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1.
Funct Integr Genomics ; 24(2): 76, 2024 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-38656411

RESUMO

Stroke is a leading cause of death and disability, and genetic risk factors play a significant role in its development. Unfortunately, effective therapies for stroke are currently limited. Early detection and diagnosis are critical for improving outcomes and developing new treatment strategies. In this study, we aimed to identify potential biomarkers and effective prevention and treatment strategies for stroke by conducting transcriptome and single-cell analyses. Our analysis included screening for biomarkers, functional enrichment analysis, immune infiltration, cell-cell communication, and single-cell metabolism. Through differential expression analysis, enrichment analysis, and protein-protein interaction (PPI) network construction, we identified HIST2H2AC as a potential biomarker for stroke. Our study also highlighted the diagnostic role of HIST2H2AC in stroke, its relationship with immune cells in the stroke environment, and our improved understanding of metabolic pathways after stroke. Overall, our research provided important insights into the pathogenesis of stroke, including potential biomarkers and treatment strategies that can be explored further to improve outcomes for stroke patients.


Assuntos
Biomarcadores , Histonas , Acidente Vascular Cerebral , Humanos , Biomarcadores/análise , Perfilação da Expressão Gênica , Mapas de Interação de Proteínas , Análise de Célula Única , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/metabolismo , Transcriptoma , Histonas/análise
2.
Chem Res Toxicol ; 37(1): 98-108, 2024 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-38150050

RESUMO

Hexafluoropropylene oxide dimer acid (HFPO-DA; trade name GenX), as a substitute for perfluorooctanoic acid (PFOA), has been attracting increasing attention. However, its impact and corresponding mechanism on hepatic lipid metabolism are less understood. To investigate the possible mechanisms of GenX for hepatotoxicity, a series of in vivo and in vitro experiments were conducted. In in vivo experiment, male mice were exposed to GenX in drinking water at environmental concentrations (0.1 and 10 µg/L) and high concentrations (1 and 100 mg/L) for 14 weeks. In in vitro experiments, human hepatocellular carcinoma cells (HepG2) were exposed to GenX at 10, 160, and 640 µM for 24 and 48 h. GenX exposure via drinking water resulted in liver damage and disruption of lipid metabolism even at environmental concentrations. The results of triglycerides (TG) and total cholesterol (TC) in this study converged with the results of the population study, for which TG increased in the liver but unchanged in the serum, whereas TC increased in both liver and serum concentrations. KEGG and GO analyses revealed that the hepatotoxicity of GenX was associated with fatty acid transport, synthesis, and oxidation pathways and that Peroxisome Proliferator-Activated Receptor (PPARα) contributed significantly to this process. PPARα inhibitors significantly reduced the expression of CD36, CPT1ß, PPARα, SLC27A1, ACOX1, lipid droplets, and TC, suggesting that GenX exerts its toxic effects through PPARα signaling pathway. In general, GenX at environmental concentrations in drinking water causes abnormal lipid metabolism via PPARα signaling pathway.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Água Potável , Fluorocarbonos , Propionatos , Camundongos , Masculino , Humanos , Animais , Metabolismo dos Lipídeos , PPAR alfa/farmacologia , Água Potável/análise , Fluorocarbonos/farmacologia , Fígado , Transdução de Sinais
3.
BMC Vet Res ; 20(1): 20, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38200549

RESUMO

BACKGROUND: Mycoplasma ovipneumoniae (M. ovipneumoniae) is a significant pathogen causing respiratory infections in goats and sheep. This study focuses on investigating vulnerability of Hu sheep to M. ovipneumoniae infection in the context of late spring's cold weather conditions through detailed autopsy of a severely affected Hu sheep and whole genome sequencing of M. ovipneumoniae. RESULTS: The autopsy findings of the deceased sheep revealed severe pulmonary damage with concentrated tracheal and lung lesions. Histopathological analysis showed tissue degeneration, mucus accumulation, alveolar septum thickening, and cellular necrosis. Immunohistochemistry analysis indicated that M. ovipneumoniae was more in the bronchi compared to the trachea. Genome analysis of M. ovipneumoniae identified a 1,014,835 bp with 686 coding sequences, 3 rRNAs, 30 tRNAs, 6 CRISPRs, 11 genomic islands, 4 prophages, 73 virulence factors, and 20 secreted proteins. CONCLUSION: This study investigates the vulnerability of Hu sheep to M. ovipneumoniae infection during late spring's cold weather conditions. Autopsy findings showed severe pulmonary injury in affected sheep, and whole genome sequencing identified genetic elements associated with pathogenicity and virulence factors of M. ovipneumoniae.


Assuntos
Doenças das Cabras , Mycoplasma ovipneumoniae , Pneumonia por Mycoplasma , Doenças dos Ovinos , Animais , Ovinos , Mycoplasma ovipneumoniae/genética , Pneumonia por Mycoplasma/veterinária , Autopsia/veterinária , Cabras , Fatores de Virulência , Sequenciamento Completo do Genoma/veterinária
4.
Funct Integr Genomics ; 23(2): 191, 2023 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-37249689

RESUMO

As a key component of Transforming growth factor-ß (TGF-ß) pathway, Smad2 has many crucial roles in a variety of cellular processes, but it cannot bind DNA without complex formation with Smad4. In the present study, the molecular mechanism in the progress of myogenesis underlying transcriptional regulation of SMAD2 and SMAD4 had been clarified. The result showed the inhibition between SMAD2 and SMAD4, which promotes and inhibits bovine myoblast differentiation, respectively. Further, the characterization of promoter region of SMAD2 and SMAD4 was analyzed, and identified C/EBPß directly bound to the core region of both SMAD2 and SMAD4 genes promoter and stimulated the transcriptional activity. However, C/EBPß has lower expression in myoblasts which plays vital function in the transcriptional networks controlling adipogenesis, while the overexpression of C/EBPß gene in myoblasts significantly increased SMAD2 and SMAD4 gene expression, induced the formation of lipid droplet in bovine myoblasts, and promoted the expression of adipogenesis-specific genes. Collectively, our results showed that C/EBPß may play an important role in the trans-differentiation and dynamic equilibrium of myoblasts into adipocyte cells via promoting an increase in SMAD2 and SMAD4 gene levels. These results will provide an important basis for further understanding of the TGFß pathway and C/EBPß gene during myogenic differentiation.


Assuntos
Proteína beta Intensificadora de Ligação a CCAAT , Gotículas Lipídicas , Animais , Bovinos , Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Gotículas Lipídicas/metabolismo , Transdução de Sinais/genética , Diferenciação Celular , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismo , Mioblastos/metabolismo
5.
BMC Musculoskelet Disord ; 24(1): 683, 2023 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-37644473

RESUMO

BACKGROUND: Alignment is indispensable for the foot and ankle function, especially in the hindfoot alignment. In the preoperative planning of patients with varus or valgus deformity, the precise measurement of the hindfoot alignment is important. A new method of photographing and measuring hindfoot alignment based on X-ray was proposed in this study, and it was applied in the assessment of flatfoot. METHODS: This study included 28 patients (40 feet) with flatfeet and 20 volunteers (40 feet) from January to December 2018. The hindfoot alignment shooting stand independently designed by our department was used to take hindfoot alignment X-rays at 10 degree, 15 degree, 20 degree, 25 degree, and 30 degree. We measured the modified tibio-hindfoot angle (THA) at the standard hindfoot aligment position (shooting at 20 degree) and evaluated consistency with the van Dijk method and the modified van Dijk method. In addition, we observed the visibility of the tibiotalar joint space from all imaging data at five projection angles and evaluated the consistency of the modified THA method at different projection angles. The angle of hindfoot valgus of flatfoot patients was measured using the modified THA method. RESULTS: The mean THA in the standard hindfoot aligment view in normal people was significantly different among the three evaluation methods (P < .001). The results from the modified THA method were significantly larger than those from the Van Dijk method (P < .001) and modified Van Dijk method (P < .001). There was no significant difference between the results of the modified THA method and the weightbearing CT (P = .605), and the intra- and intergroup consistency were the highest in the modified THA group. The tibiotalar space in the normal group was visible in all cases at 10 degree, 15 degree, and 20 degree; visible in some cases at 25 degree; and not visible in all cases at 30 degree. In the flatfoot group, the tibiotalar space was visible in all cases at 10 degree, visible in some cases at 15 degree and 20 degree, and not visible in all cases at 25 degree and 30 degree. In the normal group, the modified THA was 4.84 ± 1.81 degree at 10 degree, 4.96 ± 1.77 degree at 15 degree, and 4.94 ± 2.04 degree at 20 degree. No significant differences were found among the three groups (P = .616). In the flatfoot group, the modified THA of 18 feet, which was visible at 10 degree, 15 degree and 20 degree, was 13.58 ± 3.57 degree at 10 degree, 13.62 ± 3.83 degree at 15 degree and 13.38 ± 4.06 degree at 20 degree. There were no significant differences among the three groups (P = .425). CONCLUSIONS: The modified THA evaluation method is simple to use and has high inter- and intragroup consistency. It can be used to evaluate hindfoot alignment. For patients with flatfeet, the 10 degree position view and modified THA measurement can be used to evaluate hindfoot valgus.


Assuntos
Pé Chato , Humanos , Pé Chato/diagnóstico por imagem , , Radiografia , Extremidade Inferior , Articulação do Tornozelo
6.
Anal Biochem ; 654: 114744, 2022 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-35642804

RESUMO

MicroRNA (miRNA) and circular RNA (circRNA) are promising biomarkers for early-diagnosis of a variety of diseases, such as myocardial infarction and cancers. However, few methods reported simultaneous and sensitive detection of multiple miRNAs. Herein, we design a novel approach with an improved miRNA and circRNA detection sensitivity. There are only two probes designed with hairpin probe, namely catch probe and report probe, in the system. When target miRNA or circRNA existed, it can unfold catch probe through hybridizing with toehold section and form a rigid DNA-RNA duplex. The DNA sequence in the formed duplex is identified and digested by duplex-specific nuclease (DSN enzyme), and consequently, target miRNA is released to attend a next signal cycle. The rested DNA sequence in catch probe (initiator probe) recognizes report probe and separates its hairpin structure to generate fluorescence signals, forming a double-strand DNA (dsDNA) product. Unfold report probe sequence in the dsDNA product is then digested by DNA nicking endonuclease (NEase) and initiator is released to trigger amplified signals. Based on the DSN enzyme cooperating NEase assisted dual signal amplification, the method exhibits a greatly improved detection sensitivity.


Assuntos
Técnicas Biossensoriais , MicroRNAs , Técnicas Biossensoriais/métodos , DNA , Desoxirribonuclease I , Endonucleases , Limite de Detecção , MicroRNAs/genética , Técnicas de Amplificação de Ácido Nucleico/métodos , RNA Circular
7.
Gen Physiol Biophys ; 41(6): 591-601, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36454119

RESUMO

This study was aimed to develop a nomogram for predicting the cancer-specific survival (CSS) of patients with clear-cell renal cell carcinoma (ccRCC). Based on the Surveillance, Epidemiology, and End Results (SEER) database, 24,477 patients diagnosed with ccRCC between 2010 and 2015 were collected. They were randomly divided into a training cohort (n = 17,133) and a validation cohort (n = 7,344). Univariate and multivariate Cox regression analyses were performed in the training cohort to identify independent prognostic factors for construction of nomogram. Then, the nomogram was used to predict the 3- and 5-year CSS. The performance of nomogram was evaluated by using concordance index (C-index), net reclassification improvement (NRI), integrated discrimination improvement (IDI), calibration curve, and decision curve analysis (DCA). Moreover, the nomogram and tumor node metastasis (TNM) staging system (AJCC 7th edition) were compared. Eleven variables were screened to develop the nomogram. The area under the receiver operating characteristic (ROC) curve (AUC) and the calibration plots indicated satisfactory ability of the nomogram. Compared with the AJCC 7th edition of TNM stage, C-index, NRI, and IDI showed that the nomogram had improved performance. Furthermore, the 3- and 5-year DCA curves of nomogram yielded more net benefits than the AJCC 7th edition of TNM stage in both the training and validation sets. We developed and validated a nomogram for predicting the CSS of patients with ccRCC, which was more precise than the AJCC 7th edition of TNM staging system.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Nomogramas
8.
Int Orthop ; 46(9): 2135-2143, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35570205

RESUMO

PURPOSE: Open reduction and internal fixation (ORIF) is the most commonly used surgical technique for talar neck fracture, but there are high risks for complications and poor functional outcomes. In this study, we reported the closed reduction and percutaneous internal fixation (CRPIF) technique of the bilateral approach of the Achilles tendon for simple displaced talar neck fracture, in comparison with ORIF. METHODS: Data of 15 patients in the CRPIF group and 22 in the ORIF group were included. The American Orthopaedic Foot and Ankle Society (AOFAS) score, Visual Analog Scale (VAS) score, 12-item Short-Form Survey (SF-12) score, range of motion (ROM), complications, and radiographic results were recorded and compared. RESULTS: The mean follow-up in the CRPIF group was 33.9 months. Complications included two cases of avascular necrosis (AVN) and two cases of osteoarthritis. All patients achieved bony union and recovered their pre-operative mobility. The mean follow-up in the ORIF group was 39 months. Complications included two cases of bony nonunion, nine AVN, and seven cases of osteoarthritis. Moreover, the mobility of the ORIF group was significantly lower than the CRPIF group post-operatively. The AOFAS score, VAS score, and SF-12 physical component score (PCS) for the CRPIF group were better improved than those for the ORIF group (ALL, P < 0.05). CONCLUSIONS: The CRPIF technique of the bilateral approach of the Achilles tendon was an effective method for the treatment of simple displaced talar neck fractures. Compared with the ORIF, the limited blood supply of the talus was protected, provide better functional outcomes and biomechanical fixation, and lower incidence of resurgery and complication in the CRPIF.


Assuntos
Fraturas Ósseas , Osteoartrite , Tálus , Fixação Interna de Fraturas/efeitos adversos , Fixação Interna de Fraturas/métodos , Fraturas Ósseas/diagnóstico por imagem , Fraturas Ósseas/cirurgia , Humanos , Estudos Retrospectivos , Tálus/cirurgia , Resultado do Tratamento
9.
BMC Genomics ; 22(1): 217, 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33765915

RESUMO

BACKGROUND: Many recent studies have shown that miRNAs play important roles in the regulation of animal reproduction, including seasonal reproduction. The pineal gland is a crucial hub in the regulation of seasonal reproduction. However, little is known about the expression characteristics of pineal miRNAs in different reproductive seasons (anestrus and breeding season). Therefore, the expression profiles and regulatory roles of ovine pineal miRNAs were investigated during different reproductive stages using Solexa sequencing technology and dual luciferase reporter assays. RESULTS: A total of 427 miRNAs were identified in the sheep pineal gland. Significant differences in miRNA expression were demonstrated between anestrus and the breeding season in terms of the frequency distributions of miRNA lengths, number of expressed miRNAs, and specifically and highly expressed miRNAs in each reproductive stage. KEGG analysis of the differentially expressed (DE) miRNAs between anestrus and the breeding season indicated that they are significantly enriched in pathways related to protein synthesis, secretion and uptake. Furthermore, transcriptome analysis revealed that many target genes of DE miRNAs in the ribosome pathway showed relatively low expression in the breeding season. On the other hand, analyses combining miRNA-gene expression data with target relationship validation in vitro implied that miR-89 may participate in the negative regulation of aralkylamine N-acetyltransferase (AANAT) mRNA expression by targeting its 3'UTR at a unique binding site. CONCLUSIONS: Our results provide new insights into the expression characteristics of sheep pineal miRNAs at different reproductive stages and into the negative regulatory effects of pineal miRNAs on AANAT mRNA expression.


Assuntos
MicroRNAs , Glândula Pineal , Acetiltransferases , Animais , Feminino , Perfilação da Expressão Gênica , MicroRNAs/genética , Reprodução/genética , Ovinos/genética
10.
Invest New Drugs ; 39(3): 686-696, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33387131

RESUMO

G9a, a histone methyltransferase, has been found to be upregulated in a range of tumor tissues, and contributes to tumor growth and metastasis. However, the impact of G9a inhibition as a potential therapeutic target in nasopharyngeal carcinoma (NPC) is unclear. In the present study we aimed to investigate the anti-proliferative effect of G9a inhibition in the NPC cell lines CNE1 and CNE2, and to further elucidate the molecular mechanisms underlying these effects. The expression of G9a in NPC tumor tissues was significantly higher than that in normal nasopharyngeal tissues. The pharmacological inhibition of G9a by BIX-01294 (BIX) inhibited proliferation and induced caspase-independent apoptosis in NPC cells in vitro. Treatment with BIX induced autophagosome accumulation, which exacerbated the cytotoxic activity of BIX in NPC cells. Mechanistic studies have found that BIX impairs autophagosomes by initiating autophagy in a Beclin-1-independent way, and impairs autophagic degradation by inhibiting lysosomal cathepsin D activation, leading to lysosomal dysfunction. BIX was able to suppress tumor growth, possibly by inhibiting autophagic flux; it might therefore constitute a promising candidate for NPC therapy.


Assuntos
Antineoplásicos/farmacologia , Azepinas/farmacologia , Histona-Lisina N-Metiltransferase/antagonistas & inibidores , Carcinoma Nasofaríngeo/tratamento farmacológico , Neoplasias Nasofaríngeas/tratamento farmacológico , Quinazolinas/farmacologia , Autofagossomos/efeitos dos fármacos , Linhagem Celular Tumoral , Fenômenos Fisiológicos Celulares/efeitos dos fármacos , Antígenos de Histocompatibilidade/genética , Antígenos de Histocompatibilidade/metabolismo , Histona-Lisina N-Metiltransferase/genética , Histona-Lisina N-Metiltransferase/metabolismo , Humanos , Proteína 2 de Membrana Associada ao Lisossomo/metabolismo , Proteínas de Membrana Lisossomal/metabolismo , Lisossomos/efeitos dos fármacos , Carcinoma Nasofaríngeo/metabolismo , Neoplasias Nasofaríngeas/metabolismo , RNA Interferente Pequeno/genética
11.
J Clin Lab Anal ; 35(4): e23704, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33682960

RESUMO

OBJECTIVE: To investigate the plasma fibrinogen gamma-chain concentration in preeclampsia patients and explore its value in preeclampsia prediction and auxiliary diagnosis. METHODS: Follow-up of pregnant women who regularly attended perinatal care at two hospitals in China was performed, and clinical data and plasma samples were collected at each examination until delivery. The gamma-chain concentration was detected by Western blotting, and Quantity One Software was used for gamma-chain grayscale value measurements. RESULTS: Forty-two patients with preeclampsia and 42 control patients completed the follow-up. In the control group, the gamma-chain concentration at 32 weeks of gestation was higher than that at 20 weeks of gestation, but the difference was not statistically significant (p > 0.05). In the experimental group, the gamma-chain concentration at preeclampsia diagnosis was significantly higher than that at 20 weeks of gestation (p < 0.05). Compared with the control group, the gamma-chain concentration was higher at 20 weeks of gestation in the experimental group, but the difference was not statistically significant. However, at 32 weeks of gestation and at the time of diagnosis, the gamma-chain concentration in the experimental group was significantly higher than that in the control group (p < 0.05). At 32 weeks of gestation and at the time of diagnosis, the AUCs from ROC curve analysis of plasma fibrinogen gamma-chain concentrations were 0.64 and 0.71, respectively. CONCLUSION: Plasma fibrinogen synthesis and degradation were disrupted in preeclampsia patients before and after diagnosis, and gamma-chain concentration was significantly increased. Plasma fibrinogen gamma chain may be of some value in preeclampsia prediction and auxiliary diagnosis.


Assuntos
Fibrinogênio/metabolismo , Pré-Eclâmpsia/sangue , Adulto , Estudos de Casos e Controles , Feminino , Idade Gestacional , Humanos , Pré-Eclâmpsia/diagnóstico , Gravidez , Curva ROC
12.
BMC Med Educ ; 21(1): 532, 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34649532

RESUMO

BACKGROUND: Vertigo and dizziness (VD) are among the most frequently seen symptoms in clinics and are important for medical students, especially for those in Chinese standardized residency training (SRT). The aim of our study was to examine the PAL method's feasibility in the clinical teaching of VD-related diseases for SRT students in China. METHODS: This is a randomized, controlled, multicenter study. A total of 228 residents were invited to participate in this study, of which 198 completed the program. The students were randomized into two groups, and VD-related diseases were taught using lecture-based learning (control group) or peer-assisted learning (PAL). An examination paper and a rating scale were used to evaluate students' performance in the mastery of VD-related theoretical knowledge and clinical skills, meanwhile students' perceptions, satisfaction, and risk of burnout were also analyzed using a questionnaire. Independent-samples t-test and chi-square analysis were performed to evaluate statistical significance for continuous variables and categorical variables, respectively, using SPSS 18.0 software. RESULTS: The PAL group performed better in mastering theoretical knowledge and clinical skills than the control group. And more students believed that PAL could help improve their personal qualities such as teamwork skills. However, more students reported that PAL increased the risk of burnout. CONCLUSIONS: PAL was a suitable and effective method in the clinical teaching of some specialized diseases, especially it was recommended for students who had gained initial knowledge and skills, such as Chinese SRT students. However, we should draw attention to the increased risk of burnout if PAL is intended to be widely used in clinical teaching. TRIAL REGISTRATION: ISRCTN registry, ISRCTN53773239 , 05/07/2021, retrospectively registered.


Assuntos
Educação de Graduação em Medicina , Internato e Residência , Estudantes de Medicina , China , Tontura , Humanos , Grupo Associado , Ensino , Vertigem/diagnóstico
13.
J Foot Ankle Surg ; 60(1): 204-208, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33187902

RESUMO

We present a case of a 13-year-old female with severe varus deformity and limb discrepancy resulting from epiphyseal fracture. The preoperative tibial articular surface angle was 64.1°, and the affected tibia was 14 mm shorter than the contralateral tibia. She underwent a medial open osteotomy and fibular osteotomy with gradual distraction correction using Ilizarov fixator. The deformity was corrected at 3 months, and the external fixator was removed when bony union was achieved 6 months postoperatively. At 9 months after surgery, the patient could play basketball without feeling pain. At the last follow-up, namely 36 months after the operation, the American Orthopaedic Foot and Ankle Society hindfoot-ankle score was improved from 58 to 90, the patient was pain free, and the radiological measurements were nearly normal. Ilizarov fixator gradual distraction correction for distal tibial severe varus deformity is a safe and cost-effective method that can yield excellent radiological and clinical outcomes.


Assuntos
Hallux Varus , Técnica de Ilizarov , Adolescente , Fixadores Externos , Feminino , Fíbula/cirurgia , Humanos , Osteotomia , Tíbia , Resultado do Tratamento
14.
Int J Mol Sci ; 21(23)2020 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-33291717

RESUMO

The nonreceptor tyrosine TEC kinases are key regulators of the immune system and play a crucial role in the pathogenesis of diverse hematological malignancies. In contrast to the substantial efforts in inhibitor development for Bruton's tyrosine kinase (BTK), specific inhibitors of the other TEC kinases, including the bone marrow tyrosine kinase on chromosome X (BMX), remain sparse. Here we present a novel class of dual BMX/BTK inhibitors, which were designed from irreversible inhibitors of Janus kinase (JAK) 3 targeting a cysteine located within the solvent-exposed front region of the ATP binding pocket. Structure-guided design exploiting the differences in the gatekeeper residues enabled the achievement of high selectivity over JAK3 and certain other kinases harboring a sterically demanding residue at this position. The most active compounds inhibited BMX and BTK with apparent IC50 values in the single digit nanomolar range or below showing moderate selectivity within the TEC family and potent cellular target engagement. These compounds represent an important first step towards selective chemical probes for the protein kinase BMX.


Assuntos
Tirosina Quinase da Agamaglobulinemia/antagonistas & inibidores , Tirosina Quinase da Agamaglobulinemia/química , Descoberta de Drogas , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/farmacologia , Proteínas Tirosina Quinases/antagonistas & inibidores , Proteínas Tirosina Quinases/química , Sítios de Ligação , Descoberta de Drogas/métodos , Humanos , Janus Quinase 3/antagonistas & inibidores , Modelos Moleculares , Conformação Molecular , Estrutura Molecular , Ligação Proteica , Reprodutibilidade dos Testes , Relação Estrutura-Atividade
15.
J Foot Ankle Surg ; 59(4): 801-806, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32600562

RESUMO

This meta-analysis aimed to compare the clinical outcomes of minimally invasive surgery (MIS) and traditional open surgery for the correction of symptomatic hallux valgus. A literature search was conducted, and a total of 11 studies with 1166 (52.98%, cases) patients treated with MIS and 1035 (47.02%, cases) patients treated with traditionally open surgery were included in the meta-analyses. The pooled data (odds ratio [OR] 6.28, 95% confidence interval [CI] 3.20 to 12.32, Z = 5.35, p < .01) indicated that patients treated with MIS had a significantly higher rate of excellent-good radiographic angular results than did patients treated with open surgery. However, the incidences of complications (OR 0.67, 95% CI 0.24 to 1.91, Z = 0.75, p = .45), recovery time (standard mean difference ‒3.09, 95% CI ‒7.98 to 1.80, Z = 1.24, p = .22), and patient-reported satisfaction (OR 2.76, 95% CI 0.72 to 10.65, Z = 1.48, p = .14) were similar between patients with hallux valgus treated with MIS and patients treated with open surgery. Heterogeneity between the sources of the pooled data threatened the validity of our observations, and we used statistical methods that aimed to limit such biases. At this time, more high-quality studies are needed to confirm or refute the results of this investigation.


Assuntos
Joanete , Hallux Valgus , Hallux Valgus/diagnóstico por imagem , Hallux Valgus/cirurgia , Humanos , Procedimentos Cirúrgicos Minimamente Invasivos , Osteotomia , Satisfação do Paciente , Resultado do Tratamento
16.
Trop Anim Health Prod ; 52(3): 915-926, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32026291

RESUMO

For further understanding the genetic control mechanisms of growth and development in Tan sheep, and culturing good traits on meat performance, which is very important to both in developing local species and improving economic efficaciously. In our study, we recruited a total of 250 Tan sheep and 174 healthy Hu sheep to detect 32 SNPs in GH, GHR, NPY, Leptin, H-FABP, MSTN, and CAST by using direct sequencing techniques, in order to explore genetic marking loci which were an association with growth characters. From the results, we found different SNPs with an obvious difference for the growth traits. In the different genetic model analysis, we found SNP12, SNP29, SNP41, SNP8, SNP34, SNP35, SNP9, SNP10, SNP36, SNP45, and SNP39 were a significantly negative association with the two kinds of sheep. And SNP46, SNP42, and SNP69 with the positive association between the different trait in sheep were analyzed. From the LD and haplotype analysis, we found three blocks with the positive association in growth traits between Tan sheep and Hu sheep. The block of SNP29, SNP32, SNP34, SNP35, SNP36, SNP39, SNP41, SNP42, SNP45, and SNP46 with the genotype "AATCTACTTA" is the most significantly association with the traits. In summary, the study initially explored the genes for growth and reproduction between Tan sheep and Hu sheep and found some statistically significant results which demonstrate that there are genetic differences. These differential molecular markers may provide a scientific theoretical basis for the preferred species of Tan sheep which with good meat performance and better utilization of species resources.


Assuntos
Genótipo , Polimorfismo de Nucleotídeo Único , Ovinos/genética , Animais , Conservação dos Recursos Naturais , Marcadores Genéticos , Fenótipo
17.
BMC Musculoskelet Disord ; 20(1): 508, 2019 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-31679523

RESUMO

BACKGROUND: Hallux valgus(HV) with an increased distal metatarsal articular angle (DMAA) is one of the most common foot deformities among adults. Double metatarsal osteotomy (DMO) is effective in treating severe HV deformity with an increased DMAA. However, this technique presents the risk of avascular necrosis (AVN) of the metatarsal head and transfer metatarsalgia due to shortening of the first metatarsal. The aim of this study was to introduce a surgical procedure defined as revolving scarf osteotomy (RSO) and compare the clinical and radiological results of RSO and DMO performed for treating severe HV with an increased DMAA. METHODS: First metatarsal osteotomies and Akin osteotomy were performed in 56 patients (62 ft) with severe HV with an increased DMAA in Honghui Hospital from January 2015 to December 2017. RSO was performed in 32 ft and DMO was performed in 30 ft. The Akin osteotomy was performed in both groups. The American Orthopedic Foot and Ankle Society (AOFAS) score, visual analogue scale (VAS) score, the hallux valgus angle (HVA), intermetatarsal angle (IMA), DMAA, and first metatarsal length (FML) and the rates of complications were compared preoperatively and postoperatively in the two groups. RESULTS: The mean AOFAS score, VAS score, HVA, IMA, and DMAA showed significant improvements in both groups after surgery, but with no significant differences between the two groups. The postoperative FML was significantly larger in the RSO group than in the DMO group (p < 0.001). One of the 30 ft (3.3%) in the DMO group exhibited transfer metatarsalgia at 12 months postoperatively, while another foot (3.3%) in same group had avascular necrosis of the metatarsal head. One of the 30 ft (3.1%) in the RSO group had hallux varus. CONCLUSIONS: No differences in the clinical and radiographic results were observed between the two groups with severe HV and an increased DMAA. However, RSO does not cause shortening of the metatarsal and AVN of the metatarsal head. A long-term, randomized, controlled prospective study with a larger sample would provide higher-level evidence for confirming the clinical efficacy and safety of RSO.


Assuntos
Hallux Valgus/diagnóstico por imagem , Hallux Valgus/cirurgia , Ossos do Metatarso/diagnóstico por imagem , Ossos do Metatarso/cirurgia , Osteotomia/métodos , Índice de Gravidade de Doença , Adulto , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
18.
J Foot Ankle Surg ; 58(5): 938-945, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31474405

RESUMO

The aim of this study was to investigate the role of early functional rehabilitation in acute Achilles tendon ruptures. Eligible studies were identified from PubMed, Embase, and the Cochrane Library using the following search keywords: "Achilles tendon rupture" and "rehabilitation" or "function" or "functional" or "mobilization" and "randomized" or "random" or "blind" or "control" or "compare" or "comparative." A heterogeneity test based on I2 statistic and Cochran's Q test was conducted. The pooled risk ratio and weighted mean difference with 95% confidence interval was calculated for each outcome using the random-effect (p < .05 or I2 > 50% for significant heterogeneity) or fixed-effect (p > .05 or I2 < 50% for nonsignificant heterogeneity) model. A subgroup analysis was also performed. Fourteen randomized controlled trials were identified. Pooled data demonstrated no difference in the complication rates, time taken to return to sports, total number of patients returning to work or sports, and satisfaction rate between the early functional rehabilitation and conventional cast immobilization groups. Early functional rehabilitation significantly decreased the time taken to return to work (weighted mean difference -1.56; 95% confidence interval -3.09 to 0.04; p = .04]. Early functional rehabilitation for acute Achilles tendon ruptures appeared to be related to a shorter time taken to return to work; however, it did not affect the other variables between the groups.


Assuntos
Tendão do Calcâneo/lesões , Modalidades de Fisioterapia , Traumatismos dos Tendões/reabilitação , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Ruptura
19.
Foot Ankle Surg ; 25(6): 755-760, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30391038

RESUMO

BACKGROUND: This study intended to investigate the optimal surgical strategy in hallux valgus (HV), and to provide a basis for clinical treatment of HV. METHODS: Studies related to chevron osteotomy and scarf osteotomy for HV were enrolled from online databases. Hallux valgus angle (HVA) was the main outcome variable. Enrolled studies included posttreatment data for intermetatarsal angle (IMA), American Orthopaedic Foot & Ankle Society (AOFAS) score, and complications. A random-effects model was applied for significant heterogeneity. Otherwise, a fixed-effects model was used. Heterogeneity was assessed with Q test and I2 statistics. Publication bias was evaluated with Egger's test. Based on the influence of weighted mean difference values or odds ratios, a sensitivity analysis was performed. RESULTS: Four studies including 384 subjects were evaluated to determine the optimal surgical strategy for HV. There was no statistically significant difference between chevron and scarf groups for HVA, IMA, AOFAS score, and complication rates. Sensitivity analysis showed good stability. The likelihood of publication bias was small. CONCLUSION: The effects of chevron osteotomy and scarf osteotomy for HV are comparable. Chevron osteotomy is less technically demanding.


Assuntos
Hallux Valgus/cirurgia , Osteotomia/métodos , Humanos
20.
Opt Express ; 26(16): 20507-20518, 2018 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-30119360

RESUMO

Evolution of next generation wireless networks brings challenges to efficiently transmit a large amount of data from a base station to a remote antenna unit. We investigate a space division multiplexing technique that employs few mode fibers (FMFs) to transmit 3 × 3 MIMO wireless signals, aiming to employ a common digital signal processing (DSP) unit to equalize both the fiber and wireless channel. We optimize system parameters and obtain above 28 dB and 23 dB signal-to-interference and noise ratio (SINR) for 3 meters wireless systems with 500 m and 2 km FMF, which correspond to the transmission capacity of 578 Mb/s and 468 Mb/s using a 20 MHz bandwidth, respectively. Moreover, we analyze that the nonlinear spectrum distortion due to the combined effect of nonlinearity in the directly modulated laser and the differential mode delay in multimode fibers and validate it by simulations.

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