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1.
Clin Exp Rheumatol ; 41(6): 1262-1274, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36762746

RESUMO

OBJECTIVES: The COVID-19 pandemic caused by SARS-CoV-2 has seriously threatened the human health. Growing evidence shows that COVID-19 patients who recovery will persist with symptoms of fibromyalgia (FM). However, the common molecular mechanism between COVID-19 and FM remains unclear. METHODS: We obtained blood transcriptome data of COVID-19 (GSE177477) and FM (GSE67311) patients from GEO database, respectively. Subsequently, we applied Limma, GSEA, Wikipathway, KEGG, GO, and machine learning analysis to confirm the common pathogenesis between COVID-19 and FM, and screened key genes for the diagnosis of COVID-19 related FM. RESULTS: A total of 2505 differentially expressed genes (DEGs) were identified in the FM dataset. Functional enrichment analysis revealed that the occurrence of FM was intimately associated with viral infection. Moreover, WGCNA analysis identified 243 genes firmly associated with the pathological process of COVID-19. Subsequently, 50 common genes were screened between COVID-19 and FM, and functional enrichment analysis of these common genes primarily involved in immunerelated pathways. Among these common genes, 3 key genes were recognised by machine learning for the diagnosis of COVID-19 related FM. We also developed a diagnostic nomogram to predict the risk of FM occurrence which showed excellent predictive performance. Finally, we found that these 3 key genes were closely relevant to immune cells and screened potential drugs that interacted with the key genes. CONCLUSIONS: Our study revealed the bridge role of immune dysregulation between COVID-19 and fibromyalgia, and screened underlying biomarkers to provide new clues for further clinical research.


Assuntos
COVID-19 , Fibromialgia , Humanos , SARS-CoV-2 , Fibromialgia/diagnóstico , Fibromialgia/epidemiologia , Fibromialgia/genética , Pandemias , Transcriptoma , Aprendizado de Máquina , Biologia Computacional
2.
Comput Biol Med ; 155: 106663, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36803796

RESUMO

Deep learning networks have achieved remarkable progress in various tasks of medical imaging. Most of the recent success in computer vision highly depend on large amounts of carefully annotated data, whereas labelling is arduous, time-consuming and in need of expertise. In this paper, a semi-supervised learning method, Semi-XctNet, is proposed for volumetric images reconstruction from a single X-ray image. In our framework, the effect of regularization on pixel-level prediction is enhanced by introducing a transformation consistent strategy into the model. Furthermore, a multi-stage training strategy is designed to ameliorate the generalization performance of the teacher network. An assistant module is also introduced to improve the pixel quality of pseudo-labels, thereby further improving the reconstruction accuracy of the semi-supervised model. The semi-supervised method proposed in this paper has been extensively validated on the LIDC-IDRI lung cancer detection public data set. Quantitative results show that SSIM (structural similarity measurement) and PSNR (peak signal noise ratio) are 0.8384 and 28.7344 respectively. Compared with the state-of-the-arts, Semi-XctNet exhibits excellent reconstruction performance, thus demonstrating the effectiveness of our method on the task of volumetric images reconstruction network from a single X-ray image.


Assuntos
Neoplasias Pulmonares , Humanos , Aprendizado de Máquina Supervisionado , Tórax , Processamento de Imagem Assistida por Computador
3.
Aging (Albany NY) ; 15(4): 1158-1176, 2023 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-36842142

RESUMO

Numerous studies have documented that immune responses are crucial in the pathophysiology of spinal cord injury (SCI). Our study aimed to uncover the function of immune-related genes (IRGs) in SCI. Here, we comprehensively evaluated the transcriptome data of SCI and healthy controls (HC) obtained from the GEO Database integrating bioinformatics and experiments. First, a total of 2067 DEGs were identified between the SCI and HC groups. Functional enrichment analysis revealed substantial immune-related pathways and functions that were abnormally activated in the SCI group. Immune analysis revealed that myeloid immune cells were predominantly upregulated in SCI patients, while a large number of lymphoid immune cells were dramatically downregulated. Subsequently, 51 major IRGs were screened as key genes involved in SCI based on the intersection of the results of WGCNA analysis, DEGs, and IRGs. Based on the expression profiles of these genes, two distinct immune modulation patterns were recognized exhibiting opposite immune characteristics. Moreover, 2 core IRGs (FCER1G and NFATC2) were determined to accurately predict the occurrence of SCI via machine learning. qPCR analysis was used to validate the expression of core IRGs in an external independent cohort. Finally, the expression of these core IRGs was validated by sequencing, WB, and IF analysis in vivo. We found that these two core IRGs were closely associated with immune cells and verified the co-localization of FCER1G with macrophage M1 via IF analysis. Our study revealed the key role of immune-related genes in SCI and contributed to a fresh perspective for early diagnosis and treatment of SCI.


Assuntos
Traumatismos da Medula Espinal , Humanos , Traumatismos da Medula Espinal/diagnóstico , Traumatismos da Medula Espinal/genética , Traumatismos da Medula Espinal/metabolismo , Transcriptoma , Macrófagos/metabolismo , Biologia Computacional/métodos , Diagnóstico Precoce
4.
Int Immunopharmacol ; 115: 109684, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36630752

RESUMO

OBJECTIVES: Osteosarcoma is highly aggressive and prone to metastasis, with a poor prognosis. Increasing evidence identified anoikis has a critical effect in tumor metastasis and invasion. However, the prognostic value of anoikis-related genes (ANRGs) in osteosarcoma and their role in the immune landscape of osteosarcoma remain unclear. METHODS: The RNA sequencing and clinical data of patients with osteosarcoma were extracted from the TARGET and GEO databases, and ANRGs were identified from the GeneCards database. Unsupervised clustering analysis was employed to identify anoikis-related patterns. The ESTIMATE, TIMER and ssGSEA algorithms were used to assess the immune microenvironment of different subtypes. A prognostic signature based on the identified ANRGs was constructed via univariate, LASSO and multivariate Cox regression analyses. KEGG, GO and GSEA were used for functional enrichment of genes associated with different risk subtypes. qPCR, WB and IHC were used to validate the expression of candidate genes. RESULTS: Two anoikis-related patterns with distinct clinical features and immune statuses were identified based on prognosis-related ANRGs. Cluster 2 had more active immunogenicity and a better prognosis than Cluster 1. Subsequently, we developed and validated an anoikis prognostic signature demonstrating excellent predictive ability for the prognosis of osteosarcoma. Anoikis risk score was positively associated with osteosarcoma metastasis and was identified as an independent prognostic marker. Additionally, a nomogram was established to predict the 3- and 5-year survival probability of patients with osteosarcoma. Functional enrichment analysis revealed that immune dysregulation was correlated with poor prognosis. Besides, patients in the low-risk group had higher infiltration levels of immune cells and more active immune function than patients in the high-risk group. Drug sensitivity analysis revealed several chemotherapeutic agents for the treatment of different subtypes of osteosarcoma. CONCLUSION: Our study demonstrated the role of ANRGs in osteosarcoma progression, providing insights into clinical decision making in osteosarcoma.


Assuntos
Neoplasias Ósseas , Osteossarcoma , Humanos , Prognóstico , Anoikis/genética , Nomogramas , Osteossarcoma/genética , Neoplasias Ósseas/genética , Microambiente Tumoral
5.
Cancer Sci ; 114(4): 1240-1255, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36478349

RESUMO

Myeloid cells as a highly heterogeneous subpopulation of the tumor microenvironment (TME) are intimately associated with tumor development. Ewing sarcoma (EWS) is characterized by abundant myeloid cell infiltration in the TME. However, the correlation between myeloid signature genes (MSGs) and the prognosis of EWS patients was unclear. In this research, we synthetically characterized the expression of MSGs in a training cohort and classified EWS patients into two subtypes. Immune cell infiltration analysis revealed that MSGs subtypes correlated closely with different immune statuses. Furthermore, a three-gene prognostic model (CTSD, SIRPA, and FN1) was constructed by univariate, LASSO, and multivariate Cox analysis, and it showed excellent prognostic accuracy in EWS patients. We also developed a nomogram for better predicting the long-term survival of EWS. Functional enrichment analysis showed immune-related pathways were distinctly different in the high- and low-risk groups. Further analysis revealed that patients in the high-risk group were tightly associated with an immunosuppressive microenvironment. Finally, we validated the expression of these candidate genes by Western blot (WB), qPCR, and immunohistochemistry (IHC) analysis. To sum up, our study identified that the MSGs model was strongly linked to prognostic prediction and immune infiltration in EWS patients, providing novel insights into the clinical treatment and management of EWS patients.


Assuntos
Sarcoma de Ewing , Humanos , Sarcoma de Ewing/genética , Prognóstico , Nomogramas , Western Blotting , Imunossupressores , Microambiente Tumoral/genética
6.
Cereb Cortex ; 33(6): 3026-3042, 2023 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-35764255

RESUMO

Ventromedial prefrontal cortex (vmPFC) processes many critical brain functions, such as decision-making, value-coding, thinking, and emotional arousal/recognition, but whether vmPFC plays a role in sleep-wake promotion circuitry is still unclear. Here, we find that photoactivation of dorsomedial hypothalamus (DMH)-projecting vmPFC neurons, their terminals, or their postsynaptic DMH neurons rapidly switches non-rapid eye movement (NREM) but not rapid eye movement sleep to wakefulness, which is blocked by photoinhibition of DMH outputs in lateral hypothalamus (LHs). Chemoactivation of DMH glutamatergic but not GABAergic neurons innervated by vmPFC promotes wakefulness and suppresses NREM sleep, whereas chemoinhibition of vmPFC projections in DMH produces opposite effects. DMH-projecting vmPFC neurons are inhibited during NREM sleep and activated during wakefulness. Thus, vmPFC neurons innervating DMH likely represent the first identified set of cerebral cortical neurons for promotion of physiological wakefulness and suppression of NREM sleep.


Assuntos
Sono REM , Sono , Sono/fisiologia , Sono REM/fisiologia , Nível de Alerta , Vigília/fisiologia , Neurônios GABAérgicos/fisiologia
7.
Front Surg ; 9: 975026, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36132199

RESUMO

Purpose: To investigate the optimal immediate sagittal alignment of kyphosis in ankylosing spondylitis (AS) following corrective osteotomy. Methods: Seventy-seven AS patients who underwent osteotomy were enrolled. Radiographic parameters, including global kyphosis (GK), lumbar lordosis (LL), T1 spinopelvic inclination (T1SPI), sagittal vertical axis (SVA), T1 pelvic angle (TPA), pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), and PI and LL mismatch (PI-LL), were collected. The clinical outcome was evaluated using the Scoliosis Research Society-22 (SRS-22) questionnaire and Oswestry Disability Index (ODI). At the final follow-up, SVA > 5 cm was regarded as sagittal imbalance, and a total ODI ≤ 20 or total SRS-22 score ≥4 was considered to indicate a good clinical outcome. Results: Seventy-seven patients with an average age of 37.4 ± 8.6 years were followed up for 29.4 ± 4.2 months. At the final follow-up, GK, LL, PT, SS, TPA, and T1SPI showed some degree of correction loss (P < 0.05). The follow-up parameters could be predicted with the immediate postoperative parameters through their linear regression equation (P < 0.05). The postoperative immediate T1SPI, TPA, SVA, and PI were also highly correlated with the clinical outcome (ODI and/or SRS-22) at the final follow-up (P < 0.05). Based on the relationship, the optimal immediate sagittal alignment for obtaining good clinical outcome was determined: T1SPI ≤ 0.9°, TPA ≤ 31.5°, and SVA ≤ 9.3cm. AS patients with PI ≤ 49.2° were more likely to achieve the optimal alignment and obtained lower ODI and a lower incidence of sagittal imbalance than those with PI > 49.2° at the final follow-up (P < 0.05). Conclusion: Postoperative immediate parameters could be used to predict the final follow-up parameters and clinical outcome. The optimal postoperative immediate sagittal alignment of AS patients was T1SPI ≤ 0.9°, TPA ≤ 31.5°, and SVA ≤ 9.3 cm, providing a reference for kyphosis correction and a means for clinical outcome evaluation. Patients with a lower PI (≤49.2°) were more likely to achieve optimal alignment and obtain satisfactory clinical outcomes.

8.
Front Genet ; 13: 965126, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36092937

RESUMO

Objectives: Ewing sarcoma (EWS) is an aggressive tumor of bone and soft tissue. Growing evidence indicated lactate as a pivotal mediator of crosstalk between tumor energy metabolism and microenvironmental regulation. However, the contribution of lactate-related genes (LRGs) in EWS is still unclear. Methods: We obtained the transcriptional data of EWS patients from the GEO database and identified differentially expressed-LRGs (DE-LRGs) between EWS patient samples and normal tissues. Unsupervised cluster analysis was utilized to recognize lactate modulation patterns based on the expression profile of DE-LRGs. Functional enrichment including GSEA and GSVA analysis was conducted to identify molecular signaling enriched in different subtypes. ESTIMATE, MCP and CIBERSORT algorithm was used to explore tumor immune microenvironment (TIME) between subtypes with different lactate modulation patterns. Then, lactate prognostic risk signature was built via univariate, LASSO and multivariate Cox analysis. Finally, we performed qPCR analysis to validate candidate gene expression. Result: A total of 35 DE-LRGs were identified and functional enrichment analysis indicated that these LRGs were involved in mitochondrial function. Unsupervised cluster analysis divided EWS patients into two lactate modulation patterns and we revealed that patients with Cluster 1 pattern were linked to poor prognosis and high lactate secretion status. Moreover, TIME analysis indicated that the abundance of multiple immune infiltrating cells were dramatically elevated in Cluster 1 to Cluster 2, including CAFs, endothelial cells, Macrophages M2, etc., which might contribute to immunosuppressive microenvironment. We also noticed that expression of several immune checkpoint proteins were clearly increased in Cluster 1 to Cluster 2. Subsequently, seven genes were screened to construct LRGs prognostic signature and the performance of the resulting signature was validated in the validation cohort. Furthermore, a nomogram integrating LRGs signature and clinical characteristics was developed to predict effectively the 4, 6, and 8-year prognosis of EWS patients. Conclusion: Our study revealed the role of LRGs in immunosuppressive microenvironment and predicting prognosis in EWS and provided a robust tool to predict the prognosis of EWS patients.

9.
BMC Musculoskelet Disord ; 23(1): 790, 2022 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-35982428

RESUMO

BACKGROUND: This study aimed to determine preoperative predictors for sagittal imbalance in kyphosis secondary to ankylosing spondylitis (AS) after one-level three-column osteotomy. METHODS: A total of 55 patients with AS who underwent one-level three-column osteotomy were enrolled. The patients were divided into two groups according to sagittal vertical axis (SVA) value at the final follow-up (group A: SVA > 5 cm; group B: SVA ≤ 5 cm). The radiographic measures included global kyphosis, lumbar lordosis (LL), pelvic tilt (PT), pelvic incidence (PI), sacral slope, T1 pelvic angle (TPA), SVA, osteotomized vertebral angle and PI and LL mismatch (PI - LL). Postoperative clinical outcomes were evaluated using Scoliosis Research Society-22 questionnaire (SRS-22) and Oswestry Disability Index (ODI). RESULTS: Fifty-five AS patients had an average follow-up of 30.6 ± 10.2 months (range 24-84 months). Group A had larger preoperative and postoperative LL, PT, PI - LL, TPA and SVA values compared with group B (P < 0.05), and no significant differences were found in ODI and SRS-22 scores between the two groups (P > 0.05). Preoperative LL, PT, PI - LL, TPA, and SVA values were positively correlated with the follow-up SVA value (P < 0.05). Among them, TPA > 40.9°, PI - LL > 32.5° and SVA > 13.7 cm were the top three predictors with the best accuracy to predict sagittal imbalance. Immediate postoperative SVA value of ≤ 7.4 cm was a key factor in reducing the risk of sagittal imbalance during follow-up. CONCLUSIONS: Preoperative TPA > 40.9°, PI - LL > 32.5° and SVA > 13.7 cm could predict sagittal imbalance in AS kyphosis after one-level three-column osteotomy, and additional osteotomies were recommended for this condition. Immediate postoperative SVA ≤ 7.4 cm was an optimal indicator for preventing sagittal imbalance. LEVEL OF EVIDENCE: IV.


Assuntos
Cifose , Lordose , Anormalidades Musculoesqueléticas , Espondilite Anquilosante , Humanos , Cifose/diagnóstico por imagem , Cifose/etiologia , Cifose/cirurgia , Lordose/cirurgia , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Osteotomia/efeitos adversos , Qualidade de Vida , Estudos Retrospectivos , Sacro , Espondilite Anquilosante/complicações , Espondilite Anquilosante/diagnóstico por imagem , Espondilite Anquilosante/cirurgia , Vértebras Torácicas/diagnóstico por imagem , Vértebras Torácicas/cirurgia
10.
Comput Med Imaging Graph ; 98: 102067, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35468534

RESUMO

Conventional Computed Tomography (CT) produces volumetric images by computing inverse Radon transformation using X-ray projections from different angles, which results in high dose radiation, long reconstruction time and artifacts. Biologically, prior knowledge or experience can be utilized to identify volumetric information from 2D images to certain extents. a deep learning network, XctNet, is proposed to gain this prior knowledge from 2D pixels and produce volumetric data. In the proposed framework, self-attention mechanism is used for feature adaptive optimization; multiscale feature fusion is used to further improve the reconstruction accuracy; a 3D branch generation module is proposed to generate the details of different generation fields. Comparisons are made with the state-of-arts methods using public dataset and XctNet shows significantly higher image quality as well as better accuracy (SSIM and PSNR values of XctNet are 0.8681 and 29.2823 respectively).


Assuntos
Aprendizado Profundo , Processamento de Imagem Assistida por Computador , Artefatos , Processamento de Imagem Assistida por Computador/métodos , Tomografia Computadorizada por Raios X , Raios X
11.
Pathogens ; 11(3)2022 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-35335616

RESUMO

Biofilms are intricate bacterial assemblages that attach to diverse surfaces using an extracellular polymeric substance that protects them from the host immune system and conventional antibiotics. Biofilms cause chronic infections that result in millions of deaths around the world every year. Since the antibiotic tolerance mechanism in biofilm is different than that of the planktonic cells due to its multicellular structure, the currently available antibiotics are inadequate to treat biofilm-associated infections which have led to an immense need to find newer treatment options. Over the years, various novel antibiofilm compounds able to fight biofilms have been discovered. In this review, we have focused on the recent and intensively researched therapeutic techniques and antibiofilm agents used for biofilm treatment and grouped them according to their type and mode of action. We also discuss some therapeutic approaches that have the potential for future advancement.

12.
Front Mol Neurosci ; 15: 843754, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35299695

RESUMO

Pain and itch are intricately entangled at both circuitry and behavioral levels. Emerging evidence indicates that parvalbumin (PV)-expressing neurons in zona incerta (ZI) are critical for promoting nocifensive behaviors. However, the role of these neurons in itch modulation remains elusive. Herein, by combining FOS immunostaining, fiber photometry, and chemogenetic manipulation, we reveal that ZI PV neurons act as an endogenous negative diencephalic modulator for itch processing. Morphological data showed that both histamine and chloroquine stimuli induced FOS expression in ZI PV neurons. The activation of these neurons was further supported by the increased calcium signal upon scratching behavior evoked by acute itch. Behavioral data further indicated that chemogenetic activation of these neurons reduced scratching behaviors related to histaminergic and non-histaminergic acute itch. Similar neural activity and modulatory role of ZI PV neurons were seen in mice with chronic itch induced by atopic dermatitis. Together, our study provides direct evidence for the role of ZI PV neurons in regulating itch, and identifies a potential target for the remedy of chronic itch.

13.
Nat Commun ; 13(1): 728, 2022 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-35132099

RESUMO

Postsynaptic NMDARs at spinal synapses are required for postsynaptic long-term potentiation and chronic pain. However, how presynaptic NMDARs (PreNMDARs) in spinal nociceptor terminals control presynaptic plasticity and pain hypersensitivity has remained unclear. Here we report that PreNMDARs in spinal nociceptor terminals modulate synaptic transmission in a nociceptive tone-dependent manner. PreNMDARs depresses presynaptic transmission in basal state, while paradoxically causing presynaptic potentiation upon injury. This state-dependent modulation is dependent on Ca2+ influx via PreNMDARs. Small conductance Ca2+-activated K+ (SK) channels are responsible for PreNMDARs-mediated synaptic depression. Rather, tissue inflammation induces PreNMDARs-PKG-I-dependent BDNF secretion from spinal nociceptor terminals, leading to SK channels downregulation, which in turn converts presynaptic depression to potentiation. Our findings shed light on the state-dependent characteristics of PreNMDARs in spinal nociceptor terminals on modulating nociceptive transmission and revealed a mechanism underlying state-dependent transition. Moreover, we identify PreNMDARs in spinal nociceptor terminals as key constituents of activity-dependent pain sensitization.


Assuntos
Dor Crônica/fisiopatologia , Nociceptores/metabolismo , Terminações Pré-Sinápticas/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Animais , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Cálcio/metabolismo , Dor Crônica/genética , Dor Crônica/metabolismo , Proteína Quinase Dependente de GMP Cíclico Tipo I/genética , Proteína Quinase Dependente de GMP Cíclico Tipo I/metabolismo , Gânglios Espinais/citologia , Gânglios Espinais/fisiologia , Inflamação , Potenciação de Longa Duração , Depressão Sináptica de Longo Prazo , Camundongos , Camundongos Transgênicos , Substância Cinzenta Periaquedutal/citologia , Substância Cinzenta Periaquedutal/fisiologia , Canais de Potássio Cálcio-Ativados/genética , Canais de Potássio Cálcio-Ativados/metabolismo , Receptores de N-Metil-D-Aspartato/genética , Transmissão Sináptica
14.
Neural Regen Res ; 17(8): 1814-1820, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35017443

RESUMO

Neural stem cell (NSC) transplantation is a promising strategy for replacing lost neurons following spinal cord injury. However, the survival and differentiation of transplanted NSCs is limited, possibly owing to the neurotoxic inflammatory microenvironment. Because of the important role of glucose metabolism in M1/M2 polarization of microglia/macrophages, we hypothesized that altering the phenotype of microglia/macrophages by regulating the activity of aldose reductase (AR), a key enzyme in the polyol pathway of glucose metabolism, would provide a more beneficial microenvironment for NSC survival and differentiation. Here, we reveal that inhibition of host AR promoted the polarization of microglia/macrophages toward the M2 phenotype in lesioned spinal cord injuries. M2 macrophages promoted the differentiation of NSCs into neurons in vitro. Transplantation of NSCs into injured spinal cords either deficient in AR or treated with the AR inhibitor sorbinil promoted the survival and neuronal differentiation of NSCs at the injured spinal cord site and contributed to locomotor functional recovery. Our findings suggest that inhibition of host AR activity is beneficial in enhancing the survival and neuronal differentiation of transplanted NSCs and shows potential as a treatment of spinal cord injury.

16.
Neurobiol Stress ; 15: 100417, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34815987

RESUMO

Self-grooming is an innate, cephalo-caudal progression of body cleaning behaviors that are found in normal rodents but exhibit repetitive and stereotyped patterns in several mouse models, such as autism spectrum disorders (ASDs). It is also recognized as a marker of stress and anxiety. Mice with Shank3B gene knockout (KO) exhibit typical ASD-like behavioral abnormalities, including stereotyped self-grooming and increased levels of anxiety. However, the exact relationship between anxiety and stereotyped self-grooming in certain types of animal models is not clear. We selected three animal models with high anxiety to compare their self-grooming parameters. First, we confirmed that Shank3B KO mice (ASD model), acute restraint stress mouse model (stress model), and chronic inflammatory pain mouse model (pain model) all showed increased anxiety levels in the open field test (OFT) and elevated plus maze (EPM). We found that only the ASD model and the stress model produced increased total grooming duration. The pain model only exhibited an increasing trend of mean self-grooming duration. We used the grooming analysis algorithm to examine the self-grooming microstructure and assess the cephalo-caudal progression of grooming behavior. The results showed distinct self-grooming microstructures in these three models. The anxiolytic drug diazepam relieved the anxiety level and the total time of grooming in the ASD and stress models. The grooming microstructure was not restored in Shank3B KO mice but was partially relieved in the stress model, which suggested that anxiety aggravated stereotyped self-grooming duration but not the grooming microstructure in the ASD mouse model. Our results indicated that stereotyped behavior and anxiety may be shared by separate, but interacting, neural circuits in distinct disease models, which may be useful to understand the mechanisms and develop potential treatments for stereotyped behaviors and anxiety.

17.
J Anat ; 239(5): 1134-1140, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34235729

RESUMO

The rat is frequently used as a model to study the characteristics, aetiology and pathology of the Achilles tendon. However, though the structure of the human Achilles tendon has been extensively investigated, the anatomical structure of the rat Achilles tendon remains unclear, which impedes the ability to use rats to study Achilles tendinopathy. The purpose of this study was to reveal the structure of the rat Achilles tendon and to explore its similarities with the human Achilles tendon through an anatomical dissection of 80 rat Achilles tendons (40 female, 40 male). This study found that the subtendons of the rat Achilles tendon originating from the triceps surae muscle were twisted, and each subtendon also had its own torsion. The extent of these two types of torsion could be very different between rats. Alterations in this torsion may result in distinct stress fields in the Achilles tendon, which may play a critical role in the pathogenesis of Achilles tendinopathy. This study provides an important basis to support the use of rats as model animals to investigate the characteristics of the human Achilles tendon and Achilles tendinopathy.


Assuntos
Tendão do Calcâneo , Tendinopatia , Animais , Dissecação , Feminino , Masculino , Músculo Esquelético , Ratos
18.
Front Mol Neurosci ; 14: 819440, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35140588

RESUMO

Astrocytic glycogen plays an important role in brain energy metabolism. However, the contribution of glycogen metabolism to stress-induced depression remains unclear. Chronic social defeat stress was used to induce depression-like behaviors in mice, assessed with behavioral tests. Glycogen concentration in the medial prefrontal cortex (mPFC) and the expression of key enzymes of the glycogen metabolism were investigated using Western blots, immunofluorescent staining, electron microscopy, and biochemical assays. Stereotaxic surgery and viral-mediated gene transfer were applied to knockdown or overexpress brain-type glycogen phosphorylase (PYGB) in the mPFC. The glycogen content increased in the mPFC after stress. Glycogenolytic dysfunction due to inactivation of PYGB was responsible for glycogen accumulation. Behavioral tests on astrocyte-specific PYGB overexpression mice showed that augmenting astrocytic PYGB reduces susceptibility to depression when compared with stress-susceptible mice. Conversely, PYGB genetic down-regulation in the mPFC was sufficient to induce glycogen accumulation and depression-like behaviors. Furthermore, PYGB overexpression in the mPFC decreases susceptibility to depression, at least partially by rescuing glycogen phosphorylase activity to maintain glycogen metabolism homeostasis during stress. These findings indicate that (1) glycogen accumulation occurs in mice following stress and (2) glycogenolysis reprogramming leads to glycogen accumulation in astrocytes and PYGB contributes to stress-induced depression-like behaviors. Pharmacological tools acting on glycogenolysis might constitute a promising therapy for depression.

19.
World Neurosurg ; 145: e224-e232, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33059078

RESUMO

OBJECTIVE: An optimized Enhanced Recovery After Surgery (ERAS) program is lacking for adolescent idiopathic scoliosis (AIS). The aim of the present study was to evaluate the impact and feasibility of an optimized ERAS pathway in patients with surgically treated AIS. METHODS: In total, 79 patients with AIS who underwent corrective surgery without 3-column osteotomy were recruited from Xijing Hospital of the Fourth Military Medical University between 2012 and 2018. Forty-four patients were treated according to a traditional protocol and 35 were managed using an optimized ERAS pathway, which was designed and implemented by a multidisciplinary team. The following data were collected and retrospectively analyzed, demographic characteristics, Cobb angle, curve type (Lenke), surgical duration, fusion level, correction rate, estimated blood loss, postoperative hemoglobin level, postoperative pain score, pain relief time, hemovac drainage, drainage removal time, first ambulation time, length of hospital stay, and postoperative complications. RESULTS: There was no significant difference between the traditional and ERAS groups with respect to demographic characteristics, Cobb angle, curve type (Lenke), fusion level, and correction rate. However, the ERAS group had a shorter surgical duration, less blood loss and hemovac drainage, a higher postoperative hemoglobin level, and earlier pain relief, ambulation, and discharge. The rates of postoperative nausea and vomiting were lower in the ERAS group than in the traditional group. CONCLUSIONS: The ERAS pathway is capable of improving the perioperative status of patients with AIS by offering stronger analgesia, faster ambulation, and earlier discharge.


Assuntos
Recuperação Pós-Cirúrgica Melhorada , Escoliose/cirurgia , Adolescente , Estudos de Coortes , Feminino , Humanos , Masculino , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Estudos Retrospectivos , Fusão Vertebral/efeitos adversos , Fusão Vertebral/métodos
20.
Med Sci Monit ; 26: e923318, 2020 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-32088724

RESUMO

An Editorial decision has been made to retract the manuscript, Feng C, et al. Modified Closing-Opening Wedge Osteotomy to Correct Kyphosis in Ankylosing Spondylitis. Med Sci Monit. 2019; 25:6532-6538. It has come to our attention that the method of modified closing opening wedge osteotomy is not an original procedure developed by the authors, but has previously been described by Boissière L, et al. Spine J. 2015;15(12):2574-82, and Gao R, et al. Spine J. 2015;15(9):2009-15, and Boachie-Adjei O, et al. Spine (Phila Pa 1976). 2006;31(4):485-92.

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