Deep Learning Model for Automatic Identification and Classification of Distal Radius Fracture.

Distal radius fracture (DRF) is one of the most common types of wrist fractures. We aimed to construct a model for the automatic segmentation of wrist radiographs using a deep learning approach and further perform automatic identification and classification of DRF. A total of 2240 participants with anteroposterior wrist radiographs from one hospital between January 2015 and October 2021 were included. The outcomes were automatic segmentation of wrist radiographs, identification of DRF, and classification of DRF (type A, type B, type C). The Unet model and Fast-RCNN model were used for automatic segmentation. The DenseNet121 model and ResNet50 model were applied to DRF identification of DRF. The DenseNet121 model, ResNet50 model, VGG-19 model, and InceptionV3 model were used for DRF classification. The area under the curve (AUC) with 95% confidence interval (CI), accuracy, precision, and F1-score was utilized to assess the effectiveness of the identification and classification models. Of these 2240 participants, 1440 (64.3%) had DRF, of which 701 (48.7%) were type A, 278 (19.3%) were type B, and 461 (32.0%) were type C. Both the Unet model and the Fast-RCNN model showed good segmentation of wrist radiographs. For DRF identification, the AUCs of the DenseNet121 model and the ResNet50 model in the testing set were 0.941 (95%CI: 0.926-0.965) and 0.936 (95%CI: 0.913-0.955), respectively. The AUCs of the DenseNet121 model (testing set) for classification type A, type B, and type C were 0.96, 0.96, and 0.96, respectively. The DenseNet121 model may provide clinicians with a tool for interpreting wrist radiographs.

High precision 3 × 3 coupler demodulation algorithm with an additional phase shift judgment module.

Ellipse fitting algorithms (EFAs) have been widely used in 3×3 coupler demodulation systems to reduce the requirement for symmetry of the 3×3 couplers. Based on the relative stability of the splitting ratio and phase difference after the establishment of the 3×3 coupler demodulation system, we solve the problem that EFA fails to work when the stimulating signal is small. Depending on the existence of a symmetry point about the origin, an additional phase shift judgment module is used to determine whether the Lissajous figure is larger than π rad. If the elliptical arc exceeds π rad, the EFA is executed. Otherwise, the previous parameters are used to correct the ellipse. Parameters are updated in real time to ensure high precision. The experimental results show that the total harmonic distortion (THD) of the ameliorated algorithm is improved by 1.28% compared to the EFA without the judgment module with a stimulus amplitude of 30 mV. The proposed scheme can effectively improve the dynamic range of the 3×3 coupler demodulation to reach 125.64 dB @ 1 kHz and 1% THD. The algorithm ensures the effective operation of the EFA under small phase shift conditions and improves the accuracy of phase demodulation.

Advanced glycation end product-modified low-density lipoprotein promotes pro-osteogenic reprogramming via RAGE/NF-κB pathway and exaggerates aortic valve calcification in hamsters.

BACKGROUND: Advanced glycation end product-modified low-density lipoprotein (AGE-LDL) is related to inflammation and the development of atherosclerosis. Additionally, it has been demonstrated that receptor for advanced glycation end products (RAGE) has a role in the condition known as calcific aortic valve disease (CAVD). Here, we hypothesized that the AGE-LDL/RAGE axis could also be involved in the pathophysiological mechanism of CAVD. METHODS: Human aortic valve interstitial cells (HAVICs) were stimulated with AGE-LDL following pre-treatment with or without interleukin 37 (IL-37). Low-density lipoprotein receptor deletion (Ldlr-/-) hamsters were randomly allocated to chow diet (CD) group and high carbohydrate and high fat diet (HCHFD) group. RESULTS: AGE-LDL levels were significantly elevated in patients with CAVD and in a hamster model of aortic valve calcification. Our in vitro data further demonstrated that AGE-LDL augmented the expression of intercellular cell adhesion molecule-1 (ICAM-1), interleukin-6 (IL-6) and alkaline phosphatase (ALP) in a dose-dependent manner through NF-κB activation, which was attenuated by nuclear factor kappa-B (NF-κB) inhibitor Bay11-7082. The expression of RAGE was augmented in calcified aortic valves, and knockdown of RAGE in HAVICs attenuated the AGE-LDL-induced inflammatory and osteogenic responses as well as NF-κB activation. IL-37 suppressed inflammatory and osteogenic responses and NF-κB activation in HAVICs. The vivo experiment also demonstrate that supplementation with IL-37 inhibited valvular inflammatory response and thereby suppressed valvular osteogenic activities. CONCLUSIONS: AGE-LDL promoted inflammatory responses and osteogenic differentiation through RAGE/NF-κB pathway in vitro and aortic valve lesions in vivo. IL-37 suppressed the AGE-LDL-induced inflammatory and osteogenic responses in vitro and attenuated aortic valve lesions in a hamster model of CAVD.

Noncoding RNA regulates the expression of Krm1 and Dkk2 to synergistically affect aortic valve lesions.

Calcific aortic valve disease (CAVD) is becoming an increasingly important global medical problem, but effective pharmacological treatments are lacking. Noncoding RNAs play a pivotal role in the progression of cardiovascular diseases, but their relationship with CAVD remains unclear. Sequencing data revealed differential expression of many noncoding RNAs in normal and calcified aortic valves, with significant differences in circHIPK3 and miR-182-5p expression. Overexpression of circHIPK3 ameliorated aortic valve lesions in a CAVD mouse model. In vitro experiments demonstrated that circHIPK3 inhibits the osteogenic response of aortic valve interstitial cells. Mechanistically, DEAD-box helicase 5 (DDX5) recruits methyltransferase 3 (METTL3) to promote the N6-methyladenosine (m6A) modification of circHIPK3. Furthermore, m6A-modified circHIPK3 increases the stability of Kremen1 (Krm1) mRNA, and Krm1 is a negative regulator of the Wnt/ß-catenin pathway. Additionally, miR-182-5p suppresses the expression of Dickkopf2 (Dkk2), the ligand of Krm1, and attenuates the Krm1-mediated inhibition of Wnt signaling. Activation of the Wnt signaling pathway significantly contributes to the promotion of aortic valve calcification. Our study describes the role of the Krm1-Dkk2 axis in inhibiting Wnt signaling in aortic valves and suggests that noncoding RNAs are upstream regulators of this process.

A new strategy for the treatment of middle ear infection using ciprofloxacin/amoxicillin-loaded ethyl cellulose/polyhydroxybutyrate nanofibers.

A middle ear infection occurs due to the presence of several microorganisms behind the eardrum (tympanic membrane) and is very challenging to treat due to its unique location and requires a well-designed treatment. If not treated properly, the infection can result in severe symptoms and unavoidable side effects. In this study, excellent biocompatible ethyl cellulose (EC) and biodegradable polyhydroxybutyrate (PHB) biopolymer were used to fabricate drug-loaded nanofiber scaffolds using an electrospinning technique to overcome antibiotic overdose and insufficient efficacy of drug release during treatment. PHB polymer was produced from Halomonas sp., and the purity of PHB was found to around be 90 %. Additionally, ciprofloxacin (CIP) and amoxicillin (AMX) are highly preferable since both drugs are highly effective against gram-negative and gram-positive bacteria to treat several infections. Obtained smooth nanofibers were between 116.24 and 171.82 nm in diameter and the addition of PHB polymer and antibiotics improved the morphology of the nanofiber scaffolds. Thermal properties of the nanofiber scaffolds were tested and the highest Tg temperature resulted at 229 °C. The mechanical properties of the scaffolds were tested, and the highest tensile strength resulted in 4.65 ± 6.33 MPa. Also, drug-loaded scaffolds were treated against the most common microorganisms that cause the infection, such as S.aureus, E.coli, and P.aeruginosa, and resulted in inhibition zones between 10 and 21 mm. MTT assay was performed by culturing human adipose-derived mesenchymal stem cells (hAD MSCs) on the scaffolds. The morphology of the hAD MSCs' attachment was tested with SEM analysis and hAD MSCs were able to attach, spread, and live on each scaffold even on the day of 7. The cumulative drug release kinetics of CIP and AMX from drug-loaded scaffolds were analysed in phosphate-buffered saline (pH: 7.4) within different time intervals of up to 14 days using a UV spectrophotometer. Furthermore, the drug release showed that the First-Order and Korsmeyer-Peppas models were the most suitable kinetic models. Animal testing was performed on SD rats, matrix and collagen deposition occurred on days 5 and 10, which were observed using Hematoxylin-eosin and Masson's trichrome staining. At the highest drug concentration, a better repair effect was observed. Results were promising and showed potential for novel treatment.

The clinical effect of unilateral decompressive laminectomy plus fusion with unilateral biportal endoscopic technique for single level lumbar spinal stenosis.

PURPOSE: This study aimed to compare and analyze the effectiveness of unilateral biportal endoscopic (UBE) decompressive laminectomy plus fusion and microscope-assisted open decompressive laminectomy plus fusion. METHODS: A total of 143 patients with lumbar spinal stenosis were enrolled in this study between March 2020 and February 2021 with a minimum 2 years follow-up visit to our hospital. Sixty-five patients underwent the unilateral biportal endoscopic technique and were assigned to the UBE group, and the remaining 78 patients with microscope assistant were assigned to the Microscope group. The baseline characteristics, clinical outcomes, and radiological data were retrospectively collected and analyzed, as well as Clinical outcomes, radiological data and complications. RESULTS: There were no significant differences between the two groups in terms of baseline characteristics (P > 0.05). The UBE group was demonstrated to be significantly superior in CRP, drainage, blood loss, treatment cost and Hospital stay than the Microscope group (P < 0.05), whereas a significant longer operation time was observed (P < 0.05). The VAS-B, ODI, and JOA-L scores of the UBE group at 1 year follow-up were significantly greater than those of the Microscope group (P < 0.05). Regarding radiological data, there were no significant differences in the section area of the spinal canal and fusion grade between the two groups (P > 0.05). CONCLUSION: In view of the satisfactory clinical outcomes of patients and notable decompression at the stenosed segment, UBE is a feasible, minimally invasive technique for single level lumbar canal stenosis.

α-Ketoglutarate improves cardiac insufficiency through NAD+-SIRT1 signaling-mediated mitophagy and ferroptosis in pressure overload-induced mice.

BACKGROUND: In heart failure (HF), mitochondrial dysfunction and metabolic remodeling lead to a reduction in energy productivity and aggravate cardiomyocyte injury. Supplementation with α-ketoglutarate (AKG) alleviated myocardial hypertrophy and fibrosis in mice with HF and improved cardiac insufficiency. However, the myocardial protective mechanism of AKG remains unclear. We verified the hypothesis that AKG improves mitochondrial function by upregulating NAD+ levels and activating silent information regulator 2 homolog 1 (SIRT1) in cardiomyocytes. METHODS: In vivo, 2% AKG was added to the drinking water of mice undergoing transverse aortic constriction (TAC) surgery. Echocardiography and biopsy were performed to evaluate cardiac function and pathological changes. Myocardial metabolomics was analyzed by liquid chromatography‒mass spectrometry (LC‒MS/MS) at 8 weeks after surgery. In vitro, the expression of SIRT1 or PINK1 proteins was inhibited by selective inhibitors and siRNA in cardiomyocytes stimulated with angiotensin II (AngII) and AKG. NAD+ levels were detected using an NAD test kit. Mitophagy and ferroptosis levels were evaluated by Western blotting, qPCR, JC-1 staining and lipid peroxidation analysis. RESULTS: AKG supplementation after TAC surgery could alleviate myocardial hypertrophy and fibrosis and improve cardiac function in mice. Metabolites of the malate-aspartate shuttle (MAS) were increased, but the TCA cycle and fatty acid metabolism pathway could be inhibited in the myocardium of TAC mice after AKG supplementation. Decreased NAD+ levels and SIRT1 protein expression were observed in heart of mice and AngII-treated cardiomyocytes. After AKG treatment, these changes were reversed, and increased mitophagy, inhibited ferroptosis, and alleviated damage in cardiomyocytes were observed. When the expression of SIRT1 was inhibited by a selective inhibitor and siRNA, the protective effect of AKG was suppressed. CONCLUSION: Supplementation with AKG can improve myocardial hypertrophy, fibrosis and chronic cardiac insufficiency caused by pressure overload. By increasing the level of NAD+, the SIRT-PINK1 and SIRT1-GPX4 signaling pathways are activated to promote mitophagy and inhibit ferroptosis in cardiomyocytes, which ultimately alleviates cardiomyocyte damage.

Identification of diagnostic immune-related gene biomarkers for predicting heart failure after acute myocardial infarction.

Post-myocardial infarction heart failure (HF) is a major public health concern. Previous studies have reported the critical role of immune response in HF pathogenesis. However, limited studies have reported predictive immune-associated biomarkers for HF. So we attempted to identify potential immune-related indicators for HF early diagnosis and therapy guidance. This study identified two potential immune-related hub genes (IRHGs), namely CXCR5 and FOS, using bioinformatic approaches. The expression levels of CXCR5 and FOS and their ability to predict long-term HF were analyzed. Functional enrichment analysis revealed that the hub genes were enriched in immune system processes, including the interleukin-17 and nuclear factor-kappa B signaling pathways, which are involved in the pathogenesis of HF. Quantitative real-time polymerase chain reaction revealed that the Fos mRNA levels, but not the Cxcr5 mRNA levels, were downregulated in the mice of the HF group. This study successfully identified two IRHGs that were significantly and differentially expressed in the HF group and could predict long-term HF, providing novel insights for future studies on HF and developing novel therapeutic targets for HF.

Targeted inhibition of PTPN22 is a novel approach to alleviate osteogenic responses in aortic valve interstitial cells and aortic valve lesions in mice.

BACKGROUND: Calcific aortic valve disease (CAVD) is the most prevalent valvular disease and has high morbidity and mortality. CAVD is characterized by complex pathophysiological processes, including inflammation-induced osteoblastic differentiation in aortic valve interstitial cells (AVICs). Novel anti-CAVD agents are urgently needed. Protein tyrosine phosphatase nonreceptor type 22 (PTPN22), an intracellular nonreceptor-like protein tyrosine phosphatase, is involved in several chronic inflammatory diseases, including rheumatoid arthritis and diabetes. However, it is unclear whether PTPN22 is involved in the pathogenesis of CAVD. METHODS: We obtained the aortic valve tissue from human and cultured AVICs from aortic valve. We established CAVD mice model by wire injury. Transcriptome sequencing, western bolt, qPCR, and immunofluorescence were performed to elucidate the molecular mechanisms. RESULTS: Here, we determined that PTPN22 expression was upregulated in calcific aortic valve tissue, AVICs treated with osteogenic medium, and a mouse model of CAVD. In vitro, overexpression of PTPN22 induced osteogenic responses, whereas siRNA-mediated PTPN22 knockdown abolished osteogenic responses and mitochondrial stress in the presence of osteogenic medium. In vivo, PTPN22 ablation ameliorated aortic valve lesions in a wire injury-induced CAVD mouse model, validating the pathogenic role of PTPN22 in CAVD. Additionally, we discovered a novel compound, 13-hydroxypiericidin A 10-O-α-D-glucose (1 → 6)-ß-D-glucoside (S18), in a marine-derived Streptomyces strain that bound to PTPN22 with high affinity and acted as a novel inhibitor. Incubation with S18 suppressed osteogenic responses and mitochondrial stress in human AVICs induced by osteogenic medium. In mice with aortic valve injury, S18 administration markedly alleviated aortic valve lesions. CONCLUSION: PTPN22 plays an essential role in the progression of CAVD, and inhibition of PTPN22 with S18 is a novel option for the further development of potent anti-CAVD drugs. Therapeutic inhibition of PTPN22 retards aortic valve calcification through modulating mitochondrial dysfunction in AVICs.

Comparison Between the Clinical Effect of Percutaneous Kyphoplasty for Osteoporosis Vertebral Compression Fracture Patient with or Without Sarcopenia: A Retrospective Cohort Study.

Background: Sarcopenia and osteoporosis vertebral compression fractures (OVCF) are common diseases that increase with age. This study aimed to investigate the effects of sarcopenia on OVCF patients after percutaneous kyphoplasty (PKP). Methods: Data of 101 patients who were treated with single-level PKP between January 2021 and March 2022 at Ningbo No.6 Hospital were enrolled. Forty-five OVCF patients with sarcopenia who met our inclusion criteria were included in the Sarcopenia-PKP group (SPKP group), and 56 patients in the Normal-PKP group (NPKP group). All clinical and radiological data were collected from medical records. Baseline characteristics, operation-related parameters (operation time, time to ambulation, hospital stay, surgery segment), clinical outcomes (visual analog score [VAS], Oswestry Disability Index [ODI], Japanese Orthopaedic Association Scores [JOA] of lumber), radiological outcomes (vertebral anterior height rate and local kyphosis angle), Macnab score, and complications were evaluated and compared. Results: There were no significant differences in age, sex, surgical segment preoperative VAS score, ODI, or JOA between the two groups (P > 0.05). The SPKP group had a significantly lower body mass index (BMI), bone mineral density (BMD), and smooth muscle index (SMI) than the NPKP group (P < 0.05). Significantly longer hospital stays and time to ambulation in SPKP group than NPKP group (3.7±0.8 vs 3.4±0.5 and 2.0±0.8 vs 1.6±0.5, P < 0.05). In SPKP group, significantly better clinical outcomes at 6- and 12-months follow-up were observed in NPKP group than SPKP group (P < 0.05), and NPKP group showed significantly better in vertebral anterior height rates than SPKP group after 6-month follow-up (P < 0.05). Moreover, there were significantly more cases of complications in the SPKP group (P < 0.05). Conclusion: Sarcopenia could reduce the clinical effect of percutaneous kyphoplasty, and furthermore. Related studies are needed to verify the effect of sarcopenia on OVCF patients.

Activation of Piezo1 promotes osteogenic differentiation of aortic valve interstitial cell through YAP-dependent glutaminolysis.

Hemodynamic overload and dysregulation of cellular metabolism are involved in development of calcific aortic valve disease (CAVD). However, how mechanical stress relates to metabolic changes in CAVD remains unclear. Here, we show that Piezo1, a mechanosensitive ion channel, regulated glutaminase 1 (GLS1)-mediated glutaminolysis to promote osteogenic differentiation of valve interstitial cells (VICs). In vivo, two models of aortic valve stenosis were constructed by ascending aortic constriction (AAC) and direct wire injury (DWI). Inhibition of Piezo1 and GLS1 in these models respectively mitigated aortic valve lesion. In vitro, Piezo1 activation induced by Yoda1 and oscillatory stress triggered osteogenic responses in VICs, which were prevented by Piezo1 inhibition or knockdown. Mechanistically, Piezo1 activation promoted calcium-dependent Yes-associated protein (YAP) activation. YAP modulated GLS1-mediated glutaminolysis, which enhanced osteogenic differentiation through histone acetylation of runt-related transcription factor 2 (RUNX2) promoters. Together, our work provided a cross-talk between mechanotransduction and metabolism in the context of CAVD.

Comparison of staged lateral lumbar interbody fusion combined two-stage posterior screw fixation and two osteotomy strategies for adult degeneration scoliosis: a retrospective comparative study.

AIMS: The commonly used treatments of adult degeneration scoliosis (ADS) were posterior long segment screw fixation with osteotomies. Recently, lateral lumbar intervertebral fusion combined two-stage posterior screw fixation (LLIF + PSF) as a new strategy without osteotomy. Herein, this study aimed to compare the clinical and radiological outcomes among LLIF + PSF and pedicle subtraction osteotomy (PSO), posterior column osteotomies (PCO). METHODS: Totals of 139 ADS patients underwent operation with 2 years longer follow-up visit between January 2013 and January 2018 in Ningbo No.6 Hospital were enrolled into this study. 58 patients were included in PSO group, 45 in PCO group and 36 in LLIF + PSF group, The clinical and radiological data were reviewed from medical records. Baseline characteristic, perioperative radiological data (sagittal vertical axis (SVA), coronal balance (CB), Cobb angle of Mian curve (MC), Lumbar lordosis (LL), pelvic tilt (PT) and pelvic incidence-lumbar lordosis mismatch (PI-LL)), clinical outcomes (VAS of back and leg, Oswestry disability index (ODI) and Scoliosis Research Society 22-question Questionnaire (SRS-22)) and complications were evaluated and compared. RESULT: There were no significantly difference in baseline characteristics, preoperative radiological parameters and clinical outcomes among three groups. LLIF + PSF group was significantly shorter in operation time than other two groups (P < 0.05), whereas significant longer hospital stay was observed in LLIF + PSF group (P < 0.05). As for radiological parameters, LLIF + PSF group had significantly improvement in SVA, CB, MC, LL and PI-LL (P < 0.05). Moreover, LLIF + PSF group achieved significantly less correction loss in SVA, CB and PT than PSO and PCO group (1.5 ± 0.7 VS 2.0 ± 0.9 VS 2.2 ± 0.8, P < 0.05; 1.0 ± 0.4 VS 1.3 ± 0.5 VS 1.1 ± 0.7, P < 0.05 and 4.2 ± 2.8 VS 7.2 ± 3.1 VS 6.0 ± 2.8, P < 0.05). Significantly recovery in VAS of back and leg, ODI score and SRS-22 were found among all groups, however, LLIF + PSF shown significant better clinical therapy maintain at follow-up visit than other two groups (P < 0.05). There were no significantly difference in complications among groups (P = 0.66). CONCLUSION: Lateral lumbar interbody fusion combined two-stage posterior screw fixation (LLIF + PSF) can achieve comparable clinical therapy for adult degeneration scoliosis as osteotomy strategies. However, furthermore more studies need be taken for verifying the effect of LLIF + PSF in the future.

Metformin Collaborates with PINK1/Mfn2 Overexpression to Prevent Cardiac Injury by Improving Mitochondrial Function.

Both mitochondrial quality control and energy metabolism are critical in maintaining the physiological function of cardiomyocytes. When damaged mitochondria fail to be repaired, cardiomyocytes initiate a process referred to as mitophagy to clear defective mitochondria, and studies have shown that PTEN-induced putative kinase 1 (PINK1) plays an important role in this process. In addition, previous studies indicated that peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) is a transcriptional coactivator that promotes mitochondrial energy metabolism, and mitofusin 2 (Mfn2) promotes mitochondrial fusion, which is beneficial for cardiomyocytes. Thus, an integration strategy involving mitochondrial biogenesis and mitophagy might contribute to improved cardiomyocyte function. We studied the function of PINK1 in mitophagy in isoproterenol (Iso)-induced cardiomyocyte injury and transverse aortic constriction (TAC)-induced myocardial hypertrophy. Adenovirus vectors were used to induce PINK1/Mfn2 protein overexpression. Cardiomyocytes treated with isoproterenol (Iso) expressed high levels of PINK1 and low levels of Mfn2, and the changes were time dependent. PINK1 overexpression promoted mitophagy, attenuated the Iso-induced reduction in MMP, and reduced ROS production and the apoptotic rate. Cardiac-specific overexpression of PINK1 improved cardiac function, attenuated pressure overload-induced cardiac hypertrophy and fibrosis, and facilitated myocardial mitophagy in TAC mice. Moreover, metformin treatment and PINK1/Mfn2 overexpression reduced mitochondrial dysfunction by inhibiting ROS generation leading to an increase in both ATP production and mitochondrial membrane potential in Iso-induced cardiomyocyte injury. Our findings indicate that a combination strategy may help ameliorate myocardial injury by improving mitochondrial quality.

Association between urinary biomarkers of polycyclic aromatic hydrocarbons and severe abdominal aortic calcification in adults: data from the National Health and Examination Nutrition Survey.

OBJECTIVE: Recent studies have found that polycyclic aromatic hydrocarbons (PAHs) exposure may increase the risk of cardiovascular disease. The present study aimed to explore the association between PAHs exposure and severe abdominal aortic calcification (AAC) in adults. METHODS: Data were collected from the 2013-2014 National Health and Nutrition Examination Survey. PAHs exposure was analyzed from urinary mono hydroxylated metabolites of PAHs. Logistic regression models and subgroup analysis were performed to explore the association of PAHs exposure with severe AAC prevalence. RESULTS: A total of 1,005 eligible individuals were recruited into the study. After adjusting for confounding factors, those with the highest quartiles of 1-hydroxynaphthalene (1-NAP: OR 2.19, 95% CI 1.03-4.68, Pfor trend < 0.001), 2-hydroxynaphthalene (2-NAP: OR 2.22, 95% CI 1.04-4.64, Pfor trend < 0.001) and 1-hydroxypyrene (1-PYR: OR 2.15, 95% CI 1.06-4.33, Pfor trend < 0.001) were associated with an increased prevalence of severe AAC in the adults compared to those who in the lowest quartile. CONCLUSION: This study found that urinary 1-NAP, 2-NAP and 1-PYR were positively associated with severe AAC prevalence in adults.

Clinical performance and quality measures for heart failure management in China: the China-Heart Failure registry study.

AIMS: Heart failure (HF) remains a major public health problem with increasing prevalence in China. This study evaluated the clinical performance and quality measures for HF management to identify gaps in the standardization of care for patients hospitalized for HF in China. METHODS AND RESULTS: Following the results of China-HF stage I (2012-2015), the second stage of the China-HF was launched in 2017. Among 113 hospitals with ≥100 cases, the China-HF Stage II assessed the quality of care measures for HF and compared results with previous data in China and the US-based Get with The Guidelines-Heart Failure (GWTG-HF) registries. In total, 34 938 patients hospitalized with HF were enrolled from January 2017 to October 2020. Echocardiographic left ventricular function and natriuretic peptide test were performed in 93.7% and 93.0% of the cases, respectively. Adherence to standardized guidelines in China-HF stage II was higher than that in the China-HF stage I, but generally lower than GWTG-HF registry with 78.2% of eligible patients was prescribed oral diuretics, 78.7% renin-angiotensin-system inhibitors, and 82.2% beta-blockers. Implantable cardioverter-defibrillators and cardiac resynchronization devices were implanted in 3.9% and 14.6%, respectively. In contrast, the proportion of eligible patients discharged with spironolactone (87.8%) was higher than GWTG-HF. The median length of hospitalization was 9 (6, 12) days, and 938 (2.8%) patients died or withdrew from treatment during hospitalization. CONCLUSIONS: Despite significant improvements in the use of guideline-recommended testing and therapy, there remain major gaps in quality of care for patients hospitalized for HF in China that are generally larger than gaps observed in the United States.

Abnormally elevated EZH2-mediated H3K27me3 enhances osteogenesis in aortic valve interstitial cells by inhibiting SOCS3 expression.

BACKGROUND AND AIMS: The osteogenic transition of aortic valve interstitial cells (AVICs) plays a critical role for the progression of calcific aortic valve disease (CAVD). Enhancer of zeste homolog 2 (EZH2) is an important methyltransferase for histone H3 Lys27 (H3K27) that has been found to be involved in osteogenesis. Here, we investigated the effect and mechanism of EZH2 in CAVD progression. METHODS: High throughout mRNA sequencing, qRT-PCR and immunoblot were performed to screen differentially expressed genes in non-CAVD and CAVD aortic valves. To investigate the role of EZH2 and SOCS3 in osteogenesis, AVICs were treated with siRNA, adenovirus and specific inhibitors, then osteogenic markers and mineralized deposits were examined. In vivo, the morphology and function of aortic valves were investigated by HE stain and echocardiography in ApoE-/- mice fed a long-term western diet (WD). RESULTS: We discovered that EZH2 was upregulated and SOCS3 was downregulated in calcified aortic valves. In AVICs, inhibition or silencing of EZH2 attenuated the osteogenic responses. On the other hand, demethylases inhibitor (GSK-J4) enhanced osteogenic transition of AVICs. Moreover, SOCS3 knockdown enhanced the expression of osteogenic markers, while SOCS3 overexpression suppressed osteogenesis and calcification. The chromatin immunoprecipitation and restored experiments indicated that EZH2 directly targeted SOCS3 to promote osteogenic responses of AVICs. In vivo, treatment with EZH2 inhibitor through intraperitoneal injection attenuated aortic valve thickening, calcification and dysfunction induced by WD. CONCLUSIONS: Collectively, we found that EZH2-mediated H3K27me3 enhanced osteogenesis and microcalcification of AVICs via inhibiting SOCS3 expression, which provides potential targets for future therapeutic interventions of CAVD.

Machine learning models in heart failure with mildly reduced ejection fraction patients.

Objective: Heart failure with mildly reduced ejection fraction (HFmrEF) has been recently recognized as a unique phenotype of heart failure (HF) in current practical guideline. However, risk stratification models for mortality and HF re-hospitalization are still lacking. This study aimed to develop and validate a novel machine learning (ML)-derived model to predict the risk of mortality and re-hospitalization for HFmrEF patients. Methods: We assessed the risks of mortality and HF re-hospitalization in HFmrEF (45-49%) patients enrolled in the TOPCAT trial. Eight ML-based models were constructed, including 72 candidate variables. The Harrell concordance index (C-index) and DeLong test were used to assess discrimination and the improvement in discrimination between models, respectively. Calibration of the HF risk prediction model was plotted to obtain bias-corrected estimates of predicted versus observed values. Results: Least absolute shrinkage and selection operator (LASSO) Cox regression was the best-performing model for 1- and 6-year mortality, with a highest C-indices at 0.83 (95% CI: 0.68-0.94) over a maximum of 6 years of follow-up and 0.77 (95% CI: 0.64-0.89) for the 1-year follow-up. The random forest (RF) showed the best discrimination for HF re-hospitalization, scoring 0.80 (95% CI: 0.66-0.94) and 0.85 (95% CI: 0.71-0.99) at the 6- and 1-year follow-ups, respectively. For risk assessment analysis, Kansas City Cardiomyopathy Questionnaire (KCCQ) subscale scores were the most important predictor of readmission outcome in the HFmrEF patients. Conclusion: ML-based models outperformed traditional models at predicting mortality and re-hospitalization in patients with HFmrEF. The results of the risk assessment showed that KCCQ score should be paid increasing attention to in the management of HFmrEF patients.

Hesperetin, a Promising Dietary Supplement for Preventing the Development of Calcific Aortic Valve Disease.

BACKGROUND: No effective therapeutic agents for calcific aortic valve disease (CAVD) are available currently. Dietary supplementation has been proposed as a novel treatment modality for various diseases. As a flavanone, hesperetin is widely abundant in citrus fruits and has been proven to exert protective effects in multiple diseases. However, the role of hesperetin in CAVD remains unclear. METHODS: Human aortic valve interstitial cells (VICs) were isolated from aortic valve leaflets. A mouse model of aortic valve stenosis was constructed by direct wire injury (DWI). Immunoblotting, immunofluorescence staining, and flow cytometry were used to investigate the roles of sirtuin 7 (Sirt7) and nuclear factor erythroid 2-related factor 2 (Nrf2) in hesperetin-mediated protective effects in VICs. RESULTS: Hesperetin supplementation protected the mice from wire-injury-induced aortic valve stenosis; in vitro, hesperetin inhibited the lipopolysaccharide (LPS)-induced activation of NF-κB inflammatory cytokine secretion and osteogenic factors expression, reduced ROS production and apoptosis, and abrogated LPS-mediated injury to the mitochondrial membrane potential and the decline in the antioxidant levels in VICs. These benefits of hesperetin may have been obtained by activating Nrf2-ARE signaling, which corrected the dysfunctional mitochondria. Furthermore, we found that hesperetin could directly bind to Sirt7 and that the silencing of Sirt7 decreased the effects of hesperetin in VICs and potently abolished the ability of hesperetin to increase Nrf2 transcriptional activation. CONCLUSIONS: Our work demonstrates that hesperetin plays protective roles in the aortic valve through the Sirt7-Nrf2-ARE axis; thus, hesperetin might be a potential dietary supplement that could prevent the development of CAVD.

Comparison of Percutaneous Endoscopic Cervical Keyhole Foraminotomy versus Microscopic Anterior Cervical Discectomy and Fusion for Single Level Unilateral Cervical Radiculopathy.

Objective: To compare the clinical and radiological outcomes between microscopic anterior cervical discectomy and fusion (ACDF) and percutaneous endoscopic cervical keyhole foraminotomy (PECF) for single level unilateral cervical radiculopathy. Methods: A total of 127 patients (59 in PECF VS 68 in ACDF) were enrolled in this study from April 2016 to May 2018 with a minimum follow-up of 2 years. Clinical data including baseline data, Neck Disability Index (NDI), and Visual Analogue Scale for neck and arm (VAS-n, VAS-a) were collected and compared. Radiological evaluation such as disc height, ROM of cervical, Cobb's angle of cervical and Cobb's angle of operated segment was measured by two experienced radiologists in twice. Results: There was no significant difference between the two groups in the baseline data, and hospital stay was significantly decreased in PECF group than ACDF group (P < 0.001). PECF group did not yield superior better outcomes in NDI, VAS-a and VAS-n than ACDF group except at 1-month follow-up. As for radiological outcomes, PECF group has significantly better cervical motion, cervical angle and segmental angle than ADCF group at 12- and 24-month follow-up visit (P < 0.05); however, ACDF had shown better disc height restoration and maintenance than PECF (P < 0.05). More complications including surface hematoma and swallowing difficulty were occurred in ADCF group. Conclusion: Percutaneous endoscopic cervical keyhole foraminotomy could be the alternative method for anterior cervical discectomy and fusion in selective cases. However, the indication should be fulfilled, more studies need to be conducted to further testify the efficacy of PECF.