Local Second Order MoÌ·ller-Plesset Theory with a Single Threshold Using Orthogonal Virtual Orbitals: A Distributed Memory Implementation.

In order to alleviate the computational burden associated with superlinear compute scalings with molecular size in electron correlation methods, researchers have developed local correlation methods that wisely treat relatively small contributions as zeros but still yield accurate energy approximation. Such local correlation techniques can also be combined with parallel computing resources to obtain further efficiency and scalability. This work focuses on the distributed memory parallel implementation of a local correlation method for second order MoÌ·ller-Plesset (MP2) theory. This method also only has a single threshold to control the dropping of terms and accuracy of different computing kernels in the algorithm. The process partitioning strategy and distributed parallel implementation with the message passing interface (MPI) are discussed. In particular, the algorithm relies on a fixed sparsity pattern matrix multiplication and a corresponding distributed conjugate gradient solver, which exhibits almost linear scaling in both strong and weak scaling analyses. Numerical experiments on a range of molecules, including linear chains and molecules with 2 and 3-dimensional characters, are reported. For example, with only 32 MPI ranks, this MP2 implementation can calculate the correlation energy of vancomycin in def2-TZVP basis within 0.003% accuracy (10-6.5 threshold) in half an hour, where the same problem is unfeasible to solve with sequential or pure shared memory implementations.

Co-Administration of Amiodarone Increases Bleeding by Affecting Rivaroxaban Pharmacokinetics in Patients with Atrial Fibrillation.

This study aimed to investigate the impact of the drug-drug interaction between rivaroxaban and amiodarone on the clinical outcomes in patients with non-valvular atrial fibrillation (NVAF), focusing on pharmacokinetic and pharmacodynamic (PK/PD) aspects. A prospective study enrolling 174 patients with NVAF who were treated with rivaroxaban was conducted. The patients were divided into two groups based on postoperative antiarrhythmic and anticoagulation strategies: the rivaroxaban group (Control group) and the rivaroxaban plus amiodarone group (Riv/Amio group). The trough plasma concentrations (Ctrough) of rivaroxaban, activated partial thromboplastin time (APTT), prothrombin time (PT), and the clinical outcomes between the two groups were compared. Patients receiving 20 mg of rivaroxaban in the Riv/Amio group had a higher concentration of rivaroxaban Ctrough than those in the Control group (p = 0.009). Furthermore, in patients with moderate to severe renal impairment, rivaroxaban Ctrough was significantly increased in the Riv/Amio group. There was no significant difference in PT and APTT between the two groups. Regarding the clinical outcomes, the combination of rivaroxaban and amiodarone medication was associated with a higher incidence of bleeding events (p = 0.041; HR = 2.83, 95% CI 1.05-7.66) and clinically relevant non-major bleeding (p = 0.021; HR = 3.65, 95% CI 1.21-10.94). Finally, independent risk factors for bleeding in NAVF patients treated with rivaroxaban were identified as its combination with amiodarone (p = 0.044; OR = 2.871, 95% CI 1.028-8.023). The combination of rivaroxaban and amiodarone led to changes in rivaroxaban pharmacokinetics and an elevated risk of bleeding events. Therefore, physicians prescribing rivaroxaban medications should assess the potential bleeding risk associated with the concurrent use of amiodarone, particularly in patients with renal impairment.

Highly stable color-tunable organic long-persistent luminescence from a single-component exciplex copolymer for in vitro antibacterial.

Developing exciplex-based organic long-persistent luminescence (OLPL) materials with high stability is very important but remains a formidable challenge in a single-component system. Here, we report a facile strategy to achieve highly stable OLPL in an amorphous exciplex copolymer system via through-space charge transfer (TSCT). The copolymer composed of electron donor and acceptor units can not only exhibit effective TSCT for intra/intermolecular exciplex emission but also construct a rigid environment to isolate oxygen and suppress non-radiative decay, thereby enabling stable exciplex-based OLPL emission with color-tunable feature for more than 100 h under ambient conditions. These single-component OLPL copolymers demonstrate robust antibacterial activity against Escherichia coli under visible light irradiation. These results provide a solid example to exploit highly stable exciplex-based OLPL in polymers, shedding light on how the TSCT mechanism may potentially contribute to OLPL in a single-component molecular system and broadening the scope of OLPL applications.

The Impact of Genetic Polymorphisms on the Anti-Hyperglycemic Effect of Dapagliflozin.

Background: The influence of genetic variants on the glucose-lowering effects of dapagliflozin remains unclear. This study aims to investigate the impact of polymorphisms in solute carrier family 5 member 2 (SLC5A2), uridine diphosphate glucuronosyltransferase 1A9 (UGT1A9), solute carrier family 2 member 2 (SLC2A2) and member 4 (SLC2A4) on the anti-hyperglycemic effect of dapagliflozin in patients with type-2 diabetes mellitus (T2DM). Methods: A total of 141 patients with T2DM were included in this prospective cohort study. Twenty-nine single nucleotide polymorphisms (SNPs) were selected and genotyped using the Sequenom MassArray platform or Sanger sequencing. Glycated hemoglobin (HbA1c) and fasting blood glucose (FBG) levels were compared before and after the treatment with dapagliflozin. Results: Among the 29 SNPs selected, 27 were successfully analyzed. After three months of dapagliflozin treatment, FBG levels were significantly reduced (8.00 mmol/L (5.45-10.71) mmol/L vs 6.40 mmol/L (5.45-9.20) mmol/L, p = 0.003) in patients with T2DM. However, there was no significant change in HbA1c levels (8.10% (6.88-10.00)% vs 8.10% (6.83-10.00)%, p = 0.452). Analysis of covariance showed that patients with the minor allele homozygote or heterozygote of rs12471030 (CT/TT), rs12988520 (AC/CC) or rs2602381 (TC/CC) had higher FBG levels compared to those with the major allele homozygote (p = 0.014, p = 0.024, and p = 0.044, respectively). After adjusting for baseline FBG level, age, gender, body mass index, use of insulin and use of metformin, three SNPs-rs12471030, rs12988520 and rs2602381-were associated with the anti-hyperglycemic effect of dapagliflozin. However, using a stringent significance threshold (p < 0.002 with Bonferroni correction), none of these selected SNPs were significantly associated with FBG and HbA1c levels after dapagliflozin treatment. Conclusion: After adjusting for confounding variables, polymorphisms in SLC5A2, UGT1A9, SLC2A2 and SLC2A4 genes were not associated with the anti-hyperglycemic effect of dapagliflozin in the Chinese population. Clinical Trial Registration Number: ChiCTR2200059645.

Thoracic endovascular aortic repair with unibody single-branched stent-graft for type B aortic dissection: A real-world multicenter study.

OBJECTIVE: To evaluate the outcome of TEVAR for TBAD and revascularization of LSA with Castor single-branched stent-graft. SUMMARY BACKGROUND DATA: One-stage thoracic endovascular aortic repair (TEVAR) and revascularization of left subclavian artery (LSA) of type B aortic dissection (TBAD) with off-the-shelf stent-graft is limited. METHODS: A multicenter study consisting of consecutive patients from 4 different centers in China treated with Castor single-branched stent-graft for TBAD was conducted. Rate of technical success, mortality, complications, and reinterventions were evaluated. RESULTS: Between September 2018 and April 2022, 180 consecutive patients with TBAD received TEVAR with Castor single-branched stent-graft. Technical success was achieved in all patients. The mean oversize ratio at the proximal landing zone was 4.9±3.8% (median, 3.7; IQR, 2.0%-6.9%). Five patients died within the first 30 days after the operation or during hospitalization. Early reintervention was performed in 1 case. The median follow-up was 18.0 months (IQR, 13-24 months). Five patients died during follow-up, including three cases of respiratory failure, one case of immune thrombocytopenia purpura, and one case of cerebral hemorrhage. Three patients had reintervention. In total, 3 cases of stroke were recorded, which were all within 30 days after the operation. Image data at 1 year presented complete thrombosis in 97.1% cases for the false lumen covered by the stent-graft. CONCLUSIONS: TEVAR with Castor device for treatment of TBAD and revascularization of LSA is a feasible and safety technique. The deployment procedure is safe, easy, and accurate. Castor devices meets the hemodynamical and biomechanical requirement of elastic aorta and could restore the physiological blood flow pattern of LSA.

Extracellular Vesicle-Inspired Minimalist Flexible Nanocapsules Assembled with Whole Active Ingredients for Highly Efficient Enhancement of DC-Mediated Tumor Immunotherapy.

The development of nanovaccines capable of eliciting tumor-specific immune responses holds significant promise for tumor immunotherapy. However, many nanovaccine designs rely heavily on incorporating multiple adjuvants and carriers, increasing the biological hazards associated with these additional components. Here, this work introduces novel flexible nanocapsules (OVAnano) designed to mimic extracellular vesicles, primarily using the ovalbumin antigen and minimal polyethylenimine adjuvant components. These results show that the biomimetic flexible structure of OVAnano facilitates enhanced antigen uptake by dendritic cells (DCs), leading to efficient antigen and adjuvant release into the cytosol via endosomal escape, and ultimately, successful antigen cross-presentation by DCs. Furthermore, OVAnano modulates the intracellular nuclear factor kappa-B (NF-κB) signaling pathway, promoting DC maturation. The highly purified antigens in OVAnano demonstrate remarkable antigen-specific immunogenicity, triggering strong antitumor immune responses mediated by DCs. Therapeutic tumor vaccination studies have also shown that OVAnano administration effectively suppresses tumor growth in mice by inducing immune responses from CD8+ and CD4+ T cells targeting specific antigens, reducing immunosuppression by regulatory T cells, and boosting the populations of effector memory T cells. These findings underscore that the simple yet potent strategy of employing minimal flexible nanocapsules markedly enhances DC-mediated antitumor immunotherapy, offering promising avenues for future clinical applications.

Which one is the best in treating deep venous thrombosis -- percutaneous mechanical thrombectomy, catheter-directed thrombolysis or combination of them?

OBJECTIVE: To compare the treatment outcomes among percutaneous mechanical thrombectomy (PMT) with AngioJet, Catheter-directed thrombolysis (CDT), and a combination of both. METHODS: One hundred forty nine patients with acute or sub-acute iliac-femoral vein thrombosis accepting CDT and/or PMT were divided into three groups respectively: PMT group, CDT group, PMT + CDT group (PMT followed by CDT). The severity of thrombosis was evaluated by venographic scoring system. Technical success was defined as restored patent deep venous blood flow after CDT and/or PMT. Clinical follow-up were assessed by ultrasound or venography imaging. The primary endpoints were recurrence of DVT, and severity level of post-thrombotic syndrome (PTS) during the follow-up. RESULTS: Technical success and immediate clinical improvements were achieved on all patients. The proportion of sub-acute DVT and the venographic scoring in PMT + CDT group were significantly higher than that in CDT group and PMT group (proportion of sub-acute DVT: p = 0.032 and p = 0.005, respectively; venographic scoring: p < 0.001, respectively). The proportion of May-Thurner Syndrome was lower in PMT group than that in CDT and PMT + CDT group (p = 0.026 and p = 0.005, respectively). The proportion of DVT recurrence/stent thrombosis was significantly higher in CDT group than that in PMT + CDT group (p = 0.04). The severity of PTS was the highest in CDT group ( χ2 = 14.459, p = 0.006) compared to PMT group (p = 0.029) and PMT + CDT group (p = 0.006). CONCLUSION: Patients with sub-acute DVT, high SVS scoring and combined May-Thurner Syndrome were recommended to take PMT + CDT treatment and might have lower rate of DVT recurrence/stent thrombosis and severe PTS. Our study provided evidence detailing of PMT + CDT therapy.

Germacrone, isolated from Curcuma wenyujin, inhibits melanin synthesis through the regulation of the MAPK signaling pathway.

Abnormal melanin synthesis causes hyperpigmentation disorders, such as chloasma, freckles, and melanoma, which are highly multiple and prevalent. There were few reports on the anti-melanogenic effect of Curcuma wenyujin Y.H. Chen et C. Ling, and the bioactive compound has not been elucidated as well. The study aims to investigate the anti-melanogenic effect of C. wenyujin, and identify the bioactive compound, and further explore its underlying mechanism. Our results showed that the Petroleum ether fraction extracted from C. wenyujin rhizome had a significant anti-melanogenic effect, and germacrone isolated from it was confirmed as the major bioactive compound. To our data, germacrone significantly inhibited tyrosinase (TYR) activity, reduced melanosome synthesis, reduced dendrites formation of B16F10 cells, and melanosome transport to keratinocytes. Moreover, germacrone effectively decreased the hyperpigmentation in zebrafish and the skin of guinea pigs in vivo. Western-blot analysis showed that germacrone down-regulated the expression of TYR, TRP-1, TRP-2, Rab27a, Cdc42, and MITF proteins via the activation of the MAPK signaling pathway. Taken together, germacrone is an effective bioactive compound for melanogenesis inhibition. Our studies suggest that germacrone may be considered a potential candidate for skin whitening.

Simultaneous Biofilm Disruption, Bacterial Killing, and Inflammation Elimination for Wound Treatment Using Silver Embellished Polydopamine Nanoplatform.

Due to the presence of spatial barriers, persistent bacteria, and excessive inflammation in bacteria biofilm-infected wounds, current nanoplatforms cannot effectively address these issues simultaneously during the therapeutic process. Herein, a novel biomimetic photothermal nanoplatform integrating silver and polydopamine nanoparticles (Ag/PDAs) that can damage biofilms, kill bacterial persisters, and reduce inflammation for wound treatment is presented. These findings reveal that Ag/PDAs exhibit a broad-spectrum antimicrobial activity through direct damage to the bacterial membrane structure. Additionally, Ag/PDAs demonstrate a potent photothermal conversion efficiency. When combined with near-infrared (NIR) irradiation, Ag/PDAs effectively disrupt the spatial structure of biofilms and synergistically eradicate the resident bacteria. Furthermore, Ag/PDAs show remarkable anti-inflammatory properties in counteracting bacterium-induced macrophage polarization. The in vivo results confirm that the topical application of Ag/PDAs significantly suppress Staphylococcus aureus biofilm-infected wounds in murine models, concurrently facilitating wound healing. This research provides a promising avenue for the eradication of bacterial biofilms and the treatment of biofilm-infected wounds.

Tetramethylpyrazine-loaded electroconductive hydrogels promote tissue repair after spinal cord injury by protecting the blood-spinal cord barrier and neurons.

Spinal cord injury (SCI) usually induces profound microvascular dysfunction. It disrupts the integrity of the blood-spinal cord barrier (BSCB), which could trigger a cascade of secondary pathological events that manifest as neuronal apoptosis and axonal demyelination. These events can further lead to irreversible neurological impairments. Thus, reducing the permeability of the BSCB and maintaining its substructural integrity are essential to promote neuronal survival following SCI. Tetramethylpyrazine (TMP) has emerged as a potential protective agent for treating the BSCB after SCI. However, its therapeutic potential is hindered by challenges in the administration route and suboptimal bioavailability, leading to attenuated clinical outcomes. To address this challenge, traditional Chinese medicine, TMP, was used in this study to construct a drug-loaded electroconductive hydrogel for synergistic treatment of SCI. A conductive hydrogel combined with TMP demonstrates good electrical and mechanical properties as well as superior biocompatibility. Furthermore, it also facilitates sustained local release of TMP at the implantation site. Furthermore, the TMP-loaded electroconductive hydrogel could suppress oxidative stress responses, thereby diminishing endothelial cell apoptosis and the breakdown of tight junction proteins. This concerted action repairs BSCB integrity. Concurrently, myelin-associated axons and neurons are protected against death, which meaningfully restore neurological functions post spinal cord injury. Hence, these findings indicate that combining the electroconductive hydrogel with TMP presents a promising avenue for potentiating drug efficacy and synergistic repair following SCI.

A comparative study on the transbrachial and transfemoral approaches for the treatment of superior mesenteric artery lesions.

BACKGROUND: Superior Mesenteric Artery (SMA) lesions present a significant challenge in endovascular surgery. Both the transbrachial (TBA) and the transfemoral (TFA) approaches have been employed for the treatment of these lesions, but the comparative effectiveness of these methods remains unclear. MATERIALS AND METHODS: A retrospective analysis was conducted on patients who underwent TBA and TFA at a tertiary center between June 2020 and February 2023. Key parameters including technical success, procedural details, and complication rates were examined. RESULTS: In a study of 99 patients, 66 underwent Transfemoral Approach (TFA) and 33 underwent Transbrachial Approach (TBA). No significant age or gender differences were noted between groups. TFA procedures were longer (90.0 vs 63.5 min, p = 0.002) and had higher fluoroscopy times (59.0 vs 43.0 min, p = 0.02) and selective SMA times (366.0 vs 245.0 min, p = 0.038) compared to TBA, especially with a smaller aortomesenteric angle (<90°). Technical success rates were high in both groups (TFA 97%, TBA 93.9%, p = 0.60). Complication rates were similar between groups, with no significant predictors for access site complications identified. CONCLUSION: Both the TBA and the TFA are effective for the treatment of SMA lesions, with TBA potentially offering advantages in terms of efficiency and patient recovery, particularly in cases with certain anatomy. No significant differences in complication rates were found between the two groups. Further research, including prospective randomized trials, is needed to confirm these findings.

Influence of Aging on Outcomes of Sacubitril/Valsartan in Hypertensive Patients with Heart Failure: A Multicenter Retrospective Study.

BACKGROUND: The aim of this study was to investigate the influence of aging on the effectiveness and tolerance of sacubitril/valsartan (sac/val) among hypertensive patients complicated with heart failure in a real-world setting. METHODS: This multicenter, retrospective study included patients (≥18 years old) admitted with a diagnosis of hypertension and heart failure, starting sac/val therapy between January 2020 and December 2021 from 3 medical centers. Patients were grouped by the cutoff age of 65 years. Outcomes were collected 31-365 days after the initiation of sac/val and were compared in a matched cohort after 1: 1 propensity score matching (PSM). RESULTS: A total of 794 patients were finally analyzed. Blood pressure and cardiac functions improved significantly compared with values at baseline. There were 269 patients in each cohort (<65 years and ≥65 years) after PSM. After PSM, the incidence of hyperuricemia and hypotension in the elderly patients (≥65 years) was significantly higher than in those <65 years of age. Kaplan-Meier estimate suggested that the cumulative incidence of new or recurrent cardiovascular events increased significantly at the age of ≥65 years after the point of 3 months (log-rank P =.00087). CONCLUSION: Sac/val benefited patients in both cohorts by improving blood pressure and cardiac function. Elderly patients (≥65 years) were susceptible to hypotension, low diastolic blood pressure, hyperuricemia, and underwent cardiac-related readmissions more frequently.

Perioperative Treatment with Rivaroxaban and Dabigatran on Changes of Coagulation and Platelet Activation Biomarkers following Left Atrial Appendage Closure.

Insufficient data exist regarding the investigation of the impact of novel oral anticoagulants (NOACs) on coagulation activation biomarkers in the context of left atrial appendage closure (LAAC) and device-related thrombosis (DRT). The study was designed to investigate the changes and presence of coagulation activation biomarkers between different antithrombotic strategies following LAAC. A total of 120 nonvalvular atrial fibrillation patients intolerant of long-term anticoagulants, who underwent successful WATCHMAN closure implantation, were enrolled (rivaroxaban, n = 82; dabigatran, n = 38). Blood samples were obtained from left atrium (LA) and left atrial appendage (LAA) during the operation and fasting blood samples on the same day of LAAC and 45 days after discharge. The biochemical indicators, thrombin-antithrombin complex (TAT), soluble P-selectin (sP-selectin), von Willebrand factor (vWF), and CD40 ligand (CD40L), were measured by enzyme-linked immunosorbent assay. The primary endpoints of this study were the efficacy and safety characteristics of different antithrombotic strategies, including DRT incidence, stroke or transient ischemic attack, systemic embolism, and clinical major and nonmajor bleeding complications during the follow-up of 180 days. The results revealed that TAT, vWF, sP-selectin, and CD40L levels in vein were significantly reduced by 2.4% (p = 0.043), 5.0% (p < 0.001), 8.7% (p < 0.001), and 2.5% (p = 0.043) from their baseline levels after rivaroxaban treatment. Conversely, no significant changes were detected in the dabigatran group. Furthermore, the plasma levels of platelet activation biomarkers (CD40L and sP-selectin) in both LA and LAA groups were significantly lower after anticoagulation with rivaroxaban, as compared to dabigatran treatment (CD40L: 554.62 ± 155.54 vs. 445.02 ± 130.04 for LA p = 0.0013, 578.51 ± 156.28 vs. 480.13 ± 164.37 for LAA p = 0.0052; sP-selectin: 2849.07 ± 846.69 vs. 2225.54 ± 799.96 for LA p = 0.0105, 2915.52 ± 1402.40 vs. 2203.41 ± 1061.67 for LAA p = 0.0022). Notably, the present study suggests that rivaroxaban may be more effective in the prevention of DRT for patients undergoing LAAC.

Clinical efficacy of clopidogrel and ticagrelor in patients undergoing off-pump coronary artery bypass grafting: a retrospective cohort study.

BACKGROUND: Ticagrelor is reportedly more effective than clopidogrel in preventing atherothrombotic events in patients with percutaneous coronary intervention. However, the optimal antiplatelet therapy strategy after off-pump coronary artery bypass grafting (OPCABG) is yet to be established. MATERIALS AND METHODS: This study was performed using the prospectively-maintained database at our institution. Patients who underwent OPCABG were divided into the clopidogrel and the ticagrelor groups. Propensity score matching analysis was performed between the two groups. The clinical outcome was the occurrence of major adverse cardiovascular event (MACE), defined as a composite of vascular death, myocardial infarction, or stroke 1-year after surgery. RESULTS: In total, 545 patients completed the entire follow-up assessment. After propensity score matching, 232 patients each were included in the clopidogrel and ticagrelor groups. The primary outcome occurred in 7.8 and 4.3% of patients in the clopidogrel and ticagrelor groups, respectively ( P =0.113). CYP2C19 variants (*2, *3, and *17) did not impact the clinical outcomes, regardless of the use of clopidogrel or ticagrelor. The rates of MACE were significantly lower in patients carrying the ABCB1 C3435T CT/TT genotypes in the ticagrelor group than in those carrying the ABCB1 C3435T CC genotype in the clopidogrel group (1.4 vs. 9.1%, adjusted P =0.030), as well as those carrying the ABCB1 C3435T CC genotype in the ticagrelor group (1.4 vs. 8.9%, adjusted P =0.036). The ABCB1 C3435T CC genotype was significantly associated with the incidence of 1-year MACE (HR=1.558, 95% CI: 1.109-2.188, P =0.011). Patients who experienced severe perioperative bleeding exhibited a significantly higher incidence of MACE than those who did not experience severe perioperative bleeding (14.0 vs. 4.9%, adjusted P =0.007). CONCLUSION: There was no significant difference in the 1-year MACE between patients receiving clopidogrel and those receiving ticagrelor after OPCABG. Notably, The ABCB1 C3435T CC genotype was related to a higher risk of MACE.

Impact of fermented feed of soybean hulls and rapeseed cake on immunity, antioxidant capacity, and gut microbiota in Chahua chicken.

The present study investigated the effects of replacing part of the basal diet with 2-stage fermented feed (FF) (soybean hulls:rapeseed cake (2:1, m/m)) on the growth performance, immunity, antioxidant capacity, and intestinal health of Chahua chicken. A total of 160 Chahua chickens were randomly divided into 4 groups to receive a control diet or diet with 5%, 10%, or 15% of the basal diet replaced by FF, respectively for 56 d. The results showed that FF significantly improved the average daily gain (ADG) and average daily feed intake (ADFI) of Chahua chickens (P < 0.05). Furthermore, the serum immunoglobulin (Ig) A, glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) in Chahua chicken receiving the diet added with 15% FF significantly increased (P < 0.05). Chahua chicken in both the 10% and 15% groups showed increased serum IgG and IgM and decreased malondialdehyde. Serum interleukin-2 and interferon-gamma significantly increased in all FF groups. Compared with the CON group, higher ileal villus height (VH) was found in the 10% FF group. Treatment with FF significantly increased the ileal villus height/crypt depth (VH/CD) ratio, jejunal VH, and jejunal VH/CD ratio while reducing ileal and jejunal CD. The modified gut microbiota composition was observed in the Chahua chicken fed a diet containing FF, in particular, with the increased abundance of Faecalibacterium and Lactobacillus. The abundance of Lactobacillus significantly increased in the 10% and 15% FF groups (all P < 0.05). Correlation analysis revealed a positive correlation between Lactobacillus and VH (R = 0.38, P = 0.10, Figure 3B), AH/CD ratio (R = 0.63, P = 0.003), and a negative correlation with CD (R = -0.72, P = 0.001). These results indicate that FF improves immunity, antioxidant capacity, and intestinal health and consequently enhances growth performance in Chahua chicken.

[Experimental study of tetramethylpyrazine-loaded electroconductive hydrogel on angiogenesis and neuroprotection after spinal cord injury].

Objective: To explore the mechanisms for repairing spinal cord injury (SCI) with tetramethylpyrazine-loaded electroconductive hydrogel (hereinafter referred to as "TGTP"). Mehtods: A total of 72 female Sprague-Dawley rats were randomly divided into 4 groups: sham operation group (group A), SCI group (group B), SCI+electroconductive hydrogel group (group C), and SCI+TGTP group (group D). Only the vertebral plate was removed in group A, while the remaining groups were subjected to a whole transection model of spinal cord with a 2 mm gap in the lesions. The recovery of hindlimb motor function was evaluated by Basso, Beattie, Bresnahan (BBB) score and modified Rivlin-Tator inclined plate test before operation and at 1, 3, 7, 14, and 28 days after operation, respectively. Animals were sacrificed at 7 days and 28 days after modeling. Neovascularisation was observed by immunofluorescence staining of CD31 and the expression levels of angiopoietin 1 (Ang-1) and Tie-2 were assessed by Western blot assay. At 28 days postoperatively, the expression levels of pro-angiogenic related proteins, including platelet-derived growth factor B (PDGF-B), PDGF receptor ß (PDGFR-ß), vascular endothelial growth factor A (VEGF-A), and VEGF receptor 2 (VEGFR-2), were also assessed by Western blot. The fibrous scar in the injured area was assessed using Masson staining, while neuronal survival was observed through Nissl staining. Furthermore, LFB staining was utilized to detect myelin distribution and regeneration. Immunofluorescence and Western blot assay were employed to evaluate the expression of neurofilament 200 (NF200). Results: The hindlimb motor function of rats in each group gradually recovered from the 3rd day after operation. The BBB score and climbing angle in group D were significantly higher than those in group B from 3 to 28 days after operation, and significantly higher than those in group C at 14 days and 28 days after operation ( P<0.05). Masson staining showed that the collagen volume fraction in groups B-D were significantly higher than that in group A, and that in group D was significantly lower than that in groups B and C ( P<0.05); a small amount of black conductive particles were scattered at the broken end in group D, and the surrounding collagen fibers were less than those in group C. Nissl and LFB staining showed that the structure of neurons and myelin sheath in the injured area of spinal cord in group D was relatively complete and continuous, and the number of Nissl bodies and the positive area of myelin sheath in group D were significantly better than those in groups B and C ( P<0.05). NF200 immunofluorescence staining and Western blot assay results showed that the relative expression of NF200 protein in group D was significantly higher than that in groups B and C ( P<0.05). CD31 immunofluorescence staining showed that the fluorescence intensity of group D was better than that of groups B and C at 28 days after operation, and tubular or linear neovascularization could be seen. The relative expressions of Ang-1 and Tie-2 proteins in group D were significantly higher than those in groups B and C at 7 and 28 days after operation ( P<0.05). The relative expressions of PDGF-B and PDGFR-ß proteins in group D were significantly higher than those in groups B and C, and group B was significantly higher than group C at 28 days after operation ( P<0.05). The relative expressions of VEGF-A and VEGFR2 proteins in group D were higher than those in groups B and C, showing significant difference when compared with group B ( P<0.05), but only the expression of VEGF-A protein was significantly higher than that in group C ( P<0.05). There was significant difference only in VEGFR-2 protein between groups B and C ( P<0.05). Conclusion: TGTP may enhance the revascularization of the injured area and protect the neurons, thus alleviating the injury of spinal cord tissue structure and promoting the recovery of neurological function after SCI in rats.

Nomogram for predicting bleeding events in nonvalvular atrial fibrillation patients receiving rivaroxaban: A retrospective study.

Background and Aims: To construct a bleeding events prediction model of nonvalvular atrial fibrillation (NVAF) patients receiving rivaroxaban. Methods: We conducted a retrospective cohort study in patients with NVAF who received rivaroxaban from June 2017 to March 2019. Demographic information and clinical characteristics were obtained from the electronic medical system. Univariate analysis was used to find the primary predictive factors of bleeding events in patients receiving rivaroxaban. Multiple analysis was conducted to screen the primary independent predictive factors selected from the univariate analysis. Finally, the independent influencing factors were applied to build a prediction model by using R software; then, a nomogram was established according to the selected variables visually, and the sensitivity and specificity of the model was evaluated. Results: Twelve primary predictive factors were selected by univariate analysis from 46 variables, and multivariate analysis showed that older age, higher prothrombin time (PT) values, history of heart failure and stroke were independent risk factors of bleeding events. The area under curve (AUC) for this novel nomogram model was 0.828 (95% CI: 0.763-0.894). The mean AUC over 10-fold stratified cross-validation was 0.787, and subgroup analysis validation also showed a satisfied AUC. In addition, the decision curve analysis showed that the PT in combination with CHA2DS2-VASc and HASBLED was more practical and accurate for predicting bleeding events than using CHA2DS2-VASc and HASBLED alone. Conclusions: PT in combination with CHA2DS2-VASc and HASBLED could be considered as a more practical and accurate method for predicting bleeding events in patients taking rivaroxaban.

A novel machine learning model to predict high on-treatment platelet reactivity on clopidogrel in Asian patients after percutaneous coronary intervention.

BACKGROUND: Various genetic and nongenetic variables influence the high on-treatment platelet reactivity (HTPR) in patients taking clopidogrel. AIM: This study aimed to develop a novel machine learning (ML) model to predict HTPR in Chinese patients after percutaneous coronary intervention (PCI). METHOD: This cohort study collected information on 507 patients taking clopidogrel. Data were randomly divided into a training set (90%) and a testing set (10%). Nine candidate Machine learning (ML) models and multiple logistic regression (LR) analysis were developed on the training set. Their performance was assessed according to the area under the receiver operating characteristic curve, precision, recall, F1 score, and accuracy on the test set. Model interpretations were generated using importance scores by transforming model variables into scaled features and representing in radar plots. Finally, we established a prediction platform for the prediction of HTPR. RESULTS: A total of 461 patients (HTPR rate: 19.52%) were enrolled in building the prediction model for HTPR. The XGBoost model had an optimized performance, with an AUC of 0.82, a precision of 0.80, a recall of 0.44, an F1 score of 0.57, and an accuracy of 0.87, which was superior to those of LR. Furthermore, the XGBoost method identified 7 main predictive variables. To facilitate the application of the model, we established an XGBoost prediction platform consisting of 7 variables and all variables for the HTPR prediction. CONCLUSION: A ML-based approach, such as XGBoost, showed optimum performance and might help predict HTPR on clopidogrel after PCI and guide clinical decision-making. Further validated studies will strengthen this finding.

A Novel Body Mass Index-Based Thromboembolic Risk Score for Overweight Patients with Nonvalvular Atrial Fibrillation.

BACKGROUND: A novel risk prediction model appears to be urgently required to improve the assessment of thrombotic risk in overweight patients with nonvalvular atrial fibrillation (NVAF). We developed a novel body mass index (BMI)-based thromboembolic risk score (namely AB2S score) for these patients. METHODS: A total of 952 overweight patients with NVAF were retrospectively enrolled in this study with a 12-month follow-up. The primary endpoint was 1-year systemic thromboembolism and the time to thrombosis (TTT). The candidate risk variables identified by logistic regression analysis were included in the final nomogram model to construct AB2S score. The measures of model fit were evaluated using area under the curve (AUC), C-statistic, and calibration curve. The performance comparison of the AB2S score to the CHADS2 and CHA2DS2-VASc score was performed in terms of the AUC and decision analysis curve (DAC). RESULTS: The AB2S score was constructed using 7 candidate risk variables, including a 3-category BMI (25 to 30, 30 to 34, or ≥35 kg/m2). It yielded a c-index of 0.885 (95% CI, 0.814-0.954) and an AUC of 0.885 (95% CI, 0.815-0.955) for predicting 1-year systemic thromboembolism in patients with NVAF. Compared to the CHADS2 score and CHA2DS2-VASc score, the AB2S score had greater AUC and DAC values in predicting the thromboembolic risk and better risk stratification in TTT (P <.0001, P =.082, respectively). CONCLUSION: Our results highlighted the importance of a BMI-based AB2S score in determining systemic thromboembolism risk in overweight patients with NVAF, which may aid in decision-making for these patients to balance the effectiveness of anticoagulation from the underlying thrombotic risk.

Ultrasound-Stimulated "Exocytosis" by Cell-Like Microbubbles Enhances Antibacterial Species Penetration and Immune Activation Against Implant Infection.

Host immune systems serving as crucial defense lines are vital resisting mechanisms against biofilm-associated implant infections. Nevertheless, biofilms hinder the penetration of anti-bacterial species, inhibit phagocytosis of immune cells, and frustrate host inflammatory responses, ultimately resulting in the weakness of the host immune system for biofilm elimination. Herein, a cell-like construct is developed through encapsulation of erythrocyte membrane fragments on the surface of Fe3 O4 nanoparticle-fabricated microbubbles and then loaded with hydroxyurea (EMB-Hu). Under ultrasound (US) stimulation, EMB-Hu undergoes a stable oscillation manner to act in an "exocytosis" mechanism for disrupting biofilm, releasing agents, and enhancing penetration of catalytically generated anti-bacterial species within biofilms. Additionally, the US-stimulated "exocytosis" by EMB-Hu can activate pro-inflammatory macrophage polarization and enhance macrophage phagocytosis for clearance of disrupted biofilms. Collectively, this work has exhibited cell-like microbubbles with US-stimulated "exocytosis" mechanisms to overcome the biofilm barrier and signal macrophages for inflammatory activation, finally achieving favorable therapeutic effects against implant infections caused by methicillin-resistant Staphylococcus aureus (MRSA) biofilms.