Midterm Outcomes of Multicenter Castor Single-Branch Stent Graft Use in the Treatment of Thoracic Aortic Diseases.

PURPOSE: The aim of this study was to evaluate the midterm efficacy and safety of a single-branch Castor stent graft in the treatment of thoracic aortic disease. MATERIALS AND METHODS: Clinical data of 106 patients with thoracic aortic disease treated with Castor single-branch stent graft at 3 centers were collected between May 2018 and June 2023. The indicators included technical success, stent-related complication, reintervention, retrograde dissection, endoleak, distal stent graft-induced entry (dSINE), branch patency, and mortality. The outcomes of the Castor stent graft for multibranch reconstruction above the arch was also analyzed. RESULTS: The technical success was 98.1% (104/106), while the surgical success was 93.4% (99/106). The reintervention was 2.8% (3/106), consisting of a case of retrograde type A dissection, an endoleak, and a dSINE. The retrograde dissection was 1.9% (2/106), while type I endoleak was 1.9% (2/106). The new dSINE was 2.8% (3/106), and the branch patency rate was 100%. The mortality was 1.9% (2/106). The mean follow-up time was 29.1±17.7 months. The 2-year post-surgery cumulative survival rate was 91.0%±3.1%, while the cumulative branch patency rate was 96.2%±2.2%. In addition, the cumulative freedom from stent-related reintervention rate was 93.2%±2.8%. A comparison showed no significant difference in the stent-related complication, branch patency, endoleak, reintervention, and mortality when the proximal end of the Castor stent graft was anchored to zones 1 or 2 of the aorta. CONCLUSION: Castor single-branch stent graft showed favorable early and midterm outcomes in the treatment of thoracic aortic disease. In addition, it was feasible to combine Castor stent graft with other advanced techniques for multibranch aortic arch reconstruction. CLINICAL IMPACT: The Castor single-branch stent graft was approval by the Chinese Food and Drug Administration in 2017. However, there were few studies on the mid-term outcomes for thoracic aortic disease after launching, which mainly focused on small single-center retrospective study. In the study, we assessed the mid-term outcomes of Castor stent graft through multi-center cases, Castor stent graft combined with other advanced techniques (such as fenestration and hybrid) for multi-branch reconstruction of aortic arch were also conducted. We found Castor single-branch stent graft showed favorable early and mid-term outcomes in the treatment of thoracic aortic disease. Additionally, it was feasible to combine Castor stent graft with other advanced technique for multi-branch aortic arch reconstruction. As an off-the-shelf branched stent graft with a wide range of models, it could be also used in most emergent situation. The Castor stent graft was expected to become more widely used in the future.

LIFU/MMP-2 dual-responsive release of repurposed drug disulfiram from nanodroplets for inhibiting vasculogenic mimicry and lung metastasis in triple-negative breast cancer.

BACKGROUND: Vasculogenic mimicry (VM), when microvascular channels are formed by cancer cells independent of endothelial cells, often occurs in deep hypoxic areas of tumors and contributes to the aggressiveness and metastasis of triple-negative breast cancer (TNBC) cells. However, well-developed VM inhibitors exhibit inadequate efficacy due to their low drug utilization rate and limited deep penetration. Thus, a cost-effective VM inhibition strategy needs to be designed for TNBC treatment. RESULTS: Herein, we designed a low-intensity focused ultrasound (LIFU) and matrix metalloproteinase-2 (MMP-2) dual-responsive nanoplatform termed PFP@PDM-PEG for the cost-effective and efficient utilization of the drug disulfiram (DSF) as a VM inhibitor. The PFP@PDM-PEG nanodroplets effectively penetrated tumors and exhibited substantial accumulation facilitated by PEG deshielding in a LIFU-mediated and MMP-2-sensitive manner. Furthermore, upon exposure to LIFU irradiation, DSF was released controllably under ultrasound imaging guidance. This secure and controllable dual-response DSF delivery platform reduced VM formation by inhibiting COL1/pro-MMP-2 activity, thereby significantly inhibiting tumor progression and metastasis. CONCLUSIONS: Considering the safety of the raw materials, controlled treatment process, and reliable repurposing of DSF, this dual-responsive nanoplatform represents a novel and effective VM-based therapeutic strategy for TNBC in clinical settings.

NIR Activated Multimodal Therapeutics Based on Metal-Phenolic Networks-Functionalized Nanoplatform for Combating against Multidrug Resistance and Metastasis.

Multidrug resistance (MDR) and metastasis in cancer have become increasingly serious problems since antitumor efficiency is greatly restricted by a single therapeutic modality and the insensitive tumor microenvironment (TME). Herein, metal-phenolic network-functionalized nanoparticles (t-P@TFP NPs) are designed to realize multiple therapeutic modalities and reshape the TME from insensitive to sensitive under multimodal imaging monitoring. After a single irradiation, a near-infrared laser-activated multistage reaction occurs. t-P@TFP NPs trigger the phase transition of perfluoropentane (PFP) to release tannic acid (TA)/ferric ion (Fe3+ )-coated paclitaxel (PTX) and cause hyperthermia in the tumor region to efficiently kill cancer cells. Additionally, PTX is released after the disassembly of the TA-Fe3+ film by the abundant adenosine triphosphate (ATP) in the malignant tumor, which concurrently inhibits ATP-dependent drug efflux to improve sensitivity to chemotherapeutic agents. Furthermore, hyperthermia-induced immunogenic cell death (ICD) transforms "cold" tumors into "hot" tumors with the assistance of PD-1/PD-L1 blockade to evoke antitumor immunogenicity. This work carefully reveals the mechanisms underlying the abilities of these multifunctional NPs, providing new insights into combating the proliferation and metastasis of multidrug-resistant tumors.

Usefulness of Therapeutic Drug Monitoring and Pharmacogenetics for a Patient Treated with Olanzapine, Buspirone, and Fluvoxamine: A Case Study.

BACKGROUND: A patient, with a mental disorder caused by an intracranial infection, treated with olanzapine, fluvoxamine, and buspirone. The plasma exposure of olanzapine was too high at standard doses, with evidence indicating that it was caused by drug-drug interactions. METHODS: Using pharmacogenomics and therapeutic drug monitoring to guide drug dose adjustment for a patient in clinical practice. RESULTS: The patient underwent pharmacogenetic testing in addition to therapeutic drug monitoring as part of a pharmacist-led comprehensive evaluation of medication therapy management in a clinical setting, resulting in improved clinical efficacy that allowed discharge from a psychiatric hospital. CONCLUSIONS: This case study demonstrates that therapeutic drug monitoring combined with pharmacogenetic-guided dose adjustment can aid in the management of patients receiving complex pharmacological treatments.

Tumor-penetrating nanoplatform with ultrasound "unlocking" for cascade synergistic therapy and visual feedback under hypoxia.

BACKGROUND: Combined therapy based on the effects of cascade reactions of nanoplatforms to combat specific solid tumor microenvironments is considered a cancer treatment strategy with transformative clinical value. Unfortunately, an insufficient O2 supply and the lack of a visual indication hinder further applications of most nanoplatforms for solid tumor therapy. RESULTS: A visualizable nanoplatform of liposome nanoparticles loaded with GOD, H(Gd), and PFP and grafted with the peptide tLyP-1, named tLyP-1H(Gd)-GOD@PFP, was constructed. The double-domain peptide tLyP-1 was used to specifically target and penetrate the tumor cells; then, US imaging, starvation therapy and sonodynamic therapy (SDT) were then achieved by the ultrasound (US)-activated cavitation effect under the guidance of MR/PA imaging. GOD not only deprived the glucose for starvation therapy but also produced H2O2, which in coordination with 1O2 produced by H(Gd), enable the effects of SDT to achieve a synergistic therapeutic effect. Moreover, the synergistic therapy was enhanced by O2 from PFP and low-intensity focused ultrasound (LIFU)-accelerated redox effects of the GOD. The present study demonstrated that the nanoplatform could generate a 3.3-fold increase in ROS, produce a 1.5-fold increase in the maximum rate of redox reactions and a 2.3-fold increase in the O2 supply in vitro, and achieve significant tumor inhibition in vivo. CONCLUSION: We present a visualizable nanoplatform with tumor-penetrating ability that can be unlocked by US to overcome the current treatment problems by improving the controllability of the O2 supply, which ultimately synergistically enhanced cascade therapy.

Near-Infrared II Nanoadjuvant-Mediated Chemodynamic, Photodynamic, and Photothermal Therapy Combines Immunogenic Cell Death with PD-L1 Blockade to Enhance Antitumor Immunity.

The efficacy of immune checkpoint inhibition in inducing death of cancer cells is affected by the immunosuppressive "cold" tumor microenvironment, which results in a poor response by the patient's antitumor immune system. However, the immunomodulatory effects of immunogenic cell death in response to irritation by heat energy and reactive oxygen species (ROS) can switch the tumor microenvironment from "cold" to "hot." This study has developed a nanoadjuvant for immune therapy using iron tungsten oxide (FeWOx)-based nanosheets with surface PEGylation (FeWOx-PEG). This FeWOx-PEG nanoadjuvant serves as a chemodynamic reagent via the Fenton reaction and acts as a photosensitizer for photodynamic and photothermal therapy under near-infrared II laser irradiation; however, it could also be used to augment tumor-infiltrating T-cells and provoke a systemic antitumor immune response by combining the immunogenic cell death triggered by ROS and photothermal therapy with the immune checkpoint blockade. This research demonstrates that application of the FeWOx-PEG nanoadjuvant under the guidance of magnetic resonance/computed tomography/photoacoustic imaging can eliminate the primary tumor and suppress the growth of distant tumors.

Amplified antitumor efficacy by a targeted drug retention and chemosensitization strategy-based "combo" nanoagent together with PD-L1 blockade in reversing multidrug resistance.

BACKGROUND: Recent studies have demonstrated that multidrug resistance (MDR) is a critical factor in the low efficacy of cancer chemotherapy. The main mechanism of MDR arises from the overexpression of P-glycoprotein (P-gp), which actively enhances drug efflux and limits the effectiveness of chemotherapeutic agents. RESULTS: In this study, we fabricated a "combo" nanoagent equipping with triple synergistic strategies for enhancing antitumor efficacy against MDR cells. Tumor homing-penetrating peptide endows the nanosystem with targeting and penetrating capabilities in the first stage of tumor internalization. The abundant amine groups of polyethylenimine (PEI)-modified nanoparticles then trigger a proton sponge effect to promote endo/lysosomal escape, which enhances the intracellular accumulation and retention of anticancer drugs. Furthermore, copper tetrakis(4-carboxyphenyl)porphyrin (CuTCPP) encapsulated in the nanosystem, effectively scavenges endogenous glutathione (GSH) to reduce the detoxification mediated by GSH and sensitize the cancer cells to drugs, while simultaneously serving as a photoacoustic imaging (PAI) contrast agent for image visualization. Moreover, we also verify that these versatile nanoparticles in combination with PD-1/PD-L1 blockade therapy can not only activate immunological responses but also inhibit P-gp expression to obliterate primary and metastatic tumors. CONCLUSION: This work shows a significant enhancement in therapeutic efficacy against MDR cells and syngeneic tumors by using multiple MDR reversing strategies compared to an equivalent dose of free paclitaxel.

[Progression on Multifunctional Nanoparticles Interfering with Cell Membrane Transporters-associated Drug Resistance].

Multi-drug resistance(MDR)refers to the loss of sensitivity of tumor cells to traditional chemotherapeutics agents under the mediation of various mechanisms,resulting in the reduction of chemotherapy efficacy.Current studies suggest that a variety of factors,including cell membrane transporter-mediated efflux of anti-tumor drugs,special microenvironment in tumor tissue,DNA self-repair and anti-apoptotic process,and epithelial-mesenchymal cell transformation,may contribute to the formation of MDR.Cell membrane transporter-mediated drug efflux refers to an increase in the amount of anti-tumor drug pumped out of the cell through the up-regulation of the ATP-binding cassette transporter on tumor cell membrane,which reduces the concentration of the drug in the cell,thus forming MDR.An effective method to inhibit the efflux pump caused by overexpression of membrane transporters plays an important role in overcoming MDR.As a promising drug delivery system,multifunctional nanoparticles have demonstrated many advantages in antitumor therapy.Meanwhile,nanoparticles with tailored design are capable of overcoming MDR when combined with a variety of strategies.This paper described in detail the studies relevant to the use of multifunctional nano-sized drug delivery system combined with different strategies,such as co-delivery of agents,external responsiveness or target modification for intervention with efflux pump in order to reverse MDR.This paper provides reference for the development of nano-sized drug delivery system and the formulation of reversal strategy in the future.

Peptide-Functionalized Phase-Transformation Nanoparticles for Low Intensity Focused Ultrasound-Assisted Tumor Imaging and Therapy.

In this study, we successfully developed novel tumor homing-penetrating peptide-functionalized drug-loaded phase-transformation nanoparticles (tLyP-1-10-HCPT-PFP NPs) for low intensity focused ultrasound (LIFU)-assisted tumor ultrasound molecular imaging and precise therapy. With the nanoscale particle size, tLyP-1-10-HCPT-PFP NPs could pass through the tumor vascular endothelial cell gap. Induced by tLyP-1 peptide with targeting and penetrating efficiency, tLyP-1-10-HCPT-PFP NPs could increase tumor accumulation and penetrate deeply into the extravascular tumor tissue, penetrating through extracellular matrix and the cellular membrane to the cytoplasm. With LIFU assistance, tLyP-1-10-HCPT-PFP NPs could phase-transform into microbubbles and enhance tumor ultrasound molecular imaging for tumor diagnosis. Furthermore, after further irradiation by LIFU, an intracellular "explosion effect" caused by acoustic droplet vaporization, ultrasound targeted microbubble destruction, and release of 10-HCPT could realize physicochemical synergistic antitumor therapy.

Correlation of COX-2 and MMP-13 expressions with gastric cancer and their effects on prognosis.

PURPOSE: To study the expressions of cyclooxygenase-2 (COX-2) and matrix metalloproteinase-13 (MMP-13) genes in gastric cancer, and to investigate the correlation between them and gastric cancer and their effects onprognosis. METHODS: 80 cases of tumor tissues and 40 cases of normal tumor-adjacent tissues were collected from patients with gastric cancer admitted to the Surgical Department of our hospital. The mRNA expression levels of COX-2 and MMP- 13 in tumor tissues and normal tumor-adjacent tissues were detected via real-time fluorescence reverse transcription polymerase chain reaction (RT-PCR). The expressions of COX-2 and MMP-13 in gastric cancer tissues and normal tumor-adjacent tissues were detected via immunohistochemical method. The clinical data of patients were recorded and the correlation between the COX-2 and MMP-13 expressions and the pathological parameters and prognosis of patients with gastric cancer were analyzed. RESULTS: RT-PCR results showed that the mRNA expressions of COX-2 and MMP-13 in gastric cancer tissues were significantly higher than those in normal tumor-adjacent tissues. Immunohistochemical results showed that the positive expression rates of COX-2 and MMP-13 in gastric cancer tissues were 76.25% (60/80) and 71.25% (57/80), respectively and the high expression was related to the invasion, metastasis and tumor stage. The 5-year overall survival of patients was 16.6% (13/80). Single-factor survival analysis showed that both COX-2 and MMP-13 were factors influencing the overall survival of patients with gastric cancer (p<0.01). CONCLUSION: The high expressions of COX-2 and MMP-13 are closely related to the pathological parameters of patients with gastric cancer, especially the invasion, metastasis and tumor stage. COX-2 and MMP-13 can be used as reference indexes to guide the treatment of gastric cancer and predict the disease prognosis.

Effect of ammonium sulfate and urea on PCDD/F formation from active carbon and possible mechanism of inhibition.

The effect of ammonium sulfate ((NH4)2SO4) and urea (CO(NH2)2) on polychlorinated dibenzo-p-dioxin and dibenzofuran (PCDD/F) formation from active carbon was investigated in this study. Both additives could significantly inhibit PCDD/F formation, and PCDD/F (TEQ) generation was reduced to 98.5% (98%) or 64.5% (77.2%) after 5% (NH4)2SO4 or CO(NH2)2 was added into model ash, respectively. The inhibition efficiency of PCDDs was higher than the value of PCDFs, however, the reduction of PCDD/F yield was mainly from PCDFs decreasing. In addition, the solid-phase products were reduced more than the gas-phase compounds by inhibitors. By the measurement of chlorine emission in the phase of ion (Cl[Cl(-)]) and molecule gas (Cl[Cl2]), it was observed that both Cl[Cl(-)] and Cl[Cl2] were reduced after inhibitors were added into ash. Cl[Cl2] was reduced to 51.0% by urea addition, which was supposed as one possible mechanism of PCDD/F inhibition.

A Wearable Fingertip Force Feedback Device System for Object Stiffness Sensing.

Virtual reality technology brings a new experience to human-computer interaction, while wearable force feedback devices can enhance the immersion of users in interaction. This paper proposes a wearable fingertip force feedback device that uses a tendon drive mechanism, with the aim of simulating the stiffness characteristics of objects within virtual scenes. The device adjusts the rotation angle of the torsion spring through a DC motor, and then uses a wire to convert the torque into a feedback force at the user's index fingertips, with an output force of up to 4 N and a force change rate of up to 10 N/s. This paper introduces the mechanical structure and design process of the force feedback device, and conducts a mechanical analysis of the device to select the appropriate components. Physical and psychological experiments are conducted to comprehensively evaluate the device's performance in conveying object stiffness information. The results show that the device can simulate different stiffness characteristics of objects, and users can distinguish objects with different stiffness characteristics well when wearing the force feedback device and interacting with the three-dimensional virtual environments.

Decomposable Nanoagonists Enable NIR-Elicited cGAS-STING Activation for Tandem-Amplified Photodynamic-Metalloimmunotherapy.

Activation of the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway has emerged as an efficient strategy to improve the therapeutic outcomes of immunotherapy. However, the "constantly active" mode of current STING agonist delivery strategies typically leads to off-target toxicity and hyperimmunity. To address this critical issue, herein a metal-organic frameworks-based nanoagonist (DZ@A7) featuring tumor-specific and near-infrared (NIR) light-enhanced decomposition is constructed for precisely localized STING activation and photodynamic-metalloimmunotherapy. The engineered nanoagonist enabled the generation of mitochondria-targeted reactive oxygen species under NIR irradiation to specifically release mitochondrial DNA (mtDNA) and inhibit the repair of nuclear DNA via hypoxia-responsive drugs. Oxidized tumor mtDNA serves as an endogenous danger-associated molecular pattern that activates the cGAS-STING pathway. Concurrently, NIR-accelerated zinc ions overloading in cancer cells further enhance the cGAS enzymatic activity through metalloimmune effects. By combining the synergistically enhanced activation of the cGAS-STING pathway triggered by NIR irradiation, the engineered nanoagonist facilitated the maturation of dendritic cells and infiltration of cytotoxic T lymphocytes for primary tumor eradication, which also established a long-term anti-tumor immunity to suppress tumor metastasis. Therefore, the developed nanoagonist enabled NIR-triggered, agonist-free, and tandem-amplified activation of the cGAS-STING pathway, thereby offering a distinct paradigm for photodynamic-metalloimmunotherapy.

Repurposing Disulfiram to Combat Acute Respiratory Distress Syndrome with Targeted Delivery by LET-Functionalized Nanoplatforms.

Acute respiratory distress syndrome (ARDS) is a serious respiratory condition characterized by a damaged pulmonary endothelial barrier that causes protein-rich lung edema, an influx of proinflammatory cells, and treatment-resistant hypoxemia. Damage to pulmonary endothelial cells and inflammation are pivotal in ARDS development with a key role played by endothelial cell pyroptosis. Disulfiram (DSF), a drug that has long been used to treat alcohol addiction, has recently been identified as a potent inhibitor of gasdermin D (GSDMD)-induced pore formation and can thus prevent pyroptosis and inflammatory cytokine release. These findings indicate that DSF is a promising treatment for inflammatory disorders. However, addressing the challenge posed by its intrinsic physicochemical properties, which hinder intravenous administration, and effective delivery to pulmonary vascular endothelial cells are crucial. Herein, we used biocompatible liposomes incorporating a lung endothelial cell-targeted peptide (CGSPGWVRC) to produce DSF-loaded nanoparticles (DTP-LET@DSF NPs) for targeted delivery and reactive oxygen species-responsive release facilitated by the inclusion of thioketal (TK) within the liposomal structure. After intravenous administration, DTP-LET@DSF NPs exhibited excellent cytocompatibility and minor systemic toxicity, effectively inhibited pyroptosis, mitigated lipopolysaccharide (LPS)-induced ARDS, and prevented cytokine storms resulting from excessive immune reactions in ARDS mice. This study presents a straightforward nanoplatform for ARDS treatment that potentially paves the way for the clinical use of this nanomedicine.

Self-Reinforced Bimetallic Mito-Jammer for Ca2+ Overload-Mediated Cascade Mitochondrial Damage for Cancer Cuproptosis Sensitization.

Overproduction of reactive oxygen species (ROS), metal ion accumulation, and tricarboxylic acid cycle collapse are crucial factors in mitochondria-mediated cell death. However, the highly adaptive nature and damage-repair capabilities of malignant tumors strongly limit the efficacy of treatments based on a single treatment mode. To address this challenge, a self-reinforced bimetallic Mito-Jammer is developed by incorporating doxorubicin (DOX) and calcium peroxide (CaO2) into hyaluronic acid (HA) -modified metal-organic frameworks (MOF). After cellular, Mito-Jammer dissociates into CaO2 and Cu2+ in the tumor microenvironment. The exposed CaO2 further yields hydrogen peroxide (H2O2) and Ca2+ in a weakly acidic environment to strengthen the Cu2+-based Fenton-like reaction. Furthermore, the combination of chemodynamic therapy and Ca2+ overload exacerbates ROS storms and mitochondrial damage, resulting in the downregulation of intracellular adenosine triphosphate (ATP) levels and blocking of Cu-ATPase to sensitize cuproptosis. This multilevel interaction strategy also activates robust immunogenic cell death and suppresses tumor metastasis simultaneously. This study presents a multivariate model for revolutionizing mitochondria damage, relying on the continuous retention of bimetallic ions to boost cuproptosis/immunotherapy in cancer.

Two-dimensional speckle tracking imaging analyses of the correlations between left atrial appendage function and stroke risk in nonvalvular atrial fibrillation patients.

Stroke incidence is the most severe complication associated with atrial fibrillation (AF), and the most common site of thrombus formation in AF patients is the left atrial appendage (LAA). This study was developed to use two-dimensional speckle tracking imaging (2D-STI) to explore associations between LAA strain/strain rate and stroke incidence and to evaluate the value of utilizing LAA strain and strain rate values to support the stratification of nonvalvular AF (NVAF) patients based on stroke risk. A total of 486 AF patients who had undergone transesophageal echocardiography to exclude potential intracardiac thrombosis between March 2021 and November 2022 were consecutively enrolled. Patients meeting the inclusion criteria were separated into two groups according to their history of stroke/transient ischemic attack (TIA). LAA strain and strain rate values in these patients were measured via 2D-STI. Multivariable logistic regression analysis was employed to determine independent risk factors for the construction of a combined predictive model. Of the 333 analyzed patients (134 females, aged 65 (56,72) years), 39 (11.71%, 39/333) had a history of stroke at the time of evaluation. Multivariate logistic regression analysis demonstrated that nonparoxysmal AF, CHA2DS2VASc score, LAA thrombus/spontaneous echo contrast (SEC), LAA strain, and strain rate were all predictors of stroke incidence among NVAF patients. The combined predictive model demonstrated excellent discriminative ability, with an AUC of 0.91 (95%CI 0.87-0.95, P < 0.001), and a sensitivity and specificity of 79.49% and 89.46%, respectively. The Hosmer-Lemeshow test confirmed good calibration, yielding a value of 0.98. Comparative decision curve analysis showed that the model provided superior net benefits compared to the CHA2DS2VASc score. Furthermore, the model exhibited improved predictive performance and reclassification for stroke when compared to the CHA2DS2VASc score (AUC 0.91 vs. 0.88, Z = 2.32, P = 0.02), accompanied by a significant increase in the net reclassification index (+ 5.44%, P < 0.001) and integrated discrimination improvement (8.21%, P < 0.001). These data demonstrate that LAA strain and strain rate, as measured via 2D-STI, can offer value when assessing LAA function in AF patients, potentially providing further predictive value to extant clinical risk scoring strategies.

Nitrogen addition regulates the effects of variation in precipitation patterns on plant biomass formation and allocation in a Leymus chinensis grassland of northeast China.

Global warming is predicted to change precipitation amount and reduce precipitation frequency, which may alter grassland primary productivity and biomass allocation, especially when interact with other global change factors, such as nitrogen deposition. The interactive effects of changes in precipitation amount and nitrogen addition on productivity and biomass allocation are extensively studied; however, how these effects may be regulated by the predicted reduction in precipitation frequency remain largely unknown. Using a mesocosm experiment, we investigated responses of primary productivity and biomass allocation to the manipulated changes in precipitation amount (PA: 150 mm, 300 mm, 450 mm), precipitation frequency (PF: medium and low), and nitrogen addition (NA: 0 and 10 g N m-2 yr-1) in a Leymus chinensis grassland. We detected significant effects of the PA, PF and NA treatments on both aboveground biomass (AGB) and belowground biomass (BGB); but the interactive effects were only significant between the PA and NA on AGB. Both AGB and BGB increased with an increment in precipitation amount and nitrogen addition; the reduction in PF decreased AGB, but increased BGB. The reduced PF treatment induced an enhancement in the variation of soil moisture, which subsequently affected photosynthesis and biomass formation. Overall, there were mismatches in the above- and belowground biomass responses to changes in precipitation regime. Our results suggest the predicted changes in precipitation regime, including precipitation amount and frequency, is likely to alter primary productivity and biomass allocation, especially when interact with nitrogen deposition. Therefore, predicting the influence of global changes on grassland structure and functions requires the consideration of interactions among multiple global change factors.

The role of left ventricular hypertrophy measured by echocardiography in screening patients with ischaemia with non-obstructive coronary arteries: a cross-sectional study.

Many patients with ischaemia with non-obstructive coronary arteries (INOCA) have a poor prognosis. This study aims to explore the diagnostic value of left ventricular hypertrophy (LVH)-related ultrasound parameters in INOCA patients. The study group consisted of 258 patients with INOCA in this retrospective cross-sectional study, and these patients were free of obstructive coronary artery disease, previous revascularization, atrial fibrillation, ejection fraction < 50%, major distortions of left ventricular geometry, suspected non-ischaemic causes. Control individuals were matched 1:1 with study group according to age, sex, cardiovascular risk factors, and time of hospital stay. According to left ventricular mass index (LVMI) and relative wall thickness, left ventricular geometry was composed of concentric hypertrophy, eccentric hypertrophy, concentric remodeling and normal geometry. LVH-related parameters, left ventricular geometry, demographic characteristics, laboratory parameters and other echocardiographic indicators were compared between the two groups. Subgroup analysis was performed based on sex. LVMI in the study group was higher than that in the control group (86.86 ± 18.83 g/m2 vs 82.25 ± 14.29 g/m2, P = 0.008). The ratio of LVH was higher in the study group (20.16% vs 10.85%, P = 0.006). After subgroup analysis based on sex, LVMI differences (85.77 ± 18.30 g/m2 vs 81.59 ± 14.64 g/m2, P = 0.014) and the ratio of LVH differences (25.00% vs 14.77%, P = 0.027) still existed in females between the two groups. There was no difference in the constituent ratio of left ventricular geometry between the two groups (P = 0.157). Sex-based subgroup analysis showed no difference in the constituent ratio of left ventricular geometry between the two groups in females (P = 0.242). The degree of LVH in the study group was higher than that in the control group, suggesting that LVH may play an important role in the occurrence and development of INOCA. Moreover, LVH-related ultrasound parameters may be of higher diagnostic value for female INOCA patients than for male INOCA patients.

PTC-MAS: A Deep Learning-Based Preoperative Automatic Assessment of Lymph Node Metastasis in Primary Thyroid Cancer.

BACKGROUND: Identifying cervical lymph node metastasis (LNM) in primary thyroid cancer preoperatively using ultrasound is challenging. Therefore, a non-invasive method is needed to assess LNM accurately. PURPOSE: To address this need, we developed the Primary Thyroid Cancer Lymph Node Metastasis Assessment System (PTC-MAS), a transfer learning-based and B-mode ultrasound images-based automatic assessment system for assessing LNM in primary thyroid cancer. METHODS: The system has two parts: YOLO Thyroid Nodule Recognition System (YOLOS) for obtaining regions of interest (ROIs) of nodules, and LMM assessment system for building the LNM assessment system using transfer learning and majority voting with extracted ROIs as input. We retained the relative size features of nodules to improve the system's performance. RESULTS: We evaluated three transfer learning-based neural networks (DenseNet, ResNet, and GoogLeNet) and majority voting, which had the area under the curves (AUCs) of 0.802, 0.837, 0.823, and 0.858, respectively. Method III preserved relative size features and achieved higher AUCs than Method II, which fixed nodule size. YOLOS achieved high precision and sensitivity on a test set, indicating its potential for ROIs extraction. CONCLUSIONS: Our proposed PTC-MAS system effectively assesses primary thyroid cancer LNM based on preserving nodule relative size features. It has potential for guiding treatment modalities and avoiding inaccurate ultrasound results due to tracheal interference.

Corrigendum: Effect of 131 I with and without artificial liver support system in patients with Graves' disease and severe liver dysfunction: A retrospective study.

[This corrects the article DOI: 10.3389/fendo.2022.1034374.].