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.

Web-Based Warfarin Management (Alfalfa App) Versus Traditional Warfarin Management: Multicenter Prospective Cohort Study.

BACKGROUND: Poor anticoagulation management of warfarin may lead to patient admission, prolonged hospital stays, and even death due to anticoagulation-related adverse events. Traditional non-web-based outpatient clinics struggle to provide ideal anticoagulation management services for patients, and there is a need to explore a safer, more effective, and more convenient mode of warfarin management. OBJECTIVE: This study aimed to compare differences in the quality of anticoagulation management and clinical adverse events between a web-based management model (via a smartphone app) and the conventional non-web-based outpatient management model. METHODS: This study is a prospective cohort research that includes multiple national centers. Patients meeting the nadir criteria were split into a web-based management group using the Alfalfa app or a non-web-based management group with traditional outpatient management, and they were then monitored for a 6-month follow-up period to collect coagulation test results and clinical events. The effectiveness and safety of the 2 management models were assessed by the following indicators: time in therapeutic range (TTR), bleeding events, thromboembolic events, all-cause mortality events, cumulative event rates, and the distribution of the international normalized ratio (INR). RESULTS: This national multicenter cohort study enrolled 522 patients between June 2019 and May 2021, with 519 (99%) patients reaching the follow-up end point, including 260 (50%) in the non-web-based management group and 259 (50%) in the web-based management group. There were no observable differences in baseline characteristics between the 2 patient groups. The web-based management group had a significantly higher TTR than the non-web-based management group (82.4% vs 71.6%, P<.001), and a higher proportion of patients received effective anticoagulation management (81.2% vs 63.5%, P<.001). The incidence of minor bleeding events in the non-web-based management group was significantly higher than that in the web-based management group (12.1% vs 6.6%, P=.048). Between the 2 groups, there was no statistically significant difference in the incidence of severe bleeding and thromboembolic and all-cause death events. In addition, compared with the non-web-based management group, the web-based management group had a lower proportion of INR in the extreme subtreatment range (17.6% vs 21.3%) and severe supertreatment range (0% vs 0.8%) and a higher proportion in the treatment range (50.4% vs 43.1%), with statistical significance. CONCLUSIONS: Compared with traditional non-web-based outpatient management, web-based management via the Alfalfa app may be more beneficial because it can enhance patient anticoagulation management quality, lower the frequency of small bleeding events, and improve INR distribution.

Risk factors for thrombolysis-related intracranial hemorrhage: a systematic review and meta-analysis.

BACKGROUND: Thrombolysis-related intracranial hemorrhage has a high mortality rate, and many factors can cause intracranial hemorrhage. Until now, systematic reviews and assessments of the certainty of the evidence have not been updated. AIM: We conducted a systematic review to identify risk factors for thrombolysis-related intracranial hemorrhage. METHOD: The protocol for this systematic review was prospectively registered with PROSPERO (CRD42022316160). All English studies that met the inclusion criteria published before January 2022 were obtained from PubMed, EMBASE, Web of Science, and Cochrane Library. Two researchers independently screened articles, extracted data, and evaluated the quality and evidence of the included studies. Risk factors for intracranial hemorrhage were used as the outcome index of this review. Random or fixed-effect models were used in statistical methods. RESULTS: Of 6083 citations, we included 105 studies in our analysis. For intracranial hemorrhage, moderate-certainty evidence showed a probable association with age, National Institutes of Health stroke scale, leukoaraiosis, hypertension, atrial fibrillation, diabetes, total cholesterol, proteinuria, fibrinogen levels, creatinine, homocysteine, early infarct signs, antiplatelet therapy and anticoagulant therapy; In addition, we found low-certainty evidence that there may be little to no association between risk of intracranial hemorrhage and weight, sex, platelet count, uric acid, albumin and white matter hyperintensity. Leukoaraiosis, cardiovascular disease, total cholesterol, white blood cell count, proteinuria, fibrinogen levels, creatinine, homocysteine and early CT hypodensities are not included in most intracranial hemorrhage risk assessment models. CONCLUSION: This study informs risk prediction for thrombolysis-related intracranial hemorrhage, it also informs guidelines for intracranial hemorrhage prevention and future research.

Safety and efficacy of direct oral anticoagulants in stroke prevention in patients with atrial fibrillation complicated with anemia and/or thrombocytopenia: a retrospective cohort study.

BACKGROUND: There are limited data about the clinical benefits and harm of direct oral anticoagulants (DOACs) in stroke prevention in patients with atrial fibrillation (AF) complicated with anemia or thrombocytopenia. METHODS: This is a multi-center retrospective cohort study involving 5469 AF patients from 15 hospitals in China. Patients were divided into three groups according to hemoglobin and platelet levels: Group 1 (hemoglobin male ≥ 130 g/L; female ≥ 120 g/L and platelet ≥ 100 × 109/L), Group 2 (hemoglobin male < 130 g/L; female < 120 g/L or platelet < 100 × 109/L), and Group 3 (hemoglobin male < 130 g/L; female < 120 g/L and platelet < 100 × 109/L). Patients in each category are further divided into two groups according to their stroke prevention strategies: rivaroxaban or dabigatran. Clinical results include major, minor, total bleeding, thrombosis, and the composite outcome of major bleeding and thrombosis. RESULTS: Higher hemoglobin levels were associated with a reduced risk of total bleeding and major bleeding, while platelet counts were not associated with any event. Compared with Group 1, Group 2 had a higher risk of major bleeding (aOR 1.70, 95%CI 1.12-2.57, P = 0.012), and the composite endpoint of major bleeding and thrombosis (aOR 1.70, 95%CI 1.19-2.44, P = 0.004). Compared with Group 1, Group 3 had a higher total bleeding risk (aOR 2.15, 95%CI 1.14-4.05, P = 0.018). Compared with dabigatran, rivaroxaban was associated with higher composite risk in Group 1 (aOR 2.91, 95% CI 1.66-5.16, P < 0.001) and Group 2 (aOR 3.05, 95%CI 1.46-6.39, P = 0.003), but there was no significant difference in Group 3 (aOR 1.78, 95%CI 0.23-13.54, P = 0.577). CONCLUSIONS: Higher hemoglobin levels are associated with a reduced risk of total bleeding and major bleeding in patients with AF. Dabigatran was associated with better clinical outcomes than rivaroxaban in patients with anemia or thrombocytopenia but not in those with anemia and thrombocytopenia.

Severe Bleeding Risk of Direct Oral Anticoagulants Versus Vitamin K Antagonists for Stroke Prevention and Treatment in Patients with Atrial Fibrillation: A Systematic Review and Network Meta-Analysis.

PURPOSE: We aimed to determine the safety of direct oral anticoagulants (DOACs) for stroke prevention and treatment in patients with atrial fibrillation (AF). METHODS: A systematic search of four databases (PubMed, EMBASE, Web of Science, and Cochrane Library) was performed to identify randomized controlled trials (RCTs) reporting severe bleeding events in patients taking DOACs or vitamin K antagonists (VKAs). In this frequency-based network meta-analysis, odds ratios and 95% confidence intervals were used for reporting. Based on the surface under the cumulative ranking curves (SUCRA), the relative ranking probability of each group was generated. RESULTS: Twenty-three RCTs met the inclusion criteria, and a total of 87,616 patients were enrolled. The bleeding safety of DOACs for stroke prevention and treatment in patients with AF was ranked from highest to lowest as follows: fatal bleeding: edoxaban (SUCRA,80.2), rivaroxaban (SUCRA,68.3), apixaban (SUCRA,48.5), dabigatran (SUCRA,40.0), VKAs (SUCRA,12.9); major bleeding: dabigatran (SUCRA,74.0), apixaban (SUCRA,71.5), edoxaban (SUCRA,66.5), rivaroxaban (SUCRA,22.7), VKAs (SUCRA,15.4); gastrointestinal bleeding: apixaban (SUCRA,55.9), VKAs (SUCRA,53.7), edoxaban (SUCRA,50.5), rivaroxaban (SUCRA,50.4), dabigatran (SUCRA,39.5); intracranial hemorrhage: dabigatran (SUCRA,84.6), edoxaban (SUCRA,74.1), apixaban (SUCRA,65.8), rivaroxaban (SUCRA,24.4), VKAs (SUCRA,1.1). CONCLUSION: Based on current evidence, for stroke prevention and treatment in patients with AF, the most safe DOAC is edoxaban in terms of fatal bleeding; dabigatran in terms of major bleeding and intracranial hemorrhage and apixaban in terms of gastrointestinal bleeding. However, given the nature of indirect comparisons, more high-quality evidence from head-to-head comparisons is still needed to confirm them.

Non-major bleeding risk of direct oral anticoagulants versus vitamin K antagonists for stroke prevention with atrial fibrillation: a systematic review and network meta-analysis.

BACKGROUND: Direct oral anticoagulants (DOACs) are associated with bleeding. Patients often stop taking DOACs due to non-major bleeding, which may lead to stroke recurrence. We aimed to determine the risk of non-major bleeding using different DOACs to prevent strokes in atrial fibrillation (AF). METHODS: A systematic search of four databases (PubMed, EMBASE, Web of Science, and Cochrane Library) was performed to identify randomized controlled trials (RCTs) reporting non-major bleeding events in patients taking DOACs or vitamin K antagonists (VKAs). In this frequency-based network meta-analysis, odds ratios and 95% confidence intervals were used for reporting. Based on the surface under the cumulative ranking curves (SUCRA), the relative ranking probability of each group was generated. RESULTS: Nineteen randomized controlled trials (RCTs) (involving 85,826 patients) were included. For clinically relevant non-major bleeding, the risk for bleeding was lowest for apixaban (SUCRA, 93.9), followed by that for VKAs (SUCRA, 47.7), dabigatran (SUCRA, 40.3), rivaroxaban (SUCRA, 35.9), and edoxaban (SUCRA, 32.2). The minor bleeding safety of DOACs was ranked from highest to lowest as follows: apixaban (SUCRA, 78.1), edoxaban (SUCRA, 69.4), dabigatran (SUCRA, 48.8), and VKAs (SUCRA, 3.7). CONCLUSIONS: Based on current evidence, for stroke prevention in patients with AF, the safest DOAC is apixaban in terms of non-major bleeding. This suggests that apixaban may have a lower risk of non-major bleeding than other anticoagulants and may help provide some clinical reference for choosing a more appropriate drug for the patient.

The application of composite scaffold materials based on decellularized vascular matrix in tissue engineering: a review.

Decellularized vascular matrix is a natural polymeric biomaterial that comes from arteries or veins which are removed the cellular contents by physical, chemical and enzymatic means, leaving only the cytoskeletal structure and extracellular matrix to achieve cell adhesion, proliferation and differentiation and creating a suitable microenvironment for their growth. In recent years, the decellularized vascular matrix has attracted much attention in the field of tissue repair and regenerative medicine due to its remarkable cytocompatibility, biodegradability and ability to induce tissue regeneration. Firstly, this review introduces its basic properties and preparation methods; then, it focuses on the application and research of composite scaffold materials based on decellularized vascular matrix in vascular tissue engineering in terms of current in vitro and in vivo studies, and briefly outlines its applications in other tissue engineering fields; finally, it looks into the advantages and drawbacks to be overcome in the application of decellularized vascular matrix materials. In conclusion, as a new bioactive material for building engineered tissue and repairing tissue defects, decellularized vascular matrix will be widely applied in prospect.

Risk Factors for Anticoagulant-Associated Intracranial Hemorrhage: A Systematic Review and Meta-analysis.

BACKGROUND: Anticoagulant-associated intracranial hemorrhage has a high mortality rate, and many factors can cause intracranial hemorrhage. Until now, systematic reviews and assessments of the certainty of the evidence have not been published. METHODS: We conducted a systematic review to identify risk factors for anticoagulant-associated intracranial hemorrhage. The protocol for this systematic review was prospectively registered with PROSPERO (CRD42022316750). All English studies that met the inclusion criteria published before January 2022 were obtained from PubMed, EMBASE, Web of Science, and Cochrane Library. Two researchers independently screened articles, extracted data, and evaluated the quality and evidence of the included studies. Risk factors for intracranial hemorrhage were used as the outcome index of this review. Random or fixed-effect models were used in statistical methods. I2 statistics were used to evaluate heterogeneity. RESULTS: Of 7322 citations, we included 20 studies in our analysis. For intracranial hemorrhage, moderate-certainty evidence showed a probable association with race, Glasgow Coma Scale, stroke, leukoaraiosis, cerebrovascular disease, tumor, atrial fibrillation, previous bleeding, international normalized ratio, serum albumin, prothrombin time, diastolic blood pressure, and anticoagulant. Low-certainty evidence may be associated with age, cerebral microbleeds, smoking, alcohol intake, platelet count, and antiplatelet drug. In addition, we found very low-certainty evidence that there may be little to no association between the risk of intracranial hemorrhage and hypertension and creatinine clearance. Leukoaraiosis, cerebral microbleeds, cerebrovascular disease, and international normalized ratio are not included in most risk assessment models. CONCLUSIONS: This study informs risk prediction for anticoagulant-associated intracranial hemorrhage and informs guidelines for intracranial hemorrhage prevention and future research.

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.

Risk of nonmajor bleeding upon use of direct oral anticoagulants for preventing and treating venous thromboembolism: A network meta-analysis.

INTRODUCTION: Direct oral anticoagulants (DOACs) are associated with bleeding. Patients often stop taking DOACs due to nonmajor bleeding, which may lead to venous thromboembolism (VTE) recurrence. We aimed to determine the risk of nonmajor bleeding using different DOACs to prevent and treat VTE. METHODS: PubMed, Embase, Web of Science, and Cochrane Library databases were searched from inception until January 6, 2021. The incidence of clinically relevant nonmajor bleeding and minor bleeding was investigated. In frequentist-based network meta-analysis, we analyzed the odds ratio (OR) with 95% CI and the surface under the cumulative ranking curves (SUCRA). RESULTS: Twenty-seven randomized controlled trials (RCTs) (involving 64,493 patients) were included. For preventing VTE, the risk for clinically relevant nonmajor bleeding was lowest for apixaban, followed by that for low-molecular weight heparin (LMWH), dabigatran, edoxaban, and rivaroxaban. The risk for minor bleeding was lowest for apixaban, followed by that for rivaroxaban, LMWH, dabigatran, and edoxaban. For treating VTE, the risk for clinically relevant nonmajor bleeding was also lowest for apixaban, followed by that for edoxaban, vitamin K antagonists (VKAs), and rivaroxaban. The risk for minor bleeding was lowest for apixaban, followed by that for rivaroxaban and VKAs. CONCLUSIONS: Regardless of whether it was used for preventing or treating VTE, apixaban had the lowest risk of nonmajor bleeding. This suggests that apixaban may have a lower risk of nonmajor bleeding than other anticoagulants and may help provide some clinical reference for choosing a more appropriate drug for the patient.

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.

Association between schizophrenia and prostate cancer risk: Results from a pool of cohort studies and Mendelian randomization analysis.

BACKGROUND: Observational studies analyzing the risk of prostate cancer in schizophrenia patients have generated mixed results. We performed a meta-analysis and a Mendelian randomization (MR) analysis to evaluate the relationship and causality between schizophrenia and the risk of prostate cancer. METHODS: A comprehensive and systematic search of cohort studies was conducted, and a random-effects model meta-analysis was performed to calculate the standardized incidence ratios (SIRs) for prostate cancer incidence among schizophrenia patients versus the general population. To investigate the correlation between genetically-predicted schizophrenia and prostate cancer risk, we used summary statistics from the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium (61,106 controls and 79,148 cases), and 75 schizophrenia-associated single nucleotide polymorphisms (SNP) from European descent as the instrumental variable. RESULTS: In the meta-analysis of 13 cohort studies with 218,076 men involved, a decreased risk of prostate cancer was observed among schizophrenia patients [SIR 0.610; 95% confidence interval (CI) 0.500-0.740; p < 0.001] with significant heterogeneity (I2 = 83.3%; p < 0.001). However, MR analysis did not sustain the link between genetically-predicted schizophrenia and prostate cancer [odds ratio (OR) 1.033; 95% CI 0.998-1.069; p = 0.065]. The result was robust against extensive sensitivity analyses. CONCLUSIONS: Our study indicated a decreased risk of prostate cancer in schizophrenia patients through meta-analysis, while MR analysis did not support the connection between schizophrenia and prostate cancer. Due to the interaction of genetic variants between binary exposures, we need to be cautious in interpreting and presenting causal associations. Moreover, further research is needed to investigate underlying factors that might link schizophrenia to the risk of prostate cancer.

Risk factors for antiplatelet drug-associated intracranial hemorrhage: a systematic review and meta-analysis.

BACKGROUND: Antiplatelet drug-associated intracranial hemorrhage has a high mortality rate, and many factors can cause antiplatelet drug-associated intracranial hemorrhage. Until now, systematic reviews and assessments of the certainty of the evidence have not been published. AIM: We conducted a systematic review to identify risk factors of antiplatelet drug-associated intracranial hemorrhage. METHOD: The protocol for this systematic review was prospectively registered with PROSPERO (CRD42022311647). All studies written in English that met the inclusion criteria published before January 2022 were obtained from PubMed, EMBASE, Web of Science, and Cochrane Library. Two researchers independently screened articles, extracted data, and evaluated the quality and evidence of the included studies. Risk factors for antiplatelet drug-associated intracranial hemorrhage were used as the outcome index of this review. Random or fixed-effect models were used in statistical methods. I2 statistics were used to evaluate heterogeneity. RESULTS: Of 2844 citations, we included 6 studies in our analysis. For intracranial hemorrhage, moderate-certainty evidence showed a probable association with race, low BMI, GCS, severe bleeding, headache or vomiting, cerebrovascular disease, lacunar small vessel disease, cardiovascular disease, blood sugar, blood pressure, CT-defined white matter hypodensity, antihypertensive drugs, and antiplatelet therapy. In addition, we found low-certainty evidence that there may be little to no association between risk of intracranial hemorrhage and age, sex, and dual antithrombotic treatment or anticoagulant. CT-defined white matter hypodensity is not included in most intracranial hemorrhage risk assessment models. CONCLUSION: This study summarizes risk factors for antiplatelet drug-associated intracranial hemorrhage, which is significant in preventing intracranial hemorrhage.

Effect of rapeseed straw-derived biochar on soil bacterial community structure at tillering stage of Oryza Sativa.

Numerous studies have reported the dynamics of microbes when biochar was applied, whereas the information on the alterations of bacterial community after application of rapeseed straw-derived biochar is limited. A pot experiment with two rapeseed straw-derived biochar application treatments (with biochar application at the rate of 200 g/pot, C1, and without biochar application, 0 g/pot, C0) was conducted. No significant differences were observed in the number of operational taxonomic units, observed species, Shannon index, Simpson index, Chao1, ACE, and phylogenetic diversity whole tree between the C1 and C0 treatments. Taxonomic analysis at the phylum level showed that the abundances of Bacteroidetes and Parcubacteria were higher in the C1 treatment compared to the C0 treatment, while Acidobacteria, Chloroflexi, Rokubacteria, Berkelbacteria, and Latescibacteria were observed with higher abundance in the C0 treatment compared to the C1 treatment. Taxonomic analysis at the genus level showed that the abundances of Gracilibacter, Lentimicrobium, unidentified Rikenellaceae, Hydrogenophaga, and Bacillus were higher in the C1 treatment compared to the C0 treatment, while Candidatus Solibacter, Candidatus Koribacter, and Lutispora abundances were found to be higher in the C0 treatment compared to the C1 treatment. Obvious clusters were observed between the C1 and C0 treatments in both principal component analysis and nonmetric multidimensional scaling. These results indicate that soil bacterial community was altered after rapeseed straw-derived biochar was applied.

Proteomic profiling reveals differentially expressed proteins associated with amylose accumulation during rice grain filling.

BACKGROUND: Amylose accumulation in rice grains is controlled by genetic and environmental factors. Amylose content is a determinant factor of rice quality in terms of cooking and eating. Great variations in amylose content in indica rice cultivars have been observed. The current study was to identify differentially expressed proteins in starch and sucrose metabolism and glycolysis/gluconeogenesis pathways and their relationships to amylose synthesis using two rice cultivars possess contrasting phenotypes in grain amylose content. RESULTS: Synthesis and accumulation of amylose in rice grains significantly affected the variations between rice cultivars in amylose contents. The high amylose content cultivar has three down-regulated differentially expressed proteins, i.e., LOC_Os01g62420.1, LOC_Os02g36600.1, and LOC_Os08g37380.2 in the glycolysis/gluconeogenesis pathway, which limit the glycolytic process and decrease the glucose-1-phosphate consumption. In the starch and sucrose metabolic pathway, an up-regulated protein, i.e., LOC_Os06g04200.1 and two down-regulated proteins, i.e., LOC_Os05g32710.1 and LOC_Os04g43360.1 were identified (Figure 4). Glucose-1-phosphate is one of the first substrates in starch synthesis and glycolysis that are catalyzed to form adenosine diphosphate glucose (ADPG), then the ADPG is catalyzed by granule-bound starch synthase I (GBSS I) to elongate amylose. CONCLUSIONS: The results indicate that decreasing the consumption of glucose-1-phosphate in the glycolytic process is essential for the formation of ADPG and UDPG, which are substrates for amylose synthesis. In theory, amylose content in rice can be regulated by controlling the fate of glucose-1-phosphate.

Construction of warfarin population pharmacokinetics and pharmacodynamics model in Han population based on Bayesian method.

The purpose of this paper is to study the genetic polymorphisms of related gene loci (CYP2C9*3, VKORC1-1639G > A) based on demographic and clinical factors, and use the maximum a posterior Bayesian method to construct a warfarin individualized dose prediction model in line with the Chinese Han population. Finally, the built model is compared and analyzed with the widely used models at home and abroad. In this study, a total of 5467 INR measurements are collected from 646 eligible subjects in our hospital, and the maximum a posterior Bayesian method is used to construct a warfarin dose prediction that conforms to the Chinese Han population on the basis of the Hamberg model. The model is verified and compared with foreign models. This study finds that body weight and concomitant use of amiodarone have a significant effect on the anticoagulant effect of warfarin. The model can provide an effective basis for individualized and rational dosing of warfarin in Han population more accurately. In the performance of comparison with different warfarin dose prediction models, the new model has the highest prediction accuracy, and the prediction percentage is as high as 72.56%. The dose predicted by the Huang model is the closest to the actual dose of warfarin. The population pharmacokinetics and pharmacodynamics model established in this study can better reflect the distribution characteristics of INR values after warfarin administration in the Han population, and performs better than the models reported in the literature.

Vegetation canopy structure mediates the response of gross primary production to environmental drivers across multiple temporal scales.

Gross primary production (GPP) is a critical component of the global carbon cycle and plays a significant role in the terrestrial carbon budget. The impact of environmental factors on GPP can occur through both direct (by influencing photosynthetic efficiency) and indirect (through the modulation of vegetation structure) pathways, but the extent to which these mechanisms contribute has been seldom quantified. In this study, we used structural equation modeling and observations from the FLUXNET network to investigate the direct and indirect effects of environmental factors on terrestrial ecosystem GPP at multiple temporal scales. We found that canopy structure, represented by leaf area index (LAI), is a crucial intermediate factor in the GPP response to environmental drivers. Environmental factors affect GPP indirectly by altering canopy structure, and the relative proportion of indirect effects decreased with increasing LAI. The study also identified different effects of environmental factors on GPP across time scales. At the half-hourly time scale, radiation was the primary driver of GPP. In contrast, the influences of temperature and vapor pressure deficit took on greater prominence at longer time scales. About half of the total effect of temperature on GPP was indirect through the regulation of canopy structure, and the indirect effect increased with increasing time scale (GPPNT-based models: 0.135 (half-hourly) vs. 0.171 (daily) vs. 0.189 (weekly) vs. 0.217 (monthly); GPPDT-based models: 0.139 vs. 0.170 vs. 0.187 vs. 0.215; all values were reported in gC m-2 d-1 °C-1, P < 0.001); while the indirect effect of radiation on GPP was comparatively lower, accounting for less than a quarter of the total effect. Furthermore, we observed a direct, negative-to-positive impact of precipitation on GPP across timescales. These findings provide crucial information on the interplay between environmental factors and LAI on GPP and enable a deeper understanding of the driving mechanisms of GPP.

Effects of intensive, targeted education by pharmacists on anticoagulant patients with atrial fibrillation: a multicenter randomized controlled trial from China.

AIMS: Many people diagnosed with atrial fibrillation (AF) may lack awareness of AF and anticoagulants. The purpose of this study is to investigate the effects of intensive, targeted education by pharmacists on anticoagulant patients with AF. METHODS AND RESULTS: Three hundred seventy-six AF patients were randomly assigned to receive standard care or pharmacist education. Follow-up is scheduled after 1, 3, 6, and 12 months. Pharmacists provided intensive education on knowledge deficits revealed by the Jessa Atrial Fibrillation Knowledge Questionnaire (JAKQ) during each visit. Patients also completed two questionnaires to assess their medication adherence and satisfaction. Clinical outcomes were recorded during follow-up. 361 patients completed follow-up. Baseline scores on the JAKQ were similar in the education group (median: 31.3%) and the standard care group (median: 31.3%) (p = 0.911). Over time, the knowledge score of the education group increased significantly (1 month: 68.8%, 3 months: 81.3%; P <0.001), while there was no significant improvement in the standard care group (1 month: 37.5%, 3 months: 37.5%; P = 0.314). Adherence scores improved significantly over time in the education group (P < 0.001) but not in the standard care group (P =0.101). Compared with standard care, pharmacist education was associated with a significantly lower risk of bleeding (P=0.034). CONCLUSIONS: Given the knowledge deficiency of AF patients in China, standardized patient education should be a part of their daily care. Pharmacist-led education intervention can significantly improve the disease-related knowledge, medication adherence, and drug treatment satisfaction of AF patients while significantly reducing the risk of bleeding.

Population Pharmacokinetic Analysis for Model-Based Therapeutic Drug Monitoring of Tacrolimus in Chinese Han Heart Transplant Patients.

BACKGROUND AND OBJECTIVE: Tacrolimus has become the first-line immunosuppressant for preventing rejection after heart transplantation. The present study aimed to investigate genetic variants and clinical factors affecting the variability of tacrolimus in Chinese Han heart transplant patients using a population pharmacokinetic approach. METHODS: The retrospective study included 53 hospitalized patients with 547 tacrolimus concentrations for analysis. Nonlinear mixed-effects modeling was used to develop the population pharmacokinetics model for tacrolimus in patients with heart transplants, followed by Monte Carlo simulations to design initial dosing regimens. RESULTS: In our study, the mutation rate of CYP3A4*18B (C>T) was 27.36%. An oral one-compartment model with first-order absorption and elimination was used to describe the pharmacokinetics of tacrolimus in heart transplant patients. In the final model, the estimated apparent clearance (CL/F) and volume of distribution (V/F) were 532.5 L/h [12.20% interindividual variability, IIV] and 16.87 L (23.16% IIV), respectively. Albumin, postoperative time, and rs2242480 (CYP3A4*18B) gene polymorphisms were the significant covariates affecting CL/F, and creatinine clearance had significant effects on the V/F. CONCLUSION: The population pharmacokinetic model of tacrolimus in heart transplant patients can better estimate the population and individual pharmacokinetic parameters of patients and can provide a reference for the design of individualized dosing regimens.