhosis.

BACKGROUND: New oral anticoagulants (NOACs) have been becoming prevalent in recent years and are increasingly used in the treatment of port vein thrombosis. The difference of the efficacy and safety between rivaroxaban and dabigatran remains unclear in the treatment of cirrhotic patients with acute portal vein thrombosis (PVT). METHODS: This retrospective study included all consecutive cirrhotic patients with acute portal vein thrombosis in our institute from January 2020 to December 2021. The patients received oral anticoagulation with rivaroxaban or dabigatran. The demographic, clinical, and imaging data of patients were collected. The diagnosis of acute PVT was confirmed by imaging examinations. The severity of liver cirrhosis was assessed using Child-Pugh score and Model for End-Stage Liver Disease (MELD) score. Outcomes included recanalization (complete, partial, and persistent occlusion), liver function, bleedings, and survival. The log-rank test was used to compare Kaplan-Meier distributions of time-to-event outcomes. The Cox proportional hazards model was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: A total of 94 patients were included, 52 patients (55%) received rivaroxaban and 42 (45%) with dabigatran. The complete and partial recanalization of PVT was observed in 41 patients. There was no significant difference in complete recanalization, partial recanalization, and persistent occlusion between the two groups. With multivariate analysis, D-dimer (HR 1.165, 95% CI 1.036-1.311, p = 0.011) was independent predictors of complete recanalization. The Child-Pugh score (p = 0.001) was significantly improved in both two groups after anticoagulation, respectively. However, there was no difference between the two groups. The probability of survival was 94%, 95% in the rivaroxaban and dabigatran groups (log-rank p = 0.830). Major bleedings were reported in 3 patients (6%) in rivaroxaban group and 1 patient (2%) in dabigatran group (p = 0.646). Six patients (12%) in rivaroxaban group experienced minor bleeding, and five (12%) from dabigatran group (p = 0.691). CONCLUSIONS: The efficacy and safety were comparable between rivaroxaban and dabigatran in the treatment of cirrhotic patients with acute portal vein thrombosis. And D-dimer can contribute to the prediction of PVT recanalization in cirrhotic patients.

Pharmacokinetic interaction study of combining imatinib with dasatinib in rats by UPLC-MS/MS.

This study examined whether oral administration of dasatinib to the rats with imatinib led to any pharmacokinetic interactions. Twenty-four rats were divided randomly into three groups, imatinib group (imatinib 25 mg/kg, n = 8), dasatinib group (dasatinib 15 mg/kg, n = 8) and co-administration group (dasatinib 15 mg/kg and imatinib 25 mg/kg, n = 8). The concentration of imatinib and dasatinib in rat plasma was determined by a sensitive and simple UPLC-MS/MS method. There was statistical pharmacokinetics difference for imatinib in the imatinib group and co-administration group, when co-oral administration imatinib with dasatinib, MRT(0-t) increased (p < 0.01). There was statistical pharmacokinetics difference for dasatinib in the dasatinib group and co-administration group, when co-oral administration dasatinib with imatinib, Cmax and AUC increased (p < 0.01), CL and V decreased (p < 0.01). These data indicate dasatinib could slightly influence the pharmacokinetic profile of imatinib in rats, and imatinib could influence the pharmacokinetic profile of dasatinib in rats, which might cause drug-drug interactions when using imatinib with dasatinib.

Microstructure and Mechanical Properties of As-Cast Al-10Ce-3Mg-xZn Alloys.

The microstructure and mechanical properties of as-cast Al-10Ce-3Mg-xZn (x = 0, 1, 3, 5 wt.%) alloys were systematically investigated, with a focus on the effect of Zn on the Al11Ce3 reinforcing phase in the alloy. The results showed that the Al-10Ce-3Mg alloy consists of α-Al, a Chinese-script Al11Ce3 eutectic phase, and a massive Al11Ce3 primary phase. With the addition of Zn content, most of the Zn atoms are enriched in the Al11Ce3 phase to form the acicular-like Al2CeZn2 phase within the Al11Ce3 phase. Increasing the Zn content can increase the volume fraction of the Al11Ce3 phase. Compared to the alloy without Zn addition, the microhardness and elastic modulus of the Al2CeZn2-reinforced Al11Ce3 phase in the alloy with 5 wt.% Zn increased by 18.9% and 9.0%, respectively. Moreover, the room-temperature mechanical properties of Al-10Ce-3Mg alloys were significantly improved due to the addition of Zn element. The alloy containing 5 wt.% Zn had the best tensile properties with an ultimate tensile strength of 210 MPa and a yield strength of 171MPa, which were 21% and 77% higher than those of the alloy without Zn, respectively. The alloy containing 5 wt.% Zn demonstrated a superior retention ratio of tensile strength at 200-300 °C, indicating that the alloy has excellent heat resistance. The improvement in the mechanical properties is primarily attributed to second-phase strengthening and solid solution strengthening.

Effects of Beryllium Addition on Microstructure, Mechanical and Corrosion Performance of Al-Mg-Li Alloys.

The Al-Mg-Li alloy is ideal for ultra-lightweight aircraft components, and its further performance improvement is of great interest in the aerospace industry. In this study, the effects of various beryllium (Be) additions (Be-free, 0.1, 0.25, 0.50 wt.%) on the microstructure, mechanical, and corrosion performance of the Al-Mg-Li alloys were systematically investigated. The optimal tensile property was obtained in the alloy which added 0.1 wt.% Be with an ultimate tensile strength (UTS), yield strength (YS), and elongation (El) of 530 MPa, 370 MPa, and 9.2%, respectively. Trace Be addition promotes the grain refinement of the as-cast alloy ingot and contributes positive effects to the recrystallization, bringing improvement of the tensile property. Meanwhile, the best anti-corrosion behavior is also presented at 0.1 wt.% Be is added, due to its potential to reduce the width of precipitates free zone (PFZ). As the Be content increases to an excessive level, the comprehensive performance decreases. Therefore, it is strongly recommended that adding trace Be elements into Al-Mg-Li alloys has a positive effect on the comprehensive service performance.

An Autophagy-Associated MITF-GAS5-miR-23 Loop Attenuates Vascular Oxidative and Inflammatory Damage in Sepsis.

BACKGROUND: Sepsis induces GAS5 expression in the vascular endothelium, but the molecular mechanism is unclear, as is the role of GAS5 in sepsis. METHODS AND RESULTS: We observed that GAS5 expression in the endothelium was significantly upregulated in a sepsis mouse model. ChIP-PCR and EMSA confirmed that the oxidative stress (OS)-activated MiT-TFE transcription factor (MITF, TFE3, and TFEB)-mediated GAS5 transcription. In vitro, GAS5 overexpression attenuated OS and inflammation in endothelial cells (ECs) while maintaining the structural and functional integrity of mitochondria. In vivo, GAS5 reduced tissue ROS levels, maintained vascular barrier function to reduce leakage, and ultimately attenuated sepsis-induced lung injury. Luciferase reporter assays revealed that GAS5 protected MITF from degradation by sponging miR-23, thereby forming a positive feedback loop consisting of MITF, GAS5, and miR-23. Despite the fact that the OS-activated MITF-GAS5-miR-23 loop boosted MITF-mediated p62 transcription, ECs do not need to increase mitophagy to exert mitochondrial quality control since MITF-mediated Nrf2 transcription exists. Compared to mitophagy, MITF-transcribed p62 prefers to facilitate the autophagic degradation of Keap1 through a direct interaction, thereby relieving the inhibition of Nrf2 by Keap1, indicating that MITF can upregulate Nrf2 at both the transcriptional and posttranscriptional levels. Following this, ChIP-PCR demonstrated that Nrf2 can also transcribe MITF, revealing that there is a reciprocal positive regulatory association between MITF and Nrf2. CONCLUSION: In sepsis, the ROS-activated MITF-GAS5-miR-23 loop integrated the antioxidant and autophagy systems through MITF-mediated transcription of Nrf2 and p62, which dynamically regulate the level and type of autophagy, as well as exert antioxidant and anti-inflammatory effects.

Effect of Combined Addition of CeLa and GdY on Microstructure and Mechanical Properties of As-Cast Al-Cu-Mn Alloys.

In this study, the effects of the combined addition of CeLa and GdY on the microstructure and mechanical properties of as-cast Al-4Cu-1Mn alloys were investigated by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and tensile testing. The results show that the minor addition of CeLa and GdY leads to a refinement of grain size. The addition of CeLa results in the formation of supersaturated vacancies in the Al matrix, whereas the addition of GdY leads to a decrease in the precipitation temperature of the Al2Cu phase. The combined CeLa and GdY additions can significantly increase ultimate tensile strength (UTS) while losing only a small amount of elongation (EL). Compared with the unmodified alloy, the grain size and SDAS of the alloy (0.2 wt.% CeLa + 0.1 wt.% GdY) were diminished by 67.2% and 58.7%, respectively, while maximum hardness and UTS rose by 31.2% and 36.9%, respectively.

Physical and mental health impairments experienced by operating surgeons and camera-holder assistants during laparoscopic surgery: a cross-sectional survey.

Introduction: Surgeons may experience physical and mental health problems because of their jobs, which may lead to chronic muscle damage, burnout, or even withdrawal. However, these are often ignored in camera-holder assistants during laparoscopic surgery. We aimed to analyze the differences between operating surgeons and camera-holder assistants. Methods: From January 1, 2022, to December 31, 2022, a cross-sectional survey was conducted to evaluate the muscle pain, fatigue, verbal scolding, and task load for operating surgeons and camera-holder assistants. The Nordic Musculoskeletal Questionnaire, the Space Administration Task Load Index, and the Surgical Task Load Index (SURG-TLX) were combined in the questionnaire. Results: 2,184 operations were performed by a total of 94 operating surgeons and 220 camera assistants. 81% of operating surgeons and 78% of camera-holder assistants reported muscle pain/discomfort during the procedure. The most affected anatomic region was the shoulders for operating surgeons, and the lower back for camera-holder assistants. Intraoperative fatigue was reported by 41.7% of operating surgeons and 51.7% of camera-holder assistants. 55.2% of camera-holder assistants reported verbal scolding from the operating surgeons, primarily attributed to lapses in laparoscope movement coordination. The SURG-TLX results showed that the distributions of mental, physical, and situational stress for operating surgeons and camera-holder assistants were comparable. Conclusion: Like operating surgeons, camera-holder assistants also face similar physical and mental health impairments while performing laparoscopic surgery. Improvements to the working conditions of the camera-holder assistant should not be overlooked.

Strategies involving low-molecular-weight heparin for the treatment and prevention of venous thromboembolism in patients with obesity: A systematic review and meta-analysis.

Introduction: Recent studies have indicated that the dosage of LMWH in patients with specific weights may be controversial. Therefore, we conducted a meta-analysis to explore an appropriate dosage of LMWH for the prevention and treatment of venous thromboembolism (VTE) in patients with obesity. Materials and methods: We searched the PubMed, EMBASE, and Cochrane Library databases up to July 23, 2022. Study selection, bias analysis, and information extraction were performed by three independent reviewers. The occurrence or recurrence of VTE and bleeding events were the primary outcomes we assessed. Results: Eleven studies (a total of 6266 patients) were included in the prevention group, and 6 studies (a total of 3225 patients) were included in the treatment group. For VTE prophylaxis, compared with the standard-dosage group, the high-dosage group had a lower incidence of VTE (OR: 0.47, 95% CI: 0.27-0.82, P=0.007) and a similar incidence of bleeding events (OR: 0.86, 95% CI: 0.69-1.08, P=0.020). For VTE therapy, compared to the standard-dosage group, the reduced-dosage group had a similar incidence of VTE recurrence (OR: 0.86, 95% CI: 0.11-6.84, P=0.89) but a lower incidence of bleeding events (OR: 0.30, 95% CI: 0.10-0.89, P=0.03). Conclusion: In patients with obesity, increasing the dosage of LMWH is a more appropriate option for the prevention of VTE. Due to the limited evidence, reducing the therapeutic dosage of LMWH requires careful consideration. Larger-scale, well-designed randomized controlled trials are necessary. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?, identifier ID=CRD42022298128.

Microstructure, Mechanical Properties and Corrosion Behaviors of Al-Li-Cu-Mg-Ag-Zn Alloys.

Combined with microstructure characterization and properties tests, the effects of Zn contents on the mechanical properties, corrosion behaviors, and microstructural evolution of extruded Al-Li-Cu-Mg-Ag alloys were investigated. The results show that the increase in Zn contents can accelerate hardening kinetics and improve the hardness of peak-aged alloys. The Zn-added alloys present non-recrystallization characteristics combined with partially small recrystallized grains along the grain boundaries, while the T1 phase with finer dimension and higher number density could explain the constantly increasing tensile strength. In addition, increasing Zn contents led to a lower corrosion current density and a shallower maximum intergranular corrosion depth, thus improving the corrosion resistance of the alloys. Zn addition, distributed in the central layer of T1 phases, not only facilitates the precipitation of more T1 phases but also reduces the corrosion potential difference between the T1 phase and the matrix. Therefore, adding 0.57 wt.% Zn to the alloy has an excellent combination of tensile strength and corrosion resistance. The properties induced by Zn under the T8 temper (solid solution treatment + water quenching + 5% pre-strain+ isothermal aging), however, are not as apparent as the T6 temper (solid solution treatment + water quenching + isothermal aging).

Effect of Rolling Temperature on Microstructure and Properties of Al-Mg-Li Alloy.

In this study, the effects of hot-rolled processes at different temperatures (420 °C, 450 °C, and 480 °C) and subsequent solid solution and aging treatments on the microstructure, mechanical properties, and corrosion properties of Al-Mg-Li alloys with trace Sc and Zr addition were investigated. The aging treatment of rolled sheets after solid solution treatment could obtain Al3Li particles and Al3(Sc, Zr)/Al3Li core-shell particles to improve the mechanical properties of Al-Mg-Li alloy products effectively. The results showed that, as the rolling temperatures increased from 420 °C to 480 °C, the alloy's ultimate tensile strengths and yield strengths increased, while the corrosion resistance decreased. The increase in rolling temperature increased the precipitation-free zone (PFZ) width of the alloy, which undermined the corrosion resistance of the alloy. Moreover, elevating the hot rolling temperature changes the texture strength of the alloy. Particularly in the 480 °C hot-rolled sample, the decrease in the Brass texture strength and the increase in the S texture and Copper texture strength led to an increase in the Taylor factor (M). The increase in rolling temperature also raised the number density of the Al3(Sc, Zr)/Al3Li core-shell particles. The presence of such particles not only inhibits grain growth but also changes the strength mechanism from dislocation cutting to Orowan bypassing. Due to the combination effect of grain morphology, texture evolution, and precipitation behavior, the 480 °C hot-rolled sample had the highest properties.

Herbal extract elemene intrathoracic injection in the treatment of lung cancer patients with malignant pleural effusion: a meta-anaylsis.

OBJECTIVE: The aim of this study was to evaluate the clinical efficacy of elemene intrapleural injection in the treatment of lung cancer with malignant pleural effusion by meta-analysis. MATERIALS AND METHODS: PubMed (1960-2014.4), EMBASE (1980-2014.4) and CNKI (1979-2014.4) data bases were searched to identify the randomized controlled trials about elemene intrapleural injection in the treatment of malignant pleural effusion caused by lung cancer. The relativel risk (RR) was used to evaluated the the clinical efficacy of elemene intrapleural injection in the treatment of pleural effusion compared to other drugs. RESULTS: A total of 1298 subjects with 14 studies were finally included in this meta-analysis. Meta-analysis showed that the objective response rate (ORR) in elemene group was much higher than that in other drugs group (RR =1.20, 95% CI:1.05-1.37, P = 0.008). We performed the sub-groups analysis according to the drugs used in the control group. And the subgroup analyzed demonstrated that the ORR in elemene group was higher than that in Cisplatin (DDP) and high sugar group with statistical difference (P < 0.05). But no statistical difference was found in the bleomycin and interleukin-2 [IL-2] subgroups (P > 0.05). CONCLUSION: High clinical efficacy of elemene was found in the treatment malignant pleural effusion in patients with lung cancer.

The clinical value of Fufangkushen injection in the treatment of stomach cancer: a meta-analysis.

OBJECTIVE: The purpose of this meta-analysis was to evaluate the effects of Fufangkushen injection combined with chemotherapy in the treatment of stomach cancer. MATERIALS AND METHODS: The relevant clinical trials about Fufangkushen injection combined with chemotherapy in the treatment of stomach cancer were search in the data bases of Pubmed, EMBASE, Cochran and CNKI. The data related to objective response rate, Karnofsky (KPS) score and toxicity were extracted and pooled using the Stata 11.0 software. Dichotomous data was presented as risk ratio (RR) and its 95% confidence interval (95% CI). RESULTS: Thirteen relevant trials were included in this meta-analysis. Heterogeneity test indicated there was no statistical heterogeneity among the studies, thus the fixed effects mode was used to calculat the results. Pooled results indicated that the objective response rate (ORR) and KPS score improvement in Fufangkushen chemotherapy group was significant higher than that of control group (RR = 1.24, P < 0.05). Synthesis data also demonstrated the Fufangkushen injection can significantly decrease the risk of developing granulocytopenia in stomach cancer patients treated with chemotherapy (RR = 0.67,P < 0.05). CONCLUSION: Fufangkushen injection combined with chemotherapy can increase the objective response rate, improve the quality of life and decrease the risk of developing granulocytopenia in patients with stomach cancer.

Evaluation of the effect of apatinib (YN968D1) on cytochrome P450 enzymes with cocktail probe drugs in rats by UPLC-MS/MS.

An accurate and validated liquid chromatography method and a triple quadrupole mass spectrometry method were developed and validated to simultaneously evaluate the cytochrome P450 (CYP) enzymes in vivo using the co-administration of these probes. Phenacetin, losartan, metoprolol and midazolam were used as the probe substrates for rat CYP1A2, CYP2C11, CYP2D4 and CYP3A1 enzymes, respectively. The purpose of the study was to investigate the effect of apatinib on these cytochrome P450 enzymes in vivo with co-administration of these probes. Plasma samples were prepared by precipitating protein with acetonitrile. The analytes were separated using a reversed-phase BEH C18 column (2.1mm×100mm, 1.7µm, Waters, USA) maintained at 40°C. The mobile phase consisted of acetonitrile and water (containing 0.1% formic acid) with a gradient elution pumped at a flow rate of 0.4mL/min. The analytes were detected with positive electrospray ionization in multiple reaction monitoring (MRM) mode for target fragment ions m/z 180.05→109.94 for phenacetin, m/z 423.1→207.2 for losartan, m/z 268.12→115.8 for metoprolol, m/z 326.02→290.99 for midazolam and m/z 285.1→193.1 for diazepam (IS). Good linearity was achieved to quantify the concentration ranges of 10-2000ng/mL for phenacetin, 10-1000ng/mL for losartan, 10-1000ng/mL for metoprolol and 1-100ng/mL for midazolam in rat plasma. The mean recoveries of phenacetin, losartan, midazolam and metoprolol from the plasma exceeded 77.07%. The intra-run and inter-run assay precisions were both less than 8.9%. This method was successfully applied to evaluate the effects of apatinib on the cytochrome P450 enzymes in rats.