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1.
Colloids Surf B Biointerfaces ; 200: 111590, 2021 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-33529926

RESUMO

Neural stem cell (NSC)-based therapy is a promising candidate for treating neurodegenerative diseases and the preclinical researches call an urgent need for regulating the growth and differentiation of such cells. The recognition that three-dimensional culture has the potential to be a biologically significant system has stimulated an extraordinary impetus for scientific researches in tissue engineering and regenerative medicine. Here, A novel scaffold for culturing NSCs, three-dimensional bacterial cellulose-graphene foam (3D-BC/G), which was prepared via in situ bacterial cellulose interfacial polymerization on the skeleton surface of porous graphene foam has been reported. 3D-BC/G not only supports NSC growth and adhesion, but also maintains NSC stemness and enhances their proliferative capacity. Further phenotypic analysis indicated that 3D-BC/G induces NSCs to selectively differentiate into neurons, forming a neural network in a short amount of time. The scaffold has good biocompatibility with primary cortical neurons enhancing the neuronal network activities. To explore the underlying mechanisms, RNA-Seq analysis to identify genes and signaling pathways was performed and it suggests that 3D-BC/G offers a more promising three-dimensional conductive substrate for NSC research and neural tissue engineering, and the repertoire of gene expression serves as a basis for further studies to better understand NSC biology.

2.
Science ; 2021 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-33602867

RESUMO

The COVID-19 pandemic caused by the SARS-CoV-2 virus continually poses serious threats to global public health. The main protease (Mpro) of SARS-CoV-2 plays a central role in viral replication. We designed and synthesized 32 new bicycloproline-containing Mpro inhibitors derived from either Boceprevir or Telaprevir, both of which are approved antivirals. All compounds inhibited SARS-CoV-2 Mpro activity in vitro with IC50 values ranging from 7.6 to 748.5 nM. The co-crystal structure of Mpro in complex with MI-23, one of the most potent compounds, revealed its interaction mode. Two compounds (MI-09 and MI-30) showed excellent antiviral activity in cell-based assays. In a SARS-CoV-2 infection transgenic mouse model, oral or intraperitoneal treatment with MI-09 or MI-30 significantly reduced lung viral loads and lung lesions. Both also displayed good pharmacokinetic properties and safety in rats.

3.
Gene ; : 145487, 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33588039

RESUMO

Lipopolysaccharide-induced TNFα factor (LITAF) is an important transcription factor which activates the transcription of TNFα and regulates cell apoptosis and inflammatory response. In the present study, a LITAF gene homologue was identified in zebrafish (Danio rerio) and was shown to be well conserved in the protein sequence, genomic organization and synteny with human LITAF. DrLITAF was constitutively expressed in tissues, with the highest expression detected in the gills. Its expression could be modulated by LPS, poly(I:C), and infection with Edwardsiella tarda, Aeromonus hydrophila and septicemia viremia of carp virus (SVCV). DrLITAF, when overexpressed, was shown to be located on the cellular membrane and nuclear membrane of HEK293T and ZF4 cells and was associated with the endoplasmic reticulum. Stimulation with LPS resulted in rapid translocation of DrLITAF into the nucleus. In addition, DrLITAF was able to induce cell apoptosis and the expression of caspase 3. The results demonstrate that DrLITAF is involved in the immune defence against bacterial and viral infection and plays a role in regulating inflammation and apoptosis.

4.
J Cell Physiol ; 2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-33559242

RESUMO

Ankylosing spondylitis (AS) is inflammatory arthritis predominantly affecting the spine, which is involved in the disorders of both immune and skeletal systems. The exact pathogenesis of AS is not fully understood. Osteoimmunology is a new subject of study in inflammatory arthritis, in particular the pathogenic events involved in the cross-regulation of both skeletal and immune systems. In this review, we discuss osteoimmunological and pathological changes of AS in the spine that are characterized by altered osteogenesis and osteolytic bone destruction, accompanied by the changes of the immune system. It was revealed that bone cells like mesenchymal stem cells, osteoblast, and osteoclast in crossing talking with immune cells such as T cells, B cells coregulate to the pathogenesis of AS. Further, an array of cytokines and molecules expressed by both skeletal and immune systems contribute to these complex interplays. Understanding the cellular and molecular mechanisms underlying the pathogenesis of AS will lay a foundation for the exploration of the potential new treatment to AS.

5.
Oncoimmunology ; 10(1): 1869388, 2021 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-33520407

RESUMO

Nuclear factor of activated T cells 3 (NFATc3) has been reported to upregulate type I interferons (IFNs) expression, and the abnormal expression and activation of NFATc3 were closely related to tumorigenesis. However, the potential function of NFATc3 in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) remains to be elucidated. In this study, we found that NFATc3 gene was frequently deleted and downregulated in HCC tumor tissues, and that the downregulation of NFATc3 was associated with poor prognosis of HCC patients. The gain- and loss-of-function experiments demonstrated that NFATc3 inhibited HCC cell proliferation and invasion, as well as HBV replication. Mechanistically, NFATc3 could bind to the promoters of IFNL1 and IFNB1 genes and prompt the production of IFNs and interferon-stimulated genes. Furthermore, retinoic acid-inducible gene-I (RIG-I) pathway activation increased NFATc3 expression and nuclear localization, and activated NFATc3 further enhanced RIG-I-mediated IFN responses. Collectively, our findings reveal a novel regulatory signaling cascade, the RIG-I/NFATc3/IFNs axis, which inhibits hepatocarcinogenesis and HBV replication by enhancing the immune response in hepatocytes, and this functional axis might potentially be exploited for therapeutic benefits in the clinical treatment of HBV-related HCC.

6.
Oxid Med Cell Longev ; 2021: 6684147, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33505586

RESUMO

Objective: Intervertebral disc degeneration (IDD) and low back pain caused by IDD have attracted public attention owing to their extremely high incidence and disability rate. Oxidative stress is a major cause of IDD. Tea polyphenols (TP) are natural-derived antioxidants extracted from tea leaves. This study explored the protective role of TP on the nucleus pulposus cells (NPCs) of intervertebral discs and their underlying mechanism. Methods: An in vitro model of H2O2-induced degeneration of NPCs was established. RT-qPCR and western blotting were used to detect the mRNA and protein expression of the targets. An in vivo model of IDD was established via acupuncture of the intervertebral disc. Radiological imaging and histological staining were performed to evaluate the protective role of TP. Results: H2O2 contributed to NPC degeneration by inducing high levels of oxidative stress. TP treatment effectively increased the expression of nucleus pulposus matrix-associated genes and reduced the expression of degeneration factors. Further mechanistic studies showed that TP delayed H2O2-mediated NPC degeneration by activating the Keap1/Nrf2/ARE pathway. In vivo experiments showed that TP delayed the degeneration of NPCs in rats through the Keap1/Nrf2/ARE pathway. Conclusion: Our study confirmed that TP activates the Keap1/Nrf2/ARE pathway to exert an antioxidative stress role, ultimately delaying the degeneration of intervertebral discs.

7.
Arthritis Res Ther ; 23(1): 45, 2021 01 30.
Artigo em Inglês | MEDLINE | ID: mdl-33514418

RESUMO

INTRODUCTION: Behcet's syndrome (BS) is a complex, heterogeneous disorder. However, classification of its subgroups is still debated. The purpose of this study was to investigate the clinical features and aggregation of patients with BS in China, based on manifestations and organ involvements. METHODS: This was a cross-sectional study of BS patients in Huadong Hospital of Fudan University between September 2012 and January 2020. We calculated relative risks (RRs) of clinical variables according to sex. Moreover, we conducted a hierarchical cluster analysis applied according to eighteen variables to determine subgroups of patients. RESULTS: A total of 860 BS patients were included. Male sex was associated with ocular involvement (RR 2.32, 95% CI 1.67, 3.22, P < 0.0001), vascular involvement (RR 2.00, 95% CI 1.23, 3.23, P = 0.004), cardiac lesion (RR 5.46, 95% CI 2.33, 12.77, P < 0.0001), and central nervous system involvement (RR 2.95, 95% CI 1.07, 6.78, P = 0.007) and was negatively associated with genital ulcers (RR 0.84, 95% CI 0.79, 0.91, P < 0.0001). Five clusters (C1-C5) were observed. C1 (n = 307) showed the skin and mucosa type. In C2 (n = 124), all had articular involvement, barely having major organ involvement except for 18 cases with intestinal lesions. In C3 (n = 156), the gastrointestinal type, 144 patients presented with intestinal involvement, and 36 patients with esophageal ulcers. In C4 (n = 142), all subjects presented with uveitis. C5 (n = 131) consisted of 44 patients with cardiac lesions, 58 with vascular involvement, and 26 cases having central nervous system involvement. CONCLUSION: Our analysis confirmed sex differences in phenotypes of BS. Cluster analysis identified gastrointestinal, uveitis, and cardiovascular involvement cluster separately in different subsets, which represents the most commonly involved organs. Further research is required to replicate and clarify the patterns of phenotype in BS.

8.
Medicine (Baltimore) ; 100(2): e24090, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33466172

RESUMO

OBJECTIVE: To understood the pathogen detection status and clinical characteristics of suspected pertussis in children and to observe the drug sensitivity and drug resistance genes of Bordetella pertussis (B. pertussis). METHODS: Three hundred fifty-one cases were collected and their nasopharyngeal swab samples were analyzed by culture and fluorescent quantitative polymerase chain reaction. The susceptibility to erythromycin, clindamycin, ampicillin, levofloxacin, and sulfamethoxazole-trimethoprim were tested by E-test for the positive strains, and the susceptibility to erythromycin was also tested for the KB disk diffusion method. The 23S rRNA gene of the positive strains was amplified and sequenced, and statistical analysis was performed in conjunction with clinical data. RESULTS: The positive rate of bacterial culture was 16.8% (59/351), and the positive rate of PCR was 62.4% (219/351). Two cases were positive about bacterial culture and negative for PCR. There were 221 confirmed cases of pertussis. The E-test results showed that the rate of the sensitivity of the 55 strains of pertussis to erythromycin and clindamycin was 50.9% (28/55), the minimum antibiotic concentration50 (MIC50) and MIC90 values were 0.094/>256 and 0.75/>256 mg/L, respectively, and the MIC50/MIC90 to ampicillin, levofloxacin, and sulfamethoxazole were 0.125/0.19, 0.38/0.5, and 0.125/0.25 mg/L, respectively. The KB disk diffusion method showed 27 of the 55 strains 49.1% (27/55) was resistant to erythromycin; all of the resistant strains had the 23S rRNA gene A2047G mutation, and their MIC of erythromycin was >256 mg/L. CONCLUSION: The diagnosis of pertussis by a fluorescent quantitative polymerase chain reaction method is more sensitive than that of bacterial culture. The resistance of B. pertussis to erythromycin was prominent. All of the strains of B. pertussis resistant to erythromycin in our center had the A2047G mutation of the 23S rRNA gene.


Assuntos
Bordetella pertussis/efeitos dos fármacos , Bordetella pertussis/genética , Farmacorresistência Bacteriana/genética , Testes de Sensibilidade Microbiana/métodos , Coqueluche/microbiologia , Antibacterianos/farmacologia , Criança , Pré-Escolar , China , Técnicas de Cultura , Eritromicina/farmacologia , Feminino , Humanos , Lactente , Masculino , Tipagem Molecular , Mutação , Reação em Cadeia da Polimerase , RNA Ribossômico 23S/genética , Coqueluche/diagnóstico
10.
Clin Rheumatol ; 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33411142

RESUMO

OBJECTIVES: To evaluate the demographics, clinical aspects, and major organ involvement of patients with late-onset Behçet's syndrome (BS) in a tertiary center in China. METHODS: We conducted a cross-sectional study of consecutive BS patients in Huadong Hospital of Fudan University from September 2012 to January 2020. We compared clinical variables between patients with disease onset before and after 40 years of age. The relative risks (RRs) of clinical variables were calculated between the two age groups. Moreover, a hierarchical cluster analysis was conducted according to 29 variables to determine homogeneous subgroups in patients with late-onset BS. RESULTS: We enrolled 152 late-onset BS patients, with a median age at onset of 47 years (interquartile range, IQR: 43-52 years). There is a higher prevalence of intestinal ulcers in late-onset BS than in early-onset BS (RR 1.47), but a lower prevalence of ocular involvements (RR 0.54) and folliculitis (RR 0.46). Female sex was associated with genital ulcers, erythema nodosum, and arthritis. Four clusters (C1-C4) were formed. C1 (n = 71), the largest cluster, was defined as the mucocutaneous group, C2 (n = 20) as the arthritis group, C3 (n = 39) as the gastrointestinal group, in which all patients presented with intestinal lesions, and five cases with esophageal ulcers. In C4 (n = 22), showing a mixture of uveitis and vascular lesions, 15 patients presented with uveitis and 8 had vascular lesions, and 1 case had central nervous system lesions. CONCLUSION: Four phenotype clusters were identified. Patients with skin lesions comprised the largest cluster, while gastrointestinal, panuveitis, and cardiovascular clusters are the most commonly involved organs in late-onset BS patients. Key Points • Our analysis demonstrated the phenotype discrepancy between early and late onset groups. • Four phenotype clusters were identified, with gastrointestinal, panuveitis and cardiovascular clusters representing commonly involved organs.

11.
Dev Comp Immunol ; 114: 103791, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32784010

RESUMO

CD3 is an essential component of the TCR-CD3 complex which plays a key role in adaptive immunity. Non-mammalian CD3 complex consists of CD3γ/δ, CD3ε and CD3ζ subunits. In this study, homologues of CD3γ/δ and CD3ε (termed CiCD3γ/δ and CiCD3ε) have been identified in grass carp (Ctenopharyngodon idella). Like their counterparts from other vertebrates, the CiCD3γ/δ and CiCD3ε are clustered in the same locus in the genome and encode proteins which are structurally conserved, comprising a signal peptide, an extracellular domain, a transmembrane domain and a cytoplasmic tail containing two ITAM motifs. Sequence analyses identified two novel conserved motifs in the cytoplasmic tail of CiCD3γ/δ and CiCD3ε, one is composed of an arginine and lysine motif (RK or RR) at the C terminus of CiCD3γ/δ and a proline rich domain (PxxPxP/Q) located at the N terminus of ITAM motifs of CiCD3ε. Both genes were highly expressed at the mRNA level in the spleen and gills of healthy fish and could be modulated by infection of Flavobacterium columnare and grass carp reovirus. A monoclonal antibody against the CiCD3γ/δ (GC38T) was produced and showed good reactivity with the native molecule in Western blotting analysis and flow cytometry. The CiCD3γ/δ+ cells were analysed in the primary leucocytes, accounting for 5.5% of lymphocytes isolated from spleen, 4.5% from head kidney and 2.8% from peripheral blood. The CiCD3γ/δ+ cells were localized in the gills and head kidney by fluorescent confocal microscopy.

12.
Dev Comp Immunol ; 115: 103895, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33065202

RESUMO

Interleukin (IL) -2, a member of the four α-helical cytokine family, has broad regulatory roles in mediating vertebrate immune response. In mammals, IL-2 and IL-15 share a common evolutionary origin and possess overlapping but distinct functions. IL-2 and IL-15 bind to distinct private receptors for signaling. However, fish appear to possess a single IL-15Rα like gene whilst lack additional gene(s) coding for IL-2Rα. Whether the IL-2 and IL-15 interact with the same receptor in fish and how their functions and receptors have evolved are not fully understood. In this study, homologues of IL-2 and IL-2/15Rα were sequenced from a teleost species, grass carp (Ctenopharyngodon idella), and the crystal structure of IL-2 was determined. The grass carp IL-2 (termed CiIL-2) displayed a classical cytokine structure consisting of four helical bundles which shares significant similarity with human IL-15. The key amino acids involved in the interface interaction of IL-2/15 and their receptors are well conserved. The CiIL-2 has been shown to bind the IL-2/15Rα like homologue with an affinity of 2.45 nM, supporting the notion that fish IL-2 and IL-15 may share a single common private receptor for exerting functions. Syntenic analysis suggests that the IL-2Rα of tetrapods has evolved from an IL-15Rα like homologue, in which a second sushi domain (D2) in the extracellular region has been duplicated to facilitate the specific interaction with IL-2. The CiIL-2 was predominantly expressed in lymphocyte-rich tissues such as the spleen, kidney and thymus, and could be induced by PHA and IL-21. In vivo challenge with grass carp reovirus and Flavobacterium columnare also resulted in upregulation of CiIL-2 expression. The recombinant CiIL-2 was shown to activate expression of STAT5b, IL-1ß, IL-22 and IFN-γ, and to promote the proliferation of the primary cell cultures from head kidney leucocytes. Our results shed lights into the co-evolution of IL-2 and its private receptor, and the functional divergence of IL-2 and IL-15 during evolution.

13.
Am J Cancer Res ; 10(11): 3947-3972, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33294279

RESUMO

The AT-rich Interactive Domain 1A (ARID1A) is one of the most frequently mutated genes in gastric cancer. Here, we found that genetic variants in noncoding regions of ARID1A associated with altered protein levels by target sequencing. Notably, tumors with ARID1A variants in the 3'untranslated region (3'UTR) exhibited remarkably increased heterogeneity of ARID1A protein. In general, genetic variants and protein deficiency of ARID1A in tumors were associated with a better survival. Strikingly, altered patterns and heterogeneity of ARID1A protein expression were observed in peritumor tissues and carried significant implications in defining tumor immune contexture by multiplex immunohistochemistry. By analyzing the spatial distribution of TILs, we showed that reduced ARID1A protein levels in both tumor and peritumor tissues were significantly correlated with increased density and proximity of TILs to tumor cells. In contrast, high heterogeneity of ARID1A expression was associated with increased TIL density, but reduced proximity of TILs to tumor cells. Collectively, our study characterized ARID1A genetic alterations and its protein expression patterns in EOGC, demonstrating new strategies for clinically assessing its molecular impact on tumor onset and progression, tumor immune response, and patient survival.

14.
Artigo em Inglês | MEDLINE | ID: mdl-33301289

RESUMO

The rapid development of CRISPR/Cas9 systems has opened up tantalizing prospects to sensitize cancers to chemotherapy using efficient targeted genome editing, but safety concerns and possible off-target effects of viral vectors remain a major obstacle for clinical application. Thus, the construction of novel nonviral tumor-targeting nanodelivery systems has great potential for the safe application of CRISPR/Cas9 systems for gene-chemo-combination therapy. Here, we report a polyamidoamine-aptamer-coated hollow mesoporous silica nanoparticle for the co-delivery of sorafenib and CRISPR/Cas9. The core-shell nanoparticles had good stability, enabled ultrahigh drug loading, targeted delivery, and controlled-release of the gene-drug combination. The nanocomplex showed >60% EGFR-editing efficiency without off-target effects in all nine similar sites, regulating the EGFR-PI3K-Akt pathway to inhibit angiogenesis, and exhibited a synergistic effect on cell proliferation. Importantly, the co-delivery nanosystem achieved efficient EGFR gene therapy and caused 85% tumor inhibition in a mouse model. Furthermore, the nanocomplex showed high accumulation at the tumor site in vivo and exhibited good safety with no damage to major organs. Due to these properties, the nanocomplex provides a versatile delivery approach for efficient co-loading of gene-drug combinations, allowing for precise gene editing and synergistic inhibition of tumor growth without apparent side effects on normal tissues.

15.
Cell Biochem Funct ; 2020 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-33354822

RESUMO

Research into the diagnosis, treatment and prevention of childhood-related diseases is the key to reducing their morbidity and mortality. Circular RNAs (circRNAs) play critical roles, both in physiology and pathology, and there is ample evidence to show that they play varying roles in tissue development and gene regulation. Studies on circRNAs in different childhood-related diseases have confirmed their great potential for disease prevention and treatment. These breakthroughs highlight the pathological role of circRNAs in cancers, as well as cardiovascular and hereditary childhood illnesses. In this review, we summarize the role of circRNAs in childhood-related diseases and cancer, and provide an update of the possible diagnostic and therapeutic application of circRNAs.

16.
iScience ; 23(11): 101682, 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33163937

RESUMO

The triboelectric nanogenerator (TENG) and piezoelectric nanogenerator (PENG) are two recently developed technologies for effective harvesting of ambient mechanical energy for the creation of self-powered systems. The advantages of TENGs and PENGs which include large open-circuit output voltage, low cost, ease of fabrication, and high conversion efficiency enable their application as new flexible sensors, wearable devices, soft robotics, and machines. This perspective provides an overview of the current state of the art in triboelectric and piezoelectric devices that are used as self-powered sensors and energy harvesters for soft robots and machines; hybrid approaches that combine the advantages of both mechanisms are also discussed. To improve system performance and efficiency, the potential of providing self-powered soft systems with a degree of multifunctionality is investigated. This includes optical sensing, transparency, self-healing, water resistance, photo-luminescence, or an ability to operate in hostile environments such as low temperature, high humidity, or high strain/stretch. Finally, areas for future research directions are identified.

17.
Front Immunol ; 11: 586889, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33178219

RESUMO

Interleukin (IL)-22 plays an important role in regulating inflammation and clearance of infectious pathogens. IL-22 homologs have been discovered in fish, but the functions and sources of IL-22 have not been fully characterized. In this study, an IL-22 homolog was identified in grass carp and its bioactivities were investigated. The grass carp IL-22 was constitutively expressed in tissues, with the highest expression detected in the gills and hindgut. It was upregulated in the spleen after infection with Flavobacterium columnare and grass carp reovirus and in the primary head kidney and spleen leukocytes stimulated with LPS and IL-34. Conversely, it was downregulated by Th2 cytokines such as IL-4/13B and IL-10. The recombinant IL-22 produced in bacteria showed a stimulatory effect on the expression of inflammatory cytokines and STAT3 in the primary head kidney leukocytes and CIK cells. Moreover, the IL-22-positive cells were found to be induced in the hindgut and head kidney 24 h after infection by F. columnare. Our data suggest that IL-22 plays an important role in regulating mucosal and systemic immunity against bacterial and viral infection.

18.
Kidney Int ; 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-33137336

RESUMO

Previously, we found that mild tubulointerstitial injury sensitizes glomeruli to subsequent injury. Here, we evaluated whether stabilization of hypoxia-inducible factor-α (HIF-α), a key regulator of tissue response to hypoxia, ameliorates tubulointerstitial injury and impact on subsequent glomerular injury. Nep25 mice, which express the human CD25 receptor on podocytes under control of the nephrin promotor and develop glomerulosclerosis when a specific toxin is administered were used. Tubulointerstitial injury, evident by week two, was induced by folic acid, and mice were treated with an HIF stabilizer, dimethyloxalylglycine or vehicle from week three to six. Uninephrectomy at week six assessed tubulointerstitial fibrosis. Glomerular injury was induced by podocyte toxin at week seven, and mice were sacrificed ten days later. At week six tubular injury markers normalized but with patchy collagen I and interstitial fibrosis. Pimonidazole staining, a hypoxia marker, was increased by folic acid treatment compared to vehicle while dimethyloxalylglycine stimulated HIF-2α expression and attenuated tubulointerstitial hypoxia. The hematocrit was increased by dimethyloxalylglycine along with downstream effectors of HIF. Tubular epithelial cell injury, inflammation and interstitial fibrosis were improved after dimethyloxalylglycine, with further reduced mortality, interstitial fibrosis, and glomerulosclerosis induced by specific podocyte injury. Thus, our findings indicate that hypoxia contributes to tubular injury and consequent sensitization of glomeruli to injury. Hence, restoring HIFs may blunt this adverse crosstalk of tubules to glomeruli.

19.
Orthopedics ; : 1-6, 2020 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-33141233

RESUMO

Osteoporotic vertebral fracture (OVF) usually occurs in the thoracolumbar region and rarely affects the low lumbar region. The characteristics of osteoporotic low lumbar fracture (OLLF) have not been reported. Lumbosacral sagittal balance plays an important role in preserving the normal physiologic function of the spine. However, it is unknown how lumbosacral parameters vary in patients with OLLF. The authors retrospectively analyzed the clinical and radiologic characteristics of patients with OLLF and osteoporotic thoracolumbar vertebral fracture (OTVF) who were treated at their institution. Vertebral height, local deformity angle, and visual analog scale and Oswestry Disability Index scores were assessed preoperatively and postoperatively for both groups. The changes in lumbosacral parameters were measured for patients with OLLF. The results showed that OLLF was more likely to occur at L3 (53.66%) and that the prevalence of severe trauma (29.27%) was higher among patients with OLLF (P<.05). The most common morphologic type of the vertebrae affected by OLLF was biconcave (58.54%, P<.05). Patients who had OLLF showed an apparent increase in pelvic tilt and a decrease in local lordosis and sacral slope. Postoperatively, vertebral height, local deformity angle, and visual analog scale and Oswestry Disability Index scores were significantly improved compared with preoperative values (P<.05). Among patients with OLLF, local lordosis and sacral slope increased significantly, whereas pelvic tilt decreased significantly after percutaneous kyphoplasty. Restoration of local lordosis had a mean value of 6.29°±4.80°. These results indicate that OLLF has unique characteristics compared with OTVF and that it results in lumbosacral sagittal imbalance. Percutaneous kyphoplasty is effective and safe for the treatment of OLLF and plays an important role in postoperative improvement of sagittal imbalance. [Orthopedics. 2021;44(x):xx-xx.].

20.
J Clin Lab Anal ; : e23640, 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33146916

RESUMO

BACKGROUND: With the initially defined thresholds, the most widely used serum biomarkers for staging liver fibrosis (ie, APRI and FIB-4 scores) proved to be ineffective among patients with chronic hepatitis B virus infection (CHB). Whether optimizing the FIB-4 and APRI thresholds could improve their diagnostic accuracy requires further research. METHODS: Using data of treat-naïve CHB patients from three tertiary hospitals, we explored the optimal FIB-4 and APRI thresholds to rule in liver fibrosis accurately. Subsequently, we validated the applicability of the newly defined thresholds to the CHB patients from another two tertiary hospitals. RESULTS: The fibrosis stages between discovery cohort (n = 433) and the external validation cohort (n = 568) were statistically different (P < .001). When ruling in significant fibrosis and advanced fibrosis by the newly defined FIB-4 thresholds (2.25 and 3.00, respectively), 24.0% and 14.3% of patients, respectively, could be classified with excellent accuracy (PPVs of 91.3% and 80.6%, respectively; misdiagnosis rates of 6.0% and 5.4%, respectively), supported by the internal and external validation tests. Regrettably, the more accurate and robust thresholds of APRI score for ruling in significant fibrosis and advanced fibrosis could not be found. Besides, the FIB-4 and APRI scores should not be recommended for ruling in cirrhosis because of poor clinical diagnostic performance. CONCLUSION: The newly defined FIB-4 thresholds for ruling in significant fibrosis and advanced fibrosis showed superior and reproducible clinical diagnostic accuracy. The well-validated threshold (≥2.25) of FIB-4 score could aid in antiviral treatment decisions for treat-naïve adult CHB patients by accurately ruling in significant fibrosis in tertiary care settings.

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