ECM-inspired calcium/zinc laden cellulose scaffold for enhanced bone regeneration.

Cellulose-based polymer scaffolds are highly diverse for designing and fabricating artificial bone substitutes. However, realizing the multi-biological functions of cellulose-based scaffolds has long been challenging. In this work, inspired by the structure and function of the extracellular matrix (ECM) of bone, we developed a novel yet feasible strategy to prepare ECM-like scaffolds with hybrid calcium/zinc mineralization. The 3D porous structure was formed via selective oxidation and freeze drying of bacterial cellulose. Following the principle of electrostatic interaction, calcium/zinc hybrid hydroxyapatite nucleated, crystallized, and precipitated on the 3D scaffold in simulated physiological conditions, which was well confirmed by morphology and composition analysis. Compared with alternative scaffold cohorts, this hybrid ion-loaded cellulose scaffold exhibited a pronounced elevation in alkaline phosphatase (ALP) activity, osteogenic gene expression, and cranial defect regeneration. Notably, the hybrid ion-loaded cellulose scaffold effectively fostered an M2 macrophage milieu and had a strong immune effect in vivo. In summary, this study developed a hybrid multifunctional cellulose-based scaffold that appropriately simulates the ECM to regulate immunomodulatory and osteogenic differentiation, setting a measure for artificial bone substitutes.

Cas13b-mediated RNA targeted therapy alleviates genetic dilated cardiomyopathy in mice.

BACKGROUND: Recent advances in gene editing technology have opened up new avenues for in vivo gene therapy, which holds great promise as a potential treatment method for dilated cardiomyopathy (DCM). The CRISPR-Cas13 system has been shown to be an effective tool for knocking down RNA expression in mammalian cells. PspCas13b, a type VI-B effector that can be packed into adeno-associated viruses and improve RNA knockdown efficiency, is a potential treatment for diseases characterized by abnormal gene expression. RESULTS: Using PspCas13b, we were able to efficiently and specifically knockdown the mutant transcripts in the AC16 cell line carrying the heterozygous human TNNT2R141W (hTNNT2R141W) mutation. We used adeno-associated virus vector serotype 9 to deliver PspCas13b with specific single guide RNA into the hTNNT2R141W transgenic DCM mouse model, effectively knocking down hTNNT2R141W transcript expression. PspCas13b-mediated knockdown significantly increased myofilament sensitivity to Ca2+, improved cardiac function, and reduced myocardial fibrosis in hTNNT2R141W DCM mice. CONCLUSIONS: These findings suggest that targeting genes through Cas13b is a promising approach for in vivo gene therapy for genetic diseases caused by aberrant gene expression. Our study provides further evidence of Cas13b's application in genetic disease therapy and paves the way for future applicability of genetic therapies for cardiomyopathy.

Asymmetric Cu-N-La Species Enabling Atomic-Level Donor-Acceptor Structure and Favored Reaction Thermodynamics for Selective CO2 Photoreduction to CH4.

Photocatalytic CO2 reduction into ideal hydrocarbon fuels, such as CH4 , is a sluggish kinetic process involving adsorption of multiple intermediates and multi-electron steps. Achieving high CH4 activity and selectivity therefore remains a great challenge, which largely depends on the efficiency of photogenerated charge separation and transfer as well as the intermediate energy levels in CO2 reduction. Herein, we construct La and Cu dual-atom anchored carbon nitride (LaCu/CN), with La-N4 and Cu-N3 coordination bonds connected by Cu-N-La bridges. The asymmetric Cu-N-La species enables the establishment of an atomic-level donor-acceptor structure, which allows the migration of electrons from La atoms to the reactive Cu atom sites. Simultaneously, intermediates during CO2 reduction on LaCu/CN demonstrate thermodynamically more favorable process for CH4 formation based on theoretical calculations. Eventually, LaCu/CN exhibits a high selectivity (91.6 %) for CH4 formation with a yield of 125.8 µmol g-1 , over ten times of that for pristine CN. This work presents a strategy for designing multi-functional dual-atom based photocatalysts.

P-Mediated Cu-N4 Sites in Carbon Nitride Realizing CO2 Photoreduction to C2 H4 with Selectivity Modulation.

Photocatalytic CO2 reduction to high value-added C2 products (e.g., C2 H4 ) is of considerable interest but challenging. The C2 H4 product selectivity strongly hinges on the intermediate energy levels in the CO2 reduction pathway. Herein, Cu-N4 sites anchored phosphorus-modulated carbon nitride (CuACs/PCN) is designed as a photocatalyst to tailor the intermediate energy levels in the the C2 H4 formation reaction pathway for realizing its high production with tunable selectivity. Theoretical calculations combined with experimental data demonstrate that the formation of the C-C coupling intermediates can be realized on Cu-N4 sites and the surrounding doped P facilitates the production of C2 H4 . Thus, CuACs/PCN exhibits a high C2 H4 selectivity of 53.2% with a yielding rate of 30.51 µmol g-1 . The findings reveal the significant role of the coordination environment and surrounding microenvironment of Cu single atoms in C2 H4 formation and offer an effective approach for highly selective CO2 photoreduction to produce C2 H4 .

Correlation between residual cholesterol and carotid intima-media thickness in non-diabetic population / 国际脑血管病杂志

Objective:To investigate the correlation between residual cholesterol (RC) and carotid intima-media thickness (cIMT) in non-diabetic population.Methods:Non-diabetes population received health examination in Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School from January 1, 2018 to December 31, 2021 were retrospectively included. According to the carotid ultrasound results, they were divided into cIMT thickening group (≥1 mm) and non-thickening group (<1 mm). The RC level was calculated according to total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). Multivariate logistic regression analysis was used to determine the correlation between RC and cIMT. Results:A total of 1 803 non-diabetes subjects, aged 58.3±15.6 years, including 1 100 males (61.0%), were enrolled. There were 916 patients (50.8%) in the cIMT thickening group and 887 (49.2%) in the non-cIMT thickening group. Compared with the non-cIMT thickening group, cIMT thickening group had significantly higher proportion of male, hypertension, hyperlipidemia, atrial fibrillation, past stroke history, smoking and alcohol consumption, as well as significantly higher age, blood glucose, triglyceride, RC, TC and LDL-C, and significantly lower HDL-C (all P<0.01). Multivariate logistic regression analysis showed that RC was independently associated with cIMT thickening ( Ptrend<0.001). Conclusion:RC is associated with cIMT thickening in non-diabetes population.

Novel quinoline-based derivatives as the PqsR inhibitor against Pseudomonas aeruginosa PAO1.

AIMS: The emerging of drug resistant Pseudomonas aeruginosa is a critical challenge and renders an urgent action to discover innovative antimicrobial interventions. One of these interventions is to disrupt the pseudomonas quinolone signal (pqs) quorum sensing (QS) system, which governs multiple virulence traits and biofilm formation. This study aimed to investigate the QS inhibitory activity of a series of new PqsR inhibitors bearing a quinoline scaffold against Ps. aeruginosa. METHODS AND RESULTS: The results showed that compound 1 suppressed the expression of QS-related genes and showed the best inhibitory activity to the pqs system of wild-type Ps. aeruginosa PAO1 with an IC50 of 20.22 µmol L-1 . The virulence factors including pyocyanin, total protease, elastase and rhamnolipid were significantly suppressed in a concentration-dependent manner with the compound. In addition, compound 1 in combination with tetracycline inhibited synergistically the bacterial growth and suppressed the biofilm formation of PAO1. The molecular docking studies also suggested that compound 1 could potentially interact with the ligand-binding domain of the Lys-R type transcriptional regulator PqsR as a competitive antagonist. CONCLUSIONS: The quinoline-based derivatives were found to interrupt the quorum sensing system via the pqs pathway and thus the production of virulence factors was inhibited and the antimicrobial susceptibility of Ps. aeruginosa was enhanced. SIGNIFICANCE AND IMPACT OF STUDY: The study showed that the quinoline-based derivatives could be used as an anti-virulence agent for treating Ps. aeruginosa infections.

Design and synthesis of quinolinium-based derivatives targeting FtsZ for antibacterial evaluation and mechanistic study.

The discovery of small molecular inhibitors targeting essential and conserved bacterial drug targets such as FtsZ protein is a promising approach to fight against multi-drug resistant bacteria. In the present study, two new series of FtsZ inhibitors based on a 1-methylquinolinium scaffold were synthesized. The inhibitors possess a variety of substituent groups including the cyclic or linear amine skeleton at the 2- and 4-position of the quinolinium ring for structure-activity relationship study. In general, the inhibitors bearing a cyclic amine substituent at the 4-position of the quinolinium ring showed better antibacterial activity (MIC down to 0.25 µg/mL) than that at the 2-position, especially against Gram-positive bacteria. Among the twenty FtsZ inhibitors examined in various assays, A3 was identified to exhibit excellent antibacterial activity against S. aureus (MIC = 0.5-1 µg/mL), S. epidermidis (MIC = 0.25 µg/mL) and E. faecium (MIC = 1-8 µg/mL). More importantly, A3 showed low hemolytic toxicity (IC5 = 64 µg/mL) and was found not readily to induce drug resistance. A3 at 2-8 µg/mL promoted the polymerization of FtsZ and interrupted the bacterial division. Furthermore, the ligand-FtsZ interaction study conducted with circular dichroism and molecular docking revealed that A3 induced secondary structure changes of FtsZ protein upon binding to the interdomain cleft of the protein. A3 is thus a potent inhibitor of FtsZ and shows potential to be used as a new antibacterial agent against drug-resistant bacteria.

Rational design of small-molecules to recognize G-quadruplexes of c-MYC promoter and telomere and the evaluation of their in vivo antitumor activity against breast cancer.

DNA G4-structures from human c-MYC promoter and telomere are considered as important drug targets; however, the developing of small-molecule-based fluorescent binding ligands that are highly selective in targeting these G4-structures over other types of nucleic acids is challenging. We herein report a new approach of designing small molecules based on a non-selective thiazole orange scaffold to provide two-directional and multi-site interactions with flanking residues and loops of the G4-motif for better selectivity. The ligands are designed to establish multi-site interactions in the G4-binding pocket. This structural feature may render the molecules higher selectivity toward c-MYC G4s than other structures. The ligand-G4 interaction studied with 1H NMR may suggest a stacking interaction with the terminal G-tetrad. Moreover, the intracellular co-localization study with BG4 and cellular competition experiments with BRACO-19 may suggest that the binding targets of the ligands in cells are most probably G4-structures. Furthermore, the ligands that either preferentially bind to c-MYC promoter or telomeric G4s are able to downregulate markedly the c-MYC and hTERT gene expression in MCF-7 cells, and induce senescence and DNA damage to cancer cells. The in vivo antitumor activity of the ligands in MCF-7 tumor-bearing mice is also demonstrated.

Vaccine Protection Against the SARS-CoV-2 Omicron Variant in Macaques

BackgroundThe rapid spread of the SARS-CoV-2 Omicron (B.1.1.529) variant, including in highly vaccinated populations, has raised important questions about the efficacy of current vaccines. Immune correlates of vaccine protection against Omicron are not known. Methods30 cynomolgus macaques were immunized with homologous and heterologous prime-boost regimens with the mRNA-based BNT162b2 vaccine and the adenovirus vector-based Ad26.COV2.S vaccine. Following vaccination, animals were challenged with the SARS-CoV-2 Omicron variant by the intranasal and intratracheal routes. ResultsOmicron neutralizing antibodies were observed following the boost immunization and were higher in animals that received BNT162b2, whereas Omicron CD8+ T cell responses were higher in animals that received Ad26.COV2.S. Following Omicron challenge, sham controls showed more prolonged virus in nasal swabs than in bronchoalveolar lavage. Vaccinated macaques demonstrated rapid control of virus in bronchoalveolar lavage, and most vaccinated animals also controlled virus in nasal swabs, showing that current vaccines provide substantial protection against Omicron in this model. However, vaccinated animals that had moderate levels of Omicron neutralizing antibodies but negligible Omicron CD8+ T cell responses failed to control virus in the upper respiratory tract. Virologic control correlated with both antibody and T cell responses. ConclusionsBNT162b2 and Ad26.COV2.S provided robust protection against high-dose challenge with the SARS-CoV-2 Omicron variant in macaques. Protection against this highly mutated SARS-CoV-2 variant correlated with both humoral and cellular immune responses.

LUBAC regulates ciliogenesis by promoting CP110 removal from the mother centriole.

Primary cilia transduce diverse signals in embryonic development and adult tissues. Defective ciliogenesis results in a series of human disorders collectively known as ciliopathies. The CP110-CEP97 complex removal from the mother centriole is an early critical step for ciliogenesis, but the underlying mechanism for this step remains largely obscure. Here, we reveal that the linear ubiquitin chain assembly complex (LUBAC) plays an essential role in ciliogenesis by targeting the CP110-CEP97 complex. LUBAC specifically generates linear ubiquitin chains on CP110, which is required for CP110 removal from the mother centriole in ciliogenesis. We further identify that a pre-mRNA splicing factor, PRPF8, at the distal end of the mother centriole acts as the receptor of the linear ubiquitin chains to facilitate CP110 removal at the initial stage of ciliogenesis. Thus, our study reveals a direct mechanism of regulating CP110 removal in ciliogenesis and implicates the E3 ligase LUBAC as a potential therapy target of cilia-associated diseases, including ciliopathies and cancers.

Fucoidan-functionalized activated platelet-hitchhiking micelles simultaneously track tumor cells and remodel the immunosuppressive microenvironment for efficient metastatic cancer treatment

Tumor metastasis is responsible for most mortality in cancer patients, and remains a challenge in clinical cancer treatment. Platelets can be recruited and activated by tumor cells, then adhere to circulating tumor cells (CTCs) and assist tumor cells extravasate in distant organs. Therefore, nanoparticles specially hitchhiking on activated platelets are considered to have excellent targeting ability for primary tumor, CTCs and metastasis in distant organs. However, the activated tumor-homing platelets will release transforming growth factor-β (TGF-β), which promotes tumor metastasis and forms immunosuppressive microenvironment. Therefore, a multitalent strategy is needed to balance the accurate tumor tracking and alleviate the immunosuppressive signals. In this study, a fucoidan-functionalized micelle (FD/DOX) was constructed, which could efficiently adhere to activated platelets through P-selectin. Compared with the micelle without P-selectin targeting effect, FD/DOX had increased distribution in both tumor tissue and metastasis niche, and exhibited excellent anti-tumor and anti-metastasis efficacy on 4T1 spontaneous metastasis model. In addition, due to the contribution of fucoidan, FD/DOX treatment was confirmed to inhibit the expression of TGF-β, thereby stimulating anti-tumor immune response and reversing the immunosuppressive microenvironment. The fucoidan-functionalized activated platelets-hitchhiking micelle was promising for the metastatic cancer treatment.

Current status and prospect of virtual reality technique's application in wound repair / 中华烧伤杂志

As a new technology of drug-free treatment, virtual reality technique has been used in various medical fields, and is being increasingly applied in the field of wound repair. Virtual reality technology can alleviate the pain caused by acute and chronic wounds, relieve the psychological anxiety of patients with wounds, and then facilitate the recovery of patients. This paper reviews the research progress of virtual reality technique's application as a clinical adjuvant therapy in wound repair in three aspects: pain treatment, psychological treatment, and functional rehabilitation, analyzes the advantages and disadvantages of this technique, and discusses the prospects of its further application in the field of wound repair.

Predictors of intracranial hemorrhage in patients with cerebral venous sinus thrombosis / 国际脑血管病杂志

Objective:To investigate the predictors of intracranial hemorrhage in patients with cerebral venous sinus thrombosis (CVST).Methods:Patients with CVST treated in Drum Tower Hospital Affiliated to Medical School of Nanjing University from January 2008 to March 2021 were retrospectively enrolled. The risk factors, clinical manifestations, imaging examination and 90 d follow-up data were collected. The complicated intracranial hemorrhage group and non-intracranial hemorrhage group were compared. Multivariate logistic regression analysis was used to determine the independent predictors of intracranial hemorrhage in patients with CVST. Results:A total of 104 patients with CVST were enrolled, including 42 males and 62 females. Their age was 35.24 ± 10.92 years old (range 22-68 years). Thirty-eight patients (36.84%) were complicated with intracranial hemorrhage, including 34 hemorrhagic cerebral infarction and 4 complicated subarachnoid hemorrhage. Univariate analysis showed that compared with the non-intracerebral hemorrhage group, the intracranial hemorrhage group was more common in puerperal/pregnant patients (60.52% vs. 48.48%; P=0.012), with more acute onset (57.89% vs. 48.48%; P=0.004), focal neurological signs (47.37% vs. 19.70%; P=0.003) and seizure (39.47% vs. 18.18%; P=0.017), and the site of thrombosis was more common in the superior sagittal sinus (57.89% vs. 36.36%; P=0.033). Multivariate logistic regression analysis showed that puerperium/pregnancy (odds ratio 2.857, 95% confidence interval 1.095-7.453; P=0.031) and superior sagittal sinus thrombosis (odds ratio 2.847, 95% confidence interval 1.110-7.302; P=0.027) were the independent predictors of intracranial hemorrhage in patients with CVST. The analysis at 90 d after onset showed that there was no significant difference in the good outcome rate between the intracranial hemorrhage group and the non-intracranial hemorrhage group (86.84% vs. 89.39%; P=0.695). Conclusions:Puerperium/pregnancy and superior sagittalsinus thrombosis are the independent risk factors for intracranial hemorrhage in patients with CVST. However, complicated with intracranial hemorrhage is not associated with 90-day clinical outcomes.

Ad26.COV2.S or BNT162b2 Boosting of BNT162b2 Vaccinated Individuals

The rapid spread of the highly mutated SARS-CoV-2 Omicron variant has raised substantial concerns about the protective efficacy of currently available vaccines. We assessed Omicron-specific humoral and cellular immune responses in 65 individuals who were vaccinated with two immunizations of BNT162b2 and were boosted after at least 6 months with either Ad26.COV2.S (Johnson & Johnson; N=41) or BNT162b2 (Pfizer; N=24) (Table S1). O_TBL View this table: org.highwire.dtl.DTLVardef@41c8baorg.highwire.dtl.DTLVardef@e14f5forg.highwire.dtl.DTLVardef@21ea87org.highwire.dtl.DTLVardef@ac4522org.highwire.dtl.DTLVardef@1eed52b_HPS_FORMAT_FIGEXP M_TBL O_FLOATNOTable S1.C_FLOATNO O_TABLECAPTIONCharacteristics of the study population C_TABLECAPTION C_TBL

Two-dimensional porphyrin covalent organic frameworks with tunable catalytic active sites for the oxygen reduction reaction.

Four novel two-dimensional porphyrin COFs (M-TP-COF, M = H2, Co, Ni and Mn) with donor-acceptor dyads were fabricated and served as electrocatalysts for the oxygen reduction reaction (ORR). The ORR catalytic activity of M-TP-COF was tuned by changing the M atom in the center of the porphyrin backbone. The experimental structure-function relationship was in accordance with the results of density functional theory calculations based on the O2-O2*-OOH*-O*-OH*-OH- route.

Chylothorax following posterior low lumbar fusion surgery: A case report.

BACKGROUND: Postoperative chylothorax is usually regarded as a complication associated with cardiothoracic surgery; however, it is one of the rare complications in orthopedic surgery. This case report describes a female patient who developed chylothorax after a successful L4-S1 transforaminal lumbar interbody fusion surgery. The etiology, diagnosis, and treatment were analyzed and discussed. CASE SUMMARY: A 50-year-old woman was admitted with repeated back and leg pain. She was diagnosed with L4 degenerative spondylolisthesis, L4/L5 and L5/S1 intervertebral disc herniation and L5 instability, and underwent successful posterior L4-S1 instrumentation and fusion surgery. Unfortunately, thoracic effusion was identified 2 d after operation. The thoracic effusion was finally confirmed to be chylous based on twice positive chyle qualitative tests. The patient was discharged after 12-d persisting drainage, 3-d total parenteral nutrition and fasting, and other supportive treatments. No recurring symptoms were observed within 12 mo follow-up. CONCLUSION: Differential diagnosis is crucial for unusual thoracic effusion. Comprehensive diagnosis and treatment of chylothorax are necessary. Thorough intraoperative protection to relieve high thoracic pressure caused by the prone position is important.

Optimization of Non-Coding Regions Improves Protective Efficacy of an mRNA SARS-CoV-2 Vaccine in Nonhuman Primates

The CVnCoV (CureVac) mRNA vaccine for SARS-CoV-2 has recently been evaluated in a phase 2b/3 efficacy trial in humans. CV2CoV is a second-generation mRNA vaccine with optimized non-coding regions and enhanced antigen expression. Here we report a head-to-head study of the immunogenicity and protective efficacy of CVnCoV and CV2CoV in nonhuman primates. We immunized 18 cynomolgus macaques with two doses of 12 ug of lipid nanoparticle formulated CVnCoV, CV2CoV, or sham (N=6/group). CV2CoV induced substantially higher binding and neutralizing antibodies, memory B cell responses, and T cell responses as compared with CVnCoV. CV2CoV also induced more potent neutralizing antibody responses against SARS-CoV-2 variants, including B.1.351 (beta), B.1.617.2 (delta), and C.37 (lambda). While CVnCoV provided partial protection against SARS-CoV-2 challenge, CV2CoV afforded robust protection with markedly lower viral loads in the upper and lower respiratory tract. Antibody responses correlated with protective efficacy. These data demonstrate that optimization of non-coding regions can greatly improve the immunogenicity and protective efficacy of an mRNA SARS-CoV-2 vaccine in nonhuman primates.

A Minimally Invasive Exosome Spray Repairs Heart after Myocardial Infarction.

Myocardial infarction (MI) remains the most common cause of death worldwide. Many MI survivors will suffer from recurrent heart failure (HF), which has been recognized as a determinant of adverse prognosis. Despite the success of improved early survival after MI by primary percutaneous coronary intervention, HF after MI is becoming the major driver of late morbidity, mortality, and healthcare costs. The development of regenerative medicine has brought hope to MI treatment in the past decade. Mesenchymal stem cell (MSC)-derived exosomes have been established as an essential part of stem cell paracrine factors for heart regeneration. However, its regenerative power is hampered by low delivery efficiency to the heart. We designed, fabricated, and tested a minimally invasive exosome spray (EXOS) based on MSC exosomes and biomaterials. In a mouse model of acute myocardial infarction, EXOS improved cardiac function and reduced fibrosis, and promoted endogenous angiomyogenesis in the post-injury heart. We further tested the feasibility and safety of EXOS in a pig model. Our results indicate that EXOS is a promising strategy to deliver therapeutic exosomes for heart repair.

Fabrication of a robust MOF/aerogel composite via a covalent post-assembly method.

A covalent post-assembly strategy is developed to prepare a composite of dispersive MOF particles in an aerogel matrix. Briefly, the anhydride group-decorated MOF (UiO-66-NH2) particles covalently coupled with polyimide (PI) monomers through a one-pot amidation polymerization reaction, succeeding a process of gel-sol, freeze-drying and thermal-imidization to obtain the UiO-66-PI aerogel. The designed composite shows outstanding catalytic activity in CO2 cycloaddition and excellent adsorption capacity for dyes.

Safety and Efficacy of Vitamin K Antagonists vs. Novel Oral Anticoagulants in Patients With Left Ventricular Thrombus: A Meta-Analysis.

Aims: A meta-analysis was conducted to evaluate the safety and efficacy of novel oral anticoagulants (NOACs) compared with vitamin K antagonists (VKAs) in patients with left ventricular thrombus (LVT). Methods and Results: We searched PubMed, Web of Science, and Cochrane Library for cohort studies comparing the use of VKAs vs. NOACs for the treatment of LVT from the earliest date available to September 30, 2020. The predetermined efficacy and safety outcomes included thromboembolic events, resolution of LVT, clinically significant bleedings, and all-cause death. Fixed-effects model was used to estimate the pooled effects. Publication bias analyses and sensitivity analyses were conducted to check the robustness of results. A total of 6 studies enrolling 837 patients (mean age 60.2 ± 1.6 years; 77.2% were male) were included. We found no significant differences in thromboembolic events [relative risk (RR) 1.69, 95% confidence interval (CI) 0.94-3.06, P 0.08, I2 12.7%], the rate of resolution of thrombus (RR 1.08, 95% CI 0.96-1.21, P 0.21, I2 4.8%), and clinically significant bleedings (RR 0.70, 95% CI 0.37-1.32, P 0.27, I2 0%) between the VKAs and NOACs group. Additionally, no significant difference in all-cause mortality was found between the two groups (RR 1.24, 95% CI 0.79-1.96, P 0.35, I2 0.0%). Sensitivity analyses, using the "1-study removed" method, detected no significant differences. Conclusion: NOACs and VKAs have similar efficacy and safety in treating LVT, prompting the inference that NOACs are the possible alternatives of VKAs in LVT therapy.