Hepatoprotective effects of Xiaoyao San formula on hepatic steatosis and inflammation via regulating the sex hormones metabolism.

BACKGROUND: The modified Xiaoyao San (MXS) formula is an adjuvant drug recommended by the National Health Commission of China for the treatment of liver cancer, which has the effect of preventing postoperative recurrence and metastasis of hepatocellular carcinoma and prolonging patient survival. However, the molecular mechanisms underlying that remain unclear. AIM: To investigate the role and mechanisms of MXS in ameliorating hepatic injury, steatosis and inflammation. METHODS: A choline-deficient/high-fat diet-induced rat nonalcoholic steatohepatitis (NASH) model was used to examine the effects of MXS on lipid accumulation in primary hepatocytes. Liver tissues were collected for western blotting and immunohistochemistry (IHC) assays. Lipid accumulation and hepatic fibrosis were detected using oil red staining and Sirius red staining. The serum samples were collected for biochemical assays and NMR-based metabonomics analysis. The inflammation/lipid metabolism-related signaling and regulators in liver tissues were also detected to reveal the molecular mechanisms of MXS against NASH. RESULTS: MXS showed a significant decrease in lipid accumulation and inflammatory response in hepatocytes under metabolic stress. The western blotting and IHC results indicated that MXS activated AMPK pathway but inhibited the expression of key regulators related to lipid accumulation, inflammation and hepatic fibrosis in the pathogenesis of NASH. The metabonomics analysis systemically indicated that the arachidonic acid metabolism and steroid hormone synthesis are the two main target metabolic pathways for MXS to ameliorate liver inflammation and hepatic steatosis. Mechanistically, we found that MXS protected against NASH by attenuating the sex hormone-related metabolism, especially the metabolism of male hormones. CONCLUSION: MXS ameliorates inflammation and hepatic steatosis of NASH by inhibiting the metabolism of male hormones. Targeting male hormone related metabolic pathways may be the potential therapeutic approach for NASH.

The Alfalfa-inpatient-CAT assessment model: a thrombotic risk assessment model for inpatient cancer patients.

PURPOSE: To construct a venous thromboembolism (VTE) risk assessment model specifically for inpatients with cancer. METHOD: Patients were included according to the inclusion criteria. Univariate and multivariate analyses of all variables were included to develop a VTE risk assessment model applicable to the derivation cohort. Hosmer-Lemeshow test and receiver operating characteristic (ROC) curve were used to test the fit degree and identification validity of the model. The patient data from separate validation cohorts verified the external population. RESULT: A total of 944 cancer patients were included in this study. Alfalfa-inpatient-CAT model, a risk assessment model for VTE in hospitalized cancer patients, was established, which mainly includes hypertension, surgical history (nearly one month), history of VTE, peripherally inserted central venous catheters (PICC), chemotherapy, PT < 12.85 s, D-dimer ≥ 1.805 µg/mL, hemoglobin ≤ 114.5 g/L, CRP ≥ 7.575 mg/L. Hosmer-Lemeshow test results showed P = 0.353 > 0.05, (χ2 = 8.872, Df = 8). The area under ROC curve was 0.906 [95%CI (0.881-0.930), P < 0.001]. The authenticity evaluation in the model database showed that the risk of thrombosis in the high-risk group (score ≥ 3) was 72.63%, significantly higher than that in the low-risk group (score 0-2) (27.37%) [χ2 = 144.00, Df = 1, P < 0.001]. CONCLUSION: This study developed a new VTE risk assessment model - Alfalfa-inpatient-CAT model - for hospitalized cancer patients at high risk of thrombosis. This model has a good fitting degree and discriminant validity. It is expected to provide some reference for the clinical treatment of inpatients with cancer through continuous optimization.

Efficacy and safety of direct oral anticoagulants for preventing venous thromboembolism in hospitalized cancer patients: a national multicenter retrospective cohort study.

Introduction: Studies on the use of direct oral anticoagulants (DOACs) for preventing venous thromboembolism (VTE) in hospitalized cancer patients are lacking. Therefore, we conducted a multicenter retrospective cohort study to evaluate the efficacy and safety of DOACs versus low-molecular-weight heparin (LMWH) for the primary prevention of VTE in hospitalized cancer patients. Methods: Clinical outcomes included thrombosis, VTE, other thrombosis, all bleeding, major bleeding, nonmajor bleeding, and all-cause death. A 1:1 cohort of rivaroxaban and LMWH patients was created by propensity score matching. Results: A total of 2,385 cancer patients were included in this study. During the 3-month follow-up period, 129 (5.4%) thrombosis events occurred, 63 (2.7%) of which were VTEs and 66 (2.8%) of which were other thrombosis events. All bleeding occurred in 163 (6.8%) patients, 68 (2.9%) had major bleeding, and 95 (4.0%) had nonmajor bleeding. All-cause deaths occurred in 113 (4.7%) patients. After adjusting for various confounders, the incidence of thrombosis and other thromboses was significantly lower in the rivaroxaban group than in the LMWH group [OR 0.543, 95% CI (0.343-0.859), p = 0.009; OR 0.461, 95% CI (0.241-0.883), p = 0.020]. There were no significant differences in incidence of VTE, total bleeding, major bleeding, nonmajor bleeding, or all-cause death. Conclusion: In oncology patients receiving thromboprophylaxis, rivaroxaban has a lower incidence of thrombosis and other thrombosis and a similar incidence of VTE as LMWH and does not increase the risk of bleeding. Rivaroxaban may be an attractive alternative to LMWH for preventing VTE in hospitalized cancer patients.

Development of a Routine Serological Test Index Panel for the Surveillance of Gastric Cancer Risk in a High-Risk Population.

OBJECTIVE: This study aims to develop a predictive model for the detection of gastric cancer risk utilizing non-invasive parameters and to assess the model's effectiveness in risk stratification for gastric cancer (GC). METHODS: A case-control study was conducted among inpatients with various gastric diseases. These individuals were categorized into two groups: the gastric cancer group (138 cases) and the chronic non-atrophic gastritis (CNAG) group (319 cases). We employed a comprehensive panel of hematological, biochemical, and coagulation parameters derived from routine blood tests. Random Forest and Logistic regression analysis was used for feature selection and model building. Statistical analyses were performed using R version 4.2.3. RESULTS: Logistic regression analysis was employed to establish risk prediction models for GC, incorporating variables such as D-dimer, carcinoembryonic antigen (CEA), carbohydrate antigen 724 (CA724), and hemoglobin (HGB). A visual nomogram was generated as the final prediction model. The area under the receiver operating characteristic curve (AUC) for the training and test sets were 0.8093 [95% confidence interval (CI), 0.7541-0.8644], and 0.8076 [95% CI 0.7237-0.8915], respectively. Furthermore, we have developed an HTML file, featuring the Logistic equation, which enables real-time assessment of GC risk scores. CONCLUSION: The performance of this predictive model demonstrates its adequacy, making it a valuable and cost-effective noninvasive tool for identifying early gastric cancer (EGC) in patients. Consequently, this model may facilitate the implementation of targeted preventive and intervention strategies in clinical practice.

Exploration of poly (ADP-ribose) polymerase inhibitor resistance in the treatment of BRCA1/2-mutated cancer.

Breast cancer susceptibility 1/2 (BRCA1/2) genes play a crucial role in DNA damage repair, yet mutations in these genes increase the susceptibility to tumorigenesis. Exploiting the synthetic lethality mechanism between BRCA1/2 mutations and poly(ADP-ribose) polymerase (PARP) inhibition has led to the development and clinical approval of PARP inhibitor (PARPi), representing a milestone in targeted therapy for BRCA1/2 mutant tumors. This approach has paved the way for leveraging synthetic lethality in tumor treatment strategies. Despite the initial success of PARPis, resistance to these agents diminishes their efficacy in BRCA1/2-mutant tumors. Investigations into PARPi resistance have identified replication fork stability and homologous recombination repair as key factors sensitive to PARPis. Additionally, studies suggest that replication gaps may also confer sensitivity to PARPis. Moreover, emerging evidence indicates a correlation between PARPi resistance and cisplatin resistance, suggesting a potential overlap in the mechanisms underlying resistance to both agents. Given these findings, it is imperative to explore the interplay between replication gaps and PARPi resistance, particularly in the context of platinum resistance. Understanding the impact of replication gaps on PARPi resistance may offer insights into novel therapeutic strategies to overcome resistance mechanisms and enhance the efficacy of targeted therapies in BRCA1/2-mutant tumors.

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).

Addition of konjac glucomannan improves spraying efficiency on fruits and vegetables: Effect of surface hydrophilicity and molecular weight.

Biomacromolecules have attracted interest as spraying additives due to their degradability, renewability, and non-toxicity. However, microscopic mechanism of the biomacromolecules regulating the droplet behavior on fruits and vegetables is still unclear. In this study, konjac glucomannan (KGM) was used to improve the spraying efficiency and the fresh-keeping performance of tea polyphenols solution. KGM increased effective spreading ratio on hydrophilic surfaces and retention ratio of the main droplet on hydrophobic surfaces, thus improving spraying efficiency. Computational fluid dynamics and Brown dynamics simulations were implemented to investigate KGM behaviors during droplets colliding on hydrophilic and hydrophobic surfaces. Most KGM molecules extended and then collapsed in gradually weakened shear flow. Meanwhile, on the hydrophobic surface, most KGM molecules were continuously stretched by the unstable flow field. As the KGM extended, the kinetic energy of droplets converted into elastic energy stored in the KGM, promoting the stability of droplets on target surfaces and improving the spraying efficiency. The KGM molecular weight of 3.8 × 105 Da was optimal from the point of energy storage density. This study provides more understanding of the mechanism of biomacromolecules on spraying efficiency and guidance to develop biomass spraying additives for fruit and vegetable preservation.

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.

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.

Oxfendazole Induces Apoptosis in Ovarian Cancer Cells by Activating JNK/MAPK Pathway and Inducing Reactive Oxygen Species Generation.

Ovarian cancer (OC) is one of the most common and high mortality type of cancer among women worldwide. The majority of patients with OC respond to chemotherapy initially; however, most of them become resistant to chemotherapy and results in a high level of treatment failure in OC. Therefore, novel agents for the treatment of OC are urgently required. Benzimidazole anthelmintics might have the promising efficacy for cancer therapy as their selectively binding activity to ß-tubulin. Recent study has shown that one of the benzimidazole anthelmintics oxfendazole inhibited cell growth of non-small cell lung cancer cells, revealing its anti-cancer activity; however, the pharmacological action and detailed mechanism underlying the effects of oxfendazole on OC cells remain unclear. Therefore, the present study investigated the cytotoxic effects of oxfendazole on OC cells. Our results demonstrated that oxfendazole significantly decreased the viability of OC cells. Oxfendazole inhibited the proliferation, induced G2/M phase arrest and apoptotic cell death in A2780 cells. The c-Jun N-terminal kinase (JNK)/mitogen-activated protein kinase (MAPK) pathway was activated and reactive oxygen species (ROS) generation was increased in OC cells treated with oxfendazole; oxfendazole-induced apoptosis was notably abrogated when co-treated with JNK inhibitor SP600125 and ROS scavenger N-acetyl-L-cysteine (NAC), indicating that JNK/MAPK pathway activation and ROS accumulation was associated with the oxfendazole-induced apoptosis of OC cells. Moreover, oxfendazole could also induce the proliferation inhibition and apoptosis of cisplatin resistant cells. Collectively, these results revealed that oxfendazole may serve as a potential therapeutic agent for the treatment of OC.

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.

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.

Tensile Performance Mechanism for Bamboo Fiber-Reinforced, Palm Oil-Based Resin Bio-Composites Using Finite Element Simulation and Machine Learning.

Plant fiber-reinforced composites have the advantages of environmental friendliness, sustainability, and high specific strength and modulus. They are widely used as low-carbon emission materials in automobiles, construction, and buildings. The prediction of their mechanical performance is critical for material optimal design and application. However, the variation in the physical structure of plant fibers, the randomness of meso-structures, and the multiple material parameters of composites limit the optimal design of the composite mechanical properties. Based on tensile experiments on bamboo fiber-reinforced, palm oil-based resin composites, finite element simulations were carried out and the effect of material parameters on the tensile performances of the composites was investigated. In addition, machine learning methods were used to predict the tensile properties of the composites. The numerical results showed that the resin type, contact interface, fiber volume fraction, and multi-factor coupling significantly influenced the tensile performance of the composites. The results of the machine learning analysis showed that the gradient boosting decision tree method had the best prediction performance for the tensile strength of the composites (R2 was 0.786) based on numerical simulation data from a small sample size. Furthermore, the machine learning analysis demonstrated that the resin performance and fiber volume fraction were critical parameters for the tensile strength of composites. This study provides an insightful understanding and effective route for investigating the tensile performance of complex bio-composites.

Band-Aid-Like Self-Fixed Barrier Membranes Enable Superior Bone Augmentation.

In guided bone regeneration surgery, a barrier membrane is usually used to inhibit soft tissue from interfering with osteogenesis. However, current barrier membranes usually fail to resist the impact of external forces on bone-augmented region, thus causing severe displacement of membranes and their underlying bone graft materials, eventually leading to unsatisfied bone augmentation. Herein, a new class of local double-layered adhesive barrier membranes (ABMs) is developed to successfully immobilize bone graft materials. The air-dried adhesive hydrogel layers with suction-adhesion properties enable ABMs to firmly adhere to the wet bone surface through a "stick-and-use" band-aid-like strategy and effectively prevent the displacement of membranes and the leakage of bone grafts in uncontained bone defect treatment. Furthermore, the strategy is versatile for preparing diverse adhesive barrier membranes and immobilizing different bone graft materials for various surgical regions. By establishing such a continuous barrier for the bone graft material, this strategy may open a novel avenue for designing the next-generation barrier membranes.

Direct oral anticoagulants for venous thromboembolism in cancer patients: a systematic review and network meta-analysis.

BACKGROUND: The efficacy and safety of direct oral anticoagulants (DOACs), including dabigatran, apixaban, rivaroxaban, and edoxaban, for preventing and treating venous thromboembolism (VTE) in patients with cancer is unclear. METHODS: We searched the PubMed, Embase, Web of Science, and Cochrane Library databases from the establishment to November 30, 2021. In the frequency-based network meta-analysis, the odds ratio with a 95% confidence interval was reported. The relative ranking probability of each group was generated based on the surface under the cumulative ranking curve (SUCRA). RESULTS: We included 15 randomized controlled trials involving a total of 6162 patients. Apixaban reduced the risk of VTE compared with low-molecular heparin [OR = 0.53, 95% CI (0.32, 0.89)]. The efficacy of drugs was ranked from highest to lowest as follows: apixaban (SUCRA, 81.0), rivaroxaban (73.0), edoxaban (65.9), dabigatran (51.4), warfarin (30.8), and low-molecular-weight heparin (LMWH) (27.4). Edoxaban increased the risk of major bleeding compared with LMWH [OR = 1.83, 95% CI (1.04, 3.22)]. The safety of drugs was ranked from highest to lowest as follows: major bleeding-apixaban (SUCRA, 68.5), LMWH (55.1), rivaroxaban (53.0), warfarin (35.9), dabigatran (29.2), edoxaban (16.5) and clinically relevant non-major bleeding-LMWH (73.0), apixaban (57.8), edoxaban (45.8), rivaroxaban (35.3), and warfarin (10.8). CONCLUSIONS: For preventing and treating VTE, in terms of VTE occurrence and major bleeding, apixaban had the lowest risk; in terms of clinically relevant non-major bleeding, LMWH had the lowest risk, followed by apixaban. Generally, apixaban is the most efficient and safest DOAC and presents better efficacy and relatively low bleeding risk among the VTE prevention and treatment drugs for patients with cancer.

Editor's Choice - Severe Bleeding Risks of Direct Oral Anticoagulants in the Prevention and Treatment of Venous Thromboembolism: A Network Meta-Analysis of Randomised Controlled Trials.

OBJECTIVE: The aim of this study was to determine the severe bleeding safety of direct oral anticoagulants (DOACs) for the prevention and treatment of venous thromboembolism (VTE). METHODS: PubMed, EMBASE, Web of Science, and the Cochrane Library databases were searched up to 6 January 2021. The incidence of severe bleeding (major, gastrointestinal [GI], intracranial, and fatal) was investigated. Using frequentist network meta-analysis, interventions that were not compared directly could be compared indirectly by the 95% confidence interval (CI), making the search results more intuitive. Based on surface under the cumulative ranking curves (SUCRA), the relative ranking probability of each group was generated. RESULTS: Thirty-one randomised controlled trials (76 641 patients) were included. For the treatment of VTE, the risk of major bleeding with apixaban was significantly lower than dabigatran (odds ratio [OR] 2.10, 95% CI 1.07 - 4.12) and edoxaban (OR 2.64, 95% CI 1.36 - 5.15). The safety of the drugs was ranked from highest to lowest as follows: major bleeding: apixaban (SUCRA 98.0), rivaroxaban (SUCRA 69.6), dabigatran (SUCRA 50.7), edoxaban (SUCRA 26.5), and vitamin K antagonists (VKAs; SUCRA 5.1); GI bleeding: apixaban (SUCRA 80.7), rivaroxaban (SUCRA 66.8), edoxaban (SUCRA 62.3), VKAs (SUCRA 34.4), and dabigatran (SUCRA 5.8); intracranial bleeding: rivaroxaban (SUCRA 74.4), edoxaban (SUCRA 70.4), dabigatran (SUCRA 58.2), apixaban (SUCRA 44.4), and VKAs (SUCRA 5.6); fatal bleeding: edoxaban (SUCRA 82.7), rivaroxaban (SUCRA 59.2), dabigatran (SUCRA 48.6), apixaban (SUCRA 43.0), and VKAs (SUCRA 16.3). For the prevention of VTE, the risk of major bleeding with apixaban was significantly lower than rivaroxaban (OR 2.14, 95% CI 1.02 - 4.52). Among the four types of bleeding, apixaban had the lowest bleeding risk among DOACs (major bleeding: SUCRA 81.6; GI bleeding: SUCRA 75.4; intracranial bleeding: SUCRA 64.1; fatal bleeding: SUCRA 73.6). CONCLUSIONS: For the treatment of VTE, in terms of major bleeding and GI bleeding, apixaban had the lowest bleeding risk; in terms of intracranial bleeding, rivaroxaban had the lowest bleeding risk; in terms of fatal bleeding, edoxaban had the lowest bleeding risk. For the prevention of VTE, apixaban had the lowest bleeding risk.

High-Frequency Ultrasound and Shear Wave Elastography in Quantitative Differential Diagnosis of High-Risk and Low-Risk Basal Cell Carcinomas.

OBJECTIVES: The purpose of this study was to investigate the value of high-frequency ultrasound and shear wave elastography (SWE) in quantitative differential diagnosis of high-risk and low-risk basal cell carcinomas (BCCs). METHODS: A total of 52 BCCs confirmed by surgical pathology were studied. Taking pathologic subtypes as reference, all the cases were classified as high-risk BCCs or low-risk BCCs. High-frequency ultrasound parameters and SWE parameters recorded preoperatively were retrospectively analyzed. The differences of two groups were compared. RESULTS: There were 12 high-risk BCCs and 40 low-risk BCCs. The maximum infiltration depth (MID) and average Young's modulus (Eave ) of high-risk BCCs were 5.76 ± 2.56 mm and 31.61 ± 12.36 kPa, whereas of low-risk BCCs were 4.29 ± 1.77 mm and 20.04 ± 4.74 kPa, respectively, P < .05. The area under the receiver operator characteristic curve of MID and Eave were 0.714 and 0.811, P > .05. Taking 5.5 mm of MID and 24.45 kPa of Eave as the threshold for the diagnosis of high-risk BCCs, the sensitivity, specificity, and accuracy were 58.3%, 82.5%, 76.9% and 75.0%, 82.5%, 80.8%, P > .05. CONCLUSIONS: The MID and Eave of the lesion can be used to determine the recurrence risk of BCCs and provide a reference for the development of individualized treatment plans.

Long non­coding RNA SNHG12 regulates cell proliferation, invasion and migration in endometrial cancer by targeting miR­4429.

Long non­coding RNA small nucleolar RNA host gene 12 (SNHG12) has been demonstrated to be oncogenic. The aim of the present study was to examine the effects of SNHG12 on the progression of endometrial cancer (EC). The expression levels of SNHG12 and microRNA (miR)­4429 were assessed in EC cell lines by reverse transcription­quantitative PCR. Plasmids, including SNHG12 short hairpin RNAs (shRNAs), shRNA negative control (NC), SNHG12 overexpression (OV), OV­NC, miR­4429 mimic and mimic­NC, were transfected into RL95­2 cells. Post­transfection, Cell Counting Kit­8, Transwell Matrigel and wound­healing assays were performed to assess cell proliferation, invasion and migration, respectively. Cell cycle phase distribution was assessed by flow cytometry. The protein expression levels of matrix metalloproteinase (MMP)2 and MMP9 were detected by western blotting. miR­4429 target genes were predicted by bioinformatics analysis using target prediction online tools; the findings of this analysis were verified using a dual­luciferase reporter system. Identified as a target of miR­4429, SNHG12 was overexpressed in EC cell lines with decreased expression of miR­4429. Further experiments demonstrated that SNHG12 silencing and overexpression of miR­4429 markedly suppressed proliferation, migration and invasion of RL95­2 cells, arrested cells in the G1 phase, and markedly downregulated the expression of MMP2 and MMP9. The opposite effects were observed in miR­4429 mimic­transfected RL95­2 cells after SNHG12 was overexpressed. The findings of the present study established the role of SNHG12 and miR­4429 in EC. Therefore, targeting the SNHG12/miR­4429 axis could serve as a potential future therapeutic target for treatment of EC.

[Chirality Self-assembling peptide for rats endometrial regeneration model].

Here we investigate the physical and chemical properties of chiral self-assembling peptides and the role of uterine trauma regeneration. The circular dichroism was used to analyze secondary structure of chiral self-assembled peptide, and Congo red staining was used to observe the macroscopic process of peptide self-assembling. Erythrocyte lysis assay was used to examine the cleavage of peptide on cell membrane. The nanofiber scaffolds self-assembled by Chiral self-assembling peptides were used as the three-dimensional culture material to observe the growth effect of Hela cell. CCK-8 (cell counting kit-8) was used to study cell viability level between 2D (2-dimensional) and 3D (3-dimensional) culture environment. Rats endometrium curettage model was founded to evaluate the changes by immunohistochemistry staining and and HE staining. The secondary structure of chiral self-assembling peptides was stable ß-sheet, and peptide could form dense membrane structure after 24 hours self-assembling cultured in salt ions. There was no harmful for the cell membrane of the peptide before and after self-assembling. Animal experiments show that chiral self-assembling peptide can significantly reduce the inflammatory response, promote the production of neovascularization, and accelerate the repair process. Chiral self-assembling peptide, as a new type of scaffold material, can construct a three-dimensional cell culture environment and used to repair uterine trauma.