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Abstract Background Deep venous thrombosis (DVT) after spinal surgery has recently attracted increasing attention. Patients with spinal metastases who undergo decompression with fixation are at a high risk of developing DVT. D-dimer levels indicate the risk of DVT, and the purpose of our study was to investigate D-dimer levels as a predictor of DVT perioperatively. Methods We prospectively evaluated 100 patients with spinal metastases. D-dimer tests were performed twice: once before surgery and one day postoperatively. DVT was diagnosed by duplex ultrasonographic assessment of both lower extremities. Pulmonary embolisms (PEs) were diagnosed using multidetector computed tomography and pulmonary angiography. Perioperative serum D-dimer levels were compared between the DVT (+) and DVT (-) groups. The cutoff value of the D-dimer level was calculated using receiver operating characteristic analysis. Results Preoperative and postoperative DVT prevalences were 8.0% (8/100) and 6.6% (6/91), respectively, and none of the patients developed PE. Before surgery, there was no significant differences in D-dimer levels between the pre-DVT (+) and pre-DVT (-) groups. After surgery, the D-dimer level one-day postoperatively for the post-DVT (+) group (17.6 ± 11.8 mg/L) was significantly higher than that of the post-DVT (-) group (5.0 ± 4.7 mg/L). The cutoff value of the postoperative D-dimer level was 9.51(mg/L), and the sensitivity and specificity for the optimum threshold were 83.3% and 89.4%, respectively. Conclusions Our findings suggest that preoperative D-dimer level may not be a predictor of DVT. Preoperative ultrasound examinations should be routinely performed in patients with spinal metastases. Postoperative D-dimer levels greater than 9.51(mg/L) are a predictive factor for the early diagnosis of DVT after spine surgery. Trial registration Our study was registered on Chinese Clinical Trial Registry (No.ChiCTR2000029737). Registered 11 February 2020 - Retrospectively registered, https://www.chictr.org.cn/index.aspx.

Objective To explore the feasibility, safety and efficacy of modified pharmacomechanical endovascular thrombolysis for chronic thrombosis of arteriovenous graft (AVG). Methods Between January 1, 2020 and December 31, 2022, retrospective analysis was performed for 81 patients on endovascular treatment for AVG thrombosis for more than 3 days. Based upon the duration of thrombosis formation, they were assigned into two groups of 3-7 d (n=66) and >7 d (n=15). Demographic profiles, fistula characteristics, thrombotic features, success rate of intracavitary treatment, incidence of complications and patency rate after pathway intervention were compared. Results Average thrombotic time was 4(3, 5) day in 3-7 d group and 14(10, 23) day in >7 d group. The success rate of intracavitary treatment was 98.77%(80/81) in both groups and clinical success rate 98.77%(80/81) without any serious complication. Technical success rate was 98.48%(65/66) in 3-7 d group and 100%(15/15) in >7 d group. Clinical success rate was 98.48%(65/66) in 3-7 d group and 100%(15/15) in >7 d group. There was no statistically significant inter-group difference. After a total follow-up period of 1 year, primary patency rates at Day 30/90/180/270/360 post-intervention were 89.39%(59/66), 69.70%(46/66), 50.00%(22/66), 33.33%(22/66) and 21.21%(12/66) in 3-7 d group and 86.67% (13/15), 80.00%(12/15), 46.67%(7/15), 26.67%(4/15) and 20.00%(3/15) in >7 d group. Both groups maintained decent 1-year cumulative patency rates. It was 78.79% in 3-7 d group and 80.00% in >7 d group. There was no significant inter-group statistical difference. Conclusions Modified pharmacomechanical endovascular thrombolysis is feasible, effective and safe for chronic AVG thrombosis. Capable of prolonging usage time of AVG, it is worthy of wider clinical promotions.

Abstract Background Endovascular thrombectomy (EVT) is a standard treatment for acute ischemic stroke (AIS) with large vessel occlusion. Hypertension and increased blood pressure variability within the first 24 h after successful reperfusion are related to a higher risk of symptomatic intracerebral hemorrhage and higher mortality. AIS patients might suffer from ischemia-reperfusion injury following reperfusion, especially within 24 h. Dexmedetomidine (DEX), a sedative commonly used in EVT, can stabilize hemodynamics by inhibiting the sympathetic nervous system and alleviate ischemia-reperfusion injury through anti-inflammatory and antioxidative properties. Postoperative prolonged sedation for 24 h with DEX might be a potential pharmacological approach to improve long-term prognosis after EVT. Methods This single-center, open-label, prospective, randomized controlled trial will include 368 patients. The ethics committee has approved the protocol. After successful reperfusion (modified thrombolysis in cerebral infarction scores 2b–3, indicating reperfusion of at least 50% of the affected vascular territory), participants are randomly assigned to the intervention or control group. In the intervention group, participants will receive 0.1~1.0 μg/kg/h DEX for 24 h. In the control group, participants will receive an equal dose of saline for 24 h. The primary outcome is the functional outcome at 90 days, measured with the categorical scale of the modified Rankin Scale, ranging from 0 (no symptoms) to 6 (death). The secondary outcome includes (1) the changes in stroke severity between admission and 24 h and 7 days after EVT, measured by the National Institute of Health Stroke Scale (ranging from 0 to 42, with higher scores indicating greater severity); (2) the changes in ischemic penumbra volume/infarct volume between admission and 7 days after EVT, measured by neuroimaging scan; (3) the length of ICU/hospital stay; and (4) adverse events and the all-cause mortality rate at 90 days. Discussion This randomized clinical trial is expected to verify the hypothesis that postoperative prolonged sedation with DEX after successful reperfusion may promote the long-term prognosis of patients with AIS and may reduce the related socio-economic burden. Trial registration ClinicalTrials.gov NCT04916197. Prospectively registered on 7 June 2021.

Objective To explore the influencing factors of restenosis after percutaneous transluminal angioplasty in hemodialysis （HD） patients and provide a basis for predicting the risk of dysfunction and prolonging the service time. Methods Retrospective analysis was performed on the clinical and follow-up data of 335 patients who underwent percutaneous transluminal angioplasty（PTA） in Haidian District, The Third Hospital of Peking University （Haidian Hospital） from January 1 2020 to January 1 2021 as study. Results There were 187 males （55.8%） and 148 females （44.2%）. Kaplan-Meier survival analysis indicated that primary patency rates were 77.31% and 50.15% at Month 6/12 post-PTA. At Month 12 post-PTA, the risk of restenosis was significantly higher in AVG patients than that of AVF （Log-rank χ2 = 719.522, P＜0.001）. The risk of restenosis in patients with old lesions was significantly higher than that of those with new lesions （Log-rank χ2 = 23.106, P＜0.001）. The risk of restenosis in patients with local anesthesia was significantly higher than that of those with brachial plexus anesthesia （Log-rank χ2＝27.415, P＜0.001）. Multivariate Cox proportional risk regression analysis at Month 6 revealed that old/new lesions （HR = 0.393, 95%CI: 0.237-0.650, P＜0.001）, type/mode of anesthesia （HR = 3.223, 95%CI: 1.956-5.311, P＜0.001） and platelet count （HR = 1.005, 95%CI: 1.001-1.008, P = 0.008） were independent risk factors for restenosis post-PTA. Multivariate Cox proportional risk regression analysis at Month 12 indicated that type of fistula AVG （HR = 0.550, 95%CI: 0.387-0.782, P = 0.001）, old/new lesions （HR = 0.587, 95%CI: 0.422-0.815, P = 0.002） and type/mode of anesthesia （HR = 2.359, 95%CI: 1.686-3.302, P＜0.001） were independent risk factors for restenosis post-PTA. Conclusion Multiple factors may affect restenosis post-PTA in HD patients. And type/mode of anesthesia, old/new lesions and type of fistula are independent risk factors for restenosis post-PTA. Preoperative examinations and postoperative comprehensive follow-ups may prevent fistula dysfunction and help to formulate accurate surgical plans and conduct timely postoperative follow-ups.

Objective: A model that considers the characteristics of dialysis patients may help predict successful fistula maturation. We evaluated factors associated with radiocephalic arteriovenous fistula (RCAVF) maturation at 3 months in dialysis patients with end-stage renal disease (ESRD). Methods: A total of 184 patients who received an initial RCAVF at Beijing Haidian Hospital (Haidian Section of Peking University Third Hospital) were recruited. Fistula maturation was assessed within 3 months. Patient characteristics and preoperative vascular assessment indices were examined. Factors associated with fistula maturation were analyzed using logistic regression and least absolute shrinkage and selection operator (LASSO) binary logistic regression. Boostrapping was used for internal validation. Results: The development data consisted of 184 ESRD patients receiving an initial RCAVF, 140 (76%) of whom achieved fistula maturation. The main predictors of RCAVF maturation in the final model were sex, age-adjusted vein dilation (eVD), radial artery volume (Vartery), and diastolic blood pressure. The difference of vein diameter with and without a tourniquet was significantly larger in the mature RCAVF group (3.0 ± 0.5 vs. 2.2 ± 0.5 mm). The area under receiver operating characteristic (AUROC) curve for prediction of fistula maturation was 0.77, and the Hosmer-Lemeshow statistic indicated agreement between observed and predicted values (P = 0.792). Analysis of internal validation using bootstrapping indicated the C-index was 0.75. Conclusion: The ratio of vein dilation and age were the major predictors of fistula maturation at 3 months in our patients. The resulting online prediction model may help in clinical decision-making for patients receiving a RCAVF.

Summary: Background: The mRNA vaccine has demonstrated significant effectiveness in protecting against SARS-CoV-2 during the pandemic, including against severe forms of the disease caused by emerging variants. In this study, we examined safety, immunogenicity, and relative efficacy of a heterologous booster of the lipopolyplex (LPP)-based mRNA vaccine (SW-BIC-213) versus a homologous booster of an inactivated vaccine (BBIBP) in Laos. Methods: In this phase 3 clinical trial, which was randomized, parallel controlled and double-blinded, healthy adults aged 18 years and above were recruited from the Southern Savannakhet Provincial Hospital and Champhone District Hospital. The primary outcomes were safety and immunogenicity, with efficacy as an exploratory endpoint. Participants who were fully immunized with a two-dose inactivated vaccine for more than 6 months were assigned equally to either the SW-BIC-213 group (25 μg) or BBIBP group. The primary safety endpoint was to describe the safety profile of all participants in each group up to 6 months post-booster immunization. The primary immunogenic outcome was to demonstrate the superiority of the neutralizing antibody response, in terms of geometric mean titers (GMTs) of SW-BIC-213, compared with BBIBP 28 days after the booster dose. The exploratory efficacy endpoint aimed to assess the relative efficacy of SW-BIC-213 compared to BBIBP against virologically confirmed symptomatic COVID-19 over a 6-month period. The trial was registered with ClinicalTrials.gov (NCT05580159). Findings: Between October 10, 2022, and January 13, 2023, 1200 participants were assigned to SW-BIC-213 group and 1203 participants in the BBIBP group. All adverse reactions observed during the study were tolerable, transient, and resolved spontaneously. Solicited local reactions were the main adverse reactions in both the SW-BIC-213 group (43.8%) and BBIBP group (14.8%) (p

This study attempted to monitor the development of microbial communities and reveal the correlation between the soil microbial community and soil nutrient factors over different years following the replanting of peach trees. The replanted soil (RS) and nonreplanted soil (NRS) were collected from peach orchards with different growth years (1, 3, 5, 7, 9, 11, and 13 years) in the same region. The soil bacterial and fungal community diversities were analyzed by high-throughput sequencing technology. Redundancy analysis (RDA) was used to show the correlation between the soil microbial community and environmental variables. The alpha diversities of the bacterial and fungal communities indicated that RS contained a higher abundance of bacterial and fungal operational taxonomic units (OTUs) than NRS. NMDS and ANOSIM analyses showed that the soil bacterial and fungal communities were significantly (P3.0). In addition, the soil nutrient contents were lower in RS than in NRS in the early stage (1–5 years), and the RDA showed that bacterial and fungal phyla are closely associated with environmental variables, including the potential of hydrogen (pH), ammonium nitrogen (AN), available phosphorus (AP) and available potassium (AK). These results lead to a deeper understanding of the microbial responses to replanting in peach orchards.

Abstract The ankle‐link complex (ALC) consists of USH2A, WHRN, PDZD7, and ADGRV1 and plays an important role in hair cell development. At present, its architectural organization and signaling role remain unclear. By establishing Adgrv1 Y6236fsX1 mutant mice as a model of the deafness‐associated human Y6244fsX1 mutation, the authors show here that the Y6236fsX1 mutation disrupts the interaction between adhesion G protein‐coupled receptor V subfamily member 1 (ADGRV1) and other ALC components, resulting in stereocilia disorganization and mechanoelectrical transduction (MET) deficits. Importantly, ADGRV1 inhibits WHRN phosphorylation through regional cAMP‐PKA signaling, which in turn regulates the ubiquitination and stability of USH2A via local signaling compartmentalization, whereas ADGRV1 Y6236fsX1 does not. Yeast two‐hybrid screening identified the E3 ligase WDSUB1 that binds to WHRN and regulates the ubiquitination of USH2A in a WHRN phosphorylation‐dependent manner. Further FlAsH‐BRET assay, NMR spectrometry, and mutagenesis analysis provided insights into the architectural organization of ALC and interaction motifs at single‐residue resolution. In conclusion, the present data suggest that ALC organization and accompanying local signal transduction play important roles in regulating the stability of the ALC.

Abstract Background In strawberry cultivation, continuous cropping (CC) obstacles seriously threaten production. A patented soil amendment (SA) can effectively relieve the CC obstacles to strawberry cultivation, but knowledge of the recovery mechanisms underlying this phenomenon is limited. Results In this study, transcriptomic profiling of strawberry roots in soil with and without the SA was conducted using RNA-Seq technology to reveal gene expression changes in response to SA treatment. In total, 188 differentially expressed genes (DEGs), including 144 upregulated and 44 downregulated DEGs, were identified. SA treatment resulted in genotype-dependent responses, and the response pattern, including an overall increase in the expression of nutrient transport genes and a decrease in the expression of defense response genes, may be a possible mechanism underlying recovery strategies in strawberry roots after the application of the SA to CC soil. We also found that 9 Hsp genes involved in plant defense pathways were all downregulated in the SA-treated roots. Conclusions This research indicated that strawberry plants reallocated defense resources to development when SA treatment alleviated the stress caused by a CC soil environment. The present study provides an opportunity to reveal the fundamental mechanisms of the tradeoff between growth and defense in strawberry.

In this study, isoliquiritigenin (ISL) incorporated nanoliposomes were prepared and their effects on colorectal cancer (CRC) cell lines were investigated. Herein, we sought to explore the anti-cancer mechanisms of ISL loaded nanoliposomes (ISL-NLs) on AMP-activated protein kinase/mammalian target of rapamycin (AMPK/mTOR) pathways mediated glycolysis. Also, the key targets such as caveolin 1 (CAV1), glucose transporters and Akt/mTOR that promote glycolysis, and are activated via the induction of α-enolase (ENO1), fructose bisphosphate aldolase A (ALDOA) and monocarboxylate transporter 4 (MCT4) expressions were also investigated. It was shown that ISL-NLs significantly suppressed the proliferation and glucose uptake of CRC cell by potentially regulating the glycolysis and lactate targets as well as pathways that formed the basis of the anti-CRC effects of ISL-NLs. The mechanism underlying this effect was further validated via the regulation of some key targets such as ENO1, ALDOA, lactate dehydrogenase A (LDHA) and MCT4 in glycolysis coupled with cellular myelocytomatosis oncogene (c-myc), hypoxia-inducible factor 1-alpha (HIF-1α) in protein kinase B/mTOR (Akt/mTOR) pathways. Moreover, the AMPK proteins were identified to be up-regulated while the lactic acid production was suppressed by ISL-NLs in the CRC cells, indicating that ISL-NLs had an inhibitory effect on AMPK mediated glycolysis and lactate production. Altogether, these results have provided insights into the mechanism underlying the key role that liposomal ISL played in the multiple inhibition of AMPK and Akt/mTOR mediated glycolysis and lactate generation, which may be regulated as the alternative metabolic pathways of CRC as well as serve as adjuvant therapy for the disease.

Rhus chinensis Mill. is a traditional Chinese medicine (TCM) which is commonly used for cancer treatments. Our previous work had proven that triterpenoids of Rhus chinensis (TER) could effectively regulate glycolysis involved in colorectal cancer (CRC) and play an important role in the prevention of T-cells dysfunction. This study aimed to systematically investigate the effects and mechanisms of TER on glucose metabolism in CRC, while the regulatory mechanisms of TER on restoring T-cells function and activity in CRC were explored as well. The extract of triterpenoids from Rhus chinensis was obtained, and production of lactic acid and glucose uptake were assayed. Also, the expression of CD8+ T-cells surface markers, cytokines secreted by CD8+ T cells, and the expression of key glycolytic enzymes and glucose deprivation induced by tumor cells were further examined. Notably, results showed that TER prevented the dysfunction in CD8+ T cells by enhancing mTOR activity and subsequent cellular metabolism. Furthermore, our findings also demonstrated that TER promoted glycolytic gene expression in CD8+ T cells in vivo, and significantly inhibited tumor growth. Altogether, our studies suggested that TER not only reversed effector CD8+ T-cells dysfunction and enhanced T-cells recognition, but also improved tumor microenvironment, thereby providing new insight into the prevention and treatment of CRC with TCM.

In this article, we investigate the initial-value problem for the sixth-order Boussinesq equation with fourth order dispersion term. Existence of a a global solution and asymptotic behavior in Morrey spaces are established under suitable conditions. The proof is mainly based on the decay properties of the solutions operator in Morrey spaces and the contraction mapping principle.

Cold atom clocks are among the most precise measuring devices and play key roles in everyday life and scientific explorations. Here the authors demonstrate the first in-orbit atomic clock using cold Rb atoms operating in microgravity and opening possibilities of space surveys and tests of fundamental physics.

Ginsenoside Rb1 (Rb1) has been demonstrated its protection for central nervous system and is apparently highly distributed to the brain. The objective of this study was to characterize Rb1 transport at the blood–brain barrier (BBB) using primary cultured rat brain microvascular endothelial cells (rBMEC), an in vitro BBB model. The initial uptake velocity of Rb1 in rBMEC was temperature- and concentration-dependent, and was significantly reduced by phloretin, an inhibitor of GLUT1 transporter, but was independent of metabolic inhibitor. Furthermore, the transport of Rb1 into rBMEC was significantly diminished in the presence of natural substrate α-D-glucose, suggesting a facilitated transport of Rb1 via GLUT1 transporter. The impact of GLUT1 on the distribution of Rb1 between brain and plasma was studied experimentally in rats. Administration of phloretin (5 mg/kg, i.v.) to normal rats for consecutive 1 week before Rb1 (10 mg/kg, i.v.) at 0.5, 2, and 6 h did not alter Rb1 concentrations in plasma, but resulted in significant decreased brain concentrations of Rb1 compared to in the phloretin-untreated normal rats (489.6 ± 58.3 versus 105.1 ± 15.1 ng/g, 193.8 ± 11.1 versus 84.8 ± 4.1 ng/g, and 114.2 ± 24.0 versus 39.9 ± 4.9 ng/g, respectively). The expression of GLUT1 in the phloretin-treated group by western blotting analysis in vitro and in vivo experiments was significantly decreased, indicating that the decreased transport of Rb1 in brain was well related to the down-regulated function and level of GLUT1. Therefore, our in vitro and in vivo results indicate that the transport of Rb1 at the BBB is at least partly mediated by GLUT1 transporter.

In this article we obtain a blow-up criterion of smooth solutions to Cauchy problem for the incompressible heat convection equations with zero heat conductivity in $mathbb{R}^2$. Our proof is based on careful H"oder estimates of heat and transport equations and the standard Littlewood-Paley theory.

Ginsenoside Rg1 has been reported to improve cognitive function in many memory-impaired animal models. However, little is known about the bioactivity of its metabolites in the central nervous system in vivo. In the present study, we employed the step through test and electrophysiological approach to investigate the effects of ginsenoside Rg1’s primary metabolite ginsenoside Rh1 and end metabolite protopanaxatriol (Ppt) on learning and memory as well as hippocampal excitability. The behavioral study showed that both ginsenoside Rh1 and Ppt significantly ameliorated memory-impaired models induced by scopolamine in mice. Consistently, the electrophysiological work revealed that ginsenoside Rh1 and Ppt as well as their precursor ginsenoside Rg1 all increased hippocampal excitability in the dentate gyrus of anesthetized rats. These results demonstrated that both ginsenoside Rh1 and Ppt had similar but more potent actions than ginsenoside Rg1 in improving memory and hippocampal excitability, suggesting the role of ginsenoside’s sugar moieties in biological activities is not as necessary as traditionally considered. Keywords:: ginsenoside Rg1, ginsenoside Rh1, protopanaxatriol, cognition, hippocampal excitability

Ras homolog family member A (RhoA) and Rho-associated coiled coil-containing protein kinases 1 and 2 (ROCK1 and 2) are key regulators of focal adhesion, actomyosin contraction and cell motility. RhoA/ROCK signaling has emerged as an attractive target for the development of new cancer therapeutics. Whether RhoA/ROCK is involved in regulating the formation of tumor cell vasculogenic mimicry (VM) is largely unknown. To confirm this hypothesis, we performed in vitro experiments using hepatocellular carcinoma (HCC) cell lines. Firstly, we demonstrated that HCC cells with higher active RhoA/ROCK expression were prone to form VM channels, as compared with RhoA/ROCK low-expressing cells. Furthermore, Y27632 (a specific inhibitor of ROCK) rather than exoenzyme C3 (a specific inhibitor of RhoA) effectively inhibited the formation of tubular network structures in a dose-dependent manner. To elucidate the possible mechanism of ROCK on VM formation, real-time qPCR, western blot and immunofluorescence were used to detect changes of the key VM-related factors, including VE-cadherin, erythropoietin-producing hepatocellular carcinoma-A2 (EphA2), phosphoinositide 3-kinase (PI3K), matrix metalloproteinase (MMP)14, MMP2, MMP9 and laminin 5γ2-chain (LAMC2), and epithelial-mesenchymal-transition (EMT) markers: E-cadherin and Vimentin. The results showed that all the expression profiles were attenuated by blockage of ROCK. In addition, in vitro cell migration and invasion assays showed that Y27632 inhibited the migration and invasion capacity of HCC cell lines in a dose-dependent manner markedly. These data indicate that ROCK is an important mediator in the formation of tumor cell VM, and suggest that ROCK inhibition may prove useful in the treatment of VM in HCC.

We consider the Cauchy problem for the damped nonlinear hyperbolic equation in n-dimensional space. Under small condition on the initial value, the global existence and asymptotic behavior of the solution in the corresponding Sobolev spaces are obtained by the contraction mapping principle.

The Cauchy problem for the Boussinesq equation in multidimensions is investigated. We prove the asymptotic behavior of the global solutions provided that the initial data are suitably small. Moreover, our global solutions can be approximated by the solutions to the corresponding linear equation as time tends to infinity when the dimension of space .

Regularity criterion for the 3D micropolar fluid equations is investigated. We prove that, for some T>0, if ∫0T∥vx3∥Lϱρdt

Hepatocellular carcinoma (HCC) is one of the most aggressive types of cancer. Although it has a high mortality rate, there is currently no effective treatment for HCC. Lenvatinib has traditionally been used as the first-line treatment for advanced HCC (aHCC); however, resistance to this therapy is common. It can be difficult to select effective second-line drugs to overcome lenvatinib resistance when treating aHCC. For patients with aHCC, poor treatment efficacy can result in patients missing the optimal treatment window and can lead to an irreversible situation. Lenalidomide has begun to be used to treat HCC; however, to the best of our knowledge, its efficacy in patients with lenvatinib-resistant HCC remains to be reported on in the literature. The present case report, to the best of our knowledge, describes the first case in the literature of a patient with lenvatinib-resistant aHCC who achieved a partial response after the treatment regimen was switched to lenalidomide. The present case report provides a promising novel route for the treatment of lenvatinib-resistant HCC. [ABSTRACT FROM AUTHOR]