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1.
BMC Musculoskelet Disord ; 25(1): 327, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38658889

RESUMO

BACKGROUND: Congenital dislocation of the knee is characterised by excessive knee extension or dislocation and anterior subluxation of the proximal tibia, and this disease can occur independently or coexist with different systemic syndromes. Nevertheless, significant controversy surrounds treating this disease when combined with hip dislocation. This paper presents a case of a 4-month-old patient diagnosed with bilateral hip dislocation combined with this disease. The study discusses the pathophysiology, diagnosis, and treatment methods and reviews relevant literature. CASE PRESENTATION: We reported a case of a 4-month-old female infant with congenital dislocation of the right knee joint, which presented as flexion deformity since birth. Due to limitations in local medical conditions, she did not receive proper and effective diagnosis and treatment. Although the flexion deformity of her right knee joint partially improved without treatment, it did not fully recover to normal. When she was 4 months old, she came to our hospital for consultation, and we found that she also had congenital dislocation of both hip joints and atrial septal defect. We performed staged treatment for her, with the first stage involving surgical intervention and plaster orthosis for her congenital dislocation of the right knee joint, and the second stage involving closed reduction and plaster fixation orthosis for her congenital hip joint dislocation. Currently, the overall treatment outcome is satisfactory, and she is still under follow-up observation. CONCLUSIONS: Early initiation of treatment is generally advised, as nonsurgical methods prove satisfactory for mild cases. However, surgical intervention should be considered in cases with severe stiffness, unresponsive outcomes to conservative treatment, persistent deformities, or diagnoses and treatments occurring beyond the first month after birth.


Assuntos
Luxação Congênita de Quadril , Luxação do Joelho , Humanos , Feminino , Luxação do Joelho/complicações , Luxação do Joelho/congênito , Luxação do Joelho/terapia , Luxação do Joelho/diagnóstico por imagem , Luxação do Joelho/cirurgia , Luxação do Joelho/diagnóstico , Luxação Congênita de Quadril/complicações , Luxação Congênita de Quadril/terapia , Luxação Congênita de Quadril/diagnóstico , Lactente , Resultado do Tratamento , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/fisiopatologia , Moldes Cirúrgicos
2.
Front Bioeng Biotechnol ; 12: 1356135, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38600948

RESUMO

Introduction: Developmental engineering based on endochondral ossification has been proposed as a potential strategy for repairing of critical bone defects. Bone development is driven by growth plate-mediated endochondral ossification. Under physiological conditions, growth plate chondrocytes undergo compressive forces characterized by micro-mechanics, but the regulatory effect of micro-mechanical loading on endochondral bone formation has not been investigated. Methods: In this study, a periodic static compression (PSC) model characterized by micro-strain (with 0.5% strain) was designed to clarify the effects of biochemical/mechanical cues on endochondral bone formation. Hydrogel scaffolds loaded with bone marrow mesenchymal stem cells (BMSCs) were incubated in proliferation medium or chondrogenic medium, and PSC was performed continuously for 14 or 28 days. Subsequently, the scaffold pretreated for 28 days was implanted into rat femoral muscle pouches and femoral condylar defect sites. The chondrogenesis and bone defect repair were evaluated 4 or 10 weeks post-operation. Results: The results showed that PSC stimulation for 14 days significantly increased the number of COL II positive cells in proliferation medium. However, the chondrogenic efficiency of BMSCs was significantly improved in chondrogenic medium, with or without PSC application. The induced chondrocytes (ichondrocytes) spontaneously underwent hypertrophy and maturation, but long-term mechanical stimulation (loading for 28 days) significantly inhibited hypertrophy and mineralization in ichondrocytes. In the heterotopic ossification model, no chondrocytes were found and no significant difference in terms of mineral deposition in each group; However, 4 weeks after implantation into the femoral defect site, all scaffolds that were subjected to biochemical/mechanical cues, either solely or synergistically, showed typical chondrocytes and endochondral bone formation. In addition, simultaneous biochemical induction/mechanical loading significantly accelerated the bone regeneration. Discussion: Our findings suggest that microstrain mechanics, biochemical cues, and in vivo microenvironment synergistically regulate the differentiation fate of BMSCs. Meanwhile, this study shows the potential of micro-strain mechanics in the treatment of critical bone defects.

3.
Front Neurol ; 15: 1374365, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38595854

RESUMO

Objectives: This study aims to elucidate the role of peripheral inflammation in Huntington's disease (HD) by examining the correlation of peripheral inflammatory markers with clinical manifestations and disease prognosis. Methods: This investigation involved 92 HD patients and 92 matched healthy controls (HCs). We quantified various peripheral inflammatory markers and calculated their derived metrics including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and systemic immune-inflammation index (SII). Clinical assessments spanning cognitive, motor, and disease severity were administered. Comparative analysis of inflammatory markers and clinical correlations between HD and controls was performed. Kaplan-Meier survival analysis and Cox regression model were used to assess the effect of inflammatory markers on survival. Results: The study revealed that HD patients had significantly reduced lymphocyte counts, and LMR. Conversely, NLR, PLR, and SII were elevated compared to HCs. Lymphocyte levels inversely correlated with the age of onset and monocyte levels inversely correlated with the UHDRS-total functional capacity (TFC) scores. After adjusting for age, sex, and CAG repeat length, lymphocyte count, NLR, PLR, and SII were significantly correlated with the progression rate of TFC scores. Elevated levels of white blood cells and monocytes were associated with an increased risk of disability and mortality in the HD cohort. Conclusion: Our findings indicate that HD patients display a distinct peripheral inflammatory profile with increased NLR, PLR, and SII levels compared to HCs. The peripheral inflammation appears to be linked with accelerated disease progression and decreased survival in HD.

4.
Mol Med ; 30(1): 38, 2024 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-38493291

RESUMO

BACKGROUND: Macrophage-derived extracellular vesicle (macrophage-EV) is highly studied for its regulatory role in atherosclerosis (AS). Our current study tried to elucidate the possible role of macrophage-EV loaded with small interfering RNA against high-mobility group box 1 (siHMGB1) affecting atherosclerotic plaque formation. METHODS: In silico analysis was performed to find critical factors in mouse atherosclerotic plaque formation. EVs secreted by RAW 264.7 cells were collected by ultracentrifugation and characterized, followed by the preparation of macrophage-EV-loaded siHMGB1 (macrophage-EV/siHMGB1). ApoE-/- mice were used to construct an AS mouse model by a high-fat diet, followed by injection of macrophage-EV/siHMGB1 to assess the in vivo effect of macrophage-EV/siHMGB1 on AS mice. RAW264.7 cells were subjected to ox-LDL, LPS or macrophage-EV/siHMGB1 for analyzing the in vitro effect of macrophage-EV/siHMGB1 on macrophage pyrophosis and inflammation. RESULTS: In silico analysis found that HMGB1 was closely related to the development of AS. Macrophage-EV/siHMGB could inhibit the release of HMGB1 from macrophages to outside cells, and the reduced HMGB1 release could inhibit foam cell formation. Besides, macrophage-EV/siHMGB also inhibited the LPS-induced Caspase-11 activation, thus inhibiting macrophage pyroptosis and preventing atherosclerotic plaque formation. CONCLUSION: Our results proved that macrophage-EV/siHMGB could inhibit foam cell formation and suppress macrophage pyroptosis, finally preventing atherosclerotic plaque formation in AS mice.


Assuntos
Aterosclerose , Vesículas Extracelulares , Proteína HMGB1 , Placa Aterosclerótica , Animais , Camundongos , Apolipoproteínas E/genética , Aterosclerose/genética , Caspases , Regulação para Baixo , Proteína HMGB1/genética , Lipopolissacarídeos/farmacologia , Macrófagos , Piroptose
5.
J Child Orthop ; 18(1): 40-48, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38348436

RESUMO

Objective: This review provides guidance and ideas for researchers through a comprehensive and comparative analysis of the present state, trends, and hotspots in the pediatric fracture literature over the past 6 years. Methods: We used Citespace 6.1.R6 software to explore the country/region distribution, institutions, journals, keyword analysis, and co-cited references of the literature from Web of Science core database. Results: There are 6472 pieces of pediatric fracture-related literature, including 2962 from 2017 to 2019 and 3510 from 2020 to 2022. The country with the most papers is the United States, and US institutions and journals also have a pivotal position in this field. Research hotspots for pediatric fractures in 2017-2019: The topic with the most attention is bone mineral density leading to related bone diseases. Treatment for pediatric fractures, including supracondylar humeral fractures, Monteggia fractures, forearm fractures, knee fractures, and ankle fractures in children, is another topic of greater interest. Brain injuries and dental injuries in children due to abuse and trauma are also concerning issues. Research hotspots for pediatric fractures in 2020-2022: comparison with 2017-2019 revealed a relative decrease regarding ankle-related epiphyseal injuries, but there is a higher focus on the epidemiology of fractures in children, risk factors, and reasons for childhood trauma. We have confirmed through literature co-citations that the literature of high interest is also in these aspects. Conclusion: Researchers and clinicians can quickly learn about topics of interest through authoritative journals and highly cited literature and rapidly master the current status and frontiers of the field through study, providing ideas for future work.

6.
J Orthop Translat ; 44: 88-101, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38282752

RESUMO

Background: Mutations in Slc26a2 cause a spectrum of autosomal-recessive chondrodysplasia with a significant and negligible influence on the quality of life. It has been reported that Slc26a2 deficiency triggers the ATF6 branch of the UPR, which may, in turn, activate the negative regulator of the FGFR3 signaling pathway. However, the correlation between the deletion of Slc26a2 and the augmentation of downstream phosphorylation of FGFR3 has not been investigated in vivo. Methods: First, we constructed Slc26a2 and Fgfr3 double knockout mouse lines and observed gross views of the born mice and histological staining of the tibial growth plates. The second approach was to construct tamoxifen-inducible Cre-ERT2 mouse models to replicate SLC26A2-related non-lethal dysplastic conditions. Pharmacological intervention was performed by administering the FGFR3 inhibitor NVP-BGJ398. The effect of NVP-BGJ398 on chondrocytes was assessed by Alcian blue staining, proliferation, apoptosis, and chondrocyte-specific markers and then verified by western blotting for variations in the downstream markers of FGFR3. The growth process was detected using X-rays, micro-CT examination, histomorphometry staining of growth plates, and immunofluorescence. Results: Genetic ablation of Fgfr3 in embryonic Slc26a2-deficient chondrocytes slightly attenuated chondrodysplasia. Subsequently, in the constructed mild dysplasia model, we found that postnatal intervention with Fgfr3 gene in Slc26a2-deficient chondrocytes partially alleviated chondrodysplasia. In chondrocyte assays, NVP-BGJ398 suppressed the defective phenotype of Slc26a2-deficient chondrocytes and restored the phosphorylation downstream of FGFR3 in a concentration-dependent manner. In addition, in vivo experiments showed significant alleviation of impaired chondrocyte differentiation, and micro-CT analysis showed a clear improvement in trabecular bone microarchitectural parameters. Conclusion: Our results suggested that inhibition of FGFR3 signaling pathway overactivation and NVP-BGJ398 has promising therapeutic implications for the development of SLC26A2-related skeletal diseases in humans. The translational potential of this article: Our data provide genetic and pharmacological evidence that targeting FGFR3 signaling via NVP-BGJ398 could be a route for the treatment of SLC26A2-associated skeletal disorders, which promisingly advances translational applications and therapeutic development.

7.
Mol Med ; 29(1): 122, 2023 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-37684563

RESUMO

BACKGROUND: Children of mothers with gestational diabetes mellitus (GDM) are more prone to acquire type 2 diabetes and obesity as adults. Due to this link, early intervention strategies that alter the gut microbiome may benefit the mother and kid long-term. This work uses metagenomic and transcriptome sequencing to investigate how probiotics affect gut microbiota dysbiosis and inflammation in GDM. METHODS: GDM and control metagenomic sequencing data were obtained from the SRA database. This metagenomic data helped us understand gut microbiota abundance and function. KEGG detected and extracted functional pathway genes. Transcriptome sequencing data evaluated GDM-related gene expression. Finally, GDM animal models were given probiotics orally to evaluate inflammatory response, regulatory immune cell fractions, and leptin protein levels. RESULTS: GDM patients had more Fusobacteria and Firmicutes, while healthy people had more Bacteroidetes. Gut microbiota composition may affect GDM by altering the L-aspartate and L-asparagine super pathways. Mannan degradation and the super pathway of L-aspartate and L-asparagine synthesis enhanced in GDM mice with leptin protein overexpression. Oral probiotics prevent GDM by lowering leptin. Oral probiotics increased Treg, Tfr, and Breg cells, which decreased TNF-α and IL-6 and increased TGF-ß and IL-10, preventing inflammation and preserving mouse pregnancy. CONCLUSION: Dysbiosis of the gut microbiota may increase leptin expression and cause GDM. Oral probiotics enhance Treg, Tfr, and Breg cells, which limit the inflammatory response and assist mice in sustaining normal pregnancy. Thus, oral probiotics may prevent GDM, enabling targeted gut microbiota modulation and maternal and fetal health.


Assuntos
Linfócitos B Reguladores , Diabetes Mellitus Tipo 2 , Diabetes Gestacional , Feminino , Gravidez , Humanos , Animais , Camundongos , Asparagina , Ácido Aspártico , Disbiose , Leptina , Linfócitos T Reguladores , Inflamação
8.
Front Pediatr ; 11: 1188179, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37601134

RESUMO

Background: Less than 1% of children develop femoral neck fractures (FNF), making them uncommon. However, they may have dangerous side effects, like avascular necrosis. Even though several risk factors for postoperative avascular necrosis have been identified, there is still debate regarding them. In this investigation, a meta-analysis was performed to examine the potential causes of postoperative avascular necrosis in children with FNF. Methods: We conducted a thorough literature search to find risk factors for avascular necrosis (AVN) after internal fixation of pediatric FNF. Until December 2022, we searched several databases, including PubMed, Embase, Cochrane Library, Web of Science, CNKI, Orthosearch, and Sinomed. Software Zotero 6.0 and Stata 17.0 were used to organise and synthesise the data. Finally, a sensitivity and publication bias test was carried out. Results: Our study includes a total of 15 case-control studies involving 814 patients. The risk of postoperative AVN increased with age at fracture encounter (95% CI: 0.64-1.88, P = 0.0003), initial fracture displacement (95% CI: 1.87-9.54, P = 0.0005), and poor fracture reduction (95% CI:1.95-22.34, P = 0.0024) were risk factors for postoperative AVN. There was no significant relationship between gender and postoperative AVN (95% CI: 0.52-1.31, P = 0.41). Conversely, Postoperative AVN and reduction methods have no connection with each other (95% CI: 0.77-2.66, P = 0.25), procedure time (95% CI: 0.43-2.99, P = 0.16), or injury mechanism (95% CI: 0.32-2.26, P = 0.75). The incidence of post-operative AVN varies between Delbet fracture types (95% CI: 0.15-0.31, P < 0.0001), with the overall trend being that the incidence of post-operative AVN is highest for type II, lowest for type IV, and close for types I and III, but it is not clear which type of fracture is the independent risk factor. Funnel plots indicate no significant publication bias. Conclusions: In line with this study, About 26% of children who underwent surgery for a femoral neck fracture suffered postoperative AVN. The main risk factors for AVN were the child's age, the initial displacement of the fractures, and poorly reduced fractures. The risk of AVN did not significantly correlate with gender, the time of the procedure, reduction methods or the mechanism of injury. The overall trend in the incidence of postoperative AVN for the different Delbet types of fracture is that the incidence of postoperative AVN is highest for type II, lowest for type IV, and close for types I and III, but it is not clear which type of fracture is the independent risk factor.

9.
Sci Transl Med ; 15(710): eadg3983, 2023 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-37611084

RESUMO

Sulfation is a widespread modification of biomolecules that has been incompletely explored to date. Through cross-phenotype meta-analysis of bone mineral density in up to 426,824 genotyped human participants along with phenotypic characterization of multiple mutant mouse lines, we identified a causative role for sulfate transporter solute carrier family 26 member A2 (SLC26A2) deficiency in osteoporosis. Ablation of SLC26A2 in osteoblasts caused severe bone loss and accumulation of immature bone cells and elicited peculiar pericellular matrix (PCM) production characterized by undersulfation coupled with decreased stiffness. These altered chemophysical properties of the PCM disrupted the formation of focal adhesions in osteoblasts. Bulk RNA sequencing and functional assays revealed that the mechanoreciprocal inhibition of focal adhesion kinase (FAK) and Yes1-associated transcriptional regulator (YAP)/WW domain containing transcription regulator 1 (TAZ) signaling impinged osteoblast maturation upon SLC26A2 deficiency. Moreover, pharmacological abrogation of the Hippo kinases and forced wheel-running ameliorated SLC26A2-deficient osteoporosis by promoting YAP/TAZ activity. Analysis of mouse single-cell RNA sequencing data suggested coordination among sulfate metabolism, focal adhesion, and YAP/TAZ activity during osteoblast-to-osteocyte transition. In addition to the SLC26A2-deficient setting, altered FAK and YAP/TAZ signaling was also observed in bone cells of ovariectomized mice and patients with osteoporosis, and pharmacological enforcing of YAP/TAZ activity ameliorated bone loss in ovariectomized mice. Collectively, these data unveil a role for sulfation in the developmental mechanoreciprocity between matrix and osteoblasts, which could be leveraged to prevent bone loss.


Assuntos
Doenças Ósseas Metabólicas , Osteoporose , Humanos , Animais , Camundongos , Osteoblastos , Osteoporose/genética , Densidade Óssea , Bioensaio , Peptídeos e Proteínas de Sinalização Intracelular
10.
Front Pediatr ; 11: 1210493, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37554152

RESUMO

Objective: This study aims to find the optimal arrangement of the Kirschner wire (K-wire) in the sagittal plane for fixation of a pediatric lateral condylar humeral fracture (Milch type II) by using finite element analysis (FEA). Methods: A model of lateral condyle fracture in a 6-year-old boy was developed, and an XYZ coordinate system was established based on this model. The YZ plane was defined as the sagittal plane to investigate the impact of the angle formed by the first and second K-wires on stability. Two configurations were studied for each angle: parallel and divergent. Evaluation indicators included the maximum displacement of the fracture fragment and the maximum von Mises stress in the pins and bone. Results: The model with a -60° angle showed the best performance in both evaluation indicators. The parallel and divergent pin configurations had different performances in each group. The displacement results for negative angles were similar, and this result was better than those for positive angles. Conclusion: We successfully created a model of pediatric lateral condyle humerus fracture (Milch type II) and performed K-wire fixation with varying sagittal plane configurations, combined with FEA. Our findings demonstrate that the angle of -60° between the two pins in the sagittal plane provided the highest level of stability, with divergent configurations proving superior to parallel pinning at this angle.

11.
Mol Med Rep ; 28(3)2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37539751

RESUMO

Subsequently to the publication of the above paper, an interested reader drew to the authors' attention that, in Fig. 2A on p. 8311, portraying the results of immunostaining experiments for osterix, the 'GIOP' and 'GIOP+TMP (20)' data panels contained overlapping data, such that these images were derived from apparently the same original source, where they were intended to show the results from differently performed experiments. Moreover, in Fig. 3A on p. 8312 showing the results from ALP staining and Alizarin Red S staining experiments, two pairs of apparently overlapping data panels were identified in the Dex 106 M / TMP 50 µM, 100 µM and 200 µM data panels. After having re­examined their original data, the authors have realized that the data featured in Figs. 2A and 3A were assembled incorrectly in these figures. Revised versions of Fig. 2 and 3, now containing replacement data for the experiments shown in Figs. 2A and 3A, are shown on the next page. Note that these errors did not adversely affect either the results or the overall conclusions reported in this study. All the authors agree with the publication of this corrigendum, and are grateful to the Editor of Molecular Medicine Reports for allowing them the opportunity to publish this. They also wish to apologize to the readership of the Journal for any inconvenience caused. [Molecular Medicine Reports 16: 8307­8314, 2017; DOI: 10.3892/mmr.2017.7610].

13.
BMJ Open ; 13(7): e072541, 2023 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-37433737

RESUMO

INTRODUCTION: Percutaneous coronary intervention (PCI)-related myocardial infarction (type 4a MI) and major periprocedural myocardial injury have been demonstrated leading to poor prognosis of patients with coronary heart disease (CHD) undergoing elective PCI and still remain high occurrence even after the therapy of dual antiplatelet agents and statins. Proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab has been shown to be effectively in reducing the risk of acute MI (AMI). However, the effect of alirocumab on preventing PCI-related MI or major periprocedural myocardial injury in patients with CHD undergoing elective PCI remains uncertain. METHODS AND ANALYSIS: Alirocumab effect on Preventing Periprocedural ischaemic Events in coronary heart diseAse patients undergoing coronary StEnting trial is a multicentre, open-label, randomised controlled trial aiming to determine whether alirocumab could reduce the incidence of type 4a MI or major periprocedural myocardial injury in patients with CHD undergoing elective PCI. In total, 422 non-AMI CHD patients planned to undergo elective PCI will be randomly assigned to receive standard pharmacotherapy of CHD (control group) or additional use of subcutaneous alirocumab 75 mg 1 day before procedure (alirocumab group). The primary outcome is type 4a MI or major periprocedural myocardial injury defined as high-sensitivity cardiac troponin elevating above 5×99 th percentile upper reference limit in 48 hours after PCI. Patients will continue receiving standard pharmacotherapy or additional biweekly subcutaneous alirocumab 75 mg for 3 months according to the initial randomisation group. We will follow up for 3 months and record all the major adverse cardiovascular events (MACEs). Incidence of PCI-related MI or major periprocedural myocardial injury, and MACE in 3 months after PCI will be compared between control group and alirocumab group. ETHICS AND DISSEMINATION: Ethics approval has been obtained from the Medical Ethics Committee of the Third Affiliated Hospital of Sun Yat-sen University with approval number: (2022)02-140-01. The results of this study will be reported through peer-reviewed journals and conference presentations. TRIAL REGISTRATION NUMBER: ChiCTR2200063191.


Assuntos
Doença das Coronárias , Infarto do Miocárdio , Intervenção Coronária Percutânea , Humanos , Anticorpos Monoclonais Humanizados/uso terapêutico , Doença das Coronárias/complicações , Doença das Coronárias/cirurgia , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como Assunto
14.
Cell Mol Life Sci ; 80(6): 171, 2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-37261512

RESUMO

Imbalance of bone homeostasis induces bone degenerative diseases such as osteoporosis. Hedgehog (Hh) signaling plays critical roles in regulating the development of limb and joint. However, its unique role in bone homeostasis remained largely unknown. Here, we found that canonical Hh signaling pathway was gradually augmented during osteoclast differentiation. Genetic inactivation of Hh signaling in osteoclasts, using Ctsk-Cre;Smof/f conditional knockout mice, disrupted both osteoclast formation and subsequent osteoclast-osteoblast coupling. Concordantly, either Hh signaling inhibitors or Smo/Gli2 knockdown stunted in vitro osteoclast formation. Mechanistically, Hh signaling positively regulated osteoclast differentiation via transactivation of Traf6 and stabilization of TRAF6 protein. Then, we identified connective tissue growth factor (CTGF) as an Hh-regulatory bone formation-stimulating factor derived from osteoclasts, whose loss played a causative role in osteopenia seen in CKO mice. In line with this, recombinant CTGF exerted mitigating effects against ovariectomy induced bone loss, supporting a potential extension of local rCTGF treatment to osteoporotic diseases. Collectively, our findings firstly demonstrate that Hh signaling, which dictates osteoclast differentiation and osteoclast-osteoblast coupling by regulating TRAF6 and CTGF, is crucial for maintaining bone homeostasis, shedding mechanistic and therapeutic insights into the realm of osteoporosis.


Assuntos
Doenças Ósseas Metabólicas , Reabsorção Óssea , Osteoporose , Feminino , Camundongos , Animais , Osteoclastos/metabolismo , Proteínas Hedgehog/genética , Proteínas Hedgehog/metabolismo , Fator 6 Associado a Receptor de TNF/metabolismo , Osteoblastos/metabolismo , Osteogênese , Transdução de Sinais , Osteoporose/genética , Osteoporose/metabolismo , Homeostase , Doenças Ósseas Metabólicas/genética , Doenças Ósseas Metabólicas/metabolismo , Diferenciação Celular , Reabsorção Óssea/metabolismo
15.
Plant Biotechnol J ; 21(9): 1873-1886, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37323119

RESUMO

Salicylic acid (SA) is an essential plant hormone that plays critical roles in basal defence and amplification of local immune responses and establishes resistance against various pathogens. However, the comprehensive knowledge of the salicylic acid 5-hydroxylase (S5H) in rice-pathogen interaction is still elusive. Here, we reported that three OsS5H homologues displayed salicylic acid 5-hydroxylase activity, converting SA into 2,5-dihydroxybenzoic acid (2,5-DHBA). OsS5H1, OsS5H2, and OsS5H3 were preferentially expressed in rice leaves at heading stage and responded quickly to exogenous SA treatment. We found that bacterial pathogen Xanthomonas oryzae pv. oryzae (Xoo) strongly induced the expression of OsS5H1, OsS5H2, and OsS5H3. Rice plants overexpressing OsS5H1, OsS5H2, and OsS5H3 showed significantly decreased SA contents and increased 2,5-DHBA levels, and were more susceptible to bacterial blight and rice blast. A simple single guide RNA (sgRNA) was designed to create oss5h1oss5h2oss5h3 triple mutants through CRISPR/Cas9-mediated gene mutagenesis. The oss5h1oss5h2oss5h3 exhibited stronger resistance to Xoo than single oss5h mutants. And oss5h1oss5h2oss5h3 plants displayed enhanced rice blast resistance. The conferred pathogen resistance in oss5h1oss5h2oss5h3 was attributed to the significantly upregulation of OsWRKY45 and pathogenesis-related (PR) genes. Besides, flg22-induced reactive oxygen species (ROS) burst was enhanced in oss5h1oss5h2oss5h3. Collectively, our study provides a fast and effective approach to generate rice varieties with broad-spectrum disease resistance through OsS5H gene editing.


Assuntos
Oryza , Xanthomonas , Resistência à Doença/genética , Sistemas CRISPR-Cas , RNA Guia de Sistemas CRISPR-Cas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Ácido Salicílico/farmacologia , Ácido Salicílico/metabolismo , Mutação/genética , Oryza/metabolismo , Doenças das Plantas/microbiologia , Regulação da Expressão Gênica de Plantas
16.
Front Pediatr ; 11: 1120256, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37056941

RESUMO

Purpose: To explore the characteristics, mechanism, treatment, and prognosis of head-neck separation type of Monteggia equivalent fractures in children. Methods: Patients with this injury were reviewed retrospectively. The lesion was characterized by a fracture of the ulnar with radial neck fracture but without dislocation of the radial head. Our classification was based on the direction of displacement and angulation of fractures on radiographs, divided into the extension-valgus type and flexion-varus type. The fractures were treated with reduction and internal fixation, depending on the fracture type. The clinical results were evaluated by using radiology and the Mayo Elbow Performance Score (MEPS). Results: A total of 12 patients were followed up for an average of 40.5 months. The ulnar fractures were treated with closed reduction (CR) and K-wire fixation in one patient, elastic stable intramedullary nail (ESIN) fixation in four patients, open reduction (OR) and plate fixation in five, with no fixation in two. CR with ESIN fixation was successful in 11 patients with radial neck fractures, but one underwent OR and K-wire fixation. All fractures healed on time, with fewer complications (avascular necrosis in one patient, and bulk formation of metaphysis in another). The therapeutic efficacy was evaluated by using MEPS and was found to be excellent in 10 patients, good in one, and fair in another. Conclusions: The head-neck separation type of Monteggia equivalent fractures in children is rare. Its characteristics are different from that of Monteggia fracture. The length and anatomic structure of the ulna should be restored and stabilized first, while the radial neck fracture should be treated with CR and ESIN fixation. Satisfactory clinical results can be achieved with fewer complications.

17.
Front Pediatr ; 11: 1124123, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37063659

RESUMO

Object: This study was designed to analyze the cartilaginous predictors of residual acetabular dysplasia (RAD) after early treatment of developmental dysplasia of the hip and their diagnostic accuracy. Study design: Databases such as PubMed, Embase, Cochrane, and Web of science were searched to screen the literature. The quality of the literature was assessed by the QUADAS-2 tool. Qualitative and quantitative synthesis of literature were performed based on extracted data. For quantitative synthesis studies, the sensitivity, specificity, diagnostic odds ratio (DOR), and summary receiver operating characteristic (SROC) curve with corresponding confidence intervals were calculated. Results: For the cartilaginous acetabular index (CAI) group, the combined values of sensitivity, specificity, and DOR were 0.80 (95% CI = 0.54-0.93), 0.73 (95% CI = 0.57-0.84), and 10.62 (95% CI = 3.96-28.53), respectively. The corresponding values in the cartilaginous center-edge angle (CCE) group were 0.71 (95% CI = 0.57-0.82), 0.78 (95% CI = 0.66-0.87), and 8.64 (95% CI = 3.08-24.25), respectively. The area under the curve (AUC) of SROC was 0.82 (95% CI = 0.78-0.85) and 0.80 (95% CI = 0.76-0.83) for the CAI and CCE groups. The CAI group had higher sensitivity, DOR, and AUC than the CCE group. Conclusion: Both of these two groups have good diagnostic accuracy, and CAI/L-AI has a little edge over CCE/L-CEA. However, there is still more research needed to determine whether they can be used as independent indications for secondary orthopedic surgery.Systematic review registration: [https://www.crd.york.ac.uk/PROSPERO/], identifier: [CRD42022338332].

18.
Front Pediatr ; 11: 1131618, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36969277

RESUMO

Background: Skeletal maturity can evaluate the growth and development potential of children and provide a guide for the management of adolescent idiopathic scoliosis (AIS). Recent studies have demonstrated the advantages of the Humeral Head Ossification System (HHOS) and the Proximal Femur Maturity Index (PFMI), based on standard scoliosis films, in the management of AIS patients. We further assessed the HHOS and the PFMI method's reliability in the interrater and intrarater. Methods: The data from 38 patients, including the humeral head and proximal femur on standard scoliosis films, were distributed to the eight raters in the form of a PowerPoint presentation. On 38 independent standard spine radiographs, raters utilized the HHOS and PFMI to assign grades. The PPT sequence was randomly changed and then reevaluated 2 weeks later. For every system, the 95% confidence interval (95% CI) and intraclass correlation coefficient (ICC) were calculated to evaluate the interrater and intrarater reliability. Results: The HHOS was extremely reliable, with an intraobserver ICC of 0.802. In the first round, the interobserver ICC reliability for the HHOS was 0.955 (0.929-0.974), while in the second round, it was 0.939 (0.905-0.964). The PFMI was extremely reliable, with an intraobserver ICC of 0.888. In the first round, the interobserver ICC reliability for the PFMI was 0.967 (0.948-0.981), while in the second round, it was 0.973 (0.957-0.984). Conclusions: The HHOS and PFMI classifications had excellent reliability. These two methods are beneficial to reduce additional exposure to radiation and expense for AIS. There are advantages and disadvantages to each classification. Clinicians should choose a personalized and reasonable method to assess skeletal maturity, which will assist in the management of adolescent scoliosis patients.

20.
Sci Rep ; 13(1): 1181, 2023 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-36681716

RESUMO

To analyze the curative effect of varying treatment types in 75 pediatric cases of radial neck fracture and explore the prognosis-related factors. Clinical data of 75 children with radial neck fractures treated in our hospital from January 2015 to December 2016 were retrospectively collected. The relationship between age, fracture type, treatment method, X-ray examination after reduction, and prognosis was analyzed. Age was related to prognosis. The excellent and good rate of treatment was 89.25% for children with age ≤ 10 and 57.89% for children over 10 years old. The type of fracture was closely related to the curative effect, 95.0% of O'Brien type I fractures had good curative effects, and the excellent and good rates of O'Brien II type and III type fractures were 87.0 and 66.7%, respectively. According to the type of fracture, the excellent and good rate of patients treated with plaster fixation was the highest (96.42%), but the excellent and good rate was 72.3% in the patients who needed to be reduced by Kirschner wire or elastic intramedullary nail. Although open reduction is superior to closed reduction in imaging evaluation, the excellent and good rate is only 50%.The prognosis of children with radial neck fracture is related to age, type of fracture, and treatment method. In pediatric patients less than 10 years with light, shifted fractures, the excellent and good prognosis rate is higher with less operative intervention. We recommend treating patients with closed reduction and elastic nail fixation according to different fracture types.


Assuntos
Fixação Intramedular de Fraturas , Fraturas da Cabeça e do Colo do Rádio , Fraturas do Rádio , Humanos , Criança , Estudos Retrospectivos , Fixação Intramedular de Fraturas/métodos , Resultado do Tratamento , Fios Ortopédicos , Fixação Interna de Fraturas/métodos , Fraturas do Rádio/diagnóstico por imagem , Fraturas do Rádio/cirurgia
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