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1.
Artigo em Inglês | MEDLINE | ID: mdl-33788674

RESUMO

Genome-wide association studies (GWASs) have identified dozens of loci associated with risk of chronic obstructive pulmonary disease (COPD). However, identifying the causal variants and their functional role in the appropriate cell type remains a major challenge. We aimed to identify putative causal variants in 82 GWAS loci associated with COPD susceptibility and predict the regulatory impact of these variants in lung cell types. We used an integrated approach featuring statistical fine-mapping, open chromatin profiling, and machine learning to identify functional variants. We generated chromatin accessibility data using the assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) for human primary lung cell types implicated in COPD pathobiology. We then evaluated the enrichment of COPD risk variants in lung-specific open chromatin regions (OCRs) and generated cell type-specific regulatory predictions for >6,500 variants corresponding to 82 COPD GWAS loci. Integration of the fine-mapped variants with lung OCRs helped prioritize 22 variants in putative regulatory elements with potential functional effects. Comparison to functional predictions from 222 ENCODE cell samples revealed cell type-specific regulatory effects of COPD variants in lung epithelium, endothelium, and immune cells. We identified potential causal variants for COPD risk by integrating fine-mapping in GWAS loci with cell-specific regulatory profiling, highlighting the importance of leveraging chromatin status in relevant cell types to predict the molecular effects of risk variants in lung disease.

2.
Sci Rep ; 11(1): 5938, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33723369

RESUMO

Obstructive sleep apnea syndrome (OSAS) is underdiagnosed in females and gender differences in clinical and polysomnographic findings have not been widely investigated in China. We examined clinical and polysomnographic differences between males and females with OSAS in order to determine the influence of gender on clinical presentation and polysomnographic features. Data were collected from 303 adult patients diagnosed with OSAS (237 males and 66 females) from 2017 to 2019. All the patients completed physical examination, Epworth sleepiness scale, and whole night polysomnography. AVONA, univariate and multivariate logistic regression analyses were conducted to assess gender differences of clinical and polysomnographic findings with OSAS. P < 0.05 was statistically significant. The average age was 48.4 ± 12.6 years for females and 43.4 ± 12.4 years for males. Compared with female patients with OSAS, male patients were taller and heavier, had higher systolic blood pressure in the morning, shorter duration of slow wave sleep, more micro-arousal events, greater AHI, and more complex sleep apnea events. There are obvious gender differences of clinical and polysomnographic characteristics with OSAS. Understanding gender differences will contribute to better clinical recognition of OSAS in females as well as the provision of proper health care and therapeutic practice.

3.
Int Wound J ; 2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33666348

RESUMO

Hypertrophic scar (HS) is a fibrotic skin disease characterised by over-productive collagen and excessive inflammatory reaction, which can be functionally and cosmetically problematic. A scar-prone constitute will accelerate HS formation and functional disorder, which deserves systemic therapy with oral medicine. To examine the oral therapeutic effectiveness on HS with convincing evidence of gross view and histological improvement, a rabbit ear HS model was employed with oral administration of asiaticoside (AS) at the doses of 12 and 24 mg kg-1 d-1 daily for 60 consecutive days. Gross observation and histological findings showed that oral AS treatment could significantly inhibit HS formation in a dose dependent manner. Semi-quantification of scar elevation index at days 7, 15, 30, and 60, and quantitative polymerase chain reaction at days 30 and 60 also provided the evidences of reduced scar thickness and inhibited fibrotic gene expressions of collagens I, III, TGF-ß1, interleukins 1ß, 6 and 8, and enhanced gene expression of SMAD 7 and PPAR-γ with a dose-dependent manner. These results indicated that AS is likely to serve as a systemic therapeutic agent of HS treatment for those who may have scar-prone constitute via anti-inflammation, inhibiting fibrotic process, and enhancing matrix degradation.

4.
J Cell Mol Med ; 2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33733611

RESUMO

Under steady-state conditions, the pool size of peripheral CD8+ T cells is maintained through turnover and survival. Beyond TCR and IL-7R signals, the underlying mechanisms are less well understood. In the present study, we found a significant reduction of CD8+ T cell proportion in spleens but not in thymi of mice with T cell-specific deletion of Mediator Subunit 1 (Med1). A competitive transfer of wild-type (WT) and Med1-deficient CD8+ T cells reproduced the phenotype in the same recipients and confirmed intrinsic role of Med1. Furthermore, we observed a comparable degree of migration and proliferation but a significant increase of cell death in Med1-deficient CD8+ T cells compared with WT counterparts. Finally, Med1-deficient CD8+ T cells exhibited a decreased expression of interleukin-7 receptor α (IL-7Rα), down-regulation of phosphorylated-STAT5 (pSTAT5) and Bim up-regulation. Collectively, our study reveals a novel role of Med1 in the maintenance of CD8+ T cells through IL-7Rα/STAT5 pathway-mediated cell survival.

6.
Bioorg Chem ; 109: 104740, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33626453

RESUMO

Six new non-classical cardenolides (1-6), and seventeen known ones (7-23) were isolated from Calotropis gigantea. All cardenolides showed inhibitory effect on hypoxia inducible factor-1 (HIF-1) transcriptional activity with IC50 of 8.85 nM-16.69 µM except 5 and 7. The novel 19-dihydrocalotoxin (1) exhibited a comparable HIF-1 inhibitory activity (IC50 of 139.57 nM) to digoxin (IC50 of 145.77 nM), a well-studied HIF-1 inhibitor, and 11, 12, 14, 16 and 19 presented 1.4-15.4 folds stronger HIF-1 inhibition than digoxin. 1 and 11 showed a dose-dependent inhibition on HIF-1α protein, which led to their HIF-1 suppressing effects. Compared with LO2 and H9c2 normal cell lines, both 1 and 11 showed selective cytotoxicity against various cancer cell lines including HCT116, HeLa, HepG2, A549, MCF-7, A2780 and MDA-MB-231. Moreover, a comprehensive structure-activity relationship was concluded for these non-classical cardenolides as HIF-1 inhibitors, which may shed some light on the rational design and development of cardenolide-based anticancer drugs.

7.
Europace ; 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33604602

RESUMO

AIMS: This study aimed to investigate possible roles and underlying mechanisms of alpha-adrenoceptor coupled signalling for the pathogenesis of Takotsubo syndrome (TTS). METHODS AND RESULTS: Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were treated with a toxic concentration of epinephrine (Epi, 0.5 mM for 1 h) to mimic the setting of TTS. Patch-clamp technique, polymerase chain reaction (PCR) and Fluorescence-activated cell sorting (FACS) were employed for the study. High concentration Epi suppressed the depolarization velocity, prolonged duration of action potentials and induced arrhythmic events in hiPSC-CMs. The Epi effects were attenuated by an alpha-adrenoceptor blocker (phentolamine), suggesting involvement of alpha-adrenoceptor signalling in arrhythmogenesis related to QT interval prolongation in the setting of TTS. An alpha 1-adrenoceptor agonist (phenylephrine) but not an alpha 2-adrenoceptor agonist (clonidine) mimicked Epi effects. Epi enhanced ROS production, which could be attenuated by the alpha- adrenoceptor blocker. Treatment of cells with H2O2 (100 µM) mimicked the effects of Epi on action potentials and a reactive oxygen species (ROS)-blocker (N-acetyl-I-cysteine, 1 mM) prevented the Epi effects, indicating that the ROS signalling is involved in the alpha-adrenoceptor actions. Nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) oxidases were involved in alpha 1-adrenoceptor signalling. A protein kinase C (PKC) blocker suppressed the effects of Epi, phenylephrine and ROS as well, implying that PKC participated in alpha 1-adrenoceptor signalling and acted as a downstream factor of ROS. The abnormal action potentials resulted from alpha 1-adrenoceptor activation-induced dysfunctions of ion channels including the voltage-dependent Na+ and L-type Ca2+ channels. CONCLUSIONS: Alpha 1-adrenoceptor signalling plays important roles for arrhythmogenesis of TTS. Alpha-adrenoceptor blockers might be clinically helpful for treating arrhythmias in patients with TTS.

9.
Biomed Res Int ; 2021: 5320941, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33490271

RESUMO

Objective: Mesothelioma (MESO) is a rare tumor derived from mesothelium cells. The aim of this study was to explore key candidate genes and potential molecular mechanisms for mesothelioma through bioinformatics analysis. Methods: The MESO expression profiles came from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. The differences in the infiltration levels of immune cells between MESO and normal tissues were assessed using CIBERSORT. Differentially expressed genes (DEGs) were identified by comprehensive analysis of multiple datasets. A protein-protein interaction (PPI) network was constructed, and a hub gene COL1A1 was selected for MESO. The expression and mutation of COL1A1 in MESO were analyzed in the cBioPortal database. The correlation between COL1A1 expression and immune cell infiltration was evaluated using the TIMER database. Gene Set Enrichment Analysis (GSEA) of COL1A1 was then performed. Finally, Kaplan-Meier survival analysis was presented to predict the survival times between high and low COL1A1 expression groups for MESO patients. Results: There were distinct differences in the infiltration levels of immune cells between MESO and normal tissues. A total of 118 DEGs were identified by comprehensively analyzing three expression profile datasets. COL1A1, a hub gene, was identified to be highly expressed in MESO compared to normal tissues. COL1A1 genetic mutation occurred in 9% of MESO samples, and amplification was the most common type of mutation. COL1A1 expression was significantly correlated to the infiltration levels of CD4+ T cells, macrophages, and neutrophils. GSEA results indicated that COL1A1 could be involved in key biological processes and pathways like extracellular matrix and PI3K-Akt pathway. Patients with high COL1A1 expression usually experienced shorten overall survival time than those with its low expression. Conclusion: Our findings revealed that COL1A1 could become a potential prognostic biomarker for MESO, which was significantly related to immune cell infiltration.

10.
Brief Bioinform ; 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33401309

RESUMO

A-to-I RNA editing, contributing to nearly 90% of all editing events in human, has been reported to involve in the pathogenesis of Alzheimer's disease (AD) due to its roles in brain development and immune regulation, such as the deficient editing of GluA2 Q/R related to cell death and memory loss. Currently, there are urgent needs for the systematic annotations of A-to-I RNA editing events in AD. Here, we built ADeditome, the annotation database of A-to-I RNA editing in AD available at https://ccsm.uth.edu/ADeditome, aiming to provide a resource and reference for functional annotation of A-to-I RNA editing in AD to identify therapeutically targetable genes in an individual. We detected 1676 363 editing sites in 1524 samples across nine brain regions from ROSMAP, MayoRNAseq and MSBB. For these editing events, we performed multiple functional annotations including identification of specific and disease stage associated editing events and the influence of editing events on gene expression, protein recoding, alternative splicing and miRNA regulation for all the genes, especially for AD-related genes in order to explore the pathology of AD. Combing all the analysis results, we found 108 010 and 26 168 editing events which may promote or inhibit AD progression, respectively. We also found 5582 brain region-specific editing events with potentially dual roles in AD across different brain regions. ADeditome will be a unique resource for AD and drug research communities to identify therapeutically targetable editing events. Significance: ADeditome is the first comprehensive resource of the functional genomics of individual A-to-I RNA editing events in AD, which will be useful for many researchers in the fields of AD pathology, precision medicine, and therapeutic researches.

11.
Brief Bioinform ; 2021 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-33497435

RESUMO

Exon skipping (ES), the most common alternative splicing event, has been reported to contribute to diverse human diseases due to the loss of functional domains/sites or frameshifting of the open reading frame (ORF) and noticed as therapeutic targets. Accumulating transcriptomic studies of aging brains show the splicing disruption is a widespread hallmark of neurodegenerative diseases such as Alzheimer's disease (AD). Here, we built ExonSkipAD, the ES annotation database aiming to provide a resource/reference for functional annotation of ES events in AD and identify therapeutic targets in exon units. We identified 16 414 genes that have ~156 K, ~ 69 K, ~ 231 K ES events from the three representative AD cohorts of ROSMAP, MSBB and Mayo, respectively. For these ES events, we performed multiple functional annotations relating to ES mechanisms or downstream. Specifically, through the functional feature retention studies followed by the open reading frames (ORFs), we identified 275 important cellular regulators that might lose their cellular regulator roles due to exon skipping in AD. ExonSkipAD provides twelve categories of annotations: gene summary, gene structures and expression levels, exon skipping events with PSIs, ORF annotation, exon skipping events in the canonical protein sequence, 3'-UTR located exon skipping events lost miRNA-binding sites, SNversus in the skipped exons with a depth of coverage, AD stage-associated exon skipping events, splicing quantitative trait loci (sQTLs) in the skipped exons, correlation with RNA-binding proteins, and related drugs & diseases. ExonSkipAD will be a unique resource of transcriptomic diversity research for understanding the mechanisms of neurodegenerative disease development and identifying potential therapeutic targets in AD. Significance AS the first comprehensive resource of the functional genomics of the alternative splicing events in AD, ExonSkipAD will be useful for many researchers in the fields of pathology, AD genomics and precision medicine, and pharmaceutical and therapeutic researches.

12.
Artigo em Inglês | MEDLINE | ID: mdl-33200710

RESUMO

BACKGROUND: CYP1B1 is recognized as a valuable target for chemotherapy. It catalyzes the bioactivation of naphthoquinone oximes within certain cancer cell lines. However, the expression level of CYP1B1 in melanoma and the functional role regulating the activity of DMAKO-20 as a representative naphthoquinone oxime against skin carcinoma is still unknown. OBJECTIVE: We sought to examine the expression level of CYP1B1 in melanoma and explore the molecular mechanism behind the anticancer effects of DMAKO-20 in melanoma. METHODS: CYP1B1 expression levels in paraffin specimens taken from melanoma patients, and its expression levels in B16/F10 cancer cells were investigated using immunohistochemical staining. The molecular mechanisms behind DMAKO20 activity against melanoma was investigated by using cytotoxicity, cell scratching, apoptotic, and immunoblotting assays. RESULTS: CYP1B1, the P450 isoform was expressed at high levels in melanoma tissues and cultured B16/F10 cells, but was undetectable in normal tissues or fibroblasts. In cell proliferation assays, the shikonin oxime DMAKO-20 exhibited potent and selective antiproliferative effects against B16/F10 melanoma cells and inhibited migration. Several mechanisms for the anticancer effects of DMAKO-20 have been identified in B16/F10 melanoma cells, including apoptosis, upregulation of mitochondrial apoptotic Bax proteins and downregulation of anti-apoptotic Bcl-2. The results from these mechanistic investigations indicated that DMAKO-20 underwent CYP1B1-mediated metabolic activation to activate anticancer metabolites within melanoma cells. CONCLUSION: DMAKO-20 exhibited a selective cytotoxic effect on melanoma cells through CYP1B1-mediated activation. Using DMAKO-20 as a lead compound, further structural optimization may provide new drug entities for the treatments of malignant skin carcinomas.

13.
BMC Infect Dis ; 20(1): 807, 2020 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-33153445

RESUMO

BACKGROUND: The COVID-19 spread worldwide quickly. Exploring the epidemiological characteristics could provide a basis for responding to imported cases abroad and to formulate prevention and control strategies in areas where COVID-19 is still spreading rapidly. METHODS: The number of confirmed cases, daily growth, incidence and length of time from the first reported case to the end of the local cases (i.e., non-overseas imported cases) were compared by spatial (geographical) and temporal classification and visualization of the development and changes of the epidemic situation by layers through maps. RESULTS: In the first wave, a total of 539 cases were reported in Sichuan, with an incidence rate of 0.6462/100,000. The closer to Hubei the population centres were, the more pronounced the epidemic was. The peak in Sichuan Province occurred in the second week. Eight weeks after the Wuhan lockdown, the health crisis had eased. The longest epidemic length at the city level in China (except Wuhan, Taiwan, and Hong Kong) was 53 days, with a median of 23 days. Spatial autocorrelation analysis of China showed positive spatial correlation (Moran's Index > 0, p < 0.05). Most countries outside China began to experience a rapid rise in infection rates 4 weeks after their first case. Some European countries experienced that rise earlier than the USA. The pandemic in Germany, Spain, Italy, and China took 28, 29, 34, and 18 days, respectively, to reach the peak of daily infections, after their daily increase of up to 20 cases. During this time, countries in the African region and Southeast Asian region were at an early stage of infections, those in the Eastern Mediterranean region and region of the Americas were in a rapid growth phase. CONCLUSIONS: After the closure of the outbreak city, appropriate isolation and control measures in the next 8 weeks were key to control the outbreak, which reduced the peak value and length of the outbreak. Some countries with improved epidemic situations need to develop a continuous "local strategy at entry checkpoints" to to fend off imported COVID-19.


Assuntos
Betacoronavirus , Infecções por Coronavirus/epidemiologia , Saúde Global , Pneumonia Viral/epidemiologia , China/epidemiologia , Infecções por Coronavirus/virologia , Humanos , Incidência , Pandemias , Pneumonia Viral/virologia , Prevalência , Análise Espacial , Fatores de Tempo
14.
Front Pharmacol ; 11: 554422, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33154722

RESUMO

Short QT syndrome (SQTS) is associated with tachyarrhythmias and sudden cardiac death. So far, only quinidine has been demonstrated to be effective in patients with SQTS type 1(SQTS1). The aim of this study was to investigate the mechanisms of disopyramide underlying its antiarrhythmic effects in SQTS1 with the N588K mutation in HERG channel. Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from a patient with SQTS1 and a healthy donor, patch clamp, and calcium imaging measurements were employed to assess the drug effects. Disopyramide prolonged the action potential duration (APD) in hiPSC-CMs from a SQTS1-patient (SQTS1-hiPSC-CMs). In spontaneously beating SQTS1-hiPSC-CMs challenged by carbachol plus epinephrine, disopyramide reduced the arrhythmic events. Disopyramide enhanced the inward L-type calcium channel current (ICa-L), the late sodium channel current (late INa) and the Na/Ca exchanger current (INCX), but it reduced the outward small-conductance calcium-activated potassium channel current (ISK), leading to APD-prolongation. Disopyramide displayed no effects on the rapidly and slowly activating delayed rectifier and ATP-sensitive potassium channel currents. In hiPSC-CMs from the healthy donor, disopyramide reduced peak INa, ICa-L, IKr, and ISK but enhanced late INa and INCX. The results demonstrated that disopyramide may be effective for preventing tachyarrhythmias in SQTS1-patients carrying the N588K mutation in HERG channel by APD-prolongation via enhancing ICa-L, late INa, INCX, and reducing ISK.

15.
In Vivo ; 34(6): 3639-3648, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33144479

RESUMO

BACKGROUND/AIM: The association between ejection fraction (EF) and mortality in TTS patients as compared to ACS is limited. This study aims to investigate the association between EF and clinical outcomes in patients with TTS as compared to ACS. PATIENTS AND METHODS: This study compared in-hospital, and long-term incidence of clinical outcomes for 5 years in patients with TTS and ACS. The study was composed of two groups EF≥35% and EF<35%. RESULTS: The long-term mortality of the EF≥35% for 5 years was significantly higher in TTS patients as compared to ACS (18.1% vs. 7.7%, log-Rank; p<0.01). Irrespective of EF, a non-cardiovascular death was significantly higher in TTS as compared to ACS patients with EF≥35 (6.4% vs. 2.1%; p=0.02) and with EF<35% (21.4% vs. 7.5%; p=0.03). CONCLUSION: The long-term mortality is significantly higher in TTS as compared to ACS dominated by a non-cardiovascular cause of death at 5-years-follow-up.

16.
Signal Transduct Target Ther ; 5(1): 227, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33028824

RESUMO

Nicotinamide adenine dinucleotide (NAD+) and its metabolites function as critical regulators to maintain physiologic processes, enabling the plastic cells to adapt to environmental changes including nutrient perturbation, genotoxic factors, circadian disorder, infection, inflammation and xenobiotics. These effects are mainly achieved by the driving effect of NAD+ on metabolic pathways as enzyme cofactors transferring hydrogen in oxidation-reduction reactions. Besides, multiple NAD+-dependent enzymes are involved in physiology either by post-synthesis chemical modification of DNA, RNA and proteins, or releasing second messenger cyclic ADP-ribose (cADPR) and NAADP+. Prolonged disequilibrium of NAD+ metabolism disturbs the physiological functions, resulting in diseases including metabolic diseases, cancer, aging and neurodegeneration disorder. In this review, we summarize recent advances in our understanding of the molecular mechanisms of NAD+-regulated physiological responses to stresses, the contribution of NAD+ deficiency to various diseases via manipulating cellular communication networks and the potential new avenues for therapeutic intervention.

17.
Thorax ; 75(12): 1047-1057, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33077617

RESUMO

INTRODUCTION: Airway epithelial cells are recognised as an essential controller for the initiation and perpetuation of asthmatic inflammation, yet the detailed mechanisms remain largely unknown. This study aims to investigate the roles and mechanisms of the mechanistic target of rapamycin (MTOR)-autophagy axis in airway epithelial injury in asthma. METHODS: We examined the MTOR-autophagy signalling in airway epithelium from asthmatic patients or allergic mice induced by ovalbumin or house dust mites, or in human bronchial epithelial (HBE) cells. Furthermore, mice with specific MTOR knockdown in airway epithelium and autophagy-related lc3b -/- mice were used for allergic models. RESULTS: MTOR activity was decreased, while autophagy was elevated, in airway epithelium from asthmatic patients or allergic mice, or in HBE cells treated with IL33 or IL13. These changes were associated with upstream tuberous sclerosis protein 2 signalling. Specific MTOR knockdown in mouse bronchial epithelium augmented, while LC3B deletion diminished allergen-induced airway inflammation and mucus hyperproduction. The worsened inflammation caused by MTOR deficiency was also ameliorated in lc3b -/- mice. Mechanistically, autophagy was induced later than the emergence of allergen-initiated inflammation, particularly IL33 expression. MTOR deficiency increased, while knocking out of LC3B abolished the production of IL25 and the eventual airway inflammation on allergen challenge. Blocking IL25 markedly attenuated the exacerbated airway inflammation in MTOR-deficiency mice. CONCLUSION: Collectively, these results demonstrate that allergen-initiated inflammation suppresses MTOR and induces autophagy in airway epithelial cells, which results in the production of certain proallergic cytokines such as IL25, further promoting the type 2 response and eventually perpetuating airway inflammation in asthma.

18.
Front Bioeng Biotechnol ; 8: 559387, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33123512

RESUMO

Objective: To build a model for proximal junctional kyphosis (PJK) prognostication in Lenke 5 adolescent idiopathic scoliosis (AIS) patients undergoing long posterior instrumentation and fusion surgery by machine learning and analyze the risk factors for PJK. Materials and Methods: In total, 44 AIS patients (female/male: 34/10; PJK/non-PJK: 34/10) who met the inclusion criteria between January 2013 and December 2018 were retrospectively recruited from West China Hospital. Thirty-seven clinical and radiological features were acquired by two independent investigators. Univariate analyses between PJK and non-PJK groups were carried out. Twelve models were built by using four types of machine learning algorithms in conjunction with two oversampling methods [the synthetic minority technique (SMOTE) and random oversampling]. Area under the receiver operating characteristic curve (AUC) was used for model discrimination, and the clinical utility was evaluated by using F1 score and accuracy. The risk factors were simultaneously analyzed by a Cox regression and machine learning. Results: Statistical differences between PJK and non-PJK groups were as follows: gender (p = 0.001), preoperative factors [thoracic kyphosis (p = 0.03), T1 slope angle (T1S, p = 0.078)], and postoperative factors [T1S (p = 0.097), proximal junctional angle (p = 0.003), upper instrumented vertebra (UIV) - UIV + 1 (p = 0.001)]. Random forest using SMOTE achieved the best prediction performance with AUC = 0.944, accuracy = 0.909, and F1 score = 0.667 on independent testing dataset. Cox model revealed that male gender and larger preoperative T1S were independent prognostic factors of PJK (odds ratio = 10.701 and 57.074, respectively). Gender was also at the first place in the importance ranking of the model with best performance. Conclusion: The random forest using SMOTE model has the great value for predicting the individual risk of developing PJK after long instrumentation and fusion surgery in Lenke 5 AIS patients. Moreover, the combination of the outcomes of a Cox model and the feature ranking extracted by machine learning is more valuable than any one alone, especially in the interpretation of risk factors.

19.
J Healthc Eng ; 2020: 8886599, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33014322

RESUMO

Purpose: The objective of this study was to construct a procedural planning tool to optimize the proximal junction angle (PJA) to prevent postoperative proximal junctional kyphosis (PJK) for each scoliosis patient. Methods: Twelve patients (9 patients without PJK and 3 patients with PJK) who have been followed up for at least 2 years after surgery were included. After calculating the loading force on the cephalad intervertebral disc of upper instrumented vertebra of each patient, the finite-element method (FEM) was performed to calculate the stress of each element. The stress information was summarized into the difference value before and after operation in different regions of interest. A two-layer fully connected neural network method was applied to model the relationship between the stress information and the risk of PJK. Leave-one-out cross-validation and sensitivity analysis were implemented to assess the accuracy and stability of the trained model. The optimal PJA was predicted based on the learned model by optimization algorithm. Results: The mean prediction accuracy was 83.3% for all these cases, and the area under the curve (AUC) of prediction was 0.889. And the output variance of this model was less than 5% when the important factor values were perturbed in a range of 5%. Conclusion: Our approach integrated biomechanics and machine learning to support the surgical decision. For a new individual, the risk of PJK and optimal PJA can be simultaneously predicted based on the learned model.

20.
J Orthop Surg Res ; 15(1): 376, 2020 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-32883325

RESUMO

BACKGROUND: Posterolateral tibial plateau fractures (PTPF) remain a challenge for orthopedics surgeons because the special anatomical structures of the posterolateral corner of knee joint including the fibular head, the lateral collateral ligament, and the peroneal nerve, which impedes the exposure of the fracture fragments and need irregular implants to get a stable fixation. The purpose of present study was to introduce a new articular fracture fragments restoration technique for three patterns of PTPF and investigate the relationship between associated soft injuries and fracture patterns. METHODS: From May 2016 to April 2018, 31 patients with PTPF who had undertaken arthroscopically assisted reduction and fixation (AARF) were enrolled in present study. Demographic data, pre-operation, and post-operation X plan films, three-dimensional computed tomography (CT) scans and magnetic resonance imaging (MRI) were reviewed. Present samples were divided into three patterns with lateral inclination (LI), posterior inclination (PI), and parallel compression (PC) according to the orientation of the articular fragment inclination. Rasmussen anatomical score was used to assess the radiological results. Rasmussen functional score, Hospital for Special Surgery knee-rating Score (HSS), and range of motion (ROM) of the knee joint at the final follow-up were measured to evaluate the clinical outcomes. RESULTS: In this series, the post-operation tibial plateau angle (TPA) was 9.7° ± 3.5°(range 4.0°-15.8°) and the Rasmussen anatomical score was 17.7 ± 0.7(range 16-18); clinical outcomes showed that the HSS score was 92.7 ± 21.8 (range 90-96) and the Rasmussen functional score was 27.9 ± 1.0 (range 26-30). Of all the patients, the anterior cruciate ligament (ACL) injuries including the ACL tibial attachment ruptures occurred in 16 patients (51.6%), meniscus lesions happened in 19 patients (61.3%), medial collateral ligament (MCL) injuries were founded in 13 patients (41.9%). The number of ACL injuries including the ACL tibial attachment ruptures in the PI fracture pattern (12 cases) is significantly higher than LI (2 cases) and PC (2 cases) fracture pattern (p < 0.05). CONCLUSION: Profound understanding the different patterns of PTPF and using our reduction technique will facilitate to restore the main articular fracture fragments. The PI fracture patterns have a significant high incidence of the ACL ruptures. LEVEL OF EVIDENCE: Therapeutic study, Level IV.

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