The Identification of Fritillaria Species Using Hyperspectral Imaging with Enhanced One-Dimensional Convolutional Neural Networks via Attention Mechanism.

Combining deep learning and hyperspectral imaging (HSI) has proven to be an effective approach in the quality control of medicinal and edible plants. Nonetheless, hyperspectral data contains redundant information and highly correlated characteristic bands, which can adversely impact sample identification. To address this issue, we proposed an enhanced one-dimensional convolutional neural network (1DCNN) with an attention mechanism. Given an intermediate feature map, two attention modules are constructed along two separate dimensions, channel and spectral, and then combined to enhance relevant features and to suppress irrelevant ones. Validated by Fritillaria datasets, the results demonstrate that an attention-enhanced 1DCNN model outperforms several machine learning algorithms and shows consistent improvements over a vanilla 1DCNN. Notably under VNIR and SWIR lenses, the model obtained 98.97% and 99.35% for binary classification between Fritillariae Cirrhosae Bulbus (FCB) and other non-FCB species, respectively. Additionally, it still achieved an extraordinary accuracy of 97.64% and 98.39% for eight-category classification among Fritillaria species. This study demonstrated the application of HSI with artificial intelligence can serve as a reliable, efficient, and non-destructive quality control method for authenticating Fritillaria species. Moreover, our findings also illustrated the great potential of the attention mechanism in enhancing the performance of the vanilla 1DCNN method, providing reference for other HSI-related quality controls of plants with medicinal and edible uses.

Non-destructive prediction of isoflavone and starch by hyperspectral imaging and deep learning in Puerariae Thomsonii Radix.

Accurate assessment of isoflavone and starch content in Puerariae Thomsonii Radix (PTR) is crucial for ensuring its quality. However, conventional measurement methods often suffer from time-consuming and labor-intensive procedures. In this study, we propose an innovative and efficient approach that harnesses hyperspectral imaging (HSI) technology and deep learning (DL) to predict the content of isoflavones (puerarin, puerarin apioside, daidzin, daidzein) and starch in PTR. Specifically, we develop a one-dimensional convolutional neural network (1DCNN) model and compare its predictive performance with traditional methods, including partial least squares regression (PLSR), support vector regression (SVR), and CatBoost. To optimize the prediction process, we employ various spectral preprocessing techniques and wavelength selection algorithms. Experimental results unequivocally demonstrate the superior performance of the DL model, achieving exceptional performance with mean coefficient of determination (R2) values surpassing 0.9 for all components. This research underscores the potential of integrating HSI technology with DL methods, thereby establishing the feasibility of HSI as an efficient and non-destructive tool for predicting the content of isoflavones and starch in PTR. Moreover, this methodology holds great promise for enhancing efficiency in quality control within the food industry.

Left Ventricular Function in Patients on Maintenance Hemodialysis: A Three-Dimensional Speckle-Tracking Imaging Study.

INTRODUCTION: Although maintenance hemodialysis (MHD) in end-stage renal disease (ESRD) appears to induce some risk factors and strengthen cardiac function, the morbidity of ESRD patients receiving hemodialysis remains high. This study aimed to identify left ventricular (LV) structural and functional abnormalities in ESRD patients on MHD using three-dimensional speckle-tracking imaging (3D-STI). METHODS: Eighty-five ESRD patients with normal LV ejection fraction (LVEF >50%) participated in this study, including 55 MHD patients comprising the chronic kidney disease (CKD) V-D group and 30 nondialysis patients comprising the CKD V-ND group. Thirty age- and sex-matched control participants who had normal kidney function were enrolled as the N group. Conventional echocardiography and 3D-STI were conducted, and global longitudinal strain (GLS), global circumferential strain (GCS), global area strain (GAS), and global radial strain (GRS) values were measured. RESULTS: No substantial differences in two-dimensional LVEF were observed among the three groups, and LV hypertrophy was the most common abnormality in patients with ESRD, irrespective of whether they had received or not received MHD. There were no significant differences in the 3D LV mass index between the CKD V-ND and N groups (p > 0.05). Conversely, the 3D LV mass index was considerably higher in the CKD V-D group than in both the N and CKD V-ND groups. The GLS, GAS, and GRS values were significantly lower in the CKD V-ND group than in the N group (p < 0.05). Furthermore, the CKD V-D group had significantly lower GLS, GCS, GAS, and GRS values than the N and CKD V-ND groups (p < 0.05). The interventricular septal thickness and E/e' ratio were independently associated with LV strain values in all patients with ESRD. CONCLUSIONS: MHD can exacerbate LV deformation and dysfunction in ESRD patients with preserved LVEF, and 3D-STI can be potentially useful for detecting these asymptomatic preclinical abnormalities.

Human Plasma IgG N-Glycome Profiles Reveal a Proinflammatory Phenotype in Chronic Thromboembolic Pulmonary Hypertension.

BACKGROUND: The pathological mechanism of chronic thromboembolic pulmonary hypertension (CTEPH) is not fully understood, and inflammation has been reported to be one of its etiological factors. IgG regulates systemic inflammatory homeostasis, primarily through its N-glycans. Little is known about IgG N-glycosylation in CTEPH. We aimed to map the IgG N-glycome of CTEPH to provide new insights into its pathogenesis and discover novel markers and therapies. METHODS: We characterized the plasma IgG N-glycome of patients with CTEPH in a discovery cohort and validated our results in an independent validation cohort using matrix-assisted laser desorption/ionization time of flight mass spectrometry. Thereafter, we correlated IgG N-glycans with clinical parameters and circulating inflammatory cytokines in patients with CTEPH. Furthermore, we determined IgG N-glycan quantitative trait loci in CTEPH to reveal partial mechanisms underlying glycan changes. RESULTS: Decreased IgG galactosylation representing a proinflammatory phenotype was found in CTEPH. The distribution of IgG galactosylation showed a strong association with NT-proBNP (N-terminal pro-B-type natriuretic peptide) in CTEPH. In line with the glycomic findings, IgG pro-/anti-inflammatory N-glycans correlated well with a series of inflammatory markers and gene loci that have been reported to be involved in the regulation of these glycans or inflammatory immune responses. CONCLUSIONS: This is the first study to reveal the full signature of the IgG N-glycome of a proinflammatory phenotype and the genes involved in its regulation in CTEPH. Plasma IgG galactosylation may be useful for evaluating the inflammatory state in patients with CTEPH; however, this requires further validation. This study improves our understanding of the mechanisms underlying CTEPH inflammation from the perspective of glycomics.

A static magnetic field improves bone quality and balances the function of bone cells with regulation on iron metabolism and redox status in type 1 diabetes.

Osteoporosis is one of the chronic complications of type 1 diabetes with high risk of fracture. The prevention of diabetic osteoporosis is of particular importance. Static magnetic fields (SMFs) exhibit advantages on improvement of diabetic complications. The biological effects and mechanism of SMFs on bone health of type 1 diabetic mice and functions of bone cells under high glucose have not been clearly clarified. In animal experiment, six-week-old male C57BL/6J mice were induced to type 1 diabetes and exposed to SMF of 0.4-0.7 T for 4 h/day lasting for 6 weeks. Bone mass, biomechanical strength, microarchitecture and metabolism were determined by DXA, three-point bending assay, micro-CT, histochemical and biochemical methods. Exposure to SMF increased BMD and BMC of femur, improved biomechanical strength with higher ultimate stress, stiffness and elastic modulus, and ameliorated the impaired bone microarchitecture in type 1 diabetic mice by decreasing Tb.Pf, Ct.Po and increasing Ct.Th. SMF enhanced bone turnover by increasing the level of markers for bone formation (OCN and Collagen I) as well as bone resorption (CTSK and NFAT2). In cellular experiment, MC3T3-E1 cells or primary osteoblasts and RAW264.7 cells were cultured in 25 mM high glucose-stimulated diabetic marrow microenvironment under differentiation induction and exposed to SMF. SMF promoted osteogenesis with higher ALP level and mineralization deposition in osteoblasts, and it also enhanced osteoclastogenesis with higher TRAP activity and bone resorption in osteoclasts under high glucose condition. Further, SMF increased iron content with higher FTH1 expression and regulated the redox level through activating HO-1/Nrf2 in tibial tissues, and lowered hepatic iron accumulation by BMP6-mediated regulation of hepcidin and lipid peroxidation in mice with type 1 diabetes. Thus, SMF may act as a potential therapy for improving bone health in type 1 diabetes with regulation on iron homeostasis metabolism and redox status.

A Unique Etching-Doping Route to Fe/Mo Co-Doped Ni Oxyhydroxide Catalyst for Enhanced Oxygen Evolution Reaction.

Fe-doped Ni (oxy)hydroxide shows intriguing activity toward oxygen evolution reaction (OER) in alkaline solution, yet it remains challenging to further boost its performance. In this work, a ferric/molybdate (Fe3+ /MoO4 2- ) co-doping strategy is reported to promote the OER activity of Ni oxyhydroxide. The reinforced Fe/Mo-doped Ni oxyhydroxide catalyst supported by nickel foam (p-NiFeMo/NF) is synthesized via a unique oxygen plasma etching-electrochemical doping route, in which precursor Ni(OH)2 nanosheets are first etched by oxygen plasma to form defect-rich amorphous nanosheets, followed by electrochemical cycling to trigger simultaneously Fe3+ /MoO4 2- co-doping and phase transition. This p-NiFeMo/NF catalyst requires an overpotential of only 274 mV to reach 100 mA cm-2 in alkaline media, exhibiting significantly enhanced OER activity compared to NiFe layered double hydroxide (LDH) catalyst and other analogs. Its activity does not fade even after 72 h uninterrupted operation. In situ Raman analysis reveals that the intercalation of MoO4 2- is able to prevent the over-oxidation of NiOOH matrix from ß to γ phase, thus keeping the Fe-doped NiOOH at the most active state.

Rotating Magnetic Field Mitigates Ankylosing Spondylitis Targeting Osteocytes and Chondrocytes via Ameliorating Immune Dysfunctions.

Ankylosing spondylitis (AS) is clinically characterized by bone fusion that is induced by the pathological formation of extra bone. Unfortunately, the fundamental mechanism and related therapies remain unclear. The loss of SHP-2 (encoded by Ptpn11) in CD4-Cre;Ptpn11f/f mice resulted in the induction of AS-like pathological characteristics, including spontaneous cartilage and bone lesions, kyphosis, and arthritis. Hence, this mouse was utilized as an AS model in this study. As one of the basic physical fields, the magnetic field (MF) has been proven to be an effective treatment method for articular cartilage degeneration. In this study, the effects of a rotating magnetic field (RMF; 0.2 T, 4 Hz) on an AS-like mouse model were investigated. The RMF treatment (2 h/d, 0.2 T, 4 Hz) was performed on AS mice from two months after birth until the day before sampling. The murine specimens were subjected to transcriptomics, immunomics, and metabolomics analyses, combined with molecular and pathological experiments. The results demonstrated that the mitigation of inflammatory deterioration resulted in an increase in functional osteogenesis and a decrease in dysfunctional osteolysis due to the maintenance of bone homeostasis via the RANKL/RANK/OPG signaling pathway. Additionally, by regulating the ratio of CD4+ and CD8+ T-cells, RMF treatment rebalanced the immune microenvironment in skeletal tissue. It has been observed that RMF interventions have the potential to alleviate AS, including by decreasing pathogenicity and preventing disease initiation. Consequently, RMF, as a moderately physical therapeutic strategy, could be considered to alleviate the degradation of cartilage and bone tissue in AS and as a potential option to halt the progression of AS.

Non-fouling polymer brush grafted fluorine-doped tin oxide enabled optical and chemical enhancement for sensitive label-free antibody microarrays.

Oblique-incidence reflectivity difference (OIRD) is a compelling technique for real-time, label-free and non-destructive detection of antibody microarray chips, but its sensitivity needs essential improvement for clinical diagnosis. In this study, we report an innovative high-performance OIRD microarray by using poly[oligo(ethylene glycol) methacrylate-co-glycidyl methacrylate] (POEGMA-co-GMA) brush grafted fluorine-doped tin oxide (FTO) as the chip substrate. The polymer brush enhances the interfacial binding reaction efficiency of targets from the complicated sample matrix due to its high antibody loading and excellent anti-fouling merits; the FTO-polymer brush layered structure, on the other hand, excites the interference enhancement effect of OIRD to achieve enhanced intrinsic optical sensitivity. Synergistically, the sensitivity of this chip is significantly improved compared to rival chips, achieving a limit of detection (LOD) as low as 25 ng mL-1 for the model target C-reactive protein (CRP) in 10% human serum. This work explores the tremendous influence of the chip interfacial structure on the OIRD sensitivity and proposes a rational interfacial engineering strategy to boost the performance of the label-free OIRD based microarray and other bio-devices.

Exposure to a static magnetic field attenuates hepatic damage and function abnormality in obese and diabetic mice.

Static magnetic fields (SMFs) exhibit significant effect on health care. However, the effect of SMF on hepatic metabolism and function in obesity and diabetes are still unknown. Liver is not only the main site for glucolipid metabolism but also the core part for iron metabolism regulation. Dysregulations of iron metabolism and redox status are risk factors for the development of hepatic injury and affect glucolipid metabolism in obesity and diabetes. Mice of HFD-induced obesity and HFD/streptozocin-induced diabetes were exposed to a moderate-intensity SMF (0.4-0.7 T, direction: upward, 4 h/day, 8 weeks). Results showed that SMF attenuated hepatic damage by decreasing inflammation and fibrosis in obese and diabetic mice. SMF had no effects on improving glucose/insulin tolerance but regulated proteins (GLUT1 and GLUT4) and genes (G6pc, Pdk4, Gys2 and Pkl) participating in glucose metabolism with phosphorylation of Akt/AMPK/GSK3ß. SMF also reduced lipid droplets accumulation through decreasing Plin2 and Plin5 and regulated lipid metabolism with elevated hepatic expressions of PPARγ and C/EBPα in obese mice. In addition, SMF decreased hepatic iron deposition with lower FTH1 expression and modulated systematic iron homeostasis via BMP6-mediated regulation of hepcidin. Moreover, SMF balanced hepatic redox status with regulation on mitochondrial function and MAPKs/Nrf2/HO-1 pathway. Finally, we found that SMF activated hepatic autophagy and enhanced lipophagy by upregulating PNPLA2 expression in obese and diabetic mice. Our results demonstrated that SMF significantly ameliorated the development of hepatic injury in obese and diabetic mice by inhibiting inflammatory level, improving glycolipid metabolism, regulating iron metabolism, balancing redox level and activating autophagy.

Unsupervised Hyperspectral Band Selection via Multimodal Evolutionary Algorithm and Subspace Decomposition.

Unsupervised band selection is an essential task to search for representative bands in hyperspectral dimension reduction. Most of existing studies utilize the inherent attribute of hyperspectral image (HSI) and acquire single optimal band subset while ignoring the diversity of subsets. Moreover, the ordered property in HSI is expected to be focused in order to avoid choosing redundant bands. In this paper, we proposed an unsupervised band selection method based on the multimodal evolutionary algorithm and subspace decomposition to alleviate the problems. To explore the diversity of band subsets, the multimodal evolutionary algorithm is first employed in spectral subspace decomposition to seek out multiple global or local solutions. Meanwhile, in view of ordered property, we concentrate more on increasing the difference between neighbor band subspaces. Furthermore, to utilize the obtained multiple diverse band subsets, an integrated utilization strategy is adopted to improve the predicted performance. Experimental results on three popular hyperspectral remote sensing datasets and one collected composition prediction dataset show the effectiveness of the proposed method, and the superiority over state-of-the-art methods on predicted accuracy.

Biological effects of rotating magnetic field: A review from 1969 to 2021.

As one of the common variable magnetic fields, rotating magnetic field (RMF) plays a crucial role in modern human society. The biological effects of RMF have been studied for over half a century, and various results have been discovered. Several reports have shown that RMF can inhibit the growth of various types of cancer cells in vitro and in vivo and improve clinical symptoms of patients with advanced cancer. It can also affect endogenous opioid systems and rhythm in central nerve systems, promote nerve regeneration and regulate neural electrophysiological activity in the human brain. In addition, RMF can influence the growth and metabolic activity of some microorganisms, alter the properties of fermentation products, inhibit the growth of some harmful bacteria and increase the susceptibility of antibiotic-resistant bacteria to common antibiotics. Besides, there are other biological effects of RMF on blood, bone, prenatal exposure, enzyme activity, immune function, aging, parasite, endocrine, wound healing, and plants. These discoveries demonstrate that RMF have great application potential in health care, medical treatment, fermentation engineering, and even agriculture. However, in some cases like pregnancy, RMF exposure may need to be avoided. Finally, the specific mechanisms of RMF's biological effects remain unrevealed, despite various hypotheses and theories. It does not prevent us from using it for our good.

Protein O-GlcNAcylation in cardiovascular diseases.

O-GlcNAcylation is a post-translational modification of protein in response to genetic variations or environmental factors, which is controlled by two highly conserved enzymes, i.e. O-GlcNAc transferase (OGT) and protein O-GlcNAcase (OGA). Protein O-GlcNAcylation mainly occurs in the cytoplasm, nucleus, and mitochondrion, and it is ubiquitously implicated in the development of cardiovascular disease (CVD). Alterations of O-GlcNAcylation could cause massive metabolic imbalance and affect cardiovascular function, but the role of O-GlcNAcylation in CVD remains controversial. That is, acutely increased O-GlcNAcylation is an adaptive heart response, which temporarily protects cardiac function. While it is harmful to cardiomyocytes if O-GlcNAcylation levels remain high in chronic conditions or in the long run. The underlying mechanisms include regulation of transcription, energy metabolism, and other signal transduction reactions induced by O-GlcNAcylation. In this review, we will focus on the interactions between protein O-GlcNAcylation and CVD, and discuss the potential molecular mechanisms that may be able to pave a new avenue for the treatment of cardiovascular events.

Antitumor effect and mechanism of FZD7 polypeptide vaccine.

The resistant cells that proliferate after radiotherapy and chemotherapy are primarily tumor stem cells with high stem marker expression, and their presence is the primary cause of tumor dispersion. The Wnt signaling receptor Frizzled family receptor 7 (FZD7) is linked to the maintenance of stem cell features as well as cancer progression. Frizzled-7 (FZD7), a key receptor for Wnt/-catenin signaling, is overexpressed in TNBC, suggesting that it could be a viable target for cancer therapy. We employed bioinformatics to find the best-scoring peptide, chemically synthesized FZD7 epitope antigen, and binding toll-like receptor 7 agonists (T7). Under GMP conditions, peptides for vaccines were produced and purified (>95%). In vivo and vitro tests were used to assess tumor cell inhibition. In vitro, the FZD7-T7 vaccination can boost the maturity of BMDC cells considerably. In mice, the FZD7 - T7 vaccine elicited the greatest immunological response. Significant tumor development inhibition was seen in BALB/c mice treated with FZD7 - T7 in prevention experiments (P < 0.01). Multiple cytokines that promote cellular immune responses, such as interferon (IFN)-γ (P < 0.05), interleukin (IL)-12 (P < 0.05), and IL-2 (P < 0.01), were shown to be considerably elevated in mice inoculated with FZD7- T7. Furthermore, we evaluated safety concerns in terms of vaccine composition to aid in the creation of successful next-generation vaccines. In conclusion, the FZD7-T7 vaccine can activate the immune response in vivo and in vitro, and play a role in tumor suppression. Our findings reveal a unique tumor-suppressive role for the FZD7 peptide in TNBC.

Percutaneous Pulmonary Angioplasty for Patients With Takayasu Arteritis and Pulmonary Hypertension.

BACKGROUND: Percutaneous transluminal pulmonary angioplasty (PTPA) is a treatment modality for chronic thromboembolic pulmonary hypertension, but whether it can be applied to Takayasu arteritis-associated pulmonary hypertension (TA-PH), another chronic obstructive pulmonary vascular disease, remains unclear. OBJECTIVES: This study sought to investigate the efficacy and safety of PTPA for TA-PH. METHODS: Between January 1, 2016, and December 31, 2019, a total of 50 patients with TA-PH who completed the PTPA procedure (the PTPA group) and 21 patients who refused the PTPA procedure (the non-PTPA group) were prospectively enrolled in this cohort study. The primary outcome was all-cause mortality. The safety outcomes included PTPA procedure-related complications. RESULTS: Baseline characteristics and medical therapies were similar between the PTPA group and the non-PTPA group. During a mean follow-up time of 37 ± 14 months, deaths occurred in 3 patients (6.0%) in the PTPA group and 6 patients (28.6%) in the non-PTPA group, contributing to the 3-year survival rate of 93.7% in the PTPA group and 76.2% in the non-PTPA group (P = 0.0096 for log-rank test). The Cox regression model showed that PTPA was associated with a significantly reduced hazard of all-cause mortality in TA-PH patients (HR: 0.18; 95% CI: 0.05-0.73; P = 0.017). No periprocedural death occurred. Severe complications requiring noninvasive positive pressure ventilation occurred in only 1 of 150 total sessions (0.7%). CONCLUSIONS: PTPA tended to be associated with a reduced risk of all-cause mortality with acceptable safety profiles and seemed to be a promising therapeutic option for TA-PH patients.

Calcium Sensing Receptor Variants Increase Pulmonary Hypertension Susceptibility.

BACKGROUND: Pulmonary arterial hypertension is an incurable disease, in which the extracellular CaSR (calcium sensing receptor) is mechanistically important. This study was aimed to genetically link the CaSR gene and function to the disease severity. METHODS: Sanger sequencing, Sugen/hypoxia pulmonary arterial hypertension rat model, CaSR mutated rat, transcriptional reporter assay and measurement of CaSR activity were used. RESULTS: Sanger sequencing identified a significant association between the variant rs1042636(A>G), located in CaSR exon 7, and idiopathic pulmonary arterial hypertension (IPAH) formation in patients. The frequency of 2968G homozygotes was higher in patients with IPAH compared with healthy individuals (23.6% versus 17.5%; P=0.001, OR=1.864), and the minor alleles of rs6776158, rs1048213, and rs9883099, located in CaSR promoter, raised the IPAH odds ratio to 2.173. Patients with IPAH carrying heterozygotes or homozygotes genotype of rs1042636 showed markedly higher pulmonary artery pressure and reduced survival compared with individuals carrying the wild-type allele. The minor alleles of rs6776158, rs1048213, and rs9883099 increased CaSR expression in reporter assay. In Sugen/hypoxia pulmonary arterial hypertension rats, the point mutation replicating rs1042636 found in IPAH exacerbated pulmonary arterial hypertension severity by promoting the overexpression and the enhanced activity of CaSR. CONCLUSIONS: Our functional genomic analysis thus indicates that the CaSR minor alleles of rs1042636, rs6776158, rs1048213, and rs9883099 contribute to the development and severity of IPAH. These findings may benefit clinical prognosis and treatment for IPAH.

Experimental animal models of pulmonary hypertension: Development and challenges.

Pulmonary hypertension (PH) is clinically divided into 5 major types, characterized by elevation in pulmonary arterial pressure (PAP) and pulmonary vascular resistance (PVR), finally leading to right heart failure and death. The pathogenesis of this arteriopathy remains unclear, leaving it impossible to target pulmonary vascular remodeling and reverse the deterioration of right ventricular (RV) function. Different animal models have been designed to reflect the complex mechanistic origins and pathology of PH, roughly divided into 4 categories according to the modeling methods: non-invasive models in vivo, invasive models in vivo, gene editing models, and multi-means joint modeling. Though each model shares some molecular and pathological changes with different classes of human PH, in most cases the molecular etiology of human PH is poorly known. The appropriate use of classic and novel PH animal models is essential for the hunt of molecular targets to reverse severe phenotypes.

Association Between Anticoagulation Outcomes and Venous Thromboembolism History in Chronic Thromboembolic Pulmonary Hypertension.

Background: The association between anticoagulation outcomes and prior history of venous thromboembolism (VTE) in chronic thromboembolic pulmonary hypertension (CTEPH) has not been established. This study aimed to compare the efficacy and safety of anticoagulation treatment in CTEPH patients with and without prior history of VTE. Methods: A total of 333 CTEPH patients prescribed anticoagulants were retrospectively included from May 2013 to April 2019. The clinical characteristics were collected at their first admission. Incidental recurrent VTE and clinically relevant bleeding were recorded during follow-up. The Cox proportional regression models were used to identify potential factors associated with recurrent VTE and clinically relevant bleeding. Results: Seventy patients (21%) without a prior history of VTE did not experience recurrent VTE during anticoagulation. Compared to CTEPH patients without a prior history of VTE, those with a prior history of VTE had an increased risk of recurrent VTE [2.27/100 person-year vs. 0/100 person-year; hazard ratio (HR), 8.92; 95% confidence interval (CI), 1.18-1142.00; P = 0.029] but a similar risk of clinically relevant bleeding (3.90/100 person-year vs. 4.59/100 person-year; HR, 0.83; 95% CI, 0.38-1.78; P = 0.623). Multivariate Cox analyses suggested that a prior history of VTE and interruption of anticoagulation treatments were significantly associated with an increased risk of recurrent VTE, while anemia and glucocorticoid use were significantly associated with a higher risk of clinically relevant bleeding. Conclusions: This study is the first to reveal that a prior history of VTE significantly increases the risk of recurrent VTE in CTEPH patients during anticoagulation treatment. This finding should be further evaluated in prospective studies.

Magnetic fields as a potential therapy for diabetic wounds based on animal experiments and clinical trials.

Diabetes mellitus (DM) is a chronic metabolic disorder with various complications that poses a huge worldwide healthcare burden. Wounds in diabetes, especially diabetic foot ulcers (DFUs), are difficult to manage, often leading to prolonged wound repair and even amputation. Wound management in people with diabetes is an extremely clinical and social concern. Nowadays, physical interventions gain much attention and have been widely developed in the fields of tissue regeneration and wound healing. Magnetic fields (MFs)-based devices are translated into clinical practice for the treatment of bone diseases and neurodegenerative disorder. This review attempts to give insight into the mechanisms and applications of MFs in wound care, especially in improving the healing outcomes of diabetic wounds. First, we discuss the pathological conditions associated with chronic diabetic wounds. Next, the mechanisms involved in MFs' effects on wounds are explored. At last, studies and reports regarding the effects of MFs on diabetic wounds from both animal experiments and clinical trials are reviewed. MFs exhibit great potential in promoting wound healing and have been practised in the management of diabetic wounds. Further studies on the exact mechanism of MFs on diabetic wounds and the development of suitable MF-based devices could lead to their increased applications into clinical practice.

Association between congenital thrombophilia and outcomes in pulmonary embolism patients.

The prevalence and distribution of congenital thrombophilia is still unclear in patients with pulmonary embolism (PE). We aimed to determine the prevalence and clinical characteristics of congenital thrombophilia in PE patients and their subsequent outcomes. A prospective observational study was conducted from May 2013 to June 2018. A total of 436 consecutive patients with PE were enrolled. All patients were tested for protein C, protein S, antithrombin III (ATIII), factor V Leiden, and prothrombin G20210A mutations. The median follow-up duration was ∼800 days (range, 11-1872 days). Congenital thrombophilia was diagnosed in 31 of 436 (7.1%) patients; 12 patients had protein C deficiency (2.8%), 13 had protein S deficiency (3.0%), 5 had ATIII deficiency (1.1%), and 1 had (0.2%) factor V Leiden. Age ≤50 years at the first episode (odds ratio [OR], 5.43; 95% confidence interval [CI], 2.35-13.52; P < .001) and male sex (OR, 2.67; 95% CI, 1.15-6.78; P = .03) were 2 independent predictors of congenital thrombophilia in PE patients. There was no statistically significant difference in the prevalence of congenital thrombophilia between PE patients with and without risk factors (P = .58). We also found no significant difference in the risk of having a composite outcome of death or recurrent venous thromboembolism between patients with and without congenital thrombophilia (hazard ratio, 0.18; 95% CI, 0.02-5.69; P = .08). These results suggest that age and male sex are independently associated with the occurrence of congenital thrombophilia in PE patients but that congenital thrombophilia is not associated with the risk of recurrence or death with anticoagulation therapy.

Directly targeting glutathione peroxidase 4 may be more effective than disrupting glutathione on ferroptosis-based cancer therapy.

BACKGROUND: Cancer is one of the major threats to human health and current cancer therapies have been unsuccessful in eradicating it. Ferroptosis is characterized by iron-dependence and lipid hydroperoxides accumulation, and its primary mechanism involves the suppression of system Xc--GSH (glutathione)-GPX4 (glutathione peroxidase 4) axis. Co-incidentally, cancer cells are also metabolically characterized by iron addiction and ROS tolerance, which makes them vulnerable to ferroptosis. This may provide a new tactic for cancer therapy. SCOPE OF REVIEW: The general features and mechanisms of ferroptosis, and the basis that makes cancer cells vulnerable to ferroptosis are described. Further, we emphatically discussed that disrupting GSH may not be ideal for triggering ferroptosis of cancer cells in vivo, but directly inhibiting GPX4 and its compensatory members could be more effective. Finally, the various approaches to directly inhibit GPX4 without disturbing GSH were described. MAJOR CONCLUSIONS: Targeting system Xc- or GSH may not effectively trigger cancer cells' ferroptosis in vivo the existence of other compensatory pathways. However, directly targeting GPX4 and its compensatory members without disrupting GSH may be more effective to induce ferroptosis in cancer cells in vivo, as GPX4 is essential in preventing ferroptosis. GENERAL SIGNIFICANCE: Cancer is a severe threat to human health. Ferroptosis-based cancer therapy strategies are promising, but how to effectively induce ferroptosis in cancer cells in vivo is still a question without clear answers. Thus, the viewpoints raised in this review may provide some references and different perspectives for researchers working on ferroptosis-based cancer therapy.